Author Report for: Yuan YNo contact information in database for Yuan Y
Yan X, Chen K, Jia H, Zhao Q, Du G, Guo Q, Chen H, Yuan Y, Yue T Ref: Food Chem, 431:137172, 2024 : PubMed ESTHER: Yan_2024_Food.Chem_431_137172 PubMedSearch: Yan 2024 Food.Chem 431 137172 PubMedID: 37603997 Abstract Patulin (PAT) is a mycotoxin known to globally contaminate fruits. The economic losses and health hazards caused by PAT desires a safe and efficient strategy for detoxifying PAT. Here, a magnetic core-shell hierarchical mesoporous metal-organic framework (Fe(3)O(4)@HMUiO-66-NH(2)) was synthesized via a salt-assisted nanoemulsion guided assembly method. This mesoporous structure (centered at 4.25 nm) allowed porcine pancreatic lipase (PPL) to infiltrate into the MOF shell at an immobilized amount of 255 mg/g, providing protection for PPL and enabling rapid separation and recovery. Compared with free PPL, PPL/Fe(3)O(4)@HMUiO-66-NH(2) at 70 degreesC possessed 4.7 folds improved thermal stability in terms of half-life. The detoxification rates of immobilized enzyme for PAT in neutral water, acidic water, and apple juice were 99.6%, 60.9%, and 52.6%, respectively. Moreover, the so designed PPL/Fe(3)O(4)@HMUiO-66-NH(2) showed extraordinary storage stability, reusability, and biocompatibility. Crucially, the quality of apple juice did not change significantly after PPL/Fe(3)O(4)@HMUiO-66-NH(2) treatment, which facilitated its application in apple juice. The magnetic core-shell mesoporous structure along with the revealed mechanism of immobilized enzyme detoxification of PAT provide tremendous opportunity for designing a safe and efficient PAT detoxification method. Title: Targeting ANGPTL3 by GalNAc-conjugated siRNA ANGsiR10 lowers blood lipids with long-lasting and potent efficacy in mice and monkeys Wang J, Zheng W, Zheng S, Yuan Y, Wen W, Cui W, Xue L, Sun X, Shang H and Zhang X <3 more author(s)> Wang J, Zheng W, Zheng S, Yuan Y, Wen W, Cui W, Xue L, Sun X, Shang H, Zhang H, Xiao RP, Gao S, Zhang X (- 3) Ref: Mol Ther Nucleic Acids, 31:68, 2023 : PubMed ESTHER: Wang_2023_Mol.Ther.Nucleic.Acids_31_68 PubMedSearch: Wang 2023 Mol.Ther.Nucleic.Acids 31 68 PubMedID: 36618267 Abstract Angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipoproteins by inhibiting both lipoprotein and endothelial lipases. It has been intensively investigated as a drug target for the treatment of dyslipidemia. In the present study, a modified small interfering RNA (siRNA) conjugated with GalNAc ANGsiR10 was characterized by insvivo and insvitro studies for its effect on ANGPTL3 silencing, the reduction of plasma triglycerides (TGs), and cholesterol levels in disease models. The results showed that ANGsiR10 displayed a significant and long-lasting efficacy in reducing blood TG and cholesterol levels in both mice and monkeys. Remarkably, the maximal reductions of plasma TG levels in the hApoC3-Tg mice, a model with high TG levels, and the spontaneous dyslipidemia model of rhesus monkey were 96.3% and 67.7%, respectively, after a single dose of ANGsiR10, with long-lasting effects up to 15sweeks. The cholesterol levels were also reduced in response to treatment, especially the non-HDL-c level, without altering the ApoA/ApoB ratio. This study showed that ANGsiR10 is effective in treating dyslipidemia and is worth further development. Title: Construction of a QSAR Model Based on Flavonoids and Screening of Natural Pancreatic Lipase Inhibitors Yuan Y, Pan F, Zhu Z, Yang Z, Wang O, Li Q, Zhao L Ref: Nutrients, 15:, 2023 : PubMed ESTHER: Yuan_2023_Nutrients_15_ PubMedSearch: Yuan 2023 Nutrients 15 PubMedID: 37571426 Abstract Pancreatic lipase (PL) is a key hydrolase in lipid metabolism. Inhibition of PL activity can intervene in obesity, a global sub-health disease. The natural product is considered a good alternative to chemically synthesized drugs due to its advantages, such as low side effects. However, traditional experimental screening methods are labor-intensive and cost-consuming, and there is an urgent need to develop high-throughput screening methods for the discovery of anti-PL natural products. In this study, a high-throughput virtual screening process for anti-PL natural products is provided. Firstly, a predictable anti-PL natural product QSAR model (R(2)(train) = 0.9444, R(2)(test) = 0.8962) were developed using the artificial intelligence drug design software MolAIcal based on genetic algorithms and their conformational relationships. 1068 highly similar (FS > 0.8) natural products were rapidly enriched based on the structure-activity similarity principle, combined with the QSAR model and the ADMET model, for rapid prediction of a total of five potentially efficient anti-PL natural products (IC(50pre) < 2 microM). Subsequently, molecular docking, molecular dynamics simulation, and MMGBSA free energy calculation were performed to not only reveal the interaction of candidate novel natural products with the amino acid residues of PL but also to validate the stability of these novel natural compounds bound to PL. In conclusion, this study greatly simplifies the screening and discovery of anti-PL natural products and accelerates the development of novel anti-obesity functional foods. Title: Construction of microbial consortia for microbial degradation of complex compounds Cao Z, Yan W, Ding M, Yuan Y Ref: Front Bioeng Biotechnol, 10:1051233, 2022 : PubMed ESTHER: Cao_2022_Front.Bioeng.Biotechnol_10_1051233 PubMedSearch: Cao 2022 Front.Bioeng.Biotechnol 10 1051233 PubMedID: 36561050 Abstract Increasingly complex synthetic environmental pollutants are prompting further research into bioremediation, which is one of the most economical and safest means of environmental restoration. From the current research, using microbial consortia to degrade complex compounds is more advantageous compared to using isolated bacteria, as the former is more adaptable and stable within the growth environment and can provide a suitable catalytic environment for each enzyme required by the biodegradation pathway. With the development of synthetic biology and gene-editing tools, artificial microbial consortia systems can be designed to be more efficient, stable, and robust, and they can be used to produce high-value-added products with their strong degradation ability. Furthermore, microbial consortia systems are shown to be promising in the degradation of complex compounds. In this review, the strategies for constructing stable and robust microbial consortia are discussed. The current advances in the degradation of complex compounds by microbial consortia are also classified and detailed, including plastics, petroleum, antibiotics, azo dyes, and some pollutants present in sewage. Thus, this paper aims to support some helps to those who focus on the degradation of complex compounds by microbial consortia. Title: Bioaccumulation and toxicity of terbuthylazine in earthworms (Eisenia fetida) Li S, Yuan Y, Wang X, Cai L, Wang J, Zhao Y, Jiang L, Yang X Ref: Environ Toxicol Pharmacol, 97:104016, 2022 : PubMed ESTHER: Li_2022_Environ.Toxicol.Pharmacol_97_104016 PubMedSearch: Li 2022 Environ.Toxicol.Pharmacol 97 104016 PubMedID: 36435387 Abstract Terbuthylazine is an effective and widely used s-triazine herbicide. However, limited data exists on its toxicity and bioaccumulation in earthworms (Eisenia fetida). In this study, we investigated the bioaccumulation, antioxidant enzyme activity, detoxification enzyme activity, and DNA damage in earthworms when exposed to terbuthylazine. The results indicated that terbuthylazine in soil had low bioaccumulation in earthworms and the biota-soil accumulation factors of terbuthylazine declined with an increasing soil terbuthylazine concentration. In the enzyme activity assays, the superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST) activities showed upward trends when compared with the control. The carboxylesterase (CarE) activity increased on day 21. The 8-hydroxy-2-deoxyguanosine (8-OHdG) content, a DNA damage bioindicator, was higher than that of the control on day 21. Combined with the integrated biological response index version 2 analysis, these results can provide a comprehensive evaluation of the toxicological effects that terbuthylazine has on earthworms and soil ecosystems. Title: Valorization of Polyethylene Terephthalate to Muconic Acid by Engineering Pseudomonas Putida Liu P, Zheng Y, Yuan Y, Zhang T, Li Q, Liang Q, Su T, Qi Q Ref: Int J Mol Sci, 23:, 2022 : PubMed ESTHER: Liu_2022_Int.J.Mol.Sci_23_10997 PubMedSearch: Liu 2022 Int.J.Mol.Sci 23 10997 PubMedID: 36232310 Abstract Plastic waste is rapidly accumulating