Han J

References (77)

Title : Inhibition of cannabinoid degradation enhances hippocampal contextual fear memory and exhibits anxiolytic effects - Zhang_2024_iScience_27_108919
Author(s) : Zhang J , Yuan R , Han W , Chang Y , Kong L , Wei C , Zheng Q , Zhu X , Liu Z , Ren W , Han J
Ref : iScience , 27 :108919 , 2024
Abstract : Recent studies have demonstrated the pivotal involvement of endocannabinoids in regulating learning and memory, but the conclusions obtained from different paradigms or contexts are somewhat controversial, and the underlying mechanisms remain largely elusive. Here, we show that JZL195, a dual inhibitor of fatty acid amide hydrolase and monoacylglycerol lipase, can enhance the performance of mice in a contextual fear conditioning task and increase the time spent in open arms in the elevated zero maze (EZM). Although the effect of JZL195 on fear memory could not be inhibited by antagonists of cannabinoid receptors, the effect on the EZM seems to be mediated by CB1R. Simultaneously, hippocampal neurons are hyperactive, and theta oscillation power is significantly increased during the critical period of memory consolidation upon treatment with JZL195. These results suggest the feasibility of targeting the endocannabinoid system for the treatment of various mental disorders.
ESTHER : Zhang_2024_iScience_27_108919
PubMedSearch : Zhang_2024_iScience_27_108919
PubMedID: 38318362

Title : Alloyed Trimetallic Nanocomposite as an Efficient and Recyclable Solid Matrix for Ideonella sakaiensis Lipase Immobilization - Addai_2024_Langmuir__
Author(s) : Addai FP , Wu J , Lin F , Ma X , Han J , Liu Y , Zhou Y , Wang Y
Ref : Langmuir , : , 2024
Abstract : In this work, a trimetallic (Ni/Co/Zn) organic framework (tMOF), synthesized by a solvothermal method, was calcinated at 400 and 600 degreesC and the final products were used as a support for lipase immobilization. The material annealed at 400 degreesC (Ni-Co-Zn@400) had an improved surface area (66.01 m(2)/g) and pore volume (0.194 cm(3)/g), which showed the highest enzyme loading capacity (301 mg/g) with a specific activity of 0.196 U/mg, and could protect the enzyme against thermal denaturation at 65 degreesC. The optimal pH and temperature for the lipase were 8.0 and 45 degreesC but could tolerate pH levels 7.0-8.0 and temperatures 40-60 degreesC. Moreover, the immobilized enzyme (Ni-Co-Zn@Lipase, Ni-Co-Zn@400@Lipase, or Ni-Co-Zn@600@Lipase) could be recovered and reused for over seven cycles maintaining 80, 90, and 11% of its original activity and maintained a residual activity >90% after 40 storage days. The remarkable thermostability and storage stability of the immobilized lipase suggest that the rigid structure of the support acted as a protective shield against denaturation, while the improved pH tolerance toward the alkaline range indicates a shift in the ionization state attributed to unequal partitioning of hydroxyl and hydrogen ions within the microenvironment of the active site, suggesting that acidic residues may have been involved in forming an enzyme-support bond. The high enzyme loading capacity, specific activity, encouraging stability, and high recoverability of the tMOF@Lipase indicate that a multimetallic MOF could be a better platform for efficient enzyme immobilization.
ESTHER : Addai_2024_Langmuir__
PubMedSearch : Addai_2024_Langmuir__
PubMedID: 38626327

Title : Glucagon-like peptide-1 analogs: Miracle drugs are blooming? - Gong_2024_Eur.J.Med.Chem_269_116342
Author(s) : Gong B , Yao Z , Zhou C , Wang W , Sun L , Han J
Ref : Eur Journal of Medicinal Chemistry , 269 :116342 , 2024
Abstract : Glucagon-like peptide-1 (GLP-1), secreted by L cells in the small intestine, assumes a central role in managing type 2 diabetes mellitus (T2DM) and obesity. Its influence on insulin secretion and gastric emptying positions it as a therapeutic linchpin. However, the limited applicability of native GLP-1 stems from its short half-life, primarily due to glomerular filtration and the inactivating effect of dipeptidyl peptidase-IV (DPP-IV). To address this, various structural modification strategies have been developed to extend GLP-1's half-life. Despite the commendable efficacy displayed by current GLP-1 receptor agonists, inherent limitations persist. A paradigm shift emerges with the advent of unimolecular multi-agonists, such as the recently introduced tirzepatide, wherein GLP-1 is ingeniously combined with other gastrointestinal hormones. This novel approach has captured the spotlight within the diabetes and obesity research community. This review summarizes the physiological functions of GLP-1, systematically explores diverse structural modifications, delves into the realm of unimolecular multi-agonists, and provides a nuanced portrayal of the developmental prospects that lie ahead for GLP-1 analogs.
ESTHER : Gong_2024_Eur.J.Med.Chem_269_116342
PubMedSearch : Gong_2024_Eur.J.Med.Chem_269_116342
PubMedID: 38531211

Title : Efficacy and safety of cetagliptin as monotherapy in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled phase 3 trial - Ji_2023_Diabetes.Obes.Metab_25_3671
Author(s) : Ji L , Lu J , Gao L , Ying C , Sun J , Han J , Zhao W , Gao Y , Wang K , Zheng X , Xie D , Ding J , Zhao J , Yu Q , Wang T
Ref : Diabetes Obes Metab , 25 :3671 , 2023
Abstract : AIM: To assess the efficacy and safety of the dipeptidyl peptidase-4 inhibitor, cetagliptin, as monotherapy in Chinese patients with type 2 diabetes (T2D) and inadequate glycaemic control. MATERIALS AND METHODS: In total, 504 eligible patients with T2D were enrolled and randomized to cetagliptin 50 mg once daily, cetagliptin 100 mg once daily or placebo at a ratio of 2:2:1 for 24 weeks of double-blind treatment, then all patients received cetagliptin 100 mg once daily for 28 weeks of open-label treatment. The primary efficacy endpoint was the change in HbA1c level from baseline at week 24. RESULTS: After 24 weeks, HbA1c from baseline was significantly reduced with cetagliptin 50 mg (-1.08%) and cetagliptin 100 mg (-1.07%) compared with placebo (-0.35%). The placebo-subtracted HbA1c reduction was -0.72% with cetagliptin 50 mg and 100 mg. Patients with a baseline HbA1c of 8.5% or higher had a greater HbA1c reduction with cetagliptin than those patients with a baseline HbA1c of less than 8.5%. Both doses studied led to a significantly higher proportion of patients (42.3% with 100 mg and 45.0% with 50 mg) achieving an HbA1c of less than 7.0% compared with placebo (12.9%). Cetagliptin also significantly lowered fasting plasma glucose and 2-hour postmeal plasma glucose relative to placebo. The incidence of adverse experiences was similar between cetagliptin and placebo. No drug-related hypoglycaemia was reported. CONCLUSIONS: Cetagliptin monotherapy was effective and well tolerated in Chinese patients with T2D who had inadequate glycaemic control on exercise and diet.
ESTHER : Ji_2023_Diabetes.Obes.Metab_25_3671
PubMedSearch : Ji_2023_Diabetes.Obes.Metab_25_3671
PubMedID: 37661308

Title : Design, synthesis and biological evaluation of salicylanilides as novel allosteric inhibitors of human pancreatic lipase - Zhao_2023_Bioorg.Med.Chem_91_117413
Author(s) : Zhao Y , Zhang M , Hou X , Han J , Qin X , Yang Y , Song Y , Liu Z , Zhang Y , Xu Z , Jia Q , Li Y , Chen K , Li B , Zhu W , Ge G
Ref : Bioorganic & Medicinal Chemistry , 91 :117413 , 2023
Abstract : Obesity is a growing global health problem and is associated with increased prevalence of many metabolic disorders, including diabetes, hypertension and cardiovascular disease. Pancreatic lipase (PL) has been validated as a key target for developing anti-obesity agents, owing to its crucial role in lipid digestion and absorption. In the past few decades, porcine PL (pPL) is always used as the enzyme source for screening PL inhibitors, which generate numerous pPL inhibitors but the potent inhibitors against human PL (hPL) are rarely reported. Herein, a series of salicylanilide derivatives were designed and synthesized, while their anti-hPL effects were assayed by a fluorescence-based biochemical approach. To investigate the structure-activity relationships of salicylanilide derivatives as hPL inhibitors in detail, structural modifications on three rings (A, B and C) of the salicylanilide skeleton were performed. Among all tested compounds, 2t and 2u were found possessing the most potent anti-PL activity, showing IC(50) values of 1.86 microM and 1.63 microM, respectively. Inhibition kinetic analyses suggested that both 2t and 2u could effectively inhibit hPL in a non-competitive manner, with the k(i) value of 1.67 microM and 1.70 microM, respectively. Fluorescence quenching assays suggested that two inhibitors could quench the fluorescence of hPL via a static quenching procedure. Molecular docking simulations suggested that 2t and 2u could tightly bind on an allosteric site of hPL. Collectively, the structure-activity relationships of salicylanilide derivatives as hPL inhibitors were carefully investigated, while two newly identified reversible hPL inhibitors (2t and 2u) could be used as promising lead compounds to develop novel anti-obesity drugs.
ESTHER : Zhao_2023_Bioorg.Med.Chem_91_117413
PubMedSearch : Zhao_2023_Bioorg.Med.Chem_91_117413
PubMedID: 37490786

Title : Enhanced enzyme thermostability of a family I.3 lipase LipSR1 by T118A mutation at the calcium-binding site - Jiang_2023_Biotechnol.Lett__
Author(s) : Jiang S , Zhou Z , Han J , Fan Q , Long Z , Wang J
Ref : Biotechnol Lett , : , 2023
Abstract : OBJECTIVES: The lipase gene lipSR1 isolated from oil-contaminated soil exhibits high hydrolytic activity for short-chain fatty acid substrates. A single calcium ion is required to anchor the lid of LipSR1 in an open conformation by coordination with two aspartate residues and three other residues in the lid. The lid of LipSR1 is anchored by Ca(2+), which is coordinated by side-chain carboxyl oxygens of Asp153 and Asp157, carbonyl oxygens of Thr118 and Ser144, and the side chain of Gln120. RESULTS: D157A, D153R, Q120A, S144A, and T118A mutants were produced by site-directed mutagenesis in this study. Analyses of hydrolytic activity and thermostability showed that the properties of D157A, D153R, Q120A, and S144A were almost lost, suggesting that Asp157, Asp153, Gln120, and Ser144 are important residues for LipSR1. However, the catalytic performance of T118A was clearly maintained. Moreover, the thermostability of mutant T118A was higher than that of wild-type LipSR1. CONCLUSIONS: These results indicated that mutation of threonine at position 118 improved the stability of the enzyme at high temperature.
ESTHER : Jiang_2023_Biotechnol.Lett__
PubMedSearch : Jiang_2023_Biotechnol.Lett__
PubMedID: 37439931
Gene_locus related to this paper: lacac-q5fi30

Title : New Hydrolase from Aeromicrobium sp. HA for the Biodegradation of Zearalenone: Identification, Mechanism, and Application - Hu_2023_J.Agric.Food.Chem_71_2411
Author(s) : Hu J , Wang G , Hou M , Du S , Han J , Yu Y , Gao H , He D , Shi J , Lee YW , Mohamed SR , Dawood DH , Hong Q , Liu X , Xu J
Ref : Journal of Agricultural and Food Chemistry , 71 :2411 , 2023
Abstract : Zearalenone (ZEN) is an estrogenic mycotoxin most frequently found in cereals that can cause reproductive disorders in livestock and pose a severe threat to animal husbandry. In this study, we isolated a ZEN-degrading Aeromicrobium strain from soil and found that ZenH, a hydrolase, is responsible for the hydrolysis of ZEN through comparative proteomics and biochemical studies. ZenH exhibited the highest similarity with lactone hydrolase ZHD607 from Phialophora americana at 21.52%. ZenH displayed maximal enzymatic activity at pH 7.0 and 55 degreesC with a Michaelis constant of 12.64 microM. The catalytic triad of ZenH was identified as S117-D142-H292 by molecular docking and site-directed mutagenesis. ZenH catalyzed the hydrolysis of ZEN to a novel metabolite, (S,E)-4-hydroxy-2-(10-hydroxy-6-oxoundec-1-en-1-yl)-7-oxabicyclo[4.2.0]octa-1,3,5-trien-8-one, which exhibited significantly lower estrogenic toxicity than ZEN. This study illustrates a novel ZEN-degrading enzyme and reveals a new degradation product. Furthermore, the enzyme showed good potential for detoxifying ZEN during food processing.
ESTHER : Hu_2023_J.Agric.Food.Chem_71_2411
PubMedSearch : Hu_2023_J.Agric.Food.Chem_71_2411
PubMedID: 36701132

Title : Risk factors for hospital-acquired pneumonia among inpatients with mental disorders in a large mental health center within a tertiary general hospital - Han_2022_Am.J.Infect.Control__
Author(s) : Han J , Lv Z , Shen M , Wan Q , Xiao L , Wang G
Ref : Am J Infect Control , : , 2022
Abstract : BACKGROUND: Few researchers have investigated the incidence of and risk factors for hospital-acquired pneumonia (HAP) among inpatients with mental disorders in a general hospital. METHODS: This study included patients with mental disorders hospitalized in a large mental health center (situated in a general hospital) between January 1, 2017 and July 31, 2021 (excluding January 1, 2020 to May 31, 2020). Risk factors for HAP were identified by logistic regression analysis after propensity score matching (PSM, 1:4) for gender, age, duration of observation and hospital ward. RESULTS: The study included 16,864 patients. HAP incidence rate was 1.15% overall, 2.11% on closed wards, 0.75% on open wards, 4.45% in patients with organic mental disorders, 1.80% in patients with schizophrenia spectrum disorder, and 0.84% in patients with mood disorders. Risk factors for HAP after PSM were hypoproteinemia, chronic liver disease, use of clozapine, hospitalization during the previous 180 days, body mass index (BMI) >=18.5 kg/m(2), cholinesterase inhibitor use and mood stabilizer use. CONCLUSION: HAP was common among inpatients with mental disorders. Risk factors for HAP in patients with mental disorders include hypoproteinemia, chronic liver disease, hospitalization during the past 180 days, BMI >=18.5 kg/m(2), and use of clozapine, cholinesterase inhibitors or mood stabilizers.
ESTHER : Han_2022_Am.J.Infect.Control__
PubMedSearch : Han_2022_Am.J.Infect.Control__
PubMedID: 35728721

Title : Neurotoxicity of tetrabromobisphenol A and SiO2 nanoparticle co-exposure in zebrafish and barrier function of the embryonic chorion - Zhu_2022_Sci.Total.Environ_845_157364
Author(s) : Zhu B , Lei L , Fu K , Zhao S , Hua J , Yang L , Han J , Li R , Zhou B
Ref : Sci Total Environ , 845 :157364 , 2022
Abstract : Silicon dioxide nanoparticles (n-SiO(2)) absorb tetrabromobisphenol A (TBBPA) and modify its bioavailability and toxicity in the aquatic phase; embryonic chorion is an efficient barrier against nanoparticles (e.g., SiO(2)) and influences their toxicity. However, few studies have investigated developmental neurotoxicity in fish after co-exposure to TBBPA and n-SiO(2), especially considering the barrier function of the chorion. In the present study, zebrafish embryos were exposed to TBBPA (50, 100, and 200 microg/L) alone or in combination with n-SiO(2) (25 mg/L) until 24 or 120 h post fertilization (hpf), in the presence and absence of the chorion. The results confirmed that TBBPA exposure alone significantly downregulated the expression of neurodevelopment marker genes (mbp, alpha-tubulin, shha, and gfap), altered acetylcholinesterase activity and acetylcholine content, and affected locomotor behavior at different developmental stages. Moreover, the results indicated that n-SiO(2) promoted TBBPA-induced neurotoxic effects in zebrafish larvae at 120 hpf, including further repression of the transcription of CNS-related genes, disruption of the cholinergic system, and decrease in the average swimming speed under dark/light stimulation. However, scanning electron microscopy/energy dispersive spectroscopy analysis revealed that at 24 hpf, the embryonic chorion efficiently blocked n-SiO(2) and consequently decreased the bioaccumulation of TBBPA and TBBPA-induced neurotoxicity in dechorionated zebrafish embryos. Taken together, the results demonstrate that n-SiO(2) affected the bioavailability and neurodevelopmental toxicity of TBBPA, and their combined toxicity to zebrafish embryos was mitigated by embryonic chorion, which will facilitate risk assessment on n-SiO(2) and TBBPA and improve understanding the function of the fish embryonic chorion.
ESTHER : Zhu_2022_Sci.Total.Environ_845_157364
PubMedSearch : Zhu_2022_Sci.Total.Environ_845_157364
PubMedID: 35843329

Title : Computational redesign of a PETase for plastic biodegradation under ambient condition by the GRAPE strategy - Cui_2021_ACS.Catal_11_1340
Author(s) : Cui Y , Chen Y , Liu X , Dong S , Tian Y , Qiao Y , Mitra R , Han J , Li C , Han X
Ref : ACS Catal , 11 :1340 , 2021
Abstract : Nature has provided a fantastic array of enzymes that are responsible for essential biochemical functions but not usually suitable for technological applications. Not content with the natural repertoire, protein engineering holds promise to extend the applications of improved enzymes with tailored properties. However, engineering of robust proteins remains a difficult task since the positive mutation library may not cooperate to reach the target function in most cases owing to the ubiquity of epistatic effects. The main demand lies in identifying an efficient path of accumulated mutations. Herein, we devised a computational strategy (greedy accumulated strategy for protein engineering, GRAPE) to improve the robustness of a PETase from Ideonella sakaiensis. A systematic clustering analysis combined with greedy accumulation of beneficial mutations in a computationally derived library enabled the redesign of a variant, DuraPETase, which exhibits an apparent melting temperature that is drastically elevated by 31 C and a strikingly enhanced degradation toward semicrystalline poly(ethylene terephthalate) (PET) films (30%) at mild temperatures (over 300-fold). Complete biodegradation of 2 g/L microplastics to water-soluble products under mild conditions is also achieved, opening up opportunities to steer the biological degradation of uncollectable PET waste and further conversion of the resulting monomers to high-value molecules. The crystal structure revealed the individual mutation match with the design model. Concurrently, synergistic effects are captured, while epistatic interactions are alleviated during the accumulation process. We anticipate that our design strategy will provide a broadly applicable strategy for global optimization of enzyme performance.
ESTHER : Cui_2021_ACS.Catal_11_1340
PubMedSearch : Cui_2021_ACS.Catal_11_1340
Gene_locus related to this paper: idesa-peth

