Biology subjects

Mohammed, M.

Publications and source records attributed to Mohammed, M..

9 recordsLinked to original sources

bioRxiv2026

Aging compromises Zebrafish caudal fin regeneration by disrupting Regenerative gene networks and Cellular metabolism

Zebrafish are widely recognized as a powerful vertebrate model for studying epimorphic regeneration due to their remarkable ability to restore complex tissues. However, regenerative efficiency declines with age, potentially due to alterations in gene regulatory networks and cellular metabolism. In the present study, we investigated the molecular and bioenergetic basis of age-associated regenerative decline by comparing young adult (<1 year) and old adult (>3 years) zebrafish during caudal fin regeneration. To further examine the contribution of mitochondrial function, mitochondrial dysfunction was experimentally induced using rotenone (20 nM), a mitochondrial Complex I inhibitor. Regenerative progression was assessed morphologically at 12hpa, 1dpa, 2dpa, 3dpa, and 7dpa, revealing a pronounced delay in fin regrowth in aged and rotenone-treated fish compared with young controls. Behavioral analysis indicated subtle but non-significant changes across experimental groups. Gene expression analysis using quantitative real-time PCR revealed age- and mitochondria-associated dysregulation of key regenerative gene families involved in developmental patterning, extracellular matrix organization, cellular signaling, and mitochondrial metabolism. Proteomic profiling further identified differential expression of proteins associated with mitochondrial bioenergetics, extracellular matrix remodeling, and signaling pathways required for blastema formation and tissue outgrowth. Ultrastructural examination by transmission electron microscopy revealed pronounced mitochondrial abnormalities, including enlarged mitochondria with fragmented or disrupted cristae, in aged and rotenone-treated regenerating tissues. Collectively, our integrative analysis establishes a mechanistic link between aging, mitochondrial dysfunction, and compromised regenerative capacity in zebrafish. The findings provide broader insights into metabolic constraints underlying age-related decline in regenerative potential in vertebrates.

developmental biology↗

bioRxiv2025

Molecular identification and functional analysis of HrpZ2, a new member of harpin superfamily from Pseudomonas syringae inducing hypersensitive response in tobacco.

Harpins belong to a group of proteins with distinctive features such as heat stability, glycine richness, and absence of cysteine, and are secreted by many Gram-negative phytopathogens via the type III secretion system. Harpins are known to trigger hypersensitive response followed by induction of systemic acquired resistance in non-host plants. However, the molecular mechanism of harpin-induced hypersensitive response remained largely unexplored, mainly because of lack of structural information. In this study, we report the cloning of a new harpin gene (hrpZ2) from Pseudomonas syringae strain MTCC-11950, belonging to the harpin superfamily. In silico analysis revealed that about 50.29% of the protein consists of alpha-helices, 48.53% are random coils, and only 1.16% are beta-sheets, and nearly half (42%) of the protein consists of intrinsically disordered regions. Based on a prokaryotic predictive model and the presence of a signal peptide on its N-terminus, the subcellular localization of harpin is predicted as extracellular. To date, no experimentally determined crystal structure of any harpin protein is available. Therefore, we built and validated a three-dimentional model (with 99% of residues in allowed/additionally allowed regions and a Z-score of -5.3) of harpin. Phylogenetic analysis and functional domain studies revealed that this new harpin belongs to the harpin superfamily. Infiltration of harpin in tobacco leaves resulted in hypersensitive response, which was associated with oxidative burst, callose deposition, localized cell death, and increased activity of defense-related enzymes such as phenylalanine ammonia-lyase and polyphenol oxidase. Furthermore, infiltration of harpin in non-host plants from different angiosperm families induced hypersensitive response, indicating broad-spectrum agricultural applicability of this new harpin protein. This study elucidates the molecular and functional properties of the new harpin protein and its ability to induce hypersensitive response across a broad range of non-host plants.

