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Muhammad, M.

Publications and source records attributed to Muhammad, M..

5 recordsLinked to original sources

Molecular epidemiology of the globally spreading genetic lineage IV of peste des petits ruminants virus

Peste des petits ruminants (PPR) is a highly contagious viral disease of small ruminants caused by the peste des petits ruminants virus (PPRV), which is classified into four distinct genetic lineages (I-IV). A critical concern in the recent epidemiological history of PPRV is the rapid and widespread expansion of lineage IV (LIV) across West Africa over the past decade. This dominance suggests a potential adaptive advantage of circulating LIV strains in the regions current epidemiological context. In this study, we obtain the genome sequence of 26 new PPRV samples, including historical (pre-2000) and many recent African LIV isolates, offering the first opportunity to investigate the evolutionary history of LIV in Africa and identify genetic events potentially associated with its recent spread. Phylogenomic analyses implemented on a dataset of 167 curated PPRV genome sequences reveal that the most ancestral LIV group comprises strains circulating in Sub-Saharan Africa (designated clade LIVssa), providing robust evidence for an African origin of lineage IV. Our results further indicate that PPRV strains linked to the recent West African expansion of LIV belong to a specific LIVssa subgroup, termed NigB. We identified multiple signatures of selection pressure within the LIVssa sublineage, particularly in the NigB cluster. Several amino acid substitutions unique to LIVssa or NigB were detected, some of which may impact protein function and warrant prioritised investigation. Additional genomic data are required to confirm the association between the NigB group and the ongoing spread of LIV in West Africa. The evolutionary adaptations observed in LIVssa - potentially enhancing transmission efficiency, host range or pathogenicity - could undermine current disease control strategies in regions where PPR poses significant threats to food security and local economies. Author SummaryPeste des petits ruminants virus (PPRV) infects sheep and goats across Africa, Middle East, Asia and Europe, causing disease with major impact on global economy and food security. One genetic lineage of PPRV, called lineage IV (LIV), is at the origin of most recent expansion of the distribution of the disease, including replacement of other lineages in areas of African where PPRV is historically present. Here, we generated genome sequences from PPRV LIV isolates from different dates and places to study the evolution of this genetic lineage and explore whether its recent spread can be associated with the appearance of new mutations in the virus genome. Our results provide evidence that the PPRV LIV originated in Sub-Saharan Africa and identify mutations present only virus isolates currently spready in new regions of Africa. Further research should investigate the impact of these mutations on protein functions and capacity of transmission of PPRV.

evolutionary biology↗

Individualized Gray Matter Deviations in Children with ADHD: Insights from Structural MRI Modeling

BackgroundAttention-Deficit/Hyperactivity Disorder (ADHD) affects approximately 7.6% of children globally and exhibits heterogeneous cognitive and behavioral manifestations. Conventional group-level MRI analyses often obscure individual variability in brain structure, limiting understanding of personalized neuroanatomical profiles. ObjectiveThis study quantified individualized gray matter volume (GMV) deviations in children with ADHD using age- and sex-matched normative structural MRI references. MethodsStructural MRI data from 31 children with ADHD (16 males, 15 females; ages 7-15) and 413 typically developing controls (TDC; ages 7-22) were analyzed. Voxel-based morphometry extracted regional GMV across prefrontal cortex, striatal nuclei, and cerebellar vermis. Individual deviations were calculated as z-scores relative to normative distributions and categorized as typical, mild, moderate, strong, and extreme. ResultsLateral and orbital prefrontal regions exhibited the highest deviations: for females, the Lateral Orbital Gyrus (LOrG) showed 33.3% mild-to-strong deviations and 13.3% extreme deviations, while the Opercular Inferior Frontal Gyrus (OpIFG) had 73.3% mild-to-strong deviations. In males, the LOrG showed 31.2% moderate, 6.2% strong, and 18.8% extreme deviations. Striatal nuclei exhibited mixed patterns: female caudate volumes were typical in 33.3% of participants, moderate-to-extreme deviations occurred in 46.7%; male putamen was typical in 31.2%, with 37.5% showing strong or extreme deviations. Cerebellar vermis values were mostly typical (50-60%) with occasional mild-to-strong deviations. Medial and superior frontal regions remained largely typical (40-73%). ConclusionChildren with ADHD display heterogeneous and region-specific GMV deviations, most pronounced in lateral and orbital prefrontal cortex and select striatal regions. Individualized z-score profiling captures variability obscured in group averages, supporting personalized neuroanatomical assessment for understanding ADHD and guiding targeted treatment.

