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.
Background: Type 2 diabetes mellitus (T2DM) is a chronic disorder that constitutes a major health problem worldwide. Toxoplasma gondii is an intracellular parasite that may infect any nucleated cell. Toxoplasmosis is becoming a worldwide health threat, infecting 30–50% of the world’s human population. The studies that have been undertaken to investigate the link between T. gondii infection and diabetes have shown contradictory fi ndings. This research aimed to look at the possible link between T2DM and T. gondii infection. Methods and Subjects: The enzyme-linked immunosorbent assay (ELISA) approach was used to screen for T. gondii IgM and IgG antibodies in 69 patients with T2DM and 92 seemingly healthy persons as controls. Resul
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Background: Preeclampsia occurs in 3-5% of
pregnancies and is a major cause (12-20 %) of
maternal mortality in developed countries. It is the
leading cause of preterm birth and intra-uterine
growth restrictions (IUGR).
Objective: The study was designed to determine and
demonstrate the ultra structural changes of
endothelial cells in placenta of women suffering from
hypertensive disease.
Patients & Methods: Placental samples were
obtained from two groups of pregnant women
groups (preeclamptic and normal pregnant women).
The specimens were fixed in 2.5% gluteraldehyde
and preceded for electron microscopic examination.
Results: Placenta of women with preeclampsia has
shown marked degenerative
This paper presents a comparison between the electroencephalogram (EEG) channels during scoliosis correction surgeries. Surgeons use many hand tools and electronic devices that directly affect the EEG channels. These noises do not affect the EEG channels uniformly. This research provides a complete system to find the least affected channel by the noise. The presented system consists of five stages: filtering, wavelet decomposing (Level 4), processing the signal bands using four different criteria (mean, energy, entropy and standard deviation), finding the useful channel according to the criteria’s value and, finally, generating a combinational signal from Channels 1 and 2. Experimentally, two channels of EEG data were recorded fro
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The media plays an important role in a number of functions performed by them. Press is one of those media which had and still have a clear role in addressing the various issues, topics, and events. Journalism is no longer as expressed by owners of the liberal theory – it seeks to raise the instincts – but it began to excite the minds of readers to meet their needs. At the same time, it does not neglect the search for the truth and work to deliver it to readers. Some have identified a set of tasks carried out by the press including the interest in public affairs, the needs of the community, work to provide happiness, what is beneficial and useful and combat the negative phenomenon and to address the deviations facing society. The comi
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After the political change in Iraq in 2003, Iraq witnessed a stage of social and political development and the strengthening of the legal foundations of the state system, by the approval of the permanent Iraqi constitution of 2005, and stipulating the quota system.
Iraqi women participated in the parliamentary elections from 2005 until 2021, and despite the participation of Iraqi women in all elections, there are challenges that women in Iraq face that prevent their political participation in general and participation in parliament in particular. There are factors behind this, including those related to Iraqi women themselves, including those concerning the political institution and factors related to the nature of society, and it
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كانت وسائل الاعلام- التقليدية والحديثة – وستبقى وسيلة مهمة لتدفق المعلومات والتعبير عن المشاعر ووصف الاحداث وتشكيل الرأي العام المحلي والدولي عن مختلف القضايا التي تهم الافراد والمجتمعات وفي مقدمتها قضايا العنف بمستوياته كافة ،والتطرف الديني والارهاب بكل مسمياته وستحاول هذه الدراسة ان تقدم اجابات عن اسئلة محددة تمثل الاطار النظري لدراسات مسحية ترصد النظريات التي ترسم الاطر النظرية الت
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The Economist opinion (views) gathered on the great Importance’s of small enterprise on the production sectors at Developed or in developing countries, statistics indicate that these enterprise represent almost 90% of the total enterprises in most economies in the world.
Many of these enterprises have originated in Iraq since the beginning of last century and the question of financing these enterprises remained an issue facing the most of workers in this sector, because of the peculiarty of which are characterized by which as a lack of financial abilities and the difficulty of obtain the sources of financing in Iraq and considered the enterprise as the guarantor of fulfilling Financial obligations. Afte
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Abstract:
This research aims to the importance of oil in achieving economic
security in the Arab. Oil is not an ordinary subject and returns it significance to
the followings:
1. The importance of skipping a source of energy.
2. The importance of oil as raw material for petrochemical industry.
3. The importance of the oil sector as an area of foreign investment
4. The importance of oil in the marketing activities, transport, insurance
and various services
In addition to the importance of oil in general and the Arab oil has
additional strategic advantages such as geographic location, And the
magnitude of reserves and production of heavy investment costs are relatively
simple, And the ability to meet the
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