Biology subjects

Chatterjee, S.

Publications and source records attributed to Chatterjee, S..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Heterogeneity of white matter structure in the human brain

White-matter, which contains the long-range axons connecting different brain regions, makes up nearly half the human brain, yet the three-dimensional organization of individual axons has not been characterized. While advances in diffusion MRI have enabled macroscopic mapping of major WM pathways1, these methods are unable to resolve individual axons: their trajectories, density, and relative orientations2. Here, we present a histological and imaging pipeline optimized for post-mortem human white-matter that shows the 3D trajectories of densely stained large (diameter greater than ~1 m) projection axons. Applying our approach to multiple centimeter-scale WM regions in an adult human brain, we observed striking regional diversity in axonal organization. Specifically, we identified distinct architectural motifs ranging from loosely packed, multi-orientation meshworks (in most superficial white matter), to laminar lattice-like structures (near the basal ganglia), to tightly packed bundles of fibers (e.g. in the corpus callosum). We speculate that these patterns reflect local adaptations to spatial constraints, axonal density, and the diversity of axonal sources and targets, offering region-specific solutions to anatomical optimization problems. These findings offer new insights into the principles shaping brain connectivity and underscore the need for regionally detailed atlases of human white matter..

neuroscience↗

bioRxiv2026

Plant-derived soft electrophiles upregulate pro-resolving oxylipins in a paraquat-induced Drosophila model of Parkinson's disease.

Age-accompanied chronic, low-grade systemic inflammation (inflammaging) drives the onset and progression of neurodegenerative disorders like Parkinsons disease (PD). Currently, no disease-modifying therapies are available for PD. Exposure to environmental toxicants, including paraquat (PQ), rotenone, and neurotoxic metals, increases disease risk. Conversely, sustained consumption of dietary soft electrophiles, such as flavonoids, carotenoids, vitamin E vitamers, and essential fatty acids, has been associated with increased lifespan and delayed age-related neurological decline. Omega-3 and select omega-6 fatty acids also serve as precursors of lipid-derived specialized pro-resolving mediators (SPMs), which exert potent anti-inflammatory and inflammation-resolving activities. Here, we report the development of a robust analytical method to quantify pro-resolving oxylipins in a PQ-induced Drosophila melanogaster model of PD, enabling investigation of how dietary phytochemicals modulate anti-inflammatory and pro-resolving lipid metabolism in vivo. We hypothesized that plant-derived soft electrophiles promote active resolution of neuroinflammation by enhancing the production of pro-resolving oxylipins derived from essential fatty acids, and that their neuroprotective effects are linked to their soft electrophilic properties. Our results demonstrate that specific lipophilic plant-derived soft electrophiles significantly upregulate pro-resolving oxylipins in Drosophila heads following PQ exposure. We identify a subset of flavones and structurally related phytochemicals that selectively enhance SPM biosynthesis and show that this response involves the NF-{kappa}B orthologue relish. Additionally, feeding modality and sex-specific dimorphisms were found to influence oxylipin production. Collectively, these findings indicate that structurally related dietary soft electrophiles enhance endogenous pro-resolving lipid pathways, promote resolution of toxin-induced neuroinflammation, and have potential preventive and therapeutic relevance for neuroinflammation-associated neurodegenerative diseases. HighlightsO_LIQuantification of pro-resolving lipids in a Drosophila Parkinsons model. C_LIO_LISpecific structural features of phytochemicals contribute to in vivo bioactivity. C_LIO_LILipophilic soft electrophiles show therapeutic potential against neuroinflammation. C_LIO_LIFeeding modality and sexual dimorphism also regulate oxylipin production. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/714080v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@2088cforg.highwire.dtl.DTLVardef@1f5d026org.highwire.dtl.DTLVardef@134aa44org.highwire.dtl.DTLVardef@965e28_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2026

