Year of Publication Publication Type Title

2015

Conference Proceedings

Salim Amrita, Ugesh, k.p., Chandni, P., Sreerangini, M. R., Bipin, N., Ajith, M., Dr. Sanjay Pal, and Sreetha, H., “Isolation and characterization of bacteriophage treatment of domestic wastewater”, Proceeding of the 56th International Annual Conference of The Association of Microbiologist of India . JNU, New Delhi, 2015.

2015

Conference Paper

Prasad Megha, “Caulobacter crescentus as a novel exoelectricigen in a dual chambered Microbial Fuel Cell (MFC)”, in 56th Annual Conference of Association of Microbiologists of India and International Symposium on “Emerging Discoveries in Micrbiology(Poster), JNU, Delhi, 2015.

2015

Journal Article

T. Subbannayya, Leal-Rojas, P., Barbhuiya, M. A., Raja, R., Renuse, S., Sathe, G., Pinto, S. M., Syed, N., Nanjappa, V., Patil, A. H., and Dr. Bipin G. Nair, “Macrophage Migration Inhibitory Factor-a Therapeutic Target in Gallbladder Cancer”, BMC cancer, vol. 15, no. 1, p. 843, 2015.[Abstract]


Background

Poor prognosis in gallbladder cancer is due to late presentation of the disease, lack of reliable biomarkers for early diagnosis and limited targeted therapies. Early diagnostic markers and novel therapeutic targets can significantly improve clinical management of gallbladder cancer.

Methods

Proteomic analysis of four gallbladder cancer cell lines based on the invasive property (non-invasive to highly invasive) was carried out using the isobaric tags for relative and absolute quantitation labeling-based quantitative proteomic approach. The expression of macrophage migration inhibitory factor was analysed in gallbladder adenocarcinoma tissues using immunohistochemistry. In vitro cellular assays were carried out in a panel of gallbladder cancer cell lines using MIF inhibitors, ISO-1 and 4-IPP or its specific siRNA.

Results

The quantitative proteomic experiment led to the identification of 3,653 proteins, among which 654 were found to be overexpressed and 387 were downregulated in the invasive cell lines (OCUG-1, NOZ and GB-d1) compared to the non-invasive cell line, TGBC24TKB. Among these, macrophage migration inhibitory factor (MIF) was observed to be highly overexpressed in two of the invasive cell lines. MIF is a pleiotropic proinflammatory cytokine that plays a causative role in multiple diseases, including cancer. MIF has been reported to play a central role in tumor cell proliferation and invasion in several cancers. Immunohistochemical labeling of tumor tissue microarrays for MIF expression revealed that it was overexpressed in 21 of 29 gallbladder adenocarcinoma cases. Silencing/inhibition of MIF using siRNA and/or MIF antagonists resulted in a significant decrease in cell viability, colony forming ability and invasive property of the gallbladder cancer cells.

Conclusions

Our findings support the role of MIF in tumor aggressiveness and suggest its potential application as a therapeutic target for gallbladder cancer.

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2015

Journal Article

A. S. H. A. R. PAI and Dr. Bipin G. Nair, “Synthesis and Characterization of a Binary Oxide ZrO2–TiO2 and its Application in Chlorophyll Dye-Sensitized Solar Cell with Reduced Graphene Oxide as Counter Electrodes”, Bulletin of Materials Science, vol. 38, no. 5, pp. 1129-1133, 2015.[Abstract]


Natural dyes have been used to sensitize TiO2 nanocrystalline solar cells, but they still require pigment purification and co-adsorption of other compounds. In this study, nanocrystalline ZrO2–TiO2 films sensitized with the bioorganic dye, chlorophyll extracted from green leaves of Chromolaena odorata were investigated. The nanocrystalline ZrO2–TiO2 films were synthesized by the precipitation synthesis. The samples were characterized using X-ray diffraction, UV–vis absorption spectroscopy, Fourier transform infrared spectroscopy and scanning electron microscopy. The photoelectrodes were prepared using ZrO2–TiO2 sensitized with the chlorophyll dye and the counter electrodes using reduced graphene oxide. The shift in the absorption wavelength of chlorophyll showed an increase of adsorption of dye. The conversion efficiency was also studied.

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2015

Journal Article

V. Nanjappa, Renuse, S., Sathe, G. J., Raja, R., Syed, N., Radhakrishnan, A., Subbannayya, T., Patil, A., Marimuthu, A., Sahasrabuddhe, N. A., and Dr. Bipin G. Nair, “Chronic Exposure to Chewing Tobacco Selects for Overexpression of Stearoyl-CoA Desaturase in Normal Oral Keratinocytes”, Cancer biology & therapy, vol. 16, no. 11, pp. 1593-1603, 2015.[Abstract]


Chewing tobacco is a common practice in certain socio-economic sections of southern Asia, particularly in the Indian subcontinent and has been well associated with head and neck squamous cell carcinoma. The molecular mechanisms of chewing tobacco which leads to malignancy remains unclear. In large majority of studies, short-term exposure to tobacco has been evaluated. From a biological perspective, however, long-term (chronic) exposure to tobacco mimics the pathogenesis of oral cancer more closely. We developed a cell line model to investigate the chronic effects of chewing tobacco. Chronic exposure to tobacco resulted in higher cellular proliferation and invasive ability of the normal oral keratinocytes (OKF6/TERT1). We carried out quantitative proteomic analysis of OKF6/TERT1 cells chronically treated with chewing tobacco compared to the untreated cells. We identified a total of 3,636 proteins among which expression of 408 proteins were found to be significantly altered. Among the overexpressed proteins, stearoyl-CoA desaturase (SCD) was found to be 2.6-fold overexpressed in the tobacco treated cells. Silencing/inhibition of SCD using its specific siRNA or inhibitor led to a decrease in cellular proliferation, invasion and colony forming ability of not only the tobacco treated cells but also in a panel of head and neck cancer cell lines. These findings suggest that chronic exposure to chewing tobacco induced carcinogenesis in non-malignant oral epithelial cells and SCD plays an essential role in this process. The current study provides evidence that SCD can act as a potential therapeutic target in head and neck squamous cell carcinoma, especially in patients who are users of tobacco.

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2015

Journal Article

L. Dhevi N. Selvan, Sreenivasamurthy, S. K., Kumar, S., Yelamanchi, S. D., Madugundu, A. K., Anil, A. K., Renuse, S., Dr. Bipin G. Nair, Gowda, H., Mathur, P. P., Satishchandra, P., Shankar, S. K., Mahadevan, A., and Prasad, T. S. Keshava, “Characterization of Host Response to Cryptococcus Neoformans Through Quantitative Proteomic Analysis of Cryptococcal Meningitis Co-infected with HIV”, Mol. BioSyst., vol. 11, pp. 2529-2540, 2015.[Abstract]


Cryptococcal meningitis is the most common opportunistic fungal infection causing morbidity and mortality (>60%) in HIV-associated immunocompromised individuals caused by Cryptococcus neoformans. Molecular mechanisms of cryptococcal infection in brain have been studied using experimental animal models and cell lines. There are limited studies for the molecular understanding of cryptococcal meningitis in human brain. The proteins involved in the process of invasion and infection in human brain still remains obscure. To this end we carried out mass spectrometry-based quantitative proteomics of frontal lobe brain tissues from cryptococcal meningitis patients and controls to identify host proteins that are associated with the pathogenesis of cryptococcal meningitis. We identified 317 proteins to be differentially expressed ([greater-than-or-equal]2-fold) from a total of 3423 human proteins. We found proteins involved in immune response and signal transduction to be differentially expressed in response to cryptococcal infection in human brain. Immune response proteins including complement factors{,} major histocompatibility proteins{,} proteins previously known to be involved in fungal invasion to brain such as caveolin 1 and actin were identified to be differentially expressed in cryptococcal meningitis brain tissues co-infected with HIV. We also validated the expression status of 5 proteins using immunohistochemistry. Overexpression of major histocompatibility complexes{,} class I{,} B (HLA-B){,} actin alpha 2 smooth muscle aorta (ACTA2) and caveolin 1 (CAV1) and downregulation of peripheral myelin protein 2 (PMP2) and alpha crystallin B chain (CRYAB) in cryptococcal meningitis were confirmed by IHC-based validation experiments. This study provides the brain proteome profile of cryptococcal meningitis co-infected with HIV for a better understanding of the host response associated with the disease.

