Publications

Publication Type: Journal Article

Year of Publication Publication Type Title

2017

Journal Article

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


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

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2016

Journal Article

H. Jayalekshmi, Victus, N. Mary G., Anoop, R., Sarath, T. M., Sali, S., .Harikrishnan, C., Kaushik, N., Kumar, G. B., and Dr. Bipin G. Nair, “Combinatorial Effect of D-Amino Acids and Tetracycline Against P.aeruginosa Biofilm”, International Journal of Pharmacy and Pharmaceutical Sciences, vol. 8, no. 11, pp. 216-220., 2016.[Abstract]


Antimicrobial resistance is increasing worldwide and is of particular concern in gram-negative bacilli where there is a paucity of new and effective antimicrobial agents. Pseudomonas aeruginosa infections are associated with increased mortality and morbidity, especially in immunocompromised and burn patients respectively. The organism is capable of developing resistance to practically most classes of antibiotics and has always been considered a difficult target for antimicrobial chemotherapy because of the ability of bacteria to form biofilm. A biofilm is a structured consortium of bacteria, embedded in a self-produced polymer matrix consisting of polysaccharide, protein and DNA. Biofilm bacteria are a major concern in the treatment of infectious diseases. The objective of this work is to evaluate the efficacy of the combination of Tetracycline with different D-amino acids such as D-Leucine, D-Methionine, D-Tyrosine, and D-Tryptophan against P.aeruginosa biofilm. Sub-inhibitory concentrations of Tetracycline (0.5 MIC) along with different D-aminoacids were tested for its anti-biofilm activity. The validations of these results were done in in vitro wound dressing and ex vivo porcine skin models which shows that tetracycline-D-tryptophan combination could reduce biofilm formation. The studies using porcine skin explant confirms the efficacy of this combination for inhibiting the biofilm formation even in biological substances. The Hemocompatibility study shows no significant hemolysis by this combination. The results established the potential therapeutic application of D-aminoacids alone or in combination with tetracycline for treating biofilm associated clinical problems caused by P.aeruginosa.

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2016

Journal Article

S. Kalyanavenkataraman, Pandurangan Nanjan, Dr. Asoke Banerji, Dr. Bipin G. Nair, and Geetha B Kumar, “Discovery of arjunolic acid as a novel non-zinc binding carbonic anhydrase II inhibitor”, Bioorganic chemistry, vol. 66, pp. 72–79, 2016.[Abstract]


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

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2015

Journal Article

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


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

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2015

Journal Article

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


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

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2015

Journal Article

Hemalata Sasidharakurup, Radhamani, R., Dhanush Kumar, Dr. Shyam Diwakar, Nizar, N., Dr. Bipin G. Nair, and Dr. Krishnashree Achuthan, “Using Virtual Laboratories as Interactive Textbooks: Studies on Blended Learning in Biotechnology Classrooms”, EAI Endorsed Trans. e-Learning, Accept., 2015.[Abstract]


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

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PDF iconusing-virtual-laboratories-interactive-textbooks-studies-blended-learning-biotechnology-01july2015.pdf

2015

Journal Article

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


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

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2015

Journal Article

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


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

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2015

Journal Article

Dr. Jyotsna Nambiar, G., K., S.R., S., S.N., G., R.S., L., and Dr. Bipin G. Nair, “A Novel2-Alkoxy-3, 5-Dihydroxypyridine Mediated Regulation of Gelatinases”, International Journal of Pharma and Bio Sciences, vol. 6, pp. 779-788, 2015.

2015

Journal Article

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


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

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PDF iconstrategy-enhance-efficacy-doxorubicin-solid-tumor-cells-methyl-cyclodextrin-involvement-of-p-53-and-fas-receptor-ligand-complex-01july2015.pdf

2015

Journal Article

S. Ray, Dr. Shyam Diwakar, Srivastava, S., and Dr. Bipin G. Nair, “E-learning resources and virtual labs”, Nature India Special Issue, pp. 13-14., 2015.[Abstract]


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

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

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2015

Journal Article

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


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

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PDF iconanacardic-acid-induces-apoptosis-cell-death-rice-blast-fungus-magnaporthe-oryzae-3august2015.pdf

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.&nbsp;In vitro&nbsp;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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PDF iconmacrophage-migration-inhibitory-factor-therapeutic-target-gallbladder-cancer-2015.pdf

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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PDF iconchronic-exposure-chewing-tobacco-selects-overexpression-stearoyl-coa-desaturase-normal-oral-keratinocytes-01september2015.pdf

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 (&gt;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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2011

Journal Article

Dr. Shyam Diwakar, Dr. Krishnashree Achuthan, Prof. Nedungadi, P., and Dr. Bipin G. Nair, “Enhanced facilitation of biotechnology education in developing nations via virtual labs: analysis, implementation and case-studies”, International Journal of Computer Theory and Engineering, vol. 3, pp. 1–8, 2011.[Abstract]


Methods for educating students in biotechnology require intensive training in laboratory procedures. Laboratory procedures cost Universities in terms of equipment and experienced guidance which often come short in many developing countries. Universities need revitalizing approach and well-adapted curriculum especially in terms of laboratory practice. For enhanced education at the level of University-level laboratory courses such as those in biology or biotechnology, one of the key elements is the need to allow the student to familiarize laboratory techniques in par with regular theory. The Sakshat Amrita virtual biotechnology lab project focusing on virtualizing wet-lab techniques and integrating the learning experience has added a new dimension to the regular teaching courses at the University. Establishing virtual labs requires both domain knowledge and virtualizing skills via programming, animation and device-based feedback. This paper reports a cost-effective process used in virtualizing real biotechnology labs for education at Universities. The major challenge in setting up an effective knowledge dissemination for laboratory courses was not only the scientific approach of biotechnology, but included the virtualization aspects such as usage/design scalability, deliverability efficiency, network connectivity issues, security and speed of adaptability to incorporate and update changes into existing experiments. This paper also discusses an issue-specific case-study of a functional virtual lab in biotechnology and its many issues and challenges.

