Author Report for: Hu SNo contact information in database for Hu S
Hu S, Huang R, Keller P, Gotz M, Tamalunas A, Weinhold P, Waidelich R, Stief CG, Hennenberg M Ref: Neurourol Urodyn, 42:1522, 2023 : PubMed ESTHER: Hu_2023_Neurourol.Urodyn_42_1522 PubMedSearch: Hu 2023 Neurourol.Urodyn 42 1522 PubMedID: 37583250 Abstract BACKGROUND: Phospholipases A(2) (PLA(2) ) may be involved in alpha(1) -adrenergic contraction by formation of thromboxane A(2) in different smooth muscle types. However, whether this mechanism occurs with alpha(1) -adrenergic contractions of the prostate, is still unknown. While alpha(1) -adrenoceptor antagonists are the first line option for medical treatment of voiding symptoms in benign prostatic hyperplasia (BPH), improvements are limited, probably by nonadrenergic contractions including thromboxane A(2) . Here, we examined effects of PLA(2) inhibitors on contractions of human prostate tissues. METHODS: Prostate tissues were obtained from radical prostatectomy. Contractions were induced by electric field stimulation (EFS) and by alpha(1) -adrenergic agonists in an organ bath, after application of the cytosolic PLA(2) inhibitors ASB14780 and AACOCF3, the secretory PLA(2) inhibitor YM26734, the leukotriene receptor antagonist montelukast, or of solvent to controls. RESULTS: Frequency-dependent contractions of human prostate tissues induced by EFS were inhibited by 25% at 8 Hz, 38% at 16 Hz and 37% at 32 Hz by ASB14780 (1 microM), and by 32% at 16 Hz and 22% at 32 Hz by AACOCF3 (10 microM). None of both inhibitors affected contractions induced by noradrenaline, phenylephrine or methoxamine. YM26734 (3 microM) and montelukast (0.3 and 1 microM) neither affected EFS-induced contractions, nor contractions by alpha(1) -adrenergic agonists, while all contractions were substantially inhibited by silodosin (100 nM). CONCLUSIONS: Our findings suggest presynaptic PLA(2) functions in prostate smooth muscle contraction, while contractions induced by alpha(1) -adrenergic agonists occur PLA(2) -independent. Lacking sensitivity to montelukast excludes an involvement of PLA(2) -derived leukotrienes in promotion of contractile neurotransmission. Title: Toxic effects of isofenphos-methyl on zebrafish embryonic development Wu Y, Wang J, Xia Y, Tang K, Xu J, Wang A, Hu S, Wen L, Wang B, Yao W Ref: Ecotoxicology & Environmental Safety, 254:114723, 2023 : PubMed ESTHER: Wu_2023_Ecotoxicol.Environ.Saf_254_114723 PubMedSearch: Wu 2023 Ecotoxicol.Environ.Saf 254 114723 PubMedID: 36871354 Inhibitor(s) related to this paper: Isofenphos-methyl Abstract Isofenphos-methyl (IFP) is widely used as an organophosphorus for controlling underground insects and nematodes. However, excessive use of IFP may pose potential risks to the environment and humans, but little information is available on its sublethal toxicity to aquatic organisms. To address this knowledge gap, the current study exposed zebrafish embryos to 2, 4, and 8 mg/L IFP within 6-96 h past fertilization (hpf) and measured mortality, hatching, developmental abnormalities, oxidative stress, gene expressions, and locomotor activity. The results showed that IFP exposure reduced the rates of heart and survival rate, hatchability, and body length of embryos and induced uninflated swim bladder and developmental malformations. Reduction in locomotive behavior and inhibition of AChE activity indicated that IFP exposure may induce behavioral defects and neurotoxicity in zebrafish larvae. IFP exposure also led to pericardial edema, longer venous sinus-arterial bulb (SV-BA) distance, and apoptosis of the heart cells. Moreover, IFP exposure increased the accumulation of reactive oxygen species (ROS) and the content of malonaldehyde (MDA), also elevated the levels of antioxidant enzymes of superoxide dismutase (SOD) and catalase (CAT), but decreased glutathione (GSH) levels in zebrafish embryos. The relative expressions of heart development-related genes (nkx2.5, nppa, gata4, and tbx2b), apoptosis-related genes (bcl2, p53, bax, and puma), and swim bladder development-related genes (foxA3, anxa5b, mnx1, and has2) were significantly altered by IFP exposure. Collectively, our results indicated that IFP induced developmental toxicity and neurotoxicity to zebrafish embryos and the mechanisms may be relevant to the activation of oxidative stress and reduction of acetylcholinesterase (AChE) content. Title: Design, synthesis, and evaluation of hydrazones as dual inhibitors of ryanodine receptors and acetylcholinesterases for Alzheimer's disease Yang F, Zhao J, Chen G, Han H, Hu S, Wang N, Wang J, Chen Y, Zhou Z and Liu Y <2 more author(s)> Yang F, Zhao J, Chen G, Han H, Hu S, Wang N, Wang J, Chen Y, Zhou Z, Dai B, Hou Y, Liu Y (- 2) Ref: Bioorg Chem, 133:106432, 2023 : PubMed ESTHER: Yang_2023_Bioorg.Chem_133_106432 PubMedSearch: Yang 2023 Bioorg.Chem 133 106432 PubMedID: 36841050 Abstract Alzheimer's disease (AD) implicates neuronal loss, plaque and neurofibrillary tangle formation, and disturbed neuronal Ca(2+) homeostasis, which leads to severe dementia, memory loss, as well as thinking and behavioral perturbations that could ultimately lead to death. Calcium dysregulation and low acetylcholine levels are two main mechanisms implicated in Alzheimer's disease progression. Simultaneous inhibition of calcium oscillations (store overload-induced Ca(2+) release [SOICR]) and acetylcholinesterase (AChE) by a single molecule may bring a new breath of hope for AD treatment. Here, we described some dantrolene derivatives as dual inhibitors of the ryanodine receptor and AChE. Two series of acylhydrazone/sulfonylhydrazone derivatives with aromaticgroup were designed and synthesized. In this study, the target compounds were evaluated for their ability to inhibit SOICR and AChE in vitro, using dantrolene and donepezil as positive controls. Compound 22a exhibited excellent and balanced inhibitory potency against SOICR (inhibition (%) = 90.1, IC(50) = 0.162 microM) and AChE (inhibition (%) = 93.5, IC(50) = 0.372 microM). Docking simulations showed that several preferred compounds could bind to the active sites of both the proteins, further validating the rationality of the design strategy. Potential therapeutic effects in AD were evaluated using the Barnes maze and Morris water maze tests, which demonstrated that compound 22a significantly improved memory and cognitive behavior in AD model mice. Moreover, it was also found that compound 22a could enhance synaptic strength by measuring hippocampal long-term potentiation (LTP) in brain slices. These results suggested that the introduction of a sulfonyl-hydrazone scaffold and aromatic substitution to dantrolene derivatives provided a useful template for the development of potential chemical entities against AD. Title: Neuroprotective Effect and Possible Mechanisms of Berberine in Diabetes-Related Cognitive Impairment: A Systematic Review and Meta-Analysis of Animal Studies Hao Y, Li J, Yue S, Wang S, Hu S, Li B Ref: Front Pharmacol, 13:917375, 2022 : PubMed ESTHER: Hao_2022_Front.Pharmacol_13_917375 PubMedSearch: Hao 2022 Front.Pharmacol 13 917375 PubMedID: 35734409 Abstract Berberine, the main bioactive component of Coptis chinensis Franch., is widely used in the treatment of diabetes. Previous studies have reported that berberine supplementation may play a multitarget therapeutic role in diabetes-related cognitive impairment (DCI). This systematic review and meta-analysis evaluated the effect and possible mechanisms of berberine in animal models of DCI. Relevant studies were searched through PubMed, Web of Science, Embase, and three Chinese databases (CNKI, Wanfang, and VIP) until March 2022. Twenty studies involving 442 animals were included, and SYRCLE's risk of bias tool was used to assess methodological quality. The statistical analysis was performed using STATA 15.0 to calculate the weighted standard mean difference (SMD) with a 95% confidence interval (CI). The fasting blood glucose (FBG) and Morris water maze test (MWM) were the main outcomes to be analyzed. The overall results showed that berberine could significantly improve FBG, escape latency, the times of crossing the platform, the time spent in the target quadrant, serum insulin, 2hBG of oral glucose tolerance test (OGTT), amyloid beta (Abeta), acetylcholinesterase (AChE), oxidative stress, and inflammation levels. The present meta-analysis demonstrated that berberine could not only lower blood glucose levels but also improve learning and memory in DCI animal models, which might involve regulating glucose and lipid metabolism, improving insulin resistance, anti-oxidation, anti-neuroinflammation, inhibiting endoplasmic reticulum (ER) stress; and improving the cholinergic system. However, additional attention should be paid to these outcomes due to the significant heterogeneity. Title: Tuning the Properties of Ester-Based Degradable Polymers by Inserting Epoxides into Poly(E-caprolactone) Hu S, Liu L, Li H, Pahovnik D, Hadjichristidis N, Zhou X, Zhao J Ref: Chem Asian J, :e202201097, 2022 : PubMed ESTHER: Hu_2022_Chem.Asian.J__e202201097 PubMedSearch: Hu 2022 Chem.Asian.J e202201097 PubMedID: 36424185 Abstract A series of ester-ether copolymers were obtained via the reaction between alpha,omega-dihydroxyl poly(E-caprolactone) (PCL) and ethylene oxide (EO) or monosubstituted epoxides catalyzed by strong phosphazene bases. The two types of monomeric units were distributed in highly random manners due to the concurrence of epoxide ring-opening and fast transesterification reactions. The substituent of epoxide showed an interesting bidirectional effect on the enzymatic degradability of the copolymer. Compared with PCL, copolymers derived from EO exhibited enhanced hydrophilicity and decreased crystallinity which then resulted in higher degradability. For the copolymers derived from propylene oxide and 1,2-butylene oxide, the hydrophobic alkyl pendant groups also allowed lower crystallinity of the copolymers thus higher degradation rates. However, further enlarging the pendant groups by using styrene oxide or 2-ethylhexyl glycidyl ether caused a decrease in the degradation rate, which might be ascribed to the higher bulkiness hindering the contact of ester groups with lipase. Title: Nanosurface-immobilized lipase and its degradation of phthalate wastewater Sun Y, Guo M, Hu S, Fang X, Jin Z, Wu R Ref: Molecular Catalysis, 529:112522, 2022 : PubMed ESTHER: Sun_2022_Mol.Catal_529_112522 PubMedSearch: Sun 2022 Mol.Catal 529 112522 Abstract Phthalic acid esters (PAEs) are hard-to-degrade organic pollutants of current concern, and enzyme degradation is a green method for effective degradation of PAEs. To improve the recognition of PAEs, the combination of molecular blotting and immobilized enzyme technology is a novel and efficient method for the degradation of PAEs. In this study, molecularly imprinted carrier (MIP-HNTs) was prepared from halloysite nanotubes (HNTs), using di(2-ethylhexyl) phthalate (DEHP) as the template molecule, methyl methacrylate (MMA) as the functional monomer and (ethylene methacrylate) EDGMA as the cross-linking agent. A novel immobilized enzyme (MIP-HNTs@lipase) was prepared successfully via glutaraldehyde cross-linking, subsequently. The lipase loading efficiency was 76%. The optimal enzymatic activity conditions for MIP-HNTs@lipase were determined to be pH=9 and 50 degreesC. The MIP-HNTs@lipase exhibited good stability and efficient degradation of DEHP with a degradation rate of 94.758% when the DEHP concentration was at 5 mg.L-1. This research provided a new strategy for industrial application of enzymes and degradation of persistent pollutants. Title: Soluble Epoxide Hydrolase Deletion Attenuated Nicotine-induced Arterial Stiffness via Limiting the Loss of SIRT1 Hu S, Luo J, Fu M, Luo L, Cai Y, Li W, Li Y, Dong R, Yang Y and Xu X <1 more author(s)> Hu S, Luo J, Fu M, Luo L, Cai Y, Li W, Li Y, Dong R, Yang Y, Tu L, Xu X (- 1) Ref: American Journal of Physiology Heart Circ Physiol, :, 2021 : PubMed ESTHER: Hu_2021_Am.J.Physiol.Heart.Circ.Physiol__ PubMedSearch: Hu 2021 Am.J.Physiol.Heart.Circ.Physiol PubMedID: 34142887 Abstract Arterial stiffness, a consequence of smoking, is an underlying risk factor of cardiovascular diseases. Epoxyeicosatrienoic acids (EETs), hydrolyzed by soluble epoxide hydrolase (sEH), have beneficial effects against vascular dysfunction. However, the role of sEH knockout in nicotine-induced arterial stiffness was not characterized. We hypothesized that sEH knockout could prevent nicotine-induced arterial stiffness. In the present study, Ephx2 (the gene encodes sEH enzyme) null (Ephx2(-/-)) mice and wild-type (WT) littermate mice were infused with or without nicotine and administered with or without nicotinamide (NAM, SIRT1 inhibitor) simultaneously for four weeks. Nicotine treatment increased sEH