Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

Galectin-1 (Gal-1), a glycan-binding protein with broad antiinflammatory activities, functions as a proresolving mediator in autoimmune and chronic inflammatory disorders. However, its role in allergic airway inflammation has not yet been elucidated. We evaluated the effects of Gal-1 on eosinophil function and its role in a mouse model of allergic asthma. Allergen exposure resulted in airway recruitment of Gal-1-expressing inflammatory cells, including eosinophils, as well as increased Gal-1 in extracellular spaces in the lungs. In vitro, extracellular Gal-1 exerted divergent effects on eosinophils that were N-glycan- And dose-dependent. At concentrations ≤0.25 μM, Gal-1 increased eosinophil adhesion to vascular cell adhesion molecule-1, caused redistribution of integrin CD49d to the periphery and cell clustering, but inhibited ERK(1/2) activation and eotaxin-1-induced migration. Exposure to concentrations ≥1 μM resulted in ERK(1/2)- dependent apoptosis and disruption of the F- Actin cytoskeleton. At lower concentrations, Gal-1 did not alter expression of adhesion molecules (CD49d, CD18, CD11a, CD11b, L-selectin) or of the chemokine receptor CCR3, but decreased CD49d and CCR3 was observed in eosinophils treated with higher concentrations of this lectin. In vivo, allergen-challenged Gal-1-deficient mice exhibited increased recruitment of eosinophils and CD3+ T lymphocytes in the airways as well as elevated peripheral blood and bone marrow eosinophils relative to corresponding WT mice. Further, these mice had an increased propensity to develop airway hyperresponsiveness and displayed significantly elevated levels of TNF-α in lung tissue. This study suggests that Gal-1 can limit eosinophil recruitment to allergic airways and suppresses airway inflammation by inhibiting cell migration and promoting eosinophil apoptosis.Fil: Ge, Xiao Na. University of Minnesota; Estados UnidosFil: Ha, Sung Gil. University of Minnesota; Estados UnidosFil: Greenberg, Yana G.. University of Minnesota; Estados UnidosFil: Rao, Amrita. University of Minnesota; Estados UnidosFil: Bastan, Idil. University of Minnesota; Estados UnidosFil: Blidner, Ada Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rao, Savita P.. University of Minnesota; Estados UnidosFil: Rabinovich, Gabriel Adrián. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Sriramarao, P.. University of Minnesota; Estados Unido

Interaction Between Convection and Pulsation

This article reviews our current understanding of modelling convection dynamics in stars. Several semi-analytical time-dependent convection models have been proposed for pulsating one-dimensional stellar structures with different formulations for how the convective turbulent velocity field couples with the global stellar oscillations. In this review we put emphasis on two, widely used, time-dependent convection formulations for estimating pulsation properties in one-dimensional stellar models. Applications to pulsating stars are presented with results for oscillation properties, such as the effects of convection dynamics on the oscillation frequencies, or the stability of pulsation modes, in classical pulsators and in stars supporting solar-type oscillations.Comment: Invited review article for Living Reviews in Solar Physics. 88 pages, 14 figure

Exploring the Support Needs of Family Caregivers of Patients with Brain Cancer Using the CSNAT: A Comparative Study with Other Cancer Groups

A substantial burden is placed on family caregivers of patients diagnosed with brain cancers. Despite this, the support needs of the caregivers are often under-recognised and not addressed adequately in current routine and patient centred clinical care. The Care Support Needs Assessment Tool (CSNAT) is a validated instrument designed to systematically identify and address caregiver needs. It has been trialled in an Australian palliative care community setting using a stepped wedge cluster design involving 322 family carers of terminally ill patients. The current article reports on a subset from this trial, 29 caregivers of patients with primary brain cancer, and compares their profile and outcomes to those of other cancer groups. Caregiver strain was assessed using the Family Appraisal of Caregiving Questionnaire, caregiver physical and mental wellbeing using SF12 and caregiver workload using a questionnaire on support with activities of daily living (ADL). In comparison to caregivers of patients with all other cancers, the primary brain cancer group had significantly higher levels of caregiver strain, lower levels of mental wellbeing and a higher level of ADL workload. Their physical wellness also deteriorated significantly over time.An action plan approach led to practical solutions for addressing highlighted concerns. Four themes evolved from the family caregivers’ feedback interviews: The extremely challenging caregiver experience with brain cancer; the systematic and practical approach of the CSNAT during rapid changes; connection with health professionals, feeling acknowledged and empowered; and timely advice and assurance of support during the caregiving journey. This preliminary study has demonstrated that the CSNAT provides a practical and useful tool for assessing the support needs of family caregivers of patients with brain cancer and has provided the basis for a larger scale, longitudinal study that allows a more detailed characterisation of the evolving caregiver needs at different stages of the disease

Modulation of IL-17 and Foxp3 Expression in the Prevention of Autoimmune Arthritis in Mice

