Proyecto de climatización y producción de ACS en aparta-hotel de lujo

El presente proyecto tiene por objeto diseñar los sistemas de climatización de un grupo de Aparta-Hoteles y definir la instalación y máquinas a utilizar. Cada vivienda será climatizada de una manera diferente, para así estudiar y comparar la eficiencia de cada sistema. Además se pondrán de manifiesto los beneficios del uso de las tecnologías renovables (solar y biomasa) para aplicaciones domésticas, en especial de agua caliente sanitaria (ACS), a la vista de la legislación actual, la viabilidad económica y el impacto medioambiental. También se realizará una estimación de consumo y un estudio económico de cada vivienda, con ofertas reales de los diferentes proveedores de la maquinaria y equipos necesarios.Ingeniería Industria

Differential expression of PPP1R12A transcripts, including those harbouring alternatively spliced micro-exons, in placentae from complicated pregnancies

Introduction Placenta-associated pregnancy complications, including pre-eclampsia (PE) and intrauterine growth restriction (IUGR) are conditions postulated to originate from initial failure of placentation, leading to clinical sequelae indicative of endothelial dysfunction. Vascular smooth muscle aberrations have also been implicated in the pathogenesis of both disorders via smooth muscle contractility and relaxation mediated by Myosin Light Chain Phosphatase (MLCP) and the oppositional contractile action of Myosin Light Chain Kinase. PPP1R12A is a constituent part of the MLCP complex responsible for dephosphorylation of myosin fibrils. We hypothesize that alternative splicing of micro-exons result in isoforms lacking the functional leucine zipper (LZ) domain which may give those cells expressing these alternative transcripts a tendency towards contraction and vasoconstriction. Methods Expression was determined by qRT-PCR. Epigenetic profiling consisted of bisulphite-based DNA methylation analysis and ChIP for underlying histone modifications. Results We identified several novel transcripts with alternative micro-exon inclusion that would produce LZ- PPP1R12A protein. qRT-PCR revealed some isoforms, including the PPP1R12A canonical transcript, are differentially expressed in placenta biopsies from PE and IUGR samples compared to uncomplicated pregnancies. Discussion We propose that upregulation of PPP1R12A expression in complicated pregnancies may be due to enhanced promoter activity leading to increased transcription as a response to physiological stress in the placenta, which we show is independent of promoter DNA methylation

ADP-Ribosylation Factor 6 Expression and Activation Are Reduced in Myometrium in Complicated Pregnancies

ARF6 (ADP-ribosylation factor 6) small GTP binding protein plays critical roles in actin cytoskeleton rearrangements and membrane trafficking, including internalisation of G protein coupled receptors (GPCR). ARF6 operates by cycling between GDP-bound (inactive) and GTP-bound (active) forms and is a potential regulator of GPCR-mediated uterine activity during pregnancy and labour. ARF6 contains very low intrinsic GTP binding activity and depends on GEFs (guanine nucleotide exchange factors) such as CYTH3 (cytohesin 3) to bind GTP. ARF6 and CYTH3 were originally cloned from human placenta, but there is no information on their expression in other reproductive tissues.The expression of ARF6, ARF1, and CYTH1-4 was investigated by measuring mRNA (using RT-PCR) and protein levels (using immunoblotting) in samples of myometrium obtained from non-pregnant women, and women with normal pregnancies, before or after the spontaneous onset of labour. We also analysed myometrial samples from women with spontaneous preterm labour and from women with complicated pregnancies requiring emergency preterm delivery. The GST)-effector pull down assay was used to study the presence of active ARF6 and ARF1 in all myometrial extracts.ARF6, ARF1 and CYTH3 but not CYTH1, CYTH2 and CYTH4 were expressed in all samples and the levels did not change with pregnancy or labour. However, ARF6 and CYTH3 but not ARF1 levels were significantly reduced in complicated pregnancies. The alterations in the expression of ARF6 and its GEF in human myometrium indicate a potential involvement of this signalling system in modulating the response of myometrial smooth muscle in complicated pregnancies. The levels of ARF6-GTP or ARF1-GTP did not change with pregnancy or labour but ARF6-GTP levels were significantly decreased in women with severe complications of pregnancy.We have demonstrated a functional ARF6 system in human myometrium and a correlation between ARF6 level and activity in uterine and abnormal pregnancy

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

Altered Expression of Human Smooth Muscle Myosin Phosphatase Targeting (MYPT) Isovariants with Pregnancy and Labor

