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Evolocumab in Pediatric Heterozygous Familial Hypercholesterolemia

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四川生理科学杂志 2021年第1期43卷 114-114页

作者： Raul D Santos From the Lipid Clinic Heart Institute University of São Paulo Medical School Hospital and Hospital Israelita Albert Einstein São Paulo (R.D.S.) Amgen Thousand Oaks CA (A.R. C.E.K A.H.) the Departments of Vascular Medicine (G.K.H. J.J.P.K.) and Pediatrics (A.W. I.L.) Amsterdam UMC Amsterdam the Cardiology Department Geneva University Hospital Geneva (F.M.) the Biostatistics Department Amgen Cambridge (I.B.) and the Department of Clinical Inherited Metabolic Disorders Birmingham Children’s Hospital Birmingham (S.S.) — both in the United Kingdom the Rare Diseases and Clinical genetics Unit Academic Pediatric Department Bambino Gesù Children’s Hospital (A.B.) and the Department of Molecular Medicine Umberto I Hospital Sapienza University of Rome (C.S.) Rome the Lipid Clinic Department of Medicine Centre Hospitalier Universitaire de Québec-Université Laval Quebec (J.B.) and the Clinical Lipidology and Rare Lipid Disorders Unit Community Genomic Medicine Centre and ECOGENE-21 Department of Medicine Université de Montréal Chicoutimi QC (D.G.) — both in Canada the 2nd Department of Pediatrics Semmelweis University Budapest Hungary (T.S.) the Department of Internal Medicine Centres Hospitaliers Jolimont La Louvière Belgium (O.S.D.) and the Division of Pediatric Pulmonology Allergology and Endocrinology Department of Pediatrics and Adolescent Medicine Medical University of Vienna Vienna (S.G.-P.).

Background:Evolocumab,a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9,is widely used in adult patients to lower low-density lipoprotein(LDL)cholesterol *** effects in pediatric patients with heterozygous familial hypercholesterolemia are not ***:We conducted a 24-week,randomized,double-blind,placebo-controlled trial to evaluate the efficacy and safety of evolocumab in pediatric patients with heterozygous familial *** 10 to 17 years of age who had received stable lipid-lowering treatment for at least 4 weeks before screening and who had an LDL cholesterol level of 130 mg per deciliter(3.4 mmol per liter)or more and a triglyceride level of 400 mg per deciliter(4.5 mmol per liter)or less were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab(420 mg)or *** primary end point was the percent change in LDL cholesterol level from baseline to week 24;key secondary end points were the mean percent change in LDL cholesterol level from baseline to weeks 22 and 24 and the absolute change in LDL cholesterol level from baseline to week 24.

关键词： cholesterol Evolocumab lipoprotein

Phased,chromosome-scale genome assemblies of tetraploid potato reveal a complex genome,transcriptome,and predicted proteome landscape underpinning genetic diversity

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Molecular Plant 2022年第3期15卷 520-536页

作者： Genevieve Hoopes Xiaoxi Meng John P.Hamilton Sai Reddy Achakkagari Fernanda de Alves Freitas Guesdes Marie E.Bolger Joseph J.Coombs Danny Esselink Natalie R.Kaiser Linda Kodde Maria Kyriakidou Brian Lavrijssen Natascha van Lieshout Rachel Shereda Heather K.Tuttle Brieanne Vaillancourt Joshua C.Wood Jan Mde Boer Nolan Bornowski Peter Bourke David Douches Herman Jvan Eck Dave Ellis Max J.Feldman Kyle M.Gardner Johannes C.P.Hopman Jiming Jiang Walter S.De Jong Joseph C.Kuhl Richard G.Novy Stan Oome Vidyasagar Sathuvalli Ek Han Tan Remco A.Ursum M.Isabel Vales Kelly Vining Richard G.F.Visser Jack Vossen G.Craig Yencho Noelle L.Anglin Christian W.B.Bachem Jeffrey B.Endelman Laura M.Shannon Martina V.Stromvik Helen H.Tai Bjorn Usadel C.Robin Buell Richard Finkers Department of Plant biology Michigan State UniversityEast LansingMI 48824USA Department of Horticultural Science University of MinnesotaSt.PaulMN 55108USA Department of Plant Science McGill UniversitySainte-Anne-de-BellevueQC H9X 3V9Canada Plant Breeding Wageningen University&ResearchPlant Breeding6708 PB Wageningenthe Netherlands IBG-4 Bioinformatics Forschungszentrum JülichWilhelm Johnen Str52428 JülichGermany Department of Plant Soiland Microbial SciencesMichigan State UniversityEast LansingMI 48824USA Bayer Crop Science WoodlandCA 95695USA Averis Seeds B.V. 9640 AA Veendamthe Netherlands International Potato Center 1895 Avenida La MolinaLimaPeru USDA-ARS ProsserWA 99350USA Agriculture and Agri-Food Canada Fredericton Research and Development Centre FrederictonNB E3B 4Z7Canada School of Integrative Plant Science Cornell UniversityIthacaNY 14853-1901USA Department of Plant Sciences University of IdahoMoscowID 83844USA USDA-ARS Small Grains and Potato Germplasm ResearchAberdeenID 83210USA HZPC Research B.V. Edisonweg 58501 XG Jourethe Netherlands Department of Crop and Soil Science Oregon State UniversityHermistonOR 97838USA School of biology and Ecology University of Maine5735 Hitchner Hall OronoME 04469USA Department of Horticultural Sciences Texas A&M UniversityCollege StationTX 77843-2133USA Department of Horticulture Oregon State UniversityCorvallisOR 97331USA Department of Horticultural Science North Carolina State UniversityRaleighNC 27695-7609USA Department of Horticulture University of Wisconsin-MadisonMadisonWI 53706USA Department of Horticulture Michigan State UniversityEast LansingMI 48824USA Institute for Biological Data Science Heinrich Heine UniversityDusseldorf40225 DusseldorfGermany Plant Resilience Institute Michigan State UniversityEast LansingMI 48824USA Present address:GenNovation B.V. Wageningenthe Netherlands

