2 obras de Azpiazu y Lafita, en Madrid, España

<B>Block of flats</b> This building is devoted to residential flats, and has three and a half floor levels above the ground plus an attic, and a basement, garage and utility space below ground. The carefully tended garden, including a swimming pool, has been planned with elaborate simplicity: the best rooms of the building and the many balconies look out over this pleasant green space. This building is eminently functional and organic, and it has a formal elegance that is enhanced by the well chosen and valuable materials of which it is made. <b>Building of the offices of Laboratorios Liade, S. A. </b>This building has three floor levels and an attic, in addition to two basements. It is correctly designed for its function. It has a very diaphanous internal arrangement and is highly adaptable to the flexible needs, both present and future, for which it is built. It is expressed in careful and formal outlines by means of rich and durables materials of easy maintenance.<br><br><b>Edificio de viviendas</b> Está destinado a viviendas residenciales, disponiendo de tres plantas y media, más ático, utilizadas para este fin, y sótano para garaje, trastero e instalaciones. El cuidado jardín, con piscina, que rodea la edificación, ha sido tratado con depurada sencillez y al cual se abren las estancias más nobles de las viviendas y las pródigas terrazas. Caracterizan a la construcción su funcionalismo orgánico, la elegancia formal del bloque y los selectos y valiosos materiales utilizados en su construcción. <b>Edificio de oficinas de los Laboratorios Liade, S.A.</b> Este edificio organizado en tres plantas elevadas y ático, además de sótano y semisótano, presenta características idóneas a la función a que se destina, con distribución muy diáfana y adaptable a las necesidades flexibles del momento o futuras, cuidadas y puras líneas formales y materiales ricos y perdurables de fácil entretenimiento

Periscope Proteins are variable-length regulators of bacterial cell surface interactions

Changes at the cell surface enable bacteria to survive in dynamic environments, such as diverse niches of the human host. Here, we reveal “Periscope Proteins” as a widespread mechanism of bacterial surface alteration mediated through protein length variation. Tandem arrays of highly similar folded domains can form an elongated rod-like structure; thus, variation in the number of domains determines how far an N-terminal host ligand binding domain projects from the cell surface. Supported by newly available long-read genome sequencing data, we propose that this class could contain over 50 distinct proteins, including those implicated in host colonization and biofilm formation by human pathogens. In large multidomain proteins, sequence divergence between adjacent domains appears to reduce interdomain misfolding. Periscope Proteins break this “rule,” suggesting that their length variability plays an important role in regulating bacterial interactions with host surfaces, other bacteria, and the immune system

Domain shuffling of a highly mutable ligand-binding fold drives adhesin generation across the bacterial kingdom

\ua9 2023 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC. Bacterial fibrillar adhesins are specialized extracellular polypeptides that promote the attachment of bacteria to the surfaces of other cells or materials. Adhesin-mediated interactions are critical for the establishment and persistence of stable bacterial populations within diverse environmental niches and are important determinants of virulence. The fibronectin (Fn)-binding fibrillar adhesin CshA, and its paralogue CshB, play important roles in host colonization by the oral commensal and opportunistic pathogen Streptococcus gordonii. As paralogues are often catalysts for functional diversification, we have probed the early stages of structural and functional divergence in Csh proteins by determining the X-ray crystal structure of the CshB adhesive domain NR2 and characterizing its Fn-binding properties in vitro. Despite sharing a common fold, CshB_NR2 displays an ~1.7-fold reduction in Fn-binding affinity relative to CshA_NR2. This correlates with reduced electrostatic charge in the Fn-binding cleft. Complementary bioinformatic studies reveal that homologues of CshA/B_NR2 domains are widely distributed in both Gram-positive and Gram-negative bacteria, where they are found housed within functionally cryptic multi-domain polypeptides. Our findings are consistent with the classification of Csh adhesins and their relatives as members of the recently defined polymer adhesin domain (PAD) family of bacterial proteins

Anaerobic removal of 1-methoxy-2-propanol under ambient temperature in an EGSB reactor

