Biology subjects

Nair, S. S.

Publications and source records attributed to Nair, S. S..

At least 19 recordsLinked to original sources

bioRxiv2026

Impaired value estimation over space explains turn-induced freezing of gait in Parkinson's disease: A cortico-basal ganglia-inspired reinforcement learning model

Parkinson's disease (PD) gait is characterized by reduced walking speed, short shuffling steps, increased double stance time, and increased step time variability. The most debilitating symptom in PD is freezing of gait (FOG), a context-dependent locomotion arrest, mostly occurring while encountering turns, obstacles, and narrow pathways. FOG is more pronounced during turning, a complex task that challenges motor planning and execution. Here, we simulate this phenomenon using a computational model inspired by the cortico-basal ganglia circuitry, based on reinforcement learning (RL) principles. In the model, the agent was trained to learn a value profile while navigating a path that involved turning. To simulate PD conditions, we clamped the temporal difference (TD) error, typically associated with dopaminergic signaling. Our model results show that compared to healthy controls (HC), PD non-freezers and PD freezers exhibit a reduction in turning velocity and step length, alongside an attenuated compensatory step-width widening at the sharpest turn, more pronounced in PD freezers, who additionally show increased step time variability. These kinematic impairments worsen during tighter turns. Ultimately, this model implicates FOG as a problem of impaired estimation of value over space and could potentially represent a generalized deficit in gait impairments in PD.

neuroscience↗

bioRxiv2026

Cell-type specific inhibitory dynamics shape binocular response normalization in visual cortex

Response normalization during sensory processing is a canonical cortical computation thought to emerge from inhibition-stabilized networks (ISNs). A key prediction from ISNs is that inhibition tracks and scales with excitation, leading to sublinear response summation, but which interneuron classes mediate this operation is unclear. Here, we investigate temporal dynamics and response summation in parvalbumin (PV) and somatostatin (SST) interneurons in mouse binocular visual cortex (bV1). We find that both PV and SST interneurons are binocular but exhibit distinct temporal dynamics and summation profiles. Binocular responses in PV interneurons tracked pyramidal neuron responses, exhibiting sublinear summation consistent with ISN models. In contrast, binocular responses SST interneurons exhibited rapid temporal dynamics and linear or supralinear summation, deviating from ISN predictions. While both PV and SST neurons received excitatory drive via interhemispheric callosal input, they exhibited distinct cellular properties, synaptic dynamics and input-output transformations. Biophysically constrained simulations indicated that cellular and synaptic differences alone were insufficient to reproduce the observed response dynamics in vivo during binocular integration, which were better explained by class-specific differences in local inhibitory circuit motifs. Together, our results indicate that heterogeneous, cell-type-specific inhibitory dynamics shape response normalization in bV1, with PV but not SST interneurons having ISN-like properties.

neuroscience↗

bioRxiv2026

Attentional selection is a neuroeconomic decision

Sensorimotor decisions require balancing extrinsic rewards against intrinsic action costs. How these signals are integrated during rapid eye-movement choices remains unclear. We show that human saccade selection follows cost-benefit computations consistent with neuroeconomic decision-making. Across two experiments, participants maximized rewards and minimized effort-costs. Reward titration revealed that more effortful saccades required higher monetary rewards to be chosen equally often. While effort-costs affected choices linearly, small reward differences shifted choices more than equally-sized larger ones. Furthermore, effort-cost (but not reward) differences regulated decision engagement: Deliberation was extended only when cost differences were large. Together, costs and rewards play dissociable roles in saccade selection, positioning eye movements as a tractable model system for economic decision-making.

neuroscience↗

bioRxiv2026

Homozygous c.820G>A variant in MGME1 contributes to multi-systemic mitochondrial dysfunction in an Indian patient cohort

