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Rana, D.

Publications and source records attributed to Rana, D..

12 recordsLinked to original sources

There is no silver bullet: Tiger corridors do not ensure multispecies carnivore connectivity

Connectivity is critical to sustaining endangered carnivores in speciose yet fragmented landscapes such as in the global south. Corridors to mitigate fragmentation are designed based on charismatic species or habitat-based approaches, but their multispecies effectiveness for maintaining functional connectivity remains poorly tested. We combined landscape genetic analyses across five sympatric carnivores - Panthera tigris, Panthera pardus, Prionailurus viverrinus, Felis chaus, and Melursus ursinus, to evaluate how landscape features shape functional connectivity in a globally important felid landscape. We then assessed the efficiency of existing tiger corridors and single-species surrogates for maintaining multispecies functional connectivity. Species exhibited contrasting responses to landscape variables, producing distinct resistance surfaces and connectivity corridors. Spatial similarity of connectivity between species pairs was highly variable (r = 0.14-0.93), but no single species effectively captured connectivity patterns of the broader carnivore community (maximum mean overlap of <0.7 across species). Moreover, genetically optimized corridors were over 70% more efficient in capturing connectivity compared to existing tiger corridors, demonstrating mismatches between structural and functional connectivity. Our results highlight limitations of surrogate-based corridor planning and demonstrate that integrating multispecies functional connectivity can substantially improve conservation planning in human-dominated landscapes.

ecology↗

Glutamatergic neuron-tumor synapses shape human glioblastoma cell states through radial glia plasticity

Glioblastoma (GBM) is a devastating primary brain tumor with remarkable inter- and intra-tumoral heterogeneity. GBM cells assume a spectrum of neurodevelopmental-like phenotypes and co-opt normal neurophysiological processes, which include synaptic integration with their neuronal microenvironment. This is mediated by neuron-tumor synapses (NTS) that predominantly involve glutamatergic receptors, which drive calcium elevations that promote tumor proliferation and invasion. The exact relationship between synaptic signaling and tumor cell fate specification, however, remains largely unexplored. Here, we develop and leverage a synapse-optimized human organoid tumor transplantation (so-HOTT) model of GBM to decipher how glutamatergic signaling impacts GBM lineage trajectories. so-HOTT preserves patient tumor heterogeneity, features excitatory NTS, and enables clonal lineage tracing of tumor cells after NTS perturbations. Genetic and pharmacological inhibition of AMPA and kainate receptors in so-HOTT shifts tumor cell composition from neuronal fates toward progenitor-proximal astrocytic/mesenchymal states. This occurs through the attenuation of calcium signaling and reduced plasticity of malignant radial glia (RG)-like progenitors, a previously unrecognized target of NTS. Through the integration of inputs from the neuronal microenvironment into glutamatergic signaling, progenitor populations modulate their transcriptional programs and cell fate, ultimately shaping GBM tumor heterogeneity. Targeting synaptic input may thus constrain the heterogeneity that fuels GBM adaptation and therapeutic escape.

cancer biology↗

Lower-middle-income countries disproportionately face the burden of the Open Access publication model

While the Open Access (OA) publishing model may promote equity in the readership of scientific publications, its implications for global research authorship remain poorly quantified. We analysed 504,723 publications over the past decade from 350 Scopus-indexed ecology and evolution journals to compare publication rates and institutional diversity a) between Subscription-Based (SB) and OA publishing models, and b) before and after journals transitioned to fully OA, across country income groups. We found that both publication rates and institutional diversity were lower in the OA publishing model, but with variable differences across country groups. These differences were weaker (by [~]140%) in low-income countries (where full waivers on Article Publishing Charges (APCs) are automatically provided) compared to middle-income countries (where only discounts on APCs are provided). For journals transitioning to a fully OA publication model, publication diversity decreased in middle-income countries and increased significantly in low-income countries. Therefore, OA disproportionately concentrates publishing potential within a few institutions, undermining authorship equity. The OA model, despite its egalitarian philosophy, risks amplifying geographic and institutional disparities in ecology and conservation science. Incorporating models that account for individual and institutional-level variations in funding availability, or providing alternative pathways for publishing, may help reduce this disparity.

ecology↗

Genetic Erosion at the Edge: Landscape fragmentation and connectivity in sloth bears of the Indian terai

