Biology subjects

Tan, J. J.

Publications and source records attributed to Tan, J. J..

8 recordsLinked to original sources

bioRxiv2026

Detection-Guided Beamforming for Efficient Bat Localisation

Passive acoustic monitoring is widely used to study wildlife, but current approaches provide limited insight into the spatial behaviour of animals. In bat ecology, reconstructing flight trajectories is essential for studying habitat use, movement patterns, and interactions, yet it remains difficult to achieve under field conditions. Acoustic cameras offer a potential solution by enabling sound source localisation, but their practical application is limited by the computational cost of beamforming and by the non-stationary, broadband, and transient nature of echolocation calls. In particular, exhaustive beamforming over wide ultrasonic bandwidths and dense spatial grids becomes infeasible for continuous monitoring. In this work, we propose a detection-guided beamforming framework for efficient localisation of free-flying bats. The method exploits the sparsity of echolocation signals by restricting beamforming to detector-identified time-frequency regions and combines this with physically consistent short-time analysis parameters and dense spatial sampling. The framework is evaluated on field recordings acquired with a Sorama CAM iV64s acoustic camera. Results show that detection-guided processing reduces the number of beamformer evaluations by approximately 77 times, corresponding to a reduction of about 98.7 % in computational effort, while preserving spatial resolution. At the same time, the proposed parameter configuration improves the stability and sharpness of reconstructed trajectories by avoiding artefacts associated with temporal averaging. These findings demonstrate that high-resolution acoustic localisation can be achieved under realistic computational constraints, supporting the integration of acoustic cameras into ecological monitoring workflows. The proposed framework enables the extraction of spatial trajectories from passive acoustic monitoring data, facilitating spatially resolved analyses of bat behaviour in field conditions.

bioinformatics↗

bioRxiv2025

Dynamic epigenetic and transcriptional regulatory network in pepper fruit development and ripening

Pepper (Capsicum) is among the most widely cultivated and consumed vegetable crops worldwide. Although extensive studies in model fruit crops such as tomato have provided insights into the genetic and epigenetic regulation of fruit development and ripening, comparable knowledge in pepper remains limited. Here, we employ a multi- omics approach to investigate transcriptome and epigenome dynamics during pepper fruit pericarp development and ripening. Our analyses reveal coordinated changes in chromatin accessibility and histone modifications accompanying transcriptome reprogramming, with changes in H3K27ac closely associated with chromatin accessibility dynamics, and H3K27me3 dynamics potentially contributing to the transition from fruit growth to ripening. Moreover, construction of the transcriptional regulatory network underlying pepper fruit development and ripening suggests that several ripening regulators identified in the climacteric tomato may also play critical roles in governing ripening in the non-climacteric pepper. During ripening, DNA methylation, particularly in the CG and CHG contexts, undergoes global demethylation, especially at promoter regions, which is accompanied by increased chromatin accessibility and likely enhances transcription factor binding activity. We further demonstrate transcriptional and epigenetic regulation of carotenoid and ascorbic acid (vitamin C) biosynthesis pathways. Collectively, this study provides a comprehensive resource for mechanistic dissection and comparative analysis of fruit development and ripening, with practical implications for improving key fruit traits.

plant biology↗

bioRxiv2025

Single cell level analysis of ATP release kinetics and cell fate following ultrasound targeted microbubble cavitation using microscopy techniques

It is known that ultrasound-targeted microbubble cavitation (UTMC) can induce vasodilation. This image guided spatially targeted approach is called provascular therapy when used as a radiotherapy sensitizer in radiation oncology. Extracellular adenosine-5-triphosphate (eATP), which plays an important role in vascular tone regulation, is released by cells following UTMC, possibly through sonoporation (formation of temporary and non-deadly pores in the cell membrane) and/or cell death. Herein, we were interested in quantifying UTMC-mediated ATP released in vitro using a microfluidics-based model and study its relationship with UTMC-mediated cell fate to better understand and improve UTMC mediated bioeffects. Lipid microbubbles (MB, Definity(R)), luciferin-luciferase (LL - for eATP quantification), and propidium iodide (PI - poration tracer) were flown over HUVEC cells cultured in a microfluidic device. Ultrasounds at 1 MHz, varying in pressure (300, 400 kPa) and length (10, 100, 1000 cycles) were applied to the chip. The LL chemiluminescent signal after the ultrasound pulse was acquired with an EMCCD camera to characterize ATP release kinetics. Then, a viability assay was performed with calcein-AM. An in-house MATLAB program pairing eATP kinetics with PI/calcein data was used to classify cells into three categories (sonoporated, dead, and untreated). Within the testing conditions, a single UTMC pulse caused between 4% and 55% PI-positive (PI+) cells in the ultrasound-treated area. Amongst PI+ cells, we generally found more dead cells than sonoporated cells, except for milder pulses (300 kPa; 10 and 100 cycles). The analysis of individual responses of ATP release demonstrated that dead cells released more ATP (up to 22.4 {+/-} 12.2 fmol/cell) than sonoporated cells (6.8 {+/-} 3.4 fmol/cell) and at a faster release rate which peaked at 4s. This study showed that sonoporation plays a significant role in UTMC-mediated ATP release, advancing our understanding of UTMCs potential use as a radiosensitizer in solid tumors.

