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...

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 cell-cell 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...

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...

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-...

Hyperammonemia contributes to altered neurotransmission and cognition in patients with hepatic encephalopathy. Hyperammonemia in rats affects differently high- and low-affinity AMPA receptors (AMPARs) in cerebellum. We hypothesized that hyperammonemia would alter differently membrane expression of AMPARs GluA1 and GluA2 subunits by altering its phosphorylation. This work aims were: 1) assess if hyperammonemia alters GluA1 and GluA2 subunits membrane expression in cerebellum and 2) analyze the...

Charcot-Marie-Tooth disease is a rare peripheral neuropathy for which there is no specific treatment. Some forms of Charcot-Marie-Tooth are due to mutations in the GDAP1 gene. A striking feature of mutations in GDAP1 is that they have a variable clinical manifestation, according to disease onset and progression, histology and mode of inheritance. Studies in cellular and animal models have revealed a role of GDAP1 in mitochondrial morphology and distribution, calcium homeostasis and oxidative...

Single nucleotide polymorphisms near the Ink4/Arf locus have been associated with type-2 diabetes mellitus. Previous studies indicate a protective role of the locus in the carbohydrate metabolism derangement associated with ageing in wild-type mice. The present study demonstrates that the increased Ink4/Arf locus expression in 1-year-old mice, partially-deficient for the insulin receptor substrate (IRS)2 (Irs2 +/-SuperInk4/Arf mice) ameliorates hepatic steatosis, inflammation and insulin...

In the gene expression field, different steps have been traditionally viewed as discrete and unconnected events. Nowadays, genetic and functional studies support the model of a coupled network of physical and functional connections to carry out mRNA biogenesis. Gene expression is a coordinated process that comprises different linked steps like transcription, RNA processing, export to the cytoplasm, translation and degradation of mRNAs. Its regulation is essential for cellular survival and can...

miRNAs involved in the biosynthesis of artemisinin, an anti-malarial compound form the plant Artemisia annua, have been identified using computational approaches to find conserved pre-miRNAs in available A. annua UniGene collections. Eleven pre-miRNAs were found from nine families. Targets predicted for these miRNAs were mainly transcription factors for conserved miRNAs. No target genes involved in artemisinin biosynthesis were found. However, miR390 was predicted to target a gene involved in...

The SUS1 gene of Saccharomyces cerevisiae is unusual as it contains two introns and undergoes alternative splicing, retaining one or both introns depending on growth conditions. The exon located between the two introns can be skipped during splicing and has been detected in circular form. This exon (E2) has also been found to influence the splicing of the flanking introns, an unusual situation in budding yeast where splicing mainly relies on intron recognition. Using SHAPE (selective 2'-...

Circulating histones have been proposed as targets for therapy in sepsis and hyperinflammatory symptoms. However, the proposed strategies have failed in clinical trials. Although different mechanisms for histone-related cytotoxicity are being explored, those mediated by circulating histones are not fully understood. Extracellular histones induce endothelial cell death, thereby contributing to the pathogenesis of complex diseases such as sepsis and septic shock. Therefore, the comprehension of...

The pathomechanisms underlying oxidative phosphorylation (OXPHOS) diseases are not well-understood, but they involve maladaptive changes in mitochondria-nucleus communication. Many studies on the mitochondria nucleus cross-talk triggered by mitochondrial dysfunction have focused on the role played by regulatory proteins, while the participation of miRNAs remains poorly explored. MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is mostly caused by mutation m....

The expression and function of TRPV1 are influenced by its interaction with cellular proteins. Here, we identify Whirlin, a cytoskeletal PDZ-scaffold protein implicated in hearing, vision and mechanosensory transduction, as an interacting partner of TRPV1. Whirlin associates with TRPV1 in cell lines and in primary cultures of rat nociceptors. Whirlin is expressed in 55% of mouse sensory C-fibers, including peptidergic and non-peptidergic nociceptors, and co-localizes with TRPV1 in 70% of them....