<div><p>Background</p><p>Myosin light-chain phosphatase is a trimeric protein that hydrolyses phosphorylated myosin II light chains (MYLII) to cause relaxation in smooth muscle cells including those of the uterus. A major component of the phosphatase is the myosin targeting subunit (MYPT), which directs a catalytic subunit to dephosphorylate MYLII. There are 5 main MYPT family members (MYPT1 (PPP1R12A), MYPT2 (PPP1R12B), MYPT3 (PPP1R16A), myosin binding subunit 85 MBS85 (PPP1R12C) and TIMAP (TGF-beta-inhibited membrane-associated protein (PPP1R16B)). Nitric oxide (NO)-mediated smooth muscle relaxation has in part been attributed to activation of the phosphatase by PKG binding to a leucine zipper (LZ) dimerization domain located at the carboxyl-terminus of PPP1R12A. In animal studies, alternative splicing of PPP1R12A can lead to the inclusion of a 31-nucleotide exonic segment that generates a LZ negative (LZ-) isovariant rendering the phosphatase less sensitive to NO vasodilators and alterations in PPP1R12ALZ- and LZ+ expression have been linked to phenotypic changes in smooth muscle function. Moreover, PPP1R12B and PPP1R12C, but not PPP1R16A or PPP1R16B, have the potential for LZ+/LZ- alternative splicing. Yet, by comparison to animal studies, the information on human MYPT genomic sequences/mRNA expressions is scant. As uterine smooth muscle undergoes substantial remodeling during pregnancy we were interested in establishing the patterns of expression of human MYPT isovariants during this process and also following labor onset as this could have important implications for determining successful pregnancy outcome.</p><p>Objectives</p><p>We used cross-species genome alignment, to infer putative human sequences not available in the public domain, and isovariant-specific quantitative PCR, to analyse the expression of mRNA encoding putative LZ+ and LZ- forms of PPP1R12A, PPP1R12B and PPP1R12C as well as canonical PPP1R16A and PPP1R16B genes in human uterine smooth muscle from non-pregnant, pregnant and in-labor donors.</p><p>Results</p><p>We found a reduction in the expression of PPP1R12A, PPP1R12BLZ+, PPP1R16A and PPP1R16B mRNA in late pregnancy (not-in-labor) relative to non-pregnancy. PPP1R12ALZ+ and PPP1R12ALZ- mRNA levels were similar in the non-pregnant and pregnant not in labor groups. There was a further reduction in the uterine expression of PPP1R12ALZ+, PPP1R12CLZ+ and PPP1R12ALZ- mRNA with labor relative to the pregnant not-in-labor group. PPP1R12A, PPP1R12BLZ+, PPP1R16A and PPP1R16B mRNA levels were invariant between the not in labor and in-labor groups.</p><p>Conclusions</p><p>MYPT proteins are crucial determinants of smooth muscle function. Therefore, these alterations in human uterine smooth muscle MYPT isovariant expression during pregnancy and labor may be part of the important molecular physiological transition between uterine quiescence and activation.</p></div

Exon map of ‘predicted’ human PPP1R12A, PPP1R12B and PPP1R12C LZ negative (LZ-) isovariants.

<p>The inferred LZ- exon maps, predicted amino acid and nucleotide sequences of the terminal exons of PPP1R12A, PPP1R12B and PPP1R12C (A-C) are displayed above.</p

Schematic representation of the exon map of mammalian PPP1R12A, PPP1R12B and PPP1R12C leucine zipper positive (LZ+) isovariants.

<p>A-C. The NCBI accession numbers, nucleotide sequence identity and exon map of known MYPT LZ positive isovariants are shown. Nucleotide and amino acid sequences depicting the 4-heptad leucine repeat within the carboxyl-terminal exons are also displayed above.</p

Human uterine PPP1R16A and PPP1R16B mRNA expression is decreased during pregnancy and in labor.

<p>PPP1R16A and PPP1R16B mRNA expression in non-pregnant (NP), pregnant not in labor (NIL) and in-labor (IL) myometrium were assessed using quantitative RT-PCR. The amount of individual MYPT mRNA in each sample was determined from human reference smooth muscle standard curve and quantified as mean fold change relative to an internal calibrator. PPP1R16A and PPP1R16B expression was significantly less in NIL and IL myometrium than in NP myometrium. PPP1R16A and PPP1R16B mRNA expression was similar in the NIL and IL groups. The bars represent mean, *p<0.05.</p

Details of donors used in this study.

<p>Details of donors used in this study.</p

Optimisation of primers directed against PPP1R12A, PPP1R12B, PPP1R12C, PPP1R16A and PPP1R16B isovariants.

<p>Panels above show PCR amplification and dissociation curves obtained for PPP1R12ALZ+, PPP1R12ALZ-, PPP1R12BLZ+, PPP1R12BLZ-, PPP1R12CLZ+, PPP1R12CLZ-, PPP1R16A and PPP1R16B Curves labelled A-E are representative of specific product formation obtained from human smooth muscle reference cDNA and human uterine cDNA samples. Similar curves were obtained for other positive controls including human skeletal and cardiac muscle samples. No specific products were obtained in reactions where the RT enzyme was excluded (RT-) or in water no template control (NTC) reactions. No specific products were obtained with PPP1R12BLZ- or PPP1R12CLZ- primer sets.</p