Biology subjects

Lahiri, S.

Publications and source records attributed to Lahiri, S..

10 recordsLinked to original sources

bioRxiv2026

A chromosome-level genome assembly of the chilli thrips Scirtothrips dorsalis Hood (Thysanoptera: Thripidae)

Thrips are known for being pests of many agricultural crops, as well as vectors of plant viruses. Yet despite their economic importance, genomic resources for this group remain limited, and no chromosome-level genome has been available for the genus Scirtothrips. One such species is the chilli thrips, Scirtothrips dorsalis Hood (Thysanoptera: Thripidae). This invasive and highly polyphagous pest is established across much of the world and transmits several tospoviruses. Genomic resources would provide a new means to understand the traits that make thrips difficult to manage. Here, we present a chromosome-level genome assembly for S. dorsalis. The assembly is 266.5 Mb, with 96.9% of the sequence anchored in 16 chromosome-scale scaffolds. It contains 20,557 genes, and repetitive elements account for 28.8% of the sequence, which is comparable to those of other sequenced Thripidae. A species tree based on 3,019 single copy orthologs placed S. dorsalis as sister to Scirtothrips hansoni, with Scirtothrips most closely related to Frankliniella, Megalurothrips, and Odontothrips. The mitochondrial genome is a single circular molecule of 15,207 bp in which the sequence of the published mini circle is integrated, in contrast to the bipartite mitogenome previously reported for the same cryptic species.

genomics↗

bioRxiv2025

Comparative Evaluation of Assumption Lean Community Detection Methods for Human Connectome Networks

Community detection on resting-state functional connectivity provides a principled lens on mesoscale organization in functional brain networks. Currently, the choice of community count K, lacks a standardized or principled guideline. We conducted a systematic benchmark of three assumption-lean approaches on weighted functional connectivity matrices: the Weighted Stochastic Block Model, Spectral Clustering, and K-means Clustering. Performance was assessed on synthetic networks with known ground truth and on three neuroimaging cohorts which included adult and infant datasets. We compared several strategies for selecting K, including the silhouette index and other approaches commonly used in the existing literature. These were evaluated alongside a likelihood-based criterion for the weighted stochastic block model that employs bootstrap confidence intervals for differences in log-likelihood between successive values of K. For the synthetic networks, WSBM and Spectral Clustering correctly identified the true number of communities, whereas K-means Clustering did not. In adult datasets, most indices did not yield a unique optimum, whereas the likelihood-based criterion selected K = 11, which is consistent with established sensory and association systems. In infants and toddlers, the same procedure supports a larger K around 15 and reveals developmentally distinct mesoscale architecture, including anterior and posterior subdivisions within default mode and fronto parietal systems.

neuroscience↗

bioRxiv2025

Self-Reactive B Cells in Artery Tertiary Lymphoid Organs Encode Pathogenic High Affinity Autoantibody in Atherosclerosis

Artery tertiary lymphoid organs (ATLOs) emerge in atherosclerosis which is a chronic inflammatory artery disease with an autoimmune component. However, whether disease-relevant autoimmune B cells emerge in ATLOs and their impacts remains unknown. To map atherosclerosis-specific humoral autoimmunity and define its roles, we isolated germinal-center (GC) B cells from ATLOs and lymph-nodes, expression-cloned 60 autoantibodies and screened them for arterial wall reactivity. ATLO-derived autoantibodies markedly skewed to atherosclerosis-relevant autoantigens versus those of lymph-nodes. One ATLO GC-derived autoantibody bound to histone 2B (H2B) with high-affinity ([~]25 nM). Moreover, vaccination with H2B or adoptive transfer of its cognate autoantibody markedly accelerated atherosclerosis suggesting that ATLOs fail to delete pathogenic high-affinity self-reactive B cells. In a human cohort, total circulating anti H2B antibody titers positively correlated with aortic and coronary artery calcification. We conclude that ATLOs harbor a dysregulated immune tolerance environment permissive for autoreactive B cells that express pathogenic autoantibodies driving atherosclerosis.

immunology↗

bioRxiv2025

Spatially resolved mapping of histones reveal selective neuronal response in Rett syndrome

