Biology subjects

Sinha, A.

Publications and source records attributed to Sinha, A..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Fungal hydrophobins unleashed from food waste: production, rodlet assembly, and functional properties in Ganoderma adspersum

Ganoderma adspersum is a white-rot fungus (WRF) that produces amphipathic, surface-active proteins, known as hydrophobins. To explore sustainable routes for protein production and waste valorization, G. adspersum was cultivated under defined shaking conditions using different carbon and nitrogen sources, including apple skin food waste. From these cultures, we report for the first time the isolation and characterization of a novel class I hydrophobin, designated as Gad1. Atomic force microscopy revealed abundant rodlet-like nanostructures consistent with class I hydrophobin assemblies, and Raman spectroscopy confirmed {beta}-sheet enrichment typical of amyloid-like organization. MALDI-TOF mass spectrometry further identified Gad1 along with additional hydrophobin-like proteins in the foam. Hydrophobin-enriched foam extracts were used to form stable oil-in-water emulsions that could be converted into porous, freezedried composite aerogels. These findings expand the known diversity of hydrophobins in whiterot fungi and demonstrate that food-waste-derived substrates can support hydrophobin production and functional biomaterial formation.

biophysics↗

bioRxiv2025

LncRNA H19 Upregulation Links Hypoplastic Left Heart Syndrome to Impaired PINK1/Parkin-Mediated Mitophagy and Ischemic Vulnerability

BACKGROUNDThe myocardium in hypoplastic left heart syndrome (HLHS) exhibits immature metabolic programming, impaired mitochondrial quality control, and heightened susceptibility to ischemic and hypoxic injury during palliative surgery. The long non-coding RNA H19 suppresses translation of PTEN-induced putative kinase 1 (PINK1) mRNA and modulates mitochondrial quality control and ischemia/reperfusion injury (IRI) in adult hearts. Whether--and how--H19 regulates mitophagy and IRI in HLHS or in immature animals remains unknown. METHODSWe investigated H19 regulation and its role in mitophagy and ischemia/reperfusion or hypoxia/reoxygenation injury in myocardial tissue from HLHS patients, HLHS-specific induced pluripotent stem cell-derived cardiomyocytes (HLHS-iPSC-CMs), and immature rat hearts. Mechanistic interactions among H19, PINK1/Parkin signaling, and mitophagosome formation were assessed using loss-of-function approaches. RESULTSHLHS myocardium exhibited markedly elevated H19 expression, accompanied by reduced PINK1 and Parkin protein abundance and diminished mitophagosome formation. Similar findings were observed in HLHS-iPSC-CMs exposed to hypoxia/reoxygenation and in immature rat hearts subjected to myocardial IRI. H19 knockdown in HLHS-iPSC-CMs attenuated hypoxia/reoxygenation-induced lactate dehydrogenase release and restored PINK1 and Parkin protein levels. In immature rats, myocardial H19 silencing reduced infarct size, enhanced mitochondrial PINK1 and Parkin expression, and improved post-reperfusion cardiac function for up to 28 days. Conversely, knockdown of PINK1 or Parkin reduced mitophagosome formation and exacerbated functional deterioration during IRI. CONCLUSIONSH19 upregulation impairs PINK1/Parkin-dependent mitophagy and increases susceptibility to ischemic and hypoxic injury in HLHS and the immature heart. These findings identify H19 as a key regulator of mitochondrial quality control and a potential therapeutic target for mitigating IRI in early-life cardiac disease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/694773v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@193defdorg.highwire.dtl.DTLVardef@114ce7forg.highwire.dtl.DTLVardef@1010d05org.highwire.dtl.DTLVardef@1fdeac1_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG Novelty and SignificanceO_ST_ABSWhat Is Known?C_ST_ABSO_LIThe myocardium in hypoplastic left heart syndrome (HLHS) exhibits immature metabolic programming, abnormal coronary perfusion, and impaired mitochondrial quality control, rendering it highly susceptible to ischemic and hypoxic injury. C_LIO_LIBoth structural limitations and intrinsic mitochondrial dysfunction contribute to the reduced ischemic tolerance of the HLHS heart, particularly during surgical and hemodynamic stress. C_LIO_LIThe long noncoding RNA H19 regulates mitochondrial quality control and modulates myocardial ischemia/reperfusion injury (IRI) in adult hearts. C_LIO_LIH19 inhibits the binding of the translation initiation factor eIF4A2 to PTEN-induced putative kinase 1 (PINK1) mRNA, thereby suppressing PINK1 protein synthesis and influencing PINK1-dependent mitophagy in adult mice. C_LI What New Information Does This Article Contribute?O_LIThis study identifies robust upregulation of H19 in HLHS myocardium, HLHS-specific induced pluripotent stem cell-derived cardiomyocytes (HLHS-iPSC-CMs) exposed to hypoxia/reoxygenation, and in immature rats subjected to myocardial IRI. C_LIO_LIElevated H19 is associated with suppressed PINK1/Parkin-dependent mitophagy, exacerbated IRI, and adverse post-injury remodeling. C_LIO_LIKnockdown of H19 restores mitochondrial PINK1 and Parkin protein levels, enhances mitophagy, reduces infarct size, and improves long-term recovery of cardiac function--demonstrating a previously unrecognized pathogenic role for H19 in the immature heart under stress. C_LIO_LIKnockdown of PINK1 or Parkin decreases mitophagosomes and exacerbates myocardial IRI in immature rats. C_LI

