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Browsing by Author "Yadav, Gitanjali"

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    An advanced draft genome assembly of a desi type chickpea (Cicer arietinum L.)
    (Nature Publishing Group, 2015) Parween, Sabiha; Nawaz, Kashif; Roy, Riti; Pole, Anil K.; Venkata Suresh, B.; Misra, Gopal; Jain, Mukesh; Yadav, Gitanjali; Parida, Swarup K.; Tyagi, Akhilesh K.; Bhatia, Sabhyata; Chattopadhyay, Debasis
    Chickpea (Cicer arietinum L.) is an important pulse legume crop. We previously reported a draft genome assembly of the desi chickpea cultivar ICC 4958. Here we report an advanced version of the ICC 4958 genome assembly (version 2.0) generated using additional sequence data and an improved genetic map. This resulted in 2.7-fold increase in the length of the pseudomolecules and substantial reduction of sequence gaps. The genome assembly covered more than 94% of the estimated gene space and predicted the presence of 30,257 protein-coding genes including 2230 and 133 genes encoding potential transcription factors (TF) and resistance gene homologs, respectively. Gene expression analysis identified several TF and chickpea-specific genes with tissue-specific expression and displayed functional diversification of the paralogous genes. Pairwise comparison of pseudomolecules in the desi (ICC 4958) and the earlier reported kabuli (CDC Frontier) chickpea assemblies showed an extensive local collinearity with incongruity in the placement of large sequence blocks along the linkage groups, apparently due to use of different genetic maps. Single nucleotide polymorphism (SNP)-based mining of intra-specific polymorphism identified more than four thousand SNPs differentiating a desi group and a kabuli group of chickpea genotypes.
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    AI & ethics: charting a responsible future
    (NATL INST SCIENCE COMMUNICATION-NISCAIR, 2024) Yadav, Gitanjali; Munshi, Angad; Kumari, Renu; Singh, Dhananjay; Kumari, Neeraj; Munshi, Usha Mujoo
    Artificial intelligence (AI) is rapidly transforming the world, but its development and deployment raise critical ethical questions. This paper explores the key themes that emerged from a national conclave on AI and Ethics in India, bringing together industry and academic leaders. We examine the potential of AI for various sectors, with a thematic case study for the Genome Biology sector, alongside concerns about bias, privacy, and accountability. AI development and use, while underscoring the need for an ethical framework to guide its evolution, emphasizes the need for collaboration between academia and industry to develop ethical frameworks and translate principles into practical applications. In summary, ethical AI may serve as a moral framework of AI technologies to ensure that our technological capability aligns with fundamental societal values and human dignity on the road to progress. This framework by definition would not be a static set of commandments but a dynamic constantly evolving idea about the use of technologies like AI.
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    Arabidopsis target of rapamycin coordinates with transcriptional and epigenetic machinery to regulate thermotolerance
    (Frontiers Media S.A., 2021) Sharma, Mohan; Jamsheer, K.M.; Shukla, Brihaspati Narayan; Sharma, Manvi; Awasthi, Prakhar; Mahtha, Sanjeet Kumar; Yadav, Gitanjali; Laxmi, Ashverya
    Global warming exhibits profound effects on plant fitness and productivity. To withstand stress, plants sacrifice their growth and activate protective stress responses for ensuring survival. However, the switch between growth and stress is largely elusive. In the past decade, the role of the target of rapamycin (TOR) linking energy and stress signalling is emerging. Here, we have identified an important role of Glucose (Glc)-TOR signalling in plant adaptation to heat stress (HS). Glc via TOR governs the transcriptome reprogramming of a large number of genes involved in heat stress protection. Downstream to Glc-TOR, the E2Fa signalling module regulates the transcription of heat shock factors through direct recruitment of E2Fa onto their promoter regions. Also, Glc epigenetically regulates the transcription of core HS signalling genes in a TOR-dependent manner. TOR acts in concert with p300/CREB HISTONE ACETYLTRANSFERASE1 (HAC1) and dictates the epigenetic landscape of HS loci to regulate thermotolerance. Arabidopsis plants defective in TOR and HAC1 exhibited reduced thermotolerance with a decrease in the expression of core HS signalling genes. Together, our findings reveal a mechanistic framework in which Glc-TOR signalling through different modules integrates stress and energy signalling to regulate thermotolerance.
