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1.
Highly pathogenic avian influenza H5N1 virus clades 2.3.4, 2.3.2, and 7 are the dominant cocirculating H5N1 viruses in poultry in China. However, humans appear to be clinically susceptible mostly to the 2.3.4 virus clade. Here, we demonstrated that A549 cells and human macrophages infected with clade 2.3.4 viruses produced significantly more viruses than those infected with the other two clades. Likewise, clade 2.3.4-infected macrophages caused the most severe cellular damage and strongest proinflammatory response.  相似文献   
2.
The causes of recurrent spontaneous abortion (RSA) and fetal malformations are multifactorial and unclear in most cases. Environmental, maternal, and genetic factors have been shown to contribute to these defects. Whole-exome sequencing (WES) is widely used to detect genetic variations associated with human diseases and has recently been successfully applied to unveil genetic causes of unexplained recurrent spontaneous abortion (URSA) and fetal malformations. Here, we review the current discovery and diagnosis strategies to identify the underlying pathogenic mutations of URSA and fetal malformations using WES technology and propose to further develop WES, both to advance our understanding of these diseases and to eventually lead to targeted therapies for reproductive disorders.  相似文献   
3.
Hepatic lipid metabolism is controlled by integrated metabolic pathways. Excess accumulation of hepatic TG is a hallmark of nonalcoholic fatty liver disease, which is associated with obesity and insulin resistance. Here, we show that KH-type splicing regulatory protein (KSRP) ablation reduces hepatic TG levels and diet-induced hepatosteatosis. Expression of period 2 (Per2) is increased during the dark period, and circadian oscillations of several core clock genes are altered with a delayed phase in Ksrp−/− livers. Diurnal expression of some lipid metabolism genes is also disturbed with reduced expression of genes involved in de novo lipogenesis. Using primary hepatocytes, we demonstrate that KSRP promotes decay of Per2 mRNA through an RNA-protein interaction and show that increased Per2 expression is responsible for the phase delay in cycling of several clock genes in the absence of KSRP. Similar to Ksrp−/− livers, both expression of lipogenic genes and intracellular TG levels are also reduced in Ksrp−/− hepatocytes due to increased Per2 expression. Using heterologous mRNA reporters, we show that the AU-rich element-containing 3′ untranslated region of Per2 is responsible for KSRP-dependent mRNA decay. These findings implicate that KSRP is an important regulator of circadian expression of lipid metabolism genes in the liver likely through controlling Per2 mRNA stability.  相似文献   
4.
5.
By integrating next‐generation sequencing (NGS), bioinformatics, electron microscopy and conventional molecular biology tools, a new virus infecting kiwifruit vines has been identified and characterized. Being associated with double‐membrane‐bound bodies in infected tissues and having a genome composed of RNA segments, each one containing a single open reading frame in negative polarity, this virus shows the typical features of members of the genus Emaravirus. Five genomic RNA segments were identified. Additional molecular signatures in the viral RNAs and in the proteins they encode, together with data from phylogenetic analyses, support the proposal of creating a new species in the genus Emaravirus to classify the novel virus, which is tentatively named Actinidia chlorotic ringspot‐associated virus (AcCRaV). Bioassays showed that AcCRaV is mechanically transmissible to Nicotiana benthamiana plants which, in turn, may develop chlorotic spots and ringspots. Field surveys disclosed the presence of AcCRaV in four different species of kiwifruit vines in five different provinces of central and western China, and support the association of the novel virus with symptoms of leaf chlorotic ringspots in Actinidia. Data on the molecular features of small RNAs of 21–24 nucleotides, derived from AcCRaV RNAs targeted by host RNA silencing mechanisms, are also reported, and possible molecular pathways involved in their biogenesis are discussed.  相似文献   
6.
Mutations in CLN3 gene cause juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease), an early-onset neurodegenerative disorder that is characterized by the accumulation of ceroid lipofuscin within lysosomes. The function of the CLN3 protein remains unclear and is presumed to be related to Endoplasmic reticulum (ER) stress. To investigate the function of CLN3 in the ER stress signaling pathway, we measured proliferation and apoptosis in cells transfected with normal and mutant CLN3 after treatment with the ER stress inducer tunicamycin (TM). We found that overexpression of CLN3 was sufficient in conferring increased resistance to ER stress. Wild-type CLN3 protected cells from TM-induced apoptosis and increased cell proliferation. Overexpression of wild-type CLN3 enhanced expression of the ER chaperone protein, glucose-regulated protein 78 (GRP78), and reduced expression of the proapoptotic protein CCAAT/-enhancer-binding protein homologous protein (CHOP). In contrast, overexpression of mutant CLN3 or siRNA knockdown of CLN3 produced the opposite effect. Together, our data suggest that the lack of CLN3 function in cells leads to a failure of management in the response to ER stress and this may be the key deficit in JNCL that causes neuronal degeneration.  相似文献   
7.

Background

Interleukin-10 is an important cytokine that regulates immune response. Previous studies have shown that human cytomegalovirus can trigger cell autophagy during the early stages of infection. To our knowledge, whether IL-10 inhibits HCMV-induced autophagy and virus replication has not been studied previously.

Objectives

We investigated whether IL-10 affects cell viability and autophagy under the conditions of starvation and HCMV infection by using the MRC5 cell line. We also explored the role of IL-10-mediated autophagy on HCMV replication.

