The Role of the Deubiquitylase MYSM1 During Alphavirus Infection Amer Nubgan The members of the genus Alphavirus are positive-sense RNA viruses and it is one of two within the family Togaviridae. Most alphaviruses are predominantly transmitted to susceptible vertebrates by a mosquito vector. Alphavirus disease in humans can be severely debilitating, and depending on the particular viral species, infection may result in encephalitis and possibly life threatening symptoms. Chikungunya virus (CHIKV) is the aetiological agent represents a substantial health burden to affected populations, with clinical symptoms that include severe joint and muscle pain, rashes, and fever, as well as prolonged periods of disability in some patients. In recent years, CHIKV has received significant attention from public health authorities as a consequence of the dramatic emergence infections in the Indian Ocean islands and the Caribbean as well as the recent emergence of CHIKV in the Americas. Infections have also been reported around Europe such as in Italy, France and Greece. Currently, no safe, approved or effective vaccine or treatment exists for CHIKV infection. The ubiquitin-proteasome system (UPS), the major intracellular proteolytic pathway, mediates different kinds of cellular processes, which may be targeted by viruses to aid their replication within cells. In recent years it has been well established that both the forward reaction of ubiquitination, and the reverse reaction of deubiquitination are targeted during virus infection to enhance their replication, either by targeting of cellular proteins or encoding viral homologues of key pathway proteins. The reverse reaction is undertaken by a large family of enzymes termed deubiquitylases or DUBs, and many of these have been shown to play a crucial role, not only in virus replication but also in the regulation of the immune system and vesicle trafficking. The DUBs are attractive drug targets and have increasingly been implicated in cellular processes germane to malignancy which makes the continued characterisation of the role of DUBs during virus infection a worthwhile objective. In on-going experiments in the research group a DUB siRNA pools library screen identified 12 DUBs (USP1, USP4, USP5, USP34, USP45, USP46, OTUD6A, UCHL1, JOSD2, BRCC3 and MYSM1). Depletion of these hits in HeLa cells lead to an increase in cell viability following Semiliki Forest Virus (SFV) infection (and predicted to be pro-viral) and thus could potential be candidate antiviral targets. Inroads into understanding the role of the DUB hits during the alphavirus infection, focusing initial on the BSL2 model virus SFV, and extending this to CHIKV (at BSL3). In the present study, further screening focused on the deconvolution siRNA pools for the DUB hits. Investigation of the subsequent follow up experiments with one strong candidate DUB from this list, MYSM1. Two different approaches were taken. Firstly, the effect of depletion of MYSM1 by siRNA treatment was further investigated in HeLa cells. Secondly, the analysis was extended to investigate the role of MYSM1 in fibroblasts utilising MYSM1 genetic knockout murine embryo fibroblasts. Results from this study indicate that depletion of MYSM1 in HeLa cells by siRNAs resulted in a reduction in both SFV and CHIKV replication, as assayed by measuring RNA levels and plaque formation. It was also found that MYSM1 genetic knockout in MEF cells lead to increase in both SFV and CHIKV replication. In addition, depletion of MYSM1 by siRNAs in MRC-5 cells lead to increase in SFV replication. In conclusion, MYSM1 generated interesting data, implying a role during virus infection that appeared to depend on the cell type being infected. Up to now it is unclear what the effector mechanisms are that contribute to these observations, subject to further mechanistic and functional studies, may increase the options available for targeting this vital DUB during Alphavirus infections.
