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 current research aims to measure the level of entrepreneurial orientation and its dimensions (creativity, independence, proactivity, risk tolerance, and achievement) in the National Security Chancellery, as its importance and role in guiding senior leaders of the chancellery to make strategic decisions with high quality in various Iraqi concerns, more specifically the security aspect. The data was collected from 94 individuals (the research sample) from the research community (120) individuals at different administrative levels and intentionally where the questionnaire was adopted as a main tool for data collection and the primary data was analyzed through descriptive and inferential statistical methods (arithmetic mean, standard dev
... Show MoreDistribution of light intensity in the flat photobioreactor for microalgae cultivation as a step design for production of bio-renewable energy was addressed in the current study. Five sizes of bioreactors with specific distances from the main light source were adopted as independent variables in experiential design model. The results showed that the bioreactor’s location according to the light source, determines the nature of light intensity distribution in the reactor body. However, the cross-section area plays an important role in determining the suitable location of reactor to achieve required light homogeneity. This area could change even the expected response of the light passing through the reactor if Beer-Lambert's law is adopted.
... Show MoreThe linguistic meaning of the verse in the Arabic dictionaries applies very much to the reality of rent and its effect. This is true of economic growth as a continuous increase in real per capita income in addition to the same thing. Therefore, development does not necessarily achieve a comprehensive and structural increase of the various economic sectors. As the rent came in the sense of a terrible land open Maim any fertilized. And the camel is a ma'aya and a ra'i: that is, it goes in the pasture and returns itself. This is similar to the extraction of oil after it is ready for investment and earn its revenue as soon as it exists or is extracted by external parties. If the rent is first linked to agriculture, especially the fertile lan
... Show MoreSamples of marsh frog included 148 sexually mature males were collected in Baghdad
from December 1992 to December 1993 to December 1993. The testis weight was expressed
as percentage of the body weight. The percent mean weights of testis were at their minimal
weight (0.255%) during April (spawning period).
Testis weight has increased until reached its greatest average weight in August (0.785%).
During the winter there is a slight decrease in weight with a more obvious fall at the spawning
months. From the results obtained from the present work on Rana ridibunda and from the
observations on annual cycle in testis weight of some temperate zone anurans we notice that
testes tend to be lowest after spawning and the te
The accounting system of government is considered an important tool to follow up the financial transactions that reflect the activities of governmental units and by which the useful information for estimating governmental annual revenues and expenditures are provided through the state public budget because it is an information system that provides detailed past performance, as well as measures the efficiency of the governmental agencies performance in implementing the budget, and the of success governmental units is measured through the type of services and programs offered, their size and the possibility of achieving the objectives assigned to them. The medical evacuation program is one of the medical and curative health services provid
... Show MoreAchieving a connection between sustainability processes and environmental protection, or what is known as sustainable development, requires paying more attention to environmental and sustainability issues for various projects and their effects on environmental problems. It involves determining the most appropriate ways to deal with them within pillars of sustainability (environmental, social, economic, and natural resources. As cement is a fundamental component of industrial services and construction in cities, it has a direct and significant interaction with the development process, making it one of the most important industries in Iraq. Because of the clinker particles and combustio
Everywhere carriers incur a measure of liability for the safety of the goods. Carriers are liable for any damage or for the loss of the goods that are in their possession as carriers unless they prove that the damage or loss is attributable to certain excepted causes. Damaged and lost items can unfortunately be a common problem when shipping freight. Legal responsibilities arise due to loss or damage during transit while cargo is in their care. This study intends to investigate the nature of the liability of the maritime carrier when this liability is realized, and the extent to which it can be paid or disposed of given the risks realized from the transportation process, which may result in damage or loss of the goods, and the damag
... Show MoreRadiotherapy is medical use of ionizing radiation, and commonly applied to the cancerous tumor because of its ability to control cell growth. The amount of radiation used in photon radiation therapy called dose (measured in grey unit), which depend on the type and stage of cancer being treated. In our work, we studied the dose distribution given to the tumor at different depths (zero-20 cm) treated with different field size (4×4- 23×23 cm). Results show that the deeper treated area has less dose rate at the same beam quality and quantity. Also it has been noted increasing in the field increasing in the depth dose at the same depth even if the radiation energy is constant. Increasing in radiation dose attributed to the scattere
... Show MoreRasheed Street has had great importance by the nature of what was seen as being of vital events of a key facility in the Iraqi capital Baghdad since ancient times until now .
And such as cultural and historical memory-rich street for Iraq, pulsating nerve since the beginning of the last century thanks to the commercial and intellectual stature, as well as being a tourist landmark frequented alleys most of the tourists coming to Iraq , which counted for them a source of tourist attraction, given the religious diversity of fungal who excelled by the street, as we find in exchange for his Church of the Virgin Mary, the time which was built in the middle of the Caliphs Mosque towering minarets and promised that the oldest and largest of t