Cytokine expanded myeloid precursors function as regulatory antigen presenting cells and induce tolerance through IL-10 producing regulatory T cells

The initiation of graft vs. host disease (GVHD) after stem cell transplantation is dependent on direct antigen presentation by host antigen presenting cells (APC) while the effect of indirect antigen presentation by donor APC is unknown. We have studied the role of indirect antigen presentation in allogenic responses by adding populations of cytokine-expanded donor APC to haematopoietic grafts that would otherwise induce lethal GVHD. Progenipoietin-1 (a synthetic G-CSF/Flt-3 L molecule) and G-CSF expanded myeloid DC, plasmacytoid DC and a novel granulocyte-monocyte precursor population (GM) that differentiate into class IIpos, CD80/CD86pos, CD40neg APC during GVHD. Whereas addition of plasmacytoid and myeloid donor DC augmented GVHD, GM cells induced transplant tolerance via MHC class II restricted generation of IL-10-secreting regulatory T cells. Thus a population of cytokine expanded granulocyte-monocyte precursors function as regulatory antigen presenting cells, suggesting that G-CSF derivatives may have application in disorders characterised by a loss of self-tolerance.

In the eye of the storm: exploring the introduction of environmental issues in the production function in Brazilian companies

This article aims to analyse the introduction of environmental issues in the context of the production function, which has been referred to as the organisational area to lead corporate environmental management. With that purpose, the theoretical references for corporate environmental management and the necessary alterations in production function have been organised to include environmental aspects, especially in terms of product and process development, quality management, and logistics. Considering that this research field still lacks empirical evidence for Brazilian companies, four case studies were conducted using companies located in the country. The environmental management maturity level of those companies tends to follow the rate with which the environmental issue is introduced in production sub-areas, especially in the product development process. However, in most cases we found that the companies had difficulties in structuring the insertion of the environmental dimension in logistics. The final notes point out the distance observed between what is recommended by international literature and the reality of Brazilian companies in the challenge of making the production function environmentally friendly.

Alterations in cardiac dihydropyridine receptors and calcium channel function in mdx mice

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular condition affecting approximately one in 3500 live male births resulting from the lack of the myocyte protein dystrophin. The absence of dystrophin in cardiac myocytes is associated with calcium overload which in turn activates calcium-dependent proteolytic enzymes contributing to congestive heart failure, muscle necrosis and fibrosis. To date, the basis for the calcium overload has not been determined. Since L-type calcium channels are a major mediator of calcium influx we determined their potential contribution to the calcium overload. Male muscular dystrophy (mdx) mice and control C57BL10ScSn (C57) mice aged 12– 16 weeks were used in all experiments. In tissue bath studies, isolated contracting left atria from mdx revealed a reduced potency to the dihydropyridine (DHP) agonist BayK8644 and antagonist nifedipine (P < 0.05). Similarly, radioligand binding studies using the DHP antagonist [3H]-PN 200-110 showed a reduced potency (P < 0.05) in isolated membranes, associated with an increased receptor density (P < 0.05). The increased receptor density was supported by RT-PCR experiments revealing increased RNAfor the DHP receptor. Patch clamp studies revealed the presence of a diltiazem sensitive calcium current that showed delayed inactivation in isolated mdx myocytes (P < 0.01). In conclusion, the increased number of DHP binding sites and the delay in L-type current inactivation may both contribute to increased calcium influx and hence calcium overload in the dystrophin deficient mdx cardiac myocytes.

Developmental characterization, function and regulation of a Laccase2 encoding gene in the honey bee, Apis mellifera (Hymenoptera, Apinae)

