Shaping mechanisms of metal specificity in a family of metazoan Metallothioneins: evolutionary differentiation of Mollusc MTs.

Background: The degree of metal binding specificity in metalloproteins such as metallothioneins (MTs) can be crucial for their functional accuracy. Unlike most other animal species, pulmonate molluscs possess homometallic MT isoforms loaded with Cu+ or Cd2+. They have, so far, been obtained as native metal-MT complexes from snail tissues, where they are involved in the metabolism of the metal ion species bound to the respective isoform. However, it has not as yet been discerned if their specific metal occupation is the result of a rigid control of metal availability, or isoform expression programming in the hosting tissues or of structural differences of the respective peptides determining the coordinative options for the different metal ions. In this study, the Roman snail (Helix pomatia) Cu-loaded and Cd-loaded isoforms (HpCuMT and HpCdMT) were used as model molecules in order t o elucidate the biochemical and evolutionary mechanisms permitting pulmonate MTs to achieve specificity for their cognate metal ion. Results: HpCuMT and HpCdMT were recombinantly synthesized in the presence of Cd2+, Zn2+ or Cu2+ and corresponding metal complexes analysed by electrospray mass spectrometry and circular dichroism (CD) and ultra violet-visible (UV-Vis) spectrophotometry. Both MT isoforms were only able to form unique, homometallic and stable complexes (Cd6-HpCdMT and Cu12-HpCuMT) with their cognate metal ions. Yeast complementation assays demonstrated that the two isoforms assumed metal-specific functions, in agreement with their binding preferences, in heterologous eukaryotic environments. In the snail organism, the functional metal specificity of HpCdMT and HpCuMT was contributed by metal-specific transcription programming and cell-specific expression. Sequence elucidation and phylogenetic analysis of MT isoforms from a number of snail species revealed that they possess an unspecific and two metal-specific MT isoforms, whose metal specificity was achieved exclusively by evolutionary modulation of non-cysteine amino acid positions. Conclusion: The Roman snail HpCdMT and HpCuMT isoforms can thus be regarded as prototypes of isoform families that evolved genuine metal-specificity within pulmonate molluscs. Diversification into these isoforms may have been initiated by gene duplication, followed by speciation and selection towards opposite needs for protecting copper-dominated metabolic pathways from nonessential cadmium. The mechanisms enabling these proteins to be metal-specific could also be relevant for other metalloproteins.

Cognate peptide-receptor ligand mapping by directed phage display

Background: A rapid phage display method for the elucidation of cognate peptide specific ligand for receptors is described. The approach may be readily integrated into the interface of genomic and proteomic studies to identify biologically relevant ligands.Methods: A gene fragment library from influenza coat protein haemagglutinin (HA) gene was constructed by treating HA cDNA with DNAse I to create 50 ¿ 100 bp fragments. These fragments were cloned into plasmid pORFES IV and in-frame inserts were selected. These in-frame fragment inserts were subsequently cloned into a filamentous phage display vector JC-M13-88 for surface display as fusions to a synthetic copy of gene VIII. Two well characterized antibodies, mAb 12CA5 and pAb 07431, directed against distinct known regions of HA were used to pan the library. Results: Two linear epitopes, HA peptide 112 ¿ 126 and 162¿173, recognized by mAb 12CA5 and pAb 07431, respectively, were identified as the cognate epitopes.Conclusion: This approach is a useful alternative to conventional methods such as screening of overlapping synthetic peptide libraries or gene fragment expression libraries when searching for precise peptide protein interactions, and may be applied to functional proteomics.

Afrontamiento positivo a la salud mental en pacientes diagnosticados de bipolaridad

El objetivo es llevar a cabo una serie de actividades, actuaciones necesarias que me permitiránconocer a los participantes y a partir de ello, diseñar unas sesiones grupales donde sefomentará la mejora del mal afrontamiento a la patología, Trastornos Bipolares, de lospacientes seleccionados.Introducción: Tras valorar las necesidades personales que me llevaron a seleccionar lapatología estudiada, me plantee la realización de un estudio que me permitieradesarrollar una intervención enfermera dirigida al afrontamiento de ésta nuevasituación de vida en personas a las que se le había diagnosticado.Métodos: Diseño cualitativo a través de un grupo de participantes diagnosticados de trastornobipolar que muestran un afrontamiento inefectivo de la nueva situación de salud. Seprocederá a realizar una encuesta a cada uno de los participantes para poder conocer aquellostemas que más les preocupan, aquello que les hace mantener ese afrontamiento negativo,para posteriormente realizar entrevistas individuales donde se trataran los temas clave de lasencuestas para profundizar los temas y aclarar dudas. Posteriormente a partir de aquí seanalizarán los datos y se podrán desarrollar las sesiones grupales.Participarán aproximadamente 15 personas, entre 20 y 24 años sin diferenciación entre sexos,todos ellos extraídos de la asociación ABV. Todas ellas diagnosticadas de Trastorno Bipolar conafrontamiento inefectivo. Se pedirá consentimiento informado, para la participación en elestudio, así como para algunas intervenciones como grabación de conversaciones.