in the environment and becoming a huge global challenge. Many studies have highlighted the role of microbial metabolic engineering for the valorization of polyethylene terephthalate (PET) waste. In this study, we proposed a new conceptual scheme for upcycling of PET. We constructed a multifunctional Pseudomonas putida KT2440 to simultaneously secrete PET hydrolase LCC, a leaf-branch compost cutinase, and synthesize muconic acid (MA) using the PET hydrolysate. The final product MA and extracellular LCC can be separated from the supernatant of the culture by ultrafiltration, and the latter was used for the next round of PET hydrolysis. A total of 0.50 g MA was produced from 1 g PET in each cycle of the whole biological processes, reaching 68% of the theoretical conversion. This new conceptual scheme for the valorization of PET waste should have advantages over existing PET upcycling schemes and provides new ideas for the utilization of other macromolecular resources that are difficult to decompose, such as lignin. Title: Antibacterial Efficacy and Mechanisms of Curcumin-Based Photodynamic Treatment against Staphylococcus aureus and Its Application in Juices Yuan Y, Liu Q, Huang Y, Qi M, Yan H, Li W, Zhuang H Ref: Molecules, 27:, 2022 : PubMed ESTHER: Yuan_2022_Molecules_27_ PubMedSearch: Yuan 2022 Molecules 27 PubMedID: 36296729 Abstract Antimicrobial Photodynamic Treatment (aPDT) is a non-thermal sterilization technology, which can inactivate common foodborne pathogens. In the present study, photodynamic inactivation on Staphylococcus aureus (S. aureus) with different concentrations of curcumin and light dose was evaluated and the mechanisms were also investigated. The results showed that curcumin-based aPDT could inactivate S. aureus cells by 6.9 log CFU/mL in phosphate buffered saline (PBS). Moreover, the modified Gompertz model presented a good fit at the inactivation data of S. aureus. Photodynamic treatment caused cell membrane damage as revealed by analyzing scanning electron microscopy (SEM) images. Leakage of intracellular constituents further indicated that cell membrane permeability was changed. Flow cytometry with double staining demonstrated that cell membrane integrity and the activity of nonspecific esterase were destroyed. Compared with the control group, intracellular reactive oxygen species (ROS) levels caused by photodynamic treatment significantly increased. Furthermore, curcumin-based aPDT reduced S. aureus by 5 log CFU/mL in juices. The color of the juices was also tested using a Chromatic meter, and it was found that b* values were the most markedly influenced by photodynamic treatment. Overall, curcumin-based aPDT had strong antibacterial activity against S. aureus. This approach has the potential to remove foodborne pathogens from liquid food. Title: Evaluation of PET Degradation Using Artificial Microbial Consortia Qi X, Ma Y, Chang H, Li B, Ding M, Yuan Y Ref: Front Microbiol, 12:778828, 2021 : PubMed ESTHER: Qi_2021_Front.Microbiol_12_778828 PubMedSearch: Qi 2021 Front.Microbiol 12 778828 PubMedID: 35003008 Abstract Polyethylene terephthalate (PET) biodegradation is regarded as an environmentally friendly degradation method. In this study, an artificial microbial consortium composed of Rhodococcus jostii, Pseudomonas putida and two metabolically engineered Bacillus subtilis was constructed to degrade PET. First, a two-species microbial consortium was constructed with two engineered B. subtilis that could secrete PET hydrolase (PETase) and monohydroxyethyl terephthalate hydrolase (MHETase), respectively; it could degrade 13.6% (weight loss) of the PET film within 7 days. A three-species microbial consortium was further obtained by adding R. jostii to reduce the inhibition caused by terephthalic acid (TPA), a breakdown product of PET. The weight of PET film was reduced by 31.2% within 3 days, achieving about 17.6% improvement compared with the two-species microbial consortium. Finally, P. putida was introduced to reduce the inhibition caused by ethylene glycol (EG), another breakdown product of PET, obtaining a four-species microbial consortium. With the four-species consortium, the weight loss of PET film reached 23.2% under ambient temperature. This study constructed and evaluated the artificial microbial consortia in PET degradation, which demonstrated the great potential of artificial microbial consortia in the utilization of complex substrates, providing new insights for biodegradation of complex polymers. Title: Current Advances in the Biodegradation and Bioconversion of Polyethylene Terephthalate Qi X, Yan W, Cao Z, Ding M, Yuan Y Ref: Microorganisms, 10:, 2021 : PubMed ESTHER: Qi_2021_Microorganisms_10_ PubMedSearch: Qi 2021 Microorganisms 10 PubMedID: 35056486 Abstract Polyethylene terephthalate (PET) is a widely used plastic that is polymerized by terephthalic acid (TPA) and ethylene glycol (EG). In recent years, PET biodegradation and bioconversion have become important in solving environmental plastic pollution. More and more PET hydrolases have been discovered and modified, which mainly act on and degrade the ester bond of PET. The monomers, TPA and EG, can be further utilized by microorganisms, entering the tricarboxylic acid cycle (TCA cycle) or being converted into high value chemicals, and finally realizing the biodegradation and bioconversion of PET. Based on synthetic biology and metabolic engineering strategies, this review summarizes the current advances in the modified PET hydrolases, engineered microbial chassis in degrading PET, bioconversion pathways of PET monomers, and artificial microbial consortia in PET biodegradation and bioconversion. Artificial microbial consortium provides novel ideas for the biodegradation and bioconversion of PET or other complex polymers. It is helpful to realize the one-step bioconversion of PET into high value chemicals. Title: Bio-Potency and Molecular Docking Studies of Isolated Compounds from Grewia optiva J.R. Drumm. ex Burret Ul Bari W, Ur Rehman N, Khan A, Ahsan Halim S, Yuan Y, Blaskovich MAT, Ziora ZM, Zahoor M, Naz S and Al-Harrasi A <2 more author(s)> Ul Bari W, Ur Rehman N, Khan A, Ahsan Halim S, Yuan Y, Blaskovich MAT, Ziora ZM, Zahoor M, Naz S, Ullah R, Alotaibi A, Al-Harrasi A (- 2) Ref: Molecules, 26:, 2021 : PubMed ESTHER: Ul_2021_Molecules_26_ PubMedSearch: Ul 2021 Molecules 26 PubMedID: 33916198 Abstract In the study, two novel compounds along with two new compounds were isolated from Grewia optiva. The novel compounds have never been reported in any plant source, whereas the new compounds are reported for the first time from the studied plant. The four compounds were characterized as: 5,5,7,7,11,13-hexamethyl-2-(5-methylhexyl)icosahydro-1H-cyclopenta[a]chrysen-9-ol (IX), docosanoic acid (X), methanetriol mano formate (XI) and 2,2'-(1,4-phenylene)bis(3-methylbutanoic acid (XII). The anticholinesterase, antidiabetic, and antioxidant potentials of these compounds were determined using standard protocols. All the isolated compounds exhibited a moderate-to-good degree of activity against acetylcholinesterases (AChE) and butyrylcholinesterase (BChE). However, compound XII was particularly effective with IC(50) of 55 microg/mL (against AChE) and 60 microg/mL (against BChE), and this inhibitory activity is supported by in silico docking studies. The same compound was also effective against DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) radicals with IC(50) values of 60 and 62 microg/mL, respectively. The compound also significantly inhibited the activities of alpha-amylase and alpha-glucosidase in vitro. The IC(50) values for inhibition of the two enzymes were recorded as 90 and 92 microg/mL, respectively. The in vitro potentials of compound XII to treat Alzheimer's disease (in terms of AchE and BChE inhibition), diabetes (in terms of alpha-amylase and alpha-glucosidase inhibition), and oxidative stress (in terms of free radical scavenging) suggest further in vivo investigations of the compound for assessing its efficacy, safety profile, and other parameters to proclaim the compound as a potential drug candidate. Title: Congenital myasthenic syndrome in China: genetic and myopathological characterization Zhao Y, Li Y, Bian Y, Yao S, Liu P, Yu M, Zhang W, Wang Z, Yuan Y Ref: Ann Clin Transl Neurol, :, 2021 : PubMed ESTHER: Zhao_2021_Ann.Clin.Transl.Neurol__ PubMedSearch: Zhao 2021 Ann.Clin.Transl.Neurol PubMedID: 33756069 Abstract OBJECTIVE: We aimed to summarize the clinical, genetic, and myopathological features of a cohort of Chinese patients with congenital myasthenic syndrome, and follow up on