Mitochondrial DNA (mtDNA) maintenance disorders arise from defects in mtDNA replication or repair, frequently resulting in extensive deletions or depletion of mtDNA. Mitochondrial genome maintenance exonuclease 1 (MGME1) is a nuclear-encoded nuclease essential for mtDNA replication and genome stability, and biallelic pathogenic variants in MGME1 cause mitochondrial DNA depletion syndrome 11. Here, we report a novel homozygous MGME1 missense variant c.820G>A (p. Ala274Thr) in five affected individuals from unrelated South Indian families presenting with proximal myopathy, chronic progressive external ophthalmoplegia, and cardiac and renal involvement. Patient-derived cells exhibited a significant reduction in mtDNA copy number, consistent with impaired mtDNA maintenance. Mechanistic analyses combining imaging-based and biochemical approaches demonstrated that the MGME1 variant disrupts both mtDNA replication and repair. Functional characterization further revealed defective oxidative phosphorylation and reduced mitochondrial membrane potential, confirming mitochondrial dysfunction. Collectively, our findings establish the pathogenicity of this novel MGME1 variant and expand the clinical and molecular spectrum of MGME1-associated mitochondrial disease, linking impaired mtDNA replication to multisystemic mitochondrial dysfunction. Graphical abstract summarySchematic overview of mitochondrial DNA (mtDNA) replication in wild-type and MGME1 mutant conditions. In wild-type cells, the coordinated activity of the mitochondrial replication machinery (TWNK, POLG, LIG3, TFAM, and MGME1) maintains mtDNA integrity and supports normal oxidative phosphorylation and ATP production. In contrast, the MGME1 mutation disrupts mtDNA replication and processing, leading to replication defects, mtDNA depletion, and mitochondrial dysfunction. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=116 SRC="FIGDIR/small/725852v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@406ce7org.highwire.dtl.DTLVardef@1adc863org.highwire.dtl.DTLVardef@3ef92aorg.highwire.dtl.DTLVardef@585559_HPS_FORMAT_FIGEXP M_FIG C_FIG

genetics↗

bioRxiv2025

Frontotemporal bursting supports human working memory

Cortical neural activity varies dynamically during memory periods, when relevant information is not present in the environment. But how those dynamics are related to a code defining working memory (WM) performance is not known. Recent data shows brief bursts of activity in the high gamma (70-140 Hz) and beta (12-30 Hz) band within non-human primate lateral prefrontal cortex (PFC) is associated with WM processing. However, WM may be related to activity within a network of frontal executive and posterior sensory areas involved in stimulus perception. Here we tested whether gamma and beta bursting exist in lateral PFC and multisensory lateral temporal areas in humans during visual WM, and whether these areas are coupled via a phase-burst code. We used intracranial macroelectrode recordings from the middle frontal gyrus (MFG), which includes dorsolateral PFC, and from the middle temporal gyrus (MTG), an area important for visual processing. High gamma bursting increased in human left PFC during encoding and delay periods while beta bursting decreased. Interestingly, beta bursting increased in multisensory areas during encoding and remained high during the delay period, more so on the right. These effects varied with WM performance. Finally, we quantify the degree to which delay-period gamma bursting is locked to beta phase within and between regions of this network using a proposed metric termed phase-burst coupling (PBC). We find evidence that delay-period gamma bursting in temporal areas is locked to beta phase in PFC. Our findings suggest that WM may use bursting to support memory maintenance until readout. Significance StatementWorking memory is critical for everyday functioning and its disruption results in significant disability in patients with dementia, traumatic brain injury, and stroke. We recorded human intracranial data during a visual working memory task. We found that prefrontal cortex and multisensory temporal brain areas show neural bursting activity during the memory period and that such bursting is related to trial performance. Furthermore, these two areas may be coupled by a phase-burst code. Bursting has been found in non-human primates, rodents, and even crows, suggesting it is a general feature of memory, and perhaps of other aspects of cognition.

neuroscience↗

bioRxiv2025

Anatomical and functional mapping of vagal nociceptive sensory nerve subsets innervating the mouse lower airways by intersectional genetics