Habitat fragmentation is a major global threat to biodiversity, particularly for species at the periphery of their range where populations are smaller and historically more isolated. Fragmented landscapes reduce connectivity, erode genetic diversity, and elevate inbreeding risk, potentially leading to local extinction. Landscape genetics offers a powerful framework to assess how land-use patterns influence gene flow and population viability. We investigated the endemic sloth bear (Melursus ursinus) populations in the Indian Central Terai landscape, a multi-use, high human density region exemplifying fragmentation and range-edge pressures. Using a ddRAD-seq based approach on non-invasively collected faecal samples (n=209), we generated genomic data, and identified 66 individuals using 964 SNP markers. Despite weak spatial genetic structure, with Dudhwa populations showing the highest differentiation (FST = 0.30). The populations exhibited extremely low heterozygosity (HO = 0.073) and high fixation index (FIS = 0.45), indicating recent bottlenecks and isolation. Landscape genetic analyses revealed agriculture density as the primary barrier to gene flow, followed by road density. Compared to sloth bear populations in Central India and Nepal Terai, CTL bears exhibit markedly reduced genetic variation, likely driven by historic fragmentation and peripheral range effects. This study provides the first genomic baseline for sloth bears in the CTL and underscores the urgency of integrating genetic monitoring with habitat management to prevent further erosion of genetic diversity and ensure long-term population persistence.

ecology↗

Landscape matters: Deriving a generalizable understanding of population connectivity using empirical data and graph theory

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/674386v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1226384org.highwire.dtl.DTLVardef@b3949eorg.highwire.dtl.DTLVardef@1e24ae0org.highwire.dtl.DTLVardef@1a1c773_HPS_FORMAT_FIGEXP M_FIG C_FIG Human impacts on ecosystems have accelerated globally, driving a 10% decline in terrestrial biodiversity and a 70% decline in wildlife populations over the past five decades. These losses are closely linked to habitat modification and fragmentation, highlighting the urgent need for management strategies grounded in a clear understanding of how wildlife use landscapes and navigate human-altered areas. Connectivity between populations is critical for species persistence and is shaped by the interplay between landscape features and species movement. Most connectivity studies pursue application-focused goals, such as designing corridors or assessing land-use effects, often targeting single species within specific landscapes. While these approaches provide depth, they limit the development of general principles that apply across species and regions. Graph theory offers a powerful framework to distill complex connectivity patterns into comparable metrics, creating opportunities to identify such generalities. In this study, we examined connectivity patterns for 11 Indian carnivore species distributed across heterogeneous landscapes. Using secondary data, we developed habitat networks from species distribution models that incorporated both habitat quality and matrix resistance. We then applied graph theory to generate networks based on connectivity between identified habitat nodes, enabling comparisons across species and landscapes. Our results show that while connectivity patterns differ markedly among species, broad trends emerge. Larger-bodied species like tigers, which in our study are often threatened species, can overcome the effects of fragmentation better than smaller bodied species, however their connectivity is dependent on the existence of high-quality patches. Fragmented and heterogenous landscapes were always associated with modular, less efficient networks irrespective of the species. Importantly, landscape characteristics had greater influence on network-level connectivity properties, while species traits more strongly determined node-level structural complexity of the network. By integrating network theory with multispecies analyses across diverse landscapes, our work moves beyond single-species case studies to identify general drivers of connectivity. In terms of conservation, our approach allows us to generate broad insights into drivers of population connectivity informing strategies for lesser-known species and guide more effective, landscape-scale management in an era of rapid environmental change.

ecology↗

Thalamic NRXN1-Mediated Input to Human Cortical Progenitors Drives Upper Layer Neurogenesis

According to the protocortex hypothesis, extrinsic thalamic signaling is necessary for refining cortical areas and cell types, but the mechanism by which these inputs shape the development and expansion of the human cortex remains largely unexplored. We fuse cortical and thalamic organoids to study this process. Using single-nuclei RNA-sequencing and cellular imaging, we discover that thalamic signals during a critical period promote human cortical upper-layer neurogenesis. In assembloid models and human primary cortex, we find NRXN1 mediates thalamic axon contact with primate-enriched outer radial glia, driving developmental gene expression changes. Genetic perturbation of NRXN1 in thalamic neurons reduces these contacts and attenuates cortical upper-layer neurogenesis. These findings in human developmental models suggest a novel role for thalamic regulation of primate outer radial glia cell fate.

neuroscience↗

From single species to communities: microsatellite amplicon sequencing to monitor felids using Feliplex