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    Cavity architecture based modulation of ligand binding tunnels in plant START domains
    (Elsevier B.V., 2023) Mahtha, Sanjeet Kumar; Kumari, Kamlesh; Gaur, Vineet; Yadav, Gitanjali
    The Steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain represents an evolutionarily conserved superfamily of lipid transfer proteins widely distributed across the tree of life. Despite significant expansion in plants, knowledge about this domain remains inadequate in plants. In this work, we explore the role of cavity architectural modulations in START protein evolution and functional diversity. We use deep-learning approaches to generate plant START domain models, followed by surface accessibility studies and a comprehensive structural investigation of the rice START family. We validate 28 rice START domain models, delineate binding cavities, measure pocket volumes, and compare these with mammalian counterparts to understand evolution of binding preferences. Overall, plant START domains retain the ancestral α/β helix-grip signature, but we find subtle variation in cavity architectures, resulting in significantly smaller ligand-binding tunnels in the plant kingdom. We identify cavity lining residues (CLRs) responsible for reduction in ancestral tunnel space, and these appear to be class specific, and unique to plants, providing a mechanism for the observed shift in domain function. For instance, mammalian cavity lining residues A135, G181 and A192 have evolved to larger CLRs across the plant kingdom, contributing to smaller sizes, minimal STARTs being the largest, while members of type-IV HD-Zip family show almost complete obliteration of lipid binding cavities, consistent with their present-day DNA binding functions. In summary, this work quantifies plant START structural & functional divergence, bridging current knowledge gaps.
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    Characterization and genetic linkage mapping of the horticulturally important mutation leafless inflorescence (lli) in periwinkle Catharanthus roseus
    (Elsevier, 2011) Chaudhary, Swati; Sharma, Vishakha; Prasad, Manoj; Bhatia, Sabhyata; Tripathi, Bhumi Nath; Yadav, Gitanjali; Kumar, Sushil
    Catharanthus roseus is a seasonal to perennial garden plant and the exclusive source of the anticancer drugs vincristine and vinblastine. Its horticultural importance is due to the compound racemose inflorescence architecture of branches in which pairs of prominent flowers are subtended by one of the two leaves per node. Here is reported the construction of a molecular framework genetic linkage map and mapping on it of the LEAF-LESS INFLORESCENCE (LLI) locus. It is quantitatively shown that the adult lli mutant plants produce altered inflorescence of improved horticultural value, wherein axes are excessively branched, two flowers are formed per node that are bare of subtending leaves, and several times more open flowers are displayed each day, as compared to LLI plants.
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    The chickpea genomic web resource: visualization and analysis of the desi-type Cicer arietinum nuclear genome for comparative exploration of legumes
    (BioMed Central Ltd, 2014) Misra, Gopal; Priya, Piyush; Bandhiwal, Nitesh; Bareja, Neha; Jain, Mukesh; Bhatia, Sabhyata; Chattopadhyay, Debasis; Tyagi, Akhilesh K.; Yadav, Gitanjali
    Background: Availability of the draft nuclear genome sequences of small-seeded desi-type legume crop Cicer arietinum has provided an opportunity for investigating unique chickpea genomic features and evaluation of their biological significance. The increasing number of legume genome sequences also presents a challenge for developing reliable and information-driven bioinformatics applications suitable for comparative exploration of this important class of crop plants. Results: The Chickpea Genomic Web Resource (CGWR) is an implementation of a suite of web-based applications dedicated to chickpea genome visualization and comparative analysis, based on next generation sequencing and assembly of Cicer arietinum desi-type genotype ICC4958. CGWR has been designed and configured for mapping, scanning and browsing the significant chickpea genomic features in view of the important existing and potential roles played by the various legume genome projects in mutant mapping and cloning. It also enables comparative informatics of ICC4958 DNA sequence analysis with other wild and cultivated genotypes of chickpea, various other leguminous species as well as several non-leguminous model plants, to enable investigations into evolutionary processes that shape legume genomes. Conclusions: CGWR is an online database offering a comprehensive visual and functional genomic analysis of the chickpea genome, along with customized maps and gene-clustering options. It is also the only plant based web resource supporting display and analysis of nucleosome positioning patterns in the genome. The usefulness of CGWR has been demonstrated with discoveries of biological significance made using this server. The CGWR is compatible with all available operating systems and browsers, and is available freely under the open source license at http://www.nipgr.res.in/CGWR/home.php.