©2010 Duarte 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.Background: Rheumatoid Arthritis (RA) is a chronic immune mediated disease associated with deregulation of many cell types. It has been reported that different T cell subsets have opposite effects in disease pathogenesis, in particular Th17 and Treg cells. Methodology and Findings: We investigated whether non-depleting anti-CD4 monoclonal antibodies, which have been reported as pro-tolerogenic, can lead to protection from chronic autoimmune arthritis in SKG mice – a recently described animal model of RA – by influencing the Th17/Treg balance. We found that non-depleting anti-CD4 prevented the onset of chronic autoimmune arthritis in SKG mice. Moreover, treated mice were protected from the induction of arthritis up to 60 days following anti-CD4 treatment, while remaining able to mount CD4-dependent immune responses to unrelated antigens. The antibody treatment also prevented disease progression in arthritic mice, although without leading to remission. Protection from arthritis was associated with an increased ratio of Foxp3, and decreased IL-17 producing T cells in the synovia. In vitro assays under Th17-polarizing conditions showed CD4-blockade prevents Th17 polarization, while favoring Foxp3 induction. Conclusions: Non-depleting anti-CD4 can therefore induce long-term protection from chronic autoimmune arthritis in SKG mice through reciprocal changes in the frequency of Treg and Th17 cells in peripheral tissues, thus shifting the balance towards immune tolerance.This work was funded by SUDOE, grant number IMMUNONET-SOE1/1P1/E014, and supported by a research grant from Fundação para a Ciência e Tecnologia (FCT), Portugal (FCT/POCI/SAU-MMO/55974/2004). JD, AA-D, and VGO are funded with scholarships from FCT (SFRH/BD/23631/2005, SFRH/BD/49093/2008, and SFRH/BPD/22575/2005)

Utilization of Benchtop Next Generation Sequencing Platforms Ion Torrent PGM and MiSeq in Noninvasive Prenatal Testing for Chromosome 21 Trisomy and Testing of Impact of In Silico and Physical Size Selection on Its Analytical Performance

OBJECTIVES: The aims of this study were to test the utility of benchtop NGS platforms for NIPT for trisomy 21 using previously published z score calculation methods and to optimize the sample preparation and data analysis with use of in silico and physical size selection methods. METHODS: Samples from 130 pregnant women were analyzed by whole genome sequencing on benchtop NGS systems Ion Torrent PGM and MiSeq. The targeted yield of 3 million raw reads on each platform was used for z score calculation. The impact of in silico and physical size selection on analytical performance of the test was studied. RESULTS: Using a z score value of 3 as the cut-off, 98.11% - 100% (104-106/106) specificity and 100% (24/24) sensitivity and 99.06% - 100% (105-106/106) specificity and 100% (24/24) sensitivity were observed for Ion Torrent PGM and MiSeq, respectively. After in silico based size selection both platforms reached 100% specificity and sensitivity. Following the physical size selection z scores of tested trisomic samples increased significantly-p = 0.0141 and p = 0.025 for Ion Torrent PGM and MiSeq, respectively. CONCLUSIONS: Noninvasive prenatal testing for chromosome 21 trisomy with the utilization of benchtop NGS systems led to results equivalent to previously published studies performed on high-to-ultrahigh throughput NGS systems. The in silico size selection led to higher specificity of the test. Physical size selection performed on isolated DNA led to significant increase in z scores. The observed results could represent a basis for increasing of cost effectiveness of the test and thus help with its penetration worldwide

First nationwide survey on cardiovascular risk factors in Grand-Duchy of Luxembourg (ORISCAV-LUX)

BACKGROUND: The ORISCAV-LUX study is the first baseline survey of an on-going cardiovascular health monitoring programme in Grand-Duchy of Luxembourg. The main objectives of the present manuscript were 1) to describe the study design and conduct, and 2) to present the salient outcomes of the study, in particular the prevalence of the potentially modifiable and treatable cardiovascular disease risk factors in the adult population residing in Luxembourg. METHOD: ORISCAV-LUX is a cross-sectional study based on a random sample of 4496 subjects, stratified by gender, age categories and district, drawn from the national insurance registry of 18-69 years aged Luxembourg residents, assuming a response rate of 30% and a proportion of 5% of institutionalized subjects in each stratum. The cardiovascular health status was assessed by means of a self-administered questionnaire, clinical and anthropometric measures, as well as by blood, urine and hair examinations. The potentially modifiable and treatable risk factors studied included smoking, hypertension, dyslipidemia, diabetes mellitus, and obesity. Both univariate and multivariate statistical analyses used weighted methods to account for the stratified sampling scheme. RESULTS: A total of 1432 subjects took part in the survey, yielding a participation rate of 32.2%. This figure is higher than the minimal sample size of 1285 subjects as estimated by power calculation. The most predominant cardiovascular risk factors were dyslipidemia (69.9%), hypertension (34.5%), smoking (22.3%), and obesity (20.9%), while diabetes amounted 4.4%. All prevalence rates increased with age (except smoking) with marked gender differences (except diabetes). There was a significant difference in the prevalence of hypertension and of lipid disorders by geographic region of birth. The proportion of subjects cumulating two or more cardiovascular risk factors increased remarkably with age and was more predominant in men than in women (P<0.0001). Only 14.7% of men and 23.1% of women were free of any cardiovascular risk factor. High prevalence of non-treated CVRF, notably for hypertension and dyslipidemia, were observed in the study population. CONCLUSION: The population-based ORISCAV-LUX survey revealed a high prevalence of potentially modifiable and treatable cardiovascular risk factors among apparently healthy subjects; significant gender and age-specific differences were seen not only for single but also for combined risk factors. From a public health perspective, these preliminary findings stress the urgent need for early routine health examinations, preventive interventions and lifestyle behavioural changes, even in young asymptomatic adults, to decrease cardiovascular morbidity and mortality in Luxembourg

