Year of Publication Publication Type Title
2016 Journal Article Ja H., Omanakuttan, Aa, Pandurangan, Na, Vargis, VbS., Maneesh, Mc, Nair, BaG., and Kumar, GaB., “Clove bud oil reduces kynurenine and inhibits pqs A gene expression in P. aeruginosa”, Applied Microbiology and Biotechnology, pp. 1-12, 2016.[Abstract]

Quorum sensing (QS), a communication system involved in virulence of pathogenic bacteria like Pseudomonas aeruginosa is a promising target to combat multiple drug resistance. In vitro studies using clove bud oil (CBO) in P. aeruginosa revealed a concentration dependent attenuation of a variety of virulence factors including motility, extracellular DNA, exopolysaccharides and pigment production. Furthermore, treatment with CBO demonstrated a distinct dose-dependent reduction in biofilm formation as well as promoting dispersion of already formed biofilm, observations that were also supported by porcine skin ex vivo studies. Expression studies of genes involved in signalling systems of P. aeruginosa indicated a specific decrease in transcription of pqsA, but not in the lasI or rhlI levels. Additionally, the expression of vfr and gacA genes, involved in regulation, was also not affected by CBO treatment. CBO also influenced the PQS signalling pathway by decreasing the levels of kynurenine, an effect which was reversed by the addition of exogenous kynurenine. Though the synthesis of the signalling molecules of the Las and Rhl pathways was not affected by CBO, their activity was significantly affected, as observed by decrease in levels of their various effectors. Molecular modelling studies demonstrated that eugenol, the major component of CBO, favourably binds to the QS receptor by hydrophobic interactions as well as by hydrogen bonding with Arg61 and Tyr41 which are key amino acid residues of the LasR receptor. These results thus elucidate the molecular mechanism underlying the action of CBO and provide the basis for the identification of an attractive QS inhibitor. © 2016 Springer-Verlag Berlin Heidelberg More »»
2016 Journal Article V. Özdemir and Kolker, E., “Precision Nutrition 4.0: A Big Data and Ethics Foresight Analysis-Convergence of Agrigenomics, Nutrigenomics, Nutriproteomics, and Nutrimetabolomics”, OMICS A Journal of Integrative Biology, vol. 20, pp. 69-75, 2016.[Abstract]

Nutrition is central to sustenance of good health, not to mention its role as a cultural object that brings together or draws lines among societies. Undoubtedly, understanding the future paths of nutrition science in the current era of Big Data remains firmly on science, technology, and innovation strategy agendas around the world. Nutrigenomics, the confluence of nutrition science with genomics, brought about a new focus on and legitimacy for 'variability science' (i.e., the study of mechanisms of person-To-person and population differences in response to food, and the ways in which food variably impacts the host, for example, nutrient-related disease outcomes). Societal expectations, both public and private, and claims over genomics-guided and individually-Tailored precision diets continue to proliferate. While the prospects of nutrition science, and nutrigenomics in particular, are established, there is a need to integrate the efforts in four Big Data domains that are naturally allied-agrigenomics, nutrigenomics, nutriproteomics, and nutrimetabolomics-that address complementary variability questions pertaining to individual differences in response to food-related environmental exposures. The joint use of these four omics knowledge domains, coined as Precision Nutrition 4.0 here, has sadly not been realized to date, but the potentials for such integrated knowledge innovation are enormous. Future personalized nutrition practices would benefit from a seamless planning of life sciences funding, research, and practice agendas from 'farm to clinic to supermarket to society,' and from 'genome to proteome to metabolome.' Hence, this innovation foresight analysis explains the already existing potentials waiting to be realized, and suggests ways forward for innovation in both technology and ethics foresight frames on precision nutrition. We propose the creation of a new Precision Nutrition Evidence Barometer for periodic, independent, and ongoing retrieval, screening, and aggregation of the relevant life sciences data. For innovation in Big Data ethics oversight, we suggest 'nested governance' wherein the processes of knowledge production are made transparent in the continuum from life sciences and social sciences to humanities, and where each innovation actor reports to another accountability and transparency layer: scientists to ethicists, and ethicists to scholars in the emerging field of ethics-of-ethics. Such nested innovation ecosystems offer safety against innovation blind spots, calibrate visible/invisible power differences in the cultures of science or ethics, and ultimately, reducing the risk of 'paper values'-what people say-and 'real values'-what innovation actors actually do. We are optimistic that the convergence of nutrigenomics with nutriproteomics, nutrimetabolomics, and agrigenomics can build a robust, sustainable, and trustworthy precision nutrition 4.0 agenda, as articulated in this Big Data and ethics foresight analysis. © Copyright 2016, Mary Ann Liebert, Inc. 2016.

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2016 Journal Article S. Diwakar, Radhamani, R., Sasidharakurup, H., Kumar, D., Nizar, N., Dr. Achuthan, K., and Bipin G. Nair Dr., “Assessing students and teachers experience on simulation and remote biotechnology virtual labs: A case study with a light microscopy experiment”, Lecture Notes of the Institute for Computer Sciences, Social-Informatics and Telecommunications Engineering, LNICST, vol. 160, pp. 44-51, 2016.[Abstract]

With recent trends of using Information and Communication Technologies in education, virtual labs have become more prevalent in classrooms of most schools and universities, especially in South India. The purpose of this paper was to perform a comparative analysis of virtual learning components such as animations, simulations and real-time remotely controlled experiments. As a part of this study, we conducted a series of biotechnology virtual lab workshops for University-level users within India and collected feedback related to the usage of virtual labs via direct approach. The survey amongst the students and teachers suggested simulation-based labs were more preferred in enhancing teaching and learning strategy compared to graphics-mediated animations and remotely controlled experiments. This paper also reports some of the issues faced by virtual lab users. Studies indicated that even though the web-based technologies are a new venture in education, it still poses adaptability issues. © Institute for Computer Sciences, Social Informatics and Telecommunications Engineering 2016.

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2016 Journal Article S. Nair and Kong, A. H. T., “Pharmacometrics of nutraceutical sulforaphane and its implications in prostate cancer prevention”, Journal of Chinese Pharmaceutical Sciences, vol. 25, pp. 12-22, 2016.[Abstract]

Sulforaphane (SFN), found in broccoli and other cruciferous vegetables, has a beneficial effect in chemoprevention of prostate cancer, whose incidence and associated mortality have gradually increased worldwide. There is great enthusiasm for bench-to-bedside development of SFN as a potent chemopreventive agent, possibly alone or as an adjunct to existing chemotherapy regimens, in the oncology care setting to reduce toxicity of chemotherapeutics and potentially enhance their cancer cell-kill efficacy. In this review, we appreciate existing knowledge on SFN using a pharmacometrics approach, which is fast becoming a gold standard in discovery research and validation of New Chemical Entities and New Biological Entities in pharmaceutical industry. We discuss the epistemology of SFN target engagement and quantitative systems pharmacology with due emphasis on mechanistic pharmacology, pharmacodynamics, pharmacogenomics and metabolism of SFN. In addition, we explore the quantitative freeway to SFN translational medicine by assessing the preclinical and clinical PK/metabolism aspects of SFN that form the cornerstone of SFN pharmacometric evaluation, as well as the promise of SFN in prostate cancer. Taken together, we share perspectives on the exciting developments in translational cancer chemoprevention, with emphasis on the pharmacometric aspects, of the nutraceutical SFN which is currently in clinical trials, and suggest that the pharmacometric approach holds great promise in the SFN translational pharmacology paradigm for prostate cancer. © 2016 Journal of Chinese Pharmaceutical Sciences.

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2016 Journal Article S. Dr. Diwakar, Kumar, D., Radhamani, R., Sasidharakurup, H., Nizar, N., Dr. Achuthan, K., Prema Nedungadi, Raman, R., and Bipin G. Nair Dr., “Complementing Education via Virtual Labs: Implementation and Deployment of Remote Laboratories and Usage Analysis in South Indian Villages”, International Journal of Online Engineering (iJOE), vol. 12, pp. 8–15, 2016.[Abstract]

ICT-enabled virtual and remote labs have become a platform augmenting user engagement in blended education scenarios enhancing University education in rural India. A novel trend is the use of remote laboratories as learning and teaching tools in classrooms and elsewhere. This paper reports case studies based on our deployment of 20 web-based virtual labs with more than 170+ online experiments in Biotechnology and Biomedical engineering discipline with content for undergraduate and postgraduate education. Via hands-on workshops and direct feedback using questionnaires, we studied the role of remote lab experiments as learning and teaching tools. Although less reliable than direct feedback, we also included online feedback to perceive blended and remote learning styles among various users. Student and teacher user groups suggested significant usage adaptability of experimental process and indicated usage of remote labs as supplementary tools for complementing laboratory education. Usage analysis implicated the role of online labs as interactive textbooks augmenting student interaction and positive correlates to learning. More »»
2016 Journal Article V. Özdemir and Hekim, N., “Innovation Management? Orienting Sepsis R&D and Technology Transfer Towards Stratified Medicine”, EBioMedicine, 2016.
2016 Journal Article S. Kalyanavenkataraman, Nanjan, P., Banerji, A., Nair, B. G., and Kumar, G. B., “Discovery of arjunolic acid as a novel non-zinc binding carbonic anhydrase II inhibitor”, Bioorganic Chemistry, vol. 66, pp. 72–79, 2016.[Abstract]

