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Maladaptive, Th2-polarized inflammatory responses are integral to the pathogenesis of allergic asthma. As regulators of T cell activation, dendritic cells (DCs) are important mediators of allergic asthma, yet the precise signals which render endogenous DCs \"pro-asthmatic\", and the extent to which these signals are regulated by the pulmonary environment and host genetics, remains unclear. Comparative phenotypic and functional analysis of pulmonary DC populations in mice susceptible (A/J), or resistant (C3H) to experimental asthma, revealed that susceptibility to airway hyperresponsiveness is associated with preferential myeloid DC (mDC) allergen uptake, and production of Th17-skewing cytokines (IL-6, IL-23), whereas resistance is associated with increased allergen uptake by plasmacytoid DCs. Surprisingly, adoptive transfer of syngeneic HDM-pulsed bone marrow derived mDCs (BMDCs) to the lungs of C3H mice markedly enhanced lung IL-17A production, and rendered them susceptible to allergen-driven airway hyperresponsiveness. Characterization of these BMDCs revealed levels of antigen uptake, and Th17 promoting cytokine production similar to that observed in pulmonary mDCs from susceptible A/J mice. Collectively these data demonstrate that the lung environment present in asthma-resistant mice promotes robust pDC allergen uptake, activation, and limits Th17-skewing cytokine production responsible for driving pathologic T cell responses central to the development of allergen-induced airway hyperresponsiveness.

Among human food-borne pathogens, gastroenteritis-causing Salmonella strains have the most real-world impact. Like all pathogens, their success relies on efficient transmission. Biofilm formation, a specialized physiology characterized by multicellular aggregation and persistence, is proposed to play an important role in the Salmonella transmission cycle. In this manuscript, we used luciferase reporters to examine the expression of csgD, which encodes the master biofilm regulator. We observed that the CsgD-regulated biofilm system responds differently to regulatory inputs once it is activated. Notably, the CsgD system became unresponsive to repression by Cpx and H-NS in high osmolarity conditions and less responsive to the addition of amino acids. Temperature-mediated regulation of csgD on agar was altered by intracellular levels of RpoS and cyclic-di-GMP. In contrast, the addition of glucose repressed CsgD biofilms seemingly independent of other signals. Understanding the fine-tuned regulation of csgD can help us to piece together how regulation occurs in natural environments, knowing that all Salmonella strains face strong selection pressures both within and outside their hosts. Ultimately, we can use this information to better control Salmonella and develop strategies to break the transmission cycle.

Complement component 5 (C5) has been described as either promoting or protecting against airway hyperresponsiveness (AHR) in experimental allergic asthma, suggesting pleomorphic effects of C5. Here we report that local pharmacological targeting of the C5a receptor (C5aR) prior to initial allergen sensitization in murine models of inhalation tolerance or allergic asthma resulted in either induction or marked enhancement of Th2-polarized immune responses, airway inflammation, and AHR. Importantly, C5aR-deficient mice exhibited a similar, increased allergic phenotype. Pulmonary allergen exposure in C5aR-targeted mice resulted in increased sensitization and accumulation of CD4+ CD69+ T cells associated with a marked increase in pulmonary myeloid, but not plasmacytoid, DC numbers. Pulmonary DCs from C5aR-targeted mice produced large amounts of CC chemokine ligand 17 (CCL17) and CCL22 ex vivo, suggesting a negative impact of C5aR signaling on pulmonary homing of Th2 cells. In contrast, C5aR targeting in sensitized mice led to suppressed airway inflammation and AHR but was still associated with enhanced production of Th2 effector cytokines. These data suggest a dual role for C5a in allergic asthma, i.e., protection from the development of maladaptive type 2 immune responses during allergen sensitization at the DC/T cell interface but enhancement of airway inflammation and AHR in an established inflammatory environment.

Create a school environment that ensures improvement ideas are more likely to succeed by using the guidelines and strategies from this book. After the authors present the foundational principles of group decision-making in a collaborative school, they explain the functions that are key to a dynamic school that embraces change and improvement: (1) Establishing and managing effective study groups that reflect on current school practices and investigate new approaches; (2) Developing and supporting coaching relationships that foster professional development throughout the staff; (3) Designing and managing mentoring programs that maximize the talents and resources of veteran and beginning teachers; and (4) Promoting and sustaining shared leadership that focuses everyone on mutually agreed-upon goals. Learn how these functions come together to form a learning community that is committed to a continuous improvement cycle.

With the exception of a few studies, little systematic attention has been given to individuals in their postdeviant careers. Drawing on data collected through participant observation and informal interviews with 146 nonchronic ex-psychiatric patients, this article explicates dimensions of their exit process and social reintegration. Specifically, attention is given to ex-patients' perceptions of mental illness as a stigmatizable/stigmatizing attribute, the problems they faced, the manner by which they manage discreditable/discrediting information about themselves, and the consequences of such for altering their deviant identities and social reintegration. This article suggests that ex-psychiatric patients are strategists and negotiators who play active roles in attempting to shape their deviant outcomes, techniques which have implications for identity transformation and reintegration.

The plight of the homeless mentally ill (HMI) in Canada & the US is examined, & results of a study on the effects of deinstitutionalization are reported. Data from participant observation of, & interviews with, 285 chronic & nonchronic ex-psychiatric patients living in 8 metropolitan areas in southern Ontario show that the origins of the HMI are closely connected with changing conceptions of mental illness, mental health, professional self-interest, power, prestige, & various economic issues. Perceptions of the HMI about their plight are explored, & the many failed policy attempts to deal with the HMI are discussed. It is argued that the massive expenditures on social programs promised in the 1970s & 1980s by policymakers & politicians never materialized. Policy suggestions are offered. 51 References.

During the past two decades, advances in computer technologies combined with telecommunication technologies have led to the development of the Internet and its most popular application, the World Wide Web WWW. Like many other technologies, the WWW has not been free of problems and challenges. A Delphi technique was utilized to assess a list of issues identified in the existing literature. In addition to this list, the panel of experts who participated in the Delphi study identified other critical issues and eventually ranked them in their order of priority and importance. The critical issue identified provides closer insights into issues affecting the overall utilization and management of Webenabled technologies, and offers many implications and challenges for businesses, governments and the user community.