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2015

Conference Paper

J. H, Kumar, G., and Dr. Bipin G. Nair, “Antibiofilm Activity of Biosurfactants from Bacterial Strains Isolated from Oil Contaminated Soil and Sewage.”, in International conference-NHBT 2015, 2015.[Abstract]


<p>Biosurfactants are surface active molecules produced by various organisms, which have beneficial in structural diversity, low toxicity and biodegradability. These properties makes these compounds for a variety of potential applications, including cosmetics– pharmaceutical formulations, agricultural, food industry, oil recovery and environment protection technology. Furthermore, the biological properties of biosurfactants have also augment interest of industrial application. Biosurfactants are grouped into three categories of origin: microbial derived, animal-derived and plant-derived biosurfactants. In this study it is possible to isolate two bacterial strains which produce biosurfactants, from two very cheaper resources - oil contaminated soil and sewage water. The bacterial strains were tested for the ability to produce biosurfactants and screened for biosurfactant activity by oil displacement method. The highest biosurfactant producing strains were selected and identified by microscopic appearance and biochemical activities. The extracted biosurfactant’s emulsification activities were compared with synthetic surfactants. Simultaneously the biosurfactant produced by these strains were tested for its antibiofilm activity against various pathogenic microbes and found to have significant antibiofilm activity. The beneficial property of&nbsp; biosurfactant production&nbsp; make the strains an efficient bioremediation tool for various environmental application and represent greater significance in future biomedical applications.</p>

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2015

Conference Paper

Dr. Jyotsna Nambiar, Kumar, G. B., Pandurangan Nanjan, Dr. Asoke Banerji, and Dr. Bipin G. Nair, “Regulation of Gelatinases by (I-3,II-3)-Biacacetin, a Novel Non-zinc Binding Inhibitor of MMP-2 and MMP-9”, in The XXXIX All India Cell Biology Conference, 2015.[Abstract]


Gelatinases (MMP-2 and MMP-9) play a significant role in cancer progression by cleaving the major components of the extracellular matrix thereby promoting the migration of tumor cells. Majority of the MMP inhibitors reported are zinc chelating compounds which bind to the catalytic zinc via hydroxamate, carboxylate, thiol or phosphonic acid moieties. The extensive homology between catalytic domains of the MMPs makes these effective zinc binding inhibitors non-selective and toxic. To overcome such non selective toxicity, novel non-zinc binding MMP inhibitors have been developed.(I-3,II-3)-Biflavones form a small group of dimeric flavonoids which have not been extensively studied due to their limited occurrence. Among several differently substituted biflavones having hydroxy, methoxy, furano and cinnamyl moieties,(I-3,II-3)-biacacetin showed maximum inhibition of gelatinases without interfering with the zinc in the catalytic site.This novel non-zinc binding interaction of (I-3,II-3)-biacacetin was further confirmed by treating the cells with ZnCl2 along with(I-3,II-3)-biacacetin and showing that the inhibition remained unaffected even in the presence of ZnCl2.(I-3,II-3)-biacacetin showed significant reduction in migration of highly metastatic fibrosarcoma cell line, HT1080. The mechanism of (I-3,II-3)-biacacetinmediated modulation of cell migration through inhibition of gelatinases was further established by treating the cells with phorbol myristate acetate (PMA)along with (I-3,II-3)-biacacetinand using the same conditioned media for the migration assay. (I-3,II-3)-biacacetininhibitedPMA-stimulated gelatinase activity as well as migration of HT1080 cells in a concentration-dependent manner.These results suggests the use of (I-3,II-3)-biacacetin as a novel template for design and synthesis of analogswith improved potency and selectivity.

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2015

Conference Paper

D. G., Ashokan, L., Dr. Jyotsna Nambiar, Shaji, S. K., S, L., Kumar, G. B., and Dr. Bipin G. Nair, “In Vitro Culture of Primary Cells from Cancer Patients- Screening for Potent MMP-9 Inhibitors”, in The XXXIX All India Cell Biology Conference , 2015.[Abstract]


Breast cancer is the most prevalent form of cancer among women worldwide. Established cancer cell lines generated over years have been used for studying the biology of breast cancer. These cell lines which have been passaged innumerable times creates genetic drift which makes the observations biologically less relevant. In vitro culture of primary cells from fresh surgical specimens provides a more accurate means for understanding the behavior of cancer cells and the adjacent normal cells. We have developed a simple and rapid method for isolating primary cultures from breast tumor and normal cells. Two different methods were employed for isolating primary cultures- one involving enzymatic digestion and the other using explant culture which is independent of enzymatic treatment and feeder cells. The primary cells obtained were further characterized by immunocytochemistry staining for Vimentin and Cytokeratin 18. The cells stained positive for Vimentin and negative for Cytokeratin 18 which indicated that they are of mesenchymal origin. Since gelatinases play a prominent role in promoting breast cancer metastasis, the primary cells were assessed for gelatinase activity. Our observations clearly show that the cancer cells had up-regulated gelatinases activity compared to the adjacent normal cells. These cells when treated with several natural products showed a dose-dependent inhibition of gelatinase activity. The results obtained were consistent in all the primary cell lines generated from different patient samples. These studies with the primary cell lines will therefore help in obtaining biological responses that more accurately mimics the tumor/cancer micro environment.

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2015

Conference Paper

S. K. Shaji, Kumar, D. Sunil, G, D., Dr. Bipin G. Nair, and Kumar, G. B., “MicroRNA-491 Functions to Down Regulate Gelatinase B and Inhibit Cell Migration in MDA-MB-231 Triple Negative Breast Cancer Cells”, in The XXXIX All India Cell Biology Conference , 2015.[Abstract]


Breast cancer is one of the most prevalent malignancies among women worldwide. There is no targeted therapy currently available for the treatment of patients with triple negative breast cancer (TNBC). Metastasis is the primary cause of death in cancer patients. Gelatinase B (MMP-9) plays a central role in invasion and metastasis of breast cancer cells. Here we show that, in triple negative MDA-MB-231 breast cancer cell line, hsa-mir-491 directly down regulate MMP-9 expression. Bioinformatics tool analysis showed that hsa-mir-491 may target MMP-9 and has binding sites in its 3’ UTR. Luciferase reporter assay confirms the direct regulation of MMP-9 by hsa-miR-491. miRNA over expressing stable cell lines were established by lentiviral transduction of MDA-MB-231 cells with hsa-mir-491 lenti-viral vector construct. qRT-PCR studies showed down regulation of MMP-9 mRNA in miRNA over expressing cells lines compared to the normal MDA-MB-231 cells. Even though the miRNA did not have any effect on cell cycle profiles, hsa-miR-491 over expressing stable cell line showed significantly low migratory potential in assays indicating the therapeutic potential of this micorRNA as a novel means of controlling breast cancer metastasis. Our results provide the first evidence for inhibition of MMP-9 by hsa-mir-491 in breast cancer cells.

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2015

Conference Paper

A. Omanakuttan, Dr. Geetha Kumar, and Dr. Bipin G. Nair, “Ecdysterone Mediates Wound Healing in a Nitric Oxide Dependent Manner in 3T3L1 Fibroblasts.”, in The XXXIX All India Cell Biology Conference , 2015.[Abstract]


Ecdysteroids are insect moulting hormones which are structurally different from mammalian steroids, but have been shown to have several beneficial effects in mammals. Ecdysterone is known to enhance wound healing in rabbits by a faster granulation tissue formation and epithelial cell proliferation. In this study, we focused our efforts on elucidating the molecular mechanism involved in Ecdysterone mediated wound healing. In order to achieve this, we employed an in vitro wound healing assay using 3T3L1 cells treated with Ecdysterone, isolated from Sesuvium portulacastrum. The assay demonstrated that Ecdysterone enhanced in vitro wound healing activity in a dose dependent manner. Further studies demonstrated that Ecdysterone enhanced cell proliferation and cell migration in a nitric oxide dependent manner. Additionally, fluorescence studies with DAF FM diacetate, a specific indicator for nitric oxide, demonstrated that Ecdysterone enhances nitric oxide (NO) production in a dose dependent manner through activation of Nitric oxide Synthase (NOS). These results demonstrate that Ecdysterone can enhance the wound healing process in a nitric oxide (NO) dependent manner