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    Co-authorship networks among DRDO life science scientists
    (Defence Research & Development Organization, 2016) Babu, S; Yadav, Gitanjali
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    Co-regulation of biomass partitioning by leafblade morphology genes AFILA, MULTIFOLIATE-PINNA, TENDRIL-LESS and UNIFOLIATA in grain pea Pisum sativum
    (Indian National Science Academy, 2010) Kumar, Sushil; Mishra, Raghvendra Kumar; Chaudhary, Swati; Pandey, Richa; Yadav, Gitanjali
    In grain pea Pisum sativum, 16 genotypes constructed by combining wild type and mutant alleles of MULTIFOLIATE- PINNA (MFP), AFILA (AF), TENDRIL-LESS (TL) and UNIFOLIATA (UNI) genes, which differed in leaf blade morphology, were quantitatively phenotyped for allometry. The biomass partitioning among root, stem, stipule, leaf blade and seeds was unique for these genotypes suggesting that MFP, AF, TL and UNI genes determined leaf blade and plant architecture. Gene actions were inferred on the basis of mutant phenotypes. Biomass of all the organs was found to be increased in the tl single mutant. The af mutation singly and in combination with mfp, mfp tl, mfp uni-tac or mfp tl uni-tac decreased biomass of all the organs. Allocation of biomass to leaves was increased at the expense of that to seeds or seeds and stems by a single mfp mutation or in combination with uni-tac, af tl, tl uni-tac and af tl uni-tac mutations. The AF and MFP functions are essential in pea cultivars for high yield of grains.The mechanism for simultaneous control of leaf blade and plant architecture suggested by mutant phenotypes has three elements. The MFP, AF, TL and UNI genes exercise control over meristematic activity in all the organs. Their determination of leaf blade morphology and size affect net photosynthesis or metabolite supply. The quantities of available metabolites determine numbers and sizes of organs or partitioned total biomass. The tl allele is identified as a genetic marker/determinant for breeding tendril-less prolific pea cultivars for obtaining herbage and grains in high yields.
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    Common and distinguishing characteristics of genes and genomes and their evolution in the genome sequenced legumes
    (Indian National Science Academy, 2013) Kumar, Sushil; Kumari, Renu; Sharma, Vishakha; Yadav, Gitanjali
    By March 2013, genome sequences have been published for five legume species- Cicer arietinum (pulse crop chickpea), Cajanus cajan (pulse crop pigeonpea), Glycine max (pulse-cum-oil seed crop soybean), Lotus japonicus and Medicago truncatula (both model plants). The genome sequenced legumes belong to the subfamily papilionoideae of the angiosperm family leguminoseae, C. arietinum, L. japonicus and M. truncatula to the galegoid clade and C. cajan and G. max to millettioid clade. These diploid species have 2n number varying from 12 in L. japonicus, 16 in M. truncatula and C. arietinum, 22 in C. cajan and 40 in G. max. Comparisons among their genome sequences have revealed several important properties about structure and evolution of their genomes. Thirty five to 60% of genome is in the form of repititive elements, mainly transposons. Genome carries less than 50,000 protein-coding genes, 56 to 87% in two or more copies. All the five species arose from a common pre-papilionoid parent produced by inter-species hybridization accompanied by whole genome duplication (WGD or allotetraploidy) about 58 million years ago (Mya). Separation of clades and speciation occurred via sequence changes, over a period of > 40 million years. Individual genes underwent substitution and frameshift mutations. Chromosomal level rearrangements involved deletions, inversions, translocations, fission and fusions. There was spread of individual genes or blocks of genes followed by their tandem duplication. Deletion of orthologues was also involved in lineage specific changes. Ancestors of Glycine underwent an allotetraploid event after separation of C. cajan in the millettioid clade about 13 Mya. Developments relating to the applications of legume genome sequence knowledge are also discussed.
