Amyloid-β acts as a regulator of neurotransmitter release disrupting the interaction between synaptophysin and VAMP2.

BACKGROUND: It is becoming increasingly evident that deficits in the cortex and hippocampus at early stages of dementia in Alzheimer's disease (AD) are associated with synaptic damage caused by oligomers of the toxic amyloid-β peptide (Aβ42). However, the underlying molecular and cellular mechanisms behind these deficits are not fully understood. Here we provide evidence of a mechanism by which Aβ42 affects synaptic transmission regulating neurotransmitter release. METHODOLOGY/FINDINGS: We first showed that application of 50 nM Aβ42 in cultured neurones is followed by its internalisation and translocation to synaptic contacts. Interestingly, our results demonstrate that with time, Aβ42 can be detected at the presynaptic terminals where it interacts with Synaptophysin. Furthermore, data from dissociated hippocampal neurons as well as biochemical data provide evidence that Aβ42 disrupts the complex formed between Synaptophysin and VAMP2 increasing the amount of primed vesicles and exocytosis. Finally, electrophysiology recordings in brain slices confirmed that Aβ42 affects baseline transmission. CONCLUSIONS/SIGNIFICANCE: Our observations provide a necessary and timely insight into cellular mechanisms that underlie the initial pathological events that lead to synaptic dysfunction in Alzheimer's disease. Our results demonstrate a new mechanism by which Aβ42 affects synaptic activity

Incomplete Transition Complexity of Basic Operations on Finite Languages

The state complexity of basic operations on finite languages (considering complete DFAs) has been in studied the literature. In this paper we study the incomplete (deterministic) state and transition complexity on finite languages of boolean operations, concatenation, star, and reversal. For all operations we give tight upper bounds for both description measures. We correct the published state complexity of concatenation for complete DFAs and provide a tight upper bound for the case when the right automaton is larger than the left one. For all binary operations the tightness is proved using family languages with a variable alphabet size. In general the operational complexities depend not only on the complexities of the operands but also on other refined measures.Comment: 13 page

Scanning X-Ray Microanalysis of Microcarrier Cultured Endothelial Cells: Elemental Changes During the Transition to Confluency and the Effect of Ionophore A23187

Porcine endothelial cells were grown on microcarrier beads and examined by scanning electron microscopy (SEM) at various times after initiation of culture. Total cell coverage on the bead surface varied from mean values of approximately 7% (3h) to 80% (96h). Beam penetration into the subcellular matrix presents a major problem with SEM X-ray microanalysis of microcarrier cultured cells and necessitates the use of an accelerating voltage not exceeding 10kV. At this voltage and below, X-ray contribution from elements present in the microcarrier bead has minimal effect on the determination of cell elemental levels. Washing the cells with 0.15M sucrose was the least perturbing of the rinsing techniques investigated. removing surface culture medium but not internal diffusible ions. X-ray microanalysis revealed detectable levels of Na, P, S, Cl, K and Ca in the cells, with well-marked changes from initial attachment to confluency. The level of K decreased from approximately 1.0% at 3h to 0.4% at 24h, with a corresponding decrease in the K/Na ratio. This unexpectedly low level of K was invariably observed after 24h, and is a genuine feature of established microcarrier culture. The effect of ionophore A23187 was determined at the 3h culture stage, and resulted in significant increases in the concentration of divalent cations (Mg2+, Ca2+), monovalent ions (Na+, Cl-) and a decrease in the level of K+

Barriers and facilitators to social prescribing in child and youth mental health: Perspectives from the frontline

