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 aims to know the role of strategic leadership to achieving competitiveness in industrial establishments by identifying the respondents’ perceptions about the level of availability of dimensions of leadership strategies (creativity and innovation, risk tolerance, available opportunities) in Bashir Al-Siksek & Partners Company for the manufacture of sanitary and plastic ware in Gaza strip
To achieve this, a questionnaire was developed and distributed to a sample of managers, auditors, accountants, and administrative employees in the study sample company. The questionnaire tool was distributed to 60 employees and employees, of which (52) were retrieved, or 86.6%, and (8) were excluded for la
... Show MoreThe angiotensin converting enzyme (ACE) I\D gene polymorphism influences the blood ACE enzyme activity. Renoprotective effect of ACE inhibitors (ACEIs) varies among patients due to genetic variation, particularly in Renin-Angiotensin-Aldosterone System genes. This study investigates the genetic variations of ACE I\D and AGT1RA1166C gene polymorphisms in the antiproteinuric effect of ACEI therapy in type 2 diabetes mellitus (T2DM) patients. This is a cross-sectional study that included 76 T2DM patients who are ACEI users, divided into two groups: T2DM without diabetic kidney disease (DKD) included 31 patients, and T2DM with DKD included 45 patients. Urine samples were taken for measurement of urine albumin and creatinine, then calcul
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The clinical spectrum of cutaneous leishmaniasis (CL), an intracellular parasitic pathogen, ranges from a single sore healing to chronic crusty lesions with a manifestation of treatment resistance. The complicated interaction between Leishmania bodies and the early immune response, including innate and adaptive mechanisms, determines the evolution of nodules. This study examined the levels of the chemoattractant interleukin 8 (IL-8), pro-inflammatory nitric oxide (NO), and immunoregulatory macrophage inhibitory factor (MIF) in the serum of subjects recently diagnosed with cutaneous leishmaniasis, in parallel with patients being monitored during consecutive sodium stibogluconate (Pentostam) treatment. A total of 161 serum samples of newly di
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The expansion of the social media environment has created its own linguistic realities which involve more colloquial communication and practical employment of language. This research focuses on nominalizations in detail, which are originally formed words that have been changed for a noun role. These nominalizations are examined within the context of Facebook posts. The research aims to discover the various nominalizations used and how often they appear in a large sample of data from Public Facebook Posts Corpora. Computational linguistics opened new fields of study and enabled researchers to study large amounts of data easily, making it easier to identify patterns. Two computational methods of identifying nominalization in a large dataset w
... Show MoreThe study has tackled three important variables on the strategic and organizational level, that are : (Administrative skill, strategic Entrepreneurship and organizational flexibility). Through the statistical analysis is, the research hers have sought to identify the relation among them. The study has been applied on a sample of (44) private banks in Iraq. A questionnaire, which has been designed according to a number of international standards, has been used. It's made of (29) items that cover the three variables to test their hypotheses. A number of statistical tools have been used A number of conclusion have been reached and recommendations have also been suggested.
This work aims to detect the associations of C-peptide and the homeostasis model assessment of beta-cells function (HOMA2-B%) with inflammatory biomarkers in pregnant-women in comparison with non-pregnant women. Sera of 28 normal pregnant women at late pregnancy versus 27 matched age non-pregnant women (control), were used to estimate C-peptide, triiodothyronine (T3), and thyroxin (T4) by Enzyme-linked-immunosorbent assay (ELISA), fasting blood sugar (FBS) by automatic analyzer Biolis 24i, hematology-tests by hematology analyzer and the calculation of HOMA2-B% and homeostasis model assessment of insulin sensitivity (HOMA2-S%) by using C-peptide values instead of insulin. The comparisons, correlations, regression analysis tests were perfo
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Objectives: Assessment of glycodelin (GD) as a marker for unruptured ectopic pregnancy (EP) in the first trimester of pregnancy. Materials and Methods: This case-control study was conducted during June 2016 to May 2017 in the Obstetrics and Gynecological Department of Baghdad University at Baghdad teaching hospital/medical city complex. In this study, 100 pregnant women in their first trimester of pregnancy were included after clinical and ultrasonic findings. Results: Based on the results, GD levels in EP were significantly lower than those with normal intrauterine pregnancy (1.58 ± 1.18 vs. 30.1 ± 11.9). In addition, using receiver operator curve analysis, the cut-off GD level of 9.5 and less had acceptable validity results (100
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Background: Ultrasound is a valuable tool for evaluating fetal problems throughout pregnancy. Amniotic fluid anomalies have been associated with unfavorable maternal, fetal, and obstetrical outcomes. Objective: To determine the effect of echogenic amniotic fluid during term pregnancy on the presence of meconium stain liquor and pregnancy outcome. Methods: A cross-sectional study was conducted on 1080 term pregnant women who visited Al-Elwiya Maternity Teaching Hospital from May 1st, 2021, to May 1st, 2023. Ultrasound was used to analyze echogenic amniotic fluid and turbid liquor. The liquor state was tested either after an artificial membrane rupture in the vaginal delivery trial or during a cesarean section. Results: Echogenic amni
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Background: Imaging has a critical role in the diagnosis and evaluation of cardiac diseases, beginning with chest radiography and fluoro-scopy and progressing to coronary angio-graphy, echocardiography, nuclear medicine and recently multidetector computed tomo-graphy (MDCT) as well as magnetic resonance (MR) imaging
Objective: To highlight the role of Multi-detector CT in the evaluation of coronary artery disease and its importance of being noninvasive diagnostic technique.
Methods: A cross sectional study for 20 patients. Patients were asked to fast 6 hours prior to the examination and the patients with heart rates above 65 beats per minute were given cardio-
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Abstract:
The research aims to diagnose the relationship between the environmental tax and the development of the sustainable social dimension, where the environmental tax is considered a tool in promoting sustainable development according to its economic, social and environmental dimensions through the application of legislation and instructions for environmental protection, and that imposing an environmental tax will have a clear impact in achieving the dimensions of sustainable development and compliance With regard to the social dimension, the research relied on the financial data for the years (2019-2022) in obtaining information. The research reached a set of results, the most prominent of which was
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