253 research outputs found

    T cell GM-CSF expression in juvenile arthritis is contingent upon Th17 plasticity.

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    Objectives Granulocyte monocyte colony stimulating factor (GM-CSF) is a potent inflammatory mediator responsible for recruitment and activation of innate immune cells. Recent murine data have identified Th17 cells as a key source of GM-CSF, and suggest that T cell derived GM-CSF is instrumental in the induction of autoimmune disease. We analysed the expression of T cell derived GM-CSF in the joints of patients with Juvenile idiopathic arthritis (JIA) and investigated the development links between Th17 and GM-CSF+ T helper cells. Methods 24 patients with JIA were analysed for expression of GM-CSF and the Th17 marker CD161 in synovial and peripheral blood compartments using flow cytometry and RT-PCR. A cytokine capture assay was used to purify Th17 cells and test the plasticity of cytokine production in response to IL-12 and IL-23. Results The frequency of GM-CSF producing T helper cells were significantly enriched in JIA synovial fluid mononuclear cells (SFMC) compared to PBMC (24.1% vs 2.9% of CD4+ T cells) and closely correlated with ESR levels (r(2) =0.91, p=<0.001). Synovial GM-CSF+ T cells were predominantly CD161 positive and co-expressed interferon gamma (IFNγ) but not IL-17. Culture of Th17 cells in the presence of IL-12 led to rapid upregulation of GM-CSF and IFNγ, recapitulating the phenotype of GM-CSF expressing cells within the joint. Conclusions Our results identify a novel outcome of Th17 plasticity in humans that may account for the enrichment of GM-CSF expressing T cells found within the JIA joint. The association of GM-CSF expression with systemic inflammation highlights the potential role for Th17 related cytokines in the pathology of JIA. © 2014 American College of Rheumatology

    Spatiotemporal distribution and sexual segregation in the Critically Endangered angelshark Squatina squatina in Spain’s largest marine reserve

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    Establishing how threatened wildlife are distributed spatially and temporally is essential for effective conservation and management planning. While many shark species are threatened globally, knowledge on sex-specific differences in behaviour and fine-scale habitat use remains limited, hindering the implementation of appropriate conservation actions. Here, acoustic telemetry was used to investigate sex-specific space use in the Critically Endangered angelshark Squatina squatina in the Canary Islands (Atlantic Ocean), a key stronghold for the species. We collected data on space use, residency and movement of adult males (n = 32) and females (n = 72) in Spain’s largest marine reserve (La Graciosa Marine Reserve) over 4 yr (2018-2022). Presence in offshore sites (>80 m depth) indicated long-term utilisation of deep-water habitat, not previously observed in this species. Males were more likely to be detected in deep water and displayed significantly greater levels of activity and roaming behaviour than females. Patterns of behaviour in shallow waters indicated both social and habitat sexual segregation. Diel variability was also recorded, with greater activity occurring nocturnally. This study demonstrates the importance of considering the spatiotemporal distribution of both sexes, horizontally and vertically, when designing effective conservation measures

    Comedian Hosts and the Demotic Turn

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    Podcasting is a showcase for what cultural studies scholar Graeme Turner coined “the demotic turn” or the increasing visibility of the ordinary person in the today’s media landscape. Collins argues that the emergence of a particular breed of podcasts – comedian-hosted interviews with celebrities – function in an “off-label” manner as a form of self-help or vicarious therapy. The emergence and rapid growth of this genre can attributed to three main factors: a confessional culture, the triumph of experience over expertise, and the democratization allowed by the form’s technology. She explores the link between emotional intimacy and comedy, and analyzes podcasts like Marc Maron’s WTF that are, in expression, a rejection of the pedestal version of stardom

    In the Laboratory and during Free-Flight: Old Honey Bees Reveal Learning and Extinction Deficits that Mirror Mammalian Functional Decline

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    Loss of brain function is one of the most negative and feared aspects of aging. Studies of invertebrates have taught us much about the physiology of aging and how this progression may be slowed. Yet, how aging affects complex brain functions, e.g., the ability to acquire new memory when previous experience is no longer valid, is an almost exclusive question of studies in humans and mammalian models. In these systems, age related cognitive disorders are assessed through composite paradigms that test different performance tasks in the same individual. Such studies could demonstrate that afflicted individuals show the loss of several and often-diverse memory faculties, and that performance usually varies more between aged individuals, as compared to conspecifics from younger groups. No comparable composite surveying approaches are established yet for invertebrate models in aging research. Here we test whether an insect can share patterns of decline similar to those that are commonly observed during mammalian brain aging. Using honey bees, we combine restrained learning with free-flight assays. We demonstrate that reduced olfactory learning performance correlates with a reduced ability to extinguish the spatial memory of an abandoned nest location (spatial memory extinction). Adding to this, we show that learning performance is more variable in old honey bees. Taken together, our findings point to generic features of brain aging and provide the prerequisites to model individual aspects of learning dysfunction with insect models

