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
The aim of the current research is to identify the level of availability of written expression skills included in the Arabic language curriculum document among middle school students from the teachers' point of view. The researcher used the descriptive approach. To analyze the data and access the research results, he used the (SPSS) program. The research was conducted during the first semester of the academic year 1442/1443 AH on a random sample of Arabic language teachers in the Bisha Education Department. They reached about (213) male and female teachers. The results revealed a number of indicators: the level of availability of written expression skills among middle school students in Bisha governorate
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The study aims to reveal the level of inclusion of citizenship values in the English language textbooks (We Can) series for elementary education in the Kingdom of Saudi Arabia. To achieve this objective, the "content analysis" methodology was used. A content analysis card was designed to include (6) main areas of citizenship values, it consisted of (28) sub-indicators of citizenship values that were supposed to be included in the English language textbook series (We Can) for elementary education. The study sample consisted of all the English language textbooks (We Can) series for elementary education, which consisted of (6) textbooks, two for each class. The results of the study indicated that there is a
... Show MoreCurrent research aims to find out:
- Effect of using the active learning in the achievement of third grade intermediate students in mathematics.
- Effect of using of active learning in the tendency towards the study of mathematics for students of third grade intermediate.
In order to achieve the goals of the research, the researcher formulated the following two hypotheses null:
- There is no difference statistically significant at the level of significance (0.05) between two average of degrees to achievement
The research aims to know The Effect Of Flexible Grouping Strategy and Three Step Interview strategy on achievement of the history material among student of the first literary class, The Researcher used the experimental design of the two experimental groups and the control group and with post test, researcher group (a) represent the experimental group taught according the Flexible Grouping Strategy , and Division (c) to represent the second experimental group which studied according Three Step Interview strategy and Division (b ) to represent the control group taught in the traditional method, the number of students (99) students of (33) female students in each division. T
... Show MoreThe objective of this study is to attempt to provide a quantitative analysis to the causes of unemployment in Iraq and its mechanisms of generation, as well as a review of the most important types of both visible and invisible unemployment, and an attempt to measure the disguised unemployment and analyze the causes. The problem of the research lies in the fact that the Iraqi Economy has been suffered for a long time although its characterized by abundant physical and natural resources, from the existence of the phenomenon of unemployment in the previous two types. Causing a lot of economic problems, represented by the great waste of resources and
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The study aimed to explore the effectiveness of using rational judgment strategy in teaching science to develop scientific thinking for second-grade students. The researcher utilized the quasi-experimental approach based on (the pre/post designing) of two groups: experimental and control. As for tools: a test of scientific thinking prepared by the researcher that proved its verification of their validity and reliability. The test applied on a random sample of (66) students, divided into two groups: (34) experimental, and (32) control. The results showed that the experimental group outperformed the control group in the post-application of the scientific thinking test, In each skill separately, and in the total skills. The study recommende
... Show MoreBanks represents financial institutions that influence the economy of any country and their evolution and development is the need to seek all states , communities, maintain and control a guarantee of the beneficiaries investors and to promote confidence, so the specialized organizations trying to set principles and rules must be adhered to and are Basel (II) of the necessary effects to be introduced and work on their application. Banks exposed by various risks one of them operational risks that have multiple effects on the activity of the institution itself, as well as the national economy, so this study was to find out what those effects and to find solutions and appropriate proposals to avoid Iraqi banks from the effects of risk,
... Show MoreThe Contemporary Business Environment is Surrounded by many quick and continues variable and changes which has an effect on the economic units. These variables and changes like the high competition which need many tools to help them to continue and achieve The critical success. So to achieve this they have many competitive strategies like cost leadership strategy, differentiation strategy and focus strategy.
Budget is regarded one of main tools to execute objectives polices and programs of the economic units, beside show how the economic units had execute the available economic resources.
Activity based on budgeting is regarded one of the modern technique in the m
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This study aims to analyze the spectral properties of plasma produced from rice husk(Rh) using the laser breakdown spectroscopy (LIBS) method. The plasma generation process used the fundamental harmonic (1064 nm) of a Q-switched Nd:YAG laser. Yttrium aluminum garnet (YAG) is a man-made crystalline material. The laser fired pulses with a duration of 10 ns and a repetition rate of 6 Hz. Thus, the energy outputs achieved were 50–200 mJ at the wavelength of 1064 (nm). The silica content in the rice hulls was verified using an XRF measurement, which revealed the presence of silica in the rice hulls in a high percentage. Precise beam focusing was achieved by focusing the laser on the target material. This target material is placed with
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