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    Complex networks of prion-like proteins reveal cross talk between stress and memory pathways in plants
    (Frontiers Media S.A., 2021) Garai, Sampurna; Citu; Singla-Pareek, Sneh L.; Sopory, Sudhir K.; Kaur, Charanpreet; Yadav, Gitanjali
    Prions are often considered as molecular memory devices, generating reproducible memory of a conformational change. Prion-like proteins (PrLPs) have been widely demonstrated to be present in plants, but their role in plant stress and memory remains unexplored. In this work, we report the widespread presence of PrLPs in plants through a comprehensive meta-analysis of 39 genomes representing major taxonomic groups. We find diverse functional roles associated with these proteins in various species and term the full complement of PrLPs in a genome as its “prionome.” In particular, we found the rice prionome being significantly enriched in transposons/retrotransposons (Ts/RTRs) and identified over 60 rice PrLPs that were differentially regulated in stress and developmental responses. This prompted us to explore whether and to what extent PrLPs may build stress memory. By integrating the available rice interactome, transcriptome, and regulome data sets, we could find links between stress and memory pathways that would not have otherwise been discernible. Regulatory inferences derived from the superimposition of these data sets revealed a complex network and cross talk between PrLPs, transcription factors (TFs), and the genes involved in stress priming. This integrative meta-analysis connects transient and transgenerational memory mechanisms in plants with PrLPs, suggesting that plant memory may rely upon protein-based signals in addition to chromatin-based epigenetic signals. Taken together, our work provides important insights into the anticipated role of prion-like candidates in stress and memory, paving the way for more focused studies for validating the role of the identified PrLPs in memory acclimation.
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    Complex networks reveal biological functions of START domains in rice: Insights from computational systems biology
    (Springer Nature Publishing AG, 2022) Mahtha, Sanjeet Kumar; Citu; Prasad, Abhishek; Yadav, Gitanjali
    With the advancement of high throughput technologies, there has been a massive surge in the omics data generation and there is a growing need to integrate this data gain insights into the patterns that shape biological interactions. Complex networks not only enable representation of such interactions, but also offer a mechanism for visualization and understanding of big data at a systems level. In this work, we use a complex network approach to investigate functions of the plant amplified StAR-related lipid transfer (START) domains in rice. We analyse the data at three levels; namely the transcriptome, proteome, and regulome. Each of these distinct datasets was superimposed after generation of the respective co-expression, protein-protein interaction, and gene regulatory networks for rice START genes, to reveal domain specific features in the family. This work thus serves as a protocol for network-based approaches to understand biological processes of genes and to complement experimental strategy.
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    Cytosine hypomethylation at CHG and CHH sites in the pleiotropic mutants of Mendelian inheritance in Catharanthus roseus
    (Indian Academy of Sciences, 2013) Kumari, Renu; Yadav, Gitanjali; Sharma, Vishakha; Sharma, Vinay; Kumar, Sushil
    The 5S and 18S rDNA sequences of Catharanthus roseus cv 'Nirmal' (wild type) and its leafless inflorescence (lli), evergreen dwarf (egd) and irregular leaf lamina (ill) single mutants and lli egd, lli ill and egd ill double mutants were characterized. The lli, egd and ill mutants of Mendelian inheritance bore the names after their most conspicuous morphological feature(s). They had been chemically induced and isolated for their salt tolerance. The double mutants were isolated as morphological segregants from crosses between single mutants. The morphological features of the two parents accompanied salt tolerance in the double mutants. All the six mutants were hypomethylated at repeat sequences, upregulated and downregulated for many genes and carried pleiotropic alterations for several traits. Here the 5S and 18S rDNAs of C. roseus were found to be relatively low in cytosine content. Cytosines were preponderantly in CG context (53%) and almost all of them were methylated (97%). The cytosines in CHH and CHG (where H = A, T or C) contexts were largely demethylated (92%) in mutants. The demethylation was attributable to reduced expression of RDR2 and DRM2 led RNA dependant DNA methylation and CMT3 led maintenance methylation pathways. Mutants had gained some cytosines by substitution of C at T sites. These perhaps arose on account of errors in DNA replication, mediated by widespread cytosine demethylation at CHG and CHH sites. It was concluded that the regulation of cytosine ethylation mechanisms was disturbed in the mutants. ILL, EGD and LLI genes were identified as the positive regulators of other genes mediating the RdDM and CMT3 pathways, for establishment and maintenance of cytosine methylation in C. roseus.
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    Data for development and the role of CODATA of the International Science Council (ISC)
    (NATL INST SCIENCE COMMUNICATION-NISCAIR, 2024) Selematsela, Daisy; Mujoomunshi, Usha; Yadav, Gitanjali
    While the discussion on data for development gains traction in society especially with the focus on Sustainable Development Goals(SDGs), there is the need for more insight into the long-standing global perspectives on data and information for science. The International Science Council (ISC) established in 1932 as International Council for Scientific Unions (ICSU) aims to strengthen international science for the benefit of society. The key principle is the "Universality of Science"1which interprets science as a collective effort working for the common good, but a growing number of scientists, policy-makers, and social scientists argue that science is often too isolated from society to fulfil this promise. This brings in the concept of 'Open Science' to close the gap between science and society by democratizing scientific knowledge, for the benefit of everyone. The Committee on Data (CODATA), an interdisciplinary body of ISC is the focus of this paper, along with recent perspectives regarding its role and needs of science in the present information-driven society.
