Expression of CD74 is increased in neurofibrillary tangles in Alzheimer's disease

Alzheimer disease (AD) is a chronic neurodegenerative disease that is characterized by progressive memory loss. Pathological markers of AD include neurofibrillary tangles, accumulation of amyloid-β plaques, neuronal loss, and inflammation. The exact events that lead to the neuronal dysfunction and loss are not completely understood. However, pro-inflammatory cytokines, such as interleukin-1β, interleukin-6, and tumor necrosis factor α, are increased in AD, along with gene expression of major histocompatibility complex (MHC) class II molecules and macrophage migration inhibitory factor (MIF). MHC class II molecules are found in microglia of the brain, while MIF is found in both microglia and neurons of the hypothalamus, hippocampus, and cortex. MIF is not only a lymphocyte mediator but also a pituitary factor with endocrine properties and can mediate phosphorylation of the extracellular signal-regulated kinase-1/2 MAP kinases pathway. In this study, we looked at CD74, an integral membrane protein that acts as both a chaperone for MHC class II molecules as well as a receptor binding site for MIF. CD74 was recently found to be increased in microglia in AD cases compared to age-matched controls, but has not been reported in neurons. In our analysis, immunohistochemistry revealed a significant increase in CD74 primarily in neurofibrillary tangles, amyloid-β plaques, and microglia. This is the first finding to our knowledge that CD74 is increased in neurons of AD cases compared to age-matched control cases.     

EGFR和Ki-67在胶质瘤中表达的研究进展

胶质瘤是颅内常见的原发恶性肿瘤,而某些癌基因的激活、过表达或扩增、重排导致脑胶质瘤的形成。主要讨论脑胶质瘤的生物学特点,指出当前研究某些与肿瘤增殖活性及侵袭能力相关的基因改变、蛋白表达,推测其增殖和侵袭活动的具体过程,这是攻克脑胶质瘤的基础和关键。在众多与肿瘤相关的蛋白和基因中,选择了主要反映脑胶质瘤增殖活性和侵袭能力的相关基因——EGFR、Ki-67进行综述。从分子生物学水平评估脑胶质瘤细胞增殖和侵袭状态,在分析和判断胶质瘤的生长、分化程度,指导治疗方案的选择及预后的判断等方面有着重要的实用价值;但对于患者的预后,还需结合年龄、肿瘤位置、病理分级以及其他标记物等进行综合评价。     

基于红外相机数据的贵州高原山地环境野猪生境选择研究

近年来野猪(Sus scrofa)在我国南方山地森林生态系统中种群数量激增、生态影响强烈,是人兽冲突的典型代表,然而对其生境选择规律仍缺乏深入研究。利用2015年7月至2020年1月的长时红外相机监测数据,对贵州高原几处环境中野猪的生境选择进行了研究,共得到野猪利用样方201个,非利用样方121个。(1)Vanderploeg和Scavia选择指数分析表明,野猪喜爱活动于坡度≤20°、乔木郁闭度>0.8和草本盖度为0.2—0.4的生境类型;不喜爱的生境类型为海拔>1600 m,坡度>25°,草本盖度<0.1,距道路距离≤100 m。(2)野猪生境资源选择函数为Logit(P)=3.226-海拔×0.002-坡度×0.161+乔木郁闭度×2.078+灌木平均高×0.401+草本盖度×3.566+距道路距离×0.001+距居民点距离×0.0003,选择概率为P=e⁽logit(p))/(1+e⁽logit(p))),受试者工作特征曲线(ROC)评估模型的预测精度为87.8%,能够较好预测野猪的生境选择。(3)利用Mann-...     

贵州苗岭地区野猪肠道菌群结构与功能分析

野猪是当前南方山地森林生态系统中数量激增的主要有蹄类。为揭示贵州苗岭地区野猪肠道细菌的群落结构、多样性及菌群功能,本研究采用16S rRNA高通量测序技术检测了4头野猪胃肠道(胃、回肠、结肠和直肠)的细菌群落,共获得1 268 577条有效序列。经质控过滤,所有序列归类于1 019个OTU,包含19门292属。在门分类水平上,野猪肠道内核心菌群主要为厚壁菌门(Firmicutes)、拟杆菌门(Bacteroidetes)、变形菌门(Proteobacteria)和放线菌门(Actinobacteria),优势菌属包括普雷沃氏菌属(Prevotella)、乳酸杆菌属(Lactobacillus)、大肠—志贺氏菌属(Escherichia-Shigella)和双歧杆菌属(Bifidobacterium)等15个菌属。稀疏曲线表明测序深度已基本覆盖样品中所有细菌,测序充分。alpha多样性指数中,结肠和直肠的Chao1和Shannon指数显著高于胃和回肠(P<0.05),证明结肠和直肠比胃和回肠具有更高的菌群丰富度和多样性。主坐标分析(PCoA)和相似性分析(Anosim)结果也同样表...     