Semantic-Aware Energy-Efficient Operation inSmart Capsule Endoscopy

Goal-oriented semantic communication has recently emerged in wireless sensor-actuator networks, emphasizing the meaning and relevance of information over raw data delivery, thereby enabling resource-efficient telecommunication. This paradigm offers significant benefits for intra-body or implantable sensor-actuator networks, including dramatic reductions in bandwidth requirements, latency, and power consumption. In this paper, we address a patch-based energy-efficient anomaly detection method for smart capsule endoscopy. We propose a deep learningbased algorithm that employs the similarity between features extracted from measured images and a reference (normal) image as the detection metric. The algorithm is evaluated using a clinical dataset of capsule-captured images, combined with a simulated intra-body channel model. The results demonstrate that even with only 60% of the transmission power (relative to a standard link design for QPSK modulation) and 65% of the light intensity, the probability of anomaly detection remains above 85%, and it gradually improves as power and illumination levels increase. This improvement translates into a potential battery life extension of over 43%. The findings highlight the potential of semanticaware, energy-efficient intra-body devices for more sustainable and effective medical interventions.

bioinformatics↗

bioRxiv2026

Mechanical Signaling Drives Tunneling Nanotubes to Preserve Cytoskeleton Tension and Lamin Integrity Against α-Synuclein-Induced Senescence in Astroglia

Astroglia can counteract the harmful effects of -synuclein (-SYN) protofibrils and reverse premature cellular senescence by promoting tunneling nanotubes (TNTs). However, the mechanism behind this recovery is unknown. This study is the first to examine TNT-mediated mechanical stability in senescent astroglial recovery. We demonstrate that disruption of Lamin A/C in -SYN-protofibrils-treated senescent cells reduces actin-cytoskeleton stress, as measured by nucleus flatness index and isometric scale factor from quantitative microscopy. ROCK (Rho-associated kinase) inhibition, which is crucial for reducing actin-cytoskeleton tension, promotes TNTs. Small molecules like Cytochalasin-D, Nocodazole, and Jasplakinolide, which inhibit TNTs by altering actin tension other than ROCK pathway, cannot reverse senescence. RNA-sequence heatmaps reveal changes in senescence-, integrin-, and ROCK-pathway genes; STRING links these to the Hippo pathway. Experimental results show that cytosolic YAP translocation, a key regulator of Hippo pathway, is vital for TNT formation and actin-based stability in U87-MG astrocytoma and primary astrocytes. Interestingly, TNTs form between two cells with different actin tensions: one exhibits low actin tension with Hippo signaling on, while the other has higher actin tension with Hippo signaling off. The most notable observation is the high abundance of YAP inside the TNTs, along with actin. The study shows that TNTs maintain mechanical stability through Lamin A/C integrity and actin tension in -SYN-induced senescent astroglia, thereby protecting the cells, reversing senescence. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/711517v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@192307dorg.highwire.dtl.DTLVardef@ad8b75org.highwire.dtl.DTLVardef@19ece78org.highwire.dtl.DTLVardef@1056395_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2026

Multi-omics definition of the sex-specific glycoproteome of murine tissues

Sex-specific differences in the glycoproteome remain poorly defined despite growing evidence that protein glycosylation is a key determinant of sex biology. Here we present a tissue-resolved glycoproteome atlas of adult male and female C57BL/6J mice, integrating transcriptomics, proteomics and glycoproteomics with sialic acid speciation and lectin microarray profiling across 19 tissues. Quantitative analysis of >26,800 protein- and site-specific N-glycoforms from 1,512 glycoproteins revealed highly distinct tissue glycoproteomes shaped by coordinated regulation of protein abundance and glyco-enzyme expression. Multi-omics integration identified strong glycophenotype-enzyme relationships, including control of tissue sialylation by Cmas and Cmah, suggesting rate-limiting roles in glycosylation. Pronounced sex-linked glycophenotypes were observed in salivary gland, liver and kidney, driven by differences in fucosylation, sialylation and protein abundance, whereas the brain glycome was largely conserved between sexes. An interactive online database (https://igcore.cloud/mta/atlas-viewer/) provides a resource for exploring sex-biased glycosylation across mouse tissues.

cell biology↗

bioRxiv2026

Sod1 trisomy causes ENS developmental defects and susceptibility to Hirschsprung disease via neuronal Ret suppression and glial remodeling

