Year of Publication Publication Type Title

2018

Journal Article

H. S. Solanki, Babu, N., Jain, A. P., Bhat, M. Younis, Puttamallesh, V. N., Advani, J., Raja, R., Mangalaparthi, K. K., Kumar, M. M., Prasad, T. S. Keshava, Mathur, P. Prakash, Sidransky, D., Gowda, H., and Chatterjee, A., “Cigarette smoke induces mitochondrial metabolic reprogramming in lung cells.”, Mitochondrion, vol. 40, pp. 58-70, 2018.[Abstract]


Cellular transformation owing to cigarette smoking is due to chronic exposure and not acute. However, systematic studies to understand the molecular alterations in lung cells due to cigarette smoke are lacking. To understand these molecular alterations induced by chronic cigarette smoke exposure, we carried out tandem mass tag (TMT) based temporal proteomic profiling of lung cells exposed to cigarette smoke for upto 12months. We identified 2620 proteins in total, of which 671 proteins were differentially expressed (1.5-fold) after 12months of exposure. Prolonged exposure of lung cells to smoke for 12months revealed dysregulation of oxidative phosphorylation and overexpression of enzymes involved in TCA cycle. In addition, we also observed overexpression of enzymes involved in glutamine metabolism, fatty acid degradation and lactate synthesis. This could possibly explain the availability of alternative source of carbon to TCA cycle apart from glycolytic pyruvate. Our data indicates that chronic exposure to cigarette smoke induces mitochondrial metabolic reprogramming in cells to support growth and survival.

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2018

Journal Article

C. Porayath, Suresh, M. K., Biswas, R., Dr. Bipin G. Nair, Dr. Nandita Mishra, and Dr. Sanjay Pal, “Autolysin Mediated Adherence of Staphylococcus Aureus with Fibronectin, Gelatin and Heparin”, International Journal of Biological Macromolecules, 2018.

2018

Journal Article

Priyanka Somanath, Bush, K. M., and Knoepfler, P. S., “ERBB3-Binding Protein 1 (EBP1) Is a Novel Developmental Pluripotency-Associated-4 (DPPA4) Cofactor in Human Pluripotent Cells”, STEM CELLS, p. n/a–n/a, 2018.[Abstract]


Developmental Pluripotency-Associated-4 (DPPA4) is one of the few core pluripotency genes lacking clearly defined molecular and cellular functions. Here, we used a proteomics screening approach of human embryonic stem cell (hESC) nuclear extract to determine DPPA4 molecular functions through identification of novel cofactors. Unexpectedly, the signaling molecule ERBB3-binding protein 1 (EBP1) was the strongest candidate binding partner for DPPA4 in hESC. EBP1 is a growth factor signaling mediator present in two isoforms, p48 and p42. The two isoforms generally have opposing functions, however their roles in pluripotent cells have not been established. We found that DPPA4 preferentially binds p48 in pluripotent and NTERA-2 cells, but this interaction is largely absent in non-pluripotent cells and is reduced with differentiation. The DPPA4–EBP1 interaction is mediated at least in part in DPPA4 by the highly conserved SAF-A/B, Acinus and PIAS (SAP) domain. Functionally, we found that DPPA4 transcriptional repressive function in reporter assays is significantly increased by specific p48 knockdown, an effect that was abolished with an interaction-deficient DPPA4 ΔSAP mutant. Thus, DPPA4 and EBP1 may cooperate in transcriptional functions through their physical association in a pluripotent cell specific context. Our study identifies EBP1 as a novel pluripotency cofactor and provides insight into potential mechanisms used by DPPA4 in regulating pluripotency through its association with EBP1. Stem Cells 2018

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2018

Journal Article

N. Babu, Advani, J., Solanki, H. S., Patel, K., Jain, A. P., Khan, A. Ahmad, Radhakrishnan, A., Sahasrabuddhe, N. A., Mathur, P. Prakash, Dr. Bipin G. Nair, Prasad, T. S. Keshava, Chang, X., Sidransky, D., Gowda, H., and Chatterjee, A., “miRNA and proteomic dysregulation in non-small cell lung cancer in response to cigarette smoke.”, Microrna, 2018.[Abstract]


BACKGROUND: Dysregulation of miRNAs is associated with the development of non-small cell lung cancer (NSCLC). It is imperative to study the dysregulation of miRNAs by cigarette smoke which will affect their targets, either leading to the overexpression of oncoproteins or downregulation of tumor suppressor proteins.

OBJECTIVE AND METHODS: In this study, we carried out miRNA sequencing and SILAC-based proteomic analysis of H358 cells chronically exposed to cigarette smoke condensate. Using bioinformatics analysis, we mapped the dysregulated miRNAs to differentially expressed target proteins identified in our data. Gene ontology-based enrichment and pathway analysis was performed using the deregulated targets to study the role of cigarette smoke-mediated miRNA dysregulation in NSCLC cell line.

RESULTS: miRNA sequencing resulted in the identification of 208 miRNAs, of which 6 miRNAs were found to be significantly dysregulated (2 fold, Log Base 2; p-value ≤ 0.05) in H358-Smoke cells. Proteomic analysis of the smoke exposed cells compared to the untreated parental cells resulted in the quantification of 2,610 proteins, of which 690 proteins were found to be differentially expressed (fold change ≥ 2). Gene ontology based analysis of target proteins revealed enrichment of proteins driving metabolism and a decrease in expression of proteins associated with immune response in the cells exposed to cigarette smoke. Pathway study using Ingenuity Pathway Analysis (IPA) revealed activation of NRF2-mediated oxidative stress response and actin-cytoskeleton signaling, and repression of protein kinase A signaling in H358-Smoke cells. We also identified 5 novel miRNAs in H358-Smoke cells using unassigned reads of small RNA-Seq dataset.

CONCLUSION: In summary, this study indicates that chronic exposure to cigarette smoke leads to widespread dysregulation of miRNAs and their targets, resulting in signaling aberrations in NSCLC cell line. The miRNAs and their targets identified in the study need to be further investigated to explore their role as potential therapeutic targets and/or molecular markers in NSCLC especially in smokers.

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2018

Journal Article

P. Rajagopalan, Nanjappa, V., Patel, K., Jain, A. P., Mangalaparthi, K. K., Patil, A. H., Nair, B., Mathur, P. P., Prasad, T. S. Keshava, Califano, J. A., Sidransky, D., Gowda, H., and Chatterjee, A., “Role of protein kinase N2 (PKN2) in cigarette smoke-mediated oncogenic transformation of oral cells.”, J Cell Commun Signal, 2018.[Abstract]


Smoking is the leading cause of preventable death worldwide. Though cigarette smoke is an established cause of head and neck cancer (including oral cancer), molecular alterations associated with chronic cigarette smoke exposure are poorly studied. To understand the signaling alterations induced by chronic exposure to cigarette smoke, we developed a cell line model by exposing normal oral keratinocytes to cigarette smoke for a period of 12 months. Chronic exposure to cigarette smoke resulted in increased cellular proliferation and invasive ability of oral keratinocytes. Proteomic and phosphoproteomic analyses showed dysregulation of several proteins involved in cellular movement and cytoskeletal reorganization in smoke exposed cells. We observed overexpression and hyperphosphorylation of protein kinase N2 (PKN2) in smoke exposed cells as well as in a panel of head and neck cancer cell lines established from smokers. Silencing of PKN2 resulted in decreased colony formation, invasion and migration in both smoke exposed cells and head and neck cancer cell lines. Our results indicate that PKN2 plays an important role in oncogenic transformation of oral keratinocytes in response to cigarette smoke. The current study provides evidence that PKN2 can act as a potential therapeutic target in head and neck squamous cell carcinoma, especially in patients with a history of smoking.