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2015

Conference Paper

D. Sunil Kumar, Bose, C., Shaji, S. K., Dr. Asoke Banerji, Kumar, G. B., and Dr. Bipin G. Nair, “Cocos Nucifera Shell Extract Down Regulates MMP-2, MMP-9 and Cell Migration in A375 Cells”, in The XXXIX All India Cell Biology Conference , 2015.[Abstract]


Melanoma is the least common but most fatal form of skin cancer. An essential step in melanoma cell migration, invasion, and metastasis is the degradation of basement membranes and extracellular matrix. Matrix metalloproteinases (MMPs) and their tissue inhibitors play a crucial role in these complex multistep processes. We investigated the effect of extract from coconut (Cocos nucifera) shell on human melanoma cell line A375. The coconut shell extract was fractionated and the bioactivity screening was carried out. The ethyl methyl ketone (EMK) extract, which was identified as being most potent was further purified to yield two main subfractions (F1 and F2). Comparative studies with gelatin zymography demonstrated that the ‘F1’ significantly down regulated the gelatinolytic activity of MMP-2 and MMP-9. Similarly ,the gene expression studies with ‘F1’ showed down regulation of MMP-2, MMP-9, VEGF and COX-2 all of which play key roles in metastasis, angiogenesis and tumor promoting inflammation. Further, studies confirmed that ‘F1’ inhibited migration and caused arrest at G2/M phase of the cell cycle. Susequently, the structural characterization by LC-MS/MS and NMR studies determined the active fraction, ‘F1’to be oxyresveratrol, a stilbenoid. Thus, we report for the first time the isolation and characterization of the compound, oxyresveratrol from coconut shell and also show its regulation of MMPs in human melanoma which suggests its therapeutic potential in cancer.

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2015

Journal Article

Raghu Raman, Dr. Krishnashree Achuthan, Prof. Nedungadi, P., Dr. Shyam Diwakar, and Bose, R., “The VLAB OER Experience: Modeling Potential-Adopter Students' Acceptance”, IEEE Transactions on Education, vol. 57, pp. 235–241, 2015.[Abstract]


Virtual Labs (VLAB) is a multi-institutional Open Educational Resources (OER) initiative, exclusively focused on lab experiments for engineering education. This project envisages building a large OER repository, containing over 1650 virtual experiments mapped to the engineering curriculum. The introduction of VLAB is a paradigm shift in an educational system that is slow to change. Treating VLAB OER as an educational technology innovation, its adoption by potential-adopter engineering students (N=131) is modeled based on Roger's theory of perceived attributes. Regression and factor analysis were used to analyze the data. Results indicate that the attributes of Compatibility, Ease of Use, Relative Advantage, and Trialability significantly influence potential-adopter students' intention to adopt an innovation like VLAB. The study also observed that using OER (such as VLAB) on desktops and low-cost tablets had similar effects in student performance to using physical labs. This has interesting implications for education policy-makers who are looking to reduce the digital divide.

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2015

Journal Article

N. Syed, Barbhuiya, M. A., Pinto, S. M., Nirujogi, R. S., Renuse, S., Datta, K. K., Khan, A. A., Srikumar, K., Prasad, T. S. K., Kumar, M. V., Kumar, R. V., Chatterjee, A., Pandey, A., and Gowda, H., “Phosphotyrosine profiling identifies ephrin receptor A2 as a potential therapeutic target in esophageal squamous-cell carcinoma”, Proteomics, vol. 15, pp. 374-382, 2015.[Abstract]


Esophageal squamous-cell carcinoma (ESCC) is one of the most common malignancies in Asia. Currently, surgical resection of early-stage tumor is the best available treatment. However, most patients present late when surgery is not an option. Data suggest that chemotherapy regimens are inadequate for clinical management of advanced cancer. Targeted therapy has emerged as one of the most promising approaches to treat several malignancies. A prerequisite for developing targeted therapy is prior knowledge of proteins and pathways that drive proliferation in malignancies. We carried out phosphotyrosine profiling across four different ESCC cell lines and compared it to non-neoplastic Het-1A cell line to identify activated tyrosine kinase signaling pathways in ESCC. A total of 278 unique phosphopeptides were identified across these cell lines. This included several tyrosine kinases and their substrates that were hyperphosphorylated in ESCC. Ephrin receptor A2 (EPHA2), a receptor tyrosine kinase, was hyperphosphorylated in all the ESCC cell lines used in the study. EPHA2 is reported to be oncogenic in several cancers and is also known to promote metastasis. Immunohistochemistry-based studies have revealed EPHA2 is overexpressed in nearly 50% of ESCC. We demonstrated EPHA2 as a potential therapeutic target in ESCC by carrying out siRNA-based knockdown studies. Knockdown of EPHA2 in ESCC cell line TE8 resulted in significant decrease in cell proliferation and invasion, suggesting it is a promising therapeutic target in ESCC that warrants further evaluation. © 2014 The Authors. PROTEOMICS published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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2015

Book Chapter

Dr. Shyam Diwakar, “Computational Modeling of Neuronal Dysfunction at Molecular Level Validates the Role of Single Neurons in Circuit Functions in Cerebellum Granular Layer”, in Validating Neuro-Computational Models of Neurological and Psychiatric Disorders, Springer, 2015, pp. 189–220.[Abstract]


Using mathematical modelling, we attempted to reconstruct the information transmission at the granular layer of the cerebellum, a circuit whose functions and dysfunctions remain yet to be explored in detail. Information transmission at the Mossy Fiber (MF)—Granule cell (GrC) synaptic relay is crucial to understand mechanisms of signal coding in the cerebellum and related impacts of connectivity mechanisms. Using biophysically detailed multi-compartmental models, simple spiking neurons we reconstructed granular layer micro-circuitry and estimated both single neuron behaviour and network activity in terms of center-surround patterns, as observed during sensory and tactile stimulation. The chapter also includes local field potential reconstructions to show plasticity mechanisms at the molecular level is reflected at the network activity level, indicating network LFP in the granular layer is a regulated activity signal arising from the underlying granule cells and the feed-forward inhibition from the Golgi cells. The role of selective inhibition by Golgi cells for coincidence detection is presented. Exploring the EPSP-spike complex in granular neurons revealed potential mechanisms for sparse recoding in cerebellum and quantification of information encoding in individual neurons of the cerebellar granular layer. We also look into two specific forms of neuronal dysfunction with ataxia-like behaviour in knockout mice models and in NMDAR-related autism. While network activity was severely affected, the amplitude of damage is critical of the mechanisms at the cellular or molecular level. The study further enhances our understanding of specific coding geometries in the cerebellum and spatio-temporal processing in a primary circuit of the cerebellum. More »»

2015

Journal Article

F. Zeidán-Chuliá, Gürsoy, M., de Oliveira, B. - H. Neves, Ozdemir, V., Könönen, E., and Gürsoy, U. K., “A Systems Biology Approach to Reveal Putative Host-Derived Biomarkers of Periodontitis by Network Topology Characterization of MMP-REDOX/NO and Apoptosis Integrated Pathways.”, Front Cell Infect Microbiol, vol. 5, p. 102, 2015.[Abstract]


<p>Periodontitis, a formidable global health burden, is a common chronic disease that destroys tooth-supporting tissues. Biomarkers of the early phase of this progressive disease are of utmost importance for global health. In this context, saliva represents a non-invasive biosample. By using systems biology tools, we aimed to (1) identify an integrated interactome between matrix metalloproteinase (MMP)-REDOX/nitric oxide (NO) and apoptosis upstream pathways of periodontal inflammation, and (2) characterize the attendant topological network properties to uncover putative biomarkers to be tested in saliva from patients with periodontitis. Hence, we first generated a protein-protein network model of interactions ("BIOMARK" interactome) by using the STRING 10 database, a search tool for the retrieval of interacting genes/proteins, with "Experiments" and "Databases" as input options and a confidence score of 0.400. Second, we determined the centrality values (closeness, stress, degree or connectivity, and betweenness) for the "BIOMARK" members by using the Cytoscape software. We found Ubiquitin C (UBC), Jun proto-oncogene (JUN), and matrix metalloproteinase-14 (MMP14) as the most central hub- and non-hub-bottlenecks among the 211 genes/proteins of the whole interactome. We conclude that UBC, JUN, and MMP14 are likely an optimal candidate group of host-derived biomarkers, in combination with oral pathogenic bacteria-derived proteins, for detecting periodontitis at its early phase by using salivary samples from patients. These findings therefore have broader relevance for systems medicine in global health as well.</p>

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2015

Conference Proceedings

Dr. Dalia Vishnudasan and Khurana, P., “Wheat biotechnology for herbicide resistance”, Souvenir issue of National Binennial Conference, ISWS . Dept. Agronomy and Agrometerology, PAU, Ludhiana, pp. 7 -15, 2015.

