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.
Insulin like growth factor-1 has metabolic and growth-related roles all over the body and is strongly associated and regulated by growth hormone. It is produced by almost any type of tissue, especially the liver. The study aimed to measure insulin like growth factor in growth hormone deficient patients and find its relation with other studied parameters. The Subjects in the study were 180 studied in the National Diabetic Center for Treatment and Research/Al-Mustansiriya University in Baghdad/Iraq for the period from November 2021 to April 2022. Blood was drawn and investigated for the levels of IGF-1, IGFBP-3, LH, and FSH. Also testosterone and statistical analysis was carried out to find the potential correlations. The results relived t
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In this study new derivatives of O-[2-{''2-Substituted Aryl (''1,''3,''4 thiadiazolyl) ['3,'4-b]-'1,'2,'4- Triazolyl]-Ethyl]-p- chlorobenzald oxime (6-11)have been synthesized from the starting material p-chloro – E- benzaldoxime 1.Compound 2 was synthesized by the reaction of p-chloro – E- benzaldoxime with ethyl acrylate in basic medium. Refluxing compound 2 with hydrazine hydrate in ethanol absolute afforded 3. Derivative 4 was prepared by the reaction of 3 with carbon disulphide, treated of compound 4 with hydrazine hydrate gave 5. The derivatives (6-11) were prepared by the reaction of 5 with different substitutesof aromatic acids. The structures of these compounds were characterized from their melting points, infrared spectroscopy
... Show MoreA new, simple, accurate, fast and sensitive spectrophotometric method has been developed for the analysis of amiloride in pure and pharmaceutical formulations by continuous flow injection analysis. The method was based on the oxidation of the drug with Ce(IV)sulfate in acidic medium to formed a pinkish-red color species which determined using homemade Ayah 3SBGR x3-3D solar cell flow injection photometer. Optimum conditions were obtained using a high intensity green light emitted diode as a source. The linear dynamic range for the instrument response versus amiloride concentration was 0.0005- 10 mmol.L-1 while the L.O.D was of 9.471 ng / sample. The correlation coefficient (r) was 0.9824 while percentage linearity (r2%) was 96.50%. RSD%
... Show MoreLimitations of the conventional diagnostic techniques urged researchers to seek novel methods to predict, diagnose, and monitor periodontal disease. Use of the biomarkers available in oral fluids could be a revolutionary surrogate for the manual probing/diagnostic radiograph. Several salivary biomarkers have the potential to accurately discriminate periodontal health and disease. This study aimed to determine the diagnostic sensitivity and specificity of salivary interleukin (IL)‐17, receptor activator of nuclear factor‐κB ligand (RANKL), osteoprotegerin (OPG), RANKL/OPG for differentiating (1) periodontal health from disease and (2) stable a
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The Co (II), Ni (II) ,Cu(II), Zn(II) ,Cd(II) and Hg(II) complexes of mixed of amino acid (L-Alanine ) and Trimethoprim antibiotic were synthesized. The complexes were characterized using melting point, conductivity measurement and determination the percentage of the metal in the complexes by flame (AAS). Magnetic susceptibility, Spectroscopic Method [FT-IR and UV-Vis]. The general formula have been given for the prepared mixed ligand complexes [M(Ala)2(TMP)(H2O)] where L- alanine (abbreviated as (Ala ) = (C5H9NO2) deprotonated primary ligand, L- Alanine ion .= (C5H8NO2-) Trimethoprim (abbreviated as (TMP ) = C10H11N3O3S M(II) = Co (II),Ni(II) ,Cu(II), Zn(II) ,Cd(II) and Hg(II). The results showed that the deprotonated L- Alanine b
... Show MoreThis article describes how to predict different types of multiple reflections in pre-track seismic data. The characteristics of multiple reflections can be expressed as a combination of the characteristics of primary reflections. Multiple velocities always come in lower magnitude than the primaries, this is the base for separating them during Normal Move Out correction. The muting procedure is applied in Time-Velocity analysis domain. Semblance plot is used to diagnose multiples availability and judgment for muting dimensions. This processing procedure is used to eliminate internal multiples from real 2D seismic data from southern Iraq in two stages. The first is conventional Normal Move Out correction and velocity auto picking and
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به نظر میآید که عالم هستی ، بر مسألهی « حرکت» استوار دارد ، و روح ، همیشه دنبال دگرگونی و تکامل و برتری میگردد. حرکت ، همهی چیزها در عالم إمکان را در بر میگیرد. حرکت در بنیادهای فکر مولانا جای مهمی دارد .اشعار مولانا مقدار زیادی از پویایی و حرکت برخوردارست، و از آنجایی که فعل ، عنصر تکانبخش جمله ، و کانون دلالت است ، ترجیح دادیم - علاوه بر دیگر عنا
... Show MoreThe nuclear charge density distributions, form factors and
corresponding proton, charge, neutron, and matter root mean square
radii for stable 4He, 12C, and 16O nuclei have been calculated using
single-particle radial wave functions of Woods-Saxon potential and
harmonic-oscillator potential for comparison. The calculations for the
ground charge density distributions using the Woods-Saxon potential
show good agreement with experimental data for 4He nucleus while
the results for 12C and 16O nuclei are better in harmonic-oscillator
potential. The calculated elastic charge form factors in Woods-Saxon
potential are better than the results of harmonic-oscillator potential.
Finally, the calculated root mean square
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Sildenafil, tadalafil, and vardenafil are phosphodiesterase type 5 enzyme (PDE-5) inhibitors used for the treatment of male erectile dysfunction. This present study aims to investigate 55 herbal products indicated for men’s sexual health from the Malaysian market for adulteration of PDE-5 inhibitors and analogues. The screening and identification of 20 PDE-5 inhibitors and analogues in herbal products of various forms (powder, capsules, tablets, and pastels) were conducted using gas chromatography–electron impact-mass spectrometer (GC-EI-MS). The analysis has shown that 19 herbal products were adulterated with PDE-5 inhibitors and analogues. Unique ion fragmentations and the presence of molecular
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In this research, the preparation of bidentate Schiff base was carried out via the condensation reaction of both the salicylaldehyde with 1-phenyl-2,3-dimethyl-4-amino-5-oxo-pyrazole to form the ligand (L). The mentioned ligand was used to prepare complexes with transition metal ions Mn(II), Co(II), Ni(II), Cu(II) and Zn(II). The resulting complexes were separated and characterized by FTIR and UV-Vis spectroscopic technique. Elemental analysis for Carbon, Hydrogen and Nitrogen elements, electronic spectra of the ligand and complexes were obtained, and the magnetic susceptibility tests were also achieved to measure the dipole moments. The molar conductivities were also measured and determination of chlorine content in the complexes and
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