Year of Publication Publication Type Title

2019

Journal Article

Melethadathil N., Chellaiah P., Heringa J., 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) , vol. 15, no. 2, 2019.[Abstract]


With the rapid growth in the numbers of scientific publications in domains such as neuroscience and medicine, visually interlinking documents in online databases such as PubMed with the purpose of indicating the context of a query results can improve the multi-disciplinary relevance of the search results. Translational medicine and systems biology rely on studies relating basic sciences to applications, often going through multiple disciplinary domains. This paper focuses on the design and development of a new scientific document visualization platform, which allows inferring translational aspects in biosciences within published articles using machine learning and natural language processing (NLP) methods. From online databases, this software platform effectively extracted relationship connections between multiple sub-domains within neuroscience derived from abstracts related to user query. In our current implementation, the document visualization platform employs two clustering algorithms namely Suffix Tree Clustering (STC) and LINGO. Clustering quality was improved by mapping top-ranked cluster labels derived from an UMLS-Metathesaurus using a scoring function. To avoid non-clustered documents, an iterative scheme, called auto-clustering was developed and this allowed mapping previously uncategorized documents during the initial grouping process to relevant clusters. The efficacy of this document clustering and visualization platform was evaluated by expert-based validation of clustering results obtained with unique search terms. Compared to normal clustering, auto-clustering demonstrated better efficacy by generating larger numbers of unique and relevant cluster labels. Using this implementation, a Parkinson’s disease systems theory model was developed and studies based on user queries related to neuroscience and oncology have been showcased as applications.

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2019

Conference Paper

Asha R. Pai, Parvathy,, and Dr. Bipin G. Nair, “Biosynthesis of ZnO@Ag from Gracinia Cambogia linn and its structural Characterisation using XPS (Poster)”, in 5th International conference on Nanoscience and Nanotechnology-ICONN 2019, 2019.

2019

Journal Article

Asha R. Pai and Dr. Bipin G. Nair, “Synthesis and characterisation of Sb-doped ZrO2 and TiO2 nanoparticles (InPress)”, International Journal of Microstructure and Materials Properties, 2019.

2019

Journal Article

C. Nutakki, Radhakrishnan, S., Dr. Bipin G. Nair, and Dr. Shyam Diwakar, “Modeling fMRI BOLD signals and temporal mismatches in the cerebellar cortex”, CSI Transactions on ICT, 2019.[Abstract]


To understand brain activity relating neurons to circuits to learning and behavior, we explored a bottom-up computational reconstruction of population signals arising from cerebellum granular layer. As a first implementation, using bio-realistic computational models of cerebellum granule cell, in vivo spike train patterns were computed and then translated into functional Magnetic Resonance Imaging, Blood Oxygen-Level Dependent (BOLD) signals. The BOLD response was generated from averaged activity arising from center-surround organization modeled by using excitatory-inhibitory ratios related to experimental data. The averaged responses were converted to BOLD signals using the balloon and modified Windkessel models. Although both models generated BOLD responses corresponding to neural activity, the temporal mismatch was attributed to the response by the delayed compliance parameter in the Windkessel model. The modeling suggests that experimental variability observed in the cerebellar micro-zones could be related to compliance chances, activation patterns and number of neurons. Although detailed neuro-vasculature information was not modeled, the advantage in this methodology is that cerebellar cortex may allow seemingly linear transformations of underlying spiking that could be then used to validate network reconstructions.

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2019

Journal Article

K. Naidu Bobba, Anupama Binoy, Koo, S., Nedungadi, D., Podder, A., Sharma, A., Dr. Nandita Mishra, Kim, J. Seung, and Bhuniya, S., “Direct readout protonophore induced selective uncoupling and dysfunction of individual mitochondria within cancer cells”, Chemical Communications, vol. 55, no. 45, pp. 6429-6432, 2019.[Abstract]


Concurrently, manipulation of mitochondrial activity and its monitoring have enormous significance in cancer therapy and diagnosis. In this context, a fluorescent probe MitoDP has been developed for validating H2S mediated protonophore (2,4-dinitrophenol, DNP) induced mitochondrial membrane potential change, ROS formation and ATP depletion in cancer cells. The extent of protonophore activation for mitochondrial dysfunction is monitored through fluorescence signalling at 450 nm. The current study provides a proof for the concept of endogenous H2S-mediated controlled and spatial release of bioactive agents, or toxins specifically in mitochondria of cancer cells.

