Genomics in the “CEntury of Biology”
完整基因组测序已为包括肺癌在内的若干种癌症类型的突变谱提供了线索。最新测序技术意味着，现在有可能从全基因组范围内来观察突变差异，而且现在研究人员对肺癌已经做到了这一点
CEll and chemical biology of mitosis
纳米生物效应与安全性实验室在2004年首次发现内含Gd原子的金属富勒烯三明治纳米结构颗粒可以直接作为肿瘤的高效低毒化疗药物以来，已经从分子免疫、神经调控、干细胞分化、血管生成等诸多方面对纳米颗粒直接作为高效低毒化疗药物的药效和机制，进行了长达6年多的研究，在国际学术刊物上连续发表了一系列的研究成果，逐渐形成较大的国际影响力。
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).
全球疫苗免疫联盟CEO塞斯•伯克莱2014世界免疫周致辞
全球疫苗免疫联盟（GAVI）首席执行官塞斯•伯克莱博士在2014年世界免疫周的致辞。本视频由Health Talk授权播出。
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.
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.
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.
Immunoblot Analysis Sean Gallagher(UVP,LLC)and Deb Chakravart(Proteomic CEnter)
Immunoblot Analysis Sean Gallagher(UVP,LLC)and Deb Chakravart(Proteomic CEnter)