Down syndrome (DS; trisomy 21) confers a [~]100-fold increased risk of Hirschsprung disease (HSCR), yet the causal contributions of specific chromosome 21 genes remain unresolved. Here we show that increased dosage of SOD1 alone is sufficient to perturb enteric nervous system (ENS) development. We engineered a humanized SOD1 trisomic mouse line by inserting a 28 kb human SOD1 locus into ROSA26 and genetically profiled the distal colon at postnatal day 0 using single-cell RNA-seq and immunofluorescence. Sod1/SOD1 was elevated [~]1.5X in the ENS but varied by cell type, with transcriptionally active progenitors showing the greatest increase. Cell composition shifted toward transcriptionally active cells and glia, with concomitant loss of excitatory and inhibitory motor neurons and interneurons. Genetically, Sod1/SOD1 trisomy downregulated synaptic and neuronal communication programs but upregulated DNA replication/cell-cycle and genome maintenance pathways, especially within glia. Consequently, key HSCR genes were dysregulated: Ret, Ednrb, and Sema3c were decreased, while Sema3a ,a negative guidance cue, was increased. Ret was selectively reduced in inhibitory and excitatory motor neurons and progenitors, unchanged in glia, and reduced at the protein level in vivo. Within glia, Sod1/SOD1 was particularly elevated in proliferating/active glia with a glia-specific bias toward endogenous mouse Sod1 expression. Taken together, these data support a dual mechanism whereby increased Sod1/SOD1 dosage suppresses RET-dependent neurogenesis while independently promoting reactive/proliferative glial states. Thus, SOD1 is sufficient to alter ENS development significantly and provide the susceptibility substrate for HSCR with further reductions in RET gene expression leading to aganglionosis.

genomics↗

bioRxiv2026

KAMALA, a genome edited rice variety with improved yield by finetuning cytokinin oxidase activity released in India

Increasing yield is of major importance for Asian and African food security. Knock out mutants in the rice cytokinin oxidase gene CKX2 had shown potential for yield improvement. Here we explored whether subtle changes in CKX2 activity by editing FAD and cytokinin binding site sequences could improve the Indian mega-variety Samba Mahsuri. Knock out and single mutants in FAD and cytokinin binding sites induced by CRISPR/Cas12a caused moderate yield increases. Among 80 CKX2 alleles, five lines with in-frame mutations in both FAD and cytokinin binding domains produced even higher yield. One line, KAMALA, showed superior agronomic performance in 18 field locations (irrigated and rainfed ecologies) over three seasons in trials conducted by AICRPR (All India Coordinated Research Project on Rice), with an average 19% grain yield increase, early maturity, complete panicle emergence, and unaltered grain quality. KAMALA was registered as the first genome-edited variety ready for cultivation by Indian farmers.

plant biology↗

bioRxiv2026

Spatial Decoding of Tertiary Lymphoid Structure Maturation in Non-Small Cell Lung Cancer Using Deep Neural Networks

Understanding the role of tertiary lymphoid structures (TLS) is crucial in non-small cell lung cancer (NSCLC), as they are associated with patient prognosis and treatment outcomes. Specific cellular ecosystems that originate anti-tumor activity or predict immunotherapy response remain poorly characterized. To this end, we developed a high-resolution, multimodal spatial atlas jointly profiling transcriptomics, proteomics, and histology to characterize TLS maturation in NSCLC alongside secondary lymph organs as a baseline. Using this atlas, we proposed a pathologist-in-the-loop framework that combines a variational graph autoencoder (VGAE) with diffusion pseudotime to refine human expert annotations and characterize TLS maturation. These spatial molecular representations were extended to H&E whole-slide images via a vision transformer-based foundation model. Next, we resolved cellular composition, spatial organization, and cell-cell interactions within these data and defined two divergent spatial ecosystems. Clinical evidence suggests that these ecosystems are associated with distinct patient outcomes: a mature germinal center niche with favorable prognoses, and a tumor-macrophage-fibroblast niche with unfavorable prognoses. In summary, our work decodes key components of TLS heterogeneity, identifies hallmark spatial patterns involved in NSCLC adaptive immunity, and provides a framework for translating spatial omics insights into clinical applications.

genomics↗

bioRxiv2026

circDiscoverer: A resource for curated and predicted circRNA-Protein interactions with experimental support tools

