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.
Functional dyspepsia is one of the most common gastrointestinal symptoms and attributed to various causes including Helicobacter pylori infection. AIM OF THE STUDY: To correlate Helicobacter pylori infection to functional dyspepsia and to identify the possible risk factors for this infection. PATIENTS AND METHODS: Fifty patients who were referred to the endoscopy unit for dyspepsia symptoms, secondary gastric causes of dyspepsia were excluded during endoscopy, gastric biopsies were taken for histopathological study and for bedside urease test for detection of Helicobacter pylori infection. RESULTS: 62% of non-ulcer dyspeptic patients were infected with Helicobacter pylori, 74.2% of the patients were above 30 years old, female gender patient
... Show MoreBackground: To elucidate the possible role of human cytomegalovirus in pregnancy loss through induction of certain pro-inflammatory adhesion molecules.
Methods: Paraffin embedded sections of curate samples were obtained from 34 women had spontaneous abortion, and 5 women had elective termination of pregnancy (as control), and then subjected for immunohistochemistry analysis to detect human cytomegalovirus (HCMV) early protein and VCAM-1 molecule.
Results: Nine out of 34 women with spontaneous abortion were positive for HCMV early protein, with a
significantly higher expression of VCAM-1 in HCMV positive cases as compared with HCMV negative and the control groups (p = 0.05, 0.001 respectively).
Conclusion: HCMV infection may p
500 samples of diarrhea stool were collected from different ages(less than 1year –upto30years) and for both genders from some patients in (Alwiya hospital for children, Al-kendi, central health public laboratory and some gavernarated labs) period(1/11/2009—1/10/2010). Kinds of bacteria and parasites agents were isolated and identified from patients with diarrhea. Nine species of gram negative bacteria from enterobacteriaceae were isolated, E. coli isolated are the higher ratio 4.8% of all, then Salmonella typhi4.6% while the lowest ratios is Citrobacterfreundii 0.4%, while the other identified species were be among the previous rotios. also Plesomonasshigelloides was isolated which concedride one of the bacterial local studies.many met
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The aim of the study is to prepare a measure of the role of academic coaches in handball skill performance from the point of view of the researchers. The researchers used the descriptive approach in the research procedures as it is an appropriate approach in achieving the research objectives. The next question is: To what extent will the players benefit from the academic coach in developing their skill performance? This is the measure of the role of academic coaches. From 16 items, the research community included players (Al-Karkh Club - Al-Hashd Sports Club) and the number of players was (Al-Karkh 14 - Al-Hashd 14). The research sample was intentional and represented (the research community 100% The researchers concluded that measuring the
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The aim of the research is to develop specific skills of 21 century, one schedule, renewable: (sex, years of experience, academic degree) from the viewpoint of the research sample. The descriptive tool was used to collect information for research purposes. It was applied to a sample of (339) male and female teachers in Al-Ardhah governorate schools to teach Jazan. The application was carried out in the second semester of the year 1442 AH. The research concluded with a set of results, the most important of which are: the approval of the sample members to a large extent on the expressions of the role of school leaders in the practice of developing male and female teachers in acquiring these three skills fr
... Show MoreThis study dealt with the management strategy as an independent variable and the integrated industrial distribution as a variable. The study aimed at finding the integrated industrial distribution that fits with the management strategy in providing the needs of the firm on the one hand and reducing the cost of management that is reflected in increasing its profits.
The researcher selected the data from (130) decision makers in the corporation and used the questionnaire as a tool for collecting data and used a set of statistical tools and tools suitable for the nature of information and were processed using the data analysis system (SPSS version 24) Based on the analysis of the responses of the sample and the test of correlation and
Since the COVID-19 pandemic alarm was made by the severe acute respiratory syndrome (SARS)-coronavirus (CoV) 2, several institutions and agencies have pursued to clarify the viral virulence and infectivity. The fast propagation of this virus leads to an unprecedented rise in the number of cases worldwide. COVID-19 virus is exceptionally contagious that spreads through droplets, respiratory secretions, and direct contact. The enveloped, single-stranded RNA virus has a specific envelop region called (S) region encoding (S protein) that specifically binds to the host cell receptor. Viral infection requires receptors' participation on the host cell membrane's surface, a key- step for the viral invasion of susceptible cells.
Rec
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Abstract To estimate the seroprevalence of HCV infection among HIV-infected haemophiliacs and to demonstrate the most prevalent HCV genotype, 47 HIV-infected haemophilia patients were screened for anti-HCV antibodies. By performing polymerase chain reaction and DNA enzyme immunoassay, HCV-RNA was detected with subsequent genotyping. Seroprevalence of anti-HCV antibodies was 66.0%. Of 31 HCV/HIV co-infected patients, 21 (67.7%) had no history of blood transfusion. We detected 4 HCV genotypes: 1a, 1b, 4 and 4 mixed with 3a, HCV-1b being the most frequent. Contaminated factor VIII (clotting factor) could be responsible for disease acquisition.
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Benign prostatic hyperplasia (BPH) is a prevalent condition among elderly and middle-aged men characterized by symptoms such as dysuria, urinary incontinence, and frequent micturition. The gold standard procedure for relieving BPH symptoms is transurethral resection of the prostate (TURP). However, some patients undergoing TURP are at risk of developing urinary tract infections (UTIs) due to uropathogenic bacteria. This prospective study aimed to investigate post TURP bacteruria alongside with multifactoria risk factors that implicated postoperatively compared to preoperative and intraoperative periods. Ninety patients undergoing TURP and 30 control subjects were included in the study. Urine specimen for urine analysis from pateints
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