Biology subjects

Pathak, A.

Publications and source records attributed to Pathak, A..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Bioprospecting Native Oleaginous Microalgae for Wastewater Nutrient Remediation and Lipid Production

Subtropical climate in Florida offers a unique opportunity for sustainable biofuel production using native microalgae cultivated in untreated wastewater. This study bioprospected oleaginous microalgal consortia from a wastewater holding tank at the Thomas P. Smith Water Reclamation Facility in Tallahassee, Florida, aiming to identify strains capable of both nutrient remediation and lipid accumulation. Using Fluorescence Activated Cell Sorting (FACS), chlorophyll-containing cells were isolated and cultured on BG-11 media. Shotgun metagenomics revealed that the most robust consortia- labeled C3, C4, and C9, were dominated by Chlamydomonas, Acutodesmus, and Volvox spp., alongside diverse bacterial, fungal, and archaeal communities. Functional gene analysis indicated active pathways for photosynthesis, lipid biosynthesis, and nutrient assimilation. In microcosm experiments, these consortia achieved up to 100% ammonia, 95% phosphorus, and 89% nitrate removal, outperforming control treatments. Lipid screening confirmed significant accumulation, with consortium C9 showing the highest yield. These findings underscore the potential of native microalgal consortia for integrated wastewater treatment and biofuel production, advancing circular bioeconomy strategies for subtropical regions.

microbiology↗

bioRxiv2025

Highly Pathogenic Avian Influenza A (H5N1) Clade 2.3.2.1a virus infection in domestic cats, India, 2025

In January 2025, the highly pathogenic avian influenza A(H5N1) virus clade 2.3.2.1a infection was detected in domestic cats and whole-genome sequencing of two cat H5N1 isolates was performed using the Oxford Nanopore MinION sequencing platform. Phylogenetic analysis revealed the circulation of triple reassortant viruses in cats. Although cat viruses lacked classic mammalian adaptation markers they carried mutations associated with enhanced polymerase activity in mammalian cells and increased affinity for 2-6 sialic acid receptor suggesting their potential role in facilitating infection in cats. The identification of reassortant HPAI H5N1 clade 2.3.2.1a viruses in domestic cats in India highlights the urgent need for enhanced surveillance in domestic poultry, wild birds, and mammals, including humans, to track genomic diversity and molecular evolution of circulating strains.

microbiology↗

bioRxiv2024

Beyond associations: A benchmark Causal Relation Extraction Dataset (CRED) of disease-causing genes, its comparative evaluation, interpretation and application

Information on causal relationships is essential to many sciences, including biomedical science, and beneficial (e.g., causative rather than merely associative gene-disease relations can lead to better treatments). Despite much work on Relation Extraction (RE), automatically extracting causal relations from large text corpora remains less explored. Few existing studies on CRE (Causal RE) are limited to extracting causality within a sentence or for a particular disease, mainly due to the lack of a diverse benchmark dataset. Here, we carefully curate a new CRE Dataset (CRED) of 3639 (causal and non-causal) gene-disease pairs, spanning 204 diseases and 500 genes, within or across sentences of 267 published abstracts. CRED is assembled in two phases to reduce class imbalance, and its inter-annotator agreement is 89%. To assess CREDs utility in classifying causal vs. non-causal pairs, we compared multiple classifiers and found SVM (Support Vector Machine) trained on embeddings from a deep learning transformer model called BioBERT to perform the best (F1 score 0.70). CRED outperformed a state-of-the-art RE dataset in terms of classifier performance and model interpretability, i.e., whether the model focuses importance/attention on words with causal connotations in abstracts. Moving from benchmark to real-world settings, application of our CRED-trained BioBERT+SVM model on all PubMed abstracts on Parkinsons disease (PD) revealed both well- and less-studied PD-causing genes. For instance, genes predicted to be causal for PD in at least 50 abstracts by our model were already linked to PD in books; and lends confidence to further explore the other genes predicted to be causal in fewer abstracts. Our systematically curated and evaluated CRED, and its associated classification model and gene-disease causality scores, thus offer concrete resources for advancing future research in CRE from biomedical literature.