Circular RNAs (circRNAs) regulate various cellular processes by interacting with miRNAs, proteins, and by encoding peptides. Compared to circRNA-miRNA interactions, circRNA-protein interactions (CPIs) and circRNA modifications have been relatively less explored. Here, we developed a comprehensive user-friendly web resource, CircDiscoverer, to explore CPIs and modification landscapes across multiple species, including Homo sapiens, Mus musculus, Drosophila melanogaster, and Arabidopsis thaliana. CircDiscoverer integrates manually curated literature-supported CPIs with computationally predicted interactions. Furthermore, it offers comprehensive insights into protein-binding profiles and detailed information on interacting circRNAs, including qRT-PCR primer sequences, guide RNAs for experimental validation and potential RNA modifications, thereby providing an integrated platform for further research. CircDiscoverer is available at https://aclab.iiserb.ac.in.

bioinformatics↗

bioRxiv2026

Mettl3-catalyzed m6A methylation determines CD8+ T cell differentiation fate in tumor

The heterogeneity in patient responses to immune checkpoint blockade (ICB) is dictated by the relative abundance of exhausted CD8 T cell (Tex) subsets with distinct therapeutic responsiveness. Progenitor exhausted (pTex) cells remain sensitive to ICB, whereas terminally exhausted (tTex) cells are refractory; however, the molecular cues that bias differentiation toward these divergent fates remain poorly defined. Here, we identify the RNA methyltransferase Mettl3 as a central regulator of Tex fate. Across murine tumor models, human T cells, and adoptive transfer systems, Mettl3 expression is selectively enriched in tTex cells and inversely correlated with TCF1 pTex populations. Mechanistically, Mettl3 drives terminal exhaustion by stabilizing DNMT3B transcripts via mA modification, enforcing CpG methylation and chromatin compaction at memory-associated loci. Inhibition of the Mettl3-Dnmt3b axis reprograms chromatin accessibility toward memory-like states, thereby preserving progenitor potential and effector function. Consequently, T cells lacking Mettl3-Dnmt3b activity persist longer, mount robust recall responses, and achieve superior tumor control with enhanced responsiveness to PD-1 blockade. These findings establish the Mettl3-mA-Dnmt3b axis as a molecular rheostat of CD8 T cell fate, coupling epitranscriptomic regulation to epigenetic remodeling, and reveal a tractable pathway to improve the durability of cancer immunotherapy.

immunology↗

bioRxiv2026

ReMeDy: A Flexible Statistical Framework For Region-based Detection of DNA Methylation Dysregulation

Region-based epigenome-wide association studies have demonstrated improved statistical power and bio-logical interpretability compared with probe-wise analyses of DNA methylation data. However, most existing region-based methods characterize methylation dysregulation primarily through changes in mean methylation levels associated with a phenotype of interest. Substantial evidence indicates that phenotype-associated methylation alterations may also manifest through changes in methylation variability or through joint shifts in mean and variability. Despite this, no existing statistical framework jointly models mean-variance methylation changes in a region-based manner. We propose ReMeDy, a flexible statistical framework that uses a hierarchical likelihood approach within a generalized linear model setting to identify differentially methylated regions, variably methylated regions, and regions exhibiting joint differential and variable methylation at a genome-wide scale. Unlike existing models, ReMeDy operates directly on biologically defined co-methylated regions, allowing it to naturally capture spatial correlation inherent in DNA methylation array data, while avoiding reliance on heuristic, user-defined tuning parameters such as smoothing spans and kernel bandwidths that can substantially influence results and introduce subjectivity. Through extensive simulation studies and comprehensive benchmarking against popular models, we demonstrate that ReMeDy maintains false discovery and type-I error rates at nominal levels while achieving consistently higher statistical power across a wide range of realistic scenarios. Application to population-level DNA methylation data further shows that ReMeDy identifies biologically meaningful regions and pathways implicated in complex human diseases that are not captured by conventional mean-based analyses alone. ReMeDy is implemented as an open-source R package and is freely available at https://github.com/SChatLab/ReMeDy.

genomics↗

bioRxiv2025

A spatially-aware unsupervised pipeline to identify co-methylation regions in DNA methylation data