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2018

Journal Article

D. Nedungadi, Binoy, A., Nanjan Pandurangan, Pal, S., Dr. Bipin G. Nair, and Dr. Nandita Mishra, “6-Shogaol Induces Caspase-independent Paraptosis in Cancer Cells Via Proteasomal Inhibition”, Exp Cell Res, vol. 364, no. 2, pp. 243-251, 2018.[Abstract]


An α, β-unsaturated carbonyl compound of ginger, 6-Shogaol (6S), induced extensive cytoplasmic vacuolation and cell death in breast cancer cell (MDA-MB-231) and non-small lung cancer (A549) cells. In the presence of autophagic inhibitors the cells continued to exhibit cytoplasmic vacuolation and cell death clearly distinguishing it from the classic autophagic process. 6S induced death did not exhibit the characteristic apoptotic features like caspase cleavage, phosphatidyl serine exposure and DNA fragmentation. The immunofluorescence with the Endoplasmic Reticulum (ER) resident protein, calreticulin indicated that the vacuoles were of ER origin, typical of paraptosis. This was supported by the increase in level of microtubule associated protein light chain 3B (LC3 I and LC3 II) and polyubiquitin binding protein, p62. The level of ER stress markers like polyubiquitinated proteins, Bip and CHOP also consistently increased. We have found that 6S inhibits the 26S proteasome. The proteasomal inhibitory activity was elucidated by a) molecular docking of 6S onto the active site of β5 subunit and b) reduced fluorescence by the fluorogenic substrate of the chymotrypsin-like subunit. In conclusion these studies demonstrate for the first time that proteasomal inhibition by 6S induces cell death via paraptosis. So 6-shogaol may act as a template for anti-cancer lead discovery against the apoptosis resistant cancer cells.

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2018

Journal Article

V. Ozdemir and Springer, S., “What does "Diversity" Mean for Public Engagement in Science? A New Metric for Innovation Ecosystem Diversity.”, OMICS, 2018.[Abstract]


Diversity is increasingly at stake in early 21st century. Diversity is often conceptualized across ethnicity, gender, socioeconomic status, sexual preference, and professional credentials, among other categories of difference. These are important and relevant considerations and yet, they are incomplete. Diversity also rests in the way we frame questions long before answers are sought. Such diversity in the framing (epistemology) of scientific and societal questions is important for they influence the types of data, results, and impacts produced by research. Errors in the framing of a research question, whether in technical science or social science, are known as type III errors, as opposed to the better known type I (false positives) and type II errors (false negatives). Kimball defined "error of the third kind" as giving the right answer to the wrong problem. Raiffa described the type III error as correctly solving the wrong problem. Type III errors are upstream or design flaws, often driven by unchecked human values and power, and can adversely impact an entire innovation ecosystem, waste money, time, careers, and precious resources by focusing on the wrong or incorrectly framed question and hypothesis. Decades may pass while technology experts, scientists, social scientists, funding agencies and management consultants continue to tackle questions that suffer from type III errors. We propose a new diversity metric based on the hitherto neglected diversities in knowledge framing for robust, responsible, and inclusive design of innovation ecosystems with foresight. The FDI would be positively correlated with epistemological diversity and technological democracy, and inversely correlated with prevalence of type III errors in innovation ecosystems, consortia, and knowledge networks. We suggest that the FDI can usefully measure (and prevent) type III error risks in innovation ecosystems, and help broaden the concepts and practices of diversity and inclusion in science, technology, innovation and society.

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2018

Journal Article

P. Mol, Kannegundla, U., Dey, G., Gopalakrishnan, L., Dammalli, M., Kumar, M., Patil, A. H., Basavaraju, M., Rao, A., Ramesha, K. P., and Prasad, T. Subrahmany, “Bovine Milk Comparative Proteome Analysis from Early, Mid, and Late Lactation in the Cattle Breed, Malnad Gidda (Bos indicus).”, OMICS, 2018.[Abstract]


Bovine milk is important for both veterinary medicine and human nutrition. Understanding the bovine milk proteome at different stages of lactation has therefore broad significance for integrative biology and clinical medicine as well. Indeed, different lactation stages have marked influence on the milk yield, milk constituents, and nourishment of the neonates. We performed a comparative proteome analysis of the bovine milk obtained at different stages of lactation from the Indian indigenous cattle Malnad Gidda (Bos indicus), a widely available breed. The milk differential proteome during the lactation stages in B. indicus has not been investigated to date. Using high-resolution mass spectrometry-based quantitative proteomics of the bovine whey proteins at early, mid, and late lactation stages, we identified a total of 564 proteins, out of which 403 proteins were found to be differentially abundant at different lactation stages. As is expected of any body fluid proteome, 51% of the proteins identified in the milk were found to have signal peptides. Gene ontology analyses were carried out to categorize proteins altered across different lactation stages based on biological process and molecular function, which enabled us to correlate their significance in each lactation stage. We also investigated the potential pathways enriched in different lactation stages using bioinformatics pathway analysis tools. To the best of our knowledge, this study represents the first and largest inventory of milk proteins identified to date for an Indian cattle breed. We believe that the current study broadly informs both veterinary omics research and the emerging field of nutriproteomics during lactation stages.

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2018

Journal Article

P. H, Dr. Bipin G. Nair, G, N., E, D. ’A., and Dr. Shyam Diwakar, “Understanding Cerebellum Granular Layer Network Computations through Mathematical Reconstructions of Evoked Local Field Potentials”, Annals of Neuroscience, vol. 25, pp. 11-24, 2018.[Abstract]


Background: The cerebellar granular layer input stage of cerebellum receives information from tactile and sensory regions of the body. The somatosensory activity in the cerebellar granular layer corresponds to sensory and tactile input has been observed by recording Local Field Potential (LFP) from the Crus-IIa regions of cerebellum in brain slices and in anesthetized animals. Purpose: In this paper, a detailed biophysical model of Wistar rat cerebellum granular layer network model and LFP modelling schemas were used to simulate circuit’s evoked response. Methods: Point Source Approximation and Line Source Approximation were used to reconstruct the network LFP. The LFP mechanism in in vitro was validated in network model and generated the in vivo LFP using the same mechanism. Results: The network simulations distinctly displayed the Trigeminal and Cortical (TC) wave components generated by 2 independent bursts implicating the generation of TC waves by 2 independent granule neuron populations. Induced plasticity was simulated to estimate granule neuron activation related population responses. As a prediction, cerebellar dysfunction (ataxia) was also studied using the model. Dysfunction at individual neurons in the network was affected by the population response. Conclusion: Our present study utilizes available knowledge on known mechanisms in a single cell and associates network function to population responses.

