A novel frequency reconfigurable antenna for smart grid applications in TV white space band

This paper presents the design and analysis of a frequency reconfigurable, aperture coupled rectangular patch antenna for use in smart grid applications in TV white space bands. The proposed antenna model has been realized on multi-substrate layers of Polylactic acid (PLA) material (εr=2.65, tanδ=0.003) with a ground plane sandwiched in between them. An aperture has been made in the ground plane for coupling energy to the patch. The overall system dimensions are 270×270 mm. The feature of frequency reconfigurability has been achieved by incorporating a switch and varying the reactance of the feed line on the bottom substrate. A rectangular slot on the long feed line improves impedance matching. The ON and OFF states of the switch provide two operating frequency bands namely 630.13 to 636.7 MHz and 619.16 to 625.3 MHz respectively. The proposed aperture coupled reconfigurable system operates with a maximum gain of 6.4 dB and average efficiency of 78.5% in both bands. The measured results are satisfactory and the proposed antenna will be suitable for operation in the smart grid environment

LRRK2 and RIPK2 variants in the NOD 2-mediated signaling pathway are associated with susceptibility to Mycobacterium leprae in Indian populations

In recent years, genome wide association studies have discovered a large number of gene loci that play a functional role in innate and adaptive immune pathways associated with leprosy susceptibility. The immunological control of intracellular bacteria M. leprae is modulated by NOD2-mediated signaling of Th1 responses. In this study, we investigated 211 clinically classified leprosy patients and 230 ethnically matched controls in Indian population by genotyping four variants in NOD2 (rs9302752A/G), LRRK2 (rs1873613A/G), RIPK2 (rs40457A/G and rs42490G/A). The LRRK2 locus is associated with leprosy outcome. The LRRK2 rs1873613A minor allele and respective rs1873613AA genotypes were significantly associated with an increased risk whereas the LRRK2 rs1873613G major allele and rs1873613GG genotypes confer protection in paucibacillary and leprosy patients. The reconstructed GA haplotypes from RIPK2 rs40457A/G and rs42490G/A variants was observed to contribute towards increased risk whereas haplotypes AA was observed to confer protective role. Our results indicate that a possible shared mechanisms underlying the development of these two clinical forms of the disease as hypothesized. Our findings confirm and validates the role of gene variants involved in NOD2-mediated signalling pathways that play a role in immunological control of intracellular bacteria M. leprae

Association of increased risk of asthma with elevated arginase & interleukin-13 levels in serum & rs2781666 G/T genotype of arginase I

Background & objectives: High expression of arginase gene and its elevated level in serum and bronchial lavage reported in animal models indicated an association with the pathogenesis of asthma. This study was undertaken to assess the serum arginase activity in symptomatic asthma patients and healthy controls and to correlate it with cytokine levels [interleukin (IL)-4 and IL-13] and arginase I (ARG1) gene polymorphism. Methods: Asthma was confirmed by lung function test according to the GINA guidelines in patients attending Allergy and Pulmonology Clinic, Bhagwan Mahavir Hospital and Research Centre, Hyderabad, India, a tertiary care centre, during 2013-2015. Serum arginase was analyzed using a biochemical assay, total IgE and cytokine levels by enzyme-linked immunosorbent assay and genotyping of ARG1 for single-nucleotide polymorphisms (SNPs) rs2781666 and rs60389358 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: There was a significant two-fold elevation in the arginase activity in asthmatics as compared to healthy controls which correlated with disease severity. Non-atopic asthmatics showed elevated activity of arginase compared to atopics, indicating its possible role in intrinsic asthma. Levels of serum IL-13 and IL-4 were significantly high in asthma group which correlated with disease severity that was assessed by spirometry. A positive correlation was observed between arginase activity and IL-13 concentration. Genetic analysis of ARG1 SNPs revealed that rs2781666 G/T genotype, T allele and C-T haplotype (rs60389358 and rs2781666) were associated with susceptibility to asthma. Interpretation & conclusions: This study indicated that high arginase activity and IL-13 concentration in the serum and ARG1 rs2781666 G/T genotype might increase the risk of asthma in susceptible population. Further studies need to be done with a large sample to confirm these findings

IL-17 and IL-22 production in HIV+ individuals with latent and active tuberculosis

