Calpain-Mediated Processing of Adenylate Cyclase Toxin Generates a Cytosolic Soluble Catalytically Active N-Terminal Domain

Bordetella pertussis, the whooping cough pathogen, secretes several virulence factors among which adenylate cyclase toxin (ACT) is essential for establishment of the disease in the respiratory tract. ACT weakens host defenses by suppressing important bactericidal activities of the phagocytic cells. Up to now, it was believed that cell intoxication by ACT was a consequence of the accumulation of abnormally high levels of cAMP, generated exclusively beneath the host plasma membrane by the toxin N-terminal catalytic adenylate cyclase (AC) domain, upon its direct translocation across the lipid bilayer. Here we show that host calpain, a calcium-dependent Cys-protease, is activated into the phagocytes by a toxin-triggered calcium rise, resulting in the proteolytic cleavage of the toxin N-terminal domain that releases a catalytically active "soluble AC''. The calpain-mediated ACT processing allows trafficking of the "soluble AC'' domain into subcellular organella. At least two strategic advantages arise from this singular toxin cleavage, enhancing the specificity of action, and simultaneously preventing an indiscriminate activation of cAMP effectors throughout the cell. The present study provides novel insights into the toxin mechanism of action, as the calpain-mediated toxin processing would confer ACT the capacity for a space- and time-coordinated production of different cAMP "pools'', which would play different roles in the cell pathophysiology.

"I'm on it 24/7 at the moment" : A qualitative examination of multi-screen viewing behaviours among UK 10-11 year olds

Background: Screen-viewing has been associated with increased body mass, increased risk of metabolic syndrome and lower psychological well-being among children and adolescents. There is a shortage of information about the nature of contemporary screen-viewing amongst children especially given the rapid advances in screen-viewing equipment technology and their widespread availability. Anecdotal evidence suggests that large numbers of children embrace the multi-functionality of current devices to engage in multiple forms of screen-viewing at the same time. In this paper we used qualitative methods to assess the nature and extent of multiple forms of screen-viewing in UK children. Methods: Focus groups were conducted with 10-11 year old children (n = 63) who were recruited from five primary schools in Bristol, UK. Topics included the types of screen-viewing in which the participants engaged; whether the participants ever engaged in more than one form of screen-viewing at any time and if so the nature of this multiple viewing; reasons for engaging in multi-screen-viewing; the room within the house where multi-screen-viewing took place and the reasons for selecting that room. All focus groups were transcribed verbatim, anonymised and thematically analysed. Results: Multi-screen viewing was a common behaviour. Although multi-screen viewing often involved watching TV, TV viewing was often the background behaviour with attention focussed towards a laptop, handheld device or smart-phone. There were three main reasons for engaging in multi-screen viewing: 1) tempering impatience that was associated with a programme loading; 2) multi-screen facilitated filtering out unwanted content such as advertisements; and 3) multi-screen viewing was perceived to be enjoyable. Multi-screen viewing occurred either in the child's bedroom or in the main living area of the home. There was considerable variability in the level and timing of viewing and this appeared to be a function of whether the participants attended after-school clubs. Conclusions: UK children regularly engage in two or more forms of screen-viewing at the same time. There are currently no means of assessing multi-screen viewing nor any interventions that specifically focus on reducing multi-screen viewing. To reduce children's overall screen-viewing we need to understand and then develop approaches to reduce multi-screen viewing among children.

Dietary vitamin E inhibits the trans 10-18:1 shift in beef backfat

[EN]Forty feedlot steers were fed a barleygrain-based finishing diet typical for western Canada, with two levels of supplementary vitamin E (468 or 1068 IU head_1 d_1) and the effect on backfat trans-18:1 isomeric profile was determined. Feeding 1068 IU vitamin E reduced the total trans-18:1 content in backfat (P<0.01), as well as the percentage of trans 10-18:1 (P<0.001), which are related to an increased risk for cardiovascular diseases. On the other hand, trans 11-18:1 (vaccenic acid) the precursor for cis 9,trans 11- 18:2 (rumenic acid), which have several purported health benefits, increased (P<0.01). Vitamin E could, therefore, be used to decrease trans-18:1 in beef and improve its isomeric profile.

Serie Vídeos tutoriales para fonética. Video 10. Praat: doing phonetics by computer (Parte 6: Manipulación y síntesis de señales sonoras)

Esta es una colección de 10 vídeos tutoriales que pueden ser empleados como material educativo en los cursos de fonética básica en el ámbito universitario. Los vídeos 1-3 tratan aspectos relacionados con la grabación: el tipo de micrófonos que se emplean, las clases de espacios en las que se suelen llevar a cabo la captura de señales de audio y las grabadoras que se suelen emplear. El vídeo 4 explora técnicas de captura y observación de datos de flujo y presión en fonética aerodinámica. Los vídeos 5-10 presentan información sobre los principales usos que se le brindan al programa Praat (Boersma y Weenink, 2014) en los estudios actuales de fonética acústica, desde la clase de información sobre modos de articulación de las consonantes que se puede identificar en oscilogramas hasta la creación de señales sonoras sintetizadas por medio de unos procedimientos que tiene el programa para tal propósito, los cuales son susceptibles de ser empleados en experimentos de percepción auditiva.