Cultivated potato is a clonally propagated autotetraploid species with a highly heterogeneous *** assemblies of six cultivars including two chromosome-scale phased genome assemblies revealed extensive allelic diversity,including altered coding and transcript sequences,preferential allele expression,and structural variation that collectively result in a highly complex transcriptome and predicted proteome,which are distributed across the homologous *** species contribute to the extensive allelic diversity in tetraploid cultivars,demonstrating ancestral introgressions predating modern breeding *** a clonally propagated autotetraploid that undergoes limited meiosis,dysfunctional and deleterious alleles are not purged in tetraploid *** a quarter of the loci bore mutations are predicted to have a high negative impact on protein function,complicating breeder’s efforts to reduce genetic *** StCDF1 locus controls maturity,and analysis of six tetraploid genomes revealed that 12 allelic variants of StCDF1 are correlated with maturity in a dosage-dependent *** of the complexity of the tetraploid potato genome with its rampant structural variation and embedded deleterious and dysfunctional alleles will be key not only to implementing precision breeding of tetraploid cultivars but also to the construction of homozygous,diploid potato germplasm containing favorable alleles to capitalize on heterosis in F1 hybrids.

关键词： potato allele diversity phased assembly polyploid pan-genome wild introgressions

Discriminating endoscopic features of sessile serrated lesions

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Chinese Medical Journal 2023年第10期136卷 1237-1239页

作者： Wen Shi Yuelun Zhang Hanyue Ding Feng Xie Yang Chen Martin CSWong Jingnan Li Dong Wu Department of Gastroenterology Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100730China Medical Research Center Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100730China State key laboratory of Complex Severe and Rare Diseases Peking Union Medical College HospitalBeijing 100730China Department of Epidemiology and Biostatistics School of Population Medicine and Public HealthPeking Union Medical CollegeChinese Academy and Medical SciencesBeijing 100730China Department of Family Medicine and Primary Care JC School of Public Health and Primary CareFaculty of MedicineChinese University of Hong KongHong Kong 999077China Department of Health Research Methods Evidence and ImpactMcMaster UniversityHamiltonOntario L8S4L8Canada Centre for Health Economics and Policy Analysis McMaster UniversityHamiltonOntario L8S4L8Canada Clinical Epidemiology Unit International Clinical Epidemiology NetworkBeijing 100730China

To the Editor:Colorectal cancer(CRC)remains a leading cause of cancer-related death worldwide.[1]In addition to the classical adenoma-to-carcinoma model of colorectal carcinogenesis,the serrated neoplastic pathway accounts for 20%–30%of *** serrated lesions(SSLs),the most common premalignant serrated polyp subtype,share many of the genomic characteristics of post-colonoscopy CRCs and are thus recognized as their precursor ***,SSLs can be easily missed due to their flat shape and subtle endoscopic *** they can also be difficult to distinguish from other types of polyps,especially hyperplastic polyps(HPs),which are believed to have no malignant potential.[2]Approximately 10%of polyps initially diagnosed as HPs endoscopically are reclassified as SSLs after histopathological examination,reflecting diagnostic difficulties in colonoscopy.[3,4]Current guidelines recommend“diagnose-and-leave”and“resect-and-discard”strategies for diminutive polyps,which might lead to SSLs being left in situ or diagnoses being missed,[5]raising the risk of recurrence and post-colonoscopy ***,it remains debatable in the gastrointestinal community whether the risks of resecting SSLs outweigh the reduction in cancer *** strategy that improves the diagnostic accuracy of SSLs could have a meaningful clinical impact.