Abstract Background IL-17 and IL-22 cytokines play an important role in protective immune responses against Mycobacterium tuberculosis (Mtb) infection. Information on the production of these cytokines and the factors that regulate their production in the context of human immunodeficiency virus (HIV) and latent tuberculosis infection (LTBI) or active tuberculosis disease (ATB) is limited. In the current study, we compared the production of these two cytokines by PBMC of HIV-LTBI+ and HIV + LTBI+ individuals in response to Mtb antigens CFP-10 (culture filtrate protein) and ESAT-6 (Early Secretory Antigenic Target). We also determined the mechanisms involved in their production. Methods We cultured Peripheral Blood Mononuclear Cells (PBMCs) from HIV- individuals and HIV+ patients with latent tuberculosis and active disease with CFP-10 and ESAT-6. Production of IL-17, IL-22 and PD1 (Programmed Death 1), ICOS (Inducible T-cell Costimulator), IL-23R and FoxP3 (Forkhead box P3) expression on CD4+ T cells was measured. Results In response to Mtb antigens CFP-10 and ESAT-6, freshly isolated PBMCs from HIV+ LTBI+ and HIV+ active TB patients produced less IL-17 and IL-22 and more IL-10, expressed less IL-23R, and more PD1 and expanded to more FoxP3+ cells. Active TB infection in HIV+ individuals further inhibited antigen specific IL-17 and IL-22 production compared to those with LTBI. Neutralization of PD1 restored IL-23R expression, IL-17 and IL-22 levels and lowered IL-10 production and reduced expansion of FoxP3 T cells. Conclusions In the current study we found that increased PD1 expression in HIV + LTBI+ and HIV+ active TB patients inhibits IL-17, IL-22 production and IL-23R expression in response to Mtb antigens CFP-10 and ESAT-6

Correction: IL-22 produced by type 3 innate lymphoid cells (ILC3s) reduces the mortality of type 2 diabetes mellitus (T2DM) mice infected with Mycobacterium tuberculosis.

[This corrects the article DOI: 10.1371/journal.ppat.1008140.]

Alcohol enhances type 1 interferon-α production and mortality in young mice infected with <i>Mycobacterium tuberculosis</i>

<div><p>In the current study, we used a mouse model and human blood samples to determine the effects of chronic alcohol consumption on immune responses during <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) infection. Alcohol increased the mortality of young mice but not old mice with <i>Mtb</i> infection. CD11b+Ly6G+ cells are the major source of IFN-α in the lungs of <i>Mtb</i>-infected alcohol-fed young mice, and IFN-α enhances macrophage necroptosis in the lungs. Treatment with an anti-IFNAR-1 antibody enhanced the survival of <i>Mtb</i>-infected alcohol-fed young mice. In response to <i>Mtb</i>, peripheral blood mononuclear cells (PBMCs) from alcoholic young healthy individuals with latent tuberculosis infection (LTBI) produced significantly higher amounts of IFN-α than those from non-alcoholic young healthy LTBI+ individuals and alcoholic and non-alcoholic old healthy LTBI+ individuals. Our study demonstrates that alcohol enhances IFN-α production by CD11b+Ly6G+ cells in the lungs of young <i>Mtb</i>-infected mice, which leads to macrophage necroptosis and increased mortality. Our findings also suggest that young alcoholic LTBI+ individuals have a higher risk of developing active TB infection.</p></div

IFN-α production in <i>Mtb</i>-infected young alcoholic mice is associated with the expression of molecules involved in necroptosis.

<p><b>a.</b> Young (one to two months of age) and old (17 to 22 months of age) mice were fed control and alcohol diets for one month as detailed in the methods section; then, they were infected with 50–100 CFU of aerosolized <i>Mtb</i> H37Rv, and control and alcohol diet feeding was continued. At six months p.i., lung homogenates from uninfected control and alcohol diet-fed mice and <i>Mtb</i>-infected control and alcohol diet-fed mice were collected, and RIP-1 and RIP-3 gene expression was determined by quantitative real-time PCR. Control and alcohol diet-fed young mice were infected with 50–100 CFU of aerosolized <i>Mtb</i>. At three months p.i., lungs from uninfected control and alcohol diet-fed mice as well as from <i>Mtb</i>-infected control and <i>Mtb</i>-infected alcohol diet-fed mice were isolated and formalin fixed. Paraffin-embedded tissue sections were prepared and analyzed by confocal microscopy for <b>b</b>. RIP-1+ and RIP-3+ cells (red). Representative images of staining patterns were taken of multiple fields at 40X and 63X with oil immersion. The immunofluorescence intensities for these groups were calculated. <b>c.</b> RIP-1- and RIP-3 (red)-expressing F4/80 macrophages (green). <b>d.</b> Lung paraffin-embedded tissue sections were analyzed by confocal microscopy to determine IFN-α (Green), Ly6G (Magenta or Far-red) and RIP1/3 (red) colocalization. Scale bar: 10 μm. The rightmost panel shows a higher magnification for representation, and the yellow squares represent IFN-α-expressing Ly6G<i>+</i> cells. <b>e.</b> Representative images of RIP-1 and RIP-3 expression in lung F4/80 macrophages from anti-IFNAR-1 antibody-treated and isotype control antibody (IgG1)-treated mice are shown. Five mice per group were used for each group. The mean values, p-values and SEs are shown.</p