therapeutic outcomes. METHODS: The clinical spectrum, mutational frequency of genes, and pathological diagnostic clues of various subtypes of patients with congenital myasthenic syndrome were summarized. Therapeutic effects were followed up. RESULTS: Thirty-five patients from 29 families were recruited. Ten genes were identified: GFPT1 (27.6%), AGRN (17.2%), CHRNE (17.2%), COLQ (13.8%), GMPPB (6.9%), CHAT, CHRNA1, DOK7, COG7, and SLC25A1 (3.4% each, respectively). Sole limb-girdle weakness was found in patients with AGRN (1/8) and GFPT1 (7/8) mutations, whereas distal weakness was all observed in patients with AGRN (6/8) mutations. Tubular aggregates were only found in patients with GFPT1 mutations (5/6). The patients with GMPPB mutations (2/2) had decreased alpha-dystroglycan. Acetylcholinesterase inhibitor therapy resulted in no response or worsened symptoms in patients with COLQ mutations, a diverse response in patients with AGRN mutations, and a good response in patients with other subtypes. Albuterol therapy was effective or harmless in most subtypes. Therapy effects became attenuated with long-term use in patients with COLQ or AGRN mutations. INTERPRETATION: The genetic distribution of congenital myasthenic syndrome in China is distinct from that of other ethnic origins. The appearance of distal weakness, selective limb-girdle myasthenic syndrome, tubular aggregates, and decreased alpha-dystroglycan were indicative of the specific subtypes. Based on the follow-up findings, we suggest cautious evaluation of the long-term efficacy of therapeutic agents in congenital myasthenic syndrome. Title: The toxicity assessment of extract of Peganum harmala L. seeds in Caenorhabditis elegans Miao X, Zhang X, Yuan Y, Zhang Y, Gao J, Kang N, Liu X, Wu J, Liu Y, Tan P Ref: BMC Complement Med Ther, 20:256, 2020 : PubMed ESTHER: Miao_2020_BMC.Complement.Med.Ther_20_256 PubMedSearch: Miao 2020 BMC.Complement.Med.Ther 20 256 PubMedID: 32807143 Abstract BACKGROUND: Peganum harmala L. is a medicinal herb extensively used in traditional Chinese medicine (TCM). So far, relevant reports on the toxicity of Peganum harmala L. seeds (PHS) are hardly available. Especially, we still know little about the in vivo mechanism for PHS toxicity. This study aims to evaluate the toxicity effects of PHS in Caenorhabditis elegans (C. elegans), investigate the possible mechanism of the toxicity effects of PHS, and provide reference for the pharmacological research of PHS. METHODS: In the present study, the C. elegans was exposed to 0.25, 0.50, 1.00 mg/mL of PHS in nematode growth medium (NGM) at 22 degC in the presence of food. Lethality, lifespan, growth, reproduction, and locomotion behavior assays were performed to evaluate the toxicity effects of PHS in C. elegans. We then determined the mechanism of the toxicity effect of PHS by quantitative real-time polymerase chain reaction (qRT-PCR), acetylcholinesterase (AChE) activity assay, and oxidative stress resistance assays. The main components of PHS were detected by high performance liquid chromatography (HPLC). RESULTS: Compared with the control group, the lethality of C. elegans was significantly increased when they were exposed to the ethanol extract of PHS at 0.25, 0.50 and 1.00 mg/mL (P < 0.01), and the mean lifespan was significantly decreased (P < 0.01). We also observed that PHS exposure could induce the toxicity on body length, brood size, and locomotion behavior. CONCLUSION: Our study shows that the ethanol extract of PHS exerts obvious toxic effects on C. elegans, which would provide new ideas and methods for the biological evaluation of the toxicity of Chinese medicinal materials. Title: Runx2 Regulates Mouse Tooth Root Development Via Activation of WNT Inhibitor NOTUM Wen Q, Jing J, Han X, Feng J, Yuan Y, Ma Y, Chen S, Ho TV, Chai Y Ref: J Bone Miner Res, 35:2252, 2020 : PubMed ESTHER: Wen_2020_J.Bone.Miner.Res_35_2252 PubMedSearch: Wen 2020 J.Bone.Miner.Res 35 2252 PubMedID: 32569388 Abstract Progenitor cells are crucial in controlling organ morphogenesis. Tooth development is a well-established model for investigating the molecular and cellular mechanisms that regulate organogenesis. Despite advances in our understanding of how tooth crown formation is regulated, we have limited understanding of tooth root development. Runt-related transcription factor 2 (RUNX2) is a well-known transcription factor in osteogenic differentiation and early tooth development. However, the function of RUNX2 during tooth root formation remains unknown. We revealed in this study that RUNX2 is expressed in a subpopulation of GLI1+ root progenitor cells, and that loss of Runx2 in these GLI1+ progenitor cells and their progeny results in root developmental defects. Our results provide in vivo evidence that Runx2 plays a crucial role in tooth root development and in regulating the differentiation of root progenitor cells. Furthermore, we identified that Gli1, Pcp4, NOTUM, and Sfrp2 are downstream targets of Runx2 by integrating bulk and single-cell RNA sequencing analyses. Specifically, ablation of Runx2 results in downregulation of WNT inhibitor NOTUM and upregulation of canonical WNT signaling in the odontoblastic site, which disturbs normal odontoblastic differentiation. Significantly, exogenous NOTUM partially rescues the impaired root development in Runx2 mutant molars. Collectively, our studies elucidate how Runx2 achieves functional specificity in regulating the development of diverse organs and yields new insights into the network that regulates tooth root development. 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). Title: Effect of Tannic Acid on Nutrition and Activities of Detoxification Enzymes and Acetylcholinesterase of the Fall Webworm (Lepidoptera: Arctiidae) Yuan Y, Li L, Zhao J, Chen M Ref: J Insect Sci, 20:, 2020 : PubMed ESTHER: Yuan_2020_J.Insect.Sci_20_ PubMedSearch: Yuan 2020 J.Insect.Sci 20 PubMedID: 32061083 Abstract Plant tannins, polyphenolic plant secondary metabolites are involved in important chemical defense processes in plants. In this study, tannic acid was used as the standard of plant tannins to determine the effects on nutritional indices and activities of glutathione S-transferases (GSTs), cytochrome P450 monooxygenase (CYP450), carboxylesterase (CarE), and acetylcholinesterase (AChE) in fourth-instar larvae of Hyphantria cunea (Drury) by feeding on an artificial diet containing tannic acid under different treatments. We found that tannic acid significantly affected the digestive capacity and food utilization rate of H. cunea larvae. A tannic acid concentration of less than 2.0% promoted feeding and the utilization of undesirable food by H. cunea larvae, while inhibitory effects were observed at high concentrations (>2.5%). Tannic acid had a significant effect on the activity of detoxification enzymes and AChE in H. cunea larvae in concentration-dependent and time-dependent manners (P < 0.05). These results provide new insights into the potential mechanisms underlying detoxification in H. cunea larvae against tannic acid in host plants. Title: Molecular Basis of Binding between Middle East Respiratory Syndrome Coronavirus and CD26 from Seven Bat Species Yuan Y, Qi J, Peng R, Li C, Lu G, Yan J, Wang Q, Gao GF Ref: J Virol, 94:e01387, 2020 : PubMed ESTHER: Yuan_2020_J.Virol_94_e01387 PubMedSearch: Yuan 2020 J.Virol 94 e01387 PubMedID: 31776269 Gene_locus related to this paper: myods-l5lq33 Abstract Continued reports of Middle East respiratory syndrome coronavirus (MERS-CoV) infecting humans have occurred since the identification of this virus in 2012. MERS-CoV is prone to cause endemic disease in the Middle East, with several dozen spillover infections to other continents. It is hypothesized that MERS-CoV originated from bat coronaviruses and that dromedary camels are its natural reservoir. Although gene segments identical to MERS-CoV were sequenced from certain species of bats and one species experimentally shed the virus, it is still unknown whether other bats can transmit the virus. Here, at the molecular level, we found that all purified bat CD26s (bCD26s) from a diverse range of species interact with the receptor binding domain (RBD) of MERS-CoV, with equilibrium dissociation constant values ranging from several to hundreds at the micromolar level. Moreover, all bCD26s expressed in this study mediated the entry of pseudotyped MERS-CoV to receptor-expressing cells, indicating the broad potential engagement of bCD26s as MERS-CoV receptors. Further structural analysis indicated that in the bat receptor, compared to the human receptor, substitutions of key