Biology subjects

Khalil, I.

Publications and source records attributed to Khalil, I..

5 recordsLinked to original sources

bioRxiv2026

Plaque-associated oligodendrocyte proteostatic failure underlies myelin loss in Alzheimers disease

Alzheimers disease (AD) features amyloid-{beta} plaques and tau pathology, yet the mechanism underlying early and clinically significant myelin loss remains unresolved. Here, we report human iPSC-derived forebrain organoids with doxycycline-inducible expression of SOX10, OLIG2, and NKX6-2 (SON), which generate robust, mature oligodendrocytes and compact myelin in vitro and in vivo. Introducing amyloid precursor protein (APP) pathogenic mutations produces extracellular amyloid-{beta} plaques and phosphorylated tau, accompanied by reduced myelin basic protein (MBP) expression and disrupted myelin ultrastructure. Single-cell and spatial transcriptomics combined with amyloid plaque imaging reveal that oligodendrocytes in plaque-dense regions show pathological changes in calcium signaling, immune activation, lipid remodeling, and protein catabolic pathways. Notably, MBP protein is reduced despite elevated myelin-related transcription, suggesting plaque-induced degradation of myelin proteins. Consistent with this, proteasomal inhibition restores MBP protein levels and improves compact myelin ultrastructure in AD organoids. In human AD brain tissue, protein catabolic pathways are similarly upregulated with increasing plaque density. Together, these findings identify plaque-associated oligodendrocyte proteostatic failure as a candidate mechanism of myelin loss and a potential therapeutic pathway in AD.

neuroscience↗

bioRxiv2026

Participatory Systems Mapping and Experimental Games to Explore Biosecurity Adoption in Broiler Production in Bangladesh

IntroductionAntimicrobial Resistance (AMR) presents a critical public health challenge, particularly in smallholder broiler farming, where antibiotics are often used preventively in the absence of effective biosecurity measures. ObjectiveThis study investigates the adoption of biosecurity practices as a sustainable alternative to antibiotics through Participatory Systems Mapping and Experimental Games. MethodsA participatory mixed-methods study was conducted in southern Bangladesh (September 2024-June 2025). Causal Loop Diagrams (CLDs) were co-created with farmers, dealers, and veterinary officers. Ten broiler farmers from single village were selected via purposive and snowball sampling. Experimental games simulated four production cycles where farmers chose Option A (biosecurity, adopters) or Option B (antibiotics, non-adopters) after several interactive trainings. Key metrics including biosecurity compliance (0-12 scale), mortality, FCR, antibiotic use, outbreak history, and economic outcomes were recorded. ResultsCLD analysis revealed a reinforcing loop of increased antibiotic reliance driven by fear of mortality, and balancing loops involving training, biosecurity practices, and consumer incentives to reduce use. Five farmers chose Option A, and both groups remained stable until Round 4. Adopters had flock sizes of 800-2000 birds (non-adopters, 600-1000; mean for both = 1000), were younger, and more educated compared to non-adopters. At baseline, both groups had similar biosecurity scores (0). Adopters had higher mean outbreaks (2 vs. 1.4), mortality (5.6 vs. 4.2), antibiotic use (3.6 vs. 3), and FCR (1.8 vs. 1.6) compared to non-adopters. By Round 4, adopters improved biosecurity scores by 125%, eliminated outbreaks, reduced mortality by 52.6%, stopped antibiotic use, improved FCR by 13.3%, and gained 71.72% profit per bird compared to non-adopters. Non-adopters, influenced by adopters, increased biosecurity scores by 25%, reducing outbreaks, mortality, antibiotic use, and FCR. Adopters also increased direct sales to consumers, yielding a 10%-16% profit gain per bird each round. ConclusionThis study highlights the successful adoption of biosecurity practices by farmers, replacing antibiotics and improving production outcomes. Farmer-driven adoption of these practices fosters long-term sustainability and supports a healthier planet within the One Health framework.

microbiology↗

bioRxiv2025

SPACE: spatially resolved multiomic analysis for high-throughput CRISPR screening in 3D models

