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 and Aims: Interleukin-10 (IL-10) is an immunosuppressive cytokine that may promote tumor growth and metastasis in later stages of cancer development. DNA sequence variations in IL-10 gene may lead to altered production and/or activity, and this can modulate an individual's susceptibility to urothelial bladder cancer (UBC). To test this hypothesis, we investigated the association of rs 1800896 and rs 3021097 polymorphisms in IL-10 gene and their haplotypes with the risk of UBC in a Northern Indian population. Methods: We analyzed two single nucleotide polymorphisms of IL-10 gene at G-1082A (rs 1800896) and C-819T (rs 3021097) in 214 histologically confirmed UBC patients and 385 matched controls by allele-specific polymerase chain reaction (AS-PCR). Results: IL-10 C-819T CT, TT genotypes and T carriers (CT + TT) had significant association with UBC susceptibility (OR 1.75, 95% CI 1.09-2.80; OR 1.81, 95% CI 1.09-3.01 and OR 1.77, 95% CI 1.14-2.75, respectively). Similarly, GA, AA genotypes and A carriers (G-1082A) demonstrated increased risk for UBC (OR 1.91, 95% CI 1.04-3.50; OR 2.01, 95% CI 1.08-3.74 and OR 1.95, 95% CI 1.09-3.50, respectively). TT (C-819T) and T carriers showed protective association with high-risk tumors; (OR 0.34, 95% CI 0.13-0.88 and OR 0.41, 95% CI 0.17-0.97, respectively). We did not observe any association of IL-10 polymorphisms with smoking habits and UBC risk. Conclusions: The study suggested that the low-producing genotypes of IL-10 (C-819T and G-1082A) polymorphisms are associated with increased UBC risk. Individuals with (C-819T) TT genotype and T carriers, however, showed a protective association with high-risk tumors. Our data suggest that IL-10 G-1082A and C-819T polymorphisms may be used as a molecular marker of urothelial bladder cancer. © 2009 IMSS.

World University root node

Archives of medical research

Interleukin-10 G-1082A and C-819T polymorphisms as possible molecular markers of urothelial bladder cancer

The nucleotide-binding domain, leucine-rich repeat (NLR) proteins are a recently discovered family of intracellular pathogen and danger signal sensors. NLRs have emerged as important contributors to innate immunity in animals. The physiological impact of these genes is increasingly evident, underscored by the genetic association of variant family members with an array of inflammatory diseases. The association of mutations in NLR genes with autoinflammatory diseases indicates an important function of these genes in inflammation in vivo. This review summarizes the role of the inflammasome NLR proteins in innate immunity and inflammatory diseases and explores the possible utility of some of these NLRs as pharmacological targets. Copyright © 2009 by The American Association of Immunologists, Inc.

Journal of Immunology

Inflammasome-associated nucleotide-binding domain, leucine-rich repeat proteins and inflammatory diseases

Implant associated infections are of increasing importance. To minimize the risks of implant-associated infections recent biomedical strategies have led to the modification of the medical device surfaces. The modifications are in the terms of increasing surface biocompatibility and decreasing bacterial adherence, which can be achieved by applying a coating of biocompatible polymer onto the said surfaces. Entrapping anti-infective agents in a polymer matrix provides an approach to kill bacteria and combat the possibility of any residual infection. We have prepared a biodegradable polyester urethane coat for implant materials, which have the property to accommodate antibiotics within itself. These polyurethane coating materials were characterized by FTIR spectroscopy, swelling property in SBF, gravimetric analysis, drug release, and biocompatibility study. Drug release rates, bacterial colonization and morphological features were also evaluated to predict and understand the antimicrobial activity of these delivery systems. Drug release characteristics were investigated and the physico-chemical mechanisms of the delivery were discussed. Results suggest that the polyester urethane can be used as an implant coating material and can be used as a matrix for the sustained delivery of anti-infective agent. © 2008 Springer Science+Business Media, LLC.

