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 research dealt with the design of the cost accounting system for the transport service and its Role in improving the efficiency of pricing decisions through the application of the cost system based on ABC activities. The main activities were defined and cost guides were to measure the cost of each service and to determine the cost of each service for the purpose of providing management with appropriate information and pricing decisions The problem of research in the lack of adoption by some public companies in the service sector on the cost accounting system to calculate the cost of service as well as the lack of identification of productive activities and service activities and therefore cannot make the appropriate decision t
... Show More
(1)
This study aims to know the role of strategic leadership to achieving competitiveness in industrial establishments by identifying the respondents’ perceptions about the level of availability of dimensions of leadership strategies (creativity and innovation, risk tolerance, available opportunities) in Bashir Al-Siksek & Partners Company for the manufacture of sanitary and plastic ware in Gaza strip
To achieve this, a questionnaire was developed and distributed to a sample of managers, auditors, accountants, and administrative employees in the study sample company. The questionnaire tool was distributed to 60 employees and employees, of which (52) were retrieved, or 86.6%, and (8) were excluded for la
... Show MoreThe angiotensin converting enzyme (ACE) I\D gene polymorphism influences the blood ACE enzyme activity. Renoprotective effect of ACE inhibitors (ACEIs) varies among patients due to genetic variation, particularly in Renin-Angiotensin-Aldosterone System genes. This study investigates the genetic variations of ACE I\D and AGT1RA1166C gene polymorphisms in the antiproteinuric effect of ACEI therapy in type 2 diabetes mellitus (T2DM) patients. This is a cross-sectional study that included 76 T2DM patients who are ACEI users, divided into two groups: T2DM without diabetic kidney disease (DKD) included 31 patients, and T2DM with DKD included 45 patients. Urine samples were taken for measurement of urine albumin and creatinine, then calcul
... Show More
The clinical spectrum of cutaneous leishmaniasis (CL), an intracellular parasitic pathogen, ranges from a single sore healing to chronic crusty lesions with a manifestation of treatment resistance. The complicated interaction between Leishmania bodies and the early immune response, including innate and adaptive mechanisms, determines the evolution of nodules. This study examined the levels of the chemoattractant interleukin 8 (IL-8), pro-inflammatory nitric oxide (NO), and immunoregulatory macrophage inhibitory factor (MIF) in the serum of subjects recently diagnosed with cutaneous leishmaniasis, in parallel with patients being monitored during consecutive sodium stibogluconate (Pentostam) treatment. A total of 161 serum samples of newly di
... Show More
(6)
(1)
One of the management accounting tools is responsible accounting. In this system, the organisation is divided into responsibility centres that help to connect an individual performance responsible to perform through a combined system of reports according to the implementation of the mechanism of exception tools which gives assistance in planning. The exploitation of the organisation's available resources is achieved through the application of responsible accounting. Also, the best exploitation will lead to the provision of low-cost products through the disposal of all types of waste or loss during the cost centres. By providing products at a lower cost and satisfying the wishes of the needs of customers, the result reflects the competitive
... Show More
Designing cloth is a part from culture and civilization of the area of every state to prove its being in all times because it is grown with Man to establish both goals: usefulness and beauty.It is necessary that designer puts in his mind the importance of the designing sources that he derives his designs from , because those sources are also important in that time especially :The Iraqi Ancient Civilization , the Islamic Civilization and Iraqi Folklores . Not to use the cloth sources that doesn't have well known roots in addition to lacking of elements and bases of balance in its different aspects. In conclusion to that studying research subject comes. (Balance Role in designing cloth curtains) The idea or the problem of the research is t
... Show More
The research aims to release the concept of auditing reporting and its role in the rationalization of economic decisions in the companies listed in the Iraq Stock Exchange from the viewpoint of academics, professionals, investors and lenders. Auditor reporting witnessed the great progress in many areas addressed many of the previous studies compare with Iraqi auditors reporting because there are some defects in these aria .The research problem focused whether the auditor report in Iraq is contains useful information to rationalize investment decisions & lending decisions in the shareholding companies listed on the Iraq Stock Exchange , and under that premise , " There is statistically significant relationship between the reporting au
... Show More
Forty different samples (water and soil) were collected from different places in Iraq and Syria. Only (6) isolates showed the ability to grow and utilize agar as a sole source of carbon and energy. Morphological, cultural characterization and biochemical tests confirmed that These isolates belonging to genus Pseudomonas (HK1-HK6) .Plasmid profiles results showed that these isolates were harbored (2 -3) small Plasmids . HK1 isolate was selected because of its efficiency and ability to grow in high density on agar media for transformation and curing experiments, these were checked by transformation experiments after their expression in E. coli MM294. The genes responsible for agar utilization were located on thes
... Show MoreAbstract:
The research aims to diagnose the relationship between the environmental tax and the development of the sustainable social dimension, where the environmental tax is considered a tool in promoting sustainable development according to its economic, social and environmental dimensions through the application of legislation and instructions for environmental protection, and that imposing an environmental tax will have a clear impact in achieving the dimensions of sustainable development and compliance With regard to the social dimension, the research relied on the financial data for the years (2019-2022) in obtaining information. The research reached a set of results, the most prominent of which was
... Show More