DNA methylation (DNAm) plays a central role in modern epigenetic research; however, the high dimensionality of DNAm data comprising hundreds of thousands of spatially ordered probes continues to present major analytical challenges. The multiple testing burden in these data introduces redundancy and reduces statistical power, contributing to the limited reproducibility often observed in association studies. Moreover, DNAm probes frequently exhibit correlated methylation patterns with neighboring sites, reflecting underlying biological co-regulation and spatial dependence along the genome. Ignoring these spatial correlations can bias parameter and standard error estimates, inflate type I error rates, and obscure biologically meaningful effects. Existing methods for detecting methylation co-regulation and reducing DNAm data dimensions, typically rely on fixed distance or correlation thresholds and arbitrary hyperparameter settings that lack data adaptivity. In this study, we introduce SACOMA (Spatially-Aware Clustering for Co-Methylation Analysis), a flexible, data-driven, and unsupervised framework designed to identify co-methylated regions which are genomic regions where adjacent sites show correlated methylation levels. SACOMA employs spatially constrained hierarchical clustering to group neighboring DNAm sites based on both spatial proximity and methylation similarity. A tunable, data-adaptive mixing parameter allows SACOMA to avoid rigid assumptions and remain robust to hyperparameter choices. Although developed for DNAm array data, SACOMA provides a generalizable framework applicable to any data exhibiting spatial dependence, enabling the identification of spatially correlated features across diverse domains. Through extensive simulations, SACOMA demonstrated superior sensitivity while maintaining effective false-positive control compared to existing methods. In population-level DNAm data analyses, SACOMA successfully identified biologically relevant co-regulated methylation regions with functional roles. Overall, SACOMA reduces the multiple-testing burden and enhances both the discovery and specificity of statistical associations, leading to improved reproducibility and more reliable biological inference.

bioinformatics↗

bioRxiv2025

A switch from histone methyltransferase-EZH2 to demethylase KDM6A activity marks reinitiation of proliferation of drug treated colorectal cancer cells

Colorectal cancer (CRC) is one of the deadliest cancers, ranking third in cancer incidence worldwide. These tumor cells often adopt unique strategies under drug stress to attain a reversible drug-tolerant state and evade cell death. However, the molecular adaptations associated with this transitory emergence of the drug-tolerant state remain elusive. Herein, epigenetic alterations often dictate such reversible dynamic changes, and this study aims to characterize the role of specific epigenetic modifiers governing CRC cell survival under drug pressure and their subsequent relapse. We observed that under drug stress there is a drastic increase in the histone-repressive mark-H3K27me3, linked to an enhanced expression of EZH2 driving transcriptional inhibition of cell proliferation-associated genes and a proliferative arrest. Interestingly, drug-induced oxidative stress increased the expression of the P65 protein, which was found to interact and regulate EZH2 expression. Quenching of ROS, drug vacation, or P65 inactivation compromised EZH2 activity concurrent with a re-initiation of cell proliferation. Interestingly, this reversal to proliferative state was associated with an elevated activity of the histone lysine demethylase-KDM6A. The promoter elements of the proliferative genes were now occupied by KDM6A instead of EZH2. Accordingly, a genetic knockdown or pharmacological inhibition of KDM6A in vitro not only resulted in increased cell death but also prevented emergence of the re-proliferative CRC cells. Furthermore, KDM6A inhibition in combination with chemotherapy drug, resulted in an increased tumor regression in vivo. Our study thus highlights the importance of KDM6A as a therapeutic target in preventing CRC growth and relapse which can have future therapeutic implications.

cancer biology↗

bioRxiv2025

A cytokinin-auxin antagonistic module regulates nitrogen-triggered tiller outgrowth in rice