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2018

Journal Article

Dr. Shyam Diwakar, Dr. Bipin G. Nair, Medini, K. Chaitanya, Asha Vijayan, and Rajendran, A. G., “Computational Modelling of Cerebellum Granule Neuron Temporal Responses for Auditory and Visual Stimuli”, International Journal of Advanced Intelligence Paradigms, vol. 10, p. 1, 2018.

2018

Journal Article

Pandurangan Nanjan, Chinch Bose, M. Sreejith, Veni C K, Anjana M Amrita, and Anjana R P., “Synthesis, bioactivities and in-silico docking studies of azaleatin-a quercetin partial methyl ether; SAR study.”, vol. 14, 2018.[Abstract]


Azaleatin- a lesser known partially methylated flavonoid, has been synthesized efficiently through MOM protection and deprotections from quercetin. The synthesized compound and closely related partially methylated flavonoids (SAR) were subjected for the investigation of α-amylase and antioxidant activities. Among the compounds tested, azaleatin was found to be best inhibitor for α-amylase with acceptable radical scavenging activity than closely related compounds. Further, in-silico modelling studies indicated that azaleatin forms hydrogen bonds with the key amino acid residues such as Gln63, Arg195 and Asp197 of α-amylase receptor. Acarbose was used as positive control for α-amylase inhibition.

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2018

Journal Article

K. R. Raghi, Sherin, D. R., Saumya, M. J., Arun, P. S., Sobha, V. N., and Manojkumar, T. K., “Computational study of molecular electrostatic potential, docking and dynamics simulations of gallic acid derivatives as ABL inhibitors.”, Comput Biol Chem, vol. 74, pp. 239-246, 2018.[Abstract]


Chronic myeloid leukemia (CML), a hematological malignancy arises due to the spontaneous fusion of the BCR and ABL gene, resulting in a constitutively active tyrosine kinase (BCR-ABL). Pharmacological activity of Gallic acid and 1,3,4-Oxadiazole as potential inhibitors of ABL kinase has already been reported. Objective of this study is to evaluate the ABL kinase inhibitory activity of derivatives of Gallic acid fused with 1,3,4-Oxadiazole moieties. Attempts have been made to identify the key structural features responsible for drug likeness of the Gallic acid and the 1,3,4-Oxadiazole ring using molecular electrostatic potential maps (MESP). To investigate the inhibitory activity of Gallic acid derivatives towards the ABL receptor, we have applied molecular docking and molecular dynamics (MD) simulation approaches. A comparative study was performed using Bosutinib as the standard which is an approved CML drug acting on the same receptor. Furthermore, the novel compounds designed and reported here in were evaluated for ADME properties and the results indicate that they show acceptable pharmacokinetic properties. Accordingly these compounds are predicted to be drug like with low toxicity potential.

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2018

Journal Article

P. Rajagopalan, Patel, K., Jain, A. P., Nanjappa, V., Datta, K. K., Subbannayya, T., Mangalaparthi, K. K., Kumari, A., Manoharan, M., Coral, K., Murugan, S., Dr. Bipin G. Nair, Prasad, T. S. Keshava, Mathur, P. P., Gupta, R., Gupta, R., Khanna-Gupta, A., Califano, J., Sidransky, D., Gowda, H., and Chatterjee, A., “Molecular alterations associated with chronic exposure to cigarette smoke and chewing tobacco in normal oral keratinocytes.”, Cancer Biol Ther, pp. 1-13, 2018.[Abstract]


Tobacco usage is a known risk factor associated with development of oral cancer. It is mainly consumed in two different forms (smoking and chewing) that vary in their composition and methods of intake. Despite being the leading cause of oral cancer, molecular alterations induced by tobacco are poorly understood. We therefore sought to investigate the adverse effects of cigarette smoke/chewing tobacco exposure in oral keratinocytes (OKF6/TERT1). OKF6/TERT1 cells acquired oncogenic phenotype after treating with cigarette smoke/chewing tobacco for a period of 8 months. We employed whole exome sequencing (WES) and quantitative proteomics to investigate the molecular alterations in oral keratinocytes chronically exposed to smoke/ chewing tobacco. Exome sequencing revealed distinct mutational spectrum and copy number alterations in smoke/ chewing tobacco treated cells. We also observed differences in proteomic alterations. Proteins downstream of MAPK1 and EGFR were dysregulated in smoke and chewing tobacco exposed cells, respectively. This study can serve as a reference for fundamental damages on oral cells as a consequence of exposure to different forms of tobacco.

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2018

Journal Article

M. Younis Bhat, Advani, J., Rajagopalan, P., Patel, K., Nanjappa, V., Solanki, H. S., Patil, A. H., Bhat, F. A., Mathur, P. P., Dr. Bipin G. Nair, Prasad, T. S. Keshava, Califano, J. A., Sidransky, D., Gowda, H., and Chatterjee, A., “Cigarette smoke and chewing tobacco alter expression of different sets of miRNAs in oral keratinocytes.”, Sci Rep, vol. 8, no. 1, p. 7040, 2018.[Abstract]


Carcinogenic effect of tobacco in oral cancer is through chewing and/or smoking. Significant differences exist in development of oral cancer between tobacco users and non-users. However, molecular alterations induced by different forms of tobacco are yet to be fully elucidated. We developed cellular models of chronic exposure to chewing tobacco and cigarette smoke using immortalized oral keratinocytes. Chronic exposure to tobacco resulted in increased cell scattering and invasiveness in immortalized oral keratinocytes. miRNA sequencing using Illumina HiSeq 2500 resulted in the identification of 10 significantly dysregulated miRNAs (4 fold; p ≤ 0.05) in chewing tobacco treated cells and 6 in cigarette smoke exposed cells. We integrated this data with global proteomic data and identified 36 protein targets that showed inverse expression pattern in chewing tobacco treated cells and 16 protein targets that showed inverse expression in smoke exposed cells. In addition, we identified 6 novel miRNAs in chewing tobacco treated cells and 18 novel miRNAs in smoke exposed cells. Integrative analysis of dysregulated miRNAs and their targets indicates that signaling mechanisms leading to oncogenic transformation are distinct between both forms of tobacco. Our study demonstrates alterations in miRNA expression in oral cells in response to two frequently used forms of tobacco.

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2018

Journal Article

S. Jayaram, Balakrishnan, L., Singh, M., Zabihi, A., Ganesh, R. A., Mangalaparthi, K. K., Sonpatki, P., Gupta, M. Kumar, Amaresha, C. B., Prasad, K., Mariswamappa, K., Pillai, S., Lakshmikantha, A., Shah, N., and Sirdeshmukh, R., “Identification of a Novel Splice Variant of Neural Cell Adhesion Molecule in Glioblastoma Through Proteogenomics Analysis.”, OMICS, vol. 22, no. 6, pp. 437-448, 2018.[Abstract]


Splice variants are known to be important in the pathophysiology of tumors, including the brain cancers. We applied a proteogenomics pipeline to identify splice variants in glioblastoma (GBM, grade IV glioma), a highly malignant brain tumor, using in-house generated mass spectrometric proteomic data and public domain RNASeq dataset. Our analysis led to the identification of a novel exon that maps to the long isoform of Neural cell adhesion molecule 1 (NCAM1), expressed on the surface of glial cells and neurons, important for cell adhesion and cell signaling. The presence of the novel exon is supported with the identification of five peptides spanning it. Additional peptides were also detected in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel separated proteins from GBM patient tissue, underscoring the presence of the novel peptides in the intact brain protein. The novel exon was detected in the RNASeq dataset in 18 of 25 GBM samples and separately validated in additional 10 GBM tumor tissues using quantitative real-time-polymerase chain reaction (qRT-PCR). Both transcriptomic and proteomic data indicate downregulation of NCAM1, including the novel variant, in GBM. Domain analysis of the novel NCAM1 sequence indicates that the insertion of the novel exon contributes extra low-complexity region in the protein that may be important for protein-protein interactions and hence for cell signaling associated with tumor development. Taken together, the novel NCAM1 variant reported in this study exemplifies the importance of future multiomics research and systems biology applications in GBM.

