Biology subjects

Raghavan, M.

Publications and source records attributed to Raghavan, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Mapping reward processing circuits: the orbitofrontal-nucleus accumbens white matter pathways and their associations to psychopathological traits

Dysfunctions in reward circuits, including projections from the orbitofrontal cortex (OFC) to the nucleus accumbens (NAcc), have been implicated in psychopathology. The OFC is functionally divided into the medial OFC (mOFC), which processes rewards, and the lateral OFC (lOFC), which responds to non-reward or punishment stimuli. We investigated the structural connectivity of the lOFC-NAcc and mOFC-NAcc pathways and their associations with psychopathological traits using tractography-defined ROI analysis. Diffusion-weighted imaging data from 165 participants (aged 22 - 35, 53% male) in the Human Connectome Project (HCP) were analysed using spherical deconvolution tractography. MegaTrack, a novel tool, enabled tract segmentation via a single manual dissection mapped back to native space. Virtual dissection identified four bilateral pathways connecting the lOFC and mOFC to the NAcc, from which fractional anisotropy (FA) was extracted, and an lOFC/mOFC ratio was computed. Psychopathological traits were measured using HCP Achenbach Adult Self-Report scores. The lOFC-NAcc pathway showed positive associations with psychopathology and the mOFC-NAcc pathway negative associations. The lOFC/mOFC ratio emerged as a stronger predictor than individual pathways, with significant associations for depression, somatic problems, anti-social personality traits, and inattention. Effects were lateralized to the left hemisphere. These findings show that the lOFC-NAcc and mOFC-NAcc pathways can be structurally separated with tractography and display opposing correlations with psychopathological traits in a healthy population. Their ratio may index reward-processing dysfunction, and future research should test whether it is sensitive to dysfunction in clinical populations.

neuroscience↗

bioRxiv2026

Range-wide phylogeography, population genomics, and demography of three widespread Ara macaws (Psittacidae)

Macaws of the genus Ara comprise eight extant species distributed throughout the Neotropics. Among them, four have broad geographic ranges, yet little is known about the evolutionary history and demographic processes that shaped their genomic variation and present-day distributions. This is particularly relevant because, although these wide-ranging macaws are classified as Least Concern by the IUCN, many of their populations are declining due to habitat fragmentation, illegal trade, and climate change. Here, we used nuclear and mitochondrial genomic data to characterize the evolutionary relationships, population structure, genetic diversity, and demographic histories of three widely distributed species (A. ararauna, A. chloropterus, and A. severus) across their geographic distributions. We identified two main populations within Ara severus, and this species showed the highest heterozygosity levels among the three species. In A. ararauna and A. chloropterus, we observed four main genetic clusters corresponding to two populations in the Amazon rainforest biome and and two populations in the Cerrado savanna biome. Cerrado populations in both species exhibited markedly reduced heterozygosity and elevated inbreeding relative to Amazonian populations, consistent with smaller effective population sizes and increased isolation. Genome-wide scans suggested that genetic drift and divergent demographic histories played a predominant role in driving the strong differentiation between Amazon and Cerrado in these two species. Nevertheless, we detected two candidate genes, NALCN and RBBP6, with convergent selection signals across A. ararauna and A. chloropterus, suggesting possible local adaptation to the Cerrado biome.

evolutionary biology↗

bioRxiv2026

Ancient human genomes from Ladakh reveal Tibetan, South Asian, and Central Asian admixture over the last three millennia