bioinformatics↗

bioRxiv2024

A pontine-specific axonal niche supports de novo gliomagenesis

Diffuse intrinsic pontine gliomas (DIPGs), a major type of pediatric high-grade gliomas located in the pons, are the leading cause of death in children with brain cancer. A subset (20-25%) of DIPGs harbor a lysine 27-to-methionine (K27M) mutation in HIST1H3B, which encodes histone H3.1, and an activating ACVR1 mutation. The occurrence of this pair of mutations in DIPGs, but not in pediatric gliomas in other anatomical locations, suggests the existence of a pontine-specific niche that favors DIPG gliomagenesis. Unfortunately, the identity of the underlying pontine niche remains elusive as available mouse models fail to recapitulate the anatomic specificity that characterizes DIPGs. Herein we show that the trigeminal root entry zone (TREZ), a pontine structure where several major axon tracts intersect, is enriched with proliferating oligodendrocyte-lineage cells during brainstem development. Introducing both H3.1K27M and activating Acvr1 and Pik3ca mutations (which co-occur frequently with H3.1K27M in human DIPGs) into the mouse brain leads to rapid gliomagenesis. This pathology recapitulates the pons specificity of DIPGs as glioma cells proliferate on axon tracts at the TREZ. We further show that a hyaluronan receptor important for cell stemness (HMMR) plays a key role in glioma cell proliferation at the TREZ. We propose that H3.1K27M and its co-occurring mutations drive pontine specific gliomagenesis by inducing a proliferative response of oligodendrocyte-lineage cells with enhanced stemness on large TREZ axon tracts. One-Sentence SummaryThe trigeminal root entry zone underlies pontine-specific gliomagenesis driven by H3.1K27M and its co-occurring mutations.

cancer biology↗

bioRxiv2024

γ-aminobutyric acid receptor B signaling drives glioblastoma in females in an immune-dependent manner

Sex differences in immune responses impact cancer outcomes and treatment response, including in glioblastoma (GBM). However, host factors underlying sex specific immune-cancer interactions are poorly understood. Here, we identify the neurotransmitter {gamma}-aminobutyric acid (GABA) as a driver of GBM-promoting immune response in females. We demonstrated that GABA receptor B (GABBR) signaling enhances L-Arginine metabolism and nitric oxide synthase 2 (NOS2) expression in female granulocytic myeloid-derived suppressor cells (gMDSCs). GABBR agonist and GABA analog promoted GBM growth in females in an immune-dependent manner, while GABBR inhibition reduces gMDSC NOS2 production and extends survival only in females. Furthermore, female GBM patients have enriched GABA transcriptional signatures compared to males, and the use of GABA analogs in GBM patients is associated with worse short-term outcomes only in females. Collectively, these results highlight that GABA modulates anti-tumor immune response in a sex-specific manner, supporting future assessment of GABA pathway inhibitors as part of immunotherapy approaches.

cancer biology↗

bioRxiv2024

3D Imaging Reveals Changes in the Neurovascular Architecture of the Murine Calvarium with Aging

Calvarial nerves, along with vasculature, influence skull formation during development and following injury, but it remains unclear how calvarial nerves are spatially distributed during postnatal growth and aging. Studying the spatial distribution of nerves in the skull remains challenging due to a lack of methods to image and quantify 3D structures in intact bone. To visualize calvarial 3D neurovascular architecture, we imaged nerves and endothelial cells with lightsheet microscopy. We employed machine-learning-based segmentation to facilitate high-resolution characterization from post-natal day 0 (P0) to Week 80 (80wk). We found that TUBB3+ nerve density decreased with aging with the frontal bone demonstrating earlier onset age-related nerve loss than the parietal bone. In addition, nerves in the periosteum and dura mater exhibited similar yet distinct temporal patterns of nerve growth and loss. While no difference was observed in TUBB3+ nerves during skeletal maturation (P0 {longrightarrow} 12wk), we did observe an increase in the volume of unmyelinated nerves in the dura mater. Regarding calvarial vasculature, larger CD31hiEmcn- vessel density increased with aging, while CD31hiEmcnhi vessel density was reduced. For all nerve markers studied, calvarial nerves maintained a preferential spatial association with CD31hiEmcnhi vessels that decreased with aging. Additionally, we used a model of Apert syndrome that demonstrates early coronal suture fusion to explore the impact of suture-related disease on neurovascular architecture. We identified a mild dysregulation of dural nerves and minor shifts in vessel populations. Collectively, this 3D, spatiotemporal characterization of calvarial nerves throughout the lifespan and provides new insights into age-induced neurovascular architecture.

