La apertura de Gijón al futuro: La revisión limitada del Catálogo Monumental

[EN] Gijón, also known as Xixón, is an important city that rivals Oviedo, the historical capital of the Autonomous Region and Principality of Asturias (Spain), in historical demographic and economic terms. It has traditionally been a port and, more recently, an industrial city, which experienced very rapid population growth and with little planning. After the industrial crisis of the 80s, the city wanted to become a tourist location more than an industrial harbor. Both its privileged location and the historical urban heritage that still remain are corner stones to make this change possible. However, the late and strict legislation (improvised to protect the last remains of a previously uncontrolled development) impeded a necessary urban re-design in order to shelter the new touristic supplies. This paper proposes some urban solutions to selectively modify the catalogue according with the cultural and touristic potentials of the city. These solutions were agreed by the working group set up by Gijón City Council and ERDU (Estudio de Renovación y Desarrollos Urbanos -Urban Renovation and Development Studio).[ES] Gijón, también conocida como Xixón, es una ciudad importante que rivaliza con Oviedo, la capital histórica de la Comunidad Autónoma y Principado de Asturias (España), en términos demográficos y económicos históricos. Ha sido tradicionalmente un puerto y, más recientemente, una ciudad industrial, que experimentó un crecimiento muy rápido de la población y con poca planificación. Después de la crisis industrial de los años 80, la ciudad quería llegar a ser un lugar turístico más de un puerto industrial. Tanto su ubicación privilegiada como lo que se conserva de su rico patrimonio histórico, son piedras angulares para hacer posible este cambio. Sin embargo, la legislación tardía y estricta (improvisada para proteger los últimos restos de un desarrollo incontrolado anterior) impidió un re-diseño urbano necesario para albergar a los nuevos suministros turísticos. Este documento propone algunas soluciones urbanas para modificar selectivamente el catálogo de acuerdo con los potenciales culturales y turísticos de la ciudad. Estas soluciones fueron acordados por el grupo de trabajo creado por el AyuntamientoLatorre, J.; Sola, J. (2016). Opening Gijón to Future: The Limited Revision of the Official Urban Catalogue. VLC arquitectura. Research Journal. 3(2):149-172. doi:10.4995/vlc.2016.5747.SWORD14917232Ábalos, I-aki. Naturaleza y artificio. El ideal pintoresco en la arquitectura y el paisajismo contemporáneos. Barcelona: Gustavo Gili, 2009.Ayús y Rubio, Manuel. Régimen Jurídico de los Entornos de Protección de los Bienes de Interés Cultural. Alicante: Universidad de Alicante, 2013.Bermúdez Sánchez, Javier, El derecho de propiedad: límites derivados de la protección arqueológica. Editorial Madrid: Montecorvo SA., 2003.Calles Oyarbide, I-igo and Álvarez Areces, Miguel Ángel. Paisajes de la industrialización asturiana. Gijón: Editorial TREA y Principado de Asturias, 2009.Cortina Frade, Isidoro. Catálogo histórico y monumental de Gijón: San Julián de Lavandera, San Juan de Fano y Santa Eulalia de Baldornón. Oviedo: Ayuntamiento de Oviedo, 1981.García García, María Jesús. La conservación de los inmuebles históricos a través de técnicas urbanísticas y rehabilitadoras. Pamplona: Editorial Aranzadi, 2000.González-Varas Ibá-ez, Santiago. La rehabilitación urbanística. Pamplona: Editorial Aranzadi, 1998.Llordén Mi-ambres, Moisés. The Economic and Urban Development of Gijón in the 19th and 20th centuries. Oviedo: Universidad de Oviedo, 1994.Pi-era, Luis Miguel. Las calles de Gijón. Historia de sus nombres. Gijón: Ayuntamiento de Gijón, 2005.Sánchez Mesa Martínez, Leonardo. La restauración inmobiliaria en la regulación del patrimonio histórico. Pamplona: Editorial Aranzadi, 2004.Sendín García, Manuel Ángel. Las transformaciones en el paisaje urbano de Gijón (1834-1939). Oviedo: Real Instituto de Estudios Asturianos, 1995

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Indexing the Pseudomonas specialized metabolome enabled the discovery of poaeamide B and the bananamides

