Author Report for: Chen ZNo contact information in database for Chen Z
Chen Z, Yu J, Sun K, Song J, Chen L, Jiang Y, Wang Z Ref: Analyst, :, 2023 : PubMed ESTHER: Chen_2023_Analyst__ PubMedSearch: Chen 2023 Analyst PubMedID: 36661088 Abstract In vivo selective fluorescence imaging of carboxylesterase 2 (CES2) remains a great challenge because existing fluorescence probes can potentially suffer from interference by other hydrolases. In addition, some fluorescent probes that have been separately reported for measuring CES2 activity in vitro are affected by autofluorescence and absorption of the biological matrix due to their limited emission wavelength or short Stokes shift. Herein, based on the substrate preference and catalytic performance of CES2, a novel and NIR fluorescent probe was developed, in which a hemi-cyanine dye ester derivative was used as the basic fluorescent group. In the presence of CES2, the probe was hydrolyzed to expose the fluorophore CZX-OH (lambda(abs) - 675 nm, lambda(em) - 850 nm), which led to a notable red-shift in the fluorescence (-175 nm) spectrum. Confocal imaging of cells and live mice demonstrated that the fluorescent signal of this probe was related to the real activities of CES2 in cancer cells. All these results will powerfully promote the screening of CES2 regulators and the analysis of CES2-related physiological and pathological processes. Title: High-efficiency depolymerization/degradation of polyethylene terephthalate plastic by a whole-cell biocatalyst Fang Y, Chao K, He J, Wang Z, Chen Z Ref: 3 Biotech, 13:138, 2023 : PubMed ESTHER: Fang_2023_3.Biotech_13_138 PubMedSearch: Fang 2023 3.Biotech 13 138 PubMedID: 37124986 Abstract Polyethylene terephthalate (PET) is the most abundantly produced plastic due to its excellent performance, but is also the primary source of poorly degradable plastic pollution. The development of environment-friendly PET biodegradation is attracting increasing interest. The leaf-branch compost cutinase mutant ICCG (F243I/D238C/S283C/Y127G) exhibits the best hydrolytic activity and thermostability of all known PET hydrolases. However, its superior PET degradation is highly dependent on its preparation as a purified enzyme, which critically reduces its industrial utility. Herein, we report the use of rational design and combinatorial mutagenesis to develop a novel ICCG mutant RITK (D53R/R143I/D193T/E208K) that demonstrated excellent whole-cell biocatalytic activity. Whole cells expressing RITK showed an 8.33-fold increase in biocatalytic activity compared to those expressing ICCG. Thermostability was also improved. After reacting at 85 degreesC for 3 h, purified RITK exhibited a 12.75-fold increase in depolymerization compared to ICCG. These results will greatly enhance the industrial utility of PET hydrolytic enzymes and further the progress of PET recycling. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-023-03557-4. Title: Inhibition of Th17 cells by donepezil ameliorates experimental lung fibrosis and pulmonary hypertension Guo Y, He Z, Chen Z, Chen F, Wang C, Zhou W, Liu J, Liu H, Shi R Ref: Theranostics, 13:1826, 2023 : PubMed ESTHER: Guo_2023_Theranostics_13_1826 PubMedSearch: Guo 2023 Theranostics 13 1826 PubMedID: 37064881 Abstract Rationale: Pulmonary hypertension (PH) secondary to lung fibrosis belongs to WHO Group III, one of the most common subgroups of PH; however, it lacks effective treatment options. Cholinesterase inhibitor donepezil (DON) has been shown to effectively improve Group I PH. However, its effects on Group III PH are unknown. Methods: A lung fibrosis-induced PH mouse model was constructed using a single intratracheal instillation of bleomycin (BLM), after which DON was administered daily. Pulmonary artery and right ventricle (RV) remodeling were evaluated at the end of the study. Lung tissue in each group was analyzed using RNA sequencing, and the results were further verified with datasets from patients with PH. The mechanisms underlying DON-induced effects on PH were verified both in vivo and in vitro. Results: DON effectively improved pulmonary artery and RV remodeling in the BLM-induced mouse model. Transcriptomic profiles of lung tissue indicated that the expression of inflammatory and fibrotic genes was significantly changed in this process. In the animal model and patients with PH, T helper 17 lymphocytes (Th17) were the most common inflammatory cells infiltrating the lung tissue. DON significantly inhibited lung fibroblast activation; thus, preventing lung fibrosis and reducing the inflammatory response and Th17 cell infiltration in the BLM-induced lung tissue. In addition, Th17 cells could activate lung fibroblasts by secreting IL17A, and DON-mediated inhibition of Th17 cell differentiation was found to depend on the alpha7nAchR-JAK2-STAT3 pathway. Conclusion: DON can alleviate lung fibrosis and PH in an experimental mouse model. It inhibited pro-inflammatory Th17 cell differentiation, which is dependent on a cholinergic receptor pathway, thereby regulating fibroblast activation. Title: Rational Design of Esterase-Insensitive Fluorogenic Probes for In Vivo Imaging Guo WY, Fu YX, Mei LC, Chen Z, Zhang ZY, Wang F, Yang WC, Liu G, Yang GF Ref: ACS Sens, :, 2023 : PubMed ESTHER: Guo_2023_ACS.Sens__ PubMedSearch: Guo 2023 ACS.Sens PubMedID: 37146071 Abstract Small-molecule fluorogenic probes are indispensable tools for performing research in biomedical fields and chemical biology. Although numerous cleavable fluorogenic probes have been developed to investigate various bioanalytes, few of them meet the baseline requirements for in vivo biosensing for disease diagnosis due to their insufficient specificity resulted from the remarkable esterase interferences. To address this critical issue, we developed a general approach called fragment-based fluorogenic probe discovery (FBFPD) to design esterase-insensitive probes for in vitro and in vivo applications. With the designed esterase-insensitive fluorogenic probe, we successfully achieved light-up in vivo imaging and quantitative analysis of cysteine. This strategy was further extended to design highly specific fluorogenic probes for other representative targets, sulfites, and chymotrypsin. The present study expands the bioanalytical toolboxes available and offers a promising platform to develop esterase-insensitive cleavable fluorogenic probes for in vivo biosensing and bioimaging for the early diagnosis of diseases. Title: Salicylic acid attenuates brassinosteroid signaling via protein de-S-acylation Liu X, Chen Z, Huang L, Ouyang Y, Wang Z, Wu S, Ye W, Yu B, Zhang Y and Lai J <1 more author(s)> Liu X, Chen Z, Huang L, Ouyang Y, Wang Z, Wu S, Ye W, Yu B, Zhang Y, Yang C, Lai J (- 1) Ref: EMBO j, :e112998, 2023 : PubMed ESTHER: Liu_2023_EMBO.J__e112998 PubMedSearch: Liu 2023 EMBO.J e112998 PubMedID: 37211868 Gene_locus related to this paper: arath-AT5G20520 Abstract Brassinosteroids (BRs) are important plant hormones involved in many aspects of development. Here, we show that BRASSINOSTEROID SIGNALING KINASEs (BSKs), key components of the BR pathway, are precisely controlled via de-S-acylation mediated by the defense hormone salicylic acid (SA). Most Arabidopsis BSK members are substrates of S-acylation, a reversible protein lipidation that is essential for their membrane localization and physiological function. We establish that SA interferes with the plasma membrane localization and function of BSKs by decreasing their S-acylation levels, identifying ABAPT11 (ALPHA/BETA HYDROLASE DOMAIN-CONTAINING PROTEIN 17-LIKE ACYL PROTEIN THIOESTERASE 11) as an enzyme whose expression is quickly induced by SA. ABAPT11 de-S-acylates most BSK family members, thus integrating BR and SA signaling for the control of plant development. In summary, we show that BSK-mediated BR signaling is regulated by SA-induced protein de-S-acylation, which improves our understanding of the function of protein modifications in plant hormone cross talk. Title: Insecticidal potential of a Consolida ajacis extract and its major compound (ethyl linoleate) against the diamondback moth, Plutella xylostella Peng J, Chen Z, Chen X, Zheng R, Lu S, Seyab M, Yang F, Li Q, Tang Q Ref: Pestic Biochem Physiol, 195:105557, 2023 : PubMed ESTHER: Peng_2023_Pestic.Biochem.Physiol_195_105557 PubMedSearch: Peng 2023 Pestic.Biochem.Physiol 195 105557 PubMedID: 37666618 Abstract The diamondback moth (Plutella xylostella) is one of the most destructive lepidopteran pests of cruciferous vegetables. However, DBM has developed resistance to current chemical and biological insecticides used for its control, indicating the necessity for finding new insecticides against it. Bio-insecticides derived from plant extracts are eco-friendly alternatives to synthetic pesticides. The aims of this study were to evaluate the insecticidal activity of Consolida ajacis seed extracts against DBM, the underlying mechanism of the control effect of promising extracts, and the identification of the main insecticidal compounds of these extracts. The results showed that ethyl acetate extract of C. ajacis seed exhibited strong contact toxicity (LC(50): 5.05 mg/mL), ingestion toxicity, antifeedant, and oviposition deterrent activities against DBM, among the extracts evaluated. At 72 h, glutathiase, acetylcholinesterase, carboxylesterase, peroxidase, and superoxide dismutase activities were inhibited, but catalase activity was activated. The main compound identified from the extract was ethyl linoleate, which had the most significant insecticidal activity on the diamondback moths. This study's findings provide a better understanding of the insecticidal activity of ethyl acetate extract obtained from C. ajacis and its main component (ethyl linoleate). This will help in the development of new insecticides to control DBM. Title: Lonicera japonica polysaccharides alleviate D-galactose-induced oxidative stress and restore gut microbiota in ICR mice Sun W, Zhu J, Qin G, Huang Y, Cheng S, Chen Z, Zhang Y, Shu Y, Zeng X, Guo R Ref: Int J Biol Macromol, :125517, 2023 : PubMed ESTHER: Sun_2023_Int.J.Biol.Macromol__125517 PubMedSearch: Sun 2023 Int.J.Biol.Macromol 125517 PubMedID: 37353132 Abstract Lonicera japonica polysaccharides (LJPs) exhibit anti-aging effect in nematodes. Here, we further studied the function of LJPs on aging-related disorders in D-galactose (D-gal)-induced ICR mice. Four groups of mice including the control group, the D-gal-treated group, the intervening groups with low and high dose of LJPs (50 and 100 mg/kg/day) were raised for 8 weeks. The results showed that intragastric administration with LJPs improved the organ indexes of D-gal-treated mice. Moreover, LJPs improved the activity of superoxide dismutase (SOD), catalase (CAT) as well as glutathione peroxidase (GSH-Px) and decreasing the malondialdehyde (MDA) level in serum, liver and brain. Meanwhile, LJPs restored the content of acetylcholinesterase (AChE) in the brain. Further, LJPs reversed the liver tissue damages in aging mice. Mechanistically, LJPs alleviate oxidative stress at least partially through regulating Nrf2 signaling. Additionally, LJPs restored the gut microbiota composition of D-gal-treated mice by adjusting the Firmicutes/Bacteroidetes ratio at the phylum level and upregulating the relative abundances of Lactobacillaceae and Bifidobacteriacesa. Notably, the KEGG pathways involved in hazardous substances degradation and flavone and flavonol biosynthesis were significantly enhanced by LJPs treatment. Overall, our study uncovers the role of LJPs in modulating oxidative stress and gut microbiota in the D-gal-induced aging mice. Title: Post-Stroke Neuropsychiatric Complications: Types, Pathogenesis, and Therapeutic Intervention Zhou J, Fangma Y, Chen Z, Zheng Y Ref: Aging Dis, :, 2023 : PubMed ESTHER: Zhou_2023_Aging.Dis__ PubMedSearch: Zhou 2023 Aging.Dis PubMedID: 37199575 Abstract Almost all stroke survivors suffer physical disabilities and neuropsychiatric disturbances, which can be briefly divided into post-stroke neurological diseases and post-stroke psychiatric disorders. The former type mainly includes post-stroke pain, post-stroke epilepsy, and post-stroke dementia while the latter one includes post-stroke depression, post-stroke anxiety, post-stroke apathy and post-stroke fatigue. Multiple risk factors are related to these post-stroke neuropsychiatric complications, such as age, gender, lifestyle, stroke type, medication, lesion location, and comorbidities. Recent studies have revealed several critical mechanisms underlying these complications, namely inflammatory response, dysregulation of the hypothalamic pituitary adrenal axis, cholinergic dysfunction, reduced level of 5-hydroxytryptamine, glutamate-mediated excitotoxicity and mitochondrial dysfunction. Moreover, clinical efforts have successfully given birth to many practical pharmaceutic strategies, such as anti-inflammatory medications, acetylcholinesterase inhibitors, and selective serotonin reuptake inhibitors, as well as diverse rehabilitative modalities to help patients physically and mentally. However, the efficacy of these interventions is still under debate. Further investigations into these post-stroke neuropsychiatric complications, from both basic and clinical perspectives, are urgent for the development of effective treatment strategies. Title: Design, synthesis, and evaluation of 8-aminoquinoline-melatonin derivatives as effective multifunctional agents for Alzheimer's disease Chen Z, Yu X, Chen L, Xu L, Cai Y, Hou S, Zheng M, Liu F Ref: Ann Transl Med, 10:303, 2022 : PubMed ESTHER: Chen_2022_Ann.Transl.Med_10_303 PubMedSearch: Chen 2022 Ann.Transl.Med 10 303 PubMedID: 35433950 Abstract BACKGROUND: Alzheimer's disease (AD) is thought to be a complex, multifactorial syndrome with many related molecular lesions contributing to its pathogenesis. Thus, multi-target-directed ligands are considered an effective way of treating AD. This study sought to evaluate 8-aminoquinoline-melatonin derivatives as effective multifunctional agents for AD. METHODS: Thioflavin-T fluorescence assays were used to detect the inhibitory potency of 8-aminoquinoline-melatonin hybrids (a1-a5, b1-b5, and c1-c5) on self- and acetylcholinesterase (AChE)-induced amyloid-beta (Abeta) aggregation. The AChE and butyrylcholinesterase (BuChE) inhibitory potency within the compounds was evaluated by Ellman's assays. Methyl thiazolyl tetrazolium (MTT) assays were performed to evaluate the cytotoxicity of the compounds to C17.2 cells. MTT assay was used to detect the cell viability of HT22 cells to evaluate the antioxidant effect of the compounds. Metal chelation property was measured by ultraviolet-visible spectrophotometry. RESULTS: Compounds c3 and c5 had superior inhibitory activity against self-induced Abeta aggregation (with inhibitory rates of 41.4+/-2.1 and 25.5+/-3.2 at 10 microM, respectively) compared to the other compounds. Compounds in the carbamate group (i.e., a4, a5, b4, b5, c4, and c5) showed significant BuChE inhibitory activity and excellent selectivity over AChE. Most of the compounds exhibited low cytotoxicity in the C17.2 cells. Notably, a2, a3, b2, and b3 and series c (c1-c5) exhibited strong protective effects. Additionally, a3 and c1 specifically chelated with copper ions. CONCLUSIONS: Taking all of the promising results together, 8-aminoquinoline-melatonin hybrids can serve as lead molecules in the further development of new multi-functional anti-AD agents. Title: Intact aleurone cells limit the hydrolysis of endogenous lipids in wheat bran during storage Chen Z, Shen J, Yang Y, Wang H, Xu B Ref: Food Res Int, 161:111799, 2022 : PubMed ESTHER: Chen_2022_Food.Res.Int_161_111799 PubMedSearch: Chen 2022 Food.Res.Int 161 111799 PubMedID: 36192945 Abstract This work aimed to elucidate the effect of aleurone cell integrity on the hydrolysis of endogenous lipids in wheat bran and flour. The distribution of lipases in the bran dissected layers (aleurone layer, outer pericarp and intermediate layer) and the lipid hydrolysis in the bran fractions and flour containing the aleurone cells with different integrity were investigated. The results indicated that 80% of the lipase activities in bran layers were associated with the aleurone layer. After centrifugal impact milling, the aleurone layer in commercial bran could be detached into the monolayer cell clusters with decreasing integrities as the particle size decreased. In the oil phase, intact aleurone cells did not limit the lipase activities in the bran fractions because the oil could penetrate into aleurone cells. During storage, the hydrolysis rates of endogenous lipids in the bran fractions and their mixed flour increased as the integrity of aleurone cells decreased; while after the aleurone cells were broken, the hydrolysis rates of endogenous lipids increased to be in line with the lipase activities in bran fractions, indicating the limitation of intact aleurone cells on lipid hydrolysis. These results gave a new understanding of the effect of aleurone cell structure on the interaction between lipases and lipids in wheat bran, and will facilitate the production of stable wheat bran and whole wheat flour. Title: Biodegradation of highly crystallized poly(ethylene terephthalate) through cell surface codisplay of bacterial PETase and hydrophobin Chen Z, Duan R, Xiao Y, Wei Y, Zhang H, Sun X, Wang S, Cheng Y, Wang X and Wang Z <5 more author(s)> Chen Z, Duan R, Xiao Y, Wei Y, Zhang H, Sun X, Wang S, Cheng Y, Wang X, Tong S, Yao Y, Zhu C, Yang H, Wang Y, Wang Z (- 5) Ref: Nat Commun, 13:7138, 2022 : PubMed ESTHER: Chen_2022_Nat.Commun_13_7138 PubMedSearch: Chen 2022 Nat.Commun 13 7138 PubMedID: 36414665 Gene_locus related to this paper: idesa-peth Abstract The process of recycling poly(ethylene terephthalate) (PET) remains a major challenge due to the enzymatic degradation of high-crystallinity PET (hcPET). Recently, a bacterial PET-degrading enzyme, PETase, was found to have the ability to degrade the hcPET, but with low enzymatic activity. Here we present an engineered whole-cell biocatalyst to simulate both the adsorption and degradation steps in the enzymatic degradation process of PETase to achieve the efficient degradation of hcPET. Our data shows that the adhesive unit hydrophobin and degradation unit PETase are functionally displayed on the surface of yeast cells. The turnover rate of the whole-cell biocatalyst toward hcPET (crystallinity of 45%) dramatically increases approximately 328.8-fold compared with that of purified PETase at 30 degreesC. In addition, molecular dynamics simulations explain how the enhanced adhesion can promote the enzymatic degradation of PET. This study demonstrates engineering the whole-cell catalyst is an efficient strategy for biodegradation of PET. Title: A novel monoacylglycerol lipase-targeted (18)F-labeled probe for positron emission tomography imaging of brown adipose tissue in the energy network Cheng R, Fujinaga M, Yang J, Rong J, Haider A, Ogasawara D, Van RS, Shao T, Chen Z and Liang SH <14 more author(s)> Cheng R, Fujinaga M, Yang J, Rong J, Haider A, Ogasawara D, Van RS, Shao T, Chen Z, Zhang X, Calderon Leon ER, Zhang Y, Mori W, Kumata K, Yamasaki T, Xie L, Sun S, Wang L, Ran C, Shao Y, Cravatt B, Josephson L, Zhang MR, Liang SH (- 14) Ref: Acta Pharmacol Sin, :, 2022 : PubMed ESTHER: Cheng_2022_Acta.Pharmacol.Sin__ PubMedSearch: Cheng 2022 Acta.Pharmacol.Sin PubMedID: 35513432 Gene_locus related to this paper: human-MGLL Inhibitor(s) related to this paper: FEPAD Abstract Monoacylglycerol lipase (MAGL) constitutes a serine hydrolase that orchestrates endocannabinoid homeostasis and exerts its function by catalyzing the degradation of 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA). As such, selective inhibition of MAGL represents a potential therapeutic and diagnostic approach to various pathologies including neurodegenerative disorders, metabolic diseases and cancers. Based on a unique 4-piperidinyl azetidine diamide scaffold, we developed a reversible and peripheral-specific radiofluorinated MAGL PET ligand [(18)F]FEPAD. Pharmacokinetics and binding studies on [(18)F]FEPAD revealed its outstanding specificity and selectivity towards MAGL in brown adipose tissue (BAT) - a tissue that is known to be metabolically active. We employed [(18)F]FEPAD in PET studies to assess the abundancy of MAGL in BAT deposits of mice and found a remarkable degree of specific tracer binding in the BAT, which was confirmed by post-mortem tissue analysis. Given the negative regulation of endocannabinoids on the metabolic BAT activity, our study supports the concept that dysregulation of MAGL is likely linked to metabolic disorders. Further, we now provide a suitable imaging tool that allows non-invasive assessment of MAGL in BAT deposits, thereby paving the way for detailed mechanistic studies on the role of BAT in endocannabinoid system (ECS)-related pathologies. Title: EstG is a novel esterase required for cell envelope integrity in Caulobacter Daitch AK, Orsburn BC, Chen Z, Alvarez L, Eberhard CD, Sundararajan K, Zeinert R, Kreitler DF, Jakoncic J and Goley ED <3 more author(s)> Daitch AK, Orsburn BC, Chen Z, Alvarez L, Eberhard CD, Sundararajan K, Zeinert R, Kreitler DF, Jakoncic J, Chien P, Cava F, Gabelli SB, Goley ED (- 3) Ref: Current Biology, :, 2022 : PubMed ESTHER: Daitch_2022_Curr.Biol__ PubMedSearch: Daitch 2022 Curr.Biol PubMedID: 36516849 Abstract Proper regulation of the bacterial cell envelope is critical for cell survival. Identification and characterization of enzymes that maintain cell envelope homeostasis is crucial, as they can be targets for effective antibiotics. In this study, we have identified a novel enzyme, called EstG, whose activity protects cells from a variety of lethal assaults in the -proteobacterium Caulobacter crescentus. Despite homology to transpeptidase family cell wall enzymes and an ability to protect against cell-wall-targeting antibiotics, EstG does not demonstrate biochemical activity toward cell wall substrates. Instead, EstG is genetically connected to the periplasmic enzymes OpgH and BglX, responsible for synthesis and hydrolysis of osmoregulated periplasmic glucans (OPGs), respectively. The crystal structure of EstG revealed similarities to esterases and transesterases, and we demonstrated esterase activity of EstG insvitro. Using biochemical fractionation, we identified a cyclic hexamer of glucose as a likely substrate of EstG. This molecule is the first OPG described in Caulobacter and establishes a novel class of OPGs, the regulation and modification of which are important for stress survival and adaptation to fluctuating environments. Our data indicate that EstG, BglX, and OpgH comprise a previously unknown OPG pathway in Caulobacter. Ultimately, we propose that EstG is a novel enzyme that instead of acting on the cell wall, acts on cyclic OPGs to provide resistance to a variety of cellular stresses. Title: Hydrophobic cell surface display system of PETase as a sustainable biocatalyst for PET degradation Jia Y, Samak NA, Hao X, Chen Z, Wen Q, Xing J Ref: Front Microbiol, 13:1005480, 2022 : PubMed ESTHER: Jia_2022_Front.Microbiol_13_1005480 PubMedSearch: Jia 2022 Front.Microbiol 13 1005480 PubMedID: 36246227 Abstract Remarkably, a hydrolase from Ideonella sakaiensis 201-F6, termed PETase, exhibits great potential in polyethylene terephthalate (PET) waste management due to it can efficiently degrade PET under moderate conditions. However, its low yield and poor accessibility to bulky substrates hamper its further industrial application. Herein a multigene fusion strategy is introduced for constructing a hydrophobic cell surface display (HCSD) system in Escherichia coli as a robust, recyclable, and sustainable whole-cell catalyst. The truncated outer membrane hybrid protein FadL exposed the PETase and hydrophobic protein HFBII on the surface of E. coli with efficient PET accessibility and degradation performance. E. coli containing the HCSD system changed the surface tension of the bacterial solution, resulting in a smaller contact angle (83.9 +/- 2 degrees vs. 58.5 +/- 1 degrees) of the system on the PET surface, thus giving a better opportunity for PETase to interact with PET. Furthermore, pretreatment of PET with HCSD showed rougher surfaces with greater hydrophilicity (water contact angle of 68.4 +/- 1 degrees vs. 106.1 +/- 2 degrees) than the non-pretreated ones. Moreover, the HCSD system showed excellent sustainable degradation performance for PET bottles with a higher degradation rate than free PETase. The HCSD degradation system also had excellent stability, maintaining 73% of its initial activity after 7 days of incubation at 40 degreesC and retaining 70% activity after seven cycles. This study indicates that the HCSD system could be used as a novel catalyst for efficiently accelerating PET biodegradation. Title: The benefit of exercise rehabilitation guided by 6-minute walk test on lipoprotein-associated phospholipase A2 in patients with coronary heart disease undergoing percutaneous coronary intervention: a prospective randomized controlled study Liu X, Zhou W, Fan W, Li A, Pang J, Chen Z, Li X, Hu X, Zeng Y, Tang L Ref: BMC Cardiovasc Disord, 22:177, 2022 : PubMed ESTHER: Liu_2022_BMC.Cardiovasc.Disord_22_177 PubMedSearch: Liu 2022 BMC.Cardiovasc.Disord 22 177 PubMedID: 35430800 Abstract BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been taken as a biomarker of inflammation in patients with acute coronary diseases. Regular exercise rehabilitation could attenuate inflammation and promote the rehabilitation of coronary heart disease (CHD). The level of Lp-PLA2 is negatively correlated with 6-min walk test (6-MWT). The exercise prescription of appropriate intensity is the basis of exercise rehabilitation. 6-MWT is associated with maximal oxygen consumption, and can be used to determine the intensity of exercise prescription guiding patients how to do exercise rehabilitation. The aim of this study was to observe the benefit of 6-MWT guided exercise rehabilitation on the level of Lp-PLA2 in patients with CHD undergoing percutaneous coronary intervention (PCI). METHODS: We prospectively, consecutively enrolled 100 patients between Dec 2018 and Dec 2020 in the fourth ward of the Department of Cardiology, Yuebei People's Hospital Affiliated to Shantou University. Eligible patients were 1:1 divided into Group A, with no exercise rehabilitation, and Group B, with regular exercise rehabilitation, using random number table method of simple randomization allocation. Clinical data such as general information, the profile of lipids and the level of Lp-PLA2 were collected at baseline and at 12-week follow-up. RESULTS: There were no statistically significant differences of the percentages of gender, hypertension, type-2 diabetes mellitus (T2DM), the profile of lipids and level of Lp-PLA2 between the groups at baseline (P > 0.05). The level of Lp-PLA2 decreased at 12-week follow-up, moreover, the decline of the Lp-PLA2 level in Group B was more significant than that in Group A (t = 2.875, P = 0.005). Multivariate linear regression analysis indicated that exercise rehabilitation was independently correlated with the level of Lp-PLA2 (beta' = - 0.258, t = - 2.542, P = 0.013). CONCLUSION: Exercise rehabilitation for 12 weeks guided by 6-MWT can further reduce the level of LP-PLA2 in patients with CHD undergoing PCI. Trial registration This trial was registered on the Chinese Clinical Trial Registry: ChiCTR2100048124, registered 3 July 2021- Retrospectively registered. The study protocol adheres to the CONSORT guidelines. Title: Genes, Structural, and Biochemical Characterization of Four Chlorophyllases from Solanum lycopersicum Liu G, Meng X, Ren Y, Zhang M, Chen Z, Zhang Z, Pang X, Zhang X Ref: Int J Mol Sci, 23:11716, 2022 : PubMed ESTHER: Liu_2022_Int.J.Mol.Sci_23_11716 PubMedSearch: Liu 2022 Int.J.Mol.Sci 23 11716 PubMedID: 36233017 Abstract Recent studies have confirmed that chlorophyllase (CLH), a long-found chlorophyll (Chl) dephytylation enzyme for initiating Chl catabolism, has no function in leaf senescence-related Chl breakdown. Yet, CLH is considered to be involved in fruit degreening and responds to external and hormonal stimuli. The purpose of this work was to elucidate in detail the biochemical, structural properties, and gene expression of four CLHs from the Solanum lycopersicum genome so as to understand the roles of Solanum lycopersicum chlorophyllases (SlCLHs). SlCLH1/4 were the predominantly expressed CLH genes during leaf and fruit development/ripening stages, and SlCLH1 in mature green fruit was modulated by light. SlCLH1/2/3/4 contained a highly conserved GHSXG lipase motif and a Ser-Asp-His catalytic triad. We identified Ser159, Asp226, and His258 as the essential catalytic triad by site-directed mutagenesis in recombinant SlCLH1. Kinetic analysis of the recombinant enzymes revealed that SlCLH1 had high hydrolysis activities against Chl a, Chl b, and pheophytin a (Phein a), but preferred Chl a and Chl b over Phein a; SlCLH2/3 only showed very low activity to Chl a and Chl b, while SlCLH4 showed no Chl dephytylation activity. The recombinant SlCLH1/2/3 had different pH stability and temperature optimum. Removal of the predicted N-terminal processing peptide caused a partial loss of activity in recombinant SlCLH1/2 but did not compromise SlCLH3 activity. These different characteristics among SlCLHs imply that they may have different physiological functions in tomato. Title: Bladder epithelial cell phosphate transporter inhibition protects mice against uropathogenic Escherichia coli infection Pang Y, Cheng Z, Zhang S, Li S, Li X, Zhang X, Feng Y, Cui H, Chen Z and Feng L <6 more author(s)> Pang Y, Cheng Z, Zhang S, Li S, Li X, Zhang X, Feng Y, Cui H, Chen Z, Liu L, Li Q, Huang J, Zhang M, Zhu S, Wang L, Feng L (- 6) Ref: Cell Rep, 39:110698, 2022 : PubMed ESTHER: Pang_2022_Cell.Rep_39_110698 PubMedSearch: Pang 2022 Cell.Rep 39 110698 PubMedID: 35443182 Abstract Urinary tract infections are predominantly caused by uropathogenic Escherichia coli (UPEC). UPEC infects bladder epithelial cells (BECs) via fusiform vesicles, escapes into the cytosol to evade exocytosis, and establishes intracellular bacterial communities (IBCs) for the next round of infection. The UPEC vesicle escape mechanism remains unclear. Here we show that UPEC senses host immune responses and initiates escape by upregulating a key phospholipase. The UPEC phospholipase PldA disrupts the vesicle membrane, and pldA expression is activated by phosphate reduction in vesicles. The host phosphate transporter PIT1 is located on the fusiform vesicle membrane, transporting phosphate into the cytosol. UPEC infection upregulates PIT1 via nuclear factor kappaB (NF-kappaB), resulting in phosphate reduction. Silencing PIT1 blocks UPEC vesicle escape in BECs, inhibits IBC formation in mouse bladders, and protects mice from UPEC infection. Our results shed light on pathogenic bacteria responding to intracellular phosphate shortage and tackling host defense and provide insights for development of new therapeutic agents to treat UPEC infection. Title: [(18)F]MAGL-4-11 positron emission tomography molecular imaging of monoacylglycerol lipase changes in preclinical liver fibrosis models Shao T, Chen Z, Rong J, Belov V, Chen J, Jeyarajan A, Deng X, Fu H, Yu Q and Liang SH <5 more author(s)> Shao T, Chen Z, Rong J, Belov V, Chen J, Jeyarajan A, Deng X, Fu H, Yu Q, Rwema SH, Lin W, Papisov M, Josephson L, Chung RT, Liang SH (- 5) Ref: Acta Pharm Sin B, 12:308, 2022 : PubMed ESTHER: Shao_2022_Acta.Pharm.Sin.B_12_308 PubMedSearch: Shao 2022 Acta.Pharm.Sin.B 12 308 PubMedID: 35127387 Abstract Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into the proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an (18)F-labeled MAGL inhibitor ([(18)F]MAGL-4-11) for PET imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [(18)F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation (BDL) and carbon tetrachloride (CCl(4)) models of liver cirrhosis; we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models; [(18)F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [(18)F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosis severity, while its levels in normal liver tissue are high; in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that [(18)F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [(18)F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues. Title: Plant GDSL Esterases/Lipases: Evolutionary, Physiological and Molecular Functions in Plant Development Shen G, Sun W, Chen Z, Shi L, Hong J, Shi J Ref: Plants (Basel), 11:, 2022 : PubMed ESTHER: Shen_2022_Plants.