Journal of Materials Science: Materials in Medicine

Sustained release of antibiotic from polyurethane coated implant materials

Cells are equipped with an efficient quality control system to selectively eliminate abnormally folded and damaged proteins. Initially the cell tries to refold the unfolded proteins with the help of molecular chaperones, and failure to refold leads to their degradation by the ubiquitin proteasome system. But how this proteolytic machinery recognizes the abnormally folded proteins is poorly understood. Here, we report that E6-AP, a HECT domain family ubiquitin ligase implicated in Angelman syndrome, interacts with the substrate binding domain of Hsp70/ Hsc70 chaperones and promotes the degradation of chaperone bound substrates. The expression of E6-AP was dramatically induced under a variety of stresses, and overexpression of E6-AP was found to protect against endoplasmic reticulum stress-induced cell death. The inhibition of proteasome function not only increases the expression of E6-AP but also causes its redistribution around microtubule-organizing center, a subcellular structure for the degradation of the cytoplasmic misfolded proteins. E6-AP is also recruited to aggresomes containing the cystic fibrosis transmembrane conductance regulator or expanded polyglutamine proteins. Finally, we demonstrate that E6-AP ubiquitinates misfolded luciferase that is bound by Hsp70. Our results suggest that E6-AP functions as a cellular quality control ubiquitin ligase and, therefore, can be implicated not only in the pathogenesis of Angelman syndrome but also in the biology of neurodegenerative disorders involving protein aggregation. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

Fulltext

Journal of Biological Chemistry

The ubiquitin ligase E6-AP is induced and recruited to aggresomes in response to proteasome inhibition and may be involved in the ubiquitination of Hsp70-bound misfolded proteins

A compressive applied force at the zero frequency limit applied on confined granular alignments is shown to result in tunable and higher frequency nonlinear granular breathing. We use extensive dynamical simulations and simple arguments to probe the origins of these breathing processes. In the presence of dissipation, the breathing has a lifetime that is inversely proportional to the dissipation constant. The possible use of the concept of nonlinear granular breathing in recovering the energy released at the beaches by surface gravity waves using a system made largely of nonmoving parts is mentioned as a possible application. © 2009 American Institute of Physics.

Applied Physics Letters

Nonlinear breathing processes in granular alignments

Objective: To investigate the association of tumour necrosis factor-α gene (TNF-α) polymorphisms T-1031C, C-863A, and C-857T with bladder cancer risk and recurrence after bacille Calmette-Guérin (BCG) immunotherapy, as TNF-α regulates inflammatory process influencing bladder cancer susceptibility and outcome of BCG immunotherapy. PATIENTS AND METHODS In all, 220 patients with bladder cancer and 206 controls were recruited. Genotyping was done using allele specific-polymerase chain reaction. RESULTS A T-1031C, CC genotype and haplotype -1031C/-863C/-857T showed enhanced susceptibility to bladder cancer, with an odds ratio (OR) of 2.23 and 95% confidence interval (CI) of 1.17-4.26; and an OR of 6.05 and 95%CI of 2.46-14.90, respectively. A T-1031C, CC genotype had a reduced risk of recurrence after BCG treatment (hazard ratio 0.38, 95%CI 0.14-0.98). CONCLUSION The present data suggests that T-1031C (CC) genotype and C/C/T haplotype may confer risk for bladder cancer, moreover T-1031C (CC) decreased the risk of recurrence after BCG immunotherapy. © 2009 BJU International.

BJU International

Association of tumour necrosis factor-α gene (T-1031C, C-863A, and C-857T) polymorphisms with bladder cancer susceptibility and outcome after bacille Calmette-Guérin immunotherapy

The programmed cell death gene 4 (Pdcd4) gene has been implicated as a new tumor suppressor gene in the development of several types of human cancer. Pdcd4 interacts with the translation initiation factor, eIF4A, and is thought to act as a translation inhibitor. Here, we have used the chicken B-cell line DT40 to disrupt the Pdcd4 gene by homologous recombination. Our study shows that cells lacking a functional Pdcd4 gene are viable and have no obvious defects when cultivated under normal growth conditions. However, Pdcd4 knockout cells show an increased sensitivity to agents that cause DNA damage, such as UV light, etoposide or ethyl-methanesulfonate. In summary, our findings show that Pdcd4 has an important function in the cellular response to DNA damage. Low Pdcd4 expression, which is frequently observed in tumor cells, might therefore contribute to tumorigenesis by disturbing the cellular DNA-damage response. © 2009 Macmillan Publishers Limited All rights reserved.

