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.

&nbsp;

IIT Palakkad

Proinflammatory cytokines are critically involved in the alteration of adipose tissue biology leading to deterioration of glucose homeostasis in obesity. Here we show a pronounced proinflammatory signature of adipose tissue macrophages in type 2 diabetic obese patients, mainly driven by increased NLRP3-dependent interleukin (IL)-1β production. IL-1β release increased with glycemic deterioration and decreased after gastric bypass surgery. A specific enrichment of IL-17- and IL-22-producing CD4+ T cells was found in adipose tissue of type 2 diabetic obese patients. Coculture experiments identified the effect of macrophagederived IL-1β to promote IL-22 and IL-17 production by human adipose tissue CD4+ T cells. Reciprocally, adipose tissue macrophages express IL-17 and IL-22 receptors, making them sensitive to IL-17 and IL-22. IL-22 increased IL-1β release by inducing pro-IL-1β transcription through activation of C-Jun pathways in macrophages. In sum, these human data identified IL-1β and the T-cell cytokine IL-22 as key players of a paracrine inflammatory pathway previously unidentified in adipose tissue, with a pathological relevance to obesity-induced type 2 diabetes. These results provide an additional rationale for targeting IL-1β in obesity-linked type 2 diabetes and may have important implications for the conception of novel combined anti-IL-1β and anti-IL-22 immunotherapy in human obesity. © 2014 by the American Diabetes Association.

World University root node

Fulltext

Diabetes

T cell+derived IL-22 amplifies IL-1β+driven inflammation in human adipose tissue: Relevance to obesity and type 2 diabetes

Ophthalmology

Re: Kaiser: Emerging therapies for neovascular age-related macular degeneration: Drugs in the pipeline (Ophthalmology 2013;120:S11-S15)

Naturally occurring autoantibodies (NAbs) with germline or close to germline configurations are specific to self- and altered self-components and they exist in the serum of healthy individuals, independent of deliberate immunization with a target antigen. Human intravenous immunoglobulin (IVIg) consists of pooled immunoglobulin (IgG) from several thousand healthy volunteers. In addition to immune deficiency, IVIg is used in the treatment of several autoimmune and inflammatory conditions. The polyreactive, low- to moderate-affinity but high-avidity NAbs are an important part of the composition of IVIg. It is well established that NAbs play a significant role in maintaining tissue and immune homeostasis in a healthy individual. It is thus conceivable that NAbs present within IVIg may participate in exerting the beneficial effects observed during the course of treatment of patients with autoimmune and inflammatory diseases. Understanding the mechanisms by which NAbs operate under different clinical settings is of critical significance. In this chapter, we summarize the roles of NAbs in IVIg. © 2014 Elsevier B.V. All rights reserved.

Autoantibodies, Third Edition

Autoantibodies in Therapeutic Preparations of Human Intravenous Immunoglobulin (IVIg)

We report a simple method for decorating carboxyl functionalized few-layer graphene with titania (TiO2) nanoparticles by sonication and stirring under room temperature. The nanocomposites showed a remarkable improvement in visible light driven photocatalysis. From Raman and XRD analysis the number of layers of graphene was found to be 3. The TiO2 decorated few-layer graphene (FLG) sheets were characterized by electron microscopy, Raman spectroscopy, infrared spectroscopy, XRD and UV-vis spectroscopy. Titania nanoparticles were uniformly decorated on FLG matrix. The incorporation of titania on FLG enhanced the visible light photocatalytic activity of titania, lowered the electron hole recombination and improved the electron hole mobility. The enhanced life time of the charge carriers was confirmed from the photocurrent measurements. Compared to bare TiO2 nanoparticles the FLG-TiO2 nanocomposites exhibited rapid degradation of Rhodamine B (Rhd B) under solar radiation. It was found that adsorption of dye molecules and the rate of degradation have been greatly enhanced in the FLG decorated with TiO2. The rapid degradation of Rhd B using carboxyl functionalized FLG-TiO2 within 8min under solar radiation and 20min under 30W UV tube with very low concentration (0.01wt.%) of the photocatalyst is the highlight of the present report. The mechanism of degradation and charge separation ability of the nanocomposite are also explored. {\textcopyright} 2014 Elsevier Inc.

Journal of Colloid and Interface Science

Synthesis of nanotitania decorated few-layer graphene for enhanced visible light driven photocatalysis

Aging process can affect T cell and antibody response to vaccination and an age-related decline in the expression of CD62L on CD8+ T-lymphocyte is one of the important factors that contribute. A recent report demonstrated that percentage of CD3+CD8+CD62L+ cells and CD8+ T-lymphocyte microRNA-92a levels significantly decline with the age and were positively correlated. These results suggested that the age-related attrition of human naïve T cells could be connected to a reduced microRNA-92a in T-lymphocytes and downregulation of the microRNA-92a level might indicate exhaustion of naïve T-cells due to alteration of the immunologic condition with aging. Further studies are necessary to evaluate whether targeting microRNA-92a as microRNA mimics could be one of the therapeutic strategies in improving vaccine response in elderly. © 2014 Landes Bioscience.

Human Vaccines and Immunotherapeutics

An age-related decline of CD62L and vaccine response: A role of microRNA 92a?

