Biology subjects

Arif, A.

Publications and source records attributed to Arif, A..

11 recordsLinked to original sources

bioRxiv2026

A Locally Produced Bioinoculant (H-Start) Increases Field Pea (Pisum sativum) Yield Using Reduced Fertilizer: A Pilot Study with Implications for Low-Input Agriculture

Modern agriculture is an intensive process that disrupts the natural soil microbiome through the use of toxic chemicals such as fungicides. This reduces the soil's ability to support robust biomass production, lowering yields. Complex bioinoculants are heterogeneous mixtures of organisms from natural sources, such as compost, that can be added to soil to restore the natural soil microbiome. H-Start is one such bioinoculant (HumaTerra Regen Ag Inc.). Due to the lack of literature on complex bioinoculants, we aim to present a pilot study to identify potential effects of interest (alpha = 0.10) to inform future experimental designs. To achieve this, field pea (Pisum sativum cv. AAC Carver) was grown in Saskatchewan field soil in a growth chamber, with or without H-Start, at 75% or 100% of the recommended monoammonium phosphate (MAP) rate (n = 3 pots per treatment). By monitoring leaf size, leaf count, height, yield, and soil characteristics, we found that plants treated with H-Start were taller between days 21 and 28 (p = 0.089) and had a greater leaf size index (number of leaves x primary vein length2) over time (p = 0.002). H-Start at 75% MAP also produced the highest yield (p = 0.077). These results suggest H-Start influences the soil microbiome and the plants that depend on it. This is important because complex bioinoculants can be produced locally. Thus, bioinoculants may become increasingly relevant in low-income areas, which often lack the economic ability to sustain food imports and are the first to be affected by disruptions to the agri-chemical supply chain.

microbiology↗

bioRxiv2026

OncoGenRAG: Evidence-Grounded Retrieval and BioBERT Classification for Precision Oncology Variant Interpretation

The increasing use of tumor sequencing has intensified the need for fast, traceable interpretation of genomic variants. General-purpose large language models can produce fluent answers, but unsupported statements, weak provenance, and stale knowledge limit their suitability for clinical genomics. We developed OncoGenRAG, a research framework that combines a parameter-efficiently fine-tuned BioBERT classifier with an entity-aware retrieval system over a curated, multi-source oncology knowledge base. The reported knowledge base contains 933 harmonized records derived from CIViC, ClinVar/dbSNP, Open Targets, UniProtKB/Swiss-Prot, Ensembl Variation, and linked PubMed literature. The classifier assigns one of five labels: Pathogenic, Likely Pathogenic, Variant of Uncertain Significance, Benign, or Oncogenic; the retrieval component ranks evidence records using subword TF-IDF similarity and explicit gene, variant, and cancer-type matches. A rejection rule suppresses answers when retrieval support is below a prespecified threshold. In the authors held-out evaluation, the classifier achieved 92.40% accuracy, 93.15% weighted precision, 92.40% weighted recall, and 92.65% weighted F1 score. In a separate benchmark of 100 clinical-style queries, OncoGenRAG achieved reported Precision@1 of 94.5%, Precision@3 of 96.8%, and 100% database grounding. No hallucinated answer was observed under the study operational definition, compared with a 41.0% no-hallucination rate for the ungrounded baseline. These results should be interpreted as internal validation rather than proof of universal safety because query construction, annotator agreement, class-specific performance, calibration, and external validation data were not available for independent analysis. OncoGenRAG provides a transparent design for evidence retrieval and abstention, but it is a research prototype and must not be used to select treatment without expert review.

bioinformatics↗

bioRxiv2026

Integrative Cross-Cohort Meta-Analysis Reveals a Conserved Dysbiotic Signature of Streptococcaceae and Lachnospiraceae in Multiple Sclerosis

