Manipal University

About: Manipal University is a education organization based out in Manipal, Karnataka, India. It is known for research contribution in the topics: Population & Health care. The organization has 9525 authors who have published 11207 publications receiving 110687 citations.

Polymorphisms in Radio-Responsive Genes and Its Association with Acute Toxicity among Head and Neck Cancer Patients

Abstract: Cellular and molecular approaches are being explored to find a biomarker which can predict the development of radiation induced acute toxicity prior to radiation therapy. SNPs in radiation responsive genes may be considered as an approach to develop tools for finding the inherited basis of clinical radiosensitivity. The current study attempts to screen single nucleotide polymorphisms/deletions in DNA damage response, DNA repair, profibrotic cytokine as well as antioxidant response genes and its predictive potential with the normal tissue adverse reactions from 183 head and neck cancer patients undergoing platinum based chemoradiotherapy or radiotherapy alone. We analysed 22 polymorphisms in 17 genes having functional relevance to radiation response. Radiation therapy induced oral mucositis and skin erythema was considered as end point for clinical radiosensitivity. Direct correlation of heterozygous and mutant alleles with acute reactions as well as haplotype correlation revealed NBN variants to be of predictive significance in analysing oral mucositis prior to radiotherapy. In addition, genetic linkage disequilibrium existed in XRCC1 polymorphisms for >grade 2 oral mucositis and skin reaction indicating the complex inheritance pattern. The current study indicates an association for polymorphism in NBN with normal tissue radiosensitivity and further warrants the replication of such studies in a large set of samples.

Optical diagnosis of cervical cancer by fluorescence spectroscopy technique

Abstract: In the present work, we examine normal and malignant stage IIIB cervical tissue by laser induced fluorescence, with 2 different objectives. (i) Development of the fluorescence spectroscopy technique as a standard optical method for discrimination of normal and malignant tissue samples and, (ii) Optimization of the technique by the method of matching of a sample spectrum with calibration sets of spectra of pathologically certified samples. Laser-induced fluorescence spectra were measured using samples from 62 subjects at different excitation wavelengths. Principal component analysis (PCA) of spectra and intensity ratios of curve-resolved fluorescence peaks were tested for discrimination. It was found that PCA of total fluorescence at 325 nm excitation gives specificity and sensitivity over 95%. Use of calibration sets of spectra of histo-pathologically certified samples combined with PCA for matching and pass/fail classification of test samples is shown to have high sensitivity/specificity for routine diagnostic purposes as well as for possible staging of the disease. Further, the multi-component origin of the fluorescence spectra is illustrated by curve resolution and fluorescence spectra of separated proteins of tissue homogenates.

Salmonella Engages Host MicroRNAs To Modulate SUMOylation: a New Arsenal for Intracellular Survival

Abstract: Posttranslational modifications (PTMs) can alter many fundamental properties of a protein. One or combinations of them have been known to regulate the dynamics of many cellular pathways and consequently regulate all vital processes. Understandably, pathogens have evolved sophisticated strategies to subvert these mechanisms to achieve instantaneous control over host functions. Here, we present the first report of modulation by intestinal pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) of host SUMOylation, a PTM pathway central to all fundamental cellular processes. Both in cell culture and in a mouse model, we observed that S. Typhimurium infection led to a dynamic SUMO-conjugated proteome alteration. The intracellular survival of S. Typhimurium was dependent on SUMO status as revealed by reduced infection and Salmonella-induced filaments (SIFs) in SUMO-upregulated cells. S. Typhimurium-dependent SUMO modulation was seen as a result of depletion of crucial SUMO pathway enzymes Ubc-9 and PIAS1, at both the protein and the transcript levels. Mechanistically, depletion of Ubc-9 relied on upregulation of small noncoding RNAs miR30c and miR30e during S. Typhimurium infection. This was necessary and sufficient for both down-modulation of Ubc-9 and a successful infection. Thus, we demonstrate a novel strategy of pathogen-mediated perturbation of host SUMOylation, an integral mechanism underlying S. Typhimurium infection and intracellular survival.

Epigenetic Modulation of Macrophage Polarization- Perspectives in Diabetic Wounds

Abstract: Diabetes is a chronic metabolic disorder that poses a global burden to healthcare Increasing incidence of diabetes-related complications in the affected population includes a delay in wound healing that often results in non-traumatic limb amputations Owing to the intricacies of the healing process and crosstalk between the multitude of participating cells, the identification of hyperglycaemia-induced changes at both cellular and molecular levels poses a challenge Macrophages are one of the key participants in wound healing and continue to exert functional changes at the wound site since the time of injury In the present review, we discuss the role of these cells and their aberrant functions in diabetic wounds We have extensively studied the process of macrophage polarization (MP) and its modulation through epigenetic modifications Data from both pre-clinical and clinical studies on diabetes have co-related hyperglycaemia induced changes in gene expression to an increased incidence of diabetic complications Hyperglycaemia and oxidative stress, create an environment prone to changes in the epigenetic code, that is manifested as an altered inflammatory gene expression Here, we have attempted to understand the different epigenetic modulations that possibly contribute towards dysregulated MP, resulting in delayed wound healing

Boomerang: Rebounding the Consequences of Reputation Feedback on Crowdsourcing Platforms

Abstract: Paid crowdsourcing platforms suffer from low-quality work and unfair rejections, but paradoxically, most workers and requesters have high reputation scores. These inflated scores, which make high-quality work and workers difficult to find, stem from social pressure to avoid giving negative feedback. We introduce Boomerang, a reputation system for crowdsourcing platforms that elicits more accurate feedback by rebounding the consequences of feedback directly back onto the person who gave it. With Boomerang, requesters find that their highly-rated workers gain earliest access to their future tasks, and workers find tasks from their highly-rated requesters at the top of their task feed. Field experiments verify that Boomerang causes both workers and requesters to provide feedback that is more closely aligned with their private opinions. Inspired by a game-theoretic notion of incentive-compatibility, Boomerang opens opportunities for interaction design to incentivize honest reporting over strategic dishonesty.