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2010

Journal Article

D. S, K, A., Nedungadi, P., and Nair, B. G., “Enhanced Facilitation of Biotechnology Education in Developing Nations via Virtual Labs: Analysis, Implementation and Case-studies”, Intl Journal of Computer Technology and Engineering, 2010.

2009

Journal Article

T. .Ramachandran and Dr. Bipin G. Nair, “A Highly Selective and Sensitive Ascorbic Acid Sensor Using Electrodeposited Gold Nanoparticles on Polyaniline Modified Titanium Dioxide Nanotube Arrays”, Journal of Physical Chemistry (communicated), 2009.

2001

Journal Article

L. S. Nadler, Dr. Geetha Kumar, and Nathanson, N. M., “Identification of a basolateral sorting signal for the M3 muscarinic acetylcholine receptor in Madin-Darby canine kidney cells”, Journal of Biological Chemistry, vol. 276, pp. 10539–10547, 2001.

2000

Journal Article

K. A. Alvi, Dr. Bipin G. Nair, Rabenstein, J., Davis, G., and Baker, D. B., “CD45 Tyrosine Phosphatase Inhibitory Components from Aspergillus niger”, J. Antibiotics, no. 53, pp. 110-113, 2000.[Abstract]


Two inhibitors of CD45 tyrosine phosphatase, dihydrocarolic acid (1) and penitricin D (2), were isolated from a fermentation broth of the fungus Aspergillus niger and purified by HSCCC (high speed countercurrent chromatography) followed by HPLC. The structures were determined by NMR. The inhibitory activities of both compounds were specific to tyrosine phosphatases. More »»

2000

Journal Article

Dr. Bipin G. Nair, Alvi, K. A., Baker, D. B., Steinecker, V., and .Hosken, M., “Identification of Inhibitors of Inducible Nitric Oxide Synthase from Microbial Extracts”, J. Antibiotics, vol. 53, pp. 496-501, 2000.[Abstract]


A new member of the angucycline family, vineomycin C (3), together with four known metabolites saquayamycin A1 (1), A-7884 (2), rabelomycin (5) and xanthomegnin (6) were isolated from microbial extracts. The structures were determined by 1D and 2D NMR techniques and chemical degradation. Compounds 1-3 and 5 were isolated from a fermentation of Streptomyces sp., while 6 was isolated from a fungal fermentation extract. All five compounds have shown potent inhibitory activity in the inducible nitric oxide synthase (iNOS) assay. More »»

1999

Journal Article

L. S. Nadler, Dr. Geetha Kumar, Hinds, T. R., Migeon, J. C., and Nathanson, N. M., “Asymmetric distribution of muscarinic acetylcholine receptors in Madin-Darby canine kidney cells”, American Journal of Physiology-Cell Physiology, vol. 277, pp. C1220–C1228, 1999.

1998

Journal Article

K. A. Alvi, Casey, A., and Dr. Bipin G. Nair, “Pulchellalactam: a CD45 protein tyrosine phosphatase inhibitor from the marine fungus Corollospora pulchella”, The Journal of antibiotics, Japan Antibiotics Research Association, vol. 51, pp. 515–517, 1998.

1997

Journal Article

K. A. Alvi, Dr. Bipin G. Nair, Gallo, C., and Baker, D., “Screening of microbial extracts for tyrosine kinase inhibitors”, Journal of antibiotics, vol. 50, pp. 264–266, 1997.

1997

Journal Article

K. A. Alvi, Dr. Bipin G. Nair, Pu, H., Ursino, R., Gallo, C., and Mocek, U., “Phomacins: Three Novel Antitumor Cytochalasan Constituents Produced by a Phoma sp.”, The Journal of organic chemistry, vol. 62, pp. 2148–2151, 1997.[Abstract]


Three novel cytochalasans, phomacins A, B and C, were isolated from a fermentation broth of the fungus Phoma sp. and purified by HSCCC (high speed countercurrent chromatography) followed by HPLC. The structures were determined by 1D and 2D NMR techniques. All three compounds have shown potent inhibitory activity against the HT29 colonic adenocarcinoma cell line. More »»

1996

Journal Article

T. B. Patel, .Sun, H., .Poppleton, H., Dr. Bipin G. Nair, .M.Rashed, H., and .Yu, Y., “Epidermal growth factor mediated regulation of G-proteins and adenylyl cyclase in cardiac muscle”, Methods in Neurosci, no. 29, pp. 319-343, 1996.[Abstract]


