Bayesian Network Analysis Reveals Alterations to Default Mode Network Connectivity in Individuals at Risk for Alzheimer's Disease

Alzheimer''s disease (AD) is associated with abnormal functioning of the default mode network (DMN). Functional connectivity (FC) changes to the DMN have been found in patients with amnestic mild cognitive impairment (aMCI), which is the prodromal stage of AD. However, whether or not aMCI also alters the effective connectivity (EC) of the DMN remains unknown. We employed a combined group independent component analysis (ICA) and Bayesian network (BN) learning approach to resting-state functional MRI (fMRI) data from 17 aMCI patients and 17 controls, in order to establish the EC pattern of DMN, and to evaluate changes occurring in aMCI. BN analysis demonstrated heterogeneous regional convergence degree across DMN regions, which were organized into two closely interacting subsystems. Compared to controls, the aMCI group showed altered directed connectivity weights between DMN regions in the fronto-parietal, temporo-frontal, and temporo-parietal pathways. The aMCI group also exhibited altered regional convergence degree in the right inferior parietal lobule. Moreover, we found EC changes in DMN regions in aMCI were correlated with regional FC levels, and the connectivity metrics were associated with patients'' cognitive performance. This study provides novel sights into our understanding of the functional architecture of the DMN and adds to a growing body of work demonstrating the importance of the DMN as a mechanism of aMCI.     

Protein phosphatase 5 is required for ATR-mediated checkpoint activation

In response to DNA damage or replication stress, the protein kinase ATR is activated and subsequently transduces genotoxic signals to cell cycle control and DNA repair machinery through phosphorylation of a number of downstream substrates. Very little is known about the molecular mechanism by which ATR is activated in response to genotoxic insults. In this report, we demonstrate that protein phosphatase 5 (PP5) is required for the ATR-mediated checkpoint activation. PP5 forms a complex with ATR in a genotoxic stress-inducible manner. Interference with the expression or the activity of PP5 leads to impairment of the ATR-mediated phosphorylation of hRad17 and Chk1 after UV or hydroxyurea treatment. Similar results are obtained in ATM-deficient cells, suggesting that the observed defect in checkpoint signaling is the consequence of impaired functional interaction between ATR and PP5. In cells exposed to UV irradiation, PP5 is required to elicit an appropriate S-phase checkpoint response. In addition, loss of PP5 leads to premature mitosis after hydroxyurea treatment. Interestingly, reduced PP5 activity exerts differential effects on the formation of intranuclear foci by ATR and replication protein A, implicating a functional role for PP5 in a specific stage of the checkpoint signaling pathway. Taken together, our results suggest that PP5 plays a critical role in the ATR-mediated checkpoint activation.     

植物甜蛋白des-pGlu1-Brazzein基因在乙醇氧化酶缺陷型甲醇酵母中的表达及其活性分析

采用BglⅡ酶切重组表达载体pPIC9K-Bra,纯化后电击转化甲醇酵母菌GS115,构建乙醇氧化酶缺陷型表达菌株GS115-pPIC9K-Bra,筛选鉴定后,以0.5％的甲醇进行诱导,表达的目的蛋白约占上清总蛋白的95％,纯度较高,并具有一定的甜度.成功构建了乙醇氧化酶缺陷型的甲醇酵母表达菌株,为深入研究其应用奠定了基础.     

BDCA2/Fc?RIγ Complex Signals through a Novel BCR-Like Pathway in Human Plasmacytoid Dendritic Cells

Dendritic cells are equipped with lectin receptors to sense the extracellular environment and modulate cellular responses. Human plasmacytoid dendritic cells (pDCs) uniquely express blood dendritic cell antigen 2 (BDCA2) protein, a C-type lectin lacking an identifiable signaling motif. We demonstrate here that BDCA2 forms a complex with the transmembrane adapter FcɛRIγ. Through pathway analysis, we identified a comprehensive signaling machinery in human pDCs, similar to that which operates downstream of the B cell receptor (BCR), which is distinct from the system involved in T cell receptor (TCR) signaling. BDCA2 crosslinking resulted in the activation of the BCR-like cascade, which potently suppressed the ability of pDCs to produce type I interferon and other cytokines in response to Toll-like receptor ligands. Therefore, by associating with FcɛRIγ, BDCA2 activates a novel BCR-like signaling pathway to regulate the immune functions of pDCs.     