Generic brands and product differentiation strategies

Generic or own brand products were initially only lesser expensive copies of the branded label alternative, but nowadays, pricing alone is not enough in order to survive in the Fast Moving Consumer Goods (FMCG) or Consumer Packaged Goods (CPG)markets. With this in mind manufacturers of generic brands have adapted to this rapidlygrowing niche by investing in design and marketing during the initial phase in order to be perceived as having a quality product comparable to that of the branded products. In addition, they have gone further ahead with a second phase and resorted to innovativeproduct differentiation strategies and even pure innovation in many cases. These strategies have granted generic brands constantly increasing market shares and a position of equals relative to national brands.Using previous analyses and case studies, this paper will provide conceptual and empirical evidence to explain the surprisingly fast growth and penetration of generic supermarket brands, which in their relatively short lifespan, have grown to rival the historical market leaders, the branded products. According to this analysis, the main conclusion is that the growth in generic brands can be explained not only by price competition, but also by the use of innovative product differentiation strategies.

Satisfaction survey of Directed Experiential Learning (DEL)

The aim of this questionnaire is to assess your experience of the DEL learning process as developed by your university. The questionnaire is anonymous and it should not take more than fifteen minutes to complete.

Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation

Asparagine N-Glycosylation is one of the most important forms of protein post-translational modification in eukaryotes. This metabolic pathway can be subdivided into two parts: an upstream sub-pathway required for achieving proper folding for most of the proteins synthesized in the secretory pathway, and a downstream sub-pathway required to give variability to trans-membrane proteins, and involved in adaptation to the environment and innate immunity. Here we analyze the nucleotide variability of the genes of this pathway in human populations, identifying which genes show greater population differentiation and which genes show signatures of recent positive selection. We also compare how these signals are distributed between the upstream and the downstream parts of the pathway, with the aim of exploring how forces of population differentiation and positive selection vary among genes involved in the same metabolic pathway but subject to different functional constraints. Our results show that genes in the downstream part of the pathway are more likely to show a signature of population differentiation, while events of positive selection are equally distributed among the two parts of the pathway. Moreover, events of positive selection are frequent on genes that are known to be at bifurcation points, and that are identified as being in key position by a network-level analysis such as MGAT3 and GCS1. These findings indicate that the upstream part of the Asparagine N-Glycosylation pathway has lower diversity among populations, while the downstream part is freer to tolerate diversity among populations. Moreover, the distribution of signatures of population differentiation and positive selection can change between parts of a pathway, especially between parts that are exposed to different functional constraints. Our results support the hypothesis that genes involved in constitutive processes can be expected to show lower population differentiation, while genes involved in traits related to the environment should show higher variability. Taken together, this work broadens our knowledge on how events of population differentiation and of positive selection are distributed among different parts of a metabolic pathway.

The differentiation hypothesis and the Flynn effect

Many studies have shown that IQs have been increasing over the last half century. These increases have come to be known as «the Flynn effect». The «Flynn effect» represents a difference on ability-level between groups of the same age but different cohort. The ability-level differentiation hypothesis represents a difference on the relevance of cognitive factors between groups of high and low ability. Hence, it should be possible to imitate the ability-level differentiation effect by comparing groups of the same age but different cohort. The indifferentiation hypothesis represents no differences on the relevance of cognitive abilities in all age groups within the same cohort. The aim of the present study is to test the relationships between these phenomena. For this purpose we analyzed the American standardisation samples of the WISC, WISC-R and WISC-III. Results support the link between the Flynn effect and the differentiation hypothesis. Also, reported evidence replicate previous findings supporting the indifferentiation hypothesis. Implications for the assessment of the intelligence are discussed.

Role of the cellular prion protein in oligodendrocyte precursor cell proliferation and differentiation in the developing and adult mouse CNS

There are numerous studies describing the signaling mechanisms that mediate oligodendrocyte precursor cell (OPC) proliferation and differentiation, although the contribution of the cellular prion protein (PrPc) to this process remains unclear. PrPc is a glycosyl-phosphatidylinositol (GPI)-anchored glycoprotein involved in diverse cellular processes during the development and maturation of the mammalian central nervous system (CNS). Here we describe how PrPc influences oligodendrocyte proliferation in the developing and adult CNS. OPCs that lack PrPc proliferate more vigorously at the expense of a delay in differentiation, which correlates with changes in the expression of oligodendrocyte lineage markers. In addition, numerous NG2-positive cells were observed in cortical regions of adult PrPc knockout mice, although no significant changes in myelination can be seen, probably due to the death of surplus cells.