Publisher Summary This chapter presents a number of experimental approaches that have proved to be very useful in elucidating the mechanism(s) involved in epidermal growth factor (EGF) -mediated stimulation of cardiac adenylylcyclase. However, there are several additional questions pertaining to the detailed understanding of the mechanism(s) involved in interactions between the \{EGF\} receptor and Gs interaction. Thus, the in vitro studies demonstrate the juxtamembrane region of the \{EGF\} receptor that is important for stimulation of Gs by performing mutation(s) of key residue(s) in the juxtamembrane region of the \{EGF\} receptor, to determine whether the ability of \{EGF\} to stimulate adenylylcyclase can be obliterated. Similarly, it is important to determine the region(s) of Gsα that interact with the \{EGF\} receptor. It is also determine that what elements confer specificity to the ability of \{EGF\} to stimulate adenylylcyclase. The latter goal poses a particularly important question, because \{EGF\} does not elevate cAMP content in all cells that express the \{EGF\} receptor, Gs, and adenylylcyclase. More »»

1995

Journal Article

Dr. Bipin G. Nair, Yu, Y., Rashed, H. M., Sun, H., and Patel, T. B., “Transforming growth factor- beta 1 modulates adenylyl cyclase signaling elements and epidermal growth factor signaling in cardiomyocytes”, Journal of cellular physiology, vol. 164, pp. 232–239, 1995.[Abstract]


Studies presented in this report were designed to investigate the effects of transforming growth factor-beta 1 (TGF-beta 1) on epidermal growth factor (EGF)-mediated stimulation of cAMP accumulation in cardiac myocytes and elucidate the mechanism(s) involved in this modulation. TGF-beta 1 (20 pM) treatment of cardiac myocytes, in a time-dependent manner, decreased the ability of EGF (100 nM) to increase cAMP accumulation. Significant attenuation of EGF-elicited cAMP accumulation was observed 2 h after exposure to TGF-beta 1 and 18 h after addition of TGF-beta 1, the ability of EGF to increase cAMP accumulation was completely obliterated. TGF-beta 1 neither decreased immunoprecipitable EGF receptors in membranes from cardiomyocytes nor altered the specific binding of [125I]EGF to cardiomyocyte membranes. However, TGF-beta 1 decreased the ability of EGF to phosphorylate membrane proteins on tyrosine residues. TGF-beta 1 treatment of cardiomyocytes also decreased the ability of forskolin to augment cAMP accumulation in intact cells and stimulate adenylyl cyclase activity. Similarly, in membranes of TGF-beta 1-treated cells, neither isoproterenol nor EGF stimulated adenylyl cyclase activity. Interestingly, as assessed by the ability of A1F4- to stimulate adenylyl cyclase, TGF-beta 1 did not alter the coupling between Gs and catalytic subunits. Likewise, TGF-beta 1 did not alter the functional activity of the inhibitory regulatory element of the system, Gi. Western analysis of cellular proteins revealed that TGF-beta 1 did not alter the amounts of Ga alpha, Gi alpha 2, and Gi alpha 3. We conclude that TGF-beta 1 attenuates EGF-elicited cAMP accumulation in cardiomyocytes, in part, by decreasing the EGF receptor kinase function and that TGF-beta 1-mediated alterations in the activity of adenylyl cyclase catalytic subunit also contribute toward the regulation of adenylyl cyclase by various agonists. More »»

1995

Journal Article

T. B. Patel, Dr. Bipin G. Nair, Padmini, E., Rashed, H. M., and Sun, H., “Alterations in messenger RNA encoding atrial natriuretic hormone receptor A and C subtypes during hepatic regeneration”, Hepatology, vol. 21, pp. 1682–1689, 1995.[Abstract]


Previously, we demonstrated that, 48 hours after partial hepatectomy, in the regenerating liver the number of both atrial natriuretic hormone (ANF) receptor subtypes, the guanylyl cyclase—linked and ANF-C receptors, is increased twofold. Subsequently, we demonstrated that activation of ANF-C receptors inhibits growth of hepatocytes. Therefore, studies were performed to determine whether, during hepatic regeneration, the increase in ANF receptor subtypes is accompanied by an increase in their respective transcripts. Our data demonstrate that in the normal and regenerating rat liver, the predominant guanylyl cyclase-linked ANF receptor is of the ANF-A subtype. Moreover, messenger RNA (mRNA) encoding the ANF-A and ANF-C receptors are transiently increased after surgery; the levels of mRNA encoding both receptor subtypes remain unchanged in livers of sham-operated animals. ANF-A receptor mRNA is maximally increased 12 hours after partial hepatectomy, whereas the maximal increase in ANF-C receptor mRNA is observed between 0.5 hour and 4 hours after hepatectomy. The increase in ANF-C receptor transcript is accompanied by increased expression of protein, 4 hours after hepatectomy. However, the ANF-C receptor protein is also elevated 48 hours after partial hepatectomy when ANF-C receptor mRNA levels are not different from controls. Likewise, although ANF-A receptors are increased when hepatic levels of mRNA encoding the protein are maximally elevated, the maximal increase in ANF-A receptor protein occurs at times when transcript levels are low and similar to those in sham-operated controls. These findings demonstrate differential regulation in the expression of ANF-A and ANF-C receptors and are illustrative of regulation of expression of both receptors at the translational or posttranslational levels. More »»

1993

Journal Article

Geetha B Kumar and Black, P. N., “Bacterial long-chain fatty acid transport. Identification of amino acid residues within the outer membrane protein FadL required for activity.”, Journal of Biological Chemistry, vol. 268, pp. 15469–15476, 1993.