plant biology↗

bioRxiv2024

Angiotensin-(1-5) is a Potent Endogenous Angiotensin AT2-Receptor Agonist

BackgroundThe renin-angiotensin system involves many more enzymes, receptors and biologically active peptides than originally thought. With this study, we investigated whether angiotensin-(1-5) [Ang-(1-5)], a 5-amino acid fragment of angiotensin II, has biological activity, and through which receptor it elicits effects. MethodsThe effect of Ang-(1-5) (1{micro}M) on nitric oxide release was measured by DAF-FM staining in human aortic endothelial cells (HAEC), or Chinese Hamster Ovary (CHO) cells stably transfected with the angiotensin AT2-receptor (AT2R) or the receptor Mas. A potential vasodilatory effect of Ang-(1-5) was tested in mouse mesenteric and human renal arteries by wire myography; the effect on blood pressure was evaluated in normotensive C57BL/6 mice by Millar catheter. These experiments were performed in the presence or absence of a range of antagonists or inhibitors or in AT2R-knockout mice. Binding of Ang-(1-5) to the AT2R was confirmed and the preferred conformations determined by in silico docking simulations. The signaling network of Ang-(1-5) was mapped by quantitative phosphoproteomics. ResultsKey findings included: (1) Ang-(1-5) induced activation of eNOS by changes in phosphorylation at Ser1177eNOS and Tyr657eNOS and thereby (2) increased NO release from HAEC and AT2R-transfected CHO cells, but not from Mas-transfected or non-transfected CHO cells. (3) Ang-(1-5) induced relaxation of preconstricted mouse mesenteric and human renal arteries and (4) lowered blood pressure in normotensive mice - effects which were respectively absent in arteries from AT2R-KO or in PD123319-treated mice and which were more potent than effects of the established AT2R-agonist C21. (5) According to in silico modelling, Ang-(1-5) binds to the AT2R in two preferred conformations, one differing substantially from where the first five amino acids within angiotensin II bind to the AT2R. (6) Ang-(1-5) modifies signaling pathways in a protective RAS-typical way and with relevance for endothelial cell physiology and disease. ConclusionsAng-(1-5) is a potent, endogenous AT2R-agonist.

pharmacology and toxicology↗

bioRxiv2023

Single-cell sequencing of tumor-associated macrophages in a Drosophila model.

IntroductionTumor-associated macrophages may act to either limit or promote tumor growth, yet the molecular basis for either path is poorly characterized. MethodsWe use a larval Drosophila model that expresses a dominant-active version of the Rasoncogene (RasV12) to study dysplastic growth during early tumor progression. We performed single-cell RNA-sequencing of macrophage-like hemocytes to characterize these cells in tumor-compared to wild type larvae. Hemocytes included manually extracted tumor-associated-as well as circulating cells. Results and discussionWe identified 5 distinct hemocyte clusters. In addition to RasV12 larvae we included a tumor model where the activation of effector caspases was inhibited, mimicking an apoptosis-resistant setting. Circulating hemocytes from both tumor models differ qualitatively from control wild-type cells - they display an enrichment for genes involved in cell division, which was confirmed using proliferation assays. Split analysis of the tumor models further reveals that proliferation is strongest in the caspase-deficient setting. Similarly, depending on the tumor model, hemocytes that attach to tumors activate different sets of immune effectors - antimicrobial peptides dominate the response against the tumor alone, while caspase inhibition induces a shift toward members of proteolytic cascades. Finally, we provide evidence for transcript transfer between hemocytes and possibly other tissues. Taken together, our data support the usefulness of Drosophila to study the response against tumors at the organismic level.

cancer biology↗

bioRxiv2023

scDual-Seq of Toxoplasma gondii-infected mouse bone marrow-derived dendritic cells reveals host cell heterogeneity and differential infection dynamics

Host-parasite interactions include complex interplays between an invading and a defending organism, each continuously adapting to gain the upper hand. The protozoan parasite, Toxoplasma gondii, can invade every nucleated cell type in a vertebrate host, including immune cells while the host mounts a protective response. Here, we utilize Dual-scSeq to parse out heterogeneous transcription of bone marrow-derived dendritic cells (BMDCs) infected with T. gondii type I, RH (LDM) or type II, ME49 (PTG) parasites, over multiple time points post infection. We find that the two parasite lineages distinctly manipulate two subpopulations of infected BMDCs. Co-expression networks establish host and parasite genes, with implications for modulation of host immunity and host-pathogen interactions. Integration of published data validates immune pathways and suggests novel candidate genes involved in host-pathogen interactions. This study aims to provide a comprehensive resource for future characterization of host-pathogen interplay among other protozoan parasites within their host niches, as well as that of bacterial and viral pathogens.

microbiology↗

bioRxiv2022

Single-cell transcriptomics to define Plasmodium falciparum stage-transition in the mosquito midgut