bioengineering↗

bioRxiv2024

Transiently restricting individual amino acids protects D. melanogaster against multiple stressors

Nutrition and resilience are linked, though it is not yet clear how diet confers stress resistance or the breadth of stressors that it can protect against. We have previously shown that transiently restricting an essential amino acid can extend lifespan and also protect against nicotine exposure in Drosophila melanogaster, raising the possibility that amino acid restriction is geroprotective because of elevated detoxification capacity. Here, we sought to characterise the nature of this dietary mediated protection, and determine whether it was sex, amino acid, and/or nicotine specific. When we compared between sexes, we found that isoleucine deprivation increases female, but not male, nicotine resistance. Surprisingly, we found that this protection afforded to females was not replicated by dietary protein restriction and was instead specific to individual amino acid restriction. Other studies have documented methionine or leucine restriction conferring stress resistance, though we previously found that individually depriving them did not increase nicotine resistance. We therefore wondered whether reducing the severity of restriction of these amino acids could confer nicotine resistance. This was true for methionine restriction, and we found that flies fed a diet containing 25% methionine for 7 days protected against subsequent nicotine poisoning ([~]30% longer lived than controls with all amino acids). However, when dietary leucine was altered, nicotine resistance changed, but no single diet was protective. To understand whether these beneficial effects of diet were specific to nicotine or were generalisable across stressors, we pre-treated with amino acid restriction diets and exposed them to other types of stress. We did not find any diets that protected against heat stress or infection with the bacterium Enterococcus faecalis. However, we found that some of the diets that protected against nicotine also protected against oxidative and starvation stress, and improved survival following cold shock. Interestingly, we found that a diet lacking isoleucine was the only diet to protect against all these stressors. These data point to isoleucine as a critical determinant of robustness in the face of environmental challenges.

genetics↗

bioRxiv2021

14-3-3ζ constrains insulin secretion in pancreatic β-cells by regulating mitochondrial function

While critical for neurotransmitter synthesis in the brain, members of the 14-3-3 protein family are often assumed to have redundant, over-lapping roles due to their high sequence homology and ubiquitous expression. Despite this assumption, various mammalian 14-3-3 isoforms have now been implicated in regulating cellular and organismal metabolism; however, these functions were primarily observed in cell lines or from systemic knockout mouse models. To date, we have begun to define the contributions of 14-3-3{zeta} in adipocytes, but whether 14-3-3{zeta} has additional metabolic roles in other cell types, such as the pancreatic {beta}-cell, is unclear. We previously documented a pro-survival role of 14-3-3{zeta} in MIN6 insulinoma cells, as depletion of 14-3-3{zeta} induced cell death, but paradoxically, whole-body deletion of 14-3-3{zeta} in mice resulted in significantly enlarged {beta}-cell area with no effects on insulin secretion. To better understand the role of 14-3-3{zeta} in {beta}-cells, we generated {beta}-cell-specific 14-3-3{zeta} knockout ({beta}14-3-3{zeta}KO) mice, and while no differences in {beta}-cell mass were observed, {beta}14-3-3{zeta}KO mice displayed potentiated insulin secretion due to enhanced mitochondrial function and ATP synthesis. Deletion of 14-3-3{zeta} led to profound changes to the {beta}-cell transcriptome, where pathways associated with mitochondrial respiration and oxidative phosphorylation were upregulated. Acute treatment of mouse islets and human islets with pan-14-3-3 inhibitors recapitulated the potentiation in glucose-stimulated insulin secretion (GSIS) and mitochondrial function, suggesting that 14-3-3{zeta} is a critical isoform in {beta}-cells that regulates GSIS. In dysfunctional db/db islets and islets from type 2 diabetic donors, expression of Ywhaz/YWHAZ, the gene encoding 14-3-3{zeta}, was inversely associated with insulin secretory capacity, and pan-14-3-3 protein inhibition was capable of enhancing GSIS and mitochondrial function. Taken together, this study demonstrates important regulatory functions of 14-3-3{zeta} and its related isoforms in insulin secretion and mitochondrial function in {beta}-cells. A deeper understanding of how 14-3-3{zeta} influences {beta}-cell function will further advance our knowledge of how insulin secretion from {beta}-cells is regulated.