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2018

Journal Article

F. A. Bhat, Advani, J., Khan, A. Ahmad, Mohan, S., Pal, A., Gowda, H., Chakrabarti, P., Prasad, T. S. Keshava, and Chatterjee, A., “A network map of thrombopoietin signaling.”, J Cell Commun Signal, 2018.

2018

Journal Article

A. Sahu, Gopalakrishnan, L., Gaur, N., Chatterjee, O., Mol, P., Modi, P. Kumar, Dagamajalu, S., Advani, J., Jain, S., and Prasad, T. S. Keshava, “The 5-Hydroxytryptamine signaling map: an overview of serotonin-serotonin receptor mediated signaling network.”, J Cell Commun Signal, 2018.[Abstract]


The monoamine neurotransmitter, 5-Hydroxytryptamine or serotonin, is derived from tryptophan and synthesized both centrally and systemically. Fourteen structurally and functionally distinct receptor subtypes have been identified for serotonin, each of which mediates the neurotransmitter's effects through a range of downstream signaling molecules and effectors. Although it is most frequently described for its role in the etiology of neuropsychiatric and mood disorders, serotonin has been implicated in a slew of fundamental physiological processes, including apoptosis, mitochondrial biogenesis, cell proliferation and migration. Its roles as the neurotransmitter have also emerged in pathogenic conditions ranging from anorexia nervosa to cancer. This has necessitated the understanding of the signaling mechanisms underlying the serotonergic system, which led us to construct a consolidative pathway map, which will provide as a resource for future biomedical investigation on this pathway. Using a set of stringent NetPath annotation criteria, we manually curated molecular reactions associated with serotonin and its receptors from publicly available literature; the reaction categories included molecular associations, activation/inhibition, post-translation modification, transport, and gene regulation at transcription and translational level. We identified 90 molecules in serotonin-serotonin receptor pathway. We submitted the curated data to NetPath, a publicly available database of human signaling pathways, in order to enable the wider scientific community to readily access data and contribute further to this pathway.

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2018

Journal Article

V. Ozdemir, “Precision Medicine Goes Global: How to Get It Right? Four Ways to Mobilize Scientific Knowledge.”, OMICS, vol. 22, no. 8, pp. 539-543, 2018.[Abstract]


Globalization and knowledge mobilization (KM) are twin challenges impacting precision medicine currently. Previous KM models have been largely limited to an implementation framework whereby knowledge is imagined as a billiard ball to be simply rolled over from the laboratory to society and from developed to developing countries. This narrow and sanitized understanding of KM and science as being detached from social forces, human values, politics, and power inequities does not help to achieve robust and responsible emergence of precision medicine, not least because tailored medicines are not simple products ready to use off-the-shelf without customization in each country, local context and society. It is time to broaden the art and science of KM by rethinking knowledge as a dynamic co-product of both technology and social systems in which science is embedded. This article presents an analysis of the four possible approaches to KM available to the precision medicine community: (1) "knowledge implementation," (2) "research collaborator capacity building," (3) "collaborative entanglement" that removes the barriers between research and practice, and extends knowledge co-creation activities beyond scientists by inviting publics, patients, and clinicians as researchers, and (4) "knowledge ecosystem" approach that adopts systems thinking, addressing not only technology development but also the politics of innovation, whereby power differences in scientific practice are addressed, for example, to achieve gender parity and diversity in the scientific work force. Blending of laboratory science with KM theory and practice informs robust and responsible emergence of precision medicine innovations, and helps strike the right balance between promotion and regulation of emerging technologies.

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2018

Journal Article

S. Edathadan Sajeevan, Chatterjee, M., Paul, V., Baranwal, G., V Kumar, A., Bose, C., Banerji, A., Nair, B. G., Prasanth, B. Paul, and Biswas, R., “Impregnation of Catheters with Anacardic Acid from Cashew Nut Shell Prevents Staphylococcus aureus Biofilm Development.”, J Appl Microbiol, 2018.[Abstract]


<strong>AIM: </strong>The effect of anacardic acid impregnation on catheter surfaces for the prevention of S. aureus attachments and biofilm formations were evaluated.

<strong>METHODS AND RESULTS: </strong>Silicon catheter tubes were impregnated using different concentrations of anacardic acids (0.002% to 0.25%). Anacardic acids are anti-bacterial phenolic lipids from Cashew nut (Anacardium occidentale) shell oil. Anacardic acids impregnated silicon catheters revealed no significant hemolytic activity and were cytocompatible against fibroblast cell line (L929). Sustained release of anacardic acids were observed for 4 days. Anacardic acid impregnated silicon catheters efficiently inhibited S. aureus colonization and the biofilm formation on its surface. The in vivo anti-biofilm activity of Anacardic acid impregnated catheters was tested in an intra-peritoneal catheter associated Medaka fish infection model. Significant reduction in S. aureus colonization on anacardic acid impregnated catheter tubes was observed.

<strong>CONCLUSIONS: </strong>Our data suggest that anacardic acid impregnated silicon catheters may help in preventing catheter-related staphylococcal infections.

<strong>SIGNIFICANCE AND IMPACT OF THE STUDY: </strong>This study opens new directions for designing antimicrobial phytochemical coated surfaces with ideal anti-biofilm properties and could be of great interest for bio-medical research scientists. This article is protected by copyright. All rights reserved.

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2018

Journal Article

M. Vanuopadath, Sajeev, N., Murali, A. Radhamony, Sudish, N., Kangosseri, N., Sebastian, I. Rose, Jain, N. Dalpatraj, Pal, A., Raveendran, D., Nair, B. Gopalakris, and Nair, S. Sadasivan, “Mass spectrometry-assisted venom profiling of Hypnale hypnale found in the Western Ghats of India incorporating de novo sequencing approaches.”, Int J Biol Macromol, 2018.[Abstract]


Hypnale hypnale (hump-nosed pit viper) is considered to be one among the medically important venomous snake species of India and Sri Lanka. In the present study, venom proteome profiling of a single Hypnale hypnale from Western Ghats of India was achieved using SDS-PAGE based protein separation followed by LC-MS/MS analysis. The identities of the proteins that were not established using the Mascot search were determined through de novo sequencing tools such as Novor followed by MS-BLAST based sequence similarity search algorithm and PEAKS proteomics software. The combined proteomics analysis revealed a total of 37 proteins belonging to nine different snake venom families, in which 7 proteins were exclusively identified through de novo strategies. The enzymatic and non-enzymatic venom protein families identified include serine proteases, metalloproteases, phospholipase A, thrombin-like enzymes, phospholipase B, C-type lectins/snaclecs, disintegrins, cysteine rich secretory proteins and nerve growth factor. Among these, disintegrins, nerve growth factor, phospholipase B and cysteine rich secretory protein families were identified for the first time in HPV venom. This could possibly explain the regiospecific venom variation seen across snake species. Taken together, the venom proteome profiling on Indian Hypnale hypnale venom correlates with the clinical manifestations often seen in the envenomed victims.