expression and activity in the aortas of WT mice. Nicotine infusion significantly induced vascular remodeling, arterial stiffness, and SIRT1 deactivation in WT mice, which was attenuated in Ephx2(-/-) mice without NAM treatment. However, the arterial protective effects were gone in Ephx2(-/-) mice with NAM treatment. In vitro, 11,12-EET treatment attenuated nicotine-induced MMP2 upregulation via SIRT1-mediated YAP deacetylation. In conclusion, sEH knockout attenuated nicotine-induced arterial stiffness and vascular remodeling via SIRT1-induced YAP deacetylation. Title: Hormetic Effects of Dimethachlone on Mycelial Growth and Virulence of Sclerotinia sclerotiorum Hu S, Li J, Wang P, Zhu F Ref: Phytopathology, 111:1166, 2021 : PubMed ESTHER: Hu_2021_Phytopathology_111_1166 PubMedSearch: Hu 2021 Phytopathology 111 1166 PubMedID: 33107780 Abstract Fungicide hormesis has implications for the application of fungicides to control plant diseases. We investigated the hormetic effects of the dicarboximide fungicide dimethachlone on mycelial growth and virulence of the necrotrophic plant pathogen Sclerotinia sclerotiorum. Dimethachlone at sublethal doses in potato dextrose agar (PDA) increased the mycelial growth of S. sclerotiorum. After the growth-stimulated mycelia were subcultured on fresh PDA and inoculated on rapeseed leaves, increased mycelial growth and virulence were observed, indicating that hormetic traits were passed down to the next generation. Dimethachlone applied to leaves at 0.002 to 500 microg/ml stimulated virulence, with a maximum stimulation amplitude (MSA) of 31.4% for the isolate HLJ4, which occurred at 2 microg/ml. Dimethachlone-resistant isolates and transformants had a mean virulence MSA of 30.4%, which was significantly higher (P = 0.008) than the MSA for sensitive isolates (16.2%). Negative correlations were detected between MSA and virulence in the absence of any fungicide (r = -0.872, P < 0.001) and between MSA and mycelial growth on PDA (r = -0.794, P = 0.002). Studies on hormetic mechanisms indicated that dimethachlone had no significant effects on expression levels of three virulence-associated genes, that is, a cutinase-encoding gene SsCut, a polygalacturonase gene SsPG1, or an oxaloacetate acetylhydrolase gene SsOah1. The results will contribute to understanding hormesis and have implications for the judicious application of fungicides to control plant diseases. Title: Inhibition of soluble epoxide hydrolase alleviates insulin resistance and hypertension via downregulation of SGLT2 in the mouse kidney Luo J, Hu S, Fu M, Luo L, Li Y, Li W, Cai Y, Dong R, Yang Y and Xu X <1 more author(s)> Luo J, Hu S, Fu M, Luo L, Li Y, Li W, Cai Y, Dong R, Yang Y, Tu L, Xu X (- 1) Ref: Journal of Biological Chemistry, :100667, 2021 : PubMed ESTHER: Luo_2021_J.Biol.Chem__100667 PubMedSearch: Luo 2021 J.Biol.Chem 100667 PubMedID: 33864813 Abstract The epoxyeicosatrienoic acid (EET) exerts beneficial effects on insulin resistance and/or hypertension. EETs could be readily converted to less biological active diols by soluble epoxide hydrolase (sEH). However, whether sEH inhibition can ameliorate the comorbidities of insulin resistance and hypertension, and the underlying mechanisms of this relationship, are unclear. In this study, C57BL/6 mice were rendered hypertensive and insulin resistant through a high-fat and high-salt (HF-HS) diet. The sEH inhibitor trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was used to treat mice (1 mg/kg/d) for 8 weeks, followed by analysis of metabolic parameters. The expression of sEH and the sodium-glucose cotransporter 2 (SGLT2) were markedly upregulated in the kidneys of mice fed a HF-HS diet. We found that TPPU administration increased kidney EET levels, improved insulin resistance, and reduced hypertension. Furthermore, TPPU treatment prevented upregulation of SGLT2, and the associated increased urine volume and the excretion of urine glucose and urine sodium. Importantly, TPPU alleviated renal inflammation. In vitro, human renal proximal tubule epithelial cells (HK-2 cells) were used to further investigate the underlying mechanism. We observed that 14,15-EET or sEH knock-down or inhibition prevented the upregulation of SGLT2 upon treatment with palmitic acid or NaCl by inhibiting the IKKalpha/beta/NF-kappaB signaling pathway. In conclusion, sEH inhibition by TPPU alleviated insulin resistance and hypertension induced by a HF-HS diet in mice. The increased urine excretion of glucose and sodium was mediated by decreased renal SGLT2 expression due to inactivation of the IKKalpha/beta/NF-kappaB-induced inflammatory response. Title: Promising tacrine/huperzine A-based dimeric acetylcholinesterase inhibitors for neurodegenerative disorders: From relieving symptoms to modifying diseases through multitarget Mak S, Li W, Fu H, Luo J, Cui W, Hu S, Pang Y, Carlier PR, Tsim KW and Han Y <1 more author(s)> Mak S, Li W, Fu H, Luo J, Cui W, Hu S, Pang Y, Carlier PR, Tsim KW, Pi R, Han Y (- 1) Ref: Journal of Neurochemistry, :, 2021 : PubMed ESTHER: Mak_2021_J.Neurochem__ PubMedSearch: Mak 2021 J.Neurochem PubMedID: 33930191 Inhibitor(s) related to this paper: Bis7-tacrine, Bis3-tacrine, (S,S)-(-)-bis(12)-hupyridone, Hupyridone Abstract Neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, are devastating diseases in the elderly world, which are closely associated with progressive neuronal loss induced by a variety of genetic and/or environmental factors. Unfortunately, currently available treatments for neurodegenerative disorders can only relieve the symptoms but not modify the pathological processes. Over the past decades, our group by collaborating with Profs. Yuan-Ping Pang and Paul R. Carlier has developed three series of homo/hetero dimeric acetylcholinesterase inhibitors derived from tacrine and/or huperzine A. The representative dimers bis(3)-Cognitin (B3C), bis(12)-hupyridone, and tacrine(10)-hupyridone might possess disease-modifying effects through the modulation of N-methyl-d-aspartic acid receptors, the activation of myocyte enhancer factor 2D gene transcription, and the promotion of neurotrophic factor secretion. In this review, we summarize that the representative dimers, such as B3C, provide neuroprotection against a variety of neurotoxins via multiple targets, including the inhibitions of N-methyl-d-aspartic acid receptor with pathological-activated potential, neuronal nitric oxide synthase, and beta-amyloid cascades synergistically. More importantly, B3C might offer disease-modifying potentials by activating myocyte enhancer factor 2D transcription, inducing neuritogenesis, and promoting the expressions of neurotrophic factors in vitro and in vivo. Taken together, the novel dimers might offer synergistic disease-modifying effects, proving that dimerization might serve as one of the strategies to develop new generation of therapeutics for neurodegenerative disorders. Title: Dimeric Tacrine(10)-hupyridone as a Multitarget-Directed Ligand To Treat Alzheimer's Disease Xuan Z, Gu X, Yan S, Xie Y, Zhou Y, Zhang H, Jin H, Hu S, Mak MSH and Cui W <4 more author(s)> Xuan Z, Gu X, Yan S, Xie Y, Zhou Y, Zhang H, Jin H, Hu S, Mak MSH, Zhou D, Tsim KWK, Carlier PR, Han Y, Cui W (- 4) Ref: ACS Chem Neurosci, 12:2462, 2021 : PubMed ESTHER: Xuan_2021_ACS.Chem.Neurosci_12_2462 PubMedSearch: Xuan 2021 ACS.Chem.Neurosci 12 2462 PubMedID: 34156230 Inhibitor(s) related to this paper: (R)-Tacrine(10)-Hupyridone, Hupyridone Abstract Alzheimer's disease (AD) is a neurodegenerative disorder with multiple pathological features. Therefore, a multitarget-directed ligands (MTDLs) strategy has been developed to treat AD. We have previously designed and synthesized dimeric tacrine(10)-hupyridone (A10E), a novel tacrine derivative with acetylcholinesterase (AChE) inhibition and brain-derived neurotrophic factor (BDNF) activation activity, by linking tacrine and a fragment of huperzine A. However, it was largely unknown whether A10E could act on other AD targets and produce cognitive-enhancing ability in AD animal models. In this study, A10E could prevent cognitive impairments in APP/PS1 transgenic mice and beta-amyloid (Abeta) oligomers-treated mice, with higher potency than tacrine and huperzine A. Moreover, A10E could effectively inhibit Abeta production and deposition, alleviate neuroinflammation, enhance BDNF expression, and elevate cholinergic neurotransmission in vivo. At nanomolar concentrations, A10E could inhibit Abeta oligomers-induced neurotoxicity via the activation of tyrosine kinase receptor B (TrkB)/Akt pathway in SH-SY5Y cells. Furthermore, Abeta oligomerization and fibrillization could be directly disrupted by A10E. Importantly, A10E at high concentrations did not produce obvious hepatotoxicity. Our results indicated that A10E could produce anti-AD neuroprotective effects via the inhibition of Abeta aggregation, the activation of the BDNF/TrkB pathway, the alleviation of neuroinflammation, and the decrease of AChE activity. As MTDLs could produce additional benefits, such as overcoming the deficits of drug combination and enhancing the compliance of AD patients, our results also suggested that A10E might be developed as a promising MTDL lead for the treatment of AD. Title: Comprehensive Interrogation on Acetylcholinesterase Inhibition by Ionic Liquids Using Machine Learning and Molecular Modeling Yan J, Yan X, Hu S, Zhu H, Yan B Ref: Environ Sci Technol, :, 2021 : PubMed ESTHER: Yan_2021_Environ.Sci.Technol__ PubMedSearch: Yan 2021 Environ.Sci.Technol PubMedID: 34636548 Abstract Quantitative structure-activity relationship (QSAR) modeling can be used to predict the toxicity of ionic liquids (ILs), but most QSAR models have been constructed by arbitrarily selecting one machine learning method and ignored the overall interactions between ILs and biological systems, such as proteins. In order to obtain more reliable and interpretable QSAR models and reveal the related molecular mechanism, we performed a systematic analysis of acetylcholinesterase (AChE) inhibition by 153 ILs using machine learning and molecular modeling. Our results showed that more reliable and stable QSAR models (R(2) > 0.85 for both cross-validation and external validation) were obtained by combining the results from multiple machine learning approaches. In addition, molecular docking results revealed that the cations and organic anions of ILs bound to specific amino acid residues of AChE through noncovalent interactions such as Pi interactions and hydrogen bonds. The calculation results of binding free energy showed that an electrostatic interaction (deltaE(ele) < -285 kJ/mol) was the main driving force for the binding of ILs to AChE. The overall findings from this investigation demonstrate that a systematic approach is much more convincing. Future research in this direction will help design the next generation of biosafe ILs. 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: A new fluorescent probe for sensing of biothiols and screening of acetylcholinesterase inhibitors Wu S, Li Y, Deng T, Wang X, Hu S, Peng G, Huang XA, Ling Y, Liu F Ref: Org Biomol Chem, :, 2020 : PubMed ESTHER: Wu_2020_Org.Biomol.Chem__ PubMedSearch: Wu 2020 Org.Biomol.Chem PubMedID: 32167516 Abstract A new N2O-type BODIPY probe (LF-Bop) has been proposed for the selective and sensitive detection of biologically relevant small molecular thiols. This detection is based on the Michael addition reaction between the thiol and nitrostyrene groups in the probe, which decreases the quenching effect from the nitro group, thus resulting in the recovery of the deep-red fluorescence from the BODIPY structure. The results show that LF-Bop is able to detect all tested free thiols through a fluorescence turn-on assay. The lowest limit of detection (LOD) for glutathione was found to be down to nanomolar levels (220 nM). Based on this probe, we have developed a new fluorescence assay for the screening of acetylcholinesterase inhibitors. In total, 11 natural and synthetic alkaloids have been evaluated. Both experimental measurements and theoretical molecular docking results reveal that both natural berberine and its synthetic derivative dihydroberberine are potential inhibitors of acetylcholinesterase. Title: Hepatocyte-Specific Expression of Human Carboxylesterase 1 Attenuates Diet-Induced Steatohepatitis and Hyperlipidemia in Mice Xu Y, Zhu Y, Bawa FC, Hu S, Pan X, Yin L, Zhang Y Ref: Hepatol Commun, 4:527, 2020 : PubMed ESTHER: Xu_2020_Hepatol.Commun_4_527 PubMedSearch: Xu 2020 Hepatol.Commun 4 527 PubMedID: 32258948 Abstract Rodents have at least five carboxylesterase 1 (Ces1) genes, whereas there is only one CES1 gene in humans, raising the question as to whether human CES1 and mouse Ces1 genes share the same functions. In this study, we investigate the role of human CES1 in the development