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2008北京国际生理科学学术大会

作者： ALLEn David G WHITEHEAD nicholas P GERVASIO Othon L Bosch Institute and School of Medical Sciences University of Sydney F13NSW 2006Australia

Duchenne muscular dystrophy(DMD)causes severe damage and atrophy in skeletal muscle and a dilated cardiomyopathy in the *** disease is caused by absence of the cytoskeletal protein,*** mdx mouse also lacks dystrophin and is a model of *** with the absence of dystrophin,the disease is characterized by reduced levels of all the dystrophin-associated proteins includingβ-dystroglycan and nnOS(neuronal nitric oxide synthase)and increased levels of CAV3(caveolin 3,a scaffolding protein for muscle caveolae),TRPC1 (a candidate protein for the stretch-activated channel found in muscle),src kinase(a ubiquitous tyrosine kinase) and various sub-units of nADPH oxidase(a superoxide producing enzyme present in muscle).All of the above proteins are found in the *** studies of the mdx mouse found that a stretch-activated channel(SAC) was activated and we showed that blocking this channel(with Gd or streptomycin or GsMTx-4)lowered stretchinduced intracellular Caand reduced muscle damage(Yeung et al.2005).Subsequently we have found that the activation of SACs and the resulting Caentry can be caused by reactive oxygen species(ROS)(Gervasio et al., 2008).Furthermore,scavenging ROS can reduce the rise of intracellular Cain isolated mdx muscles(Gervasio et al.,2008)and the ROS scavenger,n-acetylcysteine,reduced the skeletal and cardiac muscle damage in intact mdx mice(Whitehead et al.,2008,Williams and Allen,2007).ROS also activated src kinase and blocked src kinase with PP2 reduced ROS-induced Caentry in a cell line expressing TRPC1 and CAV3 and reduced stretch-induced muscle damage in isolated mdx muscles(Gervasio et al.,2008).Our current working hypothesis is that abnormalities in the caveolae and associated proteins lead to increased ROS production which triggers a range of damage pathways in mdx muscle.A clearer understanding of the damage pathways may lead to therapeutic interventions that could reduce the severity of muscle and cardiac damage in

关键词： calcium muscular dystrophy reactive oxygen species damage pathnys

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Foregut bypass *** bariatric procedures for nonalcoholic fatty liver disease:a meta-analysis of 3,355 individuals

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Hepatobiliary Surgery and nutrition 2023年第5期12卷 658-670,I0001-I0003页

作者： Wen Hui Lim Snow Yunni Lin Cheng Han ng Darren Jun Hao Tan Jieling Xiao Jie ning Yong Phoebe Wen Lin Tay nicholas Syn Yip Han Chin Kai En Chan Chin Meng Khoo nicholas Chew Roger S.Y.Foo Asim Shabbir Eunice X.Tan Daniel Q.Huang Mazen noureddin Arun J.Sanyal Mohammad Shadab Siddiqui Mark D.Muthiah Yong Loo Lin School of Medicine National University of SingaporeSingaporeSingapore Division of Endocrinology Department of MedicineNational University HospitalSingaporeSingapore Department of Cardiology National University Heart CentreNational University HospitalSingaporeSingapore Division of General Surgery(Upper Gastrointestinal Surgery) Department of SurgeryNational University HospitalSingaporeSingapore Division of Gastroenterology and Hepatology Department of MedicineNational University HospitalSingaporeSingapore national University Centre for Organ Transplantation National University Health SystemSingaporeSingapore Cedars-Sinai Fatty Liver Program Division of Digestive and Liver DiseasesDepartment of MedicineComprehensive Transplant CenterCedars-Sinai Medical CentreLos AngelesCAUSA Division of Gastroenterology Hepatology and NutritionDepartment of Internal MedicineVirginia Commonwealth UniversityRichmondVAUSA

Background:Bariatric surgery represents an important treatment option for severely obese patients with nonalcoholic fatty liver disease(nAFLD).However,there remains inadequate data regarding the effects of different bariatric procedures on various nAFLD parameters,especially for histological ***,this meta-analysis aimed to compare the effects of restrictive bariatric procedures and foregut bypass on the metabolic,biochemical,and histological parameters for patients with ***:Medline and Embase were searched for articles relating to bariatric procedures and *** meta-analysis was conducted to compare efficacy of bariatric procedures ***-procedure with subgroup analysis to further compare restrictive against foregut bypass ***:Thirty-one articles involving 3,355 patients who underwent restrictive bariatric procedures(n=1,460)and foregut bypass(n=1,895)were *** foregut bypass(Pnd restrictive procedures(P=0.03)significantly increased odds of fibrosis *** to restrictive procedures,foregut bypass resulted in a borderline non-significant decrease in fibrosis score(P=0.06)and significantly lower steatosis score(Pnificantly lowered body mass index(P=0.003)and low-density lipoprotein(P=0.008)compared to restrictive *** significant differences were observed between both procedures for aspartate aminotransferase(P=0.17)and alkaline phosphatase(P=0.61).However,foregut bypass resulted in significantly lower gamma-glutamyl transferase than restrictive procedures(P=0.01)while restrictive procedures resulted in significantly lower alanine transaminase than foregut bypass(P=0.02).Conclusions:The significant histological and metabolic advantages and comparable improvements in biochemical outcomes support the choice of foregut bypass over restrictive bariatric procedures in nAFLD management.

