Department of Bioscience & Bioengineering

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Flexibility in curriculum, in all its academic programs, encompassing elements of teaching, research, creativity, innovation and entrepreneurship is the most unique feature of IIT Jodhpur. The Department of Science and Technology (DST), under the National Mission on Cyber Physical Systems, has identified IIT Jodhpur as a Technology &amp; Innovation Hub in the area of Augmented Reality and Virtual Reality. The institute has also been nominated as the coordinator for the Jodhpur City and Knowledge Cluster by the Office of Principal Scientific Adviser, Government of India.

The sprawling 852-acre IIT Jodhpur campus is a majestic tribute to the deep-rooted diverse cultural heritage of the region. The campus is an architectural masterpiece, which is slated to become an international exemplar of sustainability with net-zero energy, and advanced water and waste management strategies.&rdquo;

IIT Jodhpur

Background & objectives: spinocerebellar ataxia 7 (SCA7) is a rare form of neurodegenerative disorder with the clinical manifestation of cerebellar ataxia and retinal degeneration. In this study we describe the clinico-genetic characteristics of nine SCA7 families of Indian origin and cross compare these with other available worldwide studies. Methods: Thirty five individuals from nine SCA7 families were clinico-genetically characterized and CAG repeat distribution analysis was carried out in 382 control DNA samples from healthy controls (derived from 21 diverse Indian populations based on ethnic and linguistic and geographical location). Results: Of the nine families studied, 22 affected individuals and one asymptomatic carrier were identified. The average age at disease onset was 23.4±12.6 yr. The length of expanded CAG ranged from 40-94 with mean value of 53.2±13.9. The main clinical findings in affecteds individuals included cerebellar ataxia, and retinal degeneration along with hyper-reflexia (95%), slow saccades (85%) and spasticity (45%). Analysis of the association of number of CAG repeats with disease onset revealed that <49 repeats were associated with earlier age at onset in South East Asians compared to European populations. Further analysis of CAG repeats from 21 diverse Indian populations showed pre-mutable repeats (28-34) alleles in the IE-N-LP2 population. Six of the nine families identified in this study belonged to the same ethnic population. Interpretations & conclusion: Our results show that presenece of SCA7 is relatively rare and confined to one ethnic group from Haryana region of India. We observed a homogeneous phenotypic expression of SCA7 mutation as described earlier and an earlier age of onset in our patients with CAG <49. The identification of pre-mutable allele in IE-N-LP2 suggests this population to be at the risk of SCA7. © 2015, Indian Council of Medical Research. All rights reserved.

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Indian Journal of Medical Research

Spinocerebellar ataxia 7 (SCA7) in Indian population: Predilection of ATXN7-CAG expansion mutation in an ethnic population

The purpose of this research was to synthesize and characterize gelatin and tamarind gum (TG)/carboxymethyl tamarind (CMT) gum-based phase-separated hydrogels. The hydrogels were thoroughly characterized using bright-field microscope, FTIR spectroscope, differential scanning calorimeter, mechanical tester, and impedance analyzer. The mucoadhesivity, biocompatibility, and swelling property of the hydrogels were also evaluated. The antimicrobial efficiency of ciprofloxacin (model antimicrobial drug) loaded hydrogels was studied against E. coli. The in vitro drug release was carried out in both gastric and intestinal pHs. Microstructural analysis suggested the formation of phase-separated hydrogels. FTIR studies suggested that CMT gum altered the secondary structure of the gelatin molecules. Presence of the polysaccharides within the hydrogels resulted in the increase in the enthalpy and entropy for evaporation of the moisture from the hydrogels. The mechanical studies indicated viscoelastic nature of the hydrogels. Electrical analysis suggested an increase in the impedance of the hydrogels in the presence of the TG. The presence of CMT gum resulted in the decrease in the impedance of the hydrogels. The hydrogels exhibited good mucoadhesivity, biocompatibility, and pH-dependent swelling behavior. The drug-loaded hydrogels showed good antimicrobial activity and the drug release from the hydrogels was pH dependent and diffusion mediated. © 2015 Taylor & Francis.