Rett Syndrome (RTT), a severe neurological disorder caused by loss-of-function mutations in the X-linked MECP2 gene, results in profound life-long neurological dysfunction. RTT patients live an apparently normal initial life until 12-18 months of age following which, a progressive accumulation of a wide range of phenotypic manifestations sets in. While MeCP2 is known to regulate chromatin, its impact on global histone composition and dynamics remains poorly understood. Here, we combine mass spectrometry imaging (MSI) and laser capture microdissection (LCM) coupled to LC-MS/MS to systematically profile histone proteoforms in three key brain regions: the dentate gyrus (DG) and cornu ammonis (CA) of the hippocampus, and the cerebellum (Cb). Our analysis reveals striking neuron-specific differences in histone composition between Mecp2-deficient and wildtype (WT) mice. Interestingly, the expression of a pathogenic Mecp2 missense mutant (Y120D) results in subtler changes in histone composition that are distinct from the null mutations. This study provides the first spatially resolved epigenetic atlas of histone proteoforms in RTT and suggests that Mecp2 loss perturbs chromatin homeostasis in a neuron- and mutation-dependent manner. Our findings underscore the critical need for cell-type-resolved analyses to unravel the mechanistic underpinnings of RTT and emphasize the importance of personalised therapeutic strategies that consider both the affected cell-type and particular Mecp2 mutation.

neuroscience↗

bioRxiv2024

Dbf4-Dependent Kinase Finetunes INO80 Function at Chromosome Replication Origins

The highly conserved Dbf4-Dependent Kinase (DDK) plays a pivotal role in the nucleus during S phase, where it directly phosphorylates the replicative helicase, the minichromosome maintenance (MCM) complex. This leads to the initiation of chromosome replication. However, aside from the MCM complex, few other targets have been identified to date, leaving DDK an understudied kinase. Here, we describe a two-pronged mass spectrometry-based approach and define the nuclear DDK-dependent phosphoproteome, which consists of approximately 400 phosphorylation events. Within this network, we found that DDK directly phosphorylates the Arp8 subunit of the multi-subunit chromatin remodeler complex INO80. Arp8 phosphorylation stabilises INO80s intramolecular complex integrity, which finetunes its nucleosome spacing activity at replication origins. This adjustment of origin chromatin architecture stimulates replication and is important for the response to replication stress. Our results represent a significant advance in our understanding of the molecular mechanisms underlying the regulation of replication origins.

biochemistry↗

bioRxiv2024

Atrial Proteomic Profiling Reveals a Switch Towards Profibrotic Gene Expression Program in CREM-IbΔC-X Mice with Persistent Atrial Fibrillation

BackgroundOverexpression of the CREM (cAMP response element-binding modulator) isoform CREM-Ib{Delta}C-X in transgenic mice (CREM-Tg) causes the age-dependent development of spontaneous AF. PurposeTo identify key proteome signatures and biological processes accompanying the development of persistent AF through integrated proteomics and bioinformatics analysis. MethodsAtrial tissue samples from three CREM-Tg mice and three wild-type littermates were subjected to unbiased mass spectrometry-based quantitative proteomics, differential expression and pathway enrichment analysis, and protein-protein interaction (PPI) network analysis. ResultsA total of 98 differentially expressed proteins were identified. Gene ontology analysis revealed enrichment for biological processes regulating actin cytoskeleton organization and extracellular matrix (ECM) dynamics. Changes in ITGAV, FBLN5, and LCP1 were identified as being relevant to atrial fibrosis and remodeling based on expression changes, co-expression patterns, and PPI network analysis. Comparative analysis with previously published datasets revealed a shift in protein expression patterns from ion-channel and metabolic regulators in young CREM-Tg mice to profibrotic remodeling factors in older CREM-Tg mice. Furthermore, older CREM-Tg mice exhibited protein expression patterns that resembled those of humans with persistent AF. ConclusionsThis study uncovered distinct temporal changes in atrial protein expression patterns with age in CREM-Tg mice consistent with the progressive evolution of AF. Future studies into the role of the key differentially abundant proteins identified in this study in AF progression may open new therapeutic avenues to control atrial fibrosis and substrate development in AF. Graphical abstractGraphical abstract summarizing key findings of this paper. The atrial proteome in 9-month-old CREM- Tg mice with chronic persistent AF (perAF) was compared with age-matched WT littermates. In addition, proteome changes in these old CREM-Tg mice were compared with proteome changes previously identified in young CREM-Tg mice with paroxysmal AF (pAF). Moreover, an interspecies comparison was performed between old CREM-Tg mice and human patients with perAF. The major findings are that in pAF, key changes were identified in proteins involved in metabolism, energy production, DNA synthesis, and cell proliferation and growth. On the other hand, in mice and humans with perAF, key changes were found in the expression of proteins involved in collagen production, extracellular matrix remodeling, actin cytoskeleton organization, and tissue repair. O_FIG O_LINKSMALLFIG WIDTH=159 HEIGHT=200 SRC="FIGDIR/small/575097v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@603dbaorg.highwire.dtl.DTLVardef@74a168org.highwire.dtl.DTLVardef@110b834org.highwire.dtl.DTLVardef@ad96e3_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2023