genomics↗

bioRxiv2025

Neonatal BCG Vaccination Engages the Vasculature to Elicit γδ T Cell-Mediated Protection against Tuberculosis

The Bacillus Calmette-Guerin (BCG) vaccine remains the only approved vaccine against tuber-culosis (TB). Although its efficacy against pulmonary TB in adults is limited, BCG provides re-markable protection against miliary TB when administered during infancy. Despite more than 100 million infants worldwide receiving BCG annually, the mechanisms underlying its neonatal protective effects remain poorly defined. Here, we demonstrate that subcutaneous neonatal BCG vaccination (BCG-sc) induces a marked expansion of {gamma}{delta} T cells producing IL-17 and IL-22, which mediated protection against subsequent Mycobacterium tuberculosis (Mtb) experimental infection. A similar expansion of {gamma}{delta} T cells was observed in a longitudinal cohort of infants, from birth to three months of infants followed after intradermal BCG vaccination. Mechanistical-ly, BCG-mediated protection in neonates was linked to its early vascular dissemination through the distinct structure of neonatal skin, resembling the protective effects of intravenous BCG in adults. Moreover, neonatal BCG-sc vaccination generated a distinct BCG-induced microbiome signature, characterized by enrichment of Prevotellaceae, Tannerellaceae, and Bifidobacteriaceae, which was associated with protection. Together, these findings identify {gamma}{delta} T cells as key mediators of early-life BCG-induced immunity and highlight the role of the gut-lung axis in long-term protection against TB from infancy into adulthood.

immunology↗

bioRxiv2025

Mapping Allosteric Rewiring in Viral RNA: Sequence-Encoded Control of Protein Binding Mechanisms