residues and their adjacent amino acids leads to decreased binding affinity to the MERS-RBD. These results add more evidence to the existing belief that bats are the original source of MERS-CoV and suggest that bCD26s in many species can mediate the entry of the virus, which has significant implications for the surveillance and control of MERS-CoV infection.IMPORTANCE In this study, we found that bat CD26s (bCD26s) from different species exhibit large diversities, especially in the region responsible for binding to the receptor binding domain (RBD) of Middle East respiratory syndrome coronavirus (MERS-CoV). However, they maintain the interaction with MERS-RBD at varied affinities and support the entry of pseudotyped MERS-CoV. These bat receptors polymorphisms seem to confer evolutionary pressure for the adaptation of CD26-binding virus, such as the ancestor of MERS-CoV, and led to the generation of diversified CD26-engaging CoV strains. Thus, our data add more evidence to support that bats are the reservoir of MERS-CoV and similar viruses, as well as further emphasize the necessity to survey MERS-CoV and other CoVs among bats. Title: [Distribution characteristics and correlation analysis of antibody detection value in myasthenia gravis] Liu YL, Zheng YM, Luo JJ, Zhang W, Gao F, Yuan Y, Hao HJ Ref: Zhonghua Yi Xue Za Zhi, 99:3221, 2019 : PubMed ESTHER: Liu_2019_Zhonghua.Yi.Xue.Za.Zhi_99_3221 PubMedSearch: Liu 2019 Zhonghua.Yi.Xue.Za.Zhi 99 3221 PubMedID: 31694116 Abstract Objective: To determine the factors affecting distribution and magnitude of antibody detection value in myasthenia gravis (MG). Methods: A total of 406 MG patients diagnosed at Department of Neurology, Peking University First Hospital from May 2015 to November 2017 were included.All of them exhibited muscle fatigue with decreased response in repetitive nerve stimulation test. There were 200 males and 206 females whose ages ranged from 2 to 85 years old. According to clinical classification of MG recommended by Myasthenia Gravis Foundation of America (MGFA), patients assigned to class I to class V included 200,140, 46, 15 and 5 cases, respectively. There were 33 cases of thymic hyperplasia and 63 cases of thymoma confirmed by radiological or pathological findings. Quantile plots and quantile regression model were used to determine the effects of age, gender and MGFA classification, thymus disease on acetylcholine receptors (AChR)antibody, acetylcholinesterase (AChE) antibody, Titin antibody, ryanodine receptor (RyR) antibody and muscle-specific tyrosine kinase (MuSK) antibody detection values detected by enzyme-linked immunosorbent assay (ELISA). Results: MGFA classification had effects on distribution of AChR antibody level. There was a positive correlation between age and AChR antibody level(P<0.05). Negative correlation was found between age and AChE, Titin and RyR antibody level (P<0.05). No significant correlation was shown between any factors and MuSK antibody level(P>/=0.05). MGFA classification had a positive correlation with AChR antibody level (P<0.05) and no correlation with other antibody levels (P>0.05). Gender and thymus disease had no correlation with any tested antibody levels (P>0.05). Conclusion: MGFA classification has significant effects on distribution of AChR antibody level. Age and MGFA classification have positive correlation with AChR antibody level. Title: Functional analysis of the GbDWARF14 gene associated with branching development in cotton Wang P, Zhang S, Qiao J, Sun Q, Shi Q, Cai C, Mo J, Chu Z, Yuan Y and Cai Y <3 more author(s)> Wang P, Zhang S, Qiao J, Sun Q, Shi Q, Cai C, Mo J, Chu Z, Yuan Y, Du X, Miao Y, Zhang X, Cai Y (- 3) Ref: PeerJ, 7:e6901, 2019 : PubMed ESTHER: Wang_2019_PeerJ_7_e6901 PubMedSearch: Wang 2019 PeerJ 7 e6901 PubMedID: 31143538 Abstract Plant architecture, including branching pattern, is an important agronomic trait of cotton crops. In recent years, strigolactones (SLs) have been considered important plant hormones that regulate branch development. In some species such as Arabidopsis, DWARF14 is an unconventional receptor that plays an important role in the SL signaling pathway. However, studies on SL receptors in cotton are still lacking. Here, we cloned and analysed the structure of the GbD14 gene in Gossypium barbadense and found that it contains the domains necessary for a SL receptor. The GbD14 gene was expressed primarily in the roots, leaves and vascular bundles, and the GbD14 protein was determined via GFP to localize to the cytoplasm and nucleus. Gene expression analysis revealed that the GbD14 gene not only responded to SL signals but also was differentially expressed between cotton plants whose types of branching differed. In particular, GbD14 was expressed mainly in the axillary buds of normal-branching cotton, while it was expressed the most in the leaves of nulliplex-branch cotton. In cotton, the GbD14 gene can be induced by SL and other plant hormones, such as indoleacetic acid, abscisic acid, and jasmonic acid. Compared with wild-type Arabidopsis, GbD14-overexpressing Arabidopsis responded more rapidly to SL signals. Moreover, we also found that GbD14 can rescue the multi-branched phenotype of Arabidopsis Atd14 mutants. Our results indicate that the function of GbD14 is similar to that of AtD14, and GbD14 may be a receptor for SL in cotton and involved in regulating branch development. This research provides a theoretical basis for a profound understanding of the molecular mechanism of branch development and ideal plant architecture for cotton breeding improvements. Title: Online acetylcholinesterase inhibition evaluation by high-performance liquid chromatography-mass spectrometry hyphenated with an immobilized enzyme reactor Yuan Y, Zhao M, Riffault-Valois L, Ennahar S, Bergaentzle M, Marchioni E Ref: Journal of Chromatography A, :460506, 2019 : PubMed ESTHER: Yuan_2019_J.Chromatogr.A__460506 PubMedSearch: Yuan 2019 J.Chromatogr.A 460506 PubMedID: 31526637 Abstract A high-performance liquid chromatography-mass spectrometry technique hyphenated on-line with an immobilized enzyme reactor (IMER) was developed by the use of 3 known acetylcholinesterase (AChE) inhibitors (galanthamine, huperzine A and tacrine). This bioanalytical device allows qualitative comparison of the inhibitory strengths of AChE inhibitors. The AChE inhibitory strengths were evaluated and compared by the corresponding acetylcholine peak areas (mass signal) obtained after a chromatographic separation and the elution through the IMER. Only one injection of the analytes is needed to get this comparative analysis. This bioanalytical device was then applied to the extract of a natural plant, Lycoris radiata, which is known to contain AChE inhibitors such as galanthamine and lycoramine. Aside from the demonstration of the inhibitory activity of the two known AChE inhibitors, the AChE inhibitory activity of another compound (dihydro-latifaliumin C) was revealed. This is the first report describing the AChE inhibitory activity of this compound. Title: Structure-based virtual screening leading to discovery of highly selective butyrylcholinesterase inhibitors with solanaceous alkaloid scaffolds Zhou S, Yuan Y, Zheng F, Zhan CG Ref: Chemico-Biological Interactions, 308:372, 2019 : PubMed ESTHER: Zhou_2019_Chem.Biol.Interact_13ChEPon_308_372 PubMedSearch: Zhou 2019 Chem.Biol.Interact 13ChEPon 308 372 PubMedID: 31152736 Inhibitor(s) related to this paper: Solanidine Abstract According to recent research advance, it is interesting to identify new, potent and selective inhibitors of human butyrylcholinesterase (BChE) for therapeutic treatment of both the Alzheimer's disease (AD) and heroin abuse. In this study, we carried out a structure-based virtual screening followed by in vitro activity assays, with the goal to identify new inhibitors that are selective for BChE over acetylcholinesterase (AChE). As a result, a set of new, selective inhibitors of human BChE were identified from natural products with solanaceous alkaloid scaffolds. The most active one of the natural products (compound 1) identified has an IC50 of 16.8nM against BChE. It has been demonstrated that the desirable selectivity of these inhibitors for BChE over AChE is mainly controlled by three key residues in the active site cavity, i.e. residues Q119, A277, and A328 in BChE versus the respective residues Y124, W286, and Y337 in AChE. Based on this structural insight, future rational design of new, potent and selective BChE inhibitors may focus on these key structural differences in the active site cavity. Title: New amide alkaloids from Delphinium brunonianum Zou YS, Dawa Z, Lin CZ, Zhang QY, Yao YF, Yuan Y, Zhu CC, Wang ZY Ref: Fitoterapia, :104186, 2019 : PubMed ESTHER: Zou_2019_Fitoterapia__104186 PubMedSearch: Zou 2019 Fitoterapia 104186 PubMedID: 31150769 Abstract Five new amide alkaloids, named delamide A-E (1-5), along with five known ones, methyl-N-(3-carboxy-2-methylpropanoyl) anthranilate (6), benzoic acid, 2-[(1-oxodecyl) amino]-methylester (7), puberline (8), benzoic acid, 2-[(4-methoxy-2-methyl-1, 4-dioxobutyl) amino]-methylester (9) and benzoic acid, 2-[(4-methoxy-3-methyl-1, 4-dioxobutyl) amino]-methylester (10) were isolated from the extract of Delphinium brunonianum. Their structures were elucidated by extensive spectroscopic analyses (including 1D-, 2D-NMR, and HR-ESI-MS). 