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 research aims to reveal the role of financial analysis in rationalizing the investor decision on the Iraqi stock Exchange market, by studying the relationship and impact techniques and methods of financial analysis on the decisions of investors in the market. The most important techniques and methods discussed in this study were: analysis (financial ratios analysis, comparison of financial statements analysis, cash flow statement analysis) for companies listed in the Iraqi stock Exchange market. The researcher adopted the analytical descriptive method which depends on the collection of data on the phenomenon and its interpretation. The questionnaire wa
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The phenotypic characteristics in the interior spaces are seeing the result of the ability of the designer in his handling of the vocabulary and the elements to deliver a specific meaning for the recipient , and is working to stir up the receiver and make it effective in the process of perception of space. So the theme of the role of phenotypic characteristics is of great significance in the process of analyzing spaces to reach the goal of the main idea , and show those qualities through relationships design in terms of shape, color and texture ... etc. , to reach also designs more beautiful , and creating an internal environment , creative and continuous with its external environment , Hence the importance of research in that it tries t
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In this paper, we present a study of examples of writings that are known in the science of Semitic research compared to the texts (Jewish-Arab, Samaritan-Arabic) written in Hebrew script and texts from the Bible. We try to explain the role of these literary works in Islamic history and civilization, as one of the most important documents are the writings (Gniza), which contributed to provide a full presentation on life in the Islamic community in all aspects of life, especially religious activity and showed the sincere relationship in dealing with the other under tolerance The University of Cambridge has prepared Islamic documents and kept them in separate boxes and presented them to researchers to convey the Islamic heritage written by
... Show MoreThis study was design to characterize the immune response in experimentally Pseudomonas aeruginosa mastitis mice treated probiotic bifidocin and cazacin of Bifidobacterium spp. and Lactobacillus casei. We quantified the level of the IFN-γ and TNF-α cytokines in blood by ELISA technique. IFN-γ level was significantly higher in infected group compared to control (340.21 ± 41.61, 8.45 ± 0.83 pg/ml, respectively). While the level of IFN-γ was significantly higher in mastitis mice than bifidocin and cazacin treated mice. Also, TNF-α level showed a significant increase in mastitis mice compared to controls (320.11±40.33, 8.45±0.83pg/ml, respectively). Among mastitis and bifidocin (9 and 18 mg/ml), cazacin (11 and 22 mg/ml) treate
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The research aims at clarifying the role of green human resource management practices in achieving sustainable development. The research problem is that the health sector is less concerned with environmental aspects, specifically green human resource management practices, Which are reflected on sustainable development with their economic, environmental and social dimensions as well as reducing costs, waste minimization and recycling, And the research started from two main hypotheses to explore the correlation and influence between the variables of the research by analyzing the answers of the research sample, which included (136) employees of the Al-Imamein Al-kadhemein medical city, Data and information were collected using quest
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This review focuses on conservation agriculture (CA) and its effects on increasing the soil’s resistance to erosion. CA involves minimum soil disturbance (minimum tillage/ no-till), diversified crop rotation, and maintenance of the soil cover to increase soil fertility and reduce erosion. CA reduces soil loss by up to 90% and water erosion by approximately 50 to 70% from runoff as it increases the health of the soil, yield of crops, and water-retention capacity of the soil by incorporating soil organic matter and promoting biodiversity. Crop rotation prevents the replenishment and depletion of soil nutrients by atmospheric fixation of nitrogen/biological nitrogen fixation. Controlled traffic farming (CTF) is a new strategy in which travel
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Background: Axillary lymph node (ALN) enlargement with diffuse cortical thickening and conserved echogenic hilum may represent a diagnostic and therapeutic challenge. Sonographic strain elastography may help the characterization of borderline ALN.
Aim: To evaluate the strain elastography of borderline ALN and to calculate a cutoff value of strain ratio (SR) that can identify suspicious ALN with the highest sensitivity and specificity to reduce unnecessary invasive procedures.
Subjects and Methods: A prospective study included 45 patients who attended the Breast clinic in Oncology Teaching Hospital with borderline axillary lymphadenopathy (intact hilum and diffusely thic
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In Iraq, there is a limited research work exploring the clinical pharmacists' role from the point of view of other healthcare professionals. To investigate physicians' assessment of clinical pharmacy services at Baghdad hospitals, and compare junior physicians with senior physicians' point of view. The study was conducted in twelve governmental hospitals in Baghdad, Iraq. Data was collected from a sample of two hundred physicians, and through a validated, self-administered questionnaire, which comprised twenty statements in addition to a non-personal information form that precedes the questionnaire The study findings reveal a somewhat positive point of view towards clinical pharmacists' performance in Baghdad h
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Colorectal cancer is the world's 3rd most frequent malignant neoplasm and the 4th most common cancer in Iraq. Leptin and Adiponectin are two major Adipocytokines produced by adipose cells that have opposite effects on the formation of colorectal tumors. Leptin induces tumor growth and metastasis, whereas Adiponectin inhibits it. 1,25-Dihydroxyvitamin D controls and limits cancer cell proliferation, differentiation, and survival. Vitamin C deficiency, on the other hand, has been regularly detected in cancer tissues and has potent anti-cancer properties. The purpose of this study was to look at the biochemical role of circulatory Adipocytokine levels (Adiponectin and Leptin) as well as the anti-cancer potentials of Vi
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