bioengineering↗

bioRxiv2024

Emotion arousal but not valence is strongly represented in aperiodic EEG activity stemming from thalamocortical interactions

Oscillatory EEG signals contain both periodic and aperiodic (1/f components), segregating which is important for gaining insights into the underlying neural computations. Several studies have explored the periodic features underlying neural basis of emotion processing, while 1/f component is less explored. Hence, the present study sought to determine whether seeing emotionally laden music video clips have an impact on aperiodic components along with the periodic components and their underlying basis by conceptualizing a biophysically realistic computational model. Using the publicly available Data for Emotional Analysis using Physiological Signals (DEAP) dataset we elucidate that there is a significant increase in exponent and offset of aperiodic background during high arousal compared to low arousal trials. In contrast, there were no discernible variations between the aperiodic components during the high and low valence categories. In high arousal, we also discovered reduction in alpha power in line with previous studies. Finally, to elucidate the underlying mechanisms, we employed a biophysically realistic and previously established thalamo-cortical model of neural field activity, which which allowed us to characterize that heightened emotional arousal appears emerge from an increased cooperation in information communication between neuronal populations in reticular and relay nuclei of thalamus. Significance statementDissociation of emotion and valence and arousal is an established theory in affective neuroscience. Are these dimensions represented in aperiodic background of macrocscopic electrophysiological scales of EEG? We sought to ask this question in the publicly available DEAP data. Our findings of increased aperiodic components during high arousal in contrast to low arousal suggest heightened neural activity alongside an inhibitory influence. Using a neural field model of thalamo-cortical interactions reveals a mechanistic approach that suggests heightened arousal corresponds to an enhanced inhibitory coupling between thalamic reticular and relay neuronal populations. In essence, this study advances our understanding of the intricate relationship between electrophysiological signals and emotion dimensions, shedding light on the mechanisms underlying arousal-related emotional responses.

neuroscience↗

bioRxiv2024

Oviposition status and sugar availability influence measures of transmission potential in malaria-infected mosquitoes.

BackgroundLike other oviparous organisms, the gonotrophic cycle of mosquitoes is not complete until they have selected a suitable habitat to oviposit. In addition to the evolutionary constraints associated with selective oviposition behavior, the physiological demands relative to an organisms oviposition status also influences their nutrient requirement from the environment. Yet, studies that measure transmission potential (vectorial capacity or competence) of mosquito-borne parasites rarely consider if the rates of parasite replication and development could be influenced by these constraints resulting from whether mosquitoes have completed their gonotrophic cycle. MethodsAnopheles stephensi mosquitoes were infected with Plasmodium berghei the rodent analog of human malaria and maintained on 1% or 10% dextrose and either provided oviposition sites ( oviposited herein) to complete their gonotrophic cycle or forced to retain eggs ( non-oviposited). Transmission potential in the four groups was measured up to 27 days post-infection as 1) the rates of vector survival, 2) rates of sporozoite migration to the salivary glands ( extrinsic incubation period or EIP), and 3), sporozoite densities. ResultsIn the two groups of oviposited mosquitoes, rates of sporozoite migration and densities in the salivary glands were clearly higher in mosquitoes fed 10% dextrose. In non-oviposited mosquitoes however, rates of sporozoite migration and densities were independent of sugar concentrations, although both measures were slightly lower than oviposited mosquitoes fed 10% dextrose. Rates of vector survival were higher in non-oviposited mosquitoes. ConclusionsTaken together, these results suggest vectorial capacity for malaria parasites may be dependent on nutrient availability and oviposition/gonotrophic status and as such, argue for more careful consideration of this interaction when estimating transmission potential; costs to parasite fitness and vector survival were buffered against changes in nutritional availability from the environment in non-oviposited mosquitoes, but not oviposited mosquitoes. In general, however, these patterns suggest parasite fitness may be dependent on complex interactions between physiological (nutrition) and evolutionary (egg-retention) trade-offs in the vector, with potential implications for disease transmission and management. For instance, while reducing availability of oviposition sites and environmental sources of nutrition are key components of integrated vector management strategies, their abundance and distribution is under strong selection pressure from the patterns associated with climate change. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/577126v2_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@152dd45org.highwire.dtl.DTLVardef@13d140forg.highwire.dtl.DTLVardef@efeb93org.highwire.dtl.DTLVardef@15312d7_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2023

