Biology subjects

Anwar, F.

Publications and source records attributed to Anwar, F..

8 recordsLinked to original sources

bioRxiv2025

Harnessing Immunoinformatic for HIV-2: Multi-Epitope Vaccine Design Targeting the env Protein (CAA28914.1)

A[Formula][s][t]rac[t]O_ST_ABSBackgroundC_ST_ABSHIV-2 is a major threat to human health because of its rising global incidence. As a result, the development of effective immunostimulatory molecules for vaccine design against HIV-2 has garnered increasing interest. ObjectiveThe main objective was to make a multi Targeting epitoptpic vaccine for HIV-2 envelope protein using immunoinformatic approaches. MethodsSequence were retrieved from NCBI. B & T-cell epitopes were predicted with assessments of antigenicity, allergenicity, and cytokine-inducing potential. Physicochemical properties, docking studies, and codon optimization for expression was also performed using different software tools. FindingsThe designed vaccine construct (477 amino acids, molecular weight of 54 kDa) showed a strong antigenicity with VaxiJen score of 0.7146 which was non-allergenic and non-toxic with favorable physicochemical parameters (Mw: [~]53 kDa; pI: 9.89; stable and soluble). The construct demonstrated broad population coverage for MHC-I (West Africa: 69.51%, Pakistan: 78%, Global: 82%) and MHC-II (Global: 99%). Out of 16 peptides analyzed, 7 were predicted as IL-10 inducers 2 as a strong IL-4 inducer, and 2 were IFN-{gamma} inducing epitopes. Structural validation confirmed high-quality folding (96% residues in favored regions; ERRAT score: 84.35). Docking results revealed a strong binding affinity to TLR2 (PDB ID: 2AOZ; energy: -1481.1 kcal/mol). MD simulation confirmed structural stability (RMSD [~]1.37 nm; Rg [~]3.65 nm). Immune simulation predicted robust humoral and cellular responses with sustained antibody production and cytokine activation. Codon optimization is given to a Codon Adaptation Index (CAI) of 0.628 with a guanine (G) and cytosine (C) nucleotides content of 65.48%, suitable for E. coli expression. ConclusionThis vaccine construct is immunogenic, stable, and able to elicit both antibody-mediated immunity and cell-mediated immunity responses. Furthermore, In-vitro or In-Vivo Validations are recommended to verify its effectiveness O_FIG O_LINKSMALLFIG WIDTH=178 HEIGHT=200 SRC="FIGDIR/small/658249v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@c3660corg.highwire.dtl.DTLVardef@60cc61org.highwire.dtl.DTLVardef@10a1e87org.highwire.dtl.DTLVardef@15a5aa1_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2024

Apoptosis is increased in cortical neurons of female Marfan Syndrome mice

Marfan Syndrome (MFS) is an autosomal dominant genetic disorder that affects connective tissue throughout the body due to mutations in the FBN1 gene. Individuals with MFS display symptoms in different organs, particularly in the vasculature, but the mechanisms of this multi-system dysfunction are still under investigation. There is still a gap in our understanding of the impact of monogenic connective tissue aberrations on the brain. This study aims to determine the impact of MFS on neurodegeneration, in cortical brain tissue of male and female MFS mice. Brain tissue of 6-month-old female and male mice with the FBN1C1041G/+ mutation and wildtype litter mates was collected and stained for active caspase-3 (ac3), brain derived neurotrophic factor (BDNF), and neuronal nuclei (NeuN) or with TUNEL and DAPI. Data revealed increased levels of ac3 in neurons within the sensory and motor cortical areas of female MFS mice compared to sex- and age-matched controls. We confirm increased levels of apoptosis in MFS mice using TUNEL staining within the same brain areas. We also report increased levels of neuronal BDNF levels in cortical brain tissue of male and female MFS mice. These results indicate a heightened susceptibility for neurodegeneration in the mouse model of MFS. Significance StatementThe study revealed that female mice with a FBN1C1041G/+ mutation have more apoptotic neurons in sensory and motor cortical brain tissue compared to wildtype litter mates.

neuroscience↗

bioRxiv2024

Maternal dietary deficiencies in folic acid and choline change metabolites levels in offspring after ischemic stroke