Elevated levels of carbonic anhydrase II (CA II) have been shown to be associated with cardiac hypertrophy and heart failure. Although arjunolic acid (AA) has a diverse range of therapeutic applications including cardio-protection, there have been no reports on the effect of AA on CA II. The present study describes for the first time, the novel zinc independent inhibition of CA II by AA. The molecular docking studies of AA indicated that the hydroxyl group at C2 of the A-ring, which hydrogen bonds with the catalytic site residues (His64, Asn62 and Asn67), along with the gem-dimethyl group at C20 of the E-ring, greatly influences the inhibitory activity, independent of the catalytic zinc, unlike the inhibition observed with most CA II inhibitors. Among the triterpenoids tested viz. arjunolic acid, arjunic acid, asiatic acid, oleanolic acid and ursolic acid, AA was the most potent in inhibiting CA II in vitro with an IC50 of 9 μM. It was interesting to note, that in spite of exhibiting very little differences in their structures, these triterpenoids exhibited vast differences in their inhibitory activities, with IC50 values ranging from 9 μM to as high as 333 μM. Furthermore, AA also inhibited the cytosolic activity of CA in H9c2 cardiomyocytes, as reflected by the decrease in acidification of the intracellular pH (pHi). The decreased acidification reduced the intracellular calcium levels, which further prevented the mitochondrial membrane depolarization. Thus, these studies provide a better understanding for establishing the novel molecular mechanism involved in CA II inhibition by the non-zinc binding inhibitor AA. More »»
2016 Journal Article G. Salini, Madhusoodhanan, A., Joseph, A., Mohan, A., Navya, R. K., and Nair, V. V., “Glutaminase free L-asparaginase producing endophytes from mangroves”, Asian Journal of Pharmaceutical and Clinical Research, vol. 9, pp. 360-362, 2016.[Abstract]

Objective: To screen endophytes isolated from mangroves for their potential to produce glutaminase free L-asparaginase. Methods: Endophytes were isolated from leaves and stems of three mangrove plants using surface sterilization technique followed by inoculation of the plant parts in nutrient media. Bacterial and fungal endophytes isolated were tested for production of glutaminase free L-asparaginase by inoculating them in modified M9 and modified czapek dox media, respectively, supplemented with asparagine/glutamine. L-asparaginase activity in glutaminase free L-asparaginase producers was measured by Nesslerization method. Results: Six bacterial endophytes and one fungal endophyte were found to produce glutaminase free L-asparaginase. The highest L-asparaginase activity was shown by bacterial endophytes of the mangrove Sonneratia caseolaris. Conclusion: Endophytes isolated in the present study hold the potential to produce glutaminase free L-asparaginase, and they need to be considered further in the search of L-asparaginase with high therapeutic index. © 2016, Asian Journal of Pharmaceutical and Clinical Research. All rights reserved.

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2016 Journal Article D. Nair, Vanuopadath, M., Bipin G. Nair Dr., Gopalakrishnapai, J., and S, S., “Identification and characterization of a library of surfactins and fengycins from a marine endophytic Bacillus sp.”, Journal of Basic Microbiology, 2016.[Abstract]

An endophytic bacterial strain from a marine green alga, Ulva lactuca, was isolated and identified by 16S rRNA gene sequencing method. The bacterial isolate was found to secrete two major families of cyclic depsilipopeptides, surfactins, and fengycins. Sequencing of the isolated lipopeptides was carried out using the MS(n) data obtained from an electrospray ionization (ESI) ion trap mass spectrometer coupled to an HPLC system. The assigned sequences were confirmed by a chemical derivatization approach involving esterification followed by mass spectrometric analysis. Distinction of leucine residues from isoleucine was established through a combined electron transfer dissociation-collision-induced dissociation (ETD-CID) method. The fengycins described in this study were found to cause significant delay of growth of two plants, Vigna radiata (mung bean) and Oryza sativa (rice). To the best of our knowledge, this is the first study describing identification and characterization of cyclic peptides from an endophytic Bacillus sp. isolated from marine algae.

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2016 Journal Article K. Kab Datta, Patil, A. Hab, Patel, Kac, Dey, Gad, Madugundu, A. Kae, Renuse, Sac, Kaviyil, J. Ef, Sekhar, Rae, Arunima, Ab, Daswani, Bg, Kaur, Ih, Mohanty, Ji, Sinha, Rj, Jaiswal, Sb, Sivapriya, Sk, Sonnathi, Yl, Chattoo, B. Bm, Gowda, Hab n, Ravikumar, Rf, and Prasad, T. S. Kan o, “Proteogenomics of Candida tropicalis - An Opportunistic Pathogen with Importance for Global Health”, OMICS A Journal of Integrative Biology, vol. 20, pp. 239-247, 2016.[Abstract]

The frequency of Candida infections is currently rising, and thus adversely impacting global health. The situation is exacerbated by azole resistance developed by fungal pathogens. Candida tropicalis is an opportunistic pathogen that causes candidiasis, for example, in immune-compromised individuals, cancer patients, and those who undergo organ transplantation. It is a member of the non-albicans group of Candida that are known to be azole-resistant, and is frequently seen in individuals being treated for cancers, HIV-infection, and those who underwent bone marrow transplantation. Although the genome of C. tropicalis was sequenced in 2009, the genome annotation has not been supported by experimental validation. In the present study, we have carried out proteomics profiling of C. tropicalis using high-resolution Fourier transform mass spectrometry. We identified 2743 proteins, thus mapping nearly 44% of the computationally predicted protein-coding genes with peptide level evidence. In addition to identifying 2591 proteins in the cell lysate of this yeast, we also analyzed the proteome of the conditioned media of C. tropicalis culture and identified several unique secreted proteins among a total of 780 proteins. By subjecting the mass spectrometry data derived from cell lysate and conditioned media to proteogenomic analysis, we identified 86 novel genes, 12 novel exons, and corrected 49 computationally-predicted gene models. To our knowledge, this is the first high-throughput proteomics study of C. tropicalis validating predicted protein coding genes and refining the current genome annotation. The findings may prove useful in future global health efforts to fight against Candida infections. © Copyright 2016, Mary Ann Liebert, Inc.

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2016 Journal Article S. Va Nair, Baranwal, Ga, Chatterjee, Ma, Sachu, Ac, V.A. Kumar, Bose, C., Banerji, A., and R.a Biswas, “Antimicrobial activity of plumbagin, a naturally occurring naphthoquinone from Plumbago rosea, against Staphylococcus aureus and Candida albicans”, International Journal of Medical Microbiology, vol. 306, pp. 237-248, 2016.[Abstract]

Candida albicans and Staphylococcus aureus are opportunistic pathogens. Despite causing a number of independent infections, both pathogens can co-infect to cause urinary tract infections, skin infections, biofilm associated infections, sepsis and pneumonia. Infections of these two pathogens especially their biofilm associated infections are often difficult to treat using currently available anti-bacterial and anti-fungal agents. In order to identify a common anti-microbial agent which could confer a broad range of protection against their infections, we screened several phytochemicals and identified plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), a phytochemical from Plumbago species as a potent antimicrobial agent against S. aureus and C. albicans, with a minimum inhibitory concentration of 5 μg/ml. Antimicrobial activity of plumbagin was validated using an ex-vivo porcine skin model. For better understanding of the antimicrobial activity of plumbagin, a Drosophila melanogaster infection model was used, where D. melanogaster was infected using S. aureus and C. albicans, or with both organisms. The fly's survival rate was dramatically increased when infected flies were treated using plumbagin. Further, plumbagin was effective in preventing and dispersing catheter associated biofilms formed by these pathogens. The overall results of this work provides evidence that plumbagin, possesses an excellent antimicrobial activity which should be explored further for the treatment of S. aureus and C. albicans infections. © 2016 Elsevier GmbH.