2015

Conference Proceedings

D. Nedungadi, ,, Pandurangan Nanjan, Nair, B. G., Dr. Asoke Banerji, and Mishra, N., “Caspase Independent Cell Death in Malignant Breast Cancer Cells MDA MB-231 by Chalcone Derivatives”, XXXIX All India Cell Biology Conference,IISER. Trivandrum, India, 2015.

2015

Conference Paper

C. Nutakki, Asha Vijayan, Dr. Bipin G. Nair, and Dr. Shyam Diwakar, “Implementing Cerebellar Biophysics for Trajectory planning in Robotic arms”, in Proceedings of the International symposium on Translational Neuroscience & XXXIII Annual Conference of the Indian Academy of Neurosciences, Panjab University, Chandigarh , India, 2015.

2015

Journal Article

Dr. Rajaguru Aradhya, Zmojdzian, M., Da Ponte, J. Philippe, and Jagla, K., “Muscle niche-driven Insulin-Notch-Myc cascade reactivates dormant Adult Muscle Precursors in Drosophila”, eLife, vol. 4, p. e08497, 2015.[Abstract]


How stem cells specified during development keep their non-differentiated quiescent state, and how they are reactivated, remain poorly understood. Here, we applied a Drosophila model to follow in vivo behavior of adult muscle precursors (AMPs), the transient fruit fly muscle stem cells. We report that emerging AMPs send out thin filopodia that make contact with neighboring muscles. AMPs keep their filopodia-based association with muscles throughout their dormant state but also when they start to proliferate, suggesting that muscles could play a role in AMP reactivation. Indeed, our genetic analyses indicate that muscles send inductive dIlp6 signals that switch the Insulin pathway ON in closely associated AMPs. This leads to the activation of Notch, which regulates AMP proliferation via dMyc. Altogether, we report that Drosophila AMPs display homing behavior to muscle niche and that the niche-driven Insulin-Notch-dMyc cascade plays a key role in setting the activated state of AMPs. More »»

2015

Journal Article

Dr. Rajaguru Aradhya, Zmojdzian, M., Da Ponte, J. Philippe, and Jagla, K., “Translating Ribosome Affinity Purification from Rare Cell Populations of Drosophila Embryos”, JOVE, no. 103, 2015.[Abstract]


Measuring levels of mRNAs in the process of translation in individual cells provides information on the proteins involved in cellular functions at a given point in time. The protocol dubbed Translating Ribosome Affinity Purification (TRAP) is able to capture this mRNA translation process in a cell-type-specific manner. Based on the affinity purification of polysomes carrying a tagged ribosomal subunit, TRAP can be applied to translatome analyses in individual cells, making it possible to compare cell types during the course of developmental processes or to track disease development progress and the impact of potential therapies at molecular level. Here we report an optimized version of the TRAP protocol, called TRAP-rc (rare cells), dedicated to identifying engaged-in-translation RNAs from rare cell populations. TRAP-rc was validated using the Gal4/UAS targeting system in a restricted population of muscle cells in Drosophila embryos. This novel protocol allows the recovery of cell-type-specific RNA in sufficient quantities for global gene expression analytics such as microarrays or RNA-seq. The robustness of the protocol and the large collections of Gal4 drivers make TRAP-rc a highly versatile approach with potential applications in cell-specific genome-wide studies. More »»

2015

Journal Article

S. Paul, A. Bhardwaj, S. K. Bag, E. V. Sokurenko, and S. Chattopadhyay, “PanCoreGen — Profiling, Detecting, Annotating Protein-coding Genes in Microbial Genomes”, Genomics, vol. 106, pp. 367 - 372, 2015.[Abstract]


A large amount of genomic data, especially from multiple isolates of a single species, has opened new vistas for microbial genomics analysis. Analyzing the pan-genome (i.e. the sum of genetic repertoire) of microbial species is crucial in understanding the dynamics of molecular evolution, where virulence evolution is of major interest. Here we present PanCoreGen — a standalone application for pan- and core-genomic profiling of microbial protein-coding genes. PanCoreGen overcomes key limitations of the existing pan-genomic analysis tools, and develops an integrated annotation-structure for a species-specific pan-genomic profile. It provides important new features for annotating draft genomes/contigs and detecting unidentified genes in annotated genomes. It also generates user-defined group-specific datasets within the pan-genome. Interestingly, analyzing an example-set of Salmonella genomes, we detect potential footprints of adaptive convergence of horizontally transferred genes in two human-restricted pathogenic serovars — Typhi and Paratyphi A. Overall, PanCoreGen represents a state-of-the-art tool for microbial phylogenomics and pathogenomics study

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2015

Journal Article

P. V. Suneesh, Vargis, V. Sara, Ramachandran, T., Dr. Bipin G. Nair, and Babu, T. G. Satheesh, “Co–Cu alloy nanoparticles decorated TiO2 nanotube arrays for highly sensitive and selective nonenzymatic sensing of glucose”, Sensors and Actuators B: Chemical, vol. 215, pp. 337 - 344, 2015.[Abstract]


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

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2014

Journal

D. S, H, P., C, M., R, R., and al, N. P. et., “Complementing Neurophysiology Education for Developing Countries via Cost-Effective Virtual Labs”. 2014.

2014

Journal Article

A. Bera, Das, F., Ghosh-Choudhury, N., Li, X., Gorin, Y., Kasinath, B. S., Abboud, H. E., Choudhury, G. Ghosh, and Dr. Sanjay Pal, “A positive feedback loop involving Erk5 and Akt turns on mesangial cell proliferation in response to PDGF”, American Journal of Physiology-Cell Physiology, vol. 306, pp. C1089–C1100, 2014.[Abstract]


Platelet-derived growth factor BB and its receptor (PDGFRβ) play a pivotal role in the development of renal glomerular mesangial cells. Their roles in increased mesangial cell proliferation during mesangioproliferative glomerulonephritis have long been noted, but the operating logic of signaling mechanisms regulating these changes remains poorly understood. We examined the role of a recently identified MAPK, Erk5, in this process. PDGF increased the activating phosphorylation of Erk5 and tyrosine phosphorylation of proteins in a time-dependent manner. A pharmacologic inhibitor of Erk5, XMD8-92, abrogated PDGF-induced DNA synthesis and mesangial cell proliferation. Similarly, expression of dominant negative Erk5 or siRNAs against Erk5 blocked PDGF-stimulated DNA synthesis and proliferation. Inhibition of Erk5 attenuated expression of cyclin D1 mRNA and protein, resulting in suppression of CDK4-mediated phosphorylation of the tumor suppressor protein pRb. Expression of cyclin D1 or CDK4 prevented the dominant negative Erk5- or siErk5-mediated inhibition of DNA synthesis and mesangial cell proliferation induced by PDGF. We have previously shown that phosphatidylinositol 3-kinase (PI3-kinase) contributes to PDGF-induced proliferation of mesangial cells. Inhibition of PI3-kinase blocked PDGF-induced phosphorylation of Erk5. Since PI3-kinase acts through Akt, we determined the role of Erk5 on Akt phosphorylation. XMD8-92, dominant negative Erk5, and siErk5 inhibited phosphorylation of Akt by PDGF. Interestingly, we found inhibition of PDGF-induced Erk5 phosphorylation by a pharmacological inhibitor of Akt kinase and kinase dead Akt in mesangial cells. Thus our data unfold the presence of a positive feedback microcircuit between Erk5 and Akt downstream of PI3-kinase nodal point for PDGF-induced mesangial cell proliferation.