The trans-Himalayan region of Ladakh occupies a strategic position at the crossroads of South Asia, the Tibetan Plateau, and Central Asia, with archaeological evidence pointing to long-term cultural exchanges across these regions. However, the human genetic history of Ladakh remains largely unexplored. We generated paleogenomic data from seven individuals recovered from two sites in Western Ladakh - the Old Lady Spider Cave and Hanu - of which six are dated to 531-585 CE and one to the 19th century CE. The older individuals share substantial genetic ancestry with Tibetan groups but also harbor major contributions from two additional sources: one corresponding to the currently-oldest observation of the Ancestral North Indian genetic component that characterizes several present-day populations in North India and Pakistan, and another related to ancient Central Asian groups, with admixture events occurring between [~]2,100-2,500 years ago. In contrast, the later individual falls within a previously described ancient northern Himalayan genetic cline based on [~]1,100-1,300-year-old individuals from Himachal Pradesh, with ancestries related to ancient Tibetan and Steppe-related sources. Stable isotope analysis suggests that these individuals were local to Ladakh in late life and practiced an agro-pastoralist subsistence. Our study establishes that Ladakhs central role in Eurasian economic and socio-cultural networks was shaped by dynamic and sustained gene flow linking high-altitude Himalayan groups with both lowland South Asia and Inner Asia.

genetics↗

bioRxiv2026

Distinct trajectories of urbanization shape the human gut microbiome across South Asia

Human gut microbiomes respond to lifestyle transitions, yet the extent to which these responses are conserved across spatio-cultural contexts remains undercharacterized. We present the South Asian MicroBiome ARray (SAMBAR), a population-scale 16S gut microbiome study of 575 adults from ten geographically and socio-culturally diverse South Asian communities. Each community was sampled in ancestral villages and urban centers, enabling controlled comparisons of geography and lifestyle. Relative to global cohorts, SAMBAR microbiomes occupy a distinct compositional space with stronger correlation to geography and community membership than lifestyle. Although urbanization is consistently associated with increased abundance of disease-linked taxa, microbiome responses to lifestyle transitions are largely community-driven, including the acquisition of wheat- and dairying-associated microbial modules in some communities that may facilitate non-genetic adaptation to lactase non-persistence. Microbiome responses to urbanization are heterogeneous even at regional scales, reflecting local culture and geography and underscoring the need for community-specific investigations of health impacts.

microbiology↗

bioRxiv2025

Effects of Calreticulin Mutations on HLA Class I Expression in Myeloproliferative Neoplasms

Calreticulin (CRT) is important for human leukocyte antigen (HLA) class I assembly. Somatic mutations of the CRT gene (CALR) in hematopoietic lineage cells cause myeloproliferative neoplasms (MPNs). Typically, MPN patient cells have one copy each of the wild-type and mutant CALR allele. We find that heterozygous knock-in of a MPN CALR mutation into human cell lines maintains or slightly induces surface expression of HLA class I allotypes. However, full deficiency of wild-type CRT variably reduces the surface expression of HLA class I allotypes, and MPN CRT mutants fail to restore expression for all tested allotypes. Consistent with the largely heterozygous nature of CALR mutations in MPN, surface HLA class I expression in platelets and monocytes from MPN patients with CALR mutations generally falls within the normal range, with higher average expression measured in monocytes from patients treated with interferon alpha compared with other treatments. Overall, the studies indicate that loss of HLA class I expression in cells deficient in wild-type CRT (the CRT dependency) is allele-dependent and correlates with known effects of the assembly factor tapasin. Furthermore, heterozygous knock-in of a MPN-linked CALR mutation has no effect on some allotypes and slightly induces HLA class I expression for CRT-dependent allotypes.

immunology↗

bioRxiv2025

Effects of calreticulin deficiency and myeloproliferative neoplasm (MPN)-linked mutation on cellular calcium signaling

