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Roy, A.

Publications and source records attributed to Roy, A..

173 records · Page 10Linked to original sources

Spatiotemporal input reorganization and enhancement of input-output gain sharpen cortical direction selectivity during development

Some neural circuits are constructed through an overproduction of initial connections followed by activity-dependent refinement. Under this paradigm, functional receptive fields would be expected to be narrowed from a diffuse immature condition to a sharper mature condition. Alternatively, neural activity might lead to formation of new connections, leading to expansion of an initially compact receptive field. In the simple cells of the ferret visual cortex undergoing developmental enhancement of direction selectivity, we found evidence for a mixed mechanism: an expansion of the spatiotemporal receptive fields along the temporal dimension combined with a narrowing in space-time through a marked loss of inputs with certain space-time selectivities. Further, the resulting increase in subthreshold direction selectivity was accompanied by increases in near-spike-threshold excitability and input-output gain that resulted in dramatically increased spiking responses. Increases in subthreshold membrane responses and the increased input-output spiking gain were both necessary to explain firing rates in experienced ferrets. These results demonstrate that cortical direction selectivity develops through a combination of plasticity in synaptic and cell-intrinsic properties.

neuroscience↗

An early phase of instructive plasticity in visual cortex before the typical onset of sensory experience

While early experience with moving stimuli is necessary for the development of direction selectivity in visual cortex of carnivores, it is unclear whether experience exerts a permissive or instructive influence. To test if the specific parameters of the experienced stimuli could instructively sculpt the emergent responses, visually naive ferrets were exposed to several hours of experience with unusual spatiotemporal patterns. In the most immature ferrets, cortical neurons developed selectivity to these patterns, indicating an instructive influence. In animals that were 1-10 days more mature, exposure to the same patterns led to a developmentally-typical increase in direction selectivity. We conclude that visual development progresses via an early phase of instructive plasticity, when the specific patterns of neural activity shape the specific parameters of the emerging response properties, followed by a late phase of permissive maturation, when sensory-driven activity merely serves to enhance the response properties already seeded in cortical circuits.

neuroscience↗

Heterogeneous disease-propagating stem cells in juvenile myelomonocytic leukemia

Juvenile Myelomonocytic Leukemia (JMML) is a poor prognosis childhood leukemia usually caused by germline or somatic RAS-activating mutations. The cellular hierarchy in JMML is poorly characterized, including the identity of leukemia stem cells (LSCs). FACS and single-cell RNA-sequencing reveal marked heterogeneity of JMML hematopoietic stem/progenitor cells (HSPCs), including an aberrant Lin-CD34+CD38-CD90+CD45RA+ population. Single-cell HSPC index-sorting and clonogenic assays show that (1) all somatic mutations can be backtracked to the phenotypic HSC compartment with RAS-activating mutations as a \"first hit\", (2) mutations are acquired with both linear and branching patterns of clonal evolution and (3) mutant HSPCs are present after allogeneic HSC transplant before molecular/clinical evidence of relapse. Stem cell assays reveal inter-patient heterogeneity of JMML-LSCs which are present in, but not confined to, the phenotypic HSC compartment. RNA-sequencing of JMML-LSCs reveals upregulation of stem cell and fetal genes (HLF, MEIS1, CNN3, VNN2, HMGA2) and candidate therapeutic targets/biomarkers (MTOR, SLC2A1, CD96) paving the way for LSC-directed disease monitoring and therapy in this disease.

cancer biology↗

Deciphering the structural intricacy in virulence effectors for proton-motive force mediated unfolding and type-III protein secretion

Many gram-negative pathogenic bacteria use type III secretion system (T3SS) to inject virulence effectors directly into the cytosol of targeted host cells. Given that the protein unfolding requisite for secretion via nano-size pore of T3SS injectisome is an energetically unfavorable process, "How do pathogenic bacteria unfold and secrete hundreds of toxic proteins in seconds" remain largely unknown. In this study, first, from an in-depth analysis of folding and stability of T3SS effector ExoY, we show that the proton-concentration gradient ([~]pH 5.8-6.0) generated by proton-motive force (PMF) can significantly amortize tertiary structural folding and stability of effectors without significant entropic cost. Strikingly, it was found that the lower energetic cost associated with the global unfolding of ExoY is mainly due to its weakly folded geometry and abundance of geometrical frustrations stemming from buried water molecules and native-like folded intermediates in the folded cores. From in-silico structural analysis of 371 T3SS effectors, it can be curtained that T3SS effectors belong to typical class (disorder globules) of IDPs and have evolved similar conserved intrinsic structural archetypes to mediate early-stage unfolding. The slower folding kinetics in effector proteins requisite for efficient T3SS-mediated secretion mostly stems from reduced hydrophobic density and enhanced polar-polar repulsive interactions in their sequence landscapes. Lastly, the positively evolved histidine-mediated stabilizing interactions and gate-keeper residues in effector proteins shed light on collaborative role of evolved structural chemistry in T3SS effectors and PMF in the spatial-temporal regulation of effector folding and stability essential for maintaining balance in secretion and function trade-off.