Qualitative social differentiation in tertiary education in Spain

[cat] En aquest treball, s'estudia si la hipòtesi de la desigualtat efectivament mantinguda “effectively maintained inequality” es cumpleix a Espanya. Es postula que en les transicions terciàries a Espanya, les influències dels pares no es manifesten tant a través de la probabilitat de fer la transició, sinó més aviat a través de les diferències qualitatives associades a aquesta transició en termes de les qualitats dels programes educatius. Analitzem dues característiques qualitatives dels estudis universitaris: la durada del programa i el seu prestigi acadèmic. Identifiquem per a quins individus la influència parental és més important en cada cas.

Qualitative social differentiation in tertiary education in Spain

[cat] En aquest treball, s'estudia si la hipòtesi de la desigualtat efectivament mantinguda “effectively maintained inequality” es cumpleix a Espanya. Es postula que en les transicions terciàries a Espanya, les influències dels pares no es manifesten tant a través de la probabilitat de fer la transició, sinó més aviat a través de les diferències qualitatives associades a aquesta transició en termes de les qualitats dels programes educatius. Analitzem dues característiques qualitatives dels estudis universitaris: la durada del programa i el seu prestigi acadèmic. Identifiquem per a quins individus la influència parental és més important en cada cas.

New method for measuring longitudinal fuctuations and directed flow in ultrarelativistic heavy ion reactions

It has been shown in recent ALICE@LHC measurements that the odd flow harmonics, in particular, a directed flow v1, occurred to be weak and dominated by random fluctuations. In this work we propose a new method, which makes the measurements more sensitive to the flow patterns showing global collective symmetries. We demonstrate how the longitudinal center of mass rapidity fluctuations can be identified, and then the collective flow analysis can be performed in the event-by-event center of mass frame. Such a method can be very effective in separating the flow patterns originating from random fluctuations, and the flow patterns originating from the global symmetry of the initial state.

Growth factor- and cytokine-driven pathways governing liver stemness and differentiation.

Liver is unique in its capacity to regenerate in response to injury or tissue loss. Hepatocytes and other liver cells are able to proliferate and repopulate the liver. However, when this response is impaired, the contribution of hepatic progenitors becomes very relevant. Here, we present an update of recent studies on growth factors and cytokine-driven intracellular pathways that govern liver stem/progenitor cell expansion and differentiation, and the relevance of these signals in liver development, regeneration and carcinogenesis. Tyrosine kinase receptor signaling, in particular, c-Met, epidermal growth factor receptors or fibroblast growth factor receptors, contribute to proliferation, survival and differentiation of liver stem/progenitor cells. Different evidence suggests a dual role for the transforming growth factor (TGF)-β signaling pathway in liver stemness and differentiation. On the one hand, TGF-β mediates progression of differentiation from a progenitor stage, but on the other hand, it contributes to the expansion of liver stem cells. Hedgehog family ligands are necessary to promote hepatoblast proliferation but need to be shut off to permit subsequent hepatoblast differentiation. In the same line, the Wnt family and β-catenin/T-cell factor pathway is clearly involved in the maintenance of liver stemness phenotype, and its repression is necessary for liver differentiation during development. Collectively, data indicate that liver stem/progenitor cells follow their own rules and regulations. The same signals that are essential for their activation, expansion and differentiation are good candidates to contribute, under adequate conditions, to the paradigm of transformation from a pro-regenerative to a pro-tumorigenic role. From a clinical perspective, this is a fundamental issue for liver stem/progenitor cell-based therapies.

Ancient DNA of the extinct Lava shearwater (Puffinus olsoni) from the Canary Islands reveals incipient differentiation within the P. puffinus complex

The loss of species during the Holocene was, dramatically more important on islands than on continents. Seabirds from islands are very vulnerable to human-induced alterations such as habitat destruction, hunting and exotic predators. For example, in the genus Puffinus (family Procellariidae) the extinction of at least five species has been recorded during the Holocene, two of them coming from the Canary Islands.

Niche Differentiation and Fine-Scale Projections for Argentine Ants Based on Remotely Sensed Data

Modeling ecological niches of species is a promising approach for predicting the geographic potential of invasive species in new environments. Argentine ants (Linepithema humile) rank among the most successful invasive species: native to South America, they have invaded broad areas worldwide. Despite their widespread success, little is known about what makes an area susceptible - or not - to invasion. Here, we use a genetic algorithm approach to ecological niche modeling based on high-resolution remote-sensing data to examine the roles of niche similarity and difference in predicting invasions by this species. Our comparisons support a picture of general conservatism of the species' ecological characteristics, in spite of distinct geographic and community contexts

Biochemical differentiation between Ophidion Barbatum and o. Rochei (Pisces, Ophidiidae)

El gènere Ophidion esta representat al Mediterrani per dues espècies, 0. barbatum L. i O.rochei Müller. Són dues espècies molt similars en aspecte i difícils d'identificar només apartir dels seus caràcters morfològics externs. El treball descriu en primer lloc, i a partir de dades obtingudes per tècniques electroforètiques, alguns marcadors bioquímics que permetendiferenciar les dues espècies. En segon lloc, i a partir del càlcul de la 'Distància Genèticade Nei', es fa una estimació del temps de divergència entre O. barbatum i 0. rochei