Calreticulin (CRT) is an endoplasmic reticulum (ER) chaperone with low affinity calcium binding sites in its C-terminal domain. This region is altered by somatic mutations in the CRT gene (CALR), which drive a subset of myeloproliferative neoplasms (MPN). Perturbations in ER calcium storage and signaling are reported for the MPN type I mutant, CRTDel52, and are linked to disease pathogenesis. Using recombinant CRT proteins, we found similar low affinity calcium binding characteristics for wild-type CRT and CRTDel52, as determined by isothermal titration calorimetry (ITC). Residues 340-349, conserved in both wild-type CRT and CRTDel52, contribute to binding. Furthermore, ER and cytosolic calcium levels and store-operated calcium entry (SOCE) were comparable in CRT knockout (CRT-KO) cells reconstituted with wild-type CRT or CRTDel52. Notably, the CRT-KO induces expression of multiple ER proteins known to contain low affinity calcium binding sites or regulate ER calcium levels. Overall, these findings indicate that CRTDel52 retains at least some low affinity calcium binding capacity and that CRT-deficiency induces compensatory cellular changes that maintain ER calcium homeostasis. SummaryPathogenic CRTDel52 retains at least partial low-affinity calcium-binding capacity. Additionally, live-cell imaging and flow cytometry with ratiometric calcium probes indicate that ER and cytosolic calcium levels, as well as store-operated calcium entry (SOCE), are comparable in CRT-deficient cells rescued with either wild-type CRT or CRTDel52.

cancer biology↗

bioRxiv2025

Paired primary-metastasis patient-derived organoids and mouse models identify phenotypic evolution and druggable dependencies of peritoneal metastasis from appendiceal cancer

Peritoneal carcinomatosis is a common yet deadly manifestation of gastrointestinal cancers, with few effective treatments. To identify targetable determinants of peritoneal metastasis, we focused on appendiceal adenocarcinoma (AC), a gastrointestinal cancer that metastasizes almost exclusively to the peritoneum. Current treatments are extrapolated from colorectal cancer (CRC), yet AC has distinct genomic alterations, mucinous morphology and peritoneum restricted metastatic pattern. Further, no stable preclinical models of AC exist, limiting drug discovery and representing an unmet clinical need. We establish a first-in-class stable biobank of 16 long-term cultured AC patient-derived organoids (PDOs), including 3 matched, simultaneously resected primary AC-peritoneal carcinomatosis (AC-PC) pairs. By enriching for cancer cells, AC PDOs enable accurate genomic characterization relative to paucicellular AC tissue. We establish an organoid orthotopic intraperitoneal xenograft model that recapitulates diffuse peritoneal carcinomatosis and show that PC-organoids retain increased metastatic capacity, decreased growth factor dependency and sensitivity to standard of care chemotherapy relative to matched primary AC organoids. Single cell profiling of AC-PC pairs reveals dedifferentiation from mucinous differentiated states in primary AC into intestinal stem cell and fetal progenitor states in AC-PC, with upregulation of oncogenic signaling pathways. Through hypothesis-driven drug testing, we identify KRASMULTI-ON inhibitor RMC-7977 and Wnt-targeting tyrosine kinase inhibitor WNTinib as novel, clinically actionable strategies to target AC-PC more effectively.

cancer biology↗

bioRxiv2024

Modeling cardiorespiratory coherence in exercise anticipation

Volitional motor activity is associated with a feedforward cardiorespiratory response to actual or impending movements. We have previously shown in the CRC study that the expectation of physical exercise causes a decrease in cardiorespiratory coherence that scales with the anticipated load. The present work uses a modeling approach to investigate the mechanisms that can cause a fall in cardiorespiratory coherence (CRC). We devised a Hodgkin-Huxley model of a cardiac pacemaker cell using the NEURON module. We simulated the effect of autonomic tone, sympathetic & respiratory-vagal modulation, and respiratory irregularity on pacemaker cell output by injecting efflux/influx current to model the parasympathetic/sympathetic effects, respectively. The vago-sympathetic tone was modeled by altering the direct current bias of the injected current and the respiratory-vagal effect by the periodic modulation of the injected current at a frequency of 0.2 Hz, corresponding to a respiratory rate of 12 breaths/min. Sympathetic modulation was simulated by injecting a low-frequency current close to Mayer wave frequency (0.08 Hz). We computed the coherence between the instantaneous pacemaker rate and respiratory-vagal modulation current as a model analog to experimental CRC. We found that sympathetic modulation, low vagal tone/high sympathetic tone, and respiratory irregularity can cause a decrease in CRC. We corroborated the model results with the actual data from the CRC study. In conclusion, we employ a novel approach combining insights from the experimental study and a physiologically plausible modeling framework to understand the mechanisms underlying the fall of cardiorespiratory coherence induced by the expectation of exercise. NEW & NOTEWORTHY Cardiorespiratory coherence is diminished in response to respiratory irregularity, low vagal/high sympathetic tone, and prominent low-frequency sympathetic modulation. Expectation of physical activity induces respiratory irregularity and increased sigh frequency and that contributes to diminished cardiorespiratory coherence in expectation of exercise. There is a greater fall of coherence with the non-linear (logistic) transformation of injected current, indicating the non-linear nature of cardiorespiratory interactions preceding the onset of exercise.

