Biology subjects

Kumar, S.

Publications and source records attributed to Kumar, S..

At least 469 records · Page 26Linked to original sources

bioRxiv2021

Microenvironmental correlates of immune checkpoint inhibitor response in human melanoma brain metastases revealed by T cell receptor and single-cell RNA sequencing

Melanoma-derived brain metastases (MBM) represent an unmet clinical need due to central nervous system (CNS) progression as a frequent, end-stage site of disease. Immune checkpoint inhibition (ICI) represents a clinical opportunity against MBM; however, the MBM tumor microenvironment (TME) has not been fully elucidated in the context of ICI. To dissect unique MBM-TME elements and correlates of MBM-ICI response, we collected 32 fresh MBM and performed single cell RNA sequencing of the MBM-TME and T cell receptor clonotyping on T cells from MBM and matched blood and extracranial lesions. We observed myeloid phenotypic heterogeneity, most notably multiple distinct neutrophil states including an IL-8 expressing population that correlated with malignant cell epithelial-to-mesenchymal transition. Additionally, we observe significant relationships between intracranial T cell phenotypes and the distribution of T cell clonotypes intracranially and peripherally. We found that the phenotype, clonotype, and overall number of MBM-infiltrating T cells were associated with response to ICI, suggesting that ICI-responsive MBMs interact with peripheral blood in a manner similar to extracranial lesions. These data demonstrate unique features of the MBM-TME, which may represent potential targets to improve clinical outcomes for patients with MBM.

cancer biology↗

bioRxiv2021

Comparative kinetic analysis of ascorbate (Vitamin-C) recycling dehydroascorbate reductases from plant and human.

Ascorbate, a primary antioxidant, gets readily oxidized to dehydroascorbate (DHA). Hence, recycling by dehydroascorbate reductase (DHAR) enzymes is vital for protection from cellular oxidative stress in eukaryotes. However, a detailed kinetic analysis of plant DHARs and their human orthologs; chloride intracellular channels (HsCLICs) is lacking. We demonstrate that DHAR from stress adapted pearl millet Pennisetum glaucum (PgDHAR) shows the highest turnover rate whereas HsCLIC1, 3, and 4 reduce DHA, albeit at lower rates. We further show that the catalytic cysteine is susceptible to varying levels of oxidation, supported by crystal structures and mass-spectrometry analysis. The differences in kinetic parameters among plant and human DHA reductases corroborate with the levels of reactive oxygen species H2O2 encountered in their respective intracellular environment. Our findings may have broader implications in crop improvement using pearl millet DHAR, and anti-cancer therapeutics targeting Vitamin-C recycling capability of human CLICs.

biochemistry↗

bioRxiv2021

The genome trilogy of Anopheles stephensi, an urban malaria vector, reveals structure of a locus associated with adaptation to environmental heterogeneity

BackgroundAnopheles stephensi is the most menacing malaria vector to watch for in newly urbanizing parts of the world. The fitness is reported to be a direct consequence of the vector adapting to laying eggs in over-head water tanks with street-side water puddles polluted by oil and sewage. Large frequent inversions of malaria vectors are implicated in adaptation. ResultsWe report the assembly of a strain of An. stephensi of the type-form, collected from a construction site from Chennai (IndCh) in 2016. The genome completes the trilogy with respect to a 16 Mbp inversion (2Rb) in An. stephensi associated with adaptation to environmental heterogeneity. Comparative genome analysis revealed breakpoint structure and allowed extraction of 22,650 segregating SNPs for typing this inversion. Using whole genome sequencing of 82 individual mosquitoes, we conclude that one third of both wild and laboratory populations maintain heterozygous genotype of 2Rb. The large number of SNPs are tailored to assign inversion genotype directly from 1740 exonic SNPs 80% of which are expressed in various developmental stages. ConclusionsThe genome trilogy approach accelerates study of fine structure and typing of important inversions in malaria vectors putting the genome resources for the much understudied An. stephensi, on par with the extensively studied malaria vector, Anopheles gambiae. We argue that the IndCh genome is relevant for field translation work compared to those reported earlier by showing that individuals from diverse populations cluster with IndCh pointing to significant commerce between cities, perhaps, allowing for survival of the fittest strain.

genomics↗

bioRxiv2021

Deep phylo-taxono genomics reveals Xylella as a variant lineage of plant associated Xanthomonas with Stenotrophomonas and Pseudoxanthomonas as misclassified relatives