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2018

Journal Article

J. Nambiar, Vijayakumar, G., Drishya, G., Shaji, S. K., Pandurangan, N., Kumar, G. B., and Dr. Bipin G. Nair, “(I-3,II-3)-Biacacetin-mediated cell death involves mitochondria.”, Mol Cell Biochem, 2018.[Abstract]


Dysregulation of the dynamic balance between cell proliferation and cell death leads to several malignancies including cancer. Biflavones are known to possess anti-proliferative activity against numerous cancer cell lines. The current study was undertaken to understand the mechanism of action of the biflavonoid&nbsp;(I-3,II-3)-biacacetin on MDA-MB-231. Biacacetin induces dose-dependent cell death in MDA-MB-231 cells from concentrations as low as 0.5&nbsp;μM, which was further confirmed by an increase in sub-G1 cells. Furthermore, the cell death induced by biacacetin was found to be mitochondria-dependent, since cells devoid of mitochondria were viable in the presence of biacacetin even at the highest concentration tested (25&nbsp;μM). Fluorescence studies clearly indicated nuclear changes and apoptotic body formation that are characteristic of apoptosis. These results were further corroborated by studies that demonstrate biacacetin to regulate several key markers of apoptosis like Caspase 3, p53, Bax, and poly-ADP-ribose polymerase-1. Furthermore, biacacetin did not induce cell death in normal macrophage cell line, RAW at concentrations up to 15&nbsp;μM. In addition to MDA-MB-231 cells, biacacetin also induces apoptotic cell death in the highly chemo-resistant cell line, OVISE, where the cells stained positive for annexin. Biacacetin also induces cell death in the highly malignant fibrosarcoma cell line HT1080. Furthermore, biacacetin also induces significant cell death (50%) in 3D tumor spheroids, at a concentration of 25&nbsp;μM. Taken together, these results provide an understanding&nbsp;of biacacetin-mediated cell death and thereby provides a strong basis for the use of such compounds as novel templates for anti-cancer therapeutics.

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2018

Journal Article

D. Nair, Krishna, J. Gopala, Panikkar, M. Velayudhan, Dr. Bipin G. Nair, Pai, J. Gopalakris, and Nair, S. Sadasivan, “Identification, purification, biochemical and mass spectrometric characterization of novel phycobiliproteins from a marine red alga, Centroceras clavulatum.”, Int J Biol Macromol, vol. 114, pp. 679-691, 2018.[Abstract]


Phycobilisomes are light-harvesting protein complexes and are widely distributed in red algae and cyanobacteria. Each phycobilisome contains highly fluorescent protein components called phycobiliproteins. Based upon the distinct physiochemical properties, phycobiliproteins are classified as allophycocyanin, phycocyanin, phycoerythrin and phycoerythrocyanin. In the present study, we describe purification and structural characterization of a novel phycocyanin and phycoerythrin isolated from a marine red macroalga, Centroceras clavulatum. The absorbance and fluorescence studies indicated that the purified proteins belong to R-Phycocyanin (R-PC) and R-Phycoerythrin (R-PE). The single bands under native-polyacrylamide gel electrophoresis revealed the intact molecular weights of R-PC and R-PE as 110kDa and 250kDa. The polypeptide compositions of the two proteins were demonstrated by SDS-PAGE. The result showed that R-PC contains two bands at 17 and 21kDa and were identified as α and β subunits through mass spectrometry based proteomics experiments. SDS-PAGE of R-PE showed three distinct bands at 18, 19 and 35kDa and was subsequently identified as α, β and γ subunits. The near-complete amino acid sequences of α and β subunits of R-PC and R-PE were derived from mass spectrometric data combined with Mascot software and multiple de novo sequencing tools followed by homology search and manual validation.

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2018

Journal Article

Manjusha Nair, Jinesh, M. K., Jayaraman, B., Dr. Bipin G. Nair, and Dr. Shyam Diwakar, “Temporal constrained objects for modelling neuronal dynamics”, PeerJ Computer Science, vol. 4, p. e159, 2018.[Abstract]


Background Several new programming languages and technologies have emerged in the past few decades in order to ease the task of modelling complex systems. Modelling the dynamics of complex systems requires various levels of abstractions and reductive measures in representing the underlying behaviour. This also often requires making a trade-off between how realistic a model should be in order to address the scientific questions of interest and the computational tractability of the model. Methods In this paper, we propose a novel programming paradigm, called \textit{temporal constrained objects,} which facilitates a principled approach to modelling complex dynamical systems. \textit{Temporal constrained objects} are an extension of \textit{constrained objects} with a focus on the analysis and prediction of the dynamic behaviour of a system. The structural aspects of a neuronal system are represented using objects, as in object-oriented languages, while the dynamic behaviour of neurons and synapses are modelled using declarative temporal constraints. Computation in this paradigm is a process of constraint satisfaction within a time-based simulation. Results We identified the feasibility and practicality in automatically mapping different kinds of neuron and synapse models to the constraints of \textit{temporal constrained objects}. Simple neuronal networks were modelled by composing circuit components, implicitly satisfying the internal constraints of each component and interface constraints of the composition. Simulations show that \textit{temporal constrained objects} provide significant conciseness in the formulation of these models. The underlying computational engine employed here automatically finds the solutions to the problems stated, reducing the code for modelling and simulation control. All examples reported in this paper have been programmed and successfully tested using the prototype language called TCOB. The code along with the programming environment are available at http://github.com/compneuro/TCOB_Neuron. Discussion \textit{Temporal constrained objects} provide powerful capabilities for modelling the structural and dynamic aspects of neural systems. Capabilities of the constraint programming paradigm, such as declarative specification, the ability to express partial information and non-directionality, and capabilities of the object-oriented paradigm especially aggregation and inheritance, make this paradigm the right candidate for complex systems and computational modelling studies. With the advent of multi-core parallel computer architectures and techniques or parallel constraint-solving, the paradigm of \textit{temporal constrained objects} lends itself to highly efficient execution which is necessary for modelling and simulation of large brain circuits.

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2018

Conference Proceedings

Dr. Shyam Diwakar, ,, ,, Sandeep Bodda, and Dr. Bipin G. Nair, “Experimental Recording and Assessing Gait Phases Using Mobile Phone Sensors and EEG”, Proceedings of the Seventh International Conference on Advances in Computing, Communications and Informatics (ICACCI-2018), Bangalore, Karnataka, India. 2018.

2018

Conference Paper

Dr. Shyam Diwakar, Dr. Bipin G. Nair, Manjusha Nair, D, K., M, K., L., E., R, R., and N, N., “Design and Implementation of an Open-Source Browser-based Laboratory Platform for EEG Data Analysis”, in Proceedings of the Seventh International Conference on Advances in Computing, Communications and Informatics (ICACCI-2018), Bangalore, Karnataka, India, 2018.

