Modified lipids from LDL in the blood during mid-life increase blood brain barrier permeability

Low density lipoprotein levels (LDL) are consistently elevated in cardiovascular disease. It has been suggested that those with high circulating LDL levels in mid-life may be susceptible to develop neurodegenerative diseases in later life. In the circulation, high levels of LDL are associated with increased oxidative modification (oxLDL) and nitration. We have investigated the hypothesis that disruption of blood brain barrier function by oxLDL and their lipids may increase risk of neurodegeneration in later life and that statin intervention in mid-life can mitigate the neurodegenerative effects of hyperlipidaemia. Blood from statin-naïve, normo- and hyperlipidaemic subjects (n=10/group) was collected at baseline. Hyperlipidaemic subjects received statin-intervention whereas normolipidaemic subjects did not prior to a second blood sampling, taken after 3 months. The intervention will be completed in June 2013. Plasma was separated by centrifugation (200g, 30min) and LDL was isolated by potassium bromide density gradient ultracentrifugation. Total homocysteine, LDL cholesterol, 8-isoprostane F2α levels were measured in plasma using commercial kits. LDL were analysed by agarose gel electrophoresis. LDL-lipids were extracted by partitioning in 1:1 chloroform:methanol (v/v) and conjugated to fatty acid free-BSA in serum-free EGM-2 medium (4hrs, 370C) for co-culture with human microvascular endothelial cells (HMVEC). HMVEC were maintained on polycarbonate inserts for two weeks to create a microvascular barrier. Change in barrier permeability was measured by trans-endothelial electrical resistance (TER), FITC-dextran permeability and immunohistochemistry. HMVEC glutathione (GSH) levels were measured after 2 hours by GSH-glo assay. LDL isolated from statin-naïve hyperlipidaemic subjects had higher mobility by agarose gel electrophoresis (Rf;0.53±0.06) and plasma 8-isoprostane F2α (43.5±8.42 pg/ml) compared to control subjects (0.46±0.05 and 24.2±5.37 pg/ml; p<0.05). Compared to HMVEC treatment with the LDL-lipids (5μM) from normolipidaemic subjects, LDL-lipids from hyperlipidaemic subjects increased barrier permeability (103.4±12.5 Ωcm2 v 66.7±7.3 Ωcm2,P<0.01) and decreased GSH (18.5 nmol/mg v 12.3 nmol/mg; untreated cells 26.2±3.6 nmol/mg).

Paradoxical decrease in HDL-cholesterol and apolipoprotein A1 with simvastatin and atorvastatin in a patient with type 2 diabetes

Statins are agents widely used to lower LDL-cholesterol (LDL-C) in primary and secondary prevention of coronary heart disease. The five statins available in the UK (simvastatin, pravastatin, fluvastatin, atorvastatin and rosuvastatin) differ in many of their pharmacologic properties. In addition to lowering LDL-C, statins also increase HDL-cholesterol (HDL-C) moderately. There have been rare reports of significant HDL-C decreases in patients commenced on fibrates and when thiazolidinediones are added to fibrates. This is known as a 'paradoxical HDL-C decrease' as both groups of agents usually increase HDL-C. This phenomenon has never been clearly documented following statin therapy. We now describe a patient with type 2 diabetes who showed this paradoxical fall in HDL-C (baseline HDL-C: 1.8 mmol/L; on simvastatin 40 mg HDL-C 0.6 mmol/L; on atorvastatin 20 mg HDL-C 0.9 mmol/L) with a similar decrease in apolipoprotein A1. No similar decrease was observed with pravastatin and rosuvastatin therapy. This phenomenon appeared to be associated with statin treatment and not a statin/fibrate combination. Our patient clearly demonstrated a paradoxical HDL-C fall with simvastatin and atorvastatin, but not pravastatin or rosuvastatin. Simvastatin and atorvastatin share many pharmacokinetic properties such as lipophilicity while pravastatin and rosuvastatin are relatively hydrophilic and are not metabolized by cytochrome P450 3A4. However, these characteristics do not explain the dramatic reductions in HDL-C observed.

