Biology subjects

Khan, N. S.

Publications and source records attributed to Khan, N. S..

6 recordsLinked to original sources

bioRxiv2026

Propagule and Juvenile-derived Foraminiferal eDNA across intertidal habitats and its implications for accurate sea-level reconstruction

Foraminiferal environmental DNA (eDNA) assemblages have recently emerged as a robust and complementary proxy for relative sea level (RSL) reconstruction. However, unlike traditional morphological methods, eDNA assemblages are influenced by diverse DNA sources, including propagules and juveniles, whose effects on RSL reconstruction remain poorly understood. To assess how foraminiferal eDNA from different life stages vary in taxa composition and impact RSL reconstruction, we analyzed foraminiferal eDNA from bulk, 500-63 m and <63 m size fraction sediments from mangrove and mudflat environments in subtropical Hong Kong. The eDNA assemblages in size-fractioned sediments displayed distinct patterns from those in bulk sediment eDNA across different environments. The propagule and juvenile-derived eDNA <63 m fraction exhibited a similar community structure to bulk eDNA in mudflat environments but diverged in mangrove environments, indicating a greater contribution of propagule and juvenile eDNA to the total eDNA pool in the mudflat environment. We applied Bayesian transfer function modeling to estimate the elevation of samples using different size fractions. eDNA assemblages from the <63 m fraction systematically underpredicted elevation in mangrove environments, while elevations inferred from the 500-63 m fraction and bulk sediment eDNA were accurate. Conversely, all eDNA assemblages in the mudflat-mangrove transitional zone led to the overprediction of RSL. These findings confirm the reliability of bulk sediment eDNA for RSL reconstruction in mangrove environments, while highlighting the need for caution when reconstructing RSL in transitional zones.

ecology↗

bioRxiv2025

Temporal and spatial variability of mudflat and mangrove foraminiferal eDNA assemblages and its implication for sea-level reconstruction

Reconstructing relative sea level (RSL) is essential for understanding coastal evolution and mitigating impacts of climate change. Foraminiferal assemblages are established proxies for past sea levels, but their composition can vary seasonally and spatially, affecting the reliability of morphological reconstructions. Environmental DNA (eDNA) enables high-resolution, non-invasive monitoring of foraminiferal communities and supports high-precision RSL reconstruction. However, the spatiotemporal stability of eDNA assemblages in (sub)tropical intertidal zones--and their influence on RSL reconstruction--remains uncertain. We conducted a two-year eDNA monitoring study at three intertidal stations of varying tidal elevation in Hong Kong, sampling during both dry and wet seasons to assess variability in mangrove and mudflat environments. Mid-mangrove eDNA communities exhibited temporal and spatial stability. In contrast, eDNA assemblages in mudflat and upper-mangrove environments, particularly among monothalamous foraminifera taxa, showed pronounced seasonal shifts primarily driven by environmental changes. Despite this variability in the upper-mangrove, eDNA-based elevation estimates in mangrove consistently aligned with observed elevations (within 95% credible intervals), demonstrating reliability of RSL reconstructions in these environments. However, samples from mudflats, especially during the wet season, exhibited an overprediction bias, reflecting their heightened sensitivity to seasonal and exogenous eDNA inputs. These findings highlight the need to account for seasonal and environmental variability in eDNA-based RSL reconstruction. Stable mangroves are optimal for transfer functions, while transitional/mudflat zones require caution due to higher variability. Our study provides guidance for foraminiferal eDNA application in complex, dynamic coastal settings.

ecology↗

bioRxiv2025

Foraminiferal environmental DNA reveals late Holocene sea-level changes

Reconstructing past relative sea level (RSL) provides critical insight into the mechanisms driving RSL change and informs future projections. Foraminifera are widely used sea-level indicators, but their application is often limited by poor preservation. Here, we demonstrate that foraminiferal environmental DNA (eDNA) and sedimentary ancient DNA (sedaDNA) provide a complementary approach to traditional morphological methods for RSL reconstruction. By analyzing surface sediments and a core from subtropical intertidal environments in the Pearl River Delta, we found that foraminiferal eDNA and sedaDNA assemblages exhibit clear vertical zonation, consistent with morphological results. An eDNA-based transfer function enabled high-resolution RSL reconstructions with decadal temporal and decimeter vertical precision from two periods: 290-1703 CE and 1956-present. Notably, eDNA preservation extended RSL reconstruction far earlier than morphological analyses (1956 CE). The eDNA reconstruction closely matched tide-gauge and geological RSL records, underscoring its potential as a robust tool for reconstructing past RSL and its driving mechanisms.

