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., Dr. Raja Biswas, 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

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 (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 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 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 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 μM. Taken together, these results provide an understanding 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

S. E. Sajeevan, Chatterjee, M., Paul, V., Baranwal, G., Kumar, V. A., Bose, C., Banerji, A., Nair, B. G., Prasanth, B. P., and Biswas, R., “Impregnation of catheters with anacardic acid from cashew nut shell prevents Staphylococcus aureus biofilm development.”, J Appl Microbiol, vol. 125, no. 5, pp. 1286-1295, 2018.[Abstract]


AIM: The effect of anacardic acid impregnation on catheter surfaces for the prevention of Staphylococcus aureus attachments and biofilm formations were evaluated.

METHODS AND RESULTS: Silicon catheter tubes were impregnated using different concentrations of anacardic acids (0·002-0·25%). Anacardic acids are antibacterial phenolic lipids from cashew nut (Anacardium occidentale) shell oil. Anacardic acid-impregnated silicon catheters revealed no significant haemolytic activity and were cytocompatible against fibroblast cell line (L929). Sustained release of anacardic acids was observed for 4 days. Anacardic acid-impregnated silicon catheters efficiently inhibited S. aureus colonization and the biofilm formation on its surface. The in vivo antibiofilm activity of anacardic acid-impregnated catheters was tested in an intraperitoneal catheter-associated medaka fish infection model. Significant reduction in S. aureus colonization on anacardic acid-impregnated catheter tubes was observed.

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

SIGNIFICANCE AND IMPACT OF THE STUDY: This study opens new directions for designing antimicrobial phytochemical-coated surfaces with ideal antibiofilm properties and could be of great interest for biomedical research scientists.

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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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2018

Journal Article

V. Ozdemir, “The Dark Side of the Moon: The Internet of Things, Industry 4.0, and The Quantified Planet.”, OMICS, 2018.[Abstract]


Industry 4.0 is an innovation framework launched initially at the 2011 Hanover Fair in Germany. It is premised on extreme digital connectivity to build smart factories and deliver extreme automation in science and society. Industry 4.0 has recently scaled up worldwide beyond Germany and Europe. Industry 4.0 employs the Internet of Things (IoT) to connect, communicate, and collect big data from embedded sensors in living and inanimate objects. When we add artificial intelligence (AI) powered real-time data analyses to the IoT, a state of worldwide extreme connectivity, or "The Quantified Planet," is created. By its focus on connectivity at a systems scale, the Industry 4.0 is of interest to health products manufacturing and service automation in medicine, biology, ecology, and society. But there are also unchecked assumptions. This article poses a question that has so far been neglected in the Industry 4.0 innovation echo chamber. Is it always good to have pervasive connectivity and extreme integration to the point that "everything is connected to everything else"? For example, extreme connectivity creates an "All Your Eggs in One Basket" problem and thus potential for complete network collapse in a domino effect when a component in a highly integrated system fails. Digital connectivity cultivates a fertile ground for new social and political power structures for authoritarian governance (i.e., a worrisome state of "pansurveillance") by one person in total control of knowledge networks in science and society, directly or through connected proxies. Filter bubbles created by extreme digital connectivity and AI can result in compressed foresight, lackluster innovation, and monocultures in laboratory life. The way forward is to harness Industry 4.0 and connectivity without such digital network toxicity. Similar to fire exits in skyscrapers and other built environments, designing innovation systems with extreme connectivity demands that we also think of "exit plans" from the omnipresent digital networks, IoT, and The Quantified Planet-both for safety and sustained creativity. Finally, the relationship between new technologies and society is far from being a simple one-directional interaction; it is not the technologies that cause social disruption. On the contrary, it is the value-loaded decisions made by individuals, organizations, and other social actors that shape sociotechnical change. Recognizing the latter narrative is important because it informs how we do science and can best respond to uncertainties and opaque assumptions embedded in emerging technologies such as AI, IoT, and Industry 4.0.