(Basel)_11_ PubMedSearch: Shen 2022 Plants.(Basel) 11 PubMedID: 35214802 Abstract GDSL esterases/lipases (GELPs), present throughout all living organisms, have been a very attractive research subject in plant science due mainly to constantly emerging properties and functions in plant growth and development under both normal and stressful conditions. This review summarizes the advances in research on plant GELPs in several model plants and crops, including Arabidopsis, rice, maize and tomato, while focusing on the roles of GELPs in regulating plant development and plant-environment interactions. In addition, the possible regulatory network and mechanisms of GELPs have been discussed. Title: Role of Natural Compounds and Target Enzymes in the Treatment of Alzheimer's Disease Wang S, Kong X, Chen Z, Wang G, Zhang J, Wang J Ref: Molecules, 27:, 2022 : PubMed ESTHER: Wang_2022_Molecules_27_ PubMedSearch: Wang 2022 Molecules 27 PubMedID: 35807418 Abstract Alzheimer's disease (AD) is a progressive neurological condition. The rising prevalence of AD necessitates the rapid development of efficient therapy options. Despite substantial study, only a few medications are capable of delaying the disease. Several substances with pharmacological activity, derived from plants, have been shown to have positive benefits for the treatment of AD by targeting various enzymes, such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), beta-secretase, gamma-secretase, and monoamine oxidases (MAOs), which are discussed as potential targets. Medicinal plants have already contributed a number of lead molecules to medicine development, with many of them currently undergoing clinical trials. A variety of medicinal plants have been shown to diminish the degenerative symptoms associated with AD, either in their raw form or as isolated compounds. The aim of this review was to provide a brief summary of AD and its current therapies, followed by a discussion of the natural compounds examined as therapeutic agents and the processes underlying the positive effects, particularly the management of AD. Title: LIPG is a novel prognostic biomarker and correlated with immune infiltrates in lung adenocarcinoma Wang S, Chen Z, Lv H, Wang C, Wei H, Yu J Ref: J Clin Lab Anal, :e24824, 2022 : PubMed ESTHER: Wang_2022_J.Clin.Lab.Anal__e24824 PubMedSearch: Wang 2022 J.Clin.Lab.Anal e24824 PubMedID: 36572999 Gene_locus related to this paper: human-LIPG Abstract BACKGROUND: Although many biomarkers for lung adenocarcinoma (LUAD) have been identified, their specificity and sensitivity remain unsatisfactory. Endothelial lipase gene (LIPG) plays an important role in a variety of cancers, but its role in lung adenocarcinoma remains unclear. METHODS: TCGA, GEO, K-M plotter, CIBERSORT, GSEA, HPA, and GDSC were used to analyze LIPG in LUAD. Data analysis was mainly achieved by R 4.0.3. RESULTS: The expression of LIPG in LUAD tissues was higher than that in adjacent normal tissues, especially in women, patients aged >65 years, and those with lymph node metastasis. High expression predicted a poor prognosis. The results of enrichment analysis suggest that LIPG may exert profound effects on the development of LUAD through multiple stages of lipid metabolism and immune system regulation. In addition, LIPG expression was significantly correlated with the expression levels of multiple immune checkpoint genes and the abundance of multiple immune infiltrates, including the activated memory CD4 T cell, M1 macrophage, neutrophil, plasma cells, and T follicular helper (Tfh) cells in the LUAD microenvironment content. At the same time, patients with high LIPG expression respond well to a variety of antitumor drugs and have a low rate of drug resistance. CONCLUSIONS: LIPG is a prognostic marker and is associated with lipid metabolism and immune infiltration in LUAD. Title: Bioactivity-Guided Separation of Anti-Cholinesterase Alkaloids from Uncaria rhynchophlly (Miq.) Miq. Ex Havil Based on HSCCC Coupled with Molecular Docking Yu P, Chen Z, Liu Y, Gu Z, Wang X, Zhang Y, Ma Y, Dong M, Tian Z Ref: Molecules, 27:2013, 2022 : PubMed ESTHER: Yu_2022_Molecules_27_2013 PubMedSearch: Yu 2022 Molecules 27 2013 PubMedID: 35335376 Abstract As an important source of cholinesterase inhibitors, alkaloids in natural products have high potential value in terms of exerting pharmacological activities. In this study, a strategy for targeted preparation of cholinesterase inhibitors in Uncaria rhynchophlly (Miq.) Miq. ex Havil (UR) by high-speed counter-current chromatography was provided. In the method, a two-phase polar solvent system composed of ethyl acetate/n-butanol/water (1:4:5, v/v/v) was used, which isolated five alkaloids from the UR extract for the first time. All alkaloids were identified by HR-ESI-MS and NMR as 7-epi-javaniside (1), vincosamide (2), strictosamide (3), cadambine (4), and 3alpha-dihydrocadambine (5). The poorly resolved compounds 2 and 3 were separated by preparative HPLC (prep-HPLC). Among them, compounds 1, 4, and 5 were firstly obtained from UR. The purity of these plant isolates was 98.8%, 98.7%, 99.2%, 95.7%, and 98.5%, respectively. Compounds 1-5 exhibited an inhibitory effect on acetyl-cholinesterase and butyryl-cholinesterase with an IC(50) from 1.47 to 23.24 microg/mL and 1.01 to 18.24 microg/mL. Molecular docking and inhibitory activities indicated that compound 1 showed stronger inhibitory activity on acetyl-cholinesterase and butyryl-cholinesterase. Title: Novel aerosol treatment of airway hyper-reactivity and inflammation in a murine model of asthma with a soluble epoxide hydrolase inhibitor Zhang C, Li W, Li X, Wan D, Mack S, Zhang J, Wagner K, Wang C, Tan B and Yang J <7 more author(s)> Zhang C, Li W, Li X, Wan D, Mack S, Zhang J, Wagner K, Wang C, Tan B, Chen J, Wu CW, Tsuji K, Takeuchi M, Chen Z, Hammock BD, Pinkerton KE, Yang J (- 7) Ref: PLoS ONE, 17:e0266608, 2022 : PubMed ESTHER: Zhang_2022_PLoS.One_17_e0266608 PubMedSearch: Zhang 2022 PLoS.One 17 e0266608 PubMedID: 35443010 Inhibitor(s) related to this paper: TPPU Abstract Asthma currently affects more than 339 million people worldwide. In the present preliminary study, we examined the efficacy of a new, inhalable soluble epoxide hydrolase inhibitor (sEHI), 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), to attenuate airway inflammation, mucin secretion, and hyper-responsiveness (AHR) in an ovalbumin (OVA)-sensitized murine model. Male BALB/c mice were divided into phosphate-buffered saline (PBS), OVA, and OVA+TPPU (2- or 6-h) exposure groups. On days 0 and 14, the mice were administered PBS or sensitized to OVA in PBS. From days 26-38, seven challenge exposures were performed with 30 min inhalation of filtered air or OVA alone. In the OVA+TPPU groups, a 2- or 6-h TPPU inhalation preceded each 30-min OVA exposure. On day 39, pulmonary function tests (PFTs) were performed, and biological samples were collected. Lung tissues were used to semi-quantitatively evaluate the severity of inflammation and airway constriction and the volume of stored intracellular mucosubstances. Bronchoalveolar lavage (BAL) and blood samples were used to analyze regulatory lipid mediator profiles. Significantly (p < 0.05) attenuated alveolar, bronchiolar, and pleural inflammation; airway resistance and constriction; mucosubstance volume; and inflammatory lipid mediator levels were observed with OVA+TPPU relative to OVA alone. Cumulative findings indicated TPPU inhalation effectively inhibited inflammation, suppressed AHR, and prevented mucosubstance accumulation in the murine asthmatic model. Future studies should determine the pharmacokinetics (i.e., absorption, distribution, metabolism, and excretion) and pharmacodynamics (i.e., concentration/dose responses) of inhaled TPPU to explore its potential as an asthma-preventative or -rescue treatment. Title: Novel AP2238-clorgiline hybrids as multi-target agents for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation Zhong G, Guo J, Pang C, Su D, Tang C, Jing L, Zhang F, He P, Yan Y and Jiang N <2 more author(s)> Zhong G, Guo J, Pang C, Su D, Tang C, Jing L, Zhang F, He P, Yan Y, Chen Z, Liu J, Jiang N (- 2) Ref: Bioorg Chem, 130:106224, 2022 : PubMed ESTHER: Zhong_2022_Bioorg.Chem_130_106224 PubMedSearch: Zhong 2022 Bioorg.Chem 130 106224 PubMedID: 36332315 Abstract Cholinesterase and monoamine oxidase are potential targets for the therapy of Alzheimer's disease. A series of novel AP2238-clorgiline hybrids as multi-target agents were designed, synthesized and investigated in vitro for their inhibition of cholinesterases and monoamine oxidases. Many compounds displayed balanced and good inhibitory activity against AChE, BuChE and MAO-B with an obvious selective inhibitory effect on MAO-B. Among them, Compound 5l showed the most balanced potency to inhibit ChEs (eeAChE: IC(50) = 4.03 +/- 0.03 microM, eqBuChE: IC(50) = 5.64 +/- 0.53 microM; hAChE: IC(50) = 8.30 +/- 0.04 microM, hBuChE: IC(50) = 1.91 +/- 0.06 microM) and hMAO-B (IC(50) = 3.29 +/- 0.09 microM). Molecular modeling and kinetic studies showed that 5l was a mixed inhibitor for both AChE and BuChE, and a competitive MAO-B inhibitor. Compound 5l exhibited no toxicity to PC12 and BV-2 cells at 12.5 microM and no acute toxicity at a dosage of 2500 mg/kg. Moreover, 5l can improve the memory function of mice with scopolamine-induced memory impairment and have an excellent ability to cross the blood-brain barrier. Overall, these findings suggested that compound 5l could be deemed as a promising, balanced multi-target drug candidate against Alzheimer's disease. Title: Development of a highly-specific (18)F-labeled irreversible positron emission tomography tracer for monoacylglycerol lipase mapping Chen Z, Mori W, Rong J, Schafroth MA, Shao T, Van RS, Ogasawara D, Yamasaki T, Hiraishi A and Liang SH <12 more author(s)> Chen Z, Mori W, Rong J, Schafroth MA, Shao T, Van RS, Ogasawara D, Yamasaki T, Hiraishi A, Hatori A, Chen J, Zhang Y, Hu K, Fujinaga M, Sun J, Yu Q, Collier TL, Shao Y, Cravatt BF, Josephson L, Zhang MR, Liang SH (- 12) Ref: Acta Pharm Sin B, 11:1686, 2021 : PubMed ESTHER: Chen_2021_Acta.Pharm.Sin.B_11_1686 PubMedSearch: Chen 2021 Acta.Pharm.Sin.B 11 1686 PubMedID: 34221877 Gene_locus related to this paper: human-MGLL Inhibitor(s) related to this paper: PF-06795071 Abstract As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified 14 as a lead compound, which was then radiolabeled with fluorine-18 via a facile S(N)Ar reaction to form 2-[(18)F]fluoropyridine scaffold. Good blood-brain barrier permeability and high in vivo specific binding was demonstrated for radioligand [(18)F]14 (also named as [(18)F]MAGL-1902). This work may serve as a roadmap for clinical translation and further design of potent (18)F-labeled MAGL PET tracers. Title: Yeast cell surface display of bacterial PET hydrolase as a sustainable biocatalyst for the degradation of polyethylene terephthalate Chen Z, Xiao Y, Weber G, Wei R, Wang Z Ref: Methods Enzymol, 648:457, 2021 : PubMed ESTHER: Chen_2021_Methods.Enzymol_648_457 PubMedSearch: Chen 2021 Methods.Enzymol 648 457 PubMedID: 33579416 Gene_locus related to this paper: idesa-peth Abstract Enzymatic hydrolysis of polyethylene terephthalate (PET) is considered to be an environmentally friendly method for the recycling of plastic waste. Recently, a bacterial enzyme named IsPETase was found in Ideonella sakaiensis with the ability to degrade amorphous PET at ambient temperature suggesting its possible use in recycling of PET. However, applying the purified IsPETase in large-scale PET recycling has limitations, i.e., a complicated production process, high cost of single-use, and instability of the enzyme. Yeast cell surface display has proven to be an effectual alternative for improving enzyme degradation efficiency and realizing industrial applications. This chapter deals with the construction and application of a whole-cell biocatalyst by displaying IsPETase on the surface of yeast (Pichia pastoris) cells. Title: Determination of methomyl in grain using deep eutectic solvent-based extraction combined with fluorescence-based enzyme inhibition assays Guo Y, Wang H, Chen Z, Jing X, Wang X Ref: Spectrochim Acta A Mol Biomol Spectrosc, 266:120412, 2021 : PubMed ESTHER: Guo_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_266_120412 PubMedSearch: Guo 2021 Spectrochim.Acta.A.Mol.Biomol.Spectrosc 266 120412 PubMedID: 34597870 Abstract A deep eutectic solvent (DES)-based extraction method is established to facilitate the determination of methomyl in grain via enzyme inhibition fluorescence. The environmentally-friendly DES was synthesized from proline and ethylene glycol and used as a green replacement for traditional extraction solvents that are generally toxic. The DES was added to grain samples and vortex extraction of methomyl, the supernatant was then collected for fluorescence detection. Biomass carbon quantum dots (CQDs) synthesized from millet were used as fluorescent probes. Acetylcholinesterase catalyzes the hydrolysis of acetylthiocholine iodide to thiocholine. The positively-charged thiocholine interacts electrostatically with the negatively-charged quantum dots resulting in the quenching of their fluorescent emission. The pesticide extract solution blocks the enzyme activity and thus recovers the fluorescent from the quantum dots. The fluorescence response was correlated with the amount of methomyl residue in the grain over the range 0.01 to 5 mg kg(-1). The limit of detection was found to be 0.003 mg kg(-1), and the limit of quantification 0.01 mg kg(-1). Recoveries of 86.5% to 107.8% were obtained using real samples, including millet, rice, wheat, and barley, with a relative standard deviation of less than 3.8%. The method is efficient and convenient and has good application prospects for extracting and detecting pesticides in grain samples. Title: Overexpression of serum lncRNA-ABHD11-AS1 as poor prognosis of patients with papillary thyroid carcinoma Hou S, Zhuang YY, Lin QY, Chen Z, Zhao HG, Zhang L, Lin CH Ref: Exp Mol Pathol, 121:104658, 2021 : PubMed ESTHER: Hou_2021_Exp.Mol.Pathol_121_104658 PubMedSearch: Hou 2021 Exp.Mol.Pathol 121 104658 PubMedID: 34102210 Abstract This paper was aimed at exploring the correlation of long non-coding RNA (lncRNA)-ABHD11 Antisense RNA1 (ABHD11-AS1) with the poor prognosis of patients with papillary thyroid carcinoma (PTC) and at investigating its effects on the survival of PTC cells. Serum was respectively collected from 64 PTC patients who were admitted to our hospital (PTC group) and from 50 healthy controls who underwent physical examinations (HC group) both from April 2011 to April 2015. The expression levels of ABHD11-AS1 in the serum were detected, and the values of it for diagnosis and prognosis (5-year follow-ups) were analyzed. The knockdown and overexpression models of ABHD11-AS1 in were constructed to explore the effects of the models on their proliferation, cycles and apoptosis. According to the data, the expression levels of serum ABHD11-AS1 in the PTC patients were remarkably higher than those in the healthy controls, and the area under the curve (AUC) for distinguishing the patients from the controls was 0.920. In the analysis of prognosis, the levels in patients with a poor prognosis were remarkably higher than those in patients with a good prognosis. According to the curves of overall survival rates (OSRs), the high levels of ABHD11-AS1 were remarkably correlated with the poor prognosis (a lower 5-year OSR). COX analysis showed that TNM staging, lymph node metastasis and ABHD11-AS1 were the independent prognostic factors of PTC patients. In the cell experiments, knocking down ABHD11-AS1 remarkably inhibited PTC cells from proliferation, arrested them in G0/G1 phase, and induced their apoptosis, negatively affecting their survival indices. Overexpressing this RNA had positive effects on the survival indices. Taken together, high levels of serum ABHD11-AS1 are related to the poor prognosis of PTC patients, and knocking down its expression can inhibit the survival of PTC cells. Title: An ABHD17-like hydrolase screening system to identify de-S-acylation enzymes of protein substrates in plant cells Liu X, Li M, Li Y, Chen Z, Zhuge C, Ouyang Y, Zhao Y, Lin Y, Xie Q and Lai J <1 more author(s)> Liu X, Li M, Li Y, Chen Z, Zhuge C, Ouyang Y, Zhao Y, Lin Y, Xie Q, Yang C, Lai J (- 1) Ref: Plant Cell, :, 2021 : PubMed ESTHER: Liu_2021_Plant.Cell__ PubMedSearch: Liu 2021 Plant.Cell PubMedID: 34338800 Gene_locus related to this paper: arath-AT1G66900, arath-AT2G24320, arath-AT4G31020, arath-AT5G20520, arath-AT5G38220, arath-F3C3.3, arath-AT1G13610, arath-At5g14390, arath-F22K18.40, arath-At3g01690, arath-Q9LI62 Abstract Protein S-acylation is an important post-translational modification in eukaryotes, regulating the subcellular localization, trafficking, stability, and activity of substrate proteins. The dynamic regulation of this reversible modification is mediated inversely by protein S-acyltransferases and de-S-acylation enzymes, but the de-S-acylation mechanism remains unclear in plant cells. Here we characterized a group of putative protein de-S-acylation enzymes in Arabidopsis thaliana, including 11 members of ABHD17 (Alpha/Beta Hydrolase Domain-containing Protein 17)-like Acyl Protein Thioesterases (ABAPTs). A robust system was then established for the screening of de-S-acylation enzymes of protein substrates in plant cells, based on the effects of substrate localization and confirmed via the protein S-acylation levels. Using this system, the ABAPTs, which specifically reduced the S-acylation levels and disrupted the plasma membrane localization of five immunity-related proteins, were identified respectively in Arabidopsis. Further results indicated that the de-S-acylation of RIN4 (RPM1 Interacting Protein 4), which was mediated by ABAPT8, resulted in an increase of cell death in Arabidopsis and Nicotiana benthamiana, supporting the physiological role of the ABAPTs in plants. Collectively, our current work provides a powerful and reliable system to identify the pairs of plant protein substrates and de-S-acylation enzymes for further studies on the dynamic regulation of plant protein S-acylation. Title: A survey of insecticide resistance-conferring mutations in multiple targets in Anopheles sinensis populations across Sichuan, China Qian W, Liu N, Yang Y, Liu J, He J, Chen Z, Li M, Qiu X Ref: Parasit Vectors, 14:169, 2021 : PubMed ESTHER: Qian_2021_Parasit.Vectors_14_169 PubMedSearch: Qian 2021 Parasit.Vectors 14 169 PubMedID: 33743789 Abstract BACKGROUND: Sichuan province is located in the southwest of China, and was previously a malaria-endemic region. Although no indigenous malaria case has been reported since 2011, the number of imported cases is on the rise. Insecticide-based vector control has played a central role in the prevention of malaria epidemics. However, the efficacy of this strategy is gravely challenged by the development of insecticide resistance. Regular monitoring of insecticide resistance is essential to inform evidence-based vector control. Unfortunately, almost no information is currently available on the status of insecticide resistance and associated mechanisms in Anopheles sinensis, the dominant malaria vector in Sichuan. In this study, efforts were invested in detecting the presence and frequency of insecticide resistance-associated mutations in three genes that encode target proteins of several classes of commonly used insecticides. METHODS: A total of 446 adults of An. sinensis, collected from 12 locations across Sichuan province of China, were inspected for resistance-conferring mutations in three genes that respectively encode acetylcholinesterase (AChE), voltage-gated sodium channel (VGSC), and GABA receptor (RDL) by DNA Sanger sequencing. RESULTS: The G119S mutation in AChE was detected at high frequencies (0.40-0.73). The predominant ace-1 genotype was GGC/AGC (119GS) heterozygotes. Diverse variations at codon 1014 were found in VGSC, leading to three different amino acid substitutions (L1014F/C/S). The 1014F was the predominant resistance allele and was distributed in all 12 populations at varying frequencies from 0.03 to 0.86. The A296S mutation in RDL was frequently present in Sichuan, with 296SS accounting for more than 80% of individuals in six of the 12 populations. Notably, in samples collected from Chengdu (DJY) and Deyang (DYMZ), almost 30% of individuals were found to be resistant homozygotes for all three targets. CONCLUSIONS: Resistance-related mutations in three target proteins of the four main classes of insecticides were prevalent in most populations. This survey reveals a worrisome situation of multiple resistance genotypes in Sichuan malaria vector. The data strengthen the need for regular monitoring of insecticide resistance and establishing a region-customized vector intervention strategy. Title: Novel Reversible-Binding PET Ligands for Imaging Monoacylglycerol Lipase Based on the Piperazinyl Azetidine Scaffold Rong J, Mori W, Xia X, Schafroth MA, Zhao C, Van RS, Yamasaki T, Chen J, Xiao Z and Liang SH <23 more author(s)> Rong J, Mori W, Xia X, Schafroth MA, Zhao C, Van RS, Yamasaki T, Chen J, Xiao Z, Haider A, Ogasawara D, Hiraishi A, Shao T, Zhang Y, Chen Z, Pang F, Hu K, Xie L, Fujinaga M, Kumata K, Gou Y, Fang Y, Gu S, Wei H, Bao L, Xu H, Collier TL, Shao Y, Carson RE, Cravatt BF, Wang L, Zhang MR, Liang SH (- 23) Ref: Journal of Medicinal Chemistry, :, 2021 : PubMed ESTHER: Rong_2021_J.Med.Chem__ PubMedSearch: Rong 2021 J.Med.Chem PubMedID: 34569803 Gene_locus related to this paper: human-MGLL Inhibitor(s) related to this paper: ZYH-deriv-F Abstract Monoacylglycerol lipase (MAGL) is a 33 kDa serine protease primarily responsible for hydrolyzing 2-arachidonoylglycerol into the proinflammatory eicosanoid precursor arachidonic acid in the central nervous system. Inhibition of MAGL constitutes an attractive therapeutic concept for treating psychiatric disorders and neurodegenerative diseases. Herein, we present the design and synthesis of multiple reversible MAGL inhibitor candidates based on a piperazinyl azetidine scaffold. Compounds 10 and 15 were identified as the best-performing reversible MAGL inhibitors by pharmacological evaluations, thus channeling their radiolabeling with fluorine-18 in high radiochemical yields and favorable molar activity. Furthermore, evaluation of [(18)F]10 and [(18)F]15 ([(18)F]MAGL-2102) by autoradiography and positron emission tomography (PET) imaging in rodents and nonhuman primates demonstrated favorable brain uptakes, heterogeneous radioactivity distribution, good specific binding, and adequate brain kinetics, and [(18)F]15 demonstrated a better performance. In conclusion, [(18)F]15 was found to be a suitable PET radioligand for the visualization of MAGL, harboring potential for the successful translation into humans. Title: Profibrotic mechanisms of DPP8 and DPP9 highly expressed in the proximal renal tubule epithelial cells Zhang Y, Li K, Li Y, Zhao W, Wang L, Chen Z, Ma X, Yao T, Wang J and Fu R <3 more author(s)> Zhang Y, Li K, Li Y, Zhao W, Wang L, Chen Z, Ma X, Yao T, Wang J, Dong W, Li X, Tian X, Fu R (- 3) Ref: Pharmacol Res, 169:105630, 2021 : PubMed ESTHER: Zhang_2021_Pharmacol.Res_169_105630 PubMedSearch: Zhang 2021 Pharmacol.Res 169 105630 PubMedID: 33932609 Gene_locus related to this paper: human-DPP8, human-DPP9 Abstract BACKGROUND: DPP8 and DPP9 have been demonstrated to play important roles in multiple diseases. Evidence for increased gene expression of DPP8 and DPP9 in tubulointerstitium was found to be associated with the decline of kidney function in chronic kidney disease (CKD) patients, which was observed in the Nephroseq human database. To examine the role of DPP8 and DPP9 in the tubulointerstitial injury, we determined the efficacy of DPP8 and DPP9 on epithelial-to-mesenchymal transition (EMT) and tubulointerstitial fibrosis (TIF) as well as the underlying mechanisms. METHODS: We conducted the immunofluorescence of DPP8 and DPP9 in kidney biopsy specimens of CKD patients, established unilateral ureteral obstruction (UUO) animal model, treated with TC-E5007 (a specific inhibitor of both DPP8 and DPP9) or Saxagliptin (positive control) or saline, and HK-2 cells model. RESULTS: We observed the significantly increased expression of DPP8 and DPP9 in the renal proximal tubule epithelial cells of CKD patients compared to the healthy control subjects. DPP8/DPP9 inhibitor TC-E5007 could significantly attenuate the EMT and extracellular matrix (ECM) synthesis in UUO mice, all these effects were mediated via interfering with the TGF-beta1/Smad signaling. TC-E5007 treatment also presented reduced renal inflammation and improved renal function in the UUO mice compared to the placebo-treated UUO group. Furthermore, the siRNA for DPP8 and DPP9, and TC-E5007 treatment decreased EMT- and ECM-related proteins in TGF-beta1-treated HK-2 cells respectively, which could be reversed significantly by transduction with lentivirus-DPP8 and lentivirus-DPP9. CONCLUSION: These data obtained provide evidence that the DPP8 and DPP9 could be potential therapeutic targets against TIF. Title: Melatonin inhibits lipid accumulation to repress prostate cancer progression by mediating the epigenetic modification of CES1 Zhou L, Zhang C, Yang X, Liu L, Hu J, Hou Y, Tao H, Sugimura H, Chen Z and Chen K <1 more author(s)> Zhou L, Zhang C, Yang X, Liu L, Hu J, Hou Y, Tao H, Sugimura H, Chen Z, Wang L, Chen K (- 1) Ref: Clin Transl Med, 11:e449, 2021 : PubMed ESTHER: Zhou_2021_Clin.Transl.Med_11_e449 PubMedSearch: Zhou 2021 Clin.Transl.Med 11 e449 PubMedID: 34185414 Gene_locus related to this paper: human-CES1 Abstract BACKGROUND: Androgen deprivation therapy (ADT) is the main clinical treatment for patients with advanced prostate cancer (PCa). However, PCa eventually progresses to castration-resistant prostate cancer (CRPC), largely because of androgen receptor variation and increased intratumoral androgen synthesis. Several studies have reported that one abnormal lipid accumulation is significantly related to the development of PCa. Melatonin (MLT) is a functionally pleiotropic indoleamine molecule and a key regulator of energy metabolism. The aim of our study is finding the links between CRPC and MLT and providing the basis for MLT treatment for CRPC. METHODS: We used animal CRPC models with a circadian rhythm disorder, and PCa cell lines to assess the role of melatonin in PCa. RESULTS: We demonstrated that MLT treatment inhibited tumor growth and reversed enzalutamide resistance in animal CRPC models with a circadian rhythm disorder. A systematic review and meta-analysis demonstrated that MLT is positively associated with an increased risk of developing advanced PCa. Restoration of carboxylesterase 1 (CES1) expression by MLT treatment significantly reduced lipid droplet (LD) accumulation, thereby inducing apoptosis by increasing endoplasmic reticulum stress, reducing de novo intratumoral androgen synthesis, repressing CRPC progression and reversing the resistance to new endocrine therapy. Mechanistic investigations demonstrated that MLT regulates the epigenetic modification of CES1. Ces1-knockout (Ces(-/-) ) mice verified the important role of endogenous Ces1 in PCa. CONCLUSIONS: Our findings provide novel preclinical and clinical information about the role of melatonin in advanced PCa and characterize the importance of enzalutamide combined with MLT administration as a therapy for advanced PCa. Title: Toxic effects of different-sized graphene oxide particles on zebrafish embryonic development Chen Z, Yu C, Khan IA, Tang Y, Liu S, Yang M Ref: Ecotoxicology & Environmental Safety, 197:110608, 2020 : PubMed ESTHER: Chen_2020_Ecotoxicol.Environ.Saf_197_110608 PubMedSearch: Chen 2020 Ecotoxicol.Environ.Saf 197 110608 PubMedID: 32305822 Abstract Graphene oxide (GO) has broad application potential in many fields, such as biomedicine and energy. Due to the wide-ranging GO applications, its entry into the environment is inevitable along with the potential for ecological and environmental risks. In the present study, we systematically investigated the dose-dependent effects of three different-sized GO particles (50-200 nm, <500 nm, and >500 nm) on zebrafish during the very early developmental stages (4-124 h post-fertilization). The results showed that GOs could accumulate in the eyes, heart, yolk sac, and blood vessels of fish larvae. Consequently, their effects on multiple toxic endpoints were observed, including delayed hatching times, shortened body lengths, alterations in heart rate and blood flow, changes in swimming activity and responses to photoperiod stimulation, and the enhanced activity of total superoxide dismutase, inducible nitric oxide synthase, acetylcholinesterase, caspase-3, and induction of apoptosis-related gene expression. As a result, the occurrence of oxidative stress and the induction of apoptosis are suggested in fish larvae exposed to all three different-sized GO particles. In addition, our results highlight the impacts of waterborne-GO exposure on zebrafish during early development, which were not merely dependent on GO concentration but also on the associated GO sizes. This study hereby provides a basis for the potential ecological and health risks of GO exposure. Title: sEH Inhibitor Tppu Ameliorates Cecal Ligation and Puncture-Induced Sepsis by Regulating Macrophage Functions Chen Z, Tang Y, Yu J, Dong R, Yang Y, Fu M, Luo J, Hu S, Wang DW and Xu X <1 more author(s)> Chen Z, Tang Y, Yu J, Dong R, Yang Y, Fu M, Luo J, Hu S, Wang DW, Tu L, Xu X (- 1) Ref: Shock, 53:761, 2020 : PubMed ESTHER: Chen_2020_Shock_53_761 PubMedSearch: Chen 2020 Shock 53 761 PubMedID: 31318834 Abstract BACKGROUND: Sepsis is a life-threatening organ dysfunction initiated by a dysregulated response to infection, with imbalanced inflammation and immune homeostasis. Macrophages play a pivotal role in sepsis. N-[1-(1-oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy)phenyl)-urea (TPPU) is an inhibitor of soluble epoxide hydrolase (sEH), which can rapidly hydrolyze epoxyeicosatrienoic acids (EETs) to the bio-inactive dihydroxyeicosatrienoic acids. TPPU was linked with the regulation of macrophages and inflammation. Here, we hypothesized that sEH inhibitor TPPU ameliorates cecal ligation and puncture (CLP)-induced sepsis by regulating macrophage functions. METHODS: A polymicrobial sepsis model induced by CLP was used in our study. C57BL/6 mice were divided into four groups: sham+ phosphate buffer saline (PBS), sham+TPPU, CLP+PBS, CLP+TPPU. Mice were observed 48h after surgery to assess the survival rate. For other histological examinations, mice were sacrificed 6h after surgery. Macrophage cell line RAW264.7 was used for in vitro studies. RESULTS: TPPU treatment, accompanied with increased EETs levels, markedly improved the survival of septic mice induced by CLP surgery, which was associated with alleviated organ damage and dysfunction triggered by systemic inflammatory response. Moreover, TPPU treatment significantly inhibited systemic inflammatory response via EETs-induced inactivation of mitogen-activated protein kinase signaling due to enhanced macrophage phagocytic ability and subsequently reduced bacterial proliferation and dissemination, and decreased inflammatory factors release. CONCLUSION: sEH inhibitor TPPU ameliorates cecal ligation and puncture-induced sepsis by regulating macrophage functions, including improved phagocytosis and reduced inflammatory response. Our data indicate that sEH inhibition has potential therapeutic effects on polymicrobial-induced sepsis. Title: Efficient biodegradation of highly crystallized polyethylene terephthalate through cell surface display of bacterial PETase Chen Z, Wang Y, Cheng Y, Wang X, Tong S, Yang H, Wang Z Ref: Sci Total Environ, 709:136138, 2020 : PubMed ESTHER: Chen_2020_Sci.Total.Environ_709_136138 PubMedSearch: Chen 2020 Sci.Total.Environ 709 136138 PubMedID: 31887523 Abstract Polyethylene terephthalate (PET) is one of the most widely used plastics in the world. Accumulation of the discarded PET in the environment is creating a global environmental problem. Recently, a bacterial enzyme named PETase was found to have the novel ability to degrade the highly crystallized PET. However, the enzymatic activity of native PETase is still low limiting its possible use in recycling of PET. In this study, we developed a whole-cell biocatalyst by displaying PETase on the surface of yeast (Pichia pastoris) cell to improve its degradation efficiency. Our data shows that PETase could be functionally displayed on the yeast cell with enhanced pH and thermal stability. The turnover rate of the PETase-displaying yeast whole-cell biocatalyst towards highly crystallized PET dramatically increased about 36-fold compared with that of purified PETase. Furthermore, the whole-cell biocatalyst showed stable turnover rate after seven repeated use and under some chemical/solvent conditions, and its ability to degrade different commercial highly crystallized PET bottles. Our results reveal that PETase-displaying whole-cell biocatalyst affords a promising route for efficient biological recycling of PET. Title: Monobutyl phthalate (MBP) can dysregulate the antioxidant system and induce apoptosis of zebrafish liver Jiao Y, Tao Y, Yang Y, Diogene T, Yu H, He Z, Han W, Chen Z, Wu P, Zhang Y Ref: Environ Pollut, 257:113517, 2020 : PubMed ESTHER: Jiao_2020_Environ.Pollut_257_113517 PubMedSearch: Jiao 2020 Environ.Pollut 257 113517 PubMedID: 31761585 Abstract In this paper, the acute toxicity of monobutyl phthalate (MBP), the main hydrolysis product of dibutyl phthalate, on adult zebrafish liver antioxidant system was studied. Compared the toxicity effect of MBP and DBP by histopathology and apoptosis experiments, we speculated that the toxic effects of DBP on animals may be caused by its metabolite MBP. The results indicated that the antioxidant Nrf2-Keap1 pathway was insufficient to resist MBP-induced hepatotoxicity and led to an imbalance of membrane ion homeostasis and liver damage. Decreased cell viability, significant tissue lesions and early hepatocyte apoptosis were observed in the zebrafish liver in MBP exposure at high concentration (10 mg/L). The activities of antioxidant enzymes and ATPases in zebrafish liver were inhibited with increased malondialdehyde (MDA) content and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Integrated biomarker response (IBR) calculation results indicated that MBP mainly inhibited catalase (CAT) activity. Simultaneously, the expression of antioxidant-related genes (SOD, CAT, GPx, Nrf2, HO-1) was down-regulated, while apoptosis-related genes (p53, bax, cas3) were significantly up-regulated. Title: Colorimetric Differentiation of Flavonoids Based on Effective Reactivation of Acetylcholinesterase Induced by Different Affnities between Flavonoids and Metal Ions Li S, Liu X, Liu QY, Chen Z Ref: Analytical Chemistry, 92:3361, 2020 : PubMed ESTHER: Li_2020_Anal.Chem_92_3361 PubMedSearch: Li 2020 Anal.Chem 92 3361 PubMedID: 31983197 Abstract Flavonoids are closely related to human health, and the distinguishiment of flavonoids is an important but difficult issue. We herein unveil a novel colorimetric sensor array for the rapid identification of 7 flavonoids (e.g., gallocatechin (GC), morin hydrate (MH), puerarin (Pu), epigallocatechin gallate (EGCG), catechin (C), rac Naringenin (rN), and Flavone (Fla)) for the first time. The colorimetric performances of gold nanoparticles (AuNPs) are characteristically correlated with thiocholine, which is issued from the enzymatic hydrolysis of acetylcholine (AcCh). Therefore, as a proof-of-concept design, three sensors (Cu2+/ acetylcholinesterase (AcChE)/AcCh/AuNPs, Zn2+/AcChE/AcCh/AuNPs, and Mn2+/AcChE/AcCh/AuNPs) were constructed to form our sensor array. The distinct affnities between flavonoids and metal ions would cause varying degrees of effective reactivation of AcChE, leading to unique colorimetric response patterns upon being challenged with the seven flavonoids for their pattern recognition, enabling an excellent identification of the seven flavonoids at a concentration of 20 nM and different concentrations of individual flavonoids, as well as mixtures of them. Title: A dual-mode nanoprobe for the determination of parathion methyl based on graphene quantum dots modified silver nanoparticles Li Y, Chen S, Lin D, Chen Z, Qiu P Ref: Anal Bioanal Chem, 412:5583, 2020 : PubMed ESTHER: Li_2020_Anal.Bioanal.Chem_412_5583 PubMedSearch: Li 2020 Anal.Bioanal.Chem 412 5583 PubMedID: 32572544 Abstract We developed a highly sensitive and selective method for double-signal analysis (fluorescence and ultraviolet-visible spectrophotometry) of organophosphorus pesticides (OPs), based on reversible quenching of graphene quantum dots (GQDs; fluorophores) with silver nanoparticles (AgNPs; absorbers). We used acetylcholinesterase to catalytically convert acetylthiocholine into thiocholine. In turn, by competitive binding to the AgNPs, the produced thiocholine displaces AgNPs from the GQDs and thus induces fluorescence recovery. However, OP analytes inhibit the activity of acetylcholinesterase and, in so doing, retain the silver-graphene nanoparticle complex and fluorescence quenching. The degree of quenching is proportional to the concentration of OPs; the detection limit is as low as 0.017 microg/L. The ultraviolet-visible absorption of GQDs/AgNPs at 390 nm decreases-because of AgNP aggregation that occurs after desorption from the GQDs-and the absorbance is linearly proportional to the OP concentration. Our system has good selectivity to substances that are commonly present in water and vegetables. We successfully applied our method to OP analysis in water, apple, and carrot samples. Title: Supplementation with gamma-glutamylcysteine (gamma-GC) lessens oxidative stress, brain inflammation and amyloid pathology and improves spatial memory in a murine model of AD Liu Y, Chen Z, Li B, Yao H, Zarka M, Welch J, Sachdev P, Bridge W, Braidy N Ref: Neurochem Int, :104931, 2020 : PubMed ESTHER: Liu_2020_Neurochem.Int__104931 PubMedSearch: Liu 2020 Neurochem.Int 104931 PubMedID: 33276023 Abstract INTRODUCTION: The accumulation of oxidative stress, neuroinflammation and abnormal aggregation of amyloid beta-peptide (Abeta) have been shown to induce synaptic dysfunction and memory deficits in Alzheimer's disease (AD). Cellular depletion of the major endogenous antioxidant Glutathione (GSH) has been linked to cognitive decline and the development of AD pathology. Supplementation with gamma-glutamylcysteine (gamma-GC), the immediate precursor and the limiting substrate for GSH biosynthesis, can transiently augment cellular GSH levels by bypassing the regulation of GSH homeostasis. METHODS: In the present study, we investigated the effect of dietary supplementation of gamma-GC on oxidative stress and Abeta pathology in the brains of APP/PS1 mice. The APP/PS1 mice were fed gamma-GC from 3 months of age with biomarkers of apoptosis and cell death, oxidative stress, neuroinflammation and Abeta load being assessed at 6 months of age. RESULTS: Our data showed that supplementation with gamma-GC lowered the levels of brain lipid peroxidation, protein carbonyls and apoptosis, increased both total GSH and the glutathione/glutathione disulphide (GSH/GSSG) ratio and replenished ATP and the activities of the antioxidant enzymes (superoxide dismutase (SOD), catalase, glutamine synthetase and glutathione peroxidase (GPX)), the latter being a key regulator of ferroptosis. Brain Abeta load was lower and acetylcholinesterase (AChE) activity was markedly improved compared to APP/PS1 mice fed a standard chow diet. Alteration in brain cytokine levels and matrix metalloproteinase enzymes MMP-2 and MMP-9 suggested that gamma-GC may lower inflammation and enhance Abeta plaque clearance in vivo. Spatial memory was also improved by gamma-GC as determined using the Morris water maze. CONCLUSION: Our data collectively suggested that supplementation with gamma-GC may represent a novel strategy for the treatment and/or prevention of cognitive impairment and neurodegeneration. Title: Design, synthesis and biological evaluation of novel O-carbamoyl ferulamide derivatives as multi-target-directed ligands for the treatment of Alzheimer's disease Sang Z, Wang K, Bai P, Wu A, Shi J, Liu W, Zhu G, Wang Y, Lan Y and Tan Z <4 more author(s)> Sang Z, Wang K, Bai P, Wu A, Shi J, Liu W, Zhu G, Wang Y, Lan Y, Chen Z, Zhao Y, Qiao Z, Wang C, Tan Z (- 4) Ref: Eur Journal of Medicinal Chemistry, 194:112265, 2020 : PubMed ESTHER: Sang_2020_Eur.J.Med.Chem_194_112265 PubMedSearch: Sang 2020 Eur.J.Med.Chem 194 112265 PubMedID: 32240904 Abstract A novel series of O-carbamoyl ferulamide derivatives were designed by multitarget-directed ligands (MTDLs) strategy, the derivatives were synthesized and evaluated to treat Alzheimer's disease (AD). In vitro biological evaluation demonstrated that compound 4f was the best pseudo-irreversible hBChE (human butyrylcholinesterase) inhibitor with an IC50 value of 0.97 muM 4f was a potent selective MAO-B (monoamine oxidase-B) inhibitor (IC50 = 5.3 muM), and could inhibit (58.2%) and disaggregate (43.3%) self-mediated Abeta aggregation. 4f also could reduce the levels of pathological tau and APP clearance, and displayed a wide safe range hepatotoxicity on LO2 cells. The in vivo studies revealed that 4f exhibited fascinating dyskinesia recovery rate and response efficiency on AlCl3-mediated zebrafish, and demonstrated significant protective effect on vascular injury caused by Abeta1-40. PET-CT imaging demonstrated that [(11)C]4f exhibited high BBB penetration (especially could reach to hippocampus and striatum of brain) and had a fast brain uptake after intravenous bolus injection. Furthermore, compound 4f could improve scopolamine-induced cognitive impairment. Further, the metabolism in vitro of 4f was also investigated, and presented 3 metabolites in rat liver microsome metabolism, 4 metabolites in human liver microsome, and 4 metabolites in rat intestinal flora, providing previous data for the preclinical study. Therefore, these results implied that compound 4f was an advanced multi-function agent and deserved further preclinical study against mild-to-serve Alzheimer's disease. Title: Multicolor nitrogen dots for rapid detection of thiram and chlorpyrifos in fruit and vegetable samples Tang Z, Chen Z, Li G, Hu Y Ref: Anal Chim Acta, 1136:72, 2020 : PubMed ESTHER: Tang_2020_Anal.Chim.Acta_1136_72 PubMedSearch: Tang 2020 Anal.Chim.Acta 1136 72 PubMedID: 33081951 Abstract The development of sensitive fluorescence sensors and efficient preparation of samples is a challenge in the detection of pesticides in complex samples. In this study, multicolor nitrogen dots (M-Ndots) were synthesised via microwave irradiation at 140 degreeC for 10 min with 5-amino-1H-tetrazole and p-phenylenediamine as precursors, which have a high fluorescence quantum yield of up to 31%. Furthermore, the M-Ndots were employed as fluorescence sensors for pesticide detection by being combined with a gas membrane separation device, to eliminate the interference from the complex sample matrix. In this process, the M-Ndots were used for sensing thiram and chlorpyrifos through their affinities to Cu(2+) and Fe(3+), respectively. Because thiram could decompose into volatile CS(2), its derivate was sensed using the fluorescence of M-Ndots via a complexation reaction with Cu(2+). Chlorpyrifos, due to its volatility, can reduce the Fe(3+) ion by inhibiting the activity of acetylcholinesterase, which produces H(2)O(2) to oxidise Fe(2+). In a real application, the time consumption for 96 samples was less than 30 min in one run of the gas membrane separation device. The recoveries for thiram and chlorpyrifos ranged from 90.0% to 115.0%, and the analytical results were validated using LC-MS/MS methods, with relative errors ranging from -7.4% to 10.1%. Title: OSBPL2 Is Required for the Binding of COPB1 to ATGL and the Regulation of Lipid Droplet Lipolysis Wang T, Wei Q, Liang L, Tang X, Yao J, Lu Y, Qu Y, Chen Z, Xing G, Cao X Ref: iScience, 23:101252, 2020 : PubMed ESTHER: Wang_2020_iScience_23_101252 PubMedSearch: Wang 2020 iScience 23 101252 PubMedID: 32650117 Abstract The accumulation of giant lipid droplets (LDs) increases the risk of metabolic disorders including obesity and insulin resistance. The lipolysis process involves the activation and transfer of lipase, but the molecular mechanism is not completely understood. The translocation of ATGL, a critical lipolysis lipase, from the ER to the LD surface is mediated by an energy catabolism complex. Oxysterol-binding protein-like 2 (OSBPL2/ORP2) is one of the lipid transfer proteins that regulates intracellular cholesterol homeostasis. A recent study has proven that Osbpl2(-/-) pigs exhibit hypercholesterolemia and obesity phenotypes with an increase in adipocytes. In this study, we identified that OSBPL2 links the endoplasmic reticulum (ER) with LDs, binds to COPB1, and mediates ATGL transport. We provide important insights into the function of OSBPL2, indicating that it is required for the regulation of lipid droplet lipolysis. Title: GDSL esterase/lipases OsGELP34 and OsGELP110/OsGELP115 are essential for rice pollen development Zhang H, Wang M, Li Y, Yan W, Chang Z, Ni H, Chen Z, Wu J, Xu C and Tang X <1 more author(s)> Zhang H, Wang M, Li Y, Yan W, Chang Z, Ni H, Chen Z, Wu J, Xu C, Deng XW, Tang X (- 1) Ref: J Integr Plant Biol, :, 2020 : PubMed ESTHER: Zhang_2020_J.Integr.Plant.Biol__ PubMedSearch: Zhang 2020 J.Integr.Plant.Biol PubMedID: 32068333 Abstract Pollen exine contains complex biopolymers of aliphatic lipids and phenolics. Abnormal development of pollen exine often leads to plant sterility. Molecular mechanisms regulating exine formation have been studied extensively but remain ambiguous. Here we report the analyses of three GDSL esterase/lipase protein genes, OsGELP34, OsGELP110, and OsGELP115, for rice exine formation. OsGELP34 was identified by cloning of a male sterile mutant gene. OsGELP34 encodes an endoplasmic reticulum protein and was mainly expressed in anthers during pollen exine formation. osgelp34 mutant displayed abnormal exine and altered expression of a number of key genes required for pollen development. OsGELP110 was previously identified as a gene differentially expressed in meiotic anthers. OsGELP110 was most homologous to OsGELP115, and the two genes showed similar gene expression patterns. Both OsGELP110 and OsGELP115 proteins were localized in peroxisomes. Individual knockout of OsGELP110 and OsGELP115 did not affect the plant fertility, but double knockout of both genes altered the exine structure and rendered the plant male sterile. OsGELP34 is distant from OsGELP110 and OsGELP115 in sequence, and osgelp34 and osgelp110/osgelp115 mutants were different in anther morphology despite both were male sterile. These results suggested that OsGELP34 and OsGELP110/OsGELP115 catalyze different compounds for pollen exine development. This article is protected by copyright. All rights reserved. Title: Structures and esterolytic reactivity of novel binuclear copper(ii) complexes with reduced l-serine Schiff bases as mimic carboxylesterases Zhang Q, Shu J, Zhang Y, Xu Z, Yue J, Liu X, Xu B, Chen Z, Jiang W Ref: Dalton Trans, 49:10261, 2020 : PubMed ESTHER: Zhang_2020_Dalton.Trans_49_10261 PubMedSearch: Zhang 2020 Dalton.Trans 49 10261 PubMedID: 32672259 Abstract Three novel binuclear copper(ii) complexes with reduced l-serine Schiff bases were synthesized and their structures were analyzed with single-crystal X-ray diffraction and DFT calculations. The crystal data revealed that all of these binuclear complexes are chiral. Both 5-halogenated (bromo- and chloro-) binuclear complexes exhibit right-handed helix structural character. Interestingly, the 5-methyl-containing analogue has a two-dimensional pore structure. In this paper, the esterolysis reactivity of the as-prepared complexes shows that in the hydrolysis of p-nitrophenyl acetate (PNPA) these three complexes provide 26, 18, 40-fold rate acceleration as compared to the spontaneous hydrolysis of PNPA at pH 7.0, respectively. Under selected conditions, in excess buffered aqueous solution a rate enhancement by three orders of magnitude was observed for the catalytic hydrolysis of another carboxylic ester, p-nitrophenyl picolinate (PNPP). These complexes efficiently promoted PNPP hydrolysis in a micellar solution of cetyltrimethylammonium bromide (CTAB), giving rise to a rate enhancement in excess of four orders of magnitude, which is approximately 2.0-3.2 times higher than that in the buffer. Title: Metabolism and pharmacological activities of the natural health-benefiting compound diosmin Zheng Y, Zhang R, Shi W, Li L, Liu H, Chen Z, Wu L Ref: Food Funct, 11:8472, 2020 : PubMed ESTHER: Zheng_2020_Food.Funct_11_8472 PubMedSearch: Zheng 2020 Food.Funct 11 8472 PubMedID: 32966476 Abstract Diosmin is a famous natural flavonoid for treating chronic venous insufficiency and varicose veins. Recently, extensive study has indicated that diosmin possesses diverse pharmacological activities, including anti-inflammation, anti-oxidation, anti-diabetes, anti-cancer, anti-microorganism, liver protection, neuro-protection, cardiovascular protection, renoprotection, and retinal protection activities. Due to its low water solubility, diosmin is dramatically limited in clinical application. Expectedly, many potential strategies have been developed for improving its pharmacokinetic values and bioavailability. This health-benefiting compound has been explored as the major component of Daflon and micronized purified flavonoid fraction (MPFF), which have been used in clinics to improve micro-circulation. However, no specific drug targets for diosmin are reported, although some potential factors have been involved in screening, such as P-glycoprotein (P-gp), IKKbeta, acetylcholinesterase (AChE), and aldose reductase (AR). More investigations on the underlying mechanisms of diosmin in mediating cellular processes with high specificity is still needed. Title: Effects of Bread Yeast Cell Wall Beta-Glucans on Mice with Loperamide-Induced Constipation Chen Z, Lin S, Jiang Y, Liu L, Jiang J, Chen S, Tong Y, Wang P Ref: J Med Food, 22:1009, 2019 : PubMed ESTHER: Chen_2019_J.Med.Food_22_1009 PubMedSearch: Chen 2019 J.Med.Food 22 1009 PubMedID: 31536448 Abstract Constipation is a common gastrointestinal disorder characterized by changes in intestinal habits. Increasing evidence indicates that long-term use of irritant laxatives causes serious side effects. Meanwhile, more than 50% of patients are dissatisfied with sense of use of non-prescriptional laxatives. beta-glucans are natural polysaccharides widely found in yeast, fungus, and plants, which have been reported to exhibit various pharmacological effects. The aim of this study was to characterize the effect of beta-glucans extracted from the bread yeast cell wall on loperamide-induced constipation mice. Forty mice were fed with loperamide (10 mg/kg) to make the constipation model and a diet supplemented with 2.5, 5, and 10 mg/kg beta-glucan. We assessed the defecation frequency, intestinal transit function of mice, as well as used high-throughput sequencing to analyze the intestinal microbiota composition and functional biological profiles data. Meanwhile, we detected expression of neurotransmitters including acetylcholinesterase, substance P, and serotonin (5-HT) and expression of tight junction protein (TJP) including zonula occludens-1 and mucin-2 in distal colon to characterize the possible molecular mechanisms. beta-glucans significantly enhanced intestinal motility and provided a possibility to regulate the expression of neurotransmitters and TJP in mice. The intestinal microecological portion of the treatment group partially recovered and was closer to the normal group. This study showed that beta-glucans can influence the intestinal microbiota and restore microecological balance to regulate the express of neurotransmitters and TJP to recover intestinal epithelial mechanical barrier. We suggested that beta-glucans could be used as an active nutritional supplement to protect the damaged intestinal barrier and help patients who have constipation complications and dysbiosis. Title: Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a Tail Switching Strategy on a Piperazinyl Azetidine Skeleton Chen Z, Mori W, Deng X, Cheng R, Ogasawara D, Zhang G, Schafroth MA, Dahl K, Fu H and Liang SH <24 more author(s)> Chen Z, Mori W, Deng X, Cheng R, Ogasawara D, Zhang G, Schafroth MA, Dahl K, Fu H, Hatori A, Shao T, Zhang Y, Yamasaki T, Zhang X, Rong J, Yu Q, Hu K, Fujinaga M, Xie L, Kumata K, Gou Y, Chen J, Gu S, Bao L, Wang L, Collier TL, Vasdev N, Shao Y, Ma JA, Cravatt BF, Fowler C, Josephson L, Zhang MR, Liang SH (- 24) Ref: Journal of Medicinal Chemistry, 62:3336, 2019 : PubMed ESTHER: Chen_2019_J.Med.Chem_62_3336 PubMedSearch: Chen 2019 J.Med.Chem 62 3336 PubMedID: 30829483 Gene_locus related to this paper: human-MGLL Abstract Monoacylglycerol lipase (MAGL) is a serine hydrolase that degrades 2-arachidonoylglycerol (2-AG) in the endocannabinoid system (eCB). Selective inhibition of MAGL has emerged as a potential therapeutic approach for the treatment of diverse pathological conditions, including chronic pain, inflammation, cancer, and neurodegeneration. Herein, we disclose a novel array of reversible and irreversible MAGL inhibitors by means of "tail switching" on a piperazinyl azetidine scaffold. We developed a lead irreversible-binding MAGL inhibitor 8 and reversible-binding compounds 17 and 37, which are amenable for radiolabeling with (11)C or (18)F. [(11)C]8 ([(11)C]MAGL-2-11) exhibited high brain uptake and excellent binding specificity in the brain toward MAGL. Reversible radioligands [(11)C]17 ([(11)C]PAD) and [(18)F]37 ([(18)F]MAGL-4-11) also demonstrated excellent in vivo binding specificity toward MAGL in peripheral organs. This work may pave the way for the development of MAGL-targeted positron emission tomography tracers with tunability in reversible and irreversible binding mechanisms. Title: Design, Synthesis, and Evaluation of (18)F-Labeled Monoacylglycerol Lipase Inhibitors as Novel Positron Emission Tomography Probes Chen Z, Mori W, Fu H, Schafroth MA, Hatori A, Shao T, Zhang G, Van RS, Zhang Y and Liang SH <17 more author(s)> Chen Z, Mori W, Fu H, Schafroth MA, Hatori A, Shao T, Zhang G, Van RS, Zhang Y, Hu K, Fujinaga M, Wang L, Belov V, Ogasawara D, Giffenig P, Deng X, Rong J, Yu Q, Zhang X, Papisov MI, Shao Y, Collier TL, Ma JA, Cravatt BF, Josephson L, Zhang MR, Liang SH (- 17) Ref: Journal of Medicinal Chemistry, 62:8866, 2019 : PubMed ESTHER: Chen_2019_J.Med.Chem_62_8866 PubMedSearch: Chen 2019 J.Med.Chem 62 8866 PubMedID: 31518130 Inhibitor(s) related to this paper: PF-06795071 Abstract Dysfunction of monoacylglycerol lipase (MAGL) is associated with several psychopathological disorders, including drug addiction and neurodegenerative diseases. Herein we design, synthesize, and evaluate several irreversible fluorine-containing MAGL inhibitors for positron emission tomography (PET) ligand development. Compound 6 (identified from a therapeutic agent) was advanced for (18)F-labeling via a novel spirocyclic iodonium ylide (SCIDY) strategy, which demonstrated high brain permeability and excellent specific binding. This work supports further development of novel (18)F-labeled MAGL PET probes. Title: Molecular recognition of organophosphorus compounds in water and inhibition of their toxicity to acetylcholinesterase Liu WE, Chen Z, Yang LP, Au-Yeung HY, Jiang W Ref: Chem Commun (Camb), 55:9797, 2019 : PubMed ESTHER: Liu_2019_Chem.Commun.(Camb)_55_9797 PubMedSearch: Liu 2019 Chem.Commun.