1993

Journal Article

Dr. Bipin G. Nair and Patel, T. B., “Regulation of cardiac adenylyl cyclase by Epidermal Growth Factor (EGF): Role of EGF receptor protein tyrosine kinase activity”, Biochemical pharmacology, vol. 46, pp. 1239–1245, 1993.[Abstract]


We have shown previously that the α subunit of the stimulatory GTP binding regulatory component of adenylyl cyclase (Gsα) mediates epidermal growth factor (EGF)-elicited stimulation of rat cardiac adenylyl cyclase (Nair et al., J Biol Chem265: 21317–21322, 1990). Employing purified protein phosphotyrosine phosphatase, and benzylidene derivatives (tyrphostins: compounds 11 and 12) that selectively inhibit EGF receptor protein tyrosine kinase (EGFRK) activity, the role of EGFRK in EGF-mediated stimulation of cardiac adenylyl cyclase was investigated. The ability of the tyrphostins to inhibit the EGFRK activity in cardiac membranes was determined by monitoring tyrosine phosphorylation of either the 170 kDa protein or immunoprecipitated EGF receptor at 0° and room temperature, respectively. Compounds 11 and 12, in a concentration-dependent manner, inhibited EGF receptor tyrosine kinase activity. In assays of adenylyl cyclase activity neither compound 11 nor compound 12 altered Gpp(NH)p- or isoproterenol-stimulated activity. However, both compounds, in a concentration-dependent manner, attenuated the ability of EGF to stimulate adenylyl cyclase activity without altering specific binding of [125I]EGF to cardiac membranes. Similarly, protein phosphotyrosine phosphatase obliterated the ability of EGF, but not isoproterenol, to stimulate adenylyl cyclase. Thus, we conclude that protein tyrosine kinase activity of the EGF receptor is essential for the stimulation of cardiac adenylyl cyclase by EGF. More »»

1993

Journal Article

Dr. Bipin G. Nair, Rashed, H. M., and Patel, T. B., “Epidermal growth factor produces inotropic and chronotropic effects in rat hearts by increasing cyclic AMP accumulation”, Growth Factors, vol. 8, pp. 41–48, 1993.[Abstract]


Previously we have shown that epidermal growth factor (EGF) stimulates cardiac adenylyl cyclase and increases cAMP accumulation in the rat heart (Nair et al., Biochem. J. 264, 563-571, 1989). Moreover, we have shown that the stimulation of adenylyl cyclase by EGF in heart is mediated via activation of the stimulatory GTP binding regulatory protein Gs alpha (Nair et al., J. Biol. Chem. 265, 21317-21322, 1990). Since cAMP increases the beating rate of hearts, studies were performed to investigate the effects of EGF on mechanical function of the heart and the role of cAMP in mediating the cardiac effects of EGF. In isolated perfused rat hearts EGF (15 nM) decreased perfusion pressure, increased ventricular contractility and heart rate in a manner similar to that observed with the beta-adrenergic receptor agonist isoproterenol (10 nM). In the presence of the adenosine A1 receptor agonist (-)-N6-(R-phenylisopropyl)-adenosine (PIA, 100 nM) which via activation of the inhibitory GTP binding protein Gi inhibits adenylyl cyclase, the effects of EGF on cAMP accumulation in the heart were markedly attenuated. PIA also decreased the ability of EGF and isoproterenol to alter cardiac contractility and beating rate. However, PIA did not attenuate the increase in heart rate and contractility induced by the alpha-adrenergic agonist phenylephrine which does not stimulate cAMP accumulation in the heart. These data suggest that EGF alters cardiac function by increasing cellular cAMP accumulation. More »»

1993

Journal Article

A. R. Amin, Swenson, C. D., Xue, B., Ishida, Y., Dr. Bipin G. Nair, Patel, T. B., Chused, T. M., and G Thorbecke, J., “Regulation of IgD-Receptor Expression on Murine T Cells: II. Upregulation of IgD Receptors Is Obtained after Activation of Various Intracellular Second-Messenger Systems; Tyrosine Kinase Activity Is Required for the Effect of IgD”, Cellular immunology, vol. 152, pp. 422–439, 1993.[Abstract]