1-10 were also evaluated for their acetylcholinesterase (AChE) inhibiting activity by the Ellman's method. Delamide A (1) showed highly selective AChE inhibition activity. The kinetic analysis revealed that 1 was a mixed-type reversible inhibitor of AChE. Title: Lipolysis Triggers a Systemic Insulin Response Essential for Efficient Energy Replenishment of Activated Brown Adipose Tissue in Mice Heine M, Fischer AW, Schlein C, Jung C, Straub LG, Gottschling K, Mangels N, Yuan Y, Nilsson SK and Heeren J <5 more author(s)> Heine M, Fischer AW, Schlein C, Jung C, Straub LG, Gottschling K, Mangels N, Yuan Y, Nilsson SK, Liebscher G, Chen O, Schreiber R, Zechner R, Scheja L, Heeren J (- 5) Ref: Cell Metab, 28:644, 2018 : PubMed ESTHER: Heine_2018_Cell.Metab_28_644 PubMedSearch: Heine 2018 Cell.Metab 28 644 PubMedID: 30033199 Abstract The coordination of the organ-specific responses regulating systemic energy distribution to replenish lipid stores in acutely activated brown adipose tissue (BAT) remains elusive. Here, we show that short-term cold exposure or acute beta3-adrenergic receptor (beta3AR) stimulation results in secretion of the anabolic hormone insulin. This process is diminished in adipocyte-specific Atgl(-/-) mice, indicating that lipolysis in white adipose tissue (WAT) promotes insulin secretion. Inhibition of pancreatic beta cells abolished uptake of lipids delivered by triglyceride-rich lipoproteins into activated BAT. Both increased lipid uptake into BAT and whole-body energy expenditure in response to beta3AR stimulation were blunted in mice treated with the insulin receptor antagonist S961 or lacking the insulin receptor in brown adipocytes. In conclusion, we introduce the concept that acute cold and beta3AR stimulation trigger a systemic response involving WAT, beta cells, and BAT, which is essential for insulin-dependent fuel uptake and adaptive thermogenesis. Title: Enhanced Poly(ethylene terephthalate) Hydrolase Activity by Protein Engineering Ma Y, Yao M, Li B, Ding M, He B, Chen S, Zhou X, Yuan Y Ref: Engineering (Beijing), 4:888, 2018 : PubMed ESTHER: Ma_2018_Engineering.(Beijing)_4_888 PubMedSearch: Ma 2018 Engineering.(Beijing) 4 888 Gene_locus related to this paper: idesa-peth Abstract Poly(ethylene terephthalate) hydrolase (PETase) from Ideonella sakaiensis exhibits a strong ability to degrade poly(ethylene terephthalate) (PET) at room temperature, and is thus regarded as a potential tool to solve the issue of polyester plastic pollution. Therefore, we explored the interaction between PETase and the substrate (a dimer of the PET monomer ethylene terephthalate, 2PET), using a model of PETase and its substrate. In this study, we focused on six key residues around the substrate-binding groove in order to create novel high-efficiency PETase mutants through protein engineering. These PETase mutants were designed and tested. The enzymatic activities of the R61A, L88F, and I179F mutants, which were obtained with a rapid cell-free screening system, exhibited 1.4 fold, 2.1 fold, and 2.5 fold increases, respectively, in comparison with wild-type PETase. The I179F mutant showed the highest activity, with the degradation rate of a PET film reaching 22.5 mg per micromol/L PETase per day. Thus, this study has created enhanced artificial PETase enzymes through the rational protein engineering of key hydrophobic sites, and has further illustrated the potential of biodegradable plastics. Title: Regulation of growth, antioxidant capacity, fatty acid profiles, hematological characteristics and expression of lipid related genes by different dietary n-3 highly unsaturated fatty acids in juvenile black seabream (Acanthopagrus schlegelii) Jin M, Lu Y, Yuan Y, Li Y, Qiu H, Sun P, Ma H-N, Ding L-Y, Zhou Q-C Ref: Aquaculture, 471:55, 2017 : PubMed ESTHER: Jin_2017_Aquaculture_471_55 PubMedSearch: Jin 2017 Aquaculture 471 55 Gene_locus related to this paper: acasc-a0a1s5r938 Abstract An 8-week feeding trial was conducted to investigate the effects of dietary n-3 highly unsaturated fatty acid (n-3HUFA) on growth performance, antioxidant capacity, fatty acid profiles, hematological characteristics and expression of some lipid related genes of juvenile black seabream (Acanthopagrus schlegelii) (initial weight 3.770.00g). Five isonitrogenous and isolipidic experimental diets were formulated with graded levels of n-3 HUFA (0.23, 0.87, 1.29, 1.75 and 2.53% of dry weight, DHA/EPA ratio approximately at 1.0). The results revealed that fish fed the diet containing 1.75% n-3 HUFA had higher weight gain (WG) and specific growth rate (SGR) than those fed the control diet. Fish fed diets containing 1.29% and 1.75% n-3 HUFA had higher feed efficiency (FE) than those fed the other diets. Hepatic and muscular fatty acid profiles reflected that of diets. The content of malondialdehyde (MDA) increased both in the serum and liver of fish fed high n-3 HUFA level diets, and the highest hepatic activity of glutathione peroxidase (GSH-PX) was recorded in fish fed the diet containing 1.29% n-3 HUFA. The expression of acc, g6pd, fas, srebp-1, lpl, atgl, hsl, elovl5 and fads2 was down-regulated in fish fed the diets with high n-3 HUFA levels. However, the expression levels of 6pgd and ppar significantly increased when the dietary contents of n-3 HUFA increased from 0.23% to 1.29% and then decreased when dietary n-3 HUFA levels increased from 1.75% to 2.53%. The highest expression of cpt1a was found in fish fed the diet containing 1.75% n-3 HUFA. The content of cholesterol (CHOL) in serum increased along with n-3 HUFA level. Over all, this study indicated that fish fed moderate dietary n-3 HUFA (1.341.80% n-3 HUFA) could enhance growth, feed utilization and antioxidant capacity. Different dietary levels of n-3 HUFA could strongly affect expression levels of some lipid metabolism relevant genes of the juvenile black seabream. This may contribute to our understanding of the mechanisms related to lipid metabolism (anabolism and catabolism) effects of different dietary levels of n-3 HUFA. Title: Molecular interaction studies of acetylcholinesterase with potential acetylcholinesterase inhibitors from the root of Rhodiola crenulata using molecular docking and isothermal titration calorimetry methods Li FJ, Liu Y, Yuan Y, Yang B, Liu ZM, Huang LQ Ref: Int J Biol Macromol, 104:527, 2017 : PubMed ESTHER: Li_2017_Int.J.Biol.Macromol_104_527 PubMedSearch: Li 2017 Int.J.Biol.Macromol 104 527 PubMedID: 28625836 Abstract (-)-Epicatechin gallate ((-)-ECG), 1,2,3,4,6-O-pentagalloylglucose (PGG), rhodionin, herbacetin and rhodiosin isolated from the root of Rhodiola crenulata exhibited potent, dose-dependent inhibitory effects on acetylcholinesterase (AChE) with IC50 ranged from 57.50+/-5.83 to 2.43+/-0.34mug/mL. With the aim of explaining the differences in activity of these active ingredients and clarifying how they inhibit AChE, the AChE-inhibitor interactions were further explored using molecular docking and isothermal titration calorimetry (ITC) methods in the present study. Molecular docking studies revealed that all compounds except PGG showed binding energy values ranging from -10.30 to -8.00kcal/mol while the binding energy of galantamine, a known AChE inhibitor, was -9.53kcal/mol; they inhibited the AChE by binding into the ligand pocket with the similar binding pattern to that of galantamine by interacting with Glu199 of AChE. Inhibition constant of these active ingredients had a positive correlation with binding energy. The interaction between AChE and PGG was further evaluated with the ITC method and the results indicated that the PGG-AChE interaction was relevant to AChE concentration. The results revealed a possible mechanism for the AChE inhibition activity of these bioactive ingredients, which may provide some help in lead compounds optimization in the future. Title: Putative Receptor