Students' recollections of participating in a first year residential learning community experience

The purpose of this qualitative study was to gain an understanding of what participation in a first year residential learning community meant to students 2–3 years after their involvement in the program. Various theories including environmental, student involvement, psychosocial and intellectual, were used as a framework for this case study. Each of the ten participants was a junior or senior level student at the time of the study, but had previously participated in a first year residential learning community at Florida International University. The researcher held two semi-structured interviews with each participant, and collected data sheets from each. ^ The narrative data produced from the interviews were transcribed, coded and analyzed to gain insights into the experiences and perspectives of the participants. Member checking was used after the interview process. A peer reviewer offered feedback during the data analysis. The resulting data was coded into categories, with a final selection of four themes and 15 sub-themes, which captured the essence of the participants' experiences. The four major themes included: (a) community, (b) involvement, (c) identity, and (d) academics. The community theme is used to describe how students perceived the environment to be. The involvement theme is used to describe the students' participation in campus life and their interaction with other members of the university community. The identity theme is used to describe the students' process of development, and the personal growth they underwent as a result of their experiences. The academics theme refers to the intellectual development of students and their interaction around academic issues. ^ The results of this study showed that the participants valued greatly their involvement in the First Year Residents Succeeding Together program (FYRST) and can articulate how it helped them succeed as students. In describing their experience, they most recall the sense of community that existed, the personal growth they experienced, the academic development process they went through, and their involvement, both with other people and with activities in their community. Recommendations are provided for practice and research, including several related to enhancing the academic culture, integrating faculty, utilizing peer influence and providing further opportunities to create a seamless learning environment. ^

Students' recollections of participating in a first year residential learning community experience

The purpose of this qualitative study was to gain an understanding of what participation in a first year residential learning community meant to students 2-3 years after their involvement in the program. Various theories including environmental, student involvement, psychosocial and intellectual, were used as a framework for this case study. Each of the ten participants was a junior or senior level student at the time of the study, but had previously participated in a first year residential learning community at Florida International University. The researcher held two semi-structured interviews with each participant, and collected data sheets from each. The narrative data produced from the interviews were transcribed, coded and analyzed to gain insights into the experiences and perspectives of the participants. Member checking was used after the interview process. A peer reviewer offered feedback during the data analysis. The resulting data was coded into categories, with a final selection of four themes and 15 sub-themes, which captured the essence of the participants' experiences. The four major themes included: (a) community, (b) involvement, (c) identity, and (d) academics. The community theme is used to describe how students perceived the environment to be. The involvement theme is used to describe the students' participation in campus life and their interaction with other members of the university community. The identity theme is used to describe the students' process of development, and the personal growth they underwent as a result of their experiences. The academics theme refers to the intellectual development of students and their interaction around academic issues. The results of this study showed that the participants valued greatly their involvement in the First Year Residents Succeeding Together program (FYRST) and can articulate how it helped them succeed as students. In describing their experience, they most recall the sense of community that existed, the personal growth they experienced, the academic development process they went through, and their involvement, both with other people and with activities in their community. Recommendations are provided for practice and research, including several related to enhancing the academic culture, integrating faculty, utilizing peer influence and providing further opportunities to create a seamless learning environment.