Metastability indexes global network effects post brain stimulation

Several studies have shown that coordination among neural ensembles is a key to understand human cognition. A well charted path is to identify coordination states associated with cognitive functions from spectral changes in the oscillations of EEG or MEG. A growing number of studies suggest that the tendency to switch between coordination states, sculpts the dynamic repertoire of the brain and can be indexed by a measure known as metastability. In this article, we characterize perturbations in the metastability of global brain network dynamics following Transcranial Magnetic Stimulation that could quantify the duration for which information processing is altered, thus, allowing researchers to understand the network effects of brain stimulation, standardise stimulation protocols and design experimental tasks. We demonstrate the effect empirically using publicly available datasets and use a digital twin (a whole brain connectome model) to understand the dynamic principles that generate such observations. We observed a significant reduction in metastability, concurrent with an increase in coherence following single-pulse TMS reflecting the existence of a window where neural coordination is altered. The reduction in complexity was validated by an additional measure based on the Lempel-Ziv complexity of microstate labelled EEG data. Interestingly, higher frequencies in the EEG signal showed faster recovery in metastability than lower frequencies. The digital twin shed light on how the phase resetting introduced by the single-pulse TMS in local cortical networks can propagate globally across the whole brain and give rise to changes in metastability and coherence.

neuroscience↗

bioRxiv2023

New learning principles emerge from biomimetic computational primitives

Although computational models have deepened our understanding of neuroscience, it is still highly challenging to link actual low-level physiological activity (spiking, field potentials) and biochemistry (transmitters and receptors) with high-level cognitive abilities (decision-making, working memory) nor with corresponding disorders. We introduce an anatomically-organized multi-scale model directly generating simulated physiology from which extended neural and cognitive phenomena emerge. The model produces spiking, fields, phase synchronies, and synaptic change, directly generating working memory, decisions, and categorization, all of which were then validated on extensive experimental macaque data from which the model received zero prior training of any kind. Moreover, the simulation uncovered a previously unknown neural code specifically predicting upcoming erroneous ("incongruous") behaviors, also subsequently confirmed in empirical data. The biomimetic model thus directly and predictively links novel decision and reinforcement signals, of computational interest, with novel spiking and field codes, of potential behavioral and clinical relevance.