Title : Hevin-calcyon interaction promotes synaptic reorganization after brain injury - Kim_2021_Cell.Death.Differ__
Author(s) : Kim JH , Jung HG , Kim A , Shim HS , Hyeon SJ , Lee YS , Han J , Jung JH , Lee J , Ryu H , Park JY , Hwang EM , Suk K
Ref : Cell Death Differ , : , 2021
Abstract : Hevin, also known as SPARC-like protein 1 (SPARCL1 or SC1), is a synaptogenic protein secreted by astrocytes and modulates the formation of glutamatergic synapses in the developing brain by interacting with synaptic adhesion proteins, such as neurexin and neuroligin. Here, we identified the neuron-specific vesicular protein calcyon as a novel interaction partner of hevin and demonstrated that this interaction played a pivotal role in synaptic reorganization after an injury in the mature brain. Astrocytic hevin was upregulated post-injury in a photothrombotic stroke model. Hevin was fragmented by MMP3 induced during the acute stage of brain injury, and this process was associated with severe gliosis. At the late stage, the functional hevin level was restored as MMP3 expression decreased. The C-terminus of hevin interacted with the N-terminus of calcyon. By using RNAi and binding competitor peptides in an ischemic brain injury model, we showed that this interaction was crucial in synaptic and functional recoveries in the sensory-motor cortex, based on histological and electrophysiological analyses. Regulated expression of hevin and calcyon and interaction between them were confirmed in a mouse model of traumatic brain injury and patients with chronic traumatic encephalopathy. Our study provides direct evidence for the causal relationship between the hevin-calcyon interaction and synaptic reorganization after brain injury. This neuron-glia interaction can be exploited to modulate synaptic reorganization under various neurological conditions.
ESTHER : Kim_2021_Cell.Death.Differ__
PubMedSearch : Kim_2021_Cell.Death.Differ__
PubMedID: 33753902

Title : Rational Design of Highly Selective Near-Infrared Two-Photon Fluorogenic Probe for Imaging Orthotopic Hepatocellular Carcinoma Chemotherapy - Wu_2021_Angew.Chem.Int.Ed.Engl__
Author(s) : Wu X , Wang R , Qi S , Kwon N , Han J , Kim H , Li H , Yu F , Yoon J
Ref : Angew Chem Int Ed Engl , : , 2021
Abstract : Selective fluorescence imaging of biomarker in vivo and in situ for evaluating orthotopic hepatocellular carcinoma (HCC) chemotherapy remains a great challenge due to current imaging agents suffering from the potential interferences of other hydrolases. Herein, we observed that carbamate unit showed a high selectivity toward HCC-related biomarker (carboxylesterase, CE) for evaluation of treatment. A near-infrared two-photon fluorescent probe was developed to not only specially image CE activity in vivo and in situ but also target orthotopic liver tumor after systemic administration. In vivo signals of probe correlating well with tumor apoptosis make it possible to evaluate the status of treatment. Excellent property of probe enables the first imaging of CE activity in situ with high resolution three-dimensional view. This study may promote advancements in optical imaging approach for precise imaging-guided diagnosis of HCC in situ and its evaluation of treatment.
ESTHER : Wu_2021_Angew.Chem.Int.Ed.Engl__
PubMedSearch : Wu_2021_Angew.Chem.Int.Ed.Engl__
PubMedID: 33942436

Title : Residual behaviors and metabolic pathway of ethylparaben in Drosophila melanogaster - Wang_2021_Ecotoxicol.Environ.Saf_230_113124
Author(s) : Wang Y , Qin M , Wang X , Han J , Chen R , Zhang M , Gu W
Ref : Ecotoxicology & Environmental Safety , 230 :113124 , 2021
Abstract : OBJECTIVE: Parabens are commonly used as preservatives in foodstuffs, cosmetics, and pharmaceutical products. The widespread use of parabens has led to their leaking into the environment. Concerns about the safety of parabens have recently increased due to their potential endocrine-disrupting effects as an emerging contaminant. Thus, it is necessary to study the metabolism of parabens in vivo. METHODS: In this study, Drosophila melanogaster in males and females were exposed to ethylparaben (EP) concentration group (300 mg/L, 700 mg/L, and 1000 mg/L), and control group (0 mg/L) by the capillary feeding assay (CAFE). We quantified the activity of the detoxification-related carboxylesterase (CarE). The contents of EP metabolites in D. melanogaster, including p-hydroxybenzoic acid (PHBA), methylparaben (MP), and intact EP were carried out by high-performance liquid chromatography (HPLC). The regression model between EP metabolites (PHBA and MP) and CarE was developed using the Fourier series fitting method. RESULTS: The general level of EP metabolites (PHBA, MP, and intact EP) accumulation was accounted for 5.6-11.5% in D. melanogaster. As EP accumulated, the activity of CarE increased, and the activity of CarE in females was higher than males, which is inconsistent with the result of EP intake dose. Additionally, there were significant differences in the proportion of EP metabolites between female and male flies, and the results of sex comparison were different depending on the EP treated groups and EP metabolites. In general, PHBA of EP hydrolytic product and MP of EP transesterification product in D. melanogaster were 41.4-63.9% and 10.4-24.6%, respectively. In terms of the rest of the EP existed in intact form and ranged from 22.4% to 34.0%. Moreover, the EP metabolites in the conjugated form were higher than those in the free form. The regression model between EP metabolites and CarE was established, showing that the CarE activity can be used to estimate the content of PHBA and MP. CONCLUSION: The result indicates that the EP can accumulate in the body through food. Hydrolysis is the main metabolic pathway of EP in D. melanogaster, and transesterification is another metabolic pathway of EP. Additionally, the EP metabolites in flies mainly exist in conjugated form. Furthermore, the Fourier series fitting method model between EP metabolites and CarE, providing theoretical support to study the dose-effect relationship between metabolites of parabens and CarE. This study not only provides a mathematical basis for the safety evaluation of parabens, but also provides support for the further study of the toxicological effects of parabens.
ESTHER : Wang_2021_Ecotoxicol.Environ.Saf_230_113124
PubMedSearch : Wang_2021_Ecotoxicol.Environ.Saf_230_113124
PubMedID: 34968799

Title : Effects of perioperative interventions for preventing postoperative delirium: A protocol for systematic review and meta-analysis of randomized controlled trials - Li_2021_Medicine.(Baltimore)_100_e26662
Author(s) : Li X , Wang Y , Liu J , Xiong Y , Chen S , Han J , Xie W , Wu Q
Ref : Medicine (Baltimore) , 100 :e26662 , 2021
Abstract : BACKGROUND: Postoperative delirium (POD) not only increases the medical burden but also adversely affects patient prognosis. Although some cases of delirium can be avoided by early intervention, there is no clear evidence indicating whether any of these measures can effectively prevent POD in specific patient groups. OBJECTIVE: The aim of this meta-analysis was to compare the efficacy and safety of the existing preventive measures for managing POD. METHODS: The PubMed, OVID (Embase and MEDLINE), Web of Science, and the Cochrane Library databases were searched for articles published before January 2020. The relevant randomized controlled trials (RCTs) were selected based on the inclusion and exclusion criteria. Data extraction and methodological quality assessment were performed according to a predesigned data extraction form and scoring system, respectively. The interventions were compared on the basis of the primary outcome like incidence of POD, and secondary outcomes like duration of delirium and the length of intensive care unit and hospital stay. RESULTS: Sixty-three RCTs were included in the study, covering interventions like surgery, anesthesia, analgesics, intraoperative blood glucose control, cholinesterase inhibitors, anticonvulsant drugs, antipsychotic drugs, sleep rhythmic regulation, and multi-modal nursing. The occurrence of POD was low in 4 trials that monitored the depth of anesthesia with bispectral index during the operation (P<.0001). Two studies showed that supplementary analgesia was useful for delirium prevention (P=.002). Seventeen studies showed that perioperative sedation with alpha2-adrenergic receptor agonists prevented POD (P=.0006). Six studies showed that both typical and atypical antipsychotic drugs can reduce the incidence of POD (P=.002). Multimodal nursing during the perioperative period effectively reduced POD in 6 studies (P<.00001). Furthermore, these preventive measures can reduce the duration of delirium, as well as the total and postoperative length of hospitalized stay for non-cardiac surgery patients. For patients undergoing cardiac surgery, effective prevention can only reduce the length of intensive care unit stay. CONCLUSION: Measures including intraoperative monitoring of bispectral index, supplemental analgesia, alpha2-adrenergic receptor agonists, antipsychotic drugs, and multimodal care are helpful to prevent POD effectively. However, larger, high-quality RCTs are needed to verify these findings and develop more interventions and drugs for preventing postoperative delirium.
ESTHER : Li_2021_Medicine.(Baltimore)_100_e26662
PubMedSearch : Li_2021_Medicine.(Baltimore)_100_e26662
PubMedID: 34398027

Title : DECR1 directly activates HSL to promote lipolysis in cervical cancer cells - Zhou_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159090
Author(s) : Zhou H , Zhang J , Yan Z , Qu M , Zhang G , Han J , Wang F , Sun K , Wang L , Yang X
Ref : Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids , :159090 , 2021
Abstract : Fatty acids have a high turnover rate in cancer cells to supply energy for tumor growth and proliferation. Lipolysis is particularly important for the regulation of fatty acid homeostasis and in the maintenance of cancer cells. In the current study, we explored how 2,4-Dienoyl-CoA reductase (DECR1), a short-chain dehydrogenase/reductase associated with mitochondrial and cytoplasmic compartments, promotes cancer cell growth. We report that DECR1 overexpression significantly reduced the triglyceride (TAG) content in HeLa cells; conversely, DECR1 silencing increased intracellular TAG content. Subsequently, our experiments demonstrate that DECR1 promotes lipolysis via effects on hormone sensitive lipase (HSL). The direct interaction of DECR1 with HSL increases HSL phosphorylation and activity, facilitating the translocation of HSL to lipid droplets. The ensuing enhancement of lipolysis thus increases the release of free fatty acids. Downstream effects include the promotion of cervical cancer cell migration and growth, associated with the enhanced levels of p62 protein. In summary, high levels of DECR1 serves to enhance lipolysis and the release of fatty acid energy stores to support cervical cancer cell growth.
ESTHER : Zhou_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159090
PubMedSearch : Zhou_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159090
PubMedID: 34896618

Title : Mechanistic Insight into the Design of Chemical Tools to Control Multiple Pathogenic Features in Alzheimer's Disease - Han_2021_Acc.Chem.Res__
Author(s) : Han J , Du Z , Lim MH
Ref : Acc Chem Res , : , 2021
Abstract : ConspectusAlzheimer's disease (AD) is the most common form of dementia and is characterized by memory loss and cognitive decline. Approximately 50 million people worldwide are suffering from AD and related dementias. Very recently, the first new drug targeting amyloid-beta (Abeta) aggregates has been approved by the United States Food and Drug Administration, but its efficacy against AD is still debatable. Other available treatments temporarily relieve the symptoms of AD. The difficulty in discovering effective therapeutics for AD originates from its complicated nature, which results from the interrelated pathogenic pathways led by multiple factors. Therefore, to develop potent disease-modifying drugs, multiple pathological features found in AD should be fully elucidated.Our laboratory has been designing small molecules as chemical tools to investigate the individual and interrelated pathologies triggered by four pathogenic elements found in the AD-affected brain: metal-free Abeta, metal-bound Abeta, reactive oxygen species (ROS), and acetylcholinesterase (AChE). Abeta peptides are partially folded and aggregate into oligomers, protofibrils, and fibrils. Abeta aggregates are considered to be neurotoxic, causing membrane disruption, aberrant cellular signaling, and organelle dysfunction. In addition, highly concentrated metal ions accumulate in senile plaques mainly composed of Abeta aggregates, which indicates that metal ions can directly interact with Abeta. Metal binding to Abeta affects the aggregation and conformation of the peptide. Moreover, the impaired homeostasis of redox-active Fe(II/III) and Cu(I/II) induces the overproduction of ROS through Fenton chemistry and Fenton-like reactions, respectively. Dysregulated ROS prompt oxidative-stress-damaging biological components such as lipids, proteins, and nucleic acids and, consequently, lead to neuronal death. Finally, the loss of cholinergic transmission mediated by the neurotransmitter acetylcholine (ACh) contributes to cognitive deficits observed in AD.In this Account, we illustrate the design principles for small-molecule-based chemical tools with reactivities against metal-free Abeta, metal-bound Abeta, ROS, and AChE. More importantly, mechanistic details at the molecular level are highlighted with some examples of chemical tools that were developed by our group. The aggregation of metal-free Abeta can be modulated by modifying amino acid residues responsible for self-assembling Abeta or disassembling preformed fibrils. To alter the aggregation and cytotoxicity profiles of metal-bound Abeta, ternary complexation, metal chelation, and modifications onto metal-binding residues can be effective tactics. The presence and production of ROS are able to be controlled by small molecules with antioxidant and metal-binding properties. Finally, inhibiting substrate access or substrate binding at the active site of AChE can diminish its activity, which restores the levels of ACh. Overall, our rational approaches demonstrate the feasibility of developing small molecules as chemical tools that can target and modulate multiple pathological factors associated with AD and can be useful for gaining a greater understanding of the multifaceted pathology of the disease.
ESTHER : Han_2021_Acc.Chem.Res__
PubMedSearch : Han_2021_Acc.Chem.Res__
PubMedID: 34606227

Title : A Roadmap to the Structure-Related Metabolism Pathways of Per- and Polyfluoroalkyl Substances in the Early Life Stages of Zebrafish (Danio rerio) - Han_2021_Environ.Health.Perspect_129_77004
Author(s) : Han J , Gu W , Barrett H , Yang D , Tang S , Sun J , Liu J , Krause HM , Houck KA , Peng H
Ref : Environmental Health Perspectives , 129 :77004 , 2021
Abstract : BACKGROUND: Thousands of per- and polyfluoroalkyl substances (PFAS) with diverse structures have been detected in the ambient environment. Apart from a few well-studied PFAS, the structure-related toxicokinetics of a broader set of PFAS remain unclear. OBJECTIVES: To understand the toxicokinetics of PFAS, we attempted to characterize the metabolism pathways of 74 structurally diverse PFAS samples from the U.S. Environmental Protection Agency's PFAS screening library. METHODS: Using the early life stages of zebrafish (Danio rerio) as a model, we determined the bioconcentration factors and phenotypic toxicities of 74 PFAS. Then, we applied high-resolution mass spectrometry-based nontargeted analysis to identify metabolites of PFAS in zebrafish larvae after 5 d of exposure by incorporating retention time and mass spectra. In vitro enzymatic activity experiments with human recombinant liver carboxylesterase (hCES1) were employed to validate the structure-related hydrolysis of 11 selected PFAS. RESULTS: Our findings identified five structural categories of PFAS prone to metabolism. The metabolism pathways of PFAS were highly related to their structures as exemplified by fluorotelomer alcohols that the predominance of beta-oxidation or taurine conjugation pathways were primarily determined by the number of hydrocarbons. Hydrolysis was identified as a major metabolism pathway for diverse PFAS, and perfluoroalkyl carboxamides showed the highest in vivo hydrolysis rates, followed by carboxyesters and sulfonamides. The hydrolysis of PFAS was verified with recombinant hCES1, with strong substrate preferences toward perfluoroalkyl carboxamides. CONCLUSIONS: We suggest that the roadmap of the structure-related metabolism pathways of PFAS established in this study would provide a starting point to inform the potential health risks of other PFAS. https://doi.org/10.1289/EHP7169.
ESTHER : Han_2021_Environ.Health.Perspect_129_77004
PubMedSearch : Han_2021_Environ.Health.Perspect_129_77004
PubMedID: 34288731

Title : Neuroligin 2 regulates absence seizures and behavioral arrests through GABAergic transmission within the thalamocortical circuitry - Cao_2020_Nat.Commun_11_3744
Author(s) : Cao F , Liu JJ , Zhou S , Cortez MA , Snead OC , Han J , Jia Z
Ref : Nat Commun , 11 :3744 , 2020
Abstract : Epilepsy and autism spectrum disorders (ASD) are two distinct brain disorders but have a high rate of co-occurrence, suggesting shared pathogenic mechanisms. Neuroligins are cell adhesion molecules important in synaptic function and ASD, but their role in epilepsy remains unknown. In this study, we show that Neuroligin 2 (NLG2) knockout mice exhibit abnormal spike and wave discharges (SWDs) and behavioral arrests characteristic of absence seizures. The anti-absence seizure drug ethosuximide blocks SWDs and rescues behavioral arrests and social memory impairment in the knockout mice. Restoring GABAergic transmission either by optogenetic activation of the thalamic reticular nucleus (nRT) presynaptic terminals or postsynaptic NLG2 expression in the thalamic neurons reduces the SWDs and behavioral arrests in the knockout mice. These results indicate that NLG2-mediated GABAergic transmission at the nRT-thalamic circuit represents a common mechanism underlying both epileptic seizures and ASD.
ESTHER : Cao_2020_Nat.Commun_11_3744
PubMedSearch : Cao_2020_Nat.Commun_11_3744
PubMedID: 32719346

