CD28 between tolerance and autoimmunity: The side effects of animal models [version 1; referees: 2 approved]

Regulation of immune responses is critical for ensuring pathogen clearance and for preventing reaction against self-antigens. Failure or breakdown of immunological tolerance results in autoimmunity. CD28 is an important co-stimulatory receptor expressed on T cells that, upon specific ligand binding, delivers signals essential for full T-cell activation and for the development and homeostasis of suppressive regulatory T cells. Many in vivo mouse models have been used for understanding the role of CD28 in the maintenance of immune homeostasis, thus leading to the development of CD28 signaling modulators that have been approved for the treatment of some autoimmune diseases. Despite all of this progress, a deeper understanding of the differences between the mouse and human receptor is required to allow a safe translation of pre-clinical studies in efficient therapies. In this review, we discuss the role of CD28 in tolerance and autoimmunity and the clinical efficacy of drugs that block or enhance CD28 signaling, by highlighting the success and failure of pre-clinical studies, when translated to humans

Depression und Arbeitswelt

In der WHO-Charta von Ottawa aus dem Jahre 1986 steht zu lesen: >>Die Art und Weise, wie eine Gesellschaft die Arbeit und die Arbeitsbedingungen organisiert, sollte eine Quelle der Gesundheit und nicht der Krankheit sein.<< Diese Forderung ist in der spätmodernen Arbeitsgesellschaft nach wie vor nicht eingelöst. Und Erwerbsarbeit ist kein Lebensbereich wie jeder andere. Über das Einkommen sichert sie das materielle Auskommen der Gesellschaftsmitglieder und ermöglicht ihnen, sich sozial zu integrieren und zu partizipieren. Deshalb sind Arbeitsplatzunsicherheit (Sverke, Hellgren u. N ä swall, 2006) und Arbeitslosigkeit (Paulu. Moser, 2009) kritische Lebensereignisse, die kränken undkrank machen. Was die Arbeitsplatzunsicherheit betrifft, so ist es nicht allein die Sorge, den Arbeitsplatz zu verlieren, die belastet. Gleiches gilt für die verbreitete Erfahrung, dass sich die Arbeitsbedingungen der Arbeitnehmer und Arbeitnehmerinnen auf Kosten ihrer psychischen Gesundheit gravierend verschlechtern. Deshalb muss es alarmieren, wenn Besch ä ftigtenbefragungen gegenw ä rtig darauf hinweisen, dass etwa jeder Zweite seine gesundheitlichen Probleme in einen ursächlichen Zusammenhang mit den Arbeitsbedingungen an seinem Arbeitsplatz bringt (Zok, 2010)

LCA applied to perennial cropping systems: a review focused on the farm stage

International audienc

Exploiting bacterial DNA gyrase as a drug target: current state and perspectives

DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials. The fluoroquinolones are examples of very successful gyrase-targeted drugs, but the rise in bacterial resistance to these agents means that we not only need to seek new compounds, but also new modes of inhibition of this enzyme. We review known gyrase-specific drugs and toxins and assess the prospects for developing new antibacterials targeted to this enzyme

Extending our vision of developmental growth and engaging in empirical scrutiny: proposals for the future of faith development theory

Streib H. Extending our vision of developmental growth and engaging in empirical scrutiny: proposals for the future of faith development theory. Religious Education. 2004;99(4):427-434.This article evaluates the portrait of faith development theory and research in James Fowler’s article, “Faith Development at 30.” Questions are raised: Does Fowler’s emphasis on the practical-theological and pastoral focus of faith development contradict its aspiration and disposition for empirical scrutiny? Does Fowler’s principal concern with the reactions from Christian theologians and religious educators indicate disregard of and from psychology? Both questions can be denied with reference to the large amount of research projects which use and apply the faith development perspective. The article suggests further engagement in theory discussion, methodological clarification and empirical research; it invites networking among researchers and indicates future research strategies. But also the practical-theological relevance of faith development theory, especially for religious education, are demonstrated with reference to recent research. The article concludes, in agreement with Fowler, with a proposal to notice the importance of the Conjunctive Faith style for social bodies, and to include this in religious education. With the latter, the article moves beyond a wide-spread faith development application and argues against the false assumption as if children and adolescents could not understand and consider Conjunctive Faith

Effect of Head-Down Tilt Bedrest (10 Days) on Lymphocyte Reactivity

Immunological responses of six healthy males to 10 days of headdown tilt bedrest (HDT) were assessed. Lymphocyte responsiveness was severely reduced immediately before, during, and immediately after the HDT, even though the lymphocyte numbers did not change. By contrast, delayed-type hypersensitivity was not affected. No dramatic changes were found in WBC counts and lymphocyte subpopulations, with the only exception of natural killer (NK) cells which transiently decreased immediatley after HDT. Plasma cortisol levels were elevated above normal immediately before and during the HDT. The data suggest that the mitogenic response of lymphocytes was affected by psychological and fluid shift stress. These results are compared with data obtained during and after spaceflight. We conclude that the stress of HDT induces changes in immunological responsiveness that are strikingly similar to those arising from the stress of spaceflight