非酒精性脂肪肝大鼠脂质代谢及病理变化的动态观察

目的通过高脂饮食建立NAFLD大鼠模型,连续监测4～16周模型动物肝功能、脂质代谢、胰岛素抵抗及肝细胞凋亡在NAFLD进展过程中的变化情况及相互关系,为该模型在脂肪肝发病机制、脂肪肝治疗药物评价等方面的应用提供参考依据。方法 SD大鼠50只,除正常对照组外,其余动物饲喂高脂饲料,分别检测4,8,12,16周大鼠血清GLU、CHO、TG、HDL、LDL、GPT、GOT及胰岛素水平,肝脏组织切片进行病理学及细胞凋亡观察,进一步分析大鼠肝功能、脂质代谢、胰岛素抵抗及肝细胞凋亡对肝组织病理改变的影响。结果模型组大鼠4周后就出现肝功能损伤,脂质代谢紊乱、胰岛素抵抗,肝细胞凋亡8 W后明显增加,肝细胞脂变及炎症为肝组织病理变化的主要特征,且造模时间越长,病变程度越严重。结论经过高脂饲料的喂养,SD大鼠在4～16周内可形成病变程度逐步加重的NAFLD模型,肝功能损伤,脂质代谢紊乱及肝细胞凋亡是引起非酒精性脂肪肝中脂肪变性和炎症的重要因素,该模型可应用于脂肪肝治疗药物评价等方面。     

几种旱生灌木种子萌发对干旱胁迫的响应

以不同渗透势的PEG(6 0 0 0 )溶液 (- 0 .3～ - 2 .7MPa)为模拟干旱胁迫条件 ,研究了柠条 (Caraganakorshinskii)、花棒 (Hedysarumscoparium)和白沙蒿 (Artemisiasphaerocephala)种子发芽、幼苗生长和累积吸水率对干旱胁迫的响应 ,讨论了参试种子发芽特性、初生根长度与幼苗建植成活率的关系 .结果表明 ,干旱胁迫下柠条发芽率最高 ,其次为花棒 ,白沙蒿最低 . - 0 .3～ - 0 .6MPa渗透势下白沙蒿发芽 10d的初生根长度显著大于花棒和柠条 (P <0 .0 5 ) ,三者的测量值依次为 7.9、4 .5和 3.1cm .干旱胁迫条件下参试种子发芽率与种子 72h累积吸水率均呈极显著的正相关 (P <0 .0 1) .     

Characterization of a mutated IgA2 antibody of the m(1) allotype against the epidermal growth factor receptor for the recruitment of monocytes and macrophages

IgA antibodies constitute an important part of the mucosal immune system, but their immunotherapeutic potential remains rather unexplored, in part due to biotechnological issues. For example, the IgA2m(1) allotype carries an unusual heavy and light chain pairing, which may confer production and stability concerns. Here, we report the generation and the biochemical and functional characterization of a P221R-mutated IgA2m(1) antibody against the epidermal growth factor receptor (EGFR). Compared with wild type, the mutated antibody demonstrated heavy chains covalently linked to light chains in monomeric as well as in joining (J)-chain containing dimeric IgA. Functional studies with wild type and mutated IgA2m(1) revealed similar binding to EGFR and direct effector functions such as EGFR down-modulation and growth inhibition. Furthermore, both IgA molecules triggered similar levels of indirect tumor cell killing such as antibody-dependent cell-mediated cytotoxicity (ADCC) by isolated monocytes, activated polymorphonuclear cells, and human whole blood. Interestingly, the dimeric IgA antibodies demonstrated higher efficiency in direct as well as in indirect effector mechanisms compared with their respective monomeric forms. Both wild type and mutated antibody triggered effective FcαRI-mediated tumor cell killing by macrophages already at low effector to target cell ratios. Interestingly, also polarized macrophages mediated significant IgA2-mediated ADCC. M2 macrophages, which have been described as promoting tumor growth and progression, may convert to ADCC-mediating effector cells in the presence of EGFR-directed antibodies. In conclusion, these results provide further insight into the immunotherapeutic potential of recombinant IgA antibodies for tumor immunotherapy and suggest macrophages as an additional effector cell population.     

Cytokinesis: regulated by destruction

Important transitions in the cell cycle are regulated by ubiquitin-dependent degradation of specific proteins. Recent data indicate that cytokinesis is also regulated by proteolysis.     