of steatohepatitis or dyslipidemia in C57BL/6 mice. Hepatocyte-specific expression of human CES1 prevented Western diet or alcohol-induced steatohepatitis and hyperlipidemia. Mechanistically, human CES1 induced lipolysis and fatty acid oxidation, leading to a reduction in hepatic triglyceride and free fatty acid levels. Human CES1 also reduced hepatic-free cholesterol levels and induced low-density lipoprotein receptor. In addition, human CES1 induced hepatic lipoprotein lipase and apolipoprotein C-II expression. Conclusion: Hepatocyte-specific overexpression of human CES1 attenuates diet-induced steatohepatitis and hyperlipidemia. Title: Hepatocyte-specific Expression of Human Carboxylesterase 2 Attenuates Non-alcoholic Steatohepatitis in Mice Xu Y, Pan X, Hu S, Zhu Y, Cassim Bawa F, Li Y, Yin L, Zhang Y Ref: American Journal of Physiology Gastrointest Liver Physiol, :, 2020 : PubMed ESTHER: Xu_2020_Am.J.Physiol.Gastrointest.Liver.Physiol__ PubMedSearch: Xu 2020 Am.J.Physiol.Gastrointest.Liver.Physiol PubMedID: 33325808 Abstract Human carboxylesterase 2 (CES2) has triacylglycerol hydrolase (TGH) activities and plays an important role in lipolysis. In this study, we aim to determine the role of human CES2 in the progression or reversal of steatohepatitis in diet-induced or genetically obese mice. High-fat/high-cholesterol/high-fructose (HFCF) diet-fed C57BL/6 mice or db/db mice were i.v. injected with an adeno-associated virus expressing human CES2 under the control of an albumin promoter. Human CES2 protected against HFCF diet-induced non-alcoholic fatty liver disease (NAFLD) in C57BL/6J mice and reversed steatohepatitis in db/db mice. Human CES2 also improved glucose tolerance and insulin sensitivity. Mechanistically, human CES2 reduced hepatic triglyceride and free fatty acid levels by inducing lipolysis and fatty acid oxidation and inhibiting lipogenesis via suppression of sterol regulatory element-binding protein 1. Furthermore, human CES2 overexpression improved mitochondrial respiration and glycolytic function, and inhibited gluconeogenesis, lipid peroxidation, apoptosis and inflammation. Our data suggest that hepatocyte-specific expression of human CES2 prevents and reverses steatohepatitis. Targeting hepatic CES2 may be an attractive strategy for treatment of NAFLD. Title: Gene polymorphism associated with Angiotensinogen(M235T), Endothelial lipase (584C/T) and susceptibility to coronary artery disease: A meta-analysis Zhao H, Zhao R, Hu S, Rong J Ref: Bioscience Reports, :, 2020 : PubMed ESTHER: Zhao_2020_Biosci.Rep__ PubMedSearch: Zhao 2020 Biosci.Rep PubMedID: 32667032 Abstract OBJECTIVE: To explore the association between the variant M235T locus of angiotensinogen (AGT) gene, 584C/T locus of Endothelial lipase (EL) gene, and coronary artery disease (CAD) by meta-analysis. METHODS: The case-control studies on the association between AGT/EL gene polymorphism and CAD were collected through searching PubMed, EMbase, Web of Science, CNKI and Wanfang database up to March 1, 2020. Stata 15.0 software was used for analysis. RESULTS: A total of 29 articles met the inclusion criteria. After analyzing, it was found that the M235T polymorphism of AGT gene was associated with the occurrence of CAD. In the allele model (T vs. M), OR=1.38 (P < 0.05). In other heredity, there was also statistically significant. Subgroup analysis indicated that except the heterozygous genetic model of the Chinese population, other genetic models of the Caucasian and Chinese population were also statistically significant. The 584C/T polymorphism of EL gene was associated with the occurrence of CAD, with OR=0.83 (P < 0.05) in the allele model (T vs. C) and OR=0.80 (P < 0.05) in the dominant gene model. Also, in the allele model of Caucasian subgroup, OR=0.83 (P < 0.05), while in Asian subgroup, there was no statistically significant genetic model. CONCLUSION: AGT M235T and EL 584C/T polymorphisms are associated with CAD susceptibility. The genotype TT, TC or allele T of AGT M235T and genotype CC or allele C of EL 584C/T might be the genetic risk factors for the development of CAD. Title: Directed Evolution of Sulfonylurea Esterase and Characterization of a Variant with Improved Activity Liu B, Peng Q, Sheng M, Hu S, Qian M, Fan B, He J Ref: Journal of Agricultural and Food Chemistry, 67:836, 2019 : PubMed ESTHER: Liu_2019_J.Agric.Food.Chem_67_836 PubMedSearch: Liu 2019 J.Agric.Food.Chem 67 836 PubMedID: 30585487 Gene_locus related to this paper: 9rhiz-g9i933 Abstract Esterase SulE detoxicates a variety of sulfonylurea herbicides through de-esterification. SulE exhibits high activity against thifensulfuron-methyl but low activity against other sulfonylureas. In this study, two variants, m2311 (P80R) and m0569 (P80R and G176A), with improved activity were screened from a mutation library constructed by error-prone PCR. Variant m2311 showed a higher activity against sulfonylureas in comparison variant m0569 and was further investigated. The kcat/ Km value of variant m2311 for metsulfuron-methyl, sulfometuron-methyl, chlorimuron-ethyl, tribenuron-methyl, and ethametsulfuron-methyl increased by 3.20-, 1.72-, 2.94-, 2.26- and 2.96-fold, respectively, in comparison with the wild type. Molecular modeling suggested that the activity improvement of variant m2311 is due to the substitution of Pro80 by arginine, leading to the formation of new hydrogen bonds between the enzyme and substrate. This study facilitates further elucidation of the structure and function of SulE and provides an improved gene resource for the detoxification of sulfonylurea residues and the genetic engineering of sulfonylurea-resistant crops. Title: Excipient-free nanodispersion of 7-ethyl-10-hydroxycamptothecin exerts potent therapeutic effects against pancreatic cancer cell lines and patient-derived xenografts Zhang L, Zhou J, Yan Y, Zhou X, Zhou Q, Du R, Hu S, Ge W, Huang Y and Wang W <5 more author(s)> Zhang L, Zhou J, Yan Y, Zhou X, Zhou Q, Du R, Hu S, Ge W, Huang Y, Xu H, Kong Y, Zheng H, Ding Y, Shen Y, Wang W (- 5) Ref: Cancer Letters, 465:36, 2019 : PubMed ESTHER: Zhang_2019_Cancer.Lett_465_36 PubMedSearch: Zhang 2019 Cancer.Lett 465 36 PubMedID: 31479691 Abstract Irinotecan (CPT-11) is an anti-tumor drug and formulated as nanomedicines to reduce side effects and improve efficacy. In vivo, CPT-11 must be hydrolyzed by carboxylesterase to its active form 7-ethyl-10-hydroxycamptothecin (SN-38) to exert anti-tumor activity, but the lack of this enzyme in humans causes inefficient generation of SN-38. Thus, direct delivery of SN-38, not relying on carboxylesterase, will potentially achieve higher efficacy. However, it is difficult to effectively formulate SN-38 using current excipients due to its hydrophobicity and tendency to crystallize. Herein, we report the nanodispersion of SN-38 with its amphiphilic prodrug, CPT-11, as an effective treatment for pancreatic cancer (PC). SN-38 and CPT-11 formed stable nanoparticles without any other excipients, and showed potent cytotoxicity against PC cells in vitro, slowed tumor growth in vivo, namely subcutaneously and orthotopically xenografted mice, with minimal adverse effects, and prolonged their overall survival. Even in clinically-relevant patient-derived xenograft (PDX) models, the nanodispersion showed greater anti-tumor efficacy than CPT-11. Importantly, the nanodispersion directly released SN-38, resulting in carboxylesterase-independent anti-tumor activity, in contrast to carboxylesterase-dependent CPT-11. These characteristics may enable the excipient-free nanodispersion to exert potent therapeutic effects in patients. Title: Tacrine(10)-hupyridone, a dual-binding acetylcholinesterase inhibitor, potently attenuates scopolamine-induced impairments of cognition in mice Chen H, Xiang S, Huang L, Lin J, Hu S, Mak SH, Wang C, Wang Q, Cui W, Han Y Ref: Metabolic Brain Disease, 33:1131, 2018 : PubMed ESTHER: Chen_2018_Metab.Brain.Dis_33_1131 PubMedSearch: Chen 2018 Metab.Brain.Dis 33 1131 PubMedID: 29564727 Inhibitor(s) related to this paper: Hupyridone Abstract Tacrine(10)-hupyridone (A10E) was designed as a dual-binding acetylcholinesterase (AChE) inhibitor from the modification of tacrine and a fragment of huperzine A. We have found that A10E effectively inhibited AChE in a mixed competitive manner, with an IC50 of 26.4 nM, which is more potent than those of tacrine and huperzine A. Most importantly, we have shown, for the first time that A10E attenuated scopolamine-induced cognitive impairments without affecting motor function in mice. A10E effectively attenuated impairments of learning and memory to a similar extent as donepezil, an inhibitor of AChE used for treating Alzheimer's disease (AD). In addition, A10E significantly decreased AChE activity in the brain of mice, suggesting that A10E might cross the brain blood-barrier. Taken together, our results demonstrated that A10E, a designed dual-binding AChE inhibitor, could effectively reverse cognitive impairments, indicating that A10E might provide therapeutic efficacy for AD treatment. Title: Inhibitory Influence of Panax notoginseng Saponins on Aspirin Hydrolysis in Human Intestinal Caco-2 Cells Sun Z, Wu Y, Yang B, Zhu B, Hu S, Lu Y, Zhao B, Du S Ref: Molecules, 23:, 2018 : PubMed ESTHER: Sun_2018_Molecules_23_ PubMedSearch: Sun 2018 Molecules 23 PubMedID: 29463025 Abstract Herb-drug interactions are important safety concerns in clinical practice. The interactions occur firstly in the intestinal absorption for orally administered drugs. Aspirin and Panax notoginseng saponins (PNS)-based drugs are often combined in China to prevent larger-artery atherosclerosis. Here, we aimed to characterize the aspirin transport across Caco-2 cell monolayers, a model of the intestinal absorption, and further to evaluate the influence of PNS on aspirin hydrolysis and the relating mechanisms. Transcellular transport of aspirin and the influence of PNS were explored using Caco-2 cell monolayers. The protein expression of human carboxylesterase 1 (hCE1) and hCE2 in Caco-2 cells after PNS treatment was analyzed by ELISA, and the mRNA level were determined by qRT-PCR. In the study, Caco-2 cells showed high level of hydrolase activity, and most aspirin was hydrolyzed inside the cells during the transport process. Interestingly, PNS were demonstrated to inhibit the esterase activities responsible for aspirin hydrolysis in Caco-2 cells. PNS could also decrease the protein expression of hCE1 and hCE2, whereas exhibited minor effect on the mRNA expression. These results indicated that oral administration of PNS-based drugs might inhibit the hydrolysis of aspirin during intestinal absorption thus promoting its bioavailability. Title: Effects of Panax Notoginseng Saponins on Esterases Responsible for Aspirin Hydrolysis In Vitro Sun Z, Wu Y, Liu S, Hu S, Zhao B, Li P, Du S Ref: Int J Mol Sci, 19:, 2018 : PubMed ESTHER: Sun_2018_Int.J.Mol.Sci_19_ PubMedSearch: Sun 2018 Int.J.Mol.Sci 19 PubMedID: 30322078 Abstract Herb(-)drug interactions strongly challenge the clinical combined application of herbs and drugs. Herbal products consist of complex pharmacological-active ingredients and perturb the activity of drug-metabolizing enzymes. Panax notoginseng saponins (PNS)-based drugs are often combined with aspirin in vascular disease treatment in China. PNS was found to exhibit inhibitory effects on aspirin hydrolysis using Caco-2 cell monolayers. In the present study, a total of 22 components of PNS were separated and identified by UPLC-MS/MS. Using highly selective probe substrate analysis, PNS exerted robust inhibitory potency on human carboxylesterase 2 (hCE2), while had a minor influence on hCE1, butyrylcholinesterase (BChE) and paraoxonase (PON). These effects were also verified through molecular docking analysis. PNS showed a concentration-dependent inhibitory effect on hydrolytic activity of aspirin in HepaRG cells. The protein level of hCE2 in HepaRG cells was suppressed after PNS treatment, while the level of BChE or PON1 in the extracellular matrix were elevated after PNS treatment. Insignificant effect was observed on the mRNA expression of the esterases. These findings are important to understand the underlying efficacy and safety of co-administration of PNS and aspirin in clinical practice. Title: The binding interaction between cadmium-based, aqueous-phase quantum dots with Candida rugosa lipase Zhao L, Hu S, Meng Q, Xu M, Zhang H, Liu R Ref: J Mol Recognit, :e2712, 2018 : PubMed ESTHER: Zhao_2018_J.Mol.Recognit__e2712 PubMedSearch: Zhao 2018 J.Mol.Recognit e2712 PubMedID: 29655217 Abstract As a promising biolabeling biomaterials, quantum dots (QDs) present a great potential. However, the toxicity of QDs to organisms has attracted wide attention. In our research, we introduced an in vitro method to study the molecular mechanisms for the structure and activity alterations of Candida rugosa lipase (CRL) with the binding of 3-mercaptopropionic acid-capped CdTe QDs. Multiple spectroscopic methods, isothermal titration calorimetry, and enzyme activity measurements were used in this paper. QDs statically quenched the intrinsic fluorescence of CRL with the quenching constant decreases from 2.46 x 10(13) to 1.64 x 10(13) L mol(-1) second(-1) (298 to 310 K). It binds to CRL through hydrophobic force with 1 binding site, unfolding and loosening the skeleton and changed its secondary structure. Rather than aggregating on the surface, it enters the pocket of the CRL to interact with Ser-209 (2.43 A) and the residues surrounding Ser-209, making the catalytic triad more exposed. Furthermore, the activity of CRL was inhibited by approximately 15%. This work demonstrates that 3-mercaptopropionic acid-capped CdTe QDs may cause negative effects to CRL and obtains a molecular mechanism on QD-induced toxicity to proteins in vitro. Title: Hydrolysis mechanism of carbendazim hydrolase from the strain Microbacterium sp. djl-6F Lei J, Wei S, Ren L, Hu S, Chen P Ref: J Environ Sci (China), 54:171, 2017 : PubMed ESTHER: Lei_2017_J.Environ.Sci.