关键词： Bariatric surgery non-alcoholic fatty liver disease(nAFLD) obesity fibrosis endoscopy

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Establish an allele-specific real-time PCR for Leishmania species identification

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Infectious Diseases of Poverty 2022年第3期11卷 91-91页

作者： Yun Wu Mengyuan Jiang Shaogang Li nicholas R.Waterfield Guowei Yang Beijing Institute of Tropical Medicine Beijing Friendship HospitalCapital Medical University95 Yong’an RoadXi Cheng DistrictBeijing100050China 不详

Background:Leishmaniasis is a serious neglected tropical disease that may lead to life-threatening outcome, which species are closely related to clinical diagnosis and patient management. The current Leishmania species determination method is not appropriate for clinical application. new Leishmania species identification tool is needed using clinical samples directly without isolation and cultivation of ***:A probe-based allele-specific real-time PCR assay was established for Leishmania species identification between Leishmania donovani and L. infantum for visceral leishmaniasis (VL) and among L. major, L. tropica and L. donovani/L. infantum for cutaneous leishmaniasis (CL), targeting hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and spermidine synthase (SPDSYn) gene with their species-specific single nucleotide polymorphisms (SnPs). The limit of detection of this assay was evaluated based on 8 repeated tests with intra-assay standard deviation nd inter-assay coefficients of variability nA samples obtained from Plasmodium falciparum, Toxoplasma gondii, Brucella melitensis and Orientia tsutsugamushi. Total 42 clinical specimens were used to evaluate the ability of this assay for Leishmania species identification. The phylogenetic tree was constructed using HGPRT and SPDSYn gene fragments to validate the performance of this ***:This new method was able to detect 3 and 12 parasites/reaction for VL and CL respectively, and exhibited no cross-reaction with P. falciparum, T. gondii, B. melitensis, O. tsutsugamushi and non-target species of Leishmania. Twenty-two samples from VL patients were identified as L. donovani (n = 3) and L. infantum (n = 19), and 20 specimens from CL patients were identified as L. major (n = 20), providing an agreement of 100% compared with sequencing results. For further validation, 29 sequences of HGPRT fragment from nine Leishmania species and 22 seque

关键词： Leishmania Species identification Allele-specific real-time PCR SnPs

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neither autophagy nor exercise training mode affect exercise-induced beneficial adaptations in high fat-fed mice

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Sports Medicine and Health Science 2020年第1期2卷 44-53页

作者： Megan E.Rosa-Caldwell Lisa T.Jansen Seongkyun Lim Kirsten R.Dunlap Wesley S.Haynie Tyrone A.Washington nicholas P.Greene Integrative Muscle Metabolism Laboratory Exercise Science Research CenterDepartment of Human Health Performance and RecreationUniversity of ArkansasUSA Exercise Muscle Biology Laboratory Exercise Science Research CenterDepartment of Human Health Performance and RecreationUniversity of ArkansasUSA

Exercise mitigates obesity-associated pathologies;however,there is controversy regarding optimal exercise ***,is known to decrease during obesity and is an important moderator for exercise ***:To investigate individual and combined effects of different exercise interventions and autophagy inhibition on exercise adaptations during ***:C57BL/6J mice initiated 45%high fat diet at 8 weeks of *** 6 weeks of diet,animals were divided into moderate(MOD)or high intensity interval training interventions(HIIT),animals were further divided into autophagy inhibition or vehicle conditions(n=10/group).Animals exercised and autophagy was inhibited 3X/week by nSC185058 injections,thereby blocking autophagosome *** continued for 4 ***:High fat diet impaired glucose handling~17%;exercise interventions normalized glucoregulation to prehigh fat diet levels,without differences between any *** fat diet induced~25%decrease in aerobic capacity,which returned to baseline after exercise interventions,with no differences between any *** effects of autophagy inhibition were ***:HIIT and MOD training confer similar health-related adaptations.

