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Cosmc和T-合酶在黏蛋白型O-聚糖合成中的重要作用及其与人类疾病的相关性

第八届全国复合糖生物化学与分子生物学学术会议

作者： richard d.cummings department of Biochemistry & Molecular Biology and Oklahoma Center for Medical Glycobiology University of Oklahoma Health Sciences Center Oklahoma CityOK 73104U.S.A.

The mucin type O-glycans in human glycoprotein and mucins are important in many aspects of biologicalprocess,including in leukocyte *** biosynthesis of mucin type O-glycan is orchestrated by s set ofN-acetylgalactosaminyltransferases that transfer GalNAc to specific Ser/Thr residues to generate the struc-ture GalNAC-α1-Ser/Ther,also known as the Tn ***,this precursor is acted upon by thecore 1 b3-galactosyltransferase(Core 1 β3-Gal-T.T-synthase)to generate the core 1 O-glycan Galβ1-

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生命科学 2011年第7期23卷 630-642页

作者：巨同忠 richard d.cummings 靳嘉巍查锡良埃莫里大学医学院生物化学系复旦大学上海医学院生物化学与分子生物学系

从核心1结构(Galβ1,3GalNAcα1-O-Ser/Thr,core 1 structure,T antigen)中衍生出来的黏蛋白型O-聚糖在很多生理过程中发挥重要的生物学功能。T-合酶(core 1β3-galactosyltransferase,T-synthase)是合成核心1结构的唯一糖基转移酶,它主要的功能是将半乳糖(Galactose)添加到GalNAcα1-Ser/Thr(Tn抗原)糖链上。但是在人体和其他脊椎动物中有活性的T-合酶的形成需要一个重要的伴侣分子Cosmc;Cosmc功能丧失将直接导致T-合酶失活,其结果是机体细胞只能合成Tn抗原以及唾液酰化Tn(sialylTn,STn,Neu5Acα2,6GalNAcα1-O-Ser/Thr)。综述目前对T-合酶和Cosmc的研究以及在人类疾病(如异常O-聚糖表达相关的Tn综合征、IgA肾病和肿瘤)发生发展中的作用。

关键词： O-聚糖 T-合酶分子伴侣 Cosmc Tn抗原

Regulation of Mucin-type O-Glycan Biosynthesis Through the Cosmc and T-synthase—Implications in Human diseases

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Regulation of Mucin-type O-Glycan Biosynthesis Through the C...

determining minimum sample size for the conditioned Latin hypercube sampling algorithm

21st IUBMB and 12th FAOBMB International Congress of Biochemistry and Molecular Biology

作者： Tongzhong Ju Yingchun Wang Xiaokun ding Rajindra P.Aryal Wenyl Wang Caleb J.Stowell richard d.cummings department of Biochemistry Emory University School of MedicineAtlantaGA 30322USA

＜正＞The T-synthase（core 1 3-galactosyltransferase） is a glycosyl transferase responsible for converting GalNAcl-Ser/Thr（Tn antigen） to ***1- Ser/Thr（core 1 structure,T antigen）,which is a precursor for many mucin type O-glycans on animal *** of T-synthase in mice results in embryonic lethality due to impaired ***,

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Pedosphere 2024年第3期34卷 530-539页

作者： daniel d.SAURETTE Asim BISWAS richard J.HECK Adam W.GILLESPIE Aaron A.BERG School of Environmental Sciences University of Guelph50 Stone Rd EastGuelph ON N1G 2W1(Canada) Ontario Ministry of Agriculture Food and Rural Affairs1 Stone Rd WestGuelph ON N1G 2Y4(Canada) Geography Environment&GeomaticsUniversity of Guelph50 Stone Rd EastGuelph ON N1G 2W1(Canada)

In digital soil mapping(dSM),a fundamental assumption is that the spatial variability of the target variable can be explained by the predictors or environmental *** to adequately sample the predictors have been well documented,with the conditioned Latin hypercube sampling(cLHS)algorithm receiving the most attention in the dSM *** advances in sampling design,a critical gap remains in determining the number of samples required for dSM *** propose a simple workflow and function coded in R language to determine the minimum sample size for the cLHS algorithm based on histograms of the predictor variables using the Freedman-diaconis rule for determining optimal bin *** preprocessing was included to correct for multimodal and non-normally distributed data,as these can affect sample size determination from the *** on a user-selected quantile range(QR)for the sample plan,the densities of the histogram bins at the upper and lower bounds of the QR were used as a scaling factor to determine minimum sample *** technique was applied to a field-scale set of environmental covariates for a well-sampled agricultural study site near Guelph,Ontario,Canada,and tested across a range of *** results showed increasing minimum sample size with an increase in the QR *** sample size increased from 44 to 83 when the QR increased from 50% to 95% and then increased exponentially to 194 for the 99%*** technique provides an estimate of minimum sample size that can be used as an input to the cLHS algorithm.