(Camb) 55 9797 PubMedID: 31360962 Abstract Molecular tubes with hydrogen bonding donors in their deep hydrophobic cavities are able to selectively bind organophosphorus compounds in water through hydrogen bonding and the hydrophobic effect. They can also be used as a fluorescent sensor for nerve agent simulants and as an inhibitor to reduce the toxicity of paraoxon to acetylcholinesterase. Title: Rhodopseudomonas palustris wastewater treatment: Cyhalofop-butyl removal, biochemicals production and mathematical model establishment Wu P, Chen Z, Zhang Y, Wang Y, Zhu F, Cao B, Wu Y, Li N Ref: Bioresour Technol, 282:390, 2019 : PubMed ESTHER: Wu_2019_Bioresour.Technol_282_390 PubMedSearch: Wu 2019 Bioresour.Technol 282 390 PubMedID: 30884459 Abstract Simultaneous (SPW and cyhalofop-butyl) wastewater treatment and the production of biochemicals by Rhodopseudomonas palustris (R. palustris) was investigated with supplementation of soybean processing wastewater (SPW). Compared to control group, cyhalofop-butyl was removed and single cell protein, carotenoid, bacteriochlorophyll productions were enhanced with the supplementation of SPW. Cyhalofop-butyl removal reached 100% after 5days under 4000mg/L COD group. Cyhalofop-butyl induced chbH gene expression to synthesize cyhalofop-butyl-hydrolyzing carboxylesterase through activating MAPKKKs, MAPKKs, MAPKs genes in MAPK signal transduction pathway. The induction process took one day for R. palustris. However, lack of organics in original wastewater did not maintain R. palustris growth for over one day. The supplementation of SPW provided sufficient carbon source. This new method resulted in the mixed wastewater treatment and improvement of biochemicals simultaneously, as well as the realization of reutilization of R. palustris. High-order non-linear mathematical model of the relationship between Rchb, Xc, and Xt was established. Title: The removal of cyhalofop-butyl in soil by surplus Rhodopseudanonas palustris in wastewater purification Wu P, Mo W, Chen Z, Wang Y, Cui Y, Zhang Y, Song Y, Jin L, Hou Y and Li N <2 more author(s)> Wu P, Mo W, Chen Z, Wang Y, Cui Y, Zhang Y, Song Y, Jin L, Hou Y, Zhu F, Cao B, Li N (- 2) Ref: J Environ Manage, 245:168, 2019 : PubMed ESTHER: Wu_2019_J.Environ.Manage_245_168 PubMedSearch: Wu 2019 J.Environ.Manage 245 168 PubMedID: 31152960 Abstract The biorestoration of cyhalofop-butyl and fertility in soil using Rhodopseudanonas palustris (R. palustris) in the treated wastewater were investigated in this research. Cyhalofop-butyl was not degraded under control group. The treated wastewater containing R. palustris degraded cyhalofop-butyl and remediated fertility. Interestingly, the cyhalofop-butyl-hydrolyzing carboxylesterase gene was expressed after inoculation 24h. Subsequently, the cyhalofop-butyl-hydrolyzing carboxylesterase were synthesized to degrade cyhalofop-butyl. The cyhalofop-butyl started to be degraded after inoculation 24h. The cyhalofop-butyl as stimulus signal induced cyhalofop-butyl-hydrolyzing carboxylesterase gene expression through signal transduction pathway. This process took 24h for R. palustris as they were ancient bacteria. The residual organics in the wastewater provided sufficient carbon sources and energy for R. palustris under three dosage groups. The new method completed the remediation of cyhalofop-butyl pollution, the improvement of soil fertility and soybean processing wastewater treatment simultaneously, and realized the resource reutilization of wastewater and R. palustris as sludge. Title: A Simple 3D-Printed Enzyme Reactor Paper Spray Mass Spectrometry Platform for Detecting BuChE Activity in Human Serum Yang Y, Liu H, Chen Z, Wu T, Jiang Z, Tong L, Tang B Ref: Analytical Chemistry, 91:12874, 2019 : PubMed ESTHER: Yang_2019_Anal.Chem_91_12874 PubMedSearch: Yang 2019 Anal.Chem 91 12874 PubMedID: 31518111 Abstract To achieve personalized healthcare, a quick, accurate, and high-throughput method to detect disease biomarkers is essential. In the traditional practice, mass spectrometry is one of the most powerful tools and is widely studied. However, the test of human serum usually requires complicated sample pretreatment, tedious operations, and precise condition control, especially for the detection of enzymes as biomarkers. As butyrylcholinesterase (BuChE) has an indicative significance in detecting degenerative disease, liver injury, and organophosphate poisoning, the quick quantification of BuChE is of vital importance to the clinic. In this paper, we report the design and fabrication of a portable 3D-printed enzyme reactor paper spray cartridge (3D ER-PS) with integrated functions: temperature control, enzyme reaction, analyte transfer, and paper spray ionization. Coupled with mass spectrometry, quantitative testing of BuChE activity in human serum was realized conveniently and accurately. While it only requires very simple sample preparation, the results from current 3D ER-PS approach are well consistent with those obtained using Ellman's method. This 3D ER-PS platform not only provides a novel solution for the liquid biopsy of BuChE in clinics but also contributes to the development of quick and targeted medical approaches for analyzing other types of serum biomarker molecules in the field of disease diagnosis. Title: Guided Evolution of Recombinant Bombyx mori Acetylcholinesterase II by Homology Modeling to Change Pesticide Sensitivity Cai J, Wang B, Li J, Chen Z, Rao M, Muyldermans S, Hua X, Xie X, Wang H and Sun Y <3 more author(s)> Cai J, Wang B, Li J, Chen Z, Rao M, Muyldermans S, Hua X, Xie X, Wang H, Yang J, Xu Z, Shen Y, Sun Y (- 3) Ref: Int J Mol Sci, 19:, 2018 : PubMed Title: In Vitro and in Vivo Evaluation of (11)C-Labeled Azetidinecarboxylates for Imaging Monoacylglycerol Lipase by PET Imaging Studies Cheng R, Mori W, Ma L, Alhouayek M, Hatori A, Zhang Y, Ogasawara D, Yuan G, Chen Z and Liang SH <16 more author(s)> Cheng R, Mori W, Ma L, Alhouayek M, Hatori A, Zhang Y, Ogasawara D, Yuan G, Chen Z, Zhang X, Shi H, Yamasaki T, Xie L, Kumata K, Fujinaga M, Nagai Y, Minamimoto T, Svensson M, Wang L, Du Y, Ondrechen MJ, Vasdev N, Cravatt BF, Fowler C, Zhang MR, Liang SH (- 16) Ref: Journal of Medicinal Chemistry, 61:2278, 2018 : PubMed ESTHER: Cheng_2018_J.Med.Chem_61_2278 PubMedSearch: Cheng 2018 J.Med.Chem 61 2278 PubMedID: 29481079 Abstract Monoacylglycerol lipase (MAGL) is the principle enzyme for metabolizing endogenous cannabinoid ligand 2-arachidonoyglycerol (2-AG). Blockade of MAGL increases 2-AG levels, resulting in subsequent activation of the endocannabinoid system, and has emerged as a novel therapeutic strategy to treat drug addiction, inflammation, and neurodegenerative diseases. Herein we report a new series of MAGL inhibitors, which were radiolabeled by site-specific labeling technologies, including (11)C-carbonylation and spirocyclic iodonium ylide (SCIDY) radiofluorination. The lead compound [(11)C]10 (MAGL-0519) demonstrated high specific binding and selectivity in vitro and in vivo. We also observed unexpected washout kinetics with these irreversible radiotracers, in which in vivo evidence for turnover of the covalent residue was unveiled between MAGL and azetidine carboxylates. This work may lead to new directions for drug discovery and PET tracer development based on azetidine carboxylate inhibitor scaffold. Title: Treatment of secondary brain injury by perturbing postsynaptic density protein-95-NMDA receptor interaction after intracerebral hemorrhage in rats Wang Z, Chen Z, Yang J, Yang Z, Yin J, Duan X, Shen H, Li H, Chen G Ref: Journal of Cerebral Blood Flow & Metabolism, :271678X18762637, 2018 : PubMed ESTHER: Wang_2018_J.Cereb.Blood.Flow.Metab__271678X18762637 PubMedSearch: Wang 2018 J.Cereb.Blood.Flow.Metab 271678X18762637 PubMedID: 29513122 Abstract Postsynaptic density protein-95 (PSD95) plays important roles in the formation, differentiation, remodeling, and maturation of neuronal synapses. This study is to estimate the potential role of PSD95 in cognitive dysfunction and synaptic injury following intracerebral hemorrhage (ICH). The interaction between PSD95 and NMDA receptor subunit NR2B-neurotransmitter nitric oxide synthase (nNOS) could form a signal protein complex mediating excitatory signaling. Besides NR2B-nNOS, PSD95 also can bind to neurexin-1-neuroligin-1 to form a complex and participates in maintaining synaptic function. In this study, we found that there were an increase in the formation of PSD95-NR2B-nNOS complex and a decrease in the formation of neurexin-1-neuroligin-1-PSD95 complex after ICH, and this was accompanied by increased neuronal death and degeneration, and behavior dysfunction. PSD95 inhibitor Tat-NR2B9c effectively inhibited the interaction between PSD95 and NR2B-nNOS, and promoted the formation of neurexin-1-nueuroligin-1-PSD95 complex. In addition, Tat-NR2B9c treatment significantly reduced neuronal death and degeneration and matrix metalloproteinase 9 activity, alleviated inflammatory response and neurobehavioral disorders, and improved the cognitive and learning ability of ICH rats. Inhibition of the formation of PSD95-NR2B-nNOS complex can rescue secondary brain injury and behavioral cognitive impairment after ICH. PSD95 is expected to be a target for improving the prognosis of patients with ICH. Title: Trefoil Factor 3, Cholinesterase and Homocysteine: Potential Predictors for Parkinson's Disease Dementia and Vascular Parkinsonism Dementia in Advanced Stage Zou J, Chen Z, Liang C, Fu Y, Wei X, Lu J, Pan M, Guo Y, Liao X and Wang Q <5 more author(s)> Zou J, Chen Z, Liang C, Fu Y, Wei X, Lu J, Pan M, Guo Y, Liao X, Xie H, Wu D, Li M, Liang L, Wang P, Wang Q (- 5) Ref: Aging Dis, 9:51, 2018 : PubMed ESTHER: Zou_2018_Aging.Dis_9_51 PubMedSearch: Zou 2018 Aging.Dis 9 51 PubMedID: 29392081 Abstract Trefoil factor 3 (TFF3), cholinesterase activity (ChE activity) and homocysteine (Hcy) play critical roles in modulating recognition, learning and memory in neurodegenerative diseases, such as Parkinson's disease dementia (PDD) and vascular parkinsonism with dementia (VPD). However, whether they can be used as reliable predictors to evaluate the severity and progression of PDD and VPD remains largely unknown. METHODS: We performed a cross-sectional study that included 92 patients with PDD, 82 patients with VPD and 80 healthy controls. Serum levels of TFF3, ChE activity and Hcy were measured. Several scales were used to rate the severity of PDD and VPD. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of PDD and VPD patients compared to healthy subjects. RESULTS: Compared with healthy subjects, the serum levels of TFF3 and ChE activity were lower, while Hcy was higher in the PDD and VPD patients. These findings were especially prominent in male patients. The three biomarkers displayed differences between PDD and VPD sub-groups based on genders and UPDRS (III) scores' distribution. Interestingly, these increased serum Hcy levels were significantly and inversely correlated with decreased TFF3/ChE activity levels. There were significant correlations between TFF3/ChE activity/Hcy levels and PDD/VPD severities, including motor dysfunction, declining cognition and mood/gastrointestinal symptoms. Additionally, ROC curves for the combination of TFF3, ChE activity and Hcy showed potential diagnostic value in discriminating PDD and VPD patients from healthy controls. CONCLUSIONS: Our findings suggest that serum TFF3, ChE activity and Hcy levels may underlie the pathophysiological mechanisms of PDD and VPD. As the race to find biomarkers or predictors for these diseases intensifies, a better understanding of the roles of TFF3, ChE activity and Hcy may yield insights into the pathogenesis of PDD and VPD. Title: Engineered Surface-Immobilized Enzyme that Retains High Levels of Catalytic Activity in Air Badieyan S, Wang Q, Zou X, Li Y, Herron M, Abbott NL, Chen Z, Marsh EN Ref: Journal of the American Chemical Society, 139:2872, 2017 : PubMed ESTHER: Badieyan_2017_J.Am.Chem.Soc_139_2872 PubMedSearch: Badieyan 2017 J.Am.Chem.Soc 139 2872 PubMedID: 28191945 Abstract In the absence of aqueous buffer, most enzymes retain little or no activity; however, "water-free" enzymes would have many diverse applications. Here, we describe the chemically precise immobilization of an enzyme on an engineered surface designed to support catalytic activity in air at ambient humidity. Covalent immobilization of haloalkane dehalogenase on a surface support displaying poly(sorbitol methacrylate) chains resulted in approximately 40-fold increase in activity over lyophilized enzyme powders for the gas-phase dehalogenation of 1-bromopropane. The activity of the immobilized enzyme in air approaches 25% of the activity obtained in buffer for the immobilized enzyme. Poly(sorbitol methacrylate) appears to enhance activity by replacing protein-water interactions, thereby preserving the protein structure. Title: Effect of Linker Length and Flexibility on the Clostridium thermocellum Esterase Displayed on Bacillus subtilis Spores Chen H, Wu B, Zhang T, Jia J, Lu J, Chen Z, Ni Z, Tan T Ref: Appl Biochem Biotechnol, 182:168, 2017 : PubMed ESTHER: Chen_2017_Appl.Biochem.Biotechnol_182_168 PubMedSearch: Chen 2017 Appl.Biochem.Biotechnol 182 168 PubMedID: 27933482 Abstract In fusion protein design strategies, the flexibility and length of linkers are important parameters affecting the bioactivity of multifunctional proteins. A series of fusion proteins with different linkers were constructed. The effect of temperature, pH, and organic solvents was investigated on the enzymatic activity. Fusion proteins with P1(PTPTPT) and P2((PTPTPT)2) linkers remained highly active with wide temperature range. At pH 9.6, the relative activity of fusion proteins with (PTPTPT)2 and S2(EGKSSGSGSESKST) linkers was 70 and 62 % (1.75 and 1.5 times of that of non-linker ones). Fusion proteins with S3((GGGGS)4) linker retained 55 % activity after 5 h of incubation at 80 degrees C (1.2-fold of that of non-linker fusion proteins and 1.9-fold of GGGGS-linker fusion proteins). Finally, the relative activity of fusion proteins having different linkers was increased with 20 % dimethyl sulfoxide (DMSO) and methanol; relative activity of fusion proteins with EGKSSGSGSESKST linkers was enhanced 1.5- and 2.2-fold, respectively. These results suggest that longer flexible linker can enhance the activity and stability of displayed esterase than shorter flexible linker. Optimizing peptide linkers with length, flexibility, and amino acid composition could improve the thermostability and activity of the displayed enzyme. Title: Human Neutralizing Monoclonal Antibody Inhibition of Middle East Respiratory Syndrome Coronavirus Replication in the Common Marmoset Chen Z, Bao L, Chen C, Zou T, Xue Y, Li F, Lv Q, Gu S, Gao X and Jin Q <3 more author(s)> Chen Z, Bao L, Chen C, Zou T, Xue Y, Li F, Lv Q, Gu S, Gao X, Cui S, Wang J, Qin C, Jin Q (- 3) Ref: J Infect Dis, 215:1807, 2017 : PubMed ESTHER: Chen_2017_J.Infect.Dis_215_1807 PubMedSearch: Chen 2017 J.Infect.Dis 215 1807 PubMedID: 28472421 Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) infection in humans is highly lethal, with a fatality rate of 35%. New prophylactic and therapeutic strategies to combat human infections are urgently needed. We isolated a fully human neutralizing antibody, MCA1, from a human survivor. The antibody recognizes the receptor-binding domain of MERS-CoV S glycoprotein and interferes with the interaction between viral S and the human cellular receptor human dipeptidyl peptidase 4 (DPP4). To our knowledge, this study is the first to report a human neutralizing monoclonal antibody that completely inhibits MERS-CoV replication in common marmosets. Monotherapy with MCA1 represents a potential alternative treatment for human infections with MERS-CoV worthy of evaluation in clinical settings. Title: Discovery of novel rivastigmine-hydroxycinnamic acid hybrids as multi-targeted agents for Alzheimer's disease Chen Z, Digiacomo M, Tu Y, Gu Q, Wang S, Yang X, Chu J, Chen Q, Han Y and Pi R <5 more author(s)> Chen Z, Digiacomo M, Tu Y, Gu Q, Wang S, Yang X, Chu J, Chen Q, Han Y, Chen J, Nesi G, Sestito S, Macchia M, Rapposelli S, Pi R (- 5) Ref: Eur Journal of Medicinal Chemistry, 125:784, 2017 : PubMed ESTHER: Chen_2017_Eur.J.Med.Chem_125_784 PubMedSearch: Chen 2017 Eur.J.Med.Chem 125 784 PubMedID: 27736684 Abstract A series of rivastigmine-caffeic acid and rivastigmine-ferulic acid hybrids were designed, synthesized, and evaluated as multifunctional agents for Alzheimer's disease (AD) in vitro. The new compounds exerted antioxidant neuroprotective properties and good cholinesterases (ChE) inhibitory activities. Some of them also inhibited amyloid protein (Abeta) aggregation. In particular, compound 5 emerged as promising drug candidates endowed with neuroprotective potential, ChE inhibitory, Abeta self-aggregation inhibitory and copper chelation properties. These data suggest that compound 5 offers an attractive starting point for further lead optimization in the drug-discovery process against AD. Title: Genomic adaptation to polyphagy and insecticides in a major East Asian noctuid pest Cheng T, Wu J, Wu Y, Chilukuri RV, Huang L, Yamamoto K, Feng L, Li W, Chen Z and Mita K <28 more author(s)> Cheng T, Wu J, Wu Y, Chilukuri RV, Huang L, Yamamoto K, Feng L, Li W, Chen Z, Guo H, Liu J, Li S, Wang X, Peng L, Liu D, Guo Y, Fu B, Li Z, Liu C, Chen Y, Tomar A, Hilliou F, Montagne N, Jacquin-Joly E, d'Alencon E, Seth RK, Bhatnagar RK, Jouraku A, Shiotsuki T, Kadono-Okuda K, Promboon A, Smagghe G, Arunkumar KP, Kishino H, Goldsmith MR, Feng Q, Xia Q, Mita K (- 28) Ref: Nat Ecol Evol, 1:1747, 2017 : PubMed ESTHER: Cheng_2017_Nat.Ecol.Evol_1_1747 PubMedSearch: Cheng 2017 Nat.Ecol.Evol 1 1747 PubMedID: 28963452 Abstract The tobacco cutworm, Spodoptera litura, is among the most widespread and destructive agricultural pests, feeding on over 100 crops throughout tropical and subtropical Asia. By genome sequencing, physical mapping and transcriptome analysis, we found that the gene families encoding receptors for bitter or toxic substances and detoxification enzymes, such as cytochrome P450, carboxylesterase and glutathione-S-transferase, were massively expanded in this polyphagous species, enabling its extraordinary ability to detect and detoxify many plant secondary compounds. Larval exposure to insecticidal toxins induced expression of detoxification genes, and knockdown of representative genes using short interfering RNA (siRNA) reduced larval survival, consistent with their contribution to the insect's natural pesticide tolerance. A population genetics study indicated that this species expanded throughout southeast Asia by migrating along a South India-South China-Japan axis, adapting to wide-ranging ecological conditions with diverse host plants and insecticides, surviving and adapting with the aid of its expanded detoxification systems. The findings of this study will enable the development of new pest management strategies for the control of major agricultural pests such as S. litura. Title: HANAC Col4a1 Mutation in Mice Leads to Skeletal Muscle Alterations due to a Primary Vascular Defect Guiraud S, Migeon T, Ferry A, Chen Z, Ouchelouche S, Verpont MC, Sado Y, Allamand V, Ronco P, Plaisier E Ref: American Journal of Pathology, 187:505, 2017 : PubMed ESTHER: Guiraud_2017_Am.J.Pathol_187_505 PubMedSearch: Guiraud 2017 Am.J.Pathol 187 505 PubMedID: 28056338 Abstract Collagen IV is a major component of basement membranes (BMs). The alpha1(IV) chain, encoded by the COL4A1 gene, is expressed ubiquitously and associates with the alpha2(IV) chain to form the alpha1alpha1alpha2(IV) heterotrimer. Several COL4A1 mutations affecting a conformational domain containing integrin-binding sites are responsible for the systemic syndrome of hereditary angiopathy, nephropathy, aneurysms, and cramps (HANAC). To analyze the pathophysiology of HANAC, Col4a1 mutant mice bearing the p.Gly498Val mutation were generated. Analysis of the skeletal muscles of Col4a1G498V mutant animals showed morphologic characteristics of a muscular dystrophy phenotype with myofiber atrophy, centronucleation, focal inflammatory infiltrates, and fibrosis. Abnormal ultrastructural aspects of muscle BMs was associated with reduced extracellular secretion of the mutant alpha1alpha1alpha2(IV) trimer. In addition to muscular dystrophic features, endothelial cell defects of the muscle capillaries were observed, with intracytoplasmic accumulation of the mutant alpha1alpha1alpha2(IV) molecules, endoplasmic reticulum cisternae dilation, and up-regulation of endoplasmic reticulum stress markers. Induction of the unfolded protein response in Col4a1 mutant muscle tissue resulted in an excess of apoptosis in endothelial cells. HANAC mutant animals also presented with a muscular functional impairment and increased serum creatine kinase levels reflecting altered muscle fiber sarcolemma. This extensive description of the muscular phenotype of the Col4a1 HANAC murine model suggests a potential contribution of primary endothelial cell defects, together with muscle BM alterations, to the development of COL4A1-related myopathy. Title: GLP-1 acts on habenular avoidance circuits to control nicotine intake Tuesta LM, Chen Z, Duncan A, Fowler CD, Ishikawa M, Lee BR, Liu XA, Lu Q, Cameron M and Kenny PJ <3 more author(s)> Tuesta LM, Chen Z, Duncan A, Fowler CD, Ishikawa M, Lee BR, Liu XA, Lu Q, Cameron M, Hayes MR, Kamenecka TM, Pletcher M, Kenny PJ (- 3) Ref: Nat Neurosci, 20:708, 2017 : PubMed ESTHER: Tuesta_2017_Nat.Neurosci_20_708 PubMedSearch: Tuesta 2017 Nat.Neurosci 20 708 PubMedID: 28368384 Abstract Tobacco smokers titrate their nicotine intake to avoid its noxious effects, sensitivity to which may influence vulnerability to tobacco dependence, yet mechanisms of nicotine avoidance are poorly understood. Here we show that nicotine activates glucagon-like peptide-1 (GLP-1) neurons in the nucleus tractus solitarius (NTS). The antidiabetic drugs sitagliptin and exenatide, which inhibit GLP-1 breakdown and stimulate GLP-1 receptors, respectively, decreased nicotine intake in mice. Chemogenetic activation of GLP-1 neurons in NTS similarly decreased nicotine intake. Conversely, Glp1r knockout mice consumed greater quantities of nicotine than wild-type mice. Using optogenetic stimulation, we show that GLP-1 excites medial habenular (MHb) projections to the interpeduncular nucleus (IPN). Activation of GLP-1 receptors in the MHb-IPN circuit abolished nicotine reward and decreased nicotine intake, whereas their knockdown or pharmacological blockade increased intake. GLP-1 neurons may therefore serve as 'satiety sensors' for nicotine that stimulate habenular systems to promote nicotine avoidance before its aversive effects are encountered. Title: Hormone-sensitive lipase deficiency alters gene expression and cholesterol content of mouse testis Wang F, Chen Z, Ren X, Tian Y, Liu C, Jin P, Li Z, Zhang F, Zhu B Ref: Reproduction, 153:175, 2017 : PubMed ESTHER: Wang_2017_Reproduction_153_175 PubMedSearch: Wang 2017 Reproduction 153 175 PubMedID: 27920259 Abstract Hormone-sensitive lipase-knockout (HSL-/-) mice exhibit azoospermia for unclear reasons. To explore the basis of sterility, we performed the following three experiments. First, HSL protein distribution in the testis was determined. Next, transcriptome analyses were performed on the testes of three experimental groups. Finally, the fatty acid and cholesterol levels in the testes with three different genotypes studied were determined. We found that the HSL protein was present from spermatocyte cells to mature sperm acrosomes in wild-type (HSL+/+) testes. Spermiogenesis ceased at the elongation phase of HSL-/- testes. Transcriptome analysis indicated that genes involved in lipid metabolism, cell membrane, reproduction and inflammation-related processes were disordered in HSL-/- testes. The cholesterol content was significantly higher in HSL-/- than that in HSL+/+ testis. Therefore, gene expression and cholesterol ester content differed in HSL-/- testes compared to other testes, which may explain the sterility of male HSL-/- mice. Title: Sesquiterpenes and a monoterpenoid with acetylcholinesterase (AchE) inhibitory activity from Valeriana officinalis var. latiofolia in vitro and in vivo Chen HW, He XH, Yuan R, Wei BJ, Chen Z, Dong JX, Wang J Ref: Fitoterapia, 110:142, 2016 : PubMed ESTHER: Chen_2016_Fitoterapia_110_142 PubMedSearch: Chen 2016 Fitoterapia 110 142 PubMedID: 26976216 Abstract Acetylcholinesterase Inhibitor (AchEI) is the most extensive in all anti-dementia drugs. The extracts and isolated compounds from the Valeriana genus have shown anti-dementia bioactivity. Four new sesquiterpenoids (1-4) and a new monoterpenoid (5) were isolated from the root of Valeriana officinalis var. latiofolia. The acetylcholinesterase (AchE) inhibitory activity of isolates was evaluated by modified Ellman method in vitro. Learning and memory ability of compound 4 on mice was evaluated by the Morris water maze. The contents of acetylcholine (Ach), acetylcholine transferase (ChAT) and AchE in mice brains were determined by colorimetry. The results showed IC50 of compound 4 was 0.161muM in vitro. Compared with the normal group, the learning and memory ability of mice and the contents of Ach and ChAT decreased in model group mice (P<0.01), while the AchE increased (P<0.01). Compared with the model group, Ach and ChAT in the positive control group, the high-dose group and the medium-dose group increased (P<0.01), while the AchE decreased (P<0.01). Compound 4 can improve the learning and memory abilities of APPswe/PSDeltaE9 double-transgenic mice, and the mechanism may be related to the regulation of the relative enzyme in the cholinergic system. Title: Z-Guggulsterone Improves the Scopolamine-Induced Memory Impairments Through Enhancement of the BDNF Signal in C57BL/6J Mice Chen Z, Huang C, Ding W Ref: Neurochem Res, 41:3322, 2016 : PubMed ESTHER: Chen_2016_Neurochem.Res_41_3322 PubMedSearch: Chen 2016 Neurochem.Res 41 3322 PubMedID: 27677871 Abstract Memory impairment is a common symptom in patients with neurodegenerative disorders, and its suppression could be beneficial to improve the quality of life of those patients. Z-guggulsterone, a compound extracted from the resin of plant Commiphora whighitii, exhibits numerous pharmacological effects in clinical practice, such as treatment of inflammation, arthritis, obesity and lipid metabolism disorders. However, the role and possible mechanism of Z-guggulsterone on brain-associated memory impairments are largely unknown. This issue was addressed in the present study in a memory impairment model induced by scopolamine, a muscarinic acetylcholine receptor antagonist, using the passive avoidance, Y-maze and Morris water maze tests. Results showed that scopolamine significantly decreased the step-through latency and spontaneous alternation of C57BL/6J mice in passive avoidance and Y-maze test, whereas increased the mean escape latency and decreased the swimming time in target quadrant in Morris water maze test. Pretreatment of mice with Z-guggulsterone at doses of 30 and 60 mg/kg effectively reversed the scopolamine-induced memory impairments. Mechanistic studies revealed that Z-guggulsterone pretreatment reversed the scopolamine-induced increase in acetylcholinesterase (AchE) activity, as well as decreases in brain-derived neurotrophic factor (BDNF) protein expression and cAMP response element-binding protein (CREB), extracellular regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) phosphorylation levels in the hippocampus and cortex. Inhibition of the BDNF signal, however, blocked the memory-enhancing effect of Z-guggulsterone. Therefore, these findings demonstrate that Z-guggulsterone attenuates the scopolamine-induced memory impairments mainly through activation of the CREB-BDNF signaling pathway, thereby exhibiting memory-improving effects. Title: Postconditioning with sevoflurane ameliorates spatial learning and memory deficit after hemorrhage shock and resuscitation in rats Hu X, Wang J, Zhang Q, Duan X, Chen Z, Zhang Y Ref: J Surg Res, 206:307, 2016 : PubMed ESTHER: Hu_2016_J.Surg.Res_206_307 PubMedSearch: Hu 2016 J.Surg.Res 206 307 PubMedID: 27884324 Abstract BACKGROUND: Severe hemorrhage shock and resuscitation are a systemic ischemia-reperfusion phenomenon which can induce learning and memory deficit in human and rats. Sevoflurane postconditioning has been proved to offer neuroprotection under different setting of cerebral ischemia-reperfusion in rats. The aim of this study was to investigate whether sevoflurane postconditioning could improve spatial learning and memory ability after hemorrhage shock and resuscitation in rats. Title: Genome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts Ma L, Chen Z, Huang da W, Kutty G, Ishihara M, Wang H, Abouelleil A, Bishop L, Davey E and Kovacs JA <34 more author(s)> Ma L, Chen Z, Huang da W, Kutty G, Ishihara M, Wang H, Abouelleil A, Bishop L, Davey E, Deng R, Deng X, Fan L, Fantoni G, FitzGerald M, Gogineni E, Goldberg JM, Handley G, Hu X, Huber C, Jiao X, Jones K, Levin JZ, Liu Y, Macdonald P, Melnikov A, Raley C, Sassi M, Sherman BT, Song X, Sykes S, Tran B, Walsh L, Xia Y, Yang J, Young S, Zeng Q, Zheng X, Stephens R, Nusbaum C, Birren BW, Azadi P, Lempicki RA, Cuomo CA, Kovacs JA (- 34) Ref: Nat Commun, 7:10740, 2016 : PubMed ESTHER: Ma_2016_Nat.Commun_7_10740 PubMedSearch: Ma 2016 Nat.Commun 7 10740 PubMedID: 26899007 Gene_locus related to this paper: pnec8-a0a0w4zi95, pnemu-m7nra0, pnej8-l0pgn2 Abstract Pneumocystis jirovecii is a major cause of life-threatening pneumonia in immunosuppressed patients including transplant recipients and those with HIV/AIDS, yet surprisingly little is known about the biology of this fungal pathogen. Here we report near complete genome assemblies for three Pneumocystis species that infect humans, rats and mice. Pneumocystis genomes are highly compact relative to other fungi, with substantial reductions of ribosomal RNA genes, transporters, transcription factors and many metabolic pathways, but contain expansions of surface proteins, especially a unique and complex surface glycoprotein superfamily, as well as proteases and RNA processing proteins. Unexpectedly, the key fungal cell wall components chitin and outer chain N-mannans are absent, based on genome content and experimental validation. Our findings suggest that Pneumocystis has developed unique mechanisms of adaptation to life exclusively in mammalian hosts, including dependence on the lungs for gas and nutrients and highly efficient strategies to escape both host innate and acquired immune defenses. Title: A phenome-wide association study of a lipoprotein-associated phospholipase A2 loss-of-function variant in 90 000 Chinese adults Millwood IY, Bennett DA, Walters RG, Clarke R, Waterworth D, Johnson T, Chen Y, Yang L, Guo Y and Chen Z <10 more author(s)> Millwood IY, Bennett DA, Walters RG, Clarke R, Waterworth D, Johnson T, Chen Y, Yang L, Guo Y, Bian Z, Hacker A, Yeo A, Parish S, Hill MR, Chissoe S, Peto R, Cardon L, Collins R, Li L, Chen Z (- 10) Ref: Int J Epidemiol, 45:1588, 2016 : PubMed ESTHER: Millwood_2016_Int.J.Epidemiol_45_1588 PubMedSearch: Millwood 