野大豆(Glycine soja)叶绿体的光谱及其激子能量转移

野大豆叶绿体在低温(77K)时出现三条荧光发射谱带,它们来源于不同的色素蛋白复合体。 在纳秒脉冲激光激发下,捕光天线色素的相对荧光量子产额,随激光强度的增加有明显下降现象。用激子理论和动力学方程讨论和计算了激子扩散参量。指出激子转移是随机的,非相干的。     

Histochemical examination of cathepsin K,MMP1 and MMP2 in compressed periodontal ligament during orthodontic tooth movement in periostin deficient mice

The purpose of this study was to investigate immunolocalization of collagenolytic enzymes including cathepsin K, matrix metalloproteinase (MMP) 1 and 2 in the compressed periodontal ligament (PDL) during orthodontic tooth movement using a periostin deficient (Pn-/-) mouse model. Twelve-week-old male mice homozygous for the disrupted periostin gene and their wild type (WT) littermates were used in these experiments. The tooth movement was performed according to Waldo’s method, in which elastic bands of 0.5 mm thickness were inserted between the first and second upper molars of mice under anesthesia. At 1 and 3 days after orthodontic force application, mice were fixed with transcardial perfusion of 4 % paraformaldehyde in 0.1 M phosphate buffer (pH 7.4), and the first molars and peripheral alveolar bones were extracted for histochemical analyses. Compared with WT mice, immunolocalization of cathepsin K, MMP1 and MMP2 was significantly decreased at 1 and 3 days after orthodontic tooth movement in the compressed PDL of Pn-/- mice, although MMP1-reactivity and MMP2-reactivity decreased at different amounts. Very little cathepsin K-immunoreactivity was observed in the assessed regions of Pn-/- mice, both before and after orthodontic force application. Furthermore, Pn-/- mice showed a much wider residual PDL than WT mice. Taken together, we concluded that periostin plays an essential role in the function of collagenolytic enzymes like cathepsin K, MMP1 and MMP2 in the compressed PDL after orthodontic force application.     

Characterization of full-length enterovirus 71 strains from severe and mild disease patients in northeastern China

Human enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) has been a leading cause of childhood infection in China since 2008. Epidemic and molecular characteristics of HFMD have been examined in many areas of China, including the central and southern regions. However, clinical and genetic characterization of EV71 in the northeastern region of China is scarce. In this study, a series of analyses were performed on seven full-length EV71 sequences from HFMD patients who had either severe or mild disease. We have determined that these seven circulating EV71 viruses from Changchun, China are actually complex recombinant viruses involving multiple type A human enterovirus (HEV). Classified as EV71 subtype C4 (EV71 C4), these Changchun EV71 viruses contain genetic recombination events between the CA4, CA5, EV71B4 and EV71C1 strains. Most of the structural protein region (P1) of these viruses resembled that of the prototype EV71 C1 strains. The non-structural protein domains (P2 and P3) showed a high degree of similarity with CA4, CA5 and EV71 B4 in different regions. The 5'UTR had unclassified recombination,while partial 3D region of these viruses showed a high degree of similarity to CA16. Phylogenetic analysis of full-length or partial sequences of isolates from severe or mild disease patients in Changchun always formed a single cluster in various phylogenetic analyses of different genomic regions, suggesting that all seven strains originated from one single common ancestor. There was no correlation between viral genomic sequence and virulence. Thus, we found that circulating recombinant forms of EV71 are prevalent among HFMD patients in Northeastern China. The existence of a unique cluster of EV71 related viruses in Northeast China has important implications for vaccine development that would address the increasing prevalence of HFMD.     

