Biology subjects

Iyer, L.

Publications and source records attributed to Iyer, L..

7 recordsLinked to original sources

bioRxiv2025

Unveiling the Human Nasopharyngeal Microbiome Compendium: Systematic Characterization of Community Architecture and Function Through a Comprehensive Meta-Analysis

The nasopharyngeal microbiome is critical for respiratory health, yet its compositional architecture remains largely uncharacterized, underlying conflicting reports of increased, decreased, or unchanged diversity during infection. Here, we demonstrate that these contradictions arise from a fundamentally overlooked factor: the nasopharynx is organized into six reproducible nasopharyngeal community state types (NPCSTs) that are associated with intrinsic diversity baselines independent of disease status. By uniformly reprocessing 7,790 16S rRNA gene sequencing samples from 28 studies, we show that NPCSTs explain 52% of community variance, four-fold more than study effects, and that disease-diversity associations are attenuated by over 92% after NPCST adjustment. To identify genuine disease markers, we applied NPCST-aware differential abundance testing to SARS-CoV-2 as a case study. Leave-one-study-out (LOSO) cross-validation across 10 cohorts confirmed 13 reproducible taxa with opposing shifts: obligate anaerobes typically studied in other body compartments were enriched, while resident hub genera were depleted with high directional consistency across LOSO iterations. Co-occurrence network analysis independently validated this pattern, identifying the depleted taxa as structural backbone hubs across all NPCSTs. To bridge microbiome ecology and clinical application, we developed the Nasopharyngeal Microbiome Health Index (NMHI), a continuous community-level wellness score achieving AUC of 0.90 and 0.92 in internal and external validations, respectively, with robust performance across all six NPCSTs (AUC: 0.848-0.953). An independent clinical cohort of 147 specimens confirmed that these NPCST and NMHI characteristics are reproducible. Unlike binary classifiers, NMHI quantifies nasopharyngeal health along a spectrum, establishing NPCST-aware analysis as a foundation for precision respiratory microbiome research.

bioinformatics↗

bioRxiv2025

Neuroanatomical and behavioral characterization of corticotropin releasing factor-expressing lateral Habenula neurons in mice

The lateral habenula (LHb) is a critical hub for stress-related behaviors, yet the sources of its corticotropin-releasing factor (CRF) inputs remain poorly defined. Using high-resolution imaging, RNAscope, and viral tracing, we identified a novel, intrinsic population of CRF-expressing LHb neurons (LHbCRF). These neurons are primarily VGLUT2+, though a rostral subpopulation co-expresses GAD2. While chemogenetic activation of LHbCRF neurons did not impact place preference or anxiety-like behaviors, it selectively biased defensive strategies toward passive action-locking during the Visual Looming Shadow Test (VLST). Notably, this activation prolonged escape latencies in males and post-escape shelter stays in females. Electrophysiological and optogenetic characterization revealed significant sexual dimorphism: male LHbCRF neurons are more numerous and intrinsically excitable, whereas female LHbCRF neurons exhibit stronger local excitatory connectivity. These findings establish LHbCRF neurons as a sexually dimorphic circuit component that could modulate sex-specific defensive strategies under threat via divergent cellular and synaptic mechanisms between the sexes.

neuroscience↗

bioRxiv2024

Post-Critical Period Transcriptional and Physiological Adaptations of Thalamocortical Connections after Sensory Loss

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=95 SRC="FIGDIR/small/624130v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@100f64aorg.highwire.dtl.DTLVardef@29907corg.highwire.dtl.DTLVardef@cccd63org.highwire.dtl.DTLVardef@1c02318_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG Unilateral whisker denervation activates plasticity mechanisms and circuit adaptations in adults. Single nucleus RNA sequencing and multiplex fluorescence in situ hybridization revealed differentially expressed genes related to altered glutamate receptor distributions and synaptogenesis in thalamocortical (TC) recipient layer 4 (L4) neurons of the sensory cortex, specifically those receiving input from the intact whiskers after whisker denervation. Electrophysiology detected increased spontaneous excitatory events at L4 neurons, confirming an increase in synaptic connections. Elevated expression levels of Gria2 mRNA and functional GluA2 subunit of AMPA receptors at the TC synapse indicate the presence of stabilized and potentiated TC synapses to L4 excitatory neurons along the intact pathway after unilateral whisker denervation. These adaptations likely underlie the increased cortical activity observed in rodents during intact whisker sensation after unilateral whisker denervation. Our findings provide new insights into the mechanisms by which the adult brain supports recovery after unilateral sensory loss.

neuroscience↗

bioRxiv2023

Sex-dependent effects of angiotensin type 2 receptor expressing medial prefrontal cortex (mPFC) interneurons in fear extinction learning