2016 Int.J.Epidemiol 45 1588 PubMedID: 27301456 Gene_locus related to this paper: human-PLA2G7 Abstract BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been implicated in development of atherosclerosis; however, recent randomized trials of Lp-PLA(2) inhibition reported no beneficial effects on vascular diseases. In East Asians, a loss-of-function variant in the PLA2G7 gene can be used to assess the effects of genetically determined lower Lp-PLA(2) METHODS: PLA2G7 V279F (rs76863441) was genotyped in 91 428 individuals randomly selected from the China Kadoorie Biobank of 0.5 M participants recruited in 2004-08 from 10 regions of China, with 7 years' follow-up. Linear regression was used to assess effects of V279F on baseline traits. Logistic regression was conducted for a range of vascular and non-vascular diseases, including 41 ICD-10 coded disease categories. RESULTS: PLA2G7 V279F frequency was 5% overall (range 3-7% by region), and 9691 (11%) participants had at least one loss-of-function variant. V279F was not associated with baseline blood pressure, adiposity, blood glucose or lung function. V279F was not associated with major vascular events [7141 events; odds ratio (OR) = 0.98 per F variant, 95% confidence interval (CI) 0.90-1.06] or other vascular outcomes, including major coronary events (922 events; 0.96, 0.79-1.18) and stroke (5967 events; 1.00, 0.92-1.09). Individuals with V279F had lower risks of diabetes (7031 events; 0.91, 0.84-0.98) and asthma (182 events; 0.53, 0.28-0.98), but there was no association after adjustment for multiple testing. CONCLUSIONS: Lifelong lower Lp-PLA(2) activity was not associated with major risks of vascular or non-vascular diseases in Chinese adults. Using functional genetic variants in large-scale prospective studies with linkage to a range of health outcomes is a valuable approach to inform drug development and repositioning. Title: Evolution of Digestive Enzymes and RNASE1 Provides Insights into Dietary Switch of Cetaceans Wang Z, Xu S, Du K, Huang F, Chen Z, Zhou K, Ren W, Yang G Ref: Molecular Biology Evolution, 33:3144, 2016 : PubMed ESTHER: Wang_2016_Mol.Biol.Evol_33_3144 PubMedSearch: Wang 2016 Mol.Biol.Evol 33 3144 PubMedID: 27651393 Gene_locus related to this paper: souch-a0a1d8i1n4 Abstract Although cetaceans (whales, porpoises, and dolphins) have multi-chambered stomachs, feeding habits of modern cetaceans have dramatically changed from herbivorous to carnivorous. However, the genetic basis underlying this dietary switch remains unexplored. Here, we present the first systematic investigation of 10 digestive enzymes genes (i.e., CYP7A1, CTRC, LIPC, LIPF, PNLIP, PGC, PRSS1, SI, SLC5A1, and TMPRSS15) of representative cetaceans, and the evolutionary trajectory of RNASE1 in cetartiodactylans. Positive selections were detected with proteinases (i.e., CTRC, PRSS1, and TMPRSS15) and lipases (i.e., CYP7A1, LIPF, and PNLIP) suggesting that cetaceans have evolved an enhanced digestion capacity for proteins and lipids, the major nutritional components of their prey (fishes and invertebrates). In addition, it was found that RNASE1 gene duplicated after the cetartiodactylan speciation and two independent gene duplication events took place in Camelidae and Ruminantia. Positive selection was detected with RNASE1 of Camelidae and Bovidae, suggesting enhanced digestive efficiency in the ruminants. Remarkably, even though the ancestors of cetaceans were terrestrial artiodactyls that are herbivorous, modern cetaceans lost the pancreatic RNASE1 copy with digestive function, which is in accordance with the dietary change from herbivorous to carnivorous. In sum, this is the first study that provides new insights into the evolutionary mechanism of dietary switch in cetaceans. Title: Expression and display of a novel thermostable esterase from Clostridium thermocellum on the surface of Bacillus subtilis using the CotB anchor protein Chen H, Zhang T, Jia J, Vastermark A, Tian R, Ni Z, Chen Z, Chen K, Yang S Ref: J Ind Microbiol Biotechnol, 42:1439, 2015 : PubMed ESTHER: Chen_2015_J.Ind.Microbiol.Biotechnol_42_1439 PubMedSearch: Chen 2015 J.Ind.Microbiol.Biotechnol 42 1439 PubMedID: 26318029 Abstract Esterases expressed in microbial hosts are commercially valuable, but their applications are limited due to high costs of production and harsh industrial processes involved. In this study, the esterase-DSM (from Clostridium thermocellum) was expressed and successfully displayed on the spore surface, and the spore-associated esterase was confirmed by western blot analysis and activity measurements. The optimal temperature and pH of spore surface-displayed DSM was 60 and 8.5 degrees C, respectively. It also demonstrates a broad temperature and pH optimum in the range of 50-70, 7-9.5 degrees C. The spore surface-displayed esterase-DSM retained 78, 68 % of its original activity after 5 h incubation at 60 and 70 degrees C, respectively, which was twofold greater activity than that of the purified DSM. The recombinant spores has high activity and stability in DMSO, which was 49 % higher than the retained activity of the purified DSM in DMSO (20 % v/v), and retained 65.2 % of activity after 7 h of incubation in DMSO (20 % v/v). However, the recombinant spores could retain 77 % activity after 3 rounds of recycling. These results suggest that enzyme displayed on the surface of the Bacillus subtilis spore could serve as an effective approach for enzyme immobilization. Title: Alteration of osa-miR156e expression affects rice plant architecture and strigolactones (SLs) pathway Chen Z, Gao X, Zhang J Ref: Plant Cell Rep, 34:767, 2015 : PubMed ESTHER: Chen_2015_Plant.Cell.Rep_34_767 PubMedSearch: Chen 2015 Plant.Cell.Rep 34 767 PubMedID: 25604991 Abstract Overexpressing osa--miR156e in rice produced a bushy mutant and osa--miR156e regulation of tillering may do this through the strigolactones (SLs) pathway. Appropriate downregulation of osa--miR156 expression contributed to the improvement of plant architecture. Tillering is one of the main determinants for rice architecture and yield. In this study, a bushy mutant of rice was identified with increased tiller number, reduced plant height, prolonged heading date, low seed setting, and small panicle size due to a T-DNA insertion which essentially elevated the expression of osa-miR156e. Transgenic plants with constitutive expression of osa-miR156e also had the bushy phenotype, which showed osa-miR156 may control apical dominance and tiller outgrowth via regulating the strigolactones signaling pathway. Furthermore, the extent of impaired morphology was correlated with the expression level of osa-miR156e. In an attempt to genetically improve rice architecture, ectopic expression of osa-miR156e under the GAL4-UAS system or OsTB1 promoter was conducted. According to agronomic trait analysis, pTB1:osa-miR156e transgenic plants significantly improved the grain yield per plant compared to plants overexpressing osa-miR156e, even though the yield was still inferior to the wild type, making it a very interesting albeit negative result. Our results suggested that osa-miR156 could serve as a potential tool for modifying rice plant architecture through genetic manipulation of the osa-miR156 expression level. Title: Surface display of the thermophilic lipase Tm1350 on the spore of Bacillus subtilis by the CotB anchor protein Chen H, Tian R, Ni Z, Zhang Q, Zhang T, Chen Z, Chen K, Yang S Ref: Extremophiles, 19:799, 2015 : PubMed ESTHER: Chen_2015_Extremophiles_19_799 PubMedSearch: Chen 2015 Extremophiles 19 799 PubMedID: 26026992 Abstract Lipases expressed in microbial hosts have great commercial value, but their applications are restricted by the high costs of production and harsh conditions used in industrial processes, such as high temperature and alkaline environment. In this study, an Escherichia coli-Bacillus subtilis shuttle vector (pHS-cotB-Tm1350) was constructed for the spore surface display of the lipase Tm1350 from hyperthermophilic bacterium Thermotoga maritima MSB8. Successful display of the CotB-Tm1350 fusion protein on spore surface was confirmed by Western blot analysis and activity measurements. The optimal catalytic temperature and pH of the spore surface-displayed Tm1350 were 80 degreesC and 9, respectively, which were higher than non-immobilized Tm1350 (70 degreesC and pH 7.5). Analysis of thermal and pH stability showed that spore surface-displayed Tm1350 retained 81 or 70 % of its original activity after 8 h of incubation at pH 8 or pH 9 (70 degreesC), which were 18 % higher than the retained activity of the non-immobilized Tm1350 under the same conditions. Meanwhile, recycling experiments showed that the recombinant spores could be used for up to three reaction cycles without a significant decrease in the catalytic rate (84 %). These results suggested that enzyme display on the surface of the B. subtilis spore could serve as an effective approach for enzyme immobilization, which has potential applications in the harsh biochemical industry. Title: Synthesis and pharmacological evaluation of multifunctional tacrine derivatives against several disease pathways of AD Digiacomo M, Chen Z, Wang S, Lapucci A, Macchia M, Yang X, Chu J, Han Y, Pi R, Rapposelli S Ref: Bioorganic & Medicinal Chemistry Lett, 25:807, 2015 : PubMed ESTHER: Digiacomo_2015_Bioorg.Med.Chem.Lett_25_807 PubMedSearch: Digiacomo 2015 Bioorg.Med.Chem.Lett 25 807 PubMedID: 25597007 Abstract A novel series of tacrine derivatives were designed and synthesized by combining caffeic acid (CA), ferulic acid (FA) and lipoic acid (LA) with tacrine. The antioxidant study revealed that all the hybrids have much more antioxidant capacities compared to CA. Among these compounds, 1b possessed a good ability to inhibit the beta-amyloid protein (Abeta) self-aggregation, sub-micromole acetylcholinesterase (AChE)/butyrylcholinesterase (BCHE) inhibitory, modest BACE1 inhibitory. Moreover, compound 1b also was a DPPH radical scavenger and copper chelatory as well as had potent neuroprotective effects against glutamate-induced cell death with low toxicity in HT22 cells. Our findings suggest that the compound 1b might be a promising lead multi-targeted ligand and worthy of further developing for the therapy of Alzheimer's disease. Title: In vitro acaricidal activity of 1,8-cineole against Sarcoptes scabiei var. cuniculi and regulating effects on enzyme activity Hu Z, Chen Z, Yin Z, Jia R, Song X, Li L, Zou Y, Liang X, He C and Shi F <5 more author(s)> Hu Z, Chen Z, Yin Z, Jia R, Song X, Li L, Zou Y, Liang X, He C, Yin L, Lv C, Zhao L, Su G, Ye G, Shi F (- 5) Ref: Parasitol Res, 114:2959, 2015 : PubMed ESTHER: Hu_2015_Parasitol.Res_114_2959 PubMedSearch: Hu 2015 Parasitol.Res 114 2959 PubMedID: 25924796 Abstract 1,8-Cineole found in many essential oils is a monoterpene and acts as a repellent against Sarcoptes scabiei var. cuniculi. In the present study, the acaricidal activity of 1,8-cineole against S. scabiei var. cuniculi was evaluated and the acaricidal mechanism was also investigated by assaying enzyme activities. The results showed that the lethal concentration of 50 % (LC50) value (95 % confidence limit (CL)) and the lethal time of 50 % (LT50) value (95 % CL) of 1,8-cineole were 2.77 mg/mL and 3.606 h, respectively. The pathological changes under transmission electron microscopy showed that the morphology of the mitochondria was abnormal, the cell nuclear membrane was damaged, and the nuclear chromatin was dissoluted. The activities of superoxide dismutase (SOD), glutathione-s-transferases (GSTs), monoamine oxidase (MAO), nitric oxide synthase (NOS), and acetylcholinesterase (AChE) were significantly changed after treatment with 1,8-cineole for 4, 8, 12, and 24 h. SOD and GSTs are associated with the protection mechanism of scabies mites. And, the activities of SOD and GSTs were increased as compared with the control group. MAO, AChE, and NOS are associated with the nervous system of scabies mites. The activity of MAO was increased whereas the AChE was suppressed. The activity of NOS was suppressed in the high-dose group whereas increased in the middle-dose group and low-dose group. These results indicated that the mechanism of 1,8-cineole mainly attributed to the changes of these enzyme activities related to the nervous system of scabies mites. Title: The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia Munoz JF, Gauthier GM, Desjardins CA, Gallo JE, Holder J, Sullivan TD, Marty AJ, Carmen JC, Chen Z and Cuomo CA <16 more author(s)> Munoz JF, Gauthier GM, Desjardins CA, Gallo JE, Holder J, Sullivan TD, Marty AJ, Carmen JC, Chen Z, Ding L, Gujja S, Magrini V, Misas E, Mitreva M, Priest M, Saif S, Whiston EA, Young S, Zeng Q, Goldman WE, Mardis ER, Taylor JW, McEwen JG, Clay OK, Klein BS, Cuomo CA (- 16) Ref: PLoS Genet, 11:e1005493, 2015 : PubMed ESTHER: Munoz_2015_PLoS.Genet_11_E1005493 PubMedSearch: Munoz 2015 PLoS.Genet 11 E1005493 PubMedID: 26439490 Gene_locus related to this paper: ajedr-c5gqv9, 9euro-a0a2b7ztc4, 9euro-a0a2b7wr51, blags-a0a179v0z0, 9euro-a0a0h1bel0, blags-a0a179udh1, ajedr-kex1, ajedr-cbpya Abstract Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics of genome evolution and of factors contributing to virulence in Blastomyces. Title: Sex and parasites: genomic and transcriptomic analysis of Microbotryum lychnidis-dioicae, the biotrophic and plant-castrating anther smut fungus Perlin MH, Amselem J, Fontanillas E, Toh SS, Chen Z, Goldberg J, Duplessis S, Henrissat B, Young S and Cuomo CA <11 more author(s)> Perlin MH, Amselem J, Fontanillas E, Toh SS, Chen Z, Goldberg J, Duplessis S, Henrissat B, Young S, Zeng Q, Aguileta G, Petit E, Badouin H, Andrews J, Razeeq D, Gabaldon T, Quesneville H, Giraud T, Hood ME, Schultz DJ, Cuomo CA (- 11) Ref: BMC Genomics, 16:461, 2015 : PubMed ESTHER: Perlin_2015_BMC.Genomics_16_461 PubMedSearch: Perlin 2015 BMC.Genomics 16 461 PubMedID: 26076695 Gene_locus related to this paper: ustv1-u5h5e5 Abstract BACKGROUND: The genus Microbotryum includes plant pathogenic fungi afflicting a wide variety of hosts with anther smut disease. Microbotryum lychnidis-dioicae infects Silene latifolia and replaces host pollen with fungal spores, exhibiting biotrophy and necrosis associated with altering plant development. RESULTS: We determined the haploid genome sequence for M. lychnidis-dioicae and analyzed whole transcriptome data from plant infections and other stages of the fungal lifecycle, revealing the inventory and expression level of genes that facilitate pathogenic growth. Compared to related fungi, an expanded number of major facilitator superfamily transporters and secretory lipases were detected; lipase gene expression was found to be altered by exposure to lipid compounds, which signaled a switch to dikaryotic, pathogenic growth. In addition, while enzymes to digest cellulose, xylan, xyloglucan, and highly substituted forms of pectin were absent, along with depletion of peroxidases and superoxide dismutases that protect the fungus from oxidative stress, the repertoire of glycosyltransferases and of enzymes that could manipulate host development has expanded. A total of 14% of the genome was categorized as repetitive sequences. Transposable elements have accumulated in mating-type chromosomal regions and were also associated across the genome with gene clusters of small secreted proteins, which may mediate host interactions. CONCLUSIONS: The unique absence of enzyme classes for plant cell wall degradation and maintenance of enzymes that break down components of pollen tubes and flowers provides a striking example of biotrophic host adaptation. Title: Role of Neurexin-1beta and Neuroligin-1 in Cognitive Dysfunction After Subarachnoid Hemorrhage in Rats Shen H, Chen Z, Wang Y, Gao A, Li H, Cui Y, Zhang L, Xu X, Wang Z, Chen G Ref: Stroke, 46:2607, 2015 : PubMed ESTHER: Shen_2015_Stroke_46_2607 PubMedSearch: Shen 2015 Stroke 46 2607 PubMedID: 26219651 Abstract BACKGROUND AND PURPOSE: Neurexin-1beta and neuroligin-1 play an important role in the formation, maintenance, and regulation of synaptic structures. This study is to estimate the potential role of neurexin-1beta and neuroligin-1 in subarachnoid hemorrhage (SAH)-induced cognitive dysfunction. Title: 'Obesity' is healthy for cetaceans? Evidence from pervasive positive selection in genes related to triacylglycerol metabolism Wang Z, Chen Z, Xu S, Ren W, Zhou K, Yang G Ref: Sci Rep, 5:14187, 2015 : PubMed ESTHER: Wang_2015_Sci.Rep_5_14187 PubMedSearch: Wang 2015 Sci.Rep 5 14187 PubMedID: 26381091 Gene_locus related to this paper: delle-a0a2y9m8t8, lipve-a0a0n6wyt2 Abstract Cetaceans are a group of secondarily adapted marine mammals with an enigmatic history of transition from terrestrial to fully aquatic habitat and subsequent adaptive radiation in waters around the world. Numerous physiological and morphological cetacean characteristics have been acquired in response to this drastic habitat transition; for example, the thickened blubber is one of the most striking changes that increases their buoyancy, supports locomotion, and provides thermal insulation. However, the genetic basis underlying the blubber thickening in cetaceans remains poorly explored. Here, 88 candidate genes associated with triacylglycerol metabolism were investigated in representative cetaceans and other mammals to test whether the thickened blubber matched adaptive evolution of triacylglycerol metabolism-related genes. Positive selection was detected in 41 of the 88 candidate genes, and functional characterization of these genes indicated that these are involved mainly in triacylglycerol synthesis and lipolysis processes. In addition, some essential regulatory genes underwent significant positive selection in cetacean-specific lineages, whereas no selection signal was detected in the counterpart terrestrial mammals. The extensive occurrence of positive selection in triacylglycerol metabolism-related genes is suggestive of their essential role in secondary adaptation to an aquatic life, and further implying that 'obesity' might be an indicator of good health for cetaceans. Title: Expression and Characterization of a New Thermostable Esterase from Clostridium thermocellum Zhang T, Chen H, Ni Z, Tian R, Jia J, Chen Z, Yang S Ref: Appl Biochem Biotechnol, 177:1437, 2015 : PubMed ESTHER: Zhang_2015_Appl.Biochem.Biotechnol_177_1437 PubMedSearch: Zhang 2015 Appl.Biochem.Biotechnol 177 1437 PubMedID: 26373940 Gene_locus related to this paper: clotm-q4cf59 Abstract The thermostable esterase from the thermophilic bacterium Clostridium thermocellum DSM 1313 was expressed in Escherichia coli and purified by Ni(2+) affinity chromatography. Its molecular weight was approximately 35 kDa according to 12 % sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The enzyme exhibited the highest specific activity with p-nitrophenyl butyrate (285 s(-1) mM(-1)). The activity of the esterase was greatest at 65 degrees C, and the esterase maintained residual activity levels of 70 and 50 % after 3 h incubation at 65 and 70 degrees C, respectively. Its activity was optimal at pH 7.0, was enhanced in the presence of Ca(2+) and Mg(2+), and was inhibited by Ni(2+) and Cu(2+). The addition of surfactants, such as Tween-20, Tween-80, Triton X-100, and SDS, at concentrations of 5 % (v/v) significantly inhibited the lipolytic action of the esterase. Enzyme activity was relatively stable in 10 % methanol, and 50 % residual activity was seen in 10 % DMSO, demonstrating its potential in biodiesel production and industrial applications. Title: Comparative genomic and transcriptomic analysis of wangiella dermatitidis, a major cause of phaeohyphomycosis and a model black yeast human pathogen Chen Z, Martinez DA, Gujja S, Sykes SM, Zeng Q, Szaniszlo PJ, Wang Z, Cuomo CA Ref: G3 (Bethesda), 4:561, 2014 : PubMed ESTHER: Chen_2014_G3.(Bethesda)_4_561 PubMedSearch: Chen 2014 G3.(Bethesda) 4 561 PubMedID: 24496724 Gene_locus related to this paper: exodn-h6bmp3, exodn-h6btr2, exodn-h6c4y3 Abstract Black or dark brown (phaeoid) fungi cause cutaneous, subcutaneous, and systemic infections in humans. Black fungi thrive in stressful conditions such as intense light, high radiation, and very low pH. Wangiella (Exophiala) dermatitidis is arguably the most studied phaeoid fungal pathogen of humans. Here, we report our comparative analysis of the genome of W. dermatitidis and the transcriptional response to low pH stress. This revealed that W. dermatitidis has lost the ability to synthesize alpha-glucan, a cell wall compound many pathogenic fungi use to evade the host immune system. In contrast, W. dermatitidis contains a similar profile of chitin synthase genes as related fungi and strongly induces genes involved in cell wall synthesis in response to pH stress. The large portfolio of transporters may provide W. dermatitidis with an enhanced ability to remove harmful products as well as to survive on diverse nutrient sources. The genome encodes three independent pathways for producing melanin, an ability linked to pathogenesis; these are active during pH stress, potentially to produce a barrier to accumulated oxidative damage that might occur under stress conditions. In addition, a full set of fungal light-sensing genes is present, including as part of a carotenoid biosynthesis gene cluster. Finally, we identify a two-gene cluster involved in nucleotide sugar metabolism conserved with a subset of fungi and characterize a horizontal transfer event of this cluster between fungi and algal viruses. This work reveals how W. dermatitidis has adapted to stress and survives in diverse environments, including during human infections. Title: Phaeodactylibacter xiamenensis gen. nov., sp. nov., a member of the family Saprospiraceae isolated from the marine alga Phaeodactylum tricornutum Chen Z, Lei X, Lai Q, Li Y, Zhang B, Zhang J, Zhang H, Yang L, Zheng W and Zheng T <3 more author(s)> Chen Z, Lei X, Lai Q, Li Y, Zhang B, Zhang J, Zhang H, Yang L, Zheng W, Tian Y, Yu Z, Xu H, Zheng T (- 3) Ref: Int J Syst Evol Microbiol, 64:3496, 2014 : PubMed ESTHER: Chen_2014_Int.J.Syst.Evol.Microbiol_64_3496 PubMedSearch: Chen 2014 Int.J.Syst.Evol.Microbiol 64 3496 PubMedID: 25052393 Gene_locus related to this paper: 9bact-a0a098s2s4, 9bact-a0a098s0v5 Abstract A novel Gram-staining-negative, aerobic, rod-shaped, non-motile, reddish-orange and chemoheterotrophic bacteria, designated strain KD52(T), was isolated from a culture of the alga Phaeodactylum tricornutum from Xiamen, Fujian Province, China. 16S rRNA gene sequence comparison showed that strain KD52(T) was a member of the family Saprospiraceae, forming a distinct lineage with 'Portibacter lacus' KCTC 23747. The 16S rRNA gene sequence similarity between strain KD52(T) and the type strains of species of the family Saprospiraceae ranged from 86% to 89%. Growth occurred at 20-37 degrees C (optimum, 28 degrees C), in the presence of 1-9% (w/v) NaCl (optimum, 2.5%) and at pH 5-8.5 (optimum, pH 6.0). The dominant fatty acids (>10%) of strain KD52(T) were iso-C15:0 (33.1%), iso-C15:1 G (14.8%) and summed feature 3 (comprising C16:1omega7c and/or C16:1omega6c, 13.8%). The major polar lipids were diphosphatidylglycerol, three unidentified phospholipids, four unknown lipids and one unidentified aminolipid. The DNA G+C content was 51 mol% and the major respiratory quinone was menaquinone-7 (MK-7). On the basis of phenotypic data and phylogenetic inference, strain KD52(T) represents a novel species of a new genus, for which the name Phaeodactylibacter xiamenensis gen. nov., sp. nov., is proposed. The type strain is KD52(T) ( = MCCC 1F01213(T) = KCTC 32575(T)). Title: Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization Qin C, Yu C, Shen Y, Fang X, Chen L, Min J, Cheng J, Zhao S, Xu M and Zhang Z <58 more author(s)> Qin C, Yu C, Shen Y, Fang X, Chen L, Min J, Cheng J, Zhao S, Xu M, Luo Y, Yang Y, Wu Z, Mao L, Wu H, Ling-Hu C, Zhou H, Lin H, Gonzalez-Morales S, Trejo-Saavedra DL, Tian H, Tang X, Zhao M, Huang Z, Zhou A, Yao X, Cui J, Li W, Chen Z, Feng Y, Niu Y, Bi S, Yang X, Cai H, Luo X, Montes-Hernandez S, Leyva-Gonzalez MA, Xiong Z, He X, Bai L, Tan S, Liu D, Liu J, Zhang S, Chen M, Zhang L, Zhang Y, Liao W, Wang M, Lv X, Wen B, Liu H, Luan H, Yang S, Wang X, Xu J, Li X, Li S, Wang J, Palloix A, Bosland PW, Li Y, Krogh A, Rivera-Bustamante RF, Herrera-Estrella L, Yin Y, Yu J, Hu K, Zhang Z (- 58) Ref: Proc Natl Acad Sci U S A, 111:5135, 2014 : PubMed ESTHER: Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135 PubMedSearch: Qin 2014 Proc.Natl.Acad.Sci.U.S.A 111 5135 PubMedID: 24591624 Gene_locus related to this paper: capch-q75qh4, capan-a0a1u8fuf5, capan-a0a1u8gmz3, capan-a0a1u8f879, capan-a0a1u8ftr2, capan-a0a1u8g8s6 Abstract As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded approximately 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of approximately 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs. Title: Molecular traces of alternative social organization in a termite genome Terrapon N, Li C, Robertson HM, Ji L, Meng X, Booth W, Chen Z, Childers CP, Glastad KM and Liebig J <32 more author(s)> Terrapon N, Li C, Robertson HM, Ji L, Meng X, Booth W, Chen Z, Childers CP, Glastad KM, Gokhale K, Gowin J, Gronenberg W, Hermansen RA, Hu H, Hunt BG, Huylmans AK, Khalil SM, Mitchell RD, Munoz-Torres MC, Mustard JA, Pan H, Reese JT, Scharf ME, Sun F, Vogel H, Xiao J, Yang W, Yang Z, Zhou J, Zhu J, Brent CS, Elsik CG, Goodisman MA, Liberles DA, Roe RM, Vargo EL, Vilcinskas A, Wang J, Bornberg-Bauer E, Korb J, Zhang G, Liebig J (- 32) Ref: Nat Commun, 5:3636, 2014 : PubMed ESTHER: Terrapon_2014_Nat.Commun_5_3636 PubMedSearch: Terrapon 2014 Nat.Commun 5 3636 PubMedID: 24845553 Gene_locus related to this paper: zoone-a0a067r283, zoone-a0a067qst6, zoone-a0a067rbc7, zoone-a0a067qz43, zoone-a0a067qn94, zoone-a0a067rbw9, zoone-a0a067qx93, zoone-a0a067rcf4, zoone-a0a067r8q8, zoone-a0a067rh81, zoone-a0a067r506, zoone-a0a067qxd4, zoone-a0a067qy86, zoone-a0a067qsw2, zoone-a0a067qfp9, zoone-a0a067ru91, zoone-a0a067rwu7, zoone-a0a067rmu8, zoone-a0a067r773, zoone-a0a067qlt8, zoone-a0a067qhm6, zoone-a0a067qjz2, zoone-a0a067qs20, zoone-a0a067rmu4, zoone-a0a067qty7, zoone-a0a067rk35, zoone-a0a067rk64, zoone-a0a067rj74, zoone-a0a067rp97, zoone-a0a067rjm1 Abstract Although eusociality evolved independently within several orders of insects, research into the molecular underpinnings of the transition towards social complexity has been confined primarily to Hymenoptera (for example, ants and bees). Here we sequence the genome and stage-specific transcriptomes of the dampwood termite Zootermopsis nevadensis (Blattodea) and compare them with similar data for eusocial Hymenoptera, to better identify commonalities and differences in achieving this significant transition. We show an expansion of genes related to male fertility, with upregulated gene expression in male reproductive individuals reflecting the profound differences in mating biology relative to the Hymenoptera. For several chemoreceptor families, we show divergent numbers of genes, which may correspond to the more claustral lifestyle of these termites. We also show similarities in the number and expression of genes related to caste determination mechanisms. Finally, patterns of DNA methylation and alternative splicing support a hypothesized epigenetic regulation of caste differentiation. Title: An eco-friendly, simple, and sensitive fluorescence biosensor for the detection of choline and acetylcholine based on C-dots and the Fenton reaction Wei J, Ren J, Liu J, Meng X, Ren X, Chen Z, Tang F Ref: Biosensors & Bioelectronics, 52:304, 2014 : PubMed ESTHER: Wei_2014_Biosens.Bioelectron_52_304 PubMedSearch: Wei 2014 Biosens.Bioelectron 52 304 PubMedID: 24080209 Abstract A simple and novel method is proposed for the preparation of Carbon dots (C-dots) with excellent properties. We firstly demonstrated that the fluorescence of C-dots decreased apparently in the presence of H2O2 and Fe(2+). Based on the this finding, C-dots are successfully adopted as probes for the detection of H2O2. After the experimental conditions are optimized, the limit of detection (LOD) for H2O2 is found to be 0.1 muM. Furthermore, we established an eco-friendly, simple and sensitive biosensor for the detection of choline and acetylcholine (ACh) based on the detection of H2O2 using C-dots as probes. The detection limit for choline is 0.1 muM and the linear range is 0.1-40 muM. The detection limit for ACh is found to be 0.5 muM and the linear range is 0.5-60 muM. The excellent performance of the proposed biosensor shows that this method possesses the potential for practical application. Title: Complete genome sequencing and comparative analysis of the linezolid-resistant Enterococcus faecalis strain DENG1 Yu Z, Chen Z, Cheng H, Zheng J, Li D, Deng X, Pan W, Yang W, Deng Q Ref: Arch Microbiol, 196:513, 2014 : PubMed ESTHER: Yu_2014_Arch.Microbiol_196_513 PubMedSearch: Yu 2014 Arch.Microbiol 196 513 PubMedID: 24800692 Abstract Genome level analysis of bacterial strains provides information on genetic composition and resistance mechanisms to clinically relevant antibiotics. To date, whole genome characterization of linezolid-resistant Enterococcus faecalis isolated in the clinic is lacking. In this study, we report the entire genome sequence, genomic characteristics and virulence factors of a pathogenic E. faecalis strain, DENG1. Our results showed considerable differences in genomic characteristics and virulence factors compared with other E. faecalis strains (V583 and OG1RF). The genome of this LZD-resistant E. faecalis strain can be used as a reference to study the mechanism of LZD resistance and the phylogenetic relationship of E. faecalis strains worldwide. Title: Specific adaptation of Ustilaginoidea virens in occupying host florets revealed by comparative and functional genomics Zhang Y, Zhang K, Fang A, Han Y, Yang J, Xue M, Bao J, Hu D, Zhou B and Sun W <18 more author(s)> Zhang