关键词： lesions endoscopic meaningful

百脉根BIO和豌豆突变位点ELE2的比较基因组定位(英文)

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基因组学与应用生物学 2010年第1期29卷 3-9页

作者：李信赫圣博庄黎丽 Sato Shusei TabataSatoshi Ambrose Mike Rameau Catherine 杨军胡筱荷罗达上海交通大学生命科学技术学院上海200240 Kazusa DNA Research Institute 2-6-7 Kazusa-kamatariKisarazuChiba 292-0818 Department of Crop genetics John Innes CentreColneyNorwich NR47UH Station de Genetique et d'Amelioration des Plantes Institut J.P.BourginUR2541NRA 中国科学院上海生命科学研究院植物生理生态研究所植物分子遗传学国家重点实验室上海200032

豆科两侧对称花的花瓣具有背腹(DV)的分化以及可变的器官内部(IN)非对称性,在大小与形状上显示出不同的发育特征;因而花瓣的发育为克隆决定植物器官的形状与大小的关键基因提供了很好的实验系统。本研究对百脉根中BIO基因进行研究。百脉... 详细信息

豆科两侧对称花的花瓣具有背腹(DV)的分化以及可变的器官内部(IN)非对称性,在大小与形状上显示出不同的发育特征;因而花瓣的发育为克隆决定植物器官的形状与大小的关键基因提供了很好的实验系统。本研究对百脉根中BIO基因进行研究。百脉根bio突变体具有多效性,既影响花器官内部的对称性也影响器官的大小和育性,豌豆ele突变体的表型与bio相似。定位结果表明BIO和ELE2位于豆科基因组的共线性区段,提示BIO和ELE2可能是同源基因突变所致。本研究利用比较基因组定位方法,将BIO和ELE2候选基因锚定在豆科模式植物百脉根和蒺藜苜蓿基因组含有11个同源基因的BAC重叠群上。BIO和ELE2基因的克隆将有助于揭示豆科花瓣形态和大小调控的分子机理,进而为豆科作物遗传改良提供分子理论基础。

关键词：器官的形状和大小百脉根 BIO基因 ELE2基因比较基因组定位

Genetic mechanisms of critical illness in Covid-19

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四川生理科学杂志 2020年第4期42卷 455-455页

作者： Erola Pairo-Castineira Roslin Institute University of Edinburgh Edinburgh UK MRC Human genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Western General Hospital Edinburgh UK genomics England London UK Centre for Inflammation Research The Queen’s Medical Research Institute University of Edinburgh Edinburgh UK Centre for genomic and Experimental Medicine Institute of Genetics and Molecular Medicine University of Edinburgh Western General Hospital Edinburgh UK Edinburgh Clinical Research Facility Western General Hospital University of Edinburgh Edinburgh UK Intensive Care National Audit & Research Centre London UK Institute for Molecular Bioscience The University of Queensland Brisbane Queensland Australia Biostatistics Group School of Life Sciences Sun Yat-sen University Guangzhou China The Crick Institute London UK Intensive Care Unit Royal Infirmary of Edinburgh Edinburgh UK School of Life Sciences Westlake University Hangzhou China Westlake laboratory of Life Sciences and Biomedicine Hangzhou China Wellcome Centre for Human genetics University of Oxford Oxford UK Department of Medicine University of Cambridge Cambridge UK Department of Intensive Care Medicine Guy’s and St Thomas’ NHS Foundation Trust London UK School of Immunology and Microbial Sciences King’s College London London UK NIHR Health Protection Research Unit for Emerging and Zoonotic Infections Institute of Infection Veterinary and Ecological Sciences University of Liverpool Liverpool UK MRC-University of Glasgow Centre for Virus Research Institute of Infection Immunity and Inflammation College of Medical Veterinary and Life Sciences University of Glasgow Glasgow UK William Harvey Research Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London London UK Centre for Tropical Medicine and Global Health Nuffield Department of Medicine University of Oxford Oxford UK Clinical Research Centre at St Vincent’s University Hospital Un

Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by *** genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the genomicC(genetics Of Mortality In Critical Care)genome-wide association study(GWAS)in 2244 critically ill Covid-19 patients from 208 UK intensive care units(ICUs).We identify and replicate novel genome-wide significant associations,on chr12q24.13(rs10735079,p=1.65[Formula:see text]10-8)in a gene cluster encoding antiviral restriction enzyme activators(OAS1,OAS2,OAS3),on chr19p13.2(rs2109069,p=2.3[Formula:see text]10-12)near the gene encoding tyrosine kinase 2(TYK2),on chr19p13.3(rs2109069,p=3.98[Formula:see text]10-12)within the gene encoding dipeptidyl peptidase 9(DPP9),and on chr21q22.1(rs2236757,p=4.99[Formula:see text]10-8)in the interferon receptor gene *** identify potential targets for repurposing of licensed medications:using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2,and high expression of TYK2,to life-threatening disease;transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe *** results identify robust genetic signals relating to key host antiviral defence mechanisms,and mediators of inflammatory organ damage in *** mechanisms may be amenable to targeted treatment with existing ***-scale randomised clinical trials will be essential before any change to clinical practice.

关键词： lung drugs critical

群体构成方式对大豆百粒重全基因组选择预测准确度的影响

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作物学报 2018年第1期44卷 43-52页

作者：马岩松刘章雄文自翔魏淑红杨春明王会才杨春燕卢为国徐冉张万海吴纪安胡国华栾晓燕付亚书郭泰王曙明韩天富张孟臣张磊苑保军郭勇 Jochen C.REIF 江勇李文滨王德春邱丽娟中国农业科学院作物科学研究所/国家农作物基因资源与遗传改良重大科学工程/农业部作物种质资源与生物技术重点开放实验室北京100081 东北农业大学农学院黑龙江哈尔滨150030 DepartmentofPlant SoilandMicrobialSciencesMichiganStateUniversityEastLansingMI48824USA 黑龙江省农业科学院育种研究所黑龙江哈尔滨150081 吉林省农业科学院大豆研究所吉林长春130033 内蒙古赤峰市农科所内蒙古赤峰024031 河北省农业科学院粮油作物研究所河北石家庄050031 河南省农业科学院经济作物研究所河南郑州450002 山东省农业科学院作物研究所山东济南250010 内蒙古呼伦贝尔市农科所内蒙古呼伦贝尔021000 黑龙江省农业科学院黑河分院黑龙江黑河164300 黑龙江省农垦科研育种中心黑龙江哈尔滨150090 黑龙江省农业科学院大豆研究所黑龙江哈尔滨150086 黑龙江省农业科学院绥化分院黑龙江绥化152052 黑龙江省农业科学院佳木斯分院黑龙江佳木斯154007 安徽省农业科学院作物研究所安徽合肥230031 河南省周口市农业科学院河南周口466001 Department of Breeding Research Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) Gatersleben 06466 Germany

百粒重是大豆产量的重要构成因子,在一定条件下与产量呈显著正相关。百粒重是一个复杂的数量性状,用传统的育种方法其遗传增益不明显。本研究对280份大豆品种进行了多年多点田间鉴定,通过混合线性模型预测获得品种百粒重的最佳线性无偏... 详细信息

百粒重是大豆产量的重要构成因子,在一定条件下与产量呈显著正相关。百粒重是一个复杂的数量性状,用传统的育种方法其遗传增益不明显。本研究对280份大豆品种进行了多年多点田间鉴定,通过混合线性模型预测获得品种百粒重的最佳线性无偏预测值。同时利用分布在大豆全基因组的5361个SNP标记鉴定参试品种基因型,结合随机回归最佳线性无偏预测模型和交互验证方法,探讨了群体构成方式对大豆百粒重的全基因组选择预测准确度的影响。结果表明,大豆百粒重的全基因组选择预测准确度变化范围为–0.15^+0.75;群体构成方式对百粒重的预测准确度影响明显;亚群内的预测准确度(+0.24^+0.75)高于亚群间(-0.15^+0.29);当群体间遗传距离由0.1566增加到0.2201时,预测准确度下降27.87%;相比随机构建的训练群体,基于群体遗传结构构建的训练群体能将百粒重的预测准确度提高2.34%。本研究明确了大豆百粒重的全基因组选择预测准确度,阐明了群体结构对大豆百粒重的全基因组选择预测准确度的影响,为大豆分子育种提供了新的思路和方法。

关键词：大豆百粒重全基因组选择预测准确度遗传结构