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    Decision support systems based on scientific evidence: bibliometric networks of invasive Lantana camara
    (Indian National Science Academy, 2021) Mishra, Preet; Prasad, Abhishek; Babu, Suresh; Yadav, Gitanjali
    Extraction and analysis of useful knowledge from the vast amount of relevant published literature can add valuable insights to any research theme or area of interest. We introduce a simplifed bibliometric data analysis protocol for gaining substantial insights into research thematics, which can also serve as a handy practical skill for researchers while working from home. In this paper, we provide ways of developing a holistic research strategy using bibliometric-data driven approaches that integrate network analysis and information management, without the need for full paper access. This protocol is a comprehensive multi-modular pathway for analysis of metadata obtained from major scientifc publishing houses by the use of a Decision Support System (DSS). A simple case study on the invasive species Lantana camara has been presented as a proof-of-concept to show how one can implement this DSS based protocol. Some perspectives are also provided on how the outcomes can be used directly or scaled up for long term research interventions. We hope that this work will simplify exploratory literature review, and enable rational design of research objectives for scholars, as well as the development of comprehensive grant proposals that address gaps in research.
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    Diversification of the Histone Fold Motif (HFM) in plants: Evolution of new functional roles
    (Defence Research & Development Organization, 2016) Amish, K; Yadav, Gitanjali
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    A draft genome sequence of the pulse crop chickpea (Cicer arietinum L.)
    (John Wiley & Sons, 2013) Jain, Mukesh; Misra, Gopal; Patel, Ravi K.; Priya, Pushp; Jhanwar, Shalu; Khan, Aamir W.; Shah, Niraj; Singh, Vikas K.; Garg, Rohini; Jeena, Ganga; Yadav, Manju; Kant, Chandra; Sharma, Priyanka; Yadav, Gitanjali; Bhatia, Sabhyata; Tyagi, Akhilesh K.; Chattopadhyay, Debasis
    Cicer arietinum L. (chickpea) is the third most important food legume crop. We have generated the draft sequence of a desi-type chickpea genome using next-generation sequencing platforms, bacterial artificial chromosome end sequences and a genetic map. The 520-Mb assembly covers 70% of the predicted 740-Mb genome length, and more than 80% of the gene space. Genome analysis predicts the presence of 27,571 genes and 210 Mb as repeat elements. The gene expression analysis performed using 274 million RNA-Seq reads identified several tissue-specific and stress-responsive genes. Although segmental duplicated blocks are observed, the chickpea genome does not exhibit any indication of recent whole-genome duplication. Nucleotide diversity analysis provides an assessment of a narrow genetic base within the chickpea cultivars. We have developed a resource for genetic markers by comparing the genome sequences of one wild and three cultivated chickpea genotypes. The draft genome sequence is expected to facilitate genetic enhancement and breeding to develop improved chickpea varieties.
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    Ecological networks in urban forest fragments reveal species associations between native and invasive plant communities
    (MDPI AG, 2022) Chauhan, Sonali; Yadav, Gitanjali; Babu, Suresh
    Forest fragments are characteristic features of many megacities that have survived the urbanisation process and are often represented by unique assemblages of flora and fauna. Such woodlands are representations of nature in the city—often dominated by non-native and invasive species that coexist with resilient native congeners and purposefully introduced flora. These forest fragments also provide significant ecosystem services to urban society and therefore, understanding their compositional patterns is of considerable importance for conservation and management. In this work, we use a complex network approach to investigate species assemblages across six distinct urban forest fragments in the South Delhi Ridge area of the National Capital Territory, India. We generate bipartite ecological networks using conventional vegetation sampling datasets, followed by network partitioning to identify multiple cliques across the six forest fragments. Our results show that urban woodlands primarily form invasive–native associations, and that major invasive species, such as Prosopis juliflora and Lantana camara exclude each other while forming cliques. Our findings have implications for the conservation of these urban forests and highlight the importance of using network approaches in vegetation analysis.