neuroscience↗

bioRxiv2023

Microbiome Analysis of the Eastern Oyster As a Function of Ploidy and Seasons

Shellfish, such as the eastern oysters (Crassostrea virginica) are not only valued as seafood but also for the ecosystem services they provide, including improving water quality and reducing eutrophication. Excess N causes eutrophication, harmful algal blooms, fish kills and overall decline of estuarine ecosystems resulting in economic losses. Oyster reefs sequester N and enhance denitrification processes, however, information on the N cycling oyster microbiome is scarce with most studies focusing on random grab samples or on pathogens, such as Vibrio spp. Further, triploid oysters are often used for aquaculture, as they grow faster than diploids, but there is little information on potential microbiome differences with ploidy. To address these knowledge gaps, diploid and triploid farmed oysters were collected at monthly intervals over one year and analyzed using a coupled approach encompassing shotgun metagenomics and quantitative microbial elemental cycling (QMEC) qPCR assays. Overall, the genus Psychrobacter dominated the core microbiome across all samples, regardless of season or ploidy, followed by Synechococcus, Pseudomonas, Pseudoalteromonas and Clostridium. Psychrobacter abundances increased significantly in the colder months; the same trend was also observed in the alpha and beta diversity. However, warmer months had increased bacterial diversity relative to colder months. Gene functional profiles were similar among seasons and ploidy, with respiration and metabolism of carbohydrates, RNA, and proteins as dominant functions. There were strong positive correlations between abundance of the "core" microbiome taxa and gene functions associated with central metabolism, DNA and carbohydrate metabolism, strongly suggesting the functional role of Psychrobacter in the microbiome. Metagenome assembly was performed to characterize dominant species, followed by phylogenetic analysis of select MAGs (metagenome-assembled genomes), further supporting the presence of multiple Psychrobacter spp. Sequence-based identification of denitrification genes in the Pyschrobacter MAGs indicated the presence of norB, narH, narI, nirK, and norB. QMEC analysis indicated C and N cycling genes were most abundant, with no discernable patterns due to seasons or ploidy. Among N cycling genes, the nosZII clade was dominant, which is likely responsible for the eastern oysters potential for bioextraction and enhancing water quality via denitrification.

microbiology↗

bioRxiv2023

Transitions in density, pressure, and effective temperature drive collective cell migration into confining environments

Epithelial cell collectives migrate through tissue interfaces and crevices to orchestrate processes of development, tumor invasion, and wound healing. Naturally, traversal of cell collective through confining environments involves crowding due to the narrowing space, which seems tenuous given the conventional inverse relationship between cell density and migration. However, physical transitions required to overcome such epithelial densification for migration across confinements remain unclear. Here, in contiguous microchannels, we show that epithelial (MCF10A) monolayers accumulate higher cell density before entering narrower channels; however, overexpression of breast cancer oncogene +ErbB2 reduced this need for density accumulation across confinement. While wildtype MCF10A cells migrated faster in narrow channels, this confinement sensitivity reduced after +ErbB2 mutation or with constitutively-active RhoA. The migrating collective developed pressure differentials upon encountering microchannels, like fluid flow into narrowing spaces, and this pressure dropped with their continued migration. These transitions of pressure and density altered cell shapes and increased effective temperature, estimated by treating cells as granular thermodynamic system. While +RhoA cells and those in confined regions were effectively warmer, cancer-like +ErbB2 cells remained cooler. Epithelial reinforcement by metformin treatment increased density and temperature differentials across confinement, indicating that higher cell cohesion could reduce unjamming. Our results provide experimental evidence for previously proposed theories of inverse relationship between density and motility-related effective temperature. Indeed, we show across cell lines that confinement increases pressure and effective temperature, which enable migration by reducing density. This physical interpretation of collective cell migration as granular matter could advance our understanding of complex living systems.

biophysics↗

bioRxiv2023

Epithelial multicellular clustering enabled by polarized macrophages on soft matrices

Formation of epithelial structures of variegated geometries and sizes is essential for organogenesis, tumor growth, and wound repair. Although epithelial cells are predisposed with potential for multicellular clustering, it remains unclear whether immune cells and mechanical cues from their microenvironment influence this process. To explore this possibility, we co-cultured human mammary epithelial cells with pre-polarized macrophages on soft or stiff hydrogels. In the presence of M1 (proinflammatory) macrophages on soft matrices, epithelial cells migrated faster and subsequently formed larger multicellular clusters, compared to co-cultures with M0 (unpolarized) or M2 (anti-inflammatory) macrophages. By contrast, stiff extracellular matrix (ECM) disabled active clustering of epithelial cells due to their enhanced migration and cell-ECM adhesion, regardless of macrophage polarization. We found that the co-presence of soft matrices and M1 macrophages reduced focal adhesions, but enhanced fibronectin deposition and non-muscle myosin-IIA expression, which altogether optimize conditions for epithelial clustering. Upon Rho-associated kinase (ROCK) inhibition, epithelial clustering was abrogated, indicating a requirement for optimized cellular forces. In these co-cultures, Tumor Necrosis Factor (TNF)- secretion was the highest with M1 macrophages and Transforming growth factor (TGF)-{beta} secretion was exclusively detectable in case of M2 macrophages on soft gels, which indicated potential role of macrophage secreted factors in the observed epithelial clustering. Indeed, exogenous addition of TGB-{beta} promoted epithelial clustering with M1 co-culture on soft gels. According to our findings, optimization of both mechanical and immune factors can tune epithelial clustering responses, which could have implications in tumor growth, fibrosis, and would healing. SummaryAuthors show proinflammatory macrophages on soft matrices enable epithelial cells to form multicellular clusters. This phenomenon is disabled on stiff matrices due to increased stability of focal adhesions. Inflammatory cytokine secretion is macrophage-dependent, and external addition of cytokines accentuates epithelial clustering on soft matrices. Impact StatementFormation of multicellular epithelial structures is critical to tissue homeostasis. However, it has not been shown how the immune system and mechanical environment affect these structures. The present work illustrates how macrophage type affects epithelial clustering in soft and stiff matrix environments.

