Tau isoform-specific enhancement of L-type calcium current and augmentation of afterhyperpolarization in rat hippocampal neurons.

This is the final version. Available from Springer Nature via the DOI in this record. Data availability: All materials, data and associated protocols will be made available to readers upon reasonable request to Prof. N.V. Marrion ([email protected]), without undue qualifications.Accumulation of tau is observed in dementia, with human tau displaying 6 isoforms grouped by whether they display either 3 or 4 C-terminal repeat domains (3R or 4R) and exhibit no (0N), one (1N) or two (2N) N terminal repeats. Overexpression of 4R0N-tau in rat hippocampal slices enhanced the L-type calcium (Ca2+) current-dependent components of the medium and slow afterhyperpolarizations (AHPs). Overexpression of both 4R0N-tau and 4R2N-tau augmented CaV1.2-mediated L-type currents when expressed in tsA-201 cells, an effect not observed with the third 4R isoform, 4R1N-tau. Current enhancement was only observed when the pore-forming subunit was co-expressed with CaVβ3 and not CaVβ2a subunits. Non-stationary noise analysis indicated that enhanced Ca2+ channel current arose from a larger number of functional channels. 4R0N-tau and CaVβ3 were found to be physically associated by co-immunoprecipitation. In contrast, the 4R1N-tau isoform that did not augment expressed macroscopic L-type Ca2+ current exhibited greatly reduced binding to CaVβ3. These data suggest that physical association between tau and the CaVβ3 subunit stabilises functional L-type channels in the membrane, increasing channel number and Ca2+ influx. Enhancing the Ca2+-dependent component of AHPs would produce cognitive impairment that underlie those seen in the early phases of tauopathies.Alzheimer´s Research U

Disarticulation and the Crisis of Neoliberalism in the United States

Neoliberal policies instituted since the 1980s have transformed the United States economy in ways that have produced serious structural distortions in the basic operation of capitalism. Using Samir Amin’s concept of disarticulation, previously applied exclusively to the periphery of the world economy, this article argues that the twin and mutually reinforcing features of neoliberalism – global corporate restructuring and financialization – have now generated disarticulation in the core nations. This disarticulated structure is responsible for the economic stagnation and sharply unequal income/wealth distributional outcomes that characterize contemporary U.S. capitalism

Public service media in the age of SVoDs: A comparative study of PSM strategic responses in Flanders, Italy and the UK

Netflix and other transnational online video streaming services are disrupting long-established arrangements in national television systems around the world. In this paper we analyse how public service media (PSM) organisations (key purveyors of societal goals in broadcasting) are responding to the fast-growing popularity of these new services. Drawing on Philip Napoli’s framework for analysing strategic responses by established media to threats of competitive displacement by new media, we find that the three PSM organisations in our study exhibit commonalities. Their responses have tended to follow a particular evolution starting with different levels of complacency and resistance before settling into more coherent strategies revolving around efforts to differentiate PSM offerings, while also diversifying into activities, primarily across new platforms, that mimic SVoD approaches and probe production collaborations. Beyond these similarities, however, we also find that a range of contextual factors (including path-dependency, the role and status of PSM in each country, the degree of additional government support, cultural factors and market size) help explain nuances in strategic responses between our three cases

Implications of Flavor Dynamics for Fermion Triplet Leptogenesis

We analyze the importance of flavor effects in models in which leptogenesis proceeds via the decay of Majorana electroweak triplets. We find that depending on the relative strengths of gauge and Yukawa reactions the $B-L$ asymmetry can be sizably enhanced, exceeding in some cases an order of magnitude level. We also discuss the impact that such effects can have for TeV-scale triplets showing that as long as the $B-L$ asymmetry is produced by the dynamics of the lightest such triplet they are negligible, but open the possibility for scenarios in which the asymmetry is generated above the TeV scale by heavier states, possibly surviving the TeV triplet related washouts. We investigate these cases and show how they can be disentangled at the LHC by using Majorana triplet collider observables and, in the case of minimal type III see-saw models even through lepton flavor violation observables.Comment: 22 pages, 9 figures, extended discussion on collider phenomenology, references added. Version matches publication in JHE

Southampton PRegnancy Intervention for the Next Generation (SPRING):protocol for a randomised controlled trial