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2014

Book

D. Gopakumar and P. K. Krishnan Namboori, Bioinformatics Structural and Sequence Analysis. New Delhi: Narosa Publishers, 2014.[Abstract]


Bioinformatics, the application of computers in biological sciences and especially analysis of biological sequence data, is becoming an essential tool in molecular biology as genome projects generate vast quantities of data. With new sequences being added to DNA databases, on average, there is a vital requisite to convert this information into biochemical and biophysical knowledge by explaining the structural, functional of biological sequences. This book begins by introducing the most popular databases (protein and nucleic acid), information resources and analysis methods (sequence alignment and pattern recognition) currently available providing the basis for readers to progress to hands-on practical sequence analysis. It explains some basic algorithms in bioinformatics to readers who have exposure to computer science, mathematics, and statistics. The text also explains the structural bioinformatics that lies at the interface of structural biology and informatics, each of which derive their principles from highly interdisciplinary areas that goes beyond traditional bioinformatics knowledge.

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2014

Journal Article

L. Dhevi Naga Selvan, Kaviyil, J. Embekkat, Nirujogi, R. Sekhar, Muthusamy, B., Puttamallesh, V. N., Subbannayya, T., Syed, N., Radhakrishnan, A., Kelkar, D. S., Ahmad, S., and Dr. Bipin G. Nair, “Proteogenomic analysis of pathogenic yeast Cryptococcus neoformans using high resolution mass spectrometry”, Clinical proteomics, vol. 11, no. 1, p. 1, 2014.[Abstract]


Curcumin, derived from the rhizome Curcuma longa, is a natural anti-cancer agent and has been shown to inhibit proliferation and survival of tumor cells. Although the anti-cancer effects of curcumin are well established, detailed understanding of the signaling pathways altered by curcumin is still lacking. In this study, we carried out SILAC-based quantitative proteomic analysis of a HNSCC cell line (CAL 27) to investigate tyrosine signaling in response to curcumin. More »»

2014

Journal Article

J. Kurian Thomas, Kim, M. - S., Balakrishnan, L., Nanjappa, V., Raju, R., Marimuthu, A., Radhakrishnan, A., Muthusamy, B., Khan, A. Ahmad, Sakamuri, S., Dr. Bipin G. Nair, Tankala, S. Gupta, Singal, M., Sirdeshmukh, R., Chatterjee, A., Prasad, T. S. Keshava, Maitra, A., Gowda, H., Hruban, R. H., and Pandey, A., “Pancreatic Cancer Database: An integrative resource for pancreatic cancer.”, Cancer biology & therapy, vol. 15, pp. 963-967, 2014.[Abstract]


Pancreatic cancer is the fourth leading cause of cancer-related death in the world. The etiology of pancreatic cancer is heterogeneous with a wide range of alterations that have already been reported at the level of the genome, transcriptome, and proteome. The past decade has witnessed a large number of experimental studies using high-throughput technology platforms to identify genes whose expression at the transcript or protein levels is altered in pancreatic cancer. Based on expression studies, a number of molecules have also been proposed as potential biomarkers for diagnosis and prognosis of this deadly cancer. Currently, there are no repositories which provide an integrative view of multiple Omics data sets from published research on pancreatic cancer. Here, we describe the development of a web-based resource, Pancreatic Cancer Database (http://www.pancreaticcancerdatabase.org), as a unified platform for pancreatic cancer research. PCD contains manually curated information pertaining to quantitative alterations in miRNA, mRNA, and proteins obtained from small-scale as well as high-throughput studies of pancreatic cancer tissues and cell lines. We believe that PCD will serve as an integrative platform for scientific community involved in pancreatic cancer research.

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2014

Journal Article

S. Bab Dwivedi, Muthusamy, Bac, Kumar, Pa, Kim, M. - Sd, Nirujogi, R. Sac, Getnet, Dd, Ahiakonu, Pe, De, Gaf, Dr. Bipin G. Nair, Gowda, Ha, Prasad, T. S. Kab c f, Kumar, Ng, Pandey, Aad h, and Okulate, Me, “Brain proteomics of anopheles gambiae”, OMICS A Journal of Integrative Biology, vol. 18, pp. 421-437, 2014.[Abstract]


Anopheles gambiae has a well-adapted system for host localization, feeding, and mating behavior, which are all governed by neuronal processes in the brain. However, there are no published reports characterizing the brain proteome to elucidate neuronal signaling mechanisms in the vector. To this end, a large-scale mapping of the brain proteome of An. gambiae was carried out using high resolution tandem mass spectrometry, revealing a repertoire of >1800 proteins, of which 15% could not be assigned any function. A large proportion of the identified proteins were predicted to be involved in diverse biological processes including metabolism, transport, protein synthesis, and olfaction. This study also led to the identification of 10 GPCR classes of proteins, which could govern sensory pathways in mosquitoes. Proteins involved in metabolic and neural processes, chromatin modeling, and synaptic vesicle transport associated with neuronal transmission were predominantly expressed in the brain. Proteogenomic analysis expanded our findings with the identification of 15 novel genes and 71 cases of gene refinements, a subset of which were validated by RT-PCR and sequencing. Overall, our study offers valuable insights into the brain physiology of the vector that could possibly open avenues for intervention strategies for malaria in the future. © Copyright 2014, Mary Ann Liebert, Inc. 2014.

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2014

Journal Article

V. Kumar. A, Dr. Sreekala C. O., M, M., Ashok, A., and Rasheed, R., “Benchtop Nanoscale Patterning using Soft Lithography for the Printing of DNA Molecules”, International journal of Engineering research and technology, vol. 3, 2014.

2014

Journal Article

Aa Marimuthu, Huang, T. - Cb, Selvan, L. D. Nac, Renuse, Sac, Nirujogi, R. Sad, Kumar, Pa, Pinto, S. Mae, Rajagopalan, Sf, Pandey, Abg h i, Harsha, H. Ca, and Chatterjee, Aa, “Identification of targets of miR-200b by a SILAC-based quantitative proteomic approach”, EuPA Open Proteomics, vol. 4, pp. 10-17, 2014.[Abstract]


miRNAs regulate gene expression by binding to cognate mRNAs causing mRNA degradation or translational repression. Mass spectrometry-based proteomic analysis is being widely used to identify miRNA targets. The miR-200b miRNA cluster is often overexpressed in multiple cancer types, but the identity of the targets remains elusive. Using SILAC-based analysis, we examined the effects of overexpression of a miR-200b mimic or a control miRNA in fibrosarcoma cells. We identified around 300 potential targets of miR-200b based on a change in the expression of protein levels. We validated a subset of potential targets at the transcript level using quantitative PCR.

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2014

Journal Article

Ka Amrutha, Pandurangan Nanjan, Shaji, S. Ka, Sunilkumar, Da, Subhalakshmi, Ka, Rajakrishna, Lb, and Dr. Asoke Banerji, “Discovery of lesser known flavones as inhibitors of NF-κB signaling in MDA-MB-231 breast cancer cells-A SAR study”, Bioorganic and Medicinal Chemistry Letters, vol. 24, no. 19, pp. 4735-4742, 2014.[Abstract]


<p>Seventeen flavonoids with different substitutions were evaluated for inhibition of nuclear factor-κB (NF-κB) signaling in the invasive breast cancer cell line MDA-MB-231. They were screened using an engineered MDA-MB-231 cell line reporting NF-κB activation. The modulation of expression of two NF-κB regulated genes involved in tumorigenesis, matrix metalloproteinase-9 (MMP-9), and cyclooxygenase-2 (COX-2) were also analyzed in these cells. Among the compounds tested, all except gossypetin and quercetagetin inhibited the activation of NF-κB, and the expression of MMP-9 and COX-2 to different degree. Methylated flavone, chrysoeriol (luteolin-3′-methylether), was found to be the most potent inhibitor of MMP-9 and COX-2 expressions. The effect of chrysoeriol on cell proliferation, cell cycle, apoptosis and metastasis was analyzed by established methods. Chrysoeriol caused cell cycle arrest at G2/M and inhibited migration and invasion of MDA-MB-231 cells. The structure-activity relations amongst the flavonoids as NF-κB signaling inhibitors was studied. The study indicates differences between the actions of various flavonoids on NF-κB activation and on the biological activities of breast cancer cells. Flavones in general, were more active than the corresponding flavonols. © 2014 Elsevier Ltd. All rights reserved.</p>

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2014

Journal Article

Sab Nair, Liew, Cbc, Khor, T. Ob, Cai, Ld, and Kong, A. - Nb, “Differential signaling regulatory networks governing hormone refractory prostate cancers”, Journal of Chinese Pharmaceutical Sciences, vol. 23, pp. 511-524, 2014.[Abstract]


