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.
Fraud crimes, which is a form of crimes against the funds in public office, is one of the crimes of traditional and cutting-edge in the same time, but it took a distinct character from other traditional crimes because of what is based upon, behavioral fundamentals and foundations and expressive image of personal qualities, concentrated in the mental work, the inventive sophistication, and skillful abilities of the perpetrators of these crimes, in addition to what is owned by crooks today a behavioral ability represented in underestimating laws and instructions. Fraud is considered one of the organized crime methods It is the most important method of its methods, all crimes practiced by the cro
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Media theories and studies have provided many diligences on the concept of social media and the circle of influence, including the theory of social marketing which deals with how to promote ideas espoused by the elite in a society to become a recognized social value. The emergence of social networks provided a revolutionary breakthrough, taking the media to unprecedented horizons; and giving its users great opportunities to influence and move across borders without restrictions and censorship, except in a relatively limited manner. So, the emergence of social media has created channels of live broadcasting from its audience in a method of development that changes the essence of the known communication theories; and stops the monopoly of th
... Show MoreBackground: This study aimed to determine the gender of a sample of Iraqi adults utilizing the mesio-distal width of maxillary canines, inter-canine width and standard maxillary canine index, and to determine the percentage of dimorphism as an aid in forensic odontology. Materials and methods: The sample included 200 sets of study models belong to 200 subjects (100 males and 100 females) with an age ranged between 17-23 years. The mesio-distal crown dimension was measured manually, from the contact points for the maxillary canines (both sides), in addition to the inter-canine width using digital vernier. Descriptive statistics were obtained for the measurements for both genders; independent samples t-test was performed to evaluate the gende
... Show MoreThe aim of the research is to clarify the role of service quality through its dimensions represented by (tangibility, reliability, safety, response, empathy) in tax compliance with taxpayers, i.e. performance of the duties and obligations of the taxpayer through its dimensions (registration, accounting, payment of the amount of tax), and to know For this role, a sample was taken from the taxpayers of the branches of the General Authority for Taxes spread in the governorate of Baghdad and its affiliated districts, which amount to (15) tax branches, as (215) questionnaires were distributed to know the impressions and reactions of the taxpayers regarding the level of service quality through the aforementioned dimensions. Using the statistic
... Show MoreSports marketing is one of the most important areas to attract capital and the most important economic activities at the present time and the sports field is one of the most important areas that can be used in marketing products and services and the need for sports marketing in Iraq is shown to increase the benefits and returns of sports clubs due to a lack of material resource and weakness In the available capabilities presented to it. The research problem was the lack of sufficient knowledge of the role of sports marketing in the value of the customer by members of the administrative body of Iraqi sports clubs. The research aims to know the role of sports marketing in the value of the customer in the Iraqi Premier League clubs.
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Abstract: The term extremism refers to the distance from moderation, excess and hyperbole, and it is a relative term that varies from one society to another, according to the prevailing traditions, values and culture, as the problem of extremism is one of the main issues that contemporary societies are concerned with is a phenomenon that has its roots in the intellectual formation of societies. By knowing the concept of extremism, we can identify the reasons that contributed to the existence of extremism as a phenomenon, on the one hand; on the other hand, to clarify the role of women in combating extremism and developing effective solutions to reduce this phenomenon. As women play a major role in society, starting from the family to educa
... Show MoreTo investigate the relationship between increased lipid peroxidation, and the lowering of both plasma total proteins and albumin in lead-exposed workers, and the effectiveness of antioxidants (vit. C and E) in modulating oxidative stress in those workers.
Thirty male and females workers employed in the Iraqi storage battery (age range 20-40 years) were participating in this study. Additionally, 11 healthy subjects were served as healthy controls, with the same age range compared to workers group, to avoid the effects of age variations on the studied parameters. Blood lead levels, erythrocytes and plasma MDA, erythrocytes and plasma GSH, total protein and albumin levels in healthy controls and lead-exposed workers pre- and post-tr
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Aim: The purpose of this study is to compare the effect of epineurotomy of median nerve with just division of the transverse carpal ligament in the treatment of carpal tunnel syndrome. Patients & Methods: We conducted a prospective, random study to evaluate the effect of epineurotomy on the outcome of operative treatment of established median-nerve compression in the carpal canal. Fifty hands (forty-four patients) were selected randomly into two groups: group I had a release of the transverse carpal ligament alone, and group II had a release and adjuvant epineurotomy of the median nerve. The groups were similar with regard to age group, gender, duration of symptoms, and preoperative physical findings. All patients had electrophysiological e
... Show MoreMedia theories and studies have provided many diligences on the concept of social media and the circle of influence, including the theory of social marketing which deals with how to promote ideas espoused by the elite in a society to become a recognized social value. The emergence of social networks provided a revolutionary breakthrough, taking the media to unprecedented horizons; and giving its users great opportunities to influence and move across borders without restrictions and censorship, except in a relatively limited manner.
So, the emergence of social media has created channels of live broadcasting from its audience in a method of development that changes the essence of the known communication theories; a
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The research aims to study and analysis of concurrent engineering (CE) and cost optimization (CO), and the use of concurrent engineering inputs to outputs to improve the cost, and the statement of the role of concurrent engineering in improving the quality of the product, and achieve savings in the design and manufacturing time and assembly and reduce costs, as well as employing some models to determine how much the savings in time, including the model (Lexmark) model (Pert) to determine the savings in design time for manufacturing and assembly time.
To achieve the search objectives, the General Company for Electrical and Electronic Industries \ Refrigerated Engine
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