bioengineering↗

bioRxiv2022

Antibiotic-degrading resistance changes bacterial community structure via species-specific responses

Some bacterial resistance mechanisms degrade antibiotics, potentially protecting neighbouring susceptible cells from antibiotic exposure. We do not yet understand how such effects influence bacterial communities of more than two species, which are typical in nature. Here, we used experimental multispecies communities to test the effects of clinically important pOXA-48-plasmid-encoded resistance on community-level responses to antibiotics. We found resistance in one community member reduced antibiotic inhibition of other species, but some benefitted more than others. Further experiments with supernatants and pure-culture growth assays showed the susceptible species profiting most from detoxification were those that grew best at degraded antibiotic concentrations (greater than zero, but lower than the starting concentration). This pattern was also observed on agar surfaces. By contrast, we found no evidence of a role for higher-order interactions or horizontal plasmid transfer in community-level responses to detoxification in our experimental communities. Our findings suggest carriage of an antibiotic-degrading resistance mechanism by one species can drastically alter community-level responses to antibiotics, and the identities of the species that profit most from antibiotic detoxification are predicted by their intrinsic ability to grow at degraded antibiotic concentrations.

microbiology↗

bioRxiv2022

Evaluation of the safety, immunogenicity and efficacy of a new live-attenuated lumpy skin disease vaccine in India

Lumpy skin disease (LSD) was reported for the first time in India in 2019 and since then, it has become endemic. Since a homologous (LSD-virus based) vaccine was not available in the country, goatpox virus (GPV)-based heterologous vaccine was authorized for mass immunization against LSD in cattle. This study describes the evaluation of safety, immunogenicity and efficacy of a new live-attenuated LSD vaccine developed using an Indian field strain (LSDV/India/2019/Ranchi). The virus was attenuated by continuous passage (P=50) in Vero cells. The vaccine (50th LSDV passage in Vero cells, named as Lumpi-ProVacInd) did not induce any local or systemic reaction upon its experimental inoculation in calves (n=10). At day 30 post-vaccination (pv), the vaccinated animals were shown to develop antibody- and cell-mediated immune response and exhibited complete protection upon virulent LSDV challenge. We observed a minimum Neethling response (0.018% animals; 5 out of 26940 animals) of the vaccine in field trials among 26940 animals. There was no significant reduction in the milk yield in lactating animals (n=10108), besides there was no abortion or any other reproductive disorder in the pregnant animals (n=2889). Sero-conversion was observed in 85.18% animals in the field by day 30 pv.

microbiology↗

bioRxiv2022

A fast yet force-effective mode of collective cell migration on aligned fibers due to rapid stabilization of contractile forces

