BUSCADOR RECOLECTA

This article looks at the way culture is represented in 3 commonly used course books of Dutch as a foreign language. According to the author, everyday culture of the regions where Dutch is spoken, is presented from a nationalistic point of view, i.e. it is limited to either cultural, historical and social aspects of The Netherlands or cultural, historical and social aspects of the Flemish Community in Belgium. The existence of the other region or country where the same language is spoken is not...

Mutations in DKC1, NOP10, and TINF2 genes, coding for proteins in telomerase and shelterin complexes, are responsible for diverse diseases known as telomeropathies and ribosomopathies, including dyskeratosis congenita (DC, ORPHA 1775). These genes contribute to the DC phenotype through mechanisms that are not completely understood. We previously demonstrated in models of DC that oxidative stress is an early and independent event that occurs prior to telomere shortening. To clarify the...

Previous research suggests a potential involvement of the cytokine LIGHT (TNFSF14) in atherosclerosis. In this study, the genetic inactivation of Light in Apolipoprotein E deficient mice (male and female C57BL) augmented plaque size and vulnerability while decreasing Treg cells. Human and mouse transcriptomic results demonstrated deranged immune pathways in human atheromas with low LIGHT expression levels and in Light-deficient murine atheromas. In agreement with this, in vitro LIGHT-treatment...

BACKGROUND AND AIMS: The stiffening of the extracellular matrix, and changes in its cellular and molecular composition, have been reported in the pathogenesis of fibrosis. We analyze the mechanisms that perpetuate ileal fibrosis in surgical resections of complicated Crohn's disease patients. METHODS: Ileal resections were obtained from affected and non-affected tissue of stenotic or penetrating Crohn's disease behavior. Ilea from non-IBD patients were used as control tissue. All...

The medical use of nitroglycerin (GTN) is limited by patient tolerance. The present study evaluated the role of mitochondrial Complex I in GIN biotransformation and the therapeutic effect of mitochondrial antioxidants. The development of GIN tolerance (in rat and human vessels) produced a decrease in mitochondrial 02 consumption. Co-incubation with the mitochondria-targeted antioxidant mitoquinone (MQ 10(-6) mol/L) or with glutathione ester (GEE, 10(-4) mol/L) blocked GTN tolerance and the...

Response to hyperosmotic stress in the yeast Saccharomyces cerevisiae involves the participation of the general stress response mediated by Msn2/4 transcription factors and the HOG pathway. One of the transcription factors activated through this pathway is Hot1, which contributes to the control of the expression of several genes involved in glycerol synthesis and flux, or in other functions related to adaptation to adverse conditions. This work provides new data about the interaction mechanism...

BCL2 family proteins are important regulators of mitochondrial outer membrane permeabilization (MOMP). In recent years, BCL2 family proteins have also been linked to the regulation of mitochondrial bioenergetics and dynamics. Given their overexpression in breast cancer cells, we sought to explore whether two key members of this family, BCL2 and BCL(X)L impacted on mitochondrial fusion/fission processes. By employing a single cell imaging and RNA sequencing we found that overexpression of BCL2...

Background: Eukaryotic cells have a continuous transit of macromolecules between the cytoplasm and the nucleus. Several carrier proteins are involved in this transport. One of them is importin alpha, which must form a complex with importin beta to accomplish its function, by domain-swapping its 60-residue-long N terminus. There are several human isoforms of importin alpha; among them, importin alpha 3 has a particularly high flexibility. Methods: We studied the conformational stability of...

Intrinsically disordered proteins (IDPs) explore diverse conformations in their free states and, a few of them, also in their molecular complexes. This functional plasticity is essential for the function of IDPs, although their dynamics in both free and bound states is poorly understood. NUPR1 is a protumoral multifunctional IDP, activated during the acute phases of pancreatitis. It interacts with DNA and other IDPs, such as prothymosin alpha (ProT alpha), with dissociation constants of similar...

Background: The p53, p63 and p73 proteins belong to the p53 family of transcription factors, playing key roles in tumour suppression. The alpha-splice variant of p73 (p73 alpha) has at its C terminus a sterile alpha motif (SAM); this domain, SAMp73, formed by five helices (alpha 1 to alpha 5), is thought to mediate in protein-protein interactions. The E3-ligase MDM2 binds to p73 at its N terminus transactivation domain (TA), but it does not promote its degradation via ubiquitination; however,...

Background: NUPR1 is a multifunctional intrinsically disordered protein (IDP) involved, among other functions, in chromatin remodelling, and development of pancreatic ductal adenocarcinoma (PDAC). It interacts with several biomolecules through hydrophobic patches around residues A1a33 and Thr68. The drug trifluoperazine (TFP), which hampers PDAC development in xenografted mice, also binds to those regions. Because of the large size of the hot-spot interface of NUPR1, small molecules could not...

Plakophilin 1 (PKP1), a member of the armadillo repeat family of proteins, is a key structural component of cellcell adhesion scaffolds, although it can also be found in other cell locations, including the cytoplasm and the nucleus. PADI4 (peptidyl-arginine deiminase 4) is one of the human isoforms of a family of enzymes engaged in the conversion of arginine to citrulline, and is present in monocytes, macrophages, granulocytes, and in several types of cancer cells. It is the only family member...