Most vagal sensory afferents innervating the lower airways are activated by noxious stimuli including irritants (e.g. TRPV1 agonist capsaicin) and inflammatory mediators, causing nociceptive cardiorespiratory reflexes (e.g. cough, bronchospasm, changes in respiratory drive and heart rate). Vagal ganglia are comprised of embryologically distinct nodose and jugular neurons, but little is known of their specific contribution to nociceptive reflexes. Using a novel TRPV1Flp mouse in combination with P2X2Cre, Tac1Cre, intersectional reporter mice and AAV we mapped and modulated distinct nociceptive afferents. TRPV1+P2X2+ neurons were found exclusively in the nodose ganglion and were activated by {beta}mATP and capsaicin but rarely expressed Tac1. TRPV1+P2X2+ fibers innervated the lungs (many projected into the alveoli) but not the trachea. Centrally they innervated the nucleus tractus solitarius (nTS). >90% of TRPV1+Tac1+ neurons were found in the jugular ganglion and were activated by capsaicin but not {beta}mATP. TRPV1+Tac1+ fibers innervated the lungs (although none projected into the alveoli) and the trachea submucosa. They terminated solely in the paratrigeminal complex (Pa5). Many TRPV1-Tac1+ neurons were found in both nodose and jugular ganglia that innervated the trachea and large pulmonary airways. These projected to both nTS and Pa5. Using intersectional chemogenetics we selectively stimulated lower airway afferent subsets using intravenous injections of clozapine-N-oxide (CNO). Activation of TRPV1+, TRPV1+P2X2+ or TRPV1+Tac1+ fibers evoked bradycardia and bradypnea. Activation of Tac1+ fibers evoked tachycardia and tachypnea. Activation of vagal TRPV1-Tac1+ neurons only evoked tachycardia. These data show the distinct innervation patterns and reflex function of multiple nociceptive vagal afferent subsets.

physiology↗

bioRxiv2024

A Computational Model of Deep Brain Stimulation for Parkinsons Disease Tremor

Parkinsons Disease (PD) is a progressive neurological disorder that is typically characterized by a range of motor dysfunctions and its impact extends beyond physical abnormalities into emotional well-being and cognitive symptoms. The loss of dopaminergic neurons in the Substantia nigra pars compacta (SNc) leads to an array of dysfunctions in the functioning of Basal Ganglia (BG) circuitry that manifests into PD. While active research is being carried out in finding the root cause of SNc cell deaths, various therapeutic techniques are prevalent to manage the symptoms of PD. The most common approach in managing the symptoms is replenishing the lost dopamine in the form of taking dopaminergic medications such as Levodopa amidst its long-term complications. Another commonly used intervention for PD is deep brain stimulation (DBS), which is a invasive technique where an electrode is surgically inserted into the skull and a high frequency current of appropriate characteristics is delivered to the brain region. DBS is most commonly used when levodopa medication efficacy reduces and also in combination with levodopa medication that will help reducing the required dosage of medication prolonging the therapeutic effect. DBS is also a go to option when motor complications such as dyskinesias emerge as a side effect of medication. Several studies have also reported that though DBS is found to be effective in suppressing severe motor symptoms such as tremor and rigidity, it has adverse effect on cognitive capabilities. Henceforth it is important to understand the exact mechanism of DBS in alleviating the motor symptoms. A computational model of DBS stimulation for motor symptoms will offer great insights in understanding the mechanisms underlying the DBS and in this line in our current study we model a cortico-basal ganglia circuitry of arm reaching where we simulate healthy controls (HC) and PD symptoms as well as the DBS effect on the PD tremor. With DBS current characteristics of 220 pA, 130 Hz and 100 microseconds pulse-width we were able to see maximum therapeutic effect using our model. This model can be extended to accommodate cognitive dynamics in future so as to study the impact of DBS on cognitive symptoms and optimizing the parameters to get optimal performance effect across modalities.

