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.
Background: Data on the impact of neonatal and total pediatric admissions volume on neonatal mortality are sparse. Objectives: This study is done to estimate the neonatal mortality in relation to neonatal admissions and to total hospital admissions in Al-Alwyia Pediatric Teaching Hospital through years 2005-2012 Type of the study: A retrospective study.Methods: statistical records of all cases admitted to APTH were studied during 2005-2012.Results: Neonatal mortality decreased to the nadir at last year of study period (2012) and reached 6.1% of neonatal admissions compared to 2005 level which was 9.7 %. Mortality rate among premature and low birth weight (LBW) infants decreased also. The study also reveals that neonatal mortality constit
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Objective(s): The study aims at evaluating pregnancy-related health behaviors for pregnant women, and to identify the association between pregnancy-related health behaviors and their demographic characteristics of pregnant woman’s age, education, employment, residential area and monthly income.
Methodology: A descriptive study is carried out for the period from December 14th, 2020 to June 20th, 2021. This study was conducted through a non-probability (convenience) sample of 150 pregnant women attending, Abo Ghareeb primary health care sector in Abo Ghareeb spend. The sample has been collected by using the instrument to gather data and accomplish the study's objectives. A questionnaire is composed of (29) items and it is divided into
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The aims of this study the infection with parasites Entamoeba histolytica and Giardia lamblia and prevalence rates and their relationship with gende , age group , the number of family members and source of drinking water among the patients at attending the Bint Al Huda and Al- Hussin Teaching hospital in Nassriyia city in Thi- Qar province , it was noticed that the percentage of parasitic infection at females was 38.55% and at males was 61.45% and the percentage of parasitic infection with Entamoeba histolytica 97% was higher than the percentage of parasitic infection with Giardia lamblia 3%,and the reduction of percentage of infection is associated with increasing of the number of family member ,the percentage of infection was 49% at the
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COVID-19 is a pandemic disease that has a wide spectrum of symptoms from asymptomatic to severe fatal cases due to hyperactivation of the immune system and secretion of pro-inflammatory cytokines. This study aimed to assess the level and impact of interleukin (IL)-13, IL-33, and tumor necrosis factor (TNF)-α cytokines on immune responses in mild and moderate COVID-19-infected Iraqi patients. A prospective case-control study was conducted from January 2023 to January 2024; it included 80 patients infected with moderate COVID-19 infection who consulted in different private clinics and 40 healthy controls. The serum of both groups was tested for quantification of serum IL-13, IL-33, and TNF-α using the human enzyme-linked immunosorbe
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This research seeks to identify the dimensions of the development of staff performance (training ', incentives, management skills) and its impact on the settlement of compensatory claims adopted in the current research in the Iraqi insurance company،This research aims to highlight the role of developing insurance company’s workers’ performance in settling insurance compensation, and to check this process, the research was applied in the general Iraqi insurance company as it considered as the research community, and a sample was taken from this community that represented by company’s insurance department workers or by collecting actual data that is related to the research’s sample, in addition to the financial compensation data.<
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The present research aims to present a theoretical framework for the application of takaful insurance in Iraq, as well as to identify the level of impact on the development of insurance services in the Iraqi market, and to make recommendations and suggestions that lead to increased interest in this area, and thus contribute to the development and integration of insurance service in the Iraqi market,
The research adopted the descriptive analytical method, and the questionnaire was used to survey the opinions of the research sample consisting of department managers and their assistants and some employees of the graduate degrees in addition to employees of the departments of electronic calculator in the Iraqi insurance sector, and t
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