Y, Zhang K, Fang A, Han Y, Yang J, Xue M, Bao J, Hu D, Zhou B, Sun X, Li S, Wen M, Yao N, Ma LJ, Liu Y, Zhang M, Huang F, Luo C, Zhou L, Li J, Chen Z, Miao J, Wang S, Lai J, Xu JR, Hsiang T, Peng YL, Sun W (- 18) Ref: Nat Commun, 5:3849, 2014 : PubMed ESTHER: Zhang_2014_Nat.Commun_5_3849 PubMedSearch: Zhang 2014 Nat.Commun 5 3849 PubMedID: 24846013 Gene_locus related to this paper: ustvr-a0a063bxn3 Abstract Ustilaginoidea virens (Cooke) Takah is an ascomycetous fungus that causes rice false smut, a devastating emerging disease worldwide. Here we report a 39.4 Mb draft genome sequence of U. virens that encodes 8,426 predicted genes. The genome has ~25% repetitive sequences that have been affected by repeat-induced point mutations. Evolutionarily, U. virens is close to the entomopathogenic Metarhizium spp., suggesting potential host jumping across kingdoms. U. virens possesses reduced gene inventories for polysaccharide degradation, nutrient uptake and secondary metabolism, which may result from adaptations to the specific floret infection and biotrophic lifestyles. Consistent with their potential roles in pathogenicity, genes for secreted proteins and secondary metabolism and the pathogen-host interaction database genes are highly enriched in the transcriptome during early infection. We further show that 18 candidate effectors can suppress plant hypersensitive responses. Together, our analyses offer new insights into molecular mechanisms of evolution, biotrophy and pathogenesis of U. virens. Title: Genome Sequence of Klebsiella oxytoca M5al, a Promising Strain for Nitrogen Fixation and Chemical Production Bao G, Zhang Y, Du C, Chen Z, Li Y, Cao Z, Ma Y Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Bao_2013_Genome.Announc_1_E00074 PubMedSearch: Bao 2013 Genome.Announc 1 E00074 PubMedID: 23405358 Gene_locus related to this paper: kleox-z5vsa8, 9entr-g9z5g4, kleox-v3ks46 Abstract Klebsiella oxytoca is an important microorganism for nitrogen fixation and chemical production. Here, we report an annotated draft genome of K. oxytoca strain M5al that contains 5,256 protein-coding genes and 95 structural RNAs, which provides a genetic basis for a better understanding of the physiology of this species. Title: Quantum dots-based fluorescent probes for turn-on and turn-off sensing of butyrylcholinesterase Chen Z, Ren X, Meng X, Tan L, Chen D, Tang F Ref: Biosensors & Bioelectronics, 44C:204, 2013 : PubMed ESTHER: Chen_2013_Biosens.Bioelectron_44C_204 PubMedSearch: Chen 2013 Biosens.Bioelectron 44C 204 PubMedID: 23428734 Abstract A novel turn-on and turn-off sensor based on the fluorescence change of quantum dots (QDs) has been developed to detect the activity of butyrylcholinesterase (BChE). In the turn-on sensing system, we realized the detection of BChE with just one enzyme. A linear calibration plot of the activity of BChE was obtained in the wide amounts range from 10 to 1000U/L and the detection limit was 10U/L. In the turn-off sensing system, we realized the sensing of BChE with a wide linear relationship of 10-2000U/L which was much wider than many other detection methods. We also studied the application in serum sample detection. The BChE sensor shows great performances. Furthermore, the turn-on and turn-off sensing mechanisms were studied extensively. These results showed that our strategy would most probably be applicable in assembling diagnostic micro-device for realizing the rapid clinical analysis of BChE. Title: Decoding Alzheimer's disease from perturbed cerebral glucose metabolism: Implications for diagnostic and therapeutic strategies Chen Z, Zhong C Ref: Prog Neurobiol, 108:21, 2013 : PubMed ESTHER: Chen_2013_Prog.Neurobiol_108_21 PubMedSearch: Chen 2013 Prog.Neurobiol 108 21 PubMedID: 23850509 Abstract Alzheimer's disease (AD) is an age-related devastating neurodegenerative disorder, which severely impacts on the global economic development and healthcare system. Though AD has been studied for more than 100 years since 1906, the exact cause(s) and pathogenic mechanism(s) remain to be clarified. Also, the efficient disease-modifying treatment and ideal diagnostic method for AD are unavailable. Perturbed cerebral glucose metabolism, an invariant pathophysiological feature of AD, may be a critical contributor to the pathogenesis of this disease. In this review, we firstly discussed the features of cerebral glucose metabolism in physiological and pathological conditions. Then, we further reviewed the contribution of glucose transportation abnormality and intracellular glucose catabolism dysfunction in AD pathophysiology, and proposed a hypothesis that multiple pathogenic cascades induced by impaired cerebral glucose metabolism could result in neuronal degeneration and consequently cognitive deficits in AD patients. Among these pathogenic processes, altered functional status of thiamine metabolism and brain insulin resistance are highly emphasized and characterized as major pathogenic mechanisms. Finally, considering the fact that AD patients exhibit cerebral glucose hypometabolism possibly due to impairments of insulin signaling and altered thiamine metabolism, we also discuss some potential possibilities to uncover diagnostic biomarkers for AD from abnormal glucose metabolism and to develop drugs targeting at repairing insulin signaling impairment and correcting thiamine metabolism abnormality. We conclude that glucose metabolism abnormality plays a critical role in AD pathophysiological alterations through the induction of multiple pathogenic factors such as oxidative stress, mitochondrial dysfunction, and so forth. To clarify the causes, pathogeneses and consequences of cerebral hypometabolism in AD will help break the bottleneck of current AD study in finding ideal diagnostic biomarker and disease-modifying therapy. Title: Draft Genome Sequences of Two Clinical Isolates of Lactobacillus rhamnosus from Initial Stages of Dental Pulp Infection Chen Z, Wilkins MR, Hunter N, Nadkarni MA Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Chen_2013_Genome.Announc_1_E00073 PubMedSearch: Chen 2013 Genome.Announc 1 E00073 PubMedID: 23405363 Gene_locus related to this paper: lacrh-B2CZF3, lacrh-pepr, lacrl-pip Abstract Here we report the draft genomic sequences of two clinical isolates of Lactobacillus rhamnosus from infected dental pulps representing the initial stages of infection of pulp tissue. Based on 454 FLX+ pyrosequencing, the two clinical isolates infecting vital pulp had a genome length of 2.9 Mbp with distinct genomic signatures. Title: Dp44mT targets the AKT, TGF-beta and ERK pathways via the metastasis suppressor NDRG1 in normal prostate epithelial cells and prostate cancer cells Dixon KM, Lui GY, Kovacevic Z, Zhang D, Yao M, Chen Z, Dong Q, Assinder SJ, Richardson DR Ref: Br J Cancer, 108:409, 2013 : PubMed ESTHER: Dixon_2013_Br.J.Cancer_108_409 PubMedSearch: Dixon 2013 Br.J.Cancer 108 409 PubMedID: 23287991 Abstract BACKGROUND: Effective treatment of prostate cancer should be based on targeting interactions between tumour cell signalling pathways and key converging downstream effectors. Here, we determined how the tumourigenic phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), tumour-suppressive phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and transforming growth factor-beta (TGF-beta) pathways are integrated via the metastasis suppressor, N-myc downstream-regulated gene-1 (NDRG1). Moreover, we assessed how the novel anti-tumour agent, Dp44mT, may target these integrated pathways by increasing NDRG1 expression. Title: Cloning, expression and characterization of a new enantioselective esterase from a marine bacterium Pelagibacterium halotolerans B2T Wei X, Jiang X, Ye L, Yuan S, Chen Z, Wu M, Yu H Ref: J Mol Catal B Enzym, 97:270, 2013 : PubMed ESTHER: Wei_2013_J.Mol.Catal.B.Enzym_97_270 PubMedSearch: Wei 2013 J.Mol.Catal.B.Enzym 97 270 Gene_locus related to this paper: pelhb-g4rfi7 Abstract An esterase, designated as PE8 (219 aa, 23.19 kDa), was cloned from a marine bacterium Pelagibacterium halotolerans B2T and overexpressed in Escherichia coli Rosetta, resulting an active, soluble protein which constituted 23.1% of the total cell protein content. Phylogenetic analysis of the protein showed it was a new member of family VI lipolytic enzymes. Biochemical characterization analysis showed that PE8 preferred short chain p-nitrophenyl esters (C2-C6), exhibited maximum activity toward p-nitrophenyl acetate, and was not a metalloenzyme. PE8 was an alkaline esterase with an optimal pH of 9.5 and an optimal temperature of 45 C toward p-nitrophenyl acetate. Furthermore, it was found that PE8 exhibited activity and enantioselectivity in the synthesis of methyl (R)-3-(4-fluorophenyl)glutarate ((R)-3-MFG) from the prochiral dimethyl 3-(4-fluorophenyl)glutarate (3-DFG). (R)-3-MFG was obtained in 71.6% ee and 73.2% yield after 36 h reaction under optimized conditions (0.6 M phosphate buffer (pH 8.0) containing 17.5% 1,4-dioxane under 30C). In addition, PE8 was tolerant to extremely strong basic and high ionic strength solutions as it exhibited high activity even at pH 11.0 in 1 M phosphate buffer. Given its highly soluble expression, alkalitolerance, halotolerance and enantioselectivity, PE8 could be a promising candidate for the production of (R)-3-MFG in industry. The results also demonstrate the potential of the marine environment as a source of useful biocatalysts. Title: Effects of Di-n-butyl Phthalate and Diethyl Phthalate on Acetylcholinesterase Activity and Neurotoxicity Related Gene Expression in Embryonic Zebrafish Xu H, Shao X, Zhang Z, Zou Y, Chen Y, Han S, Wang S, Wu X, Yang L, Chen Z Ref: Bulletin of Environmental Contamination & Toxicology, 91:635, 2013 : PubMed ESTHER: Xu_2013_Bull.Environ.Contam.Toxicol_91_635 PubMedSearch: Xu 2013 Bull.Environ.Contam.Toxicol 91 635 PubMedID: 24042840 Gene_locus related to this paper: danre-ACHE Abstract In the present study, zebrafish embryos were used to assess the neurotoxicity of di-n-butyl phthalate (DBP), diethyl phthalate (DEP) and their mixture. Four-hour post-fertilization (hpf) zebrafish embryos were exposed to various concentrations of DBP, DEP and their mixture (DBP-DEP) until 96 hpf. The transcriptions levels of selected neuron-related genes reported as neurotoxicity biomarkers were analyzed. The results showed that transcripts of growth associated protein 43 (gap43), embryonic lethal abnormal vision-like 3 (elavl3), glial fibrillary acidic protein (gfap), myelin basic protein (mbp), alpha1-tubulin and neurogenin1 (ngn1) were significantly up-regulated after DBP, DEP and DBP-DEP mixture exposure. In addition, acetylcholinesterase activity was significantly inhibited in the embryos. These results indicate that DBP and DEP have the potential neurotoxicity in zebrafish embryos. Title: The genome of the hydatid tapeworm Echinococcus granulosus Zheng H, Zhang W, Zhang L, Zhang Z, Li J, Lu G, Zhu Y, Wang Y, Huang Y and Wang S <21 more author(s)> Zheng H, Zhang W, Zhang L, Zhang Z, Li J, Lu G, Zhu Y, Wang Y, Huang Y, Liu J, Kang H, Chen J, Wang L, Chen A, Yu S, Gao Z, Jin L, Gu W, Wang Z, Zhao L, Shi B, Wen H, Lin R, Jones MK, Brejova B, Vinar T, Zhao G, McManus DP, Chen Z, Zhou Y, Wang S (- 21) Ref: Nat Genet, 45:1168, 2013 : PubMed ESTHER: Zheng_2013_Nat.Genet_45_1168 PubMedSearch: Zheng 2013 Nat.Genet 45 1168 PubMedID: 24013640 Gene_locus related to this paper: echgr-k4epc5, echmu-u6hbw4, echgr-w6ugl0, echgr-w6u7y4, echgr-w6vaq5, echgr-a0a068wxj3, echgr-a0a068wgw1, echgr-a0a068wl60 Abstract Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is responsible for considerable human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat and control. We present a draft genomic sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons with the genome sequences from other taxa show that E. granulosus has acquired a spectrum of genes, including the EgAgB family, whose products are secreted by the parasite to interact and redirect host immune responses. We also find that genes in bile salt pathways may control the bidirectional development of E. granulosus, and sequence differences in the calcium channel subunit EgCavbeta1 may be associated with praziquantel sensitivity. Our study offers insights into host interaction, nutrient acquisition, strobilization, reproduction, immune evasion and maturation in the parasite and provides a platform to facilitate the development of new, effective treatments and interventions for echinococcosis control. Title: Small molecule activation of lecithin cholesterol acyltransferase modulates lipoprotein metabolism in mice and hamsters Chen Z, Wang SP, Krsmanovic ML, Castro-Perez J, Gagen K, Mendoza V, Rosa R, Shah V, He T and Johns DG <9 more author(s)> Chen Z, Wang SP, Krsmanovic ML, Castro-Perez J, Gagen K, Mendoza V, Rosa R, Shah V, He T, Stout SJ, Geoghagen NS, Lee SH, McLaren DG, Wang L, Roddy TP, Plump AS, Hubbard BK, Sinz CJ, Johns DG (- 9) Ref: Metabolism, 61:470, 2012 : PubMed ESTHER: Chen_2012_Metabolism_61_470 PubMedSearch: Chen 2012 Metabolism 61 470 PubMedID: 22001333 Abstract The objective was to assess whether pharmacological activation of lecithin cholesterol acyltransferase (LCAT) could exert beneficial effects on lipoprotein metabolism. A putative small molecule activator (compound A) was used as a tool compound in in vitro and in vivo studies. Compound A increased LCAT activity in vitro in plasma from mouse, hamster, rhesus monkey, and human. To assess the acute pharmacodynamic effects of compound A, C57Bl/6 mice and hamsters received a single dose (20 mg/kg) of compound A. Both species displayed a significant increase in high-density lipoprotein cholesterol (HDLc) and a significant decrease in non-HDLc and triglycerides acutely after dosing; these changes tracked with ex vivo plasma LCAT activity. To examine compound A's chronic effect on lipoprotein metabolism, hamsters received a daily dosing of vehicle or of 20 or 60 mg/kg of compound A for 2 weeks. At study termination, compound treatment resulted in a significant increase in HDLc, HDL particle size, plasma apolipoprotein A-I level, and plasma cholesteryl ester (CE) to free cholesterol ratio, and a significant reduction in very low-density lipoprotein cholesterol. The increase in plasma CE mirrored the increase in HDL CE. Triglycerides trended toward a dose-dependent decrease in very low-density lipoprotein and HDL, with multiple triglyceride species reaching statistical significance. Gallbladder bile acids content displayed a significant and more than 2-fold increase with the 60 mg/kg treatment. We characterized pharmacological activation of LCAT by a small molecule extensively for the first time, and our findings support the potential of this approach in treating dyslipidemia and atherosclerosis; our analyses also provide mechanistic insight on LCAT's role in lipoprotein metabolism. Title: Comparative genome analysis of Trichophyton rubrum and related dermatophytes reveals candidate genes involved in infection Martinez DA, Oliver BG, Graser Y, Goldberg JM, Li W, Martinez-Rossi NM, Monod M, Shelest E, Barton RC and White TC <18 more author(s)> Martinez DA, Oliver BG, Graser Y, Goldberg JM, Li W, Martinez-Rossi NM, Monod M, Shelest E, Barton RC, Birch E, Brakhage AA, Chen Z, Gurr SJ, Heiman D, Heitman J, Kosti I, Rossi A, Saif S, Samalova M, Saunders CW, Shea T, Summerbell RC, Xu J, Young S, Zeng Q, Birren BW, Cuomo CA, White TC (- 18) Ref: MBio, 3:e00259, 2012 : PubMed ESTHER: Martinez_2012_MBio_3_e00259 PubMedSearch: Martinez 2012 MBio 3 e00259 PubMedID: 22951933 Gene_locus related to this paper: artgp-e4uup9, artgp-e4v450, artgp-e5qzf5, artgp-e5r1t8, artoc-c5fc55, artoc-c5fds1, artoc-c5fig8, artoc-c5fj58, artoc-c5fme4, artoc-c5fva9, triec-f2ph15, triec-f2plk8, triec-f2pwm2, trirc-f2sf42, trirc-f2sn39, trirc-f2srv5, trirc-f2sy06, triru-q5j6j0, triru-SCPB, triru-SPCA, trit1-f2rna8, trit1-f2s2t8, trivh-d4dbr9, artbc-d4avu9, artoc-c5fsf7, artgp-e4unv7, artoc-c5g0v3, triec-f2pub4, triec-f2pi43, artgp-e4v6t4, trit1-f2s3n3, artoc-c5fnl7, artgp-e4upq1, artgp-e4uzl7, triec-f2pp24, triru-a0a022u299, 9euro-a0a059jk56, artoc-c5fu24, artoc-c5fic4, artgp-e4uza8, triec-f2pqf3, artgp-e4uv28, artoc-c5fiv8, triru-a0a022w2d0, artgp-e4uvk8, triru-a0a178f289, artoc-c5fyj1, artoc-cbpya, artoc-kex1 Abstract The major cause of athlete's foot is Trichophyton rubrum, a dermatophyte or fungal pathogen of human skin. To facilitate molecular analyses of the dermatophytes, we sequenced T. rubrum and four related species, Trichophyton tonsurans, Trichophyton equinum, Microsporum canis, and Microsporum gypseum. These species differ in host range, mating, and disease progression. The dermatophyte genomes are highly colinear yet contain gene family expansions not found in other human-associated fungi. Dermatophyte genomes are enriched for gene families containing the LysM domain, which binds chitin and potentially related carbohydrates. These LysM domains differ in sequence from those in other species in regions of the peptide that could affect substrate binding. The dermatophytes also encode novel sets of fungus-specific kinases with unknown specificity, including nonfunctional pseudokinases, which may inhibit phosphorylation by competing for kinase sites within substrates, acting as allosteric effectors, or acting as scaffolds for signaling. The dermatophytes are also enriched for a large number of enzymes that synthesize secondary metabolites, including dermatophyte-specific genes that could synthesize novel compounds. Finally, dermatophytes are enriched in several classes of proteases that are necessary for fungal growth and nutrient acquisition on keratinized tissues. Despite differences in mating ability, genes involved in mating and meiosis are conserved across species, suggesting the possibility of cryptic mating in species where it has not been previously detected. These genome analyses identify gene families that are important to our understanding of how dermatophytes cause chronic infections, how they interact with epithelial cells, and how they respond to the host immune response. Title: Lifestyle transitions in plant pathogenic Colletotrichum fungi deciphered by genome and transcriptome analyses O'Connell RJ, Thon MR, Hacquard S, Amyotte SG, Kleemann J, Torres MF, Damm U, Buiate EA, Epstein L and Vaillancourt LJ <57 more author(s)> O'Connell RJ, Thon MR, Hacquard S, Amyotte SG, Kleemann J, Torres MF, Damm U, Buiate EA, Epstein L, Alkan N, Altmuller J, Alvarado-Balderrama L, Bauser CA, Becker C, Birren BW, Chen Z, Choi J, Crouch JA, Duvick JP, Farman MA, Gan P, Heiman D, Henrissat B, Howard RJ, Kabbage M, Koch C, Kracher B, Kubo Y, Law AD, Lebrun MH, Lee YH, Miyara I, Moore N, Neumann U, Nordstrom K, Panaccione DG, Panstruga R, Place M, Proctor RH, Prusky D, Rech G, Reinhardt R, Rollins JA, Rounsley S, Schardl CL, Schwartz DC, Shenoy N, Shirasu K, Sikhakolli UR, Stuber K, Sukno SA, Sweigard JA, Takano Y, Takahara H, Trail F, van der Does HC, Voll LM, Will I, Young S, Zeng Q, Zhang J, Zhou S, Dickman MB, Schulze-Lefert P, Ver Loren van Themaat E, Ma LJ, Vaillancourt LJ (- 57) Ref: Nat Genet, 44:1060, 2012 : PubMed ESTHER: O'Connell_2012_Nat.Genet_44_1060 PubMedSearch: O'Connell 2012 Nat.Genet 44 1060 PubMedID: 22885923 Gene_locus related to this paper: colgm-kex1, colhi-h1vve5, colhi-h1vkk5, colgm-e3qtg4, colhi-h1vbq5, colgm-e3qyh7, colgm-e3q7u5, colhi-h1vs61, colgm-e3qip4, colgm-e3qv97, colhi-h1v665, colgm-e3qky4, colhi-h1vd91, colhi-h1uvl1, colhi-h1v7k5, colgm-e3qu96, colhi-h1vhh1, colhi-h1v638, colhi-h1vcz3, colgm-e3qwt6, colgm-e3q3z6, colhi-h1vmh6, colgm-e3qqq8, colhi-h1v0e8, colgm-e3qyt9, colgm-e3qby6, colgm-e3qsm5, colgm-e3q6f6, colgm-e3qwt4, colgm-e3qb89, colhi-h1vh96, colgm-e3qwz9, colgm-e3qbd3, colgm-e3qtz0, colhi-h1w5n4, colgm-e3q7y3, colgm-e3qpz1, colhi-h1v2e4, colgm-e3qux5, colgm-e3qx16, colgm-cbpya Abstract Colletotrichum species are fungal pathogens that devastate crop plants worldwide. Host infection involves the differentiation of specialized cell types that are associated with penetration, growth inside living host cells (biotrophy) and tissue destruction (necrotrophy). We report here genome and transcriptome analyses of Colletotrichum higginsianum infecting Arabidopsis thaliana and Colletotrichum graminicola infecting maize. Comparative genomics showed that both fungi have large sets of pathogenicity-related genes, but families of genes encoding secreted effectors, pectin-degrading enzymes, secondary metabolism enzymes, transporters and peptidases are expanded in C. higginsianum. Genome-wide expression profiling revealed that these genes are transcribed in successive waves that are linked to pathogenic transitions: effectors and secondary metabolism enzymes are induced before penetration and during biotrophy, whereas most hydrolases and transporters are upregulated later, at the switch to necrotrophy. Our findings show that preinvasion perception of plant-derived signals substantially reprograms fungal gene expression and indicate previously unknown functions for particular fungal cell types. Title: Draft genome sequence of Alicyclobacillus hesperidum strain URH17-3-68 Wang P, Li L, Chen X, Jiang N, Liu G, Chen L, Xu J, Song H, Chen Z, Ma Y Ref: Journal of Bacteriology, 194:6348, 2012 : PubMed ESTHER: Wang_2012_J.Bacteriol_194_6348 PubMedSearch: Wang 2012 J.Bacteriol 194 6348 PubMedID: 23105079 Gene_locus related to this paper: 9bacl-h2esd6, 9bacl-j9e7t9 Abstract Alicyclobacillus hesperidum is a thermoacidophilic bacterium. We isolated strain URH17-3-68 from hot spring sludge in Tengchong, Yunnan province, China. Its extracellular products include heat- and acid-stable enzymes which are important for industrial applications. Here we report the draft genome of this strain. Title: Genome sequence of the plant growth-promoting rhizobacterium Bacillus sp. strain 916 Wang X, Luo C, Chen Z Ref: Journal of Bacteriology, 194:5467, 2012 : PubMed ESTHER: Wang_2012_J.Bacteriol_194_5467 PubMedSearch: Wang 2012 J.Bacteriol 194 5467 PubMedID: 22965091 Gene_locus related to this paper: baca2-a7z924 Abstract Bacillus sp. strain 916, isolated from the soil, showed strong activity against Rhizoctonia solani. Here, we present the high-quality draft genome sequence of Bacillus sp. strain 916. Its 3.9-Mb genome reveals a number of genes whose products are possibly involved in promotion of plant growth or antibiosis. Title: Complete genome sequence of Riemerella anatipestifer reference strain Wang X, Zhu D, Wang M, Cheng A, Jia R, Zhou Y, Chen Z, Luo Q, Liu F and Chen XY <1 more author(s)> Wang X, Zhu D, Wang M, Cheng A, Jia R, Zhou Y, Chen Z, Luo Q, Liu F, Wang Y, Chen XY (- 1) Ref: Journal of Bacteriology, 194:3270, 2012 : PubMed ESTHER: Wang_2012_J.Bacteriol_194_3270 PubMedSearch: Wang 2012 J.Bacteriol 194 3270 PubMedID: 22628503 Abstract Riemerella anatipestifer is an infectious pathogen causing serositis in ducks. We had the genome of the R. anatipestifer reference strain ATCC 11845 sequenced. The completed draft genome consists of one circular chromosome with 2,164,087 bp. There are 2,101 genes in the draft, and its GC content is 35.01%. Title: Genomic analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Botrytis cinerea Amselem J, Cuomo CA, van Kan JA, Viaud M, Benito EP, Couloux A, Coutinho PM, de Vries RP, Dyer PS and Dickman M <62 more author(s)> Amselem J, Cuomo CA, van Kan JA, Viaud M, Benito EP, Couloux A, Coutinho PM, de Vries RP, Dyer PS, Fillinger S, Fournier E, Gout L, Hahn M, Kohn L, Lapalu N, Plummer KM, Pradier JM, Quevillon E, Sharon A, Simon A, ten Have A, Tudzynski B, Tudzynski P, Wincker P, Andrew M, Anthouard V, Beever RE, Beffa R, Benoit I, Bouzid O, Brault B, Chen Z, Choquer M, Collemare J, Cotton P, Danchin EG, Da Silva C, Gautier A, Giraud C, Giraud T, Gonzalez C, Grossetete S, Guldener U, Henrissat B, Howlett BJ, Kodira C, Kretschmer M, Lappartient A, Leroch M, Levis C, Mauceli E, Neuveglise C, Oeser B, Pearson M, Poulain J, Poussereau N, Quesneville H, Rascle C, Schumacher J, Segurens B, Sexton A, Silva E, Sirven C, Soanes DM, Talbot NJ, Templeton M, Yandava C, Yarden O, Zeng Q, Rollins JA, Lebrun MH, Dickman M (- 62) Ref: PLoS Genet, 7:e1002230, 2011 : PubMed ESTHER: Amselem_2011_PLoS.Genet_7_E1002230 PubMedSearch: Amselem 2011 PLoS.Genet 7 E1002230 PubMedID: 21876677 Gene_locus related to this paper: botci-cutas, botci-q6rki2, botf4-g2y7k8, botfb-dapb, botfu-g2xyd8, botfu-g2ynh8, scls1-a7e814, scls1-a7edc9, scls1-a7edh1, scls1-a7emm0, scls1-a7eti8, scls1-a7eu48, scls1-a7f208, scls1-dapb, botf4-g2xqp7, scls1-a7eqq8, botf4-g2xqc6, scls1-a7ebs4, botf4-g2xn51, scls1-a7f5m9, botf4-g2xti4, botf4-g2xtu7, botf4-g2yfp1, scls1-a7f534, botf4-g2yys3, scls1-a7erz9, botf4-g2y037, botf4-g2y0e1, scls1-a7f706, scls1-a7ewt6, botf4-g2yuj6, botf1-m7u3d1, botf1-m7u430, botf1-m7tei8, botf1-m7u0w9, botf1-m7tij6, botf1-m7u819, botf1-m7u6d8, botf1-m7tzd4, botf1-m7tqd7, botf1-m7tyz9, botf1-m7unl9, botf1-m7u429, botf1-m7u4s5, botf1-m7ul92, botf1-m7tx42, botf1-m7u9h4, botf1-m7u187, botf1-m7uz64, botf1-m7u4q4, botf1-m7u2f6, botf1-m7tt59, botf1-m7v3h2, botf1-m7u6c9, botf1-m7tud9, botf1-m7u309, scls1-a7et87, botf4-g2ylt4, scls1-a7f5a0, scls1-a7f900, botf4-g2yib9, scls1-a7f3m9, scls1-a7er46, botf4-g2y3y4, botf4-g2xyy5, botf1-m7uct5, scls1-a7ea78, scls1-kex1, scls1-cbpya, botfb-cbpya Abstract Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38-39 Mb genomes include 11,860-14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared to <1% of B. cinerea. The arsenal of genes associated with necrotrophic processes is similar between the species, including genes involved in plant cell wall degradation and oxalic acid production. Analysis of secondary metabolism gene clusters revealed an expansion in number and diversity of B. cinerea-specific secondary metabolites relative to S. sclerotiorum. The potential diversity in secondary metabolism might be involved in adaptation to specific ecological niches. Comparative genome analysis revealed the basis of differing sexual mating compatibility systems between S. sclerotiorum and B. cinerea. The organization of the mating-type loci differs, and their structures provide evidence for the evolution of heterothallism from homothallism. These data shed light on the evolutionary and mechanistic bases of the genetically complex traits of necrotrophic pathogenicity and sexual mating. This resource should facilitate the functional studies designed to better understand what makes these fungi such successful and persistent pathogens of agronomic crops. Title: Complete genome sequence of Clostridium acetobutylicum DSM 1731, a solvent-producing strain with multireplicon genome architecture Bao G, Wang R, Zhu Y, Dong H, Mao S, Zhang Y, Chen Z, Li Y, Ma Y Ref: Journal of Bacteriology, 193:5007, 2011 : PubMed ESTHER: Bao_2011_J.Bacteriol_193_5007 PubMedSearch: Bao 2011 J.Bacteriol 193 5007 PubMedID: 21742891 Gene_locus related to this paper: cloab-q97db4, cloac-pnbae Abstract Clostridium acetobutylicum is an important microorganism for solvent production. We report the complete genome sequence of C. acetobutylicum DSM 1731, a genome with multireplicon architecture. Comparison with the sequenced type strain C. acetobutylicum ATCC 824, the genome of strain DSM1731 harbors a 1.7-kb insertion and a novel 11.1-kb plasmid, which might have been acquired during evolution. Title: Study of sensory and motor fascicles in brachial plexus and establishment of a digital three-dimensional graphic model Chen Z, Zhang J, Chen T, Li H, Zhang EW, Lineaweaver WC, Zhang F Ref: Ann Plast Surg, 67:615, 2011 : PubMed ESTHER: Chen_2011_Ann.Plast.Surg_67_615 PubMedSearch: Chen 2011 Ann.Plast.Surg 67 615 PubMedID: 22123540 Abstract To investigate a 3-dimensional (3D) model of human brachial plexus including its topography of sensory and motor fascicles with the assistance of the computer technology, 2 brachial plexus were serially horizontally sliced. Each slice was stained by Karnovsky-Roots acetylcholinesterase histochemical method. The stained sections were scanned, and the image was put into the computer serially. At last, the 3D diagram of brachial plexus was made. The internal structure of the brachial plexus was found to be very complicated. The fascicles bifurcated and recombined with one another with no fixed rules. All fascicles were mixed sensory and motor fibers. Acetylcholinesterase histochemical staining from a serial tissue section is a useful technique to distinguish sensory fibers from motor ones. The 3D visualization of the brachial plexus may help to develop a computerized database of the fascicle topography to provide an anatomical reference in fascicular repair of brachial plexus. Title: A naked-eye visible and fluorescence turn-on probe for acetyl-cholinesterase assay and thiols as well as imaging of living cells Cui K, Chen Z, Wang Z, Zhang G, Zhang D Ref: Analyst, 136:191, 2011 : PubMed ESTHER: Cui_2011_Analyst_136_191 PubMedSearch: Cui 2011 Analyst 136 191 PubMedID: 20927440 Abstract A resorufin derivative with a DBS group (probe 1) was designed and investigated for the detection of acetylcholinesterase (AChE) and inhibitor screening. The new assay is based on cascade enzymatic and chemical reactions of ATC, AChE and probe 1, and it can be carried out in a dual-signal detection mode. Moreover, the results show that probe 1 can be used for cell fluorescence staining. Title: Comparative genomics yields insights into niche adaptation of plant vascular wilt pathogens Klosterman SJ, Subbarao KV, Kang S, Veronese P, Gold SE, Thomma BP, Chen Z, Henrissat B, Lee YH and Ma LJ <19 more author(s)> Klosterman SJ, Subbarao KV, Kang S, Veronese P, Gold SE, Thomma BP, Chen Z, Henrissat B, Lee YH, Park J, Garcia-Pedrajas MD, Barbara DJ, Anchieta A, de Jonge R, Santhanam P, Maruthachalam K, Atallah Z, Amyotte SG, Paz Z, Inderbitzin P, Hayes RJ, Heiman DI, Young S, Zeng Q, Engels R, Galagan J, Cuomo CA, Dobinson KF, Ma LJ (- 19) Ref: PLoS Pathog, 7:e1002137, 2011 : PubMed ESTHER: Klosterman_2011_PLoS.Pathog_7_E1002137 