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.
Fish are regarded as a crucial indicator of alterations in the aquatic environment due to their position at the apex of the food chain. Monitoring these alterations is crucial for identifying modifications in the aquatic ecosystem. The principal elements influencing fish health are temperature, pH, dissolved oxygen, salinity, pesticide contamination, microplastics, and algal presence. These elements substantially influence fish health regarding development, reproduction, respiration, oxygen stress, and the internal enzymes associated with digesting and other metabolic functions. Alterations in global environmental conditions and anthropogenic pollutants result in modifications to fish populations, their lives, and their behavior and
... Show More
(2)
Abstract
This research aims to highlight the Cooperate Governance concept and determine its accounting dimensions, especially what has connected with development the management accountant role concerning the nature, scope and its location in the organizational structure in the companies as to be complied with implementing the cooperate governance principles and mechanisms in the modern businesses environment. This research has focus on clear shortage in the management accountant role in the companies, regarding to implement the governance mechanisms, especially his role to provide the information and consultations to the internal & external parties (stakeholders) . This
... Show More
The study aimed to get acquainted with kindergarten teachers in the development of
emotional intelligence in children, To achieve this a study too, which consisted of 40 items,
within four areas was condncted: (managing emotions, emotional knowledge, empathy, social
networking) The study tool was applied to the sample amounting (200) teachers of the
kindergarten teachers in the province of Jerash and after analyzing the results statistically
using arithmetic averages standard deviations and variance analysis quartet the following
results were reached :
- presence of statistically significant differences at the level of (α =0,05) is attributable to the
impact of the educational level in the areas of empathy and so
A vital instrument to foster the long-term goal of high-quality education has developed in the form of digital technologies. The educational system has been found to be significantly impacted by these technologies. The recent COVID- Pandemic has strengthened the legitimacy of using digital tools in education. The entire educational system has undergone a paradigm shift as a result of these digital technologies. Along with sharing knowledge, it also serves as a mentor, an assessor, and a co-creator of information. Students' lives have been simpler as a result of educational technology advancements. Nowadays, students prepare presentations and projects utilizing a variety of software and tools rather than pen and paper. The weig
... Show MoreThe importance of operational risks increases with the increase in technological development, the development of banking operations, the extent of banking compliance, and the attempt of many banks to achieve quality in banking services. And the extent of the position occupied by Iraqi banks for banking compliance and reducing operational risks. The Basel Committee (2) paid its attention to operational risks and the interest of international banks to follow policies that work to ensure banking compliance and cover operational risks, because of its role in reducing losses due to increased costs and achieving an increase in profits. Realizing and working to confront the best possible and traditional methods, that some risks Operational problem
... Show More
The study tries to answer several questions posed by the subject, one of the important: How the Internet promotes rumor? And what are the most Internet applications that promote rumor? And the practical ways to reduce these negative? Using the process of in vestige and reading theoretical heritage available in this field, and inferred the numbers and statistics marked the uses of the Internet and its applications over recent years, and the characteristics of each these tools in the field of collection, processing, and dissemination of information
This research seeks to explore the impact of notifications on enhancing user engagement with websites, primarily through user subscriptions and their interaction with notifications on these websites. The significance of this study lies in its implications for crafting compelling headlines that capture users' attention, streamline their access to journalistic content, and align with the objectives and editorial policies of news websites. It sheds light on the factors influencing users' preferences for specific notifications and their engagement with content based on their individual interests, motivations, and the satisfaction derived from such interactions.
The researcher has reached several key findings, inc
(1)
Article information: COVID-19 has roused the scientic community, prompting calls for immediate solutions to avoid the infection or at least reduce the virus's spread. Despite the availability of several licensed vaccinations to boost human immunity against the disease, various mutated strains of the virus continue to emerge, posing a danger to the vaccine's ecacy against new mutations. As a result, the importance of the early detection of COVID-19 infection becomes evident. Cough is a prevalent symptom in all COVID-19 mutations. Unfortunately, coughing can be a symptom of various of diseases, including pneumonia and inuenza. Thus, identifying the coughing behavior might help clinicians diagnose the COVID-19 infection earlier and distinguish
... Show More