Modulatory Role of the Ovarian Function in Neuroimmunoendocrine Axis Activity.

The aim of this study was to evaluate the effect of ovariectomy on the acute-phase response of inflammatory stress. Ex vivo adrenocortical, peripheral mononuclear cell (PMNC) and adipocyte activities were studied in intact and ovariectomized mice. Endotoxemia was mimicked by intraperitoneal administration of bacterial lipopolysaccharide (LPS; 25 mg per mouse) to sham-operated and 21-day ovariectomized mice. Circulating corticosterone, tumor necrosis factor-alpha (TNFalpha) and leptin concentrations were monitored before and 30-120 min after the administration of LPS. Additionally, in vitro experiments were performed with isolated corticoadrenal cells, PMNCs and omental adipocytes from sham-operated and ovariectomized mice incubated with specific secretagogues. The results indicate that while ovariectomy enhanced TNFalpha secretion after in vivo administration of LPS, it reduced corticoadrenal response and abrogated LPS-elicited leptin secretion into the circulation. While the corticoadrenal sensitivity to ACTH stimulation was reduced by ovariectomy, the LPS-induced PMNC response was not affected. Exogenous leptin enhanced baseline PMNC function regardless of surgery. Finally, ovariectomy drastically reduced in vitro adipocyte functionality. Our data support the notion that ovariectomy modified neuroendocrine-immune-adipocyte axis function and strongly suggest that ovarian activity could play a pivotal role in the development of an adequate immune defense mechanism after injury.

The debate over the effector function of eosinophils in helminth infection: new evidence from studies on the regulation of vaccine immunity by IL-12

The production of Th1-type cytokines is associated with strong cell-mediated immunity while Th2-type cytokines are typically involved in the generation of humoral immune responses. In mice vaccinated a single time (1X) with attenuated cercariae of Schistosoma mansoni, the immunity induced is highly dependent on CD4+ T cells and IFN-gamma. In contrast, mice vaccinated multiple times (3X) have decreased IFN-gamma expression, develop a more dominant Th2-type cytokine response as well as protective antibodies which can passively transfer immunity to naive recipients. Previously, we demonstrated the ability of IL-12, a potent IFN-gamma-inducing cytokine to enhance (1X) schistosome cell-mediated immunity when administered during the period of immunization. More recently, we asked what effects IL-12 would have on the development humoral-based immunity. While multiply-immunized/saline-treated mice demonstrated a 70-80% reduction in parasite burden, 3X/IL-12-vaccinated animals displayed an even more striking >90% reduction in challenge infection, with many mice in the later group demonstrating complete protection. Analysis of pulmonary cytokine mRNA responses demonstrated that control challenged mice elicited a dominant Th2-type response, 3X/saline-vaccinated produced a mixed Th1/Th2-type cytokine response, while 3X/IL-12-immunized animals displayed a dominant Th1-type response. The IL-12-treated group also showed a marked reduction in total serum IgE and tissue eosinophilia while SWAP-specific IgG2a and IgG2b Abs were elevated. Interestingly, animals vaccinated with IL-12 also showed a highly significant increase in total Ig titers specific for IrV-5, a known protective antigen. More importantly, 3X/IL-12 serum alone, when transferred to naive mice reduced worm burdens by over 60% while 3X/saline serum transferred significantly less protection. Nevertheless, animals vaccinated in the presence of IL-12 also develop macrophages with enhanced nitric oxide dependent killing activity against the parasites. Together, these observations suggest that IL-12, initially described as an adjuvant for cell-mediated immunity, may also be used as an adjuvant for promoting both humoral and cell-mediated protective responses.

In Bacillus subtilis W23, the duet sigmaXsigmaM, two sigma factors of the extracytoplasmic function subfamily, are required for septum and wall synthesis under batch culture conditions.