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    Editorial: Plant transcription factors associated with abiotic stress tolerance in crops and wild-relatives
    (Frontiers Media S.A., 2024) Puglia, Giuseppe Diego; Frugis, Giovanna; Yadav, Gitanjali
    Editorial on the Research Topic Plant transcription factors associated with abiotic stress tolerance in crop and wild-relatives Global climate change (GCC), by altering the intensity and frequency of potentially damaging weather events such as droughts, waterlogging, heat waves, and cold spells, has altered seasonal weather patterns, causing severe problems for plant crops and wildlife species (Cramer et al., 2011; Asseng et al., 2015; Minoli et al., 2019). To cope with these challenges, plants have evolved complex regulatory mechanisms that enable them to respond and adapt to changing environmental conditions, while maintaining a balance between optimal growth and stress (Eckardt et al., 2023). This Research Topic brings together several contributions that highlight the role of transcriptional regulation in plant responses to abiotic stresses and hypothesise its role in stress tolerance. The studies published in this Research Topic deal with well-recognised groups of transcription factors (TFs), but also with new ones whose association with the response to abiotic stresses has been demonstrated by recent molecular advances. This evidence allows us to shed light on the mechanisms by which plants respond to different stresses, with a focus on abiotic stresses such as salt, drought, cold, and waterlogging.
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    EssOilDB: A database of essential oils reflecting terpene composition and variability in the plant kingdom
    (Oxford University Press, 2014) Kumari, Sangita; Pundhir, Sachin; Priya, Piyush; Jeena, Ganga; Punetha, Ankita; Chawla, Konika; Jafaree, Zohra Firdos; Mondal, Subhasish; Yadav, Gitanjali
    Plant essential oils are complex mixtures of volatile organic compounds, which play indispensable roles in the environment, for the plant itself, as well as for humans. The potential biological information stored in essential oil composition data can provide an insight into the silent language of plants, and the roles of these chemical emissions in defense, communication and pollinator attraction. In order to decipher volatile profile patterns from a global perspective, we have developed the ESSential OIL DataBase (EssOilDB), a continually updated, freely available electronic database designed to provide knowledge resource for plant essential oils, that enables one to address a multitude of queries on volatile profiles of native, invasive, normal or stressed plants, across taxonomic clades, geographical locations and several other biotic and abiotic influences. To our knowledge, EssOilDB is the only database in the public domain providing an opportunity for context based scientific research on volatile patterns in plants. EssOilDB presently contains 123 041 essential oil records spanning a century of published reports on volatile profiles, with data from 92 plant taxonomic families, spread across diverse geographical locations all over the globe. We hope that this huge repository of VOCs will facilitate unraveling of the true significance of volatiles in plants, along with creating potential avenues for industrial applications of essential oils. We also illustrate the use of this database in terpene biology and show how EssOilDB can be used to complement data from computational genomics to gain insights into the diversity and variability of terpenoids in the plant kingdom. EssOilDB would serve as a valuable information resource, for students and researchers in plant biology, in the design and discovery of new odor profiles, as well as for entrepreneurs--the potential for generating consumer specific scents being one of the most attractive and interesting topics in the cosmetic industry. Database URL: http://nipgr.res.in/Essoildb/
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    Evidence for inhibitory interaction of hyaluronan binding protein 1 with S. pneumoniae hyaluronidase
    (The American Society for Biochemistry and Molecular Biology, Inc., 2009) Yadav, Gitanjali; Prasad, Ramachandra L. A.; Jha, Babal Kant; Rai, Vivek; Bhakuni, Vinod; Datta, Kasturi
    Bacterial hyaluronan lyase enzymes are the major virulence factors that enable greater microbial ingress by cleaving hyaluronan (HA) polymers present predominantly in extracellular space of vertebrates. Based on the premise that effective inhibitors may bind to and stabilize HA thereby protecting it from degradation, here we investigated inhibitory activity of human hyaluronan-binding protein 1 (HABP1) on bacterial hyaluronidase because it is highly specific to HA and localized on the cell surface. Biochemical characterization revealed that HABP1 is a competitive inhibitor of Streptococcus pneumoniae hyaluronate lyase (SpnHL) with an IC50 value of 22 uM. This is thus the first report of an endogenous protein inhibitor that may be used dur- ing natural antibacterial defense. Our findings also support a novel multipronged mechanism for the high efficacy of HABP1- mediated inhibition based on structural modeling of enzyme, substrate, and inhibitor. Evidence from docking simulations and contact interface interactions showed that the inherent charge asymmetry of HABP1 plays a key role in the inhibitory activity. This novel role of HABP1 may pave the way for peptide inhibitors as alternatives to synthetic chemicals in antibacterial research.
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