A quantitative method to assess extrasynaptic NMDA receptor function in the protective effect of synaptic activity against neurotoxicity

<p>Abstract</p> <p>Background</p> <p>Extrasynaptic NMDA receptors couple to a CREB shut-off pathway and cause cell death, whereas synaptic NMDA receptors and nuclear calcium signaling promote CREB-mediated transcription and neuronal survival. The distribution of NMDA receptors (synaptic versus extrasynaptic) may be an important parameter that determines the susceptibility of neurons to toxic insults. Changes in receptor surface expression towards more extrasynaptic NMDA receptors may lead to neurodegeneration, whereas a reduction of extrasynaptic NMDA receptors may render neurons more resistant to death. A quantitative assessment of extrasynaptic NMDA receptors in individual neurons is needed in order to investigate the role of NMDA receptor distribution in neuronal survival and death.</p> <p>Results</p> <p>Here we refined and verified a protocol previously used to isolate the effects of extrasynaptic NMDA receptors using the NMDA receptor open channel blocker, MK-801. Using this method we investigated the possibility that the known neuroprotective shield built up in hippocampal neurons after a period of action potential bursting and stimulation of synaptic NMDA receptors is due to signal-induced trafficking of extrasynaptic NMDA receptors or a reduction in extrasynaptic NMDA receptor function. We found that extrasynaptic NMDA receptor-mediated calcium responses and whole cell currents recorded under voltage clamp were surprisingly invariable and did not change even after prolonged (16 to 24 hours) periods of bursting and synaptic NMDA receptor activation. Averaging a large number of calcium imaging traces yielded a small (6%) reduction of extrasynaptic NMDA receptor-mediated responses in hippocampal neurons that were pretreated with prolonged bursting.</p> <p>Conclusion</p> <p>The slight reduction in extrasynaptic NMDA receptor function following action potential bursting and synaptic NMDA receptor stimulation could contribute to but is unlikely to fully account for activity-dependent neuroprotection. Other factors, in particular calcium signaling to the nucleus and the induction of survival promoting genes are more likely to mediate acquired neuroprotection.</p

Misleading transitions in Germany when the labour market needs qualified workforce. An opportunity for a socio-educational turn in training for work

Este artículo contribuye a la reflexión sobre la responsabilidad de la intervención socioeducativa con jóvenes en sus transiciones al mercado de trabajo. La reflexión que se realiza es doble: Por una parte, una fundamentación antropológica sobre el sujeto, su voluntad y su capacidad de decisión, que ha de ser la consideración principal de cualquier intervención educativa. Por otra parte, la revisión de la tradición alemana de la práctica socioeducativa, de la Educación Social como ciencia de la educación, y de la tensión que provoca el encargo que la sociedad le hace, en términos de control y de promoción de las capacidades del sujeto en situación de riesgo. A partir de algunosejemplos tomados de la práctica de la formación e intermediación en el marco de los programas de transición, se proponen una serie de principios reguladores de la intervención para salvaguardar su carácter educativo frente a una posible instrumentalización que resulta perjudicial para el sujeto, así como para el mercado de trabajo.This paper is a contribution to the reflection upon the responsibility underlying socioeducational practice with Young people in their transitions into the labor market. This reflection is twofold: On the one side, it consists of an anthropological justification on the subject, his/her will and his/her ability to take decisions, which is behind any socioeducational intervention. On other side, the paper reviews the German tradition on Social Education as one among the educational sciences, and the tensión it suffers upon the mandate received from society, consisting of a control practice as well as an empowering one, particularly with people at risk. Upon several examples taken from training practice within programs framed by transition systems, the author suggests a series of principles ruling intervention in order to guarantee its true educational value before any instrumentalization which ends up damaging both the subject as well as the labor market.Universidad de Granada. Departamento de Didáctica y Organización Escolar. Grupo FORCE (HUM-386

Transiciones en fuera de juego en alemania ante un mercado de trabajo necesitado de mano de obra. Función de la educación social en la formación e intermediación laboral

Resumen:Este artículo contribuye a la reflexión sobre la responsabilidad de la intervención socioeducativa con jóvenes en sus transiciones al mercado de trabajo. La reflexión que se realiza es doble: Por una parte, una fundamentación antropológica sobre el sujeto, su voluntad y su capacidad de decisión, que ha de ser la consideración principal de cualquier intervención educativa. Por otra parte, la revisión de la tradición alemana de la práctica socioeducativa, de la Educación Social como ciencia de la educación, y de la tensión que provoca el encargo que la sociedad le hace, en términos de control y de promoción de las capacidades del sujeto en situación de riesgo. A partir de algunos  ejemplos tomados de la práctica de la formación e intermediación en el marco de los programas de transición, se proponen una serie de principios reguladores de la intervención para salvaguardar su carácter educativo frente a una posible instrumentalización que resulta perjudicial para el sujeto, así como para el mercado de trabajo. Abstract:This paper is a contribution to the reflection upon the responsibility underlying socioeducational practice with Young people in their transitions into the labor market. This reflection is twofold: On the one side, it consists of an anthropological justification on the subject, his/her will and his/her ability to take decisions, which is behind any socioeducational intervention. On other side, the paper reviews the German tradition on Social Education as one among the educational sciences, and the tensión it suffers upon the mandate received from society, consisting of a control practice as well as an empowering one, particularly with people at risk. Upon several examples taken from training practice within programs framed by transition systems, the author suggests a series of principles ruling intervention in order to guarantee its true educational value before any instrumentalization which ends up damaging both the subject as well as the labor market

Behaviour change and Pay-As-You-Drive insurance. Rewards, punishment, and persuasive information delivery:PAYD-1. Feedback from Pay-As-You-Drive insurance, both outside and inside the car