(China)_54_171 PubMedSearch: Lei 2017 J.Environ.Sci.(China) 54 171 PubMedID: 28391926 Gene_locus related to this paper: 9acto-c8cp46 Abstract The carbendazim (MBC) hydrolyzing enzyme gene was cloned and heterologously expressed in Escherichia coli BL21 (DE3) from a newly isolated MBC-degrading bacterium strain Microbacterium sp. strain djl-6F. High performance liquid chromatography-mass spectrometry (HPLC-MS) analysis revealed that purified MheI-6F protein catalyzes direct hydrolysis of MBC into 2-aminobenzimidazole (2-AB) with a high turnover rate and moderate affinity (K(m) of 6.69micromol/L and k(cat) of 160.88/min) without the need for any cofactors. The optimal catalytic condition of MheI-6F was identified as 45 degreesC, pH7.0. The enzymatic activity of MheI-6F was found to be diminished by metal ions, and strongly inhibited by sodium dodecyl sulfate (SDS). Through generating amino acid mutations in MheI-6F, Cys16 and Cys222 were identified as the catalytic groups that are essential for the hydrolysis of MBC. This is the first report on the biodegradation of MBC at the enzymatice level. Title: Resting-State Functional Connectivity of the Basal Nucleus of Meynert in Cigarette Smokers: Dependence Level and Gender Differences Zhang S, Hu S, Fucito LM, Luo X, Mazure CM, Zaborszky L, Li CR Ref: Nicotine Tob Res, 19:452, 2017 : PubMed ESTHER: Zhang_2017_Nicotine.Tob.Res_19_452 PubMedSearch: Zhang 2017 Nicotine.Tob.Res 19 452 PubMedID: 27613921 Abstract Introduction: Numerous studies have characterized impaired cerebral functioning in nicotine-addicted individuals. Whereas nicotine interacts with multiple neurotransmitters in cortical and subcortical circuits, it directly targets the cholinergic system, sourced primarily from the basal nucleus of Meynert (BNM). However, no studies have examined how this cholinergic system is influenced by cigarette smoking. Here, we addressed this gap of research. Methods: Using a dataset from the Functional Connectome Projects, we investigated this issue by contrasting seed-based BNM connectivity of 40 current smokers and 170 age- and gender-matched nonsmokers. We followed our data analytic routines in recent work and examined differences between smokers and nonsmokers in men and women combined as well as separately. Results: Compared to nonsmokers, female but not male smokers demonstrated greater positive BNM connectivity to the supplementary motor area, bilateral anterior insula, and right superior temporal/supramarginal gyri as well as greater negative connectivity to the posterior cingulate cortex and precuneus. Further, BNM connectivity to the supplementary motor area is negatively correlated to the Fagerstrom Test for Nicotine Dependence score in male but not female smokers. Conclusions: Along with a previous report of upregulated nicotinic acetylcholine receptor in male but not female smokers, these new findings highlight functional changes of the cholinergic systems in cigarette smokers. The results suggest sex-specific differences in cholinergic dysregulation and a need for multiple imaging modalities to capture the neural markers of nicotine addiction. Implications: Nicotine influences cognition via cholinergic projections of the basal forebrain to the cerebral cortex. This study examined changes in resting-state whole-brain functional connectivity of the BNM in cigarette smokers. The new findings elucidate for the first time sex differences in BNM-cerebral connectivity in cigarette smoking. Title: Structure activity relationship studies on chemically non-reactive glycine sulfonamide inhibitors of diacylglycerol lipase Chupak LS, Zheng X, Hu S, Huang Y, Ding M, Lewis MA, Westphal RS, Blat Y, McClure A, Gentles RG Ref: Bioorganic & Medicinal Chemistry, 24:1455, 2016 : PubMed ESTHER: Chupak_2016_Bioorg.Med.Chem_24_1455 PubMedSearch: Chupak 2016 Bioorg.Med.Chem 24 1455 PubMedID: 26917221 Abstract N-Benzylic-substituted glycine sulfonamides that reversibly inhibit diacylglycerol (DAG) lipases are reported. Detailed herein are the structure activity relationships, profiling characteristics and physico-chemical properties for the first reported series of DAG lipase (DAGL) inhibitors that function without covalent attachment to the enzyme. Highly potent examples are presented that represent valuable tool compounds for studying DAGL inhibition and constitute important leads for future medicinal chemistry efforts. Title: Sunitinib, a Clinically Used Anticancer Drug, Is a Potent AChE Inhibitor and Attenuates Cognitive Impairments in Mice Huang L, Lin J, Xiang S, Zhao K, Yu J, Zheng J, Xu D, Mak SH, Hu S and Wang Q <12 more author(s)> Huang L, Lin J, Xiang S, Zhao K, Yu J, Zheng J, Xu D, Mak SH, Hu S, Nirasha S, Wang C, Chen X, Zhang J, Xu S, Wei X, Zhang Z, Zhou D, Zhou W, Cui W, Han YF, Hu Z, Wang Q (- 12) Ref: ACS Chem Neurosci, 7:1047, 2016 : PubMed ESTHER: Huang_2016_ACS.Chem.Neurosci_7_1047 PubMedSearch: Huang 2016 ACS.Chem.Neurosci 7 1047 PubMedID: 27046396 Abstract Sunitinib, a tyrosine kinase inhibitor, is clinically used for the treatment of cancer. In this study, we found for the first time that sunitinib inhibits acetylcholinesterase (AChE) at submicromolar concentrations in vitro. In addition, sunitinib dramatically decreased the hippocampal and cortical activity of AChE in a time-dependent manner in mice. Molecular docking analysis further demonstrates that sunitinib might interact with both the catalytic anion and peripheral anionic sites within AChE, which is in accordance with enzymatic activity results showing that sunitinib inhibits AChE in a mixed pattern. Most importantly, we evaluated the effects of sunitinib on scopolamine-induced cognitive impairments in mice by using novel object recognition and Morris water maze tests. Surprisingly, sunitinib could attenuate cognitive impairments to a similar extent as donepezil, a marketed AChE inhibitor used for the treatment of Alzheimer's disease. In summary, our results have shown that sunitinib could potently inhibit AChE and attenuate cognitive impairments in mice. Title: The Effects of Methylphenidate on Resting-State Functional Connectivity of the Basal Nucleus of Meynert, Locus Coeruleus, and Ventral Tegmental Area in Healthy Adults Kline RL, Zhang S, Farr OM, Hu S, Zaborszky L, Samanez-Larkin GR, Li CS Ref: Front Hum Neurosci, 10:149, 2016 : PubMed ESTHER: Kline_2016_Front.Hum.Neurosci_10_149 PubMedSearch: Kline 2016 Front.Hum.Neurosci 10 149 PubMedID: 27148006 Abstract BACKGROUND: Methylphenidate (MPH) influences catecholaminergic signaling. Extant work examined the effects of MPH on the neural circuits of attention and cognitive control, but few studies have investigated the effect of MPH on the brain's resting-state functional connectivity (rsFC). Title: Comparative transcriptome analyses of deltamethrin-susceptible and -resistant Culex pipiens pallens by RNA-seq Lv Y, Wang W, Hong S, Lei Z, Fang F, Guo Q, Hu S, Tian M, Liu B and Zhu C <5 more author(s)> Lv Y, Wang W, Hong S, Lei Z, Fang F, Guo Q, Hu S, Tian M, Liu B, Zhang D, Sun Y, Ma L, Shen B, Zhou D, Zhu C (- 5) Ref: Mol Genet Genomics, 291:309, 2016 : PubMed ESTHER: Lv_2016_Mol.Genet.Genomics_291_309 PubMedSearch: Lv 2016 Mol.Genet.Genomics 291 309 PubMedID: 26377942 Abstract The widespread and improper use of pyrethroid insecticides, such as deltamethrin, has resulted in the evolution of resistance in many mosquito species, including Culex pipiens pallens. With the development of high-throughput sequencing, it is possible to massively screen pyrethroid resistance-associated gene. In this study, we used Illumina-Solexa transcriptome sequencing to identify genes that are expressed differently in deltamethrin-susceptible and -resistant strains of Culex pipiens pallens as a critical knowledge base for further studies. A total of 4,961,197,620 base pairs and 55,124,418 reads were sequenced, mapped to the Culex quinquefasciatus genome and assembled into 17,679 known genes. We recorded 1826 significantly differentially expressed genes (DEGs). Among them, 1078 genes were up-regulated and 748 genes were down-regulated in the deltamethrin-resistant strain compared to -susceptible strain. These DEGs contained cytochrome P450 s, cuticle proteins, UDP-glucuronosyltransferases, lipases, serine proteases, heat shock proteins, esterases and others. Among the 1826 DEGs, we found that the transcriptional levels of CYP6AA9 in the laboratory populations was elevated as the levels of deltamethrin resistance increased. Moreover, the expression levels of the CYP6AA9 were significantly higher in the resistant strains than the susceptible strains in three different field populations. We further confirmed the association between the CYP6AA9 gene and deltamethrin resistance in mosquitoes by RNA interfering (RNAi). Altogether, we explored massive potential pyrethroid resistance-associated genes and demonstrated that CYP6AA9 participated in the pyrethroid resistance in mosquitoes. Title: Pretreatment serum pseudocholinesterase level as a novel prognostic biomarker for upper tract urothelial carcinoma Zhang B, Shen C, Jin J, Song Y, Zhao Z, Zhang X, Wang G, Fan Y, Mi Y and Han W <5 more author(s)> Zhang B, Shen C, Jin J, Song Y, Zhao Z, Zhang X, Wang G, Fan Y, Mi Y, Hu S, Cui Y, Zhou L, He Z, Yu W, Han W (- 5) Ref: International Urology & Nephrology, 48:1993, 2016 : PubMed ESTHER: Zhang_2016_Int.Urol.Nephrol_48_1993 PubMedSearch: Zhang 2016 Int.Urol.Nephrol 48 1993 PubMedID: 27554671 Abstract PURPOSE: Pretreatment serum pseudocholinesterase (PChE) has been reported to be a prognostic predictor in several cancers. However, the prognostic significance of serum PChE level in patients with upper tract urothelial carcinoma (UTUC) remains unknown. Title: Inhibiting beta-Amyloid-Associated Alzheimer's Pathogenesis In Vitro and In Vivo by a Multifunctional Dimeric Bis(12)-hupyridone Derived from Its Natural Analogue Hu S, Wang R, Cui W, Zhang Z, Mak SH, Xu D, Choi C, Tsim KWK, Carlier PR and Han Y <1 more author(s)> Hu S, Wang R, Cui W, Zhang Z, Mak SH, Xu D, Choi C, Tsim KWK, Carlier PR, Lee M, Han Y (- 1) Ref: Journal of Molecular Neuroscience, 55:1014, 2015 : PubMed ESTHER: Hu_2015_J.Mol.Neurosci_55_1014 PubMedSearch: Hu 2015 J.Mol.Neurosci 55 1014 PubMedID: 25407821 Abstract Fibrillar aggregates of beta-amyloid protein (Abeta) is the main constituent of senile plaques and considered to be one of the causative events in the pathogenesis of Alzheimer's disease (AD). Compounds that could inhibit the formation of Abeta fibrils and block Abeta fibrils-associated toxicity may have therapeutic potential to combat AD. Bis(12)-hupyridone (B12H) is a multifunctional homodimer derived from huperzine A, which is an anti-AD drug in China. In the current study, the inhibitory effect of B12H on the formation of Abeta fibrils and their associated toxicity was investigated both in vitro and in vivo. By using Thioflavin T fluorescence assay, we found that B12H (0.3-3 muM) directly inhibited Abeta fibrils formation following co-incubation of B12H and Abeta1-40 at 37 degrees C for 6 days in vitro. However, huperzine A, at the same concentrations, did not show significant inhibitory effect on Abeta1-40 fibrils formation. Moreover, B12H markedly reduced Abeta1-40-induced cytotoxicity in cultured SH-SY5Y cells, as evidenced by the increase in cell viability, the decrease in lactate dehydrogenase release, and the reduction of apoptotic nuclei. Most importantly, B12H (0.2 and 0.4 mg/kg) reduced intracerebroventricular Abeta1-40 infusion-induced cognitive and memory impairments in rats, as evidenced by the decrease in escape latency and the increase in the spatial bias in