Recent advances in the identification of the host factors involved in dengue virus replication

Dengue virus (DENV) belongs to the genus Flavivirus of the family Flaviviridae and it is primarily transmitted via Aedes aegypti and Aedes albopictus mosquitoes. The life cycle of DENV includes attachment, endocytosis, protein translation, RNA synthesis, assembly, egress, and maturation. Recent researches have indicated that a variety of host factors, including cellular proteins and microRNAs, positively or negatively regulate the DENV replication process. This review summarizes the latest findings (from 2014 to 2016) in the identification of the host factors involved in the DENV life cycle and Dengue infection.

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MicroRNAs in alcoholic liver disease: Recent advances and future applications

Alcoholic liver disease (ALD) is characterized by hepatocyte damage, inflammatory cell activation, and increased intestinal permeability leading to the clinical manifestations of alcoholic hepatitis. Selected members of the family of microRNAs (miRNAs) are affected by alcohol, resulting in an abnormal miRNA profile in the liver and circulation in ALD. Increasing evidence suggests that miRNAs that regulate inflammation, lipid metabolism and promote cancer are affected by excessive alcohol administration in mouse models of ALD. This communication highlights recent findings in miRNA expression and functions as they relate to the pathogenesis of ALD. The cell-specific distribution of miRNAs, as well as the significance of circulating extracellular miRNAs, is discussed as potential biomarkers. Finally, the prospects of miRNA-based therapies are evaluated in ALD.     

Recent advances in discovery,heterologous expression,and molecular engineering of cyclodextrin glycosyltransferase for versatile applications

Cyclodextrin glycosyltransferase (CGTase) is an important enzyme with multiple functions, in particular the production of cyclodextrins. It is also widely applied in baking and carbohydrate glycosylation because it participates in various types of catalytic reactions. New applications are being found with novel CGTases being isolated from various organisms. Heterologous expression is performed for the overproduction of CGTases to meet the requirements of these applications. In addition, various directed evolution techniques have been applied to modify the molecular structure of CGTase for improved performance in industrial applications. In recent years, substantial progress has been made in the heterologous expression and molecular engineering of CGTases. In this review, we systematically summarize the heterologous expression strategies used for enhancing the production of CGTases. We also outline and discuss the molecular engineering approaches used to improve the production, secretion, and properties (e.g., product and substrate specificity, catalytic efficiency, and thermal stability) of CGTase.     

布洛芬微生物降解研究进展

布洛芬是苯丙酸类非甾体类抗炎药物的典型代表,属于重要的药物及个人护理品类物质。大量生产和广泛使用的布洛芬在为人类减轻病痛的同时,也带来诸多环境污染危害,已经成为重要潜在环境污染物之一。本文简要介绍布洛芬的使用情况和环境中布洛芬残留的潜在风险,重点总结布洛芬的微生物降解及降解机理研究,提出应当关注污水、脱水污泥、河流沉积物和湿地中布洛芬的微生物降解,强调开展布洛芬降解基因克隆和功能分析以及从分子水平阐明布洛芬降解机理研究的必要性及紧迫性。     

细菌降解萘、菲的代谢途径及相关基因的研究进展

多环芳烃(Polycyclic aromatic hydrocarbons,PAHs)是一类在环境中广泛存在的具有毒性的污染物,微生物降解是其在自然界中降解的主要途径,因而尤为重要。随着研究的深入,关于微生物降解PAHs的分子降解机制、途径等的认识逐渐积累。以下对细菌降解萘、菲的研究进展进行了概述,介绍了萘的水杨酸降解途径,菲的水杨酸、邻苯二甲酸及其他降解途径,同时也包括降解过程中涉及的降解基因簇,如nah-like、phn、phd、nid和nag等以及细菌在PAHs胁迫条件下其他相关基因的表达与调节等方面的最新进展。这些进展可为降解菌株的分子及遗传机制研究提供理论依据,将促进通过基因工程优化降解菌、更有效地检测PAHs环境污染及实现PAHs污染的生物修复。     

