A potential new, stable state of the E-cadherin strand-swapped dimer in solution

E-cadherin is a transmembrane glycoprotein that facilitates inter-cellular adhesion in the epithelium. The ectodomain of the native structure is comprised of five repeated immunoglobulin-like domains. All E-cadherin crystal structures show the protein in one of three alternative conformations: a monomer, a strand-swapped trans homodimer and the so-called X-dimer, which is proposed to be a kinetic intermediate to forming the strand-swapped trans homodimer. However, previous studies have indicated that even once the trans strand-swapped dimer is formed, the complex is highly dynamic and the E-cadherin monomers may reorient relative to each other. Here, molecular dynamics simulations have been used to investigate the stability and conformational flexibility of the human E-cadherin trans strand-swapped dimer. In four independent, 100 ns simulations, the dimer moved away from the starting structure and converged to a previously unreported structure, which we call the Y-dimer. The Y-dimer was present for over 90% of the combined simulation time, suggesting that it represents a stable conformation of the E-cadherin dimer in solution. The Y-dimer conformation is stabilised by interactions present in both the trans strand-swapped dimer and X-dimer crystal structures, as well as additional interactions not found in any E-cadherin dimer crystal structures. The Y-dimer represents a previously unreported, stable conformation of the human E-cadherin trans strand-swapped dimer and suggests that the available crystal structures do not fully capture the conformations that the human E-cadherin trans homodimer adopts in solution

Psicología Y educación a distancia : una revisión de la literatura

O presente estudo investigou as contribuições da Psicologia para a educação a distância – EAD. Para isso, realizou-se revisão bibliográfica de publicações nacionais, entre 1999 e 2009, nas bases de dados SciELO, Lilacs, PsycINFO, BVS e Google Acadêmico. Foram selecionados 69 estudos, dos quais se excluíram 15, por não serem compatíveis com a pesquisa. Os resultados evidenciaram nove eixos temáticos: (1) tecnologia educacional a distância com fundamentos psicológicos, (2) afeição, (3) papel do tutor/professor, (4) teorias psicológicas, (5) interatividade, (6) evasão, (7) relatos de experiências, (8) avaliação de treinamento, desenvolvimento e educação a distância e (9) outros. Os temas tecnologia educacional a distância com fundamentos psicológicos e afeição obtiveram maior frequência nas publicações. Neste estudo, registrou-se, também, que, embora em ascensão desde 2006, os anos de maiores publicações da Psicologia na educação a distância foram 2008 e 2009. Sugere-se que estudos futuros ampliem esta pesquisa para incluir bases de dados internacionais.This study investigated the contributions of Psychology to Distance Learning. A literature review of national publications between 1999 to 2009 was made in the electronic databases SciELO, LILACS, PsycINFO, BVS and Google Scholar. From the 69 studies selected, 15 were excluded because they were not compatible with the research. The results showed nine themes: (1) the distance learning technology with psychological grounding, (2) affection, (3)the role of the tutor/professor, (4) psychological theories, (5) interactivity, (6) dropout, (7) reports of experiences, (8) assessment of distance training, development and education and (9) others. The topics distance education technology with psychological grounding and affection had a larger frequency in the publications. Since 2006, there was an increasing number of publications in psychology distance education, but the years of major publications were from 2008 to 2009. It is suggested that future studies expand this research including international databases.El presente estudio investigó las contribuciones de la Psicología para la Educación a Distancia – EAD. Para eso, fue realizada una revisión bibliográfica de publicaciones nacionales, entre 1999 y 2009 en las bases de datos SciELO, Lilacs, PsycINFO, BVS y Google Académico. Fueron seleccionados 69 estudios, de los cuales se excluyeron 15, por no ser compatibles con la pesquisa. Los resultados evidenciaron nueve ejes temáticos (1) tecnología educacional la distancia con fundamentos psicológicos; (2) afección; (3) papel del tutor/profesor; (4) teorías psicológicas; (5) interactividad; (6) evasión; (7) relatos de experiencias, (8) evaluación de entrenamiento, desarrollo y educación distancia y (9) otros. Los temas tecnología educacional a distancia con fundamentos psicológicos y afección obtuvieron mayor frecuencia en las publicaciones. En ese estudio se registró, también, que, aunque en ascensión desde 2006, los años de mayores publicaciones de la psicología en la educación a distancia, fueron 2008 y 2009. Se sugiere que estudios futuros amplíen esa pesquisa para incluir bases de datos internacionales

Innocuous pressure sensation requires A-type afferents but not functional ΡΙΕΖΟ2 channels in humans.

