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.
Complications associated with diabetes are a consequence of acute disturbance in glucose metabolism in a human body. The most significant complication of diabetes is bone disorders which contributes to high levels of bone disability. This study included 118 diabetic patients, 56 males, 62 females, and 60 healthy non-diabetic controls, 30 males, 30 females. The patients and controls were age matched. Circulating levels of bone function markers (osteoprotegerin, vitamin D, PTH, total calcium and inorganic phosphorus) were determined in all subject groups. The data obtained from this study showed that the serum levels of osteoprotegerin had significantly increased in both diabetic male & female in both age ranges which were 4
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Lung cancer is one of the most serious and prevalent diseases, causing many deaths each year. Though CT scan images are mostly used in the diagnosis of cancer, the assessment of scans is an error-prone and time-consuming task. Machine learning and AI-based models can identify and classify types of lung cancer quite accurately, which helps in the early-stage detection of lung cancer that can increase the survival rate. In this paper, Convolutional Neural Network is used to classify Adenocarcinoma, squamous cell carcinoma and normal case CT scan images from the Chest CT Scan Images Dataset using different combinations of hidden layers and parameters in CNN models. The proposed model was trained on 1000 CT Scan Images of cancerous and non-c
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The present study was conducted on sixty five pregnant women that infected with acute toxoplasmosis, serum samples were tested for detection specific anti-Toxoplasma gondii IgM using the rapid Toxo IgG/IgM Chromatographic immune assay test cassette and ELISA, and fifty healthy married women (not pregnant) as was considered as control group. The level of serum IL-6, IL-8, IL-12, TNF-α, TGF-β1, IP-10, MIP-1, MIG and ICAM were significantly increased (P <0.005) in pregnant patients infected with acute toxoplasmosis, while serum level of MCP-1(14.46 ± 1.38pg/ml) was not significantly increased when compared to controls(11.25 ± 0.24pg/ml) , these levels can be used as i
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The skill of management educational activities gradually grow with the experience, but they differ from personal skill educator to another, because each style nanny personally and the way to work. There educator and active movement and vitality that look like happiness and clear during the implementation of the activity, and the other runs educational activities quietly, efficiently and without emotion and clear (dry, 2001: p. 274). And the stage of childhood is one of the most important stages that are based upon the future life as a whole because the man also confirmed by the School of analysis psychological is the son of his childhood and the best example to us what the Holy Prophet Muhammad (peace be upon him): (Every child i
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This work aimed to produce PVA and PVA/Ag nanofibers ultra-high sensitivity photodetector by electrospinning. The electrospinning process was used to successfully prepare PVA nanofibers and a PVA-Ag nanofiber composite. FE-SEM, XRD, UV, I-V characterizations are used to study the morphological, structural, optical, and electrical properties of the material. In contrast, the PVA-Ag nanofiber composite film displayed a cubic structure with favored orientation (200) that indicated the presence of Ag NPs in the PVA-Ag nanofibers film. While the optical energy gap for PVA was 3.96 eV, it was only 2.14 eV for PVA-Ag nanofibers composite film, making this composite sensitive to visible light, particularly green light at 550 nm with a 65% photosens
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Hypothyroidism is a frequent disorder in the general population, especially among women, is defined as adeficiency of thyroid activity that results from insufficient production or action of thyroid hormones leading to a totaldecrease of metabolic. Human leukocyte antigen is the most polymorphic genetic system in man. Genes of this regioninfluence susceptibility to certain diseases.Objectives: The purpose of the present study is to investigate the role of HLA-DRB1 genotyping in hypothyroidpatients with and without periodontitis. Sixty hypothyroid patients 30 of patients were with periodontitis and 30without periodontitis compare with 30 healthy subjects as control enrolled in this study. DNA was extracted fromblood samples, then HLA- genotyp
... Show MoreThis article investigates the relationship between foot angle and jump stability, focusing on minimizing injury risk. Here are the key points: Importance: Understanding foot angle is crucial for improving jump stability, athletic performance, and reducing jump-related injuries like ankle sprains. Ideal Foot Angle: Research suggests a forward foot angle of around 15 degrees might be ideal for many people during jumps. This angle distributes forces evenly across the foot, lowers the center of gravity, and provides more surface area for pushing off the ground. Factors Affecting Ideal Angle: The optimal angle can vary depending on the type of jump (vertical vs. long jump), fitness level, and personal preference. Incorrect Foot Angles: Landing w
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