Binding Domain of Bat-Derived Coronavirus HKU9 Spike Protein: Evolution of Betacoronavirus Receptor Binding Motifs Huang C, Qi J, Lu G, Wang Q, Yuan Y, Wu Y, Zhang Y, Yan J, Gao GF Ref: Biochemistry, 55:5977, 2016 : PubMed ESTHER: Huang_2016_Biochemistry_55_5977 PubMedSearch: Huang 2016 Biochemistry 55 5977 PubMedID: 27696819 Abstract The suggested bat origin for Middle East respiratory syndrome coronavirus (MERS-CoV) has revitalized the studies of other bat-derived coronaviruses with respect to interspecies transmission potential. Bat coronavirus (BatCoV) HKU9 is an important betacoronavirus (betaCoV) that is phylogenetically affiliated with the same genus as MERS-CoV. The bat surveillance data indicated that BatCoV HKU9 has been widely spreading and circulating in bats. This highlights the necessity of characterizing the virus for its potential to cross species barriers. The receptor binding domain (RBD) of the coronavirus spike (S) protein recognizes host receptors to mediate virus entry and is therefore a key factor determining the viral tropism and transmission capacity. In this study, the putative S RBD of BatCoV HKU9 (HKU9-RBD), which is homologous to other betaCoV RBDs that have been structurally and functionally defined, was characterized via a series of biophysical and crystallographic methods. By using surface plasmon resonance, we demonstrated that HKU9-RBD binds to neither SARS-CoV receptor ACE2 nor MERS-CoV receptor CD26. We further determined the atomic structure of HKU9-RBD, which as expected is composed of a core and an external subdomain. The core subdomain fold resembles those of other betaCoV RBDs, whereas the external subdomain is structurally unique with a single helix, explaining the inability of HKU9-RBD to react with either ACE2 or CD26. Via comparison of the available RBD structures, we further proposed a homologous intersubdomain binding mode in betaCoV RBDs that anchors the external subdomain to the core subdomain. The revealed RBD features would shed light on the evolution route of betaCoV. Title: Unexpected Reaction Pathway for butyrylcholinesterase-catalyzed inactivation of hunger hormone ghrelin Yao J, Yuan Y, Zheng F, Zhan CG Ref: Sci Rep, 6:22322, 2016 : PubMed ESTHER: Yao_2016_Sci.Rep_6_22322 PubMedSearch: Yao 2016 Sci.Rep 6 22322 PubMedID: 26922910 Abstract Extensive computational modeling and simulations have been carried out, in the present study, to uncover the fundamental reaction pathway for butyrylcholinesterase (BChE)-catalyzed hydrolysis of ghrelin, demonstrating that the acylation process of BChE-catalyzed hydrolysis of ghrelin follows an unprecedented single-step reaction pathway and the single-step acylation process is rate-determining. The free energy barrier (18.8 kcal/mol) calculated for the rate-determining step is reasonably close to the experimentally-derived free energy barrier (~19.4 kcal/mol), suggesting that the obtained mechanistic insights are reasonable. The single-step reaction pathway for the acylation is remarkably different from the well-known two-step acylation reaction pathway for numerous ester hydrolysis reactions catalyzed by a serine esterase. This is the first time demonstrating that a single-step reaction pathway is possible for an ester hydrolysis reaction catalyzed by a serine esterase and, therefore, one no longer can simply assume that the acylation process must follow the well-known two-step reaction pathway. Title: High-throughput proteomics integrated with gene microarray for discovery of colorectal cancer potential biomarkers Yu J, Li X, Zhong C, Li D, Zhai X, Hu W, Guo C, Yuan Y, Zheng S Ref: Oncotarget, 7:75279, 2016 : PubMed ESTHER: Yu_2016_Oncotarget_7_75279 PubMedSearch: Yu 2016 Oncotarget 7 75279 PubMedID: 27661117 Abstract Proteins, as executives of genes' instructions, are responsible for cellular phenotypes. Integratingproteomics with gene microarray, we conducted this study to identify potential protein biomarkers of colorectal cancer (CRC). Isobaric tags with related and absolute quantitation (iTRAQ) labeling mass spectrometry (MS) was applied to screen and identify differentially expressed proteins between paired CRC and adjacent normal mucosa. Meanwhile, Affymetrix U133plus2.0 microarrays were used to perform gene microarray analysis. Verification experiments included immunohistochemistry (IHC), western blot and enzyme-linked immunosorbent assay (ELISA) of selected proteins. Overall, 5469 differentially expressed proteins were detected with iTRAQ-MS from 24 matched CRC and adjacent normal tissues. And gene microarray identified 39859 differential genes from 52 patients. Of these, 3083 differential proteins had corresponding differentially expressed genes, with 245 proteins and their genes showed >1.5-fold change in expression level. Gene ontology enrichment analysis revealed that up-regulated proteins were more involved in cell adhesion and motion than down-regulated proteins. In addition, up-regulated proteins were more likely to be located in nucleus and vesicles. Further verification experiments with IHC confirmed differential expression levels of 5 proteins (S100 calcium-binding protein A9, annexin A3, nicotinamide phosphoribosyltransferase, carboxylesterase 2 and calcium activated chloride channel A1) between CRC and normal tissues. Besides, western blot showed a stepwise increase of annexin A3 abundance in normal colorectal mucosa, adenoma and CRC tissues. ELISAresults revealed significantly higher serum levels of S100 calcium-binding protein A9 and annexin A3 in CRC patients than healthy controls, validating diagnostic value of these proteins. Cell experiments showed that inhibition of annexin A3 could suppress CRC cell proliferation and aggressiveness. S100 calcium-binding protein A9, annexin A3, nicotinamide phosphoribosyltransferase, carboxylesterase 2 and calcium activated chloride channel A1 were probably potential biomarkers of colorectal cancer. Annexin A3 was a potentially valuable therapeutic target of CRC. Title: The Toxicity and Detoxifying Mechanism of Cycloxaprid and Buprofezin in Controlling Sogatella furcifera (Homoptera: Delphacidae) Chang X, Yuan Y, Zhang T, Wang D, Du X, Wu X, Chen H, Chen Y, Jiao Y, Teng H Ref: J Insect Sci, 15:, 2015 : PubMed ESTHER: Chang_2015_J.Insect.Sci_15_ PubMedSearch: Chang 2015 J.Insect.Sci 15 PubMedID: 26175461 Abstract The effects of cycloxaprid (a modified neonicotinoid insecticide) and buprofezin (a thiadiazine insecticide) on mortality of the white-backed planthopper (WBPH), Sogatella furcifera, were determined in laboratory assays. Cycloxaprid killed WBPH nymphs and adults but buprofezin killed only nymphs, and cycloxaprid acted faster than buprofezin. One day after infestation, mortality of third-instar nymphs was >65% with cycloxaprid at 125 mg liter(-1) but was <38% with buprofezin at 148 mg liter(-1). By the 4th day after infestation, however, control of nymphs by the two insecticides was similar, and cycloxaprid at 125 mg liter(-1) caused >/=80% mortality of adults but buprofezin at 148 mg liter(-1) (the highest rate tested) caused almost no adult mortality. LC50 values for cycloxaprid were lowest with nymphs, intermediate with adult males, and highest with adult females. Although buprofezin was slower acting than cycloxaprid, its LC50 for nymphs 5 d after infestation was 3.79-fold lower than that of cycloxaprid. Mean carboxylesterase (CarE) specific activity of nymphal WBPH treated with cycloxaprid and buprofezin was higher than that of control, but there was no significant difference between cycloxaprid and control (no insecticide), and it was significantly higher for buprofezin than those of cycloxaprid and control. For glutathione S-transferase and mixed function oxygenase, the specific activity of nymphal WBPH treated with buprofezin was significantly higher than those of cycloxaprid and control, too. Title: Genome sequence of cultivated Upland cotton (Gossypium hirsutum TM-1) provides insights into genome evolution Li F, Fan G, Lu C, Xiao G, Zou C, Kohel RJ, Ma Z, Shang H, Ma X and Yu S <30 more author(s)> Li F, Fan G, Lu C, Xiao G, Zou C, Kohel RJ, Ma Z, Shang H, Ma X, Wu J, Liang X, Huang G, Percy RG, Liu K, Yang W, Chen W, Du X, Shi C, Yuan Y, Ye W, Liu X, Zhang X, Liu W, Wei H, Wei S, Zhu S, Zhang H, Sun F, Wang X, Liang J, Wang J, He Q, Huang L, Cui J, Song G, Wang K, Xu X, Yu JZ, Zhu Y, Yu S (- 30) Ref: Nat Biotechnol, 33:524, 2015 : PubMed ESTHER: Li_2015_Nat.Biotechnol_33_524 PubMedSearch: Li 2015 Nat.Biotechnol 33 524 PubMedID: 25893780 Gene_locus related to this paper: gosra-a0a0d2rxs2, gosra-a0a0d2tng2, gosra-a0a0d2twz7, goshi-a0a1u8hr03, gosra-a0a0d2vdc5, goshi-a0a1u8ljh5, gosra-a0a0d2vj24, goshi-a0a1u8pxd3, gosra-a0a0d2sr31, goshi-a0a1u8knd1, goshi-a0a1u8nhw9, goshi-a0a1u8mt09, goshi-a0a1u8kis4, goshi-a0a1u8ibk3, goshi-a0a1u8ieg2, goshi-a0a1u8iki6, goshi-a0a1u8jvp4, goshi-a0a1u8jw35, gosra-a0a0d2pzd7, goshi-a0a1u8ied7 Abstract Gossypium hirsutum has proven difficult to sequence owing to its complex allotetraploid (AtDt) genome. Here we produce a draft genome using 181-fold paired-end sequences assisted by fivefold BAC-to-BAC sequences and a high-resolution genetic map. In our assembly 88.5% of the 2,173-Mb scaffolds, which cover 89.6% approximately 96.7% of the AtDt genome, are anchored and oriented to 26 pseudochromosomes. Comparison of this G. hirsutum AtDt genome with the already sequenced diploid Gossypium arboreum (AA) and Gossypium raimondii (DD) genomes revealed conserved gene order. Repeated sequences account for 67.2% of the AtDt genome, and transposable elements (TEs) originating from Dt seem more active than from At. Reduction in the AtDt genome size occurred after allopolyploidization. The A or At genome may have undergone positive selection for fiber traits. Concerted evolution of different regulatory mechanisms for Cellulose synthase (CesA) and 1-Aminocyclopropane-1-carboxylic acid oxidase1 and 3 (ACO1,3) may be important for enhanced fiber production in G. hirsutum. Title: Perilipin 5 improves hepatic lipotoxicity by inhibiting lipolysis Wang C, Zhao Y, Gao X, Li L, Yuan Y, Liu F, Zhang L, Wu J, Hu P and Ye J <6 more author(s)> Wang C, Zhao Y, Gao X, Li L, Yuan Y, Liu F, Zhang L, Wu J, Hu P, Zhang X, Gu Y, Xu Y, Wang Z, Li Z, Zhang H, Ye J (- 6) Ref: Hepatology, 61:870, 2015 : PubMed ESTHER: Wang_2015_Hepatology_61_870 PubMedSearch: Wang 2015 Hepatology 61 870 PubMedID: 25179419 Abstract Abnormal metabolism of nonesterified fatty acids (NEFAs) and their derivatives has been reported to be the main cause of intracellular lipotoxic injury. Normally, NEFAs are stored in lipid droplets (LDs) in the form of triglyceride (TG), which could reduce the lipotoxicity of cytosolic NEFAs. Previous studies have implicated that Perilipin 5 (Plin5), an LD-binding protein, regulates the storage and hydrolysis of TG in LD. However, its roles and underlying mechanisms in the liver remain unknown. Here we found that Plin5 expression was increased in steatotic livers. Using Plin5 knockout mice, we found that Plin5 deficiency resulted in reduced hepatic lipid content and smaller-sized LDs, which was due to the elevated lipolysis rate and fatty acid utilization. Plin5-deficient hepatocytes showed increased mitochondria proliferation, which could be explained by the increased expression and activity of PPARalpha stimulated by the increased NEFA levels. Meanwhile, Plin5-deficient livers also exhibited enhanced mitochondrial oxidative capacity. We also found that Plin5 deficiency induces lipotoxic injury in hepatocytes, attributed to lipid peroxidation. Mechanistically, we found that Plin5 blocks adipose triglyceride lipase (ATGL)-mediated lipolysis by competitively binding to comparative gene identification-58 (CGI-58) and disrupting the interaction between CGI-58 and ATGL. CONCLUSION: Plin5 is an important protective factor against hepatic lipotoxicity induced by NEFAs generated from lipolysis. This provides an important new insight into the regulation of hepatic lipid storage and relation between lipid storage and lipotoxicity. Title: Bat origins of MERS-CoV supported by bat coronavirus HKU4 usage of human receptor CD26 Wang Q, Qi J, Yuan Y, Xuan Y, Han P, Wan Y, Ji W, Li Y, Wu Y and Gao GF <6 more author(s)> Wang Q, Qi J, Yuan Y, Xuan Y, Han P, Wan Y, Ji W, Li Y, Wu Y, Wang J, Iwamoto A, Woo PC, Yuen KY, Yan J, Lu G, Gao GF (- 6) Ref: Cell Host Microbe, 16:328, 2014 : PubMed ESTHER: Wang_2014_Cell.Host.Microbe_16_328 PubMedSearch: Wang 2014 Cell.Host.Microbe 16 328 PubMedID: 25211075 Gene_locus related to this paper: human-DPP4 Abstract The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) is phylogenetically closely related to the bat coronaviruses (BatCoVs) HKU4 and HKU5. However, the evolutionary pathway of MERS-CoV is still unclear. A receptor binding domain (RBD) in the MERS-CoV envelope-embedded spike protein specifically engages human CD26 (hCD26) to initiate viral entry. The high sequence identity in the viral spike protein prompted us to investigate if HKU4 and HKU5 can recognize hCD26 for cell entry. We found that HKU4-RBD, but not HKU5-RBD, binds to hCD26, and pseudotyped viruses embedding HKU4 spike can infect cells via hCD26 recognition. The structure of the HKU4-RBD/hCD26 complex revealed a hCD26-binding mode similar overall to that observed for MERS-RBD. HKU4-RBD, however, is less adapted to hCD26 than MERS-RBD, explaining its lower affinity for receptor binding. Our findings support a bat origin for MERS-CoV and indicate the need for surveillance of HKU4-related viruses in bats. Title: Fine-scale variation in meiotic recombination in Mimulus inferred from population shotgun sequencing Hellsten U, Wright KM, Jenkins J, Shu S, Yuan Y, Wessler SR, Schmutz J, Willis JH, Rokhsar DS Ref: Proc Natl Acad Sci U S A, 110:19478, 2013 : PubMed ESTHER: Hellsten_2013_Proc.Natl.Acad.Sci.U.S.A_110_19478 PubMedSearch: Hellsten 2013 Proc.Natl.Acad.Sci.U.S.A 110 19478 PubMedID: 24225854 Gene_locus related to this paper: erygu-a0a022qsc9, erygu-a0a022qjb4, erygu-a0a022px28, erygu-a0a022rcn8, erygu-a0a022r7z4, erygu-a0a022rcp2, erygu-a0a022r9s7, erygu-a0a022put8, erygu-a0a022r922, erygu-a0a022qmg0, erygu-a0a022rf01, erygu-a0a022qnf5, erygu-a0a022qs63, erygu-a0a022rvn4, erygu-a0a022rnw2, erygu-a0a022s0h3, erygu-a0a022qr26, erygu-a0a022qi72, erygu-a0a022qi30, erygu-a0a022q165, erygu-a0a022r728, erygu-a0a022r7n8, erygu-a0a022rm64, erygu-a0a022s4c6, erygu-a0a022rbl0, erygu-a0a022rwi3, erygu-a0a022rzg9 Abstract Meiotic recombination rates can vary widely across genomes, with hotspots of intense activity interspersed among cold regions. In yeast, hotspots tend to occur in promoter regions of genes, whereas in humans and mice, hotspots are largely defined by binding sites of the positive-regulatory domain zinc finger protein 9. To investigate the detailed recombination pattern in a flowering plant, we use shotgun resequencing of a wild population of the monkeyflower Mimulus guttatus to precisely locate over 400,000 boundaries of historic crossovers or gene conversion tracts. Their distribution defines some 13,000 hotspots of varying strengths, interspersed with cold regions of undetectably low recombination. Average recombination rates peak near starts of genes and fall off sharply, exhibiting polarity. Within genes, recombination tracts are more likely to terminate in exons than in introns. The general pattern is similar to that observed in yeast, as well as in positive-regulatory domain zinc finger protein 9-knockout mice, suggesting that recombination initiation described here in Mimulus may reflect ancient and conserved eukaryotic mechanisms. Title: DWARF 53 acts as a repressor of strigolactone signalling in rice Jiang L, Liu X, Xiong G, Liu H, Chen F, Wang L, Meng X, Liu G, Yu H and Li J <10 more author(s)> Jiang L, Liu X, Xiong G, Liu H, Chen F, Wang L, Meng X, Liu G, Yu H, Yuan Y, Yi W, Zhao L, Ma H, He Y, Wu Z, Melcher K, Qian Q, Xu HE, Wang Y, Li J (- 10) Ref: Nature, 504:401, 2013 : PubMed ESTHER: Jiang_2013_Nature_504_401 PubMedSearch: Jiang 2013 Nature 504 401 PubMedID: 24336200 Abstract Strigolactones (SLs) are a group of newly identified plant hormones that control plant shoot branching. SL signalling requires the hormone-dependent interaction of DWARF 14 (D14), a probable candidate SL receptor, with DWARF 3 (D3), an F-box component of the Skp-Cullin-F-box (SCF) E3 ubiquitin ligase complex. Here we report the characterization of a dominant SL-insensitive rice (Oryza sativa) mutant dwarf 53 (d53) and the cloning of D53, which encodes a substrate of the SCF(D3) ubiquitination complex and functions as a repressor of SL signalling. Treatments with GR24, a synthetic SL analogue, cause D53 degradation via the proteasome in a manner that requires D14 and the SCF(D3) ubiquitin ligase, whereas the dominant form of D53 is resistant to SL-mediated degradation. Moreover, D53 can interact with transcriptional co-repressors known as TOPLESS-RELATED PROTEINS. Our results suggest a model of SL signalling that involves SL-dependent degradation of the D53 repressor mediated by the D14-D3 complex. Title: Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26 Lu G, Hu Y, Wang Q, Qi J, Gao F, Li Y, Zhang Y, Zhang W, Yuan Y and Gao GF <4 more