Biology subjects

Narasimhan, S.

Publications and source records attributed to Narasimhan, S..

11 recordsLinked to original sources

bioRxiv2026

Isolation and introductions disrupt the homogeneity of Argentine ants in Europe.

The introduction of alien species into new habitats stands as a pressing economic and ecological challenge but it is also essential for unveiling evolutionary processes. The introduction of the Argentine ant (Linepithema humile) led to the spread of a single supercolony through different continents and thousands of kilometres like in Europe, from Northwest Spain to Greece. It was assumed that the high invasiveness of the species mainly relied on the lack of agonism among colonies, an effect derived from its introduction. However, recent studies suggest that local adaptations and evolutionary divergence could involve the disruption of the Argentine ant "empire" into a mosaic of competitive colonies. We investigated how isolation affects population divergence by comparing mainland and island populations in two distant regions colonized in Spain and in Greece with morphology, agonism, cuticular hydrocarbons, and genetic diversity of ant workers. Our results showed that all colonies sampled belonged to the most spread supercolony in Europe (main supercolony) except one sampled in Crete (Heraklion; Greece), which resulted to be a supercolony not registered in Europe. The Heraklian supercolony showed a different chemical and genetic profile and hostile agonism towards the other Greek colonies. Differences between islands and mainland colonies belonging to the main supercolony were higher in Galiza than in Greece. Surprisingly, the chemical profile of the Cretan colony belonging to the main supercolony showed more similarity with the Galizan colonies than with the Greek mainland, suggesting that L. humile may have been introduced into Greece through this island instead of the mainland. Our study suggests that local adaptations in Argentine ant colonies can trigger competition between colonies. Our data strongly support the existence of a candidate supercolony which highlights either ongoing introductions of L. humile in Europe or gaps in our understanding of its metapopulation dynamics.

evolutionary biology↗

bioRxiv2025

Complexity shapes uniqueness: Neuropil volumes and synaptic clusters shape behavioural plasticity under challenging environments in the invasive Argentine ants

Adaptation to new environments is key for organisms survival, but also for their invasiveness in their introduced areas. Behaviour is considered the fastest phenotype allowing adaptation, but its plasticity can involve costs as neural development. Although individuals investment in cognition was pointed out as unnecessary for colony behaviour in eusocial insects, recent studies are highlighting the behavioural dependence on neural traits in eusocial insects. The costs of producing behavioural and neural plastic offspring could exceed the investments of eusocial insects, in which one or certain reproductives must produce multiple offspring. Thus, we wanted to analyse the link between the neuroanatomy and the behavioural variability of Linepithema humile, an invasive species organised in supercolony units containing millions of individuals, to understand its adaptive mechanisms. We repeatedly tested same aged callow workers of L. humile in behavioural tests of increasing environmental complexity and analysed the volume of their brain functional areas (neuropils) and the synaptic clusters abundance in the mushroom body calices (information processing). Given the potential large cost of plasticity, we expected to find homogeneous interindividual neuronal structures and behavioural responses. Although L. humile is considered a monomorphic species, body size conditioned behavioural and neural traits and determined individuals efficiency in exploring simple environments. Contrary to our expectations, the increase in environmental complexity revealed the behavioural plasticity of Linepithema humile workers as well as its correlation with neuropil volumes and synaptic clusters. Our results highlight the relevance of the central complex and the mushroom bodies on exploration efficiency rather than optic and olfactory lobes. Behavioural plasticity under complex environments relied on the synaptic connections of the olfactory processing area (dense lip), while individuals with higher number of synaptic connections on the visual processing area (collar) explored complex environments less efficiently. Our results suggest that behavioural differences that correlate with morphological traits might promote adaptive mechanisms in simple environments, whereas neurologically based plastic behavior may be necessary to adapt in complex environments.

animal behavior and cognition↗

bioRxiv2024

High-dimensional mediation analysis to elucidate the role of metabolites in the association between PFAS exposure and reduced SARS-CoV-2 IgG in pregnancy

