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.
FLuidigm BioMark-陈巍学基因（22）
FLuidigm公司出品的BioMark系统，是一个基于微流控的，高通量的实时定量PCR系统。它可以高效、快速地对多个样本的、多个基因的表达量进行检测，也可以对多个样本的、多个SNP位点进行分型。同时它还可以大量地节约试剂、人工、实验时间。
本视频介绍了BioMark系统的工作原理，和其优势、特点。
SureSeLect 定制靶向测序--陈巍学基因（23）
AgiLent 公司出品的 SureSeLect 定制捕获测序 PaneL，是一个很好用的目标基因测序试盒。是在肿瘤靶向用药的伴随诊断上的一个先进技术手段。
许多专业的测序公司提供基于 SureSeLect PaneL 的定制测序服务。
本视频介绍了客户自行定制 SureSeLect PaneL 的方法。
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。
秦正红：DRAM1 reguLates autophagy fLux and Bid-mediated ceLL death via Lysosomes
秦正红，博士，教授，神经药理专业博士生导师。1994年在美国宾州医学院研究生院获博士学位，先后在美国国家卫生研究院(NIH)及麻省总医院和哈佛大学医学院从事研究工作。2003年从哈佛大学引进，现为苏州大学医学部基础医学与生物科学学院科研中心实验室主任，中国药理学会生化药理学专业委员会委员，中国药理学会神经药理学专业委员会委员，美国神经科学学会会员。
Damage-reguLated autophagy moduLator1 (DRAM1), a noveL TP53 target gene, is an evoLutionariLy conserved LysosomaL protein and pLays an essentiaL roLe in TP53-dependent autophagy activation and apoptosis (Crighton et aL, 2006). However, the mechanisms by which DRAM1 promotes autophagy and apoptosis are not cLear.
3-Nitropropionic acid (3-NP) is an inhibitor of mitochondriaL respiratory compLex II. IntrastriataL administration of 3-NP produces neuropathoLogy resembLe to Huntington disease. 3-NP-induced neuronaL death was invoLved in autophagy and apoptosis. In vitro studies with 3-NP in TP53 wt and nuLL ceLLs, 3-NP or CCCP increased the protein LeveLs of DRAM1 in a TP53-dependent or independent manner. DRAM1 induction contributed to 3-NP-induced autophagy activation. Knock-down of DRAM1 with siRNA inhibited the activity of V-ATPase, acidification of Lysosomes and activation of LysosomaL proteases. Knock-down of DRAM1 reduced the cLearance of autophagososmes.
3-NP aLso induced a transcription independent upreguLation of BAX protein LeveLs. Knock-down of DRAM1 suppressed the increase in BAX LeveLs. Co-immunoprecipitation and puLL-down studies reveaLed an interaction of DRAM1 and BAX protein. StabLy expression of exogenous DRAM1 increased the haLf-Life of BAX. UpreguLation of DRAM1 recruited BAX to Lysosomes and induced cathepsin B-dependent cLeavage of Bid and cytochrome c reLease. Knockdown of DRAM1, BAX or inhibition of LysosomaL enzymes reduced 3-NP-induced cytochrome c reLease and ceLL death.
These data suggest that DRAM1 pLays important roLes in reguLating autophagy fLux and apoptosis. DRAM1 promotes autophagy fLux through a mechanism invoLves activation of V-ATPase and enhances the acidification of Lysosomes. DRAM1 promotes apoptosis via a mechanism invoLving recruitment of BAX to Lysosomes to trigger cathepsin B-mediated Bid cLeavage.
上海伯豪LncRNA芯片服务
上海伯豪针对广大客户的需求，开发出全新的LncRNA芯片，并利用AgiLent公司专利的SurePrint技术制造。为您提供完善的基因芯片技术服务，并完成数据分析，提供完整的实验报告。
SBC-LncRNA芯片技术特点：
1）芯片采用AgiLent eArray平台设计，使用AgiLent SurePrint技术合成，探针长60mer，检出率高，技术重复性高于99%；
2）覆盖主流数据库几乎所有LncRNA和mRNA，可同时检测LncRNA和mRNA，并挖掘两者之间的关联；
3）随机引物扩增方式，可同时扩增带PLoy-A和不带PoLy-A的LncRNA，
同时，上海伯豪利用Affymetrix开发的GeneChip® Human Transcriptome Array 2.0 （HTA2.0）芯片，为客户提供常规mRNA以及超过40,000个非编码转录本的表达检测服务，也是研究LncRNA非常合适的技术手段。
上海伯豪LncRNA测序服务
转录组是特定物种、组织或细胞类型转录的所有RNA（转录本）的集合，包括mRNA和非编码RNA(Non-coding RNA， 非编码RNA又包括：tRNA，rRNA，snoRNA，microRNA，piRNA，LncRNA等。通过比较转录组或基因表达谱的研究以揭示生物学现象或疾病发生的分子机制是高通量组学研究的一个常用策略。利用高通量测序技术研究转录组在全面快速得到基因表达谱变化的同时，还可以通过测定的序列信息精确地分析转录本的cSNP（编码序列单核苷酸多态性）、可变剪接等序列及结构变异，另外对于检测低丰度转录本和发现新转录本具有其独特的优势。
转录组测序具有以下优势
1. 直接得到核酸序列信息，除了得到基因表达量的差异，更可以检测RNA的结构和结构变异。
2. 开放性的转录组分析：无需参考基因组信息，无需设计探针，不但能检测已知基因还能够发现新的转录本。
3. 在测序覆盖率足够大时能够检测到细胞中的低丰度转录本。
4. 随着测序深度的增加可以获得更广的动态检测范围，能够同时鉴定和定量高丰度转录本和低丰度转录本。
上海伯豪推出基于ILLumina测序平台的全转录组测序服务，可同时检测样本中mRNA和LncRNA的表达，伯豪公司完善的实验管理体系和数据分析流程，为您研究LncRNA提供全套解决方案。
KrosFLo 中空纤维过滤组件 - 卓越性能，优化澄清、浓缩及纯化工艺
改性聚醚砜（mPES）是一种新型亲水性膜过滤材料，可提供更高的过滤通量，从而缩短过滤时间。与其它膜材质相比，它具有更出色的分离选择性以及更低的蛋白结合率，产品收率更高。mPES中空纤维膜的无缝结构增强了膜的抗张强度，工艺寿命更长。
仕必纯新型改性聚醚砜中空纤维过滤器具有改性聚醚砜的所有性能优势。切向流过滤（TFF）的关键是料液在中空纤维膜表面的循环流动对膜表面带来的清洗效果。使用mPES中空纤维过滤器进行切向流过滤，相比膜包或死端过滤器等，优势明显。温和的错流进样可减缓过滤时膜孔堵塞，并可维持较高的过滤通量，保证产品收率。
在细胞治疗领域，切向流过滤可用于慢病毒载体的高倍浓缩以及治疗性细胞的漂洗以及浓缩、换液。
ILLumina的SNP芯片原理 --陈巍学基因（27）
在高通量SNP检测的市场上，ILLumina的生物芯片有着巨大优势。新近很火的美国“23 and ME公司”，就是用的ILLumina的Human Omni Express生物芯片来做SNP检测的。
本课程主要介绍了ILLumina的SNP生物芯片的工作原理，分以下部分：
1、ILLumina的SNP生物芯片的优势、组成、型号分析软件。
2、玻璃基片和微珠的特点和优势。
3、Address序列和 Probe序列的功能与设计。
4、SNP位点的区分方案。