Title : Bioconcentration and developmental neurotoxicity of novel brominated flame retardants, hexabromobenzene and pentabromobenzene in zebrafish - Chen_2020_Environ.Pollut_268_115895
Author(s) : Chen X , Guo W , Lei L , Guo Y , Yang L , Han J , Zhou B
Ref : Environ Pollut , 268 :115895 , 2020
Abstract : The flame retardants hexabromobenzene (HBB) and pentabromobenzene (PBB) have been extensively used and become ubiquitous pollutants in the aquatic environment and biota, but their potential toxic effects on wildlife remained unknown. In this study, by using zebrafish (Danio rerio) as a model, the bioconcentration and developmental neurotoxicity were investigated. Zebrafish embryos were exposed to HBB and PBB (0, 30, 100 and 300 g/L) from 2 until 144 h post-fertilization (hpf). Chemical analysis showed bioconcentrations of both chemicals, while HBB is readily metabolized to PBB in zebrafish larvae. Embryonic exposure to both chemicals did not cause developmental toxicity, but induced locomotor behavioral anomalies in larvae. Molecular docking results indicated that both chemicals could bind to zebrafish acetylcholinesterase (AChE). Furthermore, HBB and PBB significantly inhibited AChE activities, accompanied by increased contents of acetylcholine and decreased choline in larvae. Downregulation of the genes associated with central nervous system (CNS) development (e.g., mbp, alpha1-tubulin, gfap, shha) as well as the corresponding proteins (e.g., Mbp, alpha1-Tubulin) was observed, but gap-43 was upregulated at both gene and protein levels. Together, our results indicate that both HBB and PBB exhibit developmental neurotoxicity by affecting various parameters related to CNS development and indications for future toxicological research and risk assessment of the novel brominated flame retardants.
ESTHER : Chen_2020_Environ.Pollut_268_115895
PubMedSearch : Chen_2020_Environ.Pollut_268_115895
PubMedID: 33120153

Title : In vitro biolayer interferometry analysis of acetylcholinesterase as a potential target of aryl-organophosphorus flame-retardants - Shi_2020_J.Hazard.Mater_409_124999
Author(s) : Shi Q , Guo W , Shen Q , Han J , Lei L , Chen L , Yang L , Feng C , Zhou B
Ref : J Hazard Mater , 409 :124999 , 2020
Abstract : Organophosphorus flame retardants (OPFRs) have been implicated as neurotoxicants, but their potential neurotoxicity and mechanisms remain poorly understood. Herein, we investigated the neurotoxicity of selected OPFRs using zebrafish as a model organism. Environmentally relevant concentrations (3-1500 nM) of three classes of OPFRs (aryl-OPFRs, chlorinated-OPFRs, and alkyl-OPFRs) were tested in zebrafish larvae (2-144 h post-fertilisation) alongside the neurotoxic chemical chlorpyrifos (CPF) that inhibits acetylcholinesterase (AChE). Exposure to aryl-OPFRs and CPF inhibited AChE activities, while chlorinated- and alkyl-OPFRs did not inhibit these enzymes. Biolayer interferometry (BLI) was used to probe interactions between OPFRs and AChE. The association and dissociation response curves showed that, like CPF, all three selected aryl-OPFRs, triphenyl phosphate (TPHP), tricresyl phosphate (TCP) and cresyl diphenyl phosphate (CDP), bound directly to AChE. The affinity constant (K(D)) for TPHP, TCP, CDP and CPF was 2.18 x 10(-4), 5.47 x 10(-5), 1.05 x 10(-4) and 1.70 x 10(-5) M, respectively. In addition, molecular docking revealed that TPHP, TCP, CDP and CPF bound to AChE with glide scores of - 7.8, - 8.3, - 8.1 and - 7.3, respectively. Furthermore, the calculated binding affinity between OPFRs and AChE correlated well with the K(D) values measured by BLI. The present study revealed that aryl-OPFRs can act as potent AChE inhibitors, and may therefore present a significant ecological risk to aquatic organisms.
ESTHER : Shi_2020_J.Hazard.Mater_409_124999
PubMedSearch : Shi_2020_J.Hazard.Mater_409_124999
PubMedID: 33454525

Title : Clinical characteristics and treatment of mixed-pesticide poisoning in a patient: reflections on a particular case - Tao_2020_J.Int.Med.Res_48_300060520977392
Author(s) : Tao Y , Liu T , Han J , Jian X , Kan B
Ref : J Internal Medicine Res , 48 :300060520977392 , 2020
Abstract : Patients who commit suicide often deliberately hide their medical history. Given that taking pesticides is one of the most common methods of suicide, other forms of poisoning may be neglected in clinical practice. We report here a case of mixed-pesticide poisoning. The patient was poisoned by oral administration of a coumarin rodenticide in combination with an intramuscular injection of organophosphorus (OP) pesticide. The patient was treated with vitamin K1, cholinesterase reactivators, atropine, ventilator-assisted ventilation, and bedside debridement. Her condition gradually stabilized and she eventually recovered and was discharged. Assessment of the causes of delayed diagnosis and treatment suggests that we need to improve early detection and treatment of acute poisoning. It is especially important to ask about the patient's medical history, conduct a careful physical examination, and track the clinical symptoms and differential diagnosis of common poisoning. In addition to the three common routes of poisoning-oral, inhalation, and cutaneous mucosal contact-intramuscular injection of OP can also lead to severe poisoning, which manifests as respiratory failure.
ESTHER : Tao_2020_J.Int.Med.Res_48_300060520977392
PubMedSearch : Tao_2020_J.Int.Med.Res_48_300060520977392
PubMedID: 33356707

Title : Biological evaluation of 7-O-amide hesperetin derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease - Wu_2020_Chem.Biol.Interact_334_109350
Author(s) : Wu M , Zhu X , Zhang Y , Wang M , Liu T , Han J , Li J , Li Z
Ref : Chemico-Biological Interactions , 334 :109350 , 2020
Abstract : A series of 7-O-amide hesperetin derivatives were subjected to multi-target biological evaluation of anti-Alzheimer's disease. Most of the compounds showed good in vitro inhibitory activity against cholinesterase, of which compound 7c (7-O-(4-(morpholinoethyl)-acetamide) hesperetin) was the most effective anti-eqBuChE derivative (IC(50) = 0.28 +/- 0.05 M) and exerted neuroprotective effects. Further biological evaluation found that compounds 4d, 4e and 7c showed strong antioxidant, anti-Abeta self-aggregation and anti-neuroinflammatory activities. Compound 7c could inhibit the expression of iNOS and COX-2 proteins and prevent LPS-induced inflammatory response in BV2 cells. In addition, compound 7c could chelate biometal ions such as Cu(2+) and Zn(2+). In the vivo study, the MWM test confirmed that compound 7c could improve the cognitive impairment caused by scopolamine. In summary, the above studies have shown that the optimized compound 7c has great development potential as MTDL for the treatment of AD.
ESTHER : Wu_2020_Chem.Biol.Interact_334_109350
PubMedSearch : Wu_2020_Chem.Biol.Interact_334_109350
PubMedID: 33307048

Title : Computational redesign of a PETase for plastic biodegradation by the GRAPE strategy - Cui_2020_Biorxiv__
Author(s) : Cui YL , Chen YC , Liu XY , Dong SJ , Han J , Xiang H , Chen Q , Liu HY , Han X , Liu WD , Tang SY , Wu B
Ref : Biorxiv , : , 2020
Abstract : The excessive use of plastics has been accompanied by severe ecologically damaging effects. The recent discovery of a PETase from Ideonella sakaiensis that decomposes poly(ethylene terephthalate) (PET) under mild conditions provides an attractive avenue for the biodegradation of plastics. However, the inherent instability of the enzyme limits its practical utilization. Here, we devised a novel computational strategy (greedy accumulated strategy for protein engineering, GRAPE). A systematic clustering analysis combined with greedy accumulation of beneficial mutations in a computationally derived library enabled the design of a variant, DuraPETase, which exhibits an apparent melting temperature that is drastically elevated by 31C and strikingly enhanced degradation performance toward semicrystalline PET films (23%) at mild temperatures (over two orders of magnitude improvement). The mechanism underlying the robust promotion of enzyme performance has been demonstrated via a crystal structure and molecular dynamics simulations. This work shows the capabilities of computational enzyme design to circumvent antagonistic epistatic effects and provides a valuable tool for further understanding and advancing polyester hydrolysis in the natural environment
ESTHER : Cui_2020_Biorxiv__
PubMedSearch : Cui_2020_Biorxiv__
Gene_locus related to this paper: idesa-peth

Title : Baicalein as a Potential Inhibitor against BACE1 and AChE: Mechanistic Comprehension through In Vitro and Computational Approaches - Han_2019_Nutrients_11_
Author(s) : Han J , Ji Y , Youn K , Lim G , Lee J , Kim DH , Jun M
Ref : Nutrients , 11 : , 2019
Abstract : One of the major neurodegenerative features of Alzheimer's disease (AD) is the presence of neurotoxic amyloid plaques composed of amyloid beta peptide (Abeta). beta-Secretase (BACE1) and acetylcholinesterase (AChE), which promote Abeta fibril formation, have become attractive therapeutic targets for AD. P-glycoprotein (P-gp), the major efflux pump of the blood-brain barrier (BBB), plays a critical role in limiting therapeutic molecules. In pursuit of discovering a natural anti-AD candidate, the bioactivity, physicochemical, drug-likeness, and molecular docking properties of baicalein, a major compound from Scutellaria baicalensis, was investigated. Baicalein exhibited strong BACE1 and AChE inhibitory properties (IC50 23.71 +/- 1.91 microM and 45.95 +/- 3.44 microM, respectively) and reacted in non-competitive and competitive manners with substrates, respectively. in Silico docking analysis was in full agreement with the in vitro results, demonstrating that the compound exhibited powerful binding interaction with target enzymes. Particularly, three continuous hydroxyl groups on the A ring demonstrated strong H-bond binding properties. It is also noteworthy that baicalein complied with all requirements of Lipinski's rule of five by its optimal physicochemical properties for both oral bioavailability and blood-brain barrier permeability. Overall, the present study strongly demonstrated the possibility of baicalein having in vivo pharmacological efficacy for specific targets in the prevention and/or treatment of AD.
ESTHER : Han_2019_Nutrients_11_
PubMedSearch : Han_2019_Nutrients_11_
PubMedID: 31703329

Title : Clinical analysis of Chinese anti-low-density-lipoprotein-receptor-associated protein 4 antibodies in patients with myasthenia gravis - Li_2019_Eur.J.Neurol_26_1296
Author(s) : Li M , Han J , Zhang Y , Lv J , Zhang J , Zhao X , Ren L , Fang H , Yang J , Cui X , Zhang Q , Li Q , Du Y , Gao F
Ref : Eur Journal of Neurology , 26 :1296 , 2019
Abstract : BACKGROUND AND PURPOSE: Low-density-lipoprotein-receptor-associated protein 4 (LRP4) autoantibodies have recently been detected in myasthenia gravis (MG), but little is known about the clinical characteristics associated with this serological type. In this study, the clinical features of Chinese patients with anti-LRP4 antibody-positive MG were characterized. METHODS: A total of 2172 MG serum samples were collected from patients in various parts of China. An enzyme-linked immunosorbent assay was used to detect acetylcholine receptor (AChR) antibody and titin antibody, and cell-based assays were used to detect muscle-specific kinase antibody and LRP4 antibody. Clinical data for patients with MG were collected from different provinces in China. RESULTS: In total, 16 (0.8%) patients with LRP4-MG were found amongst 2172 total patients, including three patients with AChR/LRP4-MG. Additionally, 13 (2.9%) patients with LRP4-MG were found amongst 455 patients with double seronegative MG. The ratio of males to females for these 13 patients was 1:1.6, and 53.8% patients were children. A total of 91.7% of cases exhibited initial ocular involvement, and 58.3% of cases exhibited simple eye muscle involvement. Responses to acetylcholinesterase inhibitors and prednisone were observed. CONCLUSION: The expanded sample confirmed that the positive rate of LRP4 antibodies in China is lower than that in western countries. Our results highlighted the differences between LRP4-MG and other antibody groups. Children and female patients with LRP4-MG have a higher prevalence, often involving the ocular muscles and limb muscles. The clinical symptoms are mild, and satisfactory responses to treatment are often achieved.
ESTHER : Li_2019_Eur.J.Neurol_26_1296
PubMedSearch : Li_2019_Eur.J.Neurol_26_1296
PubMedID: 31050101

Title : Design, synthesis, and biological evaluation of rutacecarpine derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease - Wu_2019_Eur.J.Med.Chem_177_198
Author(s) : Wu M , Ma J , Ji L , Wang M , Han J , Li Z
Ref : Eur Journal of Medicinal Chemistry , 177 :198 , 2019
Abstract : A series of 3-amino-substituted rutacecarpine derivatives were synthesized to identify novel multitarget-directed ligands (MTDLs) for the treatment of Alzheimer's disease (AD). Biological evaluation showed that most of the synthesized compounds inhibited butyrylcholinesterase (BuChE) and exerted antioxidant effects. Among the synthesized compounds, 6n was subjected to further biological evaluation. Lineweaver-Burk plotting and molecular modeling illustrated that 6n bound simultaneously to the peripheral anionic site (PAS) and catalytic sites (CAS) of BuChE. Furthermore, 6n modulated Abeta aggregation; chelated biometals; presented good absorption, distribution, metabolism, excretion, and toxicity properties; and showed remarkable neuroprotective activity. Previous research has shown that the optimized compound 6n has considerable potential for development as an MTDL for the treatment of AD.
ESTHER : Wu_2019_Eur.J.Med.Chem_177_198
PubMedSearch : Wu_2019_Eur.J.Med.Chem_177_198
PubMedID: 31136894

Title : Proteolytic maturation of Drosophila Neuroligin 3 by tumor necrosis factor alpha-converting enzyme in the nervous system - Wu_2018_Biochim.Biophys.Acta_1862_440
Author(s) : Wu J , Tao N , Tian Y , Xing G , Lv H , Han J , Lin C , Xie W
Ref : Biochimica & Biophysica Acta , 1862 :440 , 2018
Abstract : BACKGROUND: The functions of autism-associated Neuroligins (Nlgs) are modulated by their post-translational modifications, such as proteolytic cleavage. A previous study has shown that there are different endogenous forms of DNlg3 in Drosophila, indicating it may undergo proteolytic processing. However, the molecular mechanism underlying DNlg3 proteolytic processing is unknown. Here, we report a novel proteolytic mechanism that is essential for DNlg3 maturation and function in the nervous system. METHODS: Molecular cloning, cell culture, immunohistochemistry, western blotting and genetic studies were employed to map the DNlg3 cleavage region, identify the protease and characterize the cleavage manner. Behavior analysis, immunohistochemistry and genetic manipulations were employed to study the functions of different DNlg3 forms in the nervous system and neuromuscular junction (NMJs). RESULTS: Tumor necrosis factor alpha-converting enzyme (TACE) cleaved DNlg3 exclusively at its extracellular acetylcholinesterase-like domain to generate the N-terminal fragment and the short membrane-anchored fragment (sDNlg3). DNlg3 was constitutively processed in an activity-independent manner. Interestingly, DNlg3 was cleaved intracellularly in the Golgi apparatus before it arrived at the cell surface, a unique cleavage mechanism that is distinct from 'conventional' ectodomain shedding of membrane proteins, including rodent Nlg1. Genetic studies showed that sDNlg3 was essential for maintaining proper locomotor activity in Drosophila. CONCLUSIONS: Our results revealed a unique cleavage mechanism of DNlg3 and a neuron-specific role for DNlg3 maturation which is important in locomotor activity. GENERAL SIGNIFICANCE: Our study provides a new insight into a cleavage mechanism of Nlgs maturation in the nervous system.
ESTHER : Wu_2018_Biochim.Biophys.Acta_1862_440
PubMedSearch : Wu_2018_Biochim.Biophys.Acta_1862_440
PubMedID: 29107812

Title : The genome of the marine medaka Oryzias melastigma - Kim_2018_Mol.Ecol.Resour_18_656
Author(s) : Kim HS , Lee BY , Han J , Jeong CB , Hwang DS , Lee MC , Kang HM , Kim DH , Lee D , Kim J , Choi IY , Lee JS
Ref : Mol Ecol Resour , 18 :656 , 2018
Abstract : Marine medaka (Oryzias melastigma) is considered to be a useful fish model for marine and estuarine ecotoxicology studies and has good potential for field-based population genomics because of its geographical distribution in Asian estuarine and coastal areas. In this study, we present the first whole-genome draft of O. melastigma. The genome assembly consists of 8,602 scaffolds (N50 = 23.737 Mb) and a total genome length of 779.4 Mb. A total of 23,528 genes were predicted, and 12,670 gene families shared with three teleost species (Japanese medaka, mangrove killifish and zebrafish) were identified. Genome analyses revealed that the O. melastigma genome is highly heterozygous and contains a large number of repeat sequences. This assembly represents a useful genomic resource for fish scientists.
ESTHER : Kim_2018_Mol.Ecol.Resour_18_656
PubMedSearch : Kim_2018_Mol.Ecol.Resour_18_656
PubMedID: 29451363
Gene_locus related to this paper: oryme-a0a3b3dpk3 , oryme-a0a3b3c959 , oryme-a0a3b3d3r3 , oryme-a0a3b3d4c8 , oryme-a0a3b3bnt1 , oryme-a0a3b3caa8 , oryme-a0a3b3bl32 , oryme-a0a3b3da95 , oryme-a0a3b3dps7 , oryme-a0a3b3dej7 , oryme-a0a3b3bpw5 , oryme-a0a3b3c014

Title : Neurexin-Neuroligin 1 regulates synaptic morphology and function via the WAVE regulatory complex in Drosophila neuromuscular junction - Xing_2018_Elife_7_
Author(s) : Xing G , Li M , Sun Y , Rui M , Zhuang Y , Lv H , Han J , Jia Z , Xie W
Ref : Elife , 7 : , 2018
Abstract : Neuroligins are postsynaptic adhesion molecules that are essential for postsynaptic specialization and synaptic function. But the underlying molecular mechanisms of Neuroligin functions remain unclear. We found that Drosophila Neuroligin1 (DNlg1) regulates synaptic structure and function through WAVE regulatory complex (WRC)-mediated postsynaptic actin reorganization. The disruption of DNlg1, DNlg2, or their presynaptic partner Neurexin (DNrx) led to a dramatic decrease in the amount of F-actin. Further study showed that DNlg1, but not DNlg2 or DNlg3, directly interacts with the WRC via its C-terminal interacting receptor sequence. That interaction is required to recruit WRC to the postsynaptic membrane to promote F-actin assembly. Furthermore, the interaction between DNlg1 and the WRC is essential for DNlg1 to rescue the morphological and electrophysiological defects in dnlg1 knockout mutants. Our results reveal a novel mechanism by which the DNrx-DNlg1 trans-synaptic interaction coordinates structural and functional properties at the neuromuscular junction.
ESTHER : Xing_2018_Elife_7_
PubMedSearch : Xing_2018_Elife_7_
PubMedID: 29537369