Autophagy is one of the major immune mechanisms engaged to clear intracellular infectious agents. However, several pathogens have evolved strategies to evade autophagy. Here, we demonstrated that Mycobacteria, Shigella, and Listeria but not Klebsiella, Staphylococcus, and Escherichia inhibit IFNG-induced autophagy in macrophages by evoking selective and robust activation of WNT and SHH pathways via MTOR. Utilization of gain- or loss-of-function analyses as well as mir155-null macrophages emphasized the role of MTOR-responsive epigenetic modifications in the induction of Mir155 and Mir31. Importantly, cellular levels of PP2A, a phosphatase, were regulated by Mir155 and Mir31 to fine-tune autophagy. Diminished expression of PP2A led to inhibition of GSK3B, thus facilitating the prolonged activation of WNT and SHH signaling pathways. Sustained WNT and SHH signaling effectuated the expression of anti-inflammatory lipoxygenases, which in tandem inhibited IFNG-induced JAK-STAT signaling and contributed to evasion of autophagy. Altogether, these results established a role for new host factors and inhibitory mechanisms employed by the pathogens to limit autophagy, which could be targeted for therapeutic interventions. © 2014 Landes Bioscience.

Autophagy

Selective inhibition of IFNG-induced autophagy by Mir155- and Mir31-responsive WNT5A and SHH signaling

Journal of Allergy and Clinical Immunology

GM-CSF along with IL-4 but not alone is indispensable for the differentiation of human dendritic cells from monocytes

Background. Systemic sclerosis (SSc, scleroderma) is a disorder characterized by fibrosis of skin and visceral organs. Pathogenesis of scleroderma is complex and is incompletely understood as yet. Autoantibodies in SSc represent a serologic hallmark which have clinical relevance, with diagnostic and prognostic potential. Objectives. To study distribution of clinical manifestations and to identify frequency of autoantibodies among subtypes of scleroderma patients from Western India. Methodology. One hundred and ten scleroderma patients were clinically classified according to the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. All these patients were in active stage of disease. Clinical manifestations were recorded at the time of presentation. Autoantibodies were tested in them by indirect immunofluorescence test and ELISA. Immunoglobulin levels were estimated by nephelometer. These parameters were further correlated with clinical presentation of the disease. Results. Scleroderma patients had M: F ratio of 1: 10 where mean age at evaluation was 34.7 ± 10.7 years and a mean disease duration was 43.7 ± 35 months. Clinical subtypes showed that 45 patients (40.9%) had diffused cutaneous (dcSSc) lesions, 32 patients (29.1%) had limited cutaneous (lcSSc) lesions, and 33 patients (30%) had other autoimmune overlaps. The overall frequency of ANA in SSc patients studied was 85.5%. The frequency of anti-Scl70, anti-centromere, anti-endothelial cell antibodies (AECA), and anti-keratinocyte antibodies (AKA) was 62.7%, 22.7%, 30%, and 40.9%, respectively. Anti-Scl70 antibodies were significantly high (75.6% versus 46.9%) among dcSSc patients (P < 0.0115) whereas anti-centromere antibodies were significantly high (9% versus 38%) among lcSSc patients when these two subtypes were compared (P < 0.0044). Conclusion. This study supports that there are geoepidemiological variations among scleroderma patients for their clinical presentation, autoantibody profile, and immune parameters across the country. © 2014 Vandana Pradhan et al.

International Journal of Rheumatology

Clinical and autoimmune profile of scleroderma patients from Western India

In Aspergillus fumigatus, the conidial surface contains dihydroxynaphthalene (DHN)-melanin. Six-clustered gene products have been identified that mediate sequential catalysis of DHN-melanin biosynthesis. Melanin thus produced is known to be a virulence factor, protecting the fungus from the host defense mechanisms. In the present study, individual deletion of the genes involved in the initial three steps of melanin biosynthesis resulted in an altered conidial surface with masked surface rodlet layer, leaky cell wall allowing the deposition of proteins on the cell surface and exposing the otherwise-masked cell wall polysaccharides at the surface. Melanin as such was immunologically inert; however, deletion mutant conidia with modified surfaces could activate human dendritic cells and the subsequent cytokine production in contrast to the wild-type conidia. Cell surface defects were rectified in the conidia mutated in downstream melanin biosynthetic pathway, and maximum immune inertness was observed upon synthesis of vermelone onward. These observations suggest that although melanin as such is an immunologically inert material, it confers virulence by facilitating proper formation of the A. fumigatus conidial surface. © 2014, American Society for Microbiology.

Infection and Immunity

Surface structure characterization of Aspergillus fumigatus conidia mutated in the melanin synthesis pathway and their human cellular immune response

CD4+CD25+FoxP3+ regulatory T cells (Tregs) are critical for immune homeostasis and tolerance. However, because of their capacity to suppress antigen presenting cells (APC), T and B cells, Tregs could also inhibit protective immune responses to viruses and vaccines. Several viruses have been shown to exploit Tregs to evade immune response. By modulating APC and in particular by weakening the functions of dendritic cells such as their ability to secrete polarizing cytokines and expression of co-stimulatory molecules, viruses could support differentiation and expansion of Tregs. Of note, as a proof of concept, depletion of Tregs significantly enhanced the protective immune response to viruses and vaccines suggesting that Tregs are viable targets to enhance immunogenicity of vaccines. As Treg depletion or inhibition of their functions could lead to deleterious autoimmune and inflammatory disorders, any Treg-based approach for vaccination should not aim at depletion of Tregs and inhibition of their functions should be transient. Recent studies have targeted the interaction between CCR4 expressed on Tregs and its ligands CCL22 and CCL17 to inhibit transiently the recruitment of Tregs at the site of immunization. Importantly, use of CCR4 antagonists as 'molecular adjuvants' in vivo in experimental models, amplified cellular and humoral immune responses when injected in combination with various vaccine antigens. The significant adjuvant activity observed in diverse models without noticeable side effects provided strong evidence that CCR4 is a sustainable target for rational adjuvant design. © 2013 Indian Virological Society.