author(s)> Lu G, Hu Y, Wang Q, Qi J, Gao F, Li Y, Zhang Y, Zhang W, Yuan Y, Bao J, Zhang B, Shi Y, Yan J, Gao GF (- 4) Ref: Nature, 500:227, 2013 : PubMed ESTHER: Lu_2013_Nature_500_227 PubMedSearch: Lu 2013 Nature 500 227 PubMedID: 23831647 Gene_locus related to this paper: human-DPP4 Abstract The newly emergent Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe pulmonary disease in humans, representing the second example of a highly pathogenic coronavirus, the first being SARS-CoV. CD26 (also known as dipeptidyl peptidase 4, DPP4) was recently identified as the cellular receptor for MERS-CoV. The engagement of the MERS-CoV spike protein with CD26 mediates viral attachment to host cells and virus-cell fusion, thereby initiating infection. Here we delineate the molecular basis of this specific interaction by presenting the first crystal structures of both the free receptor binding domain (RBD) of the MERS-CoV spike protein and its complex with CD26. Furthermore, binding between the RBD and CD26 is measured using real-time surface plasmon resonance with a dissociation constant of 16.7 nM. The viral RBD is composed of a core subdomain homologous to that of the SARS-CoV spike protein, and a unique strand-dominated external receptor binding motif that recognizes blades IV and V of the CD26 beta-propeller. The atomic details at the interface between the two binding entities reveal a surprising protein-protein contact mediated mainly by hydrophilic residues. Sequence alignment indicates, among betacoronaviruses, a possible structural conservation for the region homologous to the MERS-CoV RBD core, but a high variation in the external receptor binding motif region for virus-specific pathogenesis such as receptor recognition. Title: The neutral hydrolysis of simple carboxylic esters in water and the rate enhancements produced by acetylcholinesterase and other carboxylic acid esterases Wolfenden R, Yuan Y Ref: Journal of the American Chemical Society, 133:13821, 2011 : PubMed ESTHER: Wolfenden_2011_J.Am.Chem.Soc_133_13821 PubMedSearch: Wolfenden 2011 J.Am.Chem.Soc 133 13821 PubMedID: 21793525 Abstract Experiments at elevated temperatures permit the determination of rate constant and thermodynamic activation parameters for the neutral hydrolysis of the neurotransmitter acetylcholine in water. At 25 degrees C, the extrapolated rate constant for the uncatalyzed (or neutral) hydrolysis of acetylcholine is 3.9 x 10(-7) s(-1) at 25 degrees C (DeltaH(double dagger) = 20.0 kcal/mol; TDeltaS(double dagger) = -6.1 kcal/mol). Acetylcholine is more susceptible to neutral and base-catalyzed hydrolysis than ethyl acetate but less susceptible to acid-catalyzed hydrolysis. For acetylcholinesterase from the electric eel, the catalytic proficiency [(k(cat)/K(m))/k(neutral)] is 2 x 10(16) M(-1), comparable in magnitude with the catalytic proficiencies of aminohydrolases that act on peptides and nucleosides. Title: Enhanced performance of lipase-catalyzed kinetic resolution of secondary alcohols in monoether-functionalized ionic liquids Zhou H, Chen J, Ye L, Lin H, Yuan Y Ref: Bioresour Technol, 102:5562, 2011 : PubMed ESTHER: Zhou_2011_Bioresour.Technol_102_5562 PubMedSearch: Zhou 2011 Bioresour.Technol 102 5562 PubMedID: 21388804 Abstract Several cationic monoether-functionalized ionic liquids (MEF-ILs) with different substituents were synthesized and used as media for kinetic resolution of secondary alcohols catalyzed by several lipases. The results indicate that Novozym 435 (an immobilized Candida antarctica Lipase B) had higher efficiency compared to other lipases in deracemization. The alkyl substituents at the 2- and 3-positions in the imidazolium ring of MEF-ILs were found to contribute to the increased enantioselectivity and enhancement of the reaction rate, respectively, while the higher stereo-hindrance of ether bonds decreased the activity. An enantioselectivity higher than 99% with 50% conversion of rac-1-phenylethanol was achieved using the catalyst system comprised of Novozym 435 and the MEF-IL 1-(3-ethoxypropyl)-2,3-dimethylimidazolium bis(trifluoromethylsulfonyl)imide. The catalytic system could be separated and reused without considerable activity loss. MEF-ILs can be a new class of enzyme-benign media suitable for lipase-catalyzed kinetic resolution of secondary alcohols. Title: [Two novel mutations in palmitoyl-protein thioesterase gene in two Chinese babies with infantile neuronal ceroid lipofuscinosis] Bi HY, Yao S, Bu DF, Wang ZX, Zhang Y, Qin J, Yang YL, Yuan Y Ref: Zhonghua Er Ke Za Zhi, 44:496, 2006 : PubMed ESTHER: Bi_2006_Zhonghua.Er.Ke.Za.Zhi_44_496 PubMedSearch: Bi 2006 Zhonghua.Er.Ke.Za.Zhi 44 496 PubMedID: 17044973 Gene_locus related to this paper: human-PPT1 Abstract OBJECTIVE: To search for possible novel mutations in palmitoyl-protein thioesterase 1 (PPT1) gene in two Chinese babies with infantile neuronal ceroid lipofuscinosis (INCL). 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 status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R and Malek J <104 more author(s)> Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J (- 104) Ref: Genome Res, 14:2121, 2004 : PubMed ESTHER: Gerhard_2004_Genome.Res_14_2121 PubMedSearch: Gerhard 2004 Genome.Res 14 2121 PubMedID: 15489334 Gene_locus related to this paper: human-AFMID, human-CES4A, human-CES5A, human-NOTUM, human-SERAC1, human-SERHL2, human-TMEM53, mouse-acot1, mouse-adcl4, mouse-Ces2f, mouse-Ces4a, mouse-notum, mouse-q6wqj1, mouse-Q9DAI6, mouse-rbbp9, mouse-SERHL, mouse-srac1, mouse-tmm53, rat-abhd6, rat-abhda, rat-abhea, rat-abheb, rat-Ldah, rat-cd029, rat-estd, rat-Kansl3, rat-nceh1, ratno-acph, ratno-CMBL, mouse-b2rwd2, rat-b5den3, rat-ab17c Abstract The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline. Title: Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen Stover CK, Pham XQ, Erwin AL, Mizoguchi SD, Warrener P, Hickey MJ, Brinkman FS, Hufnagle WO, Kowalik DJ and Olson MV <21 more author(s)> Stover CK, Pham XQ, Erwin AL, Mizoguchi SD, Warrener P, Hickey MJ, Brinkman FS, Hufnagle WO, Kowalik DJ, Lagrou M, Garber RL, Goltry L, Tolentino E, Westbrock-Wadman S, Yuan Y, Brody LL, Coulter SN, Folger KR, Kas A, Larbig K, Lim R, Smith K, Spencer D, Wong GK, Wu Z, Paulsen IT, Reizer J, Saier MH, Hancock RE, Lory S, Olson MV (- 21) Ref: Nature, 406:959, 2000 : PubMed ESTHER: Stover_2000_Nature_406_959 PubMedSearch: Stover 2000 Nature 406 959 PubMedID: 10984043 Gene_locus related to this paper: pseae-clipa, pseae-CPO, pseae-metx, pseae-PA0201, pseae-PA0231, pseae-PA0308, pseae-PA0368, pseae-PA0480, pseae-PA0502, pseae-PA0543, pseae-PA0599, pseae-PA0829, pseae-PA1166, pseae-PA1211, pseae-PA1239, pseae-PA1291, pseae-PA1304, pseae-PA1510, pseae-PA1558, pseae-PA1597, pseae-PA1621, pseae-PA1622, pseae-PA1680, pseae-PA1771, pseae-PA1888, pseae-PA1907, pseae-PA1990, pseae-PA2086, pseae-PA2098, pseae-PA2168, pseae-PA2302, pseae-PA2411, pseae-PA2425, pseae-PA2451, pseae-PA2540, pseae-PA2682, pseae-PA2689, pseae-PA2745, pseae-PA2764, pseae-PA2927, pseae-PA2934, pseae-PA2949, pseae-PA3053, pseae-PA3132, pseae-PA3226, pseae-PA3301, pseae-PA3324, pseae-PA3327, pseae-PA3429, pseae-PA3509, pseae-PA3586, pseae-PA3628, pseae-PA3695, pseae-PA3734, pseae-PA3829, pseae-PA3859, pseae-PA3994, pseae-PA4008, pseae-PA4152, pseae-PA4440, pseae-PA4968, pseae-PA5080, pseae-PA5384, pseae-PA5513, pseae-PCHC, pseae-PCHF, pseae-PHAC1, pseae-PHAC2, pseae-phaD, pseae-phag, pseae-PVDD, pseae-q9i4b9, pseae-q9i538, pseae-rhla, pseae-Y2218, pseae-q9hyv3, pseae-q9i252, pseae-q9i6m9 Abstract Pseudomonas aeruginosa is a ubiquitous environmental bacterium that is one of the top three causes of opportunistic human infections. A major factor in its prominence as a pathogen is its intrinsic resistance to antibiotics and disinfectants. Here we report the complete sequence of P. aeruginosa strain PAO1. At 6.3 million base pairs, this is the largest bacterial genome sequenced, and the sequence provides insights into the basis of the versatility and intrinsic drug resistance of P. aeruginosa. Consistent with its larger genome size and environmental adaptability, P. aeruginosa contains the highest proportion of regulatory genes observed for a bacterial genome and a large number of genes involved in the catabolism, transport and efflux of organic compounds as well as four potential chemotaxis systems. We propose that the size and complexity of the P. aeruginosa genome reflect an evolutionary adaptation permitting it to thrive in diverse environments and resist the effects of a variety of antimicrobial substances. | |||||||
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