Pseudomonads are cosmopolitan microorganisms able to produce a wide array of specialized metabolites. These molecules allow Pseudomonas to scavenge nutrients, sense population density and enhance or inhibit growth of competing microorganisms. However, these valuable metabolites are typically characterized one-molecule–one-microbe at a time, instead of being inventoried in large numbers. To index and map the diversity of molecules detected from these organisms, 260 strains of ecologically diverse origins were subjected to mass-spectrometry-based molecular networking. Molecular networking not only enables dereplication of molecules, but also sheds light on their structural relationships. Moreover, it accelerates the discovery of new molecules. Here, by indexing the Pseudomonas specialized metabolome, we report the molecular-networking-based discovery of four molecules and their evolutionary relationships: a poaeamide analogue and a molecular subfamily of cyclic lipopeptides, bananamides 1, 2 and 3. Analysis of their biosynthetic gene cluster shows that it constitutes a distinct evolutionary branch of the Pseudomonas cyclic lipopeptides. Through analysis of an additional 370 extracts of wheat-associated Pseudomonas, we demonstrate how the detailed knowledge from our reference index can be efficiently propagated to annotate complex metabolomic data from other studies, akin to the way in which newly generated genomic information can be compared to data from public databases

Validation of the spanish version of the multiple sclerosis international quality of life (musiqol) questionnaire

<p>Abstract</p> <p>Background</p> <p>The Multiple Sclerosis International Quality Of Life (MusiQoL) questionnaire, a 31-item, multidimensional, self-administrated questionnaire that is available in 14 languages including Spanish, has been validated using a large international sample. We investigated the validity and reliability of the Spanish version of MusiQoL in Spain.</p> <p>Methods</p> <p>Consecutive patients with different types and severities of multiple sclerosis (MS) were recruited from 22 centres across Spain. All patients completed the MusiQoL questionnaire, the 36-Item Short Form (SF-36) health survey, and a symptoms checklist at baseline and 21 days later. External validity, internal consistency, reliability and reproducibility were tested.</p> <p>Results</p> <p>A total of 224 Spanish patients were evaluated. Dimensions of MusiQoL generally demonstrated a high internal consistency (Cronbach's alpha: 0.70-0.92 for all but two MusiQoL domain scores). External validity testing revealed that the MusiQoL index score correlated significantly with all SF-36 dimension scores (Pearson's correlation: 0.46-0.76), reproducibility was satisfactory (intraclass correlation coefficient: 0.60-0.91), acceptability was high, and the time taken to complete the 31-item questionnaire was reasonable (mean [standard deviation]: 9.8 [11.8] minutes).</p> <p>Conclusions</p> <p>The Spanish version of the MusiQoL questionnaire appears to be a valid and reliable instrument for measuring quality of life in patients with MS in Spain and constitutes a useful instrument to measure health-related quality of life in the clinical setting.</p

Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal

The canonical Wnt/β-catenin signaling pathway governs diverse developmental, homeostatic and pathologic processes. Palmitoylated Wnt ligands engage cell surface Frizzled (Fzd) receptors and Lrp5/6 co-receptors enabling β-catenin nuclear translocation and Tcf/Lef-dependent gene transactivation1–3. Mutations in Wnt downstream signaling components have revealed diverse functions presumptively attributed to Wnt ligands themselves, although direct attribution remains elusive, as complicated by redundancy between 19 mammalian Wnts and 10 Fzds1 and Wnt hydrophobicity2,3. For example, individual Wnt ligand mutations have not revealed homeostatic phenotypes in the intestinal epithelium4, an archetypal canonical Wnt pathway-dependent rapidly self-renewing tissue whose regeneration is fueled by proliferative crypt Lgr5+ intestinal stem cells (ISCs)5–9. R-spondin ligands (Rspo1–4) engage distinct Lgr4-6 and Rnf43/Znrf3 receptor classes10–13, markedly potentiate canonical Wnt/β-catenin signaling and induce intestinal organoid growth in vitro and Lgr5+ ISCs in vivo8,14–17. However, the interchangeability, functional cooperation and relative contributions of Wnt versus Rspo ligands to in vivo canonical Wnt signaling and ISC biology remain unknown. Here, we deconstructed functional roles of Wnt versus Rspo ligands in the intestinal crypt stem cell niche. We demonstrate that the default fate of Lgr5+ ISCs is lineage commitment, escape from which requires both Rspo and Wnt ligands. However, gain-of-function studies using Rspo versus a novel non-lipidated Wnt analog reveal qualitatively distinct, non-interchangeable roles for these ligands in ISCs. Wnts are insufficient to induce Lgr5+ ISC self-renewal, but rather confer a basal competency by maintaining Rspo receptor expression that enables Rspo to actively drive and specify the extent of stem cell expansion. This functionally non-equivalent yet cooperative interplay between Wnt and Rspo ligands establishes a molecular precedent for regulation of mammalian stem cells by distinct priming and self-renewal factors, with broad implications for precision control of tissue regeneration