Results

Our data showed that IL-10 inhibited the autophagic flux of the MRC5 cells irrespective of starvation or HCMV infection, and suppressed HCMV replication. The promotion of autophagy with either a pharmacological inducer (rapamycin), or a technique to over-express the BECN1 gene reversed the effect of IL-10 on virus replication. Furthermore, the PI3K/Akt signal pathway was activated when the cells were pretreated with IL-10.

Conclusions

Our results indicated that IL-10 can suppress HCMV replication by inhibiting autophagy in host cells during the early stages of infection.  相似文献   
8.
A novel bacterial strain designated 9PNM-6T was isolated from an abandoned lead–zinc ore mine site in Meizhou, Guangdong Province, China. The isolate was found to be Gram-negative, rod-shaped, orange-pigmented, strictly aerobic, oxidase- and catalase-positive. Growth occurred at 0–4 % NaCl (w/v, optimum, 0 %), at pH 6.0–8.0 (optimum, pH 7.0) and at 15–32 °C (optimum, 28–30 °C). Phylogenetic analysis based on 16S rRNA gene sequence similarities showed that strain 9PNM-6T belongs to the genus Sphingomonas, with the highest sequence similarities with Sphingomonas jejuensis NBRC 107775T (99.7 %), Sphingomonas koreensis KCTC 2882T (95.1 %) and Sphingomonas dokdonesis KCTC 12541T (95.1 %). The chemotaxonomic characteristics of strain 9PNM-6T were consistent with those of the genus Sphingomonas. The predominant respiratory quinone was identified as ubiquinone Q-10, the major polyamine as sym-homospermidine, and the major cellular fatty acids as C18:1 ω7c, C16:0, C16:1 ω7c and/or C16:1 ω6c and C14:0 2-OH. The major polar lipids are sphingoglycolipid, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatideylcholine, an unidentified phospholipid and four unidentified aminolipids. The genomic DNA G+C content of strain 9PNM-6T was determined to be 69.2 ± 0.6 mol%. Based on comparative analyses of morphological, physiological and chemotaxonomic data, and levels of DNA–DNA relatedness values, strain 9PNM-6T is considered to represent a novel species of the genus Sphingomonas, for which the name Sphingomonas gimensis sp. nov. (Type strain 9PNM-6T = GIMCC 1.655T = CGMCC 1.12671T = DSM 27569T) is proposed.  相似文献   
9.
野生大豆抗感大豆孢囊线虫材料内生细菌多样性分析   总被引:2,自引:0,他引:2  
【目的】对抗感野生大豆材料根内生细菌的多样性进行比较分析,为研究野生大豆内生细菌与大豆孢囊线虫之间的相互关系奠定基础。【方法】在野生大豆抗大豆孢囊线虫3号生理小种筛选基础上,利用扩增核糖体DNA限制性分析(Amplified ribosomal DNA restriction analysis,ARDRA)和16S rDNA克隆文库测序相结合的方法,对抗感野生大豆根系内生细菌多样性及群落结构进行分析。【结果】野生大豆根内生细菌分属于6大类群,其中变形菌门(Proteobacteria)和厚壁菌门(Firmicutes)为优势类群,相对丰度分别为46.8%和13.6%,另外有少量的放线菌门(Actinobacteria)、拟杆菌门(Bacteroidetes)、酸杆菌门(Acidobacteria)、异常球菌-栖热菌门(Deincoccus-Thermus)和古细菌(Archaea),18.8%克隆序列与环境中未培养细菌的16S rDNA序列有较高的相似性。野生大豆高抗材料内生细菌的多样性比高感材料更为丰富,且抗感材料内生细菌优势菌群存在明显差异,中慢生根瘤菌(Mesorhizobium tamadayense)、肠杆菌(Enterobacter ludwigii)和巨大芽孢杆菌(Bacillus megaterium)为野生大豆高抗材料特有的可操作分类单元(Operational Taxonomic Units,OTUs)中的优势种群。【结论】研究结果表明抗感野生大豆根内生细菌的优势种群存在明显差异,而内生细菌的优势种群与大豆孢囊线虫的相互关系正在深入分析研究。  相似文献   
10.
超高压对单增李斯特菌细胞膜的损伤和致死机理   总被引:4,自引:0,他引:4  
【目的】研究超高压对病原微生物单增李斯特菌细胞膜损伤的影响。【方法】本文以单增李斯特菌为研究对象,探讨了不同压力处理(100-500 MPa)对单增李斯特菌的灭活作用,利用透射电镜观察高压处理对细菌细胞超微结构的影响,通过紫外分光光度法、原子吸收分光光度法和荧光分光光度法测定高压处理对细菌细胞膜通透性的影响,采用超微量Na+/K+-ATP酶试剂盒测定高压处理对细菌细胞膜Na+/K+-ATP酶活力的影响。【结果】25℃经300、350、400 MPa压力处理15 min后,单增李斯特菌总数由9.00分别降至5.20、3.27、1.35个对数单位,经450MPa及以上的压力处理后,单增李斯特菌的致死率达到100%。超高压处理对单增李斯特菌的细胞超微结构造成明显的损伤,细胞结构不完整,细胞壁局部被破坏,细胞膜通透性增大,细胞内物质聚合,出现透电子区。由于细胞膜的损伤使得细胞内无机盐离子、紫外吸收物质流出,细胞膜上的Na+/K+-ATPase失活。【结论】超高压处理造成单增李斯特菌细胞形态结构明显损伤,改变细胞膜的通透性,降低细胞膜上Na+/K+-ATP酶活力,最终使得细胞内无机盐离子和胞内大分子物质外流而死亡。  相似文献   
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