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Biology subjects

Kaul, G.

Publications and source records attributed to Kaul, G..

3 recordsLinked to original sources

DAMM for the detection and tracking of multiple animals within complex social and environmental settings

Accurate detection and tracking of animals across diverse environments are crucial for behavioral studies in various disciplines, including neuroscience. Recently, machine learning and computer vision techniques have become integral to the neuroscientists toolkit, enabling high-throughput behavioral studies. Despite advancements in localizing individual animals in simple environments, the task remains challenging in complex conditions due to intra-class visual variability and environmental diversity. These limitations hinder studies in ethologically- relevant conditions, such as when animals are concealed within nests or in obscured environments. Moreover, current tools are laborious and time-consuming to employ, requiring extensive, setup-specific annotation and model training/validation procedures. To address these challenges, we introduce the Detect Any Mouse Model (DAMM), a pretrained object detector for localizing mice in complex environments, capable of robust performance with zero to minimal additional training on new experimental setups. Our approach involves collecting and annotating a diverse dataset that encompasses single and multi-housed mice in various lighting conditions, experimental setups, and occlusion levels. We utilize the Mask R-CNN architecture for instance segmentation and validate DAMMs performance with no additional training data (zero-shot inference) and with few examples for fine-tuning (few-shot inference). DAMM excels in zero- shot inference, detecting mice, and even rats, in entirely unseen scenarios and further improves with minimal additional training. By integrating DAMM with the SORT algorithm, we demonstrate robust tracking, competitively performing with keypoint-estimation-based methods. Finally, to advance and simplify behavioral studies, we made DAMM accessible to the scientific community with a user-friendly Python API, shared model weights, and a Google Colab implementation. SignificancePresent deep learning tools for animal localization require extensive laborious annotation and time-consuming training for the creation of setup-specific models, slowing scientific progress. Additionally, the effectiveness of these tools in naturalistic settings is impeded by visual variability of objects and environmental diversity, hindering animal detection in complex environments. Our study presents the Detect Any Mouse Model (DAMM), a robustly validated object detector designed for localizing mice in complex environments. DAMM excels in generalization, robustly performing with zero to minimal additional training on previously unseen setups and multi-animal scenarios. Its integration with the SORT algorithm permits robust tracking, competitively performing with keypoint-estimation-based tools. These developments, along with our dissemination of DAMM, mark a significant step forward in streamlining ethologically-relevant animal behavioral studies.

animal behavior and cognition↗

Intracellular Accumulation-Driven Potentiation of Moxifloxacin Against non-replicating drug-tolerant Mycobacterium tuberculosis through a Prodrug

Most front-line tuberculosis drugs are ineffective against hypoxic non-replicating drug-tolerant Mycobacterium tuberculosis (Mtb) contributing to phenotypic antimicrobial resistance (AMR). This is largely due to the poor permeability in the thick and waxy cell wall of persister cells, leading to diminished drug accumulation and reduced drug-target engagement. Here, using an "arm-to-disarm" prodrug approach, we demonstrate that non-replicating Mtb persisters can be sensitized to Moxifloxacin (MXF), a front-line TB drug. We design and develop a series of nitroheteroaryl MXF prodrugs that are substrates for bacterial nitroreductases (NTR), a class of enzymes that are over-expressed in hypoxic Mtb. Enzymatic activation involves electron-transfer to the nitroheteroaryl compound followed by protonation via water that contributes to the rapid cleavage rate of the protective group by NTR to produce the active drug. Phenotypic and genotypic data are fully consistent with MXF-driven lethality of the prodrug in Mtb with the protective group being a relatively innocuous bystander. The prodrug increased intracellular concentrations of MXF than MXF alone and is more lethal than MXF in non-replicating persisters. Hence, arming drugs to improve permeability, accumulation and drug-target engagement is a new therapeutic paradigm to disarm phenotypic AMR.

microbiology↗

ZnO nanoparticles and SWCNT induced general stress response pathway in HepG2 cells at non-cytotoxic doses revealed by RNA sequencing

Nanoparticles (NPs) are important in a variety of sectors, including disease diagnostics, medicine, nutrition, and many other industries. The risk of human exposure demands an early evaluation of both the basic dynamics of NPs interaction with biological systems and their potential consequences. Deciphering these occurrences will provide critical information regarding the health hazards and safety advantages associated with next-generation nanoformulations in clinical practice. We examined the HepG2 cell line in a systematic manner to determine the cellular response to single-walled carbon nanotubes (SWCNTs) and zinc oxide (ZnO) NPs. With the use of high-throughput transcriptomic methods, we found that both NPs induce comparable dysregulation of the endocytic and proteasomal complex genes in liver hepatocellular carcinoma cells, at levels (> 80 percent cell viability) that do not cause over-toxicity at early incubation period (6 h). SWCNT and ZnO NPs were shown to enter cells through clathrin-mediated pathways, affecting cytoskeleton gene expression, DNA damage and repair, protein ubiquitination, and cell transcriptional machinery. Our findings indicate that early response strategies activate stress-related mechanisms. Finally, this method for studying nanomaterial-cell interactions demonstrates how changes in the transcriptome profile may predict downstream consequences even at doses that do not cause acute toxicity.

pharmacology and toxicology↗