neuroscience↗

bioRxiv2024

Spatially targeted inhibitory rhythms differentially affect neuronal integration

Pyramidal neurons form dense recurrently connected networks with multiple types of inhibitory interneurons. A major differentiator between interneuron subtypes is whether they synapse onto perisomatic or dendritic regions. They can also engender local inhibitory rhythms, beta (12-35 Hz) and gamma (40-80 Hz). The interaction between the rhythmicity of inhibition and its spatial targeting on the neuron may determine how it regulates neuronal integration. Thus, we sought to understand how rhythmic perisomatic and distal dendritic inhibition impacted integration in a layer 5 pyramidal neuron model with realistic dendrites supporting Na+, NMDA, and Ca2+ spikes. We found that inhibition regulated the coupling between dendritic spikes and action potentials in a location and rhythm-dependent manner. Perisomatic inhibition principally regulated action potential generation, while distal dendritic inhibition regulated the incidence of dendritic spikes and their temporal coupling with action potentials. Perisomatic inhibition was most effective when provided at gamma frequencies, while distal dendritic inhibition functioned best at beta. Moreover, beta modulated responsiveness to distal inputs in a phase-dependent manner, while gamma did so for proximal inputs. These results may provide a functional interpretation for the reported association of soma-targeting parvalbumin positive interneurons with gamma, and dendrite-targeting somatostatin interneurons with beta.

neuroscience↗

bioRxiv2023

A Basal Ganglia Model for understanding Working Memory Functions in Healthy and Parkinson's Conditions

Working memory is considered as the scratchpad to write, read, and process information to perform cognitive tasks. Basal Ganglia (BG) and Prefrontal Cortex are two important parts of the brain that are involved in working memory functions and both the structures receive projections from dopaminergic nuclei. In this modelling study, we specifically focus on modelling the working memory functions of the BG, the working memory deficits in Parkinsons disease conditions, and the impact of dopamine deficiency on different kinds of working memory functions. Though there are many experimental and modelling studies of working memory properties, there is a paucity of models of the BG that provide insights into the contributions of the BG in working memory functions. The proposed model of the BG is a unified model that can explain the working memory functions of the BG over a wide variety of tasks in normal and Parkinsons disease conditions.

neuroscience↗

bioRxiv2022

3D-Beacons: Decreasing the gap between protein sequences and structures through a federated network of protein structure data resources

While scientists can often infer the biological function of proteins from their 3-dimensional quaternary structures, the gap between the number of known protein sequences and their experimentally determined structures keeps increasing. A potential solution to this problem is presented by ever more sophisticated computational protein modelling approaches. While often powerful on their own, most methods have strengths and weaknesses. Therefore, it benefits researchers to examine models from various model providers and perform comparative analysis to identify what models can best address their specific use cases. To make data from a large array of model providers more easily accessible to the broader scientific community, we established 3D-Beacons, a collaborative initiative to create a federated network with unified data access mechanisms. The 3D-Beacons Network allows researchers to collate coordinate files and metadata for experimentally determined and theoretical protein models from state-of-the-art and specialist model providers and also from the Protein Data Bank.

bioinformatics↗

bioRxiv2022

A Generalized Reinforcement Learning-Based Deep Neural Network (GRL-DNN) Agent Model for Diverse Cognitive Constructs

Human cognition is characterized by a wide range of capabilities including goal-oriented selective attention, distractor suppression, decision making, response inhibition, and working memory. Much research has focused on studying these individual components of cognition in isolation, whereas in several translational applications for cognitive impairment, multiple cognitive functions are altered in a given individual. Hence it is important to study multiple cognitive abilities in the same subject or, in computational terms, model them using a single model. To this end, we propose a unified, reinforcement learning-based agent model comprising of systems for representation, memory, value computation and exploration. We successfully modelled the aforementioned cognitive tasks and show how individual performance can be mapped to model meta-parameters. This model has the potential to serve as a proxy for cognitively impaired conditions, and can be used as a clinical testbench on which therapeutic interventions can be simulated first before delivering to human subjects.

