A comparison of ecological optima of soft-bodied benthic algae in Norwegian and Austrian rivers and consequences for river monitoring in Europe.

Alpine and Nordic rivers are often considered as being among the most pristine in Europe. Nevertheless, acidification and eutrophication impact surface waters in these regions. Soft-bodied, i.e. non-diatom, benthic algae are used as indicators for eutrophication and acidification in both Norway and Austria, but consistency of indicator values has never been tested. We compared species optima with respect to pH, conductivity, total phosphorus (TP), and NO3(-)-N concentration for 21 species, derived from geographically and temporally extensive datasets from Norway and Austria, respectively. The ranges of all four measured parameters were different between Norway and Austria, with Austria having generally higher values for all measured parameters. Optima for all 21 species with respect to pH, conductivity and NO3(-)-N were significantly different between Norway and Austria, while 5 of the 21 taxa showed no significant differences for TP. Nevertheless, species optima for Norway and Austria were significantly correlated with each other for TP, pH and conductivity. This indicates that positions of species optima relative to each other may be stable across ecoregions, in spite of the absolute values of species optima being different. In contrast, optima with respect to NO3(-)-N were not correlated, possibly suggesting a lesser importance of NO3(-) in shaping benthic algal assemblages than TP and pH. We conclude that the use of eutrophication and acidification models across different ecoregions may give meaningful results, but requires regional testing of species optima.

Cutting edge: introduction of an endopeptidase cleavage motif into a determinant flanking region of hen egg lysozyme results in enhanced T cell determinant display.

The choice of which determinants of a whole Ag will be presented on cell surface MHC class II molecules after uptake and processing by APC is the result of the interplay between structural characteristics of the Ag and the processing machinery of the APC. In this study, we demonstrate that introduction of a dibasic motif adjacent to a subdominant determinant enhances the presentation of this determinant from the whole molecule. This is the first report showing that a single amino acid substitution in a whole Ag, designed to introduce an endopeptidase recognition site, enhances display of class II-restricted determinants, most likely by creating a peptide chain cleavage in the antigenic molecule. Our findings have important implications for the understanding of immunodominance and for vaccine design.

In vivo priming of T cells against cryptic determinants by dendritic cells exposed to interleukin 6 and native antigen.

T cells recognizing poorly displayed self determinants escape tolerance mechanisms and persist in the adult repertoire. The process by which these T cells are primed is not clear, but once activated, they can cause autoimmunity. Here, we show that dendritic cells treated with interleukin 6 (IL-6) process and present determinants from a model native antigen in a qualitatively altered hierarchy, activating T cells in vitro and in vivo against determinants that were previously cryptic because of poor display. IL-6 does not induce conventional maturation of dendritic cells but alters the pH of peripheral, early endosomal compartments and renders the cells more susceptible to killing by chloroquine. Acidification of endosomes by ouabain mimics the effect of IL-6 and allows processing of the same cryptic determinant. These results suggest that cytokines such as IL-6 could initiate and help to propagate an autoimmune disease process by differentiating dendritic cells into a state distinct from that induced by normal maturation.

Tolerance and determinant hierarchy.

The overall T cell response to a multideterminant antigen consists of the sum of responses to a limited number of different determinants on the protein. Antigen-presenting cells (APCs) are crucial in delimiting the determinants on the protein to which a response will be mounted. This influence is apparent at two levels. First, the determinants that are generated and displayed by APCs in the thymus are pivotal in shaping the T cell repertoire that will be available for responding to antigen determinants in the periphery. Second, antigen processing affects the selection of determinants that become displayed by the various peripheral APC populations that are involved in inducing and promoting a T cell response. We have studied the effect of the display hierarchy on tolerance induction to individual determinants in transgenic mice expressing different serum levels of hen egg lysozyme. We have also analysed aspects of the processing machinery that contribute to shaping the hierarchy of determinant display on MHC class II molecules: proteolysis and reduction of disulfide bonds.

Attention-deficit hyperactivity disorder. Pharmacotherapy and beyond.

Management of ADHD is a challenge that requires time, commitment, and great sensitivity on the part of the physician. Use of stimulant medications is often successful at improving symptoms, but it has become the knee-jerk treatment response for many. Given the wide-ranging effects of ADHD on aspects of patients' lives and the availability of various treatment alternatives, a multimodal approach is considered optimal. As more studies evaluate nonpharmacologic approaches such as behavior therapy, parent education, and neurofeedback and more physicians implement multimodal treatment, outcomes for patients with ADHD are expected to be even more positive.

Antigen processing differences among APC.

