The host inflammatory response contributes to disease severity in Crimean-Congo hemorrhagic fever virus infected mice

Crimean-Congo hemorrhagic fever virus (CCHFV) is an important human pathogen. In cell culture, CCHFV is sensed by the cytoplasmic RNA sensor retinoic acid-inducible gene I (RIG-I) molecule and its adaptor molecule mitochondrial antiviral signaling (MAVS) protein. MAVS initiates both type I interferon (IFN-I) and proinflammatory responses. Here, we studied the role MAVS plays in CCHFV infection in mice in both the presence and absence of IFN-I activity. MAVS-deficient mice were not susceptible to CCHFV infection when IFN-I signaling was active and showed no signs of disease. When IFN-I signaling was blocked by antibody, MAVS-deficient mice lost significant weight, but were uniformly protected from lethal disease, whereas all control mice succumbed to infection. Cytokine activity in the infected MAVS-deficient mice was markedly blunted. Subsequent investigation revealed that CCHFV infected mice lacking TNF-α receptor signaling (TNFA-R-deficient), but not IL-6 or IL-1 activity, had more limited liver injury and were largely protected from lethal outcomes. Treatment of mice with an anti-TNF-α neutralizing antibody also conferred partial protection in a post-virus exposure setting. Additionally, we found that a disease causing, but non-lethal strain of CCHFV produced more blunted inflammatory cytokine responses compared to a lethal strain in mice. Our work reveals that MAVS activation and cytokine production both contribute to CCHFV pathogenesis, potentially identifying new therapeutic targets to treat this disease.     

Vascular Endothelial Growth Factor +936C/T, –634G/C, –2578C/A,and –1154G/A Polymorphisms with Risk of Preeclampsia: A Meta-Analysis

Background

Emerging evidence showed that VEGF gene polymorphisms are involved in the regulation of VEGF protein expression, thus increasing an individual''s susceptibility to preeclampsia (PE); but individually published results are inconclusive. The aim of this meta-analysis was to investigate the associations between VEGF gene polymorphisms and PE risk.

Methods

A systematic literature search of MEDLINE, Embase, Web of Science, and CNKI (Chinese National Knowledge Infrastructure) databases was conducted. Statistical analyses were performed using STATA 12.0 software and Review manager 5.1. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.

Results

According to the inclusion criteria, 11 case-control studies were finally included in this meta-analysis. A total of 1,069 PE cases and 1,315 controls were included in this study. Our meta-analysis indicated that VEGF +936C/T (T vs. C, OR = 1.52, 95%CI = 1.08–2.12) or −634G/C polymorphism (C vs. G, OR = 1.24, 95% CI = 1.03–1.50) was associated with the risk of PE, whereas there was no association between −2578C/A (A vs. C, OR = 0.98, 95%CI = 0.82–1.16) or −1154G/A (A vs. G, OR = 1.30, 95%CI = 0.94–1.78) polymorphism and PE risk in our study.

Conclusion

Our meta-analysis suggested that VEGF −2578C/A or −1154G/A polymorphism had no association with PE risk in all examined patients, whereas there was an association between VEGF +936C/T or −634G/C polymorphism and risk of PE.     

Light‐Driven Highly Selective Conversion of CO2 to Formate by Electrosynthesized Enzyme/Cofactor Thin Film Electrode

The highly selective electrochemical reduction of carbon dioxide (CO₂) is reported to formate (HCOO^‐) at a compactly integrated bioelectrode. The enzymatic biocatalytic cathode is fabricated by single‐step electropolymerization of a multifunctional polydopamine film in which enzyme/cofactor couples are uniquely embedded. Interestingly, this thin biohybrid system of nanoscale thickness assures unprecedentedly prolonged catalytic enzyme stability for about two weeks. Mimicking the natural photosynthesis, combination with the photoanode utilizing the water oxidation, steadily produces formate at a faradaic efficiency of 99.18 ± 6.77% with little degradation at least for 1 d under 1 sun illumination and no external bias.     

Crinkly4 receptor-like kinase is required to maintain the interlocking of the palea and lemma, and fertility in rice, by promoting epidermal cell differentiation

The palea and lemma are unique organs in grass plants that form a protective barrier around the floral organs and developing kernel. The interlocking of the palea and lemma is critical for maintaining fertility and seed yield in rice; however, the molecules that control the interlocking structure remain largely unknown. Here, we showed that when OsCR4 mRNA expression was knocked down in rice by RNA interference, the palea and lemma separated at later spikelet stages and gradually turned brown after heading, resulting in the severe interruption of pistil pollination and damage to the development of embryo and endosperm, with defects in aleurone. The irregular architecture of the palea and lemma was caused by tumour-like cell growth in the outer epidermis and wart-like cell masses in the inner epidermis. These abnormal cells showed discontinuous cuticles and uneven cell walls, leading to organ self-fusion that distorted the interlocking structures. Additionally, the faster leakage of chlorophyll, reduced silica content and elevated accumulation of anthocyanin in the palea and lemma indicated a lesion in the protective barrier, which also impaired seed quality. OsCR4 is an active receptor-like kinase associated with the membrane fraction. An analysis of promoter::GUS reporter plants showed that OsCR4 is specifically expressed in the epidermal cells of paleas and lemmas. Together, these results suggest that OsCR4 plays an essential role in maintaining the interlocking of the palea and lemma by promoting epidermal cell differentiation.     

