伪狂犬病毒跨突触示踪视觉系统神经网络的研究进展

伪狂犬病毒（PRV）作为一种亲神经性的病毒,它以其自我复制、跨突触、特异性传递的三大优势在揭示神经系统中功能性神经元之间的连接发挥着重大的作用。经基因重组后的伪狂犬病毒不但继承了原有病毒的优势,同时还延伸出其他特异性的功能,如重组后加入了荧光蛋白的伪狂犬病毒在视觉系统神经通路的研究中发挥了重要作用。本文就目前伪狂犬病毒跨突触示踪视觉系统神经网络中的研究做一综述。     

The pro‐inflammatory effect of NR4A3 in osteoarthritis

NR4A3 is a member of nuclear receptor subfamily 4, which is an important regulator of cellular function and inflammation. In this study, high expression of NR4A3 in human osteoarthritis (OA) cartilage was firstly observed. To explore the relationship between NR4A3 and OA, we used a lentivirus overexpression system to simulate its high expression and study its role in OA. Additionally, siRNA‐mediated knockdown of NR4A3 was used to confirm the findings of overexpression experiments. The results showed the stimulatory effect of IL‐1β on cartilage matrix‐degrading enzyme expression such as MMP‐3, 9, INOS and COX‐2 was enhanced in NR4A3‐overexpressed chondrocytes and decreased in NR4A3‐knockdown chondrocytes at both mRNA and protein levels, while IL‐1β‐induced chondrocyte‐specific gene (collagen 2 and SOX‐9) degradation was only regulated by NR4A3 at protein level. Furthermore, overexpression of NR4A3 would also enhance EBSS‐induced chondrocytes apoptosis, while knockdown of NR4A3 decreased apoptotic level after EBSS treatment. A pathway study indicated that IL‐1β‐induced NF‐κB activation was enhanced by NR4A3 overexpression and reduced by NR4A3 knockdown. We suggest that NR4A3 plays a pro‐inflammatory role in the development of OA, and we also speculate that NR4A3 mainly regulates cartilage matrix‐degrading gene expression under inflammatory conditions via the NF‐κB pathway.     

On the Status and Comparison of Glucose Intolerance in Female Breast Cancer Patients at Initial Diagnosis and during Chemotherapy through an Oral Glucose Tolerance Test

Aims

This study is to estimate the status and comparison of glucose intolerance in female breast cancer patients at initial diagnosis and during chemotherapy through an oral glucose tolerance test (OGTT), as well as to learn the effect of chemotherapy on the glucose metabolism of breast cancer patients.

Methods

All the 79 breast cancer patients at initial diagnosis, with the mean age of 53.2 years, and 96 breast cancer patients before the 5th or 6th cycle of chemotherapy, with the mean age of 51.5 years, participated in the study from December 2012 to October 2013. After an overnight fast, participants underwent OGTT test, and fasting and 2-hour glucose levels were measured to identify undiagnosed diabetes and prediabetes (i.e., impaired fasting glucose or impaired glucose tolerance) in them. Previously diagnosed diabetes among the female breast cancer patients was determined on the self-report and the medical record.

Results

The overall incidences of total normal glucose tolerance, prediabetes, diabetes in female breast cancer patients at initial diagnosis and during chemotherapy were 24.1% and 38.5% (p<0.05), 50.6% and 28.1% (p<0.05), and 25.3% and 33.3% (p>0.05), respectively, and the differences of normal glucose tolerance and prediabetes instead of diabetes between the two groups were statistically significant. About 84% of the total diabetes and prediabetes in the female breast cancer patients at initial diagnosis and 79.7% of those during chemotherapy need to be diagnosed with OGTT.

Conclusions

Breast cancer patients have high incidences of diabetes and prediabetes. After chemotherapy even with steroids, some breast cancer patients with abnormal glucose metabolism may even become normal. Isolated hyperglycemia 2 hours after glucose loading is common, and OGTT should be made for breast cancer patients at initial diagnosis and during chemotherapy.     

黄河三角洲刺槐臭椿混交林与纯林土壤细菌群落结构和多样性特征分析

为研究黄河三角洲地区混交人工林土壤细菌群落特征,应用高通量测序技术,比较分析了刺槐臭椿混交林以及臭椿和刺槐纯林土壤细菌结构及多样性,并结合土壤理化性质进行分析。试验结果表明：在细菌门分类水平上,臭椿纯林、刺槐纯林、刺槐臭椿混交林土壤中分别检测出27、25、31门细菌,3种不同林分土壤中酸杆菌门、变形菌门、放线菌门、硝化螺旋菌门、绿弯菌门、浮霉菌门、芽单胞菌门、疣微菌门8种细菌是土壤中的主要细菌群落,其中酸杆菌门、变形菌门和放线菌门为优势细菌群落。不同类型人工林土壤中各门细菌相对丰度差异显著。混交林土壤细菌物种数和Shannon指数值分别为1910和9.1高于两种纯林。通过对土壤主要细菌群落与土壤理化性质进行主成分分析发现,3种不同林分之间在土壤细菌群落结构上有较高程度的分离,差异显著（P < 0.05）,有效磷含量与混交林土壤细菌群落有较强的正相关关系。因此可以得出结论,不同林分类型、土壤理化性质和细菌群落结构三者相互影响,刺槐臭椿混交增加了土壤细菌群落多样性,土壤理化性质在一定程度上影响土壤细菌结构和多样性。     