Absolute number of lung leukocyte populations in <i>Mtb</i>-infected alcohol and control diet-fed mice.

<p>Young control and alcohol diet-fed mice were infected with 50–100 CFU of aerosolized <i>Mtb</i>. At three months p.i., lungs from uninfected control and alcohol diet-fed mice and from <i>Mtb</i>-infected control and alcohol diet-fed mice were isolated. The absolute numbers of various leukocyte populations, namely, <b>a</b>. CD3+ <b>b</b>. CD4+ <b>c</b>. CD8+ <b>d</b>. CD11b+Ly6G+ <b>e</b>. CD11c+ <b>f</b>. CD11b+ <b>g</b>. CD11b+Ly6G- and <b>h</b>. CD3-NK1.1+ cells, per 10⁶ total lung cells were determined by flow cytometry. The data are representative of two independent experiments. Five mice per group were used for each independent experiment. The mean values, p-values and SEs are shown.</p

Alcohol enhances IFN-α production in young mice infected with <i>Mtb</i>.

<p>Young mice were fed control and alcohol diets as detailed in the methods section; then, they were infected with 50–100 CFU of aerosolized <i>Mtb</i> H37Rv, and control and alcohol diet feeding was continued. <b>a.</b> At three months p.i., lung homogenates from uninfected control and alcohol diet-fed and <i>Mtb</i>-infected control and alcohol diet-fed mice were collected, and cytokine and chemokine levels were determined by multiplex ELISA. <b>b-d.</b> At three months p.i., lungs from uninfected control and alcohol diet-fed mice as well as from <i>Mtb</i>-infected control and <i>Mtb</i>-infected alcohol diet-fed mice were isolated and formalin fixed. Paraffin-embedded tissue sections were prepared, and hematoxylin and eosin staining was performed. Inflamed lung areas were compared between the groups. <b>b.</b> A representative figure is shown. <b>c.</b> The lesion area and <b>d</b>. % lung lesions were calculated. The data are representative of two independent experiments. Five mice per group were used for each independent experiment. The mean values, p-values and SEs are shown.</p

IFN-α reduces the survival of <i>Mtb</i>-infected alcohol diet-fed young mice.

<p>Control and alcohol diet-fed young mice were infected with 50–100 CFU of aerosolized <i>Mtb</i>. At three months p.i., some of the alcohol-fed <i>Mtb</i>-infected young mice were treated with either an anti-IFNAR-1 mAb or IgG1 isotype-matched control mAb (0.3 mg per mouse, starting 3 months p.i. every 4 days for 3 months). <b>a.</b> Survival rates of <i>Mtb</i>-infected alcohol-fed young mice treated with the anti-IFNAR-1 mAb or IgG1 isotype-matched control mAb. The data from two independent experiments were pooled. Five mice per group were used for each independent experiment. The survival curves were compared using the log-rank test (P<0.001). <b>b to d.</b> At three months p.i., <i>Mtb</i>-infected alcohol diet-fed mice were treated with either the anti-IFNAR-1 mAb or IgG1 isotype-matched control mAb. Lungs were isolated and formalin-fixed. Paraffin-embedded tissue sections were prepared, and hematoxylin and eosin staining was performed. <b>b.</b> A representative figure is shown. <b>c.</b> The % lung lesions and <b>d.</b> lesion area were calculated. The data from two independent experiments were pooled. Three mice per group were used for each independent experiment (n = 6). The mean values, p-values and SEs are shown.</p