BackgroundMultiple Sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation and demyelination in central nervous system (CNS). Although increasing evidence suggests that gut microbial dysbiosis contributes to MS pathogenesis through the microbiota-gut-brain axis, reproducible microbial signatures associated with disease progression across independent clinical cohorts remain incompletely characterized. ObjectiveThis study aimed to identify conserved gut microbial alterations associated with Multiple Sclerosis by integrating publicly available human gut microbiome datasets and characterizing disease-associated microbial signatures linked to immune dysregulation. DesignHuman gut metagenomic 16S rRNA sequencing data from MS patients and healthy controls obtained from publicly available repositories (NCBI, Bioproject). Raw sequencing reads were processed using a standardized microbiome analysis workflow, including quality control, denoising, taxonomic assignment, phylogenetic reconstruction, diversity analyses, and differential abundance testing. Microbial community structure was evaluated using alpha- and beta-diversity analyses, while statistically significant differences between study groups were assessed using PERMANOVA, Kruskal-Wallis, and ANCOM to identify disease-associated bacterial taxa. ResultsIntegration of independent cohorts revealed consistent alterations in the gut microbial composition of MS patients compared with healthy controls. Significant reductions in microbial diversity and distinct microbial community structures were observed in MS. Differential abundance analysis demonstrated enrichment of the pro-inflammatory family Streptococcaceae, whereas beneficial short-chain fatty acid-producing taxa, particularly Lachnospiraceae, were significantly depleted in MS patients. These conserved microbial alterations indicate disruption of immune-regulatory bacterial communities and support the involvement of gut microbial dysbiosis in MS-associated neuroinflammation. ConclusionThis study identifies a reproducible gut microbial dysbiosis signature associated with Multiple Sclerosis, characterized by expansion of pro-inflammatory bacterial taxa and depletion of beneficial SCFA-producing microorganisms. These findings strengthen the evidence supporting the microbiota-gut-brain axis in MS pathogenesis and highlight microbial community signatures that may contribute to future biomarker development and microbiome- based therapeutic strategies.

microbiology↗

bioRxiv2025

A multi-tiered microDicer with hierarchical blades achieves protein-preserving microdissection down to 10 microns

To study tissue heterogeneity at the sub-millimeter scale, laser capture microdissection (LCM) has been the leading technology for isolating regions of interest (ROI) for downstream molecular profiling. As the ROI approaches cellular dimensions ([~]10 m), laser-induced photothermal damage and challenges in capturing microtissues in conventional LCM can compromise protein preservation and quantitative fidelity. This work introduces multi-tiered Dicers, fabricated by two-photon polymerization, to mechanically dissect tissue slices into uniform microtissues down to 10 m. The hierarchical blade architecture limits instantaneous blade-tissue engagement and lowers the cutting force relative to single-tier designs. For benchmarking, proteomic analysis is performed on ethanol-fixed human squamous cell carcinoma microtissues generated by Dicers and by LCM. Under identical Nanodroplet Processing in One pot for Trace Samples (nanoPOTS) and liquid chromatography-mass spectrometry (LC-MS) conditions, Dicers yield more peptides and proteins than LCM, with the largest gains at 10-20 m spatial resolution. Confocal imaging shows catapult-associated cavities in LCM-generated microtissues. This material loss, along with membrane-limited protein extraction, likely reduces protein coverage. In contrast, multi-tiered Dicers enables reproducible microdissection down to 10 m while maintaining high protein coverage. With spatial registration of microtissues under development, Dicers have potential to complement LCM for next-generation spatial proteomic workflows.

bioengineering↗

bioRxiv2025

Transcriptome Network Biology Reveals the Neuroprotective Potential of Rosmarinic Acid Against Frontotemporal Dementia

Frontotemporal dementia (FTD) is a neurodegenerative disorder characterised by impaired behaviour and language. It affects individuals between 45 and 65 years of age. The present study aims to identify potential phytochemicals against target receptor of FTD. Transcriptome data analysis guided computer-aided drug design (CADD) was conducted to investigate molecular interactions between active phytochemicals present in Indian spices and differentially expressed genes. In present study, samples for patients with FTD were obtained from GEO dataset [GSE92340]. The samples were pre-processed followed by differential gene expression analysis using DESeq2. The patient sample was analyzed for 1882 upregulated genes. Hub gene out of DEGs was identified using CytoHubba Plugin of Cytoscape based on eleven parameters (Degree, Edge Percolated Component (EPC), Maximum Neighbourhood Component (MNC), Density of Maximum Neighbourhood Component (DMNC), Maximal Clique Centrality (MCC), Bottleneck, EcCentricity, Closeness, Radiality, Betweenness, and Stress). HDAC1 gene was identified as hub gene and key target in case of FTD. CADD pipeline was used to identify phytochemicals against HDAC1 gene. A list of eighty-one phytochemicals found in Indian spices was analyzed for their drug likeness abilities using molinspiration and toxicity prediction using ProTox-II, which identified twenty-three phytochemicals as safe drug-like compounds. PatchDock was employed to examine interactions between phytochemical compounds and HDAC1. Molecular interactions revealed rosmarinic acid derived from rosemary (Salvia rosmarinus) as the most effective drug for FTD having lowest ACE value of -395 kcal/mol. In conclusion, this study demonstrates essential role of HDAC1 in pathogenesis of FTD and demonstrates the neuroprotective potential of rosmarinic acid against FTD.