Host variations in SARS-CoV-2 infection

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the zoonotic pathogen that causes the “Coronavirus Disease of 2019 (COVID-19)”, and COVID-19 itself is yet to be thoroughly understood. Both the disease as well as the mechanisms by which the host interacts with the SARS-CoV-2 have not been fully enlightened. The epidemiological factors –e.g. age, sex, race-, the polymorphisms of the host proteins, the blood types and individual differences have all been in discussions about affecting the progression and the course of COVID-19 both individually and collectively, as their effects are mostly interwoven. We focused mainly on the effect of polymorphic variants of the host proteins that have been shown to take part in and/or affect the pathogenesis of COVID-19. Additionally, how the procedures of diagnosing and treating COVID-19 are affected by these variants and what possible changes can be implemented are the other questions, which are sought to be answered.     

Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives

The continually increasing wealth of knowledge about the role of genes involved in acquired or hereditary diseases renders the delivery of regulatory genes or nucleic acids into affected cells a potentially promising strategy. Apart from viral vectors, non-viral gene delivery systems have recently received increasing interest, due to safety concerns associated with insertional mutagenesis of retro-viral vectors. Especially cationic polymers may be particularly attractive for the delivery of nucleic acids, since they allow a vast synthetic modification of their structure enabling the investigation of structure-function relationships. Successful clinical application of synthetic polycations for gene delivery will depend primarily on three factors, namely (1) an enhancement of the transfection efficiency, (2) a reduction in toxicity and (3) an ability of the vectors to overcome numerous biological barriers after systemic or local administration. Among the polycations presently used for gene delivery, poly(ethylene imine), PEI, takes a prominent position, due to its potential for endosomal escape. PEI as well as derivatives of PEI currently under investigation for DNA and RNA delivery will be discussed.This review focuses on structure-function relationships and the physicochemical aspects of polyplexes which influence basic characteristics, such as complex formation, stability or in vitro cytotoxicity, to provide a basis for their application under in vivo conditions. Rational design of optimized polycations is an objective for further research and may provide the basis for a successful cationic polymer-based gene delivery system in the future.     

Recent Advances in Genetics of Salt Tolerance in Tomato

Salinity is an important environmental constraint to crop productivity in arid and semi-arid regions of the world. Most crop plants, including tomato, Lycopersicon esculentum Mill., are sensitive to salinity throughout the ontogeny of the plant. Despite considerable research on salinity in plants, there are only a few instances where salt-tolerant cultivars have been developed. This is due in part to the complexity of the trait. A plant's response to salt stress is modulated by many physiological and agronomical characteristics, which may be controlled by the actions of several to many genes whose expressions are influenced by various environmental factors. In addition, salinity tolerance is a developmentally regulated, stage-specific phenomenon; tolerance at one stage of plant development is often not correlated with tolerance at other stages. Specific ontogenic stages should be evaluated separately for the assessment of tolerance and the identification, characterization, and utilization of useful genetic components. In tomato, genetic resources for salt tolerance have been identified largely within the related wild species, and considerable efforts have been made to characterize the genetic controls of tolerance at various developmental stages. For example, the inheritance of several tolerance-related traits has been determined and quantitative trait loci (QTLs) associated with tolerance at individual developmental stages have been identified and characterized. It has been determined that at each stage salt tolerance is largely controlled by a few QTLs with major effects and several QTLs with smaller effects. Different QTLs have been identified at different developmental stages, suggesting the absence of genetic relationships among stages in tolerance to salinity. Furthermore, it has been determined that in addition to QTLs which are population specific, several QTLs for salt tolerance are conserved across populations and species. Research is currently underway to develop tomatoes with improved salt tolerance throughout the ontogeny of the plant by pyramiding QTLs through marker-assisted selection (MAS). Transgenic approaches also have been employed to gain a better understanding of the genetics of salt tolerance and to develop tomatoes with improved tolerance. For example, transgenic tomatoes with overexpression of a single-gene-controlled vacuolar Na⁺/H⁺ antiport protein, transferred from Arabidopsis thaliana, have exhibited a high level of salt tolerance under greenhouse conditions. Although transgenic plants are yet to be examined for field salt tolerance and salt-tolerant tomatoes are yet to be developed by MAS, the recent genetic advances suggest a good prospect for developing commercial cultivars of tomato with enhanced salt tolerance in near future.     