The sensation of pressure allows us to feel sustained compression and body strain. While our understanding of cutaneous touch has grown significantly in recent years, how deep tissue sensations are detected remains less clear. Here, we use quantitative sensory evaluations of patients with rare sensory disorders, as well as nerve blocks in typical individuals, to probe the neural and genetic mechanisms for detecting non-painful pressure. We show that the ability to perceive innocuous pressures is lost when myelinated fiber function is experimentally blocked in healthy volunteers and that two patients lacking Aβ fibers are strikingly unable to feel innocuous pressures at all. We find that seven individuals with inherited mutations in the mechanoreceptor PIEZO2 gene, who have major deficits in touch and proprioception, are nearly as good at sensing pressure as healthy control subjects. Together, these data support a role for Aβ afferents in pressure sensation and suggest the existence of an unknown molecular pathway for its detection

Molecular mechanisms underlying sensory-motor circuit dysfunction in SMA

Activation of skeletal muscle in response to acetylcholine release from the neuromuscular junction triggered by motor neuron firing forms the basis of all mammalian locomotion. Intricate feedback and control mechanisms, both from within the central nervous system and from sensory organs in the periphery, provide essential inputs that regulate and finetune motor neuron activity. Interestingly, in motor neuron diseases, such as spinal muscular atrophy (SMA), pathological studies in patients have identified alterations in multiple parts of the sensory-motor system. This has stimulated significant research efforts across a range of different animal models of SMA in order to understand these defects and their contribution to disease pathogenesis. Several recent studies have demonstrated that defects in sensory components of the sensory-motor system contribute to dysfunction of motor neurons early in the pathogenic process. In this review, we provide an overview of these findings, with a specific focus on studies that have provided mechanistic insights into the molecular processes that underlie dysfunction of the sensory-motor system in SMA. These findings highlight the role that cell types other than motor neurons play in SMA pathogenesis, and reinforce the need for therapeutic interventions that target and rescue the wide array of defects that occur in SMA

Populations of Lobaria pulmonaria (L.) Hoffm. in the Cansiglio Regional Forest (Veneto, Pre-Alps, north-east Italy): Distribution, diversity and conservation issues

The distribution of the epiphytic macrolichen Lobaria pulmonaria (L.) Hoffm. was surveyed in the Regional Forest of Cansiglio, extending over 3,500 ha in the eastern part of the Veneto Pre-Alps (north-east Italy). Data on the main characteristics of the forest sites and on Lobaria trees were collected with the aim to evaluate the main ecological factors, related to forest composition and management, affecting the distribution of Lobaria pulmonaria . Lichen diversity was surveyed on 15 randomly selected Lobaria trees. A good correlation between macrolichens and the total number of species was found. The largest Lobaria populations are concentred in the north-eastern part of the forest, where mixed and multi-plane silver fir - beech formations prevail, and selective cutting is carried out. Our data has enabled us to develop some criteria for the identification of priority conservation sites for Lobaria pulmonaria and lichen diversity in the study area, improving the focus on biodiversity in the management of the forest. \ua9 2006 Societ\ue0 Botanica Italiana

Couleur de fleur d’orchidées et insectes

International audienceno abstrac

8C.05: EPOXYEICOSATRIENOIC ACIDS ARE INCREASED IN PLACENTAS OF PREECLAMPTIC PREGNANCIES

Plasma concentration of epoxyeicosatrienoic acids (EETs) derived from cytochrome P450 (CYP)-dependent metabolism of arachidonic acid is increased in women with preeclampsia (PE) as compared to normal pregnancy (N), and is even higher in fetal plasma (Herse et al. Circulation 2012, Jiang et al. Am J Hypertens 2013). We hypothesized that differences in EET synthesis or metabolism in the feto-placental unit underlie the observed differences in circulating EETs