抑郁症易感基因和抗抑郁药物靶点相关[]神经细胞类型及相互作用网络分析

基于抑郁症的全基因组关联分析研究(GWAS),对于获得的单核苷酸多态性位点(SNP)使用Haploreg软件进行基因注释,得到SNP注释的102个易感基因.。使用MAGMA软件对GWAS的汇总统计数据做基因水平的分析,获得了270个校正之后显著的基因,两者合并共得到320个抑郁症易感基因。通过药物数据库Drugbank获取133个抗抑郁药物靶点基因。使用EWCE包对抑郁症易感基因和抗抑郁药物靶点在三套脑组织单细胞测序数据中,分别进行神经细胞类型富集分析。结果发现大脑皮质的GABA神经元(抑制性神经元)和谷氨酸能神经元(兴奋性神经元)是抑郁症易感基因和抗抑郁药物靶点共同的神经元。这两种类型的神经细胞可能是抗抑郁药物与抑郁症易感基因相互作用的神经细胞,另外少突胶质前体细胞可能是抑郁症特有的易感神经细胞。使用Network Calculator软件构建网络并进行进行网络拓扑学参数分析。结果表明抑郁症易感基因与抗抑郁药物靶点组成了一个具有显著的相互连接的网络。本研究从单细胞层面揭示抑郁症的遗传机制,在网络层面为寻找新的抗抑郁药物靶点提供了一定的启示。     

土壤不同水分条件对长春花(Catharanthus roseus)生活史型的影响

为了研究土壤中不同水分条件对长春花生活史型形成及生理代谢的影响,设置对照、轻度干旱、中度干旱和重度干旱等土壤水分梯度,对长春花(Catharanthus roseus(L.)G.Don)幼苗进行处理。对长春花形态指标进行聚类分析发现选择的20个聚类实体被分为2组,第1组为对照(CK)和轻度干旱(LD)处理的植株,第2组为中度干旱(MD)和重度干旱(HD)处理的植株。运用主成分分析(Principal component analysis,PCA)方法对不同土壤水分条件下长春花营养生长(Vegetative growth,V)、有性生殖(Sexual reproduction,S)和无性繁殖(Clone reproduction,C)等3类15种性状进行统计。结果显示,长春花在对照条件下生活史型为V0.39S0.54C0.07,轻度干旱为V0.36S0.50C0.14,中度干旱为V0.53S0.27C0.20,重度干旱为V0.45S0.09C0.46,干旱程度加强显著提高了无性繁殖的比重,降低了有性生殖的比例。同时,对长春花中文朵灵、长春质碱和脱水长春碱等生物碱的含量进行了动态测定,发现重度干旱下的文朵灵、长春质碱和脱水长春碱的含量在16d时分别是对照水平的1.5倍、2.3倍和3.1倍,表明干旱胁迫诱导生物碱积累,为长春花高效栽培提供了理论依据。     

Specific endotoxic lipopolysaccharide-binding receptors on murine splenocytes. III. Binding specificity and characterization.

In previously published studies, we employed a photoreactive radioiodinated derivative of LPS from Escherichia coli 0111:B4 to identify and characterize a membrane-localized specific LPS binding protein of approximately 80-kDa molecular mass. Our more recent studies demonstrating that mAb with specificity for this 80-kDa protein will act as an agonist in mediating macrophage activation have established that this protein serves as a specific receptor for LPS. In the experiments reported here, we have more accurately determined the apparent molecular mass of this protein to be 73 kDa (p73). We have also extended the sources of LPS-derivatized photo-cross-linking preparations (including Re-LPS) to determine generality of LPS binding to this receptor. Binding to the p73 LPS receptor is demonstrated with all of the LPS derivatives synthesized in our laboratory, as well as probes synthesized by other investigators. Binding of S-LPS is readily inhibited by Re chemotype LPS, and we have shown that this competitive inhibition is most likely not the result of formation of LPS aggregates. These results confirm and extend our earlier studies suggesting that the binding of LPS to the p73 receptor is lipid A specific. We further demonstrate that, in contrast to results published in a recent report, the p73 LPS receptor has no significant binding specificity for a variety peptidoglycan polymer preparations. Finally, we show that this LPS receptor can be detected on murine fibroblast, macrophage, and mastocytoma cell lines. Differences have been observed in the level of expression of LPS receptors on the various cell lines studied.     

Engineering mouse apolipoprotein A-I into a monomeric, active protein useful for structural determination

Apolipoprotein AI (apoAI), the major protein component of HDL, is one of the best predictors of coronary artery disease (CAD), with high apoAI and HDL levels being correlated with low occurrences of CAD. The primary function of apoAI is to recruit phospholipid and cholesterol for assembly of HDL particles. Like other exchangeable apolipoproteins, lipid-free apoAI forms a mixture of different oligomers even at 1.0 mg/mL. This self-association property of the exchangeable apolipoproteins is closely associated with the lipoprotein-binding activity of this protein family. It is unclear if the self-association property of apolipoprotein is required for its lipoprotein-binding activity. We developed a novel method for engineering an oligomeric protein to a monomeric, biologically active protein. Using this method, we generated a monomeric mouse apoAI mutant that is active. This mutant contains the first 216 residues of mouse apoAI and replaces six hydrophobic residues with either polar or smaller hydrophobic residues at the defined positions (V118A/A119S/L121Q/T191S/T195S/T199S). Cross-linking results show that this mutant is greater than 90% monomeric at 8 mg/mL. CD, DSC, and NMR results indicate that the mutant maintains an identical secondary, tertiary structure and stability as those of the wild-type mouse apoAI. Lipid-binding assays suggest that the mutant shares an equal lipoprotein-binding activity as that of the wild-type apoAI. In addition, both the monomeric mutant and the wild-type protein make nearly identical rHDL particles. With this monomeric mouse apoAI, high-quality NMR data has been collected, allowing for the NMR structural determination of lipid-free apoAI. On the basis of these results, we conclude that this apoAI mutant is a monomeric, active apoAI useful for structural determination.     