钙调素一级结构保守性和变异性的数量分析Ⅱ钙结合区和疏水穴保守性和变异性的数量分析

用计算机为工具对３２种生物钙调素（ＣａＭ）的四个钙结合区和两个疏水穴一级结构的保守性和变异性进行了数量分析。结果表明第一、二钙结合区（Ｎ端）比第三、四钙结合区（Ｃ端）更保守;即大多数物种ＣａＭ的第一、二钙结合区的同源性大于它们全序列间的同源性。而第三、四钙结合区则因亲缘关系和高低等生物而异,情况较复杂。Ｎ端疏水穴比Ｃ端疏水火保守,前者的同源性高于它们全序列间的同源性;而后者亦因亲缘关系及高低等生物而异规律不明显。     

Extracellular calmodulin-binding proteins in plants: purification of a 21-kDa calmodulin-binding protein

A 21-kDa calmodulin (CaM)-binding protein and a 19-kDa calmodulin-binding protein were detected in 0.1 M CaCl₂ extracts of Angelica dahurica L. suspension-cultured cells and carrot (Daucus carota L.) suspension-cultured cells, respectively, using a biotinylated cauliflower CaM gel-overlay technique in the presence of 1 mM Ca²⁺. No bands, or very weak bands, were shown on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels overlayed with biotinylated cauliflower CaM when 1 mM Ca²⁺ was replaced by 5 mM EGTA, indicating that the binding of these two CaM-binding proteins to CaM was dependent on Ca²⁺. Less 21-kDa CaM-binding protein was found in culture medium of Angelica dahurica suspension cells; however, a 21-kDa protein was abundant in the cell wall. We believe that the 21-kDa CaM-binding protein is mainly in the cell wall of Angelica dahurica. Based on its reaction with periodic acid-Schiff (PAS) reagent, this 21-kDa protein would appear to be a glycoprotein. The 21-kDa CaM-binding protein was purified by a procedure including Sephadex G-100 gel filtration and CM-Sepharose cation-exchange column chromatography. The purity reached 91% according to gel scanning. The purified 21-kDa CaM-binding protein inhibited the activity of CaM-dependent NAD kinase and the degree of inhibition increased with augmentation of the 21-kDa protein, which appeared to be the typical characteristic of CaM-binding protein.     

Extracellular calmodulin: A polypeptide signal in plants?

Traditionally, calmodulin (CaM) was thought to be a multi-functional receptor for intra-cellular Ca2+ signals. But in the last ten years, it was found that CaM also exists and acts extracel-lularly in animal and plant cells to regulate many important physiological functions. Laboratory studies by the authors showed that extracellular CaM in plant cells can stimulate the proliferation of suspension cultured cell and protoplast; regulate pollen germination and pollen tube elongation, and stimulate the light-independent gene expression of Rubisco small subunit (rbcS). Furthermore, we defined the trans-membrane and intracellular signal transduction pathways for extracellular CaM by using a pollen system. The components in this pathway include heterotrimeric G-protein, phospholipase C, IP3, calcium signal and protein phosphorylation etc. Based on our findings, we suggest that extracellular CaM is a polypeptide signal in plants. This idea strongly argues against the traditional concept that there is no interce     

植物细胞质外体多肽与蛋白研究

细胞质膜以外的质外体是植物细胞的重要组成部分,质外体是植物细胞的重要信号源和细胞器。当植物遭受生物或非生物环境刺激时,可能首先引起质外体信号系统的变化;同时质外体作为植物细胞之间最方便的通道,在细胞间信号传递和信息交流上起重要作用,从而成为协调植物细胞分化、器官形成和整体生长发育的决定性因素之一。本文概括地介绍了我室在此领域的一些研究进展。     

细胞信号系统研究进展

细胞信号系统是80年代以来生物学研究领域中最活跃的课题之一．其主要研究对象是生物体对外界刺激做出反应时,细胞内发生的一系列生理生化变化,也即外界刺激信号在细胞内的传递过程．文章简述了该研究领域中近年来的新进展．     

海南尖峰岭中华穿山甲的分布与保护现状

中华穿山甲(Manis pentadactyla)是国家I级重点保护野生动物, 被IUCN红色名录列为极危(CR)物种, 也被列入CITES附录I。分布现状信息的匮乏是制约该物种保护规划制定与保护行动开展的关键因素。本文利用红外相机陷阱法和样线调查法, 于2020年8月至2021年11月在海南尖峰岭林区进行中华穿山甲海南亚种(M. p. pusilla)的监测调查, 分析评估了其分布与保护现状。调查发现: (1)尖峰岭林区7个公里网格内的8台红外相机拍摄到10次中华穿山甲出没的影像, 且在11个网格内见到35个觅食洞穴, 其中在红外相机损失率较低的南中区域记录到的中华穿山甲实体数量和洞穴数最多; (2)中华穿山甲主要分布于尖峰岭林区400-1,000 m海拔区域, 林区的国家公园一般控制区内仍然有3台红外相机拍摄到中华穿山甲及调查记录到18个觅食洞穴。结果表明: 海南尖峰岭林区仍然存在中华穿山甲种群, 目前可能被海拔等因素隔离为3个小种群; 人为干扰是影响该物种种群恢复的重要因素之一。因此, 本文提出如下建议: (1)管理部门要落实各项管护制度并加强巡护管理力度以把人为干扰程度降到最低; (2)管理部门在今后国家公园总体规划调整时可将有中华穿山甲等极危物种分布的一般控制区调整为核心保护区, 而在未调整规划前则要重点加强该区域的管理, 对建设项目布局等要尽量避开该区域; (3)尽快开展尖峰岭林区中华穿山甲的生境适宜性分析及廊道研究, 以使该物种得到更有效的保护和管理; (4)今后要定期开展其监测与保护研究, 明确尖峰岭林区中华穿山甲种群数量的动态变化; (5)在海南岛范围内开展中华穿山甲资源调查, 明确该物种在海南的种群数量及分布等情况。