关键词： bin width digital soil mapping normal distribution quantile range sampling design

New analytical modelling of fractional generalized Kuramoto-Sivashinky equation via Atangana-Baleanu operator and J-transform method

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Journal of Ocean Engineering and Science 2024年第1期9卷 66-88页

作者： Metonou richard Weidong Zhao Shehu Maitama School of Mathematics Shandong UniversityJinanShandongChina

In this paper,we propose a new analytical modelling of the well-known fractional generalized Kuramoto-Sivashinky equation(FGKSE)using fractional operator with non-singular kernel and the homotopy anal-ysis transform method via J-transform ***,using fixed-point theorem,we prove the existence and uniqueness of our proposed solution to the fractional Kuramoto-Sivashinky *** further val-idate the efficiency of the suggested technique,we proved the convergence analysis of the method and provide the error *** obtained solutions of the FGKSE,describing turbulence processes in the field of ocean engineering are analytically and numerically compared to show the behaviors of many parameters of the present model.

关键词： Homotopy analysis J-transform method J-transform method Fractional generalized Kuramoto-Sivashinky equation Fixed-point theorem Numeric-symbolic computation

Conservation genomic investigation of an endangered conifer,Thuja sutchuenensis,reveals low genetic diversity but also low genetic load

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Plant diversity 2024年第1期46卷 78-90页

作者： Tongzhou Tao richard IMilne Jialiang Li Heng Yang Shiyang Wang Sihan Chen Kangshan Mao Key Laboratory for Bio-Resource and Eco-Environment of Ministry of Education&Sichuan Zoige Alpine Wetland Ecosystem National Observation and Research Station College of Life ScienceSichuan UniversityChengduChina Institute of Molecular Plant Science School of Biological ScienceUniversity of EdinburghEdinburgh EH93BFUK College of Science Tibet UniversityLhasa 850000Xizang Autonomous RegionPR China

Endangered species generally have small populations with low genetic diversity and a high genetic *** sutchuenensis is an endangered conifer endemic to southwestern *** was once considered extinct in the wild,but in 1999 was ***,little is known about its genetic *** collected 67 individuals from five wild,isolated *** populations,and used 636,151 SNPs to analyze the level of genetic diversity and genetic load in *** to delineate the conservation units of ***,based on whole transcriptome sequencing data,as well as target capture sequencing *** found that populations of *** could be divided into three *** groups had low levels genetic diversity and were moderately genetically *** findings also indicate that *** suffered two severe bottlenecks around the Last Glaciation Period and Last Glacial *** Thuja species,*** presented the lowest genetic load and hence might have purged deleterious mutations efficiently through purifying ***,distribution of fitness effects analysis indicated a high extinction risk for *** lines of evidence identified three management units for *** *** possesses a low genetic load,low genetic diversity,suboptimal fitness,and anthropogenic pressures all present an extinction risk for this rare *** might also hold true for many endangered plant species in the mountains all over the world.

关键词： Sichuan Arborvitae Genetic load deleterious mutations demographic history Conservation genomics

Preclinical and clinical evidence of the association of colibactinproducing Escherichia coli with anxiety and depression in colon cancer

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World Journal of Gastroenterology 2024年第21期30卷 2817-2826页

作者： Fabien Rondepierre Maëva Meynier Johan Gagniere Vincent deneuvy Anissa deneuvy Gwenaelle Roche Elodie Baudu Bruno Pereira richard Bonnet Nicolas Barnich Frédéric Antonio Carvalho denis Pezet Mathilde Bonnet Isabelle Jalenques Service de Psychiatrie de l’Adulte A et Psychologie Médicale CHU Clermont-FerrandClermont-Ferrand 63000France M2iSH UMR 1071INSERMUniversity of Clermont AuvergneINRAE USC 1382Clermont-Ferrand 63001France Neurodol UMR 1107INSERMUniversity of Clermont AuvergneClermont-Ferrand 63001France department of digestive Surgery CHU de Clermont-FerrandClermont-Ferrand 63001France Biostatistics Unit Department of Clinical Research and InnovationCHU Clermont-FerrandClermont-Ferrand 63000France department of Bacteriology CHU de Clermont-FerrandClermont-Ferrand 63001France UniversitéClermont Auvergne INPCNRSClermont Auvergne Institut PascalClermont-Ferrand 63000France