Morris water maze test along with increasing choline acetyltransferase activity and decreasing acetylcholinesterase activity. Collectively, our study provided novel sights into the potential application of B12H in AD treatment. Title: Purification and Characterization of a Lipase with High Thermostability and Polar Organic Solvent-Tolerance from Aspergillus niger AN0512 Liu G, Hu S, Li L, Hou Y Ref: Lipids, 50:1155, 2015 : PubMed ESTHER: Liu_2015_Lipids_50_1155 PubMedSearch: Liu 2015 Lipids 50 1155 PubMedID: 26216145 Abstract An extracellular lipase (EC 3.1.1.3, AN0512Lip) from Aspergillus niger AN0512 was purified and its characteristics were investigated. After the process of ammonium sulfate precipitation followed by ion-exchange chromatography and gel filtration, the purified lipase was achieved with 203.6-fold purification and 22.1 % recovery. AN0512Lip exhibited the highest activity at 50 degrees C and pH 5.0. It was thermostable and pH-stable, as indicated by that more than 50 % activity retained at 60 degrees C for 20 h and more than 90 % activity retained at pH 3.0 for 20 h, respectively. AN0512Lip activity was stimulated by some divalent metal ions (especially Cu(2+), Ca(2+)), while greatly suppressed by EDTA, indicating that AN0512Lip was a metal-activated enzyme. Moreover, AN0512Lip exhibited high tolerance for various polar organic solvents with log P < 0.8, and the highest lipase activity (476 % of its original activity) was achieved after addition of 90 % (V/V) isopropanol to the reaction mixture. AN0512Lip also displayed 3-regiospecificity and great affinity for the long-chain fatty ester. The preliminary test showed that AN0512Lip was a candidate for enriching EPA and DHA in fish oil. All the unique properties, such as thermostability, Cu(2+)-dependent, 3-regiospecificity, and polar organic solvent-tolerance, indicated that AN0512Lip could have potential applications in the food industry, even in organic synthesis and the pharmaceutical industry. Title: The Report of Sustained Low-Efficiency Dialysis (SLED) Treatment in Fifteen Patients of Severe Snakebite Cheng J, Wang D, Hu S, Jiang H, Lu H, Lei Q, Liu J, Yuan F, Chen R Ref: Cell Biochem Biophys, 69:71, 2014 : PubMed ESTHER: Cheng_2014_Cell.Biochem.Biophys_69_71 PubMedSearch: Cheng 2014 Cell.Biochem.Biophys 69 71 PubMedID: 24068524 Abstract To investigate the therapeutic efficacy of sustained low-efficiency dialysis (SLED) in severe snakebite patients. Fifteen patients of severe snakebite was treated with SLED from July 2005 to August 2009 were included in the study. Central venous access was established in all patients. SLED was administered using Dialog(+) dialyzer (B. Braun, Germany). SLED sessions were 6-12 h in duration at a blood flow rate of 200 ml/min and a dialysate flow rate of 300 ml/min. Heparin or low molecular weight heparin was used as anticoagulant. Biochemical indicators, APACHE II scores before and after SLED, and clinical outcomes were evaluated. The levels of serum creatinine, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, creatine kinase isozyme MB, and creatine kinase were significantly lower than the level before SLED (P < 0.05); the level of cholinesterase was significantly higher after SLED (P < 0.01); the APACHE II score before SLED was 14.1 +/- 3.8, but decreased significantly to 7.9 +/- 1.4, 6.2 +/- 1.1, and 4.2 +/- 0.8 on days 1, 2, and 7 after SLED, respectively (P < 0.01). Three patients died on days 1, 3, and 4 after SLED, respectively. The remaining twelve patients were either cured or showed improvement at the time of discharge. The survival rate was 80 % where as mortality was 20 %. SLED may be an effective treatment option in severe snakebite patients. It can reduce mortality, thereby, resulting in increased survival rates. Title: Resting state functional connectivity of the basal nucleus of Meynert in humans: in comparison to the ventral striatum and the effects of age Li CS, Ide JS, Zhang S, Hu S, Chao HH, Zaborszky L Ref: Neuroimage, 97:321, 2014 : PubMed ESTHER: Li_2014_Neuroimage_97_321 PubMedSearch: Li 2014 Neuroimage 97 321 PubMedID: 24736176 Abstract The basal nucleus of Meynert (BNM) provides the primary cholinergic inputs to the cerebral cortex. Loss of neurons in the BNM is linked to cognitive deficits in Alzheimer's disease and other degenerative conditions. Numerous animal studies described cholinergic and non-cholinergic neuronal responses in the BNM; however, work in humans has been hampered by the difficulty of defining the BNM anatomically. Here, on the basis of a previous study that delineated the BNM of post-mortem human brains in a standard stereotaxic space, we sought to examine functional connectivity of the BNM, as compared to the nucleus accumbens (or ventral striatum, VS), in a large resting state functional magnetic resonance imaging data set. The BNM and VS shared but also showed a distinct pattern of cortical and subcortical connectivity. Compared to the VS, the BNM showed stronger positive connectivity with the putamen, pallidum, thalamus, amygdala and midbrain, as well as the anterior cingulate cortex, supplementary motor area and pre-supplementary motor area, a network of brain regions that respond to salient stimuli and orchestrate motor behavior. In contrast, compared to the BNM, the VS showed stronger positive connectivity with the ventral caudate and medial orbitofrontal cortex, areas implicated in reward processing and motivated behavior. Furthermore, the BNM and VS each showed extensive negative connectivity with visual and lateral prefrontal cortices. Together, the distinct cerebral functional connectivities support the role of the BNM in arousal, saliency responses and cognitive motor control and the VS in reward related behavior. Considering the importance of BNM in age-related cognitive decline, we explored the effects of age on BNM and VS connectivities. BNM connectivity to the visual and somatomotor cortices decreases while connectivity to subcortical structures including the midbrain, thalamus, and pallidum increases with age. These findings of age-related changes of cerebral functional connectivity of the BNM may facilitate research of the neural bases of cognitive decline in health and illness. Title: Synergistic inhibition on acetylcholinesterase by the combination of berberine and palmatine originally isolated from chinese medicinal herbs Mak SH, Luk WW, Cui W, Hu S, Tsim KWK, Han Y Ref: Journal of Molecular Neuroscience, 53:511, 2014 : PubMed ESTHER: Mak_2014_J.Mol.Neurosci_53_511 PubMedSearch: Mak 2014 J.Mol.Neurosci 53 511 PubMedID: 24793543 Inhibitor(s) related to this paper: Palmatine, Berberine Abstract Alzheimer's disease is a multi-factorial neurodegenerative disorder devastatingly affecting the aged population worldwide. Previous studies have shown that medicinal herbs used in traditional Chinese medicine might be benefit to Alzheimer's disease patients. Berberine and palmatine, two isoquinoline alkaloids found in several medicinal herbs, were used for memory enhancement in China. In this study, the inhibitory effects of combined berberine and palmatine on acetylcholinesteras were evaluated using recombinant human acetylcholinesterase. Our results showed that the combination of berberine and palmatine inhibited acetylcholinesterase in a mixed competitive pattern. By the median-effect principle, the calculated combination index of the combination was less than 1, suggesting that berberine and plamatine inhibited acetylcholinesterase synergistically. Furthermore, the drug-reducing index of berberine and palmatine were 2.98 and 2.66, respectively. Taken together, the results showed that the combination of the two alkaloids might potentially be developed as a more effective therapeutic strategy for Alzheimer's disease patients. Title: Genome sequence of the date palm Phoenix dactylifera L Al-Mssallem IS, Hu S, Zhang X, Lin Q, Liu W, Tan J, Yu X, Liu J, Pan L and Yu J <34 more author(s)> Al-Mssallem IS, Hu S, Zhang X, Lin Q, Liu W, Tan J, Yu X, Liu J, Pan L, Zhang T, Yin Y, Xin C, Wu H, Zhang G, Ba Abdullah MM, Huang D, Fang Y, Alnakhli YO, Jia S, Yin A, Alhuzimi EM, Alsaihati BA, Al-Owayyed SA, Zhao D, Zhang S, Al-Otaibi NA, Sun G, Majrashi MA, Li F, Tala, Wang J, Yun Q, Alnassar NA, Wang L, Yang M, Al-Jelaify RF, Liu K, Gao S, Chen K, Alkhaldi SR, Liu G, Zhang M, Guo H, Yu J (- 34) Ref: Nat Commun, 4:2274, 2013 : PubMed ESTHER: Al-Mssallem_2013_Nat.Commun_4_2274 PubMedSearch: Al-Mssallem 2013 Nat.Commun 4 2274 PubMedID: 23917264 Gene_locus related to this paper: phodc-a0a2h3y3d5, phodc-a0a2h3z529, phodc-a0a2h3y147, phodc-a0a2h3xrz4, phodc-a0a3q0ic37, phodc-a0a2h3yxf0, phodc-a0a2h3zh01, phodc-a0a3q0hs32 Abstract Date palm (Phoenix dactylifera L.) is a cultivated woody plant species with agricultural and economic importance. Here we report a genome assembly for an elite variety (Khalas), which is 605.4 Mb in size and covers >90% of the genome (~671 Mb) and >96% of its genes (~41,660 genes). Genomic sequence analysis demonstrates that P. dactylifera experienced a clear genome-wide duplication after either ancient whole genome duplications or massive segmental duplications. Genetic diversity analysis indicates that its stress resistance and sugar metabolism-related genes tend to be enriched in the chromosomal regions where the density of single-nucleotide polymorphisms is relatively low. Using transcriptomic data, we also illustrate the date palm's unique sugar metabolism that underlies fruit development and ripening. Our large-scale genomic and transcriptomic data pave the way for further genomic studies not only on P. dactylifera but also other Arecaceae plants. Title: Seasonally variable intestinal metagenomes of the red palm weevil (Rhynchophorus ferrugineus) Jia S, Zhang X, Zhang G, Yin A, Zhang S, Li F, Wang L, Zhao D, Yun Q and Yu J <7 more author(s)> Jia S, Zhang X, Zhang G, Yin A, Zhang S, Li F, Wang L, Zhao D, Yun Q, Tala, Wang J, Sun G, Baabdullah M, Yu X, Hu S, Al-Mssallem IS, Yu J (- 7) Ref: Environ Microbiol, 15:3020, 2013 : PubMed ESTHER: Jia_2013_Environ.Microbiol_15_3020 PubMedSearch: Jia 2013 Environ.Microbiol 15 3020 PubMedID: 24102776 Abstract The intestinal microbes residing in the red palm weevil (RPW, Rhynchophorus ferrugineus) larva consume tender interior fibrous tissues of date palm trunks. The understanding of such microbiota at molecular level provides vital clues for the biological control of this devastating pest. Using pyrosequencing and shotgun strategy, we first study taxonomic profiles of the microbiota sampled at different months (March, July and November), and then confirm the impact of high-temperature stress on the microbial populations based on data from 16S rRNA amplicons using both field and laboratory samples. We further identify Klebsiella pneumoniae in November and Lactococcus lactis in July as the dominant species of the microbiota. We find that the RPW gut microbiota degrades polysaccharides and sucrose with hydrolases and that different active bacterial species in November and July are responsible for the symbiotic relationship between the microbiota and the host. Our results provide vital information for pest control and cellulolytic bacterial species characterization. Title: The genomes of four tapeworm species reveal adaptations to parasitism Tsai IJ, Zarowiecki M, Holroyd N, Garciarrubio A, Sanchez-Flores A, Brooks KL, Tracey A, Bobes RJ, Fragoso G and Berriman M <42 more author(s)> Tsai IJ, Zarowiecki M, Holroyd N, Garciarrubio A, Sanchez-Flores A, Brooks KL, Tracey A, Bobes RJ, Fragoso G, Sciutto E, Aslett M, Beasley H, Bennett HM, Cai J, Camicia F, Clark R, Cucher M, De Silva N, Day TA, Deplazes P, Estrada K, Fernandez C, Holland PW, Hou J, Hu S, Huckvale T, Hung SS, Kamenetzky L, Keane JA, Kiss F, Koziol U, Lambert O, Liu K, Luo X, Luo Y, Macchiaroli N, Nichol S, Paps J, Parkinson J, Pouchkina-Stantcheva N, Riddiford N, Rosenzvit M, Salinas G, Wasmuth JD, Zamanian M, Zheng Y, Cai X, Soberon X, Olson PD, Laclette JP, Brehm K, Berriman M (- 42) Ref: Nature, 496:57, 2013 : PubMed ESTHER: Tsai_2013_Nature_496_57 PubMedSearch: Tsai 2013 Nature 496 57 PubMedID: 23485966 Gene_locus related to this paper: echgr-k4epc5, hymmi-a0a068x9f5, echmu-u6hbw4, echgr-w6ugl0, echmu-u6hr32, echmu-a0a068y5f4, hymmi-a0a068xag4, hymmi-a0a068x810, hymmi-a0a068xcc1, echmu-a0a068yf54, echgr-a0a068wxj3, echgr-a0a068wgw1, hymmi-a0a068xge7, hymmi-a0a068x8h9, echmu-a0a068y747, hymmi-a0a068xgj7, echgr-a0a068wl60 Abstract Tapeworms (Cestoda) cause neglected diseases that can be fatal and are difficult to treat, owing to inefficient drugs. Here we present an analysis of tapeworm genome sequences using the human-infective species Echinococcus multilocularis, E. granulosus, Taenia solium and the laboratory model Hymenolepis microstoma as examples. The 115- to 141-megabase genomes offer