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2016 Journal Article A. Radhakrishnan, Nanjappa, V., Raja, R., Sathe, G., Chavan, S., Nirujogi, R. Sekhar, Patil, A. H., Solanki, H., Renuse, S., Sahasrabuddhe, N. A., Mathur, P. P., Prasad, T. S. Keshava, Kumar, P., Califano, J. A., Sidransky, D., Pandey, A., Gowda, H., and Chatterjee, A., “Dysregulation of splicing proteins in head and neck squamous cell carcinoma.”, Cancer Biol Ther, vol. 17, no. 2, pp. 219-29, 2016.[Abstract]

<p>Signaling plays an important role in regulating all cellular pathways. Altered signaling is one of the hallmarks of cancers. Phosphoproteomics enables interrogation of kinase mediated signaling pathways in biological systems. In cancers, this approach can be utilized to identify aberrantly activated pathways that potentially drive proliferation and tumorigenesis. To identify signaling alterations in head and neck squamous cell carcinoma (HNSCC), we carried out proteomic and phosphoproteomic analysis of HNSCC cell lines using a combination of tandem mass tag (TMT) labeling approach and titanium dioxide-based enrichment. We identified 4,920 phosphosites corresponding to 2,212 proteins in six HNSCC cell lines compared to a normal oral cell line. Our data indicated significant enrichment of proteins associated with splicing. We observed hyperphosphorylation of SRSF protein kinase 2 (SRPK2) and its downstream substrates in HNSCC cell lines. SRPK2 is a splicing kinase, known to phosphorylate serine/arginine (SR) rich domain proteins and regulate splicing process in eukaryotes. Although genome-wide studies have reported the contribution of alternative splicing events of several genes in the progression of cancer, the involvement of splicing kinases in HNSCC is not known. In this study, we studied the role of SRPK2 in HNSCC. Inhibition of SRPK2 resulted in significant decrease in colony forming and invasive ability in a panel of HNSCC cell lines. Our results indicate that phosphorylation of SRPK2 plays a crucial role in the regulation of splicing process in HNSCC and that splicing kinases can be developed as a new class of therapeutic target in HNSCC.</p>

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2016 Journal Article S. Muzaffar, Bose, C., Banerji, A., Nair, B. G., and Chattoo, B. B., “Anacardic acid induces apoptosis-like cell death in the rice blast fungus Magnaporthe oryzae.”, Appl Microbiol Biotechnol, vol. 100, no. 1, pp. 323-35, 2016.[Abstract]

<p>Anacardic acid (6-pentadecylsalicylic acid), extracted from cashew nut shell liquid, is a natural phenolic lipid well known for its strong antibacterial, antioxidant, and anticancer activities. Its effect has been well studied in bacterial and mammalian systems but remains largely unexplored in fungi. The present study identifies antifungal, cytotoxic, and antioxidant activities of anacardic acid in the rice blast fungus Magnaporthe oryzae. It was found that anacardic acid causes inhibition of conidial germination and mycelial growth in this ascomycetous fungus. Phosphatidylserine externalization, chromatin condensation, DNA degradation, and loss of mitochondrial membrane potential suggest that growth inhibition of fungus is mainly caused by apoptosis-like cell death. Broad-spectrum caspase inhibitor Z-VAD-FMK treatment indicated that anacardic acid induces caspase-independent apoptosis in M. oryzae. Expression of a predicted ortholog of apoptosis-inducing factor (AIF) was upregulated during the process of apoptosis, suggesting the possibility of mitochondria dependent apoptosis via activation of apoptosis-inducing factor. Anacardic acid treatment leads to decrease in reactive oxygen species rather than increase in reactive oxygen species (ROS) accumulation normally observed during apoptosis, confirming the antioxidant properties of anacardic acid as suggested by earlier reports. Our study also shows that anacardic acid renders the fungus highly sensitive to DNA damaging agents like ethyl methanesulfonate (EMS). Treatment of rice leaves with anacardic acid prevents M. oryzae from infecting the plant without affecting the leaf, suggesting that anacardic acid can be an effective antifungal agent.</p>

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2016 Journal Article H. Parasuram, Bipin G. Nair Dr., D‘Angelo, E., Hines, M., Naldi, G., and Dr. Diwakar, S., “Computational Modeling of Single Neuron Extracellular Electric Potentials and Network Local Field Potentials using LFPsim”, Frontiers in Computational Neuroscience, vol. 10, 2016.[Abstract]

Local Field Potentials (LFPs) are population signals generated by complex spatiotemporal interaction of current sources and dipoles. Mathematical computations of LFPs allow the study of circuit functions and dysfunctions via simulations. This paper introduces LFPsim, a NEURON-based tool for computing population LFP activity and single neuron extracellular potentials. LFPsim was developed to be used on existing cable compartmental neuron and network models. Point source, line source, and RC based filter approximations can be used to compute extracellular activity. As a demonstration of efficient implementation, we showcase LFPs from mathematical models of electrotonically compact cerebellum granule neurons and morphologically complex neurons of the neocortical column. LFPsim reproduced neocortical LFP at 8, 32, and 56 Hz via current injection, in vitro post-synaptic N2a, N2b waves and in vivo T-C waves in cerebellum granular layer. LFPsim also includes a simulation of multi-electrode array of LFPs in network populations to aid computational inference between biophysical activity in neural networks and corresponding multi-unit activity resulting in extracellular and evoked LFP signals.

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2016 Journal Article E. Kolker, Ozdemir, V., and Kolker, E., “How Healthcare Can Refocus on Its Super-Customers (Patients, n =1) and Customers (Doctors and Nurses) by Leveraging Lessons from Amazon, Uber, and Watson.”, OMICS, vol. 20, no. 6, pp. 329-33, 2016.[Abstract]

<p>Healthcare is transforming with data-intensive omics technologies and Big Data. The "revolution" has already happened in technology, but the bottlenecks have shifted to the social domain: Who can be empowered by Big Data? Who are the users and customers? In this review and innovation field analysis, we introduce the idea of a "super-customer" versus "customer" and relate both to 21st century healthcare. A "super-customer" in healthcare is the patient, sample size of n = 1, while "customers" are the providers of healthcare (e.g., doctors and nurses). The super-customers have been patients, enabled by unprecedented social practices, such as the ability to track one's physical activities, personal genomics, patient advocacy for greater autonomy, and self-governance, to name but a few. In contrast, the originally intended customers-providers, doctors, and nurses-have relatively lagged behind. With patients as super-customers, there are valuable lessons to be learned from industry examples, such as Amazon and Uber. To offer superior quality service, healthcare organizations have to refocus on the needs, pains, and aspirations of their super-customers by enabling the customers. We propose a strategic solution to this end: the PPT-DAM (People-Process-Technology empowered by Data, Analytics, and Metrics) approach. When applied together with the classic Experiment-Execute-Evaluate iterative methodology, we suggest PPT-DAM is an extremely powerful approach to deliver quality health services to super-customers and customers. As an example, we describe the PPT-DAM implementation by the Benchmarking Improvement Program at the Seattle Children's Hospital. Finally, we forecast that cognitive systems in general and IBM Watson in particular, if properly implemented, can bring transformative and sustainable capabilities in healthcare far beyond the current ones.</p>

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2016 Journal Article G. Sathe, Pinto, S. M., Syed, N., Nanjappa, V., Solanki, H. S., Renuse, S., Chavan, S., Khan, A. Ahmad, Patil, A. H., Nirujogi, R. Sekhar, Nair, B., Mathur, P. Prakash, Prasad, T. S. Keshava, Gowda, H., and Chatterjee, A., “Phosphotyrosine profiling of curcumin-induced signaling.”, Clin Proteomics, vol. 13, p. 13, 2016.[Abstract]

<p><b>BACKGROUND: </b>Curcumin, derived from the rhizome Curcuma longa, is a natural anti-cancer agent and has been shown to inhibit proliferation and survival of tumor cells. Although the anti-cancer effects of curcumin are well established, detailed understanding of the signaling pathways altered by curcumin is still lacking. In this study, we carried out SILAC-based quantitative proteomic analysis of a HNSCC cell line (CAL 27) to investigate tyrosine signaling in response to curcumin.</p><p><b>RESULTS: </b>Using high resolution Orbitrap Fusion Tribrid Fourier transform mass spectrometer, we identified 627 phosphotyrosine sites mapping to 359 proteins. We observed alterations in the level of phosphorylation of 304 sites corresponding to 197 proteins upon curcumin treatment. We report here for the first time, curcumin-induced alterations in the phosphorylation of several kinases including TNK2, FRK, AXL, MAPK12 and phosphatases such as PTPN6, PTPRK, and INPPL1 among others. Pathway analysis revealed that the proteins differentially phosphorylated in response to curcumin are known to be involved in focal adhesion kinase signaling and actin cytoskeleton reorganization.</p><p><b>CONCLUSIONS: </b>The study indicates that curcumin may regulate cellular processes such as proliferation and migration through perturbation of the focal adhesion kinase pathway. This is the first quantitative phosphoproteomics-based study demonstrating the signaling events that are altered in response to curcumin. Considering the importance of curcumin as an anti-cancer agent, this study will significantly improve the current knowledge of curcumin-mediated signaling in cancer.</p>

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2016 Journal Article M. Bhattacharjee, Balakrishnan, L., Renuse, S., Advani, J., Goel, R., Sathe, G., Prasad, T. S. Keshava, Nair, B., Jois, R., Shankar, S., and Pandey, A., “Synovial fluid proteome in rheumatoid arthritis.”, Clin Proteomics, vol. 13, p. 12, 2016.[Abstract]

