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 current research aims to identify the Vocational Self of the educational counselors as well as to identify the significant difference in the professional self according to the gender variable (male-female). The researcher adopted the scale of al-hasani (2015), which consisted of (34) items. It was applied to a sample of (300) school counselors (male-female) who were randomly selected from the six directorates in the Baghdad governorate for the academic year 2020/2021. The results showed that the research sample of educational counselors has a vocational self-concept. There are no statistically significant differences in the vocational self-concept between males and females among the educational counselors.
All modern critical approaches attempt to cover the meanings and overtones of the text, claiming that they are better than others in the analysis and attainment of the intended meanings of the text. The structural approach claims to be able to do so more than any other modern critical approach, as it claimed that it is possible to separate what is read from the reader, on the presumed belief that it is possible to read the text with a zero-memory. However, the studies in criticism of criticism state that each of these approaches is successful in dealing with the text in one or more aspects while failing in one or more aspects. Consequently, the criticism whether the approach possesses the text, or that the text rejects this possession, r
... Show MoreThe issue of dignity is one of the topics that do not pass as long as the earths and the heavens remain; Because the earth is not devoid of the righteous, the believers, the saints, and the pious, and these do not cease from them aid, dignity, insight, or good vision, and from here the authorship in this section was continuous; Because the people’s need for it is confirmed as time progresses, and in that, Ibn Taymiyyah says in the sum of his fatwas, “And from what it should be known is that dignities may be according to the man’s need, so if the weak needs them Faith or the needy, he is given from it what strengthens his faith and fulfills his needs, and he who is more complete is the guardianship of God than him. He is independent
... Show MoreLinking adverbials are used to organize and bridge together extended stretches of discourse to make the text coherent. They are explicit indicators of the communicative function of the sentence and writers use them to let their readers follow what has already been said and to help them anticipate what is about to follow.
Linking adverbials include those relations of addition, enumeration, summation, apposition and so on. Through the use of these adverbials, the writer is able to organize and develop his ideas and help the reader follow him from one sentence to another. Thus, a linking adverbial is a semantic relation used to show the way in which what is to follow is systematically connected to what has gone before. So, they have anap
The bony pelvis has a major role in weight transmission to the lower limbs. The complexities of its geometric form, material properties, and loading conditions render it an open subject to biomechanical analysis.
The present study deals with area measurement, and three-dimensional finite element analysis of the hip bone to investigate magnitudes, load direction, and stress distribution under physiological loading conditions.
The surface areas of the auricular surface, lunate surface, and symphysis pubis were measured in (35) adult hip bones. A solid model was translated into ANSYS parametric design language to be analyzed by finite element analysis method under different loading conditions.
The surface
... Show MoreThis paper exclusively deals with medical encounters. . Structurally and thematically, it manifests itself in five parts. The First part deals with medical encounters as well as essential speech activities which cover (a) frames (certain types of talk) (b) the patient’s account and the patient’s story or more precisely the patient telling his story and (c) the act of questioning the patient. The Second part revolves round genre and register. The former, in most cases, suggests that the format of medical encounters is conversational. With register; we have a converse reality that restrictively tries to narrow things and give them a certain flavor. The Third part realizes the technicalities of medical encounters (a) the setting of an inte
... Show MoreAbstract: Various peoples have contributed to building the Islamic civilization through the achievements and creativity of their scholars. In particular, the Kurdish scholars have provided new and great services to the Holy Qur’an that deserves attention. For example, it is no secret that Sheikh Ahmadian, with his interpretation, rendered a great service to the Glorious Book of God. His style is distinguished by modernity, seriousness and objectivity, and represents a lively response to the needs of the Kurdish Muslim people. Due to the importance of Ahmadian’s interpretation of the Qur’an, therefore, I have demonstrated his approach in this research in terms of dealing with his interpretation of the Qur’an with the Qur’an, the
... Show MoreThe pleomorphic adenoma is a benign salivary gland tumor, presenting usually in the parotid gland. This case report describes an unusual case of 29 years old female with a single, nodular swelling evident in the upper lip which was diagnosed as pleomorphic adenoma of the minor salivary glands in the upper lip .The lesion measured 1.0 x 1.0 cm in size for 2 years duration cause depression of labial cortical bone apical to lateral and canine teeth. It is characterized by slow growth. Complete excision was performed and the histopathological analysis supported by immunohistochemistry showed pleomorphic adenoma .It did not recur 18 months after operation.
the chormanal some complement of barbus grypius is found to be 98 consisting of 22 melaccntricsomes it is probably a tetraploid species and more advanced than other speice haveing the same ehromosome under and belonging yo the genus barbus