Genus Xanthomonas is a group of phytopathogens which is phylogenetically related to Xylella, Stenotrophomonas and Pseudoxanthomonas following diverse lifestyles. Xylella is a lethal plant pathogen with highly reduced genome, atypical GC content and is taxonomically related to these three genera. Deep phylo-taxono-genomics reveals that Xylella is a variant Xanthomonas lineage that is sandwiched between Xanthomonas species. Comparative studies suggest the role of unique pigment and exopolysaccharide gene clusters in the emergence of Xanthomonas and Xylella clades. Pan genome analysis identified set of unique genes associated with sub-lineages representing plant associated Xanthomonas clade and nosocomial origin Stenotrophomonas. Overall, our study reveals importance to reconcile classical phenotypic data and genomic findings in reconstituting taxonomic status of these four genera. Significance StatementXylella fastidiosa is a devastating pathogen of perennial dicots such as grapes, citrus, coffee, and olives. The pathogen is transmitted by an insect vector to its specific host wherein the infection leads to complete wilting of the plants. The genome of X. fastidiosa is extremely reduced both in terms of size (2Mb) and GC content (50%) when compared with its relatives such as Xanthomonas, Stenotrophomonas, and Pseudoxanthomonas that have higher GC content (65%) and larger genomes (5Mb). In this study, using systematic and in-depth genome-based taxonomic and phylogenetic criteria along with comparative studies, we assert the need of unification of Xanthomonas with its misclassified relatives (Xylella, Stenotrophomonas and Pseudoxanthomonas). Interestingly, Xylella revealed itself as a minor lineage embedded within two major Xanthomonas lineages comprising member species of different hosts.

genomics↗

bioRxiv2021

SMC protein RecN drives translocation and remodelling of RecA filament for homology search

While the molecular repertoire of the homologous recombination pathway is well-studied, the search mechanism that enables recombination between distant homologous regions is poorly understood. Earlier work suggests that the recombinase RecA, an essential component for homology search, forms an elongated filament, nucleating at the break site. How this RecA structure carries out long distance search remains unclear. Here, we follow the dynamics of RecA after induction of a single double-strand break on the Caulobacter chromosome. We find that the RecA-nucleoprotein filament, once formed, rapidly translocates in a directional manner in the cell, undergoing several pole-to-pole traversals, until homology search is complete. Concomitant with translocation, we observe dynamic remodelling of the filament. Importantly in vivo, the RecA filament alone is incapable of such long distance movement; both translocation and dynamic remodelling are contingent on action of SMC-like protein RecN, via its ATPase cycle. We provide a stochastic description of RecN-regulated changes in filament length during translocation via modulation of RecA assembly-disassembly. In summary, we have uncovered the three key elements of homology search driven by RecN: mobility of a finite segment of RecA, filament remodelling and ability to conduct multiple pole-to-pole traversals, which together point to a novel optimal search strategy.

cell biology↗

bioRxiv2021

Cross-sectional genomic perspective of epidemic waves of SARS-CoV-2: a pan India study

COVID-19 has posed unforeseen circumstances and throttled major economies worldwide. India has witnessed two waves affecting around 31 million people representing 16% of the cases globally. To date, the epidemic waves have not been comprehensively investigated to understand pandemic progress in India. In the present study, we aim for a cross-sectional analysis since its first incidence up to 26th July 2021. We have performed the pan Indian evolutionary study using 20,086 high-quality complete genomes of SARS-CoV-2. Based on the number of cases reported and mutation rates, we could divide the Indian epidemic into seven different phases. First, three phases constituting the pre-first wave had a very less average mutation rate (<11), which increased in the first wave to 17 and then doubled in the second wave (~34). In accordance with the mutation rate, variants of concern (alpha, beta, gamma and delta) and interest (eta and kappa) also started appearing in the first wave (1.5% of the genomes), which dominated the second (~96% of genomes) and post-second wave (100% of genomes) phases. Whole genome-based phylogeny could demarcate the post-first wave isolates from previous ones by the point of diversification leading to incidences of VOCs and VOIs in India. Nation-wide mutational analysis depicted more than 0.5 million events with four major mutations in ~97% of the total 20,086 genomes in the study. These included two mutations in coding (spike (D614G) and NSP 12b (P314L) of RNA dependent RNA polymerase), one silent mutation (NSP3 F106F) and one extragenic mutation (5 UTR 241). Large scale genome-wide mutational analysis is crucial in expanding knowledge on evolution of deadly variants of SARS-CoV-2 and timely management of the pandemic.