Cell collectives, like other motile entities, generate and use forces to move forward. Here, we ask whether environmental configurations alter this proportional force-speed relationship, since aligned extracellular matrix fibers are known to cause directed migration. We show that aligned fibers serve as active conduits for spatial propagation of cellular mechanotransduction through matrix exoskeleton, leading to efficient directed collective cell migration. Epithelial (MCF10A) cell clusters adhered to soft substrates with aligned collagen fibers (AF) migrate faster with much lesser traction forces, compared to random fibers (RF). Fiber alignment causes higher motility waves and transmission of normal stresses deeper into cell monolayer while minimizing shear stresses and increased cell-division based fluidization. By contrast, fiber randomization induces cellular jamming due to breakage in motility waves, disrupted transmission of normal stresses, and heightened shear driven flow. Using a novel motor-clutch model, we explain that such force-effective fast migration phenotype occurs due to rapid stabilization of contractile forces at the migrating front, enabled by higher frictional forces arising from simultaneous compressive loading of parallel fiber-substrate connections. We also model haptotaxis to show that increasing ligand connectivity (but not continuity) increases migration efficiency. According to our model, increased rate of front stabilization via higher resistance to substrate deformation is sufficient to capture durotaxis. Thus, our findings reveal a new paradigm wherein the rate of leading-edge stabilization determines the efficiency of supracellular collective cell migration.

biophysics↗

bioRxiv2022

Synaptotagmin-9 and Tomosyn-1 molecular complex regulates Stx1A SNAREs to inhibit insulin secretion from pancreatic beta-cells

Stimulus-coupled insulin secretion from {beta}-cells involves the fusion of insulin granules to the plasma membrane (PM) via SNARE complex formation--a cellular process key for maintaining whole-body glucose homeostasis. Optimal insulin secretion depends on how the clamping of SNAREs is released, rendering granules fusogenic. We show that an insulin granule protein synaptotagmin-9 (Syt9) deletion in lean mice increased glucose clearance, random-fed plasma insulin levels, and insulin secretion (in vivo and ex vivo islets) without affecting insulin sensitivity. These outcomes demonstrate that Syt9 has an inhibitory function in insulin secretion. Moreover, Syt9 interacts with PM-Stx1A and soluble Tomosyn-1 proteins to form non-fusogenic complexes between PM and insulin granules, preventing Stx1A-SNARE formation and insulin secretion. Furthermore, Syt9 inhibits SNARE-complex formation by posttranscriptional regulation of Tomosyn-1. We conclude that Syt9 and Tomosyn-1 are endogenous inhibitors that modulate Stx1A availability to determine {beta}-cell secretory capacity. HighlightsO_LISynaptotagmin-9 inhibits biphasic insulin secretion from {beta}-cells. C_LIO_LISynaptotagmin-9, syntaxin-1A, and Tomosyn-1 forms a molecular complex that decreases the availability of syntaxin-1A to form SNARE complexes in insulin secretion. C_LIO_LISynaptotagmin-9-mediated inhibition of insulin secretion occurs through post-transcriptional regulation of Tomosyn-1. C_LI

cell biology↗

bioRxiv2022

Dehydration alters transcript levels in the midgut, likely facilitating rapid rehydration

The mosquito midgut is an important site for bloodmeal regulation while also acting as a primary site for pathogen exposure within the mosquito. Recent studies show that exposure to dehydrating conditions alters mosquito bloodfeeding behaviors as well as post-feeding regulation, likely altering how pathogens interact with the mosquito. Unfortunately, few studies have explored the underlying dynamics between dehydration and bloodmeal utilization, and the overall impact on disease transmission dynamics remains veiled. In this study, we find that dehydration-based feeding in the yellow fever mosquito, Aedes aegypti, prompts alterations to midgut gene expression, as well as subsequent physiological factors involving water control and post-bloodfeeding (pbf) regulation. Altered expression of ion transporter genes in the midgut of dehydrated mosquitoes and rapid reequilibration of hemolymph osmolality after a bloodmeal indicate an ability to expedite fluid and ion processing. These alterations ultimately indicate that female A. aegypti employ mechanisms to ameliorate the detriments of dehydration by imbibing a bloodmeal, providing an effective avenue for rehydration. Continued research into bloodmeal utilization and the resulting effects on arthropod-borne transmission dynamics becomes increasingly important as drought prevalence is increased by climate change.

physiology↗