Background and aims: The stiffening of the extracellular matrix, and changes in its cellular and molecular composition, have been reported in the pathogenesis of fibrosis. We analyze the mechanisms that perpetuate ileal fibrosis in surgical resections of complicated Crohn's disease patients.Methods: Ileal resections were obtained from affected and non-affected tissue of stenotic or penetrating Crohn's disease behavior. Ilea from non-IBD patients were used as control tissue. All...

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by disrupted immune function. Indeed, gut microbiota dysbiosis and metabolomic profile alterations, are hallmarks of IBD. In this scenario, metabolite-sensing G-protein coupled receptors (GPCRs), involved in several biological processes, have emerged as pivotal players in the pathophysiology of IBD. The aim of this study was to characterize the axis microbiota-metabolite-GPCR in...

A highly prevalent IgE-binding protein band of 28kDa is observed when Salsola kali pollen extract is incubated with individual sera from Amaranthaceae pollen sensitized patients. By an immunoproteomic analysis of S. kali pollen extract, we identified this protein band as an allergenic polygalacturonase enzyme. The allergen, named Sal k 6, exhibits a pI of 7.14 and a molecular mass of 39,554.2Da. It presents similarities to Platanaceae, Poaceae, and Cupressaceae allergenic...

Signat a la ciutat de Barcelona el 31-10-2001 per Joan Clos, alcalde de Barcelona, assistit pel secretari general de l'Ajuntament, Francesc Lliset i Borrell, i per Zhou Muyao, vicealcalde de Xangai, Digitalitzat per la Direcció de Relacions Internacionals

Low-density lipoprotein (LDL) binding to arterial proteoglycans initiates LDL retention and modification in the arterial wall, triggering atherosclerosis. The details of this binding, its effectors, and its ramifications are incompletely understood. We combined heparin affinity chromatography with biochemical, spectroscopic and electron microscopic techniques to show that brief binding to heparin initiates irreversible pro-atherogenic remodeling of human LDL. This involved decreased structural...

Mimetic peptides are promising therapeutic agents for atherosclerosis prevention. A 10-residue class G* peptide from apolipoprotein J (apoJ), namely, D-[113-122]apoJ, possesses anti-inflammatory and anti-atherogenic properties. This prompted us to determine its effect on the aggregation process of low-density lipoprotein (LDL) particles, an early event in the development of atherosclerosis. LDL particles with and without [113-122]apoJ peptide were incubated at 37 degrees C with sphingomyelinase...

Aggregated LDL is the first ligand reported to interact with the cluster II CR9 domain of low-density lipoprotein receptor-related protein 1 (LRP1). In particular, the C-terminal half of domain CR9, comprising the region Gly(1127)-Cys(1140) exclusively recognizes aggregated LDL and it is crucial for aggregated LDL binding. Our aim was to study the effect of the sequence Gly(1127)-Cys(1140) (named peptide LP3 and its retro-enantio version, named peptide DP3) on the structural characteristics of...

Very low-density lipoprotein (VLDL) is the main plasma carrier of triacylglycerol that is elevated in pathological conditions such as diabetes, metabolic syndrome, obesity and dyslipidemia. How variations in triacylglycerol levels influence structural stability and remodeling of VLDL and its metabolic product, low-density lipoproteins (LDL), is unknown. We applied a biochemical and biophysical approach using lipoprotein remodeling by lipoprotein lipase and cholesterol ester transfer protein,...

Marfan syndrome (MFS) is caused by mutations in the protein fibrillin-1 (FBN1) which affects the integrity of connective tissue elastic fibres. The most severe clinical outcome is the formation of ascending aortic aneurysms. FBN1 mutations are extremely variable and the prediction of disease phenotype and aortic risk is challenging under the prevailing mutation type classification. Finding a better correlation between mutation type and disease development is crucial for patient treatment. By...

Objective: Electronegative LDL (LDL(-) is involved in atherosclerosis through the activation of the TLR4/CD14 inflammatory pathway in monocytes. Matrix metalloproteinases (MMP) and their inhibitors (tissue inhibitors of metalloproteinase [TIMP]) are also crucially involved in atherosclerosis, but their modulation by LDL(- has never been investigated. The aim of this study was to examine the ability of LDL(-)to release MMPs and TIMPs in human monocytes and to determine whether sulodexide (SDX),...

Hydrolysis of VLDL triacylglycerol (TG) by lipoprotein lipase (LpL) is a major step in energy metabolism and VLDL-to-LDL maturation. Most functional LpL is anchored to the vascular endothelium, yet a small amount circulates on TG-rich lipoproteins. As circulating LpL has low catalytic activity, its role in VLDL remodeling is unclear. We use pre-heparin plasma and heparin-sepharose affinity chromatography to isolate VLDL fractions from normolipidemic, hypertriglyceridemic, or type-2 diabetic...

Adverse cardiac remodeling after myocardial infarction (MI) causes impaired ventricular function and heart failure. Histopathological characterization is commonly used to detect the location, size and shape of MI sites. However, the information about chemical composition, physical structure and molecular mobility of peri- and infarct zones post-MI is rather limited. The main objective of this work was to explore the spatiotemporal biochemical and biophysical alterations of key cardiac...