关键词： Insulin resistance Exercise capacity Glucose tolerance Obesity

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Cryo-EM structure of the plant 26S proteasome

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Plant Communications 2022年第3期3卷 116-126页

作者： Susanne Kandolf Irina Grishkovskaya Katarina Belacic Derek L.Bolhuis Sascha Amann Brent Foster Richard Imre Karl Mechtler Alexander Schleiffer Hemant D.Tagare Ellen D.Zhong Anton Meinhart nicholas G.Brown David Haselbach Research Institute of Molecular Pathology(IMP) Vienna BioCenter(VBC)Campus-Vienna-BioCenter 11030 ViennaAustria Department of Radiology and Biomedical Imaging Yale UniversityNew HavenCT 06510USA Department of Pharmacology and Lineberger Comprehensive Cancer Center University of North Carolina School of MedicineChapel HillNC 27599USA Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of TechnologyCambridgeMA 02139USA Vienna BioCenter PhD Program Doctoral School of the University at Vienna and Medical University of ViennaVienna BioCenter(VBC)ViennaAustria Institute of Physical Chemistry University of FreiburgAlbertstraße 21Freiburg 79104Germany CIBSS Centre for Integrative Biological Signalling Studies University of FreiburgFreiburgGermany

Targeted proteolysis is a hallmark of *** is especially important in long-lived cells that can be found in higher eukaryotes,like *** task is mainly fulfilled by the ubiquitin–proteasome ***,proteolysis by the 26S proteasome is vital to development,immunity,and cell *** the yeast and animal proteasomes are well characterized,there is only limited information on the plant *** determined the first plant 26S proteasome structure from Spinacia oleracea by single-particle electron cryogenic microscopy at an overall resolution of 3.3 A°.We found an almost identical overall architecture of the spinach proteasome compared with the known structures from mammals and ***,we noticed a structural difference in the proteolytic active b1 ***,we uncovered an unseen compression state by characterizing the proteasome’s conformational *** suspect that this new conformation of the 20S core protease,in correlation with a partial opening of the unoccupied gate,may contribute to peptide release after *** data provide a structural basis for the plant proteasome,which is crucial for further studies.

关键词： 26S proteasome spinach UPS cryo-EM conformational landscape

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Effect of preoperative biliary drainage on outcome of classical pancreaticoduodenectomy

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World Journal of Gastroenterology 2007年第8期13卷 1240-1242页

作者： Chandra Shekhar Bhati Chandrashekhar Kubal Pankaj Kumar Sihag Ankur Atal Gupta Raj Kamal Jenav nicholas G Inston Jagdish M Mehta Upgraded Department of Surgery SMS Medical CollegeJaipurIndia Liver UnitQueen Elizabeth Hospital Birmingham United Kingdom Liver Unit Queen Elizabeth Hospital Birmingham United Kingdom Upgraded Department of Surgery SMS Medical CollegeJaipurIndia

AIM: To investigate the role of preoperative biliary drainage (PBD) in the outcome of classical pancreaticodu odenectomy. METHODS: A 10-year retrospective data analysis was performed on patients (n = 48) undergoing pancreaticoduodenectomy from March 1994 to March 2004 in department of surgery at SMS medical college, Jaipur, India. Demographic variables, details of preoperative stenting, operative procedure and post operative complications were noted. RESULTS: Preoperative biliary drainage was performed in 21 patients (43.5%). The incidence of septic complications was significantly higher in patients with biliary stent placement (P nts also had a significantly higher minor biliary leak rate. Mortality and hospital stay in each group was comparable. COnCLUSIOn: Within this study population the use of PBD by endoscopic stenting was associated with a high incidence of infective complications. These findings do not support the routine use of biliary stenting in patients prior to pancreatico-duodenectomy.

关键词： Whipple's operation Preoperative stenting Sepsis Preoperative biliary drainage

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Quantification of the expression of chitinolytic enzyme encoding genes ech30, ech42 and nag1 in Trichoderma atroviride P1 under varying growth conditions using a real-time RT-PCR assay

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浙江大学学报（农业与生命科学版） 2004年第4期30卷 428-428页

作者： Jihong Liu Clarke Arne Tronsmo nicholas Clarkel Sonja Sletner Klemsdal The norwegian Crop Research Institute Plant Protection Centre HФgskoleveien 7 N-1432s Norway Department of Chemistry Biotechnology and Food Science Agricultural University of Norway N-1432 s NorwayThe Norwegian Forest Research Institute HФgskoleveien 12 N-1432 s NorwayThe Norwegian Forest Research Institute HФgskoleveien 12 N-1432 s Norway

The quantitative expression and the regulation of chitinase-encoding genes ech30, ech42 and nag1 in Trichoderma atroviride P1 under varying growth conditions were investigated using real-time RT-PCR, principle component and multivariate analyses. Twelve media combinations including 0.1% and 3% glucose as carbon source and no (0 mmol/L), low (10 mmol/L) and high (100 mmol/L) ammonium acetate as nitrogen source combined with or without colloidal chitin at 3 time intervals and 2 replications were applied to current study. The real-time RT-PCR analysis showed that the expression of ech30, ech42 and nag1 was regulated by the interaction of nitrogen, glucose and chitin under different growth conditions. The highest and earliest expressions of ech30 were induced by glucose and nitrogen starvation i.e. 0.1% glucose and 10 mmol/L ammonium acetate in the growth media. This was also the case for ech42 and nag1 but at a relatively low level. In contrast, high (3%) glucose and high (100 mmol/L) ammonium acetate concentrations repressed the expression of all the genes studied. These results were confirmed by principle component and multivariate analyses. The effect of chitin on ech30, ech42 and nag1 expression varied depending on the concentrations of glucose and ammonium acetate.