Title : Novel Method of Preparation and Activity Research on Arctigenin from Fructus Arctii - Cai_2018_Pharmacogn.Mag_14_87
Author(s) : Cai E , Han J , Yang L , Zhang W , Zhao Y , Chen Q , Guo M , He X
Ref : Pharmacogn Mag , 14 :87 , 2018
Abstract : Background: Arctigenin has many pharmacological activities with clinical significance and is derived from Arctium lappa L. However, the present extraction method is inefficient and does not have meaningful industrial production. Objective: A new method to directly prepare arctigenin was established by combining enzyme-assisted extraction and central composite design. Arctigenin's further pharmacological activity was also surveyed in vitro. Materials and Methods: beta-D-Glucosidase, a food-grade enzyme, was added directly to the fruits of A. lappa L. to hydrolyze the arctiin to arctigenin, and the obtained samples were subsequently subjected to ethanol (30%, v/v) extraction. The pharmacological activity of the extraction and arctigenin was determined by inhibiting acetylcholinesterase (AChE) and scavenging nitrite. Results: The factors investigated include the enzyme concentration (0.5%-2.5%), ultrasound time (10 min(-3) 0 min), and extraction temperature (30 degrees C-50 degrees C). From the analysis of the results by Design-Expert (V8.0.6), the optimal extraction conditions were obtained: enzyme concentration (1.4%), ultrasound time (25 min), and extraction temperature (45 degrees C). The highest yield of arctigenin, obtained under the optimal conditions was 6.39%, representing an increase of 28.15% compared to the reference extraction without enzyme processing. The IC50 values of the extraction and arctigenin, respectively, for inhibiting AChE were 0.572 mg/ml and 0.462 mg/ml, and those for nitrite-scavenging were 34.571 mg/ml and 17.49 mg/ml. Conclusions: The results demonstrate that using an enzyme directly in the production is an effective means for extracting arctigenin from Fructus arctii. The extraction has the activities of inhibiting AChE and scavenging nitrite, probably because there has arctigenin in it. It is implied that the extraction and arctigenin could contribute to human health in clinical applications. SUMMARY: The new method of adding enzyme directly to the preparation of arctigenin was carried out instead of preparing arctigenin by two-step methodThree factors affecting the efficiency of preparation were analyzed and discussed include the enzyme concentration, ultrasound time, and extraction temperature by central composite designThis new method of preparing arctigenin improved the yield significantly than other methodsArctigenin has remarkable pharmacological activities of inhibiting acetylcholinesterase and scavenging nitrite. Abbreviations used: AChE: Acetylcholinesterase, CCD: Central composite design, TCM: Traditional Chinese medicines, AD.
ESTHER : Cai_2018_Pharmacogn.Mag_14_87
PubMedSearch : Cai_2018_Pharmacogn.Mag_14_87
PubMedID: 29576707

Title : Theoretical Study on Zearalenol Compounds Binding with Wild Type Zearalenone Hydrolase and V153H Mutant - Liu_2018_Int.J.Mol.Sci_19_
Author(s) : Liu Y , Wan Y , Zhu J , Yu Z , Tian X , Han J , Zhang Z , Han W
Ref : Int J Mol Sci , 19 : , 2018
Abstract : Zearalenone hydrolase (ZHD) is the only reported alpha/beta-hydrolase that can detoxify zearalenone (ZEN). ZHD has demonstrated its potential as a treatment for ZEN contamination that will not result in damage to cereal crops. Recent researches have shown that the V153H mutant ZHD increased the specific activity against alpha-ZOL, but decreased its specific activity to beta-ZOL. To understand whyV153H mutation showed catalytic specificity for alpha-ZOL, four molecular dynamics simulations combining with protein network analysis for wild type ZHD alpha-ZOL, ZHD beta-ZOL, V153H alpha-ZOL, and V153H beta-ZOL complexes were performed using Gromacs software. Our theoretical results indicated that the V153H mutant could cause a conformational switch at the cap domain (residues Gly161(-)Thr190) to affect the relative position catalytic residue (H242). Protein network analysis illustrated that the V153H mutation enhanced the communication with the whole protein and residues with high betweenness in the four complexes, which were primarily assembled in the cap domain and residues Met241 to Tyr245 regions. In addition, the existence of alpha-ZOL binding to V153H mutation enlarged the distance from the OAE atom in alpha-ZOL to the NE2 atom in His242, which prompted the side chain of H242 to the position with catalytic activity, thereby increasing the activity of V153H on the alpha-ZOL. Furthermore, alpha-ZOL could easily form a right attack angle and attack distance in the ZHD and alpha-ZOL complex to guarantee catalytic reaction. The alanine scanning results indicated that modifications of the residues in the cap domain produced significant changes in the binding affinity for alpha-ZOL and beta-ZOL. Our results may provide useful theoretical evidence for the mechanism underlying the catalytic specificity of ZHD.
ESTHER : Liu_2018_Int.J.Mol.Sci_19_
PubMedSearch : Liu_2018_Int.J.Mol.Sci_19_
PubMedID: 30231501
Gene_locus related to this paper: biooc-ZHD101

Title : Protection of Grain Products from Sitophilus oryzae (L.) Contamination by Anti-Insect Pest Repellent Sachet Containing Allyl Mercaptan Microcapsule - Chang_2017_J.Food.Sci_82_2634
Author(s) : Chang Y , Lee SH , Na JH , Chang PS , Han J
Ref : J Food Sci , 82 :2634 , 2017
Abstract : The purpose of this study was to develop an anti-insect pest repellent sachet to prevent Sitophilus oryzae (L.) (Coleoptera: Curculionidae) contamination in grain packaging. The anti-insect pest activities of essential oils (EOs) from garlic (Allium Sativum), ginger (Zingiber Officinalis), black pepper (Piper nigrum), onion (Allium cepa), and fennel (Foeniculum vulgare) as well as major compounds (allyl disulfide, AD; allyl mercaptan, AM) isolated from of garlic and onion (AD and AM) were measured against S. oryzae. The results revealed that garlic EO, onion EO, AD, and AM showed strong fumigant insecticidal activities. Among these, AM showed the highest acetylcholinesterase (AChE) inhibition rate, indicating that the fumigation insecticidal efficacy of AM is related with its AChE inhibition ability. Subsequently, the microcapsules were produced with a high efficiency (80.02%) by using AM as a core material and rice flour as a wall material. Finally, sachet composed of rice flour microcapsule containing 2% AM (RAM) was produced. Repellent assay was performed to measure anti-insect pest ability of the RAM sachet, showed remarkable repelling effect within 48 h both in the presence or absence of attractant. In a release profile of RAM sachet, it was expected to last over 20 mo during the distribution period of brown rice. Moreover, RAM sachet showed no undesirable changes to the sensory properties of the rice both before and after cooking. Taken together, these results suggest that the newly developed RAM sachet could be used as a packaging material to protect grain products from S. oryzae contamination. PRACTICAL APPLICATION: The rice weevil, Sitophilus oryzae (L.) (Coleoptera: Curculionidae), causes damages to stored products and its contamination in grain products has become a major problem in cereal market. To preserve brown rice, an anti-insect pest repellent sachet containing 2% allyl mercaptan was newly developed and it showed remarkable repellent abilities against S. oryzae. It could be used as an active food packaging system to protect grain products from insect pest contamination.
ESTHER : Chang_2017_J.Food.Sci_82_2634
PubMedSearch : Chang_2017_J.Food.Sci_82_2634
PubMedID: 29030875

Title : Proteolytic cleavage is required for functional neuroligin 2 maturation and trafficking in Drosophila - Tu_2017_J.Mol.Cell.Biol_9_231
Author(s) : Tu R , Qian J , Rui M , Tao N , Sun M , Zhuang Y , Lv H , Han J , Li M , Xie W
Ref : J Molecular & Cellular Biology , 9 :231 , 2017
Abstract : Neuroligins (Nlgs) are transmembrane cell adhesion molecules playing essential roles in synapse development and function. Genetic mutations in neuroligin genes have been linked with some neurodevelopmental disorders such as autism. These mutated Nlgs are mostly retained in the endoplasmic reticulum (ER). However, the mechanisms underlying normal Nlg maturation and trafficking have remained largely unknown. Here, we found that Drosophila neuroligin 2 (DNlg2) undergoes proteolytic cleavage in the ER in a variety of Drosophila tissues throughout developmental stages. A region encompassing Y642-T698 is required for this process. The immature non-cleavable DNlg2 is retained in the ER and non-functional. The C-terminal fragment of DNlg2 instead of the full-length or non-cleavable DNlg2 is able to rescue neuromuscular junction defects and GluRIIB reduction induced by dnlg2 deletion. Intriguingly, the autism-associated R598C mutation in DNlg2 leads to similar marked defects in DNlg2 proteolytic process and ER export, revealing a potential role of the improper Nlg cleavage in autism pathogenesis. Collectively, our findings uncover a specific mechanism that controls DNlg2 maturation and trafficking via proteolytic cleavage in the ER, suggesting that the perturbed proteolytic cleavage of Nlgs likely contributes to autism disorder.
ESTHER : Tu_2017_J.Mol.Cell.Biol_9_231
PubMedSearch : Tu_2017_J.Mol.Cell.Biol_9_231
PubMedID: 28498949

Title : Neurexin Restricts Axonal Branching in Columns by Promoting Ephrin Clustering - Liu_2017_Dev.Cell_41_94
Author(s) : Liu L , Tian Y , Zhang XY , Zhang X , Li T , Xie W , Han J
Ref : Dev Cell , 41 :94 , 2017
Abstract : Columnar restriction of neurites is critical for forming nonoverlapping receptive fields and preserving spatial sensory information from the periphery in both vertebrate and invertebrate nervous systems, but the underlying molecular mechanisms remain largely unknown. Here, we demonstrate that Drosophila homolog of alpha-neurexin (DNrx) plays an essential role in columnar restriction during L4 axon branching. Depletion of DNrx from L4 neurons resulted in misprojection of L4 axonal branches into neighboring columns due to impaired ephrin clustering. The proper ephrin clustering requires its interaction with the intracellular region of DNrx. Furthermore, we find that Drosophila neuroligin 4 (DNlg4) in Tm2 neurons binds to DNrx and initiates DNrx clustering in L4 neurons, which subsequently induces ephrin clustering. Our study demonstrates that DNrx promotes ephrin clustering and reveals that ephrin/Eph signaling from adjacent L4 neurons restricts axonal branches of L4 neurons in columns.
ESTHER : Liu_2017_Dev.Cell_41_94
PubMedSearch : Liu_2017_Dev.Cell_41_94
PubMedID: 28366281

Title : Hydrogen sulfide may attenuate methylmercury-induced neurotoxicity via mitochondrial preservation - Han_2016_Chem.Biol.Interact_263_66
Author(s) : Han J , Yang X , Chen X , Li Z , Fang M , Bai B , Tan D
Ref : Chemico-Biological Interactions , 263 :66 , 2016
Abstract : Hydrogen sulfide (H2S) is a protective molecule and a novel gaseous mediator. Here we explored whether H2S donor (NaHS) could attenuate methylmercury (MeHg)-induced neurotoxicity in rats. The adult rats were randomly divided into four groups, i.e., control, NaHS, MeHg, and NaHS + MeHg groups. Rats of the NaHS + MeHg group were intraperitoneally (i.p) injected with 5.6 mg/kg/d of NaHS together with 5 mug/kg/d of MeHg. Rats of the MeHg group and NaHS group were injected with 5 mug/kg/d of MeHg and 5.6 mg/kg/d of NaHS, respectively. All treatments were continued for 20 d, and the cerebral cortex of the rats was evaluated. The results showed that NaHS significantly reduced MeHg-induced oxidative stress, as indicated by reduced lipid peroxide content, and increased glutathione levels and glutathione peroxidase and thioredoxin reductase activities. NaHS attenuated MeHg-induced mitochondrial damage, as indicated by increased mitochondrial activity, reduced mitochondrial swelling, and the release of cytochrome C and apoptosis-inducing factors. NaHS also decreased the number of apoptotic cells compared to that observed in MeHg only-treated rats, as indicated in a TUNEL assay. Finally, NaHS increased DNA and RNA content, and the activities of acetylcholinesterase and Na+/K+-ATPase. These indices were all lower in the MeHg group than in the control group, and NaHS alone did not observably influence any of these indices compared to the control. Our results demonstrate that H2S may protect against MeHg-induced neurotoxicity, and the mechanisms appear to involve the inhibition of oxidative stress and the protection of mitochondria.
ESTHER : Han_2016_Chem.Biol.Interact_263_66
PubMedSearch : Han_2016_Chem.Biol.Interact_263_66
PubMedID: 28027877

Title : CHRNA5 risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis--a meta-analysis - Chen_2015_J.Natl.Cancer.Inst_107_
Author(s) : Chen LS , Hung RJ , Baker T , Horton A , Culverhouse R , Saccone N , Cheng I , Deng B , Han Y , Hansen HM , Horsman J , Kim C , Lutz S , Rosenberger A , Aben KK , Andrew AS , Breslau N , Chang SC , Dieffenbach AK , Dienemann H , Frederiksen B , Han J , Hatsukami DK , Johnson EO , Pande M , Wrensch MR , McLaughlin J , Skaug V , van der Heijden HF , Wampfler J , Wenzlaff A , Woll P , Zienolddiny S , Bickeboller H , Brenner H , Duell EJ , Haugen A , Heinrich J , Hokanson JE , Hunter DJ , Kiemeney LA , Lazarus P , Le Marchand L , Liu G , Mayordomo J , Risch A , Schwartz AG , Teare D , Wu X , Wiencke JK , Yang P , Zhang ZF , Spitz MR , Kraft P , Amos CI , Bierut LJ
Ref : J Natl Cancer Inst , 107 : , 2015
Abstract : BACKGROUND: Recent meta-analyses show strong evidence of associations among genetic variants in CHRNA5 on chromosome 15q25, smoking quantity, and lung cancer. This meta-analysis tests whether the CHRNA5 variant rs16969968 predicts age of smoking cessation and age of lung cancer diagnosis.
METHODS: Meta-analyses examined associations between rs16969968, age of quitting smoking, and age of lung cancer diagnosis in 24 studies of European ancestry (n = 29 072). In each dataset, we used Cox regression models to evaluate the association between rs16969968 and the two primary phenotypes (age of smoking cessation among ever smokers and age of lung cancer diagnosis among lung cancer case patients) and the secondary phenotype of smoking duration. Heterogeneity across studies was assessed with the Cochran Q test. All statistical tests were two-sided.
RESULTS: The rs16969968 allele (A) was associated with a lower likelihood of smoking cessation (hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.91 to 0.98, P = .0042), and the AA genotype was associated with a four-year delay in median age of quitting compared with the GG genotype. Among smokers with lung cancer diagnoses, the rs16969968 genotype (AA) was associated with a four-year earlier median age of diagnosis compared with the low-risk genotype (GG) (HR = 1.08, 95% CI = 1.04 to 1.12, P = 1.1*10(-5)). CONCLUSION: These data support the clinical significance of the CHRNA5 variant rs16969968. It predicts delayed smoking cessation and an earlier age of lung cancer diagnosis in this meta-analysis. Given the existing evidence that this CHRNA5 variant predicts favorable response to cessation pharmacotherapy, these findings underscore the potential clinical and public health importance of rs16969968 in CHRNA5 in relation to smoking cessation success and lung cancer risk.
ESTHER : Chen_2015_J.Natl.Cancer.Inst_107_
PubMedSearch : Chen_2015_J.Natl.Cancer.Inst_107_
PubMedID: 25873736

Title : Transcriptome Analysis of the Carmine Spider Mite, Tetranychus cinnabarinus (Boisduval, 1867) (Acari: Tetranychidae), and Its Response to beta-Sitosterol - Bu_2015_Biomed.Res.Int_2015_794718
Author(s) : Bu C , Li J , Wang XQ , Shi G , Peng B , Han J , Gao P , Wang Y
Ref : Biomed Res Int , 2015 :794718 , 2015
Abstract : Tetranychus cinnabarinus (Acari: Tetranychidae) is a worldwide polyphagous agricultural pest that has the title of resistance champion among arthropods. We reported previously the identification of the acaricidal compound beta-sitosterol from Mentha piperita and Inula japonica. However, the acaricidal mechanism of beta-sitosterol is unclear. Due to the limited genetic research carried out, we de novo assembled the transcriptome of T. cinnabarinus using Illumina sequencing and conducted a differential expression analysis of control and beta-sitosterol-treated mites. In total, we obtained >5.4 G high-quality bases for each sample with unprecedented sequencing depth and assembled them into 22,941 unigenes. We identified 617 xenobiotic metabolism-related genes involved in detoxification, binding, and transporting of xenobiotics. A highly expanded xenobiotic metabolic system was found in mites. T. cinnabarinus detoxification genes-including carboxyl/cholinesterase and ABC transporter class C-were upregulated after beta-sitosterol treatment. Defense-related proteins, such as Toll-like receptor, legumain, and serine proteases, were also activated. Furthermore, other important genes-such as the chloride channel protein, cytochrome b, carboxypeptidase, peritrophic membrane chitin binding protein, and calphostin-may also play important roles in mites' response to beta-sitosterol. Our results demonstrate that high-throughput-omics tool facilitates identification of xenobiotic metabolism-related genes and illustration of the acaricidal mechanisms of beta-sitosterol.
ESTHER : Bu_2015_Biomed.Res.Int_2015_794718
PubMedSearch : Bu_2015_Biomed.Res.Int_2015_794718
PubMedID: 26078964