Tillering is a key trait that shapes aboveground architecture and directly contributes to rice yield. However, integration of environmental cues to genetic regulators for controlling tiller outgrowth remains poorly understood. We investigated the effects of nitrogen, one of the critical environmental factors, on the early stages of tiller bud outgrowth. Comprehensive temporal transcriptomic analyses in response to two nitrogen forms, nitrate (NO -) and ammonium (NH +), identified gene-regulatory networks for nitrogen-triggered tiller outgrowth, with phytohormone signaling as the central interface. Pharmacological, molecular, and genetic experiments established cytokinin-auxin antagonism as a central regulator of the nitrogen-mediated tillering. Cytokinin promoted bud outgrowth by repressing the TCP transcription factor OsTB1, the key inhibitor of tillering, via Cytokinin Response Factors OsERF53/54. OsERF53/54 further reduced polar auxin transport by repressing OsPIN1a to promote bud activation. Conversely, auxin promoted bud dormancy by inducing OsTB1 and OsPIN1a via OsARF11/16. Both NO - and NH + triggered tiller outgrowth and induced largely overlapping transcriptional responses, with a temporal delay for NO -. Adequate nitrogen supplies induced cytokinin signaling while inhibiting auxin signaling and transport in tiller buds, thereby triggering bud outgrowth. Together, we identify a key regulatory role of auxin-cytokinin antagonistic module for integrating nitrogen signals to determine tiller bud fate.

plant biology↗

bioRxiv2025

Erucamide regulates retinal neurovascular crosstalk

Neurovasculoglial crosstalk is critical in establishing and maintaining a functional neurovascular unit. Breakdown in the unit is central to many neurodegenerative disorders of the CNS of which the retina is a component. A growing literature indicated that primary fatty acid amides (PFAMs) can regulate this crosstalk between vasculature and neuronal tissues. In this study we describe a central role for erucamide, a 22:1 mono-unsaturated omega-9 fatty acid amide, in degenerating retinal tissues. Using high-resolution global mass spectrometry-based metabolomics, we cataloged metabolites in murine models of retinal degeneration and show that while PFAMs, in general, are highly dysregulated, erucamide is the one most significantly diminished during photoreceptor atrophy. Using rodent models of retinal degeneration and novel organosilane-modified porous silicon nanoparticles (pSiNPs) for the in vivo delivery of erucamide, we demonstrate that erucamide activates CD11b+ myeloid cells, leading to the upregulation of angiogenic and neurotrophic cytokines that stabilize retinal degeneration. We identified TMEM19 as a novel binding protein for erucamide that is crucial for human iPSC-derived macrophage precursor cells activation and subsequent neurotrophic and angiogenic factor production. These findings reveal a previously unknown PFAM pathway that is modulated during retinal degenerative diseases, demonstrating that erucamide or functional analogues and their action through TMEM19 may be useful as a therapeutic alternative to neuroprotective and stem cell-based approaches for the treatment of retinal degenerative diseases.

neuroscience↗

bioRxiv2025

Sequence-Specific Installation of Aryl Groups in RNA via DNA-Catalyst Conjugates

Installing functional groups at specific sites in existing RNA molecules remains a challenge for modification, labeling, and therapeutic strategies. Here we describe the use of DNA oligonucleotides carrying a catalytic amine group to effect the aqueous SNAr arylation of 2'-OH groups at sequence-complementary sites in RNAs. Chloro-pyrimidine electrophiles are shown to react with amino-DNA conjugates, resulting in a proposed transient ammonium aryl intermediate that can react with RNA near the DNA binding site, delivering the heterocycle to the RNA in high yields. In a test of utility, we construct an aryl electrophile carrying an azide group, and apply this strategy to fluorescently label messenger RNAs locally at the polyA tail. We also employ the approach to direct in vitro arylation in the coding region of a messenger RNA, knocking down protein expression selectively in the presence of another coding RNA. This sequence-directed catalytic strategy enables multiple applications in RNA labeling and modification.

biochemistry↗

bioRxiv2025

Spatial transcriptomic profiling uncovers the molecular effects of the neurotoxicant polychlorinated biphenyls (PCBs) in the brains of adult mice