Ischemic stroke is a debilitating disease, with nutrition being a modifiable risk factor. Changes in levels of metabolites can be used to measure the alterations in the gut, a significant marker for the etiology of diseases. This study utilized untargeted metabolomics to investigate changes in fecal samples of offspring in response to maternal dietary deficiencies and ischemic stroke. Female mice were placed on control (CD), folic acid- (FADD), or choline-deficient (ChDD) diets prior to, during pregnancy, and lactation. Offspring were weaned on to CD and at 2 months of age an ischemic stroke was induced. Fecal samples were collected prior to ischemic stroke, and at 1- and 4-weeks post-stroke for analysis. Sex and maternal dietary differences in metabolites were observed at both the 1- and 4-week post-stroke timepoints. At the 1-week post-stroke, female FADD offspring had more changes in metabolites than males. Comparatively, at the 4-week post-stroke timepoint, female offspring on either FADD or ChDD demonstrated metabolite changes. This study demonstrates a long-lasting impact of maternal dietary deficiencies on central nervous system and gut microbiome function after ischemic stroke. Summary StatementOur study investigated metabolite changes in female and male offspring fecal samples from mothers maintained on folic acid or choline deficient diet. We report that female offspring metabolite levels were impacted.

neuroscience↗

bioRxiv2023

Date milk enriched with vitamin D: nutrient content and acceptability as a food additive for preschoolers

Products that combine liquid milk and date flesh are still minimal. Milk is an excellent source of protein and dates are a food ingredient that is rich in vitamins and minerals that are suitable for growth as well as phytochemical components which function to enhance the sensory properties of dates so that they can be used as a flavor enhancer in various dairy products such as cookies, yogurt, ice cream, and cakes. The purpose of this study was to create a vitamin D-enriched date milk product as an alternative nutritional supplement for preschool children aged 48-59 months. The study used a completely randomized design with three percentage addition of date flesh treatments, namely F1 (10%), F2 (15%), and F3 (20%). The results showed that the formulas significantly differed between the water, protein, and carbohydrate contents (P < 0.05). In contrast, the energy, ash, fat, zinc, iron, and calcium content were not statistically significant (P > 0.05). Kruskal-Wallis analysis product acceptance data showed only color and aroma attributes that were quite different between formulas (P < 0.05). In contrast, taste, thickness, mouthfeel, aftertaste, and overall characteristics were not statistically different (P > 0.05). Formula F2 (15%) was selected based on the hedonic rating and ranking tests. Formula F2 (15%) can be accepted quite well, with the percentage that consumes drinks without residue as much as 60% and those who can finish at least [1/2] portion of drinks as much as 93.3%.

biochemistry↗

bioRxiv2022

A superoxide reductase contributes to Clostridioides difficile resistance to oxygen

Clostridioides difficile causes a serious diarrheal disease and is a common healthcare-associated bacterial pathogen. Although it has a major impact on human health, mechanistic details of C. difficile intestinal colonization remain undefined. C. difficile is highly sensitive to oxygen and requires anaerobic conditions for in vitro growth. However, the mammalian gut is not entirely devoid of oxygen, and C. difficile tolerates moderate oxidative stress in vivo. The C. difficile genome encodes several antioxidant proteins, including a predicted superoxide reductase (SOR) that is upregulated upon exposure to antimicrobial peptides. The goal of this study was to establish SOR enzymatic activity and assess its role in protecting C. difficile against oxygen exposure. Insertional inactivation of sor rendered C. difficile more sensitive to superoxide indicating that SOR contributes to antioxidant defense. Heterologous C. difficile sor expression in Escherichia coli conferred protection against superoxide-dependent growth inhibition, and the corresponding cell lysates showed superoxide scavenging activity. Finally, a C. difficile SOR mutant exhibited global proteome changes under oxygen stress when compared to its parent strain. Collectively, our data establish the enzymatic activity of C. difficile SOR, confirm its role in protection against oxidative stress, and demonstrate its broader impacts on the vegetative cell proteome. ImportanceClotridioides difficile is an important pathogen strongly associated with healthcare settings and capable of causing severe diarrheal disease. While considered a strict anaerobe in vitro, C. difficile has been shown to tolerate low levels of oxygen in its mammalian host. Among other well-characterized antioxidant proteins, the C. difficile genome includes a predicted superoxide reductase (SOR), an understudied component of antioxidant defense in pathogens. The significance of the research reported herein is the characterization of the enzymatic activity of the putative SOR protein, including confirmation of its role in protection of C. difficile against oxidative stress. This furthers our understanding of C. difficile pathogenesis and presents a potential new avenue for targeted therapies.

