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.
This study aims to assess the effect of adding twisted fins in a triple-tube heat exchanger used for latent heat storage compared with using straight fins and no fins. In the proposed heat exchanger, phase change material (PCM) is placed between the middle annulus while hot water is passed in the inner tube and outer annulus in a counter-current direction, as a superior method to melt the PCM and store the thermal energy. The behavior of the system was assessed regarding the liquid fraction and temperature distributions as well as charging time and energy storage rate. The results indicate the advantages of adding twisted fins compared with those of using straight fins. The effect of several twisted fins was also studied to discover
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This paper is focused on studying the effect of cutting parameters (spindle speed, feed and depth of cut) on the response (temperature and tool life) during turning process. The inserts used in this study are carbide inserts coated with TiAlN (Titanum, Aluminium and Nitride) for machining a shaft of stainless steel 316L. Finite difference method was used to find the temperature distribution. The experimental results were done using infrared camera while the simulation process was performed using Matlab software package. The results showed that the maximum difference between the experimental and simulation results was equal to 19.3 , so, a good agreement between the experimental and simulation results was achieved. Tool life w
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Construction is the opening of the important pillars of the construction of the film as a whole for this, we find that the first of any narrative of my film begin at the borders of this construction is the window that we look through the contents tale and puzzle narrative is of significance that degrade traveler when reservoirs expression later in reasoning and find justifications ills that came by those initiation, this initiation may be the window that lead us to the core, understanding the story through signals received to the recipient to sail because of the paths of pickling what is which is encoded, but this initiation may serve as keys that understanding the be puppies and signals that beset and surrounded to what He holds inevita
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This research has been applied on 100 children (age 4 – 6 years) from three kindergartens distributed on basis of 43 children from the college of Education for women kindergarten (A) , 27 children from the governmental Al- Mustafa kindergarten (B) , and 30 children from the private Al – Baraom kindergarten (C) . Details concerning their school meals, already prepared at home , have been analyzed according to their dietary components taken from the tables of the dietary values .The statistical analysis results have shown no significant difference (p< 0.01) in the intake of energy , protein and thiamin between the children of A and C kindergartens while these children have significantly recieved higher amounts of the above nutrien
... Show MoreThe launch of the EU’s Eastern Partnership in 2009 intended to signal a new, elevated level of EU engagement with its Eastern neighborhood. Yet there remain several long-simmering and potentially destabilizing conflicts in the region, with which EU engagement thus far has been sporadic at best. The Union’s use of its Common Security and Defense Policy (CSDP) in the region and to help solve these disputes has been particularly ad hoc and inconsistent, wracked by inter-institutional incoherence and undermined by Member States’ inability to agree on a broad strategic vision for engagement with the area.
The three CSDP missions deployed to the region thus far have all suffered from this incoherence to various extents. In particu
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The success of an organization is significantly influenced by strategic performance, a focal point in recent scholarly investigations and regulatory considerations. This study delves into the examination of the impact of strategy formulation, implementation, and evaluation on the strategic performance within the context of the oil industry in Iraq. Additionally, the research explores the moderating influence of leadership style on the relationship between strategy formulation, implementation, evaluation, and strategic performance in the Iraqi oil industry. Data collection involved the utilization of survey questionnaires distributed to selected employees of Iraqi oil companies. Statistical analysis, specifically SPSS-AMOS, was employed to s
... Show MoreDuring his tenure in Iraq, al-Hadjjaj bin Yusif undertook administrative and economic reforms as well as linguistic reform.
The efforts exerted by Abu al-Aswad al-Dawali to control the reading of the Holy Quran were not sufficient, so the melody and error continued and became more pronounced, especially since the letters were written until then without any distinguishing features.
Al- Hadjjaj bin Yusuf realized the seriousness of the continuation of these errors and what he talked with the days of the causes of division and disagreement between the Muslim community ordered his book to put these suspicious characters marks was at the head of the book Nasr bin Asim and Yehi bin Muammar
The current environment is witnessing several developments as a result of the changes taking place in all areas of economic, social , political and legal that led to the transformation of the industrial economy , which depends based on quantitative production to a knowledge economy which relies based on information and knowledge , as the central pillar of this economy during the trading of these information and knowledge between all individuals in general and decision makers , in particular, through information and communication technology of computers and the Internet to achieve sustainable human development in the social dimension. &
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Background: Laparoscopic cholecystectomy (LC) has become the standard treatment for symptomatic cholelithiasis. Bile duct injury and accidental gallbladder perforation with spillage of bile and stone are common complications of LC. This study was carried out to assess the early complications of gallbladder perforation during LC, and identify the risk factor of that perforation.
Objectives: to evaluate the early complications which may occur after the perforation of the gallbladder during laparoscopic cholecystectomy and to determine the risk factors which are associated with the perforation of the gall bladder.
Subjects and methods: A prospective comparative study o
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The current study aimed to investigate the viability of biofilm formation klebsilla pneumoniae and Staphylococcus aureus. 440 urine samples were collected from patients suffering from urinary tract infection (UTI) from those who were admitted and visitors to Al-Ramadi Teaching Hospital, Al-Yarmouk Teaching Hospital, Al-Ramadi Teaching Hospital for women and children and , Teaching Laboratories in the Medical City for both genders for a period extended from 5 July, 2017 to 10 October, 2017. Samples were diagnosed by culturing them on a selective media and by biochemical testes , also, diagnosis was ensured by using VITEK-2 compact system. Results showed that K.pneumoniae isolation ratio was 17.1%(68) and S.aureus ratio was 13.1%(52). Thei
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