Lipids in the body are transported via lipoproteins that are nanoparticles comprised of lipids and amphipathic proteins termed apolipoproteins. This family of lipid surface-binding proteins is over-represented in human amyloid diseases. In particular, all major proteins of high-density lipoproteins (HDL), including apoA-I, apoA-II and serum amyloid A, can cause systemic amyloidoses in humans upon protein mutations, post-translational modifications or overproduction. Here, we begin to explore...

Background: Niemann-Pick type C (NPC) disease is characterized by lysosomal accumulation of cholesterol. Interestingly, NPC patients' brains also show increased levels of amyloid-l3 (Ap) peptide, a key protein in Alzheimer's disease pathogenesis. We previously reported that the c-Abl tyrosine kinase is active in NPC neurons and in AD animal models and that lmatinib, a specific c-Abl inhibitor, decreased the amyloid burden in brains of the AD mouse model. Active c-Abl was shown to...

Low-density lipoprotein (LDL) aggregation is central in triggering atherogenesis. A minor fraction of electronegative plasma LDL, termed LDL(-), plays a special role in atherogenesis. To better understand this role, we analyzed the kinetics of aggregation, fusion and disintegration of human LDL and its fractions, LDL(+) and LDL(-). Thermal denaturation of LDL was monitored by spectroscopy and electron microscopy. Initially, LDL(-) aggregated and fused faster than LDL(+), but later the order...

Aims: Electronegative LDL (LDL(-)) is a plasma LDL subfraction that induces cytokine release in monocytes through toll-like receptor 4 (TLR4) activation. However, the intracellular pathways induced by LDL(-) downstream TLR4 activation are unknown. We aimed to identify the pathways activated by LDL(-) leading to cytokine release in monocytes. Methods and results: We determined LDL(-)-induced activation of several intracellular kinases in protein extracts from monocytes using a multikinase ELISA...

Whereas LDL-derived cholesterol accumulates in atherosclerotic lesions, HDL particles are thought to facilitate removal of cholesterol from the lesions back to the liver thereby promoting its fecal excretion from the body. Because generation of cholesterol-loaded macrophages is inherent to atherogenesis, studies on the mechanisms stimulating the release of cholesterol from these cells and its ultimate excretion into feces are crucial to learn how to prevent lesion development or even induce...

Background: Electronegative LDL (LDL(-)), a modified LDL fraction found in blood, induces the release of inflammatory mediators in endothelial cells and leukocytes. However, the inflammatory pathways activated by LDL(-) have not been fully defined. We aim to study whether LDL(-) induced release of the first-wave proinflammatory IL-1 beta in monocytes and monocyte-derived macrophages (MDM) and the mechanisms involved. Methods: LDL(-) was isolated from total LDL by anion exchange chromatography...

Clinical translation of emerging technologies aiming at cartilage resurfacing is hindered by neither the appropriate scaffold design nor the optimal cell source having been defined. Here, critical-sized, chondral-only focal defects were created in sheep and treated with clinical-grade, co-polymeric poly-lactide:polyglycolic acid scaffolds either alone or seeded with 3.3 x 10(6) +/- A 0.4 x 10(6) autologous bone marrow-derived mesenchymal stromal cells and studied over 12 month follow-up. An...

Hepatic lipase (HL) and endothelial lipase (EL) are negative regulators of plasma HDL cholesterol (HDLc) levels and presumably could affect two main HDL atheroprotective functions, macrophage-to-feces reverse cholesterol transport (RCT) and HDL antioxidant properties. In this study, we assessed the effects of both HL and EL deficiency on macrophage-specific RCT process and HDL ability to protect against LDL oxidation. HL- and EL-deficient and wild-type mice were injected intraperitoneally with...

Gemfibrozil and fenofibrate, two of the fibrates most used in clinical practice, raise HDL cholesterol (HDLc) and are thought to reduce the risk of atherosclerotic cardiovascular disease. These drugs act as PPARa agonists and upregulate the expression of genes crucial in reverse cholesterol transport (RCT). In the present study, we determined the effects of these two fibrates on RCT from macrophages to feces in vivo in human apoA-I transgenic (hApoA-ITg) mice. [3H]cholesterol-labeled mouse...

Mutations in ABCG5 or ABCG8 transporters are responsible for sitosterolemia, an autosomal recessive disease characterized by the accumulation of plant sterols. The aim of this study was to investigate the effects of ABCG5 and ABCG8 deficiency on TG metabolism in mice. Experiments were carried out in wild-type (G5/G8+/+) mice, mice heterozygous for ABCG5 and ABCG8 deficiency (G5/G8+/-) and ABCG5/G8-deficient (G5/G8-/-) mice fed a chow diet. Plasma TG were 2.6 and 4.3-fold higher in fasted G5/G8...

Metabolic adaptations are associated with changes in enzyme activities. These adaptations are characterized by patterns of positive and negative changes in metabolic fluxes and concentrations of intermediate metabolites. Knowledge of the mechanism and parameters governing enzyme kinetics is rarely available. However, the signs-increases or decreases-of many of these changes can be predicted using the signs of metabolic control coefficients. These signs require the only knowledge of the...