A novel functional gene associated with cold tolerance at the seedling stage in rice

Identification and cloning of cold‐tolerant genes that can stably express under different cold environments are crucial for molecular rice breeding for cold tolerance. In the previous study, we identified a cold‐tolerant QTL at the seedling stage, qCTS‐9 which could be detected under different cold environments using a recombinant inbred line (RIL) population derived from a cold‐tolerant variety Lijiangxintuanheigu (LTH) and a cold‐sensitive variety Shanhuangzhan 2 (SHZ‐2). In this study, eight candidate genes within the qCTS‐9 interval were identified through integrated analysis of QTL mapping with genomewide differential expression profiling of LTH. The qRT‐PCR assay showed that only Os09g0410300 exhibited different expression patterns between LTH and SHZ‐2 during cold stress, and significantly positive correlation was found between cold induction of Os09g0410300 and seedling cold tolerance in the RI lines. Five SNPs and one InDel in the promoters of Os09g0410300 were detected between LTH and SHZ‐2, and the InDel marker ID410300 designed based on the insertion–deletion polymorphism in the promoter was significantly associated with seedling cold tolerance in RIL population. Further, Os09g0410300 over‐expression plants exhibited enhanced cold tolerance at the seedling stage compared with the wild‐type plants. Thus, our results suggest that Os09g0410300 is the functional gene underlying qCTS‐9. To our knowledge, it is a novel gene contributed to enhance cold tolerance at the seedling stage in rice. Identification of the functional gene underlying qCTS‐9 and development of the gene‐specific marker will facilitate molecular breeding for cold tolerance at the seedling stage in rice through transgenic approach and marker‐assisted selection (MAS).     

番茄丛矮病毒的分子生物学研究进展

近年来,多种植物RNA病毒载体被广泛地应用于外源基因的表达、植物病毒学和植物病理学基础理论的研究中.番茄丛矮病毒(Tomato bushy stunt virus,TBSV)是番茄丛矮病毒科(Tombusviridae)番茄丛矮病毒属(Tombusvirus)的典型成员.TBSV病毒基因组复制、转录和翻译等分子机制的研究取得了巨大的进展,使得利用TBSV构建稳定、高效的表达载体成为可能.     

CK2 signaling in androgen-dependent and -independent prostate cancer

Protein serine/threonine kinase casein kinase 2 (CK2) is a key player in cell growth and proliferation but is also a potent suppressor of apoptosis. CK2 has been found to be dysregulated in all the cancers that have been examined, including prostate cancer. Investigations of CK2 signaling in the prostate were originally initiated in this laboratory, and these studies have identified significant functional activities of CK2 in relation to normal prostate growth and to the pathobiology of androgen-dependent and -independent prostate cancer. We present a brief overview of these developments in the context of prostate biology. An important outcome of these studies is the emerging concept that CK2 can be effectively targeted for cancer therapy.     

Sodium salicylate modulates inflammatory responses through AMP‐activated protein kinase activation in LPS‐stimulated THP‐1 cells