insights into the evolution of parasitism. Synteny is maintained with distantly related blood flukes but we find extreme losses of genes and pathways that are ubiquitous in other animals, including 34 homeobox families and several determinants of stem cell fate. Tapeworms have specialized detoxification pathways, metabolism that is finely tuned to rely on nutrients scavenged from their hosts, and species-specific expansions of non-canonical heat shock proteins and families of known antigens. We identify new potential drug targets, including some on which existing pharmaceuticals may act. The genomes provide a rich resource to underpin the development of urgently needed treatments and control. Title: Complete genome and transcriptomes of Streptococcus parasanguinis FW213: phylogenic relations and potential virulence mechanisms Geng J, Chiu CH, Tang P, Chen Y, Shieh HR, Hu S, Chen YY Ref: PLoS ONE, 7:e34769, 2012 : PubMed ESTHER: Geng_2012_PLoS.One_7_e34769 PubMedSearch: Geng 2012 PLoS.One 7 e34769 PubMedID: 22529932 Abstract Streptococcus parasanguinis, a primary colonizer of the tooth surface, is also an opportunistic pathogen for subacute endocarditis. The complete genome of strain FW213 was determined using the traditional shotgun sequencing approach and further refined by the transcriptomes of cells in early exponential and early stationary growth phases in this study. The transcriptomes also discovered 10 transcripts encoding known hypothetical proteins, one pseudogene, five transcripts matched to the Rfam and additional 87 putative small RNAs within the intergenic regions defined by the GLIMMER analysis. The genome contains five acquired genomic islands (GIs) encoding proteins which potentially contribute to the overall pathogenic capacity and fitness of this microbe. The differential expression of the GIs and various open reading frames outside the GIs at the two growth phases suggested that FW213 possess a range of mechanisms to avoid host immune clearance, to colonize host tissues, to survive within oral biofilms and to overcome various environmental insults. Furthermore, the comparative genome analysis of five S. parasanguinis strains indicates that albeit S. parasanguinis strains are highly conserved, variations in the genome content exist. These variations may reflect differences in pathogenic potential between the strains. Title: Complete genome sequence of the metabolically versatile halophilic archaeon Haloferax mediterranei, a poly(3-hydroxybutyrate-co-3-hydroxyvalerate) producer Han J, Zhang F, Hou J, Liu X, Li M, Liu H, Cai L, Zhang B, Chen Y and Xiang H <2 more author(s)> Han J, Zhang F, Hou J, Liu X, Li M, Liu H, Cai L, Zhang B, Chen Y, Zhou J, Hu S, Xiang H (- 2) Ref: Journal of Bacteriology, 194:4463, 2012 : PubMed ESTHER: Han_2012_J.Bacteriol_194_4463 PubMedSearch: Han 2012 J.Bacteriol 194 4463 PubMedID: 22843593 Abstract Haloferax mediterranei, an extremely halophilic archaeon, has shown promise for production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) from unrelated cheap carbon sources. Here we report the complete genome (3,904,707 bp) of H. mediterranei CGMCC 1.2087, consisting of one chromosome and three megaplasmids. Title: Comparative analysis of the genomes of two field isolates of the rice blast fungus Magnaporthe oryzae Xue M, Yang J, Li Z, Hu S, Yao N, Dean RA, Zhao W, Shen M, Zhang H and Peng YL <8 more author(s)> Xue M, Yang J, Li Z, Hu S, Yao N, Dean RA, Zhao W, Shen M, Zhang H, Li C, Liu L, Cao L, Xu X, Xing Y, Hsiang T, Zhang Z, Xu JR, Peng YL (- 8) Ref: PLoS Genet, 8:e1002869, 2012 : PubMed ESTHER: Xue_2012_PLoS.Genet_8_E1002869 PubMedSearch: Xue 2012 PLoS.Genet 8 E1002869 PubMedID: 22876203 Gene_locus related to this paper: maggr-q0pnd2, mago7-g4mk92, mago7-g4mkc6, mago7-g4mkk9, mago7-g4mns9, mago7-g4ms19, mago7-g4mvm8, mago7-g4mvw5, mago7-g4mvw6, mago7-g4n6j4, mago7-g4nal1, mago7-g4nba0, mago7-g4nbs0, mago7-g4nc41, mago7-g4ncz9, mago7-g4nhn9, mago7-g4nil3, mago7-g4nky6, mago7-g5ehg6, mago7-g5ehv6, mago7-g4msm5, magoy-l7il05, magoy-l7i6m7, magoy-l7ic25 Abstract Rice blast caused by Magnaporthe oryzae is one of the most destructive diseases of rice worldwide. The fungal pathogen is notorious for its ability to overcome host resistance. To better understand its genetic variation in nature, we sequenced the genomes of two field isolates, Y34 and P131. In comparison with the previously sequenced laboratory strain 70-15, both field isolates had a similar genome size but slightly more genes. Sequences from the field isolates were used to improve genome assembly and gene prediction of 70-15. Although the overall genome structure is similar, a number of gene families that are likely involved in plant-fungal interactions are expanded in the field isolates. Genome-wide analysis on asynonymous to synonymous nucleotide substitution rates revealed that many infection-related genes underwent diversifying selection. The field isolates also have hundreds of isolate-specific genes and a number of isolate-specific gene duplication events. Functional characterization of randomly selected isolate-specific genes revealed that they play diverse roles, some of which affect virulence. Furthermore, each genome contains thousands of loci of transposon-like elements, but less than 30% of them are conserved among different isolates, suggesting active transposition events in M. oryzae. A total of approximately 200 genes were disrupted in these three strains by transposable elements. Interestingly, transposon-like elements tend to be associated with isolate-specific or duplicated sequences. Overall, our results indicate that gain or loss of unique genes, DNA duplication, gene family expansion, and frequent translocation of transposon-like elements are important factors in genome variation of the rice blast fungus. Title: Bis(12)-hupyridone, a novel multifunctional dimer, promotes neuronal differentiation more potently than its monomeric natural analog huperzine A possibly through alpha7 nAChR Cui W, Cui GZ, Li W, Zhang Z, Hu S, Mak SH, Zhang H, Carlier PR, Choi CL and Han YF <2 more author(s)> Cui W, Cui GZ, Li W, Zhang Z, Hu S, Mak SH, Zhang H, Carlier PR, Choi CL, Wong YT, Lee SM, Han YF (- 2) Ref: Brain Research, 1401:10, 2011 : PubMed ESTHER: Cui_2011_Brain.Res_1401_10 PubMedSearch: Cui 2011 Brain.Res 1401 10 PubMedID: 21665194 Abstract The cause of many neurodegenerative disorders can be ascribed to the loss of functional neurons, and thus agents capable of promoting neuronal differentiation may have therapeutic benefits to patients of these disorders. In this study, the effects and underlying mechanisms of bis(12)-hupyridone (B12H), a novel dimeric acetylcholinesterase inhibitor modified from huperzine A (HA), on neuronal differentiation were investigated using both the rat PC12 pheochromocytoma cell line and adult rat hippocampus neural stem cells. B12H (3-30 muM), characterized by morphological changes and expression of GAP-43, induced neurite outgrowth in a concentration- and time-dependent manner, with almost 3-fold higher efficacy than that of HA in PC12 cells. Furthermore, B12H (2.5-10 muM), but not HA, promoted neuronal differentiation as shown by the percentage increase of betaIII-tubulin positive neurons in neural stem cells. The activities of extracellular signal-regulated kinase (ERK), as well as its downstream transcription factors Elk-1 and cAMP response element-binding protein (CREB) were elevated in the B12H-treated PC12 cells. Mitogen-activated protein kinase kinase inhibitors and alpha7-nicotinic acetylcholine receptor (alpha7nAChR) antagonist blocked the neurite outgrowth and the activation of ERK induced by B12H. All these findings suggest that B12H potently induces pro-neuronal cells into differentiated neurons by activating the ERK pathway possibly via regulating alpha7nAChR. These findings support the recent proposition that alpha7nAChR is required for the neuronal dendritic arborization and differentiation in the adult mice hippocampus, and provide insights into the possible therapeutic potential of B12H in treating neurodegenerative disorders. Title: Complete genome sequence of the ureolytic Streptococcus salivarius strain 57.I Geng J, Huang SC, Li S, Hu S, Chen YY Ref: Journal of Bacteriology, 193:5596, 2011 : PubMed ESTHER: Geng_2011_J.Bacteriol_193_5596 PubMedSearch: Geng 2011 J.Bacteriol 193 5596 PubMedID: 21914897 Abstract Streptococcus salivarius 57.I is one of the most abundant and highly ureolytic bacteria in the human mouth. It can utilize urea as the sole nitrogen source via the activity of urease. Complete genome sequencing of S. salivarius 57.I revealed a chromosome and a phage which are absent in strain SK126. Title: Complete genome sequence of Bifidobacterium longum subsp. longum BBMN68, a new strain from a healthy chinese centenarian Hao Y, Huang D, Guo H, Xiao M, An H, Zhao L, Zuo F, Zhang B, Hu S and Ren F <2 more author(s)> Hao Y, Huang D, Guo H, Xiao M, An H, Zhao L, Zuo F, Zhang B, Hu S, Song S, Chen S, Ren F (- 2) Ref: Journal of Bacteriology, 193:787, 2011 : PubMed ESTHER: Hao_2011_J.Bacteriol_193_787 PubMedSearch: Hao 2011 J.Bacteriol 193 787 PubMedID: 21097614 Gene_locus related to this paper: biflo-BL0073, biflo-BL0336, biflo-BL0581, biflo-BL0582, biflo-BL0682, biflo-BL0787, biflo-BL0807, biflo-BL1109, biflo-BL1514, biflo-PAP, biflo-PTRB Abstract Bifidobacterium longum subsp. longum BBMN68 was isolated from the feces of a healthy centenarian living in an area of BaMa, Guangxi, China, known for longevity. Here we report the main genome features of B. longum strain BBMN68 and the identification of several predicted proteins associated with the ecological niche of longevity. Title: Comparative genomic and transcriptomic analysis revealed genetic characteristics related to solvent formation and xylose utilization in Clostridium acetobutylicum EA 2018 Hu S, Zheng H, Gu Y, Zhao J, Zhang W, Yang Y, Wang S, Zhao G, Yang S, Jiang W Ref: BMC Genomics, 12:93, 2011 : PubMed ESTHER: Hu_2011_BMC.Genomics_12_93 PubMedSearch: Hu 2011 BMC.Genomics 12 93 PubMedID: 21284892 Gene_locus related to this paper: cloab-CAC2917, cloab-q97db4, cloac-CAC0719, cloac-CAC1022, cloac-CAC1962, cloac-CAC2246, cloac-CAC3407, cloac-CAP0071, cloac-pnbae Abstract BACKGROUND: Clostridium acetobutylicum, a gram-positive and spore-forming anaerobe, is a major strain for the fermentative production of acetone, butanol and ethanol. But a previously isolated hyper-butanol producing strain C. acetobutylicum EA 2018 does not produce spores and has greater capability of solvent production, especially for butanol, than the type strain C. acetobutylicum ATCC 824. Title: UNC-73/trio RhoGEF-2 activity modulates Caenorhabditis elegans motility through changes in neurotransmitter signaling upstream of the GSA-1/Galphas pathway Hu S, Pawson T, Steven RM Ref: Genetics, 189:137, 2011 : PubMed ESTHER: Hu_2011_Genetics_189_137 PubMedSearch: Hu 2011 Genetics 189 137 PubMedID: 21750262 Abstract Rho-family GTPases play regulatory roles in many fundamental cellular processes. Caenorhabditis elegans UNC-73 RhoGEF isoforms function in axon guidance, cell migration, muscle arm extension, phagocytosis, and neurotransmission by activating either Rac or Rho GTPase subfamilies. Multiple differentially expressed UNC-73 isoforms contain a Rac-specific RhoGEF-1 domain, a Rho-specific RhoGEF-2 domain, or both domains. The UNC-73E RhoGEF-2 isoform is activated by the G-protein subunit Galphaq and is required for normal rates of locomotion; however, mechanisms of UNC-73 and Rho pathway regulation of locomotion are not clear. To better define UNC-73 function in the regulation of motility we used cell-specific and inducible promoters to examine the temporal and spatial requirements of UNC-73 RhoGEF-2 isoform function in mutant rescue experiments. We found that UNC-73E acts within peptidergic neurons of mature animals to regulate locomotion rate. Although unc-73 RhoGEF-2 mutants have grossly normal synaptic morphology and weak resistance to the acetylcholinesterase inhibitor aldicarb, they are significantly hypersensitive to the acetylcholine receptor agonist levamisole, indicating alterations in acetylcholine neurotransmitter signaling. Consistent with peptidergic neuron function, unc-73 RhoGEF-2 mutants exhibit a decreased level of neuropeptide release from motor neuron dense core vesicles (DCVs). The unc-73 locomotory phenotype is similar to those of rab-2 and unc-31, genes with distinct roles in the DCV-mediated secretory pathway. We observed that constitutively active Galphas pathway mutations, which compensate for DCV-mediated signaling defects, rescue unc-73 RhoGEF-2 and rab-2 lethargic movement phenotypes. Together, these data suggest UNC-73 RhoGEF-2 isoforms are required for proper neurotransmitter signaling and may function in the DCV-mediated