<p><b>BACKGROUND: </b>Rheumatoid arthritis (RA) is a chronic autoinflammatory disorder that affects small joints. Despite intense efforts, there are currently no definitive markers for early diagnosis of RA and for monitoring the progression of this disease, though some of the markers like anti CCP antibodies and anti vimentin antibodies are promising. We sought to catalogue the proteins present in the synovial fluid of patients with RA. It was done with the aim of identifying newer biomarkers, if any, that might prove promising in future.</p><p><b>METHODS: </b>To enrich the low abundance proteins, we undertook two approaches-multiple affinity removal system (MARS14) to deplete some of the most abundant proteins and lectin affinity chromatography for enrichment of glycoproteins. The peptides were analyzed by LC-MS/MS on a high resolution Fourier transform mass spectrometer.</p><p><b>RESULTS: </b>This effort was the first total profiling of the synovial fluid proteome in RA that led to identification of 956 proteins. From the list, we identified a number of functionally significant proteins including vascular cell adhesion molecule-1, S100 proteins, AXL receptor protein tyrosine kinase, macrophage colony stimulating factor (M-CSF), programmed cell death ligand 2 (PDCD1LG2), TNF receptor 2, (TNFRSF1B) and many novel proteins including hyaluronan-binding protein 2, semaphorin 4A (SEMA4D) and osteoclast stimulating factor 1. Overall, our findings illustrate the complex and dynamic nature of RA in which multiple pathways seems to be participating actively.</p><p><b>CONCLUSIONS: </b>The use of high resolution mass spectrometry thus, enabled identification of proteins which might be critical to the progression of RA.</p>

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2016 Journal Article A. Hollands, Corriden, R., Gysler, G., Dahesh, S., Olson, J., Ali, S. Raza, Kunkel, M. T., Lin, A. E., Forli, S., Newton, A. C., Kumar, G. B., Nair, B. G., J Perry, J. P., and Nizet, V., “Natural Product Anacardic Acid from Cashew Nut Shells Stimulates Neutrophil Extracellular Trap Production and Bactericidal Activity.”, J Biol Chem, vol. 291, no. 27, pp. 13964-73, 2016.[Abstract]

<p>Emerging antibiotic resistance among pathogenic bacteria is an issue of great clinical importance, and new approaches to therapy are urgently needed. Anacardic acid, the primary active component of cashew nut shell extract, is a natural product used in the treatment of a variety of medical conditions, including infectious abscesses. Here, we investigate the effects of this natural product on the function of human neutrophils. We find that anacardic acid stimulates the production of reactive oxygen species and neutrophil extracellular traps, two mechanisms utilized by neutrophils to kill invading bacteria. Molecular modeling and pharmacological inhibitor studies suggest anacardic acid stimulation of neutrophils occurs in a PI3K-dependent manner through activation of surface-expressed G protein-coupled sphingosine-1-phosphate receptors. Neutrophil extracellular traps produced in response to anacardic acid are bactericidal and complement select direct antimicrobial activities of the compound.</p>

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2016 Journal Article B. Jasim, Sreelakshmi, K. S., Mathew, J., and Radhakrishnan, E. K., “Surfactin, Iturin, and Fengycin Biosynthesis by Endophytic Bacillus sp. from Bacopa monnieri.”, Microb Ecol, vol. 72, no. 1, pp. 106-19, 2016.[Abstract]

<p>Endophytic microorganisms which are ubiquitously present in plants may colonize intracellularly or intercellularly without causing any diseases. By living within the unique chemical environment of a host plant, they produce a vast array of compounds with a wide range of biological activities. Because of this, natural products of endophytic origin have been exploited for antimicrobial, antiviral, anticancer, and antioxidant properties. Also, they can be considered to function as an efficient microbial barrier to protect plants from various pathogens. In the present study, endophytic bacterium BmB 9 with antifungal and antibacterial activity isolated from the stem tissue of Bacopa monnieri was studied for the molecular and chemical basis of its activity. PCR-based genome mining for various biosynthetic gene clusters proved the presence of surfactin, iturin, and type I polyketide synthase (PKS) genes in the isolate. The LC-MS/MS based analysis of the extract further confirmed the production of surfactin derivatives (M + H(+)-1008.6602, 1022.6755), iturin (M + H(+)-1043.5697), and fengycin (M + H(+)-1491.8195, 1477.8055) by the selected bacterial isolate. The 16S rDNA sequence similarity based analysis identified the isolate BmB 9 as Bacillus sp. with 100 % identity to Bacillus sp. LCF1 (KP257289).</p>

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2016 Journal Article K. Y. Yasoda, Bobba, K. N., Nedungadi, D., Dutta, D., Kumar, M. S., Kothurkar, Nd, Mishra, N., and Bhuniya, S., “GSH-responsive biotinylated poly(vinyl alcohol)-grafted GO as a nanocarrier for targeted delivery of camptothecin”, RSC Advances, vol. 6, pp. 62385-62389, 2016.[Abstract]

A water-soluble and biocompatible polymer, i.e. biotinylated poly(vinyl alcohol)-grafted graphene oxide (GO), was used as a nanocarrier for targeted delivery of anticancer drug camptothecin (CPT). The extent of CPT release in the presence of glutathione (GSH) from GO-biotinPVA-CPT was monitored by the increase in the fluorescence intensity, at λmax = 450 nm. The cell-specific (HeLa) antiproliferative activity of GO-biotinPVA-CPT makes it suitable to be used for targeted delivery of chemotherapeutics to cancerous cells. More »»
2016 Journal Article A. Madhavan, Nanjan, P., K. Shetty, S., and Shanmugham, S., “A rapid and selective method for the quantification of naringenin in order to monitor naringinase activity”, International Journal of ChemTech Research, vol. 9, pp. 333-338, 2016.[Abstract]

Sodium acetate (NaOAc) can selectively ionize 7-OH of naringenin generating a bathochromic shift of 41nm in its UV absorbance. This principle is used in the described spectrophotometric method that can detect naringenin amidst naringin and prunin present in the incubation mixture of naringinase. The method could be adopted for real sample analysis as it remains unaffected by the presence of phenolics such as ascorbic acid, gallic acid, citric acid and cinnamic acid. © 2016, Sphinx Knowledge House. More »»
2015 Journal Article N. Syed, Chavan, S., Sahasrabuddhe, N. A., Renuse, S., Sathe, G., Nanjappa, V., Radhakrishnan, A., Raja, R., Pinto, S. M., Srinivasan, A., Prasad, T. S. K., Srikumar, K., Gowda, H., Santosh, V., Sidransky, D., Califano, J. A., Pandey, A., and Chatterjee, A., “Silencing of high-mobility group box 2 (HMGB2) modulates cisplatin and 5-fluorouracil sensitivity in head and neck squamous cell carcinoma”, Proteomics, vol. 15, pp. 383-393, 2015.[Abstract]

Dysregulation of protein expression is associated with most diseases including cancer. MS-based proteomic analysis is widely employed as a tool to study protein dysregulation in cancers. Proteins that are differentially expressed in head and neck squamous cell carcinoma (HNSCC) cell lines compared to the normal oral cell line could serve as biomarkers for patient stratification. To understand the proteomic complexity in HNSCC, we carried out iTRAQ-based MS analysis on a panel of HNSCC cell lines in addition to a normal oral keratinocyte cell line. LC-MS/MS analysis of total proteome of the HNSCC cell lines led to the identification of 3263 proteins, of which 185 proteins were overexpressed and 190 proteins were downregulated more than twofold in at least two of the three HNSCC cell lines studied. Among the overexpressed proteins, 23 proteins were related to DNA replication and repair. These included high-mobility group box 2 (HMGB2) protein, which was overexpressed in all three HNSCC lines studied. Overexpression of HMGB2 has been reported in various cancers, yet its role in HNSCC remains unclear. Immunohistochemical labeling of HMGB2 in a panel of HNSCC tumors using tissue microarrays revealed overexpression in 77% (54 of 70) of tumors. The HMGB proteins are known to bind to DNA structure resulting from cisplatin-DNA adducts and affect the chemosensitivity of cells. We observed that siRNA-mediated silencing of HMGB2 increased the sensitivity of the HNSCC cell lines to cisplatin and 5-FU. We hypothesize that targeting HMGB2 could enhance the efficacy of existing chemotherapeutic regimens for treatment of HNSCC. All MS data have been deposited in the ProteomeXchange with identifier PXD000737 ( More »»
2015 Journal Article A. R. Pai, “Green Synthesis and Characterizations of Silver Nanoparticles Using Fresh Leaf Extract Of Morinda Citrifolia And Its Anti-Microbial Activity Studies”, International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 3, pp. 459-461, 2015.[Abstract]

Objective: To develop a rapid method of synthesis of silver nanoparticles (Ag NPs) using the fresh aqueous leaf extract of Morinda Citrifolia from 0.1 M AgNO3 solution, to characterize the resulting Ag NPs and also compare their antimicrobial activity with those of standard drugs against human pathogenic bacteria. Methods: 25 ml of the aqueous extract was added to 25 ml of 0.1 M aqueous AgNO3 at room temperature. The mixture was stirred continuously for 5-10 minutes. The reduction was completed with the appearance of brownish-black colored dispersion. The resulting nanoparticles were characterized using UV-Vis absorption spectra and Particle size analysis (DLS method). Further the Antimicrobial activity was compared with the drugs against S. aureus and P. aureginosa strains using the disk diffusion method. Results: The formation of Silver nanoparticles was confirmed with the help of UV-Vis absorption spectra at ≈ 425 nm and particle size as approximately 100 nm using Particle size analysis (DLS method). The anti-microbial activity of the Ag NPs so synthesized was studied against human pathogens in wound infections such as S. aureus and P. aureginosa strains. The inhibitory activity for Ag NPs was compared with those of known drugs such as tetracycline, Ceftazidime and Amikacin at 30 mcg. The inhibitory activity of the Synthesized Ag NPs was found pronounced against P. aureginosa strains. Conclusion: A rapid method of synthesizing Ag NPs has been developed by using the fresh leaf extract of Morinda Citrifolia and it was found that the extract is a potential reducing agent to produce stable Ag NPs. The research provides a new input to the development of anti-microbial agent.