RNA recognition by proteins is governed not only by static structure but also by allostery encoded within non-local dynamic motifs. In this study, we systematically identify allosteric communication hubs in RNA and map multiple residue-connected pathways, revealing how these networks are rewired upon mutation and protein binding. To capture these effects under physiological salt conditions, we performed tens of microseconds of atomistic and steered molecular dynamics simulations and computed binding free energies for Tat-TAR complexes across three immunodeficiency virus variants, BIV, HIV-1, and HIV-2. Allosterically coupled sites were identified using contact-based principal component analysis, and communication pathways were traced through an extended graph-network algorithm--the first such application to RNA systems. Two distant motifs--the bulge and the apical loop--emerge as allosteric switches and information hubs: the bulge engages Tat, while the loop interacts with another protein partner, CycT1, both essential for transcriptional activation and antiviral targeting. We find that HIV-2 TAR, with strong loop-bulge coupling and high self-integrity, favour conformational selection and exhibits lower Tat-binding affinity. In contrast, a single C24 insertion in HIV-1 TAR reconfigures communication pathways, enabling an induced-fit mechanism with enhanced affinity. The study not only elucidates an allosteric rewiring between the loop and bulge but also highlights how this communication is dynamically reconfigured upon protein binding. Tat association at the bulge reorganizes and reorients loop residues, thereby promoting the subsequent recruitment of CycT1. This work overall underscores how sequence (even a single mutation) encoded RNA allostery can modulate not only a proteins binding mechanism and affinity but also influence downstream molecular events within transcriptional signalling cascades. STATEMENT OF SIGNIFICANCEIn vitro selection strategies such as SELEX have long underscored the therapeutic relevance of the TAR RNA-Tat protein interface, yet they remain experimentally demanding and often overlook how subtle sequence variations reshape molecular recognition and RNA-protein binding affinity. By integrating atomistic and free-energy simulations with a graph-network-based framework, the study reveals that even a single-nucleotide change can rewire RNAs allosteric communication pathways, switching between conformational selection and induced-fit mechanisms and alter binding affinity. These findings bridge molecular dynamics with experimental selection, offering a predictive, thermodynamics-based framework to rationalize sequence-structure-function relationships and guide the rational design of high-affinity RNA-protein complexes and next-generation RNA therapeutics.

biophysics↗

bioRxiv2025

VadK, a Non-Canonical Kinase that Regulates the Methylcitrate Cycle and is Essential for Mycobacterium tuberculosis Virulence

The evolution of new enzymatic functions is constrained and guided by the architecture of an organisms metabolic and regulatory networks as well as by environmental constraints. Here, we identify a previously uncharacterized kinase that has evolved from pyruvate phosphate dikinase (PPDK). Through biochemical and systems-level analyses, we show that this enzyme, encoded by Rv1127c in Mycobacterium tuberculosis (Mtb), has diverged from its ancestral role in central carbon metabolism to function as a histidine kinase in pathogenic mycobacteria and related species. We designate this enzyme Virulence Associated DiKinase (VadK), reflecting its ability to autophosphorylate and role in coordinating metabolism and virulence. VadK is essential for the utilization of exogenous carbon sources critical for survival within the host and is required for Mtb pathogenicity in murine models of tuberculosis. Furthermore, VadK interacts with key enzymes of the methylcitrate cycle, and 13C-metabolic flux analysis indicates that it fine-tunes flux through this pathway, with elevated flux proving growth limiting. Together, these findings identify VadK as a previously unrecognized regulatory kinase that integrates metabolic control with virulence in Mtb, revealing a new facet of metabolic regulation in bacterial pathogenesis and a potential target for therapeutic intervention.

microbiology↗

bioRxiv2025

GRAYU: Graph-based Database integrating Ayurvedic formulations, medicinal plants, phytochemicals and diseases

The translation of Indias extensive traditional knowledge on indigenous medicinal plants into modern therapeutic solutions is contingent upon a systematic framework. While traditional Indian medicine offers a rich source of therapeutic leads, this knowledge is often not structured for modern computational analysis, creating a barrier to systematic drug discovery. To this end, we present GRAYU, a curated and comprehensive online database that integrates data across multiple categories, connecting 1039 traditional formulations to 12,949 indigenous plants, 129,542 phytochemicals, and 13,480 indicated diseases. It also provides insights into 1,382,362 plant-phytochemical, 116,824 plant-disease, 2,405 plant-formulation, and 4,087 formulation-disease associations. Case studies on phytochemical analogs, sustainable plant substitution, and disease-network pharmacology showcased the potential of integrative graphs to decode shared molecular signatures and therapeutic networks across traditional Ayurvedic formulations. GRAYU represents a user-friendly resource for researchers to investigate complex bio-associations and formulate novel therapeutic hypotheses, with insights from traditional Indian medicine. GRAYU is available at https://caps.ncbs.res.in/GRAYU/.

bioinformatics↗

bioRxiv2025

The evolution of cavefish odor perception shifts fish response from avoidance to approach when exposed to alarm and death odors.

