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.
Urinary tract infections (UTI) are some of the most common infections experienced by humans, exceeded in frequency among ambulatory patient only by respiratory and gastrointestinal infections. It is also the most common cause of nosocomial infection in adults. A total of three hundred urine sample were collected in age (1-69 years old) in both gender, with (UTI) symptoms referred to AL-Yarmok Teaching Hospital at Baghdad city during the period from January 2010 till August 2010. The commonest isolates were Escherichia coli (E.Coli), Proteus mirabilis and Klebsiella pneumoniae (These represented 49.2%, 22 %, and16 % of isolates respectively). The percentage of bacteria incidence in females
... Show MoreThis study was conducted to evaluate the effects of black tea on Pseudomonas
aeruginosa isolated from eye infection. One hundred samples (corneal scrapings)
were obtained. Approximately, 77% of the cases were due to contact lens wear
followed by 15 % trauma and 8% with unknown history. The isolates identified as
P. aeruginosa were 30% (23/77 CL) and 25% (2/8 Unknown). On the other hand,
the Kirby-Bauer antibiotic sensitivity assay showed that 100% of the isolates were
sensitive to Neomycin, Gentamicin and Amikacin. While 91.6% were sensitive to
Carbenicillin and Ceftriaxone; 66.6% were sensitive to Cefotaxime and 0% were
sensitive to Tertacycline. Only two isolates were found to be multidrug resistant.
Screenin
The biological diversity of Klebsiella pneumoniae (K. pneumoniae) has widely been reported to be associated with pathological progress in severe nosocomial and community-acquired infections. 250 clinical specimens included sputum, urine and swabs from wound and burns samples were collected from Al-Batool Teaching Hospital (38.4%), Baqubah Teaching Hospital (61.6%) and private laboratories in Baqubah and Diyala, Iraq. Positive rates of nosocomial acquired infection were sputum 98%, urine 96%, and swabs from wound and burns 94%, while positive rates of community acquired infection were sputum 60%, urine 60%, and swabs wound and burns 30%. Positive rates of nosocomial and community acquired infections were 96% and 48%, res
... Show More
(1)
(1)
(1)
Four hundred and fifty urine samples were collected from patients suffering from urinary tract infection from the General Azadi hospital in Kurkuk province ,during the period of october 2007 till march 2008 . Results of bacteriological culture revealed that (168) out of (450) studied samples (37.3%) gave positive culture using blood agar and macConkey agar ; different species of bacterial isolates were detected using morphological and biochemical tests ,from these isolates the highest percentage of the isolates were from Escherichia coli when it was (100) isolates out of (190) isolate (52.63%) . one hundred isolates were distributed between (77) from females and (23) from
... Show MoreHelicobacter pylori (H. pylori) is one of the most common human pathogens in the world. Several studies that have investigated the correlation between H. pylori infection and type 2 diabetes mellitus (DM) found that H. pylori infection is more frequent in the patients, while the results of other studies were unclear. This paper aims to investigate the interrelation between the infection with H. pylori and type 2 DM in Dohuk governorate, Iraq. Eighty four diabetes patients (41 males, 43 females) and 92 healthy controls were involved in this study. H. pylori status was assessed in serum samples by using ELISA test. Out of the 84 patients,
... Show More
(3)
(1)
Human cytomegalovirus (CMV) is the globally highly prevalent herpesvirus worldwide. CMV infects populations of all ages according to the Center for Disease Control and Prevention (CDC) and World Health Organization (WHO). CMV infections remain the most common viral complication potentially multiple in humans and are a major cause of congenital normality in women, which is why they are critical for diagnosis in several times when it happens during pregnancy. Pregnant women with CMV infection can be in charge of abortion or congenital expandaedby. This study involves the collection a total of (90) samples taken from each aborted and pregnant woman (70 with abortion cases and 20 of pregnant without history of abortion as control subjects) r
... Show More
(4)
Objective(s): To measure serum C-reactive protein (CRP) titer as a predictive diagnosis of acute hepatitis C virus (HCV)
infection.
Methodology: Two hundred and ten patients with acute HCV infection and 234 apparently healthy individuals as
control group were enrolled in this study in Baghdad medical city (Teaching Laboratories). The patents include
74(35.2%) females and 136 (64.8%) males with mean age (27±16.5) years. The control group includes 114 (48.7%)
females and 120 (51.3%) males with mean age (26±5.8) years. Blood samples were collected from out patients from
Alfadul in Baghdad city. Sera were separated and stored at 20 0
C. The diagnosis of acute HCV infection was based on
detection of HC Ag and anti- H
The research aims present to highlight the importance of creating construction Organizational appropriate to achieve strategic success and reduce many of the negative effects experienced by organizations has been developing his questionnaire especially so was distributed to a sample of workers in the Asia-cellular as sample included (60) responsive 0 and can embody intellectual dilemma following questions (What are the dimensions of the organizational infrastructure, and what are the justifications for carrying out the reform and development cleared the organizational structure to make it more flexible) to contribute to the achievement of the strategic requirements for success of the organization surveyed.
Find recommended a number o
The researcher aims to Diagnose the reality of research variables, strategic leadership and decision support systems, and their impact on crisis management in the General Company for Steel Industries because of their important role in preventing crises and reducing their occurrence for the research company in particular and other companies in general affiliated with the Ministry of Industry and Minerals, as well as clarifying theoretical concepts of research variables As it included the answer to questions related to the research problem, including (Is there an impact of the strategic leadership in managing crises if decision support systems are used), and the researcher adopted the descriptive and analytical approach in its comp
... Show More