Fe- and S-Metabolizing Microbial Communities Dominate an AMD-Contaminated River Ecosystem and Play Important Roles in Fe and S Cycling

Indigenous Fe- and S-metabolizing bacteria play important roles both in the formation and the natural attenuation of acid mine drainage (AMD). Due to its low pH and Fe-S-rich waters, a river located in the Dabaoshan Mine area provides an ideal opportunity to study indigenous Fe- and S-metabolizing microbial communities and their roles in biogeochemical Fe and S cycling. In this work, water and sediment samples were collected from the river for physicochemical, mineralogical, and microbiological analyses. Illumina MiSeq sequencing indicated higher species richness in the sediment than in the water. Sequencing also found that Fe- and S-metabolizing bacteria were the dominant microorganisms in the heavily and moderately contaminated areas. Fe- and S-metabolizing bacteria found in the water were aerobes or facultative anaerobes, including Acidithiobacillus, Acidiphilium, Thiomonas, Gallionella, and Leptospirillum. Fe- and S-metabolizing bacteria found in the sediment belong to microaerobes, facultative anaerobes, or obligatory anaerobes, including Acidithiobacillus, Sulfobacillus, Thiomonas, Gallionella, Geobacter, Geothrix, and Clostridium. Among the dominant genera in the sediment, Geobacter and Geothrix were rarely detected in AMD-contaminated natural environments. Canonical correspondence analysis indicated that pH, S, and Fe concentration gradients were the most important factors in structuring the river microbial community. Moreover, a scheme explaining the biogeochemical Fe and S cycling is advanced in light of the Fe and S species distribution and the identified Fe- and S-metabolizing bacteria.     

A C6/C5 co‐fermenting Saccharomyces cerevisiae strain with the alleviation of antagonism between xylose utilization and robustness

During second‐generation bioethanol production from lignocellulosic biomass, the desired traits for fermenting microorganisms, such as Saccharomyces cerevisiae, are high xylose utilization and high robustness to inhibitors in lignocellulosic hydrolysates. However, as observed previously, these two traits easily showed the antagonism, one rising and the other falling, in the C6/C5 co‐fermenting S. cerevisiae strain. In this study, LF1 obtained in our previous study is an engineered budding yeast strain with a superior co‐fermentation capacity of glucose and xylose, and was then mutated by atmospheric and room temperature plasma (ARTP) mutagenesis to improve its robustness. The ARTP‐treated cells were grown in 50% (v/v) leachate from lignocellulose pretreatment with high inhibitors content for adaptive evolution. After 30 days, the generated mutant LF1‐6 showed significantly enhanced tolerance, with a six‐fold increase in cell density in the above leachate. Unfortunately, its xylose utilization dropped markedly, indicating the recurrence of the negative correlation between xylose utilization and robustness. To alleviate this antagonism, LF1‐6 cells were iteratively mutated with ARTP mutagenesis and then anaerobically grown using xylose as the sole carbon source, and xylose utilization was restored in the resulting strain 6M‐15. 6M‐15 also exhibited increased co‐fermentation performance of xylose and glucose with the highest ethanol productivity reported to date (0.525 g g^?1 h^?1) in high‐level mixed sugars (80 g L^?1 glucose and 40 g L^?1 xylose) with no inhibitors. Meanwhile, its fermentation time was shortened by 8 h compared to that of LF1. During the fermentation of non‐detoxified lignocellulosic hydrolysate with high inhibitor concentrations at pH ~3.5, 6M‐15 can efficiently convert glucose and xylose with an ethanol yield of 0.43 g g^?1. 6M‐15 is also regarded as a potential chassis cell for further design of a customized strain suitable for production of second‐generation bioethanol or other high value‐added products from lignocellulosic biomass.