We previously found that per- and polyfluoroalkyl substances (PFAS) mixture exposure is inversely associated with SARS-CoV-2 IgG (IgG) antibody levels in pregnant individuals. Here, we aim to identify metabolites mediating this relationship to elucidate the underlying biological pathways. This cross-sectional study included 59 pregnant participants from a US-based pregnancy cohort. Untargeted metabolomic profiling was performed using Liquid Chromatography-High Resolution Sass spectrometry (LC-HRMS), and weighted Quantile Sum (WQS) regression was applied to assess the PFAS and metabolites mixture effects on IgG. Metabolite indices positively or negatively associated with IgG levels were constructed separately and their mediation effects were examined independently and jointly. The PFAS- index was negatively associated with IgG levels (beta=-0.315, p<0.001), with PFHpS and PFHxS as major contributors. Two metabolite-indices were constructed, one positively (beta=1.249, p<0.001) and one negatively (beta=-1.200, p<0.001) associated with IgG. Key contributors for these indices included trigonelline, adipate, p-octopamine, and n-acetylproline. Analysis of a single mediator showed that 74.6% (95% CI: 45.9%, 98.0%) and 68.6% (95% CI: 41.8%, 94.1%) of the PFAS index-IgG total effect were mediated by the negative and positive metabolites-indices, respectively. Joint analysis of the metabolite-indices indicated a cumulative mediation effect of 83.8% (95% CI: 58.1%, 98.7%). Enriched pathways associated with these metabolites indices were phenylalanine, tyrosine, and tryptophan biosynthesis and arginine metabolism. We observed significant mediation effects of plasma metabolites on the PFAS-IgG relationship, suggesting that PFAS is associated with alteration in the balance of plasma metabolites that contributes to reduced plasma IgG production.

bioinformatics↗

bioRxiv2022

Adaptive decision making depends on pupil-linked arousal in rats performing tactile discrimination tasks

Perceptual decision making is a dynamic cognitive process and is shaped by many factors, including behavioral state, reward contingency, and sensory environment. To understand the extent to which adaptive behavior in decision making is dependent upon pupil-linked arousal, we trained head-fixed rats to perform perceptual decision making tasks and systematically manipulated the probability of Go and No-go stimuli while simultaneously measuring their pupil size in the tasks. Our data demonstrated that the animals adaptively modified their behavior in response to the changes in the sensory environment. The response probability to both Go and No-go stimuli decreased as the probability of the Go stimulus being presented decreased. Analyses within the signal detection theory framework showed that while the animals perceptual sensitivity was invariant, their decision criterion increased as the probability of the Go stimulus decreased. Simulation results indicated that the adaptive increase in the decision criterion will increase possible water rewards during the task. Moreover, the adaptive decision making is dependent upon pupil-linked arousal as the increase in the decision criterion was the largest during low pupil-linked arousal periods. Taken together, our results demonstrated that the rats were able to adjust their decision making to maximize rewards in the tasks, and that adaptive behavior in perceptual decision making is dependent upon pupil-linked arousal.

neuroscience↗

bioRxiv2022

Deep learning segmentation of the nucleus basalis of Meynert on 3T MRI

The nucleus basalis of Meynert (NBM) is a key subcortical structure that is important in arousal, cognition, brain network modulation, and has been explored as a deep brain stimulation target. It has also been implicated in several disease states, including Alzheimers disease, Parkinsons disease, and temporal lobe epilepsy (TLE). Given the small size of NBM and variability between patients, NBM is difficult to study; thus, accurate, patient-specific segmentation is needed. We investigated whether a deep learning network could produce accurate, patient-specific segmentations of NBM on commonly utilized 3T MRI. It is difficult to accurately segment NBM on 3T MRI, with 7T being preferred. Paired 3T and 7T MRI datasets of 21 healthy subjects were obtained, with 6 completely withheld for testing. NBM was expertly segmented on 7T MRI, providing accurate labels for the paired 3T MRI. An external dataset of 14 patients with TLE was used to test the model on brains with neurological disorders. A 3D-Unet convolutional neural network was constructed, and a 5-fold cross-validation was performed. The model was evaluated on healthy subjects using the held-out test dataset and the external dataset of TLE patients. The model demonstrated significantly improved dice coefficient over the standard probabilistic atlas for both healthy subjects (0.68MEAN{+/-}0.08SD vs. 0.47{+/-}0.06, p=0.0089, t-test) and TLE patients (0.63{+/-}0.08 vs. 0.38{+/-}0.19, p=0.0001). Additionally, the centroid distance was significantly decreased when using the model in patients with TLE (1.22{+/-}0.33mm, 3.25{+/-}2.57mm, p=0.0110). We developed the first model, to our knowledge, for automatic and accurate patient-specific segmentation of the NBM.

neuroscience↗

bioRxiv2022

Merging of ventral fibers at adhesions drives the remodeling of cellular contractile systems in fibroblasts.