In insects, exoskeleton (cuticle) formation at each molt cycle includes complex biochemical pathways wherein the laccase enzymes (EC 1.10.3.2) may have a key role. We identified an Amlac2 gene that encodes a laccase2 in the honey bee, Apis mellifera, and investigated its function in exoskeleton differentiation. The Amlac2 gene consists of nine exons resulting in an ORE of 2193 nucleotides. The deduced translation product is a 731 amino acid protein of 81.5 kDa and a pl of 6.05. Amlac2 is highly expressed in the integument of pharate adults, and the expression precedes the onset of cuticle pigmentation and the intensification of sclerotization. In accordance with the temporal sequence of exoskeleton differentiation from anterior to posterior direction, the levels of Amlac2 transcript increase earlier in the thoracic than in the abdominal integument. The gene expression lasts even after the bees emerge from brood cells and begin activities in the nest, but declines after the transition to foraging stage, suggesting that maturation of the exoskeleton is completed at this stage. Post-transcriptional knockdown of Amlac2 gene expression resulted in structural abnormalities in the exoskeleton and drastically affected adult eclosion. By setting a ligature between the thorax and abdomen of early pupae we could delay the increase in hemolymph ecdysteroid levels in the abdomen. This severely impaired the increase in Amlac2 transcript levels and also the differentiation of the abdominal exoskeleton. Taken together, these results indicate that Amlac2 expression is controlled by ecdysteroids and has a critical role in the differentiation of the adult exoskeleton of honey bees. (C) 2010 Elsevier Ltd. All rights reserved.

Association of tumor necrosis factor-alpha polymorphisms and ozone-induced change in lung function

Ozone is a major air pollutant with adverse health effects which exhibit marked inter-individual variability. In mice, regions of genetic linkage with ozone-induced lung injury include the tumor necrosis factor-alpha (TNF), lymphotoxin-alpha (LTA), Toll-like receptor 4 (TLR4), superoxide dismutase (SOD2), and glutathione peroxidase (GPX1) genes. We genotyped polymorphisms in these genes in 51 individuals who had undergone ozone challenge. Mean change in FEV1 with ozone challenge, as a percentage of baseline, was -3% in TNF -308G/A or A/A individuals, compared with -9% in G/G individuals (p = 0.024). When considering TNF haplotypes, the smallest change in FEV1 with ozone exposure was associated with the TNF haplotype comprising LTA +252G/TNF -1031T/TNF -308A/TNF -238G. This association remained statistically significant after correction for age, sex, disease, and ozone concentration (p = 0.047). SOD2 or GPX1 genotypes were not associated with lung function, and the TLR4 polymorphism was too infrequent to analyze. The results of this study support TNF as a genetic factor for susceptibility to ozone-induced changes in lung function in humans, and has potential implications for stratifying health risks of air pollution.

Time flies with music whatever its emotional valence

The present study used a temporal bisection task to investigate whether music affects time estimation differently from a matched auditory neutral stimulus, and whether the emotional valence of the musical stimuli (i.e., sad vs. happy music) modulates this effect. The results showed that, compared to sine wave control music, music presented in a major (happy) or a minor (sad) key shifted the bisection function toward the right, thus increasing the bisection point value (point of subjective equality). This indicates that the duration of a melody is judged shorter than that of a non-melodic control stimulus, thus confirming that ""time flies"" when we listen to music. Nevertheless, sensitivity to time was similar for all the auditory stimuli. Furthermore, the temporal bisection functions did not differ as a function of musical mode. (C) 2010 Elsevier B.V. All rights reserved.

Almost automorphic mild solutions to some partial neutral functional-differential equations and applications

The paper considers the existence and uniqueness of almost automorphic mild solutions to some classes of first-order partial neutral functional-differential equations. Sufficient conditions for the existence and uniqueness of almost automorphic mild solutions to the above-mentioned equations are obtained. As an application, a first-order boundary value problem arising in control systems is considered. (C) 2007 Elsevier Ltd. All fights reserved.

Two novel reports of semidry stigmatic surface in Asteraceae

Research documents related to the morphology and function of style branches and stigmatic surface of Asteraceae are still rather few, and the literature reports are thus controversial. We report in the present study that the stigmatic surfaces of two non-related species of Asteraceae (Lessingianthus grandiflorus and Lucilia lycopodioides) have features of semidry stigmas. Sporodermis of both species was also analyzed so that we could understand how the stigmatic surface works during pollen deposition and rehydration. Stylar branches and pollen grains (sporodermis) were studied using scanning and transmission electron microscopy (SEM and TEM) and histochemistry techniques. The inner and marginal bands of stylar branches in these species display intermediary features between the dry and wet types of stigma: the cuticle characterizes the dry stigma and cells with secretory activity characterize the wet stigma; these showed differences from what has been described to the Asteraceae family, where stigmatic surface of species from several tribes is considered dry. Pollen grains are medium-size to large with exine ornamentation (echinate and echinolophate) and abundant secretion which latter characterizes pollenkitt. We can assume that two processes might help pollen grain hydration on stigmatic surface in Lessingianthus grandiflorus and Lucilia lycopodioides: (1) the presence of pollenkitt, as observed in the secretory content inside exine cavities and around pollen grains; and (2) the secretory activity of stigmatic surface cells, whose secretion accumulates among intercellular and subcuticular spaces and leads to cuticle disruption during the floral receptive phase. Our results suggest that ultrastructural and histochemical studies should be considered when describing stigmatic surface and that the ""semidry"" feature within Asteraceae should be investigated still more in detail, so that the taxonomic or adaptation value of this trait in the family can be verified. (C) 2010 Elsevier GmbH. All rights reserved.