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2015 Journal Article Yab c Subbannayya, Syed, Nad, Barbhuiya, M. Aef, Raja, Ra, Marimuthu, Aa, Sahasrabuddhe, Na, Pinto, S. Mag, Manda, S. Sah, Renuse, Sai, Manju, H. Caj, Zameer, M. A. Lj, Sharma, Jag, Brait, Mk, Srikumar, Kd, Roa, J. Cl, Kumar, M. Vm, Kumar, K. V. Vm, Prasad, T. S. Kag h i, Ramaswamy, Gc, Kumar, R. Vj, Pandey, Ano p q, Gowda, Ha, and Chatterjee, Aa, “Calcium calmodulin dependent kinase kinase 2 - A novel therapeutic target for gastric adenocarcinoma”, Cancer Biology and Therapy, vol. 16, pp. 336-345, 2015.[Abstract]

Gastric cancer is one of the most common gastrointestinal malignancies and is associated with poor prognosis. Exploring alterations in the proteomic landscape of gastric cancer is likely to provide potential biomarkers for early detection and molecules for targeted therapeutic intervention. Using iTRAQ-based quantitative proteomic analysis, we identified 22 proteins that were overexpressed and 17 proteins that were downregulated in gastric tumor tissues as compared to the adjacent normal tissue. Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) was found to be 7-fold overexpressed in gastric tumor tissues. Immunohistochemical labeling of tumor tissue microarrays for validation of CAMKK2 overexpression revealed that it was indeed overexpressed in 94% (92 of 98) of gastric cancer cases. Silencing of CAMKK2 using siRNA significantly reduced cell proliferation, colony formation and invasion of gastric cancer cells. Our results demonstrate that CAMKK2 signals in gastric cancer through AMPK activation and suggest that CAMKK2 could be a novel therapeutic target in gastric cancer. © 2015 Taylor & Francis Group, LLC.

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2015 Journal Article Ka Dhara, Ramachandran, Ta, Bipin G. Nair Dr., and T. G. Satheesh Babu, “Single step synthesis of Au-CuO nanoparticles decorated reduced graphene oxide for high performance disposable nonenzymatic glucose sensor”, Journal of Electroanalytical Chemistry, vol. 743, pp. 1-9, 2015.[Abstract]

A nonenzymatic electrochemical glucose sensor was fabricated using gold-copper oxide nanoparticles decorated reduced graphene oxide (Au-CuO/rGO). A novel one step chemical process was employed for the synthesis of nanocomposite. Morphology and crystal planes of the nanocomposite were characterized using high resolution scanning electron microscopy (HRSEM) and X-ray diffraction (XRD) respectively. The Au-CuO/rGO nanocomposite was dispersed in N,N-dimethyl formamide (DMF) and drop-casted on the working area of the indigenously fabricated screen printed electrode (SPE). The sensor showed good electrocatalytic activity in alkaline medium for the direct electrooxidation of glucose with linear detection range of 1 μM to 12 mM and a lower detection limit of 0.1 μM. The sensor exhibited an excellent sensitivity 2356 μA mM- 1 cm- 2. Sensor was used for the determination of serum glucose concentration and the results obtained were compared with commercially available test strips. © 2015 Elsevier B.V. All rights reserved.

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2015 Journal Article Ka Erciyas, Üstün, Kb, Dove, E. Sc, Birch, Kd, Steuten, L. M. Gef, Zeidán-Chuliá, Fgh, Gürsoy, Mh, Könönen, Eh, Kolker, Eij k l, Özdemir, Vim n, and Gürsoy, U. Kh, “Personalized Dentistry Meets OMICS and "One Health": From Cinderella of Healthcare to Mainstream?”, OMICS A Journal of Integrative Biology, vol. 19, pp. 145-146, 2015.
2015 Journal Article P. V. Suneesh, Sara, V. Vidhu, Ramachandran, Ta, Bipin G. Nair Dr., and T. G. Satheesh Babu, “Co-Cu alloy nanoparticles decorated TiO2 nanotube arrays for highly sensitive and selective nonenzymatic sensing of glucose”, Sensors and Actuators, B: Chemical, vol. 215, pp. 337-344, 2015.[Abstract]

A nonenzymatic glucose sensor was fabricated by electrodepositing cobalt rich cobalt-copper alloy nanoparticles (Co-CuNPs) on vertically aligned TiO2 nanotube (TDNT) arrays. For this, TDNT arrays with tube diameter of 60 nm were synthesized by electrochemical anodization. The composition of the electrodeposited alloy was optimized based on the electrocatalytic activity towards glucose oxidation. This is achieved by controlling the concentration of electrolyte and time of deposition. Chemical composition of the optimized Co-Cu alloy nanoparticles is determined to be Cu0.15Co2.84O4 with fcc crystalline structure. The sensor showed two linear range of detection with high sensitivity of 4651.0 μA mM-1 cm-2 up to 5 mM and 2581.70 μA mM-1 cm-2 from 5 mM to 12 mM with a lower detection limit of 0.6 μM (S/N = 3). The sensor is highly selective to glucose in the presence of various exogeneous and endogeneous interfering species and other sugars. The response of the sensor towards blood serum was in good agreement with that of commercially available glucose sensors. © 2015 Elsevier B.V.

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2015 Journal Article P. Nanjan, Nambiar, J., Bipin G. Nair Dr., and Banerji, A., “Synthesis and Discovery of (I-3,II-3)-Biacacetin as a Novel Non-zinc Binding Inhibitor of MMP-2 and MMP-9”, Bioorganic & Medicinal Chemistry, vol. 23, pp. 3781 - 3787, 2015.[Abstract]

Abstract Eleven biflavones (7a–b and 9a–i) were synthesised by a simple and efficient protocol and screened for MMP-2 and MMP-9 inhibitory activities. Amongst them, a natural product-like analog, (I-3,II-3)-biacacetin (9h) was found to be the most potent inhibitor. Molecular docking studies suggest that unlike most of the known inhibitors, 9h inhibits MMP-2 and MMP-9 through non-zinc binding interactions.

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2015 Journal Article A. Banerjee, Adolph, R. S., Gopalakrishnapai, J., Kleinboelting, S., Emmerich, C., Steegborn, C., and Visweswariah, S. S., “A Universal Stress Protein (USP) in Mycobacteria binds cAMP”, Journal of Biological Chemistry, vol. 290, pp. 12731–12743, 2015.[Abstract]

Mycobacteria are endowed with rich and diverse machinery for the synthesis, utilization, and degradation of cAMP. The actions of cyclic nucleotides are generally mediated by binding of cAMP to conserved and well characterized cyclic nucleotide binding domains or structurally distinct cGMP-specific and -regulated cyclic nucleotide phosphodiesterase, adenylyl cyclase, and E. coli transcription factor FhlA (GAF) domain-containing proteins. Proteins with cyclic nucleotide binding and GAF domains can be identified in the genome of mycobacterial species, and some of them have been characterized. Here, we show that a significant fraction of intracellular cAMP is bound to protein in mycobacterial species, and by using affinity chromatography techniques, we identify specific universal stress proteins (USP) as abundantly expressed cAMP-binding proteins in slow growing as well as fast growing mycobacteria. We have characterized the biochemical and thermodynamic parameters for binding of cAMP, and we show that these USPs bind cAMP with a higher affinity than ATP, an established ligand for other USPs. We determined the structure of the USP MSMEG_3811 bound to cAMP, and we confirmed through structure-guided mutagenesis, the residues important for cAMP binding. This family of USPs is conserved in all mycobacteria, and we suggest that they serve as “sinks” for cAMP, making this second messenger available for downstream effectors as and when ATP levels are altered in the cell.

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2015 Conference Proceedings S. Subhash, J Anupama, N., Sanalkumar, A., Krishna, D. L., Das, G. S., Ajith, S., Kumar, S. S., and Bipin G. Nair Dr., “Inhibitory effect of plant extracts on siderophores production by Klebsiella pneumoniae”, Proceedings of 27 Kerala Science Congress. p. 34, 2015.
2015 Journal Article H. Sasidharakurup, Radhamani, R., Kumar, D., Dr. Diwakar, S., Nizar, N., Nair, B., and Achuthan, K., “Using Virtual Laboratories as Interactive Textbooks: Studies on Blended Learning in Biotechnology Classrooms”, EAI Endorsed Transactions on e-Learning, vol. 15, no. 6, p. e4, 2015.[Abstract]

Virtual laboratories, an ICT-based initiative, is a new venture that is becoming more prevalent in universities for improving classroom education. With geographically remote and economically constrained institutes in India as the focus, we developed web-based virtual labs for virtualizing the wet-lab techniques and experiments with the aid of graphics favoured animations, mathematical simulators and remote triggered experimentations. In this paper, we analysed perceived usefulness of Biotechnology virtual labs amongst student groups and its role in improving the student’s performance when introduced as a learning tool in a blended classroom scenario. A pedagogical survey, via workshops and online feedback, was carried out among 600 university-level students and 100 remote users of various Indian universities. Comparing learning groups on usage of blended learning approach against a control group (traditional classroom methods) and an experimental group (teacher-mediated virtual labs), our studies indicate augmented academic performance among students in blended environments. Findings also indicated usage of remotely-triggered labs aided enhancing interaction-based lab education enabling anytime-anywhere student participation scenarios.