Fulltext

Designed Monomers and Polymers

Development and characterization of gelatin-tamarind gum/carboxymethyl tamarind gum based phase-separated hydrogels: A comparative study

The present study delineates preparation, characterization and application of calcium alginate (CA)-carboxymethyl cellulose (CMC) beads for colon-specific oral drug delivery. Here, we exploited pH responsive swelling, mucoadhesivity and colonic microflora-catered biodegradability of the formulations for colon-specific drug delivery. The CA-CMC beads were prepared by ionic gelation method and its physicochemical characterization was done by SEM, XRD, EDAX, DSC and texture analyzer. The swelling and mucoadhesivity of the beads was found higher at the simulated colonic environment. Variation was more prominent in compositions with lower CMC concentrations. CA-CMC formulations degraded slowly in simulated colonic fluid, however the degradation rate increased drastically in the presence of colonic microflora. In vitro release study of anticancer drug 5-fluorouracil (5-FU) showed a release (>90%) in the presence of colonic enzymes. A critical analysis of drug release profile along with FRAP (fluorescence recovery after photobleaching) study revealed that the presence of CMC in the formulation retarded the release rate of 5-FU. 5-FU-loaded formulations were tested against colon adenocarcinoma cells (HT-29). Cytotoxicity data, nuclear condensation-fragmentation and apoptosis analysis (by flow cytometry) together confirmed the therapeutic potential of the CA-CMC formulations. In conclusion, CA-CMC beads can be used for colon-specific drug delivery. © 2015 Elsevier B.V.

International Journal of Biological Macromolecules

Calcium alginate-carboxymethyl cellulose beads for colon-targeted drug delivery

Pueraria tuberosa is known for its therapeutic potentials in cardiovascular disorders, but its effect in angiogenesis has not been studied so far. In this study, a computational approach has been applied to elucidate the role of the phytochemicals in inhibition of angiogenesis through modulation of vascular endothelial growth factor receptors: Vascular endothelial growth factor receptor-1 and vascular endothelial growth factor receptor-2, major factors responsible for angiogenesis. Metabolite structures retrieved from PubChem and KNApSAcK - 3D databases, were docked using AutoDock4.2 tool. Hydrogen bond and molecular docking, absorption, distribution, metabolism and excretion and toxicity predictions were carried out using UCSF Chimera, LigPlot+ and PreADMET server, respectively. From the docking analysis, it was observed that puerarone and tuberostan had significant binding affinity for the intracellular kinase domain of vascular endothelial growth factor receptors-1 and vascular endothelial growth factor receptor-2 respectively. It is important to mention that both the phytochemicals shared similar interaction profile as that of standard inhibitors of vascular endothelial growth factor receptors. Also, both puerarone and tuberostan interacted with Lys861/Lys868 (adenosine 5'-triphosphate binding site of vascular endothelial growth factor receptors-1/vascular endothelial growth factor receptors-2), thus providing a clue that they may enforce their inhibitory effect by blocking the adenosine 5'-triphosphate binding domain of vascular endothelial growth factor receptors. Moreover, these molecules exhibited good drug-likeness, absorption, distribution, metabolism and excretion properties without any carcinogenic and toxic effects. The interaction pattern of the puerarone and tuberostan may provide a hint for a novel drug design for vascular endothelial growth factor tyrosine kinase receptors with better specificity to treat angiogenic disorders. © 2015 Indian Journal of Pharmaceutical Sciences.

Indian Journal of Pharmaceutical Sciences

Molecular docking and interactions of pueraria tuberosa with vascular endothelial growth factor receptors

Dynamics of excited state proton transfer (ESPT) in the lysosome region of live lung cells (normal and cancer) is studied by picosecond time-resolved confocal microscopy. For this, we used a fluorescent probe, pyranine (8-hydroxy-pyrene-1,3,6-trisulfonate, HPTS). From the colocalization of HPTS with a lysotracker dye (lysotracker yellow), we confirmed that HPTS resides in the lysosome for both of the cells. The diffusion coefficient (Dt) in the lysosome region was obtained from fluorescence correlation spectroscopy (FCS). From Dt, the viscosity of lysosome is estimated to be 40 and 30 cP in the cancer and normal cells, respectively. The rate constants of the elementary steps of ESPT in a normal lung cell (WI38) are compared with those in a lung cancer cell (A549). It is observed that the time constant of the initial proton transfer process in a normal cell (τPT = 40 ps) is similar to that in a cancer cell. The recombination of the geminate ion pair is slightly faster (τrec = 25 ps) in the normal cell than that (τrec = 30 ps) in a cancer cell. The time constant of the dissociation (τdiss) of the geminate ion pair for the cancer cell (τdiss = 80 ps) is 1.5 times faster compared to that (τdiss = 120 ps) in a normal cell. © 2014 American Chemical Society.