physiology↗

bioRxiv2024

The genomic and cultural diversity of the Inka Qhapaq hucha ceremony in Chile and Argentina

The South American archaeological record has ample evidence of the socio-cultural dynamism of human populations in the past. This has also been supported through the analysis of ancient genomes, by showing evidence of gene flow across the region. While the extent of these signals is yet to be tested, the growing number of ancient genomes allows for more fine-scaled hypotheses to be evaluated. In this study, we assessed the genetic diversity of individuals associated with the Inka ritual, Qhapaq hucha. As part of this ceremony, one or more individuals were buried with Inka and local-style offerings on mountain summits along the Andes, leaving a very distinctive record. Using paleogenomic tools, we analyzed three individuals: two newly-generated genomes from El Plomo Mountain (Chile) and El Toro Mountain (Argentina), and a previously published genome from Argentina (Aconcagua Mountain). Our results reveal a complex demographic scenario with each of the individuals showing different genetic affinities. Furthermore, while two individuals showed genetic similarities with present-day and ancient populations from the southern region of the Inka empire, the third individual may have undertaken long-distance movement. The genetic diversity we observed between individuals from similar cultural contexts supports the highly diverse strategies the Inka implemented while incorporating new territories. More broadly, this research contributes to our growing understanding of the population dynamics in the Andes by discussing the implications and temporality of population movements in the region.

genomics↗

bioRxiv2023

DREDge: robust motion correction for high-density extracellular recordings across species

High-density microelectrode arrays (MEAs) have opened new possibilities for systems neuroscience in human and non-human animals, but brain tissue motion relative to the array poses a challenge for downstream analyses, particularly in human recordings. We introduce DREDge (Decentralized Registration of Electrophysiology Data), a robust algorithm which is well suited for the registration of noisy, nonstationary extracellular electrophysiology recordings. In addition to estimating motion from spikes in the action potential (AP) frequency band, DREDge enables automated tracking of motion at high temporal resolution in the local field potential (LFP) frequency band. In human intraoperative recordings, which often feature fast (period <1s) motion, DREDge correction in the LFP band enabled reliable recovery of evoked potentials, and significantly reduced single-unit spike shape variability and spike sorting error. Applying DREDge to recordings made during deep probe insertions in nonhuman primates demonstrated the possibility of tracking probe motion of centimeters across several brain regions while simultaneously mapping single unit electrophysiological features. DREDge reliably delivered improved motion correction in acute mouse recordings, especially in those made with an recent ultra-high density probe. We also implemented a procedure for applying DREDge to recordings made across tens of days in chronic implantations in mice, reliably yielding stable motion tracking despite changes in neural activity across experimental sessions. Together, these advances enable automated, scalable registration of electrophysiological data across multiple species, probe types, and drift cases, providing a stable foundation for downstream scientific analyses of these rich datasets.

neuroscience↗

bioRxiv2023

A heterozygous CEBPA mutation disrupting the bZIP domain causes MDS disease progression