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2018

Journal Article

P. Ponnachan, Vinod, V., Pullanhi, U., Varma, P., Singh, S., Biswas, R., and Kumar, A., “Antifungal Activity of Octenidine Dihydrochloride and Ultraviolet-C light against Multidrug-Resistant Candida auris.”, J Hosp Infect, 2018.[Abstract]


Outbreaks due to multidrug-resistant Candida auris have emerged as a large threat to modern medicine. Since skin colonization and environmental contamination have been identified as a precursor for outbreaks, we evaluated the antifungal activity of ultraviolet-C light using mercury vapor lamp with a peak emission of 254±2 nm and octenidine dihydrochloride against C. auris clinical isolates. Octenidine dihydrochloride was found effective at significantly lower concentrations (0.00005-0.0004%) than those currently used in the clinical setting (0.05% to 0.1%). Scanning electron microscopy images show destruction of the organism within 6 hours of exposure to 0.0005% octenidine dihydrochloride. Ultraviolet-C light could kill all C. auris with 15 minutes exposure.

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2018

Journal Article

R. Rashmi, Nedungadi, D., Podder, A., Dr. Nandita Mishra, and Bhuniya, S., “Monitoring of topoisomerase (I) inhibitor camptothecin release from endogenous redox-stimulated GO-polymer hybrid carrier”, Journal of Photochemistry and Photobiology B: Biology, vol. 189, pp. 14-20, 2018.[Abstract]


We have developed endogenous redox-responsive polymer conjugated GO-based hybrid nanomaterials (GO-PEGssFol-CPT) for delivery of anticancer drug camptothecin (CPT) to the cancer cells. The synthesized intermediate (PEGFol) and CPT loaded GO- PEGFol were characterized using Fourier transform infrared spectroscopy (FTIR) and H NMR. The morphological feature changes of TEM and AFM images have confirmed the loading of CPT on the nanocarrier and its release from the nanocarrier. The amount of CPT was loaded was found to be 14.2%. The extent of camptothecin (CPT) release from GO-BiotinPVA-CPT in the presence of different concentrations of glutathione (GSH) was monitored with the increase in the fluorescence intensity at λ 438 nm and UV-Vis absorbance at 366 nm. The time-dependent camptothecin (CPT) release was monitored in the presence of GSH. It was noticed that CPT was completely released from GO-PEGssFol-CPT within 45 min. This release process is free from interference by other ubiquitous analytes in the living system. The constant fluorescence intensity of GO-PEGssFol-CPT against acidic pH indicated that CPT would not be released in the extracellular region of cancer cells. Therefore, such delivery system could be used to prevent unwanted cytotoxicity to the healthy cells. The GO-PEGssFol-CPT showed higher antiproliferative activity against cervical cancer cells compared to the CPT. Thus, GO-PEGssFol-CPT can be a new material to deliver the anticancer drug to the target tumor region.

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2018

Journal Article

M. Younis Bhat, Solanki, H. S., Advani, J., Khan, A. Ahmad, Prasad, T. S. Keshava, Gowda, H., Thiyagarajan, S., and Chatterjee, A., “Comprehensive network map of interferon gamma signaling.”, J Cell Commun Signal, 2018.[Abstract]


Interferon gamma (IFN-γ), is a cytokine, which is an important regulator of host defense system by mediating both innate and adaptive immune responses. IFN-γ signaling is primarily associated with inflammation and cell-mediated immune responses. IFN-γ is also represented as antitumor cytokine which facilitates immunosurveillance in tumor cells. In addition, IFN-γ mediated signaling also elicits pro-tumorigenic transformations and promotes tumor progression. Impact of IFN-γ signaling in mammalian cells has been widely studied which indicate that IFN-γ orchestrates distinct cellular functions including immunomodulation, leukocyte trafficking, apoptosis, anti-microbial, and both anti- and pro-tumorigenic role. However, a detailed network of IFN-γ signaling pathway is currently lacking. Therefore, we systematically curated the literature information pertaining to IFN-γ signaling and develop a comprehensive signaling network to facilitate better understanding of IFN-γ mediated signaling. A total of 124 proteins were catalogued that were experimentally proven to be involved in IFN-γ signaling cascade. These 124 proteins were found to participate in 81 protein-protein interactions, 94 post-translational modifications, 20 translocation events, 54 activation/inhibiton reactions. Further, 236 differential expressed genes were also documented in IFN-γ mediated signaling. IFN-γ signaling pathway is made freely available to scientific audience through NetPath at ( http://www.netpath.org/pathways?path_id=NetPath_32 ). We believe that documentation of reactions pertaining to IFN-γ signaling and development of pathway map will facilitate further research in IFN-γ associated human diseases including cancer.