BACKGROUND: The nutritional status and health of mothers influence the growth and development of infants during pregnancy and postnatal life. Interventions that focus on improving the nutritional status and lifestyle of mothers have the potential to optimise the development of the fetus as well as improve the health of mothers themselves. Improving the diets of women of childbearing age is likely to require complex interventions that are delivered in a socially and culturally appropriate context. In this study we aim to test the efficacy of two interventions: behaviour change (Healthy Conversation Skills) and vitamin D supplementation, and to explore the efficacy of an intervention that combines both, in improving the diet quality and nutritional status of pregnant women. METHODS/DESIGN: Women attending the maternity hospital in Southampton are recruited at between 8 and 12 weeks gestation. They are randomised to one of four groups following a factorial design: Healthy Conversation Skills support plus vitamin D supplementation (1000 IU cholecalciferol) (n = 150); Healthy Conversation Skills support plus placebo (n = 150); usual care plus vitamin D supplementation (n = 150); usual care plus placebo (n = 150). Questionnaire data include parity, sunlight exposure, diet assessment allowing assessment of diet quality, cigarette and alcohol consumption, well-being, self-efficacy and food involvement. At 19 and 34 weeks maternal anthropometry is assessed and blood samples taken to measure 25(OH) vitamin D. Maternal diet quality and 25(OH) vitamin D are the primary outcomes. Secondary outcomes are women's level of self-efficacy at 34 weeks, pregnancy weight gain, women's self-efficacy and breastfeeding status at one month after birth and neonatal bone mineral content, assessed by DXA within the first 14 days after birth. DISCUSSION: This trial is evaluating two approaches to improving maternal diet: a behaviour change intervention and vitamin D supplementation. The factorial design of this trial has the advantage of enabling each intervention to be tested separately as well as allowing exploration of the synergistic effect of both interventions on women's diets and vitamin D levels. TRIAL REGISTRATION: ISRCTN07227232 . Registered on 13 September 2013

Non-unitary Leptonic Mixing and Leptogenesis

We investigate the relation between non-unitarity of the leptonic mixing matrix and leptogenesis. We discuss how all parameters of the canonical type-I seesaw mechanism can, in principle, be reconstructed from the neutrino mass matrix and the deviation of the effective low-energy leptonic mixing matrix from unitary. When the mass M' of the lightest right-handed neutrino is much lighter than the masses of the others, we show that its decay asymmetries within flavour-dependent leptogenesis can be expressed in terms of two contributions, one depending on the unique dimension five (d=5) operator generating neutrino masses and one depending on the dimension six (d=6) operator associated with non-unitarity. In low-energy seesaw scenarios where small lepton number violation explains the smallness of neutrino masses, the lepton number conserving d=6 operator contribution generically dominates over the d=5 operator contribution which results in a strong enhancement of the flavour-dependent decay asymmetries without any resonance effects. To calculate the produced final baryon asymmetry, the flavour equilibration effects directly related to non-unitarity have to be taken into account. In a simple realization of this non-unitarity driven leptogenesis, the lower bound on M' is found to be about 10^8 GeV at the onset of the strong washout regime, more than one order of magnitude below the bound in "standard" thermal leptogenesis.Comment: 19 pages, REVTeX4, 2 eps and 2 axodraw figure

Interaction of a supersonic, radiatively cooled plasma jet with an ambient medium

International audienc

Persistence of Environmental DNA in Freshwater Ecosystems

The precise knowledge of species distribution is a key step in conservation biology. However, species detection can be extremely difficult in many environments, specific life stages and in populations at very low density. The aim of this study was to improve the knowledge on DNA persistence in water in order to confirm the presence of the focus species in freshwater ecosystems. Aquatic vertebrates (fish: Siberian sturgeon and amphibian: Bullfrog tadpoles) were used as target species. In control conditions (tanks) and in the field (ponds), the DNA detectability decreases with time after the removal of the species source of DNA. DNA was detectable for less than one month in both conditions. The density of individuals also influences the dynamics of DNA detectability in water samples. The dynamics of detectability reflects the persistence of DNA fragments in freshwater ecosystems. The short time persistence of detectable amounts of DNA opens perspectives in conservation biology, by allowing access to the presence or absence of species e.g. rare, secretive, potentially invasive, or at low density. This knowledge of DNA persistence will greatly influence planning of biodiversity inventories and biosecurity surveys

Global and regional brain metabolic scaling and its functional consequences

Background: Information processing in the brain requires large amounts of metabolic energy, the spatial distribution of which is highly heterogeneous reflecting complex activity patterns in the mammalian brain. Results: Here, it is found based on empirical data that, despite this heterogeneity, the volume-specific cerebral glucose metabolic rate of many different brain structures scales with brain volume with almost the same exponent around -0.15. The exception is white matter, the metabolism of which seems to scale with a standard specific exponent -1/4. The scaling exponents for the total oxygen and glucose consumptions in the brain in relation to its volume are identical and equal to $0.86\pm 0.03$, which is significantly larger than the exponents 3/4 and 2/3 suggested for whole body basal metabolism on body mass. Conclusions: These findings show explicitly that in mammals (i) volume-specific scaling exponents of the cerebral energy expenditure in different brain parts are approximately constant (except brain stem structures), and (ii) the total cerebral metabolic exponent against brain volume is greater than the much-cited Kleiber's 3/4 exponent. The neurophysiological factors that might account for the regional uniformity of the exponents and for the excessive scaling of the total brain metabolism are discussed, along with the relationship between brain metabolic scaling and computation.Comment: Brain metabolism scales with its mass well above 3/4 exponen