PubMedSearch: Klosterman 2011 PLoS.Pathog 7 E1002137 PubMedID: 21829347 Gene_locus related to this paper: vera1-c9srn2, vera1-c9sn46, verdv-g2wq49, verdv-g2xca2, vera1-c9sea3, verdv-g2wzn4, vera1-c9sek2, verdv-g2wym5, verdv-g2x5f3, vera1-c9sx20, vera1-c9sw01, verdv-g2x1l1, verdv-g2wuv4, verdv-g2xaw5, verdv-g2wsb2, verdv-g2wty6, vera1-c9si59, verdv-g2xdu9, vera1-c9s818, verdv-g2xdr1, verdv-g2wsw7, verdv-g2wvq8, 9pezi-a0a0g4li73, vera1-kex1, verdv-g2x8m5 Abstract The vascular wilt fungi Verticillium dahliae and V. albo-atrum infect over 200 plant species, causing billions of dollars in annual crop losses. The characteristic wilt symptoms are a result of colonization and proliferation of the pathogens in the xylem vessels, which undergo fluctuations in osmolarity. To gain insights into the mechanisms that confer the organisms' pathogenicity and enable them to proliferate in the unique ecological niche of the plant vascular system, we sequenced the genomes of V. dahliae and V. albo-atrum and compared them to each other, and to the genome of Fusarium oxysporum, another fungal wilt pathogen. Our analyses identified a set of proteins that are shared among all three wilt pathogens, and present in few other fungal species. One of these is a homolog of a bacterial glucosyltransferase that synthesizes virulence-related osmoregulated periplasmic glucans in bacteria. Pathogenicity tests of the corresponding V. dahliae glucosyltransferase gene deletion mutants indicate that the gene is required for full virulence in the Australian tobacco species Nicotiana benthamiana. Compared to other fungi, the two sequenced Verticillium genomes encode more pectin-degrading enzymes and other carbohydrate-active enzymes, suggesting an extraordinary capacity to degrade plant pectin barricades. The high level of synteny between the two Verticillium assemblies highlighted four flexible genomic islands in V. dahliae that are enriched for transposable elements, and contain duplicated genes and genes that are important in signaling/transcriptional regulation and iron/lipid metabolism. Coupled with an enhanced capacity to degrade plant materials, these genomic islands may contribute to the expanded genetic diversity and virulence of V. dahliae, the primary causal agent of Verticillium wilts. Significantly, our study reveals insights into the genetic mechanisms of niche adaptation of fungal wilt pathogens, advances our understanding of the evolution and development of their pathogenesis, and sheds light on potential avenues for the development of novel disease management strategies to combat destructive wilt diseases. Title: Increased fat mass and insulin resistance in mice lacking pancreatic lipase-related protein 1 Ren J, Chen Z, Zhang W, Li L, Sun R, Deng C, Fei Z, Sheng Z, Wang L and Fei J <2 more author(s)> Ren J, Chen Z, Zhang W, Li L, Sun R, Deng C, Fei Z, Sheng Z, Wang L, Sun X, Wang Z, Fei J (- 2) Ref: J Nutr Biochem, 22:691, 2011 : PubMed ESTHER: Ren_2011_J.Nutr.Biochem_22_691 PubMedSearch: Ren 2011 J.Nutr.Biochem 22 691 PubMedID: 21115337 Gene_locus related to this paper: human-PNLIPRP1, mouse-1plrp Abstract Pancreatic triglyceride lipase (PTL) and its cofactor, colipase, are required for efficient dietary triglyceride digestion. In addition to PTL, pancreatic acinar cells synthesize two pancreatic lipase-related proteins (PLRP1 and PLRP2), which have a high degree of sequence and structural homology with PTL. The lipase activity of PLRP2 has been confirmed, whereas no known triglyceride lipase activity has been detected with PLRP1 up to now. To explore the biological functions of PLRP1 in vivo, we generated Plrp1 knockout (KO) mice in our laboratory. Here we show that the Plrp1 KO mice displayed mature-onset obesity with increased fat mass, impaired glucose clearance and the resultant insulin resistance. When fed on high-fat (HF) diet, the Plrp1 KO mice exhibited an increased weight gain, fat mass and severe insulin resistance compared with wild-type mice. Pancreatic juice extracted from Plrp1 KO mice had greater ability to hydrolyze triglyceride than that from the wild-type littermates. We propose that PLRP1 may function as a metabolic inhibitor in vivo of PLT-colipase-mediated dietary triglyceride digestion and provides potential anti-obesity targets for developing new drugs. Title: Comparative functional genomics of the fission yeasts Rhind N, Chen Z, Yassour M, Thompson DA, Haas BJ, Habib N, Wapinski I, Roy S, Lin MF and Nusbaum C <50 more author(s)> Rhind N, Chen Z, Yassour M, Thompson DA, Haas BJ, Habib N, Wapinski I, Roy S, Lin MF, Heiman DI, Young SK, Furuya K, Guo Y, Pidoux A, Chen HM, Robbertse B, Goldberg JM, Aoki K, Bayne EH, Berlin AM, Desjardins CA, Dobbs E, Dukaj L, Fan L, Fitzgerald MG, French C, Gujja S, Hansen K, Keifenheim D, Levin JZ, Mosher RA, Muller CA, Pfiffner J, Priest M, Russ C, Smialowska A, Swoboda P, Sykes SM, Vaughn M, Vengrova S, Yoder R, Zeng Q, Allshire R, Baulcombe D, Birren BW, Brown W, Ekwall K, Kellis M, Leatherwood J, Levin H, Margalit H, Martienssen R, Nieduszynski CA, Spatafora JW, Friedman N, Dalgaard JZ, Baumann P, Niki H, Regev A, Nusbaum C (- 50) Ref: Science, 332:930, 2011 : PubMed ESTHER: Rhind_2011_Science_332_930 PubMedSearch: Rhind 2011 Science 332 930 PubMedID: 21511999 Gene_locus related to this paper: schjy-b6jxl8, schjy-b6k0k9, schjy-b6k7s4, schjy-b6k575, schcr-s9vnl9, schoy-s9q625, schjy-kex1, schpo-ykv6 Abstract The fission yeast clade--comprising Schizosaccharomyces pombe, S. octosporus, S. cryophilus, and S. japonicus--occupies the basal branch of Ascomycete fungi and is an important model of eukaryote biology. A comparative annotation of these genomes identified a near extinction of transposons and the associated innovation of transposon-free centromeres. Expression analysis established that meiotic genes are subject to antisense transcription during vegetative growth, which suggests a mechanism for their tight regulation. In addition, trans-acting regulators control new genes within the context of expanded functional modules for meiosis and stress response. Differences in gene content and regulation also explain why, unlike the budding yeast of Saccharomycotina, fission yeasts cannot use ethanol as a primary carbon source. These analyses elucidate the genome structure and gene regulation of fission yeast and provide tools for investigation across the Schizosaccharomyces clade. Title: Three-dimensional optical coherence tomography imaging of retinal sheet implants in live rats Seiler MJ, Rao B, Aramant RB, Yu L, Wang Q, Kitayama E, Pham S, Yan F, Chen Z, Keirstead HS Ref: Journal of Neuroscience Methodsods, 188:250, 2010 : PubMed ESTHER: Seiler_2010_J.Neurosci.Methods_188_250 PubMedSearch: Seiler 2010 J.Neurosci.Methods 188 250 PubMedID: 20219535 Abstract PURPOSE: To obtain three-dimensional images from retinal transplants in live animals and evaluate the placement and structural quality of the transplants. METHODS: Donor retinal sheets were isolated from E19 fetuses of transgenic rats expressing human alkaline phosphatase (hPAP), and transplanted to the subretinal space of 19-56 days old S334ter-3 rat recipients with fast retinal degeneration (average age at surgery 32 days). A total of 143 rats were imaged 1 day to 2.8 months after surgery, using a Fourier-domain optical coherence tomography (FDOCT) system, with an axial resolution of 3.5 microm. The CCD A-line integration time was set at 200 micros for better visualization of degenerated retina. After targeting the transplant area, 139 or 199 consecutive slices were scanned. Projection images and movies of the retinal transplant area were computed and later compared with histology. RESULTS: OCT scans identified 137 of 141 transplants as a thickening of the degenerated retina. OCT indicated the laminar structure of the transplants and surgical defects, such as RPE/choroid damage with an accuracy rate between 83 and 99%. Three-dimensional projections showed the transplant position in the retina in relation to the optic disc. Histology of transplants by hPAP and hematoxylin-eosin staining was correlated with the OCT results. CONCLUSIONS: Optical coherence tomography is an excellent tool to image retinal layers in a live rat. This procedure helps to evaluate the placement and quality of the transplants in the living eye. Title: Synthesis of 4-[(diethylamino)methyl]-phenol derivatives as novel cholinesterase inhibitors with selectivity towards butyrylcholinesterase Yu L, Cao R, Yi W, Yan Q, Chen Z, Ma L, Peng W, Song H Ref: Bioorganic & Medicinal Chemistry Lett, 20:3254, 2010 : PubMed ESTHER: Yu_2010_Bioorg.Med.Chem.Lett_20_3254 PubMedSearch: Yu 2010 Bioorg.Med.Chem.Lett 20 3254 PubMedID: 20452769 Abstract A series of novel cholinesterase inhibitors, being composed of 4-[(diethylamino)methyl]-phenoxy and secondary amine which were linked with a different length alkyl chain, were designed and synthesized from the starting material p-hydroxybenzaldehyde. These compounds were evaluated as acetylcholinesterase and butyrylcholinesterase (AChE/BChE) inhibitors. Compounds 25-31 having a secondary amine moiety connected to the phenyl ring via eight CH(2) units spacer were found to be the most potent inhibitors with IC(50) value lower than 220nM and 48nM against AChE and BChE, respectively. Interestingly, these inhibitors showed a surprising selectively toward BChE, and compounds 26, 27, and 30 displayed 12.5, 18.6, and 18.8-fold higher affinity to BChE. The inhibition kinetics analyzed by Linewear-Burk plots revealed that such compounds were mix-type inhibitors. Title: Design, synthesis and evaluation of difunctionalized 4-hydroxybenzaldehyde derivatives as novel cholinesterase inhibitors Yu L, Cao R, Yi W, Yan Q, Chen Z, Ma L, Song H Ref: Chem Pharm Bull (Tokyo), 58:1216, 2010 : PubMed ESTHER: Yu_2010_Chem.Pharm.Bull.(Tokyo)_58_1216 PubMedSearch: Yu 2010 Chem.Pharm.Bull.(Tokyo) 58 1216 PubMedID: 20823602 Abstract A series of difunctionalized 4-hydroxybenzaldehyde derivatives were designed, synthesized and evaluated as cholinesterase (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)) inhibitors. The results demonstrated that all the compounds had more potent AChE and BChE inhibitory activities than galanthamine-HBr, one of the best cholinesterase inhibitors known so far. The inhibition mechanism revealed that the best active compound 4e displayed a mix-type mode of AChE and BChE by its dual-site interactions with the catalytic triad active center and the peripheral anionic site (PAS) of enzyme. All these data suggested that further development of such compounds may be of interest. Title: p75 reduces beta-amyloid-induced sympathetic innervation deficits in an Alzheimer's disease mouse model Bengoechea TG, Chen Z, O'Leary DA, Masliah E, Lee KF Ref: Proc Natl Acad Sci U S A, 106:7870, 2009 : PubMed ESTHER: Bengoechea_2009_Proc.Natl.Acad.Sci.U.S.A_106_7870 PubMedSearch: Bengoechea 2009 Proc.Natl.Acad.Sci.U.S.A 106 7870 PubMedID: 19416837 Abstract Beta-amyloid (Abeta) has adverse effects on brain cells, but little is known about its effects on the peripheral nervous system in Alzheimer's disease (AD). Several lines of in vitro evidence suggest that the neurotrophin receptor p75 mediates or exacerbates Abeta-induced neurotoxicity. Here, we show that p75-deficient sympathetic neurons are more sensitive to Abeta-induced neurite growth inhibition. To investigate the role of p75 in the sympathetic nervous system of AD, p75 mutant mice were crossed with a mouse line of AD model. The majority of p75-deficient AD mice died by 3 weeks of age. The lethality is associated with severe defects in sympathetic innervation to multiple organs. When 1 copy of the BACE1 gene encoding a protein essential in Abeta production was deleted in p75-deficient AD mice, sympathetic innervation was significantly restored. These results suggest that p75 is neuroprotective for the sympathetic nervous system in a mouse model of AD. Title: Organophosphorus pesticide residues in milled rice (Oryza sativa) on the Chinese market and dietary risk assessment Chen C, Li Y, Chen M, Chen Z, Qian Y Ref: Food Additives & Contaminants Part A Chem Anal Control Expo Risk Assess, 26:340, 2009 : PubMed ESTHER: Chen_2009_Food.Addit.Contam.Part.A.Chem.Anal.Control.Expo.Risk.Assess_26_340 PubMedSearch: Chen 2009 Food.Addit.Contam.Part.A.Chem.Anal.Control.Expo.Risk.Assess 26 340 PubMedID: 19680907 Abstract The present study investigates the occurrence of acetylcholinesterase (AChE)-inhibiting organophosphorus (OP) pesticide residues in milled rice samples obtained form local markets in China during the period 2004-2006 and estimates their cumulative exposure. Concentrations of OP pesticides were determined by gas chromatography with flame photometric detection (GC-FPD). The results showed that 9.3% of the samples contained detectable residues of at least one of the seven target OP pesticides (chlorpyrifos, dichlorvos, omethoate, methamidophos, parathion-methyl, parathion and triazophos) mainly used for agriculture in China, with concentrations ranging 0.011-1.756 mg kg(-1). Rice consumption data was obtained from an individual food consumption survey. Relative potency factors (RPFs) for each pesticide were calculated with methamidophos as the index compound (IC), using 1- or 2-year chronic non-observed adverse effect levels (NOAEL) for AChE inhibition, mostly in rat brain, obtained from international evaluations of pesticides. Exposure to AChE-inhibiting pesticides for the population above 7 years old at P99.9 represented 52-94.5% of the acceptable daily intake (ADI) expressed as methamidophos. Estimated exposure for children aged 2-4 and 4-7 years at P99.9 were 119 and 104.3% of the ADI level, respectively. This study suggests that a yearly monitoring program for OP pesticide residues and strict implementation of the national safety standard for milled rice is necessary. Title: Pharmacophore-based virtual screening versus docking-based virtual screening: a benchmark comparison against eight targets Chen Z, Li HL, Zhang QJ, Bao XG, Yu KQ, Luo XM, Zhu WL, Jiang HL Ref: Acta Pharmacol Sin, 30:1694, 2009 : PubMed ESTHER: Chen_2009_Acta.Pharmacol.Sin_30_1694 PubMedSearch: Chen 2009 Acta.Pharmacol.Sin 30 1694 PubMedID: 19935678 Abstract AIM: This study was conducted to compare the efficiencies of two virtual screening approaches, pharmacophore-based virtual screening (PBVS) and docking-based virtual screening (DBVS) methods. METHODS: All virtual screens were performed on two data sets of small molecules with both actives and decoys against eight structurally diverse protein targets, namely angiotensin converting enzyme (ACE), acetylcholinesterase (AChE), androgen receptor (AR), D-alanyl-D-alanine carboxypeptidase (DacA), dihydrofolate reductase (DHFR), estrogen receptors alpha (ERalpha), HIV-1 protease (HIV-pr), and thymidine kinase (TK). Each pharmacophore model was constructed based on several X-ray structures of protein-ligand complexes. Virtual screens were performed using four screening standards, the program Catalyst for PBVS and three docking programs (DOCK, GOLD and Glide) for DBVS. RESULTS: Of the sixteen sets of virtual screens (one target versus two testing databases), the enrichment factors of fourteen cases using the PBVS method were higher than those using DBVS methods. The average hit rates over the eight targets at 2% and 5% of the highest ranks of the entire databases for PBVS are much higher than those for DBVS. CONCLUSION: The PBVS method outperformed DBVS methods in retrieving actives from the databases in our tested targets, and is a powerful method in drug discovery. Title: Three-dimensional reconstruction and visualization of the median nerve from serial tissue sections Sun K, Zhang J, Chen T, Chen Z, Li Z, Li H, Hu P Ref: Microsurgery, 29:573, 2009 : PubMed ESTHER: Sun_2009_Microsurgery_29_573 PubMedSearch: Sun 2009 Microsurgery 29 573 PubMedID: 19308949 Abstract The purpose of this study was to definitively implement the three-dimensional visualization of sensory and motor fascicles in the human median nerve by means of acetylcholinesterase (AChe) histochemical staining and under the assistance of the computer technology. One fresh human median nerve was harvested from a male adult cadaver. The median nerve was fixed at a special holder. Then, the whole holder was embedded and rapidly frozen in the liquid nitrogen. The processed median nerve was then cut coronally every 100 microm at a 20 microm thickness along its long axis in a sliding freezing microtome. The total number of sections was 4,650 slices. All sections were stained with the AChe histochemical method. The stained sections were scanned and saved as Joint Photographic Experts Group files. These images with positively and negatively stained sections were acquired to an Intel dual Pentium computer. The Adobe Photoshop CS2 software was used to compare the reference points of images before and after staining. The two-dimensional intraneural microstructure database of median nerve was then acquired. A software of 3D nerve visualization system was developed. With the 3D nerve visualization system, the 3D visualization result of intraneural microstructure of median nerve was created. The findings may provide more accurate and detailed anatomic information for nerve repairs, specifically for the fascicular nerve repairs. The 3D nerve visualization technique may have potential for future studies of topography of peripheral nerve. (c) 2009 Wiley-Liss, Inc. Microsurgery, 2009. Title: [3D visualization research on microstructure of human ulnar nerve] Liu T, Hu P, Zhang J, Zhang M, Li H, Chen Z, Chen T Ref: Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi, 22:1026, 2008 : PubMed ESTHER: Liu_2008_Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi_22_1026 PubMedSearch: Liu 2008 Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi 22 1026 PubMedID: 18822720 Abstract OBJECTIVE: To explore the application of 3D nerve visualization system in processing 2D image information of human ulnar nerve acquired by series freezing tissue section, staining and scanning. And to draw the 3D anatomical atlas of human ulnar nerve through 3D Nerve visualization software system. METHODS: One left ulnar nerve (from medial fasciculus of brachial plexus to transverse carpal ligament, about 50 cm) was taken from a fresh donated cadaver. After marked with human hair and embedded in OCT, series freezing tissue sections were made and stained with acetylcholinesterase histochemically. Series 2D image information was obtained through high resolution scanner. Then the microstructure of ulnar nerve was reconstructed with 3D Nerve visualization software system. RESULTS: Different cross sections of ulnar nerve have different numbers, positions and characters of the internal nerve fibers. The microstructure of ulnar nerve could be observed in magnifying visual field at any cross section after reconstructed in 3D Nerve visualization soft ware system, which made it possible to track stereo course of fascicles. CONCLUSION: Reconstructed 3D Nerve visualization software system shows the whole microstructure of ulnar nerve and the 3D stereo-structure of its internal fascicles, thus provides exact topography atlas for medical teaching and facilitates precise repair of ulnar nerve injury to improve therapeutic effect. Title: Purification and identification of cutinases from Colletotrichum kahawae and Colletotrichum gloeosporioides Chen Z, Franco CF, Baptista RP, Cabral JM, Coelho AV, Rodrigues CJ, Jr., Melo EP Ref: Applied Microbiology & Biotechnology, 73:1306, 2007 : PubMed ESTHER: Chen_2007_Appl.Microbiol.Biotechnol_73_1306 PubMedSearch: Chen 2007 Appl.Microbiol.Biotechnol 73 1306 PubMedID: 17043825 Gene_locus related to this paper: colgl-cutas Abstract Colletotrichum kahawae is the causal agent of the coffee berry disease, infecting leaves and coffee berries at any stage of their development. Colletotrichum gloeosporioides is the causal agent of brown blight, infecting ripe berries only. Both fungi secrete the same pattern of carboxylesterases to the fermentation broth when cutin is used as carbon source. By using two different strategies composed of two precipitation steps (ammonium sulphate and acetic acid precipitation) and two chromatographic steps, two proteins displaying carboxylesterase activity were purified to electrophoretic homogeneity. One, with a molecular weight (MW) of 21 kDa, has a blocked N terminus and was identified as cutinase by peptide mass fingerprint and mass spectrometry/mass spectrometry data acquired after peptide derivatization with 4-sulphophenyl isothiocyanate. The second, with a MW of 40 kDa, displays significant carboxylesterase activity on tributyrin but low activity on p-nitrophenyl butyrate. N-terminal sequencing for this protein does not reveal any homology to other carboxylesterases. These two enzymes, which were secreted by both fungi, appear homologous. Title: Genome of the opportunistic pathogen Streptococcus sanguinis Xu P, Alves JM, Kitten T, Brown A, Chen Z, Ozaki LS, Manque P, Ge X, Serrano MG and Buck GA <8 more author(s)> Xu P, Alves JM, Kitten T, Brown A, Chen Z, Ozaki LS, Manque P, Ge X, Serrano MG, Puiu D, Hendricks S, Wang Y, Chaplin MD, Akan D, Paik S, Peterson DL, Macrina FL, Buck GA (- 8) Ref: Journal of Bacteriology, 189:3166, 2007 : PubMed ESTHER: Xu_2007_J.Bacteriol_189_3166 PubMedSearch: Xu 2007 J.Bacteriol 189 3166 PubMedID: 17277061 Gene_locus related to this paper: strsa-f0fga9, strsv-a3cmd5, strsv-a3cn30, strsv-a3cn31, strsv-a3cnb1, strsv-a3cp66, strsv-a3cpg5, strsv-a3cqq7, strsv-pepx, strsv-a3cnw9, strsv-a3cm57 Abstract The genome of Streptococcus sanguinis is a circular DNA molecule consisting of 2,388,435 bp and is 177 to 590 kb larger than the other 21 streptococcal genomes that have been sequenced. The G+C content of the S. sanguinis genome is 43.4%, which is considerably higher than the G+C contents of other streptococci. The genome encodes 2,274 predicted proteins, 61 tRNAs, and four rRNA operons. A 70-kb region encoding pathways for vitamin B(12) biosynthesis and degradation of ethanolamine and propanediol was apparently acquired by horizontal gene transfer. The gene complement suggests new hypotheses for the pathogenesis and virulence of S. sanguinis and differs from the gene complements of other pathogenic and nonpathogenic streptococci. In particular, S. sanguinis possesses a remarkable abundance of putative surface proteins, which may permit it to be a primary colonizer of the oral cavity and agent of streptococcal endocarditis and infection in neutropenic patients. Title: New perspectives on host-parasite interplay by comparative transcriptomic and proteomic analyses of Schistosoma japonicum Liu F, Lu J, Hu W, Wang SY, Cui SJ, Chi M, Yan Q, Wang XR, Song HD and Han ZG <11 more author(s)> Liu F, Lu J, Hu W, Wang SY, Cui SJ, Chi M, Yan Q, Wang XR, Song HD, Xu XN, Wang JJ, Zhang XL, Zhang X, Wang ZQ, Xue CL, Brindley PJ, McManus DP, Yang PY, Feng Z, Chen Z, Han ZG (- 11) Ref: PLoS Pathog, 2:e29, 2006 : PubMed ESTHER: Liu_2006_PLoS.Pathog_2_e29 PubMedSearch: Liu 2006 PLoS.Pathog 2 e29 PubMedID: 16617374 Gene_locus related to this paper: schja-q5byv1 Abstract Schistosomiasis remains a serious public health problem with an estimated 200 million people infected in 76 countries. Here we isolated ~ 8,400 potential protein-encoding cDNA contigs from Schistosoma japonicum after sequencing circa 84,000 expressed sequence tags. In tandem, we undertook a high-throughput proteomics approach to characterize the protein expression profiles of a number of developmental stages (cercariae, hepatic schistosomula, female and male adults, eggs, and miracidia) and tissues at the host-parasite interface (eggshell and tegument) by interrogating the protein database deduced from the contigs. Comparative analysis of these transcriptomic and proteomic data, the latter including 3,260 proteins with putative identities, revealed differential expression of genes among the various developmental stages and sexes of S. japonicum and localization of putative secretory and membrane antigens, enzymes, and other gene products on the adult tegument and eggshell, many of which displayed genetic polymorphisms. Numerous S. japonicum genes exhibited high levels of identity with those of their mammalian hosts, whereas many others appeared to be conserved only across the genus Schistosoma or Phylum Platyhelminthes. These findings are expected to provide new insights into the pathophysiology of schistosomiasis and for the development of improved interventions for disease control and will facilitate a more fundamental understanding of schistosome biology, evolution, and the host-parasite interplay. Title: The DNA sequence, annotation and analysis of human chromosome 3 Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A and Gibbs RA <100 more author(s)> Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Wei S, Wheeler DA, Wright MW, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clendenning J, Clerc-Blankenburg KP, Davis C, Delgado O, Dinh HH, Dong W, Draper H, Ernst S, Fu G, Gonzalez-Garay ML, Garcia DK, Gillett W, Gu J, Hao B, Haugen E, Havlak P, He X, Hennig S, Hu S, Huang W, Jackson LR, Jacob LS, Kelly SH, Kube M, Levy R, Li Z, Liu B, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Palmeiri A, Pasternak S, Perez LM, Phelps KA, Plopper FJ, Qiang B, Raymond C, Rodriguez R, Saenphimmachak C, Santibanez J, Shen H, Shen Y, Subramanian S, Tabor PE, Verduzco D, Waldron L, Wang Q, Williams GA, Wong GK, Yao Z, Zhang J, Zhang X, Zhao G, Zhou J, Zhou Y, Nelson D, Lehrach H, Reinhardt R, Naylor SL, Yang H, Olson M, Weinstock G, Gibbs RA (- 100) Ref: Nature, 440:1194, 2006 : PubMed ESTHER: Muzny_2006_Nature_440_1194 PubMedSearch: Muzny 2006 Nature 440 1194 PubMedID: 16641997 Gene_locus related to this paper: human-AADAC, human-AADACL2, human-ABHD5, human-ABHD6, human-ABHD10, human-ABHD14A, human-APEH, human-BCHE, human-CIB, human-LIPH, human-MGLL, human-NLGN1, human-PLA1A Abstract After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion. Title: Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling Wang Y, Du D, Fang L, Yang G, Zhang C, Zeng R, Ullrich A, Lottspeich F, Chen Z Ref: EMBO Journal, 25:5058, 2006 : PubMed ESTHER: Wang_2006_EMBO.J_25_5058 PubMedSearch: Wang 2006 EMBO.J 25 5058 PubMedID: 17053785 Abstract The conserved polarity complex, comprising the partitioning-defective (Par) proteins Par3 and Par6, and the atypical protein kinase C, functions in various cell-polarization events and asymmetric cell divisions. However, little is known about whether and how external stimuli-induced signals may regulate Par3 function in epithelial cell polarity. Here, we found that Par3 was tyrosine phosphorylated through phosphoproteomic profiling of pervanadate-induced phosphotyrosine proteins. We also demonstrated that the tyrosine phosphorylation event induced by multiple growth factors including epidermal growth factor (EGF) was dependent on activation of Src family kinase (SFK) members c-Src and c-Yes. The tyrosine residue 1127 (Y1127) of Par3 was identified as the major EGF-induced phosphorylation site. Moreover, we found that Y1127 phosphorylation reduced the association of Par3 with LIM kinase 2 (LIMK2), thus enabling LIMK2 to regulate cofilin phosphorylation dynamics. Substitution of Y1127 for phenylalanine impaired the EGF-induced Par3 and LIMK2 dissociation and delayed epithelial tight junction (TJ) assembly considerably. Collectively, these data suggest a novel, phosphotyrosine-dependent fine-tuning mechanism of Par3 in epithelial TJ assembly controlled by the EGF receptor-SFK signaling pathway. Title: Comparative and functional genomic analyses of the pathogenicity of phytopathogen Xanthomonas campestris pv. campestris Qian W, Jia Y, Ren SX, He YQ, Feng JX, Lu LF, Sun Q, Ying G, Tang DJ and He C <18 more author(s)> Qian W, Jia Y, Ren SX, He YQ, Feng JX, Lu LF, Sun Q, Ying G, Tang DJ, Tang H, Wu W, Hao P, Wang L, Jiang BL, Zeng S, Gu WY, Lu G, Rong L, Tian Y, Yao Z, Fu G, Chen B, Fang R, Qiang B, Chen Z, Zhao GP, Tang JL, He C (- 18) Ref: Genome Res, 15:757, 2005 : PubMed ESTHER: Qian_2005_Genome.Res_15_757 PubMedSearch: Qian 2005 Genome.Res 15 757 PubMedID: 15899963 Gene_locus related to this paper: xanax-DHAA, xanax-ENTF2, xanax-GAA, xanax-PTRB, xanax-XAC0515, xanax-XAC0628, xanax-XAC0736, xanax-XAC0753, xanax-XAC1713, xanca-acvB, xanca-BIOH, xanca-CATD, xanca-CPO, xanca-estA1, xanca-impep, xanca-META, xanca-METX, xanca-PCAD, xanca-PHBC, xanca-Q8PB04, xanca-W78, xanca-XCC0080, xanca-XCC0180, xanca-XCC0243, xanca-XCC0266, xanca-XCC0372, xanca-XCC0375, xanca-XCC0753, xanca-XCC0800, xanca-XCC0843, xanca-XCC1105, xanca-XCC1734, xanca-XCC2285, xanca-XCC2374, xanca-XCC2397, xanca-XCC2405, xanca-XCC2566, xanca-XCC2722, xanca-XCC2737, xanca-XCC2811, xanca-XCC2817, xanca-XCC2854, xanca-XCC2869, xanca-XCC3028, xanca-XCC3164, xanca-XCC3219, xanca-XCC3296, xanca-XCC3320, xanca-XCC3514, xanca-XCC3548, xanca-XCC3555, xanca-XCC3623, xanca-XCC3915, xanca-XCC3961, xanca-XCC3970, xanca-XCC4016, xanca-XCC4096, xanca-XCC4180, xanca-XYNB, xanca-XYNB2, xancb-b0rq23, xancp-q8pax3, xancp-y2094 Abstract Xanthomonas campestris pathovar campestris (Xcc) is the causative agent of crucifer black rot disease, which causes severe losses in agricultural yield world-wide. This bacterium is a model organism for studying plant-bacteria interactions. We sequenced the complete genome of Xcc 8004 (5,148,708 bp), which is highly conserved relative to that of Xcc ATCC 33913. Comparative genomics analysis indicated that, in addition to a significant genomic-scale rearrangement cross the replication axis between two IS1478 elements, loss and acquisition of blocks of genes, rather than point mutations, constitute the main genetic variation between the two Xcc strains. Screening of a high-density transposon insertional mutant library (16,512 clones) of Xcc 8004 against a host plant (Brassica