Karen Dell: iBiology:Meet the world's best biologists through the Internet
Karen Dell来自美国细胞生物学学会，她将简述通过iBiology来获取生物学学习和交流的资源。
李于：SIRT1 Regulation of Energy Metabolism: Attenuation of Hepatic Steatosis and Obesity
Fibroblast growth factor 21 (FGF21) is the hepatocyte-derived hormone that regulates fatty acid metabolism and has potential to treat obesity and diabetes. We recently indicate that hepatic overexpression of SIRT1 in diabetic mice attenuates hepatic steatosis and insulin resistance. However, the in vivo long-term consequence of hepatic SIRT1 ablation in liver physiology remains unknown.
We showed that hepatocyte-specific SIRT1 knockout (SIRT1 LKO) mice with the albumin Cre-loxP system exhibited a striking phenotype with greater propensity for obesity on a chow diet, characterized by increased whole body mass and fat mass, reduced energy expenditure, and unaltered food intake and physical activity. The obese phenotypes of SIRT1 LKO mice were associated with reduced hepatic and circulating levels of fasting FGF21.
Hepatic impairment of FGF21 repressed expression of key enzymes involving fatty acid oxidation such as CPT1α and MCAD, and inhibited expression of ketogenic enzymes including ACAT1, HMGCS2, HMGCL, and BDH1, thereby reducing plasma β–hydroxybutyrate levels in SIRT1 LKO mice. Moreover, transcriptional activity of a FGF21 promoter-driven luciferase reporter was stimulated by SIRT1 activators, resveratrol and SRT1720, in SIRT1+/+ MEFs, but not in SIRT1-/- MEFs.
The ability of resveratrol and SRT1720 to stimulate FGF21 protein was abolished by SIRT1 H335A inactive mutant or by nicotinamide and splitomicin in HepG2 cells. Induction of FGF21 by SIRT1 activators enhanced expression of key enzymes for fatty acid oxidation and ketogenesis.
These in vivo and in vitro findings characterize 1) hepatic SIRT1 as a master regulator of FGF21; 2) SIRT1-dependent activation of FGF21 in liver as a component for adaptive fasting response; and 3) defective hepatic SIRT1 and FGF21 signaling as a key pathological determinant of energy metabolic abnormality and obesity susceptibility.
Erich Gnaiger：Life Style and Mitochondrial Competence – Modern Drugs for T2 Diabetes in Aging and Degenerative Diseases.
D. Swarovski Research Laboratory (Mitochondrial Physiology), Dept. General, Visceral and Transplant Surgery, Innsbruck Medical University; and OROBOROS INSTRUMENTS, Innsbruck, Austria. - Email: erich.gnaiger@oroboros.at
The contribution of mitochondrial dysfunction to the etiology of T2 diabetes and a range of preventable metabolic diseases is the subject of intensive current research with world-wide health implications.
Recently these investigations gained depth and scope by technological advances for diagnosis of mitochondrial function by comprehensive OXPHOS analysis using high-resolution respirometry [1,2]. Fundamental questions of a causal relationship, however, between compromised mitochondrial function and development of T2 diabetes remain to be resolved [3,4] to optimize prevention and treatment of insulin resistance.
For preventable diseases such as T2 diabetes, the evolutionary background of mitochondrial competence provides a solid basis for improved and broad application of a well established modern drug, mtLSD.
Post-industrial societies are characterized by a high-energy input lifestyle with diminished physical activity and high incidence of non-transmittable diseases, in comparison to human populations where physical work is essentially important for sustaining life and in which degenerative diseases (T2 diabetes, various cancers, Alzheimer's) are essentially absent [5]. The capacity of oxidative phosphorylation (OXPHOS) is increased or maintained high by a life style involving endurance exercise and strength training [6].
Life style changes from the age of 20-30 years to the elderly, but is subject to change and intervention. Depending on group selection in cross-sectional studies, OXPHOS capacity declines from the age of 20-30 years [7,8], or is independent of age up to 80 years [9,10].
Independent of age, there is a strong decline of OXPHOS capacity in human vastus lateralis from BMI of 20 to 30 [1]. At a BMI >30, a threshold OXPHOS capacity is reached in human v. lateralis that may be characteristic of a low-grade inflammatory state (‘mitochondrial fever’).
Onset of degenerative diseases (T2 diabetes, neuromuscular degeneration, various cancers) and mitochondrial dysfunction interact in an amplification loop progressing slowly with age, such that cause and effect of mitochondrial dysfunction cannot be distinguished. Diminished antioxidant capacity at low mitochondrial density is an important mechanistic candidate in the state of mitochondrial fever.
For implementing a life style supporting mitochondrial competence and preventing degenerative diseases in modern societies, we need (1) extended research programmes focused on the causative link between mitochondrial competence and effective prevention of degenerative diseases, (2) educational programmes on mitochondrial physiology targeted at general practitioners, teachers and the society at large, (3) cooperation of health care and insurance organizations to support preventive life style activities, and (4) do not miss any opportunity in taking the lead in living the mtLife Style Drug (mtLSD).
金颖：Fox3 suppresses NFAT-mediated differentiation to maintain self-renewal of embryonic stem cells
金颖教授为分子发育生物学研究室主任，健康科学中心研究员。金教授介绍了Fox3通过抑制NFAT介导的分化维持了胚胎干细胞的自我更新的机制等前沿发现。
Pluripotency-associated transcription factor Foxd3 is required for maintaining pluripotent cells. However, molecular mechanisms underlying its function are largely unknown.
