Biology subjects

Bar, S.

Publications and source records attributed to Bar, S..

8 recordsLinked to original sources

bioRxiv2026

Scrub Data: A Framework for Reproducible Data Curation with AI Coding Agents

Data curation-the process of collecting, cleaning, and joining raw datasets for unified analysis-is a time-consuming yet crucial part of any data science project. With the emergence of powerful agentic coding tools, it is tempting to "vibe curate"-i.e., to prompt AI agents to perform data curation operations and blindly trust their outputs in order to finish work more quickly. However, this can exacerbate two key challenges that already plague manual data curation workflows: reproducibility-the ability to trace the exact set of modifications applied to raw datasets-and verifiability-the ability to audit changes and confirm that data is processed properly. To address these issues, we introduce Scrub Data, a framework that enables the use of AI agents in data curation workflows while transparently maintaining both reproducibility and verifiability. The framework involves an interactive data curation loop between a user and an AI agent, backed by a data provenance graph that tracks and versions all dataset updates. The data graph requires that all updates are formatted as self-contained executable steps, allowing any version of a dataset to be reconstructed from raw data by playing forward the transformations stored in the graph. This workflow takes place within a lightweight web application that is designed to be modified by users and agents in real-time to create custom visualization tools for identifying data curation needs and verifying outcomes. We demonstrate the usefulness of the framework with a real data curation use case from animal movement ecology. Starting with 89M raw GPS coordinates, we use the framework to curate a benchmark dataset of 2.5M coordinates to be used for machine learning or statistical analysis. The framework is available for use and extension at https://github.com/justinkay/scrubdata.

ecology↗

bioRxiv2025

Galectin-3 Mediated Endocytosis of the Orphan G-Protein-Coupled Receptor GPRC5A

Galectins, a family of glycan-binding proteins, play crucial roles in various cellular functions, acting at both intracellular and extracellular levels. Among them, Galectin-3 (Gal-3) stands out as a unique member, possessing an intrinsically disordered N-terminal interaction domain and a canonical carbohydrate-recognition domain (CRD). Gal-3 binding to glycosylated plasma membrane cargo leads to its oligomerization and membrane bending, ultimately resulting in the formation of endocytic invaginations. An interactomic assay using proteomic analysis of endogenous Gal-3 immunoprecipitates identified the orphan G protein-coupled receptor GPRC5A as a novel binding partner of Gal-3. GPRC5A, also known as Retinoic Acid-Induced protein 3 (RAI3), is transcriptionally induced by retinoic acid. Our results further demonstrate that extracellular recombinant Gal-3 stimulates GPRC5A internalization. In SW480 colorectal cancer cells, glycosylated GPRC5A interacts with Gal-3. Interestingly, while GPRC5A expression was upregulated by the addition of all-trans retinoic acid (ATRA), its endogenous internalization in SW480 cells was specifically triggered by extracellular Gal-3, but not by ATRA. This study provides new insights into the endocytic mechanisms of GPRC5A, for which no specific ligand has been identified to date. Further research may uncover additional Gal-3 mediated functions in GPRC5A cellular signaling and contribute to the development of innovative therapeutic strategies.

cell biology↗

bioRxiv2024

Inhibition of the metalloprotease ADAM19 as a Novel Senomorphic Strategy to Ameliorate gut permeability and senescence markers by modulating senescence-associated secretory phenotype (SASP)

Accumulation of DNA damage can accelerate aging through cellular senescence. Previously, we established a Drosophila model to investigate the effects of radiation-induced DNA damage on the intestine. In this model, we examined irradiation-responsive senescence in the fly intestine. Through an unbiased genome-wide association study (GWAS) utilizing 156 strains from the Drosophila Genetic Reference Panel (DGRP), we identified meltrin {beta} (the drosophila orthologue of mammalian ADAM19) as a potential modulator of the senescence-associated secretory phenotype (SASP). Knockdown of meltrin {beta} resulted in reduced gut permeability, DNA damage, and expression of the senescence marker {beta}-galactosidase (SA-{beta}-gal) in the fly gut following irradiation. Additionally, inhibition of ADAM19 in mice using batimastat-94 reduced gut permeability and inflammation in the gut. Our findings extend to human primary fibroblasts, where ADAM19 knockdown or pharmacological inhibition decreased expression of specific SASP factors and SA-{beta}-gal. Furthermore, proteomics analysis of the secretory factor of senescent cells revealed a significant decrease in SASP factors associated with the ADAM19 cleavage site. These data suggest that ADAM19 inhibition could represent a novel senomorphic strategy.

molecular biology↗

bioRxiv2022

Analysis of Larval Fish Feeding Behavior under Naturalistic Conditions

Modern research efforts concerned with animal behavior rely heavily on image and video analysis. While such data are now quick to obtain, extracting and analyzing complex behaviors under naturalistic conditions is still a major challenge, specifically when the behavior of interest is sporadic and rare. In this study, we present an end-to-end system for capturing, detecting and analyzing larval fish feeding behavior in unconstrained naturalistic environments. We first constructed a specialized system for imaging these tiny, fast-moving creatures and deployed it in large aquaculture rearing pools. We then designed an analysis pipeline using several action classification backbones, and compare their performance. A natural feature of the data was the extremely low prevalence of feeding events, leading to low sample sizes and highly imbalanced datasets despite extensive annotation efforts. Nevertheless, our pipeline successfully detected and classified the sparsely-occurring feeding behavior of fish larvae in a curated experimental setting from videos featuring multiple animals. We introduce three new annotated datasets of underwater videography, in a curated and an uncurated setting. As challenges related to data imbalance and experts annotation are common to the analysis of animal behavior under naturalistic conditions, we believe our findings can contribute to the growing field of computer vision for the study and understanding of animal behavior.

