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 current research aims to identify the level of effective leadership practices dimensions (clear vision and specific goals, good planning and effective influence, and monitoring well as evaluation) among the senior leaders in the Office of the Iraqi Interior Ministry., The researchers adopted the descriptive analytical approach to collect data through the questionnaire as a main tool, developed by relying on international standards after making adjustments to its items consisting of (25) items that included the research variable, the questionnaire was distributed to all the research community (comprehensive inventory) by 120 forms from emplo
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A Laced Reinforced Concrete (LRC) structural element comprises continuously inclined shear reinforcement in the form of lacing that connects the longitudinal reinforcements on both faces of the structural element. This study conducted a theoretical investigation of LRC deep beams to predict their behavior after exposure to fire and high temperatures. Four simply supported reinforced concrete beams of 1500 mm, 200 mm, and 240 mm length, width, and depth, respectively, were considered. The specimens were identical in terms of compressive strength ( 40 MPa) and steel reinforcement details. The same laced steel reinforcement ratio of 0.0035 was used. Three specimens were burned at variable durations and steady-state temperatures (one
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This research focuses on the epidemic of Job burnout and seeks to achieve sustainable preeminence among the employees of the University of Baghdad. It also identifies the meaning of the differences between the two genders of males and females according to the variables, and it also does the correlation between the two variables. First, the two researchers developed a test of job burnout that incorporates 18 items, which has been proven to be statistically fit. Moreover, they developed a competitive superiority measure consisting of 22 items in it, and its psychometric properties confirm their fit. The two tools were applied to a sample of 120 employees who were randomly selected from six colleges at the University of Baghdad, alongside univ
... Show Moreرافقت القسوة الانسان منذ القدم وكثيرا ما تم الخلط بينها وبين العنف لشدة التقارب بينهما , وهنا يحاول البحث ان يفصل بين كلا المفهومين ويتفرد بمفهوم القسوة, الذي سلط عليه الضوء في المسرح لأول مرة على يد الفرنسي(انطوان ارتو) في محاولة للكشف عن المعالجة الاخراجية التي قدمها المخرج العراقي(صميم حسب الله) لمفهوم القسوة في مسرحيته الموسومة (خريف) ويتضمن البحث نبذه (مفهوم القسوة في الفكر الانساني) وكذلك (الق
... Show MoreThe assessment of a river water’ quality is an essential procedure of monitor programs and isused to collect basic environmental data. The management of integrated water resources in asustainable method is also necessary to allow future generations to meet their water needs. Themain objective of this research is to assess the effect of the Diyala River on Tigris River waterquality using Geographic Information System (GIS) technique. Water samples have beencollected monthly from November 2017 to April 2018 from four selected locations in Tigris andDiyala Rivers using the grab sampling method. Fourteen parameters were studied which areTurbidity, pH, Dissolved Oxygen, Biological Oxygen Demand, Electrical Conductivity, TotalDissolved Solids,
... Show MoreIntroduction: Articaine was developed in 1969, with reported advantages which are increased potency, increased duration of its anesthetic effect and superior diffusion through bony tissue. The effectiveness of using 4% articaine infiltration for extraction of mandibular molar teeth in comparison to 2% lidocaine inferior alveolar nerve block is not settled yet. Aim: The aim of this study was to evaluate the effectiveness of using 4% articaine infiltration for extraction of mandibular molars by comparing it to the use of 2% lidocaine inferior alveolar nerve block in terms of success, the volume of local anesthetic agents and the pain experienced during the procedure. Materials and methods: A prospective randomized controlled study included
... Show MoreBackground/Aim: Endometrial abnormalities represent a diagnostic challenge due to overlapping imaging features with normal endometrium. Aim of this study was to assess accuracy of dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging (MRI) in evaluation of endometrial lesions in comparison with T2 and to assess local staging validity and degree of myometrial invasion in malignancy. Methods: Forty patients with abnormal vaginal bleeding or sonographic thickened endometrial were recruited. MRI examination of pelvis was per-formed using 1.5 T scanner with a pelvic array coil. Conventional T1-and T2, dynamic contrast-enhanced (DCE) sequences and diffusion-weighted image (DWI) were performed. Results: Mean age of pa
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Abstract
The current research aims at identifying any of the dimensions of organizational learning abilities that are more influential in the knowledge capital of the university and the extent to which they can be applied effectively at Wasit University. The current research dealt with organizational learning abilities as an explanatory variable in four dimensions (Experimentation and openness, sharing and transfer of knowledge, dialogue, interaction with the external environment ), and knowledge capital as a transient variable, with four dimensions (human capital, structural capital, client capital, operational capital). The problem of research is the following questio
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The theater has a living environment that resembles or realistically simulates the real life environment on the stage where we see the place, light and living being as elements representing a picture of the life scene and for a period of time the theater merely conveyed that image, but with the development of the world industrially and technologically, the perception of this picture has evolved with the emergence of intellectual progress where each part has advantages and Philosophical goals that are consistent with the evolution of form. The theatrical lighting, colors and landscapes have become parts in the composition of a new life component in form and content and based on the above this research is titled&nbs
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