Diseño de un programa de Surf recreativo enfocado a colectivos con Síndrome de Down de 6 a 10 años

El objetivo de este trabajo es diseñar un programa de surf recreativo enfocado a colectivos con Síndrome de Down de 6 a 10 años. El Síndrome de Down se define como una discapacidad intelectual causada por una alteración en el par de cromosomas 21 (OMS, 2011). Resulta de especial relevancia el tratamiento de dicha discapacidad de manera no farmacológica, destacando la actividad física, en este caso el surf, como elemento inclusivo a nivel físico, psicológico y social. Se analizan distintos programas de Actividad Física en el medio acuático con personas con Síndrome de Down y se presenta el Surf como elemento que provoca grandes beneficios. A continuación se presenta el diseño de un programa que podría llevarse a cabo en un entorno cercano a nuestro territorio con un atractivo elevado ya que se trata de un proyecto innovador y beneficioso para personas con Síndrome de Down y sus familiares.

"Frater, ave atque vale" (Catull. 101.10): fortuna literaria de una fórmula epigráfica

Trabajo realizado dentro del Grupo de Investigación «Tradiciones Clásicas» de la UPV/EHU (GIU-07-26)

¿Encargó Braulio de Zaragoza a Eugenio de Toledo que compusiera una Misa de San Millán?: para una interpretación de «Vita Emiliani», 3, 5-10

[EN] What is Braulio asking from Eugenius in this passage: that he requires a Mass to be celebrated (where?) in honour of San Millán, or that Eugenius himself writes the Mass, or, simply, some parts or prayers for it? Firstly, translations and interpretations provided by scholars to date are checked and criticized; then an interpretation of the passage is proposed, being based on textual criticism approaches, on the work context and on the cultural environment in which this work takes place.

La «Vita Mahometi» del códice 10 de Uncastillo (s. XIII): estudio y edición

Actas coordinadas por Maurilio Pérez González

CGP37157, an inhibitor of the mitochondrial Na+/Ca2+ exchanger, protects neurons from excitotoxicity by blocking voltage-gated Ca2+ channels

Inhibition of the mitochondrial Na+/Ca2+ exchanger (NCLX) by CGP37157 is protective in models of neuronal injury that involve disruption of intracellular Ca2+ homeostasis. However, the Ca2+ signaling pathways and stores underlying neuroprotection by that inhibitor are not well defined. In the present study, we analyzed how intracellular Ca2+ levels are modulated by CGP37157 (10 mu M) during NMDA insults in primary cultures of rat cortical neurons. We initially assessed the presence of NCLX in mitochondria of cultured neurons by immunolabeling, and subsequently, we analyzed the effects of CGP37157 on neuronal Ca2+ homeostasis using cameleon-based mitochondrial Ca2+ and cytosolic Ca2+ ([Ca2+](i)) live imaging. We observed that NCLX-driven mitochondrial Ca2+ exchange occurs in cortical neurons under basal conditions as CGP37157 induced a decrease in [Ca-2](i) concomitant with a Ca2+ accumulation inside the mitochondria. In turn, CGP37157 also inhibited mitochondrial Ca2+ efflux after the stimulation of acetylcholine receptors. In contrast, CGP37157 strongly prevented depolarization-induced [Ca2+](i) increase by blocking voltage-gated Ca2+ channels (VGCCs), whereas it did not induce depletion of ER Ca2+ stores. Moreover, mitochondrial Ca2+ overload was reduced as a consequence of diminished Ca2+ entry through VGCCs. The decrease in cytosolic and mitochondrial Ca2+ overload by CGP37157 resulted in a reduction of excitotoxic mitochondrial damage, characterized here by a reduction in mitochondrial membrane depolarization, oxidative stress and calpain activation. In summary, our results provide evidence that during excitotoxicity CGP37157 modulates cytosolic and mitochondrial Ca2+ dynamics that leads to attenuation of NMDA-induced mitochondrial dysfunction and neuronal cell death by blocking VGCCs.

Orden general nº 6 de 10 de agosto de 1937 del Comisariado General del Cuerpo de Ejército nº XIV del Ejército del Norte

Fecha : 10 de agosto de 1937. Unidad de instalación, Carpeta Rectorado G-11. 2 hojas mecanografiadas