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.
This study aimed to evaluate the preparedness and adherence of community pharmacists to the International Pharmaceutical Federation (FIP) Health Advisory COVID-19 guidelines for pharmacists (July 2020) during COVID-19 pandemic. This was a cross-sectional study based on electronic survey using google form, which was distributed from November 19, 2020 to January 1, 2021 using social media platforms. The survey measured 21 pharmacy preventive measures (PM). A multivariate regression analysis was used to identify factors influencing pharmacy implementing of PM. Hand disinfection after serving patients represented the main adopted measure (89.3%). Surprisingly, only 35.4% of participants implemented the proper ways of hand disinfection during fa
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Semliki Forest Virus (SFV), a member of the Alphavirus genus in the Togaviridae family, is a small-enveloped, positive-sense single-stranded RNA (+ssRNA) virus. The virus is spread by mosquitos and can infect humans, resulting in mild febrile disease with symptoms that include fever, myalgia, arthralgia, persistent headaches and asthenia. Virulent strains of SFV in mice cause lethal encephalitis by infecting neurons in the central nervous system. In on-going experiments in the research group using a focused siRNA screen we have investigated the role of deubiquitylases (DUBs) during SFV infection (as a model alphavirus) and monitored the effect of DUB depletion on cell viability after infection. We identified a group of DUBs that h
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BACKGROUND: SARS-CoV-2 (COVID-19) is considered a highly infectious and life threatening disease. OBJECTIVE: The present paper aims to evaluate various aspects of preventive measures and clinical management of the scheduled visits for orthodontic patients to the dental clinics during the outbreak of COVID-19, and to assess how orthodontists dealt with this challenge. METHODS: Orthodontists in private and public clinics were invited to fill a questionnaire that addressed infection control protocols and concerns about clinical management of patients in the clinics during the pandemic. Frequncies and percentages of the responses were obtained and compared using Chi-square tests. RESULTS: About 77% of those working in private clinics, a
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Toxoplasmosis is a parasitic infection that triggers immune cells to produce cytokines and inflammatory mediators that are responsible for abnormal or aborted immune responses. This study highlights the evaluation of the Dectin-1 receptor and cytokine IL-37 in the serum of 80 patients who had miscarried in the first trimester and were infected with toxoplasmosis, as well as 40 pregnant women in the first trimester who had a successful pregnancy (control groups). The serum was first screened for the T. gondii IgM and IgG antibodies by an enzyme-linked immunosorbent assay (ELISA) and then the serum levels of IL-37 and Dectin-1 were determined. The results showed that the serum level of Dectin-1 was significantly increased in anti-
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To assess the impact of COVID‐19 on oral hygiene (OH) awareness, attitude towards dental treatment, fear of infection and economic impact in the Middle East.
This survey was performed by online distribution of questionnaires in three countries in the Middle East (Jordan, Iraq and Egypt). The questionnaire consisted of five sections: the first section was aimed at collecting demographic data and the rest sections used to assess OH awareness, attitude towards dental treatment, degree of fear and economic impact of COVID‐19. The answers were either multiple choice, closed‐end (Yes or N
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The cervical cancer considered as the fourth female prevalent disease worldwide, it was once the most extensively recognized female cancer two in many low-income countries. Human Cytomegalovirus (HCMV) exhibits broader tropism and can cause infection in most of the human body organs. Although, human cytomegalovirus HCMV is not yet considered an oncogenic virus, there is increased evidences of HCMV infection implication in malignant diseases of different cancer types. The present study aims to evaluate the effect of CMV infection on the development of HPV16 positive cervical cancinoma. The current retrospective study enrolled a number of paraffinized cervical cancer tissues .included 30 cervical carcinomatous tissues and 10 biopsies from an
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This study aims to identify the issue of observing media publishing and its importance for public relations in the management of special events; and its role in building the positive image of the target audience through communication messages that illustrate the political, economic and diplomatic importance of the Arab Summit. As such Summit is one of the conferences that Iraq sought to secure the requirements of its convening to re-activate its political and diplomatic role in the Arab Ocean, especially after the circumstances and crises that Iraq went through.
The convening of the Arab Summit under the auspices of Iraq was a qualitative transition, during which Iraq sought to achieve some gains b
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One hundred fifty bacterial strains were isolated from patients with urinary tract infections (UTIs). They were belong to ten different species of gram-negative bacteria and to two genera of gram–positive bacteria. E. coli was the major causative agent and comprise 40% of all cases. Klebsiella pneumoniae and Proteus mirabilis were second and third with 18.67% & 18.0% respectively. Other gram-negative bacteria were belong to the genera Enterobacter, Acinitobacter, Pseudomonas, Citrobacter and Serratia. Ten cases (6.67%) were caused by genus Staphylococcus and seven (4.66%) were caused by Streptococcus. Out of the 150 positive cases, 96(64%) were from female patients, while 54(36%) were from males. High percentage of all
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