physiology↗

bioRxiv2021

Recapitulate Human Cardio-pulmonary Co-development Using Simultaneous Multilineage Differentiation of Pluripotent Stem Cells

The extensive crosstalk between the developing heart and lung is pivotal for their proper morphogenesis and maturation. However, there remains a lack of model systems for investigating the critical cardio-pulmonary mutual interaction during human embryogenesis. Here, we reported a novel stepwise strategy for directing simultaneous induction of both mesoderm-derived cardiac and endoderm-derived lung epithelial lineages within a single differentiation of human pluripotent stem cells (hPSCs) via temporal specific tuning of WNT and TGF-{beta} signaling in the absence of exogenous growth factors. Using 3D suspension culture, we established concentric cardio-pulmonary micro-Tissues (Ts), and observed expedited alveolar maturation in the presence of cardiac accompany. Upon withdrawal of WNT agonist, the cardiac and pulmonary components within each dual-lineage T effectively segregated from each other with concurrent initiation of cardiac contraction. We expect our multilineage differentiation model to offer an experimentally tractable system for investigating human cardio-pulmonary interplay and tissue boundary formation during embryogenesis.

developmental biology↗

bioRxiv2019

TREM-1 activation is a key regulator in driving severe pathogenesis of enterovirus 71 infection

Hand, foot and mouth disease (HFMD), caused by enterovirus 71 (EV71), presents mild to severe disease, and sometimes fatal neurological and respiratory manifestations. However, reasons for the severe pathogenesis remain undefined. To investigate this, infection and viral kinetics of EV71 isolates from clinical disease (mild, moderate and severe) from Sarawak, Malaysia, were characterized in human rhabdomyosarcoma (RD), neuroblastoma (SH-SY5Y) and peripheral blood mononuclear cells (PBMCs). High resolution transcriptomics was used to decipher EV71-host interactions in PBMCs. Ingenuity analyses revealed similar pathways triggered by all EV71 isolates, although the extent of activation varied. Importantly, several pathways were found to be specific to the severe isolate, including triggering receptor expressed on myeloid cells 1 (TREM-1) signaling. Depletion of TREM-1 in EV71-infected PBMCs with peptide LP17 resulted in decreased levels of pro-inflammatory genes, and reduced viral loads for the moderate and severe isolates. Mechanistically, this is the first report describing the transcriptome profiles during EV71 infections in primary human cells, and the involvement of TREM-1 in the severe disease pathogenesis, thus providing new insights for future treatment targets.

immunology↗

bioRxiv2017

Zika virus infection preferentially counterbalances human peripheral monocyte and/or NK-cell activity

Zika virus (ZIKV) has re-emerged in the population and caused unprecedented global outbreaks. Here, the transcriptomic consequences of ZIKV infection were studied systematically firstly in human peripheral blood CD14+ monocytes and monocyte-derived macrophages with high density RNA-sequencing. Analyses of the ZIKV genome revealed that the virus underwent genetic diversification and differential mRNA abundance was found in host cells during infection. Notably, there was a significant change in the cellular response with crosstalk between monocytes and natural killer (NK) cells as one of the highly identified pathway. Immune-phenotyping of peripheral blood from ZIKV-infected patients further confirmed the activation of NK cells during acute infection. ZIKV infection in peripheral blood cells isolated from healthy donors led to the induction of IFN{gamma} and CD107a -- two key markers of NK-cell function. Depletion of CD14+ monocytes from peripheral blood resulted in a reduction of these markers and reduced priming of NK cells during infection. This was complemented by the immunoproteomic changes observed. Mechanistically, ZIKV infection preferentially counterbalances monocyte and/or NK-cell activity, with implications for targeted cytokine immunotherapies.

immunology↗