Search bioRxiv⌕ Search

Biology subjects

Zia, A.

Publications and source records attributed to Zia, A..

9 recordsLinked to original sources

Telomere Length as an Indicator of Lifestyle-Related Biological Aging in Hypertensive Adults: A Pilot Exploratory Study

BackgroundMultiple epidemiological studies have given a global perspective that hypertension leads to changes in telomere length (TL). This study aimed to investigate the association between leukocyte telomere length and lifestyle factors among individuals with hypertension, a family history of the disease and healthy controls. MethodsThis pilot exploratory cross-sectional study included 45 participants (n = 15 per group) divided into hypertensive, familial hypertensive, and control groups. Lifestyle behaviors were assessed using the FANTASTIC Lifestyle Checklist, evaluating domains such as physical activity, diet, sleep, and stress. Relative telomere length (T/S ratio) of leucocytes was measured from peripheral blood samples using quantitative real-time PCR (qPCR). Data were analyzed using SPSS software, with ANOVA, Kruskal-Wallis test, and multivariable linear regression applied for statistical analysis. ResultsRelative telomere length differed significantly among the study groups (p = 0.008), with hypertensive participants demonstrating the highest median telomere-to-single-copy gene (T/S) ratio (2.66), followed by familial hypertensive (1.25) and control participants (0.87). Total lifestyle scores also varied significantly across groups (p < 0.001), with hypertensive individuals exhibiting higher mean scores (77.07 {+/-} 5.59) than familial hypertensive (67.20 {+/-} 3.00) and control participants (67.07 {+/-} 5.97). A modest positive correlation was observed between total lifestyle score and relative telomere length (r = 0.329, p < 0.05), suggesting that healthier lifestyle behaviors in diagnosed hypertensive subjects following healthy lifestyles and regular medications were associated with longer telomeres. However, in multivariable linear regression analyses, lifestyle score, age, gender, hypertension status, and family history of hypertension were not independently associated with telomere length (all p > 0.05). ConclusionLifestyle scores were positively associated with telomeres, and significantly higher telomere ratios in hypertensive subjects suggest complex biological interactions that require further investigation through larger longitudinal studies in the target population.

Molecular Biology↗

The Hindu Kush, not the Indus Valley, divides amphibian biogeographic realms

The boundary between the Palearctic and Oriental biogeographic realms is one of the oldest unresolved problems in Eurasian biogeography. In Central and South Asia, this transition is remarkable and has often been linked to the Indus River Valley, yet the role of adjacent mountain systems and arid landscapes has remained largely untested because critical regions, especially Afghanistan, have been chronically under-sampled due to difficult, long-term socio-political situation. Here we use a unique amphibian material from Afghanistan and adjacent northwestern Pakistan to test whether the Hindu Kush marks the effective boundary between these two realms. Combining molecular barcoding across all seven amphibian genera inhabiting the region with updated distribution records, we find a strikingly consistent lineage turnover centered on the eastern Hindu Kush and adjacent arid systems. Palearctic taxa reach their southeastern limits along the massif, whereas Oriental taxa extend only to its southern foothills. By contrast, Oriental lineages cross the Indus River without detectable phylogeographic break, indicating that the river valley does not function as a major biogeographic boundary for the taxa examined. The Hindu Kush also harbors endemic relict taxa of both Palearctic and Oriental affinities, revealing a dual role as both refugium and dispersal barrier. Thus, our results identify the Hindu Kush as the de facto boundary between the Palearctic and Oriental realms in this part of Eurasia and show that under-sampled arid-montane regions can disproportionately improve global biogeographic frameworks.

evolutionary biology↗

The archaic CUP pilus SMF-1 uses an antiparallel bundling mechanism to initiate biofilm formation

