16/6-idiotype expressing antibodies induce brain inflammation and cognitive impairment in mice: the mosaic of central nervous system involvement in lupus

Background: The 16/6-idiotype (16/6-Id) of the human anti-DNA antibody was found to induce experimental lupus in naive mice, manifested by production of autoantibodies, leukopenia and elevated inflammatory markers, as well as kidney and brain involvement. We assessed behavior and brain pathology of naive mice injected intracerebra-ventricularly (ICV) with the 16/6-Id antibody. Methods: C3H female mice were injected ICV to the right hemisphere with the human 16/6-Id antibody or commercial human IgG antibodies (control). The mice were tested for depression by the forced swimming test (FST), locomotor and explorative activity by the staircase test, and cognitive functions were examined by the novel object recognition and Y-maze tests. Brain slices were stained for inflammatory processes. Results: 16/6-Id injected mice were cognitively impaired as shown by significant differences in the preference for a new object in the novel object recognition test compared to controls (P = 0.012). Similarly, the preference for spatial novelty in the Y-maze test was significantly higher in the control group compared to the 16/6-Id-injected mice (42% vs. 9%, respectively, P = 0.065). Depression-like behavior and locomotor activity were not significantly different between the16/6-Id-injected and the control mice. Immunohistochemistry analysis revealed an increase in astrocytes and microglial activation in the hippocampus and amygdala, in the 16/6-Id injected group compared to the control. Conclusions: Passive transfer of 16/6-Id antibodies directly into mice brain resulted in cognitive impairments and histological evidence for brain inflammation. These findings shed additional light on the diverse mosaic pathophysiology of neuropsychiatric lupus.

Friendly Settlements in the Framework of the Inter- American Human Rights System

The Inter-American system for the protection of human rights provides that disputesbetween States and victims of human rights violations or their representatives can beresolved through a friendly settlement. In this arrangement, conducted before the regionalorgans of protection of human rights, the State accepts its international responsibility,commits itself to investigate and judge the responsible and makes commitmentson compensation to the offended, the victims, on his part, renounce to take the caseto the Inter-American Court of Human Rights, and the Inter-American Commissionmonitors the legal consistency of the agreement and holds the role of independentobserver. What are these agreements, what possibilities and limitations provide to theopposing parties and, above all, what kind of reparation offer to victims of humanrights violations are issues to resolve in this article.

Análisis de los informes emitidos por Human Rights Watch y su incidencia en la firma y ratificación del tratado de libre comercio entre Estados Unidos y Colombia: estudio de caso periodo 2002-2008

Este artículo tiene como objetivo analizar, la incidencia que tienen actualmente las ONG s internacionales sobre la toma de decisiones de los gobiernos de diferentes Estados. Con el fin de hacer más específico dicho análisis, el trabajo se centra en el estudio del caso de la firma del Tratado de Libre Comercio entre Estados Unidos cuyo proceso, según se explica a lo largo del texto, se vio afectado de manera significativa por la acción de Human Rights Watch. El artículo presenta una exposición de la mecánica política requerida para la aprobación de este tipo de tratados en ambos países involucrados, así como la forma en que las asimetrías de poder entre ellos abrieron el campo a la acción de Human Rights Watch.

Human biology and health studies.

Proporciona a los estudiantes los temas requeridos para el primer año del curso GCSE, especialidad biología. Es una edición revisada para el nuevo AQA GCSE en Fisiología humana y estudios de la salud.

