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.
The main factors that make it possible to get the corrosion of reinforcing steel in concrete are chloride ions and the absorption of carbon dioxide from the environment, and each of them works with a mechanism which destroys the stable immunity of rebar in the concrete. In this work the effect of carbon dioxide content in the artificial concrete solution on the corrosion behavior of carbon steel reinforcing bar (CSRB) was studied, potentiostatically using CO2 stream gas at 6 level of concentrations; 0.03 to 2.0 weight percent, and the effect of rising electrolyte temperature was also followed in the range 20 to 50ᴼ C. Tafel plots and cyclic polarization procedures were obeyed to investigate the c
... Show More
(10)
(2)
The international business environment faces many challenges, including the intensity of competition, the speed of expansion, and control of the market. This leads to its shadow on the local business environment, which prompted many economic units to adopt modern strategies, including mergers and acquisitions, for expansion and prosperity. The research was conducted to verify the role of internal audit in the governance of strategy operations (Mergers and acquisitions) and its reflection on management decisions and making them efficient and effective. Internal auditing is the independent variable related to the other variable, the governance of strategic operations and its impact on management decisions for strategic operations as a depende
... Show More
(8)
This paper aims to study the role of a prey refuge that depends on both prey and predator species on the dynamics of a food web model. It is assumed that the food transfer among the web levels occurs according to Lotka-Volterra functional response. The solution properties, such as existence, uniqueness, and uniform boundedness, are discussed. The local, as well as the global, stabilities of the solution of the system are investigated. The persistence of the system is studied with the assistance of average Lyapunov function. The local bifurcation conditions that may occur near the equilibrium points are established. Finally, numerical simulation is used to confirm our obtained results. It is observed that the system has only one type of a
... Show More
(9)
(2)
The present study was performed to spotlight the potential role of soil bacteria in the Al-Rumaila oil field as a bioindicator of heavy metals pollution. For this purpose, nine soil samples were collected from different sites, with 20cm depth, to assess the pollution status depending on the total and available concentrations of heavy metals. The result indicates pollution of the studied soils with the following metals: Cd, Cu, Fe, Zn, and Pb. The mean of total concentration for all studied metals was higher than the allowed maximum limit based on the international limit:(3.394, 3.994, 39.993, 8844.979,150.372, and 103.347 µg/g), respectively. While measuring the total Metal concentration is important in determining the de
... Show More
(2)
(2)
(1)
This study aimed at accounting for the role of talents management in consolidating organizational learning process at the Yemeni General Corporation For telecommunication. To achieve the objective of the study, the researcher designed a questionnaire and administered it. The sample of the study consisted of (166) employees (General Manager, Manager and Department Head). They were selected randomly out of a total Population of (291) employees during the Year 2019. The descriptive analytic approach was used t reach conclusions.
The finding of the study revealed existence of effect of talents management dimensions, all together and alone, (talents polarization, talents development, talents maintenance and ma
... Show MoreIntervention in International Relations from the concepts that are still highly
controversial among those he considers a breach of international law and the UN Charter and
in violation of the rule , and those who felt that the need provided, however, that this is linked
motives humanity recognized by the international community , because the international
variables proved the inadequacy of the principle of non-interference and the principle of
sovereignty as the traditional variables international , and therefore most of the international
practice came a bus with many of the behaviors that reflect a decline in its entirety to these
principles , and became adapt these principles with international reality is too compl
Nosocomial infections (NIs) are hospital-acquired associated infections, and also contracted due to the infections or toxins that exist in some location, like hospital. Therefore in our study, 4 Lactic acid bacteria (LAB) isolates were obtained from dairy product (Lactobacillus brevis, L. acidophilus, Lactococcus raffinolactis and Lactococcus lactis) and were tested for Bacteriocin production to select Lactococcus lactis among them. Cell free supernatant (CFS), Lipid and partial purification of protein La. Lactis had high inhibitory effect against test pathogens (E. coli, Bacillus cereus, Staphylococcus aureus and Streptococcus). 30 isolates that diagnosed by Vitec, were isol
... Show More
(1)
Leishmaniasis is a global illness that is endemic in many countries, including Iraq. The characteristic of cutaneous leishmaniasis (CL) is the development of skin ulcers that are controlled by the immune system. Tumor necrosis factor-alpha (TNF-α), a cytokine generated by the innate immune response to CL infection, can influence disease clearance in the human host. The effect of this pro-inflammatory cytokine in CL ulcer development during the infection is not well established. In this study TNF-α level was detected in the patients who suffered from cutaneous leishmaniasis. This level was also assessed in the newly diagnosed patients and others who were undergoing different stages of pentostam treatment. Notably the result
... Show More
(4)
(4)
AW Tarik, AW Ali T, A Salah, Journal of faculity of medicine Baghdad university, 2014 - Cited by 3