The inversion effect on gaze perception reflects processing of component information

When faces are turned upside-down they are much more difficult to recognize than other objects. This "face inversion effect" has often been explained in terms of configural processing, which is impaired when faces are rotated away from the upright. Here we report a "gaze inversion effect" and discuss whether it is related to configural face processing of the whole face. Observers reported the gaze locations of photographed upright or inverted faces. When whole faces were presented, we found an inversion effect both for constant errors and observer sensitivity. These results were closely replicated when only the eyes were visible. Together, our findings suggest that gaze processing is largely based on component-based information from the eye region. Processing this information is orientation-sensitive and does not seem to rely on configural processing of the whole face.     

Cross-reactivity between IgE-binding proteins from Anisakis German cockroach, and chironomids

Pascual CY, Crespo JF, San Martin S, Ornia N, Ortega N, Caballero T, Munoz-Pereira M, Martin-Estaban M. Cross-reactivity between IgE-binding proteins from Anisakis German cockroach, and chironomids. Anisakis simplex larvae parasitize animals used as seafood and can produce a specific immune response in man. The ingestion of seafood contaminated with stage three of A. simplex larvae can induce a specific IgE response with clinical symptoms, usually urticaria, even if the fish is cooked before ingestion and the invasive infestation power destroyed by heating. Our preliminary studies showed a strong association of A. simplex sensitization with Ascaris lumbricoides, Daphnia chironomid spp., Atlantic shrimp ‘Pandalus borealis’ and German cockroach ‘Blattella germanica’. We conducted the cross-reactivity study with cockroach, a ubiquitous insect, and Chironomidae ‘red mosquito larvae’, a work-related allergen, without any possibility of Anisakis contamination. Serum samples were collected from 60 pediatric patients, with serum specific IgE to A. simplex. Both specific-IgE and immunoblot-inhibition studies, with a serum pool from 18 patients, were performed to determine whether the association of sensitizations to nematodes and arthropods was due to immunologic cross-reactivity. In addition, serum samples from 21 of 60 patients who showed also sensitization to German cockroach were used for individual immunoblot studies. In the serum pool, dose-dependent inhibition of B. germanica and Chironomus spp. was observed after preincubation with the A. simplex extract. Immunoblot of Anisakis inhibited with Chironomus and German cockroach, yielded a partial blot inhibition but mainly on bands below 41 kDa. Blot inhibition of German cockroach and Chironomus with Anisakis was dose related. The band patterns in individual blots were heterogeneous, but most of them had bands of 30–43 kDa. None of these sera recognized allergens in the 14–kDa area. In our study, CAP-inhibition and immunoblot-inhibition analysis of Anisakis showed that several IgE-binding components could be shared by the three allergens.     

HL-A8: a genetic link with thyrotoxicosis.

The incidence of HL-A8 was significantly increased in 64 Caucasian patients with thyrotoxicosis compared with 700 Australian blood donors (42% versus 24%). No significant correlation was observed between HL-A8 and autoantibodies to thyroid components in thyrotoxic patients; thus the association of HL-A8 must be either with the disease itself, or possibly with immune responses not tested for this study.     

KCNE1 reverses the response of the human K+ channel KCNQ1 to cytosolic pH changes and alters its pharmacology and sensitivity to temperature

Previous studies have shown that heteromultimeric KCNQ1/KCNE1 (KvLQT1/minK) channels and homomultimeric KCNQ1 (KvLQT1) channels exhibit different current properties, e.g. distinct kinetics and different sensitivities to drugs. In this study we report on the divergent responses to internal pH changes and further characterize some of the current properties of the human isoforms of KCNQ1 and KCNE1 expressed in Chinese hamster ovary (CHO) cells or Xenopus laevis oocytes. Decreasing the bath temperature from 37 degrees C to 20 degrees C increased the half-activation time by a factor of 5 for KCNQ1/KCNE1 currents (IKs) but by only twofold (not significant) for KCNQ1 currents (IK) in CHO cells. Acidification of cytosolic pH (pHi) increased IKs but decreased 1K whereas intracellular alkalinization decreased I(Ks) but increased IK. pHi-induced changes in intracellular Ca2+ activity ([Ca2+]i) did not correlate with the current responses. At 20 degrees C mefenamic acid (0.1 mM) significantly augmented IKs but slightly decreased IK. It changed the slow activation kinetics of I(Ks) to an instantaneous onset. The form of the current/voltage (I/V) curve changed from sigmoidal to almost linear. In contrast, at 37 degrees C, mefenamic acid also increased I(Ks) but slowed the activation kinetics and shifted the voltage activation to more hyperpolarized values without markedly affecting the sigmoidal shape of the I/V curve. The potassium channel blockers clotrimazole and tetrapentylammonium (TPeA) inhibited I(Ks) with a lower potency than I(K). These results show that coexpression of KCNE1 reversed pH regulation of KCNQ1 from inhibition to activation by acidic pHi. In addition, KCNE1 altered the pharmacological properties and sensitivity to temperature of KCNQ1. The pH-dependence of I(Ks) might be of clinical and pathophysiological relevance in the pathogenesis of ischaemic cardiac arrhythmias.     