神农架湿地泥炭测评及其生态保护开发

对神农架大九湖湿地泥炭资源进行了调查、采样、检测与评价。结果表明,神农架泥炭中,有机质含量>70%,腐殖酸含量>30%,胡敏酸与富里酸的含量比C(胡敏酸)/C(富里酸)>5.0,水解氨基酸含量为7%。可用于医药、保健、增效、添加等系列生物制品的开发。     

Chrysophanol Relieves Cognition Deficits and Neuronal Loss Through Inhibition of Inflammation in Diabetic Mice

Patients with diabetes mellitus are easy to experience diabetic encephalopathy (DE) and other cognition dysfunction, whereas the neural alterations in developing this disease are unknown yet. Chrysophanol (CHR) is one of traditional Chinese medicine which was reported to show protective effects in cognition dysfunction and inflammatory in previously studies. In this current study, whether CHR protects learning and memory dysfunctions induced by diabetes disease or not and underlying mechanisms were studied. DE model was induced by streptozotocin (STZ, i.p.) in ICR mice. CHR was administrated 3 days after STZ treated mice which was confirmed with diabetes for consecutive 6 days. Learning and memory function was tested by Morris water maze after the CHR injection. The morphology of neuronal cells in hippocampus CA3 region was stained by HE-staining. ELISA and Western blot assay were used to determine the levels of pro-inflammation cytokines (IL-1β, IL-4, IL-6, TNF-α) in hippocampus. Here, we demonstrated that mice harboring diabetes mellitus induced by STZ exhibit high blood glucose, learning and memory deficits detected by Morris water maze behavior tests. Application with CHR right after developing diabetes disease rescues partial blood sugar increasing, learning and memory deficits. The data also indicated that the death rate of neurons and the number of astrocytes in hippocampus CA3 region was significantly improved in diabetic mice. Moreover, the underlying mechanisms of CHR’s protective effect are likely associated with anti-inflammation by downregulating the expression of pro-inflammation cytokines (IL-1β, IL-4, IL-6, TNF-α) in hippocampus and inhibiting the over-activation of astrocytes in hippocampus CA3 region. Therefore, application with CHR contributes to the learning and memory deficits induced by diabetes disease via inhibitory expressions of inflammatory in hippocampus region.     

Molecular dynamics simulations of palmitate entry into the hydrophobic pocket of the fatty acid binding protein

The entry of substrate into the active site is the first event in any enzymatic reaction. However, due to the short time interval between the encounter and the formation of the stable complex, the detailed steps are experimentally unobserved. In the present study, we report a molecular dynamics simulation of the encounter between palmitate molecule and the Toad Liver fatty acid binding protein, ending with the formation of a stable complex resemblance in structure of other proteins of this family. The forces operating on the system leading to the formation of the tight complex are discussed.     

Using reporter gene assays to identify cis regulatory differences between humans and chimpanzees

Most phenotypic differences between human and chimpanzee are likely to result from differences in gene regulation, rather than changes to protein-coding regions. To date, however, only a handful of human-chimpanzee nucleotide differences leading to changes in gene regulation have been identified. To hone in on differences in regulatory elements between human and chimpanzee, we focused on 10 genes that were previously found to be differentially expressed between the two species. We then designed reporter gene assays for the putative human and chimpanzee promoters of the 10 genes. Of seven promoters that we found to be active in human liver cell lines, human and chimpanzee promoters had significantly different activity in four cases, three of which recapitulated the gene expression difference seen in the microarray experiment. For these three genes, we were therefore able to demonstrate that a change in cis influences expression differences between humans and chimpanzees. Moreover, using site-directed mutagenesis on one construct, the promoter for the DDA3 gene, we were able to identify three nucleotides that together lead to a cis regulatory difference between the species. High-throughput application of this approach can provide a map of regulatory element differences between humans and our close evolutionary relatives.     

Cdk5 is involved in NFT-like tauopathy induced by transient cerebral ischemia in female rats

Although neurofibrillary tangle (NFT) formation is a central event in both familial and sporadic Alzheimer's disease (AD), neither cellular origin nor functional consequence of the NFTs are fully understood. This largely is due to the lack of available in vivo models for neurofibrillary degeneration (NFD). NFTs have only been identified in transgenic mice, bearing a transgene for a rare hereditary neurodegenerative disease, frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP17). Epidemiological evidence suggests a much higher occurrence of dementia in stroke patients. This may represent the underlying cause of the pathogenesis of sporadic AD, which accounts for the majority of AD cases. We examined pathological markers of AD in a rodent stroke model. Here we show that after transient cerebral ischemia, hyperphosphorylated tau accumulates in neurons of the cerebral cortex in the ischemic area, forms filaments similar to those present in human neurodegenerative tauopathies and colocalizes with markers of apoptosis. As a potential underlying mechanism, we were able to determine that transient ischemia induced tau hyperphosphorylation and NFT-like conformations are associated with aberrant activation of cyclin dependent kinase 5 (Cdk5) and can be rescued by delivery of a potent, but non-specific cyclin dependent kinase inhibitor, roscovitine to the brain. Our study further indicates that accumulation of p35 and its calpain-mediated cleavage product, p25 may account for the deregulation of Cdk5 induced by transient ischemia. We conclude that Cdk5 may be the principal protein kinase responsible for tau hyperphosphorylation and may be a hallmark of the tauopathies in this stroke model.