Title : Conversion of inhibition biosensing to substrate-like biosensing for quinalphos selective detection - Yang_2015_Anal.Chem_87_5270
Author(s) : Yang L , Han J , Liu W , Li J , Jiang L
Ref : Analytical Chemistry , 87 :5270 , 2015
Abstract : Since all of the organophosphorus pesticides (OPP) inhibit the cholinesterases with a common mechanism, it is still challenging to detect OPP selectively with inhibition-based biosensors. This study focuses on the conversion of a typical inhibition biosensing to a selective substrate-like biosensing. The interaction of quinalphos with plant-esterase involves not only a decrease in enzyme activity but also a heterolytic bond cleavage of quinalphos. The leaving group eliminated from quinalphos is an ideal biomarker due to its specificity in most OPP. Thus, using 2-hydroxyquinoxaline (HQO), the leaving group of quinalphos, as the biomarker and meso-tetra (4-sulfonatophenyl) porphine (TPPS4) as an optical probe, quinalphos can be selectively detected. The molecular recognition between TPPS4 and HQO leads to a considerable sensitivity of the detection. The spectral responses of TPPS4 show a linear dependence on quinalphos concentration in the presence of plant-esterase within the 0.01-1 mg kg(-1) range. The detection limit is 0.01 mg kg(-1), well below the maximum residue limits (MRLs) defined by European Union (0.05 mg kg(-1)) and China (0.2 mg kg(-1)).
ESTHER : Yang_2015_Anal.Chem_87_5270
PubMedSearch : Yang_2015_Anal.Chem_87_5270
PubMedID: 25921798

Title : Acetylcholinesterase Inhibitory Activity of Pigment Echinochrome A from Sea Urchin Scaphechinus mirabilis - Lee_2014_Mar.Drugs_12_3560
Author(s) : Lee SR , Pronto JR , Sarankhuu BE , Ko KS , Rhee BD , Kim N , Mishchenko NP , Fedoreyev SA , Stonik VA , Han J
Ref : Mar Drugs , 12 :3560 , 2014
Abstract : Echinochrome A (EchA) is a dark-red pigment of the polyhydroxynaphthoquinone class isolated from sea urchin Scaphechinus mirabilis. Acetylcholinesterase (AChE) inhibitors are used in the treatment of various neuromuscular disorders, and are considered as strong therapeutic agents for the treatment of Alzheimer's disease (AD). Although EchA is clinically used to treat ophthalmic diseases and limit infarct formation during ischemia/ reperfusion injury, anti-AChE effect of EchA is still unknown. In this study, we investigated the anti-AChE effect of EchA in vitro. EchA and its exhausted form which lost anti-oxidant capacity did not show any significant cytotoxicy on the H9c2 and A7r5 cells. EchA inhibited AChE with an irreversible and uncompetitive mode. In addition, EchA showed reactive oxygen species scavenging activity, particularly with nitric oxide. These findings indicate new therapeutic potential for EchA in treating reduced acetylcholine-related diseases including AD and provide an insight into developing new AChE inhibitors.
ESTHER : Lee_2014_Mar.Drugs_12_3560
PubMedSearch : Lee_2014_Mar.Drugs_12_3560
PubMedID: 24918454

Title : Drosophila neuroligin3 regulates neuromuscular junction development and synaptic differentiation - Xing_2014_J.Biol.Chem_289_31867
Author(s) : Xing G , Gan G , Chen D , Sun M , Yi J , Lv H , Han J , Xie W
Ref : Journal of Biological Chemistry , 289 :31867 , 2014
Abstract : Neuroligins (Nlgs) are a family of cell adhesion molecules thought to be important for synapse maturation and function. Mammalian studies have shown that different Nlgs have different roles in synaptic maturation and function. In Drosophila melanogaster, the roles of Drosophila neuroligin1 (DNlg1), neuroligin2, and neuroligin4 have been examined. However, the roles of neuroligin3 (dnlg3) in synaptic development and function have not been determined. In this study, we used the Drosophila neuromuscular junctions (NMJs) as a model system to investigate the in vivo role of dnlg3. We showed that DNlg3 was expressed in both the CNS and NMJs where it was largely restricted to the postsynaptic site. We generated dnlg3 mutants and showed that these mutants exhibited an increased bouton number and reduced bouton size compared with the wild-type (WT) controls. Consistent with alterations in bouton properties, pre- and postsynaptic differentiations were affected in dnlg3 mutants. This included abnormal synaptic vesicle endocytosis, increased postsynaptic density length, and reduced GluRIIA recruitment. In addition to impaired synaptic development and differentiation, we found that synaptic transmission was reduced in dnlg3 mutants. Altogether, our data showed that DNlg3 was required for NMJ development, synaptic differentiation, and function.
ESTHER : Xing_2014_J.Biol.Chem_289_31867
PubMedSearch : Xing_2014_J.Biol.Chem_289_31867
PubMedID: 25228693
Gene_locus related to this paper: drome-nlg3

Title : Genome sequencing of four Aureobasidium pullulans varieties: biotechnological potential, stress tolerance, and description of new species - Gostincar_2014_BMC.Genomics_15_549
Author(s) : Gostincar C , Ohm RA , Kogej T , Sonjak S , Turk M , Zajc J , Zalar P , Grube M , Sun H , Han J , Sharma A , Chiniquy J , Ngan CY , Lipzen A , Barry K , Grigoriev IV , Gunde-Cimerman N
Ref : BMC Genomics , 15 :549 , 2014
Abstract : BACKGROUND: Aureobasidium pullulans is a black-yeast-like fungus used for production of the polysaccharide pullulan and the antimycotic aureobasidin A, and as a biocontrol agent in agriculture. It can cause opportunistic human infections, and it inhabits various extreme environments. To promote the understanding of these traits, we performed de-novo genome sequencing of the four varieties of A. pullulans.
RESULTS: The 25.43-29.62 Mb genomes of these four varieties of A. pullulans encode between 10266 and 11866 predicted proteins. Their genomes encode most of the enzyme families involved in degradation of plant material and many sugar transporters, and they have genes possibly associated with degradation of plastic and aromatic compounds. Proteins believed to be involved in the synthesis of pullulan and siderophores, but not of aureobasidin A, are predicted. Putative stress-tolerance genes include several aquaporins and aquaglyceroporins, large numbers of alkali-metal cation transporters, genes for the synthesis of compatible solutes and melanin, all of the components of the high-osmolarity glycerol pathway, and bacteriorhodopsin-like proteins. All of these genomes contain a homothallic mating-type locus.
CONCLUSIONS: The differences between these four varieties of A. pullulans are large enough to justify their redefinition as separate species: A. pullulans, A. melanogenum, A. subglaciale and A. namibiae. The redundancy observed in several gene families can be linked to the nutritional versatility of these species and their particular stress tolerance. The availability of the genome sequences of the four Aureobasidium species should improve their biotechnological exploitation and promote our understanding of their stress-tolerance mechanisms, diverse lifestyles, and pathogenic potential.
ESTHER : Gostincar_2014_BMC.Genomics_15_549
PubMedSearch : Gostincar_2014_BMC.Genomics_15_549
PubMedID: 24984952
Gene_locus related to this paper: aurpu-a0a1a7mdx5 , 9pezi-a0a074w0m0 , 9pezi-a0a074wgq7 , aurpu-a0a074xfg8 , 9pezi-a0a074y586 , 9pezi-a0a074yqf6 , 9pezi-a0a074w5k8 , aurpu-a0a074x6a3 , 9pezi-a0a074z3s4 , 9pezi-a0a074x4q0 , 9pezi-a0a074w2e2 , 9pezi-a0a074x294 , aurpu-a0a074y1y2 , aurpu-a0a074x9w9 , 9pezi-a0a074ydw7 , 9pezi-a0a074w1z9 , 9pezi-a0a074wvx0 , 9pezi-a0a074vkc4 , 9pezi-a0a074y2z2 , 9pezi-a0a074vlb9 , aurpu-a0a074x490 , 9pezi-a0a074ydn0 , 9pezi-a0a074wng0 , 9pezi-a0a074yhi1 , 9pezi-a0a074yp94 , 9pezi-a0a074wbe1 , 9pezi-a0a074wm90 , 9pezi-a0a074ww95 , aurpu-a0a074xg41 , aurpu-a0a074xtu4 , 9pezi-a0a074y8g8 , aurpu-a0a074ysb8 , 9pezi-a0a074zem7 , 9pezi-a0a074yvw8 , 9pezi-a0a074w278 , aurpu-a0a074xxz9 , 9pezi-a0a074y9f0 , aurpu-a0a074xzv0 , 9pezi-a0a074wce5 , 9pezi-a0a074wmz5 , 9pezi-a0a074vr83 , 9pezi-a0a074w4l5 , 9pezi-a0a074wwv4 , 9pezi-a0a074w5f4 , aurpu-a0a074xir3 , aurpu-a0a074xnm6 , 9pezi-a0a074zhr2 , 9pezi-a0a074vzq8 , 9pezi-a0a074web5 , aurpu-a0a074xz32 , 9pezi-a0a074ybl0 , aurpu-a0a074xl81 , 9pezi-a0a074vaq7 , 9pezi-a0a074wuj9 , aurpu-a0a074xyu0 , 9pezi-a0a074vfi8 , 9pezi-a0a074wih8 , aurpu-a0a074xj03 , 9pezi-a0a074vze0 , 9pezi-a0a074w5u8 , 9pezi-a0a074wui5 , 9pezi-a0a074xhu0 , aurpu-a0a074xyg1 , 9pezi-a0a074yct6 , 9pezi-a0a074zd60 , 9pezi-a0a074w686 , aurpu-a0a074xr93 , 9pezi-a0a074y1r2 , 9pezi-a0a074z801 , 9pezi-a0a074y6a8 , 9pezi-a0a074vg30 , aurpu-a0a074wzm8 , 9pezi-a0a074y7g9 , 9pezi-a0a074vwd1 , 9pezi-a0a074whl7 , aurpu-a0a074x6c3 , 9pezi-a0a074yak1 , aurpu-a0a074x5y4 , 9pezi-a0a074yaq1 , aurpu-a0a074xm87 , 9pezi-a0a074wgg7 , 9pezi-a0a074vky7 , aurpu-a0a074xpr5 , 9pezi-a0a074zrg4 , 9pezi-a0a074w1f9 , aurpu-a0a074xft8 , 9pezi-a0a074y5i5 , aurpu-a0a074xla0 , 9pezi-a0a074w5n7 , 9pezi-a0a074wey0 , aurpu-a0a074y3b0 , 9pezi-a0a074vrn9 , 9pezi-a0a074zgu9 , aurpu-a0a074xlv7 , 9pezi-a0a074wgb6 , 9pezi-a0a074wgj7 , 9pezi-a0a074vrg4 , 9pezi-a0a074ya42 , 9pezi-a0a074xnr8 , aurpu-a0a074x443 , 9pezi-a0a074yex2 , 9pezi-a0a074xu89 , aurpu-a0a074xxq7 , 9pezi-a0a074vih4 , aurse-a0a074ydf4 , aurse-a0a074yt75 , aurpu-a0a074y000

Title : Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer's disease - Hager_2014_Neuropsychiatr.Dis.Treat_10_391
Author(s) : Hager K , Baseman AS , Nye JS , Brashear HR , Han J , Sano M , Davis B , Richards HM
Ref : Neuropsychiatr Dis Treat , 10 :391 , 2014
Abstract : BACKGROUND: Currently available treatments for Alzheimer's disease (AD) can produce mild improvements in cognitive function, behavior, and activities of daily living in patients, but their influence on long-term survival is not well established. This study was designed to assess patient survival and drug efficacy following a 2-year galantamine treatment in patients with mild to moderately severe AD.
METHODS: In this multicenter, double-blind study, patients were randomized 1:1 to receive galantamine or placebo. One primary end point was safety; mortality was assessed. An independent Data Safety Monitoring Board monitored mortality for the total deaths reaching prespecified numbers, using a time-to-event method and a Cox-regression model. The primary efficacy end point was cognitive change from baseline to month 24, as measured by the Mini-Mental State Examination (MMSE) score, analyzed using intent-to-treat analysis with the 'last observation carried forward' approach, in an analysis of covariance model.
RESULTS: In all, 1,024 galantamine- and 1,021 placebo-treated patients received study drug, with mean age ~73 years, and mean (standard deviation [SD]) baseline MMSE score of 19 (4.08). A total of 32% of patients (661/2,045) completed the study, 27% (554/2,045) withdrew, and 41% (830/2,045) did not complete the study and were discontinued due to a Data Safety Monitoring Board-recommended early study termination. The mortality rate was significantly lower in the galantamine group versus placebo (hazard ratio [HR] =0.58; 95% confidence interval [CI]: 0.37; 0.89) (P=0.011). Cognitive impairment, based on the mean (SD) change in MMSE scores from baseline to month 24, significantly worsened in the placebo (-2.14 [4.34]) compared with the galantamine group (-1.41 [4.05]) (P<0.001). Functional impairment, based on mean (SD) change in the Disability Assessment in Dementia score (secondary end point), at month 24 significantly worsened in the placebo (-10.81 [18.27]) versus the galantamine group (-8.16 [17.25]) (P=0.002). Incidences of treatment-emergent adverse events were 54.0% for the galantamine and 48.6% for the placebo group. CONCLUSION: Long-term treatment with galantamine significantly reduced mortality and the decline in cognition and daily living activities, in mild to moderate AD patients. IDENTIFICATION: This study is registered at ClinicalTrials.gov (NCT00679627).
ESTHER : Hager_2014_Neuropsychiatr.Dis.Treat_10_391
PubMedSearch : Hager_2014_Neuropsychiatr.Dis.Treat_10_391
PubMedID: 24591834

Title : Whole Genome Sequencing of Thermus oshimai JL-2 and Thermus thermophilus JL-18, Incomplete Denitrifiers from the United States Great Basin - Murugapiran_2013_Genome.Announc_1_e00106
Author(s) : Murugapiran SK , Huntemann M , Wei CL , Han J , Detter JC , Han CS , Erkkila TH , Teshima H , Chen A , Kyrpides N , Mavrommatis K , Markowitz V , Szeto E , Ivanova N , Pagani I , Lam J , McDonald AI , Dodsworth JA , Pati A , Goodwin L , Peters L , Pitluck S , Woyke T , Hedlund BP
Ref : Genome Announc , 1 : , 2013
Abstract : The strains Thermus oshimai JL-2 and Thermus thermophilus JL-18 each have a circular chromosome, 2.07 Mb and 1.9 Mb in size, respectively, and each has two plasmids ranging from 0.27 Mb to 57.2 kb. The megaplasmid of each strain contains a gene cluster for the reduction of nitrate to nitrous oxide, consistent with their incomplete denitrification phenotypes.
ESTHER : Murugapiran_2013_Genome.Announc_1_e00106
PubMedSearch : Murugapiran_2013_Genome.Announc_1_e00106
PubMedID: 23405355
Gene_locus related to this paper: thet2-q72hz1 , thet2-q72j75 , theth-TTC1787 , theos-k7r7w9 , theos-k7r725 , theth-h9zpz9 , theos-k7riw9 , theos-k7qw42 , theos-k7r3i4

Title : Genome of the long-living sacred lotus (Nelumbo nucifera Gaertn.) - Ming_2013_Genome.Biol_14_R41
Author(s) : Ming R , VanBuren R , Liu Y , Yang M , Han Y , Li LT , Zhang Q , Kim MJ , Schatz MC , Campbell M , Li J , Bowers JE , Tang H , Lyons E , Ferguson AA , Narzisi G , Nelson DR , Blaby-Haas CE , Gschwend AR , Jiao Y , Der JP , Zeng F , Han J , Min XJ , Hudson KA , Singh R , Grennan AK , Karpowicz SJ , Watling JR , Ito K , Robinson SA , Hudson ME , Yu Q , Mockler TC , Carroll A , Zheng Y , Sunkar R , Jia R , Chen N , Arro J , Wai CM , Wafula E , Spence A , Xu L , Zhang J , Peery R , Haus MJ , Xiong W , Walsh JA , Wu J , Wang ML , Zhu YJ , Paull RE , Britt AB , Du C , Downie SR , Schuler MA , Michael TP , Long SP , Ort DR , Schopf JW , Gang DR , Jiang N , Yandell M , dePamphilis CW , Merchant SS , Paterson AH , Buchanan BB , Li S , Shen-Miller J
Ref : Genome Biol , 14 :R41 , 2013
Abstract : BACKGROUND: Sacred lotus is a basal eudicot with agricultural, medicinal, cultural and religious importance. It was domesticated in Asia about 7,000 years ago, and cultivated for its rhizomes and seeds as a food crop. It is particularly noted for its 1,300-year seed longevity and exceptional water repellency, known as the lotus effect. The latter property is due to the nanoscopic closely packed protuberances of its self-cleaning leaf surface, which have been adapted for the manufacture of a self-cleaning industrial paint, Lotusan. RESULTS: The genome of the China Antique variety of the sacred lotus was sequenced with Illumina and 454 technologies, at respective depths of 101x and 5.2x. The final assembly has a contig N50 of 38.8 kbp and a scaffold N50 of 3.4 Mbp, and covers 86.5% of the estimated 929 Mbp total genome size. The genome notably lacks the paleo-triplication observed in other eudicots, but reveals a lineage-specific duplication. The genome has evidence of slow evolution, with a 30% slower nucleotide mutation rate than observed in grape. Comparisons of the available sequenced genomes suggest a minimum gene set for vascular plants of 4,223 genes. Strikingly, the sacred lotus has 16 COG2132 multi-copper oxidase family proteins with root-specific expression; these are involved in root meristem phosphate starvation, reflecting adaptation to limited nutrient availability in an aquatic environment. CONCLUSIONS: The slow nucleotide substitution rate makes the sacred lotus a better resource than the current standard, grape, for reconstructing the pan-eudicot genome, and should therefore accelerate comparative analysis between eudicots and monocots.
ESTHER : Ming_2013_Genome.Biol_14_R41
PubMedSearch : Ming_2013_Genome.Biol_14_R41
PubMedID: 23663246
Gene_locus related to this paper: nelnu-a0a1u8aj84 , nelnu-a0a1u8bpe4 , nelnu-a0a1u7z9m9 , nelnu-a0a1u7ywy5 , nelnu-a0a1u8aik2 , nelnu-a0a1u7zmb5 , nelnu-a0a1u8a7m7 , nelnu-a0a1u8b0n9 , nelnu-a0a1u8b461 , nelnu-a0a1u7zzj3 , nelnu-a0a1u8ave7 , nelnu-a0a1u7yn26