RNAi-mediated silencing of vitellogenin gene function turns honeybee (Apis mellifera) workers into extremely precocious foragers

The switch from within-hive activities to foraging behavior is a major transition in the life cycle of a honeybee (Apis mellifera) worker. A prominent regulatory role in this switch has long been attributed to juvenile hormone (JH), but recent evidence also points to the yolk precursor protein vitellogenin as a major player in behavioral development. In the present study, we injected vitellogenin double-stranded RNA (dsVg) into newly emerged worker bees of Africanized genetic origin and introduced them together with controls into observation hives to record flight behavior. RNA interference-mediated silencing of vitellogenin gene function shifted the onset of long-duration flights (> 10 min) to earlier in life (by 3-4 days) when compared with sham and untreated control bees. In fact, dsVg bees were observed conducting such flights extremely precociously, when only 3 days old. Short-duration flights (< 10 min), which bees usually perform for orientation and cleaning, were not affected. Additionally, we found that the JH titer in dsVg bees collected after 7 days was not significantly different from the controls. The finding that depletion of the vitellogenin titer can drive young bees to become extremely precocious foragers could imply that vitellogenin is the primary switch signal. At this young age, downregulation of vitellogenin gene activity apparently had little effect on the JH titer. As this unexpected finding stands in contrast with previous results on the vitellogenin/JH interaction at a later age, when bees normally become foragers, we propose a three-step sequence in the constellation of physiological parameters underlying behavioral development.

Aesthetic value: between universality and exclusivity

This study brings a reflection on aesthetic values, trying to consider connections between universality, social exclusion and contemporary violence.

Il-1 beta breaks tolerance through inhibition of regulatory T cell function

IL-1 is a key proinflammatory driver of several autoimmune diseases including juvenile inflammatory arthritis, diseases with mutations in the NALP/cryopyrin complex and Crohn’s disease, and is genetically or clinically associated with many others. IL-1 is a pleiotropic proinflammatory cytokine; however the mechanisms by which increased IL-1 signaling promotes autoreactive T cell activity are not clear. Here we show that autoimmune-prone NOD and IL-1 receptor antagonist-deficient C57BL/6 mice both produce high levels of IL-1, which drives autoreactive effector cell expansion. IL-1beta drives proliferation and cytokine production by CD4+CD25+FoxP3– effector/memory T cells, attenuates CD4+CD25+FoxP3+ regulatory T cell function, and allows escape of CD4+CD25– autoreactive effectors from suppression. Thus, inflammation or constitutive overexpression of IL-1beta in a genetically predisposed host can promote autoreactive effector T cell expansion and function, which attenuates the ability of regulatory T cells to maintain tolerance to self.

IL-1 breaks tolerance through inhibition of regulatory T cell function

Diverse infectious and inflammatory environmental triggers, through unknown mechanisms, initiate autoimmune disease in genetically predisposed individuals. Here we show that IL-1b, a key cytokine mediator of the inflammatory response, suppresses CD25+CD4+ regulatory T cell function. Surprisingly, suppression by IL-1b occurs only where antigen is presented simultaneously to CD25+CD4+ T cells and to CD25CD4+ antigen-specific effector T cells. Further, NOD mice show an intrinsic over-production of IL-1 that contributes to reduced CD25+CD4+ regulatory T cell function. Thus, inflammation or constitutive over-expression of IL-1b in a genetically predisposed host can initiate a positive feedback loop licensing autoantigen-specific effector cells to inhibit the regulatory T cells maintaining tolerance to self.