zoology↗

bioRxiv2021

Adipose deficiency and aberrant autophagy in a Drosophila model of MPS VII is corrected by pharmacological stimulators of mTOR

Mucopolysaccharidosis type VII (MPS VII) is a recessively inherited lysosomal storage disorder caused due to {beta}-glucuronidase ({beta}-GUS) enzyme deficiency. Prominent clinical symptoms include hydrops fetalis, musculoskeletal deformities, neurodegeneration and hepatosplenomegaly leading to premature death in most cases. Apart from these, MPS VII is also characterized as adipose storage deficiency disorder although the underlying mechanism of this lean phenotype in the patients or {beta}-GUS-deficient mice still remains a mystery. We addressed this issue using our recently developed Drosophila model of MPS VII (the CG2135-/- fly), which also exhibited a significant loss of adiposity. We report here that the lean phenotype of the CG2135-/- fly is due to fewer number of adipocytes, smaller lipid droplets and reduced adipogenesis. Our data further revealed that there is an abnormal accumulation of autophagosomes in the CG2135-/- larvae due to autophagosome-lysosome fusion defect. Decreased lysosome-mediated turnover also led to attenuated mTOR activity in the CG2135-/- flies. Interestingly, treatment of the CG2135-/- larvae with mTOR stimulators, 3BDO or glucose, led to the restoration of mTOR activity with simultaneous correction of the autophagy defect and adipose storage deficiency. Our finding thus established a hitherto unknown mechanistic link between autophagy dysfunction, mTOR downregulation and reduced adiposity in MPS VII.

cell biology↗

bioRxiv2021

Dietary restriction and clock delay eye aging to extend lifespan in D. melanogaster

Many vital processes in the eye are under circadian regulation, and circadian dysfunction has emerged as a potential driver of eye aging. Dietary restriction is one of the most robust lifespan-extending therapies and amplifies circadian rhythms with age. Herein, we demonstrate that dietary restriction extends lifespan in D. melanogaster by promoting circadian homoeostatic processes that protect the visual system from age- and light- associated damage. Disrupting circadian rhythms in the eye by inhibiting the transcription factor, Clock (CLK), or CLK-output genes, accelerated visual senescence, induced a systemic immune response, and shortened lifespan. Flies subjected to dietary restriction were protected from the lifespan-shortening effects of photoreceptor activation. Inversely, photoreceptor inactivation, achieved via mutating rhodopsin or housing flies in constant darkness, primarily extended lifespan in flies reared on a high-nutrient diet. Our findings establish the eye as a diet-sensitive modulator of lifespan and indicate that vision is an antagonistically pleiotropic process that contributes to organismal aging.

neuroscience↗

bioRxiv2020

miR-125-chinmo pathway regulates dietary restriction dependent enhancement of lifespan in Drosophila

Dietary restriction (DR) extends healthy lifespan in diverse species. Age and nutrient-related changes in the abundance of microRNAs (miRNAs) and their processing factors have been linked to organismal longevity. However, the mechanisms by which they modulate lifespan and the tissue-specific role of miRNA mediated networks in DR dependent enhancement of lifespan remains largely unexplored. We show that two neuronally enriched and highly conserved microRNAs, miR-125 and let-7 mediate the DR response in Drosophila melanogaster. Functional characterization of miR-125 demonstrates its role in neurons while its target chinmo acts both in neurons and the fat body to modulate fat metabolism and longevity. Proteomic analysis revealed that Chinmo exerts its DR effects by regulating expression of FATP, CG2017, CG9577, CG17554, CG5009, CG8778, CG9527 and FASN1. Our findings identify miR-125 as a conserved effector of DR pathway and open up the avenue for this small RNA molecule and its downstream effectors to be considered as potential drug candidates for treatment of late-onset diseases and biomarkers for healthy aging in humans.

molecular biology↗

bioRxiv2019

Proteasome subunit PSMC3 variants cause neurosensory syndrome combining deafness and cataract due to proteotoxic stress

Whole-genome sequencing was performed on patients with severe deafness and early-onset cataracts as part of a neurological, sensorial and cutaneous novel syndrome. A unique deep intronic homozygous variant in the PSMC3 gene (c.1127+337A>G, p.Ser376Argfs15*), encoding the 26S proteasome ATPase ring subunit 5 (Rpt5) was identified leading to the transcription of a cryptic exon. Patients fibroblasts exhibited impaired protein homeostasis characterized by accumulation of ubiquitinated proteins suggesting severe proteotoxic stress. Indeed, the TCF11/Nrf1 transcriptional pathway allowing proteasome recovery after proteasome inhibition is permanently activated in the patients fibroblasts. Upon chemical proteasome inhibition this pathway is however impaired. These cells were unable to compensate for proteotoxic stress although a higher proteasome content. Two different zebrafish studies led to inner ear development anomalies as well as cataracts. PSMC3 proteasome subunit dysfunction leads to various neurological manifestations, early onset cataracts and deafness and suggest that Rpt5 plays a major role in inner ear, lens and central nervous system development.

genetics↗