The presence of IgD receptors (IgD-R) on T cells during a primary response to antigen causes augmented antibody production and facilitates priming for a secondary response. Cross-linked, but not monomeric IgD leads to a rapid upregulation of these receptors on T cells. As shown in the present study, the rapid upregulation of IgD-specific receptors is also induced by cross-linking of T cell surface molecules known to mediate triggering of T cell activation, such as CD3, CD2, and Thy 1. Furthermore, IgD-R are also upregulated by pharmacologically active compounds that increase intracellular cAMP and by PMA/DiOG plus ionomycin, but not by either PMA or ionomycin alone. The upregulation of IgD-R by anti-CD3 is inhibited by both calphostin C and herbimycin A, while that due to DiOG plus ionomycin is only inhibited by calphostin C. Upregulation of IgD-R by increased cAMP is blocked by HA1004, but not by low concentrations of staurosporine or herbimycin A. IgD itself does not cause an increase in intracellular cAMP, protein kinase C translocation, influx of extracellular Ca2+, or a change in membrane potential. Relatively specific inhibitors of these activation pathways, HA1004, calphostin C, and neomycin, also fail to interfere with IgD-receptor upregulation by IgD itself. However, tyrosine kinase inhibitors, including herbimycin A, tyrphostin C11, and genistein, completely prevent the effect of IgD on IgD-R expression. Although an influx of Ca2+ is apparently not involved, a role for intracellular Ca2+ in the upregulation of IgD-R by IgD on T cells is indicated by the susceptibility to inhibition by BAPTA, W7, and FK520. We conclude that activation of at least three different second-messenger systems can cause IgD-R upregulation, but that the effect of IgD itself requires tyrosine kinase activity, perhaps in an intracellular Ca(2+)-dependent manner. More »»

1992

Journal Article

Y. Yu, Dr. Bipin G. Nair, and Patel, T. B., “Epidermal growth factor stimulates cAMP accumulation in cultured rat cardiac myocytes”, Journal of cellular physiology, vol. 150, pp. 559–567, 1992.[Abstract]


We have previously shown that epidermal growth factor (EGF) augments cAMP accumulation in the heart and stimulates cardiac adenylyl cyclase via a G protein mediated mechanism (Nair et al., 1989). More recently, employing an antibody against the carboxy-terminus decapeptide of Gs alpha, we have demonstrated that Gs alpha mediates the effects of EGF on cardiac adenylyl cyclase (Nair et al., 1990). Since the heart comprises of a variety of cell types, the purpose of the studies presented here was to determine whether or not the effects of EGF on adenylyl cyclase were mediated in cardiac myocytes or noncardiomyocytes. Therefore, cultures of ventricular cardiomyocytes and noncardiomyocytes from neonatal rat hearts were established and characterized. Apart from the differences in cellular morphology, cardiomyocytes but not the noncardiomyocytes employed in our studies expressed the alpha- and beta-myosin heavy chain (MHC) mRNA and the beta-MHC protein. Additionally, as described previously, treatment of cardiomyocytes with thyroid hormone increased alpha-MHC mRNA and decreased the expression of beta-MHC mRNA, indicating that the cardiomyocytes employed in our studies were responding in a physiologically relevant manner. EGF in a time-dependent manner increased cAMP accumulation in the cardiomyocytes but not in noncardiomyocytes. Maximum and half-maximum effects were observed at 100 nM and 2 nM concentrations of EGF, respectively. As determined by the presence of immunoreactive EGF receptors and tyrosine phosphorylation of the 170 kDa protein in membranes of cardiomyocytes and noncardiomyocytes, both the cell populations contained functional EGF receptors. Therefore, the differential effects of EGF on cAMP accumulation in the two cell populations appear to be due to differential coupling of the EGF receptors to the adenylyl cyclase system rather than the absence of EGF receptors in noncardiomyocytes. Consistent with our previous findings in isolated membranes and perfused rat hearts, EGF-elicited increase in cAMP accumulation in cardiomyocytes did not involve activation of beta-adrenoreceptors and was abolished by prior treatment of cells with cholera toxin. Overall, our findings demonstrate that EGF-elicited increase in cAMP accumulation in the heart is the reflection of changes in cAMP content of cardiomyocytes and not noncardiomyocytes. More »»

1991

Journal Article

Geetha B Kumar and Black, P. N., “Linker mutagenesis of a bacterial fatty acid transport protein. Identification of domains with functional importance.”, Journal of Biological Chemistry, vol. 266, pp. 1348–1353, 1991.

1991

Journal Article

Dr. Bipin G. Nair, Steinke, L., Yu, Y. M., Rashed, H. M., Seyer, J. M., and Patel, T. B., “Increase in the number of atrial natriuretic hormone receptors in regenerating rat liver.”, Journal of Biological Chemistry, vol. 266, pp. 567–573, 1991.[Abstract]


Forty-eight hours after partial (approximately 67%) hepatectomy the activity of the particulate guanylate cyclase was increased by 2-fold in the regenerating rat liver. This increase was not an artifact of membrane isolation procedures, and as determined by 125I-labeled Tyr-28 atrial natriuretic hormone-(1-28) ANF binding, was accompanied by a 2-fold increase in the number of ANF receptors. The Kd of the receptors in membranes of regenerating livers was not significantly different from the Kd of the receptors in livers of sham-operated rats. The linear synthetic descysteine analog of ANF, analog I, which binds only to the 66-kDa receptors, displaced approximately 40% of the specifically bound 125I-ANF in liver membranes from both hepatectomized and sham-operated (control) animals. Affinity cross-linking studies with 125I-ANF confirmed the increase in the 116-kDa ANF receptor in membranes of regenerating livers. In perfused livers derived from control and hepatectomized animals, the basal rates of cGMP production were not significantly different. However, atriopeptin II-stimulated cGMP production was twice as great in regenerating livers as compared with controls. These data demonstrate that the increase in particulate guanylate cyclase activity observed during liver regeneration is due to an increase in the 116-kDa ANF receptor-associated activity. Additionally, our data demonstrate that the regenerating rat liver may be a valuable model with which to study the role of the hepatic ANF receptor/particulate guanylate cyclase. More »»