biophysics↗

Performance evaluation of biosurfactant stabilized microbubbles in enhanced oil recovery

Microbubble technology is increasingly finding applications in biomedical engineering, soil remediation and wastewater treatment. Recently, the use of surfactant microbubbles has been studied as an alternate to aqueous solution in pollutant remediation since they have the advantage of improving the contact with the contaminant due to their surface properties. In this research endeavor, the application potential of microbubble suspension generated using a lipopeptide biosurfactant produced by a marine strain of Bacillus megaterium in tertiary oil recovery was investigated. The microbubbles were generated using a high speed homogenizer and their properties such as stability and size distribution were studied. The microbubble suspension was used as flooding agent to recover gear oil from an artificially saturated sand packed column. The performance of microbubbles in tertiary oil recovery was compared with that of aqueous biosurfactant solution. It was found that microbubble suspension generated using biosurfactant had higher oil recovery efficiency (46%) than aqueous solution (36%).\n\nMoreover, the pressure buildup across the sand packed column was fairly low while using microbubble suspension. The increased oil recovery using microbubbles can be attributed to their effective permeation through the pores of sand packed column and closer contact between biosurfactant molecules and oil. Thus, the results obtained in this study convincingly indicate that biosurfactant stabilized microbubble suspension, due to its higher performance and lower injection pressure requirement, can serve as a potentially efficient flooding agent for tertiary oil recovery.

bioengineering↗

A comparative study of ‘safe and just operating space’ for the south and south-east Asian countries

The world is presently maintaining a delicate balance of continuing well-being and social development for the people through consumption of biophysical resources of nature without topping global average per capita availability. In this paper, we have framed a per capita top-down framework to survey national safe and just operating space (NSJOS) for the countries of south and southeast Asia to understand past variations and as a consequence, the present scenario. Amalgamating 27 indicators, all regarding Sustainable Development Goals (except - SDG 17), in consort with their respective environmental boundaries or desirable social development thresholds, this study explores into both biophysical (for ecological stress) and social development (for social deprivation) attributes of 19 countries of south and southeast Asia. This analysis shows, only 2 have remained either unchanged (political voice) or declining (social equity) among the 12 dimensions of social development in countries of this region. The remaining 10 dimensions of social development showing positive progress and will meet corresponding desired thresholds of United Nations Sustainable Development Goals 2015. All the 7 indicators showing tendencies of overconsumption of biophysical resources, that might be leading to exceeding per capita global average planetary boundaries in forthcoming future. However, ecological boundaries have remained protected to a decent degree so far for these countries. The challenge would be to maintain and increase the pace of social development and bringing it in equal strata of a global standard in future without depleting drivers of these, i.e. biophysical resources. National policy adaptations are crucial if these countries of south and southeast Asia desire to bring about adequacy in biophysical resources reserve whilst granting social equity in access and exploitation of these resources for the people towards the persistant social development in impending decades.

ecology↗

A national ‘safe and just operating space’ for all in India: Past, Present and Futurea

With 1.3 billion populaces on the commencement of the 21st century, India is currently impending towards upholding a subtle equilibrium between persisting social development and well-being without depleting existing biophysical resources at the national level or surpassing global average per capita obtainability. In this paper, we have structured a top-down per capita framework to explore national safe and just operating space (NSJOS) to apprehend not only past fluctuations that bring about the present conditions but also the plausible future consequences, with India as a case study. Coalescing 27 indicators, all pertaining to Sustainable Development Goals (except - SDG 17), accompanied by their corresponding environmental boundaries or preferred social thresholds, present study probes into both biophysical (for environmental stress) and social development (for social deficit) attributes of India. This analysis shows India has already crossed three of seven dimensions of biophysical boundaries (freshwater, nitrogen and phosphorus use). Also, at the existing rate, India is going to cross the remainder of the boundaries within 2045-2050 (climate change, arable land use, ecological and material footprint). Of 20 indicators used for social development, only five have already or will meet corresponding desired thresholds of United Nations Sustainable Development Goals 2015. Using tendencies of past variations, the results indicate that if lowest per capita consumption can be attained and uphold, even with projected population growth, total consumption of four biophysical resources (climate change, nitrogen use, ecological and material footprint) can be slashed from todays level in 2050. Adaptations in national policy are indispensable if India wants to accomplish sufficiency in biophysical resources whilst bestowing social equity in access and exploitation of those resources towards the continuance of social developments in forthcoming times.

