Biological Sciences and Engineering

Indian Institute of Technology Palakkad&nbsp;(IIT Palakkad or IIT PKD) is a public autonomous&nbsp;engineering&nbsp;and&nbsp;research&nbsp;institute located in&nbsp;Palakkad,&nbsp;Kerala. It was&nbsp;one of the five new&nbsp;IITs&nbsp;proposed in the&nbsp;2014 Union budget of India. The campus was inaugurated on 3 August 2015. The institute has 94 faculty, 978 students, and 63 non-teaching staffs.

IT Palakkad currently offers four-year Bachelor of Technology (B.Tech) and two years MS programmes in 8 different engineering disciplines including&nbsp;Computer Science, Electrical, Mechanical, Civil among others.

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IIT Palakkad

Enterococcus faecalis is a commensal bacterium residing in the gastrointestinal tract of mammals, but in certain situations it is also an opportunistic pathogen which can cause serious disease. Macrophages have been shown to play a critical role in controlling infections by commensal enterococci and also have an important role in mediating chromosomal instability and promoting colon cancer during high-level enterococcal colonization in genetically susceptible mice. However, the molecular mechanisms involved in the interaction of macrophages with enterococci during infection are not fully understood. In this study, using BMDM and RAW264.7 macrophages we show that enterococcal infection activates ERK, JNK and p38 MAPK as well as NF-KB, and drives polarization of macrophages towards the M1 phenotype. Inhibition of NF-KB activation significantly reduced the expression of TNF-α and IL-1β, as did the inhibition of ERK, JNK and p38 MAPK, although to differing extent. Enterococci-induced activation of these pathways and subsequent cytokine expression was contact dependent, modest compared to activation by E. coli and, required the adaptor protein MyD88. Phagocytosis of enterococci by macrophages was enhanced by preopsonization with E. faecalis antiserum and involved the ERK and JNK signaling pathways, with the adaptor protein MyD88 as an important mediator. This study of the interaction of macrophages with enterococci could provide a foundation for studying the pathogenesis of infection by this opportunistic pathogen and to developing new therapeutic approaches to combat enterococcal infection. © 2015 Zou, Shankar.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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PLoS ONE

Roles of TLR/MyD88/MAPK/NF-KB signaling pathways in the regulation of phagocytosis and proinflammatory cytokine expression in response to E. faecalis infection

In this work, we report a simple strategy for signal amplification using appropriately functionalized gold nanoparticles in an electrochemical genosensor which led to attomolar detection of breast cancer 1 (BRCA1) gene. The sensor was developed by the layer-by-layer assembly of mercaptopropionic acid (MPA), polyethylene glycol (PEG) functionalized gold nanoparticle (AuNPPEG), capture DNA (DNA-c), target BRCA1 DNA (DNA-t) and gold nanoparticle labeled reporter DNA (DNA-r.AuNP) on gold electrode. PEG functionalized gold nanoparticles on the MPA surface provided good electron conducting path nullifying the insulating effect of MPA and also act as a proper immobilization platform for the DNA-c by the large number of carboxyl groups present on the functionalized gold nanoparticles. We demonstrated that the incorporation of MPA functionalized gold nanoparticles (AuNPMPA) as an electrochemical label in this sensor design could significantly enhance the sensitivity in the detection. The DNA hybridization of DNA-r.AuNP with target probe was measured by chronoamperometry, electrochemical impedance spectroscopy (EIS) and scanning tunnelling spectroscopy (STS). Electrochemical quartz crystal microbalance (EQCM) experiments were used to support the detection and also to calculate the number of adsorbed molecules on the surface. Under optimum conditions the present sensor exhibited high sensitivity and a very low detection limit of 50attomolar DNA target (294.8attogram BRCA1gene/ml). It shows excellent selectivity against non complementary sequences and 3 base mismatch complementary targets. It also shows good reproducibility, stability and reusability and the developed sensor surface is suitable for point-of care applications.

Biosensors and Bioelectronics

Attomolar detection of BRCA1 gene based on gold nanoparticle assisted signal amplification

Increased incidence of fungal infections in the immunocompromised individuals and fungi-mediated allergy and inflammatory conditions in immunocompetent individuals is a cause of concern. Consequently, there is a need for efficient therapeutic alternatives to treat fungal infections and inflammation. Several studies have demonstrated that antibodies or immunoglobulins have a role in restricting the fungal burden and their clearance. However, based on the data from monoclonal antibodies, it is now evident that the efficacy of antibodies in fungal infections is dependent on epitope specificity, abundance of protective antibodies, and their isotype. Antibodies confer protection against fungal infections by multiple mechanisms that include direct neutralization of fungi and their antigens, inhibition of growth of fungi, modification of gene expression, signaling and lipid metabolism, causing iron starvation, inhibition of polysaccharide release, and biofilm formation. Antibodies promote opsonization of fungi and their phagocytosis, complement activation, and antibody-dependent cell toxicity. Passive administration of specific protective monoclonal antibodies could also prove to be beneficial in drug resistance cases, to reduce the dosage and associated toxic symptoms of anti-fungal drugs. The longer half-life of the antibodies and flexibilities to modify their structure/forms are additional advantages. The clinical data obtained with two monoclonal antibodies should incite interests in translating pre-clinical success into the clinics. The anti-inflammatory and immunoregulatory role of antibodies in fungal inflammation could be exploited by intravenous immunoglobulin or IVIg. © 2014, Springer-Verlag Berlin Heidelberg.