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2018

Journal Article

J. Advani, Verma, R., Chatterjee, O., Balaya, R. Devasahaya, Najar, M. Altaf, Ravishankara, N., Suresh, S., Pachori, P. Kumar, Gupta, U. D., Pinto, S. M., Chauhan, D. S., Tripathy, S. Prasad, Gowda, H., and Prasad, T. S. Keshava, “Rise of Clinical Microbial Proteogenomics: A Multiomics Approach to Nontuberculous Mycobacterium-The Case of Mycobacterium abscessus UC22.”, OMICS, 2018.[Abstract]


Nontuberculous mycobacterial (NTM) species present a major challenge for global health with serious clinical manifestations ranging from pulmonary to skin infections. Multiomics research and its applications toward clinical microbial proteogenomics offer veritable potentials in this context. For example, the Mycobacterium abscessus, a highly pathogenic NTM, causes bronchopulmonary infection and chronic pulmonary disease. The rough variant of the M. abscessus UC22 strain is extremely virulent and causes lung upper lobe fibrocavitary disease. Although several whole-genome next-generation sequencing studies have characterized the genes in the smooth variant of M. abscessus, a reference genome sequence for the rough variant was generated only recently and calls for further clinical applications. We carried out whole-genome sequencing and proteomic analysis for a clinical isolate of M. abscessus UC22 strain obtained from a pulmonary tuberculosis patient. We identified 5506 single-nucleotide variations (SNVs), 63 insertions, and 76 deletions compared with the reference genome. Using a high-resolution LC-MS/MS-based approach (liquid chromatography tandem mass spectrometry), we obtained protein coding evidence for 3601 proteins, representing 71% of the total predicted genes in this genome. Application of proteogenomic approach further revealed seven novel protein-coding genes and enabled refinement of six computationally derived gene models. We also identified 30 variant peptides corresponding to 16 SNVs known to be associated with drug resistance. These new observations offer promise for clinical applications of microbial proteogenomics and next-generation sequencing, and provide a resource for future global health applications for NTM species.

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2018

Patent

S. V. Nair, Chandran, P., and Dr. Bipin G. Nair, “Detergent compatible assay for protein estimation”, U.S. Patent 2018410128522018.

2018

Patent

S. Pal, Dr. Bipin G. Nair, Madhavan, A., Pradeesh Babu, Amrita Salim, P., C., Stanely, J., and Babu, S., “Methods and devices for detecting antimicrobial resistant bacteria using bacteriophages”, U.S. Patent 2017410206692018.

2018

Conference Paper

V. S. Raj, Stanley, J., and Satheeshbabu, T. G., “Fabrication of a Configurable Multi-Potentiostat for LOC Applications”, in Materials Today: Proceedings, 2018, vol. 5, pp. 16732-16739.[Abstract]


This paper describes the development of a portable, cost effective reconfigurable multi-analyte detection electronics meter module for Lab-on-a-chip applications. A low costpotentiostat(LMP91000) was used as the analog front end (AFE) in this work. The advanced core microcontroller from Microchip (PIC16LF1783) was used for controlling the different operation of the meter. The current obtained by amperometrictechniques was calibrated and displayed on a graphical LCD and alsodisplayed on a smart phone using Bluetooth technology. © 2017 Elsevier Ltd.

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2018

Journal Article

M. Bayram, Aşar, R., and Ozdemir, V., “Is Space the New Frontier for Omics? Mars-Omics, Planetary Science, and the Next-Generation Technology Futurists.”, OMICS, vol. 22, no. 11, pp. 696-699, 2018.[Abstract]


Omics technologies are key to research and innovation in human health, food and nutrition, drugs, agriculture, and ecology research. Yet, the actual scope of applications is much broader. One emerging possibility is planetary science driven in part by current debates on and possibilities for travel to Mars. In July 2018, radar evidence has suggested the presence of subglacial liquid water in a 20-km-wide zone, likely a saltwater lake, in the Planum Australe region in the south pole of Mars. If confirmed, this will be a promising place to search for microbial life on the red planet. Meanwhile, existential threats to life on earth such as climate change are bolstering the current interests by spacefaring nations for manned long-term space travel to other planets. A new global space industry is also on the rise; Mars-related technology innovation could potentially allow for rapid Earth-to-Earth transport as well, for example, in times of humanitarian and ecological crisis. Against this overarching context, we coin and define here the new concept of "Mars-omics": the systems level study of how travel to and being on Mars affect human health, and how human presence on Mars impacts the life forms that might already be there, through changes such as space agriculture and other planetary transformations in Mars. Additionally, Mars-omics calls for new ways of thinking about scientific uncertainty and technology futures in such highly novel contexts. For example, how shall we frame scientific uncertainty when extrapolation of scientific unknowns across the planets is vastly difficult, nonlinear, and complex? Is uncertainty an accident or integral part of emerging technologies? These questions are important for achieving new relevance for and future progress in omics system science applications in planetary science and space explorations. In summary, this article suggests that omics has relevance in contexts beyond those on planet Earth. Moreover, past omics applications such as precision medicine may need to be reconceptualized in future novel settings, such as long-term space travel. We conclude the article with the key tenets of next-generation futurists in a context of Mars-omics. Space (still) is the final frontier for humans, medicine, engineering, and omics.