Morphology of Cycladophora davisiana davisiana from the Atlantic Ocean

In recent years, temporal fluctuations in the abundance of C. d. davisiana have been used frequently as a highresolution stratigraphic and paleoenvironmental tool. The modern ecology and morphologic variation (temporal and geographic) of this radiolarian species is evaluated to ascertain its potential stratigraphic and paleoenvironmental significance. Statistics were obtained on the width and height of all C. d. davisiana segments from Pleistocene populations of differing ages from the Northern Hemisphere (Labrador Sea and Iceland-Faeroe Ridge) and Southern Hemisphere (Namibian shelf and Meteor Rise). Results reveal that segment height variations between and within populations are more conservative than segment width. The mean sizes of the thorax and first abdominal segment have distinguishable differences between C. d. davisiana found in the North and South Atlantic. All populations have no significant difference in first abdominal segment width, however, mean heights of this segment differ greatly between populations of the North and South Atlantic. Second abdominal segment sizes show no clear population grouping. Size differences in post-cephalic segment size of these populations would appear to be related to some isolation of gene pools and possibly unknown paleoenvironmental factors. Temporal changes in the postcephalic size of C. d. davisiana may be used to: (1) identify temporally equivalent peaks in abundance of the species in a given region, (2) possibly evaluate the degree of mixing of water'masses between regions, and (3) trace the initial spread of the species from its area of origin. Cleve's 1887 plankton samples, between Greenland and Spitzsbergen, were studied and used in conjunction with other data to make the following conclusions on the modern ecology of C. d. davisiana in the Arctic and Greenland-Norwegian Seas. (1) It is presently absent in surface water plankton samples, (2) it currently lives at depths below 500 m, where it is rare, (3) it does not live in the upper 200 m under Arctic ice but is rare at greater depths, (4) it is absent in the upper 200 m near permanent Greenland Sea ice where normal oceanic salinity prevails, and (5) it is most common in deep marginal fjord environments which may serve as a refuge for the species during interglacial periods. In the Atlantic Ocean, the abundance of C. d. davisiana does not exceed 1% of the assemblage between the Subtropical Convergence of each hemisphere. In the Norwegian and Labrador Seas the species may occasionally be in the range of 1-5% of the modern radiolarian assemblage and never more than 5% in the southern high latitudes. Apparently only in the modern Sea of Okhotsk, does the species presently occur in high abundance. We concur with Morley and Hays (1983) that increased abundances are likely caused by the development of a strong low-salinity surface layer associated with seasonal sea ice melting and a strong temperature minimum above warmer and higher salinity intermediate waters. Similar conditions were frequent during the Pleistocene in the high latitudes and its modern scarcity outside the Sea of Okhotsk must be related to the absence of the presently unique conditions in the latter region.

Dysfonctions mitochondriales associées à l’acidose lactique du Saguenay-Lac-Saint-Jean révélées par l’étude d’un nouveau modèle murin de la maladie

Le syndrome de Leigh version canadienne-française (LSFC) est une maladie autosomale récessive causée par une mutation du gène LRPPRC, encodant une protéine du m��me nom. LRPPRC est impliquée dans la traduction des gènes mitochondriaux qui encodent certains complexes de la chaine respiratoire. Les répercussions biochimiques incluent un déficit tissu spécifique de la cytochrome c oxydase (COX), principalement dans le foie et le cerveau, et la survenue de crises d’acidose fatales chez 80 % des enfants atteints avant l’âge de 3-4 ans. L’identification d’options thérapeutiques demeure encore un défi de taille et ceci est en partie relié au manque de connaissances des fonctions biologiques de LRPPRC et des m��canismes impliqués dans la pathogenèse du LSFC, au niveau des dysfonctions mitochondriales résultantes. Afin d’étudier ces m��canismes, le consortium de l’acidose lactique, dont fait partie notre laboratoire, a récemment développé un modèle murin portant une ablation de LRPPRC spécifique au foie (souris H-Lrpprc-/-). L’objectif principal est de déterminer si ce modèle reproduit le phénotype pathologique observé dans les cultures de fibroblastes humains issus de biopsies de peau de patients LSFC. Dans le cadre des travaux de ce m��moire, nous avons amorc�� la caractérisation de ce nouveau modèle, en examinant le phénotype général, l’histopathologie hépatique et les fonctions mitochondriales, et en nous focalisant principalement sur les fonctions respiratoires et la capacité à oxyder divers types de substrats. Nous avons observé un retard de croissance, une hépatom��galie ainsi que plusieurs anomalies histologiques du foie chez la souris HLrpprc-/-. De plus, l’ablation de LRPPRC induit un déficit du complexe IV, mais aussi de l’ATP synthase, et affecte l’oxydation des acides gras à longues chaines. À la lumière de ces résultats, nous croyons que le modèle murin H-Lrpprc-/- contribuera à l’avancement des connaissances générales sur LRPPRC, nous permettant de mieux comprendre l’influence de la protéine sur les fonctions mitochondriales.