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2019

Journal Article

Divya Nair, Muralidharan Vanuopadath, Balasubramanian, A., Iyer, A., Ganesh, S., Anil, A. Nair, Vikraman, V., Pillai, P., Bose, C., Dr. Bipin G. Nair, Pai, J. Gopalakris, and Nair, S. Sadasivan, “Phlorotannins from Padina tetrastromatica: structural characterisation and functional studies”, Journal of Applied Phycology, pp. 1–11, 2019.[Abstract]


In this study, LC–MS/MS-based structural characterisation of phlorotannins from Padina tetrastromatica, a marine brown macroalga collected from South-West coastal region of Kerala, and its bioactivities are presented. The tandem mass spectrometric data revealed a series of phlorotannins with degree of polymerisation ranging from 2 to 18. The characteristic neutral loss of tandem mass spectra further confirmed that these molecules belong to fucophlorethol class of phlorotannins. DPPH assay of the HPLC-purified, phlorotannin-enriched fraction possesses significant free radical-scavenging activity. Cell viability assay indicated that phlorotannin concentration ranging from 1.5 to 50.0 μg mL−1 is non-toxic to THP-1 cell lines. Anti-inflammatory assay performed through gelatin zymography confirmed that phlorotannins ameliorated high-glucose-induced pro-MMP-9 expression in a dose-dependent manner whereas the level of pro-MMP-2 remains unaltered. The antimicrobial assays carried out using both the crude and HPLC-purified phlorotannin fraction showed its anti-MRSA potential.

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2019

Journal Article

K. Gondkar, Patel, K., Krishnappa, S., Patil, A., Dr. Bipin G. Nair, Meenakshisundaram, G., Tan, T. Zea, and Kumar, P., “E74 like ETS transcription factor 3 (ELF3) is a negative regulator of epithelial- mesenchymal transition in bladder carcinoma”, Cancer Biomarkers, pp. 1-10, 2019.[Abstract]


Background: Transcription factors are commonly deregulated in various cancers. Here, we evaluated role of ELF3 in pathogenesis of bladder carcinoma (BCa). Materials and methods: We confirmed ELF3 expression pattern in BCa cell lines using western blot; and in different grades of tumors using Immunohistochemistry. Cell invasion assay was employed to demonstrate potential role of ELF3 in EMT. Results and conclusion: ELF3 showed selective expression in low-grade cell lines and tumor tissues. Overexpression of ELF3 in mesenchymal cell line UMUC3 resulted in reduced invasion and decreased expression of mesenchymal markers. We observe association of low ELF3 expression with increased risk and overall poor survival using publicly available data. ELF3-modulated reversal of EMT might be a useful strategy in the treatment of bladder cancer.

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2019

Journal Article

S. SK, D, S., K, M., G, K., and Dr. Bipin G. Nair, “Analysis of microarray data for identification of key microRNAs signature in glioblastoma multiforme”, Oncology Letters, 2019.

2019

Journal Article

Anupama Binoy, Nedungadi, D., Katiyar, N., Chinchu Bose, Dr. Sahadev Shankarappa, Dr. Bipin G. Nair, and Dr. Nandita Mishra, “Plumbagin induces paraptosis in cancer cells by disrupting the sulfhydryl homeostasis and proteasomal function”, Chemico-Biological Interactions, p. 108733, 2019.[Abstract]


Plumbagin (PLB) is an active secondary metabolite extracted from the roots of Plumbago rosea. In this study, we report that plumbagin effectively induces paraptosis by triggering extensive cytoplasmic vacuolation followed by cell death in triple negative breast cancer cells (MDA-MB-231), cervical cancer cells (HeLa) and non-small lung cancer cells (A549) but not in normal lung fibroblast cells (WI-38). The vacuoles originated from the dilation of the endoplasmic reticulum (ER) and were found to be empty. The cell death induced by plumbagin was neither apoptotic nor autophagic. Plumbagin induced ER stress mainly by inhibiting the chymotrypsin-like activity of 26S proteasome as also evident from the accumulation of polyubiquitinated proteins. The vacuolation and cell death were found to be independent of reactive oxygen species generation but was effectively inhibited by thiol antioxidant suggesting that plumbagin could modify the sulfur homeostasis in the cellular milieu. Plumbagin also resulted in a decrease in mitochondrial membrane potential eventually decreasing the ATP production. This is the first study to show that Plumbagin induces paraptosis through proteasome inhibition and disruption of sulfhydryl homeostasis and thus further opens up the lead molecule to potential therapeutic strategies for apoptosis-resistant cancers.