Myelodysplastic syndrome disease (MDS) has a variable risk for progression to AML. Mutations in CEBPA are associated with a high risk of disease progression, but whether this mutation is causative for AML development is unclear. To answer this question, we generated patient-derived, MDS-specific iPSCs recapitulating the patient disease phenotype upon differentiation to blood, with hematopoietic progenitor cells showing erythroid and myeloid-dysplasia. Introduction of a frameshift mutation affecting the C/EBP bZIP domain led to disease progression, with a reduction in clonogenic potential, block in granulocyte development and increased self-renewal capacity of erythroid progenitors. ATAC-seq revealed that the acquisition of this mutation reshaped the chromatin landscape at distal cis-regulatory regions, promoting changes in clonal composition as observed by single cell RNAseq. Our work identifies mutant CEBPA as causative for MDS disease progression, providing a new isogenic MDS experimental model for drug screening to improve diagnostic and therapeutic strategies. HighlightsO_LIDevelopment of isogenic iPSC model of clonal evolution of MDS C_LIO_LIMonoallelic disruption of CEBPA bZIP domain is causative for MDS disease progression C_LIO_LIMonoallelic disruption of CEBPA bZIP reshapes chromatin landscape C_LIO_LIPatient derived iPSCs recapitulate drug responsiveness C_LI

cancer biology↗

bioRxiv2023

Lysosomal Degradation Pathways Target Mutant Calreticulin and the Thrombopoietin Receptor in Myeloproliferative Neoplasms

Somatic mutants of calreticulin (CRT) drive myeloproliferative neoplasms (MPNs) via binding to the thrombopoietin receptor (MPL) and aberrant activation of the JAK/STAT pathway. Compared with healthy donors, platelets from MPN patients with CRT mutations display low cell surface MPL. Co-expression of MPL with an MPN-linked CRT mutant (CRTDel52) reduces cell surface MPL expression, indicating the involvement of induced protein degradation, a better understanding of which could lead to new therapies. We show that lysosomal degradation is relevant to the turnover of both CRTDel52 and MPL. Drug-mediated activation of lysosomal degradation reduces CRTDel52 and MPL expression, with parallel inhibition of CRTDel52-induced cell proliferation and stem cell colony formation. Thus, reduced surface MPL, a marker of platelets from MPN patients with CRT mutations, results from mutant CRT-induced lysosomal degradation of MPL. Drug-induced activation of lysosomal degradation compromises the pathogenic effects of CRTDel52, which can be further exploited for therapeutic interventions.

cancer biology↗

bioRxiv2023

Structural modeling of cytokine-receptor-JAK2 signaling complexes using AlphaFold Multimer

Homodimeric class 1 cytokine receptors include the erythropoietin (EPOR), thrombopoietin (TPOR), granulocyte colony-stimulating factor 3 (CSF3R), growth hormone (GHR), and prolactin receptors (PRLR). They are cell-surface single-pass transmembrane (TM) glycoproteins that regulate cell growth, proliferation, and differentiation and induce oncogenesis. An active TM signaling complex consists of a receptor homodimer, one or two ligands bound to the receptor extracellular domains and two molecules of Janus Kinase 2 (JAK2) constitutively associated with the receptor intracellular domains. Although crystal structures of soluble extracellular domains with ligands have been obtained for all the receptors except TPOR, little is known about the structure and dynamics of the complete TM complexes that activate the downstream JAK-STAT signaling pathway. Three-dimensional models of five human receptor complexes with cytokines and JAK2 were generated using AlphaFold Multimer. Given the large size of the complexes (from 3220 to 4074 residues), the modeling required a stepwise assembly from smaller parts with selection and validation of the models through comparisons with published experimental data. The modeling of active and inactive complexes supports a general activation mechanism that involves ligand binding to a monomeric receptor followed by receptor dimerization and rotational movement of the receptor TM -helices causing proximity, dimerization, and activation of associated JAK2 subunits. The binding mode of two eltrombopag molecules to TM -helices of the active TPOR dimer was proposed. The models also help elucidating the molecular basis of oncogenic mutations that may involve non-canonical activation route. Models equilibrated in explicit lipids of the plasma membrane are publicly available.

biochemistry↗

bioRxiv2023

Leukemic stem cells hijack lineage inappropriate signalling pathways to promote their growth