BackgroundThe renin-angiotensin system (RAS) has been identified as a potential therapeutic target for PTSD, though its mechanisms are not well understood. Brain angiotensin type 2 receptors (AT2Rs) are a subtype of angiotensin II receptors located in stress and anxiety-related regions, including the medial prefrontal cortex (mPFC), but their function and mechanism in the mPFC remain unexplored. We therefore used a combination of imaging, cre/lox, and behavioral methods to investigate mPFC-AT2R-expressing neuron involvement in fear learning. MethodsTo characterize mPFC-AT2R-expressing neurons in the mPFC, AT2R-Cre/td-Tomato male and female mice were used for immunohistochemistry (IHC). mPFC brain sections were stained with glutamatergic or interneuron markers, and density of AT2R+ cells and colocalization with each marker was quantified. To assess fear-related behaviors in AT2R-flox mice, we selectively deleted AT2R from mPFC neurons using an AAV-Cre virus. Mice then underwent Pavlovian auditory fear conditioning, approach/avoidance, and locomotion testing. ResultsIHC results revealed that AT2R is densely expressed in the mPFC. Furthermore, AT2R is primarily expressed in somatostatin interneurons in females but not males. Following fear conditioning, mPFC-AT2R deletion impaired extinction in female but not male mice. Locomotion was unaltered by mPFC-AT2R deletion in males or females, while AT2R-deleted females had increased exploratory behavior. ConclusionThese results lend support for mPFC-AT2R+ neurons as a novel subgroup of somatostatin interneurons that influence fear extinction in a sex-dependent manner. This furthers underscores the role of mPFC in top-down regulation and a unique role for peptidergic (ie., angiotensin) mPFC regulation of fear and sex differences.

neuroscience↗

bioRxiv2023

The Impact of Chronic Phthalate Exposure on Rodent Anxiety and Cognition

There is a growing importance for environmental contributions to psychiatric disorders and understanding the impact of the exposome (i.e., pollutants and toxins). Increased biomonitoring and epidemiological studies, for example, suggest that daily phthalate chemical exposure contribute to neurological and behavioral abnormalities, however these mechanisms remain poorly understood. The current study therefore aimed to examine the effects of chronic phthalate exposure on rodent anxiety behaviors, cognition, and the impact on hypothalamic-pituitary{-} adrenal (HPA)-axis function. Adult male mice (C57BL6/J) were administered mono-2-ethylhexyl phthalate (MEHP) via drinking water (1 mg/ml), and anxiety-like behavior, cognition combined with HPA- axis and inflammatory assays were assessed after 3 weeks of MEHP exposure. MEHP-treated mice exhibited enhanced generalized anxiety-like behaviors, as demonstrated by reduced time spent in the open-arm of the elevated plus maze (EPM) and center exploration in the open field (OF). Tests of spatial, cognition and memory function were unchanged. Following MEHP administration, circulating levels of corticosterone and pro{-} inflammatory cytokines were significantly increased, while at the tissue level, MEHP-dependent reductions in glucocorticoid metabolism genes 11{beta}-hydroxysteroid dehydrogenase (11{beta}-HSD) 1 and 2. These data suggest that chronic MEHP exposure leads to enhanced generalized-anxiety behaviors independent of rodent measures of cognition and memory, which maybe driven by MEHP-dependent effects on HPA-axis and peripheral glucocorticoid metabolism function.

pharmacology and toxicology↗

bioRxiv2021

VCFCons: a versatile VCF-based consensus sequence generator for small genomes

We had developed VCFCons to address urgent need for a robust consensus sequence generator for SARS-CoV-2 viral surveillance, which presented several unique requirements, including: (a) low coverage areas should be noted with Ns, (b) low frequency or suspicious variant calls need to be filtered. We have found that, while some existing tools such as bcftools can generate the desired consensus sequence, it required multiple filtering steps and additional scripting. VCFCons can generate consensus sequences based on variant calls in a VCF format with versatile filtering criteria based on coverage and estimated variant frequency. We applied VCFCons to the Labcorp SARS-CoV-2 sequencing data and showed that it generated correct consensus sequences that were successfully submitted to GISAID and NCBI. We hope the community will find value in this tool and aim to continue developing VCFCons to handle more complex viral data in the future.

bioinformatics↗

bioRxiv2018

The unexpected provenance of components in eukaryotic nucleotide-excision-repair and kinetoplast DNA-dynamics from bacterial mobile elements

BackgroundProtein weaponry deployed in biological conflicts between selfish elements and their hosts are increasingly recognized as being re-purposed for diverse molecular adaptations in the evolution of several uniquely eukaryotic systems. The anti-restriction protein ArdC, transmitted along with the DNA during invasion, is one such factor deployed by plasmids and conjugative transposons against their bacterial hosts.\n\nResultsUsing sensitive computational methods we unify the N-terminal single-stranded DNA-binding domain of ArdC (ArdC-N) with the DNA-binding domains of the nucleotide excision repair (NER) XPC/Rad4 protein and Trypanosoma Tc-38 (p38) protein implicated in kinetoplast(k) DNA replication and dynamics. We show that the ArdC-N domain was independently acquired twice by eukaryotes from bacterial mobile elements. One gave rise to the beta-hairpin domains of XPC/Rad4 and the other to the Tc-38-like proteins in the stem kinetoplastid. Eukaryotic ArdC-N domains underwent tandem duplications to form an extensive DNA-binding interface. In XPC/Rad4, the ArdC-N domain combined with the inactive transglutaminase domain of a peptide-N-glycanase originally derived from an active archaeal version, often incorporated in systems countering invasive DNA. We also show that parallel acquisitions from conjugative elements and bacteriophages gave rise to the Topoisomerase IA, DNA polymerases IB-Ds, and DNA ligases involved in kDNA dynamics.\n\nConclusionsWe resolve two outstanding questions in eukaryote-biology: 1) origin of the unique DNA lesion-recognition component of NER; 2) origin of the unusual, plasmid-like features of kDNA. These represent a more general trend in the origin of distinctive components of systems involved in DNA dynamics and their links to the ubiquitin system.

genomics↗