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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This study was amied to determine the relationship between Helicobacter pylori infection and skin disorders, sixty six patients who suffering from skin diseases (Urticaria and atopic dermatitis) who attended at Dermatological Clinic Al-Numan Teaching Hospital. Aged (6--62) years have been investigated and compared to Twenty two samples of apparently healthy individual's were studied as control group . All the studied groups were subjected to measurement of anti- Helicobacter pylori antibodies IgA by Enzyme linked immunosorbent assay (ELISA). The results of current study revealed that there were a significant elevation (P<0.05) in the concentration of H. pylori IgA antibodies in sera of patients with chronic urticaria and atopic dermat
... Show MoreThe goal of this study is to perceive the immunological sex-differences in puberty age who have positive anti-Toxoplasma Immunoglobulin-G (IgG) specific antibodies. From the first of November 2012 till the end of April 2013, 303 blood samples were collected from students in both genders (150 males and 153 females) were divided into two age groups: group (A) which included subjects with age range (12-15) years old and group (B) which included subjects with age range (16-19) years old. Serum samples were tested for toxoplasmosis infections by using Enzyme Linked Immunosorbent Assay (ELISA) for anti-Toxoplasma IgG antibodies test. The results revealed that 107/303 (35.31%) of the studied subjects showed seropositive toxoplasmosis, 60 males
... Show MoreIn this study ,the Aspergillus fumigatus histopathological activity on the mice livers during aspergillosis became more obvious. The total number of 40 male Albino swiss mice were randomly divided into 8 groups (Five mice/group). The 1st group were immunosuppressed , while the 2nd group are not immunosuppressed , and control mice were instilled nasally with Phosphate buffer saline and Tween 20 ( five mice / control). The mice were sacrificed after 7th , 14th and 21st day post infection. It was found that immunosuppressive treatments increase substantially the susceptibility of animals to infection by invasive aspergillosis, with higher progression of disease and earlier expression of inflammatory cells comparing with the non immunosuppre
... Show MoreSemliki 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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Hepatitis B virus (HBV) infection is a global public health problem. It is estimated that there are 240 million HBV carriers in the world, of whom roughly 600,000 die annually from HBV-related liver disease. A total of 150 individuals were included in this study, 130 individuals of them had hepatitis B infection (patients group); HBs-Ag was detected in their sera by enzyme linked immunosorbent assay (ELISA) technique and was confirmed by real time PCR analysis to detect the viral genetic material, the others were control. Most of HBV patients in this study were located within 20-40 years group with a percentage of 47.7% and within the 40-60 years group with a percentage of 38.5%. Acute infection was confirmed by detection of anti-HBc IgM
... Show MoreThe secondary sex ratio (SSR) is affected by many factors, including the concentration of hormones and infection with some pathogens such as Toxoplasma gondii. This study aimed to evaluate the effect of hormone variability concentrations and toxoplasmosis infection on the secondary sex ratio. 150 pregnant women were selected, 60 infected with late toxoplasmosis (LT), 60 infected with early toxoplasmosis (ET) and 30 seronegative to toxoplasmosis. After tracking the birth outcomes of these women, we calculated SSR in each group. During the second and third trimesters of pregnancy, estrogen, testosterone, progesterone, TSH, T4 and T3 concentrations were measured. The results of the three groups were compared. The results s
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Understanding Caspase-3 (CASP-3) and interleukin-32 (IL32) roles in SARS-CoV-2 infection is critical to linearize the pathogenesis of the virus as well as the resultant disease which may uncover novel therapeutic targets in treating COVID-19 patients. This study aimed to evaluate caspase‐3 (CASP3) and interleukin 32 (IL32) roles and their correlation with the disease severity among patients. The case-control study (140 patients and 60 healthy controls) was performed with molecular and ELISA assays. CASP3 and IL32 serum levels were determined along with other clinical data of patients. CASP3 levels were classified as significantly higher (p < 0.001), while IL-32 levels were significantly lower in production (p
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