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.
This paper is focused on studying the effect of cutting parameters (spindle speed, feed and depth of cut) on the response (temperature and tool life) during turning process. The inserts used in this study are carbide inserts coated with TiAlN (Titanum, Aluminium and Nitride) for machining a shaft of stainless steel 316L. Finite difference method was used to find the temperature distribution. The experimental results were done using infrared camera while the simulation process was performed using Matlab software package. The results showed that the maximum difference between the experimental and simulation results was equal to 19.3 , so, a good agreement between the experimental and simulation results was achieved. Tool life w
... Show More
(2)
This study aims to assess the effect of adding twisted fins in a triple-tube heat exchanger used for latent heat storage compared with using straight fins and no fins. In the proposed heat exchanger, phase change material (PCM) is placed between the middle annulus while hot water is passed in the inner tube and outer annulus in a counter-current direction, as a superior method to melt the PCM and store the thermal energy. The behavior of the system was assessed regarding the liquid fraction and temperature distributions as well as charging time and energy storage rate. The results indicate the advantages of adding twisted fins compared with those of using straight fins. The effect of several twisted fins was also studied to discover
... Show More
(41)
(37)
The article approaches the characteristics of Russian literature in the time of Khrushchev or the "thaw" period a very short period of Soviet history, characterized by the easing of the dictatorship of power and relaxation in various areas of people's lives. The interest in the research is focused on the importance of interpreting the family portrait in a short but distinct period in the development of Russian/Soviet literature. The research material is the story of Sholokhov's “The Fate of Man” 1956, the story of Panova “Serioga” 1955, and Abramov’s story “Fatherless” 1961. В статье рассматриваются особенности художественной литературы периода хруще
... Show More
Vancomycin Staphylococcus aureus (VRSA) is a strain of S. aureus that is considered the main cause of bacterial skin and soft tissue infections. It has acquired resistance to vancomycin and represents a therapeutic challenge. The current study aimed to compare the possible therapeutic effects of VRSA bacteriocin (VRSAcin) on the treatment of skin infection in mice with those of an antibiotic (linezolid). The results showed that of the fifty swabs obtained from human skin wounds. One isolate was selected for VRSAcin extraction depending on its antibiotic resistance using an antibiotic susceptibility test.An agar well diffusion test was used to determine bacteriocin’s antibacterial activity, as well as its a minimum inhibitory concentration
... Show More
(5)
(4)
The phenomenon of the social movements of researchers, based on the scope of their influence on political events, and the nature of the wide role played, and its ability to influence, through its activities and various activities and various. It has practiced its activities through new and non-traditional peaceful means, with clear slogans and specific objectives. And was able to mobilize activists from different strata of the Iraqi people, and its categories and social strata. As the demands focused on freedoms, rights, dignity and social justice
Objectives: The main objective of this study is to examine the crucial role that Russian writers and intellectuals played in catalyzing the 1905 Revolution in Russia. Specifically, the study sought to analyze how their literary works, philosophical ideas, and political writings challenged Tsarist autocracy, depicted the suffering of the masses, and inspired opposition movements. The study aimed to highlight the defiant writings that contributed to the rise of political figures and the eventual overthrow of the repressive regime. Methods: The historical narrative and analytical methods were employed, conducting a comparative analysis of prominent works by renowned authors such as Tolstoy, Gorky, and Chekhov. This analysis focused on
... Show More
This study aims to identify how the Zakat Fund contributes to financing entrepreneurial projects; and the role that these projects play in achieving economic and social development, despite the importance that contracting projects have in most countries as the main engine of growth; however, they still face many challenges that In the forefront of which is the challenge of obtaining financing; in this regard, it is possible to resort to the use of Zakat funds in the Islamic economy as it is a funding source that is closely proportional to the characteristics and goals of entrepreneurial projects in achieving development;
 
... Show MoreThe study aims to identify the role of family in inculcating the moral values of voluntary work among adults, as it constitutes the basic social institution that is responsible for raising and control children. It has regarded as the first phase of constituting societies, where family plays a significant role in changing the behavior of individuals positively or negatively through provided patterns. The moral values act as organizer of human relationship in which misusing of these values would affect the interaction between people. This study focuses on how to employ the moral values in voluntary work as a civilized behavior helps in developing and strengthening societies. The researcher adopted the analytical-descriptive approach as mor
... Show MoreThe study aimed to identify the role of the teacher in confronting intellectual extremism in high school students, and identify the differences of statistical significance in the role of teacher in confronting intellectual extremism in secondary school students according to gender variable (males, females) and the duration of service (less than 5 years more than 5 years), the sample was consisted of (100) teachers with (50) male and (50) female in the city of Bayaa, Dora and Sadiya, the measure of intellectual extremism was applied by the researcher, and the study reached a role of the teacher in facing the intellectual extremism at Secondary school students, and the existence of differences of statistical significance in the role
... Show More