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2019

Journal Article

A. Choorakott Pushkaran, Vinod, V., Muralidharan Vanuopadath, Nair, S. Sadasivan, Nair, S. V., Vasudevan, A. Kumar, Biswas, R., and Mohan, C. Gopi, “Combination of Repurposed Drug Diosmin with Amoxicillin-Clavulanic acid Causes Synergistic Inhibition of Mycobacterial Growth”, Scientific reports, vol. 9, no. 1, p. 6800, 2019.[Abstract]


Effective therapeutic regimens for the treatment of tuberculosis (TB) are limited. They are comprised of multiple drugs that inhibit the essential cellular pathways in Mycobacterium tuberculosis (Mtb). The present study investigates an approach which enables a combination of Amoxicillin-Clavulanic acid (AMC) and a repurposed drug for its synergistic effect towards TB treatment. We identified Diosmin (DIO), by targeting the active site residues of L,D-transpeptidase (Ldt) enzymes involved in Mtb cell wall biosynthesis by using a structure-based drug design method. DIO is rapidly converted into aglycone form Diosmetin (DMT) after oral administration. Binding of DIO or DMT towards Ldt enzymes was studied using molecular docking and bioassay techniques. Combination of DIO (or DMT) and AMC exhibited higher mycobactericidal activity against Mycobacterium marinum as compared to individual drugs. Scanning electron microscopy study of M. marinum treated with AMC-DIO and AMC-DMT showed marked cellular leakage. M. marinum infected Drosophila melanogaster fly model showed an increased fly survival of ~60% upon treatment with a combination of AMC and DIO (or DMT). Finally, the enhanced in vitro antimicrobial activity of AMC-DIO was validated against Mtb H37Ra and a MDR clinical isolate. Our results demonstrate the potential for AMC and DIO (or DMT) as a synergistic combination for the treatment of TB.

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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]


<p>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.</p>

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2018

Journal Article

C. Porayath, Salim, A., Veedu, A. Palillam, Babu, P., Nair, B., Madhavan, A., and Pal, S., “Characterization of the bacteriophages binding to human matrix molecules.”, Int J Biol Macromol, vol. 110, pp. 608-615, 2018.[Abstract]


<p>Recent literature has suggested a novel symbiotic relationship between bacteriophage and metazoan host that provides antimicrobial defense protecting mucosal surface by binding to host matrix mucin glycoproteins. Here, we isolated and studied different bacteriophages that specifically interact with human extracellular matrix molecules such as fibronectin, gelatin, heparin and demonstrated their potency for protection to host against microbial infections. We showed that subpopulations of bacteriophages that work against clinical isolates of Escherichia coli can bind to pure gelatin, fibronectin and heparin and reduced bacterial load in human colon cell line HT29. The bacteriophages were characterized with respect to their genome sizes, melting curve patterns and host tropism (cross-reactivity with different hosts). Since, the bacteriophages are non-toxic to the host and can effectively reduce bacterial load in HT29 cell line their therapeutic potency against bacterial infection could be explored.</p>

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2018

Journal Article

A. Ahmad Khan, Advani, J., Patel, K., Nanjappa, V., Datta, K. K., Solanki, H. Singh, Kumar, P., Mathur, P. Prakash, Nair, B., Prasad, T. Subrahmany, Chatterjee, A., and Gowda, H., “Chronic Exposure to Cigarette Smoke and Chewing Tobacco Alters Expression of microRNAs in Esophageal Epithelial Cells.”, Microrna, vol. 7, no. 1, pp. 28-37, 2018.[Abstract]


<p><b>BACKGROUND: </b>Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers with high mortality rate. Cigarette smoke and chewing tobacco are well known risk factors associated with ESCC. However, molecular mechanisms associated with development of ESCC among smokers and chewers are poorly understood. MicroRNAs play an important role in regulating physiological and disease processes including esophageal cancer.</p><p><b>OBJECTIVE AND METHODS: </b>In this study, we developed an in vitro model by treating non-neoplastic Het- 1A esophageal cell line with cigarette smoke and chewing tobacco. We carried out miRNA sequencing on Illumina HiSeq 2500 platform and compared miRNA expression pattern across cigarette smoke and chewing tobacco treated Het-1A cells with untreated cells.</p><p><b>RESULTS: </b>We identified and quantified 433 miRNAs in both smoke exposed and chewing tobacco treated cells, of which 13 miRNAs showed significantly altered expression in cigarette smoke exposed cells while 25 miRNAs showed significantly altered expression in chewing tobacco treated cells. In addition, we predicted novel miRNAs from these data-sets. We evaluated miRNAs that showed selective or context dependent expression pattern in cigarette smoke exposed or chewing tobacco treated cells.</p><p><b>CONCLUSION: </b>In this study, we have comprehensively mapped miRNA expression pattern in response to cigarette smoke and chewing tobacco in Het-1A cells. We identified miRNAs that show altered expression in these cell models.</p>

