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 present study aims to identifying the effect of Eurygaster integriceps infection on the quality features of the local wheat varity IBA 99. The result revealed significant decrease in the percentage of protein of infected wheat at (4, 5)% compared to sound wheat values for the sound wheat were (10.9%) whereas those for the infected wheat were(9.0, 8.4 )% also the result revealed significant increased in the percentage of ash in the infected wheat flour. The result showed significant decrease in the percentage of wet and dry gluten in the infected wheat by sun bug at the rate of (2, 3, 4, 5)% compared to sound wheat value (27, 9% and 25, 23, 22, 22, 20%) for wet gluten and (8.2, 7.8, 7, 7.2, 6%) for dry glutin . The value of sedimentati
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Background: five clinical phases were described in patients with chronic (HBV) infection: HBeAg- positive HBV infection, HBeAg- positive chronic HB, HBeAg negative HBV infection, HBeAg-negative CHB and occult HBV infection. Aim: This study aimed to determine the incidence of the unclassified phase (gray zone) in chronic hepatitis B patients and its significant in the clinical practice. Patients and methods: The study was conducted retrospectively on 109 patients' who have HBsAg positive for more than 6 months. The data recorded include; HbeAg and anti-HBe Ab, ultrasound of the abdomen, HBV DNA load and alanine aminotransferase (ALT), accordingly; we classify the patients to known clinical phases. Patients who were unfit one of these phases
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Background: Cytomegalovirus (CMV) virus is a recognized important cause of congenital CMV infection which carries a significant risk for symptomatic disease and developmental defects in newborns. Its prevalence varies from place to other and time to time. This study is conducted to estimate its prevalence in Baghdad among infants suspected of having a congenital infection and to study the associated findings.
Subjects and Methods: The study was carried out in Al-Alwyia pediatrics teaching hospital. Data were collected, and blood samples were taken for infants suspected to have intrauterine infections over a period of one year, from 1 October 2019 to 1 October 2020. Immunoglobulin M (IgM) tests for CMV w
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This study sought to give a general picture of the organizations and formations of the ground forces of the Abbasid army in its first era, in preparation and armament and continuous development of the mechanisms to help maintain the moral and spiritual morale in the fighting.
Therefore, the caliphs' interest in building the army, organizing it, arming it, choosing competent leaders, and providing them with various weapons in terms of production and storage, as well as taking care of fortifying the cities and gaps in determination and determination, and embarked on construction and restoration, where amazing speed and acted according to the circumstances. During the first Abbasid era, there were significant developments in the military
Leishmania major is a protozoan parasite that causes cutaneous Leishmaniasis disease in human beings and animals. The disease is prevalent in tropical and semitropical countries and has great health importance. The present study aimed to identify the histological changes in the organs infected with L. major and to provide a sophisticated diagnostic method for infection through detecting TGF-β cytokine by immunohistochemistry technique(IHC) from October 2020 to January 2021. A total of 40 samples of paraffin blocks were used for different organs including skin, spleen, liver, kidney, and heart of male and female BALB/c mice, aged 6-8 weeks, which were previously infected subcutaneously with L. major promastigotes at a dose of 1×107 promast
... Show MoreIntroduction. Intraoperative rupture (IOR) of an aneurysm is a frightful complication that causes significant morbidity and mortality worldwide. IOR can be attributed to various parameters, including hypertension, increased intracranial pressure (ICP), fragility of the vessels, and inadequate anaesthesia. IOR due to insufficient anaesthesia is scarcely reported in the literature. Here, we describe a re-ruptured anterior communicating artery (ACoA) after incomplete clipping of the neck during craniotomy closure due to unintended early wake-up from anaesthesia with a discussion about the management. Case description. A 38-year-old male suddenly developed a severe headache, a brief loss of consciousness, and vomiting. Computed tomogr
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Background: During the pandemic, Corona virus forced many people, especially students, to spend more time than before on the computer and smartphone to study and communicate. The poor posture of the body may have worse effect on its body parts , most of which is the cervical spine (forward head posture). Objective: To assess the incidence of neck pain and the associated factors among undergraduate medical students related to position during E learning Subjects and Methods: Cross-sectional study was conducted among medical students in three Iraqi universities during 2021. The sample size was 152. Online questionnaire by Google forms sampling method were used to collect the data which was analysed using SPSS 25. Results: The perce
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Background: During the pandemic, Corona virus forced many people, especially students, to spend more time than before on the computer and smartphone to study and communicate. The poor posture of the body may have worse effect on its body parts , most of which is the cervical spine (forward head posture). Objective: To assess the incidence of neck pain and the associated factors among undergraduate medical students related to position during E learning Subjects and Methods: Cross-sectional study was conducted among medical students in three Iraqi universities during 2021. The sample size w |
The Battle of Kadesh is replete with many military arrangements that reflect the tremendous development of war preparations in the thirteenth century BC; where the expressive pictures the Egyptians left on some of the walls of their temples show the tremendous ability to organize and divide the forces and the great development that affected the war machine. Furthermore, the text accompanied these pictures reveal some news about that battle, which is considered one of the most important wars in the ancient world. Thus, the importance of the study lies in the fact that it examines one of the most important battles of the ancient Near East, the results of which had great repercussions on the region. This is because it is the most abundant B
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Background: Infections are common in the children attending daycare centers how act as predisposes to it. Hygienic interventions have a fundamental role in infection control and disease prevention in child care settings.
Objective: - To evaluate the knowledge, attitude, and practice of nurseries workers in infection prevention and control among the children.
Subjects and Methods: A cross-sectional study using the researcher-developed questionnaire validated by two experts and piloted and 100 nurseries-workers had participated in it.
Result: the mean age of participants was 37.5 years±12.1, (37%) aged 18-30 yrs, 58% married, and 57% with higher education, 54% of n
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