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.
Abstract:
In light of globalization and internationalization of financial markets, issues arising from financial crises have become increasingly serious and fundamental, creating a lot of debate among experts around the world. So, many studies have attempted to investigate what measures can be taken to detect and prevent crises before they devastate the economies.
Therefore, this paper examines the Effectiveness of the Monetary Policy (MP) to Avoid, Reduce or Treat the Financial Crisis in Malaysia. Scholars have yet to agree on the issue
... Show MoreTo determine the relationship between hepatitis C virus infection and Diabetic mellitus type 2 , twenty patient's with diabetic mellitus type 2 aged (30-61) years old have been investigated from 01/11/2014 to 01/02/2015 and compared with fifteen parentally healthy individuals. All the studies groups were carried out to measure anti-HCV Abs by enzyme linked immunosorbent assay (ELISA), There was significant elevation (P≤0.05) in the HCV Abs compared with control groups .The percentage of HCV Abs was 15% and there was highly significant (P≤0.01) differences between studied group, while there was non-significant differences (P≥0.05) between patients groups according to age and gender compared with control groups. These results indicated
... Show MoreBackground: Type 2 diabetes mellitus (T2DM) is a chronic disorder that constitutes a major health problem worldwide. Toxoplasma gondii is an intracellular parasite that may infect any nucleated cell. Toxoplasmosis is becoming a worldwide health threat, infecting 30–50% of the world’s human population. The studies that have been undertaken to investigate the link between T. gondii infection and diabetes have shown contradictory fi ndings. This research aimed to look at the possible link between T2DM and T. gondii infection. Methods and Subjects: The enzyme-linked immunosorbent assay (ELISA) approach was used to screen for T. gondii IgM and IgG antibodies in 69 patients with T2DM and 92 seemingly healthy persons as controls. Resul
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Generally, different propositions show that culture changes because of many factors, and acculturation has emerged out of important operations which lead to cultural change as a result of contact between different societies or cultures. Since the cultural environment with its varying effects plays a major role in the formulation of architectural products, the research defined its research problem as follows: There is need for knowledge to specify the results of acculturation at the level of plans of house architecture belong to Iraqi elites in Baghdad city during the late Ottoman rule in Iraq(1830-1917). The research depends on the comparative procedure to define the acculturation results, so the plans character of
... Show MoreOur study comes up to clarify the role of television in spreading the culture of violence with a child. This study represents one of the important studies that have tried to highlight the impact of these programmes, particularly cartoons, on the child's behaviors, actions and acquired habits.Violence considers a common phenomenon among the people, as the role of the media, particularly TV has a vital role due to its properties, characteristics and its significant impact on different segments and groups in society and in children particularly through exposure to programmes of films.The results of the study have been affected by the rising proportion of females to males, and that the contribution of real life has a big role in the child ac
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(Thimma) in Arabic means compact, and immunity. (People of Thimma) are the free non-Muslim people under Muslim rule. This includes Heavenly Religions people, i. e., Christian and Jews).
They have been called (People of Thimma) because they had paid (Jizyah: tribute) so they became safe for their souls, honor, properties at the custody of Muslims.
Islamic law had posed (Jizyah: tribute) upon the Jews and Christians who were living under Muslim rule as a reaction of not embracing Islam Faith against securing their rights and freedom.
Freedoms secured by Islam for the (People of Thimma) had been many, including the right of faith, not coercing them to be Muslim, the right to live, to possess properties, protect and secure them, the
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The international humanitarian law found the special rules to protect women meanwhile the armed conflicts whether international or non-international. These rules are adopted for woman because of two reasons : that she is from civilians and on the other hand that her special constitution demands a special protection. The international community's attention of women is increased as a result of the tragic situation that faced women around the world especially in the Middle East and particularly in Iraq during the American-British war and ISIS period, these two periods sort many negative effects that reach women such as captivity, slavery, sexual enslavement and rape women especially Yazidis and Christians....
This study aims at identifying how Baghdad Municipality employs public relations in law enforcement operations and the role played by the Municipality in communication and communicating with the public, raising their awareness and educating them to not abuse public property. As for the research tools, the researcher used the questionnaire as a data collection tool in addition to an analytical description of the means and methods of communication for public relations on Baghdad Municipality Facebook page.
The research comes out with a set of result; the most important of which are:
The means through which citizens learned about the existence of campaigns to impose the law an eliminate violati
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