neuroscience↗

Immunoinformatics design of a novel multiepitope vaccine candidate against Non-typhoidal Salmonellosis caused by Salmonella Kentucky using outer membrane proteins A, C and F

The global public health risk posed by Salmonella Kentucky, particularly due to the dissemination of antimicrobial resistance genes in human and animal populations, is rising. This serovar, widespread in Africa, has emerged as a notable cause of non-typhoidal gastroenteritis in humans. In this study, we utilized a bioinformatics approach to design a peptide-based vaccine targeting epitopes from the outer membrane proteins A, C, and F of Salmonella Kentucky, with the fliC protein from Salmonella Typhimurium serving as an adjuvant. Through this approach, we identified 14 CD8+ and 7 CD4+ T-cell epitopes, which are predicted to be restricted by various MHC class I and MHC class II alleles. When used in vaccine formulations, the predicted epitopes are expected to achieve a population coverage of 94.91%. Additionally, we identified seven highly immunogenic linear B-cell epitopes and three conformational B-cell epitopes. These T-cell and B-cell epitopes were then linked using appropriate linkers to create a multi-epitope vaccine (MEV). To enhance the immunogenicity of the peptide construct, the fliC protein from Salmonella Typhimurium was included at the N-terminal as an adjuvant. The resulting MEV construct demonstrated high structural quality and favorable physicochemical properties. Molecular docking studies with Toll-like receptors 1, 2, 4, and 5, followed by molecular dynamic simulations, suggested that the vaccine-receptor complexes are energetically feasible, stable, and robust. Immune simulation results showed that the MEV elicited significant responses, including IgG, IgM, CD8+ T-cells, CD4+ T-cells, and various cytokines (IFN-{gamma}, TGF-{beta}, IL-2, IL-10, and IL-12), along with a noticeable reduction in antigen levels. Despite these promising in silico results, further validation through preclinical and clinical trials is necessary to confirm the vaccines protective efficacy and safety.

bioinformatics↗

DFT and Raman study of all-trans astaxanthin optical isomers

Astaxanthin (AST) is a xanthophyll carotenoid widely distributed in aquatic animals, which has many physiological functions such as antioxidant, anti-inflammatory, anti-hypertensive and anti-diabetic activities. Astaxanthin has three optical isomers, including a pair of enantiomers (3S,3 S and 3R,3 R) and a meso form (3R,3 S). Different optical isomers have differences in a variety of physiological functions. Traditionally, High Performance Liquid Chromatography (HPLC) can be used to distinguish these isomers. In this work, its found that Raman spectroscopy can be employed to distinguish the three optical isomers. Because the intensities of two Raman bands at 1190 cm-1 and 1215 cm-1 of three isomers are different. DFT calculations are performed and used to analyze the spectral differences. The calculation results show that the structures of these chiral isomers are not strictly mirror-symmetrical to each other, which leads to the difference in their Raman spectra. HighlightsO_LIRaman spectroscopy can be utilized to distinguish three optical isomers of all-trans astaxanthin. C_LIO_LIThe DFT-calculated spectrum is used to explain why the Raman bands of optical isomers at 1190 and 1215 cm-1 are different. C_LIO_LIThe structural parameters of the three optical isomers have been identified. C_LI

biophysics↗

Cloning, Biochemical Characterization and inhibition of Alanine racemase from Streptococcus iniae

Streptococcus iniae is a pathogenic and zoonotic bacteria that impacted high mortality to many fish species, as well as capable of causing serious disease to humans. Alanine racemase (Alr, EC 5.1.1.1) is a pyridoxal-5'-phosphate (PLP)-containing homodimeric enzyme that catalyzes the racemization of L-alanine and D-alanine. In this study, we purified alanine racemase from the pathogenic strain of S. iniae, determined its biochemical characteristics and inhibitors. The alr gene has an open reading frame (ORF) of 1107 bp, encoding a protein of 369 amino acids, which has a molecular mass of 40 kDa. The optimal enzyme activity occurred at 35{degrees}C and a pH of 9.5. The enzyme belongs to the PLP dependent enzymes family and is highly specific to L-alanine. S.iniae Alr can be inhibited by some metal ions, hydroxylamine and dithiothreitol (DTT). The kinetic parameters Km and Vmax of the enzyme were 33.11 mM, 2426 units/mg for L-alanine and 14.36 mM, 963.6 units/mg for D-alanine. Finally, the 50% inhibitory concentrations (IC50) values and antibiotic activity of two alanine racemase inhibitors, were determined and found to be effective against both gram positive and gram negative bacteria employed in this study. The important role of alanine racemase as a target of developing new antibiotics against S. iniae highlighted the usefulness of the enzyme for new antibiotics discovery.

biochemistry↗