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2015 Conference Paper H. Sasidharakurup, Kumar, D., Radhamani, R., Nizar, N., Nair, B., Achuthan, K., and Dr. Diwakar, S., “Role of ICT enabled Virtual Laboratories in Biotechnology Education: Case studies on blended and remote learning”, in Proceedings of 18th International Conference on Interactive Collaborative Learning, Florence, Italy, 2015.
2015 Conference Paper B. Nair, Sasidharakurup, H., Radhamani, R., Kumar, D., Nizar, N., Achuthan, K., and Dr. Diwakar, S., “Assessing Students and Teachers Experience on Simulation and Remote Biotechnology Virtual labs: A Case Study with a Light Microscopy Experiment”, in Proceedings of 2nd International Conference on e-Learning e-Education and Online Training (eLEOT 2015), Novedrate, Italy, 2015.
2015 Conference Paper A. Vijayan, Medini, C., Palolithazhe, A., Muralidharan, B., Bipin G. Nair Dr., and Dr. Diwakar, S., “Modeling Pattern Abstraction in Cerebellum and Estimation of Optimal Storage Capacity”, in Proceedings of the Fourth International Conference on Advances in Computing, Communications and Informatics (ICACCI-2015), Kochi, India, 2015.[Abstract]

Precise fine-tuning of motor movements has been known to be a vital function of cerebellum, which is critical for maintaining posture and balance. Purkinje cell (PC) plays a prominent role in this fine-tuning through association of inputs and output alongside learning through error correction. Several classical studies showed that PC follows perceptron like behavior, which can be used to develop cerebellum like neural circuits to address the association and learning. With respect to the input, the PC learns the motor movement through update of synaptic weights. In order to understand how cerebellar circuits associate spiking information during learning, we developed a spiking neural network using adaptive exponential integrate and fire neuron model (AdEx) based on cerebellar molecular layer perceptron-like architecture and estimated the maximal storage capacity at parallel fiber-PC synapse. In this study, we explored information storage in cerebellar microcircuits using this abstraction. Our simulations suggest that perceptron mimicking PC behavior was capable of learning the output through modification via finite precision algorithm. The study evaluates the pattern processing in cerebellar Purkinje neurons via a mathematical model estimating the storage capacity based on input patterns and indicates the role of sparse encoding of granular layer neurons in such circuits. © 2015 IEEE.

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2015 Conference Paper C. Medini, Vijayan, A., Zacharia, R. Maria, Rajagopal, L. Priya, Bipin G. Nair Dr., and Dr. Diwakar, S., “Spike Encoding for Pattern Recognition: Comparing Cerebellum Granular Layer Encoding and BSA algorithms”, in Proceedings of the Fourth International Conference on Advances in Computing, Communications and Informatics (ICACCI-2015), Kochi, India, 2015.[Abstract]

Spiking neural encoding models allow classification of real world tasks to suit for brain-machine interfaces in addition to serving as internal models. We developed a new spike encoding model inspired from cerebellum granular layer and tested different classification techniques like SVM, Naïve Bayes, MLP for training spiking neural networks to perform pattern recognition tasks on encoded datasets. As a precursor to spiking network-based pattern recognition, in this study, real world datasets were encoded into spike trains. The objective of this study was to encode information from datasets into spiking neuron patterns that were relevant for spiking neural networks and for conventional machine learning algorithms. In this initial study, we present a new approach similar to cerebellum granular layer encoding and compared it with BSA encoding techniques. We have also compared the efficiency of the encoded dataset with different datasets and with standard machine learning algorithms. © 2015 IEEE.

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2015 Conference Paper N. Melethadathil, Chellaiah, P., Bipin G. Nair Dr., and Dr. Diwakar, S., “Classification and Clustering for Neuroinformatics: Assessing the efficacy on reverse-mapped NeuroNLP data using standard ML techniques”, in Proceedings of the Fourth International Conference on Advances in Computing, Communications and Informatics (ICACCI-2015), Kochi, India, 2015.[Abstract]

NeuroinformaticsNatural Language Processing (NeuroNLP) relies on clustering and classification for information categorization of biologically relevant extraction targets and for interconnections to knowledge-related patterns in event and text mined datasets. The accuracy of machine learning algorithms depended on quality of text-mined data while efficacy relied on the context of the choice of techniques. Although developments of automated keyword extraction methods have made differences in the quality of data selection, the efficacy of the Natural Language Processing (NLP) methods using verified keywords remain a challenge. In this paper, we studied the role of text classification and document clustering algorithms on datasets, where features were obtained by mapping to manually verified MESH terms published by National Library of Medicine (NLM). In this study, NLP data classification involved comparing 8techniques and unsupervised learning was performed with 6 clustering algorithms. Most classification techniques except meta-based algorithms namely stacking and vote, allowed 90% or higher training accuracy. Test accuracy was high (=>95%) probably due to limited test dataset. Logistic Model Trees had 30-fold higher runtime compared to other classification algorithms including Naive Bayes, AdaBoost, Hoeffding Tree. Grouped error rate in clustering was 0-4%. Runtime-wise, clustering was faster than classification algorithms on MESH-mapped NLP data suggesting clustering methods as adequate towards Medline-related datasets and text-mining big data analytic systems. © 2015 IEEE.

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2015 Journal Article E. S. Dove, İ Barlas, Ö., Birch, K., Boehme, C., Borda-Rodriguez, A., Byne, W. M., Chaverneff, F., Coşkun, Y., Dahl, M. - L., Dereli, T., Dr. Diwakar, S., Elbeyli, L., Endrenyi, L., Eroğlu-Kesim, B., Ferguson, L. R., Güngör, K., Gürsoy, U., Hekim, N., Huzair, F., Kaushik, K., Kickbusch, I., Kıroğlu, O., Kolker, E., Könönen, E., Lin, B., Llerena, A., Malha, F., Bipin G. Nair Dr., Patrinos, G. P., Şardaş, S., Sert, Ö., Srivastava, S., Steuten, L. M. G., Toraman, C., Vayena, E., Wang, W., Warnich, L., and Özdemir, V., “An Appeal to the Global Health Community for a Tripartite Innovation: An “Essential Diagnostics List,”“Health in All Policies,” and “See-Through 21st Century Science and Ethics””, Omics: a journal of integrative biology, vol. 19, pp. 435–442, 2015.[Abstract]

Diagnostics spanning a wide range of new biotechnologies, including proteomics, metabolomics, and nanotechnology, are emerging as companion tests to innovative medicines. In this Opinion, we present the rationale for promulgating an “Essential Diagnostics List.” Additionally, we explain the ways in which adopting a vision for “Health in All Policies” could link essential diagnostics with robust and timely societal outcomes such as sustainable development, human rights, gender parity, and alleviation of poverty. We do so in three ways. First, we propose the need for a new, “see through” taxonomy for knowledge-based innovation as we transition from the material industries (e.g., textiles, plastic, cement, glass) dominant in the 20th century to the anticipated knowledge industry of the 21st century. If knowledge is the currency of the present century, then it is sensible to adopt an approach that thoroughly examines scientific knowledge, starting with the production aims, methods, quality, distribution, access, and the ends it purports to serve. Second, we explain that this knowledge trajectory focus on innovation is crucial and applicable across all sectors, including public, private, or public–private partnerships, as it underscores the fact that scientific knowledge is a co-product of technology, human values, and social systems. By making the value systems embedded in scientific design and knowledge co-production transparent, we all stand to benefit from sustainable and transparent science. Third, we appeal to the global health community to consider the necessary qualities of good governance for 21st century organizations that will embark on developing essential diagnostics. These have importance not only for science and knowledge-based innovation, but also for the ways in which we can build open, healthy, and peaceful civil societies today and for future generations.

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2015 Journal Article K. R. Murthy, Rajagopalan, P., Pinto, S. M., Advani, J., Murthy, P. R., Goel, R., Subbannayya, Y., Balakrishnan, L., Dash, M., Anil, A. K., Dey, G., Chatterjee, A., Gowda, H., Chakravarti, S., Shankar, S., Sahasrabuddhe, N. A., Bipin G. Nair Dr., Somani, B. Lal, Keshava, P. T. S., and Pandey, A., “Proteomics of Human Aqueous Humor”, Omics: a journal of integrative biology, vol. 19, pp. 283–293, 2015.[Abstract]

The aqueous humor is a colorless, transparent fluid that fills the anterior chamber of the eye. It plays an important role in maintaining the intraocular pressure and providing nourishment to the lens and cornea. The constitution of the aqueous humor is controlled by the blood–aqueous barrier. Though this ocular fluid has been extensively studied, its role in ocular physiology is still not completely understood. In this study, aqueous humor samples were collected from 250 patients undergoing cataract surgery, subjected to multiple fractionation strategies and analyzed on a Fourier transform LTQ-Orbitrap Velos mass spectrometer. In all, we identified 763 proteins, of which 386 have been identified for the first time in this study. Sorbitol dehydrogenase (SORD), filensin (BFSP1), and phakinin (BFSP2) are some of the proteins that have not been previously reported in the aqueous humor. Gene Ontology analysis revealed 35% of the identified proteins to be extracellular, with a majority of them involved in cell communication and signal transduction. This study comprehensively reports 386 novel proteins that have important potential as biomarker candidates for future research into personalized medicine and diagnostics aimed towards improving visual health.