Los números cuentan. Sub-representación de la obra artística de mujeres creadoras en museos y centros de arte contemporáneos

Este artículo cuantifica la presencia de obra artística de mujeres artistas en 21 museos y centros de arte contemporáneo españoles. Los resultados constatan una nítida sub-representación de la obra exhibida, por debajo del 20 por ciento. ¿Por qué sucede esto?, ¿diferencial potencial artístico de mujeres y hombres?, ¿superioridad masculina?, ¿discriminación? o ¿un sistema de arte con sesgo androc��ntrico? En estas páginas se discute sobre la presencia de varios factores para explicar la brecha de género y se reclama, de las administraciones públicas y las instituciones de gestión cultural, el cumplimiento de la Ley para la Igualdad para garantizar la paridad.

La estructuración del espacio urbano y productivo de Gadir durante la fase urbana clásica: Cambios y perduraciones

La reafirmación del modelo político-administrativo ciudadano tras la fase arcaica colonial abre una nueva etapa de prosperidad en la antigua fundación tiria. El esplendor de Gadir en el s. V a.C. se refleja en los textos clásicos y en los hallazgos arqueológicos y, sin embargo, nuestros conocimientos sobre el desarrollo histórico de la ciudad de época púnica son muy limitados. El horizonte arcaico comienza a esclarecerse tras los hallazgos del Teatro C��mico que han sacado a la luz los restos de la fundación tiria y, sin embargo, la ciudad posterior continúa siendo una gran inc��gnita. ¿A qué lugar se traslada la población una vez que se abandona el asentamiento primitivo? ¿Quiénes son los individuos enterrados en los excepcionales sarc��fagos antropoides? ¿Qué relación jerárquica existe entre el asentamiento insular y los situados en tierra firme? ¿Qué papel jugó la industria y comercialización de las salazones? Los interrogantes planteados son m��ltiples y no hacen m��s que evidenciar la incapacidad del paradigma tradicional para explicar el desarrollo histórico de la Gadir postcolonial y la necesidad de buscar nuevos modelos interpretativos.

"Lancea", Lusitanian Word, and the "Lancienses" Ethnogenesis

Analysis of the word lancea, of Hispanic origin after Varro, and of place names, people´s names and personal names derived from it. It confirms that the spear was the most important weapon in the Bronze Age, belonging to the iuventus and used as heroic and divine symbol. This analysis confirms also the personality of the Lusitanians, a people related to the Celts but with more archaic archaeological, linguistic and cultural characteristics originated in the tradition of the Atlantic Bronze in the II millennium BC. It is also relevant to better know the organisation of Broze and Iron Age societies and the origin of Indo-Europeans peoples in Western Europe and of pre-Roman peoples of Iberia.

Quintus Curtius before his sources: the episode of Alexander and the Scythians on the Tanais

Quintus Curtius found in his sources a speech where a Scythian censured Alexander, followed by the King’s reply. Curtius drastically abridged this second discourse in order to highlight the criticism of the Macedonian. The Scythian’s words have a striking rhetorical language and some allusions taken from Greek literature, in addition to possible indirect references to Caligula. Curtius declares that he follows his source word-for-word aiming to justify these inconsistencies, but also trying to hide the manipulations he has done to achieve his own narrative purposes.

Le “brigand lusitanien” reconsidéré. Analyse du problème de la terre chez Appien

L’étude du “brigandage lusitanien” a donné lieu à une importante activité de recherche depuis la fin du XIXe siècle. Pour autant, et malgré une inflexion progressive de l’historiographie moderne vers une approche plus nuanc��e de l’origine du phénom��ne, le problème de la terre reste encore aujourd’hui au centre des préoccupations de nombre d’historiens et archéologiques. À partir d’une discussion serrée des principaux passages de Tite-Live, Diodore et surtout Appien, relatifs à la relation que d’aucuns ont voulu établir entre manque et/ou pauvreté de la terre et développement du brigandage chez les Lusitaniens, il est proposé une critique de l’interprétation socio-économique.