To understand the organization of the biological networks that might potentially govern the pathogenesis of hormone refractory prostate cancer (HRPC), we investigated the transcriptional circuitry and signaling in androgendependent 22Rv1 and MDA PCa 2b cells, androgenand estrogendependent LNCaP cells, and androgenindependent DU 145 and PC3 prostate cancer (PCa) cell lines. We used microarray analyses, quantitative realtime PCR, pathway prediction analyses, and determination of Transcription Factor Binding Site (TFBS) signatures to dissect HRPC regulatory networks. We generated graphical representations of global topology and local network motifs that might be important in prostate carcinogenesis. Many important putative biomarker 'target hubs' were identified in the current study including AP1, NF?B, EGFR, ERK1/2, JNK, p38 MAPK, TGF beta, VEGF, PDGF, CD44, Akt, PI3K, NOTCH1, CASP1, MMP2 and AR. Our results suggest that complex cellular events including autoregulation, feedback loops and crosstalk might govern progression from early lesion to clinically diagnosed PCa, as well as metastatic potential of preexistent highgrade prostate intraepithelial neoplasia (HGPIN) and/or advancement to HRPC. The identification of TFBS signatures for TCF/LEF, SOX9 and ELK1 in the regulatory elements suggests additional biomarkers for the potential development of chemopreventive/therapeutic strategies against PCa. Taken together, in this study, we have identified putative biomarker 'target hubs' in the architecture of PCa signaling networks, and investigated TFBS signatures that might enhance our understanding of key regulatory nodes in the progression and pathogenesis of HRPC.

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2014

Journal Article

Hab Pawar, Renuse, Sac, Khobragade, S. Nd, Chavan, Sae, Sathe, Gae, Kumar, Pa, Mahale, K. Nd, Gore, Kd, Kulkarni, Ad, Dixit, Td, Raju, Ra, Prasad, T. S. Ka, Harsha, H. Ca, Patole, M. Sd, and Pandey, Afg h i, “Neglected tropical diseases and omics science: Proteogenomics analysis of the promastigote stage of leishmania major parasite”, OMICS A Journal of Integrative Biology, vol. 18, pp. 499-512, 2014.[Abstract]


Among the neglected tropical diseases, leishmaniasis is one of the most devastating, resulting in significant mortality and contributing to nearly 2 million disability-adjusted life years. Cutaneous leishmaniasis is a debilitating disorder caused by the kinetoplastid protozoan parasite Leishmania major, which results in disfiguration and scars. L. major genome was the first to be sequenced within the genus Leishmania. Use of proteomic data for annotating genomes is a complementary approach to conventional genome annotation approaches and is referred to as proteogenomics. We have used a proteogenomics-based approach to map the proteome of L. major and also annotate its genome. In this study, we searched L. major promastigote proteomic data against the annotated L. major protein database. Additionally, we searched the proteomic data against six-frame translated L. major genome. In all, we identified 3613 proteins in L. major promastigotes, which covered 43% of its proteome. We also identified 26 genome search-specific peptides, which led to the identification of three novel genes previously not identified in L. major. We also corrected the annotation of N-termini of 15 genes, which resulted in extension of their protein products. We have validated our proteogenomics findings by RT-PCR and sequencing. In addition, our study resulted in identification of 266 N-terminally acetylated peptides in L. major, one of the largest acetylated peptide datasets thus far in Leishmania. This dataset should be a valuable resource to researchers focusing on neglected tropical diseases. © 2014 Mary Ann Liebert, Inc.

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2014

Journal Article

Vab c l Özdemir, Downey, R. Ad, Lin, Bef, Dove, E. Sg, Özkan, Bh, Warnich, Li, and Ferguson, L. Rjk, “Special Issue "oMICS in AFRICA": Power to the people - Moving 21st century integrative biology from lab to village to innovation ecosystems”, OMICS A Journal of Integrative Biology, vol. 18, pp. 399-401, 2014.

2014

Journal Article

Nab Hekim, Coşkun, Yc, Sinav, Ad, Abou-Zeid, A. He, Aǧirbaşli, Mf, Akintola, S. Og, Aynacioǧlu, Sh, Bayram, Mij, Bragazzi, N. Lk, Dandara, Cl, Dereli, Tim, Dove, E. Sn, Elbeyli, Lo, Endrenyi, Lp, Erciyas, Kq, Faris, Jr, Ferguson, L. Rst, Göǧüş, Fj, Güngör, Ku, Gürsoy, Mv, Gürsoy, U. Kv, Karaömerlioǧlu, M. Aw, Kickbusch, Ix, Kiliç, Ty, Kilinç, Mz, Kocagöz, Taa, Lin, Babac, Llerena, Aadae, Manolopoulos, V. Gaf, Dr. Bipin G. Nair, Özkan, Bah, Pang, Tai, Şardaş, Saj, Srivastava, Sak, Toraman, Cal, Üstün, Kq, Warnich, Lam, Wonkam, Al, Yakicier, M. Can, Yaşar, Uao, and Özdemir, Vcag al ap, “Translating biotechnology to knowledge-based innovation, peace, and development? Deploy a science peace corps - An open letter to world leaders”, OMICS A Journal of Integrative Biology, vol. 18, pp. 415-420, 2014.[Abstract]


Scholarship knows no geographical boundaries. This science diplomacy and biotechnology journalism article introduces an original concept and policy petition to innovate the global translational science, a Science Peace Corps. Service at the new Corps could entail volunteer work for a minimum of 6 weeks, and up to a maximum of 2 years, for translational research in any region of the world to build capacity manifestly for development and peace, instead of the narrow bench-to-bedside model of life science translation. Topics for translational research are envisioned to include all fields of life sciences and medicine, as long as they are linked to potential or concrete endpoints in development, foreign policy, conflict management, post-crisis capacity building, and/or peace scholarship domains. As a new instrument in the global science and technology governance toolbox, a Science Peace Corps could work effectively, for example, towards elucidating the emerging concept of "one health" - encompassing human, environmental, plant, microbial, ecosystem, and planet health - thus serving as an innovative crosscutting pillar of 21st century integrative biology. An interdisciplinary program of this caliber for development would link 21st century life sciences to foreign policy and peace, in ways that can benefit many nations despite their ideological differences. We note that a Science Peace Corps is timely. The Intergovernmental Panel on Climate Change (IPCC) of the United Nations released the Fifth Assessment Report on March 31, 2014. Worrisomely, the report underscores that no person or nation will remain untouched by the climate change, highlighting the shared pressing life sciences challenges for global society. To this end, we recall that President John F. Kennedy advocated for volunteer work that has enduring, transgenerational, and global impacts. This culminated in establishment of the Peace Corps in 1961. Earlier, President Abraham Lincoln aptly observed, "nearly all men can stand adversity, but if you want to test a man's character, give him power." We therefore petition President Barack Obama, other world leaders, and international development agencies in positions of power around the globe, to consider deploying a Science Peace Corps to cultivate the essential (and presently missing) ties among life sciences, foreign policy, development, and peace agendas. A Science Peace Corps requires support by a credible and independent intergovernmental organization or development agency for funding, and arbitration in the course of volunteer work when the global versus local (glocal) value-based priorities and human rights intersect in synergy or conflict. In all, Science Peace Corps is an invitation to a new pathway for competence in 21st century science that is locally productive and globally competitive. It can open up scientific institutions to broader considerations and broader inputs, and thus cultivate vital translational science in a world sorely in need of solidarity and sustainable responses to the challenges of 21st century science and society. © Copyright 2014, Mary Ann Liebert, Inc. 2014.