Two functionally distinct HEATR5 protein complexes are defined by fast-evolving co-factors in yeast

The highly conserved HEATR5 proteins are best known for their roles in membrane traffic mediated by the adaptor protein complex-1 (AP1). HEATR5 proteins rely on fast-evolving co-factors to bind to AP1. However, how HEATR5 proteins interact with these co-factors is unknown. Here, we report that the budding yeast HEATR5 protein, Laa1, functions in two biochemically distinct complexes. These complexes are defined by a pair of mutually exclusive Laa1-binding proteins, Laa2 and the previously uncharacterized Lft1/Yml037c. Despite limited sequence similarity, biochemical analysis and structure predictions indicate that Lft1 and Laa2 bind Laa1 via structurally similar mechanisms. Both Laa1 complexes function in intra-Golgi recycling. However, only the Laa2-Laa1 complex binds to AP1 and contributes to its localization. Finally, structure predictions indicate that human HEATR5 proteins bind to a pair of fast-evolving interacting partners via a mechanism similar to that observed in yeast. These results reveal mechanistic insight into how HEATR5 proteins bind their co-factors and indicate that Laa1 performs functions besides recruiting AP1.

cell biology↗

bioRxiv2020

Convergent acoustic community structure in South Asian dry and wet grassland birds

Although the study of bird acoustic communities has great potential to provide valuable conservation data, many aspects of their assembly and dynamics remain poorly understood. Grassland habitats in South Asia comprise distinct biomes with a unique avifauna, presenting an opportunity to address how community-level patterns in acoustic signal space arise. Similarity in signal space of different grassland bird communities may be due to phylogenetic similarity, or because different bird groups partition the acoustic resource, resulting in convergent distributions in signal space. Here, we quantify the composition, signal space and phylogenetic diversity of bird acoustic communities from the dry semiarid grasslands of Northwest India and the wet floodplain grasslands of Northeast India. We find that acoustic communities occupying these distinct biomes exhibit convergent signal space. However, dry grasslands exhibit higher phylogenetic diversity, and the two communities are not phylogenetically more similar than expected by chance. The Sylvioidea encompasses half the species in the wet grassland acoustic community, with an expanded signal space compared to the dry grasslands. Thus, dry and wet grassland communities are convergent in signal space despite differences in phylogenetic diversity. We therefore hypothesize that different clades colonizing grasslands partition the acoustic resource, resulting in convergent community structure across biomes. Many of the birds we recorded are highly threatened, and acoustic monitoring will support conservation measures in these imperiled, yet poorly-studied habitats.

ecology↗

bioRxiv2020

Imaging mass spectrometry and shotgun proteomics reveal dysregulated pathways in male infertility

Spermatogenesis is a complex multi-step process involving intricate interactions between different cell types in the male testis. Disruption of these interactions results in infertility. Combination of shotgun tissue proteomics with MALDI imaging mass spectrometry is markedly potent in revealing topological maps of molecular processes within tissues. Here, we use a combinatorial approach on a characterized mouse model of hormone induced male infertility to uncover misregulated pathways. Comparative testicular proteome of wildtype and mice overexpressing human P450 aromatase (AROM+) with pathologically increased estrogen levels unravels gross dysregulation of spermatogenesis and emergence of proinflammatory pathways in AROM+ testis. In situ MS allowed us to localize misregulated proteins/peptides to defined regions within the testis. Results suggest that infertility is associated with substantial loss of proteomic heterogeneity, which define distinct stages of seminiferous tubuli in healthy animals. Importantly, considerable loss of mitochondrial factors, proteins associated with late stages of spermatogenesis and steroidogenic factors characterise AROM+ mice. Thus, the novel proteomic approach pinpoints in unprecedented ways the disruption of normal processes in testis and provides a signature for male infertility.

biochemistry↗

bioRxiv2017

Accurate estimation of neural population dynamics without spike sorting

A central goal of systems neuroscience is to relate an organisms neural activity to behavior. Neural population analysis often begins by reducing the dimensionality of the data to focus on the patterns most relevant to a given task. A major practical hurdle to data analysis is spike sorting, and this problem is growing rapidly as the number of neurons measured increases. Here, we investigate whether spike sorting is necessary to estimate neural dynamics. The theory of random projections suggests that we can accurately estimate the geometry of low-dimensional manifolds from a small number of linear projections of the data. We re-analyzed data from three previous studies and found that neural dynamics and scientific conclusions are quite similar using multi-unit threshold crossings in place of sorted neurons. This finding unlocks existing data for new analyses and informs the design and use of new electrode arrays for laboratory and clinical use.

neuroscience↗