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中国比较医学杂志 2016年第7期26卷 1-10页

作者： grant morahan Centre for Diabetes Research The Harry Perkins Institute of Medical ResearchCentre for Medical ResearchUniversity of Western Australia

The Collaborative Cross( CC) is a powerful genetic resource with a wide range of applications in medical research. It is a multiparental genetic reference population,composed of 200 recombinant inbred mouse strains. It was designed to be a resource for rapid mapping of genes that mediate complex traits. The CC has been produced following an intense breeding program that had taken over ten years to complete. It is now becoming available to the research community. While advances in human genetic technologies over the last decade have been substantial,the CC provides the ability to make discoveries not possible with other methods or resources. It can be applied to any subject that can be measured or modelled in the mouse. Here,we discuss a range of applications for which the CC can be used,with examples taken from the early characterization of this powerful resource.

关键词：实验动物基因工程小鼠

The development and application of Laboratory Animal Science in China

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Animal Models and Experimental Medicine 2018年第4期1卷 247-249页

作者： Patri Vergara grant morahan International Council for Laboratory Animal Science (ICLAS) Centre for Diabetes Research Harry Perkins Institute of Medical Research

The 14th Scientific Congress of the Chinese Association for Laboratory Animal Science was held on October 11‐12,2018 in Qingdao,*** this congress,an international forum on the development of Laboratory Animal Sciences(LAS)worldwide was held in which participants learnt about the development of new LAS resources and technologies,as well as the progress of LAS in *** main points that were discussed are as *** nearly a century of development,there are more than 200 species of experimental animals,and more than 20 000 inbred lines,outbred lines,genetic engineered animals,animal models of diseases,and other resources all over the world,which provide abundant experimental animal resources for scientific *** resources are widely used in life science research.

关键词： Laboratory Animal Science Chinese Association Laboratory Animal Sciences(LAS)

Insulin-secreting β cells require a post-genomic concept

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World Journal of Diabetes 2016年第10期7卷 198-208页

作者： Fang-Xu Jiang grant morahan Islet Cell Development Program Harry Perkins Institute of Medical Research Nedlands WA 6009 Australia Centre for Diabetes Research the University of Western Australia Perth WA 6009 Australia

Pancreatic insulin-secretingβcells are essential in maintaining normal glucose homeostasis accomplished byhighly specialized transcription of insulin gene,of which occupies up to 40%their *** of these cells causes diabetes mellitus,a global public health *** tremendous endeavors have been made to generate insulin-secreting cells from human pluripotent stem cells(i.e.,primitive cells capable of giving rise to all cell types in the body),a regenerative therapy to diabetes has not yet been ***,the nomenclature ofβcells has become inconsistent,confusing and controversial due to the lack of standardized positive controls of developmental stagematched in vivo *** order to minimize this negative impact and facilitate critical research in this field,a postgenomic concept of pancreaticβcells might be *** this review article,we will briefly describe howβcells were discovered and islet lineage is developed that may help understand the cause of nomenclatural controversy,suggest a post-genomic definition and finally provide a conclusive remark on future research of this pivotal cell.

关键词： Beta cells Insulin Post-genome Concept

Strategies for generating mouse model resources of human disease

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Protein & Cell 2023年第12期14卷 866-870页

作者： Jirong Pan Ling Zhang Zhibing Huang Dalu Zhao He Li Yanan Fu Meng Wang Borui Chen Fuad A.Iraqi grant morahan Chuan Qin National Human Diseases Animal Model Resource Center NHC Key Laboratory of Human Disease Comparative MedicineBeijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious DiseasesBeijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInstitute of Laboratory Animal SciencesCAMS&PUMCNational Center of Technology Innovation for Animal ModelChangping National Laboratory(CPNL)Beijing 102206China Department of Clinical Microbiology and Immunology Sackler Faculty of MedicineTel-Aviv UniversityRamat AvivTel Aviv 69978Israel Harry Perkins Institute of Medical Research QEII Medical Centre and Centre for Medical ResearchUniversity of Western AustraliaNedlandsPerthWA 6009Australia