Current spatial CRISPR screening technologies are limited by targeted readouts and high costs, restricting the scope of biological discovery. Here we present SPAtial Cell Exploration (SPACE), a spatial CRISPR screening platform that integrates whole-transcriptome profiling ([~]18,000 genes), multiplexed protein detection ([~]68 markers), and CRISPR perturbation mapping at subcellular resolution. SPACE significantly reduces whole-transcriptome profiling costs compared to sequencing methods while preserving spatial context. We demonstrate SPACE by screening 43 CRISPR knockouts (KOs) across [~]100,000 cells in hundreds of cancer-associated fibroblast (CAF)-tumor spheroids, obtaining whole-transcriptome and multiplexed protein readout from the same exact cells. SPACE revealed previously unknown regulatory mechanisms on tumor extracellular matrix (ECM) remodeling, and identified spatially-resolved ligand-receptor interactions and perturbation-specific spatial gene signatures that are not detectable with dissociation-based methods. This scalable, cost-effective platform provides a transformative framework for high-throughput spatial perturbation studies in complex tissue models.

cell biology↗

bioRxiv2025

High-density extracellular recordings from the interior of intact brain organoids enable automated high-throughput functional assay

Bridging the gap between preclinical screening and clinical outcomes remains a major challenge in drug development for neurological disorders. Brain organoids, derived from human induced pluripotent stem cells, offer a scalable and physiologically relevant platform to model human neural circuits. We develop a fully automated system to record neural activity from the interior of intact human cortical organoids using a high-density microfabricated probe. The robotic system completes insertion within minutes while preserving organoid integrity and enables immediate recording of spontaneous spikes. We extract physiologically grounded and deterministic spike features, and train a long short-term memory classifier to distinguish between organoids derived from healthy individuals and those harboring familial Alzheimers disease (AD) mutations in the amyloid precursor protein. Despite intra-class variability, the classifier differentiates between organoid classes with 100% accuracy. The model classifies AD organoids treated with a drug candidate that reduces amyloid-{beta} levels as retaining an AD-like electrophysiological phenotype, demonstrating that functional readout can contradict molecular markers. The findings establish a high-throughput functional framework that may complement and extend existing drug screening assays.

neuroscience↗

bioRxiv2018

Design of an epitope-based peptide vaccine against Cryptococcus neoformans

IntroductionThis study aimed to design an immunogenic epitope for Cryptococcus neoformans the etiological agent of cryptococcosis using in silico simulations, for epitope prediction, we selected the mannoprotein antigen MP88 which its known to induce protective immunity.\n\nMaterial & methodA total of 39 sequences of MP88 protein with length 378 amino acids were retrieved from the National Center for Biotechnology Information database (NCBI) in the FASTA format were used to predict antigenic B-cell and T cell epitopes via different bioinformatics tools at Immune Epitope Database and Analysis Resource (IEDB). The tertiary structure prediction of MP88 was created in RaptorX, and visualized by UCSF Chimera software.\n\nResultA Conserved B-cell epitopes AYSTPA, AYSTPAS, PASSNCK, and DSAYPP have displayed the most promising B cell epitopes. While the YMAADQFCL, VSYEEWMNY and FQQRYTGTF they represent the best candidates T-cell conserved epitopes, the 9-mer epitope YMAADQFCL display the greater interact with 9 MHC-I alleles and HLA-A*02:01 alleles have the best interaction with an epitope. The VSYEEWMNY and FQQRYTGTF they are non-allergen while YMAADQFCL was an allergen. For MHC class II peptide binding prediction, the YARLLSLNA, ISYGTAMAV and INQTSYARL represent the most Three highly binding affinity core epitopes. The core epitope INQTSYARL was found to interact with 14 MHC-II. The allergenicity prediction reveals ISYGTAMAV, INQTSYARL were non-allergen and YARLLSLNA was an allergen. Regarding population coverage the YMAADQFCL exhibit, a higher percentage among the world (69.75%) and the average population coverage was 93.01%. In MHC-II, ISYGTAMAV epitope reveal a higher percentage (74.39%) and the average population coverage was (81.94%). This successfully designed a peptide vaccine against Cryptococcus neoformans open up a new horizon in Cryptococcus neoformans research; the results require validation by in vitro and in vivo experiments.

bioinformatics↗