O_LIThe current biodiversity crisis demands a shift from single-species to multispecies approaches in conservation, particularly for rare and endangered species. However, this transition requires tools optimised for multispecies research, which are currently limited. C_LIO_LIRecent advances in high-throughput sequencing (HTS) technologies and bioinformatics have enabled efficient and robust acquisition of genetic data. Amplicon sequencing approaches, in particular, have demonstrated potential for enhancing non-invasive genetic studies of endangered species, but their application has been mostly limited to single species. C_LIO_LITo enable multispecies genetic research, we introduce a cost-effective and robust HTS-based amplicon sequencing approach for genotyping multiple species simultaneously, designed for population monitoring, including individual identification and ascertaining patterns of population structure. C_LIO_LIWe developed Feliplex, a multiplex panel of 85 co-amplifying tetranucleotide microsatellite markers for cross-genotyping Felidae species, to demonstrate the utility of our approach. Feliplex was validated on known samples from nine Indian felid species across the genera Panthera, Prionailurus, and Felis. We applied it to invasive (blood and tissue) and non-invasive (hair and faeces) DNA extracts from 173 wild individuals obtaining respectively 70% and 56% multilocus genotyping success rates. The panel accurately identified known population clusters in tigers (Panthera tigris, n=19) and revealed hitherto unknown genetic structure in fishing cats (Prionailurus viverrinus, n=40). C_LIO_LIFeliplexs wide applicability across Felidae allows reliable multispecies genotyping from low-quality/quantity samples, while supporting cost-effective genetic studies and conservation monitoring of lesser-known species like small cats. Our approach has a broad applicability and can be adapted to develop similar multispecies panels for closely related species groups. C_LI

ecology↗

Spatiotemporally Programmed Release of Aptamer Tethered Dual Angiogenic Growth Factors

In tissue extracellular matrix (ECM), multiple growth factors (GFs) are sequestered through affinity interactions and released as needed by proteases, establishing spatial morphogen gradients in a time-controlled manner to guide cell behavior. Inspired by these ECM characteristics, we developed an "intelligent" biomaterial platform that spatially controls the combined bioavailability of multiple angiogenic GFs, specifically vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-BB). Utilizing aptamer affinity interactions and complementary sequences within a GelMA matrix, our platform achieves on-demand, triggered release of individual GFs which can be "programmed" in temporally-controlled, repeatable cycles. The platform features stable incorporation of dual aptamers specific for both GFs, functional aptamer-CS molecular recognition in a 3D microenvironment with long-term stability of at least 15 days at physiological temperature, and spatially localized sequestration of individual GFs. Additionally, the system allows differential amounts of GFs to be released from the same hydrogels at different time-points, mimicking dynamic GF presentation in a 3D matrix similar to the native ECM. This flexible control over individual GF release kinetics opens new possibilities for dynamic GF presentation, with adjustable release profiles to meet the spatiotemporal needs of growing engineered tissue. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=178 SRC="FIGDIR/small/607163v1_ufig1.gif" ALT="Figure 1"> View larger version (72K): org.highwire.dtl.DTLVardef@15f9db4org.highwire.dtl.DTLVardef@6a9834org.highwire.dtl.DTLVardef@2e896borg.highwire.dtl.DTLVardef@13fe883_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Synovial fluid transcriptome dynamics in osteoarthritis progression: Implications in pathogenesis

BackgroundOsteoarthritis, a degenerative joint disease associated with various pathological manifestations in the joint including cartilage loss, alterations in subchondral bone and synovial inflammation. ObjectiveThis study aimed to elucidate the transcriptional and molecular changes in synovial fluid associated with OA progression, focusing on differential gene expression and pathway enrichment across OA grades. MethodologyPatients with different OA grades were recruited from PGIMER, Chandigarh, following the KL classification. Microarray analysis was conducted to study the transcriptional profiles in different OA grades using a fold-change (FC) cutoff of 2 and a p-value cutoff of 0.05, followed by pathway analysis performed using GSEA and STRING database. Selected genes from microarray and pathway analysis were validated using qRT-PCR. ResultsMicroarray analysis reveals distinct gene expression patterns corresponding to different OA stages (KL grade 2 to KL grade 4). Notably, the upregulation of AMTN and DKK2, alongside the downregulation of MSLN, highlighted their roles in pathological mineralization and disrupted bone remodeling in OA. Pathway enrichment analysis revealed significant changes in immune response, inflammation related pathways and cellular processes such as autophagy and programmed cell death, indicating their involvement in disease progression. Furthermore, mitochondrial dysfunction and impaired autophagy were linked to increased inflammation in advanced OA. ConclusionThese findings suggest that targeting mineralization and inflammatory pathways could offer novel therapeutic avenues for OA management.