The number of genetically modified mouse models that mimic human disease is growing rapidly,but only a tiny fraction has been commonly *** to The Knockout Mouse Program(Lloyd,2011),a public resource of mouse embryonic stem cells containing a null mutation in every gene in the mouse genome,8,916 mutant mice lines were phenotyped up to 19 July *** to the poor correlation between the genomic responses in the mouse models and those responses in human disease,and since humans differ significantly in their genetic vulnerability to common diseases,we still need better mouse models,especially for common and chronic human diseases,including cancer,pulmonary and cardiovascular diseases,obesity and diabetes,behavioral disorders,and neurodegenerative *** new models will be placed into a public repository,The China National Human Disease Animal Model Resource Center(NAMR).This project is funded by Ministry of Science and Technology of China and specializes in the creation,introduction,collection,preservation,and supply of animal model resources forhuman diseases.

关键词： diseases cardiovascular generating

Novel spontaneous myelodysplastic syndrome mouse model

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Animal Models and Experimental Medicine 2021年第2期4卷 169-180,I0002页

作者： Weisha Li Lin Cao Mengyuan Li Xingjiu Yang Wenlong Zhang Zhiqi Song Xinpei Wang Lingyan Zhang grant morahan Chuan Qin Ran Gao NHC Key Laboratory of Human Disease Comparative Medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInstitute of Laboratory Animal SciencesChinese Academy of Medical Sciences(CAMS)and Comparative Medicine CenterPeking Union Medical College(PUMC)BeijingChina

Background:Myelodysplastic syndrome(MDS)is a group of disorders involving he-mopoietic dysfunction leading to *** recently progress has been made in identifying underlying genetic mutations,many questions still *** models of MDS have been produced by introduction of specific ***,there is no spontaneous mouse model of MDS,and an animal model to simulate natu-ral MDS pathogenesis is urgently ***:In characterizing the genetically diverse mouse strains of the Collaborative Cross(CC)we observed that one,designated JUN,had abnormal hematological *** strain was thus further analyzed for phenotypic and pathological iden-tification,comparing the changes in each cell population in peripheral blood and in bone ***:In a specific-pathogen free environment,mice of the JUN strain are rela-tively thin,with healthy ***,in a conventional environment,they become lethargic,develop wrinkled yellow hair,have loose and light stools,and are prone to *** found that the mice were cytopenic,which was due to abnor-mal differentiation of multipotent bone marrow progenitor *** are common characteristics of ***:A mouse strain,JUN,was found displaying spontaneous myelodysplas-tic *** strain has the advantage over existing models in that it develops MDS spontaneously and is more similar to human MDS than genetically modified mouse *** mice will be an important tool for pathogenesis research of MDS and for evaluation of new drugs and treatments.

关键词： myelodysplastic syndrome(MDS) spontaneous mouse model The Collaborative Cross Mice

Multipotent pancreas progenitors: Inconclusive but pivotal topic

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World Journal of Stem Cells 2015年第11期7卷 1251-1261页

作者： Fang-Xu Jiang grant morahan Islet Cell Development Program Harry Perkins Institute of Medical Research Centre for Medical Research the University of Western Australia Centre for Diabetes Research Harry Perkins Institute of Medical Research

The establishment of multipotent pancreas progenitors(MPP) should have a significant impact not only on the ontology of the pancreas, but also for the translational research of glucose-responding endocrine b-cells. Deficiency of the latter may lead to the pandemic type 1 or type 2 diabetes mellitus, a metabolic disorder. An ideal treatment of which would potentially be the replacement of destroyed or failed b-cells, by restoring function of endogenous pancreatic endocrine cells or by transplantation of donor islets or in vitro generated insulin-secreting cells. Thus, considerable research efforts have been devoted to identify MPP candidates in the preand post-natal pancreas for the endogenous neogenesis or regeneration of endocrine insulin-secreting cells. In order to advance this inconclusive but critical field, we here review the emerging concepts, recent literature and newest developments of potential MPP and propose measures that would assist its forward progression.

关键词： Multipotent pancreas progenitors Regeneration Self-renewal Clonogenesis Differentiation

Cancer susceptibility genes: update and systematic perspectives

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The Innovation 2022年第5期3卷 15-16页

作者： Xiaoshun Shi Sylvia Young Kaican Cai Jialiang Yang grant morahan Harry Perkins Institute of Medical Research QEII Medical Centre and Centre for Medical ResearchThe University of Western AustraliaNedlandsPerthWA 6009Australia Department of Thoracic Surgery Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Qingdao Geneis Institute of Big Data Mining and Precision Medicine Qingdao 266000China

A cancer susceptibility gene(CSG)is a gene whose variants can increase the cancer risk of those bearing such variants.1 By defining an individual’s CSG profile,it may be possible to assess their cancer risk and may provide insights for future prevention and treatment of *** methods used for discovery of CSGs have evolved from single candidate gene analysis to population-based next-generation sequencing.