oleraceae) identified 75 nonredundant, single-copy insertions in protein-coding sequences (CDSs) and intergenic regions. In addition to known virulence factors, full virulence was found to require several additional metabolic pathways and regulatory systems, such as fatty acid degradation, type IV secretion system, cell signaling, and amino acids and nucleotide metabolism. Among the identified pathogenicity-related genes, three of unknown function were found in Xcc 8004-specific chromosomal segments, revealing a direct correlation between genomic dynamics and Xcc virulence. The present combination of comparative and functional genomic analyses provides valuable information about the genetic basis of Xcc pathogenicity, which may offer novel insight toward the development of efficient methods for prevention of this important plant disease. Title: The DNA sequence of the human X chromosome Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, Platzer M, Howell GR, Burrows C and Bentley DR <272 more author(s)> Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, Platzer M, Howell GR, Burrows C, Bird CP, Frankish A, Lovell FL, Howe KL, Ashurst JL, Fulton RS, Sudbrak R, Wen G, Jones MC, Hurles ME, Andrews TD, Scott CE, Searle S, Ramser J, Whittaker A, Deadman R, Carter NP, Hunt SE, Chen R, Cree A, Gunaratne P, Havlak P, Hodgson A, Metzker ML, Richards S, Scott G, Steffen D, Sodergren E, Wheeler DA, Worley KC, Ainscough R, Ambrose KD, Ansari-Lari MA, Aradhya S, Ashwell RI, Babbage AK, Bagguley CL, Ballabio A, Banerjee R, Barker GE, Barlow KF, Barrett IP, Bates KN, Beare DM, Beasley H, Beasley O, Beck A, Bethel G, Blechschmidt K, Brady N, Bray-Allen S, Bridgeman AM, Brown AJ, Brown MJ, Bonnin D, Bruford EA, Buhay C, Burch P, Burford D, Burgess J, Burrill W, Burton J, Bye JM, Carder C, Carrel L, Chako J, Chapman JC, Chavez D, Chen E, Chen G, Chen Y, Chen Z, Chinault C, Ciccodicola A, Clark SY, Clarke G, Clee CM, Clegg S, Clerc-Blankenburg K, Clifford K, Cobley V, Cole CG, Conquer JS, Corby N, Connor RE, David R, Davies J, Davis C, Davis J, Delgado O, Deshazo D, Dhami P, Ding Y, Dinh H, Dodsworth S, Draper H, Dugan-Rocha S, Dunham A, Dunn M, Durbin KJ, Dutta I, Eades T, Ellwood M, Emery-Cohen A, Errington H, Evans KL, Faulkner L, Francis F, Frankland J, Fraser AE, Galgoczy P, Gilbert J, Gill R, Glockner G, Gregory SG, Gribble S, Griffiths C, Grocock R, Gu Y, Gwilliam R, Hamilton C, Hart EA, Hawes A, Heath PD, Heitmann K, Hennig S, Hernandez J, Hinzmann B, Ho S, Hoffs M, Howden PJ, Huckle EJ, Hume J, Hunt PJ, Hunt AR, Isherwood J, Jacob L, Johnson D, Jones S, de Jong PJ, Joseph SS, Keenan S, Kelly S, Kershaw JK, Khan Z, Kioschis P, Klages S, Knights AJ, Kosiura A, Kovar-Smith C, Laird GK, Langford C, Lawlor S, Leversha M, Lewis L, Liu W, Lloyd C, Lloyd DM, Loulseged H, Loveland JE, Lovell JD, Lozado R, Lu J, Lyne R, Ma J, Maheshwari M, Matthews LH, McDowall J, Mclaren S, McMurray A, Meidl P, Meitinger T, Milne S, Miner G, Mistry SL, Morgan M, Morris S, Muller I, Mullikin JC, Nguyen N, Nordsiek G, Nyakatura G, O'Dell CN, Okwuonu G, Palmer S, Pandian R, Parker D, Parrish J, Pasternak S, Patel D, Pearce AV, Pearson DM, Pelan SE, Perez L, Porter KM, Ramsey Y, Reichwald K, Rhodes S, Ridler KA, Schlessinger D, Schueler MG, Sehra HK, Shaw-Smith C, Shen H, Sheridan EM, Shownkeen R, Skuce CD, Smith ML, Sotheran EC, Steingruber HE, Steward CA, Storey R, Swann RM, Swarbreck D, Tabor PE, Taudien S, Taylor T, Teague B, Thomas K, Thorpe A, Timms K, Tracey A, Trevanion S, Tromans AC, d'Urso M, Verduzco D, Villasana D, Waldron L, Wall M, Wang Q, Warren J, Warry GL, Wei X, West A, Whitehead SL, Whiteley MN, Wilkinson JE, Willey DL, Williams G, Williams L, Williamson A, Williamson H, Wilming L, Woodmansey RL, Wray PW, Yen J, Zhang J, Zhou J, Zoghbi H, Zorilla S, Buck D, Reinhardt R, Poustka A, Rosenthal A, Lehrach H, Meindl A, Minx PJ, Hillier LW, Willard HF, Wilson RK, Waterston RH, Rice CM, Vaudin M, Coulson A, Nelson DL, Weinstock G, Sulston JE, Durbin R, Hubbard T, Gibbs RA, Beck S, Rogers J, Bentley DR (- 272) Ref: Nature, 434:325, 2005 : PubMed ESTHER: Ross_2005_Nature_434_325 PubMedSearch: Ross 2005 Nature 434 325 PubMedID: 15772651 Gene_locus related to this paper: human-NLGN3, human-NLGN4X Abstract The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence. Title: [Simultaneous determination of organophosphorus and pyrethroid pesticide residues in vegetables by GC] Hong W, Chen Z, Yang Z Ref: Se Pu, 22:289, 2004 : PubMed Title: Hematopoietic gene expression profile in zebrafish kidney marrow Song HD, Sun XJ, Deng M, Zhang GW, Zhou Y, Wu XY, Sheng Y, Chen Y, Ruan Z and Chen Z <6 more author(s)> Song HD, Sun XJ, Deng M, Zhang GW, Zhou Y, Wu XY, Sheng Y, Chen Y, Ruan Z, Jiang CL, Fan HY, Zon LI, Kanki JP, Liu TX, Look AT, Chen Z (- 6) Ref: Proc Natl Acad Sci U S A, 101:16240, 2004 : PubMed ESTHER: Song_2004_Proc.Natl.Acad.Sci.U.S.A_101_16240 PubMedSearch: Song 2004 Proc.Natl.Acad.Sci.U.S.A 101 16240 PubMedID: 15520368 Gene_locus related to this paper: danre-q6tgx0, danre-Q7ZWC2, danre-SPG21 Abstract The zebrafish kidney marrow is considered to be the organ of definitive hematopoiesis, analogous to the mammalian bone marrow. We have sequenced 26,143 ESTs and isolated 304 cDNAs with putative full-length ORF from a zebrafish kidney marrow cDNA library. The ESTs formed 7,742 assemblies, representing both previously identified zebrafish ESTs (56%) and recently discovered zebrafish ESTs (44%). About 30% of these EST assemblies have orthologues in humans, including 1,282 disease-associated genes in the Online Mendelian Inheritance in Man (OMIM) database. Comparison of the effective and regulatory molecules related to erythroid functions across species suggests a good conservation from zebrafish to human. Interestingly, both embryonic and adult zebrafish globin genes showed higher homology to the human embryonic globin genes than to the human fetal/adult ones, consistent with evo-devo correlation hypothesis. In addition, conservation of a whole set of transcription factors involved in globin gene switch suggests the regulatory network for such remodeling mechanism existed before the divergence of the teleost and the ancestor of mammals. We also carried out whole-mount mRNA in situ hybridization assays for 493 cDNAs and identified 80 genes (16%) with tissue-specific expression during the first five days of zebrafish development. Twenty-six of these genes were specifically expressed in hematopoietic or vascular tissues, including three previously unidentified zebrafish genes: coro1a, nephrosin, and dab2. Our results indicate that conserved genetic programs regulate vertebrate hematopoiesis and vasculogenesis, and support the role of the zebrafish as an important animal model for studying both normal development and the molecular pathogenesis of human blood diseases. Title: DNA sequence and comparative analysis of chimpanzee chromosome 22 Watanabe H, Fujiyama A, Hattori M, Taylor TD, Toyoda A, Kuroki Y, Noguchi H, BenKahla A, Lehrach H and Sakaki Y <35 more author(s)> Watanabe H, Fujiyama A, Hattori M, Taylor TD, Toyoda A, Kuroki Y, Noguchi H, BenKahla A, Lehrach H, Sudbrak R, Kube M, Taenzer S, Galgoczy P, Platzer M, Scharfe M, Nordsiek G, Blocker H, Hellmann I, Khaitovich P, Paabo S, Reinhardt R, Zheng HJ, Zhang XL, Zhu GF, Wang BF, Fu G, Ren SX, Zhao GP, Chen Z, Lee YS, Cheong JE, Choi SH, Wu KM, Liu TT, Hsiao KJ, Tsai SF, Kim CG, S OO, Kitano T, Kohara Y, Saitou N, Park HS, Wang SY, Yaspo ML, Sakaki Y (- 35) Ref: Nature, 429:382, 2004 : PubMed ESTHER: Watanabe_2004_Nature_429_382 PubMedSearch: Watanabe 2004 Nature 429 382 PubMedID: 15164055 Gene_locus related to this paper: pantr-a0a2j8lmv7 Abstract Human-chimpanzee comparative genome research is essential for narrowing down genetic changes involved in the acquisition of unique human features, such as highly developed cognitive functions, bipedalism or the use of complex language. Here, we report the high-quality DNA sequence of 33.3 megabases of chimpanzee chromosome 22. By comparing the whole sequence with the human counterpart, chromosome 21, we found that 1.44% of the chromosome consists of single-base substitutions in addition to nearly 68,000 insertions or deletions. These differences are sufficient to generate changes in most of the proteins. Indeed, 83% of the 231 coding sequences, including functionally important genes, show differences at the amino acid sequence level. Furthermore, we demonstrate different expansion of particular subfamilies of retrotransposons between the lineages, suggesting different impacts of retrotranspositions on human and chimpanzee evolution. The genomic changes after speciation and their biological consequences seem more complex than originally hypothesized. Title: [Influence of chronic epilepsy on spatial memory retrieval in rats] Zhang LS, Jin CL, Li Q, Sun YC, Chen Z Ref: Zhejiang Da Xue Xue Bao Yi Xue Ban, 33:205, 2004 : PubMed ESTHER: Zhang_2004_Zhejiang.Da.Xue.Xue.Bao.Yi.Xue.Ban_33_205 PubMedSearch: Zhang 2004 Zhejiang.Da.Xue.Xue.Bao.Yi.Xue.Ban 33 205 PubMedID: 15179678 Abstract OBJECTIVE: To investigate the influence of chronic epilepsy on spatial memory retrieval in rats, and to evaluate the effects of TAK-147, an acetylcholinesterase inhibitor, and histidine, the precursor of histamine, on the amnesia induced by epilepsy. Title: Evolutionary and biomedical implications of a Schistosoma japonicum complementary DNA resource Hu W, Yan Q, Shen DK, Liu F, Zhu ZD, Song HD, Xu XR, Wang ZJ, Rong YP and Han ZG <14 more author(s)> Hu W, Yan Q, Shen DK, Liu F, Zhu ZD, Song HD, Xu XR, Wang ZJ, Rong YP, Zeng LC, Wu J, Zhang X, Wang JJ, Xu XN, Wang SY, Fu G, Zhang XL, Wang ZQ, Brindley PJ, McManus DP, Xue CL, Feng Z, Chen Z, Han ZG (- 14) Ref: Nat Genet, 35:139, 2003 : PubMed ESTHER: Hu_2003_Nat.Genet_35_139 PubMedSearch: Hu 2003 Nat.Genet 35 139 PubMedID: 12973349 Gene_locus related to this paper: schja-Q86EA4, schja-Q86EV0, schja-Q86F58, schja-Q86F66, schja-Q5DDP9 Abstract Schistosoma japonicum causes schistosomiasis in humans and livestock in the Asia-Pacific region. Knowledge of the genome of this parasite should improve understanding of schistosome-host interactions, biomedical aspects of schistosomiasis and invertebrate evolution. We assigned 43,707 expressed sequence tags (ESTs) derived from adult S. japonicum and their eggs to 13,131 gene clusters. Of these, 35% shared no similarity with known genes and 75% had not been reported previously in schistosomes. Notably, S. japonicum encoded mammalian-like receptors for insulin, progesterone, cytokines and neuropeptides, suggesting that host hormones, or endogenous parasite homologs, could orchestrate schistosome development and maturation and that schistosomes modulate anti-parasite immune responses through inhibitors, molecular mimicry and other evasion strategies. Title: Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing Ren SX, Fu G, Jiang XG, Zeng R, Miao YG, Xu H, Zhang YX, Xiong H, Lu G and Zhao GP <29 more author(s)> Ren SX, Fu G, Jiang XG, Zeng R, Miao YG, Xu H, Zhang YX, Xiong H, Lu G, Lu LF, Jiang HQ, Jia J, Tu YF, Jiang JX, Gu WY, Zhang YQ, Cai Z, Sheng HH, Yin HF, Zhang Y, Zhu GF, Wan M, Huang HL, Qian Z, Wang SY, Ma W, Yao ZJ, Shen Y, Qiang BQ, Xia QC, Guo XK, Danchin A, Saint Girons I, Somerville RL, Wen YM, Shi MH, Chen Z, Xu JG, Zhao GP (- 29) Ref: Nature, 422:888, 2003 : PubMed ESTHER: Ren_2003_Nature_422_888 PubMedSearch: Ren 2003 Nature 422 888 PubMedID: 12712204 Gene_locus related to this paper: lepin-AXEA, lepin-ESTA, lepin-LA0357, lepin-LA0587, lepin-LA0823, lepin-LA0932, lepin-LA1069, lepin-LA1345, lepin-LA1541, lepin-LA1702, lepin-LA1861, lepin-LA1902, lepin-LA1936, lepin-LA1955, lepin-LA2034, lepin-LA2132, lepin-LA2501, lepin-LA2505, lepin-LA2526, lepin-LA2544, lepin-LA2857, lepin-LA2958, lepin-LA3100, lepin-LA3107, lepin-LA3147, lepin-LA3604, lepin-LA3661, lepin-LA3669, lepin-LA3672, lepin-LA3770, lepin-LA3788, lepin-LA3851, lepin-LA3897, lepin-LA3998, lepin-LA4247, lepin-LB147, lepin-LB264, lepin-LB265, lepin-METX, lepin-q8f7a8, lepin-q72tt9 Abstract Leptospirosis is a widely spread disease of global concern. Infection causes flu-like episodes with frequent severe renal and hepatic damage, such as haemorrhage and jaundice. In more severe cases, massive pulmonary haemorrhages, including fatal sudden haemoptysis, can occur. Here we report the complete genomic sequence of a representative virulent serovar type strain (Lai) of Leptospira interrogans serogroup Icterohaemorrhagiae consisting of a 4.33-megabase large chromosome and a 359-kilobase small chromosome, with a total of 4,768 predicted genes. In terms of the genetic determinants of physiological characteristics, the facultatively parasitic L. interrogans differs extensively from two other strictly parasitic pathogenic spirochaetes, Treponema pallidum and Borrelia burgdorferi, although similarities exist in the genes that govern their unique morphological features. A comprehensive analysis of the L. interrogans genes for chemotaxis/motility and lipopolysaccharide synthesis provides a basis for in-depth studies of virulence and pathogenesis. The discovery of a series of genes possibly related to adhesion, invasion and the haematological changes that characterize leptospirosis has provided clues about how an environmental organism might evolve into an important human pathogen. Title: Genome-based analysis of virulence genes in a non-biofilm-forming Staphylococcus epidermidis strain (ATCC 12228) Zhang YQ, Ren SX, Li HL, Wang YX, Fu G, Yang J, Qin ZQ, Miao YG, Wang WY and Wen YM <7 more author(s)> Zhang YQ, Ren SX, Li HL, Wang YX, Fu G, Yang J, Qin ZQ, Miao YG, Wang WY, Chen RS, Shen Y, Chen Z, Yuan ZH, Zhao GP, Qu D, Danchin A, Wen YM (- 7) Ref: Molecular Microbiology, 49:1577, 2003 : PubMed ESTHER: Zhang_2003_Mol.Microbiol_49_1577 PubMedSearch: Zhang 2003 Mol.Microbiol 49 1577 PubMedID: 12950922 Gene_locus related to this paper: staep-GEHD, staep-lipas, staep-SE0011, staep-SE0226, staep-SE0386, staep-SE0389, staep-SE0424, staep-SE0564, staep-SE0714, staep-SE0745, staep-SE0980, staep-SE1436, staep-SE1460, staep-SE1510, staep-SE1780, staep-SE1929, staep-SERP2035, staep-SE2050, staep-SE2095, staep-SE2213, staep-SE2328, staep-SE2403 Abstract Staphylococcus epidermidis strains are diverse in their pathogenicity; some are invasive and cause serious nosocomial infections, whereas others are non-pathogenic commensal organisms. To analyse the implications of different virulence factors in Staphylococcus epidermidis infections, the complete genome of Staphylococcus epidermidis strain ATCC 12228, a non-biofilm forming, non-infection associated strain used for detection of residual antibiotics in food products, was sequenced. This strain showed low virulence by mouse and rat experimental infections. The genome consists of a single 2499 279 bp chromosome and six plasmids. The chromosomal G + C content is 32.1% and 2419 protein coding sequences (CDS) are predicted, among which 230 are putative novel genes. Compared to the virulence factors in Staphylococcus aureus, aside from delta-haemolysin and beta-haemolysin, other toxin genes were not found. In contrast, the majority of adhesin genes are intact in ATCC 12228. Most strikingly, the ica operon coding for the enzymes synthesizing interbacterial cellular polysaccharide is missing in ATCC 12228 and rearrangements of adjacent genes are shown. No mec genes, IS256, IS257, were found in ATCC 12228. It is suggested that the absence of the ica operon is a genetic marker in commensal Staphylococcus epidermidis strains which are less likely to become invasive. Title: Sequence and analysis of rice chromosome 4 Feng Q, Zhang Y, Hao P, Wang S, Fu G, Huang Y, Li Y, Zhu J, Liu Y and Han B <61 more author(s)> Feng Q, Zhang Y, Hao P, Wang S, Fu G, Huang Y, Li Y, Zhu J, Liu Y, Hu X, Jia P, Zhao Q, Ying K, Yu S, Tang Y, Weng Q, Zhang L, Lu Y, Mu J, Zhang LS, Yu Z, Fan D, Liu X, Lu T, Li C, Wu Y, Sun T, Lei H, Li T, Hu H, Guan J, Wu M, Zhang R, Zhou B, Chen Z, Chen L, Jin Z, Wang R, Yin H, Cai Z, Ren S, Lv G, Gu W, Zhu G, Tu Y, Jia J, Chen J, Kang H, Chen X, Shao C, Sun Y, Hu Q, Zhang X, Zhang W, Wang L, Ding C, Sheng H, Gu J, Chen S, Ni L, Zhu F, Chen W, Lan L, Lai Y, Cheng Z, Gu M, Jiang J, Li J, Hong G, Xue Y, Han B (- 61) Ref: Nature, 420:316, 2002 : PubMed ESTHER: Feng_2002_Nature_420_316 PubMedSearch: Feng 2002 Nature 420 316 PubMedID: 12447439 Gene_locus related to this paper: orysa-Q7XTC5, orysa-Q7F959, orysa-q7f9i3, orysa-q7x7y5, orysa-q7xkj9, orysa-q7xr62, orysa-q7xr63, orysa-q7xr64, orysa-q7xsg1, orysa-q7xsq2, orysa-Q7XTM8, orysa-q7xts6, orysa-q7xue7, orysa-q7xv53, orysa-Q7XVB5, orysa-Q7XVG5, orysj-q0jaf0, orysj-q7f8x1 Abstract Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis. Title: [Effects of TAK-147, a novel acetylcholinesterase inhibitor, on spatial memory deficit as evaluated by Morris water maze of rats] Xu AJ, Chen Z, Li R, Zhu CY, Wei EQ Ref: Zhejiang Da Xue Xue Bao Yi Xue Ban, 31:98, 2002 : PubMed ESTHER: Xu_2002_Zhejiang.Da.Xue.Xue.Bao.Yi.Xue.Ban_31_98 PubMedSearch: Xu 2002 Zhejiang.Da.Xue.Xue.Bao.Yi.Xue.Ban 31 98 PubMedID: 12539269 Abstract OBJECTIVE To evalute the effects of TAK-147, a novel acetylcholinesterase inhibitor on rat spatial memory deficit using the Morris water maze. METHODS: Morris water maze was used to measure spatial memory in rats, and open field test was used to analysis locomotor activity. RESULTS: Scopolamine (0.4mg/kg,IP) significantly increased the latency period in memory acquisition. Intraperitoneal TAK-147 injection ameliorated scopolamine-induced deficit in a dose-related manner. A significant effect was obtained at doses of 0.3 and 1.0 mg/kg. Both TAK-147 (0.3 and 1.0 mg/kg) and tacrine (3 and 5 mg/kg) significantly reversed scopolamine (1.5 mg/kg) increased latency in memory retrieval. However, TAK-147 had a more potent effect than tacrine. In the locomotor test, TAK-147 created no appreciable change, compared with scopolamine or saline. CONCLUSION: A novel acetycholinesterase inhibitor, TAK-147 ameliorates the scopolamine induced impaired spatial memory in rats. Title: Effect of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1- propanone fumarate, a novel acetylcholinesterase inhibitor, on spatial cognitive impairment induced by chronic cerebral hypoperfusion in rats Xu AJ, Chen Z, Yanai K, Huang YW, Wei EQ Ref: Neuroscience Letters, 331:33, 2002 : PubMed ESTHER: Xu_2002_Neurosci.Lett_331_33 PubMedSearch: Xu 2002 Neurosci.Lett 331 33 PubMedID: 12359317 Inhibitor(s) related to this paper: TAK-147 Abstract It is of interest whether the acetylcholinesterase inhibitor, 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1- propanone fumarate (TAK-147), can improve cognitive impairment caused by chronic cerebral ischemia in rats. Two weeks after four-vessel occlusion, apparent impairments of spatial retrieval memory were observed in the Morris water maze. Both TAK-147 at doses of 0.1, 0.3 and 1.0 mg/kg and donepezil at doses of 0.3 and 1.0 mg/kg significantly ameliorated ischemia-induced memory deficits dose-dependently, but tacrine had no appreciable effect. Furthermore, we demonstrate that the intensity of staining by 2,3,5-triphenyltetrazolium in the hippocampal and cortical slices was significantly decreased by ischemia (10 min anoxia/aglycemia), and that it was also significantly restored by treatment with TAK-147 and donepezil. Title: The acetylcholinesterase gene and organophosphorus resistance in the Australian sheep blowfly, Lucilia cuprina Chen Z, Newcomb RD, Forbes E, McKenzie J, Batterham P Ref: Insect Biochemistry & Molecular Biology, 31:805, 2001 : PubMed ESTHER: Chen_2001_Insect.Biochem.Mol.Biol_31_805 PubMedSearch: Chen 2001 Insect.Biochem.Mol.Biol 31 805 PubMedID: 11378416 Gene_locus related to this paper: luccu-ACHE Abstract Acetylcholinesterase (AChE), encoded by the Ace gene, is the primary target of organophosphorous (OP) and carbamate insecticides. Ace mutations have been identified in OP resistants strains of Drosophila melanogaster. However, in the Australian sheep blowfly, Lucilia cuprina, resistance in field and laboratory generated strains is determined by point mutations in the Rop-1 gene, which encodes a carboxylesterase, E3. To investigate the apparent bias for the Rop-1/E3 mechanism in the evolution of OP resistance in L. cuprina, we have cloned the Ace gene from this species and characterized its product. Southern hybridization indicates the existence of a single Ace gene in L. cuprina. The amino acid sequence of L. cuprina AChE shares 85.3% identity with D. melanogaster and 92.4% with Musca domestica AChE. Five point mutations in Ace associated with reduced sensitivity to OP insecticides have been previously detected in resistant strains of D. melanogaster. These residues are identical in susceptible strains of D. melanogaster and L. cuprina, although different codons are used. Each of the amino acid substitutions that confer OP resistance in D. melanogaster could also occur in L. cuprina by a single non-synonymous substitution. These data suggest that the resistance mechanism used in L. cuprina is determined by factors other than codon bias. The same point mutations, singly and in combination, were introduced into the Ace gene of L. cuprina by site-directed mutagenesis and the resulting AChE enzymes expressed using a baculovirus system to characterise their kinetic properties and interactions with OP insecticides. The K(m) of wild type AChE for acetylthiocholine (ASCh) is 23.13 microM and the point mutations change the affinity to the substrate. The turnover number of Lucilia AChE for ASCh was estimated to be 1.27x10(3) min(-1), similar to Drosophila or housefly AChE. The single amino acid replacements reduce the affinities of the AChE for OPs and give up to 8.7-fold OP insensitivity, while combined mutations give up to 35-fold insensitivity. However, other published studies indicate these same mutations yield higher levels of OP insensitivity in D. melanogaster and A. aegypti. The inhibition data indicate that the wild type form of AChE of L. cuprina is 12.4-fold less sensitive to OP inhibition than the susceptible form of E3, suggesting that the carboxylesterases may have a role in the protection of AChE via a sequestration mechanism. This provides a possible explanation for the bias towards the evolution of resistance via the Rop-1/E3 mechanism in L. cuprina. Title: Point mutant mice with hypersensitive alpha 4 nicotinic receptors show dopaminergic deficits and increased anxiety Labarca C, Schwarz J, Deshpande P, Schwarz S, Nowak MW, Fonck C, Nashmi R, Kofuji P, Dang H and Lester HA <7 more author(s)> Labarca C, Schwarz J, Deshpande P, Schwarz S, Nowak MW, Fonck C, Nashmi R, Kofuji P, Dang H, Shi W, Fidan M, Khakh BS, Chen Z, Bowers BJ, Boulter J, Wehner JM, Lester HA (- 7) Ref: Proc Natl Acad Sci U S A, 98:2786, 2001 : PubMed ESTHER: Labarca_2001_Proc.Natl.Acad.Sci.U.S.A_98_2786 PubMedSearch: Labarca 2001 Proc.Natl.Acad.Sci.U.S.A 98 2786 PubMedID: 11226318 Abstract Knock-in mice were generated that harbored a leucine-to-serine mutation in the alpha4 nicotinic receptor near the gate in the channel pore. Mice with intact expression of this hypersensitive receptor display dominant neonatal lethality. These mice have a severe deficit of dopaminergic neurons in the substantia nigra, possibly because the hypersensitive receptors are continuously activated by normal extracellular choline concentrations. A strain that retains the neo selection cassette in an intron has reduced expression of the hypersensitive receptor and is viable and fertile. The viable mice display increased anxiety, poor motor learning, excessive ambulation that is eliminated by very low levels of nicotine, and a reduction of nigrostriatal dopaminergic function upon aging. These knock-in mice provide useful insights into the pathophysiology of sustained nicotinic receptor activation and may provide a model for Parkinson's disease. Title: Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB and Chen JL <19 more author(s)> Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM, Huang GY, Chen Z, Chen MD, Chen JL (- 19) Ref: Proc Natl Acad Sci U S A, 97:9543, 2000 : PubMed ESTHER: Hu_2000_Proc.Natl.Acad.Sci.U.S.A_97_9543 PubMedSearch: Hu 2000 Proc.Natl.Acad.Sci.U.S.A 97 9543 PubMedID: 10931946 Gene_locus related to this paper: human-ESD Abstract The primary neuroendocrine interface, hypothalamus and pituitary, together with adrenals, constitute the major axis responsible for the maintenance of homeostasis and the response to the perturbations in the environment. The gene expression profiling in the human hypothalamus-pituitary-adrenal axis was catalogued by generating a large amount of expressed sequence tags (ESTs), followed by bioinformatics analysis (http://www.chgc.sh.cn/ database). Totally, 25,973 sequences of good quality were obtained from 31,130 clones (83.4%) from cDNA libraries of the hypothalamus, pituitary, and adrenal glands. After eliminating 5,347 sequences corresponding to repetitive elements and mtDNA, 20,626 ESTs could be assembled into 9, 175 clusters (3,979, 3,074, and 4,116 clusters in hypothalamus, pituitary, and adrenal glands, respectively) when overlapping ESTs were integrated. Of these clusters, 2,777 (30.3%) corresponded to known genes, 4,165 (44.8%) to dbESTs, and 2,233 (24.3%) to novel ESTs. The gene expression profiles reflected well the functional characteristics of the three levels in the hypothalamus-pituitary-adrenal axis, because most of the 20 genes with highest expression showed statistical difference in terms of tissue distribution, including a group of tissue-specific functional markers. Meanwhile, some findings were made with regard to the physiology of the axis, and 200 full-length cDNAs of novel genes were cloned and sequenced. All of these data may contribute to the understanding of the neuroendocrine regulation of human life. Title: Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY and Chen Z <11 more author(s)> Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z (- 11) Ref: Genome Res, 10:1546, 2000 : PubMed ESTHER: Zhang_2000_Genome.Res_10_1546 PubMedSearch: Zhang 2000 Genome.Res 10 1546 PubMedID: 11042152 Gene_locus related to this paper: human-LYPLA1 Abstract Three hundred cDNAs containing putatively entire open reading frames (ORFs) for previously undefined genes were obtained from CD34+ hematopoietic stem/progenitor cells (HSPCs), based on EST cataloging, clone sequencing, in silico cloning, and rapid amplification of cDNA ends (RACE). The cDNA sizes ranged from 360 to 3496 bp and their ORFs coded for peptides of 58-752 amino acids. Public database search indicated that 225 cDNAs exhibited sequence similarities to genes identified across a variety of species. Homology analysis led to the recognition of 50 basic structural motifs/domains among these cDNAs. Genomic exon-intron organization could be established in 243 genes by integration of cDNA data with genome sequence information. Interestingly, a new gene named as HSPC070 on 3p was found to share a sequence of 105bp in 3' UTR with RAF gene in reversed transcription orientation. Chromosomal localizations were obtained using electronic mapping for 192 genes and with radiation hybrid (RH) for 38 genes. Macroarray technique was applied to screen the gene expression patterns in five hematopoietic cell lines (NB4, HL60, U937, K562, and Jurkat) and a number of genes with differential expression were found. The resource work has provided a wide range of information useful not only for expression genomics and annotation of genomic DNA sequence, but also for further research on the function of genes involved in hematopoietic development and differentiation. Title: The Acetylcholinesterase Gene and Organophosphorous Resistance in the Australian Sheep Blowfly, Lucilia Cuprina Chen Z, Forbes E, Newcomb RD, McKenzie JA, Batterham P Ref: In: Structure and Function of Cholinesterases and Related Proteins - Proceedings of Sixth International Meeting on Cholinesterases, (Doctor, B.P., Taylor, P., Quinn, D.M., Rotundo, R.L., Gentry, M.K. Eds) Plenum Publishing Corp.:550, 1998 : PubMed ESTHER: Chen_1998_6th.ChE.Meeting.San.Diego__550 PubMedSearch: Chen 1998 6th.ChE.Meeting.San.Diego 550 Title: Regiospecificity and catalytic triad of lysophospholipase I Wang A, Loo R, Chen Z, Dennis EA Ref: Journal of Biological Chemistry, 272:22030, 1997 : PubMed ESTHER: Wang_1997_J.Biol.Chem_272_22030 PubMedSearch: Wang 1997 J.Biol.Chem 272 22030 PubMedID: 9268342 Gene_locus related to this paper: mouse-lypla1 Abstract A 25-kDa murine lysophospholipase (LysoPLA I) has been cloned and expressed, and Ser-119 has been shown to be essential for the enzyme activity (Wang, A., Deems, R. A., and Dennis, E. A. (1997) J. Biol. Chem. 272, 12723-12729). In the present study, we show that LysoPLA I represents a new member of the serine hydrolase family with Ser-119, Asp-174, and His-208 composing the catalytic triad. The Asp-174 and His-208 are conserved among several esterases and are demonstrated herein to be essential for LysoPLA I activity as the mutation of either residue to Ala abolished LysoPLA I activity, whereas the global conformation of the mutants remained unchanged. Furthermore, the predicted secondary structure of LysoPLA I resembles that of the alpha/beta-hydrolase fold, with Ser-119, Asp-174, and His-208 occupying the conserved topological location of the catalytic triad in the alpha/beta-hydrolases. Structural modeling of LysoPLA I also indicates that the above three residues orient in such a manner that they would comprise a charge-relay network necessary for catalysis. In addition, the regiospecificity of LysoPLA I was studied using 31P NMR, and the result shows that LysoPLA I has similar LysoPLA1 and LysoPLA2 activity. This finding suggests that LysoPLA I may play an important role in removing lysophospholipids produced by both phospholipase A1 and A2 in vivo. | |||||||
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