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2014

Journal Article

Ka Güngör, Hotez, P. Jbc d, Özdemir, Vef g h i, and Aynacioǧlu, Şjk, “Glaucomics: A call for systems diagnostics for 21st century ophthalmology and personalized visual health”, OMICS A Journal of Integrative Biology, vol. 18, pp. 275-279, 2014.[Abstract]


This article analyzes and theorizes the current knowledge silos at the intersection of omics science, ophthalmology, personalized medicine, and global visual health. Visual disorders represent one of the largest health care expenditures in the United States, costing $139 billion per year. In middle-income and industrialized countries, glaucoma is a World Health Organization priority category eye disease, known for difficulties in its early diagnosis, chronic progressive nature, and large person-to-person differences in drug efficacy and safety. A complex disease, glaucoma is best conceptualized as a syndrome displaying an ostensibly common clinical end-point, but with vastly heterogeneous molecular underpinnings and host-environment interactions. About 12% of all global blindness is attributable to glaucoma. Glaucomics is a term that we coin here so as to introduce omics science and systems diagnostics to ophthalmology, a field that can benefit enormously from personalized medicine, and which has sadly lagged behind in systems diagnostics compared to fields such as oncology. We define glaucomics as the integrated use of multi-omics and systems science approaches towards rational discovery, development, and tandem applications of diagnostics and therapeutics, for glaucoma specifically, and for personalized visual health, more broadly. We propose that glaucoma is one of the neglected lowest hanging fruits and actionable targets for omics and systems diagnostics in 21st century ophthalmology for the salient reasons we describe here. Additionally, we offer an analysis on two of the most pertinent neglected tropical diseases (NTDs), trachoma and river blindness, which continue to plague visual health in developing countries. We conclude with a call for research on omics applications in glaucoma and personalized visual health. © Copyright 2014, Mary Ann Liebert, Inc. 2014.

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2014

Journal Article

Lab Balakrishnan, Bhattacharjee, Mac, Ahmad, Sad, Nirujogi, R. Sae, Renuse, Sac, Subbannayya, Yaf, Marimuthu, Aa, Srikanth, S. Mae, Raju, Ra, Dhillon, Mg, Kaur, Ng, Jois, Rh, Vasudev, Vi, Ramachandra, Y. Lb, Sahasrabuddhe, N. Aa, Prasad, T. S. Kac d, Mohan, Sj, Gowda, Ha, Shankar, Sg, and Pandey, Akl m n, “Differential proteomic analysis of synovial fluid from rheumatoid arthritis and osteoarthritis patients”, Clinical Proteomics, vol. 11, 2014.[Abstract]


Background: Rheumatoid arthritis and osteoarthritis are two common musculoskeletal disorders that affect the joints. Despite high prevalence rates, etiological factors involved in these disorders remain largely unknown. Dissecting the molecular aspects of these disorders will significantly contribute to improving their diagnosis and clinical management. In order to identify proteins that are differentially expressed between these two conditions, a quantitative proteomic profiling of synovial fluid obtained from rheumatoid arthritis and osteoarthritis patients was carried out by using iTRAQ labeling followed by high resolution mass spectrometry analysis. Results: We have identified 575 proteins out of which 135 proteins were found to be differentially expressed by ≥3-fold in the synovial fluid of rheumatoid arthritis and osteoarthritis patients. Proteins not previously reported to be associated with rheumatoid arthritis including, coronin-1A (CORO1A), fibrinogen like-2 (FGL2), and macrophage capping protein (CAPG) were found to be upregulated in rheumatoid arthritis. Proteins such as CD5 molecule-like protein (CD5L), soluble scavenger receptor cysteine-rich domain-containing protein (SSC5D), and TTK protein kinase (TTK) were found to be upregulated in the synovial fluid of osteoarthritis patients. We confirmed the upregulation of CAPG in rheumatoid arthritis synovial fluid by multiple reaction monitoring assay as well as by Western blot. Pathway analysis of differentially expressed proteins revealed a significant enrichment of genes involved in glycolytic pathway in rheumatoid arthritis. Conclusions: We report here the largest identification of proteins from the synovial fluid of rheumatoid arthritis and osteoarthritis patients using a quantitative proteomics approach. The novel proteins identified from our study needs to be explored further for their role in the disease pathogenesis of rheumatoid arthritis and osteoarthritis. Sartaj Ahmad and Raja Sekhar Nirujogi contributed equally to this article. © 2014 Balakrishnan et al.; licensee BioMed Central Ltd.

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2014

Journal Article

L. Ma Groocock, Nie, Ma, Prudden, Ja, Moiani, Db, Wang, Tc, Cheltsov, Ad, Rambo, R. Pe, Arvai, A. Sb, Hitomi, Cb, Tainer, J. Abe, Luger, Kc, Perry, J. J. Pbf, Lazzerini-Denchi, Eg, and Boddy, M. Na, “RNF4 interacts with both SUMO and nucleosomes to promote the DNA damage response”, EMBO Reports, vol. 15, pp. 601-608, 2014.[Abstract]


The post-translational modification of DNA repair and checkpoint proteins by ubiquitin and small ubiquitin-like modifier (SUMO) critically orchestrates the DNA damage response (DDR). The ubiquitin ligase RNF4 integrates signaling by SUMO and ubiquitin, through its selective recognition and ubiquitination of SUMO-modified proteins. Here, we define a key new determinant for target discrimination by RNF4, in addition to interaction with SUMO. We identify a nucleosome-targeting motif within the RNF4 RING domain that can bind DNA and thereby enables RNF4 to selectively ubiquitinate nucleosomal histones. Furthermore, RNF4 nucleosome-targeting is crucially required for the repair of TRF2-depleted dysfunctional telomeres by 53BP1-mediated non-homologous end joining. Synopsis RNF4 is an important ubiquitin ligase in the DNA damage response (DDR) that targets SUMOylated proteins. This study shows that it also contains a nucleosome-targeting motif that crucially supports the DDR genome-wide. RNF4 promotes ATM-dependent 53BP1 recruitment and repair at dysfunctional telomeres. RNF4 RING domain contains an RNF168 and RING1b-related nucleosome-targeting motif. RNF4 recognizes both SUMO and nucleosomes to support DNA repair. RNF4 is an important ubiquitin ligase in the DNA damage response (DDR) that targets SUMOylated proteins. This study shows that it also contains a nucleosome-targeting motif that crucially supports the DDR genome-wide. © 2014 The Authors.

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2014

Journal Article

Lab Balakrishnan, Nirujogi, R. Sac, Ahmad, Sad, Bhattacharjee, Mae, Manda, S. Sac, Renuse, Sae, Kelkar, D. Sae, Subbannayya, Yaf, Raju, Ra, Goel, Rab, Thomas, J. Kae, Kaur, Ng, Dhillon, Mg, Tankala, S. Gg, Jois, Rh, Vasdev, Vi, Ramachandra, Y. Lb, Sahasrabuddhe, N. Aa, Prasad, T. S. Kac d, Mohan, Sj, Gowda, Ha, Shankar, Sg, and Pandey, Akl m n, “Poteomic analysis of human osteoarthritis synovial fluid”, Clinical Proteomics, vol. 11, 2014.[Abstract]


Background: Osteoarthritis is a chronic musculoskeletal disorder characterized mainly by progressive degradation of the hyaline cartilage. Patients with osteoarthritis often postpone seeking medical help, which results in the diagnosis being made at an advanced stage of cartilage destruction. Sustained efforts are needed to identify specific markers that might help in early diagnosis, monitoring disease progression and in improving therapeutic outcomes. We employed a multipronged proteomic approach, which included multiple fractionation strategies followed by high resolution mass spectrometry analysis to explore the proteome of synovial fluid obtained from osteoarthritis patients. In addition to the total proteome, we also enriched glycoproteins from synovial fluid using lectin affinity chromatography. Results: We identified 677 proteins from synovial fluid of patients with osteoarthritis of which 545 proteins have not been previously reported. These novel proteins included ADAM-like decysin 1 (ADAMDEC1), alanyl (membrane) aminopeptidase (ANPEP), CD84, fibulin 1 (FBLN1), matrix remodelling associated 5 (MXRA5), secreted phosphoprotein 2 (SPP2) and spondin 2 (SPON2). We identified 300 proteins using lectin affinity chromatography, including the glycoproteins afamin (AFM), attractin (ATRN), fibrillin 1 (FBN1), transferrin (TF), tissue inhibitor of metalloproteinase 1 (TIMP1) and vasorin (VSN). Gene ontology analysis confirmed that a majority of the identified proteins were extracellular and are mostly involved in cell communication and signaling. We also confirmed the expression of ANPEP, dickkopf WNT signaling pathway inhibitor 3 (DKK3) and osteoglycin (OGN) by multiple reaction monitoring (MRM) analysis of osteoarthritis synovial fluid samples. Conclusions: We present an in-depth analysis of the synovial fluid proteome from patients with osteoarthritis. We believe that the catalog of proteins generated in this study will further enhance our knowledge regarding the pathophysiology of osteoarthritis and should assist in identifying better biomarkers for early diagnosis. © 2014 Balakrishnan et al.; licensee BioMed Central Ltd.