pathology↗

Bioprinting of aptamer-based programmable bioinks to modulate multiscale microvascular morphogenesis in 4D

Dynamic growth factor presentation influences how individual endothelial cells assemble into complex vascular networks. Here, we developed programmable bioinks that facilitate dynamic VEGF presentation to guide vascular morphogenesis within 3D-bioprinted constructs. We leveraged aptamers high affinity for rapid VEGF sequestration in spatially confined regions and utilized aptamer-complementary sequence (CS) hybridization to tune VEGF release kinetics temporally, days after bioprinting. We show that spatial resolution of programmable bioink, combined with CS-triggered VEGF release, significantly influences alignment, organization, and morphogenesis of microvascular networks in bioprinted constructs. The presence of aptamer-tethered VEGF and the generation of instantaneous VEGF gradients upon CS-triggering restricted hierarchical network formation to the printed aptamer regions at all spatial resolutions. Network properties improved as the spatial resolution decreased, with low-resolution designs yielding the highest network properties. Specifically, CS-treated low-resolution designs exhibited significant vascular network remodeling, with increase in vessel density(1.35-fold), branching density(1.54-fold), and average vessel length(2.19-fold) compared to non-treated samples. Our results suggests that CS acts as an external trigger capable of inducing time-controlled changes in network organization and alignment on-demand within spatially localized regions of a bioprinted construct. We envision that these programmable bioinks will open new opportunities for bioengineering functional, hierarchically self-organized vascular networks within engineered tissues.

bioengineering↗

Trace DNA from kill sites identifies predating tigers

Predation ecology and evidence-based conflict management strategies require reliable and accurate identification of individual predators. Identifying predators is, however, complex, as they are secretive and individual identification is difficult. Trace DNA that predators leave behind at kill sites might provide an effective strategy to identify them but remains poorly evaluated at scale. We use non-invasive genetic samples from kill sites to assess their utility for predator identification. We systematically investigated 198 livestock kills in two critical source tiger populations in central India: Kanha and Bandhavgarh Tiger Reserves. We collected 342 salivary swabs from carcasses, 33 scat and 395 shed hair samples as potential sources of predator DNA, and individual tigers were identified using up to 123 SNP markers. All three sample sources identified predator species with high success (>95%). We identified individuals (with at least one sample per kill site, based on >40 SNPs) at 86% of all kill sites where tigers were detected. Shed hair samples were most effective for individual identification, followed by saliva and scat. Sample source and sampling season were the primary determinants of the number of SNPs typed per sample and the success of individual identification. Based on the site and type of sample collection, we classify species and individuals into three categories: true predator (high confidence as predator), circumstantial predator (medium confidence) and predator uncertain (low confidence). Individuals were classified as a true predator at 72 sites, circumstantial predator at 34 sites and predator uncertain at 49 sites. Our protocol allowed us to differentiate between predators and scavengers, even when multiple tigers were detected at the same kill site. Surprisingly, [~]40% of Bandhavgarhs tigers were identified at at least one kill site. We suggest that when paired with systematic kill site investigation and sample collection, these methods can be effectively used to understand predation ecology better and facilitate evidence-based conflict management.

genetics↗

Aptamer based spatiotemporally controlled growth factor patterning for tunable local microvascular network formation in engineered tissues

Spatiotemporally controlled growth factor availability is of crucial importance for achieving hierarchically organized vascular network formation within engineering tissues. Even though current growth factor delivery systems can provide sustained release and growth factor delivery on demand, they generally do not facilitate temporal control over the release rates and thus adaptation in accordance with the needs of growing engineered tissue. Additionally, with conventional growth factor loading methods, growth factors are often subjected to organic solvents or harsh conditions, leading to lower bioactivity and denaturation of the proteins. To overcome these limitations, this manuscript reports on the development of VEGF specific 5 acrydite modified aptamer functionalized GelMA hydrogels. The covalently incorporated aptamers can selectively bind to proteins with high affinity and specificity, and can thus sequester the target protein from the surrounding environment. The manuscript shows that this not only provides temporal control over the growth factor release via complementary sequence hybridization, but also enables local control of microvascular network formation in 3D.

bioengineering↗