Ventral stress fibers (VSFs) are contractile actin fibers present in the ventral plane of the cell and existing in a dynamic attachment with cell-matrix focal adhesions. VSFs are critical in cellular mechanobiological functions such as traction force production, cell polarization, and migration. VSF within their intracellular network vary from short, thinner fibers that are randomly oriented to long, thick fibers that span along the whole long axis of a cell. De novo VSF formation was shown to occur by condensation from the cortical actin mesh or by crosslinking of other stress fiber subtypes (dorsal stress fibers and transverse arcs) at the cell front. However, formation of long VSFs that extend across the whole cell axis is not well understood. Here, we report a novel phenomenon of VSF merging in migratory fibroblast cells, which is guided by mechanical force balance and contributes to VSF alignment along the long cell axis. The mechanism of VSF merging involves two steps: connection of two ventral fibers by an emerging myosin II bridge at an intervening adhesion and intervening adhesion dissolution to form a cohesive, contractile VSF. Our data indicate that these two steps are interdependent, since under conditions where adhesion disassembly is slowed, formation of the myosin bridge is slowed as well. Cellular data and computational modeling show that the angle of contact between merging fibers decides successful merging, with angles closer to 180 yielding merging events and shallower angles leading to merge failure. Our data and modeling further show that merging increases the share of uniformly aligned long VSFs, which would contribute to directional traction force production. Thus, we thoroughly characterize merging as process for dynamic reorganization of VSFs in steady state, investigating the steps and variants of the process as well as its functional significance in migratory cells.

cell biology↗

bioRxiv2022

Localizing temporal lobe seizure onset zones using deep learning on SEEG cortico-cortical evoked potentials

In drug resistant temporal lobe epilepsy, automated tools for seizure onset zone (SOZ) localization using brief interictal recordings would supplement presurgical evaluations and improve care. Thus, we sought to localize SOZs by training a multi-channel convolutional neural network on stereo-EEG (SEEG) cortico-cortical evoked potentials. We performed single pulse electrical stimulation with 10 drug resistant temporal lobe epilepsy patients implanted with SEEG. Using the 500,000 unique post-stimulation SEEG epochs, we trained a multi-channel one-dimensional convolutional neural network to determine whether an SOZ was stimulated. SOZs were classified with a mean leave-one-patient-out testing sensitivity of 78.1% and specificity of 74.6%. To achieve maximum accuracy, the model requires a 0-350 ms post stimulation time period. Post-hoc analysis revealed that the model accurately classified unilateral vs bilateral mesial temporal lobe seizure onset, and neocortical SOZs. This is the first demonstration, to our knowledge, that a deep learning framework can be used to accurately classify SOZs using cortico-cortical evoked potentials. Our findings suggest accurate classification of SOZs relies on a complex temporal evolution of evoked potentials within 350 ms of stimulation. Validation in a larger dataset could provide a practical clinical tool for the presurgical evaluation of drug resistant epilepsy.

neuroscience↗

bioRxiv2022

CD36 homologs determine microbial resistance to the Lyme disease spirochete

Pattern recognition receptors sense pathogens in arthropods and mammals through distinct immune processes. Whether these molecules share a similar function and recognize the same microbe in evolutionarily distant species remain ill-defined. Here, we establish that the CD36 superfamily is required for Borrelia burgdorferi resistance in both the arthropod vector and humans. Using the blacklegged tick Ixodes scapularis and an electronic health record-linked biobank, we demonstrate that CD36 members elicit immunity to the Lyme disease spirochete. In ticks, the CD36-like protein Croquemort recognizes lipids and initiates the immune deficiency and jun N-terminal kinase pathways against B. burgdorferi. In humans, exome sequencing and clinical information reveal that individuals with CD36 loss-of-function variants have increased prevalence of Lyme disease. Altogether, we discovered a conserved mechanism of anti-bacterial immunity. One Sentence SummaryLipid receptors belonging to the CD36 superfamily exhibit a shared immune function in both ticks and humans.

immunology↗

bioRxiv2021

The Lyme Disease agent co-opts adiponectin receptor-mediated signaling in its arthropod vector

