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.
Bac kground: The transfer of the tibialis posterior tendon to the anterior aspect
of the ankle not only replaces the function of the paralyzed muscles, but also
removes the deforming force on the medial aspect of the foot.
Objec t i ves : In this study, we evaluated patients who underwent tibialis
posterior tendon transfer for the treatment of foot drop, and comparison through
interosseous membrane route versus anterior to lower tibia route of tibialis
posterior tendon transfer, with evaluation of the results according to carayon
criteria
Methods: Nine patients with foot drop secondary to different causes treated with
tibialis posterior tendon transfer from January 2011 to January 2012 were
followed up for a
Introduction: Since the hallmark of gestational trophoblastic disease is trophoblastic proliferation, Ki67 is regarded as the best marker in studying hydatidiform mole.This study was conducted to evaluate the role of this proliferative marker in distinguishing among hydropic abortion, partial and complete hydatidiform mole. Materials and methods: This is a cross sectional study involving the application of Ki67 on a total of 90 histological samples of curetting materials from molar (partial and complete mole) and non molar hydropic abortion belong to Iraqi females, so three study groups were created. Immunohistochemical expression in villous cytotrophoblasts, syncytiotrophoblasts and stromal cells were recorded separately by three i
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Backgr ound: The transfer of the tibialis posterior tendon to the anterior aspect of the ankle not only replaces the function of the paralyzed muscles, but also removes the deforming force on the medial aspect of the foot. Objecti ves: In this study, we evaluated patients who underwent tibialis posterior tendon transfer for the treatment of foot drop, and comparison through interosseous membrane route versus anterior to lower tibia route of tibialis posterior tendon transfer, with evaluation of the results according to carayon criteria Methods: Nine patients with foot drop secondary to different causes treated with tibialis posterior tendon transfer from January 2011 to January 2012 were followed up for a mean of 12 months in Al Kindy Teach
... Show MoreThe role of relaxation program for reducing anxiety of patients in dental clinic
The current research aims to analyze the role of participatory budgeting in improving performance, especially during crises such as the Covid-19 crisis. The research used the descriptive analytical method to reach the results by distributing 100 questionnaires to a number of employees in Iraqi joint stock companies and at multiple administrative levels. The research came to several important conclusions, the most important of which is that the bottom-up approach to budgeting produces more achievable budgets than the top-down approach, which is imposed on the company by senior management with much less employee participation. Additionally, there is a better information flow from the lower levels of the organization to the upper management
... Show MoreThe organizational structure of relations between states is among the main features that distinguished the twentieth century as the era of international organization, especially after the increase in the number of political units after World War II in which regionalism was crystallized as a phenomenon. It is not modern, as there are many blocs such as the European Union that have developed in it, the idea of regional bloc is prominent, especially in Europe, as it emerged after a controversy revolved around what was called globalism in the face of Globalism vs. Regionalism. Regional, as the proponents of the global orientation saw the establishment of a global organization that includes all countries, as the best way to achieve inte
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The current study aimed to reveal the role of the high school (boys) in the Governorate of Qurayyat (KSA) in promoting intellectual security of students, and whether there were differences in the estimates of the study sample due to the variables; the current position, academic qualification, teaching specialization and years of experience. This study was conducted by applying the analytical descriptive method, and used questionnaire as a tool for data collection. The survey consisted of (44) ite
... Show MoreThe genus Serrasentis is one of important acanthocephalan parasites, parasitizing fish, birds and other vertebrates. Twenty two out of 500 fish specimens (4.4%) were found to be naturally infected with adult and cyst of worms of Serrasentis sp. which were collected from the stomach and intestine of Synaptura orientalis; Johnius belangrii, Otolithus ruber and Upeneus sulphureus fish species', from locations of Khor Abdullah, Arabian Gulf, Iraqi marine waters (29°58,33, N48°28, 20E) during the year 2017.The light and SEM study revealed that the adult worm have elongated and cylindrical body, anterior extremity with hooks forming combs arranged on the ven
... Show MoreThe study explores the use of ergative verbs in constructing clauses and their impact on the backgrounding of the agent's role in two selected short stories. Contrary to hypothesis No. 1, the research indicates that changes in sentence patterns don't affect the meaning of the process. Additionally, hypothesis No. 2 is refuted as the middle structure is found to highlight the agent's role in the science fiction short story, Terra Infirmum, rather than concealing it as hypothesized for "The Invisible Man." The analysis uncovers that writers utilize ergative processes to narrate stories in various ways, including transitive/active voice, intransitive/active voice, and transitive/passive voice. Furthermore, the findings suggest that writers emp
... Show MoreThe research deals with metaphors as being one of the primary means used by Lyudmila Ulitskaya when writing the novel " Sincerely Yours Shurik ", to form diverse and multifaceted collective female images of representatives of the classic psychological patterns presented in the work. This research reflects the results of the study related to the work of Lyudmila Yevkinevna Ulitskaya, an actress of modern Russian prose. The novel "The Sincerely to You Shorek" is one of Ludmila Ulitskaya's creations (the year of writing - 2003), which, like her other works, is distinguished by a unique presentation style, rich vocabulary, lexical and semantic diversity, and a special style of writing. writer. The main objective of the research is to look at th
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