The synthesis of poly(RboP), the main Bacillus subtilis W23 teichoic acid, is encoded by tarDF-tarABIJKL operons, the latter being controlled by two promoters designated PtarA-int and PtarA-ext. Analysis by lacZ fusions reveals that PtarA-int activity exhibits sharp increases at the beginning and end of the transition between exponential and stationary growth phase. As confirmed by mRNA quantification, these increases are mediated by ECF sigma factors sigmaX and sigmaM respectively. In liquid media, strain W23 sigX sigM double mutants experience serious difficulties in the transition and stationary growth phases. Inactivation of sigmaX- and sigmaM-controlled regulons, which precludes transcription from PtarA-int, leads to (i) delays in chromosome segregation and septation and (ii) a transient loss of up to 30% of the culture OD or lysis. However, specific inactivation of PtarA-int, leading mainly to a shortage of poly(RboP), does not affect growth while, nevertheless, interfering with normal septation, as revealed by electron microscopy. The different sigM transcription in strains W23 and 168 is discussed. In W23, expression of tarA and sigM, which is shown to control divIC, is inversely correlated with growth rate, suggesting that the sigM regulon is involved in the control of cell division.

Reconstituted human polyclonal plasma-derived secretory-like IgM and IgA maintain the barrier function of epithelial cells infected with an enteropathogen.

Intravenous administration of polyclonal and monoclonal antibodies has proven to be a clinically valid approach in the treatment, or at least relief, of many acute and chronic pathologies, such as infection, immunodeficiency, and a broad range of autoimmune conditions. Plasma-derived IgG or recombinant IgG are most frequently used for intravenous or subcutaneous administration, whereas a few IgM-based products are available as well. We have established recently that secretory-like IgA and IgM can be produced upon association of plasma-derived polymeric IgA and IgM with a recombinant secretory component. As a next step toward potential future mucosal administration, we sought to unravel the mechanisms by which these secretory Igs protect epithelial cells located at the interface between the environment and the inside of the body. By using polarized epithelial Caco-2 cell monolayers and Shigella flexneri as a model enteropathogen, we found that polyspecific plasma-derived SIgA and SIgM fulfill many protective functions, including dose-dependent recognition of the antigen via formation of aggregated immune complexes, reduction of bacterial infectivity, maintenance of epithelial cell integrity, and inhibition of proinflammatory cytokine/chemokine production by epithelial cells. In this in vitro model devoid of other cellular or molecular interfering partners, IgM and secretory IgM showed stronger bacterial neutralization than secretory IgA. Together, these data suggest that mucosally delivered antibody preparations may be most effective when combining both secretory-like IgA and IgM, which, together, play a crucial role in preserving several levels of epithelial cell integrity.

Analysis of teichoic acid biosynthesis regulation reveals that the extracytoplasmic function sigma factor sigmaM is induced by phosphate depletion in Bacillus subtilis W23.

The expression of the Bacillus subtilis W23 tar genes specifying the biosynthesis of the major wall teichoic acid, the poly(ribitol phosphate), was studied under phosphate limitation using lacZ reporter fusions. Three different regulation patterns can be deduced from these beta-galactosidase activity data: (i) tarD and tarL gene expression is downregulated under phosphate starvation; (ii) tarA and, to a minor extent, tarB expression after an initial decrease unexpectedly increases; and (iii) tarO is not influenced by phosphate concentration. To dissect the tarA regulatory pattern, its two promoters were analysed under phosphate limitation: The P(tarA)-ext promoter is repressed under phosphate starvation by the PhoPR two-component system, whereas, under the same conditions, the P(tarA)-int promoter is upregulated by the action of an extracytoplasmic function (ECF) sigma factor, sigma(M). In contrast to strain 168, sigma(M) is activated in strain W23 in phosphate-depleted conditions, a phenomenon indirectly dependent on PhoPR, the two-component regulatory system responsible for the adaptation to phosphate starvation. These results provide further evidence for the role of sigma(M) in cell-wall stress response, and suggest that impairment of cell-wall structure is the signal activating this ECF sigma factor.

Inflammasome activators induce interleukin-1α secretion via distinct pathways with differential requirement for the protease function of caspase-1.

Through their capacity to sense danger signals and to generate active interleukin-1β (IL-1β), inflammasomes occupy a central role in the inflammatory response. In contrast to IL-1β, little is known about how IL-1α is regulated. We found that all inflammasome activators also induced the secretion of IL-1α, leading to the cosecretion of both IL-1 cytokines. Depending on the type of inflammasome activator, release of IL-1α was inflammasome dependent or independent. Calcium influx induced by the opening of cation channels was sufficient for the inflammasome-independent IL-1α secretion. In both cases, IL-1α was released primarily in a processed form, resulting from intracellular cleavage by calpain-like proteases. Inflammasome-caspase-1-dependent release of IL-1α and IL-1β was independent of caspase-1 catalytic activity, defining a mode of action for caspase-1. Because inflammasomes contribute to the pathology of numerous chronic inflammatory diseases such as gout and diabetes, IL-1α antagonists may be beneficial in the treatment of these disorders.

