A mechanistic framework for auxin dependent Arabidopsis root hair elongation to low external phosphate

Phosphate (P) is an essential macronutrient for plant growth. Roots employ adaptive mechanisms to forage for P in soil. Root hair elongation is particularly important since P is immobile. Here we report that auxin plays a critical role promoting root hair growth in Arabidopsis in response to low external P. Mutants disrupting auxin synthesis (taa1) and transport (aux1) attenuate the low P root hair response. Conversely, targeting AUX1 expression in lateral root cap and epidermal cells rescues this low P response in aux1. Hence auxin transport from the root apex to differentiation zone promotes auxin-dependent hair response to low P. Low external P results in induction of root hair expressed auxin-inducible transcription factors ARF19, RSL2, and RSL4. Mutants lacking these genes disrupt the low P root hair response. We conclude auxin synthesis, transport and response pathway components play critical roles regulating this low P root adaptive response

Assessment of measles immunity among infants in Maputo City, Mozambique

<p>Abstract</p> <p>Background</p> <p>The optimum age for measles vaccination varies from country to country and thus a standardized vaccination schedule is controversial. While the increase in measles vaccination coverage has produced significant changes in the epidemiology of infection, vaccination schedules have not been adjusted. Instead, measures to cut wild-type virus transmission through mass vaccination campaigns have been instituted. This study estimates the presence of measles antibodies among six- and nine-month-old children and assesses the current vaccination seroconversion by using a non invasive method in Maputo City, Mozambique.</p> <p>Methods</p> <p>Six- and nine-month old children and their mothers were screened in a cross-sectional study for measles-specific antibodies in oral fluid. All vaccinated children were invited for a follow-up visit 15 days after immunization to assess seroconversion. </p> <p>Results</p> <p>82.4% of the children lost maternal antibodies by six months. Most children were antibody-positive post-vaccination at nine months, although 30.5 % of nine month old children had antibodies in oral fluid before vaccination. We suggest that these pre-vaccination antibodies are due to contact with wild-type of measles virus. The observed seroconversion rate after vaccination was 84.2%. </p> <p>Conclusion</p> <p>These data indicate a need to re-evaluate the effectiveness of the measles immunization policy in the current epidemiological scenario.</p

Mesoporous carbon-containing voltammetric biosensor for determination of tyramine in food products

A voltammetric biosensor based on tyrosinase (TYR) was developed for determination of tyramine. Carbon material (multi-walled carbon nanotubes or mesoporous carbon CMK-3-type), polycationic polymer—i.e., poly(diallyldimethylammonium chloride) (PDDA), and Nafion were incorporated into titania dioxide sol (TiO(2)) to create an immobilization matrix. The features of the formed matrix were studied by scanning electron microscopy (SEM) and cyclic voltammetry (CV). The analytical performance of the developed biosensor was evaluated with respect to linear range, sensitivity, limit of detection, long-term stability, repeatability, and reproducibility. The biosensor exhibited electrocatalytic activity toward tyramine oxidation within a linear range from 6 to 130 μM, high sensitivity of 486 μA mM(−1) cm(−2), and limit of detection of 1.5 μM. The apparent Michaelis–Menten constant was calculated to be 66.0 μM indicating a high biological affinity of the developed biosensor for tyramine. Furthermore, its usefulness in determination of tyramine in food product samples was also verified. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00216-016-9612-y) contains supplementary material, which is available to authorized users

Novel human genetic variants associated with extrapulmonary tuberculosis: a pilot genome wide association study

