Arquitectura para las Estrellas Michelin en España

[EN] This Final Project will try deepening the understudied relationship between the gastronomical experiences with the architectural atmosphere. From the phenomenological point of view as well as the different levels of architectural experience: environment, architecture, and interior design; this project will study three concrete cases of Estrella Michelin restaurants in Spain proposing the basis of the relationship between architecture and the dining experience. We will see how each restaurant tries to create a unique gastronomical experience in relation to the personality of the chef, the architecture and the interior design of the restaurant. In conclusion we will see how the architecture of the restaurant exhorts the dining experience.[ES] Con este trabajo de Final de Grado se pretende profundizar en la relación todavía poco estudiada de la experiencia gastronómica con el ambiente arquitectónico. Atendiendo, desde la fenomenología, a los niveles de experiencia arquitectónica: entorno, arquitectura e interiorismo, se analizarán tres casos concretos de restaurantes con Estrellas Michelin en España para proponer unas bases y estudiar la relación entre arquitectura y gastronomía. Se verá cómo cada restaurante trata de crear una experiencia gastronómica única, relacionando la personalidad del chef con la arquitectura y el interiorismo. Se sacarán, finalmente, unas conclusiones sobre la ampliación que aporta la arquitectura del restaurante a la experiencia gastronómica.Roso Mares, J. (2016). Arquitectura para las Estrellas Michelin en España. http://hdl.handle.net/10251/95222TFG

Intron Evolution: Testing Hypotheses of Intron Evolution Using the Phylogenomics of Tetraspanins

BACKGROUND: Although large scale informatics studies on introns can be useful in making broad inferences concerning patterns of intron gain and loss, more specific questions about intron evolution at a finer scale can be addressed using a gene family where structure and function are well known. Genome wide surveys of tetraspanins from a broad array of organisms with fully sequenced genomes are an excellent means to understand specifics of intron evolution. Our approach incorporated several new fully sequenced genomes that cover the major lineages of the animal kingdom as well as plants, protists and fungi. The analysis of exon/intron gene structure in such an evolutionary broad set of genomes allowed us to identify ancestral intron structure in tetraspanins throughout the eukaryotic tree of life. METHODOLOGY/PRINCIPAL FINDINGS: We performed a phylogenomic analysis of the intron/exon structure of the tetraspanin protein family. In addition, to the already characterized tetraspanin introns numbered 1 through 6 found in animals, three additional ancient, phase 0 introns we call 4a, 4b and 4c were found. These three novel introns in combination with the ancestral introns 1 to 6, define three basic tetraspanin gene structures which have been conserved throughout the animal kingdom. Our phylogenomic approach also allows the estimation of the time at which the introns of the 33 human tetraspanin paralogs appeared, which in many cases coincides with the concomitant acquisition of new introns. On the other hand, we observed that new introns (introns other than 1-6, 4a, b and c) were not randomly inserted into the tetraspanin gene structure. The region of tetraspanin genes corresponding to the small extracellular loop (SEL) accounts for only 10.5% of the total sequence length but had 46% of the new animal intron insertions. CONCLUSIONS/SIGNIFICANCE: Our results indicate that tests of intron evolution are strengthened by the phylogenomic approach with specific gene families like tetraspanins. These tests add to our understanding of genomic innovation coupled to major evolutionary divergence events, functional constraints and the timing of the appearance of evolutionary novelty

<i>Lkb1</i> Loss Promotes Tumor Progression of BRAF^V600E-Induced Lung Adenomas

<div><p>Aberrant activation of MAP kinase signaling pathway and loss of tumor suppressor LKB1 have been implicated in lung cancer development and progression. Although oncogenic KRAS mutations are frequent, BRAF mutations (BRAF^V600E) are found in 3% of human non-small cell lung cancers. Contrary to KRAS mutant tumors, BRAF^V600E-induced tumors are benign adenomas that fail to progess. Interestingly, loss of tumor supressor LKB1 coexists with KRAS oncogenic mutations and synergizes in tumor formation and progression, however, its cooperation with BRAF^V600E oncogene is unknown. Our results describe a lung cell population in neonates mice where expression of BRAF^V600E leads to lung adenoma development. Importantly, expression of BRAF^V600E concomitant with the loss of only a single-copy of Lkb1, overcomes senencence–like features of BRAF^V600E-mutant adenomas leading malignization to carcinomas. These results posit LKB1 haploinsufficiency as a risk factor for tumor progression of BRAF^V600E mutated lung adenomas in human cancer patients.</p></div

Commensal Cutibacterium acnes induce epidermal lipid synthesis important for skin barrier function.

Lipid synthesis is necessary for formation of epithelial barriers and homeostasis with external microbes. An analysis of the response of human keratinocytes to several different commensal bacteria on the skin revealed that Cutibacterium acnes induced a large increase in essential lipids including triglycerides, ceramides, cholesterol, and free fatty acids. A similar response occurred in mouse epidermis and in human skin affected with acne. Further analysis showed that this increase in lipids was mediated by short-chain fatty acids produced by Cutibacterium acnes and was dependent on increased expression of several lipid synthesis genes including glycerol-3-phosphate-acyltransferase-3. Inhibition or RNA silencing of peroxisome proliferator-activated receptor-α (PPARα), but not PPARβ and PPARγ, blocked this response. The increase in keratinocyte lipid content improved innate barrier functions including antimicrobial activity, paracellular diffusion, and transepidermal water loss. These results reveal that metabolites from a common commensal bacterium have a previously unappreciated influence on the composition of epidermal lipids

Percentage of mice developing adenomas and adenocarcinomas.