Type II interleukin-1 receptor (IL-1R2) is a non-signaling decoy receptor that negatively regulates the activity of interleukin-1 (IL-1), a pro-inflammatory cytokine involved in atherogenesis. In this article we assessed the relevance of IL-1R2 in atherosclerosis by studying its expression in monocytes from hyperlipidemic patients, in THP-1 macrophages exposed to lipoproteins and in human atherosclerotic lesions. Our results showed that the mRNA and protein expression of IL-1R2 was reduced in...

A subset of HIV-1-infected patients undergoing antiretroviral treatment develops a lipodystrophy syndrome. it is characterized by loss of peripheral subcutaneous adipose tissue (face, limbs, buttocks), visceral fat accumulation, and, in some cases, lipomatosis, especially in the dorsocervical area. In addition, these patients show metabolic alterations reminiscent of the metabolic syndrome, particularly dyslipidemia and insulin resistance. These alterations lead to enhanced cardiovascular risk...

Introduction: Transplant is the replacement with therapeutic purposes, of organs, tissues or cellular material for others, from a donor who is usually a human, alive or dead. In recent years, transplant organs have been developed by the advances that have occurred with immunosuppressive drugs and medical-surgical technology. Due to the frequency of transplants that are performed today, it is common to find these patients in dental clinics. Objectives: To review the literature on oral...

Law is one of the most necessary and powerful types of intelligence. The future of humanity depends on it. We should connect legal thinking with the actual discussion on intelligence. This article presents an integrative approach that embraces both artificial, institutional and emotional intelligence. We need smart jurists, provided with new forms of thinking and trained to manage a law working increasingly as a net. Key concepts of legal rationality are components of intelligence. Smart...

Objectives: Although the safety of patients has been one of the inherent concerns of dental practice, but because the proposals made in the field of dentistry are few and improperly structured, this paper constitutes an attempt to present a proposal titled "Plan for Dental Health Care Risk Management," promoted by the General Council of Dentists of Spain, including a description of the proposed work methodology. Design: The "risk management plan" proposed in this paper is...

Papillon-Lefevre syndrome is a rare autosomal recessively inherited condition which shows features common to both dentistry and dermatology. This disease is characterized by palmoplantar hyperkeratosis and severe periodon- titis. Therefore both the dentist and the dermatologist should be aware of the same because an early diagnosis of the syndrome can help to preserve the teeth by early institution of treatment, using a multidisciplinary approach. Here we present a case report of Papillon-...

Se describe un caso de hemangioendotelioma grado I, que afectaba a la epífisis humeral superior en una paciente de cincuenta y siete años, presentándose clínicamente como una periartritis escapulo humeral. Se comenta el diagnóstico diferencial y el tratamiento que fué de resección local y sustitución del tercio superior del húmero por una prótesis isoelástica, más radioterapia complementaria. Después de ocho meses no hay evidencia de recidiva local o sistémica, ha desaparecido el dolor y la..., This is a report on a case of Hemangioendothelioma grade I located over the uppe r humeral epiphysis, in a woman aged 57, and mimicing scapulohume - ral periarthitis. The authors detail differential diagnosis and treatment consisting of partial ablation and us e a humeral isoelastic prosthesis as well as complementary radioterapy. After 8 months there is no evidence of local recidives or systemic, no pain, and the function of the limb is acceptable. They emphazise the importance of the...

Purpose: To determine the prevalence of Epstein Barr Virus (EBV) in oral hairy leukoplakia lesions (OHL) in HIV+ Venezuelan patients. Material and Method: In this case study, we evaluated 21 HIV+ adult patients with clinically present OHL lesions, 11 who were undergoing antiretroviral therapy, 10 who were not undergoing therapy and 10 HIV-negative adult patients with hyperkeratotic oral mucosal lesions. All of the subjects were assessed at the Infectious Disease Center, Faculty of Dentistry...

El texto que a continuación publicamos es la transcripción íntegra del artículo titulado HOELDERLIN, aparecido en El Heraldo. Periódico político, religioso, literario y industrial, Madrid, año 1, 1843, número 204, del 14 de marzo (parte literaria), y que unos meses después reprodujo El Siglo Diez y Nueve, México, año 2, 1843, el 25 de junio. Los dos primeros párrafos de este artículo (líneas 1-29), han sido publicados ya por Adolf Beck en Hölderlin, Sämtliche Werke, Stuttgart, 1977, (RW,34a). 1...

Se suele decir que para Nietzsche la verdad no existe, y se remite al famoso texto de Sobre verdad y mentira en sentido extramoral; detrás de tal «lectura» suelen estar o el relativismo o el cientismo ambientes. Se trata de un abuso interpretativo. Nietzsche corrige la noción de verdad, desmontando la pretensión de que tengamos acceso a las cosas en sí, a la realidad tal cual. Pero nos hace ver el origen individual de la verdad, la relación entre la experiencia vital y la palabra, por medio de...

Capitulo de libro en una editora Holandesa, En Holandes: Compassie is al meer dan 2500 jaar een belangrijk element van contemplatieve en spirituele tradities (Rahula, 1969), waarvan het boeddhisme waarschijnlijk de bekendste is. De dalai lama (1995, 2000) definieert compassie als ‘een gevoeligheid voor het lijden van jezelf en de ander, in combinatie met een diepgewortelde bereidheid om te proberen het te verlichten’. Niettemin is het bestuderen ervan door westerse onderzoekers een relatief nieuw fenomeen. Pas de laatste 20 jaar zien we...