Seminars in Immunopathology

The protective role of immunoglobulins in fungal infections and inflammation

Extensive use of Viscum album (VA) preparations in the complementary therapy of cancer and in several other human pathologies has led to an increasing number of cellular and molecular approaches to explore the mechanisms of action of VA. We have recently demonstrated that, VA preparations exert a potent anti-inflammatory effect by selectively downregulating the COX-2-mediated cytokine-induced secretion of prostaglandin E2 (PGE2), one of the important molecular signatures of inflammatory reactions. In this study, we observed a significant down-regulation of COX-2 protein expression in VA-treated A549 cells however COX-2 mRNA levels were unaltered. Therefore, we hypothesized that VA induces destabilisation of COX-2 mRNA, thereby depleting the available functional COX-2 mRNA for the protein synthesis and for the subsequent secretion of PGE2. To address this question, we analyzed the molecular degradation of COX-2 protein and its corresponding mRNA in A549 cell line. Using cyclohexamide pulse chase experiment, we demonstrate that, COX-2 protein degradation is not affected by the treatment with VA whereas experiments on transcriptional blockade with actinomycin D, revealed a marked reduction in the half life of COX-2 mRNA due to its rapid degradation in the cells treated with VA compared to that in IL-1β-stimulated cells. These results thus demonstrate that VA-mediated inhibition of PGE2 implicates destabilization of COX-2 mRNA. © 2015 Saha et al.

Viscum album-mediated COX-2 inhibition implicates destabilization of COX-2 mRNA

Helicobacter suis (H. suis) is a widespread porcine gastric pathogen, which is also of zoonotic importance. The first goal of this study was to investigate the efficacy of several vaccine adjuvants (CpG-DNA, Curdlan, Freund's Complete and Incomplete, Cholera toxin), administered either subcutaneously or intranasally along with H. suis whole-cell lysate, to protect against subsequent H. suis challenge in a BALB/c infection model. Subcutaneous immunization with Freund's complete (FC)/lysate and intranasal immunization with Cholera toxin (CT)/lysate were shown to be the best options for vaccination against H. suis, as determined by the amount of colonizing H. suis bacteria in the stomach, although adverse effects such as post-immunization gastritis/pseudo-pyloric metaplasia and increased mortality were observed, respectively. Therefore, we decided to test alternative strategies, including sublingual vaccine administration, to reduce the unwanted side-effects. A CCR4 antagonist that transiently inhibits the migration of regulatory T cells was also included as a new adjuvant in this second study. Results confirmed that immunization with CT (intranasally or sublingually) is among the most effective vaccination protocols, but increased mortality was still observed. In the groups immunized subcutaneously with FC/lysate and CCR4 antagonist/lysate, a significant protection was observed. Compared to the FC/lysate immunized group, gastric pseudo-pyloric metaplasia was less severe or even absent in the CCR4 antagonist/lysate immunized group. In general, an inverse correlation was observed between IFN-γ, IL-4, IL-17, KC, MIP-2 and LIX mRNA expression and H. suis colonization density, whereas lower IL-10 expression levels were observed in partially protected animals. © 2015 Bosschem et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Effect of different adjuvants on protection and side-effects induced by Helicobacter suis whole-cell lysate vaccination

Some patients with autoimmune and inflammatory diseases treated with intravenous immunoglobulin G (IVIg) as a first line therapy are refractory. Identification of predictive biomarker(s) to segregate responders and non-responders to IVIg therapy remains critical. A number of biomarkers, particularly in Kawasaki disease, have shown potential for predicting response to IVIg. © 2015 Elsevier Ltd.

Trends in Molecular Medicine

Molecular and immunological biomarkers to predict IVIg response

Basophils are classically known for their pathogenic role in asthma and allergic skin conditions. However, reports suggest that basophil activation mediated by autoreactive IgE, thymic stromal lymphopoietin or Toll-like receptors has an important role in the pathogenesis of lupus nephritis, eosinophilic oesophagitis and IgG4-related diseases, respectively.

Nature Reviews Rheumatology

Autoimmunity: Basophils in autoimmune and inflammatory diseases

Human Immunology

Erratum to "Basophils are inept at promoting human Th17 responses" [Hum. Immunol. 76 (2015) 176-180]

Dendritic cells (DCs) are known to regulate the functions of various immune cells. Reciprocal signaling by these immune cells also "educate" the DCs and determine the quality of the ensuing immune responses. Recently, we demonstrated that human DCs undergo maturation upon interaction with activated B cells to acquire unique abilities to promote polarization of Th2 cells. © 2015 Taylor & Francis Group, LLC.

OncoImmunology

B cells drive Th2 responses by instructing human dendritic cell maturation

A number of allergens from eggplant (Solanum melongena L.) have been previously identified. In this study, we could detect IgE reactivity of two allergic subjects' sera towards two protein bands of molecular mass of about 35 and 15. kDa. As IgE were reactive to both raw and cooked eggplant extracts, a heat-stable nature of these novel allergens is apparent. © 2015 European Federation of Immunological Societies.