bioinformatics↗

bioRxiv2025

Multiplex Gene Editing Suppresses Random Integration of Hepatitis B Virus DNA in Chronically Infected Liver

Gene editing technologies have opened the possibility of directly targeting viral DNA in therapeutic applications. In chronically infected hepatocytes with hepatitis B virus (HBV), covalently closed circular DNA (cccDNA) serves as the master template for viral transcripts and gene products. In the present study, we evaluated the outcomes of anti-HBV multiplex gene editing with the CRISPR-Cas9 endonuclease from Staphylococcus aureus (SaCas9) using primary human hepatocytes (PHHs) and HBV mouse models. Nonviral delivery of SaCas9-encoding mRNA and a pair of HBV-targeting guide RNAs (gRNAs) substantially reduced viral biomarkers and intrahepatic HBV DNA copies in vitro and in vivo, suggesting that fragmentation of HBV DNA primarily leads to its degradation. Hybridization capture sequencing analyses indicated that small insertions and deletions (indels) and structural variants including excisions and inversions of the viral sequences were accumulated in the residual HBV DNA. These assays also demonstrated that transient expression of the HBV-targeting SaCas9 significantly suppressed random integration of HBV DNA, while this therapeutic approach was unlikely to affect chromosomal translocations involving viral copies. Taken together, our results suggest that anti-HBV multiplex gene editing eliminates viral DNA from chronically infected hepatocytes, potentially reducing the risk of hepatocarcinogenesis associated with HBV DNA integration.

bioengineering↗

bioRxiv2022

Relaxed targeting rules allow PIWI-clade Argonaute proteins to silence ever-mutating transposons

In animals, piRNAs direct PIWI-clade Argonaute proteins to slice complementary transposon transcripts. Transposons can evade silencing through target site mutations. We report that PIWIs efficiently cleave transcripts only partially paired to their piRNA guide. Measurements of mouse PIWI protein affinity and cleavage rates for thousands of RNAs in vitro and in vivo show that PIWI slicing tolerates mismatches to any target nucleotide, including those flanking the scissile phosphate. Although piRNA 5 terminal nucleotides accelerate target finding, they are dispensable for binding or catalysis--unlike AGO-clade Argonautes, which require uninterrupted siRNA:target pairing from the seed to the nucleotides past the scissile bond. PIWIs are thus better equipped than AGOs to target newly acquired or rapidly diverging endogenous transposons without recourse to novel small RNA guides.

molecular biology↗

bioRxiv2021

TISON: a next-generation multi-scale modeling theatre for in silico systems oncology

Multi-scale models integrating biomolecular data from genetic, transcriptional, and translational levels, coupled with extracellular microenvironments can assist in decoding the complex mechanisms underlying system-level diseases such as cancer. To investigate the emergent properties and clinical translation of such cancer models, we present Theatre for in silico Systems Oncology (TISON, https://tison.lums.edu.pk), a next-generation web-based multi-scale modeling and simulation platform for in silico systems oncology. TISON provides a "zero-code" environment for multi-scale model development by seamlessly coupling scale-specific information from biomolecular networks, microenvironments, cell decision circuits, in silico cell lines, and organoid geometries. To compute the temporal evolution of multi-scale models, a simulation engine and data analysis features are also provided. Furthermore, TISON integrates patient-specific gene expression data to evaluate patient-centric models towards personalized therapeutics. Several literature-based case studies have been developed to exemplify and validate TISONs modeling and analysis capabilities. TISON provides a cutting-edge multi-scale modeling pipeline for scale-specific as well as integrative systems oncology that can assist in drug target discovery, repositioning, and development of personalized therapeutics.