genomics↗

bioRxiv2021

Stable Flow-induced Expression of KLK10 Inhibits Endothelial Inflammation and Atherosclerosis

IntroductionAtherosclerosis preferentially occurs in arterial regions exposed to disturbed blood flow (d-flow), while regions exposed to stable flow (s-flow) are protected. The proatherogenic and atheroprotective effects of d-flow and s-flow are mediated in part by the global changes in endothelial cell gene expression, which regulates endothelial dysfunction, inflammation, and atherosclerosis. Previously, we identified Kallikrein-Related Peptidase 10 (KLK10, a secreted serine protease) as a flow-sensitive gene in arterial endothelial cells, but its role in endothelial biology and atherosclerosis was unknown. Methods and ResultsHere, we show that KLK10 is upregulated under s-flow conditions and downregulated under d-flow conditions using in vivo mouse models and in vitro studies with cultured endothelial cells (ECs). Single-cell RNA sequencing (scRNAseq) and scATAC sequencing (scATACseq) study using the partial carotid ligation mouse model showed flow-regulated KLK10 expression at the epigenomic and transcription levels. Functionally, KLK10 protected against d-flow-induced inflammation and permeability dysfunction in human artery ECs (HAECs). Further, treatment of mice in vivo with rKLK10 decreased arterial endothelial inflammation in d-flow regions. Additionally, rKLK10 injection or ultrasound-mediated transfection of KLK10-expressing plasmids inhibited atherosclerosis in ApoE-/- mice. Studies using pharmacological inhibitors and siRNAs revealed that the anti-inflammatory effects of KLK10 were mediated by a Protease Activated Receptors (PAR1/2)-dependent manner. However, unexpectedly, KLK10 did not cleave the PARs. Through a proteomics study, we identified HTRA1 (High-temperature requirement A serine peptidase 1), which bound and cleaved KLK10. Further, siRNA knockdown of HTRA1 prevented KLK10s anti-inflammatory and barrier protective function in HAECs, suggesting that HTRA1 regulates KLK10 function. Moreover, KLK10 expression was significantly reduced in human coronary arteries with advanced atherosclerotic plaques compared to those with less severe plaques. ConclusionKLK10 is a flow-sensitive endothelial protein and, in collaboration with HTRA1, serves as an anti-inflammatory, barrier-protective, and anti-atherogenic factor.

cell biology↗

bioRxiv2021

Snrpb, the gene mutated in CCMS, is haploinsufficient and required for proper morphogenesis and splicing

Heterozygous mutations in SNRPB, an essential core component of the five small ribonucleoprotein particles of the spliceosome, are responsible for Cerebrocostomandibular Syndrome (CCMS). We show that Snrpb heterozygous embryos arrest shortly after implantation. Additionally, heterozygous deletion of Snrpb in the developing brain and neural crest cells models craniofacial malformations found in CCMS, and results in death shortly after birth. RNAseq analysis of mutant heads prior to morphological defects revealed increased exon-skipping and intron-retention in association with increased 5 splice site strength. We found increased exon-skipping in negative regulators of the P53-pathway, increased levels of nuclear P53, P53-target genes. However, removing TrP53 in Snrpb heterozygous mutant neural crest cells did not completely rescue craniofacial development. We also found a small but significant increase in exon-skipping of several transcripts required for head and midface development, including Smad2 and Rere. Furthermore, mutant embryos exhibited ectopic or missing expression of Fgf8 and Shh, which are required to coordinate face and brain development. Thus, we propose that mis-splicing of transcripts that regulate P53-activity and craniofacial-specific genes both contribute to craniofacial malformations.