Sodium salicylate (NaSal) is a nonsteroidal anti‐inflammatory drug. The putative mechanisms for NaSal's pharmacologic actions include the inhibition of cyclooxygenases, platelet‐derived thromboxane A2, and NF‐κB signaling. Recent studies demonstrated that salicylate could activate AMP‐activated protein kinase (AMPK), an energy sensor that maintains the balance between ATP production and consumption. The anti‐inflammatory action of AMPK has been reported to be mediated by promoting mitochondrial biogenesis and fatty acid oxidation. However, the exact signals responsible for salicylate‐mediated inflammation through AMPK are not well‐understood. In the current study, we examined the potential effects of NaSal on inflammation‐like responses of THP‐1 monocytes to lipopolysaccharide (LPS) challenge. THP‐1 cells were stimulated with or without 10 ug/mL LPS for 24 h in the presence or absence of 5 mM NaSal. Apoptosis was measured by flow cytometry using Annexin V/PI staining and by Western blotting for the Bcl‐2 anti‐apoptotic protein. Cell proliferation was detected by EdU incorporation and by Western blot analysis for proliferating cell nuclear antigen (PCNA). Secretion of pro‐inflammatory cytokines (TNF‐α, IL‐1β, IL‐6) was determined by enzyme‐linked immunosorbent assay (ELISA). We observed that the activation of AMPK by NaSal was accompanied by induction of apoptosis, inhibition of cell proliferation, and increasing secretion of TNF‐α and IL‐1β. These effects were reversed by Compound C, an inhibitor of AMPK. In addition, NaSal/AMPK activation inhibited LPS‐induced STAT3 phosphorylation, which was reversed by Compound C treatment. We conclude that AMPK activation is important for NaSal‐mediated inflammation by inducing apoptosis, reducing cell proliferation, inhibiting STAT3 activity, and producing TNF‐α and IL‐1β.     

The K+/H+ antiporter LeNHX2 increases salt tolerance by improving K+ homeostasis in transgenic tomato

The endosomal LeNHX2 ion transporter exchanges H⁺ with K⁺ and, to lesser extent, Na⁺. Here, we investigated the response to NaCl supply and K⁺ deprivation in transgenic tomato (Solanum lycopersicum L.) overexpressing LeNHX2 and show that transformed tomato plants grew better in saline conditions than untransformed controls, whereas in the absence of K⁺ the opposite was found. Analysis of mineral composition showed a higher K⁺ content in roots, shoots and xylem sap of transgenic plants and no differences in Na⁺ content between transgenic and untransformed plants grown either in the presence or the absence of 120 mm NaCl. Transgenic plants showed higher Na⁺/H⁺ and, above all, K⁺/H⁺ transport activity in root intracellular membrane vesicles. Under K⁺ limiting conditions, transgenic plants enhanced root expression of the high‐affinity K⁺ uptake system HAK5 compared to untransformed controls. Furthermore, tomato overexpressing LeNHX2 showed twofold higher K⁺ depletion rates and half cytosolic K⁺ activity than untransformed controls. Under NaCl stress, transgenic plants showed higher uptake velocity for K⁺ and lower cytosolic K⁺ activity than untransformed plants. These results indicate the fundamental role of K⁺ homeostasis in the better performance of LeNHX2 overexpressing tomato under NaCl stress.     

Identification of further <Emphasis Type="Italic">Craterostigma plantagineum cdt</Emphasis> mutants affected in abscisic acid mediated desiccation tolerance

The resurrection plant (Craterostigma plantagineum) is desiccation tolerant. However, callus derived from this plant, when propagated in vitro, requires exogenously applied abscisic acid (ABA) in order to survive desiccation. Treatment of callus tissue with ABA induces most of the genes that are induced by dehydration in the whole plant. This property has been exploited for the isolation of mutants that show dominant phenotypes resulting from the ectopic expression of endogenous genes induced by the insertion of a foreign promoter. Here we describe new T-DNA tagged Craterostigma desiccation-tolerant (cdt) mutants with different molecular and physiological characteristics, suggesting that different pathways of desiccation tolerance are affected. One of the mutants, cdt-2, constitutively expresses known osmoprotective Lea genes in callus and leaf tissue. Further analysis of this mutant revealed that the tagged locus is similar to a previously characterised gene, CDT-1, which codes for a signalling molecule that confers desiccation tolerance. The nature of the T-DNA insertion provides insight into the mechanism by which the CDT-1/2 gene family functions in ABA signal transduction.