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: Chronic hepatitis B virus (HBV) infection is a common health problem that has a worldwide distribution. Apart from the direct effect of the virus on the liver, there are many extrahepatic manifestations among which the probable effect on bone turnover associated with low bone mineral density (BMD). Objectives: This study aimed to determine the association between treated and untreated chronic HBV infection with BMD. Methods: This is a cross-sectional study which included a total of 48 patients with chronic HBV (28 patients treated with tenofovir-disoproxil-fumarate [TDF] antiviral drug and 20 patients have not yet started treatment). Other age- and sex-matched 30 apparently healthy individuals were recruited to represent the hea
... Show More
(1)
The aim of the present study is to compare the biochemical action of the three vaccines taken in Iraq: Pfizer Biontech, AstraZeneca Oxford and Sinopharm based on biochemical parameters. Seventy COVID-19 Iraqi patients ( males and females ) were participated in the present study and classified into 7 groups : Gc : COVID-19 patients ( without vaccine ) , Gp1: COVID-19 patients took one dose of Pfizer Biontech, Gp2 : COVID-19 patients took two doses of Pfizer Biontech, Ga1 : patients took one dose of AstraZeneca Oxford vaccine , Ga2: patients took two doses of AstraZeneca Oxford vaccine , Gs1 : patients took one dose of Sinopharm vaccine and Gs2:
... Show More
(4)
The current research aims to verify the role of strategic intelligence as an explanatory variable in organizational success as a respondent variable in the colleges of the University of Fallujah, the research community. (Dean, Associate Dean, Section Head, Division Officer, Unit Officer), The researcher used the questionnaire as the main tool to collect data that included (50) items, in addition to using personal interviews and field observations as aids in data collection. The researcher relied on statistical programs (SPSS V.25; Excel V (16) In the treatment and analysis of data through the use of the most appropriate statistical methods (arithmetic mean, standard deviation, difference coefficient, determinatio
... Show More
University libraries seek to evaluate their performance in order to correct their path and adjust it in the right direction. Therefore, they use (performance indicators), which are a tool used by institutions to evaluate the weaknesses and strengths in their work and the reasons for failure to achieve some goals sometimes. They convert (goals, procedures and actions) into a formula that can be measured mathematically, which contributes to the library determining the gap between its current performance and what those libraries are supposed to be on, clarifying the path that the library is following, controlling the risks that may befall it, and thus enhancing the process of continuous improvement to avoid areas of failure and weakness becaus
... Show MoreThis research sought to detect the level of organizational culture prevailing in the Integrity Commission as well as the level of the organizational citizenship behavior of staff of the Commission and the impact of organizational culture in these behaviors. To achieve the objectives of the research and test the validity of hypotheses have been used questionnaire derived from measurements ready modern researchers foreigners have been adapted to suit the Iraqi environment, have been distributed (189) questionnaire on the number of employees from the Integrity Commission, which represented the research sample where the research community has a number is (1365) employees in the Baghdad was the use of a number of statistical met
... Show More
Disabled people are among the most important groups that need attention, care, and financial and moral care. They cannot fulfill the requirement of life normally without care from a person to meet their special needs. The disability is either mental or physical. The Iraqi government has paid attention to this category by adopting a law for this category, represented by Law No. (38) for the year (2013), which keeps their rights and duties in Iraqi society by establishing institution of persons with disabilities and special needs of the Ministry of Labor and Social Affairs to create a modern society politically, socially, culturally or economically. In view of the importance of this group in society, the media reinforces the communit
... Show MoreInternational relations scholars have increasingly debated the evolving landscape of actors that challenge the traditional state-centric world order. A key element of this transformation is the rise of sub-state actors, which engages in alternative diplomacy parallel to the state, transcending traditional state-centric frameworks. This paper explores the significant shifts in international actorness over the late 20th century, focusing on the emergence and implications of sub-state diplomacy, or "paradiplomacy." First, the study introduces sub-state actors and their role in challenging the dominant state-centric discourse. It then examines the dynamic evolution of paradiplomacy, highlighting how sub-states have expanded their global
... Show More
After the information revolution that occurred in the Western world, and the developments in all fields, especially in the field of education and e-learning, from an integrated system based on the effective employment of information and communication technology in the teaching and learning processes through an environment rich in computer and Internet applications, the community and the learner were able to access information sources and learning at any time and place, in a way that achieves mutual interaction between the elements of the system and the surrounding environment. After the occurrence of the phenomenon of Covid 19, it led to a major interruption in all educational systems that had never happened before, and the disrupt
... Show More