An organisms survival is dependent on activating the correct behavioral circuit in response to a stimulus. While stimulus perception is largely conserved, we still do not know the evolutionary mechanisms that drive changes in stimulus perception. Therefore, we wondered how odor perception has evolved in cavefish that encounter vastly different odors compared to their surface ancestors. While surface populations show attraction to social odors and avoidance of alarm and death odors, cave populations are sexually dimorphic in their responses to social odors and exhibit attraction to alarm and death odors. Finally, we find that odor perception variation is genetically encoded and plastic, while tissue clearing and brain mapping suggest odor perception is governed by thalamic and hypothalamic circuits. Taken together, we describe a unique model for investigating the environmental, genetic, and neurological mechanisms underlying olfactory evolution in vertebrates.

evolutionary biology↗

bioRxiv2025

Epitranscriptomic Dysregulation Underpins Artemisinin Mechanism of Action

Artemisinin has long been a first-line antimalarial. Yet, its mode of action is still poorly understood. Emergence of artemisinin-resistant strains highlight the importance of addressing this question so as to develop better drugs and overcome resistance. In this study, we performed RNA-sequencing and proteomics studies on artemisinin treated parasites indicated a striking difference in the codon-usage pattern of differentially translated genes. Using a liquid chromatography-coupled mass spectrometry (LC-MS)-based platform, we have quantified the full spectrum of modified ribonucleosides on tRNA in P. falciparum in response to the drug. We found that N6-threonyl-carbomyladenosine (t6A), a universal tRNA modification found at position 37 is hypomodified in response to artemisinin induced stress. Additionally, we also found that artemisinin treatment resulted in a downregulation of PfSua5, an enzyme involved in the t6A biosynthesis machinery. These findings provide new insights into how artemisinin works. More broadly, the findings exposes the tRNA epitranscriptome as a vulnerability in the parasite that can be exploited for new drugs.

microbiology↗

bioRxiv2025

A new species of Polyrhachis Smith from Garbhanga Reserve Forest, Assam, India, with a key to the Indian species of Polyrhachis mucronata group (Hymenoptera: Formicidae)

Polyrhachis Smith, 1857 is a genus of ants, found widely across the Old-World tropics, with significant diversity across South Asia. Known to have diverse nesting habits, ranging from subterranean to arboreal, the genus is arguably one of the most taxonomically and ecologically diverse ant genera globally. The genus is, however, characterised by a unique morphology that includes prominent spines on the mesosoma and petiole, thick integuments, and brightly coloured pubescence in some species. With over 700 described species and 82 valid subspecies, Polyrhachis is also the second most diverse ant genus in India, with 71 identified species. In the state of Assam in northeastern India, the genus is the second-most diverse after Camponotus. Field sampling in the Garbhanga Reserve Forest, near the city of Guwahati in Assam, revealed a new species of Polyrhachis, which is described and named here as Polyrhachis garbhangaensis or the "Assamese Spiny Ant." The discovery of this species, which belongs to the Polyrhachis mucronata group, and its subsequent characterisation made evident the urgent need for a reassessment of the classification key of the genus, which we additionally provide here. This finding, we believe, contributes to a deeper understanding of the taxonomic diversity of Polyrhachis but, at the same time, highlights the importance of urban and fragmented forest areas in sustaining tropical ant biodiversity.

zoology↗

bioRxiv2025

Astrocytic Regulation of aberrant perineuronal net formation in Mecp2-null Neocortex