Title : Draft genome sequence of Frankia sp. strain QA3, a nitrogen-fixing actinobacterium isolated from the root nodule of Alnus nitida - Sen_2013_Genome.Announc_1_e0010313
Author(s) : Sen A , Beauchemin N , Bruce D , Chain P , Chen A , Walston Davenport K , Deshpande S , Detter C , Furnholm T , Ghodbhane-Gtari F , Goodwin L , Gtari M , Han C , Han J , Huntemann M , Ivanova N , Kyrpides N , Land ML , Markowitz V , Mavrommatis K , Nolan M , Nouioui I , Pagani I , Pati A , Pitluck S , Santos CL , Sur S , Szeto E , Tavares F , Teshima H , Thakur S , Wall L , Woyke T , Wishart J , Tisa LS
Ref : Genome Announc , 1 :e0010313 , 2013
Abstract : Members of the actinomycete genus Frankia form a nitrogen-fixing symbiosis with 8 different families of actinorhizal plants. We report a high-quality draft genome sequence for Frankia sp. strain QA3, a nitrogen-fixing actinobacterium isolated from root nodules of Alnus nitida.
ESTHER : Sen_2013_Genome.Announc_1_e0010313
PubMedSearch : Sen_2013_Genome.Announc_1_e0010313
PubMedID: 23516220
Gene_locus related to this paper: 9acto-i8qvq8 , 9actn-i8qfl2

Title : Complete Genome of Enterobacteriaceae Bacterium Strain FGI 57, a Strain Associated with Leaf-Cutter Ant Fungus Gardens - Aylward_2013_Genome.Announc_1_E00238
Author(s) : Aylward FO , Tremmel DM , Bruce DC , Chain P , Chen A , Walston Davenport K , Detter C , Han CS , Han J , Huntemann M , Ivanova NN , Kyrpides NC , Markowitz V , Mavrommatis K , Nolan M , Pagani I , Pati A , Pitluck S , Deshpande S , Goodwin L , Woyke T , Currie CR
Ref : Genome Announc , 1 : , 2013
Abstract : The Enterobacteriaceae bacterium strain FGI 57 was isolated from a fungus garden of the leaf-cutter ant Atta colombica. Analysis of its single 4.76-Mbp chromosome will shed light on community dynamics and plant biomass degradation in ant fungus gardens.
ESTHER : Aylward_2013_Genome.Announc_1_E00238
PubMedSearch : Aylward_2013_Genome.Announc_1_E00238
PubMedID: 23469353
Gene_locus related to this paper: entbf-l0m2y4 , ecolx-e0qx45 , entbf-l0lyj5 , entbf-l0m5k3 , entbf-l0m5q3

Title : Comparative genome structure, secondary metabolite, and effector coding capacity across Cochliobolus pathogens - Condon_2013_PLoS.Genet_9_e1003233
Author(s) : Condon BJ , Leng Y , Wu D , Bushley KE , Ohm RA , Otillar R , Martin J , Schackwitz W , Grimwood J , MohdZainudin N , Xue C , Wang R , Manning VA , Dhillon B , Tu ZJ , Steffenson BJ , Salamov A , Sun H , Lowry S , LaButti K , Han J , Copeland A , Lindquist E , Barry K , Schmutz J , Baker SE , Ciuffetti LM , Grigoriev IV , Zhong S , Turgeon BG
Ref : PLoS Genet , 9 :e1003233 , 2013
Abstract : The genomes of five Cochliobolus heterostrophus strains, two Cochliobolus sativus strains, three additional Cochliobolus species (Cochliobolus victoriae, Cochliobolus carbonum, Cochliobolus miyabeanus), and closely related Setosphaeria turcica were sequenced at the Joint Genome Institute (JGI). The datasets were used to identify SNPs between strains and species, unique genomic regions, core secondary metabolism genes, and small secreted protein (SSP) candidate effector encoding genes with a view towards pinpointing structural elements and gene content associated with specificity of these closely related fungi to different cereal hosts. Whole-genome alignment shows that three to five percent of each genome differs between strains of the same species, while a quarter of each genome differs between species. On average, SNP counts among field isolates of the same C. heterostrophus species are more than 25x higher than those between inbred lines and 50x lower than SNPs between Cochliobolus species. The suites of nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS), and SSP-encoding genes are astoundingly diverse among species but remarkably conserved among isolates of the same species, whether inbred or field strains, except for defining examples that map to unique genomic regions. Functional analysis of several strain-unique PKSs and NRPSs reveal a strong correlation with a role in virulence.
ESTHER : Condon_2013_PLoS.Genet_9_e1003233
PubMedSearch : Condon_2013_PLoS.Genet_9_e1003233
PubMedID: 23357949
Gene_locus related to this paper: cocsn-m2rnc6 , coch5-m2tnl8 , coch4-n4xap8 , sett2-r0j560 , cocsn-m2thl9 , coch5-m2v1s2 , coch4-n4xzy1 , cocsn-m2sqr3 , cocsn-m2rnk8 , coch4-n4xdv7 , coch5-m2uds0 , coch5-m2um94 , sett2-r0i8c5 , coch4-n4wlc8 , coch4-n4x9p3 , cocsn-m2rh47 , cocsn-m2qz08 , sett2-r0jqq6 , sett2-r0imb6 , coch4-n4x7u3 , cocsn-m2rv02 , cocsn-m2sy95 , coch5-m2ubd5 , cocsn-m2t3d2 , sett2-r0kl84 , sett2-r0jts7 , coch4-n4x2h3 , sett2-r0jxt9 , coch4-n4x7r9 , cocsn-m2sh75 , cocsn-m2t5z2 , coch5-m2ucf6 , sett2-r0k664 , cocsn-m2t3q1 , sett2-r0k4b4 , cocsn-m2t4i1 , coch5-m2th93 , cocsn-m2svm8 , cocsn-m2s6q4 , cocsn-m2s5h5 , coch4-n4xf94 , sett2-r0kdl8 , cocsn-m2qvi9 , sett2-r0kfg6 , cocsn-m2szq4 , sett2-r0j437 , coch4-n4x7j4 , coch5-m2twk3 , coch5-m2usf2 , sett2-r0kjt7 , sett2-r0k7y2 , cocsn-m2th03 , sett2-r0iy92 , sett2-r0kbr9 , sett2-r0k997 , coch5-m2sik6 , sett2-r0jzj5 , cocsn-m2r0j6 , coch4-n4x6a4 , cocsn-m2s7a5 , cocsn-m2sv79 , sett2-r0knx4 , sett2-r0ksh8 , sett2-r0ip86 , cocmi-w6yyy3 , cocsn-m2sqe4 , coch4-n4xzc8 , cocvi-w7eyp1 , cocmi-w6zf65 , cocvi-w7er28 , cocca-w6yw25 , cocvi-w7e2g6 , cocmi-w6z7k5 , cocca-w6ys73 , cocca-w6ydq2 , cocca-w6y7i5 , cocmi-w6yyr0 , cocca-w6yh47 , cocmi-w6zju4 , cocca-w6ynq5 , cocmi-w6zm44 , cocca-w6xx85 , cocmi-w6z011 , cocca-w6yre4 , cocmi-w6z9l3 , cocca-w6yfp7 , cocmi-w6zlc2 , cocca-w6yar2 , cocmi-w6yjr7 , cocca-w6yhs1 , cocca-w6xux8 , cocmi-w6z9s8 , cocca-w6yq27 , cocmi-w6zqk9 , cocca-w6xq19 , cocca-w6y1r6 , cocca-w6ygj2 , cocmi-w6zgn4 , cocca-w6ybh2 , cocmi-w6z710 , cocca-w6yk86 , cocmi-w6zjz2 , cocmi-w6z7f2 , cocca-w6xn57 , cocca-w6ybq4 , cocmi-w6yxn5 , cocmi-w6zf08 , cocsn-m2rtg8 , cocmi-w6zuj7 , cocca-w6xtb2 , cocca-w6yk97 , coch5-m2t2x3 , cocmi-w6z646 , cocsn-m2sze4 , sett2-r0kjg6 , cocmi-w6yrn5 , sett2-r0k5q0 , cocvi-w7ezb7 , sett2-r0jtm1 , cocmi-w6ywa1 , cocsn-m2t3e8 , coch5-m2ulw5 , coch5-m2urw9 , sett2-r0knn5 , cocmi-w6ysb2 , cocvi-w7eag7 , cocca-w6y1v2 , sett2-r0i9k2 , coch5-m2uul8 , cocsn-m2sl21

Title : Complete Genome of Serratia sp. Strain FGI 94, a Strain Associated with Leaf-Cutter Ant Fungus Gardens - Aylward_2013_Genome.Announc_1_e0023912
Author(s) : Aylward FO , Tremmel DM , Starrett GJ , Bruce DC , Chain P , Chen A , Davenport KW , Detter C , Han CS , Han J , Huntemann M , Ivanova NN , Kyrpides NC , Markowitz V , Mavrommatis K , Nolan M , Pagani I , Pati A , Pitluck S , Teshima H , Deshpande S , Goodwin L , Woyke T , Currie CR
Ref : Genome Announc , 1 :e0023912 , 2013
Abstract : Serratia sp. strain FGI 94 was isolated from a fungus garden of the leaf-cutter ant Atta colombica. Analysis of its 4.86-Mbp chromosome will help advance our knowledge of symbiotic interactions and plant biomass degradation in this ancient ant-fungus mutualism.
ESTHER : Aylward_2013_Genome.Announc_1_e0023912
PubMedSearch : Aylward_2013_Genome.Announc_1_e0023912
PubMedID: 23516234
Gene_locus related to this paper: serma-l0mn97 , serma-l0mh84 , serma-l0mif0

Title : Draft genome sequence of Frankia sp. strain CN3, an atypical, noninfective (Nod-) ineffective (Fix-) isolate from Coriaria nepalensis - Ghodhbane-Gtari_2013_Genome.Announc_1_e0008513
Author(s) : Ghodhbane-Gtari F , Beauchemin N , Bruce D , Chain P , Chen A , Walston Davenport K , Deshpande S , Detter C , Furnholm T , Goodwin L , Gtari M , Han C , Han J , Huntemann M , Ivanova N , Kyrpides N , Land ML , Markowitz V , Mavrommatis K , Nolan M , Nouioui I , Pagani I , Pati A , Pitluck S , Santos CL , Sen A , Sur S , Szeto E , Tavares F , Teshima H , Thakur S , Wall L , Woyke T , Tisa LS
Ref : Genome Announc , 1 :e0008513 , 2013
Abstract : We report here the genome sequence of Frankia sp. strain CN3, which was isolated from Coriaria nepalensis. This genome sequence is the first from the fourth lineage of Frankia, strains of which are unable to reinfect actinorhizal plants. At 10 Mb, it represents the largest Frankia genome sequenced to date.
ESTHER : Ghodhbane-Gtari_2013_Genome.Announc_1_e0008513
PubMedSearch : Ghodhbane-Gtari_2013_Genome.Announc_1_e0008513
PubMedID: 23516212
Gene_locus related to this paper: 9acto-g6hh93

Title : Drosophila Neuroligin 4 Regulates Sleep through Modulating GABA Transmission - Li_2013_J.Neurosci_33_15545
Author(s) : Li Y , Zhou Z , Zhang X , Tong H , Li P , Zhang ZC , Jia Z , Xie W , Han J
Ref : Journal of Neuroscience , 33 :15545 , 2013
Abstract : Sleep is an essential and evolutionarily conserved behavior that is closely related to synaptic function. However, whether neuroligins (Nlgs), which are cell adhesion molecules involved in synapse formation and synaptic transmission, are involved in sleep is not clear. Here, we show that Drosophila Nlg4 (DNlg4) is highly expressed in large ventral lateral clock neurons (l-LNvs) and that l-LNv-derived DNlg4 is essential for sleep regulation. GABA transmission is impaired in mutant l-LNv, and sleep defects in dnlg4 mutant flies can be rescued by genetic manipulation of GABA transmission. Furthermore, dnlg4 mutant flies exhibit a severe reduction in GABAA receptor RDL clustering, and DNlg4 associates with RDLs in vivo. These results demonstrate that DNlg4 regulates sleep through modulating GABA transmission in l-LNvs, which provides the first known link between a synaptic adhesion molecule and sleep in Drosophila.
ESTHER : Li_2013_J.Neurosci_33_15545
PubMedSearch : Li_2013_J.Neurosci_33_15545
PubMedID: 24068821
Gene_locus related to this paper: drome-b6idz4

Title : Norfriedelins A-C with acetylcholinesterase inhibitory activity from acerola tree (Malpighia emarginata) - Liu_2013_Org.Lett_15_1580
Author(s) : Liu JQ , Peng XR , Li XY , Li TZ , Zhang WM , Shi L , Han J , Qiu MH
Ref : Org Lett , 15 :1580 , 2013
Abstract : Three novel norfriedelanes, A-C (1-3), were isolated from the branches and roots of Malpighia emarginata . Their structures and absolute configurations were determined by 1D and 2D NMR techniques and X-ray crystallographic analysis. Norfriedelin A (possessing an alpha-oxo-beta-lactone group) and norfriedelin B (with a keto-lactone group) showed acetylcholinesterase inhibitory effects with the IC50 values of 10.3 and 28.7 muM, respectively.
ESTHER : Liu_2013_Org.Lett_15_1580
PubMedSearch : Liu_2013_Org.Lett_15_1580
PubMedID: 23484960

Title : Complete genome sequence of Dehalobacter restrictus PER-K23(T.) - Kruse_2013_Stand.Genomic.Sci_8_375
Author(s) : Kruse T , Maillard J , Goodwin L , Woyke T , Teshima H , Bruce D , Detter C , Tapia R , Han C , Huntemann M , Wei CL , Han J , Chen A , Kyrpides N , Szeto E , Markowitz V , Ivanova N , Pagani I , Pati A , Pitluck S , Nolan M , Holliger C , Smidt H
Ref : Stand Genomic Sci , 8 :375 , 2013
Abstract : Dehalobacter restrictus strain PER-K23 (DSM 9455) is the type strain of the species Dehalobacter restrictus. D. restrictus strain PER-K23 grows by organohalide respiration, coupling the oxidation of H2 to the reductive dechlorination of tetra- or trichloroethene. Growth has not been observed with any other electron donor or acceptor, nor has fermentative growth been shown. Here we introduce the first full genome of a pure culture within the genus Dehalobacter. The 2,943,336 bp long genome contains 2,826 protein coding and 82 RNA genes, including 5 16S rRNA genes. Interestingly, the genome contains 25 predicted reductive dehalogenase genes, the majority of which appear to be full length. The reductive dehalogenase genes are mainly located in two clusters, suggesting a much larger potential for organohalide respiration than previously anticipated.
ESTHER : Kruse_2013_Stand.Genomic.Sci_8_375
PubMedSearch : Kruse_2013_Stand.Genomic.Sci_8_375
PubMedID: 24501624
Gene_locus related to this paper: 9firm-w0ejt1 , 9firm-w0ekb3

Title : Complete genome sequences of Desulfosporosinus orientis DSM765T, Desulfosporosinus youngiae DSM17734T, Desulfosporosinus meridiei DSM13257T, and Desulfosporosinus acidiphilus DSM22704T - Pester_2012_J.Bacteriol_194_6300
Author(s) : Pester M , Brambilla E , Alazard D , Rattei T , Weinmaier T , Han J , Lucas S , Lapidus A , Cheng JF , Goodwin L , Pitluck S , Peters L , Ovchinnikova G , Teshima H , Detter JC , Han CS , Tapia R , Land ML , Hauser L , Kyrpides NC , Ivanova NN , Pagani I , Huntmann M , Wei CL , Davenport KW , Daligault H , Chain PS , Chen A , Mavromatis K , Markowitz V , Szeto E , Mikhailova N , Pati A , Wagner M , Woyke T , Ollivier B , Klenk HP , Spring S , Loy A
Ref : Journal of Bacteriology , 194 :6300 , 2012
Abstract : Desulfosporosinus species are sulfate-reducing bacteria belonging to the Firmicutes. Their genomes will give insights into the genetic repertoire and evolution of sulfate reducers typically thriving in terrestrial environments and able to degrade toluene (Desulfosporosinus youngiae), to reduce Fe(III) (Desulfosporosinus meridiei, Desulfosporosinus orientis), and to grow under acidic conditions (Desulfosporosinus acidiphilus).
ESTHER : Pester_2012_J.Bacteriol_194_6300
PubMedSearch : Pester_2012_J.Bacteriol_194_6300
PubMedID: 23105050
Gene_locus related to this paper: desaj-i4dc82 , desmd-j7j1v2 , desod-g7wg97 , desaj-i4d5q8

Title : Two galantamine titration regimens in patients switched from donepezil - Engedal_2012_Acta.Neurol.Scand_126_37
Author(s) : Engedal K , Davis B , Richarz U , Han J , Schauble B , Andreasen N
Ref : Acta Neurologica Scandinavica , 126 :37 , 2012
Abstract : OBJECTIVES: In addition to inhibiting acetylcholinesterase, galantamine has allosteric-modulating activity at nicotinic receptors. This may make galantamine an attractive option for patients starting treatment for Alzheimer's disease (AD), but also for those who have not benefited from their current therapy. This study explored outcomes in subjects with AD transitioning from donepezil because of insufficient tolerability or efficacy. MATERIALS AND METHODS: Subjects previously receiving donepezil for mild-to-moderate AD were enrolled in a 12-week randomized, open-label study. After screening and a 7-day washout, subjects were randomly allocated to galantamine fast (8 mg/week increments) or slow (8 mg/4 week) titration to 16-24 mg. Efficacy outcomes included the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog/11), Mini-Mental State Examination (MMSE), Clinician's Interview-Based Impression of Change - Plus Caregiver's Input (CIBIC-plus) and Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL). RESULTS: Eighty-six of 89 patients (fast titration, n = 44; slow titration, n = 45) completed the study. At week 12, ADAS-cog/11 score improved from screening by 2.6 and 0.6 in the fast- and slow-titration arms, respectively (overall, -1.6; P = 0.002). MMSE scores improved slightly in both arms (overall, +0.9; P = 0.002). Two-thirds of patients had improvement or no change on the CIBIC-plus at week 12. ADCS-ADL scores did not change significantly from screening in either treatment arm. Galantamine was generally well tolerated; nausea (5.6%) and bradycardia (4.5%) were the most commonly reported adverse events. CONCLUSIONS: Patients in whom donepezil is ineffective or poorly tolerated may benefit from a switch to galantamine.
ESTHER : Engedal_2012_Acta.Neurol.Scand_126_37
PubMedSearch : Engedal_2012_Acta.Neurol.Scand_126_37
PubMedID: 21992111