Tyrosine nitration is one of the most common post-transcriptional modifications of proteins, so affecting their structure and function. Human cytochrome c, with five tyrosine residues, is an excellent case study as it is a well-known protein playing a double physiological role in different cell compartments. On one hand, it acts as electron carrier within the mitochondrial respiratory electron transport chain, and on the other hand, it serves as a cytoplasmic apoptosis-triggering agent. In a...

Dimerisation of receptor-type protein tyrosine phosphatases (RPTPs) represents an appealing mechanism to regulate their enzymatic activity. Studies thus far mostly concern the dimerisation behaviour of RPTPs possessing two tandemly oriented catalytic PTP domains. Mouse gene Ptprr encodes four different protein isoforms (i.e. PTPBR7, PTP-SL and PTPPBS gamma-42/37) that contain a single PTP domain. Using selective membrane permeabilisation we here demonstrate that PTP-SL, like PTPBR7, is a single...

Recent evidences highlight the importance of mitochondria-nucleus communication for the clinical phenotype of oxidative phosphorylation (OXPHOS) diseases. However, the participation of small non-coding RNAs (sncRNAs) in this communication has been poorly explored. We asked whether OXPHOS dysfunction alters the production of a new class of sncRNAs, mitochondria] tRNA fragments (mt tRFs), and, if so, whether mt tRFs play a physiological role and their accumulation is controlled by the action 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...

Lafora progressive myoclonus epilepsy is a fatal rare neurodegenerative disorder characterized by the accumulation of insoluble abnormal glycogen deposits in the brain and peripheral tissues. Mutations in at least two genes are responsible for the disease: EPM2A, encoding the glucan phosphatase laforin, and EPM2B, encoding the RING-type E3-ubiquitin ligase malin. Both laforin and malin form a functional complex in which laforin recruits the substrates to be ubiquitinated by malin. We and others...

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...

Background: The phosphotransferase system (PTS) modulates the preferential use of sugars in bacteria. It is formed by a protein cascade in which the first two proteins are general (namely enzyme I, EI, and the histidine phosphocarrier protein, HPr) and the others are sugar-specific permeases; the active site of HPr is His15. The HPr kinase/phosphorylase (HPrK/P), involved in the use of carbon sources in Gram-positive, phopshorylates HPr at a serine. The regulator of sigma D protein (Rsd) also...

Channelopathies, defined as diseases that are caused by mutations in genes encoding ion channels, are associated with a wide variety of symptoms. Impaired chloride transport can cause diseases as diverse as cystic fibrosis, myotonia, epilepsy, hyperekplexia, lysosomal storage disease, deafness, renal salt loss, kidney stones and osteopetrosis. These disorders are caused by mutations in genes belonging to non-related gene families, i.e. CLC chloride channels and transporters, ABC transporters,...

Dialecto : texto en euskera navarro-labortano, S. XX -- Periodo : último euskera moderno, Euskalkia : nafar-lapurtera, XX. md. -- Aroa : azken euskara modernoa, Digitalización Vitoria-Gasteiz Archivos y Bibliotecas Julio 1995 19-41

Holandesa

Rústica, Separata de: Beiheft zum Militär-Wochenblatt

Traducción holandesa del inglés, Retrato de Don Carlos, Digitalización Vitoria-Gasteiz Fundación Sancho el Sabio 2009, Cartoné

Es fotocopia

Es fotocopia

Es fotocopia

Es fotocopia, Versión en papel de la edición electrónica de: SGIR Fifth Pan International Relations Conference "Constructing World Orders". The Hague, 9-11 september 2004

Es fotocopia

Es fotocopia

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.

It is reviewed the iconography of Dutch-Sephardic philosopher Baruch Spinoza. It reports on the recent identification of the image of the philosopher found in an anonymous portrait deposited at the Universidad Complutense coming from Simarro Legacy Foundation. Documentation is provided showing that the portrait was painted by Sorolla for the library of Dr. Simarro. Repasa la iconografía del filosofo holandés de origen español-sefardí Baruch Spinoza. Da cuenta de la reciente identificación de...