developmental biology↗

bioRxiv2021

Population structure and genetic diversity of chickpea germplasms

In various leguminous crops, chickpea is the fourth most important legume contributing 3.1% to the total legume production. Grains of chickpea are rich source of proteins, minerals and vitamins which makes them suitable for both food and feed. For any crop to be improved, the knowledge of genetic diversity of wild and elite cultivar is very important. Therefore among various available marker systems, molecular markers are more reliable and accurate, therefore are very commonly used for genetic diversity analysis, phylogenetic studies and cultivar identification. Due to several advantages of Inter Simple Sequence Repeat (ISSR) markers in present study we analyzed the genetic diversity, structure, cross-species transferability and allelic richness in 50 chickpea collection using 23 ISSR markers. The observed parameters such as allele number varied from 3 to 16, and PIC varied from 0.15 to 0.4988 respectively. Further, range of allele size varied from 150 to 1600 bp which shows the significance of ISSR markers for chickpea germplasms characterization. On the basis of ISSR marker genotypic data dendrogram were constructed which divides these 50 chickpea in group I and II showing the reliability of ISSR markers. Among 50 chickpea, the accession P 74-1 is in group I and rest are in group II. Further we made mini-core collection of 15 diverse chickpea and subgrouped them. Dendrogram, PCA, Dissimilarity matrix and Bayesian model based genetic clustering of 50 chickpea germplasms revealed that P 74-1,P 1883, P 1260 very diverse chickpea accession. Characterization of these diverse chickpea would help in maintenance breeding, conservation and in future could be used to develop climate resilient elite cultivar of chickpea. Utilization of these novel ISSRs markers in diversity analysis and population structure characterization of 50 chickpea germplasm suggests their wider efficacy in superior scale for molecular breeding studies in chickpea.

ecology↗

bioRxiv2021

Investigating the Contribution of White Matter Hyperintensities and Cortical Thickness to Empathy in Neurodegenerative and Cerebrovascular Diseases

Introduction: Change in empathy is an increasingly recognised symptom of neurodegenerative diseases and contributes to caregiver burden and patient distress. Empathy impairment has been associated with brain atrophy but its relationship to white matter hyperintensities (WMH) is unknown. We aimed to investigate the relationships amongst WMH, brain atrophy, and empathy deficits in neurodegenerative and cerebrovascular diseases. Methods: 513 participants with Alzheimers Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia (FTD), Parkinsons Disease, or Cerebrovascular Disease (CVD) were included. Empathy was assessed using the Interpersonal Reactivity Index. WMH were measured using a semi-automatic segmentation and FreeSurfer was used to measure cortical thickness. Results: A heterogeneous pattern of cortical thinning was found between groups, with FTD showing thinning in frontotemporal regions and CVD in left superior parietal, left insula, and left postcentral. Results from both univariate and multivariate analyses revealed that several variables were associated with empathy, particularly cortical thickness in the fronto-insulo-temporal and cingulate regions, sex(female), global cognition, and right parietal and occipital WMH. Conclusions: Our results suggest that cortical atrophy and WMH may be associated with empathy deficits in neurodegenerative and cerebrovascular diseases. Future work should consider investigating the longitudinal effects of WMH and atrophy on empathy deficits in neurodegenerative and cerebrovascular diseases.

neuroscience↗

bioRxiv2021

Comparable neutralization of SARS-CoV-2 Delta AY.1 and Delta in individuals sera vaccinated with BBV152

The recent emergence of the SARS-CoV-2 Variant of Concern, B.1.617.2 (Delta) variant and its high transmissibility has led to the second wave in India. BBV152, a whole-virion inactivated SARS-CoV-2 vaccine used for mass immunization in India, showed a 65.2% protection against the Delta variant in a double-blind, randomized, multicentre, phase 3 clinical trial. Subsequently, Delta has been further mutated to Delta AY.1, AY.2, and AY.3. Of these, AY.1 variant was first detected in India in April 2021 and subsequently from twenty other countries as well. Here, we have evaluated the IgG antibody titer and neutralizing potential of sera of COVID-19 naive individuals full doses of BBV152 vaccine, COVID-19 recovered cases with full dose vaccines and breakthrough cases post-immunization BBV152 vaccines against Delta, Delta AY.1 and B.1.617.3. A reduction in neutralizing activity was observed with the COVID-19 naive individuals full vaccinated (1.3, 1.5, 1.9-fold), COVID-19 recovered cases with full BBV152 immunization (2.5, 3.5, 3.8-fold) and breakthrough cases post-immunization (1.9, 2.8, 3.5-fold) against Delta, Delta AY.1 and B.1.617.3 respectively compared to B.1 variant. A minor reduction was observed in the neutralizing antibody titer in COVID-19 recovered cases full BBV152 vaccinated and post immunized infected cases compared to COVID-19 naive vaccinated individuals. However, with the observed high titers, the sera of individuals belonging to all the aforementioned groups they would still neutralize the Delta, Delta AY.1 and B.1.617.3 variants effectively.

molecular biology↗

bioRxiv2021

Identification and Characterization of novel mutants of Nsp13 Protein among Indian SARS-CoV-2 isolates.