2018

Conference Paper

Dr. Shyam Diwakar, Dr. Bipin G. Nair, R, R., A, D., A, N., ,, G, M., N, N., and K., A., “Virtual Laboratories in Biotechnology are Significant Educational Informatics Tools”, in Proceedings of the Seventh International Conference on Advances in Computing, Communications and Informatics (ICACCI-2018), Bangalore, Karnataka, India, 2018.

2018

Conference Paper

Dr. Shyam Diwakar, C, N., S., R., and Dr. Bipin G. Nair, “Modeling Nitric Oxide Induced Neural Activity and Neurovascular Coupling in a Cerebellum Circuit”, in Proceedings of the Seventh International Conference on Advances in Computing, Communications and Informatics (ICACCI-2018), Bangalore, Karnataka, India, 2018.

2018

Conference Paper

Dr. Shyam Diwakar, Dr. Bipin G. Nair, Manjusha Nair, M, K., L, E., R, R., N, N., and D, K., “Experimental Recording and Computational Analysis of EEG signals for a Squeeze Task: Assessments and Impacts for Applications”, in Proceedings of the Seventh International Conference on Advances in Computing, Communications and Informatics (ICACCI-2018), Bangalore, Karnataka, India, 2018.

2018

Conference Paper

Dr. Shyam Diwakar, Dr. Bipin G. Nair, V, S., P, R. L., S., G., H., E., and C., N., “Torque Analysis of Male-Female Gait and Identification using Machine Learning”, in Proceedings of the Seventh International Conference on Advances in Computing, Communications and Informatics (ICACCI-2018), Bangalore, Karnataka, India, Sept 19-22, 2018 (accepted)., 2018.

2018

Conference Paper

Dr. Shyam Diwakar, A., K., A., S., Dr. Krishnashree Achuthan, A., P., P, S., and D., K., “Mathematical Models as Bioscience Educational Informatics Tools”, in Proceedings of the Seventh International Conference on Advances in Computing, Communications and Informatics (ICACCI-2018), Bangalore, Karnataka, India, Sept 19-22, 2018 (accepted), 2018.

2018

Conference Paper

Dr. Shyam Diwakar, Dr. Bipin G. Nair, A, R., and A, P., “Reproducing the firing properties of a cerebellum deep cerebellar nucleus with a multi compartmental morphologically realistic biophysical model”, in Proceedings of the Seventh International Conference on Advances in Computing, Communications and Informatics (ICACCI-2018), Bangalore, Karnataka, India, Sept 19-22, 2018 (accepted)., 2018.

2018

Conference Paper

R. A., A., A., D, M., J., T., S, P., Dr. Shyam Diwakar, and Dr. Bipin G. Nair, “Trajectory tracking using a Bio-inspired neural network for a low cost robotic articulator”, in Proceedings of the Seventh International Conference on Advances in Computing, Communications and Informatics (ICACCI-2018), Bangalore, Karnataka, India, Sept 19-22, 2018 (accepted). , 2018.

2018

Conference Paper

Dr. Shyam Diwakar, Dr. Bipin G. Nair, H., S., M., P., M., B., A., P., E., P., and S., K., “Modeling of Glutamate Pathway in Alzheimer's Disease using Biochemical Systems Theory”, in Proceedings of the Seventh International Conference on Advances in Computing, Communications and Informatics (ICACCI-2018), Bangalore, Karnataka, India, Sept 19-22, 2018 (accepted). , 2018.

2018

Conference Paper

Dr. Shyam Diwakar, Dr. Bipin G. Nair, H., S., C., N., A., R., P., V., M., S., L., N., and H, M., “Spectral Correlations in Speaker-Listener Behavior During a Focused Duo Conversation using EEG”, in Proceedings of the Seventh International Conference on Advances in Computing, Communications and Informatics (ICACCI-2018), Bangalore, Karnataka, India, Sept 19-22, 2018 (accepted)., 2018.

2018

Book Chapter

S. Diwakar, Nutakki, C., Bodda, S., Rajendran, A., Vijayan, A., and Dr. Bipin G. Nair, “Mathematical Modelling of Cerebellar Granular Layer Neurons and Network Activity: Information Estimation, Population Behaviour and Robotic Abstractions”, in Mathematical and Theoretical Neuroscience: Cell, Network and Data Analysis, G. Naldi and Nieus, T. Cham: Springer International Publishing, 2018, pp. 61–85.[Abstract]


Recent studies show cerebellum having a crucial role in motor coordination and cognition, and it has been observed that in patients with movement disorders and other neurological conditions cerebellar circuits are known to be affected. Simulations allow insight on how cerebellar granular layer processes spike information and to understand afferent information divergence in the cerebellar cortex. With excitation-inhibition ratios adapted from in vitro experimental data in the cerebellum granular layer, the model allows reconstructing spatial recoding of sensory and tactile patterns in cerebellum. Granular layer population activity reconstruction was performed with biophysical modeling of fMRI BOLD signals and evoked local field potentials from single neuron and network models implemented in NEURON environment. In this chapter, evoked local field potentials have been reconstructed using biophysical and neuronal mass models interpreting averaged activity and constraining population behavior as observed in experiments. Using neuronal activity and correlating blood flow using the balloon and modified Windkessel model, generated cerebellar granular layer BOLD response. With the focus of relating neural activity to clinical correlations such models help constraining network models and predicting activity-dependent emergent behavior and manifestations. To reverse engineering brain function, cerebellar circuit functions were abstracted into a spiking network based trajectory control model for robotic articulation.

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2017

Journal Article

Asha Vijayan, Chaitanya Nutakki, Dhanush Kumar, Dr. Krishnashree Achuthan, Dr. Bipin G. Nair, and Dr. Shyam Diwakar, “Enabling a freely accessible open source remotely controlled robotic articulator with a neuro-inspired control algorithm”, International Journal of Interactive Mobile Technologies, vol. 13, no. 1, pp. 61-75, 2017.[Abstract]


Internet-enabled technologies for robotics education are gaining importance as online platforms facilitating and promoting skill training. Understanding the use and design of robotics is now introduced at university undergraduate levels, but in developing economies establishing usable hardware and software platforms face several challenges like cost, equipment etc. Remote labs help providing alternatives to some of the challenges. We developed an online laboratory for bioinspired robotics using a low-cost 6 degree-of-freedom robotic articulator with a neuro-inspired controller. Cerebellum-inspired neural network algorithm approximates forward and inverse kinematics for movement coordination. With over 210000 registered users, the remote lab has been perceived as an interactive online learning tool and a practice platform. Direct feedback from 60 students and 100 university teachers indicated that the remote laboratory motivated self-organized learning and was useful as teaching material to aid robotics skill education.