Oncogene

Disruption of the Pdcd4 tumor suppressor gene in chicken DT40 cells reveals its role in the DNA-damage response

Stratification in heterogeneous populations poses an enormous challenge in linkage disequilibrium (LD) based identification of causal loci using surrogate markers. In this study, we demonstrate the enormous potential of endogamous Indian populations for mapping mutations in candidate genes using minimal SNPs, mainly due to larger regions of LD. We show this by a case study of the PPP2R2B gene (∼400 kb) that harbours a CAG repeat, expansion of which has been implicated in spinocerebellar ataxia type 12 (SCA12). Using LD information derived from Indian Genome Variation database (IGVdb) on populations which share similar ethnic and linguistic backgrounds as the SCA12 study population, we could map the causal loci using a minimal set of three SNPs, without the generation of additional basal data from the ethnically matched population. We could also demonstrate transferability of tagSNPs from a related HapMap population for mapping the mutation. © Indian Academy of Sciences.

Journal of Genetics

Utilizing linkage disequilibrium information from Indian Genome variation database for mapping mutations: SCA12 case study

Transection of dorsal columns of the spinal cord in adult monkeys results in large-scale expansion of the face inputs into the deafferented hand region in the primary somatosensory cortex (area 3b) and the ventroposterior nucleus of thalamus. Here, we determined whether the upstream cortical areas, secondary somatosensory (S2) and parietal ventral (PV) areas, also undergo reorganization after lesions of the dorsal columns. Areas S2, PV, and 3b were mapped after long-term unilateral lesions of the dorsal columns at cervical levels in adult macaque monkeys. In areas S2 and PV, we found neurons responding to touch on the face in regions in which responses to touch on the hand and other body parts are normally seen. In the reorganized parts of S2 and PV, inputs from the chin as well as other parts of the face were observed, whereas in area 3b only the chin inputs expand into the deafferented regions. The results show that deafferentations lead to a more widespread brain reorganization than previously known. The data also show that reorganization in areas S2 and PV shares a common substrate with area 3b, but there are specific features that emerge in S2 and PV. Copyright © 2009 Society for Neuroscience.

Journal of Neuroscience

Large-scale expansion of the face representation in somatosensory areas of the lateral sulcus after spinal cord injuries in monkeys

Laccase/mediator systems are important bioremediation agents as the rates of reactions can be enhanced in the presence of the mediators. The decolorization mechanism of two triarylmethane dyes, namely, Basic Green 4 and Acid Violet 17 is reported using Cyathus bulleri laccase. Basic Green 4 was decolorized through N-demethylation by laccase alone, while in mediator assisted reactions, dye breakdown was initiated from oxidation of carbinol form of the dye. Benzaldehyde and N,N-dimethyl aniline were the major end products. With Acid Violet 17, laccase carried out N-deethylation and in mediator assisted reactions, oxidation of the carbinol form of the dye occurred resulting in formation of formyl benzene sulfonic acid, carboxy benzene sulfonic acid and benzene sulfonic acid. Toxicity analysis revealed that Basic Green 4 was toxic and treatment with laccase/mediators resulted in 80-100% detoxification. The treatment of the textile dye solution using laccase and 2,2′-azino-di-(-ethylbenzothiazoline-6-sulfonic acid) (ABTS) was demonstrated in an enzyme membrane reactor. At a hydraulic retention time of 6 h, the process was operated for a period of 15 days with nearly 95% decolorization, 10% reduction in flux and 70% recovery of active ABTS. © 2009 Elsevier B.V. All rights reserved.