SARS-CoV-2, the causative agent of COVID-19 has mutated rapidly which enabled them to adapt and evade the immune system of the host. Emerging SARS-CoV-2 variants with crucial mutations pose a global challenge in context of therapeutic drugs and vaccines being developed globally. There are currently no specific therapeutics or vaccines available to combat SARS-CoV-2 devastation. In view of this, the current study aimed to identify and characterize the mutations found in the Nsp13 of SARS-CoV-2 in Indian isolates. Non-structural protein, Nsp13 protein sequences from Indian isolates were analyzed by comparing with the first reported Severe acute respiratory syndrome Corona Virus-2 (SARS-CoV-2) protein sequence from Wuhan, China. Out of 825 Nsp13 protein sequences, a total of 38 mutations were observed among Indian isolates. Our data show that mutations in Nsp13 at various positions (H164Y, A237T, T214I, C309Y, S236I, P419S, V305E, G54S, H290Y, P53S, A308Y, and A308Y) have a significant impact on the proteins stability and flexibility. Also, the impact of Nsp13 mutations on the protein function were predicted based on PROVEAN score that includes 15 mutants as neutral and 23 mutants as deleterious effect. Furthermore, B-cell epitopes contributed by Nsp13 were identified using various predictive immunoinformatic tools. Immunological Parameters of Nsp13 such as antigenicity, allergenicity and toxicity were evaluated to predict the potential B-cell epitopes. The predicted peptide sequences were correlated with the observed mutants. Our predicted data showed that there are seven high rank linear epitopes as well as 18 discontinuous B-cell epitopes based on immunoinformatic tools. Moreover, it was observed that out of total 38 identified mutations among Indian SARS-CoV-2 Nsp13 protein, four mutant residues at position 142 (E142), 245 (H245), 247 (V247) and 419 (P419) are localised in the predicted B cell epitopic region. Altogether, the results of the present in-silico study might help to understand the impact of the identified mutations in Nsp13 protein on its stability, flexibility and function.

bioinformatics↗

bioRxiv2021

Taxonomic repositioning of twelve Xanthomonas campestris, seven Xanthomonas axonopodis and one Pseudomonas cissicola reference pathovars to Xanthomonas citri

Here on the basis of phylo-taxonogenomics criteria we present amended description of 20 pathovars to Xanthomonas citri majority (18/20) of which were first reported from India. 7/20 are currently classified as X. axonopodis, 12/20 as X. campestris and 1/20 as Pseudomonas cissicola. Here, we have generated genome sequence data for 4 pathovars and genomes of remaining 16 were used from the published data. Genome based investigation reveals that all these pathovars belong to X. citri and not to X. axonopodis or X. campestris as previously reported. Present proposal is to aid in resolving the taxonomic confusion of the X. ctiri pathovars and prevent future usage of invalid names.

genomics↗

bioRxiv2021

Fast and accurate bootstrap confidence limits on genome-scale phylogenies using little bootstraps

Felsensteins bootstrap resampling approach, applied in thousands of research articles, imposes a high computational burden for very long sequence alignments. We show that the bootstrapping of a collection of little subsamples, coupled with median bagging of subsample confidence limits, produces accurate bootstrap confidence for phylogenetic relationships in a fraction of time and memory. The little bootstraps approach will enhance rigor, efficiency, and parallelization of big data phylogenomic analyses.

evolutionary biology↗

bioRxiv2021

Combination of Antiviral Drugs to Inhibit SARS-CoV-2 Polymerase and Exonuclease as Potential COVID-19 Therapeutics