Profiling Early Lung Immune Responses in the Mouse Model of Tuberculosis

Tuberculosis (TB) is caused by the intracellular bacteria Mycobacterium tuberculosis, and kills more than 1.5 million people every year worldwide. Immunity to TB is associated with the accumulation of IFNγ-producing T helper cell type 1 (Th1) in the lungs, activation of M.tuberculosis-infected macrophages and control of bacterial growth. However, very little is known regarding the early immune responses that mediate accumulation of activated Th1 cells in the M.tuberculosis-infected lungs. To define the induction of early immune mediators in the M.tuberculosis-infected lung, we performed mRNA profiling studies and characterized immune cells in M.tuberculosis-infected lungs at early stages of infection in the mouse model. Our data show that induction of mRNAs involved in the recognition of pathogens, expression of inflammatory cytokines, activation of APCs and generation of Th1 responses occurs between day 15 and day 21 post infection. The induction of these mRNAs coincides with cellular accumulation of Th1 cells and activation of myeloid cells in M.tuberculosis-infected lungs. Strikingly, we show the induction of mRNAs associated with Gr1+ cells, namely neutrophils and inflammatory monocytes, takes place on day 12 and coincides with cellular accumulation of Gr1+ cells in M.tuberculosis-infected lungs. Interestingly, in vivo depletion of Gr1+ neutrophils between days 10–15 results in decreased accumulation of Th1 cells on day 21 in M.tuberculosis-infected lungs without impacting overall protective outcomes. These data suggest that the recruitment of Gr1+ neutrophils is an early event that leads to production of chemokines that regulate the accumulation of Th1 cells in the M.tuberculosis-infected lungs

Beyond comparisons of means: understanding changes in gene expression at the single-cell level

Traditional differential expression tools are limited to detecting changes in overall expression, and fail to uncover the rich information provided by single-cell level data sets. We present a Bayesian hierarchical model that builds upon BASiCS to study changes that lie beyond comparisons of means, incorporating built-in normalization and quantifying technical artifacts by borrowing information from spike-in genes. Using a probabilistic approach, we highlight genes undergoing changes in cell-to-cell heterogeneity but whose overall expression remains unchanged. Control experiments validate our method’s performance and a case study suggests that novel biological insights can be revealed. Our method is implemented in R and available at https://github.com/catavallejos/BASiCS

Elevated levels of endothelial-derived microparticles, and serum CXCL9 and SCGF-β are associated with unstable asymptomatic carotid plaques.

Endothelial microparticles (EMPs) are released from dysfunctional endothelial cells. We hypothesised that patients with unstable carotid plaque have higher levels of circulating microparticles compared to patients with stable plaques, and may correlate with serum markers of plaque instability and inflammation. Circulating EMPs, platelet MPs (PMPs) and inflammatory markers were measured in healthy controls and patients undergoing carotid endarterectomy. EMP/PMPs were quantified using flow cytometry. Bioplex assays profiled systemic inflammatory and bone-related proteins. Immunohistological analysis detailed the contribution of differentially-regulated systemic markers to plaque pathology. Alizarin red staining showed calcification. EMPs and PMPs were significantly higher in patients with carotid stenosis (≥70%) compared to controls, with no differences between asymptomatic vs symptomatic patients. Asymptomatic patients with unstable plaques exhibited higher levels of EMPs, CXCL9 and SCGF-β compared to those with stable plaques. CXCL9, and SCGF-β were detected within all plaques, suggesting a contribution to both localised and systemic inflammation. Osteopontin and osteoprotegerin were significantly elevated in the symptomatic vs asymptomatic group, while osteocalcin was higher in asymptomatic patients with stable plaque. All plaques exhibited calcification, which was significantly greater in asymptomatic patients. This may impact on plaque stability. These data could be important in identifying patients at most benefit from intervention