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2017

Book Chapter

Dr. Shyam Diwakar, Medini, C., Nair, M., Parasuram, H., Asha Vijayan, and Dr. Bipin G. Nair, “Computational Neuroscience of Timing, Plasticity and Function in Cerebellum Microcircuits”, in Computational Neurology and Psychiatry, vol. 6, Springer Series in Bio-/Neuroinformatics, 2017, pp. 343–371.[Abstract]


Cerebellum has been known to show homogeneity in circuit organization and hence the “modules” or various circuits in the cerebellum are attributed to the diversity of functions such as timing, pattern recognition, movement planning and dysfunctions such as ataxia related to the cerebellum. Ataxia-like conditions, induced by intrinsic excitability changes, disable spiking or bursts and thereby limit the quanta of downstream information. Understanding timing, plasticity and functional roles of cerebellum involve large-scale and microcircuit reconstructions validating molecular mechanisms in population activity. Using mathematical modelling, we attempted to reconstruct information transmission at the granular layer of the cerebellum, a circuit whose role in dysfunctions remain yet to be fully explored. We have employed spiking models to reconstruct timing roles and detailed biophysical models for extracellular activity and local field population response. The roles of inhibition, induced plasticity and their implications in information transmission were evaluated. Modulatory roles of Golgi inhibition and pattern abstraction via optimal storage were estimated. An abstraction of the granular and Purkinje layer circuit for neurorobotic roles such as pattern recognition and spike encoding via two new methods was developed. Simulations suggest plasticity at cerebellar relays may be an important element of tremendous storage capacity reliable in the learning of coordination of actions, sensorimotor or cognitive, in which the cerebellum participates. More »»

2017

Journal Article

M. Dammalli, Murthy, K. R., Pinto, S. M., Murthy, K. Babu, Nirujogi, R. Sekhar, Madugundu, A. K., Dey, G., Dr. Bipin G. Nair, Gowda, H., and Prasad, T. Subrahmany, “Toward Postgenomics Ophthalmology: A Proteomic Map of the Human Choroid-Retinal Pigment Epithelium Tissue.”, OMICS, vol. 21, no. 2, pp. 114-122, 2017.[Abstract]


Ophthalmology and visual health research have received relatively limited attention from the personalized medicine community, but this trend is rapidly changing. Postgenomics technologies such as proteomics are being utilized to establish a baseline biological variation map of the human eye and related tissues. In this context, the choroid is the vascular layer situated between the outer sclera and the inner retina. The choroidal circulation serves the photoreceptors and retinal pigment epithelium (RPE). The RPE is a layer of cuboidal epithelial cells adjacent to the neurosensory retina and maintains the outer limit of the blood-retina barrier. Abnormal changes in choroid-RPE layers have been associated with age-related macular degeneration. We report here the proteome of the healthy human choroid-RPE complex, using reverse phase liquid chromatography and mass spectrometry-based proteomics. A total of 5309 nonredundant proteins were identified. Functional analysis of the identified proteins further pointed to molecular targets related to protein metabolism, regulation of nucleic acid metabolism, transport, cell growth, and/or maintenance and immune response. The top canonical pathways in which the choroid proteins participated were integrin signaling, mitochondrial dysfunction, regulation of eIF4 and p70S6K signaling, and clathrin-mediated endocytosis signaling. This study illustrates the largest number of proteins identified in human choroid-RPE complex to date and might serve as a valuable resource for future investigations and biomarker discovery in support of postgenomics ophthalmology and precision medicine.

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2017

Journal Article

A. Ma HimaVyshnavi, Anand, C. Lb, Deepak, O. Mc, and P. K. Krishnan Namboori, “Evaluation of colorectal cancer (CRC) epidemiology a pharmacogenomic approach”, Journal of Young Pharmacists, vol. 9, pp. 36-39, 2017.[Abstract]


Background: The population-wise variation in proneness of Colorectal Cancer (CRC) has been studied in the manuscript. A population wise analysis of responsiveness towards colorectal cancer is carried out with genetic, epigenetic, metagenomic and environmental factors associated with APC mutation mainly responsible for CRC among eight different populations. Methods and Material: The APC mutation has been obtained using the 'human gene mutation database-HGMD' and the 'international cancer genome consortium-ICGC' Data Portal. The epigenetic factors affecting colon cancer have been identified through EpiGRAPH tool. The 'human oral microbiome database (HOMD) and 'comparative toxicogenomics database (CTD)' are used to find the metagenomic factors affecting CRC. Results: Variants of APC gene from the selected ethnic classes chosen from Argentina, France, Germany, India, Poland, Romania, UK and USA were characterized, where the chromosome positions 112102966-112177228 are found to be affected. It has been found that among epigenetic factors: chromosome organization, population variation, and evolutionary history are highly promising features for the prediction of DNA methylation. It has been found that consumption of linoleic acid, oleic acid, and lauric acid play a major role in preventing CRC. Conclusions:The chromosome positions 112102966-112177228 are found to be the most prone region for APC mutation. Chromosome organization, population variation, and evolutionary history are highly promising epigenetic features for the prediction of DNA methylation and further mutation. The consumption of spices, coconut oil, fish (in coastal areas), dairy products and reduced intake of red meat may be the reasons for less incidence rate of CRC among the Indian population.

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2017

Journal Article

J. Raveendran, P.E., R., Dr. Ramachandran T., Dr. Bipin G. Nair, and Dr. Satheesh Babu T. G., “Fabrication of a disposable non-enzymatic electrochemical creatinine sensor”, Sensors and Actuators B: Chemical, vol. 243, pp. 589 - 595, 2017.[Abstract]


Abstract A disposable non-enzymatic sensor for creatinine was developed by electrodepositing copper on screen printed carbon electrodes. The sensor was characterized using electrochemical and microscopic techniques. Electrochemical detection of creatinine was carried out in phosphate buffer solution of pH 7.4. The estimation was based on the formation of soluble copper-creatinine complex. The formation of copper-creatinine complex was established using the pseudoperoxidase activity of copper-creatinine complex. The sensor showed a detection limit of 0.0746 μM with a linear range of 6–378 μΜ. The sensor exhibited a stable response to creatinine and found to be free from interference from molecules like urea, glucose, ascorbic acid and dopamine. Real sample analysis was carried out with blood serum.

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2017

Journal Article

C. R. Reshmi, Menon, T., Binoy, A., Dr. Nandita Mishra, Elyas, K. K., and Sujith, A., “Poly(L-lactide-co-caprolactone)/collagen electrospun mat: Potential for wound dressing and controlled drug delivery”, International Journal of Polymeric Materials and Polymeric Biomaterials, vol. 66, no. 13, pp. 645-657, 2017.[Abstract]


Here we report a novel bioactive electrospun mat based on poly(L-lactide-co-caprolactone) (PLLC) and collagen for wound dressing and sustained drug delivery of gentamicin. PLLC/collagen electrospun mat loaded with 10% gentamicin showed bioactivity for 15 days against Gram-positive and Gram-negative bacteria. The in vitro cell culture of 3T3 fibroblasts confirmed that these electrospun mat provide an increased specific interface area and hydrophilicity to enhance cell attachment, proliferation, and migration. The modified PLLC/collagen mat provided an excellent enhancement in properties of antibacterial wound dressings with a minimum in vitro toxicity and high potency for promoting wound healing stages. © 2017 Taylor & Francis.