关键词： prevention cancer susceptibility

复杂性状遗传CC小鼠-一个适用于遗传探索和研究复杂遗传性状的遗传参考种群

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中国比较医学杂志 2016年第9期26卷 5-5页

作者： grant morahan 王谦(译) 西澳大学医学研究中心糖尿病研究中心哈利珀金斯医学实验室澳大利亚中国医学科学院医学实验动物研究所北方资源中心北京

影响公众健康的复杂性疾病,如癌症、心脑血管病、糖尿病和痴呆等,多源自遗传、发育、环境等诸多因素的相互作用,但影响遗传变异的机理大多未知。为此人们开始研究一项新的模拟人类遗传结构的实验资源,被称为复杂性状遗传CC小鼠（以下简... 详细信息

影响公众健康的复杂性疾病,如癌症、心脑血管病、糖尿病和痴呆等,多源自遗传、发育、环境等诸多因素的相互作用,但影响遗传变异的机理大多未知。为此人们开始研究一项新的模拟人类遗传结构的实验资源,被称为复杂性状遗传CC小鼠（以下简称CC小鼠）。CC小鼠是一个多亲本的遗传参考种群,其基础是充分利用重组近交系,可以快速定位调节复杂性状基因。设计用八个始建品系来解决对遗传变异的限制,其中包括数个来源于不同大洲的野生近交品系。

关键词： CC 近交品系近交系人类遗传实验资源复杂性疾病基因图性状基因心脑血管病位调节

Bioinspired nanocomposites with self-adaptive mechanical properties

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Nano Research 2024年第2期17卷 633-648页

作者： grant Kitchen Bohan Sun Sung Hoon Kang 13400 N Charles St Department of Materials Science and EngineeringJohns Hopkins UniversityBaltimore 21218USA 23400 N Charles St Department of Mechanical EngineeringJohns Hopkins UniversityBaltimore 21218USA 33400 N Charles St Hopkins Extreme Materials InstituteJohns Hopkins UniversityBaltimore 21218USA

Conventional synthetic materials have fixed mechanical properties and suffer defects,damage,and degradation over *** makes them unable to adapt to changing environments and leads to limited ***,self-adaptive materials inspired by natural materials have emerged as a solution to address these *** the ability to change their mechanical properties based on changing mechanical environments,repairing defects,and maintaining their mechanical properties,these materials can lead to improved performance while decreasing *** this review,we explore self-adaptive phenomena found in nature that have inspired the development of synthetic self-adaptive materials,and the mechanisms that have been employed to create the next generation of *** potential applications of these materials,the challenges that existing approaches face,and future research opportunities are also discussed.

关键词： nanocomposites self-adaptive materials bioinspired materials force-activated resilience

Stability Analysis and Performance Evaluation of Additive Mixed-Precision Runge-Kutta Methods

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Communications on Applied Mathematics and Computation 2024年第1期6卷 705-738页

作者： Ben Burnett Sigal Gottlieb Zachary J.grant Center for Scientific Computing and Data Science Research UMass DartmouthNorth DartmouthMassachusettsUSA CSME Michigan State UniversityEast LansingMichiganUSA

Additive Runge-Kutta methods designed for preserving highly accurate solutions in mixed-precision computation were previously proposed and *** specially designed methods use reduced precision for the implicit computations and full precision for the explicit *** this work,we analyze the stability properties of these methods and their sensitivity to the low-precision rounding errors,and demonstrate their performance in terms of accuracy and *** develop codes in FORTRAN and Julia to solve nonlinear systems of ODEs and PDEs using the mixed-precision additive Runge-Kutta(MP-ARK)*** convergence,accuracy,and runtime of these methods are *** show that for a given level of accuracy,suitably chosen MP-ARK methods may provide significant reductions in runtime.

关键词： Mixed precision Runge-Kutta methods Additive methods Accuracy