Acute Myeloid Leukemia (AML) is caused by multiple mutations which dysregulate growth and differentiation of myeloid cells. Cells adopt different gene regulatory networks specific to individual mutations, maintaining a rapidly proliferating blast cell population with fatal consequences for the patient if not treated. The most common treatment option is still chemotherapy which targets such cells. However, patients harbour a population of quiescent leukemic stem cells (LSCs) which can emerge from quiescence to trigger relapse after therapy. The processes that allow such cells to re- grow remain unknown. Here, we examined the well characterised t(8;21) AML sub-type as a model to address this question. Using a novel t(8;21) patient-derived xenograft model, we show that t(8;21) LSCs aberrantly activate the VEGF and IL-5 signalling pathways. Both pathways operate within a regulatory circuit consisting of the driver oncoprotein RUNX1::ETO and an AP-1/GATA2 axis allowing LSCs to re-enter the cell cycle while preserving self-renewal capacity.

cancer biology↗

bioRxiv2023

Mass spectrometric profiling of HLA-B44 peptidomes provides evidence for tapasin-mediated tryptophan editing

Activation of CD8+ T cells against pathogens and cancers involves the recognition of antigenic peptides bound to human leukocyte antigen (HLA) class-I proteins. Peptide binding to HLA class I proteins is coordinated by a multi-protein complex called the peptide loading complex (PLC). Tapasin, a key PLC component, facilitates the binding and optimization of HLA class I peptides. However, different HLA class I allotypes have variable requirements for tapasin for their assembly and surface expression. HLA-B*44:02 and HLA-B*44:05, which differ only at residue 116 of their heavy chain sequences, fall at opposite ends of the tapasin-dependency spectrum. HLA-B*44:02 (D116) is highly tapasin-dependent, whereas HLA-B*44:05 (Y116) is highly tapasinindependent. Mass spectrometric comparisons of HLA-B*4405 and HLA-B*44:02 peptidomes were undertaken to better understand the influences of tapasin upon HLA-B44 peptidome compositions. Analyses of the HLA-B*44:05 peptidomes in the presence and absence of tapasin reveal that peptides with the C-terminal tryptophan residues and those with higher predicted binding affinities are selected in the presence of tapasin. Additionally, when tapasin is present, C-terminal tryptophans are also more highly represented among peptides unique to B*44:02 and those shared between B*44:02 and B*44:05, compared with peptides unique to B*44:05. Overall, our findings demonstrate that tapasin influences the C-terminal composition of HLA class I-bound peptides and favors the binding of higher affinity peptides. For the HLA-B44 family, the presence of tapasin or high tapasin-dependence of an allotype results in better binding of peptides with C-terminal tryptophans, consistent with a role for tapasin in stabilizing an open conformation to accommodate bulky C-terminal residues.

immunology↗

bioRxiv2023

Distinct mutational processes shape selection of MHC class I and class II mutations across primary and metastatic tumors

Disruption of antigen presentation via loss of MHC expression is a strategy whereby cancer cells escape immune surveillance and develop resistance to immunotherapy. We developed the personalized genomics algorithm Hapster and accurately called somatic mutations within the MHC genes of 10,001 primary and 2,199 metastatic tumors, creating a catalog of 1663 nonsynonymous mutations that provide key insights into MHC mutagenesis. We found that MHC-I genes are among the most frequently mutated genes in both primary and metastatic tumors, while MHC-II mutations are more restricted. Recurrent deleterious mutations are found within haplotype and cancer-type specific hotspots associated with distinct mutational processes. Functional classification of MHC residues revealed significant positive selection for mutations disruptive to the B2M, peptide, and T-cell binding interfaces, as well as MHC chaperones. At the cohort level, all cancers with positive selection for MHC mutations are responsive to immune checkpoint inhibitors, underscoring the translational relevance of our findings.

cancer biology↗

bioRxiv2022

Imaging cortical engagement during motor imagery, mental arithmetic, and silent word generation using MEG beta rhythm