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2017

Journal Article

D. Barardo, Thornton, D., Thoppil, H., Walsh, M., Sharifi, S., Ferreira, S., Anžič, A., Fernandes, M., Monteiro, P., Grum, T., Cordeiro, R., De-Souza, E. Araújo, Budovsky, A., Araujo, N., Gruber, J., Petrascheck, M., Fraifeld, V. E., Zhavoronkov, A., Moskalev, A., and de Magalhães, J. Pedro, “The DrugAge Database of Aging-Related Drugs.”, Aging Cell, 2017.[Abstract]


Aging is a major worldwide medical challenge. Not surprisingly, identifying drugs and compounds that extend lifespan in model organisms is a growing research area. Here, we present DrugAge (http://genomics.senescence.info/drugs/), a curated database of lifespan-extending drugs and compounds. At the time of writing, DrugAge contains 1316 entries featuring 418 different compounds from studies across 27 model organisms, including worms, flies, yeast and mice. Data were manually curated from 324 publications. Using drug-gene interaction data, we also performed a functional enrichment analysis of targets of lifespan-extending drugs. Enriched terms include various functional categories related to glutathione and antioxidant activity, ion transport and metabolic processes. In addition, we found a modest but significant overlap between targets of lifespan-extending drugs and known aging-related genes, suggesting that some but not most aging-related pathways have been targeted pharmacologically in longevity studies. DrugAge is freely available online for the scientific community and will be an important resource for biogerontologists.

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2017

Journal Article

D. Sunilkumar, Bose, C., Shaji, S. K., Nanjan Pandurangan, Geetha B Kumar, Asoke Banerji, and Dr. Bipin G. Nair, “Coconut Shell Derived Bioactive Compound Oxyresveratrol Mediates Regulation Of Matrix Metalloproteinase 9”, International Journal of Pharma and Bio Sciences, vol. 8, no. 1, pp. 202 – 210, 2017.

2017

Patent

E. Schäfer and Dr. Bipin G. Nair, “Cartridge connection method for precise delivery of liquid”, 2017.

2017

Patent

Dr. Bipin G. Nair, “Non- Enzymatic Glucose Sensor. ”, 2017.

2017

Patent

Dr. Bipin G. Nair, “Dual Microcontroller-based Liquid Infusion Device”, 2017.

2017

Journal Article

V. Ozdemir, Kickbusch, I., and Coşkun, Y., “Rethinking the right to work for refugee Syrian healthcare professionals: a call for innovation in global governance.”, BMJ, vol. 357, p. j2710, 2017.

2017

Journal Article

N. Velusamy, Binoy, A., Bobba, K. Naidu, Nedungadi, D., Dr. Nandita Mishra, and Bhuniya, S., “A bioorthogonal fluorescent probe for mitochondrial hydrogen sulfide: new strategy for cancer cell labeling”, Chem Commun (Camb)., vol. 53, no. 62, pp. 8802-8805, 2017.[Abstract]


We report the application of a chemodosimeter {'}turn on{'} fluorescent probe for detecting endogenous H2S formation in cancer cells. Mito-HS showed a bathochromic shift in the UV-vis-absorption spectrum from 355 nm to 395 nm in the presence of H2S. Furthermore{,} it showed an [similar]43-fold fluorescence enhancement at [small lambda]em = 450 nm in the presence of H2S (200 [small mu ]M). The cancer cell-specific fluorescence imaging reveals that Mito-HS has the ability to distinguish cancer cells from normal cells based on the level of endogenous H2S formation. In due course{,} Mito-HS would be a powerful cancer biomarker based on its ability to estimate endogenous H2S formation in living cells.

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2017

Journal Article

J. Advani, Subbannayya, Y., Patel, K., Khan, A. Ahmad, Patil, A. H., Jain, A. P., Solanki, H. S., Radhakrishnan, A., Pinto, S. M., Sahasrabuddhe, N. A., Thomas, J. K., Mathur, P. P., Dr. Bipin G. Nair, Chang, X., Prasad, T. S. Keshava, Sidransky, D., Gowda, H., and Chatterjee, A., “Long-Term Cigarette Smoke Exposure and Changes in MiRNA Expression and Proteome in Non-Small-Cell Lung Cancer”, OMICS, vol. 21, no. 7, pp. 390-403, 2017.[Abstract]


Chronic exposure to cigarette smoke markedly increases the risk for lung cancer. Regulation of gene expression at the post-transcriptional level by miRNAs influences a variety of cancer-related interactomes. Yet, relatively little is known on the effects of long-term cigarette smoke exposure on miRNA expression and gene regulation. NCI-H292 (H292) is a cell line sensitive to cigarette smoke with mucoepidermoid characteristics in culture. We report, in this study, original observations on long-term (12 months) cigarette smoke effects in the H292 cell line, using microarray-based miRNA expression profiling, and stable isotopic labeling with amino acids in cell culture-based quantitative proteomic analysis. We identified 112 upregulated and 147 downregulated miRNAs (by twofold) in cigarette smoke-treated H292 cells. The liquid chromatography-tandem mass spectrometry analysis identified 3,959 proteins, of which, 303 proteins were overexpressed and 112 proteins downregulated (by twofold). We observed 39 miRNA target pairs (proven targets) that were differentially expressed in response to chronic cigarette smoke exposure. Gene ontology analysis of the target proteins revealed enrichment of proteins in biological processes driving metabolism, cell communication, and nucleic acid metabolism. Pathway analysis revealed the enrichment of phagosome maturation, antigen presentation pathway, nuclear factor erythroid 2-related factor 2-mediated oxidative stress response, and cholesterol biosynthesis pathways in cigarette smoke-exposed cells. In conclusion, this report makes an important contribution to knowledge on molecular changes in a lung cell line in response to long term cigarette smoke exposure. The findings might inform future strategies for drug target, biomarker and diagnostics innovation in lung cancer, and clinical oncology. These observations also call for further research on the extent to which continuing or stopping cigarette smoking in patients diagnosed with lung cancer translates into molecular and clinical outcomes.

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2017

Journal Article

J. Raveendran, Krishnan, R. G., Dr. Bipin G. Nair, and Dr. Satheesh Babu T. G., “Voltammetric determination of ascorbic acid by using a disposable screen printed electrode modified with Cu(OH)2 nanorods”, Microchimica Acta, pp. 1-7, 2017.[Abstract]


The authors describe a disposable non-enzymatic sensor for ascorbic acid (AA) that was obtained by modifying a screen printed electrode (SPE) with Cu(OH)2 nanorods (NRs). The NRs were synthesized by a wet chemical process which involves sequential addition of NH3 and NaOH to CuSO4 solution. NR formation was confirmed by thermogravimetric, spectroscopic, microscopic, and diffraction studies. The Cu(OH)2 NRs were mixed with carbon ink and printed onto an SPE. Electrochemical detection of AA was carried out at pH 7.4, at a typical voltage as low as 0 mV versus saturated calomel electrode with a scan rate of 100 mV/s, and is assumed to involve the chemical reduction of Cu(II) by AA followed by electrochemical oxidation of Cu(I). The sensor has a linear response in the 0.0125 to 10 mΜ AA concentration range. Response to AA is free from interference by urea, glucose, uric acid, dopamine, metal ions such as Fe2+, Zn2+ and Ni2+, NaCl, KCl and ethanol. It was applied to the determination of AA in a vitamin C tablet and in urine. [Figure not available: see fulltext.] © 2017 Springer-Verlag GmbH Austria

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