Adaptação cultural e validação do instrumento The Bowel Function in the Community para o Brasil

Estudos sobre hábito intestinal, considerando cultura, hábitos alimentares e de vida entre outros, não existem no Brasil. O objetivo deste artigo é apresentar o The Bowel Function in the Community, ferramenta específica para avaliação do hábito intestinal das populações, adaptado e validado para o Brasil. O processo de adaptação cultural incluiu tradução, retrotradução e avaliação por comitê de especialistas, obtendo-se uma versão traduzida do instrumento, posteriormente submetida a análises que atestaram a validade de conteúdo do mesmo. A confiabilidade inter-observadores e estabilidade (teste-reteste) foram confirmadas por níveis de concordância de boa a excelente e de moderada a excelente para a maioria das questões e agrupamentos do instrumento. Concluiu-se que a versão adaptada do instrumento pode ser aplicada em nosso meio para dar continuidade ao processo de validação, bem como para ampliar o conhecimento do hábito intestinal na população brasileira.

The externalisation of the asylum function in the European Union

This paper aims to identify and assess the main items in the strategy followed by the EU and its member states on the externalisation of their asylum function. First, it analyses the European harmonisation of the return to safe third countries and to countries of first asylum, which is carried out by means of readmission agreements. Second, it refers to the strategies defined by the Hague and the Stockholm programs concerning the External Aspects of the European Union Asylum Policy, on the detention centres for illegal immigrants abroad, and on the proposals for delocalisation of asylum applications processing centres beyond the EU borders. Finally, this paper considers whether the strategy of externalisation of the function of asylum sometimes lacks legitimacy, and to what extent there is a fair balance between the interests of the states and the protection of the human rights of refugees and asylum seekers.

The adaptative function of melanin-based colour variants

Résumé : Les mécanismes de contrôle des couleurs mélaniques chez les vertébrés sont encore discutés parmi les biologistes de l'évolution. Une hypothèse récente affirme que les effets pléiotropies du système des mélanocortines expliquent l'association fréquente entre la coloration eumélanique noire (due à la déposition d'eumélanine) et de nombreux traits physiologiques et comportementaux. De nombreuses études suggèrent, en effet, que des niveaux plus élevés des mélanocortines induisent l'assombrissement des téguments eumélaniques et affectent d'autres traits phénotypiques simultanément. Cependant, il n'est pas encore établi si ce mécanisme de pléiotropie peut s'appliquer aux colorations dues à la déposition de phaeomélanine, une autre forme commune de mélanine. Les antagonistes des mélanocortines déclenchent le phaeomélanogenèse et bloquent l'effet des mélanocortines ou ont un effet pharmacologique opposé. Nous nous proposons donc d'évaluer l'hypothèse que les effets pléiotropes des antagonistes des mélanocortines génèrent des covariations entre la coloration phaeomélanique et des aspects de la qualité individuelle. Comme prédit par cette hypothèse, nous constatons chez la chouette effraie (Tyto alba) que les traits phénotypiques (résistance au stress oxydatif et aux parasites) corrèlent positivement au degré d'expression d'une couleur eumélanique mais négativement au degré d'expression d'une coloration phaeomélanique. Puis, nous montrons chez la chouette hulotte (Strix aluco) que les associations génétiques entre la coloration phaeomélanique et la physiologie (immunité et la régulation de l'homéostasie) confèrent des avantages aux individus de différentes couleurs dans différents environnements caractérisés par l'abondance de nourriture et le niveau d'exposition aux parasites. Ainsi, nos études soutiennent l'hypothèse que les effets pléiotropes des antagonistes des mélanocortines génèrent des covariations entre les traits mélaniques et divers aspects de la qualité individuelle. Finalement, nous montrons chez le faucon crécerelle (Falco Tinnunculus) que l'expression des ornements mélaniques est sensible à la qualité de l'environnement dans lequel les individus grandissent. Ceci suggère que les gènes codant pour les mélanocortines et leurs antagonistes pourraient induire une expression des traits mélaniques dépendante de la condition de l'individu, un pattern d'expression rarement observé pour des traits généralement sous fort contrôle génétique. Summary : The information content and control mechanisms of melanin-based colour signals in vertebrates are still debated among evolutionary biologists. A recent hypothesis contends that pleiotropic effects of the melanocortin system accounts for the frequent association between black eumelanic coloration and physiological and behavioural traits. Accordingly, empirical evidence suggests that higher levels of melanocortins concurrently promote darker eumelanic integuments and affect other phenotypic traits. However, whether this mechanism may apply to signals relying on phaeomelanin, another common form of melanin pigments, remains to be established. Melanocortin antagonists trigger phaeomelanogenesis and block the effect of melanocortins or result in the opposite pharmacological effect. Therefore, we tested the hypothesis that pleiotropic effects of melanocortin antagonists and inverse agonists account for covariations between phaeomelanin-based coloration and aspects of individual quality. As predicted, we found that phenotypic traits (resistance to oxidative stress and parasites) correlated positively with a eumelanic trait and negatively with a phaeomelanic trait in the barn owl (Tyto alba). Then, we showed in the tawny owl (Strix aluco) that genetic associations between phaeomelanin-based coloration and physiology (immunity and regulation of energy homeostasis) confer benefits to differently coloured individuals under different levels of food abundance and parasite exposure. Altogether, our studies support the hypothesis that pleiotropic effects of melanocortins antagonists can indeed account for covariations between phaeomelanin-based traits and aspects of individual quality. Eventually, we show in the Eurasian kestrel (Falco Tinnunculus) that expression of melanin-based ornaments is sensitive to the environment in which individuals grow. This suggests that genes coding for melanocortins and their antagonists can mediate the condition-dependent component of melanin-based traits.

