Plasma membrane calcium ATPase isoform 4 inhibits vascular endothelial growth factor-mediated angiogenesis through interaction with calcineurin

Approach and Results - Using in vitro and in vivo assays, we here demonstrate that the interaction between PMCA4 and calcineurin in VEGF-stimulated endothelial cells leads to downregulation of the calcineurin/NFAT pathway and to a significant reduction in the subsequent expression of the NFAT-dependent, VEGF-activated, proangiogenic genes RCAN1.4 and Cox-2. PMCA4-dependent inhibition of calcineurin signaling translates into a reduction in endothelial cell motility and blood vessel formation that ultimately impairs in vivo angiogenesis by VEGF. Objective - Vascular endothelial growth factor (VEGF) has been identified as a crucial regulator of physiological and pathological angiogenesis. Among the intracellular signaling pathways triggered by VEGF, activation of the calcineurin/ nuclear factor of activated T cells (NFAT) signaling axis has emerged as a critical mediator of angiogenic processes. We and others previously reported a novel role for the plasma membrane calcium ATPase (PMCA) as an endogenous inhibitor of the calcineurin/NFAT pathway, via interaction with calcineurin, in cardiomyocytes and breast cancer cells. However, the functional significance of the PMCA/calcineurin interaction in endothelial pathophysiology has not been addressed thus far. Conclusions - Given the importance of the calcineurin/NFAT pathway in the regulation of pathological angiogenesis, targeted modulation of PMCA4 functionality might open novel therapeutic avenues to promote or attenuate new vessel formation in diseases that occur with angiogenesis.

A novel role of plasma membrane calcium atpase 4 as a negative-regulator of VEGF-induced angiogenesis

Current anti-angiogenic treatments involve the attenuation of signalling via the pro-angiogenic vascular endothelial growth factor/receptor (VEGF/VEGFR) axis. Stimulation of angiogenesis by VEGF requires the activation of the calcineurin/nuclear factor of activated T-cells (NFAT) signal transduction pathway which is inhibited by Plasma Membrane Calcium ATPase 4 (PMCA4), an endogenous calcium extrusion pump. However, PMCA4s role in calcineurin/NFAT-dependent angiogenesis is unknown. Using “gain of function” studies, we show here that adenoviral overexpression of PMCA4 in human umbilical vein endothelial cells (HUVEC) inhibited NFAT activity, decreased the expression of NFAT-dependent pro-angiogenic proteins (regulator of calcineurin 1.4 (RCAN1.4) and cyclooxygenase-2) and diminished in vitro cell migration and tube formation in response to VEGF-stimulation. Furthermore, in vivo blood vessel formation was attenuated in a matrigel plug assay by ectopic expression of PMCA4. Conversely, “loss of function” experiments by si-RNA-mediated knockdown of PMCA4 in HUVEC or isolation of mouse lung endothelial cells from PMCA4−/− mice showed increased VEGF-induced NFAT activity, RCAN1.4 expression, in vitro endothelial cell migration, tube formation and in vivo blood vessel formation. Additionally, in an in vivo pathological angiogenesis model of limb ischemia, the reperfusion of the ischemic limb of PMCA4−/− mice was augmented compared to wild-type. Disruption of the interaction between endogenous PMCA4 and calcineurin by adenoviral overexpression of the region of PMCA4 that interacts with calcineurin (residues 428–651) increased NFAT activity, RCAN1.4 protein expression and in vitro tube formation. These results identify PMCA4 as an inhibitor of VEGF-induced angiogenesis, highlighting its potential as a new therapeutic target for anti-angiogenic treatments.

Carreras de caballos en España 2011-2014: características y relación con la incidencia de lesiones músculo-esqueléticas catastróficas

Las lesiones físicas graves o accidentes catastróficos sufridos por los caballos participantes en las carreras de velocidad causan una gran preocupación a todos los integrantes del sector de este deporte ecuestre, tanto para los profesionales como para los aficionados y espectadores del mismo. La seguridad, tanto de los animales como de los jinetes que los conducen, es por tanto una prioridad de máximo nivel para las Sociedades Organizadoras y las Autoridades Hípicas. Otros puntos importantes a tener en cuenta, en lo que a lesiones catastróficas se refiere, son el propio impacto económico que tienen estas patologías en la industria del turf y la percepción e imagen pública de las carreras de caballos, sobre todo en los casos en que las lesiones ocurren durante el transcuso de las competiciones y/o ante el público...