paleontology↗

bioRxiv2023

Long-term impact of early life stress on serotonin connectivity

Chronic childhood stress is a prominent risk factor for developing mood disorders, yet mechanisms underlying this association remain unclear. Serotonin (5-HT) plays a crucial role in neurodevelopment and vulnerability to mood disorders. Maintenance of optimal 5-HT levels during early postnatal development is critical for the maturation of brain circuits. Developmental stress can alter the serotonin system, leading to chronic behavioral deficits. Yet, our understanding of the long-term impact of early life stress (ELS) on serotonin connectivity remains incomplete. Using a mouse model of chronic developmental stress, we sought to determine how ELS impacts brain-wide serotonin activity and behavior in adulthood. We established that adult female and male mice exposed to ELS during the first postnatal week show heightened anxiety-like behavior. Using in vivo fiber photometry and c-fos dependent activity mapping, we found that ELS enhances susceptibility to acute stress by disrupting the brain-wide functional connectivity of the raphe nucleus and the activity of dorsal raphe serotonin neuron population, in conjunction with a profound increase in the orbitofrontal cortex (OFC) activity. We further identified that 5-HT release in the medial OFC during environmental challenge is disrupted in mice exposed to ELS. Optogenetic stimulation of 5-HT terminals in the mOFC elicited an anxiolytic effect in ELS mice in a sex-dependent manner. Our findings hold significant insight into the mechanisms underlying long-term brain connectivity deficits induced by ELS, with potential implications for developing targeted stimulation-based treatments for affective disorders that arise from early life adversities.

neuroscience↗

bioRxiv2023

Arsenite methyltransferase 3 regulates hepatic energy metabolism which dictates the hepatic response to arsenic exposure

Inorganic arsenic (iAs(III)) is among the most pervasive environmental toxicants in the world. The iAs metabolizing enzyme, arsenite methyltransferase (AS3MT), is a key mediator of iAs(III) toxicity and has been almost exclusively investigated in the context of iAs(III) exposure. We use functional genomics approach with zebrafish as3mt mutants which lack arsenite methyltransferase activity to uncover novel, arsenic-independent functions for As3mt. Transcriptomic analysis of untreated whole larvae, and the larval and adult livers from as3mt mutants revealed thousands of differentially expressed genes (DEGs) compared to wild-type controls. These were enriched for genes functioning in the ribosome or mitochondria. Nearly all genes in the citric acid cycle and mitochondrial transport were downregulated in as3mt mutant livers. This resulted in reduction in reactive oxygen species levels by half and fatty liver in 81% of as3mt mutant larvae. An inverse expression pattern was detected for over 2,000 of the As3mt regulated DEGs in the liver of larvae with transgenic overexpression of As3mt in hepatocytes. Replacing as3mt expression in hepatocytes of as3mt mutants prevented fatty liver, demonstrating that As3mt has novel, cell-autonomous and arsenic-independent functions regulating mitochondrial metabolism. We suggest that these functions contribute to iAs toxicity, as the mitochondrial function genes that were downregulated in the liver of unexposed as3mt mutants were further downregulated upon iAs exposure and as3mt mutants were sensitized to iAs. This indicates that As3mt regulates hepatic energy metabolism and demonstrates that, in addition to its role in iAs detoxification, the physiological functions of As3mt contribute to arsenic toxicity. SIGNIFICANCEArsenic is an endemic environmental toxicant, and the current paradigm is that susceptibility to arsenic toxicity is dictated by levels of expression of the arsenite 3 methyltransferase gene (As3mt), which is dedicated enzyme involved in arsenic detoxification. Our data showing that As3mt serves arsenic-independent functions in energy metabolism challenge this paradigm. We show that zebrafish as3mt mutants have loss of mitochondrial function and develop fatty liver and suggest that as3mt mutants are sensitized to arsenic toxicity due, in part, to impaired mitochondrial function. This finding opens an entirely new area of study to identify the cellular function of As3mt and further advances the understanding of how genetic variants in As3mt confer sensitivity arsenic toxicology.

genetics↗

bioRxiv2019

Immune Profiling of Atherosclerotic Plaques Identifies Innate and Adaptive Dysregulations Associated with Ischemic Cerebrovascular Events

Atherosclerosis is driven by multifaceted contributions of the immune system within the circulation and at vascular focal sites. Yet the specific immune dysregulations within the atherosclerotic lesions that lead to clinical cerebro- and cardiovascular complications (i.e. ischemic stroke and myocardial infarction) are poorly understood. Here, using single-cell mass cytometry with Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) we found that atherosclerotic plaques were enriched in activated, differentiated, and exhausted subsets of T cells vs. blood. Next, using single-cell proteomic, transcriptomic, and cell-to-cell interaction analyses we found unique functional dysregulations of both T cells and macrophages in plaques of patients with clinically symptomatic (SYM; recent stroke of TIA) or asymptomatic (ASYM, no recent stroke) carotid artery disease. SYM plaques were enriched with a distinct CD4+ T cell subset, and T cells were activated, differentiated and presented subset specific exhaustion. SYM macrophages presented alternatively activated phenotypes including subsets associated with plaque vulnerability. In ASYM plaques, T cells and macrophages were activated and displayed a strong IL-1{beta} signaling across cell types, that was absent in SYM plaques. The identification of plaque-specific innate and adaptive immune dysregulations associated with cerebrovascular events provides the basis for the design of precisely tailored cardiovascular immunotherapies.

immunology↗