Se comentan los hallazgos de varias especies de plantas vasculares detectadas en el territorio de la Comunidad Valenciana, especialmente la provincia de Valencia, proponiéndose algunas combinaciones nomenclaturales nuevas.

Si la intución de vincular a Shakespeare con el mundo de los emblemas fue rastreada por la crítica anglosajona desde antiguo, dando lugar a estudios extensos y minuciosos, no ha sido así con la obra de Cervantes. De hecho, no podemos hablar en rigor de unos primeros —y aún tímidos— análisis de este enlace hasta principios de los años ochenta del siglo pasado, y habrá que esperar a que acabe prácticamente el siglo para contar con una mínima bibliografía dedicada. Sin duda, la multiplicación de...

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The dataset revolves around the nomenclature of thesis supervisors at a global level. It comprises 55 distinct labels originating from 116 countries and spanning across 47 different languages. The data collection process involved extracting information from university websites, official institutions, and doctoral thesis repositories

Después de su salida de Amberes, Benito Arias Montano (ca. 1525/27-1598) mantuvo una frecuente correspondencia con la oficina tipográfica de Cristóbal Plantino. Las cartas no se limitaron a intercambiar noticias públicas y privadas; el teólogo español envió muy a menudo listas de títulos de libros que él o su cenáculo de humanistas sevillanos estaban interesados en comprar. Este artículo se centra en quince listas enviadas entre 1585 y 1596 y conservadas en el Museo Plantin-Moretus de Amberes....

Coordinador del projecte: Universitat de Girona; Autoria: Bea Sándor; Adaptació a l'espanyol: Núria Sadurní, Beatriz San Román, Jose Antonio Langarita, Marisela Montenegro, Pilar Albertín i Joan Pujol; Disseny gràfic: Zsolt S. Szabó; Adaptació gràfica de la guia: Cristina de Dios, This handbook was created within the framework of the Diversity and Childhood: Changing social attitudes towards gender diversity in children across Europe (DaC) project. As its main expected results, the project seeks to raise awareness and reduce prejudice, as well as to improve protection against violence and support for LGBTI+ and gender non-conforming children and youth.1 DaC also aims to provide effective tools to stakeholders and envisages strengthening the well-being and the..., Este manual ha sido elaborado en el marco del proyecto de Diversity and Childhood: Cambiando las actitudes sociales hacia la diversidad de género en la infancia en toda Europa (DaC). Dicho proyecto trata de sensibilizar y reducir los prejuicios, así como de mejorar los mecanismos de protección contra la violencia hacia la infancia y la adolescencia LGTBI+. El proyecto DaC también tiene como objetivo proporcionar instrumentos eficaces a las profesionales, 1 fortalecer el bienestar y los..., Projecte "Diversity and childhood: changing social attitudes towards gender diversity in children across Europe", finançat pel Programa de Drets, Igualtat i Ciutadania (2014-2020) de la Unió Europea (REC-RDAP-GBV-AG-2018-856680)

Frequently Asked Questions about violence against LGBTI+ children for Interactive App in English, Hungarian, Dutch, Croatian, Polish, Greek, Lithuanian, Portuguese, Slovenian, and Spanish, Projecte "Diversity and childhood: changing social attitudes towards gender diversity in children across Europe", finançat pel Programa de Drets, Igualtat i Ciutadania (2014-2020) de la Unió Europea (REC-RDAP-GBV-AG-2018-856680)

Adverse cardiac remodeling after myocardial infarction (MI) causes impaired ventricular function and heart failure. Histopathological characterization is commonly used to detect the location, size and shape of MI sites. However, the information about chemical composition, physical structure and molecular mobility of peri- and infarct zones post-MI is rather limited. The main objective of this work was to explore the spatiotemporal biochemical and biophysical alterations of key cardiac...

Chagas disease is caused by infection with the parasite Trypanosoma cruzi, which might lead to a chronic disease state and drive to irreversible damage to the heart and/or digestive tract tissues. Endemic in 21 countries in the Americas, it is the neglected disease with a highest burden in the region. Current estimates point at similar to 6 million people infected, of which similar to 30% will progress onto the symptomatic tissue disruptive stage. There is no vaccine but there are two anti-...

Door het concept van de ‘decorated shed’ als uitgangspunt te nemen is Moneo er in geslaagd om de uitbreiding van het stadhuis van Murcia in Spanje aan het plein tegenover de kathedraal op een eigentijdse manier in te vullen. Door de compacte vorm wordt ruimte geboden aan de autonome binnenwereld van het gevraagde programma, terwijl de opengewerkte gevel uitdrukking geeft aan lastige begrippen als monumentaliteit en institutionele representatie. Tegelijkertijd gaat de gevel door zijn...