Malaria inflicts the highest rate of morbidity and mortality among the vector-borne diseases. The dramatic bottleneck of parasite numbers that occurs in the gut of the obligatory vector mosquito provides a promising target for novel control strategies. Using single-cell transcriptomics, we analyzed Plasmodium falciparum development in the mosquito gut, from unfertilized female gametes through the first 20 hours post blood feeding, including the zygote and ookinete stages. This study revealed the transcriptional trajectories of the ApiAP2 family of transcription factors, and of parasite stress genes in response to the harsh environment of the mosquito midgut. Further, employing structure-based functional predictions we found several upregulated genes predicted to encode intrinsically disordered proteins (IDPs), a category of proteins known for their importance in regulation of transcription, translation and protein-protein interactions. IDPs are known for their antigenic properties and may serve as suitable targets for antibody or peptide-based transmission suppression strategies.

microbiology↗

bioRxiv2022

Discovery of small molecule antagonists of human Retinoblastoma Binding Protein 4 (RBBP4)

RBBP4 is a nuclear WD40 motif-containing protein widely implicated in various cancers and a putative drug target. It interacts with multiple proteins within diverse complexes such as nucleosome remodeling and deacetylase (NuRD) complex and polycomb repressive complex 2 (PRC2), as well as histone H3 and H4 through two distinct binding sites. B-cell lymphoma/leukemia 11A (BCL11A), friend of GATA-1 (FOG-1), plant homeodomain finger protein 6 (PHF6) and histone H3 bind to the top of the donut-shaped seven-bladed {beta}-propeller fold of RBBP4, while suppressor of zeste 12 (SUZ12), metastasis associated protein 1 (MTA1) and histone H4 bind to a pocket on the side of the WD40 repeats of this protein. Here, we report the discovery of the first small molecule antagonists of the RBBP4 top pocket, competing with interacting peptides from proteins such as BCL11A and histone H3. We also determined the first crystal structure of RBBP4 in complex with a small molecule (OICR17251), paving the path for structure-guided design and optimization towards more potent antagonists.

biochemistry↗

bioRxiv2021

Coexistence patterns and diversity in a trait-based metacommunity on an environmental gradient

The dynamics of trait-based metacommunities have attracted much attention, but not much is known about how dispersal and spatial environmental variability mutually interact with each other to drive coexistence patterns and diversity. Here, we present a spatially-explicit model of resource competition in a metacommunity on a one-dimensional environmental gradient. We find that both the strength of dispersal and the range of spatial environmental variability affect coexistence patterns, spatial structure, trait distribution and local and regional diversity. Without dispersal, species are sorted according to their optimal growth conditions on the gradient. With the onset of dispersal source-sink effects are initiated, which increases the effects of environmental filtering and interspecific competition and generates trait lumping, so that only a few species from an environment-defined trait range can survive. Interestingly, for very large dispersal rates the system becomes spatially homogeneous, but nevertheless two species at the extreme ends of the trait-off curve can coexist for large environmental variability. Local species richness follows a classic hump-shaped dependence on dispersal rate, while local and regional diversity exhibit a pronounced peak for intermediate values of the environmental variability. Our findings provide important insights into the factors that shape the structure of trait-based metacommunities.

ecology↗

bioRxiv2018

Knowledge and attitudes of Ebola among the general public of Trinidad and Tobago during the 2014-15 West Africa outbreak

ObjectiveHealth system resilience and resilience of a country include the capacity of health personnel, institutions, and populations to prepare for and effectively respond to crises. This study investigates the knowledge and attitudes of the public concerning Ebola Virus Disease in Trinidad and Tobago.\n\nDesign and MethodsA cross sectional study whereby respondents (n = 920) were sampled from public places. Data were collected via interviewer administered questionnaires. Data were analysed using SPSS version 23.\n\nResultsThe response rate was 67.6 % (622/920). The main age category of responders was the 20 to 30 year age category (40.5%); responders were mostly female (58.0 %). Regarding knowledge, there were significant differences among occupational categories (F = 2.811, df1 = 6, df2 = 571, p-value = 0.011). Tukeys HSD post hoc test revealed that the mean knowledge scores for professional and sales occupations differed significantly (p-value = 0.003). There was a significant association between being afraid to go for treatment and age (p-value = 0.001). Significant associations were also found between occupational grouping and education attainment with opinion about the preparedness of private medical facilities, likelihood to shun family members with Ebola, being afraid to go for treatment and preference for traditional medicine (p-value <0.05).\n\nConclusionThis study highlights opportunities for community engagement to enhance health system resilience during outbreaks which would maximise national and global health security.

epidemiology↗