Bacterial biofilms represent a survival strategy that enables microbial communities to withstand environmental stress. Stenotrophomonas maltophilia is an emerging, antibiotic-resistant, Gram-negative, opportunistic pathogen that frequently colonizes the lungs of individuals with cystic fibrosis. Its chaperone-usher pathway (CUP) pilus, SMF-1, is present in nearly all clinical isolates and is essential for biofilm development; however, its molecular architecture has remained unknown. Here, we present a 4.0 [A] cryo-EM structure revealing that SMF-1 is an archaic, rather than a classic, CUP pilus. SMF-1 forms thin, zigzag filaments that assemble into defined antiparallel "pili-couples," which further aggregate into thick bundles. These bundles act as robust intercellular tethers, facilitating the rapid cell-to-cell aggregation required for biofilm initiation. Despite high sequence and structural similarity to classic CUP systems, SMF-1 lacks the interfaces required to form a rod-like architecture, suggesting it may represent an evolutionary intermediate between the CUP classes. Finally, we demonstrate that SMF-1 producing bacteria initiate biofilm formation within 24 hours and that flagella can further accelerate this process. Together, these findings uncover a conserved bundling mechanism that promotes bacterial colonization and may contribute to pathogenicity.

microbiology↗

Distinct flagellins differentially fine tune biofilm initiation via flagellar stator-associated proteins

Helicobacter pylori relies on flagellar motility to colonize the gastric niche. While H. pylori flagella serve multiple functions, including swimming motility, it has recently been appreciated that flagellar basal body properties also contribute to biofilm initiation. The H. pylori flagellar filament contains two spatially segregated flagellins, FlaA and FlaB, but their roles in the biofilm initiation process remained undefined. Here, we confirmed that both FlaA and FlaB are required for optimal motility, but found that they exert opposite effects on biofilm initiation: cells without FlaA display low biofilm initiation, while cells without FlaB display elevated initiation. To understand the molecular basis for this divergence, cryo-electron microscopy (cryo-EM) analysis of native flagellar filaments revealed that FlaA and FlaB have distinct supercoiled waveforms. We confirmed these intrinsic waveform curvatures by analyzing filaments from {Delta}flaA and {Delta}flaB mutants, providing a physical basis for their functional specialization. Genetic epistasis experiments further demonstrated that the enhanced early biofilm formation of the {Delta}flaB mutant depends on PilO, a stator-associated component of the flagellar motor recently shown to drive a reciprocal biofilm and motility response. Our findings establish that H. pylori has developed functionally specialized flagellins that work with motor-dependent signaling to dynamically balance surface colonization and motility.

microbiology↗

A Bundled Antiparallel Cytochrome Nanowire Structure Suggests Roles in Cell-Cell Electron Transfer and Biofilm Formation

Long-range extracellular electron transfer enables respiring microbes to use minerals, other organisms, or electrodes as electron acceptors by transporting electrons microns away from the cell surface. This process is primarily studied in Geobacter sulfurreducens, which produces at least three different micrometer-long, multi-heme cytochrome nanowires capable of electron transfer. However, the distribution and higher-order structure of these types of cytochrome nanowires remains largely unknown. Here, we employed cryo-electron microscopy to determine the atomic structure of a unique cytochrome nanowire from Desulfuromonas soudanensis WTL, a halophilic, iron- and electrode-reducing bacterium found in deep subsurface brine. These filaments are based on a homolog of the OmcE tetraheme cytochrome, which then assemble into highly ordered bundles of antiparallel filaments. This arrangement likely arises from the association of nanowires extending from adjacent cells. Furthermore, a similar cytochrome bundle structure was observed in Geobacter metallireducens, suggesting that this quaternary structure may be a common feature among nanowires secreted by electroactive microbes. Our findings demonstrate that cytochrome nanowires in diverse taxa can form specialized bundle interfaces, potentially facilitating conductive biofilm formation and representing a novel strategy for microbial electron exchange. More broadly, this work expands understanding of electron transfer mechanisms and demonstrates the production of multi-heme filaments across distinct lineages. These insights could guide future research into cytochrome nanowire secretion and conductive biofilm engineering, with potential applications in electrochemical technologies.