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2014

Journal Article

E. Sa Dove and Özdemir, Vbc, “The epiknowledge of socially responsible innovation”, EMBO Reports, vol. 15, pp. 462-463, 2014.

2014

Conference Paper

G. Sridevi, Dr. Amalendu Jyotishi, Dr. Sushanta Kumar Mahapatra, Bedamatta, S., and Jagadeesh, G., “Climate Change Vulnerability and Agrarian Communities-Insights from the Composite Vulnerability Index of Andhra Pradesh and Karnataka”, in International conference on climate change, Kerala University, Trivandrum, India, 2014.[Abstract]


Climate change is a main challenge for agriculture, food security and rural livelihoods for billions of people in India. Agriculture is the sector most vulnerable to climate change due to its high dependence on climate and weather conditions. Among India’s population of more than one billion people, about 68% are directly or indirectly involved in the agricultural sector. This sector is particularly vulnerable to present-day climate variability. In this contest this paper examines the Socio-economic and climate analytical study of the vulnerability index in Andhra Pradesh and Karnataka states using secondary data; it examines the vulnerability through five different Sub-indicator of socio-demographic, agriculture, occupational, common property resource (CPR), and climate in respective states among different districts. Data was used in this paper has taken from different sources, like census in India 2011, Directorate of Economics and Statistics of respective states governments. Rainfall data was collected from the India Meteorological Department (IMD). In order to capture the vulnerability from two different states the composite vulnerability index (CVI) was developed and used. This indicates the vulnerability situation of different districts under two states. The study finds that Adilabed district in Andhra Pradesh and Chamarajanagar in Karnataka had highest level of vulnerability while Hyderabad and Bangalore in respective states have least level of vulnerability. Further, it also notices that the index was mapped using Geographical Information Systems (GIS) maps and it has been observed that almost same districts from two states are found to be facing highest vulnerability.

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2014

Conference Paper

G. Sridevi, Dr. Amalendu Jyotishi, Dr. Sushanta Kumar Mahapatra, Jagadeesh, G., and Bedamatta, S., “Climate Change Vulnerability in Agriculture Sector: Indexing and Mapping of Four Southern Indian States”, Department of Economic Sciences (DSE), University of Bologna, Italy, 2014.[Abstract]


Agriculture is the sector most vulnerable to climate change due to its high dependence on climate and weather conditions. Climate change is a main challenge for agriculture, food security and rural livelihoods for millions of people in India. Among India’s population of more than one billion people, about 68% are directly or indirectly involved in the agricultural sector. This sector is particularly vulnerable to present-day climate variability. In this paper an attempt is made to map and analyze the vulnerability to climate change in different districts of four south Indian states: Andhra Pradesh, Karnataka, Tamil Nadu and Kerala. We have taken five sources of vulnerability indicators: socio-demographic, climatic, agricultural, occupational and common property resources vulnerabilities to compute the composite vulnerability index. The composite vulnerability index suggests that, Adilabad, Chamarajanagar, Thiruvarur and Kasaragod are the most vulnerable districts of Andhra Pradesh, Karnataka, Tamil Nadu
and Kerala respectively, whereas Hyderabad, Belgaum, Thoothukkudi, Kottayam are the least vulnerable districts.

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2014

Patent

A. R. Pai and Dr. Bipin G. Nair, “Method of preparing reduced graphene oxide”, U.S. Patent 626/CHE/20142014.

2014

Conference Paper

P. Aarathi, Jeethu, R., Dr. Bipin G. Nair, and Dr. Satheesh Babu T. G., “Design, Simulation and fabrication of Microfluidic Channels for Lab-on-a-Chip applications”, in International Conference on Biomaterials-2014 , Asian Polymers Association, New Delhi, 2014.

2014

Conference Paper

T. S. Sethu Parvathy, Keerthy, D., Dr. Bipin G. Nair, and Dr. Satheesh Babu T. G., “Activated Screen Printed Electrode For Highly Sensitive Ascorbic Acid Sensing”, in International Conference on Biomaterials-2014, Asian Polymers Association, New Delhi, 2014.

2014

Journal Article

R. Sharma, Zaveri, A., Dr. Jayashree G., Srinath, T., Varshney, U., and Visweswariah, S. S., “Paralogous cAMP Receptor Proteins in Mycobacterium smegmatis Show Biochemical and Functional Divergence”, Biochemistry, vol. 53, pp. 7765–7776, 2014.[Abstract]


The cyclic AMP receptor protein (CRP) family of transcription factors consists of global regulators of bacterial gene expression. Here, we identify two paralogous CRPs in the genome of Mycobacterium smegmatis that have 78% identical sequences and characterize them biochemically and functionally. The two proteins (MSMEG_0539 and MSMEG_6189) show differences in cAMP binding affinity, trypsin sensitivity, and binding to a CRP site that we have identified upstream of the msmeg_3781 gene. MSMEG_6189 binds to the CRP site readily in the absence of cAMP, while MSMEG_0539 binds in the presence of cAMP, albeit weakly. msmeg_6189 appears to be an essential gene, while the Δmsmeg_0539 strain was readily obtained. Using promoter–reporter constructs, we show that msmeg_3781 is regulated by CRP binding, and its transcription is repressed by MSMEG_6189. Our results are the first to characterize two paralogous and functional CRPs in a single bacterial genome. This gene duplication event has subsequently led to the evolution of two proteins whose biochemical differences translate to differential gene regulation, thus catering to the specific needs of the organism.

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2014

Conference Paper

Chaitanya Medini, Asha Vijayan, Egidio D'Angelo, Dr. Bipin G. Nair, and Dr. Shyam Diwakar, “Computationally Efficient Bio-realistic Reconstructions of Cerebellar Neuron Spiking Patterns”, in Proceedings of the 2014 International Conference on Interdisciplinary Advances in Applied Computing, Amrita Vishwa Vidyapeetham, Coimbatore, India, 2014.[Abstract]


Simple spiking models have been known to replicate detailed mathematical models firing properties with reliable accuracy in spike timing. We modified the adaptive exponential integrate and fire mathematical model to reconstruct different cerebellar neuronal firing patterns. We were able to reconstruct the firing dynamics of various types of cerebellar neurons and validated with previously published experimental studies. To model the neurons, we exploited particle swarm optimization to fit the parameters. The study showcases the match of electroresponsiveness of the neuronal models to data from biological neurons. Results suggest that models are close reconstructions of the biological data since frequency and spike-timing closely matched known values and were similar to those in previously published detailed computationally intensive biophysical models. Such spiking models have a number of applications including design of large-scale circuit models in order to understand physiological dysfunction and for various computational advantages.

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2014

Conference Paper

Dr. Shyam Diwakar, Sandeep Bodda, Chaitanya Nutakki, Asha Vijayan, Dr. Krishnashree Achuthan, and Dr. Bipin G. Nair, “Neural Control using EEG as a BCI Technique for Low Cost Prosthetic Arms”, in In Proceedings of the International Conference on Neural Computation Theory and Applications (NCTA-2014), Rome, Italy, 2014.[Abstract]


There have been significant advancements in brain computer interface (BCI) techniques using EEG-like methods. EEG can serve as non-invasive BMI technique, to control devices like wheelchairs, cursors and robotic arm. In this paper, we discuss the use of EEG recordings to control low-cost robotic arms by extracting motor task patterns and indicate where such control algorithms may show promise towards the humanitarian challenge. Studies have shown robotic arm movement solutions using kinematics and machine learning methods. With iterative processes for trajectory making, EEG signals have been known to be used to control robotic arms. The paper also showcases a case-study developed towards this challenge in order to test such algorithmic approaches. Non-traditional approaches using neuro-inspired processing techniques without implicit kinematics have also shown potential applications. Use of EEG to resolve temporal information may, indeed, help understand movement coordination in robotic arm.

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2014

Book Chapter

Pandurangan Nanjan, Bose, C., Singh, V., and Dr. Asoke Banerji, “Isolation, Characterization and Chemical Fingerprinting of Bioactives from Indian Seabuckthorn (Hippophae L.) Species”, in Seabuckthorn (Hippophae L.) : A Multipurpose Wonder Plant : Vol. IV: Emerging Trends in Research and Technologies, vol. 4, 2014, p. 262.

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