Here, we report that Foxd3 suppresses differentiation induced by Calcineurin-NFAT signaling to maintain the ESC identity. Mechanistically, Foxd3 interacts with NFAT proteins and recruits co-repressor Tle4, a member of the Tle suppressor family highly expressed in undifferentiated ESCs, to repress NFATc3’s transcriptional activities.
Furthermore, global transcriptome analysis shows that Foxd3 and NFATc3 co-regulate a set of differentiation-associated genes in ESCs. Collectively, our study establishes a molecular and functional link between a pluripotency-associated factor and an important ESC differentiation-inducing pathway.
贾立军：neddylation蛋白修饰-CRL 泛素连接酶通路调控肿瘤细胞自噬应答的机制与潜在应用
贾立军博士，复旦大学附属肿瘤医院肿瘤研究所研究员和博士生导师。目前主要从事“针对蛋白质翻译后修饰通路进行抗肿瘤分子靶点发现”等研究工作。
相关研究在 J Natl Cancer Inst（JNCI）、Cancer Research、Clinical Cancer Research、Autophagy、Cell Death & Differentiation、Cell Death & Disease、Int J Cancer和J Biol Chem等学术期刊发表文章40篇、获邀参编英文专著4部。主持国家自然科学基金（81372196，31071204，30500637，81172092）、国家重大科学研究计划（2012CB910302，课题负责）、上海市卫生局A类重点项目 (2010012)、上海市“浦江人才 ”资助计划（12PJ1400600）和上海高校特聘教授（东方学者）资助计划等科研项目。
学术兼职包括：国家自然科学基金委员会医学科学领域学科评审组专家、中华医学科技奖评审委员会委员、上海市免疫学会肿瘤免疫专业委员会委员、高等学校自然科学奖和技术发明奖评审专家和十余种学术期刊审稿专家。荣获上海高校特聘教授（东方学者）和上海市浦江人才等荣誉称号。
Generating B-lymphoblastoid cell lines using Epstein Barr virus transformation.
Generating immortalized B-lymphoblastoid cell lines via Epstein Barr virus transformation using the B95-8 EBV-infected and producing marmoset cell line.
我是如何成为一名科学家的 - Alfredo Quinones-Hinojosa
本视频由科普中国和生物医学大讲堂出品
Alfredo Quinones-Hinojosa（Q博士）（霍普金斯达大学）：我是如何成为一名科学家
出生于墨西哥的Q博士，19岁时翻越美国边界的栅栏，成为加利福尼亚的一名农场工人。由于他自己的决心，努力工作和自律，以及来自家庭和朋友的大量支持，他离开了农场工作，完成了大学和医学院的学业，最终成为一位非常成功的医生、科学家和脑外科医生。
关于讲师：Alfredo Quinones-Hinojosa是约翰霍普金斯大学，神经外科学和肿瘤学，神经系统的细胞与分子医学的副教授，脑肿瘤外科手术的主任。Q博士作为一个专家外科医生，他致力于干细胞，在脑肿瘤的病因和治疗领域的研究。
Alfredo Quinones-Hinojosa (Dr. Q) (Johns Hopkins): How I Became a Scientist
At age 19, Quiñones-Hinojosa jumped the fence from Mexico to become a farm worker in California. Thanks to his own determination, hard work and discipline and a lot of support from family and friends, he left farm work, completed university and medical school, and ultimately became a highly successful physician-scientist and brain surgeon.
About the speaker: Alfredo Quiñones-Hinojosa is an Associate Professor of neurosurgery and Oncology, neuroscience and Cellular and Molecular Medicine and Director of the Brain Tumor Surgery Program at Johns Hopkins University. As well as being an expert surgeon, he researches the role of stem cells both in causing brain tumors and potentially in fighting them.
This talk was first released in iBioMagazine Issue 5.
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CRISPR/Cas9 & TetraOne：基因敲除/敲入鼠模型的快速构建技术
众所周知，基因工程小鼠模型已被广泛应用于生物医药研究，但模型小鼠的构建技术复杂、耗时长且花费高，让很多实验室望而却步。在本次讲座中，欧阳应斌博士（赛业生物技术副总裁、高级科学家）主要介绍基因敲除/敲入鼠模型的快速构建技术——CRISPR/Cas9基因编辑技术与TetraOne技术，同时会简述转基因技术（PiggyBac系统）和传统ES打靶技术，并重点讲解每种技术的优势、缺点及应用。
Perkinelmer：从表型到靶点的药物研发流程
传统基于靶点（target-based）的药物研发流程耗费大量的时间（历时10年以上）和财力（数十亿美元），这种流程的成功率相当低，只在极少数的研发案例中出现能通过整个流程最终上市成为治疗疾病的药物，究其原因是从体外到体内的过程违背了药物发挥作用的基本原则，即只有在生理环境下有效果才算真正的效果。
近年来越来越多的药物研发转变为始于表型研究，继而转入靶点研究的新流程。这个流程的核心在于先确定候选药物能否引起细胞生理形态的改变，进而确认作用靶点，辅以正交实验的方法，通过大数据分析得到坚实可靠的结果。
在这次研讨会中，我们的专家将会在以下方面与您探讨：
(1).非标记检测在不用类型细胞表型研究中的应用
(2).细胞成像在表型研究中的应用
(3).靶点研究的最新实验方法
(4).通过正交方法获得坚实可靠的实验结果
Perkinelmer Company Overview
At Perkinelmer we're taking action to improve the health and safety of people and the environment. We're committed to transforming risk into safety, mystery into knowledge and ideas into action for healthier today and even better tomorrow. We are committed to delivering solutions that improve our customers' outcomes, advance human and environmental health technologies and, deliver shareholder value. Every day, we work together to ensure the way we do business is as meaningful as the solutions we provide.