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.
The study focuses on the causes of minaret tilting as well as possible solutions. The major aims of this study are to improve knowledge of historical tall structure stability and rehabilitation operations using the finite element approach to model the soil and minaret (PLAXIS 3D 2020), a platform for computational soil investigation and modeling. The numerical analysis aims to identify stresses, settlement, and deformation of the soil and minaret in various scenarios like Earthquakes, explosions, and winds. The simulation of the problem by the PLAXIS 3D revealed that the greatest lateral displacement computed at the Top Minaret is 5.5 cm, and the greatest vertical movement is calculated to be 3 cm. Seismic settlement is the effect of ear
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To determine the relationship between infertility and Helicobacter pylori infection, thirty-five infertile patients of ages (20-49) years have been investigated and compared with 10 apparently firtility individuals. All the studied groups were carried out to measure (ASA), (TNF-á), (IL-6), (anti-H.pylori IgA) and (anti-H.pyloriIgG) by Enzyme linked immunosorbent assay (ELISA) technique. The statistical analysis also demonstrated that there were a highly significant differences (P<0.01), when compared between studied group. Also, the statistical analysis demonstrated that there were a highly significant differences (P<0.01) when compare between infertility and fertility in Conc. of sperm. The percentage distribution of ASA in serum and seme
... Show MoreBackground: Recurrent laryngeal nerve injury is
an important post-thyroidectomy complication for
which different modalities of treatment were
practiced to lower its incidence.
Objectives: To estimate the incidence of
recurrent laryngeal nerve injury in thyroid surgeries
in relation to type of surgery, type of gland diseases
& nerve identification.
Methods: Different types of goiters prepared
preoperatively by indirect laryngoscopy, operated
upon with different types of surgeries, postoperative
direct laryngoscopy by the anaesthetist were done
and indirect laryngoscopy done as needed.
Results: Of of 200 patients, the overall incidence
of recurrent laryngeal nerve injury was 9
Patients (4.5%
Objective:- Women's behavior during pregnancy which can affect the health of their infant , may be influenced by their attitude toward the pregnancy. The study was carried out to assess the pattern of health behaviors for pregnant women. Methodology: A descriptive study was carried out to select randomized (100) pregnant women attending Baghdad Teaching hospital. The data were collected through personal interview by using questionnaire form constructed for the purpose of the study. Results:- The result of the study revealed that the highest percentage of study sample were in age group (21-25) years, primary graduated and house wife . The results showed that the highest percentage( 64%) of them were primigravida, (72%) of them have (1-2)
... Show MoreMost studies combine that it is important to determine the extent of the public's trust TV for two reasons. First of knowing the impact of satellite TV audience ranges and the second determining public outlets for Information Find regard to the extent of the public's confidence in knowing the contents of the satellite during the occupation of Mosul crisis by organizing the Islamic state in Iraq and the Levant And the researcher developed a questionnaire to find out the public's confidence statement satellite contents provided by the questions related to exposandscale.
The researcher audience chose the city of Baghdad to the suitabil
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The post-Corona Covid-19 world is not the world before it, the problem of perception of personality traits with two axes: the characteristics of psychological and social compatibility, and the second aspect the mental disorder during the pandemic, and the accompanying precautions and prohibitions during the academic year 2020 AD. The aim of the research is to reveal the perception of the personal characteristics of Bisha University employees (students and faculty) during the Corona Covid-19 pandemic, and to reveal statistically significant differences in the perception of the personality traits of Bisha’s members during the Covid 19 according to the scientific qualification variables (female students -faculty members), marital st
... Show MoreThe effect of local Lactobacillus gasseri filtrate against Pseudomonas aeruginosa infection in mice was studied . 0.25 ml of concentrated filtrate Lactobacillus gasseri was injected in intraperitoneally ( I.P.) 5 days before challenge with 0.2 ml viable P. aeruginosa ( 10 8 cell/ ml). Animals were sacrificed after 12 h. from challenge by cutting the femoral artery . To follow bacterial growth in the peritoneal cavity , its contents were washed out with 5 ml of PBS .The fluid was diluted, 0.1 ml from each dilution and was spread on culture media. The number of colonies in 5 ml of harvested fluid was expressed as Log 10 CFU ,and the percentage of Macrophage in t
... Show MoreA total of 41 patients with gastro duodenal symptoms (show signs of inflammation with or without duodenal ulcer) . 21 males (51.2%) and 20 female (48.8%) with an average age 0f (20 – 80) years old under going gastrointestinal endoscopy at Baghdad teaching hospital in internal disease clinical laboratory , between (February – June) 2009 . Biopsies specimen of antrum , gastric fundus ,& duodenal bulb were examined by the following methods (rapid urease test , Giemsa stain section to detect bacteria , & Haematoxilin and Eosin stained section for pathological study which are considered the gold standard methods , sera or plasma from these patients were tested by immunochromotography (ICM),serological m
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Immunological genes, including TLR3 and RIG-I, have recently been established to have linked to predisposition to coronavirus disease 2019 (COVID-19) and its severity. The purpose of this case-control study (100 recovered COVID 19 cases and 100 healthy individuals) was to determine the role of gender, age, TLR3 and RIG-I genes in COVID-19 aggressiveness. TLR3 and RIG-I gene expression was detected using a quantitative real-time polymerase chain reaction (qRT-PCR). COVID-19 infection intensity increased with age and no statistical difference between males and females (p>0.05) was found. TLR3 and RIG-I gene expression levels were higher in patients compared to hea
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(4)
Background: The COVID-19 pandemic has an immense effect not only on the social and economic lives of people but also on the surgical lives of surgeons, residents, nursing staff, and patients as well as ground level staff. Amidst this COVID pandemic, emergency surgeries were being done but at a decreased rate, whereas elective cases depended on the will of hospitals, surgeons, and patients. Study aims to promulgate a "Neo–Surgical Check Box" by amalgamating the WHO surgical checklist and the results obtained from the questionnaires.
Subjects and Methods: After receiving ethical clearance from the Institute Ethical Committee, an online questionnaire with 50 questions divided into
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