Biology subjects

Asif, S.

Publications and source records attributed to Asif, S..

5 recordsLinked to original sources

bioRxiv2026

MilliMap: interactive closed-loop analysis for spatial omics

Spatial omics analysis requires iterative interplay between statistical computation and tissue-context interpretation, yet current workflows fragment these steps across disconnected environments. We present MilliMap, an interactive framework that unifies statistical analysis with spatial exploration. By closing the analysis-visualization loop, MilliMap empowers biologists to steer parameters, refine ROIs, and validate findings within a single environment. We demonstrate its utility by delineating complex neuroanatomy and identifying niche-restricted functional states in tumor microenvironments.

bioinformatics↗

bioRxiv2026

Whole-genome sequencing of a mid-20th-century femur from central Israel in an open missing-person case

Genome-wide technologies can generate investigative leads in cold cases by determining the genetic ancestry of the forensic sample. Increasingly, DNA extraction and whole-genome sequencing or genotyping are being used to analyze early or middle-20th century skeletal remains. Here, we present the first case, to our knowledge, of whole-genome sequencing of a middle-20th-century bone sample from the Middle East. A femur discovered in a cave in Central Israel was proposed to belong to a person of Ashkenazi Jewish ancestry who was missing since 1948. Following DNA extraction and single-stranded library preparation, whole-genome sequencing generated nearly 500 million reads. However, only 0.5% of the reads mapped to the human genome, providing depth of coverage of 0.07x. After quality control and male sex inference, ancestry assignment was performed using principal components and ADMIXTURE analyses. The results suggested that the genome definitively belonged to a person of Arab ancestry, refuting the hypothesis of an Ashkenazi Jewish origin.

genetics↗

bioRxiv2025

Sex- and ketogenesis-dependent effects of intermittent fasting against diet-induced obesity and fatty liver disease

ABSTRACTSIntermittent fasting (IF) improves metabolic health, yet the requirement for hepatic ketogenesis in mediating these benefits remains unclear. Here, we investigated how hepatic ketogenesis contributes to the metabolic and hepatic effects of IF in male and female mice. In the human liver, ketogenesis-associated genes showed sex-dependent correlations with inflammatory and fibrotic pathways. In mice, fasting increased circulating ketone bodies, with females exhibiting a greater rise, indicating intrinsic sex differences in ketone metabolism. IF reduced body weight and adiposity in both sexes, and these systemic benefits persisted despite antisense oligonucleotide (ASO)-mediated knockdown of hepatic Hmgcs2. In contrast, hepatic benefits were sex- and ketogenesis-dependent. IF markedly reduced steatosis and fibrosis in male mice, but these improvements were attenuated or abolished when hepatic ketogenesis was disrupted. Female mice showed minimal hepatic benefit from IF and displayed heightened susceptibility to steatosis, fibrosis, and inflammatory activation under ketogenic insufficiency. Single-cell transcriptomic analyses identified neutrophils and myofibroblasts as key responders to hepatocyte-derived ketone bodies, and IF suppressed neutrophil-driven inflammatory signaling in a ketogenesis-dependent manner in males but not females. Together, these findings demonstrate that while systemic metabolic improvements from IF are largely ketogenesis-independent, the hepatic anti-steatotic and anti-fibrotic effects of IF are sexually dimorphic and require intact hepatic ketogenesis.

physiology↗

bioRxiv2025

Between Two Extremes: Tripsacum dactyloides Root Anatomical Responses to Drought and Waterlogging

PremisePlant roots are the critical interface between plants, soil, and microorganisms, and respond dynamically to changes in water availability. Although anatomical adaptations of roots to water stress (e.g., the formation of root cortical aerenchyma) are well documented, it remains unclear whether these responses manifest along the length of individual roots under both water deficiency and water over-abundance. MethodsWe investigated the anatomical responses of Tripsacum dactyloides L. to both drought and flood stress at high spatial resolution. Nodal roots were segmented into one-centimeter sections from the tip to the base, allowing us to pinpoint regions of maximal anatomical change. ResultsBoth stressors increased the proportion of root cortical aerenchyma, but metaxylem responses differed: flooding increased vessel area whereas drought led to smaller vessels, with both showing a lower number of vessels. Drought also significantly increased root hair formation, but only within the first two centimeters. The most pronounced anatomical changes occurred 3-7 cm from the root tip, where cortical cell density declined as aerenchyma expanded. DiscussionThese findings highlight spatial variation in root anatomical responses to water stress and provide a framework integrating various other data types where sampling effort is limiting (e.g., microbiome, transcriptome, proteome).

plant biology↗

bioRxiv2024

LAG3 marks activated but hyporesponsive NK cells.

Natural Killer (NK) cells are critical for immunosurveillance yet become dysfunctional in contexts such as chronic stimulation by viral infections or cancer. This phenomenon is similar to T cell exhaustion but less well characterized, which limits therapeutic interventions. As shown for T cells, NK cells often display an increased expression of immune checkpoint proteins (ICP) following chronic stimulation, and ICP blockade therapies are currently being explored for several cancer types, which have remarkable patient benefits. Nevertheless, the nature of ICP expression in NK cells is still poorly documented. In this study, we aimed to identify the conditions that lead to and the phenotype of immune checkpoint LAG3 (Lymphocyte-activation gene 3) expressing NK cells. Using various experimental models, we found that LAG3 is expressed by murine NK cells upon activation in different contexts, including in response to cancer and acute viral infections. LAG3 marks a subset of immature, proliferating and activated cells, which, despite activation, have a reduced capacity to respond to a broad range of stimuli. Further characterization also revealed that LAG3+ NK cells exhibit a transcriptional signature similar to that of exhausted CD8+ T cells. Taken together, our results support the use of LAG3 as a marker of dysfunctional NK cells across diverse chronic and acute inflammatory conditions.

immunology↗