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 study aims to examine the problem of forced displacement and its social and economic problems in light of the Syrian crisis. Such an aim helps to know the difficulties and challenges facing the children of displaced families in learning, and the reasons for their lack of enrolment. It also clarifies whether there are significant statistical differences at among the attitudes of the children of the displaced families towards education regarding the following variables: (the work of the head of the family, the economic level of the family, and the work of the children). The study has adopted the descriptive-analytical approach; a questionnaire was adopted as a tool to collect information. The study was applied to a sample o
... Show More
Abstract:
Rabi’a tribe lived on the land of Euphrates since the first century of the
Christ. Then that land becomes her homeland. The Persians tried many times
to drive her away from that land, but with out result.
In the course of time Rabi’a become more knowledgeable of Persia.
This tribe proved her love and sanctification to the land of Euphrates, in the
battle of Dhyqar.
Rabi’a converted to Islam quickly and helped the Muslims to conquer
Iraq with a big number of fighters in many battles like al- Qadisyyah. That
influenced the anger of Mudriat Arab tribes who were their old enemies.
Mudriat tribes did their efforts to reduce the importance of Rabi’a because of
some its branches were among of t
ABSTRACT
The research aims to study the effect of the commodity dumping phenomenon that Iraq suffered after 2003 on the consumption pattern of individuals, towards the acquisition of non-essential goods (luxury). To achieve our goal we relied on the questionnaire as a main tool for obtaining information related to the research, and it was distributed on a random sample of consumers in the city of Baghdad with 250 questionnaires. The answers of the research sample were analyzed using the statistical program (SPSS). The percentage weights and the factorial analysis method were used also to arrange the variables that affected on changing consumption patterns. The research reached a set of conclusions:
... Show MoreThe success of an organization is significantly influenced by strategic performance, a focal point in recent scholarly investigations and regulatory considerations. This study delves into the examination of the impact of strategy formulation, implementation, and evaluation on the strategic performance within the context of the oil industry in Iraq. Additionally, the research explores the moderating influence of leadership style on the relationship between strategy formulation, implementation, evaluation, and strategic performance in the Iraqi oil industry. Data collection involved the utilization of survey questionnaires distributed to selected employees of Iraqi oil companies. Statistical analysis, specifically SPSS-AMOS, was employed to s
... Show MoreABSTRACT
Background : The aim of this work is to assess the role of breast sonography and ductography in the evaluation of different causes of nipple discharge.
Methods : The study will be carried out on twenty-five female patients referred to the Radiodiagnosis department at Alexandria Main University Hospital presenting with nipple discharge.
They were divided into two groups:
Group I include 10 patients (40%) with surgically significant nipple discharge who were the patients with unilateral, uniorificial surgically significant colour type nipple discharge .They were investigated by mammography, sonography, and ductography.
Group II include 15 patients
... Show More
(1)
The emergence of COVID-19 has resulted in an unprecedented escalation in different aspects of human activities, including medical education. Students and educators across academic institutions have confronted various challenges in following the guidelines of protection against the disease on one hand and accomplishing learning curricula on the other hand. In this short view, we presented our experience in implementing e-learning to the undergraduate nursing students during the present COVID-19 pandemic emphasizing the learning content, barriers, and feedback of students and educators. We hope that this view will trigger the preparedness of nursing faculties in Iraq to deal with this new modality of learning and improve it should t
... Show More
(2)
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
This research aims to examine the relationship between learning organization and behavior of work teams. The variable of the learning organization took four dimensions depending on the study (sudhartna & Li, 2004): Common cultural values , communication, knowledge transfer and the characteristics of workers. The behavior of teams was identified on the basis of realizing of the respondents of their organization to work as a team where the research relied concepts applied in the study (Hakim , 2005) , and chose to research the case of a service organization for the study and relied on four dimensions of coordination , cooperation , sharing of information , the performance of the team, and was a curriculum approach and des
... Show More
(1)
Construction is the opening of the important pillars of the construction of the film as a whole for this, we find that the first of any narrative of my film begin at the borders of this construction is the window that we look through the contents tale and puzzle narrative is of significance that degrade traveler when reservoirs expression later in reasoning and find justifications ills that came by those initiation, this initiation may be the window that lead us to the core, understanding the story through signals received to the recipient to sail because of the paths of pickling what is which is encoded, but this initiation may serve as keys that understanding the be puppies and signals that beset and surrounded to what He holds inevita
... Show More
This research has been applied on 100 children (age 4 – 6 years) from three kindergartens distributed on basis of 43 children from the college of Education for women kindergarten (A) , 27 children from the governmental Al- Mustafa kindergarten (B) , and 30 children from the private Al – Baraom kindergarten (C) . Details concerning their school meals, already prepared at home , have been analyzed according to their dietary components taken from the tables of the dietary values .The statistical analysis results have shown no significant difference (p< 0.01) in the intake of energy , protein and thiamin between the children of A and C kindergartens while these children have significantly recieved higher amounts of the above nutrien
... Show More