There is growing interest in the role of Social Prescribing (SP) to help promote mental wellbeing and support individuals with mental health difficulties. Yet, implementation of SP to children and young people (CYP) has proved slow and underdeveloped compared with adult populations. Understanding the barriers and facilitators will help key stakeholders to better embed SP for CYP into practice. Using the Theoretical Domains Framework (TDF), a comprehensive, theoretical-led framework, underpinned by 33 behaviour change theories and 128 constructs, perceived barriers and facilitators to SP were investigated. The sample comprised of 11 Link Workers and 9 individuals involved in facilitating SP with CYP, who took part in semi-structured interviews. Transcripts were analysed using a deductive thematic analysis, and themes were coded under each theoretical domain. Overall, 33 barriers and facilitators for SP were identified across 12 domains of the TDF. Under capability, barriers and facilitators were found for knowledge, skills, memory/attention/decision making processes, and behavioural regulation. For opportunity, barriers and facilitators were found for social/professional influences, as well as environmental context and resources. Finally, for motivation, domains covered included: beliefs about consequences, beliefs about capabilities, optimism, motivations/goals, reinforcement, and emotions. Findings suggest that a wide range of barriers and facilitators affect the implementation of CYP SP to improve mental health and wellbeing. Interventions which target different domains related to capability, opportunity and motivation should be developed to better facilitate CYP SP

Elevated CO2induces a bloom of microphytobenthos within a shell gravel mesocosm

The geological storage of carbon dioxide (CO2) is expected to be an important component of future global carbon emission mitigation, but there is a need to understand the impacts of a CO2 leak on the marine environment and to develop monitoring protocols for leakage detection. In the present study, sediment cores were exposed to CO2-acidified seawater at one of five pH levels (8.0, 7.5, 7.0, 6.5 and 6.0) for 10 weeks. A bloom of Spirulina sp. and diatoms appeared on sediment surface exposed to pH 7.0 and 7.5 seawater. Quantitative PCR measurements of the abundance of 16S rRNA also indicated an increase within the pH 7.0 and 7.5 treatments after 10 weeks incubation. More detailed analysis of the microbial communities from the pH 7.0, 7.5 and 8.0 treatments confirmed an increase in the relative abundance of Spirulina sp. and Navicula sp. sequences, with changes in the relative abundance of major archaeal and bacterial groups also detected within the pH 7.0 treatment. A decreased flux of silicate from the sediment at this pH was also detected. Monitoring blooms of microphytobenthos may prove useful as an indicator of CO2 leakage within coastal area

Barriers and facilitators to social prescribing in child and youth mental health: perspectives from the frontline

There is growing interest in the role of Social Prescribing (SP) to help promote mental well-being and support individuals with mental health difficulties. Yet, implementation of SP to children and young people (CYP) has proved slow and underdeveloped compared with adult populations. Understanding the barriers and facilitators will help key stakeholders to better embed SP for CYP into practice. Using the Theoretical Domains Framework (TDF), a comprehensive, theoretical-led framework, underpinned by 33 behaviour change theories and 128 constructs, perceived barriers and facilitators to SP were investigated. The sample comprised of 11 Link Workers and 9 individuals involved in facilitating SP with CYP, who took part in semi-structured interviews. Transcripts were analysed using a deductive thematic analysis, and themes were coded under each theoretical domain. Overall, 33 barriers and facilitators for SP were identified across 12 domains of the TDF. Under capability, barriers and facilitators were found for knowledge, skills, memory/attention/decision making processes, and behavioural regulation. For opportunity, barriers and facilitators were found for social/professional influences, as well as environmental context and resources. Finally, for motivation, domains covered included: beliefs about consequences, beliefs about capabilities, optimism, motivations/goals, reinforcement, and emotions. Findings suggest that a wide range of barriers and facilitators affect the implementation of CYP SP to improve mental health and well-being. Interventions which target different domains related to capability, opportunity and motivation should be developed to better facilitate CYP SP

Profile of the U 5f magnetization in U/Fe multilayers

Recent calculations, concerning the magnetism of uranium in the U/Fe multilayer system have described the spatial dependence of the 5f polarization that might be expected. We have used the x-ray resonant magnetic reflectivity technique to obtain the profile of the induced uranium magnetic moment for selected U/Fe multilayer samples. This study extends the use of x-ray magnetic scattering for induced moment systems to the 5f actinide metals. The spatial dependence of the U magnetization shows that the predominant fraction of the polarization is present at the interfacial boundaries, decaying rapidly towards the center of the uranium layer, in good agreement with predictions.Comment: 7 pages, 6 figure