Motivating film title translation: a cognitive análisis

This proposal is a non-quantitative study based on a corpus of real data which offers a principled account of the translation strategies employed in the translation of English film titles into Spanish in terms of cognitive modeling. More specifically, we draw on Ruiz de Mendoza and Galera’s (2014) work on what they term content (or low-level) cognitive operations, based on either ‘stands for’ or ‘identity’ relations, in order to investigate possible motivating factors for translations which abide by oblique procedures, i.e. for non-literal renderings of source titles. The present proposal is made in consonance with recent findings within the framework of Cognitive Linguistics (Samaniego 2007), which evidence that this linguistic approach can fruitfully address some relevant issues in Translation Studies, the most outstanding for our purposes being the exploration of the cognitive operations which account for the use of translation strategies (Rojo and Ibarretxe-Antuñano 2013: 10), mainly expansion and reduction operations, parameterization, echoing, mitigation and comparison by contrast. This fits in nicely with a descriptive approach to translation and particularly with skopos theory, whose main aim consists in achieving functionally adequate renderings of source texts.

La inevitable inconsistencia del Zeus/J��piter épico

Durante años la investigación literaria ha encontrado fruición en buscar y encontrar inconsistencias narrativas en la Tebaida de Estacio. Concretamente, hay cierto grado de consenso respecto a que las incongruencias en que incurre J��piter son debidas a negligencia o incuria por parte del poeta. De hecho, no se puede negar que el soberano del cielo se contradice en las ocasiones en que alude a su relación con el Destino. No obstante, no será únicamente el poeta flavio el objeto de mi atención en este artículo. Hoy día se continúa acudiendo a la autoridad filosófica de Séneca (fundamentalmente a Dial. 1.5.8) siempre que el Zeus/J��piter poshom��rico (también el virgiliano) incurre en lo que hemos dado en considerar «incoherencias». Sin embargo, excepción hecha de las composiciones hesiódicas, el estatuto teológico de Zeus/J��piter es altamente inestable en toda la tradición literaria griega y romana. Quizá deberíamos aceptar, entonces, que durante siglos los que estudiamos literatura antigua hemos tendido a prescindir de la voz autorial y de su autoridad omnímoda para manipular el material literario preexistente con el objeto de generar nuevos significados y nuevas cosmovisiones. En definitiva, nos hemos mostrado proclives a calificar de inconsistencias todo aquello que no se adecua a nuestras expectativas o prejuicios.

Dysfonctions mitochondriales associées à l’acidose lactique du Saguenay-Lac-Saint-Jean révélées par l’étude d’un nouveau modèle murin de la maladie

Le syndrome de Leigh version canadienne-française (LSFC) est une maladie autosomale récessive causée par une mutation du gène LRPPRC, encodant une protéine du m��me nom. LRPPRC est impliquée dans la traduction des gènes mitochondriaux qui encodent certains complexes de la chaine respiratoire. Les répercussions biochimiques incluent un déficit tissu spécifique de la cytochrome c oxydase (COX), principalement dans le foie et le cerveau, et la survenue de crises d’acidose fatales chez 80 % des enfants atteints avant l’âge de 3-4 ans. L’identification d’options thérapeutiques demeure encore un défi de taille et ceci est en partie relié au manque de connaissances des fonctions biologiques de LRPPRC et des m��canismes impliqués dans la pathogenèse du LSFC, au niveau des dysfonctions mitochondriales résultantes. Afin d’étudier ces m��canismes, le consortium de l’acidose lactique, dont fait partie notre laboratoire, a récemment développé un modèle murin portant une ablation de LRPPRC spécifique au foie (souris H-Lrpprc-/-). L’objectif principal est de déterminer si ce modèle reproduit le phénotype pathologique observé dans les cultures de fibroblastes humains issus de biopsies de peau de patients LSFC. Dans le cadre des travaux de ce m��moire, nous avons amorc�� la caractérisation de ce nouveau modèle, en examinant le phénotype général, l’histopathologie hépatique et les fonctions mitochondriales, et en nous focalisant principalement sur les fonctions respiratoires et la capacité à oxyder divers types de substrats. Nous avons observé un retard de croissance, une hépatom��galie ainsi que plusieurs anomalies histologiques du foie chez la souris HLrpprc-/-. De plus, l’ablation de LRPPRC induit un déficit du complexe IV, mais aussi de l’ATP synthase, et affecte l’oxydation des acides gras à longues chaines. À la lumière de ces résultats, nous croyons que le modèle murin H-Lrpprc-/- contribuera à l’avancement des connaissances générales sur LRPPRC, nous permettant de mieux comprendre l’influence de la protéine sur les fonctions mitochondriales.