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2018

Journal Article

J. Advani, Sharma, K., Verma, R., Chatterjee, O., Solanki, H. S., Sharma, A., Varma, S., Modi, M., Ray, P., Sharma, M., Dhillion, M. S., Pandey, A., Gowda, H., and Prasad, T. S. Keshava, “Data on whole genome sequencing of extrapulmonary tuberculosis clinical isolates from India.”, Data Brief, vol. 20, pp. 617-622, 2018.[Abstract]


This article describes the whole genome sequencing data from 5 extrapulmonary tuberculosis clinical isolates. The whole genome sequencing was carried out on Illumina MiSeq platform to identify single nucleotide variations (SNVs) associated with drug resistance. A total of 214 SNVs in the coding and promoter regions were identified in the whole genome sequencing analysis. Among the identified SNVs, 18 SNVs were identified in genes known to be associated with first and second line drug resistance. The data is related to the research article "Whole genome sequencing of isolates from extrapulmonary sites" (Sharma et al., 2017) [1].

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2018

Journal Article

M. N, P, C., j, H., Dr. Shyam Diwakar, and Dr. Bipin G. Nair, “Mining Inter-Relationships in Online Scientific Articles and its Visualization: Natural Language Processing for Systems Biology Modeling”, International Journal of Online Engineering (iJOE) (accepted), 2018.

2018

Book

Dr. Shyam Diwakar, Dr. Bipin G. Nair, and Dr. Krishnashree Achuthan, Adoption of Virtual Laboratories in India, Learning Assessments and Roles of ICT Skill Learning Tools, Arthur Tatnall, Springer, accepted. 2018.

2018

Journal Article

S. Chattopadhyay, Chi, P. B., Minin, V. N., Berg, D. E., and Sokurenko, E. V., “Recombination-independent rapid convergent evolution of the gastric pathogen Helicobacter pylori.”, BMC Genomics, vol. 19, no. 1, p. 835, 2018.[Abstract]


BACKGROUND: Helicobacter pylori is a human stomach pathogen, naturally-competent for DNA uptake, and prone to homologous recombination. Extensive homoplasy (i.e., phylogenetically-unlinked identical variations) observed in H. pylori genes is considered a hallmark of such recombination. However, H. pylori also exhibits a high mutation rate. The relative adaptive role of homologous recombination and mutation in species diversity is a highly-debated issue in biology. Recombination results in homoplasy. While convergent mutation can also account for homoplasy, its contribution is thought to be minor. We demonstrate here that, contrary to dogma, convergent mutation is a key contributor to Helicobacter pylori homoplasy, potentially driven by adaptive evolution of proteins.

RESULTS: Our present genome-wide analysis shows that homoplastic nonsynonymous (amino acid replacement) changes are not typically accompanied by homoplastic synonymous (silent) variations. Moreover, the majority of the codon positions with homoplastic nonsynonymous changes also contain different (i.e. non-homoplastic) nonsynonymous changes arising from mutation only. This indicates that, to a considerable extent, nonsynonymous homoplasy is due to convergent mutations. High mutation rate or limited availability of evolvable sites cannot explain this excessive convergence, as suggested by our simulation studies. Rather, the genes with convergent mutations are overrepresented in distinct functional categories, suggesting possible selective responses to conditions such as distinct micro-niches in single hosts, and to differences in host genotype, physiology, habitat and diet.

CONCLUSIONS: We propose that mutational convergence is a key player in H. pylori's adaptation and extraordinary persistence in human hosts. High frequency of mutational convergence could be due to saturation of evolvable sites capable of responding to selection pressures, while the number of mutable residues is far from saturation. We anticipate a similar scenario of mutational vs. recombinational genome dynamics or plasticity for other naturally competent microbes where strong positive selection could favor frequent convergent mutations in adaptive protein evolution.

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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 »»

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