Title : Complete genome sequence of Halopiger xanaduensis type strain (SH-6(T)) - Anderson_2012_Stand.Genomic.Sci_6_31
Author(s) : Anderson I , Tindall BJ , Rohde M , Lucas S , Han J , Lapidus A , Cheng JF , Goodwin L , Pitluck S , Peters L , Pati A , Mikhailova N , Pagani I , Teshima H , Han C , Tapia R , Land M , Woyke T , Klenk HP , Kyrpides N , Ivanova N
Ref : Stand Genomic Sci , 6 :31 , 2012
Abstract : Halopiger xanaduensis is the type species of the genus Halopiger and belongs to the euryarchaeal family Halobacteriaceae. H. xanaduensis strain SH-6, which is designated as the type strain, was isolated from the sediment of a salt lake in Inner Mongolia, Lake Shangmatala. Like other members of the family Halobacteriaceae, it is an extreme halophile requiring at least 2.5 M salt for growth. We report here the sequencing and annotation of the 4,355,268 bp genome, which includes one chromosome and three plasmids. This genome is part of a Joint Genome Institute (JGI) Community Sequencing Program (CSP) project to sequence diverse haloarchaeal genomes.
ESTHER : Anderson_2012_Stand.Genomic.Sci_6_31
PubMedSearch : Anderson_2012_Stand.Genomic.Sci_6_31
PubMedID: 22675596
Gene_locus related to this paper: halxs-f8dda6

Title : High-quality draft genome sequence of the Opitutaceae bacterium strain TAV1, a symbiont of the wood-feeding termite Reticulitermes flavipes - Isanapong_2012_J.Bacteriol_194_2744
Author(s) : Isanapong J , Goodwin L , Bruce D , Chen A , Detter C , Han J , Han CS , Held B , Huntemann M , Ivanova N , Land ML , Mavromatis K , Nolan M , Pati A , Pennacchio L , Pitluck S , Szeto E , Tapia R , Woyke T , Rodrigues JL
Ref : Journal of Bacteriology , 194 :2744 , 2012
Abstract : Microbial communities in the termite hindgut are essential for degrading plant material. We present the high-quality draft genome sequence of the Opitutaceae bacterium strain TAV1, the first member of the phylum Verrucomicrobia to be isolated from wood-feeding termites. The genomic analysis reveals genes coding for lignocellulosic degradation and nitrogen fixation.
ESTHER : Isanapong_2012_J.Bacteriol_194_2744
PubMedSearch : Isanapong_2012_J.Bacteriol_194_2744
PubMedID: 22535930
Gene_locus related to this paper: 9bact-i6azi1

Title : Genome sequence of the mesophilic Thermotogales bacterium Mesotoga prima MesG1.Ag.4.2 reveals the largest Thermotogales genome to date - Zhaxybayeva_2012_Genome.Biol.Evol_4_700
Author(s) : Zhaxybayeva O , Swithers KS , Foght J , Green AG , Bruce D , Detter C , Han S , Teshima H , Han J , Woyke T , Pitluck S , Nolan M , Ivanova N , Pati A , Land ML , Dlutek M , Doolittle WF , Noll KM , Nesbo CL
Ref : Genome Biol Evol , 4 :700 , 2012
Abstract : Here we describe the genome of Mesotoga prima MesG1.Ag4.2, the first genome of a mesophilic Thermotogales bacterium. Mesotoga prima was isolated from a polychlorinated biphenyl (PCB)-dechlorinating enrichment culture from Baltimore Harbor sediments. Its 2.97 Mb genome is considerably larger than any previously sequenced Thermotogales genomes, which range between 1.86 and 2.30 Mb. This larger size is due to both higher numbers of protein-coding genes and larger intergenic regions. In particular, the M. prima genome contains more genes for proteins involved in regulatory functions, for instance those involved in regulation of transcription. Together with its closest relative, Kosmotoga olearia, it also encodes different types of proteins involved in environmental and cell-cell interactions as compared with other Thermotogales bacteria. Amino acid composition analysis of M. prima proteins implies that this lineage has inhabited low-temperature environments for a long time. A large fraction of the M. prima genome has been acquired by lateral gene transfer (LGT): a DarkHorse analysis suggests that 766 (32%) of predicted protein-coding genes have been involved in LGT after Mesotoga diverged from the other Thermotogales lineages. A notable example of a lineage-specific LGT event is a reductive dehalogenase gene-a key enzyme in dehalorespiration, indicating M. prima may have a more active role in PCB dechlorination than was previously assumed.
ESTHER : Zhaxybayeva_2012_Genome.Biol.Evol_4_700
PubMedSearch : Zhaxybayeva_2012_Genome.Biol.Evol_4_700
PubMedID: 22798451
Gene_locus related to this paper: 9bact-i2f5c1 , 9bact-i2f6q4

Title : Complete genome sequence of the metabolically versatile halophilic archaeon Haloferax mediterranei, a poly(3-hydroxybutyrate-co-3-hydroxyvalerate) producer - Han_2012_J.Bacteriol_194_4463
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
Ref : Journal of Bacteriology , 194 :4463 , 2012
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.
ESTHER : Han_2012_J.Bacteriol_194_4463
PubMedSearch : Han_2012_J.Bacteriol_194_4463
PubMedID: 22843593

Title : Complete genome sequence of the rapeseed plant-growth promoting Serratia plymuthica strain AS9 - Neupane_2012_Stand.Genomic.Sci_6_54
Author(s) : Neupane S , Hogberg N , Alstrom S , Lucas S , Han J , Lapidus A , Cheng JF , Bruce D , Goodwin L , Pitluck S , Peters L , Ovchinnikova G , Lu M , Han C , Detter JC , Tapia R , Fiebig A , Land M , Hauser L , Kyrpides NC , Ivanova N , Pagani I , Klenk HP , Woyke T , Finlay RD
Ref : Stand Genomic Sci , 6 :54 , 2012
Abstract : Serratia plymuthica are plant-associated, plant beneficial species belonging to the family Enterobacteriaceae. The members of the genus Serratia are ubiquitous in nature and their life style varies from endophytic to free-living. S. plymuthica AS9 is of special interest for its ability to inhibit fungal pathogens of rapeseed and to promote plant growth. The genome of S. plymuthica AS9 comprises a 5,442,880 bp long circular chromosome that consists of 4,952 protein-coding genes, 87 tRNA genes and 7 rRNA operons. This genome is part of the project entitled "Genomics of four rapeseed plant growth promoting bacteria with antagonistic effect on plant pathogens" awarded through the 2010 DOE-JGI Community Sequencing Program (CSP2010).
ESTHER : Neupane_2012_Stand.Genomic.Sci_6_54
PubMedSearch : Neupane_2012_Stand.Genomic.Sci_6_54
PubMedID: 22675598
Gene_locus related to this paper: serpl-s0ae95 , serpl-s0aiv6 , sersa-g0bfi6 , serp5-a8gjr8 , serpl-s4yi15

Title : Complete genome sequence of Serratia plymuthica strain AS12 - Neupane_2012_Stand.Genomic.Sci_6_165
Author(s) : Neupane S , Finlay RD , Alstrom S , Goodwin L , Kyrpides NC , Lucas S , Lapidus A , Bruce D , Pitluck S , Peters L , Ovchinnikova G , Chertkov O , Han J , Han C , Tapia R , Detter JC , Land M , Hauser L , Cheng JF , Ivanova N , Pagani I , Klenk HP , Woyke T , Hogberg N
Ref : Stand Genomic Sci , 6 :165 , 2012
Abstract : A plant-associated member of the family Enterobacteriaceae, Serratia plymuthica strain AS12 was isolated from rapeseed roots. It is of scientific interest because it promotes plant growth and inhibits plant pathogens. The genome of S. plymuthica AS12 comprises a 5,443,009 bp long circular chromosome, which consists of 4,952 protein-coding genes, 87 tRNA genes and 7 rRNA operons. This genome was sequenced within the 2010 DOE-JGI Community Sequencing Program (CSP2010) as part of the project entitled "Genomics of four rapeseed plant growth promoting bacteria with antagonistic effect on plant pathogens".
ESTHER : Neupane_2012_Stand.Genomic.Sci_6_165
PubMedSearch : Neupane_2012_Stand.Genomic.Sci_6_165
PubMedID: 22768360
Gene_locus related to this paper: serpl-s0ae95 , serpl-s0aiv6 , sersa-g0bfi6 , serpl-i3aik7 , serpl-s4yi15

Title : Complete genome sequence of the plant-associated Serratia plymuthica strain AS13 - Neupane_2012_Stand.Genomic.Sci_7_22
Author(s) : Neupane S , Finlay RD , Kyrpides NC , Goodwin L , Alstrom S , Lucas S , Land M , Han J , Lapidus A , Cheng JF , Bruce D , Pitluck S , Peters L , Ovchinnikova G , Held B , Han C , Detter JC , Tapia R , Hauser L , Ivanova N , Pagani I , Woyke T , Klenk HP , Hogberg N
Ref : Stand Genomic Sci , 7 :22 , 2012
Abstract : Serratia plymuthica AS13 is a plant-associated Gammaproteobacteria, isolated from rapeseed roots. It is of special interest because of its ability to inhibit fungal pathogens of rapeseed and to promote plant growth. The complete genome of S. plymuthica AS13 consists of a 5,442,549 bp circular chromosome. The chromosome contains 4,951 protein-coding genes, 87 tRNA genes and 7 rRNA operons. This genome was sequenced as part of the project entitled "Genomics of four rapeseed plant growth promoting bacteria with antagonistic effect on plant pathogens" within the 2010 DOE-JGI Community Sequencing Program (CSP2010).
ESTHER : Neupane_2012_Stand.Genomic.Sci_7_22
PubMedSearch : Neupane_2012_Stand.Genomic.Sci_7_22
PubMedID: 23450001
Gene_locus related to this paper: serpl-s0ae95 , serpl-s0aiv6 , sersa-g0bfi6 , serp5-a8gjr8 , serpl-s4yi15

Title : Improved high-pressure enzymatic biodiesel batch synthesis in near-critical carbon dioxide - Lee_2012_Bioprocess.Biosyst.Eng_35_105
Author(s) : Lee M , Lee D , Cho JK , Cho J , Han J , Park C , Kim S
Ref : Bioprocess Biosyst Eng , 35 :105 , 2012
Abstract : The enzymatic synthesis of biodiesel by a high-pressure semi-continuous process in near-critical carbon dioxide (NcCO(2)) was studied. Biodiesel synthesis was evaluated in both batch and semi-continuous systems to develop an effective process. Batch processing demonstrated the advantageous properties of NcCO(2) as an alternative reaction medium. Three immobilized lipases (Novozym 435, Lipozyme RM IM, and Lipozyme TL IM from Novozymes) were tested, with Lipozyme TL IM the most effective, showing the highest conversion. Biodiesel conversion from several edible and non-edible oil feedstocks reached >92%. Higher conversion (99.0%) was obtained in a shorter time by employing repeated batch processes with optimized conditions: 44.3 g (500 mM) canola oil, a substrate molar ratio (methanol:oil) of 3:1, an enzyme loading of 20 wt% (of the oil used), at 30 degreeC, 100 bar, and 300 rpm agitation. The enzyme maintained 80.2% of its initial stability after being reused eight times. These results suggest that this method produces biodiesel energy-efficiently and environment-friendly.
ESTHER : Lee_2012_Bioprocess.Biosyst.Eng_35_105
PubMedSearch : Lee_2012_Bioprocess.Biosyst.Eng_35_105
PubMedID: 21989636

Title : Luteolin enhances cholinergic activities in PC12 cells through ERK1\/2 and PI3K\/Akt pathways - El Omri_2012_Brain.Res_1437_16
Author(s) : El Omri A , Han J , Kawada K , Ben Abdrabbah M , Isoda H
Ref : Brain Research , 1437 :16 , 2012
Abstract : Luteolin, a 3', 4', 5, 7-tetrahydroxyflavone, is an active compound in Rosmarinus officinalis (Lamiacea), and has been reported to exert several benefits in neuronal cells. However cholinergic-induced activities of luteolin still remain unknown. Neuronal differentiation encompasses an elaborate developmental program which plays a key role in the development of the nervous system. The advent of several cell lines, like PC12 cells, able to differentiate in culture proved to be the turning point for gaining and understanding of molecular neuroscience. In this work, we investigated the ability of luteolin to induce PC12 cell differentiation and its effect on cholinergic activities. Our findings showed that luteolin treatment significantly induced neurite outgrowth extension, enhanced acetylcholinesterase (AChE) activity, known as neuronal differentiation marker, and increased the level of total choline and acetylcholine in PC12 cells. In addition, luteolin persistently, activated extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt; while the addition of pharmacological MEK/ERK1/2 inhibitor (U0126) and PI3k/Akt inhibitor (LY294002) attenuated luteolin-induced AChE activity and neurite outgrowth in PC12 cells. The above findings suggest that luteolin induces neurite outgrowth and enhanced cholinergic activities, at least in part, through the activation of ERK1/2 and Akt signaling.
ESTHER : El Omri_2012_Brain.Res_1437_16
PubMedSearch : El Omri_2012_Brain.Res_1437_16
PubMedID: 22226506

Title : Genome sequence of the mercury-methylating strain Desulfovibrio desulfuricans ND132 - Brown_2011_J.Bacteriol_193_2078
Author(s) : Brown SD , Gilmour CC , Kucken AM , Wall JD , Elias DA , Brandt CC , Podar M , Chertkov O , Held B , Bruce DC , Detter JC , Tapia R , Han CS , Goodwin LA , Cheng JF , Pitluck S , Woyke T , Mikhailova N , Ivanova NN , Han J , Lucas S , Lapidus AL , Land ML , Hauser LJ , Palumbo AV
Ref : Journal of Bacteriology , 193 :2078 , 2011
Abstract : Desulfovibrio desulfuricans strain ND132 is an anaerobic sulfate-reducing bacterium (SRB) capable of producing methylmercury (MeHg), a potent human neurotoxin. The mechanism of methylation by this and other organisms is unknown. We present the 3.8-Mb genome sequence to provide further insight into microbial mercury methylation.
ESTHER : Brown_2011_J.Bacteriol_193_2078
PubMedSearch : Brown_2011_J.Bacteriol_193_2078
PubMedID: 21357488
Gene_locus related to this paper: desde-f0jku0

Title : Complete genome sequence of Haloarcula hispanica, a Model Haloarchaeon for studying genetics, metabolism, and virus-host interaction - Liu_2011_J.Bacteriol_193_6086
Author(s) : Liu H , Wu Z , Li M , Zhang F , Zheng H , Han J , Liu J , Zhou J , Wang S , Xiang H
Ref : Journal of Bacteriology , 193 :6086 , 2011
Abstract : Haloarcula hispanica is an extremely halophilic archaeon that has an unusually low restriction barrier and is therefore significant for studying archaeal genetics, metabolism, and virus-host interactions. Here we report the complete genome sequence (3,890,005 bp) of H. hispanica strain CGMCC 1.2049, consisting of two chromosomes and one megaplasmid.
ESTHER : Liu_2011_J.Bacteriol_193_6086
PubMedSearch : Liu_2011_J.Bacteriol_193_6086
PubMedID: 21994921
Gene_locus related to this paper: halma-q5uym0

Title : Complete genome sequences of Krokinobacter sp. strain 4H-3-7-5 and Lacinutrix sp. strain 5H-3-7-4, polysaccharide-degrading members of the family Flavobacteriaceae - Klippel_2011_J.Bacteriol_193_4545
Author(s) : Klippel B , Lochner A , Bruce DC , Davenport KW , Detter C , Goodwin LA , Han J , Han S , Hauser L , Land ML , Nolan M , Ovchinnikova G , Pennacchio L , Pitluck S , Tapia R , Woyke T , Wiebusch S , Basner A , Abe F , Horikoshi K , Keller M , Antranikian G
Ref : Journal of Bacteriology , 193 :4545 , 2011
Abstract : Two members of the family Flavobacteriaceae were isolated from subseafloor sediments using artificial seawater with cellulose, xylan, and chitin as the sole carbon and energy sources. Here, we present the complete genome sequences of Krokinobacter sp. strain 4H-3-7-5 and Lacinutrix sp. strain 5H-3-7-4, which both encode putatively novel enzymes involved in cellulose, hemicellulose, and chitin metabolism.
ESTHER : Klippel_2011_J.Bacteriol_193_4545
PubMedSearch : Klippel_2011_J.Bacteriol_193_4545
PubMedID: 21725025
Gene_locus related to this paper: lacs5-f6gdi8 , doks4-f4b2f7

Title : Neuroligin 2 is required for synapse development and function at the Drosophila neuromuscular junction - Sun_2011_J.Neurosci_31_687
Author(s) : Sun M , Xing G , Yuan L , Gan G , Knight D , With SI , He C , Han J , Zeng X , Fang M , Boulianne GL , Xie W
Ref : Journal of Neuroscience , 31 :687 , 2011
Abstract : Neuroligins belong to a highly conserved family of cell adhesion molecules that have been implicated in synapse formation and function. However, the precise in vivo roles of Neuroligins remain unclear. In the present study, we have analyzed the function of Drosophila neuroligin 2 (dnl2) in synaptic development and function. We show that dnl2 is strongly expressed in the embryonic and larval CNS and at the larval neuromuscular junction (NMJ). dnl2 null mutants are viable but display numerous structural defects at the NMJ, including reduced axonal branching and fewer synaptic boutons. dnl2 mutants also show an increase in the number of active zones per bouton but a decrease in the thickness of the subsynaptic reticulum and length of postsynaptic densities. dnl2 mutants also exhibit a decrease in the total glutamate receptor density and a shift in the subunit composition of glutamate receptors in favor of GluRIIA complexes. In addition to the observed defects in synaptic morphology, we also find that dnl2 mutants show increased transmitter release and altered kinetics of stimulus-evoked transmitter release. Importantly, the defects in presynaptic structure, receptor density, and synaptic transmission can be rescued by postsynaptic expression of dnl2. Finally, we show that dnl2 colocalizes and binds to Drosophila neurexin (dnrx) in vivo. However, whereas homozygous mutants for either dnl2 or dnrx are viable, double mutants are lethal and display more severe defects in synaptic morphology. Altogether, our data show that, although dnl2 is not absolutely required for synaptogenesis, it is required postsynaptically for synapse maturation and function.
ESTHER : Sun_2011_J.Neurosci_31_687
PubMedSearch : Sun_2011_J.Neurosci_31_687
PubMedID: 21228178
Gene_locus related to this paper: drome-CG13772