The Strategic Impact of Clinical Practice Guidelines in Nursing on the Managerial Function of Supervision

Clinical practice guidelines in nursing (CPG-N) are tools that allow the necessary knowledge that frequently remains specialist-internalised to be made explicit. These tools are a complement to risk adjustment systems (RAS), reinforcing their effectiveness and permitting a rationalisation of healthcare costs. This theoretical study defends the importance of building and using CPG-Ns as instruments to support the figure of the nursing supervisor in order to optimise the implementation of R&D and hospital quality strategies, enabling clinical excellence in nursing processes and cost-efficient reallocation of economic resources through their linear integration with SARs.

The hypocretins and the reward function: what have we learned so far?

A general consensus acknowledges that drug consumption (including alcohol, tobacco, and illicit drugs) constitutes the leading cause of preventable death worldwide. But the global burden of drug abuse extends the mortality statistics. Indeed, the comorbid long-term debilitating effects of the disease also significantly deteriorate the quality of life of individuals suffering from addiction disorders. Despite the large body of evidence delineating the cellular and molecular adaptations induced by chronic drug consumption, the brain mechanisms responsible for drug craving and relapse remain insufficiently understood, and even the most recent developments in the field have not brought significant improvement in the management of drug dependence. Though, recent preclinical evidence suggests that disrupting the hypocretin (orexin) system may serve as an anticraving medication therapy. Here, we discuss how the hypocretins, which orchestrate normal wakefulness, metabolic health and the execution of goal-oriented behaviors, may be compromised and contribute to elicit compulsive drug seeking. We propose an overview on the most recent studies demonstrating an important role for the hypocretin neuropeptide system in the regulation of drug reward and the prevention of drug relapse, and we question the relevance of disrupting the hypocretin system to alleviate symptoms of drug addiction.

Between Equity and Differentiation: An Analytical Schema of the Social Function of Education

The educational sphere has an internal function relatively agreed by social scientists. Nonetheless, the contribution that educational systems provide to the society (i.e., their social function) does not have the same degree of consensus. Taking into consideration such theoretical precedent, the current article raises an analytical schema to grasp the social function of education considering a sociological perspective. Starting from the assumption that there is an intrinsic relationship between the internal and social functions of social systems, we suggest there are particular stratification determinants modifying the internal pedagogical function of education, which impact on its social function by creating simultaneous conditions of equity and differentiation. Throughout the paper this social function is considered a paradoxical mechanism. We highlight how this paradoxical dynamic is deployed in different structural levels of the educational sphere. Additionally, we discuss eventual consequences of this paradoxical social function for the inclusion possibilities that educational systems offer to individuals.