Rett syndrome (RTT), caused by mutations in MECP2, is a complex neurological disorder characterized by myriad physiological disruptions, including early closure of the critical period of developmental plasticity and precocious formation of perineuronal nets (PNNs). PNNs are lattice-like substructures of extracellular matrix (ECM) that enwrap specific subpopulations of neurons. PNNs are essential in the modulation of neuronal plasticity and brain maturation, and their enzymatic disruption can partially restore plasticity in adults and improve memory. Although precocious PNN formation is well-established in RTT, little is known of the cellular, molecular, or biochemical underpinnings of their precocious formation, or whether precocious PNN formation is due to cell-autonomous or non-cell-autonomous mechanisms. While PNNs form on subsets of neurons throughout the brain, astrocytes secrete many ECM components that form PNNs, and they play a central role in controlling closure of the critical period. We find that Mecp2-null astrocyte conditioned media induces the expression of the key PNN component Hapln1 and causes enhanced PNN formation on wildtype neurons, suggesting that Mecp2-null astrocytes play a key role in the precocious formation of PNNs in RTT. Further, we identify increased expression of HAPLN1 and other PNN / ECM components in the developing Mecp2-null cortex, and demonstrate that PNNs are structurally and biochemically mature at an earlier developmental stage. These results provide essential insight into the mechanisms and structure of aberrant PNNs in Mecp2-null cortex and identify potential new avenues for targeted rescue or reversal of the precocious closing of the critical period in RTT.

neuroscience↗

bioRxiv2025

Label-free DIA-NN enabled RIME (DIANNeR) reveals glucocorticoid receptor interaction networks in breast, bladder, and blood across normaluntransformed cells, cancer cell lines, and PDXs

Understanding how transcription factors execute tissue-specific programmes requires defining their protein interaction networks in physiologically relevant contexts. However, profiling normal untransformed cells presents fundamental challenges due to intrinsically limited input material. To meet this challenge we integrated data-independent acquisition (DIA), ion mobility separation, and library-free analysis to achieve a 2-fold increase in detection without loss in enrichment. Applied to the glucocorticoid receptor (GR), a ubiquitously expressed nuclear receptor driving pleiotropic responses to standard-of-care anti-inflammatory therapeutics, DIANNeR (DIA-NN enabled RIME) resolves distinct, context-dependent networks across breast, ureter and blood in normal and transformed contexts. Key findings include: detection of a HOXA5-GR interaction in normal epithelium which was undetected in malignant models; an epithelial-restricted SMARCD3-GR interaction with prognostic relevance; and a FOXP3-BCL11B-GR network in primary CD4+ T cell populations undetected by data dependant acquisition (DDA). By defining normal GR tissue interactomes, DIANNeR provides the essential comparator for interpreting network rewiring that drives disease.

cancer biology↗

bioRxiv2025

What's next for Indian Ornithology? 101 key research questions

India has a rich history of ornithology, and bird research in this field has expanded considerably in recent decades, spurred by a growing number of birdwatchers and ornithologists. Despite this progress, critical gaps remain. This paper highlights key areas where further research is needed and identifies pressing questions that will shape Indian ornithology in the coming years. Drawing from diverse inputs, we present a curated list of 101 research questions spanning across the various disciplines in ornithology - Natural History, Physiology and Disease Ecology, Behaviour, Population and Community Ecology, Habitat Ecology, Macroecology and Biogeography, Population Genetics and Evolution, Applied/Economic Ornithology and Conservation. The list was compiled through a multi-stage process, starting with a public open call for questions, followed by review and curation by a smaller panel of subject specialists. Each question was independently scored by a panel of experts based on three criteria: generality, novelty, and relevance. To account for variation in scoring styles, scores were normalised using Z-scores. The top 101 research questions were then selected based on these standardised scores. Each question is accompanied by an annotation that describes the significance of the question, and highlights opportunities to address it. While our list of research questions highlights significant research priorities, it is not intended to be exhaustive. Rather, it reflects the perspectives of those involved in its curation, who deemed these questions particularly relevant and impactful towards advancing Indian ornithology. We expect these questions to spark new project ideas among students, researchers, and citizen scientists, while guiding funders, managers, and policymakers toward priority research areas.