From "ecological tourism" to "ecotourism": lexical analysis of an emerging tourism

From ecological tourism to ecotourism: lexical analysis of an emerging tourism. This article deals with the lexicon created in connection with a recent form of tourism: the ecological tourism or ecotourism. The rise of this type of tourism encourages the creation of new concepts and products that are named with new words and expressions with different procedures of formation. From the name itself ecotourism, then expressed as the acronym ecotourism, we analyze the formation of other related words, as well as their formal variation and use. For this, we have worked with a specific corpus of electronic tourist texts and different digital sources and databases.

La culebrilla ciega de las macetas (Ramphotyphlops braminus), una nueva especie introducida en el archipiélago canario.

[ES] Uno de los problemas que más afectan a la biodiversidad de los archipiélagos es la introducción de especies alóctonas, y en el caso concreto de los reptiles la bibliografía nos recuerda algunos ejemplos especialmente significativos (Case et al., 1992; Loope & Helweg, 2004). En Canarias se han detectado numerosos reptiles foráneos. Pleguezuelos (2002) hace referencia a 21 especies diferentes que han llegado desde otros lugares del mundo, una cifra a la que habría que sumar cuatro o cinco más, resultantes del intercambio faunístico entre islas del mismo archipiélago. En algunos casos se trata de individuos aislados o de especies que, por sus requerimientos ecológicos, nunca llegarán a formar poblaciones estables en el archipiélago.

Hallux rigidus: Arthroplasty or arthrodesis. What technique produces better results?

Hallux rígidus (HR) affects the first metatarsophalangeal joint (MTPJ) between 35% and 60% of the population over 65 years and there are multiple ways of treatment. Depending on the radiological stage where you find the deformity determines the procedure to be performed; in the early stages cheilectomy techniques and corrective osteotomy is performed while the more advanced ratings, the surgeon chooses destructive techniques considered as arthrodesis and arthroplasty. This final of degree project aims to focus on 1 MTPJ destructive techniques to clarify which of the procedures generates better results by a number of parameters; outcomes of the American Orthopaedic Foot scale and Ankle Society Hallux metatarsophalangeal Interphalangeal-scale (AOFAS), range of motion (ROM) of the 1ºAMTF, radiological classification. As for the implant arthroplasty technique, this article offers information on material and design that generates better relating to patient characteristics such as age, inflammatory joint diseases, viability and durability of the implant results. The conclusion from this review is that the values obtained in the arthrodesis according AOFAS decrease due to loss of mobility, but both techniques have similar values of effectiveness and concludes with the decision that the technique used is determined taking into account various factors and patient characteristics. Keywords: Hallux rígidus; (Hallux Rígidus) and surgery treatment; Hallux Rígidus arthrodesis; Hallux Rígidus arthroplasty; Hallux Rígidus (arthroplasty and arthrodesis).

High On/Off ratio memristive switching of manganite/cuprate bilayer by interfacial magnetoelectricity

Memristive switching serves as the basis for a new generation of electronic devices. Memristors are two-terminal devices in which the current is turned on and off by redistributing point defects, e.g., vacancies, which is difficult to control. Memristors based on alternative mechanisms have been explored, but achieving both the high On/Off ratio and the low switching energy desirable for use in electronics remains a challenge. Here we report memristive switching in a La_(0.7)Ca_(0.3)MnO_(3)/PrBa_(2)Cu_(3)O_(7) bilayer with an On/Off ratio greater than 103 and demonstrate that the phenomenon originates from a new type of interfacial magnetoelectricity. Using results from firstprinciples calculations, we show that an external electric-field induces subtle displacements of the interfacial Mn ions, which switches on/off an interfacial magnetic “dead” layer, resulting in memristive behavior for spin-polarized electron transport across the bilayer. The interfacial nature of the switching entails low energy cost about of a tenth of atto Joule for write/erase a “bit”. Our results indicate new opportunities for manganite/cuprate systems and other transition-metal-oxide junctions in memristive applications.