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2018

Conference Paper

V. Amrutha., Prasad Megha, A. Lekshmija, R Anjana, S. Aleena, Dr. Bipin G. Nair, Madhavan, A., and Dr. Sanjay Pal, “Effect of compost derived lytic agents against enteric bacteria in sewage”, in InnovativeStrategies for Sustainable Water Management (ISSWM-2017), Punjab, India. , 2018.

2018

Conference Paper

Pradeesh Babu, S. J. Poornendu, Amrita Salim, Madhavan, A., Dr. Bipin G. Nair, and Dr. Sanjay Pal, “Resazurin based redox dye as an indicator for monitoring wastewater biological activity”, in Innovative Strategies for Sustainable Water Management (ISSWM-2017), Punjab, India, 2018.

2018

Conference Paper

M. Sreejith, A. P. Reghu, K. Anandakrishnan, P. J. Gopika, G. Kuriakose, M. J. Reshma, K. Vishnu, A. Madhavan, Dr. Bipin G. Nair, and Dr. Sanjay Pal, “Screening potential antimicrobial compounds by resazurin dye based viability assay”, in Innovative Strategies for Sustainable Water Management (ISSWM-2017), Punjab, India, 2018.

2018

Journal Article

Vidhya Prakash, H. Sreetha, K. H. Poornima, K. N. Lakshmimol, R. Regma, H. Fathima, T. V. Vishnu, S. Venu, Dr. Bipin G. Nair, and Dr. Sanjay Pal, “Antagonistic Effects of Bacteriocins from Lactobacillus Spp. against Enteric Pathogens”, Pollution Research Paper, vol. 37, pp. 128-134, 2018.[Abstract]


Bacteriocins from lactic acid bacteria (LAB) are natural antimicrobial peptides or proteins with potential applications in food preservation and healthcare. The study aimed at screening and characterization of bacteriocins from the secretome of five Lactobacillus strains. We were able to screen the antagonistic potential of two strains, L. fermentum and L. casei 335 against the multidrug resistant pathogens, Escherichia coli MDR (multidrug resistant) and Salmonella typhi isolated from sewage. Different dialysate fractions of the Lactobacillus strains were screened by soft agar diffusion and microtitre inhibition assay. Dialysate fractions from ammonium sulfate precipitate, at 65% (LF 65) and at 90% (LF 90) from L. fermentum were tested. LF60 (40μg/mL) was found to be inhibitory to the growth of E. coli MDR strain. Minimum Inhibitory Concentrations (MIC) against biofilm formation were found to be 40μg/mL for both E. coli MDR and Salmonella typhi, though inhibition was found at sub MIC of 20 μg/mL. Biofilm dispersal inhibition of E. coli MDR and S. typhi demonstrated a percentage inhibition rate of 50%. For initial characterization of the proteome of LAB strains, Tricine SDS-PAGE was performed which yielded a protein band of molecular size of 11 kDa from LF 60 fractions. Gel overlay assay showed an inhibitory effect on growth of E. coli MDR, indicating the presence of bacteriocin activity. Caenorhabditis elegans was employed as a nematode model to study the in vivo protection against E. coli MDR. Significant enhanced survival (91%) of the nematode was observed on treatment with LF 60. The efficacy of these partially purified preparations in inhibiting enteric pathogens showcase a prospective strategy of application of these antimicrobials in food and other environmental applications where cost of purification is of concern.

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2018

Conference Paper

S. Subhash, A. B. Kuruvelil, P. V. Aswathi, K. Deepasree, C. D. Navyamol, Das N. P. V., P. Prasad, Dr. Bipin G. Nair, and Dr. Sanjay Pal, “Screening of nematicidal activities of biocontrol fungi Aspergillus niger and Penicillium oxalicum using C. elegans as model”, in Innovative Strategies for Sustainable Water Management (ISSWM-2017) , Punjab, India. , 2018.