Neuroprotective properties of Bcl-w in Alzheimer disease

While there is a host of pro-apoptotic stimuli that target neurons in Alzheimer disease (AD), given the chronicity of the disease and the survival of many neurons, those neurons must either avoid or, at minimum, delay apoptotic death signaling. In this study, we investigated Bcl-w, a novel member of the Bcl-2 family that promotes cell survival. In AD, we found increased levels of Bcl-w associated with neurofibrillary pathology and punctate intracytoplasmic structures whereas, in marked contrast, there are only low diffuse levels of Bcl-w in the neuronal cytoplasm of age-matched control cases. Immunoblot analysis confirmed that Bcl-w levels were significantly increased in AD. By electron microscopy, we determined that the increased Bcl-w expression in AD was ultrastructurally localized to mitochondria and neurofibrillary pathology. To investigate the cause and consequence of Bcl-w up-regulation in neurons, we found that fibrillized amyloid-beta led to increased Bcl-w protein levels in M17 human neuroblastoma cells, and that overexpression of Bcl-w significantly protected neurons against staurosporine- and amyloid-beta-induced apoptosis. Taken together, these series of results suggest that Bcl-w may play an important protective role in neurons in the diseased brain and that this aspect could be therapeutically harnessed to afford neuroprotection.     

Absence of cellular stress in brain after hypoxia induced by arousal from hibernation in Arctic ground squirrels

Although hypoxia tolerance in heterothermic mammals is well established, it is unclear whether the adaptive significance stems from hypoxia or other cellular challenge associated with euthermy, hibernation, or arousal. In the present study, blood gases, hemoglobin O2 saturation (S(O2), and indexes of cellular and physiological stress were measured during hibernation and euthermy and after arousal thermogenesis. Results show that arterial O2 tension (Pa(O2)) and S(O2) are severely diminished during arousal and that hypoxia-inducible factor (HIF)-1alpha accumulates in brain. Despite evidence of hypoxia, neither cellular nor oxidative stress, as indicated by inducible nitric oxide synthase (iNOS) levels and oxidative modification of biomolecules, was observed during late arousal from hibernation. Compared with rats, hibernating Arctic ground squirrels (Spermophilus parryii) are well oxygenated with no evidence of cellular stress, inflammatory response, neuronal pathology, or oxidative modification following the period of high metabolic demand necessary for arousal. In contrast, euthermic Arctic ground squirrels experience mild, chronic hypoxia with low S(O2) and accumulation of HIF-1alpha and iNOS and demonstrate the greatest degree of cellular stress in brain. These results suggest that Arctic ground squirrels experience and tolerate endogenous hypoxia during euthermy and arousal.     

P38 Activation Mediates Amyloid-β Cytotoxicity

Amyloid-β is a leading candidate factor in the development of Alzheimer disease (AD), however the mechanisms involved are unclear. As such, there has been considerable interest in evidence showing that the neuronal damage caused by amyloid-β is mediated by oxidative stress. Notably, oxidative stress leads to activation of stress-activated protein kinases, which we and others have shown are also involved in AD pathogenesis. One SAPK in particular, p38, appears to be crucial in AD and therefore, in the current study, we investigated the role of p38 activation in amyloid-β cytotoxicity. Our data showed p38 activation was induced by amyloid-β in a concentration-dependent manner in M17 human neuroblastoma cells. Notably, amyloid-β toxicity was significantly decreased by inhibition of p38 activity by overexpressing dominant negative p38. Consistent with this, in primary cortical neurons amyloid-β also induced p38 activation and amyloid-β toxicity was significantly diminished when p38 was inhibited by its specific inhibitor, SB203580. Taken together, these data suggest that p38 is a key downstream effector of amyloid-β-induced neuronal death and blocking this pathway may be of therapeutic value.