Arku fazial birtualaren balidazioa eta optimizazioa

[EU]"Arku fazial birtualaren balidazioa eta optimizazioa". Odontologian eta, oro har, medikuntzan, prozesu birtualek geroz eta indar handiagoa hartzen dabiltza, bai espezialista baita pazienteei erraztasuna emateko asmoz. Ildo horretatik jarraituz, protesien eta hortz-errestaurazioen kasuan, ikerketa sakonak burutu dira, prozesuaren ahalik eta zatirik handiena digitalizatzeko. Digitalizazio prozesu honetan CAD/CAM sistemaren aurrerapenek ere zeresan handia izan dute; izan ere, protesi eta errestaurazioen prozesu tradizionala ordezkatzea ahalbidetu du. Prozesu digitalek hainbat onura suposatu arren, zein fidagarriak diren konprobatzea ezinbestekoa da, prozesuarentzat metodologiarik egokiena aukeratu ahal izateko. Horretan zentratzen da hain zuzen proiektu hau. Protesien diseinu birtuala egin ahal izateko, beharrezkoa da horzduren kokapen birtuala lortzea, artikulagailu birtualean kokatu ahal izateko. Horretarako arku fazial birtuala erabiliko da, baina oraindik ez da metodologiarik egokiena zein den konprobatu. Beraz, proiektu honen helburua arku fazial birtual egokiena zein den zehaztea da, horretarako metodologia ezberdinak konparatuko direlarik bai modelo ez-erreala erabiliz (in vitro) baita paziente errealekin (in vivo). Horrela, prozesu ezberdinen zehaztasuna zein den konprobatu ahal izango da, bakoitzaren egiazkotasuna eta doitasuna aztertuz. Emaitzetan oinarrituz, arku fazial birtual gisa metodologiarik egokiena zein den ondorioztatu ahal izango da.

Une analyse du processus de justice transitionnelle au Pérou à la lumière du Droit international

Le droit international, notamment le droit international des droits de l’homme, a établi des obligations étatiques pour affronter les défis des sociétés en transition : la recherche de la vérité autour des crimes du passé, la poursuite et la sanction pénale aux auteurs de ces crimes, et la réparation aux victimes. Les limitations politiques, sociales et juridiques de la justice transitionnelle sont énormes et elles représentent de grands défis pour les États et pour la communauté internationale en général. Cette recherche a pour but l’analyse du processus de la justice transitionnelle au Pérou après le conflit armé interne et le régime autoritaire de l’ex-présidente Alberto Fujimori à la lumière du droit international. L’étude conclut que le Pérou a accompli les obligations imposées par le droit international en utilisant une approche intégrale de la justice de transition. Néanmoins, il reste encore quelques défis à surmonter liés aux facteurs politiques et sociaux de la réalité péruvienne.

Une analyse du processus de justice transitionnelle au Pérou à la lumière du Droit international

Le droit international, notamment le droit international des droits de l’homme, a établi des obligations étatiques pour affronter les défis des sociétés en transition : la recherche de la vérité autour des crimes du passé, la poursuite et la sanction pénale aux auteurs de ces crimes, et la réparation aux victimes. Les limitations politiques, sociales et juridiques de la justice transitionnelle sont énormes et elles représentent de grands défis pour les États et pour la communauté internationale en général. Cette recherche a pour but l’analyse du processus de la justice transitionnelle au Pérou après le conflit armé interne et le régime autoritaire de l’ex-présidente Alberto Fujimori à la lumière du droit international. L’étude conclut que le Pérou a accompli les obligations imposées par le droit international en utilisant une approche intégrale de la justice de transition. Néanmoins, il reste encore quelques défis à surmonter liés aux facteurs politiques et sociaux de la réalité péruvienne.

Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

Increased activity of the noradrenergic system in the amygdala has been suggested to contribute to the hyperarousal symptoms associated with post-traumatic stress disorder (PTSD). However, only two studies have examined the content of noradrenaline or its metabolites in the amygdala of rats previously exposed to traumatic stress showing inconsistent results. The aim of this study was to investigate the effects of an inescapable foot shock (IFS) procedure 1) on reactivity to novelty in an open-field (as an index of hyperarousal), and 2) on noradrenaline release in the amygdala during an acute stress. To test the role of noradrenaline in amygdala, we also investigated the effects of microinjections of propranolol, a β-adrenoreceptor antagonist, and clenbuterol, a β-adrenoreceptor agonist, into the amygdala of IFS and control animals. Finally, we evaluated the expression of mRNA levels of β-adrenoreceptors (β1 and β2) in the amygdala, the hippocampus and the prefrontal cortex. Male Wistar rats (3 months) were stereotaxically implanted with bilateral guide cannulae. After recovering from surgery, animals were exposed to IFS (10 shocks, 0.86 mA, and 6 seconds per shock) and seven days later either microdialysis or microinjections were performed in amygdala. Animals exposed to IFS showed a reduced locomotion compared to non-shocked animals during the first 5 minutes in the open-field. In the amygdala, IFS animals showed an enhanced increase of noradrenaline induced by stress compared to control animals. Bilateral microinjections of propranolol (0.5 μg) into the amygdala one hour before testing in the open-field normalized the decreased locomotion observed in IFS animals. On the other hand, bilateral microinjections of clenbuterol (30 ng) into the amygdala of control animals did not change the exploratory activity induced by novelty in the open field. IFS modified the mRNA expression of β1 and β2 adrenoreceptors in the prefrontal cortex and the hippocampus. These results suggest that an increased noradrenergic activity in the amygdala contributes to the expression of hyperarousal in an animal model of PTSD.

Infralimbic cortex controls the activity of the hypothalamus-pituitary adrenal axis and the formation of aversive memory: effects of environmental enrichment

The aim of the present study was to investigate the effects of the stimulation and inhibition of the ventral part of the medial prefrontal cortex (infralimbic cortex) on basal and stress-induced plasma levels of corticosterone and on the acquisition of aversive memory in animals maintained in control and environmental enrichment (EE) conditions. Intracortical microinjections of the GABAA antagonist picrotoxin and agonist muscimol were performed in male Wistar rats to stimulate and inhibit, respectively, the activity of the infralimbic cortex. Injections were performed 60 min before foot shock stress and training in the inhibitory avoidance task. Picrotoxin injections into the infralimbic cortex increased basal plasma levels of corticosterone. These increases were higher in EE rats which suggest that EE enhances the control exerted by infralimbic cortex over the hypothalamus-pituitary-adrenal (HPA) axis and corticosterone release. Muscimol injections into the infralimbic cortex reduced the stress-induced plasma levels of corticosterone and the retention latency 24 h after training in the inhibitory avoidance performance in control and EE animals, respectively. These results further suggest that the infralimbic cortex is required for the activation of the HPA axis during stress and for the acquisition of contextual aversive memories.

Coartación aórtica

Las teorías propuestas en la fisiopatología de la CA incluyen: 1) En el periodo prenatal el flujo eyectado por el ventrículo izquierdo continua por las ramas del cayado aórtico y el del ventrículo derecho pasa a la aorta descendente a través del conducto arteriovenoso, con disminución de irrigación del istmo y alteración secundaria del calibre. 2) Patrones de migración anormales del desarrollo del arco, que ocasionan una hipoplasia tubular del istmo.

Perda na colheita do milho: quando a catação compensa?

Estudo feito pela Faculdade de Tecnologia (FATEC) de Pompeia-SP estimou perdas na colheita mecânica do milho de alta tecnologia em até 12 sacas por hectare. A maior parte desta quantidade ocorria na forma de espigas inteiras, e não de grãos soltos. Nosso objetivo foi identificar em que situação o procedimento da catação - recuperação manual das espigas perdidas durante a colheita mecanizada - é lucrativo ou não para o produtor.