Pay-As-You-Drive insurance (PAYD) where insurance customers can be charged directly for when, where, and how they drive, is now possible thanks to modern telematics technology. PAYD addresses many problems with traditional insurance in terms of more fairly, and transparently, charging users for their driving behaviour and lessens the impacts of insurance on lower socioeconomic groups in particular (Adkins, 2004; Bordoff & Noel, 2008; Litman, 2005a; Litman, 2011). Indeed, some estimates of PAYD in the USA have suggested that if it was implemented two thirds of households would benefit, with savings of around 270 USD per car per year (Bordoff & Noel, 2008; Litman, 2011). However, PAYD insurance does not only have the potential to benefit individuals. Rather, it is estimated to have significant societal impacts, including possible reductions in mileage of up to 8-12% (Adkins, 2004; Balcombe et al., 2004; Bordoff & Noel, 2008; Harvey & Deakin, 1998; Litman, 2005a; Litman, 2011), which could then be associated with accident reductions of 12-18% (Litman, 2011). Furthermore, it is also estimated that even an 8% reduction in mileage would reduce CO2 emissions by 2% and petrol consumption by 4%. This reduction in petrol consumption would be equivalent to the effect of a 1 USD per gallon increase in the price of petrol (Bordoff & Noel, 2008). It is also estimated that PAYD insurance may reduce the profits of insurance companies (Adkins, 2004; Bordoff & Noel, 2008; Litman, 2011). It is therefore recommended that, due to the significant societal gains associated with PAYD insurance, governments examine what they can do to help encourage PAYD insurance despite the potential costs to insurance companies (Adkins, 2004; Bordoff & Noel, 2008; Litman, 2011)

Behaviour change and Pay-As-You-Drive insurance. Rewards, punishment, and persuasive information delivery:PAYD-1. Feedback from Pay-As-You-Drive insurance, both outside and inside the car

Pay-As-You-Drive insurance (PAYD) where insurance customers can be charged directly for when, where, and how they drive, is now possible thanks to modern telematics technology. PAYD addresses many problems with traditional insurance in terms of more fairly, and transparently, charging users for their driving behaviour and lessens the impacts of insurance on lower socioeconomic groups in particular (Adkins, 2004; Bordoff & Noel, 2008; Litman, 2005a; Litman, 2011). Indeed, some estimates of PAYD in the USA have suggested that if it was implemented two thirds of households would benefit, with savings of around 270 USD per car per year (Bordoff & Noel, 2008; Litman, 2011). However, PAYD insurance does not only have the potential to benefit individuals. Rather, it is estimated to have significant societal impacts, including possible reductions in mileage of up to 8-12% (Adkins, 2004; Balcombe et al., 2004; Bordoff & Noel, 2008; Harvey & Deakin, 1998; Litman, 2005a; Litman, 2011), which could then be associated with accident reductions of 12-18% (Litman, 2011). Furthermore, it is also estimated that even an 8% reduction in mileage would reduce CO2 emissions by 2% and petrol consumption by 4%. This reduction in petrol consumption would be equivalent to the effect of a 1 USD per gallon increase in the price of petrol (Bordoff & Noel, 2008). It is also estimated that PAYD insurance may reduce the profits of insurance companies (Adkins, 2004; Bordoff & Noel, 2008; Litman, 2011). It is therefore recommended that, due to the significant societal gains associated with PAYD insurance, governments examine what they can do to help encourage PAYD insurance despite the potential costs to insurance companies (Adkins, 2004; Bordoff & Noel, 2008; Litman, 2011)

Competing effects of spreading rate, crystal fractionation and source variability on Fe isotope systematics in mid-ocean ridge lavas

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Richter, M., Nebel, O., Schwindinger, M., Nebel-Jacobsen, Y., & Dick, H. J. B. Competing effects of spreading rate, crystal fractionation and source variability on Fe isotope systematics in mid-ocean ridge lavas. Scientific Reports, 11(1), (2021): 4123, https://doi.org/10.1038/s41598-021-83387-7.Two-thirds of the Earth is covered by mid-ocean ridge basalts, which form along a network of divergent plate margins. Basalts along these margins display a chemical diversity, which is consequent to a complex interplay of partial mantle melting in the upper mantle and magmatic differentiation processes in lower crustal levels. Igneous differentiation (crystal fractionation, partial melting) and source heterogeneity, in general, are key drivers creating variable chemistry in mid-ocean ridge basalts. This variability is reflected in iron isotope systematics (expressed as δ57Fe), showing a total range of 0.2 ‰ from δ57Fe =  + 0.05 to + 0.25 ‰. Respective contributions of source heterogeneity and magma differentiation leading to this diversity, however, remain elusive. This study investigates the iron isotope systematics in basalts from the ultraslow spreading Gakkel Ridge in the Arctic Ocean and compares them to existing data from the fast spreading East Pacific Rise ridge. Results indicate that Gakkel lavas are driven to heavier iron isotope compositions through partial melting processes, whereas effects of igneous differentiation are minor. This is in stark contrast to fast spreading ridges showing reversed effects of near negligible partial melting effects followed by large isotope fractionation along the liquid line of descent. Gakkel lavas further reveal mantle heterogeneity that is superimposed on the igneous differentiation effects, showing that upper mantle Fe isotope heterogeneity can be transmitted into erupting basalts in the absence of homogenisation processes in sub-oceanic magma chambers.This work was supported by an ARC grant FT140101062 to O.N. H.J.B.D was supported by the NSF grants PLR 9912162, PLR 0327591, OCE 0930487 and OCE 1434452