<p>Hematoxylin and eosin staining of histological sections showing lung hyperplasia in Tyr::<i>Cre</i>^ERT2; <i>Braf^CA/+</i>; <i>Lkb1</i>^flox/+ (<b>A</b>, <b>B</b>) and CMV-<i>Cre</i>^T/+; <i>Kras</i>^+/LSLG12Vgeo mice (<b>J</b>, <b>K</b>). Higher magnification is showed in (<b>B</b>, <b>K</b>). Papillary adenomas developed in Tyr::<i>Cre</i>^ERT2; <i>Braf^CA/+</i>; <i>Lkb1</i>^flox/+ (<b>C</b>, <b>D</b>) and mixed papillary and solid adenomas developed in CMV-<i>Cre</i>^T/+; <i>K-ras</i>^+/LSLG12Vgeo (<b>L</b>, <b>M</b>). Note <b>C</b> and <b>L</b> tumors in higher magnification (<b>D</b>, <b>M</b>). Tyr::<i>Cre</i>^ERT2; <i>Braf^CA/+</i>; <i>Lkb1</i>^flox/+ adenocarcinoma (<b>E</b>) showing papillary (<b>F</b>) and solid (<b>G</b>) regions. Tyr::<i>Cre</i>^ERT2; <i>Braf^CA/+</i>; <i>Lkb1</i>^flox/+ adenocarcinoma showing intra bronchiolar tumor growth (*) (<b>H</b>). Higher magnification showing different cells populations in <b>H.</b> Atypical cells with nuclear hyperchromasia, and contour irregularities (*), cells showed enlarged nuclei displaying prominent nucleoli (**) and cells with hyperchromatic fusiform nuclei (arrows). CMV-<i>Cre</i>^T/+; <i>Kras</i>^+/LSLG12Vgeo adenomas and adenocarcinomas (<b>N</b>). Detail of solid (<b>O</b>) and mucinous (<b>P</b>) tumors. Dashed-lined squares indicate magnified areas. Bars 800 µm (<b>A</b>, <b>C</b>, <b>D</b>, <b>J</b>, <b>L</b> and <b>N</b>), 500 µm (<b>E</b>), 200 µm (<b>K</b>, <b>M</b>, <b>O</b> and <b>P</b>) and 100 µm (<b>B</b>, <b>D</b>, <b>F</b>, <b>G</b> and <b>I</b>).</p

Neonatal activation of BRAF^V600E through the expression of Tyr::<i>Cre</i>^ERT2 upon 4OHTx treatment drives aberrant proliferation of lung cells.

<p>(<b>A</b>) Schematic representation of mouse treatment and expressed proteins. (<b>B</b>) Representative images of Cre-recombinase staining in 4-days-old wild type (WT, n = 3) and Tyr::<i>Cre</i>^ERT2; <i>Braf^CA/+</i> (n = 3) mice lungs treated with 4OHTx. Bars 80 µm. (<b>C</b>) Anti-p-ERK1/2 staining of untreated (−4OHTx) and treated (+4OHTx) 4-days-old Tyr::<i>Cre</i>^ERT2; <i>Braf^CA/+</i> mice lungs. (<b>D</b>) Schematic representation of the genetic strategy to identify tyrosinase-promoter driven Cre-recombinase lung expressing cells. Representative images of EYFP, SP-C and CC10 expressing cells in Tyr::<i>Cre</i>^ERT2;ROSA-lsl-<i>EYFP</i> mice 3 days after 4OHTx treatment (n = 3 mice) are shown. Bars 80 µm. (<b>E</b>) Ki67 staining of histologically normal lungs in 8-days-old mice showed increased proliferation index in 4OHTx treated Tyr::<i>Cre</i>^ERT2; <i>Braf^CA/+</i> mice compared to untreated. Bars 500 µm. Quantification of samples is shown below. 20X fields (n = 8 and n = 11 from 3 different untreated and 4OHTx treated mice respectively) were quantified. <i>p</i>-value was calculated performing Mann-Whitney’s test.</p

Percentage of mice developing lung adenomas (L. adenomas) or lung adenocarcinomas (L. carcinomas) according to their genotype and treatment (4OHTx).

<p>Percentage of mice developing lung adenomas (L. adenomas) or lung adenocarcinomas (L. carcinomas) according to their genotype and treatment (4OHTx).</p

Immunostaining of histological sections of Tyr::<i>Cre</i>^ERT2; <i>Braf^CA/+</i> and CMV-<i>Cre</i>^T/+; <i>Kras</i>^+/LSLG12Vgeo adenomas (<i>Kras</i>^+/LSLG12Vgeo 6 months) and Tyr::<i>Cre</i>^ERT2; <i>Braf^CA/+</i>; <i>Lkb1</i>^flox/+ and CMV-<i>Cre</i>^T/+; <i>Kras</i>^+/LSLG12Vgeo adenocarcinomas (<i>Kras</i>^+/LSLG12Vgeo 11 months) with CC10, SP-C, E-Cadherin, Ki67, p53 and LKB1 antibodies.

<p>(*) indicates airways. Bars 500 µm and 80 µm for magnifications.</p