neuromodulatory regulation of locomotion rate. Title: Complete genome analysis of Sulfobacillus acidophilus strain TPY, isolated from a hydrothermal vent in the Pacific Ocean Li B, Chen Y, Liu Q, Hu S, Chen X Ref: Journal of Bacteriology, 193:5555, 2011 : PubMed ESTHER: Li_2011_J.Bacteriol_193_5555 PubMedSearch: Li 2011 J.Bacteriol 193 5555 PubMedID: 21914875 Gene_locus related to this paper: sulat-f8ic83 Abstract Sulfobacillus acidophilus strain TPY is a moderately thermoacidophilic bacterium originally isolated from a hydrothermal vent in the Pacific Ocean. Ferrous iron and sulfur oxidation in acidic environments in strain TPY have been confirmed. Here we report the genome sequence and annotation of the strain TPY, which is the first complete genome of Sulfobacillus acidophilus. Title: Genome sequence of Agrobacterium tumefaciens strain F2, a bioflocculant-producing bacterium Li A, Geng J, Cui D, Shu C, Zhang S, Yang J, Xing J, Wang J, Ma F, Hu S Ref: Journal of Bacteriology, 193:5531, 2011 : PubMed ESTHER: Li_2011_J.Bacteriol_193_5531 PubMedSearch: Li 2011 J.Bacteriol 193 5531 PubMedID: 21914861 Gene_locus related to this paper: rhird-f7u6g7 Abstract Agrobacterium tumefaciens F2 is an efficient bioflocculant-producing bacterium. But the genes related to the metabolic pathway of bioflocculant biosynthesis in strain F2 are unknown. We present the draft genome of A. tumefaciens F2. It could provide further insight into the biosynthetic mechanism of polysaccharide-like bioflocculant in strain F2. Title: Complete genome sequences of Brucella melitensis strains M28 and M5-90, with different virulence backgrounds Wang F, Hu S, Gao Y, Qiao Z, Liu W, Bu Z Ref: Journal of Bacteriology, 193:2904, 2011 : PubMed ESTHER: Wang_2011_J.Bacteriol_193_2904 PubMedSearch: Wang 2011 J.Bacteriol 193 2904 PubMedID: 21478357 Gene_locus related to this paper: brume-BMEI0552, brume-BMEI1119, brume-BMEI1365, brume-BMEI1594, brume-BMEI1608, brume-BMEII0047, brume-BMEII0681, brume-BMEII0989, brume-PCAD, brusu-BR1327 Abstract Brucella melitensis is a Gram-negative coccobacillus bacteria belonging to the Alphaproteobacteria subclass. It is an important zoonotic pathogen that causes brucellosis, a disease affecting sheep, cattle, and sometimes humans. The B. melitensis strain M5-90, a live attenuated vaccine cultured from the B. melitensis virulent strain M28, has been an effective tool to control brucellosis in goats and sheep in China. Here we report the complete genome sequences of B. melitensis M28 and M5-90, strains with different virulence backgrounds, which will serve as a valuable reference for future studies. Title: Complete genome sequence of the pathogenic bacterium Riemerella anatipestifer strain RA-GD Yuan J, Liu W, Sun M, Song S, Cai J, Hu S Ref: Journal of Bacteriology, 193:2896, 2011 : PubMed ESTHER: Yuan_2011_J.Bacteriol_193_2896 PubMedSearch: Yuan 2011 J.Bacteriol 193 2896 PubMedID: 21441509 Gene_locus related to this paper: riean-e6jh69, riean-e6jim0 Abstract Riemerella anatipestifer is a well-described pathogen of waterfowl and other avian species which can cause a great loss to the poultry industry. Here we obtained the complete genome sequence of R. anatipestifer strain RA-GD, which was isolated from an infected duck in Guangzhou, China, and was cultivated in our laboratory. Title: Tacrine(2)-ferulic acid, a novel multifunctional dimer, attenuates 6-hydroxydopamine-induced apoptosis in PC12 cells by activating Akt pathway Zhang H, Mak SH, Cui W, Li W, Han R, Hu S, Ye M, Pi R, Han YF Ref: Neurochem Int, 59:981, 2011 : PubMed ESTHER: Zhang_2011_Neurochem.Int_59_981 PubMedSearch: Zhang 2011 Neurochem.Int 59 981 PubMedID: 21939707 Abstract Oxidative stress is closely related to the pathogenesis of neurodegenerative disorders such as Parkinson's disease (PD). In this study, we investigated the neuroprotective effect of tacrine-ferulic acid dimers linked by an alkylenediamine side chain (TnFA, n=2-7), a series of novel acetylcholinesterase inhibitors, against 6-hydroxydopamine (6-OHDA)-induced apoptosis in PC12 cells. Among these dimers, pre-treatment of tacrine(2)-ferulic acid (T2FA, 3-30 muM) attenuated 6-OHDA-induced apoptosis in a concentration-dependent manner. The activations of glycogen synthase kinase 3beta (GSK3beta) and extracellular signal-regulated kinase (ERK) were observed after the treatment of 6-OHDA. Both SB415286 (an inhibitor of GSK3beta) and PD98059 (an inhibitor of ERK kinase) reduced the neurotoxicity induced by 6-OHDA, indicating that GSK3beta and ERK are involved in 6-OHDA-induced apoptosis. T2FA was able to inhibit the activation of GSK3beta, but not ERK, in an Akt-dependent manner. Furthermore, LY294002, a phosphoinositide 3-kinase inhibitor, abolished the neuroprotective effect of T2FA. Collectively, these results suggest that T2FA prevents 6-OHDA-induced apoptosis possibly by activating the Akt pathway in PC12 cells. Title: Genomic analysis of the multidrug-resistant Acinetobacter baumannii strain MDR-ZJ06 widely spread in China Zhou H, Zhang T, Yu D, Pi B, Yang Q, Zhou J, Hu S, Yu Y Ref: Antimicrobial Agents & Chemotherapy, 55:4506, 2011 : PubMed ESTHER: Zhou_2011_Antimicrob.Agents.Chemother_55_4506 PubMedSearch: Zhou 2011 Antimicrob.Agents.Chemother 55 4506 PubMedID: 21788470 Gene_locus related to this paper: aciba-f5iht4, aciba-a0a009wzt4 Abstract We previously reported that the multidrug-resistant (MDR) Acinetobacter baumannii strain MDR-ZJ06, belonging to European clone II, was widely spread in China. In this study, we report the whole-genome sequence of this clinically important strain. A 38.6-kb AbaR-type genomic resistance island (AbaR22) was identified in MDR-ZJ06. AbaR22 has a structure similar to those of the resistance islands found in A. baumannii strains AYE and AB0057, but it contained only a few antibiotic resistance genes. The region of resistant gene accumulation as previously described was not found in AbaR22. In the chromosome of the strain MDR-ZJ06, we identified the gene bla(oxa-23) in a composite transposon (Tn2009). Tn2009 shared the backbone with other A. baumannii transponsons that harbor bla(oxa-23), but it was bracketed by two ISAba1 elements which were transcribed in the same orientation. MDR-ZJ06 also expressed the armA gene on its plasmid pZJ06, and this gene has the same genetic environment as the armA gene of the Enterobacteriaceae. These results suggest variability of resistance acquisition even in closely related A. baumannii strains. Title: Complete genome sequence of Lactobacillus casei Zhang, a new probiotic strain isolated from traditional homemade koumiss in Inner Mongolia, China Zhang W, Yu D, Sun Z, Wu R, Chen X, Chen W, Meng H, Hu S, Zhang H Ref: Journal of Bacteriology, 192:5268, 2010 : PubMed ESTHER: Zhang_2010_J.Bacteriol_192_5268 PubMedSearch: Zhang 2010 J.Bacteriol 192 5268 PubMedID: 20675486 Gene_locus related to this paper: lacc3-q03b36, lacc3-q035l1, laccb-b3wcx2, lacrh-pepr, lacca-b5qt93, lacca-k0n1x0, lacpa-s2ter8, lacpa-s2rz88 Abstract Lactobacillus casei Zhang is a new probiotic bacterium isolated from koumiss collected in Inner Mongolia, China. Here, we report the main genome features of L. casei Zhang and the identification of several predicted proteins implicated in interactions with the host. Title: Genome evolution driven by host adaptations results in a more virulent and antimicrobial-resistant Streptococcus pneumoniae serotype 14 Ding F, Tang P, Hsu MH, Cui P, Hu S, Yu J, Chiu CH Ref: BMC Genomics, 10:158, 2009 : PubMed ESTHER: Ding_2009_BMC.Genomics_10_158 PubMedSearch: Ding 2009 BMC.Genomics 10 158 PubMedID: 19361343 Gene_locus related to this paper: strpi-pepx, strpj-b8zns7, strpn-AXE1, strpn-b2dz20, strpn-SP0614 Abstract BACKGROUND: Streptococcus pneumoniae serotype 14 is one of the most common pneumococcal serotypes that cause invasive pneumococcal diseases worldwide. Serotype 14 often expresses resistance to a variety of antimicrobial agents, resulting in difficulties in treatment. To gain insight into the evolution of virulence and antimicrobial resistance traits in S. pneumoniae from the genome level, we sequenced the entire genome of a serotype 14 isolate (CGSP14), and carried out comprehensive comparison with other pneumococcal genomes. Multiple serotype 14 clinical isolates were also genotyped by multilocus sequence typing (MLST). RESULTS: Comparative genomic analysis revealed that the CGSP14 acquired a number of new genes by horizontal gene transfer (HGT), most of which were associated with virulence and antimicrobial resistance and clustered in mobile genetic elements. The most remarkable feature is the acquisition of two conjugative transposons and one resistance island encoding eight resistance genes. Results of MLST suggested that the major driving force for the genome evolution is the environmental drug pressure. CONCLUSION: The genome sequence of S. pneumoniae serotype 14 shows a bacterium with rapid adaptations to its lifecycle in human community. These include a versatile genome content, with a wide range of mobile elements, and chromosomal rearrangement; the latter re-balanced the genome after events of HGT. Title: Complete genome of Phenylobacterium zucineum--a novel facultative intracellular bacterium isolated from human erythroleukemia cell line K562 Luo Y, Xu X, Ding Z, Liu Z, Zhang B, Yan Z, Sun J, Hu S, Hu X Ref: BMC Genomics, 9:386, 2008 : PubMed ESTHER: Luo_2008_BMC.Genomics_9_386 PubMedSearch: Luo 2008 BMC.Genomics 9 386 PubMedID: 18700039 Gene_locus related to this paper: phezh-b4r8z3, phezh-b4r801, phezh-b4r876, phezh-b4ras1, phezh-b4ras4, phezh-b4ray3, phezh-b4rb44, phezh-b4rd51, phezh-b4re02, phezh-b4rfb7, phezh-b4rfk3, phezh-b4rfq9, phezh-b4rfw5, phezh-b4rgf2, phezh-b4rh78, phezh-b4rh88, phezh-b4rhb1, phezh-b4rhb2, phezh-dhma, phezh-b4r875, phezh-b4rfb8, phezh-b4rbt7 Abstract BACKGROUND: Phenylobacterium zucineum is a recently identified facultative intracellular species isolated from the human leukemia cell line K562. Unlike the known intracellular pathogens, P. zucineum maintains a stable association with its host cell without affecting the growth and morphology of the latter. RESULTS: Here, we report the whole genome sequence of the type strain HLK1T. The genome consists of a circular chromosome (3,996,255 bp) and a circular plasmid (382,976 bp). It encodes 3,861 putative proteins, 42 tRNAs, and a 16S-23S-5S rRNA operon. Comparative genomic analysis revealed that it is phylogenetically closest to Caulobacter crescentus, a model species for cell cycle research. Notably, P. zucineum has a gene that is strikingly similar, both structurally and functionally, to the cell cycle master regulator CtrA of C. crescentus, and most of the genes directly regulated by CtrA in the latter have orthologs in the former. CONCLUSION: This work presents the first complete bacterial genome in the genus Phenylobacterium. Comparative genomic analysis indicated that the CtrA regulon is well conserved between C. crescentus and P. zucineum. Title: Environmental adaptation: genomic analysis of the piezotolerant and psychrotolerant deep-sea iron reducing bacterium Shewanella piezotolerans WP3 Wang F, Wang J, Jian H, Zhang B, Li S, Zeng X, Gao L, Bartlett DH, Yu J and Xiao X <1 more author(s)> Wang F, Wang J, Jian H, Zhang B, Li S, Zeng X, Gao L, Bartlett DH, Yu J, Hu S, Xiao X (- 1) Ref: PLoS ONE, 3:e1937, 2008 : PubMed ESTHER: Wang_2008_PLoS.ONE_3_E1937 PubMedSearch: Wang 2008 PLoS.ONE 3 E1937 PubMedID: 18398463 Gene_locus related to this paper: shepw-b8ci75, shepw-b8cib3, shepw-b8ciu7, shepw-b8cld5, shepw-b8cll2, shepw-b8clm3, shepw-b8cls4, shepw-b8ct86, shepw-b8ctf0, shepw-b8ctt3, shepw-b8cuq7, shepw-b8cuu6, shepw-b8cuz1, shepw-b8cvm0, shepw-b8cqh1, shepw-b8cgv9, shepw-b8chj5, shepw-b8cpv3, shepw-b8civ4, shepw-b8cn18 Abstract Shewanella species are widespread in various environments. Here, the genome sequence of Shewanella piezotolerans WP3, a piezotolerant and psychrotolerant iron reducing bacterium from deep-sea sediment was determined with related functional analysis to study its environmental adaptation mechanisms. The genome of WP3 consists of 5,396,476 base pairs (bp) with 4,944 open reading frames (ORFs). It possesses numerous genes or gene clusters which help it to cope with extreme living conditions such as genes for two sets of flagellum systems, structural RNA modification, eicosapentaenoic acid (EPA) biosynthesis and osmolyte transport and synthesis. And WP3 contains 55 open reading frames encoding putative c-type cytochromes which are substantial to its wide environmental adaptation ability. The mtr-omc gene cluster involved in the insoluble metal reduction in the Shewanella genus was identified and compared. The two sets of flagellum systems were found to be differentially regulated under low temperature and high pressure; the lateral flagellum system was found essential for its motility and living at low temperature. Title: 14,15-Dihydroxyeicosatrienoic acid activates peroxisome proliferator-activated receptor-alpha Fang X, Hu S, Xu B, Snyder GD, Harmon S, Yao J, Liu Y, Sangras B, Falck JR and Spector AA <1 more author(s)> Fang X, Hu S, Xu B, Snyder GD, Harmon S, Yao J, Liu Y, Sangras B, Falck JR, Weintraub NL, Spector AA (- 1) Ref: American Journal of Physiology Heart Circ Physiol, 290:H55, 2006 : PubMed ESTHER: Fang_2006_Am.J.Physiol.Heart.Circ.Physiol_290_H55 PubMedSearch: Fang 2006 Am.J.Physiol.Heart.Circ.Physiol 290 H55 PubMedID: 16113065 Abstract Epoxyeicosatrienoic acids (EETs), lipid mediators synthesized from arachidonic acid by cytochrome P-450 epoxygenases, are converted by soluble epoxide hydrolase (SEH) to the corresponding dihydroxyeicosatrienoic acids (DHETs). Originally considered as inactive degradation products of EETs, DHETs have biological activity in some systems. Here we examined the capacity of EETs and DHETs to activate peroxisome proliferator-activated receptor-alpha (PPARalpha). We find that among the EET and DHET regioisomers, 14,15-DHET is the most potent PPARalpha activator in a COS-7 cell expression system. Incubation with 10 microM 14,15-DHET produced a 12-fold increase in PPARalpha-mediated luciferase activity, an increase similar to that produced by the PPARalpha agonist Wy-14643 (20 microM). Although 10 microM 14,15-EET produced a threefold increase in luciferase activity, this was abrogated by the SEH inhibitor dicyclohexylurea. 