Adiponectin-mediated pathways contribute to mammalian homeostasis; however, little is known about adiponectin and adiponectin receptor signaling in arthropods. In this study, we demonstrate that Ixodes scapularis ticks have an adiponectin receptor-like protein (ISARL) but lack adiponectin - suggesting activation by alternative pathways. ISARL expression is significantly upregulated in the tick gut after Borrelia burgdorferi infection suggesting that ISARL-signaling may be co-opted by the Lyme disease agent. Consistent with this, RNA interference (RNAi)-mediated silencing of ISARL significantly reduced the B. burgdorferi burden in the tick. RNA-seq-based transcriptomics and RNAi assays demonstrate that ISARL-mediated phospholipid metabolism by phosphatidylserine synthase I is associated with B. burgdorferi survival. Furthermore, the tick complement C1q-like protein 3 interacts with ISARL, and B. burgdorferi facilitates this process. This study identifies a new tick metabolic pathway that is connected to the life cycle of the Lyme disease spirochete. Significance StatementAdiponectin binds to adiponectin receptors and participates in glucose and lipid metabolism in mammals. In this study, we found that ticks have an adiponectin receptor-like protein but lack adiponectin. Importantly, we demonstrated that the Lyme disease agent, Borrelia burgdorferi, takes advantage of the adiponectin receptor signaling pathway to establish infection in its arthropod vector, Ixodes scapularis. Our study sheds light on the understanding of Borrelia-tick interactions and provides insights into how a human infectious disease agent may evolve to manipulate host metabolism for its own benefits. Understanding this pathway may lead to new ways to interfere with the Borrelia life cycle, and this mechanism may be applicable to additional microbes that are transmitted by ticks, mosquitoes or other arthropods.

microbiology↗

bioRxiv2021

A universal pocket in FAALs ensures redirection of fatty acid pool away from CoA-based activation

Fatty acyl-AMP ligases (FAALs) channelize fatty acids towards biosynthesis of virulent lipids in mycobacteria and other pharmaceutically or ecologically important polyketides and lipopeptides in other microbes. They do so by bypassing the ubiquitous coenzyme A-dependent activation and rely on the acyl carrier protein-tethered 4-phosphopantetheine (holo-ACP). The molecular basis of how FAALs strictly reject chemically identical and abundant acceptors like coenzyme A (CoA) and accept holo-ACP unlike other members of the ANL superfamily remains elusive. We show FAALs have plugged the promiscuous canonical CoA-binding pockets and utilize highly selective alternative binding sites. These alternative pockets can distinguish adenosine 3, 5-bisphosphate-containing CoA from holo-ACP and thus FAALs can distinguish between CoA and holo-ACP. These exclusive features helped identify the omnipresence of FAAL-like proteins and their emergence in plants, fungi, and animals with unconventional domain organisations. The universal distribution of FAALs suggests they are parallelly evolved with FACLs for ensuring a CoA-independent activation and redirection of fatty acids towards lipidic metabolites.

biochemistry↗

bioRxiv2021

A Focal Adhesion Filament Cross-correlation Kit for fast, automated segmentation and correlation of focal adhesions and actin stress fibers in cells

Focal adhesions (FAs) and associated actin stress fibers (SFs) form a complex mechanical system that mediates bidirectional interactions between cells and their environment. This linked network is essential for mechanosensing, force production and force transduction, thus directly governing cellular processes like polarization, migration and extracellular matrix remodeling. We introduce a tool for fast and robust coupled analysis of both FAs and SFs named the Focal Adhesion Filament Cross-correlation Kit (FAFCK). Our software can detect and record location, axes lengths, area, orientation, and aspect ratio of focal adhesion structures as well as the location, length, width and orientation of actin stress fibers. This enables users to automate analysis of the correlation of FAs and SFs and study the stress fiber system in a higher degree, pivotal to accurately evaluate transmission of mechanocellular forces between a cell and its surroundings. The FAFCK is particularly suited for unbiased and systematic quantitative analysis of FAs and SFs necessary for novel approaches of traction force microscopy that uses the additional data from the cellular side to calculate the stress distribution in the substrate. For validation and comparison with other tools, we provide datasets of cells of varying quality that are labelled by a human expert. Datasets and FAFCK are freely available as open source under the GNU General Public License. Author summaryOur novel Focal Adhesion Filament Cross-correlation Kit (FAFCK) allows for fast, reliable, unbiased, and systematic detection of focal adhesions and actin stress fibers in cells and their mutual correlation. Detailed analysis of these structures which are both key elements in mechano-sensing and force transduction will help tremendously to improve quantitative analysis of mechanocellular experiments, key to understanding the complex interplay between cells and the extracellular matrix. In particular, sophisticated analysis methods such as model-based traction force microscopy will benefit from correlating the detailed datasets of stress fibers and focal adhesions.

biophysics↗