关键词：酶基因表达生长条件 RT-PCR 木霉属真菌

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Experimental models to study cholangiocyte biology

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World Journal of Gastroenterology 2002年第1期8卷 1-4页

作者： Pamela S.Tietz Robert C.Huebert Anatoliy Masyuk Tatyana Masyuk Patrick L.Splinter nicholas F.LaRusso Center for Basic Research in Digestive Diseases Department of Internal Medicine and Biochemistry and Molecular BiologyMayo Medical SchoolClinic and FoundationRochesterMN 55905

Cholangiocytes-the epithelial cells which line the bileducts-are increasingly recognized as importanttransporting epithelia actively involved in the absorptionand secretion of water,ions,and *** is due in part to the recent development ofnew experimental *** biologic concepts haveemerged including the identification and topography ofreceptors and flux proteins on the apical and/orbasolateral membrane which are involved in the molecularmechanisms of ductal bile *** isolatedand/or perfused bile duct units from livers of rats andmice serve as new,physiologically relevant in vitromodels to study cholangiocyte *** treedimensions and novel insights into anatomic remodeling ofproliferating bile ducts have emerged from three-dimensional reconstruction using CT scanning andsophisticated ***,new pathologicconcepts have arisen regarding the interaction ofcholangiocytes with pathogens such as *** concepts and associated methodologiesmay provide the framework to develop new therapies forthe cholangiopathies,a group of important hepatobiliarydiseases in which cholangiocytes are the target cell.

关键词： Animals Bile Ducts Biological Transport Epithelial Cells Research Support, non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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大脑可能还在进化(英文)

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大学英语 2005年第11期 10-12页

作者： nicholas Wade 刘学诚广东医学院

Two genes involved in determining the size of the human brain have undergone substantial1 evolution2 in the last 60,000years, researchers say, leading to the surprising suggestion that the brain is still undergoing ra... 详细信息

关键词：高校大学英语科技文阅读注释读物

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Investigational growth factors utilized in animal models of spinal fusion: Systematic review

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World Journal of Orthopedics 2019年第4期10卷 176-191页

作者： Ethan Cottrill A Karim Ahmed noah Lessing Zachary Pennington Wataru Ishida Alexander Perdomo-Pantoja Sheng-fu Lo Elizabeth Howell Christina Holmes C Rory Goodwin nicholas Theodore Daniel M Sciubba Timothy F Witham Department of neurosurgery The Johns Hopkins Hospital Department of neurosurgery Duke University Medical Center

BACKGROUnD Over 400000 Americans annually undergo spinal fusion surgeries, yet up to 40%of these procedures result in pseudoarthrosis even with iliac crest autograft, the current "gold standard" treatment. Tissue engineering has the potential to solve this problem via the creation of bone grafts involving bone-promoting growth factors(e.g., bone morphogenetic protein 2). A broad assessment of experimental growth factors is important to inform future work and clinical potential in this area. To date, however, no study has systematically reviewed the investigational growth factors utilized in preclinical animal models of spinal *** To review all published studies assessing investigational growth factors for spinal fusion in animal models and identify promising agents for *** We conducted a systematic review of the literature using PubMed, Embase,Cochrane Library, and Web of Science databases with searches run on May 29 th,2018. The search query was designed to include all non-human, preclinical animal models of spinal fusion reported in the literature without a timespan limit. Extracted data for each model included surgical approach, level of fusion,animal species and breed, animal age and sex, and any other relevant characteristics. The dosages/sizes of all implant materials, spinal fusion rates,and follow-up time points were recorded. The data were analyzed and the results reported in tables and text. PRISMA guidelines were followed for this systematic *** Twenty-six articles were included in this study, comprising 14 experimental growth factors: AB204(n = 1); angiopoietin 1(n = 1); calcitonin(n = 3);erythropoietin(n = 1); basic fibroblast growth factor(n = 1); growth differentiation factor 5(n = 4), combined insulin-like growth factor 1 +transforming growth factor beta(n = 4); insulin(n = 1); nELL-1(n = 5); noggin(n= 1); P-15(n = 1); peptide B2 A(n = 2); and secreted phosphoprotein 24(n = 1).The fusion rates of the current gold sta

关键词： Spinal fusion Growth factor Pseudoarthrosis Systematic review

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