Environmental toxicants, such as polychlorinated biphenyls (PCBs), are highly stable synthetic organic compounds that are present in air, water, and soil. PCBs have been identified in post-mortem human brains of individuals with neurodegenerative diseases, indicating a possible link between environmental factors and disease risk. Research has revealed an association between PCB exposure and cognitive decline. Therefore, it is crucial to evaluate how PCB mixtures relevant to humans affect brain function and cognition. To investigate the effects of PCBs on memory and transcriptomic profiles, we exposed adult male C57BL/6J mice orally to a synthetic PCB mixture daily. After seven weeks of exposure, the mice were assessed in a spatial object recognition task (SOR) to evaluate long-term spatial memory. Our findings showed that mice exposed to PCBs exhibited deficits in long-term spatial memory. To examine the molecular effects of PCB on the brain, we used a spatial transcriptomics technique to analyze gene expression changes in five brain regions: the hippocampus, neocortex, thalamus, caudal putamen, and fiber tracts. Our analysis of spatial gene expression revealed the molecular signatures influenced by PCB in these susceptible brain regions of mice. Network analysis suggests that these changes are associated with higher chlorinated PCBs present in the brain. Additionally, we show that PCB exposure disrupts the expression of tight junction proteins, which are crucial for maintaining the integrity of the blood-brain barrier (BBB). Thus, our results offer mechanistic insights into how PCB exposure affects brain function and cognition.

neuroscience↗

bioRxiv2025

Psychrophilic and cryophilic bacterial copiotrophs from a Trans-Himalayan lake-desert ecosystem as biogeothermometers of warming, mitigators of perturbation, and candidates for biodegradation

A Trans-Himalayan lake-desert ecosystem was explored for the low-to-high temperature adaptations of native copiotrophic psychrophiles that have the potentials for rendering substantive carbon remineralization under natural and/or anthropogenically influenced conditions of high organic matter delivery to the environment. Overall 27 species, classified across 15 genera of Actinomycetota, Bacillota, Bacteroidota, and Pseudomonadota, were isolated from the brackish-water and sediment-surface of Tso Moriri (a massive lacustrine body on the Changthang plateau that remains frozen for approximately one third of the year), and the fine talus covering a lake-side rocky mountain. In Luria broth, all the isolates grew at 4{degrees}C and 15{degrees}C; 13 of them grew, while 14 retained 19-99% cells in metabolically-active state, at -10{degrees}C; 23, 11, and none grew at 28{degrees}C, 37{degrees}C, and 42{degrees}C respectively. A Cryobacterium was most heat-susceptible, whereas some -10{degrees}C-growing Arthrobacter, Microbacterium, Paenarthrobacter, Pseudomonas and Streptomyces were most warming-resilient, among the present isolates. Catabolizing different simple/complex organic compounds, all isolates accomplished low/moderate/high growths at 4{degrees}C; 20 performed low growths at -10{degrees}C. Taxonomy/phylogeny did not determine the isolates growth/survival across the temperature-range tested. Lake-water and rock-dust isolates had the widest, while lake-sediment-dwellers had the narrowest, temperature-window for growth/survival. Rock-dust and lake-water isolates had more genes for low and high temperature adaptations, compared to the lake-sediment isolates. In co-cultures, most actinobacterial isolates inhibited the growth of mesophilic bacteria from warmer ecosystems, plus non-actinobacteria and actinobacteria from native/adjoining habitats. The data hold implications for biodegradation in cold/frigid territories, negative feedback control/reversal of warming, and microbiome protection from infiltration amidst climate change. IMPORTANCEPhylogenetically diverse, cold-adapted copiotrophic bacteria were retrieved from a Trans-Himalayan lake-desert ecosystem, and tested for chemoorganoheterotrophic growth at temperatures between -10{degrees}C and 42{degrees}C. Albeit growth dwindled at [≥]28{degrees}C, most of the isolates thrived on simple as well as complex organic substances under freezing condition, which makes them prospective constituents of biodegradation reactors suitable for high-altitude/latitude deployment. In the natural habitats of the psychrophilic isolates, cessation of organotrophic activities at elevated temperatures would stop simple fatty acids and CO2 production, which in turn would preempt methanogenesis, undo greenhouse effect, and reverse environmental thawing (usher cooling). Such negative feedback control of homeostasis is fraught with the danger of microbiome takeover by thermally-better-adapted foreign organisms. Consequently, ecosystem preservation rests on the native microfloras ability to resist external invasion. At 28{degrees}C, majority of the actinobacterial isolates inhibited bacteria from discrete higher-temperature ecosystems; they can, therefore, be viewed as the defenders of the cold/frigid ecosystem.

microbiology↗