Methodology to obtain the user's Human Values Scale from Smart User Models

En años recientes,la Inteligencia Artificial ha contribuido a resolver problemas encontrados en el desempeño de las tareas de unidades informáticas, tanto si las computadoras están distribuidas para interactuar entre ellas o en cualquier entorno (Inteligencia Artificial Distribuida). Las Tecnologías de la Información permiten la creación de soluciones novedosas para problemas específicos mediante la aplicación de los hallazgos en diversas áreas de investigación. Nuestro trabajo está dirigido a la creación de modelos de usuario mediante un enfoque multidisciplinario en los cuales se emplean los principios de la psicología, inteligencia artificial distribuida, y el aprendizaje automático para crear modelos de usuario en entornos abiertos; uno de estos es la Inteligencia Ambiental basada en Modelos de Usuario con funciones de aprendizaje incremental y distribuido (conocidos como Smart User Model). Basándonos en estos modelos de usuario, dirigimos esta investigación a la adquisición de características del usuario importantes y que determinan la escala de valores dominantes de este en aquellos temas en los cuales está más interesado, desarrollando una metodología para obtener la Escala de Valores Humanos del usuario con respecto a sus características objetivas, subjetivas y emocionales (particularmente en Sistemas de Recomendación).Una de las áreas que ha sido poco investigada es la inclusión de la escala de valores humanos en los sistemas de información. Un Sistema de Recomendación, Modelo de usuario o Sistemas de Información, solo toman en cuenta las preferencias y emociones del usuario [Velásquez, 1996, 1997; Goldspink, 2000; Conte and Paolucci, 2001; Urban and Schmidt, 2001; Dal Forno and Merlone, 2001, 2002; Berkovsky et al., 2007c]. Por lo tanto, el principal enfoque de nuestra investigación está basado en la creación de una metodología que permita la generación de una escala de valores humanos para el usuario desde el modelo de usuario. Presentamos resultados obtenidos de un estudio de casos utilizando las características objetivas, subjetivas y emocionales en las áreas de servicios bancarios y de restaurantes donde la metodología propuesta en esta investigación fue puesta a prueba.En esta tesis, las principales contribuciones son: El desarrollo de una metodología que, dado un modelo de usuario con atributos objetivos, subjetivos y emocionales, se obtenga la Escala de Valores Humanos del usuario. La metodología propuesta está basada en el uso de aplicaciones ya existentes, donde todas las conexiones entre usuarios, agentes y dominios que se caracterizan por estas particularidades y atributos; por lo tanto, no se requiere de un esfuerzo extra por parte del usuario.

Human amygdala responses during presentation of happy and neutral faces: correlations with state anxiety

BACKGROUND: Previous functional imaging studies demonstrating amygdala response to happy facial expressions have all included the presentation of negatively valenced primary comparison expressions within the experimental context. This study assessed amygdala response to happy and neutral facial expressions in an experimental paradigm devoid of primary negatively valenced comparison expressions. METHODS: Sixteen human subjects (eight female) viewed 16-sec blocks of alternating happy and neutral faces interleaved with a baseline fixation condition during two functional magnetic resonance imaging scans. RESULTS: Within the ventral amygdala, a negative correlation between happy versus neutral signal changes and state anxiety was observed. The majority of the variability associated with this effect was explained by a positive relationship between state anxiety and signal change to neutral faces. CONCLUSIONS: Interpretation of amygdala responses to facial expressions of emotion will be influenced by considering the contribution of each constituent condition within a greater subtractive finding, as well as 1) their spatial location within the amygdaloid complex; and 2) the experimental context in which they were observed. Here, an observed relationship between state anxiety and ventral amygdala response to happy versus neutral faces was explained by response to neutral faces.

Infection of human airway epithelium by human and avian strains of influenza a virus

We describe the characterization of influenza A virus infection of an established in vitro model of human pseudostratified mucociliary airway epithelium (HAE). Sialic acid receptors for both human and avian viruses, alpha-2,6- and alpha-2,3-linked sialic acids, respectively, were detected on the HAE cell surface, and their distribution accurately reflected that in human tracheobronchial tissue. Nonciliated cells present a higher proportion of alpha-2,6-linked sialic acid, while ciliated cells possess both sialic acid linkages. Although we found that human influenza viruses infected both ciliated and nonciliated cell types in the first round of infection, recent human H3N2 viruses infected a higher proportion of nonciliated cells in HAE than a 1968 pandemic-era human virus, which infected proportionally more ciliated cells. In contrast, avian influenza viruses exclusively infected ciliated cells. Although a broad-range neuraminidase abolished infection of HAE by human parainfluenza virus type 3, this treatment did not significantly affect infection by influenza viruses. All human viruses replicated efficiently in HAE, leading to accumulation of nascent virus released from the apical surface between 6 and 24 h postinfection with a low multiplicity of infection. Avian influenza A viruses also infected HAE, but spread was limited compared to that of human viruses. The nonciliated cell tropism of recent human H3N2 viruses reflects a preference for the sialic acid linkages displayed on these cell types and suggests a drift in the receptor binding phenotype of the H3 hemagglutinin protein as it evolves in humans away from its avian virus precursor.