ecology↗

bioRxiv2025

ACOD1 regulates microglial arginine metabolism and inflammatory responses

Itaconate is produced by inflammatory macrophages and promotes a negative feedback on inflammation. It is synthesized by aconitate decarboxylase 1 (ACOD1) from cis- aconitate, a metabolite of the tricarboxylic acid cycle. Here, we studied the role of ACOD1 in the inflammatory response of microglia, the resident macrophage-like cells of the brain. Similar to macrophages, ACOD1 deficient microglia displayed a stronger inflammatory response to lipopolysaccharide (LPS) compared to their wild type counterparts. The proinflammatory effects of ACOD1 deficiency were associated with reprogramed arginine metabolism entailing enhanced argininosuccinate synthesis at the expense of polyamine synthesis, in a manner that was dependent on ACLY. These findings provide new insights in the immunometabolic role of ACOD1 in inflammatory microglia.

immunology↗

bioRxiv2025

Molecular Basis of Ionic Suppression of ZAP-70 Dependent T Cell Receptor Activation

Ionic imbalance in the tumor microenvironment alters the tumor-infiltrating T lymphocyte function. High extracellular K+ suppresses T cell function by negatively regulating T cell receptor (TCR) signaling. In contrast, elevated extracellular Na+ enhances T cell effector function by boosting the phosphorylation of TCR signaling modules. Here, we presented a mechanism explaining how the two monovalent cations differently regulate TCR function. At rest, high intracellular K+ uncouples allosteric recruitment of ZAP-70, a key signaling module, to the TCR complex. The formation of antigen TCR complex induces K+ efflux, causing spontaneous recruitment of ZAP-70 to the TCR. Increasing extracellular K+ perturbs K+ efflux and slows ZAP-70 recruitment to the TCR complex, even upon antigen binding. This leads to defects in T cell development and arthritis-like symptoms in juvenile mice. We conclude that K+ dynamics is integral to T cell ligand discrimination and fundamental to turning off the signaling during T cell quiescence.

immunology↗

bioRxiv2025

N6-methyladenosine primes the malaria parasite for transmission

Sudden environmental changes are a recurring challenge for unicellular organisms, but a necessity for many to progress through their lifecycle. To transmit from its human host to mosquito vector, malaria parasites differentiate into male and female, semi-quiescent stages that can re-initiate development within seconds after transmission. Here, we identify the RNA modification N6-methyladenosine (m6A) as the mediator of a rapid, sex-specific, and temperature-sensitive mechanism to restructure protein synthesis during transmission. We find that male parasites maintain high levels of translation during their semi-quiescence that are rapidly repressed following mosquito uptake. This translational shutdown is essential for the continuation of male parasite development and depends on the m6A-binding protein YTH.2. We further show that m6A and YTH.2 are already present prior to transmission, but that their repressive interaction requires a temperature drop accompanying the exit from the human host. Hence, m6A appears to prime the parasite transcriptome and subsequently converts an environmental shift into a rapid translational response.

molecular biology↗

bioRxiv2025

Hypoxia Inducible Factor 1α-driven steroidogenesis impacts systemic hematopoiesis

Glucocorticoids regulate hematopoiesis, but how chronic elevation of endogenous glucocorticoid production affects hematopoietic stem cell (HSC) function and immune cell development remains incompletely understood. Using an adrenocortical cell-specific HIF1 (Hypoxia inducible Factor-1)-deficient mouse model (P2H1Ad.Cortex) resulting in elevated glucocorticoid (GC) levels, we here demonstrate that sustained GC exposure promotes hematopoietic stem and progenitor cell (HSPC) expansion while shifting HSCs toward a more quiescent and metabolically restrained state. Functionally, these HSCs exhibited enhanced regenerative potential, as evidenced by superior donor chimerism in transplantation assays. In addition, we observed a striking increase in myeloid progenitors, as well as in their progeny (monocytes and granulocytes). Conversely, B-cell differentiation in the bone marrow was severely impaired, with a strong block at the pre-pro-B cell stage. To determine whether these phenotypes were driven by glucocorticoid receptor (GR) signaling, we performed transplantation experiments using GR-deficient or WT control bone marrow into P2H1Ad.Cortex or WT littermate recipients. This approach decisively demonstrated that both the increase in myeloid cells and the block in B-cell differentiation were GR-dependent, confirming that GC-GR signaling plays a pivotal role in shaping hematopoiesis. Taken together, our findings clearly suggest a direct role for chronic glucocorticoid exposure in regulating HSC function, lineage differentiation, and stress hematopoiesis. The mouse model of adrenocortical cell-specific HIF1 deficiency provides a valuable tool to study the long-term effects of elevated glucocorticoid levels on hematopoietic regulation and may provide further insight into hematologic disorders associated with chronic therapeutic glucocorticoid administration. Article Summary- Our study aimed to elucidate how chronic elevation of glucocorticoids impacts hematopoietic stem cell function and immune cell development using an adrenocortical cell-specific HIF1-deficient mouse model. - The main conclusion is that sustained glucocorticoid exposure, through glucocorticoid receptor signaling, promotes hematopoietic stem and progenitor cell expansion with enhanced regenerative potential while skewing lineage differentiation toward myeloid expansion and impeding B-cell development.