2018

Conference Paper

D. Tharuvana, A. Sundaresh, V. J. Sreelakshmi, A. Das, Dr. Bipin G. Nair, Dr. Sanjay Pal, and Madhavan, A., “Sand and charcoal as matrices for immobilization of phages for wastewater treatment”, in Innovative Strategies for Sustainable Water Management (ISSWM-2017) , Punjab, India. , 2018.

2018

Conference Paper

A. P. Veedu, R. N. Reshma, Dr. Bipin G. Nair, Dr. Sanjay Pal, and A. Madhavan, “Activity of probiotic strains against enteric pathogens”, in Innovative Strategies for Sustainable Water Management (ISSWM-2017) , Punjab,India. , 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., Khan, A. Ahmad, Radhakrishnan, A., Sahasrabuddhe, N. A., Mathur, P. Prakash, Nair, B., Prasad, T. Subrahmany, 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, vol. 7, no. 1, pp. 38-53, 2018.[Abstract]


<p><b>BACKGROUND: </b>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.</p><p><b>OBJECTIVE AND METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSION: </b>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.</p>

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2018

Journal Article

P. Chellaiah, Dr. Bipin G. Nair, K. Achuthan, and Dr. Shyam Diwakar, “Using theme-based narrative construct of images as passwords: Implementation and assessment of remembered sequences”, International Journal of Online Engineering, vol. 13, pp. 77-93, 2018.[Abstract]


With many online engineering platforms such as virtual and remote laboratories designed for young or aged users, user authentication and passwords-based methods are being re-evaluated for tracking usage patterns and security. For ICT-enabled online engineering platforms, image-based humancentric approaches are gaining relevance for access frameworks. With the rubber- hose attacks, increased senior users, many existing systems are vulnerable to many attacks. This paper employs human uniqueness of narrative skills on an image-based password system for online platforms with focus on theme in the password generation process. To generate the secret password, a specially designed computer game was used. We used narrative constructs composed of cartoon image sequences to generate user-speci!c secret key. The durability of generated passwords and the authentication process while assessing the reconstruction process by a potential hacker was verified. For validating use of coerced attacks, under imposed psychological duress, users failed retrieving the password sequence suggesting the reliability as an anti-coercive attack cybersecurity tool. A set of experiments were used to analyze user behavior behind the image-based password system. EEG measurements demonstrated increased activity of " rhythms in F3 and FC5 channel bins and augmented levels of α rhythms in F3 and O1 channels, suggesting users added personalization to authentication more than in alpha-numeric password-based logins.

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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, vol. 12, no. 4, pp. 709-721, 2018.[Abstract]


<p>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.</p>

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2018

Journal Article

D. Nedungadi, Binoy, A., Pandurangan, N., Pal, S., Nair, B. G., and Dr. Nandita Mishra, “6-Shogaol induces caspase-independent paraptosis in cancer cells via proteasomal inhibition”, Experimental Cell Research, 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

J. Haripriyan, Omanakuttan, A., Menon, N. D., Muralidharan Vanuopadath, Nair, S. Sadasivan, Corriden, R., Nair, B. G., Nizet, V., and Kumar, G. B., “Clove Bud Oil Modulates Pathogenicity Phenotypes of the Opportunistic Human Pathogen Pseudomonas aeruginosa.”, Sci Rep, vol. 8, no. 1, p. 3437, 2018.[Abstract]


Earlier studies from our laboratory have demonstrated that clove bud oil (CBO) attenuates expression of certain virulence factors of Pseudomonas aeruginosa PAO1. Here, we probe more deeply into the effect of CBO on four pseudomonal proteases - elastase A, elastase B, protease IV and alkaline protease - each known to play key roles in disease pathogenesis. CBO inhibited the activity of these proteases present in the bacterial culture supernatant. Zymography studies indicated that these proteases can activate host matrix metalloproteases (MMPs) to establish infection, through conversion of pro-MMP-2 to active MMP-2. PAO1 is a predominant pathogen in burn wound infections and we show the modulatory effect of CBO on MMPs in an in vitro model of burn injury. Furthermore, CBO induced dose-dependent neutrophil extracellular trap formation in human neutrophils. CBO also increased the survival of C. elegans infected with PAO1, establishing an anti-infective role in a whole animal model of pathogenesis. LC-MS/MS analysis indicated that CBO treatment elicited a significant reduction of signalling molecules (Acyl-Homoserine-Lactone) involved in quorum sensing regulation. Our observations demonstrate that CBO attenuates key virulence mechanisms of this important human pathogen, while concomitantly enhancing host innate immunomodulatory functions, with potential implications for topical therapy against antibiotic-resistant infections.