Consistency of remission and outcome in bipolar and unipolar mood disorders: a 10-year prospective follow-up

BACKGROUND: Previous studies of the natural course of bipolar disorder have suggested that relapse and psychosocial impairment are more common than many would expect during treatment under routine conditions. The present research sought to identify patterns of consistency in longitudinal recovery after an index manic or depressive episode in patients formerly hospitalized for major affective disorders. The data extend prior findings from the Chicago Follow-up Study involving four successive assessments of course and outcome for bipolar and unipolar patients over a 10-year follow-up interval. METHODS: Thirty-four RDC bipolar I manic, 17 psychotic unipolar depressed, and 72 nonpsychotic unipolar depressed patients were assessed at index hospitalization and prospectively followed-up at 2, 4.5, 7.5 and 10 years. Psychosocial functioning, rehospitalization, and overall outcome were rated by standardized instruments. Patterns of consistent remission or impairment in functioning were compared across follow-up periods. RESULTS: Consistently good functioning was observed more often among patients with unipolar nonpsychotic depression than bipolar disorder or unipolar psychotic depression. Psychosis at index hospitalization was not associated with poorer outcomes for either the bipolar or unipolar groups, although it significantly predicted psychosis at follow-up more robustly for unipolar than bipolar patients. Less than half of the bipolar cohort had good work performance at each follow-up, while unipolar nonpsychotic depressed patients had consistently better work functioning. Rehospitalization was more common for the bipolar than unipolar patients at the 4.5- and 7.5-year assessments. Sustained remission across follow-ups was associated with remission at subsequent follow-ups regardless of diagnostic polarity at index hospitalization. LIMITATIONS: The observational design, small sample size, and naturalistic treatment of subjects in this protocol prompts caution when interpreting treatment outcome findings. The availability of a bipolar cohort with relatively low attrition over a 10-year period may limit the generalizability of the current findings to patients who remain engaged in sustained contact with a long-term research program. CONCLUSIONS: Over a 10-year follow-up period, about half of bipolar patients show sustained remissions or patterns of improvement, while 30-40% experience some functional decline. The degree of consistency in remission patterns over time may hold greater prognostic significance than the polarity of an index affective episode in anticipating subsequent levels of psychosocial adjustment in severe mood disorders.     

Antigen-specific suppression of a primed immune response by dendritic cells mediated by regulatory T cells secreting interleukin-10

Antigen-specific suppression of a previously primed immune response is a major challenge for immunotherapy of autoimmune disease. RelB activation is required for myeloid DC differentiation. Here, we show that antigen-exposed DCs in which RelB function is inhibited lack cell surface CD40, prevent priming of immunity, and suppress previously primed immune responses. DCs generated from CD40-deficient mice similarly confer suppression. Regulatory CD4+ T cells induced by the DCs transfer antigen-specific "infectious" tolerance to primed recipients in an interleukin-10-dependent fashion. Thus CD40, regulated by RelB activity, determines the consequences of antigen presentation by myeloid DCs. These observations have significance for autoimmune immunotherapy and suggest a mechanism by which peripheral tolerance might be constitutively maintained by RelB(-) CD40(-) DCs.     

Transgenic rat model of Huntington's disease

Huntington's disease (HD) is a late manifesting neurodegenerative disorder in humans caused by an expansion of a CAG trinucleotide repeat of more than 39 units in a gene of unknown function. Several mouse models have been reported which show rapid progression of a phenotype leading to death within 3-5 months (transgenic models) resembling the rare juvenile course of HD (Westphal variant) or which do not present with any symptoms (knock-in mice). Owing to the small size of the brain, mice are not suitable for repetitive in vivo imaging studies. Also, rapid progression of the disease in the transgenic models limits their usefulness for neurotransplantation. We therefore generated a rat model transgenic of HD, which carries a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter. This is the first transgenic rat model of a neurodegenerative disorder of the brain. These rats exhibit adult-onset neurological phenotypes with reduced anxiety, cognitive impairments, and slowly progressive motor dysfunction as well as typical histopathological alterations in the form of neuronal nuclear inclusions in the brain. As in HD patients, in vivo imaging demonstrates striatal shrinkage in magnetic resonance images and a reduced brain glucose metabolism in high-resolution fluor-deoxy-glucose positron emission tomography studies. This model allows longitudinal in vivo imaging studies and is therefore ideally suited for the evaluation of novel therapeutic approaches such as neurotransplantation.     

Development and activation of human dendritic cells in vivo in a xenograft model of human hematopoiesis

Dendritic cells (DCs) are derived from CD34+ progenitors and play a central role in the development of immune responses and in tolerance. Their therapeutic potential underscores the need for in vivo models that accurately recapitulate human DC development and function to provide a better understanding of DC biology in health and disease. Using nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice transplanted with human CD34+ cells as a model of human hematopoiesis, we examined DC ontogeny. Progenitors of both myeloid (m) and plasmacytoid (p) DCs were identified in the bone marrow of mice up to 24 weeks after transplant, indicating ongoing and sustained production of DCs after initial engraftment. To determine whether human DCs derived from transplanted stem cells were functional, their response to acute inflammation using lipopolysaccharide (LPS) was examined. Eighteen hours after LPS administration, a dramatic increase in the plasma levels of the human inflammatory cytokines interleukin (IL)-8, IL-10, tumor necrosis factor-alpha, and IL-12p70 was observed. Only mDCs and not pDCs responded in vivo to LPS by upregulating CD86 and CD83. In vivo activation of human mDCs resulted in a substantial increase in the ability of mDCs to induce the proliferation of naive human T cells. Taken together, these data indicate that human CD34+ cells seem to have differentiated appropriately within the NOD/SCID microenvironment into DCs that are developmentally, phenotypically, and functionally similar to the DC subsets found in humans.