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: COVID-19 is an ongoing disease that caused, and still causes, many challenges for humanity. In fact, COVID-19 death cases reached more than 4.5 million by the end of August 2021, although an improvement in the medical treatments and pharmaceutical protocols was obtained, and many vaccines were released. Objective: To, statistically, analyze the data of COVID-19 patients at Alshifaa Healthcare Center (Baghdad, Iraq). Methods: In this work, a statistical analysis was conducted on data included the total number, positive cases, and negative cases of people tested for COVID-19 at the Alshifaa Healthcare Center/Baghdad for the period 1 September – 31 December 2020. The number of people who got the test was 1080, where 424 w
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Background: the coronavirus leads to upper respiratory tract-associated manifestations like nasal congestion, sore throat, and smell disorder
Objectives: To reveal the impact of COVID-19 pandemic on otolaryngology symptoms using our daily medical practice.
Subject and Methods: A cross-sectional study that was carried on in the isolation wards at Al-Kindy and Al-Nu’man Teaching Hospitals during three months from the 1st of Jun. till the end of Aug. 2020. It included 1270 patients who were diagnosed with COVID-19 infection seen in the ENT consultation clinic and admitted to the isolation wards.
Results: Otolaryngological manifestations were shown
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Background: Osteoarthritis (OA) currently seems
inevitable and unavoidable for a large swath of the
population .its etiology relates to a strong ,but
complex ,non mendelian genetic basis ,combined
with mechanical and metabolic factors that cause
molecular alterations the end results of which
affect the whole joint .Glucosamine and
chondrotin sulfate alone or in combination may be
of benefit to a subgroup of individuals who have
knee pain due to OA.
Glucosamine has been shown to alter cartiage turn
over in patients with OA undergoing physical
training
Aim of the study: To find the validity of
glucosamine chondrotin sulfate in treatment of
grade 1 and 2 OA.
Methods: the sample of 280 patients
The compliance is considered
This study aimed to deduce the net atrioventricular compliance which is affected the trans mitral blood flow.
This study focuses on study group of 25 patients (15 males
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This study is concerned with the comparison of the results of some tests of passing and dribbling of the basketball of tow different years between teams of chosen young players in Baghdad. Calculative methods were used namely (Arithmetic mean, Value digression and T.test for incompatible specimens). After careful calculative treatments, it has been that there were abstract or no abstract differences in the find results of chestpass, highdribble and cross-over dribble. The clubs were: (Al-Khark, Air defence, Police and Al-Adamiyah) each one separate from the other for the year (2000-2001). After all that many findings were reached such as the lack of objective valuation (periodical tests) between one sport season and the other. In the light
... Show MoreToxoplasmosis is an infection caused by Toxoplasma gondii that leads to abortion or hydrocephalus during pregnancy.One hundered and twenty two aborted women were selected for this study. Serum samples were collected form Al-Kadhmia and Kamal Al-Samari Hospitals,and laboratories around Baghdad, and tested for specific IgG and IgM anti-toxoplasma antibodies to confirm toxoplasmosis in those women by using ELISA test.The result recorded that 51(41.8%) women had antibodies against Toxoplasma gondii, 25(59.5%) women were positive for IgG, and 17(40.5%) women were positive forIgM, while 9(17.6%)women were positive for both.
This research aims to clarify the role of Iraqi nature in the style of the artist Ayath Al-Doori. Through it, the spotlight was shed on the aesthetic of Iraqi nature, its importance and its relationship to art, and its pioneering role in the style of the Doori artist. The research included two axes: the theoretical axis and the applied axis. The first theoretical axis deals with two topics: The first topic: the aesthetic of Iraqi nature as part of the life and methods of Iraqi artists from ancient times until today, including the periodic artist. The second topic: the league artist touched on the private life of the league artist. As for the second (applied) axis, it includes the research community, the research sample models, the resear
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The role of the ABC system in determining the costs of services in Iraqi banks