    Biosurfactants produced by Bacillus subtilis A1 and Pseudomonas stutzeri NA3 reduce longevity and fecundity of Anopheles stephensi and show high toxicity against young instars

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    Anopheles stephensi acts as vector of Plasmodium parasites, which are responsible for malaria in tropical and subtropical areas worldwide. Currently, malaria management is a big challenge due to the presence of insecticide-resistant strains as well as to the development of Plasmodium species highly resistant to major antimalarial drugs. Therefore, the present study focused on biosurfactant produced by two bacteria Bacillus subtilis A1 and Pseudomonas stutzeri NA3, evaluating them for insecticidal applications against malaria mosquitoes. The produced biosurfactants were characterized using FT-IR spectroscopy and gas chromatography-mass spectrometry (GC-MS), which confirmed that biosurfactants had a lipopeptidic nature. Both biosurfactants were tested against larvae and pupae of A. stephensi. LC50 values were 3.58 (larva I), 4.92 (II), 5.73 (III), 7.10 (IV), and 7.99 (pupae) and 2.61 (I), 3.68 (II), 4.48 (III), 5.55 (IV), and 6.99 (pupa) for biosurfactants produced by B. subtilis A1 and P. stutzeri NA3, respectively. Treatments with bacterial surfactants led to various physiological changes including longer pupal duration, shorter adult oviposition period, and reduced longevity and fecundity. To the best of our knowledge, there are really limited reports on the mosquitocidal and physiological effects due to biosurfactant produced by bacterial strains. Overall, the toxic activity of these biosurfactant on all young instars of A. stephensi, as well as their major impact on adult longevity and fecundity, allows their further consideration for the development of insecticides in the fight against malaria mosquitoes

    Associations of Variants in CHRNA5/A3/B4 Gene Cluster with Smoking Behaviors in a Korean Population

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    Multiple genome-wide and targeted association studies reveal a significant association of variants in the CHRNA5-CHRNA3-CHRNB4 (CHRNA5/A3/B4) gene cluster on chromosome 15 with nicotine dependence. The subjects examined in most of these studies had a European origin. However, considering the distinct linkage disequilibrium patterns in European and other ethnic populations, it would be of tremendous interest to determine whether such associations could be replicated in populations of other ethnicities, such as Asians. In this study, we performed comprehensive association and interaction analyses for 32 single-nucleotide polymorphisms (SNPs) in CHRNA5/A3/B4 with smoking initiation (SI), smoking quantity (SQ), and smoking cessation (SC) in a Korean sample (N = 8,842). We found nominally significant associations of 7 SNPs with at least one smoking-related phenotype in the total sample (SI: P = 0.015∼0.023; SQ: P = 0.008∼0.028; SC: P = 0.018∼0.047) and the male sample (SI: P = 0.001∼0.023; SQ: P = 0.001∼0.046; SC: P = 0.01). A spectrum of haplotypes formed by three consecutive SNPs located between rs16969948 in CHRNA5 and rs6495316 in the intergenic region downstream from the 5′ end of CHRNB4 was associated with these three smoking-related phenotypes in both the total and the male sample. Notably, associations of these variants and haplotypes with SC appear to be much weaker than those with SI and SQ. In addition, we performed an interaction analysis of SNPs within the cluster using the generalized multifactor dimensionality reduction method and found a significant interaction of SNPs rs7163730 in LOC123688, rs6495308 in CHRNA3, and rs7166158, rs8043123, and rs11072793 in the intergenic region downstream from the 5′ end of CHRNB4 to be influencing SI in the male sample. Considering that fewer than 5% of the female participants were smokers, we did not perform any analysis on female subjects specifically. Together, our detected associations of variants in the CHRNA5/A3/B4 cluster with SI, SQ, and SC in the Korean smoker samples provide strong evidence for the contribution of this cluster to the etiology of SI, ND, and SC in this Asian population
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