The hierarchy of display of determinants on a protein antigen is of critical importance with respect to which T cells will be selected during thymic development, as well as in the induction of mature responses. Activation of T cells will be dependent on unfolding, reduction and chain cleavage of the antigen, and the vagaries of competition with other determinants as well as hindrance in access to the major histocompatibility complex (MHC) or subsequently of the MHC/peptide complex to the T cell receptor. We here focus on a description of the parameters that determine the generation and display of determinants on MHC class II molecules by different types of antigen presenting cells in different locations.

Attention-deficit hyperactivity disorder. In pursuit of diagnostic accuracy.

Attention-deficit behaviors create a substantial burden for healthcare facilities. The incidence of ADHD is estimated at 5% to 10% of school-age children, but it is possible that many diagnoses of ADHD are flawed. At present, because the etiology of the disorder is not well understood, the diagnosis of ADHD by DSM-IV criteria hinges on the presence of inattention, hyperactivity, impulsivity, or a combination of these. Children who do not have ADHD also exhibit such behaviors in certain environments, as do children with learning disorders, family relational problems, and emotional difficulties. Thus it is imperative that physicians take a comprehensive approach to diagnosis when a child presents with behavioral difficulties. Noting that a number of myths about ADHD (eg, that improved behavior after being given stimulant medication proves a diagnosis of ADHD) have recently gained currency, the authors recommend going beyond the first step of behavior checklists in diagnosing the disorder and describe situations in which further assessment is indicated.

Self-reactive T cell hybridomas and tolerance. Same range of antigen dose dependence but higher numbers of self-reactive T cell hybridomas from mice in which self-tolerance has been broken by antiserum treatment.

Mechanisms of self-tolerance of 4-hydroxyphenylpyruvate dioxygenase (HPPD) are explored. It is well established that negative selection based on TCR affinity occurs in the thymus. We have investigated the frequency with which self-reactive T cell hybridomas can be obtained in relation to self-tolerance. Mice immunized with the self-form of HPPD gave rise to T cell hybridomas that were able to recognize self-protein and a synthetic peptide representing the T cell epitope, at higher Ag concentration than was necessary for recognition of allo-protein. The efficiency of negative selection was then reduced by treating neonatal mice with anti-HPPD antiserum. This reduced T cell tolerance of the self-protein, as judged by in vitro proliferation, and enabled self-reactive T cell hybridomas to be generated at a higher frequency. However, the Ag concentration requirements of these hybridomas for the self-protein and the self-peptide remained unaltered. The possibility that these findings reflect an auxiliary mechanism of self-tolerance based on frequencies of self-reactive T cells is discussed.

Primed lymphocytes are boosted by type II collagen of their hosts after adoptive transfer.

A central question in understanding autoimmunity is whether an endogenous self-antigen can drive an immune response initially triggered by a foreign one. This possibility is here tested by adoptive transfer, in which T and B cells from mice primed with foreign type II collagen were transferred into irradiated syngeneic hosts. Previous work with other protein antigens has established that primed cells normally respond only if boosted after transfer with antigen. In the present case, and in respect only to that portion of the antibody response able to bind to endogenous type II collagen, that requirement did not hold. This indicates that the anti-self component is indeed driven by endogenous antigen, which the transferred lymphocytes presumably obtain from their adoptive hosts. The transfers were carried out in C57BL10.A x DBA/1 mice using donors primed with either chick or bovine collagen, and the non-boosted responses, presumably driven by endogenous antigen, could be followed in a proportion of the recipients for as long as 45 days.

Electron-phonon SAW attenuation in aluminum for all ql.

Theoretical expressions for the electron-phonon contribution to the attenuation of surface acoustic waves (SAW) propagating on a semi-infinite block of material have been obtained for all ql, where q is the sound propagation vector and l is the electron mean-free path. The calculation of the attenuation due to electron-phonon interaction for ql<<1 is straightforward; however, extension of this calculation to all ql values requires knowledge of the ql dependence of the viscous damping coefficients, chi and eta. Approximations for chi and eta for all ql are obtained by analogy with attenuation expressions derived for longitudinal transverse bulk sound waves. Curves for chi, eta, and the electron-phonon contribution to the attenuation of SAW propagating on a semi-infinite block of aluminum are presented.

The implementation of a program innovation in a community mental-health center: theory and practice.

This paper describes the innovation of a partial-hospital program into an ongoing community mental-health center which is under the auspices of the department of psychiatry housed in a city general hospital. The role of the environment and structure of this mental health system in facilitating and hindering implementation is discussed. Resistance from within the program and problems associated with institutionalization of the implementation are noted. The experience of innovation is linked with theory.