De nucleus van iedere badplaats is het Casino of het Kurhaus. Ter vervanging van haar nimmer florerende casino organiseerde de gemeente San Sebastián een besloten prijsvraag voor een nieuwe Kursaal die door Rafael Moneo nipt werd gewonnen. Gebaseerd op een ontonbaar stedebouwkundige príncipe, is het gebouw een perfecte synthese geworden. Overdag is het deel van het landschap, 's nachts gaat het op in de stad. Deze tweezijdigheid lijkt eveneens representatief te zijn voor de in het bouwwerk...

In het Domus Museum in het Spaanse La Coruña worden bezoekers in de gelegenheid gesteld kennis te nemen van het menselijk lichaam middels interactieve media. In zijn ontwerp heeft Arata Isozaki de aloude tegenstelling tussen mens en techniek tot thema verheven door het gebouw op te trekken uit onbewerkte natuursteen als tegenwicht tegen de gedematerialiseerde wereld van de informatica. Maar ook de complexiteit van de lokatie verbeeldt hij door contrasten te creëren tussen wanorde en formele...

Voor de uitbreiding van het vliegveld van Barcelona werd aan Ricardo Bofill gevraagd een concept te ontwikkelen. Hij introduceerde het typisch Barcelonese begrip ‘rambla’, waarmee alle passagiersstromen konden worden gebundeld. Daarnaast veroorzaakt de geleding van de lineaire structuur kruispunten waar bijzondere plekken gecreëerd kunnen worden.

This article looks at the way culture is represented in 3 commonly used course books of Dutch as a foreign language. According to the author, everyday culture of the regions where Dutch is spoken, is presented from a nationalistic point of view, i.e. it is limited to either cultural, historical and social aspects of The Netherlands or cultural, historical and social aspects of the Flemish Community in Belgium. The existence of the other region or country where the same language is spoken is not...

In this article I shall show how deftly Fàbregas creates in her novel Landen two separate but thematically connected stories and leads them to a very satisfying and totally unexpected ending. Landen is an intriguing psychological novel where the two main characters, Him and Her, tell, in alternating chapters, their own story in the first person. They only meet once, in the first chapter, where the Him character dies. I shall first look at the main characters’ life experiences, i.e. the car..., In this article I shall show how deftly Fàbregas creates in her novel Landen two separate but thematically connected stories and leads them to a very satisfying and totally unexpected ending. Landen is an intriguing psychological novel where the two main characters, Him and Her, tell, in alternating chapters, their own story in the first person. They only meet once, in the first chapter, where the Him character dies. I shall first look at the main characters’ life experiences, i.e. the car...

Pharmacological chaperones are small compounds that correct the folding of mutant proteins, and represent a promising therapeutic strategy for misfolding diseases. We have performed a screening of 10,000 compounds searching for pharmacological chaperones of tyrosine hydroxylase (TH), the tetrahydrobiopterin (BH4)-dependent enzyme that catalyzes the rate-limiting step in the synthesis of catecholamines. A large number of compounds bound to human TH, isoform 1 (hTH1), but only twelve...

Small heterodimer partner (SHP) is an atypical nuclear receptor expressed in heart that has been shown to inhibit the hypertrophic response. Here, we assessed the role of SHP in cardiac metabolism and inflammation. Mice fed a high-fat diet (HFD) displayed glucose intolerance accompanied by increased cardiac mRNA levels of Shp. In HL-1 cardiomyocytes, SHP overexpression inhibited both basal and insulin-stimulated glucose uptake and impaired the insulin signalling pathway (evidenced by reduced...

Cardiac lipid metabolism is the focus of attention due to its involvement in the development of cardiac disorders. Both a reduction and an increase in fatty acid utilization make the heart more prone to the development of lipotoxic cardiac dysfunction. The ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR)ß/d modulates different aspects of cardiac fatty acid metabolism, and targeting this nuclear receptor can improve heart diseases caused by altered...

Global obesity is a pandemic status, estimated to affect over 2 billion people, that has resulted in an enormous strain on healthcare systems worldwide. The situation is compounded by the fact that apart from the direct costs associated with overweight pathology, obesity presents itself with a number of comorbidities, including an increased risk for the development of neurodegenerative disorders. Alzheimer disease (AD), the main cause of senile dementia, is no exception. Spectacular failure of...

We studied whether PPARß/d deficiency modifies the effects of high fructose intake (30% fructose in drinking water) on glucose tolerance and adipose tissue dysfunction, focusing on the CD36-dependent pathway that enhances adipose tissue inflammation and impairs insulin signaling. Fructose intake for 8 weeks significantly increased body and liver weight, and hepatic triglyceride accumulation in PPARß/d-deficient mice but not in wild-type mice. Feeding PPARß/d-deficient mice with fructose...

The potentially interactive influence of attention and prediction was investigated by measuring event-related potentials (ERPs) in a spatial cueing task with attention (task-relevant) and prediction (probabilistic) cues. We identified distinct processing stages of this interactive influence. Firstly, in line with the attentional gain hypothesis, a larger amplitude response of the contralateral N1, and Nd1 for attended gratings was observed. Secondly, conforming to the attenuation-by-...

Detecting unexpected stimuli in the environment is a critical function of the auditory system. Responses to unexpected "deviant" sounds are enhanced compared to responses to expected stimuli. At the human scalp, deviance detection is reflected in the mismatch negativity (MMN) and in an enhancement of the middle-latency response (MLR). Single neurons often respond more strongly to a stimulus when rare than when common, a phenomenon termed stimulus-specific adaptation (SSA). Here we...