An Imported Case of Cystic Echinococcosis in the Liver

A 25-year-old Uzbek male presented with right upper abdominal pain for 20 days. On radiologic studies, a huge cystic mass was noticed in the right liver which was suspected as parasitic. The patient received right hepatic segmentectomy (segment 7), and the surgically resected mass was confirmed as cystic echinococcosis (CE), measuring 10.5 cm in its diameter. The inner surface of the cyst was bile-stained. The patient was discharged on the 8th hospital day, and was rechecked 6 months after the surgical intervention without any evidence of recurrence. The present report describes findings of an imported case of CE which represented ultrasound images of the ''ball of wool''.     

Detection of an intermediate during the unfolding process of the dimeric ketosteroid isomerase

Failure to detect the intermediate in spite of its existence often leads to the conclusion that two-state transition in the unfolding process of the protein can be justified. In contrast to the previous equilibrium unfolding experiment fitted to a two-state model by circular dichroism and fluorescence spectroscopies, an equilibrium unfolding intermediate of a dimeric ketosteroid isomerase (KSI) could be detected by small angle X-ray scattering (SAXS) and analytical ultracentrifugation. The sizes of KSI were determined to be 18.7A in 0M urea, 17.3A in 5.2M urea, and 25.1A in 7M urea by SAXS. The size of KSI in 5.2M urea was significantly decreased compared with those in 0M and 7M urea, suggesting the existence of a compact intermediate. Sedimentation velocity as obtained by ultracentrifugation confirmed that KSI in 5.2M urea is distinctly different from native and fully-unfolded forms. The sizes measured by pulse field gradient nuclear magnetic resonance (NMR) spectroscopy were consistent with those obtained by SAXS. Discrepancy of equilibrium unfolding studies between size measurement methods and optical spectroscopies might be due to the failure in detecting the intermediate by optical spectroscopic methods. Further characterization of the intermediate using (1)H NMR spectroscopy and Kratky plot supported the existence of a partially-folded form of KSI which is distinct from those of native and fully-unfolded KSIs. Taken together, our results suggest that the formation of a compact intermediate should precede the association of monomers prior to the dimerization process during the folding of KSI.     

益生菌Lactobacillus casei Zhang固态发酵条件的优化

利用一株分离自传统发酵酸马奶中的益生干酪乳杆菌（Lactobacillus casei Zhang）进行固态发酵（Solid State Fermentation,SSF）。以发酵物中的活菌数为主要指标,采用九因素四水平（L32（4^9））的正交试验优化固态发酵培养基,并在优化的培养基基础上研究不同的初始含水量及培养时间对Lactobacillus casei Zhang活菌数的影响。实验结果表明,在固态发酵培养基组成为4g豆粕、5g麸皮、0．6g乳清粉、0．3g葡萄糖、0．3g碳酸钙、0．02g硫酸铵、0．01g硫酸镁,初始含水量为55％的优化条件下,37℃发酵60h,发酵物中Lactobacillus casei Zhang活菌数可达到4．08×10^10CFU／g。     

Diallyl trisulfide induces apoptosis and inhibits proliferation of A549 cells in vitro and in vivo

Lung cancer is the leading cause of cancer-related mortality all over the world. In recent years, pulmonary adenocarcinoma has surpassed squamous cell carcinoma in frequency and is the predominant form of lung cancer in many countries. Epidemiological investigations have shown an inverse relationship between garlic (Allium sativum) consumption and death rate from many cancers. Diallyl trisulfide (DATS) is one of the garlic-derived compounds (also known as: organosulfer compounds, OSC). DATS can induce apoptosis and inhibit the growth of many cancer cell lines. Our study demonstrated that the apoptotic incidents induced by DATS were a mitochondria-dependent caspase cascade through a significant decrease of the anti-apoptotic Bcl-2 that resulted in up-regulation of the ratio of Bax/Bcl-2 and the activity of caspase-3, -8, and -9. Eventually, DATS induced the apoptosis and inhibited the proliferation in a concentration- and time-dependent manner. Furthermore, by establishing an animal model of female BALB/c nude mice with A549 xenografts, we found that oral gavage of DATS significantly retarded growth of A549 xenografts in nude mice without causing weight loss or any other side effects compared with the control group. All the evidence both in vitro and in vivo suggested that DATS could be an ideal anti-cancer drug.     

Faster STORM using compressed sensing

In super-resolution microscopy methods based on single-molecule switching, the rate of accumulating single-molecule activation events often limits the time resolution. Here we developed a sparse-signal recovery technique using compressed sensing to analyze images with highly overlapping fluorescent spots. This method allows an activated fluorophore density an order of magnitude higher than what conventional single-molecule fitting methods can handle. Using this method, we demonstrated imaging microtubule dynamics in living cells with a time resolution of 3 s.     

Genome-wide comparative analysis of DNAJ genes and their co-expression patterns with HSP70s in aestivation of the sea cucumber Apostichopus japonicus

Functional & Integrative Genomics - DNAJ proteins function as co-chaperones of HSP70 and play key roles in cell physiology to promote protein folding and degradation, especially under...