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2015 Journal Article J. Nambiar, G., K., S.R., S., S.N., G., R.S., L., and Bipin G. Nair Dr., “A Novel2-Alkoxy-3, 5-Dihydroxypyridine Mediated Regulation of Gelatinases”, International Journal of Pharma and Bio Sciences, vol. 6, pp. 779-788, 2015.
2015 Conference Proceedings S. Dr. Diwakar, Chellaiah, P., Bipin G. Nair Dr., and Achuthan, K., “Theme Interception Sequence Learning: Deflecting Rubber-Hose Attacks Using Implicit Learning”, Proceedings of the 3rd International Conference on Frontiers of Intelligent Computing: Theory and Applications (FICTA) 2014, Advances in Intelligent Systems and Computing, vol. 1. Springer International Publishing, Switzerland, pp. 495-502, 2015.[Abstract]

Existing cryptographic systems use strong passwords but several techniques are vulnerable to rubber-hose attacks, wherein the user is forced to reveal the secret key. This paper specifies a defence technique against rubber-hose attacks by taking advantage of image sequence-based theme selection, dependent on a user’s personal construct and active implicit learning. In this paper, an attempt to allow the human brain to generate the password via a computer task of arranging themed images through which the user learns a password without any conscious knowledge of the learned pattern. Although used in authentication, users cannot be coerced into revealing the secret key since the user has no direct knowledge on the choice of the learned secret. We also show that theme interception sequence learning tool works significantly well with mixed user age groups and can be used as a secondary layer of security where human user authentication remains a priority.

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2015 Journal Article N. Mohammad, Singh, S. Vikram, Malvi, P., Chaube, B., Athavale, D., Vanuopadath, M., Nair, S. Sadasivan, Bipin G. Nair Dr., and Bhat, M. Kumar, “Strategy to enhance efficacy of doxorubicin in solid tumor cells by methyl-β-cyclodextrin: Involvement of p53 and Fas receptor ligand complex”, Scientific reports (Article number 11853), vol. 5, 2015.[Abstract]

Doxorubicin (DOX) is one of the preferred drugs for treating breast and liver cancers. However, its clinical application is limited due to severe side effects and the accompanying drug resistance. In this context, we investigated the effect on therapeutic efficacy of DOX by cholesterol depleting agent methyl-β-cyclodextrin (MCD), and explored the involvement of p53. MCD sensitizes MCF-7 and Hepa1-6 cells to DOX, Combination of MCD and marginal dose of DOX reduces the cell viability, and promoted apoptosis through induction of pro-apoptotic protein, Bax, activation of caspase-8 and caspase-7, down regulation of anti-apoptotic protein Bcl-2 and finally promoting PARP cleavage. Mechanistically, sensitization to DOX by MCD was due to the induction of FasR/FasL pathway through p53 activation. Furthermore, inhibition of p53 by pharmacological inhibitor pifithrin-α (PFT-α) or its specific siRNA attenuated p53 function and down-regulated FasR/FasL, thereby preventing cell death. Animal experiments were performed using C57BL/6J mouse isografted with Hepa1-6 cells. Tumor growth was retarded and survival increased in mice administered MCD together with DOX to as compared to either agent alone. Collectively, these results suggest that MCD enhances the sensitivity to DOX for which wild type p53 is an important determinant.

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2015 Journal Article S. Birko, Dove, E. S., and Özdemir, V., “A Delphi technology foresight study: Mapping social construction of scientific evidence on metagenomics tests for water safety”, PLoS ONE, vol. 10, 2015.[Abstract]

Access to clean water is a grand challenge in the 21st century. Water safety testing for pathogens currently depends on surrogate measures such as fecal indicator bacteria (e.g., E. coli). Metagenomics concerns high-throughput, culture-independent, unbiased shotgun sequencing of DNA from environmental samples that might transform water safety by detecting waterborne pathogens directly instead of their surrogates. Yet emerging innovations such as metagenomics are often fiercely contested. Innovations are subject to shaping/construction not only by technology but also social systems/values in which they are embedded, such as experts' attitudes towards new scientific evidence. We conducted a classic three-round Delphi survey, comprised of 107 questions. A multidisciplinary expert panel (n = 24) representing the continuum of discovery scientists and policymakers evaluated the emergence of metagenomics tests. To the best of our knowledge, we report here the first Delphi foresight study of experts' attitudes on (1) the top 10 priority evidentiary criteria for adoption of metagenomics tests for water safety, (2) the specific issues critical to governance of metagenomics innovation trajectory where there is consensus or dissensus among experts, (3) the anticipated time lapse from discovery to practice of metagenomics tests, and (4) the role and timing of public engagement in development of metagenomics tests. The ability of a test to distinguish between harmful and benign waterborne organisms, analytical/clinical sensitivity, and reproducibility were the top three evidentiary criteria for adoption of metagenomics. Experts agree that metagenomic testing will provide novel information but there is dissensus on whether metagenomics will replace the current water safety testing methods or impact the public health end points (e.g., reduction in boil water advisories). Interestingly, experts view the publics relevant in a "downstream capacity" for adoption of metagenomics rather than a co-productionist role at the "upstream" scientific design stage of metagenomics tests. In summary, these findings offer strategic foresight to govern metagenomics innovations symmetrically: by identifying areas where acceleration (e.g., consensus areas) and deceleration/reconsideration (e.g., dissensus areas) of the innovation trajectory might be warranted. Additionally, we show how scientific evidence is subject to potential social construction by experts' value systems and the need for greater upstream public engagement on metagenomics innovations. © 2015 Birko et al.

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2015 Journal Article K. Dhara, Ramachandran, Ta, Bipin G. Nair Dr., and T. G. Satheesh Babu, “Highly sensitive and wide-range nonenzymatic disposable glucose sensor based on a screen printed carbon electrode modified with reduced graphene oxide and Pd-CuO nanoparticles”, Microchimica Acta, 2015.[Abstract]

A nanocomposite consisting of reduced graphene oxide decorated with palladium-copper oxide nanoparticles (Pd-CuO/rGO) was synthesized by single-step chemical reduction. The morphology and crystal structure of the nanocomposite were characterized by field-emission scanning electron microscopy, high resolution transmission electron microscopy and X-ray diffraction analysis. A 3-electrode system was fabricated by screen printing technology and the Pd-CuO/rGO nanocomposite was dropcast on the carbon working electrode. The catalytic activity towards glucose in 0.2 M NaOH solutions was analyzed by linear sweep voltammetry and amperometry. The steady state current obtained at a constant potential of +0.6 V (vs. Ag/AgCl) showed the modified electrode to possess a wide analytical range (6 μM to 22 mM), a rather low limit of detection (30 nM), excellent sensitivity (3355 μA∙mM−1∙cm−2) and good selectivity over commonly interfering species and other sugars including fructose, sucrose and lactose. The sensor was successfully employed to the determination of glucose in blood serum. [Figure not available: see fulltext.] © 2015 Springer-Verlag Wien

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2015 Journal Article S. Ray, Dr. Diwakar, S., Srivastava, S., and Nair, B., “E-learning resources and virtual labs”, Nature India Special Issue: Proteomics Research in Ind, 2015.[Abstract]

India’s recent strides in information technology have propelled the growth of web-based digital learning in most disciplines of science and engineering education. Distance education and open learning endeavours offer many advantages in resource-limited developing countries, where the number of potential learners is much higher than the number of experienced teachers or advanced educational institutes1.

However, these endeavours alone have proved insufficient in providing practical skills for science experiments or analysis of scientific data. Virtual laboratories, which act as free, round-the-clock replicas of actual laboratories, could be an effective alternative. Learners in a virtual laboratory can understand scientific theories and also experience practical experimental procedures2,3. As educational budgets in developing and under-developed countries continue to shrink, e-learning and open-learning programmes are gaining popularity4.