14-Hexyloxytetradec-5(Z)-enoic acid, a 14,15-EET analog that cannot be converted to a DHET, did not activate PPARalpha. However, PPARalpha was activated by 2-(14,15-epoxyeicosatrienoyl)glycerol, which was hydrolyzed and the released 14,15-EET converted to 14,15-DHET. COS-7 cells incorporated 14,15-[3H]DHET from the medium, and the cells also retained a small amount of the DHET formed during incubation with 14,15-[3H]EET. Binding studies indicated that 14,15-[3H]DHET binds to the ligand binding domain of PPARalpha with a Kd of 1.4 microM. Furthermore, 14,15-DHET increased the expression of carnitine palmitoyltransferase 1A, a PPARalpha-responsive gene, in transfected HepG2 cells. These findings suggest that 14,15-DHET, produced from 14,15-EET by the action of SEH, may function as an endogenous activator of PPARalpha. 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: The genome sequence of Salmonella enterica serovar Choleraesuis, a highly invasive and resistant zoonotic pathogen Chiu CH, Tang P, Chu C, Hu S, Bao Q, Yu J, Chou YY, Wang HS, Lee YS Ref: Nucleic Acids Research, 33:1690, 2005 : PubMed ESTHER: Chiu_2005_Nucleic.Acids.Res_33_1690 PubMedSearch: Chiu 2005 Nucleic.Acids.Res 33 1690 PubMedID: 15781495 Gene_locus related to this paper: salen-OPDB, salti-q8z717, salty-a1yjl0, salty-AES, salty-BIOH, salty-DLHH, salty-ENTF, salty-FES, salty-IROD, salty-P74847, salty-PLDB, salty-STM0332, salty-STM2547, salty-STM4506, salty-yafa, salty-YBFF, salty-ycfp, salty-YFBB, salty-YHET, salty-YQIA Abstract Salmonella enterica serovar Choleraesuis (S. Choleraesuis), a highly invasive serovar among non-typhoidal Salmonella, usually causes sepsis or extra-intestinal focal infections in humans. S. Choleraesuis infections have now become particularly difficult to treat because of the emergence of resistance to multiple antimicrobial agents. The 4.7 Mb genome sequence of a multidrug-resistant S. Choleraesuis strain SC-B67 was determined. Genome wide comparison of three sequenced Salmonella genomes revealed that more deletion events occurred in S. Choleraesuis SC-B67 and S.Typhi CT18 relative to S. Typhimurium LT2. S. Choleraesuis has 151 pseudogenes, which, among the three Salmonella genomes, include the highest percentage of pseudogenes arising from the genes involved in bacterial chemotaxis signal-transduction pathways. Mutations in these genes may increase smooth swimming of the bacteria, potentially allowing more effective interactions with and invasion of host cells to occur. A key regulatory gene of TetR/AcrR family, acrR, was inactivated through the introduction of an internal stop codon resulting in overexpression of AcrAB that appears to be associated with ciprofloxacin resistance. While lateral gene transfer providing basic functions to allow niche expansion in the host and environment is maintained during the evolution of different serovars of Salmonella, genes providing little overall selective benefit may be lost rapidly. Our findings suggest that the formation of pseudogenes may provide a simple evolutionary pathway that complements gene acquisition to enhance virulence and antimicrobial resistance in S. Choleraesuis. Title: The Genomes of Oryza sativa: a history of duplications Yu J, Wang J, Lin W, Li S, Li H, Zhou J, Ni P, Dong W, Hu S and Yang H <88 more author(s)> Yu J, Wang J, Lin W, Li S, Li H, Zhou J, Ni P, Dong W, Hu S, Zeng C, Zhang J, Zhang Y, Li R, Xu Z, Li X, Zheng H, Cong L, Lin L, Yin J, Geng J, Li G, Shi J, Liu J, Lv H, Li J, Deng Y, Ran L, Shi X, Wang X, Wu Q, Li C, Ren X, Li D, Liu D, Zhang X, Ji Z, Zhao W, Sun Y, Zhang Z, Bao J, Han Y, Dong L, Ji J, Chen P, Wu S, Xiao Y, Bu D, Tan J, Yang L, Ye C, Xu J, Zhou Y, Yu Y, Zhang B, Zhuang S, Wei H, Liu B, Lei M, Yu H, Li Y, Xu H, Wei S, He X, Fang L, Huang X, Su Z, Tong W, Tong Z, Ye J, Wang L, Lei T, Chen C, Chen H, Huang H, Zhang F, Li N, Zhao C, Huang Y, Li L, Xi Y, Qi Q, Li W, Hu W, Tian X, Jiao Y, Liang X, Jin J, Gao L, Zheng W, Hao B, Liu S, Wang W, Yuan L, Cao M, McDermott J, Samudrala R, Wong GK, Yang H (- 88) Ref: PLoS Biol, 3:e38, 2005 : PubMed ESTHER: Yu_2005_PLoS.Biol_3_e38 PubMedSearch: Yu 2005 PLoS.Biol 3 e38 PubMedID: 15685292 Gene_locus related to this paper: orysa-Q7XTC5, orysa-Q852M6, orysa-Q8GSE8, orysa-Q9S7P1, orysa-Q9FYP7, orysa-Q5ZBH3, orysa-Q5ZA26, orysa-Q5JLP6, orysa-Q8H5P9, orysa-Q8H5P5, orysa-Q7F1Y5, orysa-Q949C9, orysa-cbp1, orysa-cbp3, orysa-cbpx, orysa-Q33B71, orysa-Q8GSJ3, orysa-LPL1, orysa-Q6YSZ8, orysa-Q8S5X5, orysa-Q8LIG3, orysa-Q6K7F5, orysa-Q7F1B1, orysa-Q8H4S9, orysa-Q69UB1, orysa-Q9FW17, orysa-Q337C3, orysa-Q7F959, orysa-Q84QZ6, orysa-Q84QY7, orysa-Q851E3, orysa-Q6YTH5, orysa-Q0JK71, orysa-Q8S1D9, orysa-Q5N8V4, orysa-Q0JCY4, orysa-Q8GTK2, orysa-B9EWJ8, orysa-Q8H3K6, orysa-Q6ZDG8, orysa-Q6ZDG6, orysa-Q6ZDG5, orysa-Q6ZDG4, orysa-Q5NAI4, orysa-Q658B2, orysa-Q5JMQ8, orysa-Q5QMD9, orysa-Q5N7L1, orysa-Q8RYV9, orysa-Q8H3R3, orysa-Q5SNH3, orysa-Q8W0F0, orysa-pir7a, orysa-pir7b, orysa-q2qlm4, orysa-q2qm78, orysa-q2qm82, orysa-q2qn31, orysa-q2qnj4, orysa-q2qnt9, orysa-q2qur1, orysa-q2qx94, orysa-q2qyi1, orysa-q2qyj1, orysa-q2r051, orysa-q2r077, orysa-q2ram0, orysa-q2rat1, orysa-q2rbb3, orysa-Q4VWY7, orysa-q5na00, orysa-q5nbu1, orysa-Q5QLC0, orysa-q5smv5, orysa-Q5VP27, orysa-q5vrt2, orysa-q5w6c5, orysa-q5z5a3, orysa-q5z9i2, orysa-q5z417, orysa-q5z901, orysa-Q5ZAM8, orysa-Q5ZBI5, orysa-Q5ZCR3, orysa-q6atz0, orysa-q6ave2, orysa-q6f358, orysa-q6h6s1, orysa-q6h7i6, orysa-q6i5q3, orysa-q6i5u7, orysa-q6j657, orysa-q6k3d9, orysa-q6k4q2, orysa-q6k880, orysa-q6l5b6, orysa-Q6L5F5, orysa-q6l556, orysj-q6yse8, orysa-q6yy42, orysa-q6yzk1, orysa-q6z8b1, orysa-q6z995, orysa-q6zc62, orysa-q6zia4, orysa-q6zjq6, orysa-q7x7y5, orysa-Q7XC50, orysa-q7xej4, orysa-q7xem8, orysa-q7xkj9, orysa-q7xr62, orysa-q7xr63, orysa-q7xr64, orysa-q7xsg1, orysa-q7xsq2, orysa-q7xts6, orysa-q7xv53, orysa-Q7XVB5, orysa-Q8L562, orysa-Q8LQS5, orysa-Q8RZ40, orysa-Q8RZ79, orysa-Q8S0U8, orysa-Q8S0V0, orysa-Q8S125, orysa-Q8SAY7, orysa-Q8SAY9, orysa-Q8W3C6, orysa-Q8W3F2, orysa-Q8W3F4, orysa-Q8W3F6, orysa-Q9LHX5, orysa-q33aq0, orysa-q53lh1, orysa-q53m20, orysa-q53nd8, orysa-q60e79, orysa-q60ew8, orysa-q67iz2, orysa-q67iz3, orysa-q67iz7, orysa-q67iz8, orysa-q67j02, orysa-q67j05, orysa-q67j07, orysa-q67j09, orysa-q67j10, orysa-q67tr6, orysa-q67tv0, orysa-q67uz1, orysa-q67v34, orysa-q67wz5, orysa-q69j38, orysa-q69k08, orysa-q69md7, orysa-q69me0, orysa-q69pf3, orysa-q69ti3, orysa-q69xr2, orysa-q69y12, orysa-q69y21, orysa-q75hy2, orysa-q75i01, orysa-Q94JD7, orysa-Q0J0A4, orysa-q651a8, orysa-q651z3, orysa-q652g4, orysa-q688m0, orysa-q688m8, orysa-q688m9, orysa-Q6H8G1, orysi-a2wn01, orysi-a2xc83, orysi-a2yh83, orysi-a2z179, orysi-a2zef2, orysi-b8a7e6, orysi-b8a7e7, orysi-b8bfe5, orysi-b8bhp9, orysj-a3b9l8, orysj-b9eub8, orysj-b9eya5, orysj-b9fi05, orysj-b9fkb0, orysj-b9fn42, orysj-b9gbb7, orysj-cgep, orysj-PLA7, orysj-q0d4u5, orysj-q0djj0, orysj-q0jaf0, orysj-q5jl22, orysj-q5jlw7, orysj-q5z419, orysj-q6h7q9, orysj-q6yvk6, orysj-q6z6i1, orysj-q7f8x1, orysj-q7xcx3, orysj-q9fwm6, orysj-q10j20, orysj-q10ss2, orysj-q69uw6, orysj-q94d71, orysj-q338c0, orysi-b8bly4, orysj-b9gbs4, orysi-a2zb88, orysj-b9gbs1, orysi-b8b698, orysj-pla4, orysj-pla1 Abstract We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family. Title: Effect of soluble epoxide hydrolase inhibition on epoxyeicosatrienoic acid metabolism in human blood vessels Fang X, Weintraub NL, McCaw RB, Hu S, Harmon SD, Rice JB, Hammock BD, Spector AA Ref: American Journal of Physiology Heart Circ Physiol, 287:H2412, 2004 : PubMed ESTHER: Fang_2004_Am.J.Physiol.Heart.Circ.Physiol_287_H2412 PubMedSearch: Fang 2004 Am.J.Physiol.Heart.Circ.Physiol 287 H2412 PubMedID: 15284062 Abstract We investigated the effects of soluble epoxide hydrolase (sEH) inhibition on epoxyeicosatrienoic acid (EET) metabolism in intact human blood vessels, including the human saphenous vein (HSV), coronary artery (HCA), and aorta (HA). When HSV segments were perfused with 2 micromol/l 14,15-[3H]EET for 4 h, >60% of radioactivity in the perfusion medium was converted to 14,15-dihydroxyeicosatrienoic acid (DHET). Similar results were obtained with endothelium-denuded vessels. 14,15-DHET was released from both the luminal and adventitial surfaces of the HSV. When HSVs were incubated with 14,15-[3H]EET under static (no flow) conditions, formation of 14,15-DHET was detected within 15 min and was inhibited by the selective sEH inhibitors N,N'-dicyclohexyl urea and N-cyclohexyl-N'-dodecanoic acid urea (CUDA). Similarly, CUDA inhibited the conversion of 11,12-[3H]EET to 11,12-DHET by the HSV. sEH inhibition enhanced the uptake of 14,15-[3H]EET and facilitated the formation of 10,11-epoxy-16:2, a beta-oxidation product. The HCA and HA converted 14,15-[3H]EET to DHET, and this also was inhibited by CUDA. These findings in intact human blood vessels indicate that conversion to DHET is the predominant pathway for 11,12- and 14,15-EET metabolism and that sEH inhibition can modulate EET metabolism in vascular tissue. Title: A complete sequence of the T. tengcongensis genome Bao Q, Tian Y, Li W, Xu Z, Xuan Z, Hu S, Dong W, Yang J, Chen Y and Yang H <11 more author(s)> Bao Q, Tian Y, Li W, Xu Z, Xuan Z, Hu S, Dong W, Yang J, Chen Y, Xue Y, Xu Y, Lai X, Huang L, Dong X, Ma Y, Ling L, Tan H, Chen R, Wang J, Yu J, Yang H (- 11) Ref: Genome Res, 12:689, 2002 : PubMed ESTHER: Bao_2002_Genome.Res_12_689 PubMedSearch: Bao 2002 Genome.Res 12 689 PubMedID: 11997336 Gene_locus related to this paper: thete-DAP2, thete-LIPA3, thete-MHPC, thete-MHPC2, thete-MHPC3, thete-MHPC4, thete-PLDB, thete-TTE1809, thetn-DAP2.2 Abstract Thermoanaerobacter tengcongensis is a rod-shaped, gram-negative, anaerobic eubacterium that was isolated from a freshwater hot spring in Tengchong, China. Using a whole-genome-shotgun method, we sequenced its 2,689,445-bp genome from an isolate, MB4(T) (Genbank accession no. AE008691). The genome encodes 2588 predicted coding sequences (CDS). Among them, 1764 (68.2%) are classified according to homology to other documented proteins, and the rest, 824 CDS (31.8%), are functionally unknown. One of the interesting features of the T. tengcongensis genome is that 86.7% of its genes are encoded on the leading strand of DNA replication. Based on protein sequence similarity, the T. tengcongensis genome is most similar to that of Bacillus halodurans, a mesophilic eubacterium, among all fully sequenced prokaryotic genomes up to date. Computational analysis on genes involved in basic metabolic pathways supports the experimental discovery that T. tengcongensis metabolizes sugars as principal energy and carbon source and utilizes thiosulfate and element sulfur, but not sulfate, as electron acceptors. T. tengcongensis, as a gram-negative rod by empirical definitions (such as staining), shares many genes that are characteristics of gram-positive bacteria whereas it is missing molecular components unique to gram-negative bacteria. A strong correlation between the G + C content of tDNA and rDNA genes and the optimal growth temperature is found among the sequenced thermophiles. It is concluded that thermophiles are a biologically and phylogenetically divergent group of prokaryotes that have converged to sustain extreme environmental conditions over evolutionary timescale. | |||||||
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