Parallel Expansions of Sox Transcription Factor Group B Predating the Diversifications of the Arthropods and Jawed Vertebrates

Group B of the Sox transcription factor family is crucial in embryo development in the insects and vertebrates. Sox group B, unlike the other Sox groups, has an unusually enlarged functional repertoire in insects, but the timing and mechanism of the expansion of this group were unclear. We collected and analyzed data for Sox group B from 36 species of 12 phyla representing the major metazoan clades, with an emphasis on arthropods, to reconstruct the evolutionary history of SoxB in bilaterians and to date the expansion of Sox group B in insects. We found that the genome of the bilaterian last common ancestor probably contained one SoxB1 and one SoxB2 gene only and that tandem duplications of SoxB2 occurred before the arthropod diversification but after the arthropod-nematode divergence, resulting in the basal repertoire of Sox group B in diverse arthropod lineages. The arthropod Sox group B repertoire expanded differently from the vertebrate repertoire, which resulted from genome duplications. The parallel increases in the Sox group B repertoires of the arthropods and vertebrates are consistent with the parallel increases in the complexity and diversification of these two important organismal groups

Enhanced Botrytis cinerea resistance of Arabidopsis plants grown in compost may be explained by increased expression of defense-related genes, as revealed by microarray analysis

Composts are the products obtained after the aerobic degradation of different types of organic matter waste and can be used as substrates or substrate/soil amendments for plant cultivation. There is a small but increasing number of reports that suggest that foliar diseases may be reduced when using compost, rather than standard substrates, as growing medium. The purpose of this study was to examine the gene expression alteration produced by the compost to gain knowledge of the mechanisms involved in compost-induced systemic resistance. A compost from olive marc and olive tree leaves was able to induce resistance against Botrytis cinerea in Arabidopsis, unlike the standard substrate, perlite. Microarray analyses revealed that 178 genes were differently expressed, with a fold change cut-off of 1, of which 155 were up-regulated and 23 were down-regulated in compost-grown, as against perlite-grown plants. A functional enrichment study of up-regulated genes revealed that 38 Gene Ontology terms were significantly enriched. Response to stress, biotic stimulus, other organism, bacterium, fungus, chemical and abiotic stimulus, SA and ABA stimulus, oxidative stress, water, temperature and cold were significantly enriched, as were immune and defense responses, systemic acquired resistance, secondary metabolic process and oxireductase activity. Interestingly, PR1 expression, which was equally enhanced by growing the plants in compost and by B. cinerea inoculation, was further boosted in compost-grown pathogen-inoculated plants. Compost triggered a plant response that shares similarities with both systemic acquired resistance and ABA-dependent/independent abiotic stress responses

USP18-Based Negative Feedback Control Is Induced by Type I and Type III Interferons and Specifically Inactivates Interferon α Response

Type I interferons (IFN) are cytokines that are rapidly secreted upon microbial infections and regulate all aspects of the immune response. In humans 15 type I IFN subtypes exist, of which IFN α2 and IFN β are used in the clinic for treatment of different pathologies. IFN α2 and IFN β are non redundant in their expression and in their potency to exert specific bioactivities. The more recently identified type III IFNs (3 IFN λ or IL-28/IL-29) bind an unrelated cell-type restricted receptor. Downstream of these two receptor complexes is a shared Jak/Stat pathway. Several mechanisms that contribute to the shut down of the IFN-induced signaling have been described at the molecular level. In particular, it has long been known that type I IFN induces the establishment of a desensitized state. In this work we asked how the IFN-induced desensitization integrates into the network built by the multiple type I IFN subtypes and type III IFNs. We show that priming of cells with either type I IFN or type III IFN interferes with the cell's ability to further respond to all IFN α subtypes. Importantly, primed cells are differentially desensitized in that they retain sensitivity to IFN β. We show that USP18 is necessary and sufficient to induce differential desensitization, by impairing the formation of functional binding sites for IFN α2. Our data highlight a new type of differential between IFNs α and IFN β and underline a cross-talk between type I and type III IFN. This cross-talk could shed light on the reported genetic variation in the IFN λ loci, which has been associated with persistence of hepatitis C virus and patient's response to IFN α2 therapy