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2015 Journal Article A. Khan, Manna, K., Das, D. K., Kesh, S. B., Sinha, M., Das, U., Biswas, S., Sengupta, A., Sikder, K., Datta, S., Ghosh, M., Chakrabarty, A., Banerji, A., and Dey, S., “Gossypetin ameliorates ionizing radiation-induced oxidative stress in mice liver-a molecular approach”, Free Radical Research, vol. 49, pp. 1173-1186, 2015.[Abstract]

Radioprotective action of gossypetin (GTIN) against gamma (γ)-radiation-induced oxidative stress in liver was explored in the present article. Our main aim was to evaluate the protective efficacy of GTIN against radiation-induced alteration of liver in murine system. To evaluate the effect of GTIN, it was orally administered to mice at a dose of 30 mg/kg body weight for three consecutive days prior to γ-radiation at a dose of 5 Gy. Radioprotective efficacy of GTIN were evaluated at physiological, cellular, and molecular level using biochemical analysis, comet assay, flow cytometry, histopathology, immunofluorescence, and immunoblotting techniques. Ionizing radiation was responsible for augmentation of hepatic oxidative stress in terms of lipid peroxidation and depletion of endogenous antioxidant enzymes. Immunoblotting and immunofluorescence studies showed that irradiation enhanced the nuclear translocation of nuclear factor kappa B (NF-B) level, which leads to hepatic inflammation. To investigate further, we found that radiation induced the activation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK)-mediated apoptotic pathway and deactivation of the NF-E2-related factor 2 (Nrf2)-mediated redox signaling pathway, whereas GTIN pretreatment ameliorated these radiation-mediated effects. This is the novel report where GTIN rationally validated the molecular mechanism in terms of the modulation of cellular signaling system instead of This is the novel report where GTIN is rationally validated in molecular terms to establish it as promising radioprotective agents. This might be fruitful especially for nuclear workers and defense personnel assuming the possibility of radiation exposure. © 2015 Informa UK, Ltd.

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2015 Journal Article Sa Muzaffar, Bose, C., Banerji, A., Bipin G. Nair Dr., and Chattoo, B. Ba, “Anacardic acid induces apoptosis-like cell death in the rice blast fungus Magnaporthe oryzae”, Applied Microbiology and Biotechnology, 2015.[Abstract]

<p>Anacardic acid (6-pentadecylsalicylic acid), extracted from cashew nut shell liquid, is a natural phenolic lipid well known for its strong antibacterial, antioxidant, and anticancer activities. Its effect has been well studied in bacterial and mammalian systems but remains largely unexplored in fungi. The present study identifies antifungal, cytotoxic, and antioxidant activities of anacardic acid in the rice blast fungus Magnaporthe oryzae. It was found that anacardic acid causes inhibition of conidial germination and mycelial growth in this ascomycetous fungus. Phosphatidylserine externalization, chromatin condensation, DNA degradation, and loss of mitochondrial membrane potential suggest that growth inhibition of fungus is mainly caused by apoptosis-like cell death. Broad-spectrum caspase inhibitor Z-VAD-FMK treatment indicated that anacardic acid induces caspase-independent apoptosis in M. oryzae. Expression of a predicted ortholog of apoptosis-inducing factor (AIF) was upregulated during the process of apoptosis, suggesting the possibility of mitochondria dependent apoptosis via activation of apoptosis-inducing factor. Anacardic acid treatment leads to decrease in reactive oxygen species rather than increase in reactive oxygen species (ROS) accumulation normally observed during apoptosis, confirming the antioxidant properties of anacardic acid as suggested by earlier reports. Our study also shows that anacardic acid renders the fungus highly sensitive to DNA damaging agents like ethyl methanesulfonate (EMS). Treatment of rice leaves with anacardic acid prevents M. oryzae from infecting the plant without affecting the leaf, suggesting that anacardic acid can be an effective antifungal agent. © 2015 Springer-Verlag Berlin Heidelberg</p>

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2015 Journal Article Ö. V., E.S., D., U.K., G., S., Ş., A., Y., Ş.G., Y., İ., Ö. Barlas, K., G., A., M., and S., S., “Personalized medicine beyond genomics: alternative futures in big data—proteomics, environtome and the social proteome”, Journal of Neural Transmission, pp. 1-8, 2015.[Abstract]

No field in science and medicine today remains untouched by Big Data, and psychiatry is no exception. Proteomics is a Big Data technology and a next generation biomarker, supporting novel system diagnostics and therapeutics in psychiatry. Proteomics technology is, in fact, much older than genomics and dates to the 1970s, well before the launch of the international Human Genome Project. While the genome has long been framed as the master or “elite” executive molecule in cell biology, the proteome by contrast is humble. Yet the proteome is critical for life—it ensures the daily functioning of cells and whole organisms. In short, proteins are the blue-collar workers of biology, the down-to-earth molecules that we cannot live without. Since 2010, proteomics has found renewed meaning and international attention with the launch of the Human Proteome Project and the growing interest in Big Data technologies such as proteomics. This article presents an interdisciplinary technology foresight analysis and conceptualizes the terms “environtome” and “social proteome”. We define “environtome” as the entire complement of elements external to the human host, from microbiome, ambient temperature and weather conditions to government innovation policies, stock market dynamics, human values, political power and social norms that collectively shape the human host spatially and temporally. The “social proteome” is the subset of the environtome that influences the transition of proteomics technology to innovative applications in society. The social proteome encompasses, for example, new reimbursement schemes and business innovation models for proteomics diagnostics that depart from the “once-a-life-time” genotypic tests and the anticipated hype attendant to context and time sensitive proteomics tests. Building on the “nesting principle” for governance of complex systems as discussed by Elinor Ostrom, we propose here a 3-tiered organizational architecture for Big Data science such as proteomics. The proposed nested governance structure is comprised of (a) scientists, (b) ethicists, and (c) scholars in the nascent field of “ethics-of-ethics”, and aims to cultivate a robust social proteome for personalized medicine. Ostrom often noted that such nested governance designs offer assurance that political power embedded in innovation processes is distributed evenly and is not concentrated disproportionately in a single overbearing stakeholder or person. We agree with this assessment and conclude by underscoring the synergistic value of social and biological proteomes to realize the full potentials of proteomics science for personalized medicine in psychiatry in the present era of Big Data. © 2015 Springer-Verlag Wien

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2015 Journal Article Y. S.D., S., J., J.K., T., S., G., A.A., K., A., S., T.S., K. Prasad, A., P., B.L., S., and f, G. Ha b, “A pathway map of glutamate metabolism”, Journal of Cell Communication and Signaling, pp. 1-7, 2015.[Abstract]

Glutamate metabolism plays a vital role in biosynthesis of nucleic acids and proteins. It is also associated with a number of different stress responses. Deficiency of enzymes involved in glutamate metabolism is associated with various disorders including gyrate atrophy, hyperammonemia, hemolytic anemia, γ-hydoxybutyric aciduria and 5-oxoprolinuria. Here, we present a pathway map of glutamate metabolism representing metabolic intermediates in the pathway, 107 regulator molecules, 9 interactors and 3 types of post-translational modifications. This pathway map provides detailed information about enzyme regulation, protein-enzyme interactions, post-translational modifications of enzymes and disorders due to enzyme deficiency. The information included in the map was based on published experimental evidence reported from mammalian systems. © 2015 The International CCN Society

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2015 Journal Article N. M., B., N., S., D., C., diSerio, A., N., and R., T., “GPGPU implementation of a spiking neuronal circuit performing sparse recoding”, Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), vol. 8623, pp. 285-297, 2015.[Abstract]

Modeling and simulation techniques have been used extensively to study the complexities of brain circuits. Simulations of bio-realistic networks consisting of large number of neurons require massive computational power when they are designed to provide real-time responses in millisecond scale. A network model of cerebellar granular layer was developed and simulated here on Graphic Processing Units (GPU) which delivered a high compute capacity at low cost. We used a mathematical model namely, Adaptive Exponential leaky integrate-and-fire (AdEx) equations to model the different types of neurons in the cerebellum. The hypothesis relating spatiotemporal information processing in the input layer of the cerebellum and its relations to sparse activation of cell clusters was evaluated. The main goal of this paper was to understand the computational efficiency and scalability issues while implementing a large-scale microcircuit consisting of millions of neurons and synapses. The results suggest efficient scale-up based on pleasantly parallel modes of operations allows simulations of large-scale spiking network models for cerebellum-like network circuits. © Springer International Publishing Switzerland 2015.

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2015 Book Chapter S. S, P, B., and P., L. K., “Identification, Purification and Mass Spectrometric Characterization of Two Novel Cyclic Peptides from Clitoria ternatea”, in Biodiversity Conservation - Challenges for the Future, vol. 209-216, Bentham E-Books, 2015.[Abstract]

Kerala has a rich heritage of plant diversity and health traditions. The history of drug discovery reveals that the ethno-botanical approach is one of the most productive methods to screen bioactive compounds. Many drugs currently in use were developed after scientists began to analyze the chemical constituents of plants. Exploration of the medicinal uses of plants from traditional knowledge coupled to scientific research methodologies may be able to determine whether such plants provide therapeutically relevant drug candidates or not. Clitoria ternatea, a plant from the family Fabaceae is a slender, perennial climber used as an anti-inflammatory agent in folklore medicine. In an effort to identify biologically active molecules from Clitoria ternatea, we have isolated two novel, disulfide rich cyclic peptides using reversed phase high performance liquid chromatography (RP HPLC). Masses of these peptides were measured as 3058.8 Da and 3074.4 Da by an electrospray ionization mass spectrometer (ESI MS). Partial sequences of the peptides were assigned through manual de novo sequencing approach using tandem mass spectrometric data obtained from a matrix assisted laser desorption ionization time of flight mass spectrometer (MALDI-TOF MS).

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