Cell Fate Analysis of Embryonic Ventral Mesencephalic Grafts in the 6-OHDA Model of Parkinson's Disease

Evidence from carefully conducted open label clinical trials suggested that therapeutic benefit can be achieved by grafting fetal dopaminergic (DAergic) neurons derived from ventral mesencephalon (VM) into the denervated striatum of Parkinson''s disease (PD) patients. However, two double-blind trials generated negative results reporting deleterious side effects such as prominent dyskinesias. Heterogeneous composition of VM grafts is likely to account for suboptimal clinical efficacy.We consider that gene expression patterns of the VM tissue needs to be better understood by comparing the genetic signature of the surviving and functioning grafts with the cell suspensions used for transplantation. In addition, it is crucial to assess whether the grafted cells exhibit the DAergic phenotype of adult substantia nigra pars compacta (SNpc). To investigate this further, we used a GFP reporter mouse as source of VM tissue that enabled the detection and dissection of the grafts 6 weeks post implantation. A comparative gene expression analysis of the VM cell suspension and grafts revealed that VM grafts continue to differentiate post-implantation. In addition, implanted grafts showed a mature SNpc-like molecular DAergic phenotype with similar expression levels of TH, Vmat2 and Dat. However, by comparing gene expression of the adult SNpc with dissected grafts we detected a higher expression of progenitor markers in the grafts. Finally, when compared to the VM cell suspension, post-grafting there was a higher expression of markers inherent to glia and other neuronal populations.In summary, our data highlight the dynamic development of distinctive DAergic and non-DAergic gene expression markers associated with the maturation of VM grafts in vivo. The molecular signature of VM grafts and its functional relevance should be further explored in future studies aimed at the optimization of DAergic cell therapy approaches in PD.     

The N-terminal domain of the V-ATPase subunit 'a' is regulated by pH in vitro and in vivo

Regulation of the activity of vacuolar ATPase (V-ATPase) is a well known, yet poorly understood phenomenon, which might underlie the contribution of V-ATPases in various cellular signaling processes.(1) In yeast, V-ATPase is regulated by glucose and contributes to activation of cAMP-dependent protein kinase A (PKA). We have recently shown that, in vivo, glucose regulates V-ATPase through cytosolic pH, suggesting that V-ATPase contains a pH sensitive subunit, which regulates assembly of the holo-complex.(2) Here, we present the purification and biochemical characterization of the N-terminal domain of subunit 'a', Vph1N, which has been suggested to act as a pH sensor in mammalian cells.(3) Interestingly, our studies demonstrate pH-dependent oligomerization of this domain in vivo and in vitro. Moreover, we identify a membrane proximal region that is required for the pH-dependent oligomerization, and suggest a speculative model for the regulation of the V-ATPase holo-complex by pH.     

未净化Z：ZCLA长爪沙鼠封闭群繁育及遗传稳定性分析

目的分析未净化Z：ZCLA长爪沙鼠封闭群繁育和生长指标,并利用直接测序法分析其遗传稳定性。方法随机选择40对Z：ZCLA长爪沙鼠,记录其繁殖胎次、产子数等指标,分析其仔鼠的生长发育情况。遗传稳定性分析选择Z：ZCLA长爪沙鼠非同胞、非亲代个体33只,提取肝脏基因组DNA,PCR扩增D-Loop序列,产物纯化后双向测序,测序结果与Z：ZCLA长爪沙鼠标准序列比对。结果 Z：ZCLA长爪沙鼠每胎产仔7只,胎间隔多在20～60 d间,雄性体重高于雌性。遗传稳定性分析检测发现33只Z：ZCLA长爪沙鼠序列与标准序列完全一致。结论 Z：ZCLA长爪沙鼠群体内未发现遗传多态性,说明该群体具有较好的遗传稳定性。     

大兴安岭南部山地苔藓植物区系多样性研究

于2009～2012年对大兴安岭南部山地6个自然保护区的苔藓植物进行了野外实地调查,对所采集的1 800余号标本进行室内分析鉴定,并计算分析其种类组成、区系地理成分、地区之间相似性系数和相异系数的欧氏距离比较,及其8种生境中苔藓植物多样性指数、丰富度指数、均匀度指数和优势度指数等,为保护区的管理和建设提供基础资料。结果表明:(1)大兴安岭南部山地6个自然保护区共有苔藓植物48科,134属,330种,其中苔类16科,21属,38种,1变种;藓类32科,113属,274种,14变种,2变型,1亚种。(2)首次发现中国新记录4种:长柄紫萼藓(Grimmia longirostris Hook.),毛尖连轴藓[Schistidium lancifolium(Kindb.)Blom.],平叶真藓(Bryumlaevifilum Syed.),凹叶毛灰藓[Homomallium adnatum(Hedw.)Broth.],首次发现本地区新记录12种。(3)以丛藓科为代表的旱生藓类在本区占有优势地位;区系地理成分以温带成分(60.79%)和东亚成分(16.19%)为主。(4)大兴安岭南部山地与兴安北部和燕山北部山地亲缘关系较近;生境条件的变化对苔藓植物多样性产生了一定的影响,湿润土生和石生生境为本区苔藓植物最丰富的生境,水生生境中苔藓植物分布最少。研究发现,大兴安岭南部山地苔藓植物区系是连接华北区、东北区、蒙新区和阴山地区的过渡性地带;与燕山北部和兴安北部相比,大兴安岭南部山地大面积苔藓植物地被层分布较少的主要原因是森林密度和湿度较低。因此,建立保护区对保护大兴安岭南部山地脆弱的森林、草原过渡生态系统,保护中国野生动植物类群及其他珍稀动植物的繁衍均具有十分重要的意义。