Specificity grafting of human antibody frameworks selected from a phage display library: generation of a highly stable humanized anti-CD22 single-chain Fv fragment

A prerequisite for the enrichment of antibodies screened from phage display libraries is their stable expression on a phage during multiple selection rounds. Thus, if stringent panning procedures are employed, selection is simultaneously driven by antigen affinity, stability and solubility. To take advantage of robust pre-selected scaffolds of such molecules, we grafted single-chain Fv (scFv) antibodies, previously isolated from a human phage display library after multiple rounds of in vitro panning on tumor cells, with the specificity of the clinically established murine monoclonal anti-CD22 antibody RFB4. We show that a panel of grafted scFvs retained the specificity of the murine monoclonal antibody, bound to the target antigen with high affinity (6.4-9.6 nM), and exhibited exceptional biophysical stability with retention of 89-93% of the initial binding activity after 6 days of incubation in human serum at 37degreesC. Selection of stable human scaffolds with high sequence identity to both the human germline and the rodent frameworks required only a small number of murine residues to be retained within the human frameworks in order to maintain the structural integrity of the antigen binding site. We expect this approach may be applicable for the rapid generation of highly stable humanized antibodies with low immunogenic potential.

Genistein affects the expression of genes involved in blood pressure regulation and angiogenesis in primary human endothelial cells

Background: Several lines of evidence suggest that the dietary isoflavone genistein (Gen) has beneficial effects with regard to cardiovascular disease and in particular on aspects related to blood pressure and angiogenesis. The biological action of Gen may be, at Least in part, attributed to its ability to affect cell signalling and response. However, so far, most of the molecular mechanisms underlying the activity of Gen in the endothelium are unknown. Methods and results: To examine the transcriptional response to 2.5 mu M Gen on primary human endothelial cells (HUVEC), we applied cDNA array technology both under baseline condition and after treatment with the pro-atherogenic stimulus, copper-oxidized LDL. The alteration of the expression patterns of individual transcripts was substantiated using either RT-PCR or Northern blotting. Gen significantly affected the expression of genes encoding for proteins centrally involved in the vascular tone such as endothelin-converting enzyme-1, endothetin-2, estrogen related receptor a and atria[ natriuretic peptide receptor A precursor. Furthermore, Gen countered the effect of oxLDL on mRNA levels encoding for vascular endothelial growth factor receptor 165, types 1 and 2. Conclusions: Our data indicate that physiologically achievable levels of Gen change the expression of mRNA encoding for proteins involved in the control of blood pressure under baseline conditions and reduce the angiogenic response to oxLDL in the endothelium. (c) 2005 Elsevier B.V. All rights reserved.

Bacterial, SCFA and gas profiles of a range of food ingredients following in vitro fermentation by human colonic microbiota.

It is now apparent that there is a strong link between health and nutrition and this can be seen clearly when we talk of obesity. The food industry is trying to capitalise on this by adapting high sugar/fat foods to become healthier alternatives. In confectionery food ingredients can be used for a range of purposes including sucrose replacement. Many of these ingredients may also evade digestion in the upper gut and be fermented by the gut microbiota upon entering the colon. This study was designed to screen a range of ingredients and their activities on the gut microbiota. In this study we screened a range of these ingredients in triplicate batch culture fermentations with known prebiotics as controls. Changes in bacteriology were monitored using FISH. SCFA were measured by GC and gas production was assessed during anaerobic batch fermentations. Bacterial enumeration showed significant increases (P ≤ 0.05) in bifidobacteria and lactobacilli with polydextrose and most polyols with no significant increases in Clostridium histolyticum/perfringens. SCFA and gas formation indicated that the substrates added to the fermenters were being utilised by the gut microbiota. It therefore appears these ingredients exert some prebiotic activity in vitro. Further studies, particularly in human volunteers, are necessary.

Intact automatic imitation of human and robot actions in autism spectrum disorders

The existence of a specialized imitation module in humans is hotly debated. Studies suggesting a specific imitation impairment in individuals with autism spectrum disorders (ASD) support a modular view. However, the voluntary imitation tasks used in these studies (which require socio-cognitive abilities in addition to imitation for successful performance) cannot support claims of a specific impairment. Accordingly, an automatic imitation paradigm (a ‘cleaner’ measure of imitative ability) was used to assess the imitative ability of 16 adults with ASD and 16 non-autistic matched control participants. Participants performed a prespecified hand action in response to observed hand actions performed either by a human or a robotic hand. On compatible trials the stimulus and response actions matched, while on incompatible trials the two actions did not match. Replicating previous findings, the Control group showed an automatic imitation effect: responses on compatible trials were faster than those on incompatible trials. This effect was greater when responses were made to human than to robotic actions (‘animacy bias’). The ASD group also showed an automatic imitation effect and a larger animacy bias than the Control group. We discuss these findings with reference to the literature on imitation in ASD and theories of imitation.