Based on the previous study where phase-synchronization (PS) of gamma-band responses (GBRs) proved a reliable cerebral correlate of involuntary attention and its enhancement under threat, we measured gamma-PS elicited by novel sounds from human electroencephalogram (EEG) scalp-recordings when participants responded to visual stimuli displaying either highly motivational or neutral sceneries. We then tested the modulatory effect of the emotional conditions on auditory responses. Novel distractor...

The rapid discrimination of auditory location information enables grouping and selectively attending to specific sound sources. The typical indicator of auditory change detection is the mismatch negativity (MMN) occurring at a latency of about 100-250 ms. However, recent studies have revealed the existence of earlier markers of frequency deviance detection in the middle-latency response (MLR). Here, we measured the MLR and MMN to changes in sound location. Clicks were presented in either the...

People at high risk for alcoholism show deficits in aversive learning, as indicated by impaired electrodermal responses during fear conditioning, a basic form of associative learning that depends on the amygdala. A positive family history of alcohol dependence has also been related to decreased amygdala responses during emotional processing. In the present study we report reduced amygdala activity during the acquisition of conditioned fear in healthy carriers of a risk variant for alcoholism (...

This study uses event-related brain potentials to investigate the difficulties that high math anxious individuals face when processing dramatically incorrect solutions to simple arithmetical problems. To this end, thirteen high math-anxious (HMA) and thirteen low math-anxious (LMA) individuals were presented with simple addition problems in a verification task. The proposed solution could be correct, incorrect but very close to the correct one (small-split), or dramatically incorrect (large-...

Numerical comparison tasks are widely used to study the mental representation of numerical magnitude. In study, event-related brain potentials (ERPs) were recorded while 26 high math-anxious (HMA) and 27 low math-anxious (LMA) individuals were presented with pairs of single-digit Arabic numbers and were asked to decide which one had the larger numerical magnitude. The size of the numbers and the distance between them were manipulated in order to study the size and the distance effects. The...

Emotionally negative stimuli boost perceptual processes. There is little known, however, about the timing of this modulation. The present study aims at elucidating the phasic effects of, emotional processing on auditory processing within subsequent time-windows of visual emotional, processing in humans. We recorded the electroencephalogram (EEG) while participants responded to a, discrimination task of faces with neutral or fearful expressions. A brief complex tone, which subjects, were...

Mutations on the mitochondrial-expressed Branched Chain of-Keto acid Dehydrogenase Kinase (BCKDK) gene have been recently associated with a novel dietary-treatable form of autism. But, being a mitochondrial metabolism disease, little is known about the impact on mitochondrial performance. Here, we analyze the mitochondrial response to the BCKDK-deficiency in patient's primary fibroblasts by measuring bioenergetics, ultra structural and dynamic parameters. A two-fold increase in superoxide...

A subset of HIV-1-infected patients undergoing antiretroviral treatment develops a lipodystrophy syndrome. It is characterized by loss of peripheral subcutaneous adipose tissue (face, limbs, buttocks), visceral fat accumulation, and, in some cases, lipomatosis, especially in the dorsocervical area. In addition, these patients show metabolic alterations reminiscent of the metabolic syndrome, particularly dyslipidemia and insulin resistance. These alterations lead to enhanced cardiovascular risk...

In this study we examined the effect of the statin atorvastatin on the Akt/GSK-3beta pathway. Our findings indicate that atorvastatin treatment for 15 days inhibited pressure overload-induced cardiac hypertrophy and prevented nuclear translocation of GATA4 and c-Jun and AP-1 DNA-binding activity. In addition, atorvastatin treatment prevented the increase in the phosphorylation of Akt and GSK-3beta caused by cardiac hypertrophy, and this effect correlated with an increase in protein levels of...

In order to approach the function of the retinal dystrophy CERKL gene we generated a novel knockout mouse model by cre-mediated targeted deletion of the Cerkl first exon and proximal promoter. The excised genomic region (2.3kb) encompassed the first Cerkl exon, upstream sequences including the proximal promoter and the initial segment of the first intron. The Cerkl-/- mice were viable and fertile. The targeted Cerkl deletion resulted in a knockdown more than a knockout model, given that...

To determine to what extent lipoprotein lipase activity in the liver of the newborn rat depends on milk ingestion, its changes were studied during different nutritional conditions. Newborns were placed with nurse rats with or without ligated nipples and they were killed at 0,8 or 24 h of life. Lipoprotein lipase in newborns liver was characterized by its inhibition in the presence of 1.0 M NaCl, its specific elution at 1.5 M NaCl on heparin-Sepharose 4B column and its requirement for serum...

Solute uptake into liver plasma membrane vesicles from either lean or obese Zucker rats was monitored. D-Glucose and L-leucine uptakes at physiological concentrations of the substrate were not different in lean and obese Zucker rats. In agreement with a previous report (Ruiz et al. (1991) Biochem. J. 280, 367-372) L-alanine uptake was significantly enhanced in those preparations from obese animals. Na(+)-coupled uridine transport was markedly enhanced also in obese rats. The effect was due...