immunology↗

bioRxiv2024

Can we infer excitation-inhibition balance from the spectrum of population activity?

Networks in the brain operate in an excitation-inhibition (EI) balanced state. Altered EI balance underlies aberrant dynamics and impaired information processing. Given its importance, it is crucial to establish non-invasive measures of the EI balances. Previous studies have suggested that relative EI balance can be inferred from the spectrum of the population signals such as Local Field Potentials, Electroencephalogram and Magnetoencephalography. This idea exploits the fact that in most cases excitatory and inhibitory synapses have quite different time constants. However, it is not clear to what extent spectral slope of population activity is related to the network parameters that define the EI balance e.g. excitatory and inhibitory conductance. To address this question we simulated two different types of recurrent networks and measured spectral slope for a wide range of parameters. Our results show that the slope of the spectrum cannot predict the ratio of excitatory and inhibitory synaptic conductance. Only in a small set of simulations a change in the spectral slope was consistent with the corresponding change in the synaptic weights or inputs to the network. Thus, our results show that we should be careful in interpreting the change in the slope of the population activity spectrum. Significant statementNon-invasive signals such as electroencephalogram (EEG) and magneto-encephalogram (MEG) are routine acquired from human subjects in different functional and dysfunctional states. It is of great interest to relate properties of EEG/MEG to the underlying physiology and network properties. In this regard, recently it was proposed that the slope of the EEG/MEG spectrum can be related to excitation-inhibition balance: steeper slopes indicate higher inhibition. Here we show that such an explanation holds only for a small set of conditions. In most cases spectral slope is not informative of underlying excitation-inhibition balance. Thus, we argue that while spectral slope may be a good biomarker of brain state, it is not informative about the underlying excitation-inhibition balance or network parameters.

neuroscience↗

bioRxiv2024

EVOLVE: A Web Platform for Evolutionary Phase Analysis and New Variant Exploration from Multi-Sequence Data

Recurrent updates from the World Health Organization (WHO) on refining definitions for Variants of Concern (VOCs), Variants of Interest (VOIs), and Variants Under Monitoring (VUMs) underscore the need for systematic investigations to develop quantifiable metrics that differentiate critical phases of variant evolution. This study illustrates how protein data can be systematically analyzed by applying phase transition principles from statistical mechanics, where quantifying mutational response function (MRF) helps identify concerning variants along evolutionary paths. To support the exploration of metrics like mutational entropy, MRF, and other relevant indicators for novel or uncharacterized viruses and pathogenic bacteria, we introduce EVOLVE--a web platform that empowers researchers across diverse fields to access sequence-based analyses. EVOLVE streamlines data upload and analysis with a user-friendly interface and comprehensive tutorials. Overcoming the challenges with large sequence-space analysis its AI-driven data-learning module integrates evolutionary dynamics with microscopic mutational information, enabling the prediction of future site-specific mutations in prospective missense variants. Access EVOLVE for free at https://www.evolve-0fm3.onrender.com.

biophysics↗