1991

Journal Article

Dr. Bipin G. Nair and Patel, T. B., “Inhibition of hepatic adenylate cyclase by NADH”, Life sciences, vol. 49, pp. 915–923, 1991.[Abstract]


Adenylate cyclase activity in isolated rat liver plasma membranes was inhibited by NADH in a concentration-dependent manner. Half-maximal inhibition of adenylate cyclase was observed at 120 microM concentration of NADH. The effect of NADH was specific since adenylate cyclase activity was not altered by NAD+, NADP+, NADPH, and nicotinic acid. The ability of NADH to inhibit adenylate cyclase was not altered when the enzyme was stimulated by activating the cyclase was not altered when the enzyme was stimulated by activating the Gs regulatory element with either glucagon or cholera toxin. Similarly, inhibition of Gi function by pertussis toxin treatment of membranes did not attenuate the ability of NADH to inhibit adenylate cyclase activity. Inhibition of adenylate cyclase activity to the same extent in the presence and absence of the Gpp (NH) p suggested that NADH directly affects the catalytic subunit. This notion was confirmed by the finding that NADH also inhibited solubilized adenylate cyclase in the absence of Gpp (NH)p. Kinetic analysis of the NADH-mediated inhibition suggested that NADH competes with ATP to inhibit adenylate cyclase; in the presence of NADH (1 mM) the Km for ATP was increased from 0.24 +/- 0.02 mM to 0.44 +/- 0.08 mM with no change in Vmax. This observation and the inability of high NADH concentrations to completely inhibit the enzyme suggest that NADH interacts at a site(s) on the enzyme to increase the Km for ATP by 2-fold and this inhibitory effect is overcome at high ATP concentrations. More »»

1991

Journal Article

E. Claro, Wallace, M. A., Fain, J. N., Dr. Bipin G. Nair, Patel, T. B., Shanker, G., and Baker, H. J., “Altered phosphoinositide-specific phospholipase C and adenylyl cyclase in brain cortical membranes of cats with GM1 and GM2 gangliosidosis”, Molecular brain research, vol. 11, pp. 265–271, 1991.[Abstract]


Phosphoinositide-specific phospholipase C and adenylyl cyclase were studied in brain cortical membranes from cats with GM1 and GM2 gangliosidosis. In contrast to brain cortical membranes from unaffected control cats, phospholipase C acting against exogenously supplied phosphoinositide substrates did not respond to stimulation by GTP gamma S, carbachol or fluoroaluminate in cortical membranes of cats with gangliosidosis. However, the enzyme was activated by calcium in membranes from affected cats to the same extent as in membranes from control cats. Basal adenylyl cyclase activity was increased 3-fold in cortical membranes of cats with GM1 and GM2 gangliosidosis, compared with unaffected sibling controls. Fluoroaluminate was equally effective in stimulating adenylyl cyclase in controls and in membranes of affected and normal cats. In addition, GppNHp was able to inhibit the forskolin-activated enzyme both in membranes from cats with gangliosidosis and sibling controls. These data suggest that the activation of phosphoinositide-specific phospholipase C in brain membranes by guanine nucleotide binding proteins is markedly impaired in GM1 and GM2 gangliosidoses. More »»

1990

Journal Article

Dr. Bipin G. Nair, Parikh, B., Milligan, G., and Patel, T. B., “Gs alpha mediates epidermal growth factor-elicited stimulation of rat cardiac adenylate cyclase.”, Journal of Biological Chemistry, vol. 265, pp. 21317–21322, 1990.[Abstract]


In an earlier study we demonstrated that epidermal growth factor (EGF) increases the cellular accumulation of cAMP in perfused rat hearts by stimulating the cardiac adenylate cyclase via a stimulatory GTP-binding protein (Nair, B. G., Rashed, H. M., and Patel, T. B. (1989) Biochem. J. 264, 563-571). Employing antiserum, CS1, generated against a synthetic decapeptide RMHLRQYELL representing the carboxyl terminus of Gs alpha, the involvement of Gs in mediating the effects of EGF on cardiac adenylate cyclase was further investigated. The CS1 antiserum specifically recognized two forms, (52 and 40 kDa) of Gs alpha in rat cardiac membranes; the 52 kDa being the predominant species. In functional assays of adenylate cyclase activity, the CS1 antiserum did not alter either aluminum fluoride- or forskolin-stimulated adenylate cyclase activity. Similarly, basal adenylate cyclase activity in the absence of guanyl-5'-yl imidodiphosphate (Gpp(NH)p) was also not altered by the CS1 antiserum. However, as compared with controls performed in the presence of non-immune serum, preincubation of cardiac membranes with the CS1 antiserum resulted in a concentration-dependent inhibition of Gpp(NH)p-, isoproterenol-, and EGF-stimulated activities. In experiments which monitored Gi function as the ability of different G(pp)NHp, (-)N6-(R-phenylisopropyl)adenosine and carbachol to inhibit forskolin-stimulated adenylate cyclase, CS1 antiserum by inhibiting Gs, increased the apparent activity of Gi. Overall, our data demonstrate that the CS1 antiserum can specifically inhibit Gs function and therefore the stimulation of adenylate cyclase by agonists whose actions are mediated by Gs. In this respect, the data presented here demonstrate that Gs is the G-protein involved in mediating EGF-elicited stimulation of cardiac adenylate cyclase. Additionally, the finding that CS1 antiserum can overcome the effects of Gpp(NH)p on Gs, but not Gi, suggests that the carboxyl-terminal region of Gs alpha is important in the interactions with GTP or its analogs. More »»

1989

Journal Article

V. G. Chinchar, Turner, L. A., and Dr. Geetha Kumar, “Hemin and cyclic AMP stimulate message-dependent translation in lysates from Friend erythroleukemia cells.”, Experimental hematology, vol. 17, pp. 405–410, 1989.