ecology↗

Analysing progress of SDG 6 in India: Past, Present, and Future

Human endeavors to meet social and economic water needs at national scale might cause negative environmental manifestations and water stress from local to global scale. So, appropriation of Sustainable Development Goals requires a comprehensive monitoring and knowledge base of the water resource availability, utilization and access. Hence, scientific research progression has a significant role to facilitate the implementation of sustainable development goals through assessment and policy implementation from global to local scales. India holds a key position among developing economies with a complex interconnected web of a fast-growing population, coupled with biophysical stress, social deprivation and economic inequality related to water and sanitation. This study addresses some of these challenges related to monitoring and implementation of the targets of the United Nations Sustainable Development Goal 6 in India. Acknowledging the contribution of society and economy in sustainability paradigm, here we have chosen 28 indicators (clustered into eleven dimensions) under two major groups, concerning biophysical and social development aspects of water and sanitation. We have shown declining level of per capita biophysical water resource and slow to rapidly developing social indicators related to Sustainable Development Goal 6 in India. From past trends, we have calculated probable scenario of biophysical consumption of India up to 2050, which shows at least 1.3 times increase. This cumulative assessment framework contributes a tool to prioritize water resource appropriation, management response and policy implementations to national level sustainability of water and sanitation in India. We also advocate the necessity of restraining threats both at source and consumption process levels in order to ensure national water security for both human and biodiversity, keeping in mind the societal and economic development scenario.

ecology↗

The Virtual Metabolic Human database: integrating human and gut microbiome metabolism with nutrition and disease

A multitude of factors contribute to complex diseases and can be measured with \"omics\" methods. Databases facilitate data interpretation for underlying mechanisms. Here, we describe the Virtual Metabolic Human (VMH, http://vmh.life) database encapsulating current knowledge of human metabolism within five interlinked resources \"Human metabolism\", \"Gut microbiome\", \"Disease\", \"Nutrition\", and \"ReconMaps\". The VMH captures 5,180 unique metabolites, 17,730 unique reactions, 3,288 human genes, 255 Mendelian diseases, 818 microbes, 632,685 microbial genes, and 8,790 food items. The VMHs unique features are i) the hosting the metabolic reconstructions of human and gut microbes amenable for metabolic modeling; ii) seven human metabolic maps for data visualization; iii) a nutrition designer; iv) a user-friendly webpage and application-programming interface to access its content; and v) user feedback option for community engagement. We demonstrate with four examples the VMHs utility. The VMH represents a novel, interdisciplinary database for data interpretation and hypothesis generation to the biomedical community.

systems biology↗

Genome Sequence of Indian Peacock Reveals the Peculiar Case of a Glittering Bird

The unique ornamental features and extreme sexual traits of Peacock have always intrigued the scientists. However, the genomic evidence to explain its phenotype are yet unknown. Thus, we report the first genome sequence and comparative analysis of peacock with the available high-quality genomes of chicken, turkey, duck, flycatcher and zebra finch. The candidate genes involved in early developmental pathways including TGF-{beta}, BMP, and Wnt signaling pathway, which are also involved in feather patterning, bone morphogenesis, and skeletal muscle development, showed signs of adaptive evolution and provided useful clues on the phenotype of peacock. The innate and adaptive immune components such as complement system and T-cell response also showed signs of adaptive evolution in peacock suggesting their possible role in building a robust immune system which is consistent with the between species predictions of Hamilton-Zuk hypothesis. This study provides novel genomic and evolutionary insights into the molecular understanding towards the phenotypic evolution of Indian peacock.

genomics↗

Clingen Cancer Somatic Working Group: standardizing and democratizing access to cancer molecular diagnostic data to drive translational research

A growing number of academic and community clinics are conducting genomic testing to inform treatment decisions for cancer patients (1). In the last 3-5 years, there has been a rapid increase in clinical use of next generation sequencing (NGS) based cancer molecular diagnostic (MolDx) testing (2). The increasing availability and decreasing cost of tumor genomic profiling means that physicians can now make treatment decisions armed with patient-specific genetic information. Accumulating research in the cancer biology field indicates that there is significant potential to improve cancer patient outcomes by effectively leveraging this rich source of genomic data in treatment planning (3). To achieve truly personalized medicine in oncology, it is critical to catalog cancer sequence variants from MolDx testing for their clinical relevance along with treatment information and patient outcomes, and to do so in a way that supports large-scale data aggregation and new hypothesis generation. One critical challenge to encoding variant data is adopting a standard of annotation of those variants that are clinically actionable. Through the NIH-funded Clinical Genome Resource (ClinGen) (4), in collaboration with NLMs ClinVar database and >50 academic and industry based cancer research organizations, we developed the Minimal Variant Level Data (MVLD) framework to standardize reporting and interpretation of drug associated alterations (5). We are currently involved in collaborative efforts to align the MVLD framework with parallel, complementary sequence variants interpretation clinical guidelines from the Association of Molecular Pathologists (AMP) for clinical labs (6). In order to truly democratize access to MolDx data for care and research needs, these standards must be harmonized to support sharing of clinical cancer variants. Here we describe the processes and methods developed within the ClinGens Somatic WG in collaboration with over 60 cancer care and research organizations as well as CLIA-certified, CAP-accredited clinical testing labs to develop standards for cancer variant interpretation and sharing.

bioinformatics↗