BACKGROUNd The association between the intestinal microbiota and psychiatric disorders is becoming increasingly *** gut microbiota contributes to colorectal carcinogenesis(CRC),as demonstrated with colibactin-producing Escherichia coli(CoPEC).AIM To evaluate the association between CoPEC prevalence and anxiety-and depressive-like behaviors with both preclinical and clinical *** Patients followed after a CRC surgery and for whom the prevalence of CoPEC has been investigated underwent a psychiatric *** were compared according to the CoPEC *** parallel C57BL6/J wild type mice and mice with a CRC susceptibility were chronically infected with a CoPEC *** behavior was assessed using the Elevated Plus Maze test,the Forced Swimming Test and the Behavior recognition system PhenoTyper®.RESULTS In a limited cohort,all patients with CoPEC colonization presented with psychiatric disorders several years before cancer diagnosis,whereas only one patient(17%)without CoPEC *** result was confirmed in C57BL6/J wildtype mice and in a CRC susceptibility mouse model(adenomatous polyposis colimultiple intestinal neoplasia/+).Mice exhibited a significant increase in anxiety-and depressive-like behaviors after chronic infection with a CoPEC *** This finding provides the first evidence that CoPEC infection can induce microbiota-gut-brain axis disturbances in addition to its procarcinogenic properties.

关键词： Colorectal cancer Colibactin Escherichia coli Colibactin-producing Escherichia coli Inflammation Anxiety depression Behavior

A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 46-54页

作者： Pin Zhang Lin Wang Yueying Zhen Zhihong Wang Hesheng Zhang richard Jones Binghe Xu department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Tianjin Hemay Pharmaceutical Co. LTDTianjin 300308China

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer ***: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg Qd and 300 mg BId. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day *** samples were obtained on d 1 and d 28. Clinical responses were assessed every eight ***: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(dCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 ***: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).

关键词： Advanced breast cancer HER2-positive Hemay022 first-in-human trial

Are there sex-based disparities in cataract surgery?

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 137-143页

作者： Matthew d.Geiger Anne M.Lynch Alan G.Palestine Nathan C.Grove Karen L.Christopher richard S.davidson Michael J.Taravella Naresh Mandava Jennifer L.Patnaik department of Ophthalmology University of Colorado School of MedicineAuroraCO 80045USA

AIM:To investigate sex-based differences in the occurrence of intra-operative and post-operative complications and associated visual outcomes following cataract ***:This was a retrospective study of patients who had phacoemulsification cataract surgery at the University of Colorado School of *** collected included the patient’s health history,ocular comorbidities,operative and post-operative complications,and the post-operative best corrected visual acuity(BCVA).The data were analyzed using univariate and multivariable logistic regression with generalized estimating equations to account for the correlation of some patients having two eyes included in the ***:A total of 11977 eyes from 7253 patients were included in the *** comorbidities differed by sex,with males having significantly higher percentages of traumatic cataracts(males 0.7%vs females 0.1%),prior ocular surgery(6.7%vs 5.5%),and mature cataracts(2.8%vs 1.9%).Conversely,females had significantly higher rates of pseudoexfoliation(2.0%vs 3.2%).In unadjusted analysis,males had higher rates of posterior capsular rupture(0.8%vs 0.4%)and vitreous loss(1.0%vs 0.6%),but this difference was not significant after adjustment for *** had a significantly increased risk of post-operative retinal detachment,but in multivariable analysis this was no longer *** were significantly less likely to undergo post-operative neodymium-doped yttrium aluminum garnet(Nd:YAG)laser capsulotomy for posterior capsule opacification(OR=0.8,95%CI=0.7-0.9,P=0.0005).The BCVA was slightly worse for males pre-operatively;but post-operatively,both sexes exhibited similar visual acuity of Snellen equivalent 20/***:The study finds that in a cohort of patients presenting for cataract surgery,sex differences exist in pre-operative comorbidities and surgical characteristics that contribute to higher rates of some complications for ***,observed surgical complicatio

关键词： cataract surgery sex-based disparity phacoemulsification outcomes