Polycystic ovary syndrome (PCOS) is a complex endocrine–metabolic disorder characterized by hyperandrogenism, ovulatory dysfunction, insulin resistance, and chronic inflammation resulting in reproductive and metabolic complications. Traditional metformin therapy improves insulin sensitivity, while newer dual incretin agonists, such as tirzepatide, may offer broader metabolic and ovarian protection. The objective of this study is to investigate whether tirzepatide could alter hormonal parameters, metabolism, inflammation, and histopathology of a testosterone propionate–induced PCOS rat model compared with metformin. Thirty prepubertal female Wistar rats were divided into five groups (n = 6). PCOS was induced by testosterone propionate (1
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In latest decades, genetic methods have developed into a potent tool in a number of life-attaching applications. In research looking at demographic genetic diversity, QTL detection, marker-assisted selection, and food traceability, DNA-based technologies like PCR are being employed more and more. These approaches call for extraction procedures that provide efficient nucleic acid extraction and the elimination of PCR inhibitors. The first and most important stage in molecular biology is the extraction of DNA from cells. For a molecular scientist, the high quality and integrity of the isolated DNA as well as the extraction method's ease of use and affordability are crucial factors. The present study was designed to establish a simple, fast
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In this paper, some series of new complexes of Mn(II), Co(II), Ni (II) Cu(II) and Hg(II) are prepared from the Schiff bases (L1,L2). (L1) derived from 4-aminoantipyrine and O-phenylene dia mine then (L2) derived from (L1) and 2-benzoyl benzoic acid. Structural features are obtained from their elemental microanalyses, molar conductance, IR, UV–Vis, 1H, 13CNMR spectra and magnetic susceptibility. The magnetic susceptibility and UV–Vis, IR spectral data of the ligand (L1) complexes get square–planar and tetrahedral geometries and the complexes oflig and (L2) get an octahedral geometry. Antimicrobial examinations show good results in the sharing complexes.
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Poly(ethylene oxide) is a promising material for solid-state lithium batteries due to its safety, ease of processing, and compatibility with lithium. However, conventional linear PEO falls short of practical requirements due to its limited ionic conductivity, a consequence of the high crystallinity of its ethylene oxide chains. This crystallinity hinders the movement of lithium ions, limiting its performance in solid-state battery applications. In this study, we successfully prepared the plasticized solid polymer electrolytes (PSPEs) based on poly(ethylene oxide) (PEO)/ tetracyanoethylene (TCE) complexed with lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salt and studied the effect of TCE on structural, mechanical, electrical and elec
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Lowering specific energy consumption (SEC) in reverse osmosis (RO) plants is one of the most important criteria in water treatment industry. The present work focused on best suggested RO pilot plant configurations for minimizing specific energy consumption, finding the best configurations experimentally to recover the water with minimizing salts in permeate side in RO module, study the factors affecting the performance of single and two stage systems, TFC membrane is used in spiral wound module. Brackish water is used as feed solution with different concentrations (2000, 3000, 4000 and 5000 ppm). The operating parameters studied were permeate flux, rejection and SEC. The experimental results showed the permeate concentration increased and w
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In this paper, some series of new complexes of Mn(II), Co(II), Ni (II) Cu(II) and Hg(II) are prepared from the Schiff bases (L1,L2). (L1) derived from 4-aminoantipyrine and O-phenylene dia mine then (L2) derived from (L1) and 2-benzoyl benzoic acid. Structural features are obtained from their elemental microanalyses, molar conductance, IR, UV–Vis, 1H, 13CNMR spectra and magnetic susceptibility. The magnetic susceptibility and UV–Vis, IR spectral data of the ligand (L1) complexes get square–planar and tetrahedral geometries and the complexes oflig and (L2) get an octahedral geometry. Antimicrobial examinations show good results in the sharing complexes.
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Purpose Heavy metals are toxic pollutants released into the environment as a result of different industrial activities. Biosorption of heavy metals from aqueous solutions is a new technology for the treatment of industrial wastewater. The aim of the present research is to highlight the basic biosorption theory to heavy metal removal. Materials and methods Heterogeneous cultures mostly dried anaerobic bacteria, yeast (fungi), and protozoa were used as low-cost material to remove metallic cations Pb(II), Cr(III), and Cd(II) from synthetic wastewater. Competitive biosorption of these metals was studied. Results The main biosorption mechanisms were complexation and physical adsorption onto natural active functional groups. It is observed that
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In this study, biodiesel was prepared from chicken fat via a transesterification reaction using Mussel shells as a catalyst. Pretreatment of chicken fat was carried out using non‐catalytic esterification to reduce the free fatty acid content from 36.28 to 0.96 mg KOH/g oil using an ethanol/ fat mole ratio equal to 115:1. In the transesterification reaction, the studied variables were methanol: oil mole ratio in the range of (6:1 ‐ 30:1), catalyst loading in the range of (9‐15) wt%, reaction temperature (55‐75 °C), and reaction time (1‐7) h. The heterogeneous alkaline catalyst was greenly synthesized from waste mussel shells throughout a calcin
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