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Here we investigated the nature and functional consequences of mutations in the HIV-1tat gene within an epidemiologically-linked AIDS transmission cohort consisting of a non-progressing donor (A) and two normal progressing recipients (B and C). Multiple nonsynonymous mutations in thetat first exon were observed across time in all individuals. Some mutations demonstrated striking host specificity despite the cohort being infected with a common virus. Phylogenetic segregation of thetat clones at the time of progression to AIDS was also observed especially in recipient C. Tat clones supporting high levels of transactivation were present at all time points in all individuals, although a number of clones defective for transactivation were observed for recipient C in later time points. Here we show that thetat quasispecies in a linked transmission cohort diversify and evolve independently between hosts following transmission. It supports the belief that quasispecies variation in HIV-1 is a mechanism for selection towards defining a fitter gene variant that is capable of resisting the human immune system. 相似文献
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Heavy metals have the potential to engage in strong bonding interactions and can thus function in essential as well as toxic or therapeutic capacities. We conducted crystallographic analyses of heavy cation binding to the nucleosome core particle and found that Co2+ and Ni2+ preferentially associate with the DNA major groove, in a sequence- and conformation-dependent manner. Conversely, Rb+ and Cs+ are found to bind only opportunistically to minor groove elements of the DNA, in particular at narrow AT dinucleotide sites. Furthermore, relative to Mn2+ the aggressive coordination of Co2+ and Ni2+ to guanine bases is observed to induce a shift in histone–DNA register around the nucleosome center by stabilizing DNA stretching over one region accompanied by expulsion of two bases at an opposing location. These ‘softer’ transition metals also associate with multiple histone protein sites, including inter-nucleosomal cross-linking, and display a proclivity for coordination to histidine. Sustained binding and the ability to induce structural perturbations at specific locations in the nucleosome may contribute to genetic and epigenetic mechanisms of carcinogenesis mediated by Co2+ and Ni2+. 相似文献
305.
Summary The alluvial soils of Central Iraq are occupied by 4 main vegetation types. The soils under the riverian vegetation are characterised by medium salinity and high proportions of bivalent cations. The soils occupied by arid scrub vegetation have comparatively higher contents of clay and small amounts of soluble salts. The soils of the halophytic vegetation are highly saline and main component of this is sodium chloride. The soils under the aquatic vegetation are highest in organic matter and low in salinity. 相似文献
306.
寨卡病毒病是近年来在非洲、亚洲、南美洲等地流行的一种隐性传染病.该病由寨卡病毒(Zika virus,ZIKV)感染导致,虽然患者或携带者的病情并不明显,或在短期内很难察觉.但由于近些年来的突然流行,患者数目的 急剧增加,而且各国间贸易往来愈加繁荣,亦加快了该疾病流行的步伐.疾病的防治离不开确切的诊断,如何快速、准确检测出寨卡病毒不容小觑,是急需解决的世界性难题之一. 相似文献
307.
Hongqing Wen Lei Wang Kareem Morsy Hamida Hamdi Ayman E. El-Kenawy Attalla F. El-kott 《Journal of biochemical and molecular toxicology》2023,37(1):e23222
Chloroxine (5,7-dichloro-8-hydroxyquinoline) is a molecule utilized in some shampoos for the therapy of seborrheic dermatitis of the scalp and dandruff. In this study, we investigated the inhibition effects of 5,7-dichloro-8-hydroxyquinoline and methyl 3,4,5-trihydroxybenzoate compounds on the 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA Reductase) and urease enzymes. We have obtained results for the HMG-CoA Reductase and urease enzymes at the micromolar level. In our study, inhibition result of 5,7-dichloro-8-hydroxyquinoline and Methyl 3,4,5-trihydroxybenzoate on HMG-CoA reductase showed lower values 2.28 ± 0.78 and 33.25 ± 5.04 µg/ml, respectively. Additionally, inhibition result of 5,7-dichloro-8-hydroxyquinoline and methyl 3,4,5-trihydroxybenzoate on urease showed lower values 6.18 ± 1.38 and 8.51 ± 1.35 µg/ml, respectively. Molecular docking calculations were made for their biological activities were compared. In the present work, the structures of the related compounds ( 1 and 2 ) were drawn using Gaussian 09 software and done geometry optimization at DFT/B3LYP/6-31G* basis set with aforementioned program. Cytotoxicity potential of these compounds against human lung cancer demonstrated that these compounds had good cytotoxic effects. Both compounds significantly decreased lung cell viability from low doses. In addition, 100 µM dose of all compounds caused significant reductions in lung cell viability. In general, we can say that of the two tested compounds, 5,7-dichloro-8-hydroxyquinoline and methyl 3,4,5-trihydroxybenzoate have cytotoxic effects in all cell types, and this effect is particularly strong in lung cells. Activities were performed at concentrations of 10, 20, 50, 70, and 100 µl and we achieved good results. Lung cell viability (%) value was better at 100 µl concentration and IC50 of them were 54.28 and 48.05 µM. 相似文献
308.
奥陶纪是串管海绵早期演化的一个关键阶段,记录了该类群的首次大规模辐射演化事件(属级分类单元达15个)。然而,现有大部分奥陶系串管海绵的报道来自澳大利亚东部和北美等地,在中国至今仅发现了两个属,与前述地区相比研究程度偏低。早期研究主要基于形态学特征对串管海绵进行系统分类描述,对其滤食策略知之甚少,因此制约了对此类海绵在奥陶纪底栖生态系统作用的相关探讨。本文系新疆塔里木柯坪地区奥陶纪串管海绵的首次系统古生物学报道,详细描述凯迪阶(上奥陶统)印干组中保存完好的阔室丛花海绵(Corymbospongia amplia)化石的形态学特征,并通过研究标本外壁微孔孔径的大小分布,探讨其滤食选择性。海绵外壁微孔孔径的分析表明:小型和微型浮游生物可能是其食物的主要来源,而多细胞浮游动物因个体尺寸大于海绵外壁微孔,不能被阔室丛花海绵捕获。本研究为奥陶纪串管海绵古生态学及其地球生物学意义的探讨提供了进一步的依据。 相似文献
309.
Tingting Cui Kareem Fakhfakh Hannah Turney Gülin Güler-Gane Aleksandra Toloczko Martyn Hulley Richard Turner 《Biotechnology progress》2023,39(1):e3301
In recent years, mRNA-based therapeutics have been a fast-growing new class of biologics that can, in principle, encode any protein(s) directly in patients to treat various diseases. mRNA vaccines have been proven to work efficiently, have high potency, and can be rapidly developed and deployed, which is critical for a quick responses in the case of a pandemic. Such agile development is enabled by rapid synthesis of RNA in vitro using recombinant enzymes rather than relying on lengthy and complex cell culture processes. mRNA exhibits physical and chemical properties differing from protein-based therapeutics. It is highly negatively charged and the hydroxyl group makes mRNA less stable and more susceptible to hydrolysis and nucleophilic cleavage. This novel work shares comprehensive studies carried out to compare the performance of various mRNA purification strategies by considering its scalability and critical quality attributes. In addition, the paper provides insights on how to establish a scalable mRNA purification process that consists of ultrafiltration/diafiltration and chromatography steps with good recoveries. Alternative Oligo(dT) based columns were further explored aiming to improve total process recovery. With Oligo(dT) as a capture step, overall recoveries of 70% can be achieved for mRNAs studied here that encode anti-influenza immunoglobulin G monoclonal antibodies. 相似文献