systems biology↗

bioRxiv2021

The tiny, conserved zinc-finger protein GTSF1helps PIWI proteins achieve their full catalytic potential

Argonaute proteins use nucleic acid guides to find and bind specific DNA or RNA target sequences. Argonaute proteins can be found in all kingdoms of life, and play diverse biological functions including genome defense, gene regulation, and chromosome partitioning. Many Argonautes retain their ancestral endoribonuclease activity, cleaving the phosphodiester bond between target nucleotides t10 and t11. In animals, a specialized class of Argonautes, the PIWI proteins, use 21-35 nt PIWI-interacting RNAs (piRNAs) to direct transposon silencing, protect the germline genome, and regulate gene expression during gametogenesis1. The piRNA pathway is required for fertility in one or both sexes of nearly all animals. Both piRNA production and function require RNA cleavage catalyzed by PIWI proteins. Spermatogenesis in mice and other placental mammals requires three distinct, developmentally regulated PIWI proteins: MIWI (PIWIL1), MILI (PIWIL2), and MIWI2 (PIWIL4)2-4. The piRNA-guided endoribonuclease activities of MIWI and MILI are essential to produce functional sperm5, 6. piRNA-directed silencing in mice and insects also requires Gametocyte-Specific Factor 1 (GTSF1), a PIWI-associated protein of unknown function7-12. Here, we report that GTSF1 potentiates the weak, intrinsic, piRNA-directed RNA cleavage activities of PIWI proteins, transforming them into efficient endoribonucleases. GTSF1 represents the first example of an auxiliary protein that potentiates the catalytic activity of an Argonaute protein.

biochemistry↗

bioRxiv2021

The testis-specific transcription factor TCFL5 responds to A MYBto elaborate the male meiotic program in placental mammals

In male mice, the transcription factor (TF) A-MYB initiates reprogramming of gene expression after spermatogonia enter meiosis. We report that A-MYB activates Tcfl5, a testis-specific TF first produced in pachytene spermatocytes. Subsequently, A-MYB and TCFL5 reciprocally reinforce their own transcription to establish an extensive circuit that regulates meiosis. TCFL5 promotes transcription of genes required for mRNA turnover, pachytene piRNA production, meiotic exit, and spermiogenesis. This transcriptional architecture is conserved in rhesus macaque, suggesting TCFL5 plays a central role in meiosis and spermiogenesis in placental mammals. Tcfl5em1/em1 mutants are sterile, and spermatogenesis arrests at the mid- or late-pachytene stage of meiosis.

genetics↗

bioRxiv2020

Chronic exposure to TNF reprograms cell signaling pathways in fibroblast-like synoviocytes by establishing long-term inflammatory memory

ABSTRACTFibroblast-like synoviocytes (FLS) play a critical role in the pathogenesis of rheumatoid arthritis (RA). Chronic inflammation induces transcriptomic and epigenetic modifications that imparts a persistent catabolic phenotype to the FLS, despite their dissociation from the inflammatory environment. We analyzed high throughput gene expression and chromatin accessibility data from human and mouse FLS from our and other studies available on public repositories, with the goal of identifying the persistently reprogrammed signaling pathways driven by chronic inflammation. We found that the gene expression changes induced by short-term tumor necrosis factor-alpha (TNF) treatment were largely sustained in the FLS exposed to chronic inflammation. These changes that included both activation and repression of gene expression, were accompanied by the remodeling of chromatin accessibility. The sustained activated genes (SAGs) included established pro-inflammatory signaling components known to act at multiple levels of NF-kappaB, STAT and AP-1 signaling cascades. Interestingly, the sustained repressed genes (SRGs) included critical mediators and targets of the BMP signaling pathway. We thus identified sustained repression of BMP signaling as a unique constituent of the long-term inflammatory memory induced by chronic inflammation. We postulate that simultaneous targeting of these activated and repressed signaling pathways may be necessary to combat RA persistence.Competing Interest StatementThe authors have declared no competing interest.View Full Text

molecular biology↗