To determine the role of insulin on the in vivo modulation of liver system A activity, we used the euglycemic hyperinsulinemic clamp coupled to the measurement of solute uptakes into plasma membrane vesicles partially purified from livers of hyperinsulinemic rats and their saline-infused controls. The clamp was performed in chronically catheterized rats, either in the fasted state, 24 h after surgery (Group I), or after 3 days of recovery (Group II). System A activity, measured as the...

It was found that EGF decreased both the basal- and the glucagon-stimulated gluconeogenesis from lactate alone or from a high lactate/pyruvate ratio and that it enhanced both the basal- and the glucagon-inhibited glucose synthesis from pyruvate alone or from a low lactate/pyruvate ratio. These findings demonstrate that the effect of both EGF and glucagon on glucose production by isolated hepatocytes depends on the red-ox state of the substrate.

The present study had focused on the behavioral phenotype and gene expression profile of molecules related to insulin receptor signaling in the hippocampus of 3 and 6 month-old APPswe/PS1dE9 (APP/PS1) transgenic mouse model of Alzheimer's disease (AD). Elevated levels of the insoluble Aß (1-42) were detected in the brain extracts of the transgenic animals as early as 3 months of age, prior to the Aß plaque formation (pre-plaque stage). By the early plaque stage (6 months) both the soluble...

The role of peroxisome proliferator activator receptor (PPAR)ß/d in the pathogenesis of Alzheimer's disease has only recently been explored through the use of PPARß/d agonists. Here we evaluated the effects of PPARß/d deficiency on the amyloidogenic pathway and tau hyperphosphorylation. PPARß/d-null mice showed cognitive impairment in the object recognition task, accompanied by enhanced DNA-binding activity of NF-?B in the cortex and increased expression of IL-6. In addition, two NF-?B-...

The mechanisms linking low-grade chronic inflammation with obesity-induced insulin resistance have only been partially elucidated. PPARß/d and SIRT1 might play a role in this association. In visceral adipose tissue (VAT) from obese insulin-resistant patients we observed enhanced p65 nuclear translocation and elevated expression of the pro-inflammatory cytokines TNF-a and IL-6 compared to control subjects. Inflammation was accompanied by a reduction in the levels of SIRT1 protein and an increase...

Owing to its high fat content, the classical Western diet has a range of adverse effects on the heart, including enhanced inflammation, hypertrophy, and contractile dysfunction. Proinflammatory factors secreted by cardiac cells, which are under the transcriptional control of nuclear factor-?B (NF-?B), may contribute to heart failure and dilated cardiomyopathy. The underlying mechanisms are complex, since they are linked to systemic metabolic abnormalities and changes in cardiomyocyte phenotype...

Although abnormalities in cardiac fatty acid metabolism are involved in the development of several cardiac pathologies, the mechanisms underlying these changes are not well understood. Given the prominent role played by peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta in cardiac fatty acid metabolism, the aim of this study was to examine the effects of nuclear factor (NF)-kappaB activation on the activity of this nuclear receptor. Embryonic rat heart-derived H9c2 cells...

The mechanisms by which elevated levels of free fatty acids cause insulin resistance are not well understood, but there is a strong correlation between insulin resistance and intramyocellular lipid accumulation in skeletal muscle. In addition, accumulating evidence suggests a link between inflammation and type 2 diabetes. The aim of this work was to study whether the exposure of skeletal muscle cells to palmitate affected peroxisome proliferator-activated receptor (PPAR) beta/delta activity....

Nuclear factor (NF)-kappa B signaling pathway plays a pivotal role in cardiac hypertrophy. Although it has been reported that statins inhibit cardiac hypertrophy by reducing generation of reactive oxygen species, it is not yet known whether statins prevent NF-kappa B activation and whether this effect can be related to the reduction in the peroxisome proliferator-activated receptor (PPAR) pathway. In this study, we examined the role of atorvastatin on NF-kappa B activity and PPAR signaling in...

When exposed to enteric pathogens intestinal epithelial cells produce several cytokines and other proinflammatory mediators. To date there is no evidence that the ether-lipid platelet-activating factor (PAF) is one of these mediators. Our results revealed a significant increase in PAF production by human colonic tissue 4 h after infection by enterohemorrhagic Escherichia coli (EHEC) or Salmonella enteritidis. PAF is produced in the gut by cells of the immune system in response to bacterial...

1,2-Propanediol oxidoreductase, which reduces the L-lactaldehyde formed in the fermentation of L-fucose or L-rhamnose to L-1,2-propanediol in E. coli, was inactivated by a component of E. coli cell extracts in the presence of oxygen. Pure propanediol oxidoreductase preparations were shown to be inactivated in vitro by aerobic incubations in the presence of Fe3+ and ascorbate. The Fe3+ ascorbate-mediated inactivation reaction was inhibited by catalase, although not by superoxide dismutase...

Behavioral and electrophysiological brain responses were used to examine the relationship between the vulnerability to distraction and the orienting response in schizophrenia. Nineteen schizophrenics and nineteen matched healthy controls were instructed to ignore task-irrelevant auditory stimuli while they classified capital letters and digits. The auditory sequences contained repetitive standard tones occasionally replaced by complex novel sounds. Relative to controls, patients showed an...