The nematode, Caenorhabditis elegans is an established model system that is particularly well suited to genetic analysis. C. elegans is easily manipulated and we have an in depth knowledge of many aspects of its biology. Thus, it is an attractive system in which to pursue integrated studies of signalling pathways. C. elegans has a complement of calcium signalling molecules similar to that of other animals.

Liver fatty acid binding protein (FABP1) prevents lipotoxicity of free fatty acids and regulates fatty acid trafficking and partition. Our objective is to investigate the transcription factors controlling the human FABP1 gene and their regulation in nonalcoholic fatty liver disease (NAFLD). Adenovirus-mediated expression of multiple transcription factors in HepG2 cells and cultured human hepatocytes demonstrated that FOXA1 and PPARa are among the most effective activators of human FABP1,...

To understand how cells regulate each step in the flow of gene expression is one of the most fundamental goals in molecular biology. In this work, we have investigated several protein turnover-related steps in the context of gene expression regulation in response to changes in external temperature in model yeast Saccharomyces cerevisiae. We have found that the regulation of protein homeostasis is stricter than mRNA homeostasis. Although global translation and protein degradation rates are found...

Charcot-Marie-Tooth disease is a rare peripheral neuropathy for which there is no specific treatment. Some forms of Charcot-Marie-Tooth are due to mutations in the GDAP1 gene. A striking feature of mutations in GDAP1 is that they have a variable clinical manifestation, according to disease onset and progression, histology and mode of inheritance. Studies in cellular and animal models have revealed a role of GDAP1 in mitochondrial morphology and distribution, calcium homeostasis and oxidative...

This study examined the inhibitory control of attention to social scenes in manic, depressive, and euthymic episodes of bipolar disorder (BD). Two scenes were simultaneously presented (happy/threatening/neutral [ target] versus control). Participants were asked either to look at the emotional pictures (i.e., attend-to-emotional block) or to avoid looking at the emotional pictures (i.e., attend-to-neutral block) while their eye movements were recorded. The initial orienting (latency and...

The pathomechanisms underlying oxidative phosphorylation (OXPHOS) diseases are not well-understood, but they involve maladaptive changes in mitochondria-nucleus communication. Many studies on the mitochondria nucleus cross-talk triggered by mitochondrial dysfunction have focused on the role played by regulatory proteins, while the participation of miRNAs remains poorly explored. MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is mostly caused by mutation m....

We examined whether the initial orienting, subsequent engagement, and overall allocation of attention are determined exogenously (i.e. by the affective valence of the stimulus) or endogenously (i.e. by the participant's mood) in the manic, depressive and euthymic episodes of bipolar disorder (BD). Participants were asked to compare the affective valence of two pictures (happy/threatening/neutral [emotional] vs. neutral [control]) while their eye movements were recorded in a free-viewing...

Recent evidences highlight the importance of mitochondria-nucleus communication for the clinical phenotype of oxidative phosphorylation (OXPHOS) diseases. However, the participation of small non-coding RNAs (sncRNAs) in this communication has been poorly explored. We asked whether OXPHOS dysfunction alters the production of a new class of sncRNAs, mitochondrial tRNA fragments (mt tRFs), and, if so, whether mt tRFs play a physiological role and their accumulation is controlled by the action of...

Attentional biases to emotional information may play a key role in the onset and course of schizophrenia. The aim of this experiment was to examine the attentional processing of four emotional scenes in competition (happy, neutral, sad, threatening) in 53 patients with schizophrenia and 51 controls. The eye movements were recorded in a 20-seconds free-viewing task. The results were: (i) patients showed increased attention on threatening scenes, compared to controls, in terms of attentional...

BACKGROUND: Emotion recognition is often impaired in early Alzheimer's disease (AD) and can be evaluated using the Reading the Mind in the Eyes Test (RMET). Similarly, cortisol levels can affect cognition and could be considered a biomarker of AD. OBJECTIVES: The aim of this study was to analyse the relationship between the emotion recognition task and cortisol levels in participants with early Alzheimer Disease (AD). METHODS: Complex emotion recognition was assessed with RMET, and...

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...

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...

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...