1989

Journal Article

Dr. Bipin G. Nair, Rashed, H. M., and Patel, T. B., “Epidermal growth factor stimulates rat cardiac adenylate cyclase through a GTP-binding regulatory protein.”, Biochem. J, vol. 264, pp. 563–571, 1989.[Abstract]


In isolated perfused rat hearts, epidermal growth factor (EGF; 15 nM) increased cellular cyclic AMP (cAMP) content by 9.5-fold. In rat cardiac membranes, EGF also stimulated adenylate cyclase activity in a dose-dependent manner, with maximal stimulation (35% above control) being observed at 10 nM-EGF. Half-maximal stimulation of adenylate cyclase was observed at 40 pM-EGF. Although the beta-adrenergic-receptor antagonist propranolol markedly attenuated the isoprenaline-mediated increase in cAMP content of perfused hearts and stimulation of adenylate cyclase activity, it did not alter the ability of EGF to elevate tissue cAMP content and stimulate adenylate cyclase. The involvement of a guanine-nucleotide-binding protein (G-protein) in the activation of adenylate cyclase by EGF was indicated by the following evidence. First, the EGF-mediated stimulation of adenylate cyclase required the presence of the non-hydrolysable GTP analogue, guanyl-5'-yl-imidodiphosphate (p[NH]ppG). Maximal stimulation was observed in the presence of 10 microM-p[NH]ppG. Secondly, in the presence of 10 microM-p[NH]ppG, the stable GDP analogue guanosine 5'-[beta-thio]diphosphate at a concentration of 10 microM blocked the stimulation of the adenylate cyclase by 1 nM- and 10 nM-EGF. Third, NaF + AlCl3-stimulated adenylate cyclase activity was not altered by EGF. The ability of EGF to stimulate adenylate cyclase was not affected by pertussis-toxin treatment of cardiac membranes. However, in cholera-toxin-treated cardiac membranes, when the adenylate cyclase activity was stimulated by 2-fold, EGF was ineffective. Finally, PMA by itself did not alter the activity of cardiac adenylate cyclase, but abolished the EGF-mediated stimulation of this enzyme activity. The experimental evidence in the present paper demonstrates, for the first time, that EGF stimulates adenylate cyclase in rat cardiac membranes through a stimulatory GTP-binding regulatory protein, and this effect is manifested in elevated cellular cAMP levels in perfused hearts exposed to EGF. More »»

1986

Journal Article

M. Sonavaria, Dr. Bipin G. Nair, and CHHATPAR, H. S., “Carbon starvation mediated changes in carbohydrate metabolism inNeurospora crassa”, Journal of Biosciences, vol. 10, pp. 187–192, 1986.[Abstract]


Carbon starvation conditions were found to increase the activities of gluconeogenic enzymes such as malic enzyme, cytosolic malate dehydrogenase and isocitrate lyase along with proteases and inhibition in glucose catabolic enzymes such as G6P dehydrogenase and FDP aldolase inNeurospora crassa More »»

1984

Journal Article

S. Pinge, Patel, S., Dr. Bipin G. Nair, and CHHATPAR, H. S., “Effect of chloramphenicol on some of the cytosolic enzymes from Neurospora crassa”, Indian journal of experimental biology, vol. 22, pp. 102-103, 1984.

1984

Journal Article

S. Ram, Dr. Bipin G. Nair, and CHHATPAR, H. S., “Photoregulation of some enzymes fromNeurospora crassa”, Experientia, vol. 40, pp. 1382–1384, 1984.[Abstract]


Light-grown cultures of Neurospora crassa showed photoregulation of a number of enzymes. Proteases and cytosolic malate dehydrogenase showed an increase in activity. There was a decrease in the activity of mitochondrial malate dehydrogenase, isocitrate dehydrogenase and cytosolic glucose-6P-dehydrogenase, isocitrate dehydrogenase and isocitrate lyase. More »»

1983

Journal Article

S. SAVANT, PARIKH, N., Dr. Bipin G. Nair, and CHHATPAR, H. S., “Phosphate Mediated Biochemical-Changes In Neurospora-Crassa”, Current Science, vol. 52, pp. 1070-1072, 1983.