Accurate mapping of cortical engagement during mental imagery or cognitive tasks remains a challenging brain-imaging problem with immediate relevance to the development of brain-computer interfaces (BCI). We analyzed data from fourteen individuals who performed cued motor imagery, mental arithmetic, or silent word generation tasks during MEG recordings. During the motor imagery task, participants imagined the movement of either both hands (HANDS) or both feet (FEET) after the appearance of a static visual cue. During the cognitive task, participants either mentally subtracted two numbers that were displayed on the screen (SUB) or generated words starting with a letter cue that was presented (WORD). The MEG recordings were denoised using a combination of spatiotemporal filtering, the elimination of noisy epochs, and ICA decomposition. Cortical source power in the beta-band (17-25 Hz) was estimated from the selected temporal windows using a frequency-resolved beamforming method applied to the sensor-level MEG signals. The task-related cortical engagement was inferred from beta power decrements within non-overlapping 400 ms temporal windows between 400 and 2800 ms after cue presentation relative to a baseline 400 ms temporal window before cue onset. We estimated the significance of these power changes within each parcel of the Desikan-Killiany atlas using a non-parametric permutation test at the group level. During the HANDS and FEET movement-imagery conditions, beta-power decreased in premotor and motor areas, consistent with a robust engagement of these cortical regions during motor imagery. During WORD and SUB tasks, beta-power decrements signaling cortical engagement were lateralized to left hemispheric brain areas that are expected to engage in language and arithmetic processing within the temporal (superior temporal gyrus), parietal (supramarginal gyrus), and (inferior) frontal regions. A leave-one-subject-out cross-validation using a support vector machine (SVM) applied to beta power decrements across brain parcels yielded accuracy rates of 74% and 68% respectively, for classifying motor-imagery (HANDS-vs-FEET) and cognitive (WORD-vs-SUB) tasks. From the motor-versus-nonmotor contrasts, accuracy rates of 85% and 80% respectively, were observed for HAND-vs-WORD and HAND-vs-SUB. A multivariate Gaussian process classifier (GPC) provided an accuracy rate of 60% for a four-way (HANDS-FEET-WORD-SUB) classification problem. The regions identified by both SVM and GPC classification weight maps were largely consistent with the source modeling findings. Within-subject correlations of beta-decrements during the two task sessions provided insights into the level of engagement by individual subjects and showed moderately high correlations for most subjects. Our results show that it is possible to map the dynamics of cortical engagement during mental processes in the absence of dynamic sensory stimuli or overt behavioral outputs using task-related beta-power decrements. The ability to do so with the high spatiotemporal resolution afforded by MEG could potentially help better characterize the physiological basis of motor or cognitive impairments in neurological disorders and guide strategies for neurorehabilitation.

neuroscience↗

bioRxiv2022

Integrating genetic and oral histories of Southwest Indian populations

Over the past decade, genomic data has contributed to several insights on global human population histories. These studies have been met both with interest and critically, particularly by populations with oral histories that are records of their past and often reference their origins. While several studies have reported concordance between oral and genetic histories, there is potential for tension that may stem from genetic histories being prioritized or used to confirm community-based knowledge and ethnography, especially if they differ. To investigate the interplay between oral and genetic histories, we focused on the southwestern region of India and analyzed whole-genome sequence data from 158 individuals identifying as Bunt, Kodava, Nair, and Kapla. We supplemented limited anthropological records on these populations with oral history accounts from community members and historical literature, focusing on references to non-local origins such as the ancient Scythians in the case of Bunt, Kodava, and Nair, members of Alexander the Greats army for the Kodava, and an African-related source for Kapla. We found these populations to be genetically most similar to other Indian populations, with the Kapla more similar to South Indian tribal populations that maximize a genetic ancestry related to Andaman Islanders. We did not find evidence of additional genetic sources in the study populations than those known to have contributed to many other present-day South Asian populations. Our results demonstrate that oral and genetic histories may not always provide consistent accounts of population origins and motivate further community-engaged, multi-disciplinary investigations of non-local origin stories in these communities.

genetics↗