<p>Abstract</p> <p>Background</p> <p>Approximately 5-10% of persons infected with <it>M. tuberculosis </it>develop tuberculosis, but the factors associated with disease progression are incompletely understood. Both linkage and association studies have identified human genetic variants associated with susceptibility to pulmonary tuberculosis, but few genetic studies have evaluated extrapulmonary disease. Because extrapulmonary and pulmonary tuberculosis likely have different underlying pathophysiology, identification of genetic mutations associated with extrapulmonary disease is important.</p> <p>Findings</p> <p>We performed a pilot genome-wide association study among 24 persons with previous extrapulmonary tuberculosis and well-characterized immune defects; 24 pulmonary tuberculosis patients and 57 patients with <it>M. tuberculosis </it>infection served as controls. The Affymetrix GeneChip Human Mapping Xba Array was used for genotyping; after careful quality control, genotypes at 44,175 single nucleotide polymorphisms (SNPs) were available for analysis. Eigenstrat quantified population stratification within our sample; logistic regression, using results of the Eigenstrat analysis as a covariate, identified significant associations between groups. Permutation testing controlled the family-wise error rate for each comparison between groups. Four SNPs were significantly associated with extrapulmonary tuberculosis compared to controls with <it>M. tuberculosis </it>infection; one (rs4893980) in the gene PDE11A, one (rs10488286) in KCND2, and one (rs2026414) in PCDH15; one was in chromosome 7 but not associated with a known gene. Two additional variants were significantly associated with extrapulmonary tuberculosis compared with pulmonary tuberculosis; one (rs340708) in the gene FAM135B and one in chromosome 13 but not associated with a known gene. The function of all four genes affects cell signaling and activity, including in the brain.</p> <p>Conclusions</p> <p>In this pilot study, we identified 6 novel variants not previously known to be associated with extrapulmonary tuberculosis, including two SNPs more common in persons with extrapulmonary than pulmonary tuberculosis. This provides some support for the hypothesis that the pathogenesis and genetic predisposition to extrapulmonary tuberculosis differs from pulmonary tuberculosis. Further study of these novel SNPs, and more well-powered genome-wide studies of extrapulmonary tuberculosis, is warranted.</p

Replicating viral vector platform exploits alarmin signals for potent CD8⁺ T cell-mediated tumour immunotherapy.

Viral infections lead to alarmin release and elicit potent cytotoxic effector T lymphocyte (CTL &lt;sup&gt;eff&lt;/sup&gt; ) responses. Conversely, the induction of protective tumour-specific CTL &lt;sup&gt;eff&lt;/sup&gt; and their recruitment into the tumour remain challenging tasks. Here we show that lymphocytic choriomeningitis virus (LCMV) can be engineered to serve as a replication competent, stably-attenuated immunotherapy vector (artLCMV). artLCMV delivers tumour-associated antigens to dendritic cells for efficient CTL priming. Unlike replication-deficient vectors, artLCMV targets also lymphoid tissue stroma cells expressing the alarmin interleukin-33. By triggering interleukin-33 signals, artLCMV elicits CTL &lt;sup&gt;eff&lt;/sup&gt; responses of higher magnitude and functionality than those induced by replication-deficient vectors. Superior anti-tumour efficacy of artLCMV immunotherapy depends on interleukin-33 signalling, and a massive CTL &lt;sup&gt;eff&lt;/sup&gt; influx triggers an inflammatory conversion of the tumour microenvironment. Our observations suggest that replicating viral delivery systems can release alarmins for improved anti-tumour efficacy. These mechanistic insights may outweigh safety concerns around replicating viral vectors in cancer immunotherapy

Analysis of eight genes modulating interferon gamma and human genetic susceptibility to tuberculosis: a case-control association study

<p>Abstract</p> <p>Background</p> <p>Interferon gamma is a major macrophage-activating cytokine during infection with <it>Mycobacterium tuberculosis</it>, the causative pathogen of tuberculosis, and its role has been well established in animal models and in humans. This cytokine is produced by activated T helper 1 cells, which can best deal with intracellular pathogens such as <it>M. tuberculosis</it>. Based on the hypothesis that genes which regulate interferon gamma may influence tuberculosis susceptibility, we investigated polymorphisms in eight candidate genes.</p> <p>Methods</p> <p>Fifty-four polymorphisms in eight candidate genes were genotyped in over 800 tuberculosis cases and healthy controls in a population-based case-control association study in a South African population. Genotyping methods used included the SNPlex Genotyping System™, capillary electrophoresis of fluorescently labelled PCR products, TaqMan^®SNP genotyping assays or the amplification mutation refraction system. Single polymorphisms as well as haplotypes of the variants were tested for association with TB using statistical analyses.</p> <p>Results</p> <p>A haplotype in interleukin 12B was nominally associated with tuberculosis (p = 0.02), but after permutation testing, done to assess the significance for the entire analysis, this was not globally significant. In addition a novel allele was found for the interleukin 12B D5S2941 microsatellite.</p> <p>Conclusions</p> <p>This study highlights the importance of using larger sample sizes when attempting validation of previously reported genetic associations. Initial studies may be false positives or may propose a stronger genetic effect than subsequently found to be the case.</p

Cytokine Gene Polymorphisms in Italian Preterm Infants: Association Between Interleukin-10 –1082 G/A Polymorphism and Respiratory Distress Syndrome

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