1981

Journal Article

K. SHAH, RAO, S., Dr. Bipin G. Nair, and MODI, V. V., “Modification of Antifungal Activity of Econazole in Presence of Betamethazone”, INDIAN JOURNAL OF MEDICAL RESEARCH, vol. 73, pp. 965–969, 1981.[Abstract]


An attempt was made to find the optimal proportion of econazole to betamethasone which gives the least inhibition of antifungal activity of econazole. There was a gradual reduction in O2 consumption by Candida tropicalis (ATCC 13803) with increase in the concentration of econazole. Betamethasone stimulated the O2 consumption by C. tropicalis. The changes elicited by betamethasone in various concentrations on the antifungal activity of econazole were investigated by the Warburg manometric technique. There was no significant decrease in antifungal activity of econazole when combined with betamethasone in a 1:0.1 prooortion. The inhibition of O2 consumption was more at a 1:0.1 ratio than at 1:0.125. The minimal inhibitory concentration of econazole was found to be 0.06 .mu.g by plate assay method. It was observed by plate assay and by turbidometric assay that 1:0.075 was the optimal ratio of econazole to betamethasone, which did not give significant decrease in antifungal activity. More »»

1980

Journal Article

C. K. Pushpendran, Devasagayam, T. P. A., Chintalwar, G. J., Banerji, A., and Eapen, J., “The metabolic fate of [35S]-diallyl disulphide in mice”, Experientia, vol. 36, pp. 1000–1001, 1980.[Abstract]


Diallyl disulphide (DADS) is a major constituent of garlic oil. Uptake of [35S]-labelled diallyl disulphide by mouse liver is highest at 90 min after treatment with [35S]-DADS, 70% of the radioactivity is present in the liver cytosol of which 80% is metabolized to sulphate.

More »»

1980

Journal Article

C. K. Pushpendran, Devasagayam, T. P. A., Banerji, A., and Eapen, J., “Cholesterol-lowering effect of allitin in suckling rats.”, Indian journal of experimental biology, vol. 18, pp. 858–861, 1980.[Abstract]


Wistar rats 15 days old were given intraperitoneally allitin (diallyl disulphide 98 and diallyl trisulphide 2%, obtained from garlic (Allium sativum) oil) 100 mg/kg bodyweight. Plasma cholesterol decreased significantly within 30 min and liver cholesterol within 4 h. Total lipids in plasma decreased after 30 min and increased in liver but total lipids in microsomes of liver decreased. Lipid peroxidation in liver homogenates decreased gradually. Smaller amounts of allitin had different effects on total lipids and cholesterol in plasma and liver.

More »»

1978

Journal Article

A. Banerji, Hunter, R., Mellows, G., Sim, K. -y, and Barton, D. H. R., “Use of deuterium as a tracer with 13C nuclear magnetic resonance spectroscopy in following deuteride migration in terpenoid biosynthesis: mechanism of geranylgeranyl pyrophosphate cyclisation in fusicoccin biosynthesis”, J. Chem. Soc., Chem. Commun., pp. 843–845, 1978.

1976

Journal Article

A. Banerji, Jones, R. B., Mellows, G., Phillips, L., and Sim, K. - Y., “Fusicoccin. Part 6. Biosynthesis of fusicoccin from [3-13C]-and (4R)-[4-3H1]-mevalonic acid”, J. Chem. Soc., Perkin Trans. 1, pp. 2221–2228, 1976.

1968

Journal Article

S. R. Udupa, Banerji, A., and Chadha, M. S., “Microbiological transformation of flavanone”, Tetrahedron Letters, vol. 9, pp. 4003–4005, 1968.

Publication Type: Conference Paper

Year of Publication Publication Type Title

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>

More »»

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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2013

Conference Paper

Dr. Jyotsna Nambiar, Kumar, G. B., and Nair, B. G., “Anacardic Acid regulates Gelatinases by modulation of MT1-MMP, TIMP-2 and EGF receptor signaling in Fibrosarcoma cells”, in Amrita Bioquest, 2013.

Publication Type: Conference Proceedings

Year of Publication Publication Type Title

2014

Conference Proceedings

Dr. Shyam Diwakar, Chellaiah, P., Dr. Bipin G. Nair, and Dr. Krishnashree Achuthan, “Theme Interception Sequence Learning: Deflecting Rubber-Hose Attacks Using Implicit Learning”, In Proceedings of the 3rd International Conference on Frontiers of Intelligent Computing: Theory and Applications (FICTA) Springer International Publishing. Springer International Publishing, Switzerland, pp. 495-502, 2014.[Abstract]


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

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PDF icontheme-interception-sequence-learning-deflecting-rubber-hose-attacks-using-implicit-learning.pdf

Publication Type: Patent

Year of Publication Publication Type Title

2011

Patent

Dr. Bipin G. Nair, Guruvayoorappan, K., and Kumar, H., “Dual Microcontroller Based Liquid Infusion System”, U.S. Patent US 11/942,6102011.[Abstract]


A highly reliable and robust functioning liquid infusion system for use in biomedical applications comprises a dual microcontroller system where the first microcontroller is configured to administer the liquid and the second microcontroller is configured to monitor the accurate functioning of the system and various performance parameters such as flow rate of liquid, presence of leaks or blocks in the liquid passage, level of drug in the cartridge and battery condition. The liquid injection portion comprises a cylindrical airtight liquid holder or drug cartridge with a movable internal piston that is in contact with a movable stem, and a micromotor, which controls the drug delivery. The system is programmable with a dosing system stored into the driver/monitor microcontrollers. A low power LCD module is used to display the operating parameters with multiple language interface and alarm conditions, if any. The system is also equipped with a system of sensors that trigger an alarm to indicate abnormal conditions.

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