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2018

Journal Article

V. Özdemir and Springer, S., “What does "Diversity" Mean for Public Engagement in Science? A New Metric for Innovation Ecosystem Diversity.”, OMICS, vol. 22, no. 3, pp. 184-189, 2018.[Abstract]


<p>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, the Frame Diversity Index (FDI), based on the hitherto neglected diversities in knowledge framing. 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.</p>

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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, vol. 22, no. 3, pp. 223-235, 2018.[Abstract]


<p>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.</p>

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2018

Journal Article

Parasuram H., Dr. Bipin G. Nair, Naldi G., D’Angelo E., 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, Krishna Chaitanya Medini, Asha Vijayan, and Arathi G. Rajendran, “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]


<p>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.</p>

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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., Nair, B., 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]


<p>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.</p>

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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., Nair, B., 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, vol. 19, no. 9, pp. 773-785, 2018.[Abstract]


<p>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.</p>

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2018

Journal Article

S. Jayaram, Lavanya Balakrishnan, Singh, M., Zabihi, A., Ganesh, R. A., Kiran K. Mangalaparthi, Sonpatki, P., Gupta, M. Kumar, Amaresha, C. B., Prasad, K., Mariswamappa, K., Pillai, S., Lakshmikantha, A., Shah, N., and Ravi Sirdeshmukh, “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

Firdous A. Bhat, Jayshree Advani, Aafaque Ahmad Khan, Mohan, S., Pal, A., Harsha Gowda, Chakrabarti, P., T. S. Keshava Prasad, and Aditi Chatterjee, “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., Jayshree Advani, Jain, S., and T. S. Keshava Prasad, “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

Vural 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

Divya Nair, Jissa Gopala Krishna, Mamkoottathil Velayudhan Panikkar, Dr. Bipin G. Nair, Jayashree Gopalakris Pai, and Sudarslal Sadasivan Nair, “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, M. Chatterjee, V. Paul, G. Baranwal, V. A. Kumar, C. Bose, A. Banerji, Dr. Bipin G. Nair, B. P. Prasanth, and Dr. Raja Biswas, “Impregnation of Catheters with Anacardic Acid from Cashew nut Shell Prevents Staphylococcus aureus Biofilm Development.”, Journal of Applied Microbiology, 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

Jyotsna Nambiar, Gayathri Vijayakumar, G. Drishya, Sanu K Shaji, Nanjan Pandurangan, Geetha B. Kumar, and Dr. Bipin G. Nair, “(I-3,II-3)-Biacacetin-mediated cell death involves mitochondria.”, Molecular and cellular biochemistry, 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

Muralidharan Vanuopadath, Nithin Sajeev, Athira Radhamony Murali, Nayana Sudish, Nithya Kangosseri, Ivy Rose Sebastian, Nidhi Dalpatraj Jain, Amit Pal, Dileepkumar Raveendran, Dr. Bipin G. Nair, and Sudarslal Sadasivan Nair, “Mass spectrometry-assisted venom profiling of Hypnale hypnale found in the Western Ghats of India incorporating de novo sequencing approaches.”, International Journal of Biological Macromolecules, vol. 118, no. Part B, pp. 1736-1746, 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

Manjusha Nair, M. K. Jinesh, Bharat Jayaraman, 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, Balachandran A., Nutakki C., 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

Manjusha Nair, Kurup, R. Ramachandr, Alphonse, J., Chellaiah, P., Ramachandran, N. P., Nair, B., and Diwakar, S., “Design and Implementation of an Open-Source Browser-based Laboratory Platform for EEG Data Analysis”, in 2018 International Conference on Advances in Computing, Communications and Informatics (ICACCI), 2018.

2018

Conference Paper

Dr. Shyam Diwakar, Dr. Bipin G. Nair, Radhamani R., Divakar A, Nair A, Sivadas, Mohan G, Nizar N., and Achuthan K., “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, Nutakki C., Radhakrishnan S., 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, Krishnan M, Edison L, Radhamani R., Nizar N., and Kumar D, “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, Sasi V, Ramachandran L. P., Gunasekaran S., Edakkepravan H., and Nutakki C., “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.