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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The disruptions in supply chains have put small‐ and medium‐sized enterprises (SMEs) in dire need of resilient supply chains through which they can improve their performance. Based on the resource dependence theory, this study proposes a mediation model to improve the environmental performance (EP) of SMEs. The purpose of this study is to investigate the effect of supply chain resilience (SCR) on EP mediated by ambidextrous green innovation (AMGI). We proved a structural equation model based on questionnaire data from 261 companies in Iraq to test our hypotheses. The results show that SCR has a positive effect on AMGI for proactive and exploitative green innovation dimensions and positive impact on SMEs’ EP. AMGI plays a media
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Many countries, including the Arab countries, have sought to establish the free zones because of their important economic importance to diversify financial income, especially in rentier countries, in light of the trend towards the capitalist economy in light of what has been produced by economic globalization, in addition to that many Arab countries have turned towards establishing the free zones that many countries of the world have turned to, to support their economy, especially in the field of attracting foreign investments for these regions, and using them in transferring modern technology, and operating the national workers of the countries that have established those areas, and adopting their products in meeting the needs of t
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Nosocomial infections (NIs) are hospital-acquired associated infections, and also contracted due to the infections or toxins that exist in some location, like hospital. Therefore in our study, 4 Lactic acid bacteria (LAB) isolates were obtained from dairy product (Lactobacillus brevis, L. acidophilus, Lactococcus raffinolactis and Lactococcus lactis) and were tested for Bacteriocin production to select Lactococcus lactis among them. Cell free supernatant (CFS), Lipid and partial purification of protein La. Lactis had high inhibitory effect against test pathogens (E. coli, Bacillus cereus, Staphylococcus aureus and Streptococcus). 30 isolates that diagnosed by Vitec, were isol
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This study examines the relationship between the increase in the number of tourists coming to Tunisia and GDP during the period 1995-2017, using the methodology of joint integration, causal testing and error correction model. The research found the time series instability of the logarithm of the number of tourists coming to Tunisia and the output logarithm but after applying the first differences, these chains become stable, THUS these time series are integrated in the first differences. Using the Johansson method, we found the possibility of a simultaneous integration relationship between the logarithm of the number of tourists coming to Tunisia and the logarithm of GDP in Tunisia, and there is a causal relationship in one direc
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The 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
... Show MoreThe research aims to highlight the role of accounting disclosure in raising the quality of tax settling accounts so as to enhance confidence between taxpayers (corporates) and tax authority, standing over companies commitment to take care of their financial statements which are prepared to the appropriate accounting disclosure of tax authority. It has been noticed that a good disclosure about the results of the activity leads to the acceptance of the tax authority to the results which are stated by the financial statements and the tax is linked on its bases. The researcher depends on the deductive approach which based on Arabic and foreign references, books, researches, previous studies, scientific &nb
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The 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 aim of the research is to identify the extent of the ability to ensure the integrated reports by the auditor in verifying the credibility of these reports, and their implications for the benefit of all parties dealing with the economic unit, as well as measuring the impact of the assurance procedures followed by the auditors and their role in confirming these reports.
The research methodology was designed after studying the previous literature related to the research variables, and then the relationship between these variables was tested, through the use of a questionnaire list. A questionnaire targeting the community of auditors in the local environment, and the results of the study wer
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