neuroscience↗

bioRxiv2021

Resting state functional connectivity in relapsing remitting multiple sclerosis with mild disability - a data driven, whole brain multivoxel pattern analysis study

BackgroundMultivoxel pattern analysis (MVPA) has emerged as a powerful unbiased approach for generating seed regions of interest (ROIs) in resting-state functional connectivity (RSFC) analysis in a data-driven manner. Studies exploring RSFC in multiple sclerosis have produced diverse and often incongruent results. ObjectivesThe aim of the present study was to investigate RSFC differences between persons with relapsing-remitting multiple sclerosis (RRMS) and healthy controls (HC). MethodsWe performed a whole-brain connectome-wide MVPA in 50 RRMS patients with expanded disability status scale [≤]4 and 50 age and gender-matched HCs. ResultsSignificant group differences were noted in RSFC in three clusters distributed in the following regions; anterior cingulate gyrus, right middle frontal gyrus, and frontal medial cortex. Whole-brain seed-to-voxel RSFC characterization of these clusters as seed ROIs revealed network-specific abnormalities, specifically in the anterior cingulate cortex and the default mode network. ConclusionsThe network-wide RSFC abnormalities we report agree with the previous findings in RRMS, the cognitive and clinical implications of which are discussed herein. IMPACT STATEMENTThis study investigated resting state functional connectivity (RSFC) in relapsing remitting multiple sclerosis (RRMS) persons with mild disability (expanded disability status scale [≤]4). Whole-brain connectome-wide multivoxel pattern analysis (MVPA) was used for assessing RSFC. Compared to healthy controls (HC), we were able to identify three regions of interest for significant differences in connectivity patterns, which were then extracted as a mask for whole-brain seed-to-voxel analysis. A reduced connectivity was noted in the RRMS group, particularly in the anterior cingulate cortex and the default mode network regions, providing insights into the RSFC abnormalities in RRMS.

neuroscience↗

bioRxiv2021

Crustacean cardiac ganglion model reveals constraints on morphology and conductances

The crustacean cardiac ganglion (CG) network coordinates the rhythmic contractions of the heart muscle to control the circulation of blood. The network consists of 9 cells, 5 large motor cells (LC1-5) and 4 small endogenous pacemaker cells (SCs). We report a new three-compartmental biophysical model of an LC that is morphologically realistic and includes provision for inputs from the SCs via a gap-junction coupled spike-initiation-zone (SIZ) compartments. To determine physiologically viable LC models in this realistic configuration, maximal conductances in three compartments of an LC are determined by random sampling from a biologically-characterized 9D-parameter space, followed by a three-stage rejection protocol that checks for conformity with electrophysiological features from single cell traces. LC models that pass the single cell rejection protocol are then incorporated into a network model which is then used in a final rejection protocol stage. Using disparate experimental data, the study provides hitherto unknown structure-function insights related to the crustacean cardiac ganglion large cell, including predictions about morphology including the role of its SIZ, and the differential roles of active conductances in the three compartments. Further, we extend analyses of emergent conductance relationships and correlations in model neurons relative to their biological counterparts, allowing us to make inferences both with respect to the biological system as well as the implications of the ability to detect such relationships in populations of model neurons going forward.

neuroscience↗

bioRxiv2021

A Multiscale, Systems-level, Neuropharmacological Model of Cortico-Basal Ganglia System for Arm Reaching under Normal, Parkinsonian and Levodopa Medication Conditions

