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 aim of this research was to analyze the financial reporting requirements of segmental information that stipulated by the Iraqi accounting rules, investigating the extent of it compliance with the requirements of the International Financial Reporting Standard No.8 (IFRS 8) and the Statement of Financial Standards No.131 (SFAS 131). Also the research aimed to identify the segmental disclosure practices in listed corporations on Iraq Stock Exchange (ISX), basing on a hypotheses said that “the insufficient of Iraqi financial reporting requirements of segmental information affect<
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This paper depends on sheding some litgt on the characteristics of political
relations between the arab and the Persian during the reign of sassane kings.
"Ardashir the first, shahbour the first, shahbour the second, Bahram the fifth; kisra
Anushrwan and kisrah abruis"
And who rulled the Persian before the Islamic conquest and were adopted in this studym
as a model. It was possible to get some information from invaluable refereces in order to
arrive at a clear image as regards the nature of these relations. These relations were
differently political according to the circumstances of ruling, interests and the personality
of those kings.
The current study aimed to investigate the viability of biofilm formation klebsilla pneumoniae and Staphylococcus aureus. 440 urine samples were collected from patients suffering from urinary tract infection (UTI) from those who were admitted and visitors to Al-Ramadi Teaching Hospital, Al-Yarmouk Teaching Hospital, Al-Ramadi Teaching Hospital for women and children and , Teaching Laboratories in the Medical City for both genders for a period extended from 5 July, 2017 to 10 October, 2017. Samples were diagnosed by culturing them on a selective media and by biochemical testes , also, diagnosis was ensured by using VITEK-2 compact system. Results showed that K.pneumoniae isolation ratio was 17.1%(68) and S.aureus ratio was 13.1%(52). Thei
... Show MoreMany countries are very important in their interest not only in diversifying foreign reserves, but in determining and planning their volume in accordance with the goals set, namely facing potential external shocks, as the research aims to determine the extent of the strength of foreign reserves in the possession of the Central Bank in relation to every influential variable in the Iraqi economy. , in order to determine the minimum level of reserves that requires reconsideration of the exchange rate, as the research adopted the inductive analytical method in analyzing real (Quantitative data) for the research variables in the years of study, as the research adopted a set of analytical indicators approved by the International Moneta
... Show MoreCoronavirus 2019 (COVID-19) pandemic led to a massive global socio-economic tragedy that has impacted the ecosystem. This paper aims to contextualize urban and rural environmental situations during the COVID-19 pandemic in the Middle East and North Africa (MENA) Region.
An online survey was conducted, 6770 participants were included in the final analysis, and 64% were females. The majority of the participants were urban citizens (74%). Over 50% of the urban residents significantly (
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Background: The influence of glucose metabolism is seen in many infectious diseases, making diabetic patients more vulnerable to sepsis and other serious sequelae of bacterial invasion such as UTI and vaginitis.Patients and method: sixty two patients (women) were suffering from GUTIs consulting Al-Elwya hospital from November- 2009 to March -2010. Two samples were taken from those patients (urine samples and vaginal swabs); these samples were cultured on Blood, Chocolate, and MacConkey's agar for isolation of bacteria.Results: The study group consists of sixty two women suffering from (GUTI), their ages range from 18-55 years. Thirty eight of them were diabetic women and twenty four of them were non- diabetic women. Twenty t
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Background: Helicobacter pylorus is one of the most harmful human pathogens & carcinogen. Of the world's population, more than 50% has H. pylori in their upper gastrointestinal tracts. It has been linked to a variety of extra gastric disorders. In correlation to hepatobiliary diseases; recently, the bacterium has been implicated as a risk factor for various diseases ranging from chronic cholecystitis and primary biliary sclerosing cholangitis to gall bladder cancer and primary hepatic carcinomas. However, the association between Helicobacter pylori (H. pylori) and gallbladder diseases is still vague and is controversial.
Aim of study: To elucidate the association of H pylori and gallbladder diseases (calculu
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A total of 243 serum samples were tested for the presence of
Chlamydia antibodies by ind irect immunofluorescent antibody test.Ninety
nine females were suffering from abortions, 64 were infertile and other 80 were none aborted women. The incidence of Ch lamydia were (15%,
9.4%) and (3.8%) in abortion, infertile and non aborted group,
respecti vely. The results also showed a difference in prevalence rate between the age groups. The highest incidence was found in the age group 20-39 &
... Show MoreThis study aimed to clarify the legal provisions concerning the senses and their role in financial transactions, in the light of the definition of all the vocabulary presented by this study (senses - the definition of senses apparent: they are hearing - sight - smell - taste - touch) in the first section. The study deals with the second topic of the reference and writing denominator phrase and includes two requirements, the first requirement: the establishment of the denominator of the phrase, which has two branches: Section I: signal Akhras. Section II: Signal of the Spokesman.
The second requirement is that writing takes the place of the phrase in financial transactions. The owners argue that the sale of the blind is correct a
Phraseological or phraseological turn - unchanged in structure and composition, integral in meaning and lexically indivisible phrase or sentence, performing the function of a separate dictionary unit - lexemes. Idioms are found in any language of the world. But such a number of winged phrases, as in Russian, is nowhere else. Idioms play a role in displaying the national-cultural characteristics of any language. They very clearly and accurately reflect the characteristics of the perception of the world, the characteristic features of the material and spiritual life of native speakers, his mentality.