SARS-CoV-2 has an exonuclease-based proofreader, which removes nucleotide inhibitors such as Remdesivir that are incorporated into the viral RNA during replication, reducing the efficacy of these drugs for treating COVID-19. Combinations of inhibitors of both the viral RNA-dependent RNA polymerase and the exonuclease could overcome this deficiency. Here we report the identification of hepatitis C virus NS5A inhibitors Pibrentasvir and Ombitasvir as SARS-CoV-2 exonuclease inhibitors. In the presence of Pibrentasvir, RNAs terminated with the active forms of the prodrugs Sofosbuvir, Remdesivir, Favipiravir, Molnupiravir and AT-527 were largely protected from excision by the exonuclease, while in the absence of Pibrentasvir, there was rapid excision. Due to its unique structure, Tenofovir-terminated RNA was highly resistant to exonuclease excision even in the absence of Pibrentasvir. Viral cell culture studies also demonstrate significant synergy using this combination strategy. This study supports the use of combination drugs that inhibit both the SARS-CoV-2 polymerase and exonuclease for effective COVID-19 treatment.

pharmacology and toxicology↗

bioRxiv2021

Evolutionary Sparse Learning for phylogenomics

AO_SCPLOWBSTRACTC_SCPLOWWe introduce a supervised machine learning approach with sparsity constraints for phylogenomics, referred to as evolutionary sparse learning (ESL). ESL builds models with genomic loci--such as genes, proteins, genomic segments, and positions--as parameters. Using the Least Absolute Shrinkage and Selection Operator (LASSO), ESL selects only the most important genomic loci to explain a given phylogenetic hypothesis or presence/absence of a trait. ESL does not directly model conventional parameters such as rates of substitutions between nucleotides, rate variation among positions, and phylogeny branch lengths. Instead, ESL directly employs the concordance of variation across sequences in an alignment with the evolutionary hypothesis of interest. ESL provides a natural way to combine different molecular and non-molecular data types and incorporate biological and functional annotations of genomic loci directly in model building. We propose positional, gene, function, and hypothesis sparsity scores, illustrate their use through an example and suggest several applications of ESL. The ESL framework has the potential to drive the development of a new class of computational methods that will complement traditional approaches in evolutionary genomics. ESLs fast computational times and small memory footprint will also help democratize big data analytics and improve scientific rigor in phylogenomics.

evolutionary biology↗

bioRxiv2021

Phylo-taxonogenomics of 182 strains of genus Leuconostoc elucidates its robust taxonomy and biotechnological importance

Genus Leuconostoc is a group of a diverse range of lactic acid bacteria (LAB) majorly found in dairy, food and environmental ecology. These microbes are commercially important for several industries due to their intrinsic genomic attributes such as bacteriocins, carbohydrate-active enzymes, plasmids etc. Even though the species of Leuconostoc are commercially significant, their taxonomy is largely based on old, low resolution traditional methods. There have been several taxonomic reclassifications in the past which are inadequate for microbiologist and food industry professionals to truly demarcate any new strain of genus Leuconostoc. The current taxonomy of the genus is largely based on classical approaches, which are in utmost need of reinvestigation by whole genome-based approaches. In the present study, the taxono-phylogenomic analysis clearly depicted sixteen species including three novel genomospecies in addition to several reshufflings across the species namely, L. mesenteroides, L. pseudomesenteroides, L. gelidum and L. lactis. The presence of a wide range of carbohydrate-active enzymes, type III polyketide synthase and vector plasmids suggested the biotechnological potential of constituent strains of the genera. Further, the absence of antibiotic gene clusters reaffirms their utility in industries such as food and dairy. Such large-scale in-depth genome-based study can shed light on the nature of the genome dynamics of the species and help to obtain a more robust taxonomic classification.

genomics↗

bioRxiv2021

A specific relationship between musical sophistication and auditory working memory

Musical engagement may be associated with better listening skills, such as the perception of and working memory for notes, in addition to the appreciation of musical rules. The nature and extent of this association is controversial. In this study we assessed the relationship between musical engagement and both sound perception and working memory. We developed a task to measure auditory perception and working memory for sound using a behavioural measure for both, precision. We measured the correlation between these tasks and musical sophistication based on a validated measure (the Goldsmiths Musical Sophistication Index) that can be applied to populations of both musicians and non-musicians. The data show that musical sophistication accounts for 21% of the variance in the precision of working memory for frequency in an analysis that accounts for age and non-verbal intelligence. Musical sophistication was not significantly associated with the precision of working memory for amplitude modulation rate or with the precision of perception of either acoustic feature. The work supports a specific association between musical sophistication and working memory for sound frequency.

neuroscience↗