microbiology↗

HLA-Based Banking of Human Induced Pluripotent Stem Cells in Saudi Arabia

Human iPSCs derivation and use in clinical studies are transforming medicine. Yet, there is a high cost and long waiting time for autologous iPS-based cellular therapy, and the genetic engineering of hypo-immunogenic iPS cell lines is hampered with numerous hurdles. Therefore, it is increasingly interesting to create cell stocks based on HLA haplotype distribution in a given population. In this study, we assessed the potential of HLA-based iPS banking for the Saudi population. First, we analyzed the HLA database of the Saudi Stem Cell Donor Registry (SSCDR), which contains high-resolution HLA genotype data of 64,315 registered Saudi donors at the time of analysis. We found that only 13 iPS lines would be required to cover 30% of the Saudi population, 39 iPS lines would offer 50% coverage and 596 for more than 90% coverage. Next, As a proof-of-concept, we launched the first HLA-based banking of iPSCs in Saudi Arabia. Using clinically relevant methods, we generated the first iPSC line from a homozygous donor for the most common HLA haplotype in Saudi. The two generated clones expressed pluripotency markers, could be differentiated into all three germ layers, beating cardiomyocytes and neuronal progenitors. To ensure that our reprogramming method generates genetically stable iPSCs, we assessed the mutational burden in the generated clones and the original blood sample from which the iPSCs were derived using whole-genome sequencing. All detected variants were found in the original donor sample and were classified as benign according to current guidelines of the American College of Medical Genetics and Genomics (ACMG). This study sets a road map for introducing iPS-based cell therapy in the Kingdom of Saudi Arabia.

genetics↗

Protein Structure Refinement via DeepTracer and AlphaFold2

Understanding the structures of proteins has numerous applications, such as vaccine development. It is a slow and labor-intensive task to manually build protein structures from experimental electron density maps, therefore, machine learning approaches have been proposed to automate this process. However, most of the experimental maps are not atomic resolution, so they are insufficient for computer vision-based machine learning methods to precisely determine the protein structure. On the other hand, methods that utilize evolutionary information from protein sequences to predict structures, like AlphaFold2, have recently achieved groundbreaking accuracy but often require manual effort to refine the results. We propose DeepTracer-Refine, an automated method to refine AlphaFold structures by aligning them to DeepTracers predicted structure. We tested our method on 39 multi-domain proteins and we improved the average residue coverage from 78.2% to 90.0% and average lDDT score from 0.67 to 0.71. We also compared DeepTracer-Refine against another method, Phenixs AlphaFold refinement, to demonstrate that our method not only performs better when the initial AlphaFold model is less precise but also exceeds Phenix in run-time performance.

bioinformatics↗

TIP family aquaporins play role in chloroplast osmoregulation and photosynthesis

Photosynthetic oxygen evolution by photosystem II requires water supply into the chloroplast to reach the thylakoid lumen. A rapid water flow is also required into the chloroplast for optimal oxygen evolution and to overcome osmotic stress. The mechanisms governing water transport in chloroplasts are largely unexplored. Previous proteomics indicated the presence of three aquaporins from the tonoplast intrinsic protein (TIP) family, TIP1;1, TIP1;2 and TIP2;1, in chloroplast membranes of Arabidopsis thaliana. Here we revisited their location and studied their role in chloroplasts. Localization experiments indicated that TIP2;1 resides in the thylakoid, whereas TIP1;2 is present in both thylakoid and envelope membranes. Mutants lacking TIP1;2 and/or TIP2;1 did not display a macroscopic phenotype when grown under standard conditions. The mutant chloroplasts and thylakoids underwent less volume changes than the corresponding wild type preparations upon osmotic treatment and in the light. Significantly reduced rates of photosynthetic electron transport were obtained in the mutant leaves, with implications on the CO2 fixation rates. However, electron transport rates did not significantly differ between mutants and wild type when isolated thylakoids were examined. Less acidification of the thylakoid lumen was measured in mutants thylakoids, resulting in a slower induction of delta pH-dependent photoprotective mechanisms. These results identify TIP1;2 and TIP2;1 as chloroplast proteins and highlight their importance for osmoregulation and optimal photosynthesis. A third aquaporin, TIP1;1, is present in the chloroplast envelope, and may play role in photosynthesis under excessive light conditions, as based on the weak photosynthetic phenotype of its mutant.

plant biology↗

BPG: Seamless, Automated and Interactive Visualization of Scientific Data

We introduce BPG, an easy-to-use framework for generating publication-quality, highly-customizable plots in the R statistical environment. This open-source package includes novel methods of displaying high-dimensional datasets and facilitates generation of complex multi-panel figures, making it ideal for complex datasets. A web-based interactive tool allows online figure customization, from which R code can be downloaded for seamless integration with computational pipelines. BPG is available at http://labs.oicr.on.ca/boutros-lab/software/bpg

bioinformatics↗