The root cause of Parkinsons disease (PD) is the death of dopaminergic neurons in Substantia Nigra pars compacta (SNc). The exact cause of this cell death is still not known. Loss of SNc cells manifest as the cardinal symptoms of PD, including tremor, rigidity, bradykinesia, and postural imbalance. To investigate the PD condition in detail and understand the link between loss of cells in SNc and PD symptoms, it is important to have an integrated multiscale computational model that can replicate the symptoms at the behavioural level by evoking the key cellular and molecular underlying mechanisms that contribute to the pathology. In line with this objective, we present a multiscale integrated model of cortico-basal ganglia motor circuitry for arm reaching task, incorporating a detailed biophysical model of SNc dopaminergic neuron. Earlier researchers have shown that fluctuations in dopamine (DA) signals are analogous to reward/punishment signals, thereby prompting application of concepts from reinforcement learning (RL) to modelling the basal ganglia system. In our model, we replace the abstract representations of reward with the realistic variable of extracellular DA released by a network of SNc cells and incorporate it with the RL-based behavioural model, which simulates the arm reaching task. Our results showed that as SNc cell loss increases, the percentage success rate to reach the target decreases, and average time to reach the target increases. With levodopa (L-DOPA) medication, both the success rate and the average time to reach the target improved significantly. The proposed model also exhibits how differential dopaminergic axonal degeneration in basal ganglia results in various cardinal symptoms of PD as manifest in reaching movements. From the model results, we were able to show the side effects of L-DOPA mediation, such as wearing off and peak dosage dyskinesias. Moreover, from the results, we were able to predict the optimum dosage for varying degrees of cell loss and L-DOPA medication. The proposed model has a potential clinical application where drug dosage can be optimized as per patient characteristics. We conclude that our model presents a realistic and efficient way of simulating the PD pathology conditions and the effect of levodopa medication, thereby giving a reliable indicator towards the optimization of the drug dosage.

neuroscience↗

bioRxiv2020

DNA methylation is required to maintain DNA replication timing precision and 3D genome integrity

DNA replication timing and three-dimensional (3D) genome organisation occur across large domains associated with distinct epigenome patterns to functionally compartmentalise genome regulation. However, it is still unclear if alternations in the epigenome, in particular cancer-related DNA hypomethylation, can directly result in alterations to cancer higher order genome architecture. Here, we use Hi-C and single cell Repli-Seq, in the colorectal cancer DNMT1 and DNMT3B DNA methyltransferases double knockout model, to determine the impact of DNA hypomethylation on replication timing and 3D genome organisation. First, we find that the hypomethylated cells show a striking loss of replication timing precision with gain of cell-to-cell replication timing heterogeneity and loss of 3D genome compartmentalisation. Second, hypomethylated regions that undergo a large change in replication timing also show loss of allelic replication timing, including at cancer-related genes. Finally, we observe the formation of broad ectopic H3K4me3-H3K9me3 domains across hypomethylated regions where late replication is maintained, that potentially prevent aberrant transcription and loss of genome organisation after DNA demethylation. Together, our results highlight a previously underappreciated role for DNA methylation in maintenance of 3D genome architecture.

molecular biology↗

bioRxiv2020

PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2.

PT150 is a clinical stage molecule, taken orally, with a strong safety profile having completed Phase 1 and Phase 2 clinical trials for its original use as an anti-depressant. It has an active IND for COVID-19. Antiviral activities have been found for PT150 and other members of its class in a variety of virus families; thus, it was now tested against SARS-CoV-2 in human bronchial epithelial lining cells and showed effective 90% inhibitory antiviral concentration (EC90) of 5.55 M. PT150 is a member of an extended platform of novel glucocorticoid receptor (GR) and androgen receptor (AR) binding molecules. In vivo, their predominant net effect is one of systemic glucocorticoid antagonism, but they also show direct downregulation of AR and minor GR agonism at the cellular level. We hypothesize that anti-SARS-CoV-2 activity depends in part on this AR downregulation through diminished TMPRSS2 expression and modulation of ACE2 activity. Given that hypercortisolemia is now suggested to be a significant co-factor for COVID-19 progression, we also postulate an additive role for its potent immunomodulatory effects through systemic antagonism of cortisol.

microbiology↗

bioRxiv2020

Combining feature selection and shape analysis uncovers precise rules for miRNA regulation in Huntington's disease mice