microbiology↗

bioRxiv2022

Low-Toxin Clostridioides difficile RT027 Strains Exhibit Robust Virulence

Clostridioides difficile is a leading cause of healthcare-associated infections worldwide. Currently, there is lack of consensus on a single optimal diagnostic method for C. difficile infection (CDI). Nucleic acid amplification tests (NAAT) that detect toxin genes are highly sensitive, but their specificity limitations could inflate CDI rates. Alternate multi-step diagnostic algorithms emphasize the detection of C. difficile toxins TcdA/TcdB, and are premised on the rationale that stool toxin-negative (Tox-) CDI patients have less severe disease, shorter diarrhea duration, and fewer disease complications. There have been no systematic assessments, however, of the virulence of C. difficile strains from Tox-/NAAT+ (discrepant) specimens. In our prospective analysis of 1243 C. difficile-positive patient stool specimens from three Southern Arizona hospitals, 31% were discrepant. Ribotype 027 (RT027) strains were recovered from 221 specimens; of these, 23% were discrepant. Post-culture, RT027 strains produced a range of toxin amounts including levels lower than that of the non-epidemic strain CD630. These low-toxin RT027 (LT-027) strains harbored both tcdA and tcdB genes, and their culture supernatants were cytotoxic to cultured fibroblasts. We confirmed robust colonization and virulence of a subset of LT-027 strains using multiple rodent models; lethality in animals infected with LT-027 strains was comparable to that potentiated by a high-toxin RT027 strain. Comparative genomics and proteomics analyses of several LT-027 strains identified unique genes and altered protein abundances relative to closely-related high-toxin strains. Collectively our data highlight the robust virulence and clinical relevance of low-toxin-producing, RT027 C. difficile isolates.

microbiology↗

bioRxiv2020

Phylogenomic analysis of Clostridiodes difficile ribotype 106 strains reveals novel genetic islands and emergent phenotypes

BackgroundClostridioides difficile RT106 has emerged as a dominant molecular type in the USA in recent years, but the underlying factors contributing to its predominance remain undefined. As part of our ongoing C. difficile infection (CDI) surveillance in Arizona, we monitored RT106 frequency and characterized the genomic and phenotypic properties of the recovered isolates. ResultsFrom 2015-2018, RT106 was the second-most prevalent molecular type isolated from CDI patients in our surveillance. A representative RT106 strain displayed robust virulence and 100% lethality in the hamster model of acute CDI. We identified a unique 46 KB genomic island (GI1) in all RT106 strains, including those in public databases. GI1 was not found in its entirety in any other C. difficile clade, or indeed in any other microbial genome; however, smaller segments were detected in select Enterococcus faecium strains. Molecular clock analyses suggest that GI1 was horizontally acquired and sequentially assembled over time. Consistent with the presence of genes encoding homologs of VanZ and a SrtB-anchored collagen-binding adhesin in GI1, all tested RT106 strains had increased teicoplanin resistance and a majority displayed collagen-dependent biofilm formation. Two additional genomic islands (GI2 and GI3) were also present in a subset of RT106 strains. All three islands have features of mobile genetic elements and encode several putative virulence factors. ConclusionsConsistent with the known genetic plasticity of C. difficile, strains belonging to the RT106 clade harbor unique genetic islands. Correspondingly, emergent phenotypic properties may contribute to the relatively rapid shifts of strain distribution in patient populations.

genomics↗

bioRxiv2018

The Landscape Of Circular RNA Expression In The Human Brain

Circular RNAs (circRNAs) are enriched in the mammalian brain and are upregulated in response to neuronal differentiation and depolarisation. These RNA molecules, formed by non-canonical back-splicing, have both regulatory and translational potential. Here, we carried out an extensive characterisation of circRNA expression in the human brain, in nearly two hundred human brain samples, from both healthy individuals and autism cases. We identify hundreds of novel circRNAs and demonstrate that circRNAs are not expressed stochastically, but rather as major isoforms. We characterise inter-individual variability of circRNA expression in the human brain and show that inter-individual variability is less pronounced than variability between cerebral cortex and cerebellum. We also find that circRNA expression is dynamic during cellular maturation in brain organoids, but remains largely stable across the adult lifespan. Finally, we identify a circRNA co-expression module upregulated in autism samples, thereby adding another layer of complexity to the transcriptome changes observed in autism brain. These data provide a comprehensive catalogue of circRNAs as well as a deeper insight into their expression in the human brain, and are available as a free resource in browsable format at: http://www.voineagulab.unsw.edu.au/circ_rna

genomics↗