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 at testing test the relationship and the impact of strategic leadership (strategic vision, Core competencies , human capital, organizational culture and Ethical practices) in the talent management (to attract talent, performance management talent, developing talent and retain talent) among managers in the Ministry of Science and Technology Iraq, and figuring out a number of recommendations to the ministry to help achieve its desired objectives, and to clarify the relationship between the variables to find the main and secondary aim of the research two major hypotheses have been formed which split into ten sub-hypotheses. Collecting data on a form questionnaire has been relied on as an essenti
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Banks are considered the main basis of financial sector ,so they must be submitted to sound and strict regulatory system and so as to ensure their operations and according to instructions and regulations , in order to maintain the integrity of the banking sector and financial sector in general .One of the importance regulatory tools that are adopted by the Iraqi Central Bank to control over the banks an financial and periodic statements that are provided by the banks in accordance with planned schedules .The financial statements of the banks must reflect clearly and accurately financial situation and the result of their activities during the period in which they represent to achiveing its purposes.So it has the goal of Search is statemen
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Background A prospective clinical study was
performed to compare the efficacy of the use of lowmolecular-
weight heparin group (enoxparin group)
with control group in the prevention of deep-vein
thrombosis after total knee arthroplasty.
Aim of the study: to assess the prevalence of DVT
after total knee arthroplasty and evaluate the
importance of the use of low molecular weight
heparin in the prevention of this DVT.
Methods Thirty-three patients undergoing total
knee arthroplasty were randomly divided into two
groups. One group consisted of 12 patients who
received no prophylaxis with an anticoagulant (the
control group), other group consisted of 21 patients
who received the low-molecular-weight h
The electoral mechanism is remarkably clear, a political tool for institutional construction, directing political life, forming the political scene, and forming the partisan scene. This process was through the design of electoral laws, as elections in Tunisian political history represented the indicator of its slow and accelerated transformations, so The elections in Tunisia usually coincide with important political stages, accompanied by legislative or constitutional amendments in general, Islamic or secular forces have played a fundamental role in promoting the democratic experience and the principle of the peaceful transfer of power. This led to the formation of a national consensus that would help the country not enter into political
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The political struggle being waged by Muslims today is one of the most important issues that have preoccupied the Arab and international media, and the failures that have afflicted Muslims in our contemporary world have negatively affected the younger generations and led them, and with the influence of anti-Islam media, to rely on accusing Islam as a religion with all the negative in Islamic and Arab society . So secularism took its role in spreading these concepts by deviating from its course from the concept of science to the concept of (the religion).
From here the calls for reform rose to return the Muslims to the incubator of Islam, so people turned around them, but they turned into competing Islamic polit
The current study aimed to reveal the role of the high school (boys) in the Governorate of Qurayyat (KSA) in promoting intellectual security of students, and whether there were differences in the estimates of the study sample due to the variables; the current position, academic qualification, teaching specialization and years of experience. This study was conducted by applying the analytical descriptive method, and used questionnaire as a tool for data collection. The survey consisted of (44) ite
... Show MoreBac kground: The transfer of the tibialis posterior tendon to the anterior aspect
of the ankle not only replaces the function of the paralyzed muscles, but also
removes the deforming force on the medial aspect of the foot.
Objec t i ves : In this study, we evaluated patients who underwent tibialis
posterior tendon transfer for the treatment of foot drop, and comparison through
interosseous membrane route versus anterior to lower tibia route of tibialis
posterior tendon transfer, with evaluation of the results according to carayon
criteria
Methods: Nine patients with foot drop secondary to different causes treated with
tibialis posterior tendon transfer from January 2011 to January 2012 were
followed up for a
The organizational structure of relations between states is among the main features that distinguished the twentieth century as the era of international organization, especially after the increase in the number of political units after World War II in which regionalism was crystallized as a phenomenon. It is not modern, as there are many blocs such as the European Union that have developed in it, the idea of regional bloc is prominent, especially in Europe, as it emerged after a controversy revolved around what was called globalism in the face of Globalism vs. Regionalism. Regional, as the proponents of the global orientation saw the establishment of a global organization that includes all countries, as the best way to achieve inte
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The current research aims to analyze the role of participatory budgeting in improving performance, especially during crises such as the Covid-19 crisis. The research used the descriptive analytical method to reach the results by distributing 100 questionnaires to a number of employees in Iraqi joint stock companies and at multiple administrative levels. The research came to several important conclusions, the most important of which is that the bottom-up approach to budgeting produces more achievable budgets than the top-down approach, which is imposed on the company by senior management with much less employee participation. Additionally, there is a better information flow from the lower levels of the organization to the upper management
... Show MoreIntroduction: Since the hallmark of gestational trophoblastic disease is trophoblastic proliferation, Ki67 is regarded as the best marker in studying hydatidiform mole.This study was conducted to evaluate the role of this proliferative marker in distinguishing among hydropic abortion, partial and complete hydatidiform mole. Materials and methods: This is a cross sectional study involving the application of Ki67 on a total of 90 histological samples of curetting materials from molar (partial and complete mole) and non molar hydropic abortion belong to Iraqi females, so three study groups were created. Immunohistochemical expression in villous cytotrophoblasts, syncytiotrophoblasts and stromal cells were recorded separately by three i
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