Two laboratory-scale expanded granular sludge bed (EGSB) reactors were operated at 18 and 25 C, respectively, for the treatment of synthetic wastewater composed of ethanol and 1-methoxy-2-propanol (M2P) in a mass ratio of 4:1. Reactors were operated first with continuous wastewater supply and after with discontinuous substrate supply (5 days a week, 16 h a day) to simulate shift working conditions. Under continuous wastewater supply chemical oxygen demand (COD), removal efficiency higher than 95 % was achieved at the end of the trial applying organic loading rates (OLR) of 29 and 43 kg COD m-3 day-1 at 18 and 25 C; thus, corresponding to M2P OLR of 6.4 and 9.3 kg COD m-3 day-1, respectively. During intermittent supply of substrate, good performance was recorded at both temperatures with an OLR of 30 kg COD m-3 day-1 (M2P OLR of 6.6 kg COD m-3 day-1). After 56 h without substrate supply, a decline in methane yield of 15¿30 % was observed due to the deactivation of the biomass. Specific methanogenic activity (SMA) assays were carried out at the end of the experiments. SMA values using 1-methoxy-2-propanol as substrate were 24.3 and 7.8 ml CH4 gVSS-1 day-1 at 25 C and at 18 C, respectively. This is the first attempt to investigate the removal of 1-methoxy-2-propanol by EGSB reactors

ODZ1 allows glioblastoma to sustain invasiveness through a Myc-dependent transcriptional upregulation of RhoA

Long-term survival remains low for most patients with glioblastoma (GBM), which reveals the need for markers of disease outcome and novel therapeutic targets. We describe that ODZ1 (also known as TENM1), a type II transmembrane protein involved in fetal brain development, plays a crucial role in the invasion of GBM cells. Differentiation of glioblastoma stem-like cells drives the nuclear translocation of an intracellular fragment of ODZ1 through proteolytic cleavage by signal peptide peptidase-like 2a. The intracellular fragment of ODZ1 promotes cytoskeletal remodelling of GBM cells and invasion of the surrounding environment both in vitro and in vivo. Absence of ODZ1 by gene deletion or downregulation of ODZ1 by small interfering RNAs drastically reduces the invasive capacity of GBM cells. This activity is mediated by an ODZ1-triggered transcriptional pathway, through the E-box binding Myc protein, that promotes the expression and activation of Ras homolog family member A (RhoA) and subsequent activation of Rho-associated, coiled-coil containing protein kinase (ROCK). Overexpression of ODZ1 in GBM cells reduced survival of xenografted mice. Consistently, analysis of 122 GBM tumour samples revealed that the number of ODZ1-positive cells inversely correlated with overall and progression-free survival. Our findings establish a novel marker of invading GBM cells and consequently a potential marker of disease progression and a therapeutic target in GBM

p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes

It has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems. To investigate the roles of p21 in transcriptional control, we studied the gene expression changes in two human cell systems. Using a human leukemia cell line (K562) with inducible p21 expression and human primary keratinocytes with adenoviral-mediated p21 expression, we carried out microarray-based gene expression profiling. We found that p21 rapidly and strongly repressed the mRNA levels of a number of genes involved in cell cycle and mitosis. One of the most strongly down-regulated genes was CCNE2 (cyclin E2 gene). Mutational analysis in K562 cells showed that the N-terminal region of p21 is required for repression of gene expression of CCNE2 and other genes. Chromatin immunoprecipitation assays indicated that p21 was bound to human CCNE2 and other p21-repressed genes gene in the vicinity of the transcription start site. Moreover, p21 repressed human CCNE2 promoter-luciferase constructs in K562 cells. Bioinformatic analysis revealed that the CDE motif is present in most of the promoters of the p21-regulated genes. Altogether, the results suggest that p21 exerts a repressive effect on a relevant number of genes controlling S phase and mitosis. Thus, p21 activity as inhibitor of cell cycle progression would be mediated not only by the inhibition of CDKs but also by the transcriptional down-regulation of key genes

Fisiología y fisiopatología ósea

El tejido óseo es uno de los mayores del organismo, con funciones claras: servir de soporte y protección de las partes blandas, sustento del movimiento con el anclaje de los músculos, reservorio de minerales y almacén interactivo de la médula ósea. Para ejercer todas estas funciones el hueso debe mantener su calidad, concepto en el que se integran tanto su grado de mineralización como la microarquitectura y la capacidad de restaurar las lesiones, aspectos que se recogen en la definición amplia de osteoporosis: ¿Una enfermedad sistémica del esqueleto, caracterizada por una baja masa ósea y un deterioro de la microarquitectura del tejido óseo, que comportan un aumento de la fragilidad del hueso y el consecuente incremento del riesgo de fracturas¿, si bien desde el punto de vista clínico es necesario centrarnos en la mineralización, aspecto cuantificable, entendiendo como osteoporosis un descenso de la masa ósea mayor de 2,5 desviaciones estándar inferior a la de las pacientes jóvenes sanas. En el artículo se revisan los aspectos fisiopatológicos que influyen en el desarrollo de este frecuente cuadro clínico