Title : Complete genome sequence of Parvibaculum lavamentivorans type strain (DS-1(T)) - Schleheck_2011_Stand.Genomic.Sci_5_298
Author(s) : Schleheck D , Weiss M , Pitluck S , Bruce D , Land ML , Han S , Saunders E , Tapia R , Detter C , Brettin T , Han J , Woyke T , Goodwin L , Pennacchio L , Nolan M , Cook AM , Kjelleberg S , Thomas T
Ref : Stand Genomic Sci , 5 :298 , 2011
Abstract : Parvibaculum lavamentivorans DS-1(T) is the type species of the novel genus Parvibaculum in the novel family Rhodobiaceae (formerly Phyllobacteriaceae) of the order Rhizobiales of Alphaproteobacteria. Strain DS-1(T) is a non-pigmented, aerobic, heterotrophic bacterium and represents the first tier member of environmentally important bacterial communities that catalyze the complete degradation of synthetic laundry surfactants. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 3,914,745 bp long genome with its predicted 3,654 protein coding genes is the first completed genome sequence of the genus Parvibaculum, and the first genome sequence of a representative of the family Rhodobiaceae.
ESTHER : Schleheck_2011_Stand.Genomic.Sci_5_298
PubMedSearch : Schleheck_2011_Stand.Genomic.Sci_5_298
PubMedID: 22675581
Gene_locus related to this paper: parl1-a7hy87

Title : Genome sequence of the mercury-methylating and pleomorphic Desulfovibrio africanus Strain Walvis Bay - Brown_2011_J.Bacteriol_193_4037
Author(s) : Brown SD , Wall JD , Kucken AM , Gilmour CC , Podar M , Brandt CC , Teshima H , Detter JC , Han CS , Land ML , Lucas S , Han J , Pennacchio L , Nolan M , Pitluck S , Woyke T , Goodwin L , Palumbo AV , Elias DA
Ref : Journal of Bacteriology , 193 :4037 , 2011
Abstract : Desulfovibrio africanus strain Walvis Bay is an anaerobic sulfate-reducing bacterium capable of producing methylmercury (MeHg), a potent human neurotoxin. The mechanism of methylation by this and other organisms is unknown. We present the 4.2-Mb genome sequence to provide further insight into microbial mercury methylation and sulfate-reducing bacteria.
ESTHER : Brown_2011_J.Bacteriol_193_4037
PubMedSearch : Brown_2011_J.Bacteriol_193_4037
PubMedID: 21642452
Gene_locus related to this paper: desaf-f3ywu6

Title : Complete genome sequence of the marine cellulose- and xylan-degrading bacterium Glaciecola sp. strain 4H-3-7+YE-5 - Klippel_2011_J.Bacteriol_193_4547
Author(s) : Klippel B , Lochner A , Bruce DC , Davenport KW , Detter C , Goodwin LA , Han J , Han S , Land ML , Mikhailova N , Nolan M , Pennacchio L , Pitluck S , Tapia R , Woyke T , Wiebusch S , Basner A , Abe F , Horikoshi K , Keller M , Antranikian G
Ref : Journal of Bacteriology , 193 :4547 , 2011
Abstract : Glaciecola sp. strain 4H-3-7+YE-5 was isolated from subseafloor sediments at Suruga Bay in Japan and is capable of efficiently hydrolyzing cellulose and xylan. The complete genome sequence of Glaciecola sp. 4H-3-7+YE-5 revealed several genes encoding putatively novel glycoside hydrolases, offering a high potential for plant biomass degradation.
ESTHER : Klippel_2011_J.Bacteriol_193_4547
PubMedSearch : Klippel_2011_J.Bacteriol_193_4547
PubMedID: 21705587
Gene_locus related to this paper: glas4-f4ahz5 , glas4-f4aq74 , glas4-f4ajt2

Title : Comparison of four phaC genes from Haloferax mediterranei and their function in different PHBV copolymer biosyntheses in Haloarcula hispanica - Han_2010_Saline.Systems_6_9
Author(s) : Han J , Li M , Hou J , Wu L , Zhou J , Xiang H
Ref : Saline Systems , 6 :9 , 2010
Abstract : BACKGROUND: The halophilic archaeon Haloferax mediterranei is able to accumulate large amounts of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) with high molar fraction of 3-hydroxyvalerate (3HV) from unrelated carbon sources. A Polyhydroxyalkanoate (PHA) synthase composed of two subunits, PhaCHme and PhaEHme, has been identified in this strain, and shown to account for the PHBV biosynthesis.
RESULTS: With the aid of the genome sequence of Hfx. mediterranei CGMCC 1.2087, three additional phaC genes (designated phaC1, phaC2, and phaC3) were identified, which encoded putative PhaCs. Like PhaCHme (54.8 kDa), PhaC1 (49.7 kDa) and PhaC3 (62.5 kDa) possessed the conserved motifs of type III PHA synthase, which was not observed in PhaC2 (40.4 kDa). Furthermore, the longer C terminus found in the other three PhaCs was also absent in PhaC2. Reverse transcription PCR (RT-PCR) revealed that, among the four genes, only phaCHme was transcribed under PHA-accumulating conditions in the wild-type strain. However, heterologous coexpression of phaEHme with each phaC gene in Haloarcula hispanica PHB-1 showed that all PhaCs, except PhaC2, could lead to PHBV accumulation with various 3HV fractions. The three kinds of copolymers were characterized using gel-permeation chromatography (GPC), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Their thermal properties changed with the variations in monomer composition as well as the different molecular weights (Mw), thus might meet various application requirements. CONCLUSION: We discover three cryptic phaC genes in Hfx. mediterranei, and demonstrate that genetic engineering of these newly identified phaC genes has biotechnological potential for PHBV production with tailor-made material properties.
ESTHER : Han_2010_Saline.Systems_6_9
PubMedSearch : Han_2010_Saline.Systems_6_9
PubMedID: 20727166

Title : Horizontal gene transfer of a ColV plasmid has resulted in a dominant avian clonal type of Salmonella enterica serovar Kentucky - Johnson_2010_PLoS.One_5_e15524
Author(s) : Johnson TJ , Thorsness JL , Anderson CP , Lynne AM , Foley SL , Han J , Fricke WF , McDermott PF , White DG , Khatri M , Stell AL , Flores C , Singer RS
Ref : PLoS ONE , 5 :e15524 , 2010
Abstract : Salmonella enterica continues to be a significant cause of foodborne gastrointestinal illness in humans. A wide variety of Salmonella serovars have been isolated from production birds and from retail poultry meat. Recently, though, S. enterica subsp. enterica serovar Kentucky has emerged as one of the prominent Salmonella serovars isolated from broiler chickens. Recent work suggests that its emergence apparently coincides with its acquisition of a ColV virulence plasmid. In the present study, we examined 902 Salmonella isolates belonging to 59 different serovars for the presence of this plasmid. Of the serovars examined, the ColV plasmid was found only among isolates belonging to the serovars Kentucky (72.9%), Typhimurium (15.0%) and Heidelberg (1.7%). We demonstrated that a single PFGE clonal type of S. Kentucky harbors this plasmid, and acquisition of this plasmid by S. Kentucky significantly increased its ability to colonize the chicken cecum and cause extraintestinal disease. Comparison of the completed sequences of three ColV plasmids from S. Kentucky isolated from different geographical locales, timepoints and sources revealed a nearly identical genetic structure with few single nucleotide changes or insertions/deletions. Overall, it appears that the ColV plasmid was recently acquired by a single clonal type S. Kentucky and confers to its host enhanced colonization and fitness capabilities. Thus, the potential for horizontal gene transfer of virulence and fitness factors to Salmonella from other enteric bacteria exists in poultry, representing a potential human health hazard.
ESTHER : Johnson_2010_PLoS.One_5_e15524
PubMedSearch : Johnson_2010_PLoS.One_5_e15524
PubMedID: 21203520
Gene_locus related to this paper: ecoli-IROE

Title : Rosmarinus officinalis polyphenols activate cholinergic activities in PC12 cells through phosphorylation of ERK1\/2 - El Omri_2010_J.Ethnopharmacol_131_451
Author(s) : El Omri A , Han J , Yamada P , Kawada K , Ben Abdrabbah M , Isoda H
Ref : J Ethnopharmacol , 131 :451 , 2010
Abstract : AIM OF THE STUDY: This paper aimed to elucidate the traditional use of Rosmarinus officinalis through the investigation of cholinergic activities and neuronal differentiation in rat pheochromocytoma PC12 cells. These effects were examined in relation to the plant's habitat, the extraction procedure, and the major active compounds of R. officinalis. MATERIALS AND METHODS: Cell viability, cell differentiation, acetylcholinesterase (AChE) activity, total choline, acetylcholine (ACh) and extracellular signal-regulated kinases (ERK1/2) were determined in PC12 cells treated with extracts and HPLC-identified polyphenols of R. officinalis originated from Tunisian semi-arid and subhumid area in comparison with nerve growth factor (NGF). RESULTS: R. officinalis extracts potentiated cell differentiation and significantly enhanced AChE activity in PC12 cells. The highest AChE activity was induced by semi-arid hydro-ethanolic extract (137% of control). Among HPLC-identified and screened polyphenols, carnosic acid (CA) and rosmarinic acid (RA) significantly induced cell differentiation, increased ACh level, and enhanced AChE activity in PC12 cells. U0126, inhibitor of ERK1/2, significantly reduced CA and RA effects on cell differentiation and AChE activity. CONCLUSIONS: R. officinalis' CA and RA exhibited neurotrophic effects in PC12 cells through cell differentiation induction and cholinergic activities enhancement. These effects could be regulated by mitogen-activated protein kinase (MAPK), ERK1/2 signaling pathway.
ESTHER : El Omri_2010_J.Ethnopharmacol_131_451
PubMedSearch : El Omri_2010_J.Ethnopharmacol_131_451
PubMedID: 20633629

Title : Genetic and biochemical characterization of the poly(3-hydroxybutyrate-co-3-hydroxyvalerate) synthase in Haloferax mediterranei - Lu_2008_J.Bacteriol_190_4173
Author(s) : Lu Q , Han J , Zhou L , Zhou J , Xiang H
Ref : Journal of Bacteriology , 190 :4173 , 2008
Abstract : The haloarchaeon Haloferax mediterranei has shown promise for the economical production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), a desirable bioplastic. However, little is known at present about the genes involved in PHBV synthesis in the domain Archaea. In this study, we cloned the gene cluster (phaEC(Hme)) encoding a polyhydroxyalkanoate (PHA) synthase in H. mediterranei CGMCC 1.2087 via thermal asymmetric interlaced PCR. Western blotting revealed that the phaE(Hme) and phaC(Hme) genes were constitutively expressed, and both the PhaE(Hme) and PhaC(Hme) proteins were strongly bound to the PHBV granules. Interestingly, CGMCC 1.2087 could synthesize PHBV in either nutrient-limited medium (supplemented with 1% starch) or nutrient-rich medium, up to 24 or 18% (wt/wt) in shaking flasks. Knockout of the phaEC(Hme) genes in CGMCC 1.2087 led to a complete loss of PHBV synthesis, and only complementation with the phaEC(Hme) genes together (but not either one alone) could restore to this mutant the capability for PHBV accumulation. The known haloarchaeal PhaC subunits are much longer at their C termini than their bacterial counterparts, and the C-terminal extension of PhaC(Hme) was proven to be indispensable for its function in vivo. Moreover, the mixture of purified PhaE(Hme)/PhaC(Hme) (1:1) showed significant activity of PHA synthase in vitro. Taken together, our results indicated that a novel member of the class III PHA synthases, composed of PhaC(Hme) and PhaE(Hme), accounted for the PHBV synthesis in H. mediterranei.
ESTHER : Lu_2008_J.Bacteriol_190_4173
PubMedSearch : Lu_2008_J.Bacteriol_190_4173
PubMedID: 18408025
Gene_locus related to this paper: halme-b3frm5

Title : Molecular characterization of the phaECHm genes, required for biosynthesis of poly(3-hydroxybutyrate) in the extremely halophilic archaeon Haloarcula marismortui - Han_2007_Appl.Environ.Microbiol_73_6058
Author(s) : Han J , Lu Q , Zhou L , Zhou J , Xiang H
Ref : Applied Environmental Microbiology , 73 :6058 , 2007
Abstract : Although many haloarchaea produce biodegradable polyhydroxyalkanoates (PHAs), the genes involved in PHA synthesis in the domain of Archaea have not yet been experimentally investigated yet. In this study, we revealed that Haloarcula marismortui was able to accumulate poly(3-hydroxybutyrate) (PHB) up to 21% of cellular dry weight when cultured in a minimal medium with excessive glucose and identified the phaE(Hm) and phaC(Hm) genes, probably encoding two subunits of a class III PHA synthase. These two genes were adjacent and directed by a single promoter located 26 bp upstream of the transcriptional start site and were constitutively expressed under both nutrient-rich and -limited conditions. Interestingly, PhaC(Hm) was revealed to be strongly bound with the PHB granules, but PhaE(Hm) seemed not to be. Introduction of either the phaE(Hm) or phaC(Hm) gene into Haloarcula hispanica, which harbors highly homologous phaEC(Hh) genes, could enhance the PHB synthesis in the recombinant strains, while coexpression of the both genes always generated the highest PHB yield. Significantly, knockout of the phaEC(Hh) genes in H. hispanica led to a complete loss of the PHA synthase activity. Complementation with phaEC(Hm) genes, but not a single one, restored the capability of PHB accumulation as well as the PHA synthase activity in this phaEC-deleted haloarchaeon. These results indicated that the phaEC genes are required for biosynthesis of PHB and might encode an active PHA synthase in the Haloarcula species.
ESTHER : Han_2007_Appl.Environ.Microbiol_73_6058
PubMedSearch : Han_2007_Appl.Environ.Microbiol_73_6058
PubMedID: 17675423
Gene_locus related to this paper: halma-q5uym0

Title : Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin - Li_2005_Proc.Natl.Acad.Sci.U.S.A_102_17816
Author(s) : Li X , Gutierrez DV , Hanson MG , Han J , Mark MD , Chiel H , Hegemann P , Landmesser LT , Herlitze S
Ref : Proc Natl Acad Sci U S A , 102 :17816 , 2005
Abstract : Techniques for fast noninvasive control of neuronal excitability will be of major importance for analyzing and understanding neuronal networks and animal behavior. To develop these tools we demonstrated that two light-activated signaling proteins, vertebrate rat rhodopsin 4 (RO4) and the green algae channelrhodospin 2 (ChR2), could be used to control neuronal excitability and modulate synaptic transmission. Vertebrate rhodopsin couples to the Gi/o, pertussis toxin-sensitive pathway to allow modulation of G protein-gated inward rectifying potassium channels and voltage-gated Ca2+ channels. Light-mediated activation of RO4 in cultured hippocampal neurons reduces neuronal firing within ms by hyperpolarization of the somato-dendritic membrane and when activated at presynaptic sites modulates synaptic transmission and paired-pulse facilitation. In contrast, somato-dendritic activation of ChR2 depolarizes neurons sufficiently to induce immediate action potentials, which precisely follow the ChR2 activation up to light stimulation frequencies of 20 Hz. To demonstrate that these constructs are useful for regulating network behavior in intact organisms, embryonic chick spinal cords were electroporated with either construct, allowing the frequency of episodes of spontaneous bursting activity, known to be important for motor circuit formation, to be precisely controlled. Thus light-activated vertebrate RO4 and green algae ChR2 allow the antagonistic control of neuronal function within ms to s in a precise, reversible, and noninvasive manner in cultured neurons and intact vertebrate spinal cords.
ESTHER : Li_2005_Proc.Natl.Acad.Sci.U.S.A_102_17816
PubMedSearch : Li_2005_Proc.Natl.Acad.Sci.U.S.A_102_17816
PubMedID: 16306259

Title : Effects of organophosphorous pesticides used in china on various mammalian cells - Isoda_2005_Environ.Sci_12_9
Author(s) : Isoda H , Talorete TP , Han J , Oka S , Abe Y , Inamori Y
Ref : Environ Sci , 12 :9 , 2005
Abstract : Organophosphorous pesticides are currently widely used in China to help boost agricultural production. However, these pesticides pose various threats to organisms, including humans, and are thus a cause of concern. Five organophosphorous pesticides, monocrotophos, omethoate, parathion-methyl, phoxim and dichlorvos, were examined for their effects on mammalian cell lines to determine their potential impact on physiological functions in vivo. Results show an increased proliferation of MCF-7 cells treated with 0.2 microM monocrotophos or 0.4 microM omethoate, suggesting that these compounds can induce breast cancer cell proliferation at relatively low concentrations. Murine primary spleen cells markedly decreased in number starting at a pesticide concentration of 0.01 microM; no cytotoxicity was observed below 0.001 microM. BALB/c3T3 murine fibroblasts treated with 0.25 microM monocrotophos showed enhanced DNA synthesis, while those treated with the other pesticides showed results similar to that of the control. The different pesticides reduced the acetylcholinesterase (AChE) activity of the rat neuronal cell line PC12 in a dose-dependent manner up to 100 microM. Parathion-methyl and phoxim showed acute toxicity at 0.01 microM. Finally, phoxim and parathion-methyl significantly reduced the transepithelial electrical resistance (TEER) of human intestinal Caco-2 cells, indicating that these pesticides can disrupt the tight-junction permeability of cell monolayers. These in vitro assays, which are rapid, reproducible, simple and inexpensive, clearly show the effects of organophosphorous pesticides on mammalian cells and suggest the potential impact of these pesticides on organisms in vivo.
ESTHER : Isoda_2005_Environ.Sci_12_9
PubMedSearch : Isoda_2005_Environ.Sci_12_9
PubMedID: 15793557