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 dealt with the role of the target costs in reducing the cost of products in the General Company for soft drinks. One the modern approaches reduce costs and thus increase the ability and continuity to compete in the market. Where the problem of research in identifying the shortcomings in the traditional method used in the company sample research. Which led to a weak control of the cost and the researcher relied on data and costs of the company. The research recommended that the target cost of the company should be applied to the research sample. Training the employees. In addition, preparing training courses for them. He stressed the need to address obstacles that prevent the existence of an effective cost system. Including t
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The relative strength index (RSI) is one of the best known technical analysis indicators; it provides the speculators by prior signals about the future stock’s prices, and because the speculations in shares of companies which listed in the Iraq Stock Exchange have a high degree of risk, like risk of shares prices felling, so the speculators became committed to use some methods to reduce these risks, and one of these methods is the technical analysis by using the relative strength index (RSI) which enable the speculators of choosing the right time for buy and sell the stocks and the right time to enter or leave the market by using the historical rice data. And from here the problem of the research formulated as “Is the using of
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The problem for the search to identify the role of loyal workers through (emotional loyalty, moral loyalty, continued loyalty) in enhancing the market share of the corporate center the human resource management strategies, namely (selection, training and development, and performance evaluation, and returns the system) for the parent company of cellular Allotsalat in Baghdad ,, and show the importance of research through the benefit to the company, through the importance of the search results, it draws the attention of decision-makers and those in charge of managing these human resources on the importance of those resources and work to develop them and keep them in order to increase their loyalty towards their organization and the
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HBV and HCV are the major causes of chronic liver diseases throughout the world, and constitute a major global health risk. There is accumulated evidence that the imbalance of proinflammatory and anti-inflammatory cytokine production may play an important role in the pathogenesis of viral hepatic infections and may influence the clinical outcome and disease progression. This study was undertaken to analyze the circulating levels of Tumor Necrotic Factor (TNF-α) and Th2 cytokine IL-10 in patients infected with Hepatitis B and C virus. The study population consisted of 30 patients with chronic HBV, in addition to other 30 patients with chronic HCV infection were recruited on their first examination at the Al-Kindy General Hospital in Baghdad
... Show MoreThis study aimed to collected 150 feces sample from calves suffering sever diarrhea ,then there were isolation and purification of Cryptosporidium parvum oocyst from samples contain it. These oocysts were used to induce experimental infection in the Immunosupperessed mice, then the mice treated by Bifidium bacteria , its supernatant and local yogurt were used for bacterial isolation.
This study showed that the local yogurt was the best treatment which led to stop oocyst shedding from the mice in the 8th day after treatment under sufficient treatment (89.72%) , at the same time the mice treated with bacteria stopped the oocyst shedd
... Show MoreThe study was conducted to determine the effect Toxoplasma gondii and the efficacy of azithromycin and garlic tablets on the treatment of acute murine toxoplasmosis and observe the histopathological changes due to infection. 60 Albino mice were divided into six groups, and their survival rate, pathology, bioassay trial and immunofluorescence were observed. Results revealed that azithromycin (250 mg/kg/day) given to infected mice increased the survival rate (90% on day 7 PI) and decreased the histopathological changes when compared with the control groups. Garlic tablets (500 mg/kg/day) had lesser effect on infected mice, and the survival rate (40% at days 6 and 7 PI) was lower than the groups treated with azithromycin. The group treated wit
... Show MoreAspergillus fumigatus considered to be the most important species to cause respiratory infection cases in both humans and animals especially in cats in the last decades. In this study, we focused on the isolation and identification of Aspergillus fumigates by collecting 40 samples in deferent veterinary clinics and stray cats in Baghdad city, during the period (October 2021 to January 2022), all samples were cultured on Sabouraud dextrose agar and malt extract agar. The isolates identified by the laboratory methods, it’s depend on macroscopic and microscopic appearance. The results showed that (40) swaps taken from the pharynx of infected cats, included: Aspergillus fumigatus 16 (40%), Aspergillus spp. 7 (17.5%), Aspergillus niger
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BACKGROUND: Helicobacter pylori is an important gastrointestinal infective bacteria with many serious complications including gastric erosions and ulceration, duodenal ulcer, gastric carcinoma and MALT gastric lymphoma. The gastric biopsy is commonly performed in H. pylori-positive dyspeptic individuals, and many previous researchers studied the histopathological features of infected gastric biopsies however little previous studies focused on the histopathological findings in young population in comparison to the older one. AIM: To make a focus on the histopathological effects of H. pylori infection in young patients compared with the older one and predicts the need for endoscopy in this population, also to estimates the prevalence of
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Interleukin-35 (IL-35) is a new member of IL-12 family of cytokines, and its role in pathogenesis of hepatitis B virus (HBV) infection has been recently suggested. Accordingly, a case-control study was conducted during June - October 2018 to determine IL-35 serum level in Iraqi patients with chronic HBV infection. The results revealed that IL-35 level was significantly decreased in patients as compared to control (163 vs. 301 pg/ml; p < 0.001). However, such decreased level was more pronounced in patients at the age groups < 40 and 40 – 50 years (165 and 145 pg/ml, respectively) as compared to the corresponding age groups in control (482 and 234 pg/ml, respectively). In the case of gender groups, both male
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The study was carried out to detection of H.pylori in (200) patients who attended two teaching hospitals in Baghdad. The diagnosis done by Immunochromatography methods. Stools and blood samples was taken from each patient as well as other (30) healthy control matching in their age. The study included detection the Levels of Interleukin-40 and CRP in sera of patients and control. The result indicated presence of H pylori antigen in 115 cases 59 cases of males and 51 of females, Also, the result indicated increasing levels of IL-40, cholesterol, Triglycerides, Low density lipoprotein, Very Low density lipoprotein increased significantly while the level of High density lipoprotein decreased in patients sera in comparison with healthy c
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