Journal of Physical Chemistry B

Excited state proton transfer in the lysosome of live lung cells: Normal and cancer cells

We report in this work that the Aβ peptide directly interacts with tubulin close to the vinblastine and GTP/GDP binding site, inhibits the tubulin polymerization rate, induces tubulin aggregation, causes cell shrinking, enhances Mad2, BubR1, p53, and p21 activation in MCF7 cells and induces the apoptotic death of A549, HeLa and MCF7 cells. © The Royal Society of Chemistry 2015.

Chemical Communications

Interaction of Aβ peptide with tubulin causes an inhibition of tubulin polymerization and the apoptotic death of cancer cells

In this work, we have investigated the composition dependent anomalous behavior of dimethyl sulfoxide (DMSO)-water binary mixture by collecting the ultrafast solvent relaxation response around a well known solvation probe Coumarin 480 (C480) by using a femtosecond fluorescence up-conversion spectrometer. Recent molecular dynamics simulations have predicted two anomalous regions of DMSO-water binary mixture. Particularly, these studies encourage us to investigate the anomalies from experimental background. DMSO-water binary mixture has repeatedly given evidences of its dual anomalous nature in front of our systematic investigation through steady-state and time-resolved measurements. We have calculated average solvation times of C480 by two individual well-known methods, among them first one is spectral-reconstruction method and another one is single-wavelength measurement method. The results of both the methods roughly indicate that solvation time of C480 reaches maxima in the mole fraction of DMSO XD = 0.12-0.17 and XD = 0.27-0.35, respectively. Among them, the second region (XD = 0.27-0.35) is very common as most of the thermodynamic properties exhibit deviation in this range. Most probably, the anomalous solvation trend in this region is fully guided by the shear viscosity of the medium. However, the first region is the most interesting one. In this region due to formation of strongly hydrogen bonded 1DMSO:2H2O complexes, hydration around the probe C480 decreases, as a result of which solvation time increases. © 2015 AIP Publishing LLC.

Journal of Chemical Physics

Picosecond solvation dynamics - A potential viewer of DMSO - Water binary mixtures

Blue, green, orange-red, red and NIR emitting gold quantum clusters have been prepared in aqueous media by using a bioactive peptide glutathione (reduced) at physiological pH. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) analyses show that the core structure sizes of the five different gold clusters are Au7 (blue), Au16 (green), Au19 (orange-red), Au21 (red) and Au22 (NIR). The photo-stability and pH-stability of these quantum clusters have been measured, and these are photo-stable against continuous UV irradiation for a few hours. They also exhibit moderate to good pH-stability within the pH range of 5-12.5. A computational study reveals the organisation of gold atoms in the thiolate-protected blue quantum cluster and its several structural parameters, including the mode of interaction of ligand molecules with Au atoms in the Au7 cluster. Interestingly, it has been found that NIR emitting gold quantum cluster can easily be internalized into the adenocarcinomic human alveolar basal epithelial cell line (A549 cell line). Moreover, a MTT assay indicates that our NIR emitting gold quantum cluster show very low cytotoxicy to A549 cancer cells. © The Royal Society of Chemistry 2015.

Nanoscale

Preparation of multi-coloured different sized fluorescent gold clusters from blue to NIR, structural analysis of the blue emitting Au7 cluster, and cell-imaging by the NIR gold cluster

We have designed a novel peptide-docetaxel conjugate, which delivers docetaxel specifically to cancer cell targeting neuropilin-1 (NRP-1) receptor, thus enhancing its efficacy and acts more aggressively in breast cancer cells. © 2015 The Royal Society of Chemistry.

RSC Advances

Targeted delivery of a novel peptide-docetaxel conjugate to MCF-7 cells through neuropilin-1 receptor: Reduced toxicity and enhanced efficacy of docetaxel

Product graphs have been gainfully used in literature to generate mathematical models of complex networks which inherit properties of real networks. Realizing the duplication phenomena imbibed in the definition of corona product of two graphs, we define corona graphs. Given a small simple connected graph which we call basic graph, corona graphs are defined by taking corona product of the basic graph iteratively. We calculate the possibility of having a node of degree k in any corona graph which lead to obtain degree distribution of corona graphs. We determine explicit formulae of eigenvalues, Laplacian eigenvalues and signless Laplacian eigenvalues of corona graphs when the basic graph is regular. Computable expressions of eigenvalues and signless Laplacian eigenvalues are also obtained when the basic graph is a star graph.