BackgroundMicroRNA (miRNA) regulation is associated with several diseases, including neurodegenerative diseases. Several approaches can be used for modeling miRNA regulation. However, their precision may be limited for analyzing multidimensional data. Here, we addressed this question by integrating shape analysis and feature selection into miRAMINT, a methodology that we used for analyzing multidimensional RNA-seq and proteomic data from a knock-in mouse model (Hdh mice) of Huntingtons disease (HD), a disease caused by CAG repeat expansion in huntingtin (htt). This dataset covers 6 CAG repeat alleles and 3 age points in the striatum and cortex of Hdh mice. ResultsRemarkably, compared to previous analyzes of this multidimensional dataset, the miRAMINT approach retained only 31 explanatory striatal miRNA-mRNA pairs that are precisely associated with the shape of CAG repeat dependence over time, among which 5 pairs with a strong change of target expression levels. Several of these pairs were previously associated with neuronal homeostasis or HD pathogenesis, or both. Such miRNA-mRNA pairs were not detected in cortex. ConclusionsThese data suggest that miRNA regulation has a limited global role in HD while providing accurately-selected miRNA-target pairs to study how the brain may compute molecular responses to HD over time. These data also provide a methodological framework for researchers to explore how shape analysis can enhance multidimensional data analytics in biology and disease.

bioinformatics↗

bioRxiv2019

Coconut inflorescence sap mediated synthesis of silver nanoparticles and its diverse antimicrobial properties

Green synthesis of nanoparticles (NPs) involves the use of diverse extracts of biological origin as substrates to synthesize nanoparticles and can overcome the hazards associated with chemical methods. Coconut inflorescence sap, which is unfermented phloem sap obtained by tapping of coconut inflorescence, is a rich source of sugars and secondary metabolites. In this study, coconut inflorescence sap was used to synthesize silver nanoparticles (AgNPs). We have initially undertaken metabolomic profiling of coconut inflorescence sap from West Coast Tall cultivar to delineate its individual components. Secondary metabolites constituted the major portion of the inflorescence sap along with sugars, lipids and, peptides. The concentration of silver nitrate, inflorescence sap and incubation temperature for synthesis of AgNPs were optimized. Incubating the reaction mixture at 40{degrees}C was found to enhance AgNP synthesis. The AgNPs synthesized were characterized using UV-Visible spectrophotometry, X-Ray Diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR), Field Emission Scanning Electron Microscopy (FESEM) and Transmission Electron Microscopy (TEM). Antimicrobial property of AgNP was tested in tissue culture of arecanut (Areca catechu L.) where bacterial contamination (Bacillus pumilus) was a frequent occurrence. Significant reduction in the contamination was observed when plantlets were treated with aqueous solutions of 0.01, 0.02 and 0.03% of AgNPs for one hour. Notably, treatment with AgNPs did not affect growth and development of the arecanut plantlets. Cytotoxicity of AgNPs was quantified in HeLa cells. Viability (%) of HeLa cells declined significantly at 10 ppm concentration of AgNP and complete mortality was observed at 60 ppm. Antimicrobial properties of AgNPs synthesized from inflorescence sap were also evaluated and confirmed in human pathogenic bacteria viz., Salmonella sp., Vibrio parahaemolyticus, and Escherichia coli. The study concludes that unfermented inflorescence sap, with above neutral pH, serves as an excellent reducing agent to synthesize AgNPs from Ag+.\n\nO_FIG O_LINKSMALLFIG WIDTH=177 HEIGHT=200 SRC=\"FIGDIR/small/775940v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (64K):\norg.highwire.dtl.DTLVardef@3c3f1forg.highwire.dtl.DTLVardef@1540f6borg.highwire.dtl.DTLVardef@1c069aborg.highwire.dtl.DTLVardef@159772c_HPS_FORMAT_FIGEXP M_FIG Graphical abstract\n\nC_FIG

plant biology↗