Molecular mechanisms contributing to TARP regulation of channel conductance and polyamine block of calcium-permeable AMPA receptors.

Many properties of fast synaptic transmission in the brain are influenced by transmembrane AMPAR regulatory proteins (TARPs) that modulate the pharmacology and gating of AMPA-type glutamate receptors (AMPARs). Although much is known about TARP influence on AMPAR pharmacology and kinetics through their modulation of the extracellular ligand-binding domain (LBD), less is known about their regulation of the ion channel region. TARP-induced modifications in AMPAR channel behavior include increased single-channel conductance and weakened block of calcium-permeable AMPARs (CP-AMPARs) by endogenous intracellular polyamines. To investigate how TARPs modify ion flux and channel block, we examined the action of γ-2 (stargazin) on GluA1 and GluA4 CP-AMPARs. First, we compared the permeation of organic cations of different sizes. We found that γ-2 increased the permeability of several cations but not the estimated AMPAR pore size, suggesting that TARP-induced relief of polyamine block does not reflect altered pore diameter. Second, to determine whether residues in the TARP intracellular C-tail regulate polyamine block and channel conductance, we examined various γ-2 C-tail mutants. We identified the membrane proximal region of the C terminus as crucial for full TARP-attenuation of polyamine block, whereas complete deletion of the C-tail markedly enhanced the TARP-induced increase in channel conductance; thus, the TARP C-tail influences ion permeation. Third, we identified a site in the pore-lining region of the AMPAR, close to its Q/R site, that is crucial in determining the TARP-induced changes in single-channel conductance. This conserved residue represents a site of TARP action, independent of the AMPAR LBD

Middle and Late Pleistocene environmental history of the Marsworth area, south-central England

To elucidate the Middle and Late Pleistocene environmental history of south-central England, we report the stratigraphy, sedimentology, palaeoecology and geochronology of some deposits near the foot of the Chiltern Hills scarp at Marsworth, Buckinghamshire. The Marsworth site is important because its sedimentary sequences contain a rich record of warm stages and cold stages, and it lies close to the Anglian glacial limit. Critical to its history are the origin and age of a brown pebbly silty clay (diamicton) previously interpreted as weathered till. The deposits described infill a river channel incised into chalk bedrock. They comprise clayey, silty and gravelly sediments, many containing locally derived chalk and some with molluscan, ostracod and vertebrate remains. Most of the deposits are readily attributed to periglacial and fluvial processes, and some are dated by optically stimulated luminescence to Marine Isotope Stage (MIS) 6. Although our sedimentological data do not discriminate between a glacial or periglacial interpretation of the diamicton, amino-acid dating of three molluscan taxa from beneath it indicates that it is younger than MIS 9 and older than MIS 5e. This makes a glacial interpretation unlikely, and we interpret the diamicton as a periglacial slope deposit. The Pleistocene history reconstructed for Marsworth identifies four key elements: (1) Anglian glaciation during MIS 12 closely approached Marsworth, introducing far-travelled pebbles such as Rhaxella chert and possibly some fine sand minerals into the area. (2) Interglacial environments inferred from fluvial sediments during MIS 7 varied from fully interglacial conditions during sub-stages 7e and 7c, cool temperate conditions during sub-stage 7b or 7a, temperate conditions similar to those today in central England towards the end of the interglacial, and cool temperate conditions during sub-stage 7a. (3) Periglacial activity during MIS 6 involved thermal contraction cracking, permafrost development, fracturing of chalk bedrock, fluvial activity, slopewash, mass movement and deposition of loess and coversand. (4) Fully interglacial conditions during sub-stage 5e led to renewed fluvial activity, soil formation and acidic weathering

Increasing Student Responsibility And Active Learning In An Undergraduate Capstone Finance Course

This paper focuses on the effectiveness of factors in designing and delivering a complex, capstone course in an undergraduate major in finance. The course uses an instructional delivery system that is contrasted to the standard lecture format and has a broader set of objectives than is usually specified for a finance course. An objective of the instructional design of the course is to harness student responsibility while making them more active participants in the delivery of the content. The goal is to equip them to solve the typical non-structured problems they will deal with in their professional careers. The effect of these factors is measured by analyzing this course compared to all other finance courses taken. The outcomes of this paper show that this method is superior to the standard lecture method across a variety of scales. This provides insight into the future development of this method for this type of course, as well as ideas for developing other advanced instructional delivery systems for similar complex courses

Competition of lattice and basis for alignment of nematic liquid crystals

Due to elastic anisotropy, two-dimensional patterning of substrates can promote weak azimuthal alignment of adjacent nematic liquid crystals. Here we consider how such alignment can be achieved using a periodic square lattice of circular or elliptical motifs. In particular, we examine ways in which the lattice and motif can combine to favor differing orientations. Using Monte Carlo simulation and continuum elasticity we find, for circular motifs, that the coverage fraction controls both the polar anchoring angle and a transition in the azimuthal orientation. If the circles are generalized to ellipses, arbitrary control of the effective easy axis and effective anchoring potential becomes achievable by appropriate tuning of the ellipse motif relative to the periodic lattice patterning. This has possible applications in both monostable and bistable liquid crystal device contexts

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Marine Isotope Stage 11c in Europe:Recent advances in marine–terrestrial correlations and their implications for interglacial stratigraphy – a review

The interglacial known as MIS 11c (c. 426 000–396 000 years ago) receives intensive international interest because of its perceived role as an analogue for the current interglacial and its importance for understanding future climate change. Here we review the current understanding of the stratigraphy of this interglacial in Europe. This study considers (i) the evidence for the environmental history of this interglacial as reconstructed from the varved lake records from northern Europe, (ii) the climate history of MIS 11c as preserved in the long pollen records of southern Europe and (iii) a comparison of both of these with marine records from the North Atlantic. The result of this review is a discussion of the evidence for millennial and centennial scale climate change found in European records of MIS 11c,the patterns of warming that are seen across this interglacial and the discrepancy in aspects of the duration of this interglacial that seems to exist between the marine and terrestrial records of this warm period. A review of the recent advances in the study of MIS 11c in Europe confirms its importance for understanding both the past evolution of the Holocene and the future patterns of long-term climate change

Do temporal changes in vegetation structure additional to time since fire predict changes in bird occurrence?

Fire is a major ecological process in ecosystems globally. Its impacts on fauna can be both direct (e.g., mortality) and indirect (e.g., altered habitat), resulting in population recovery being driven by several possible mechanisms. Separating direct from indirect impacts of fire on faunal population recovery can be valuable in guiding management of biodiversity in fire-prone environments. However, resolving the influence of direct and indirect processes remains a key challenge because many processes affecting fauna can change concomitantly with time since fire. We explore the mechanisms influencing bird response to fire by posing the question, can temporal changes in vegetation structure predict changes in bird occurrence on sites, and can these be separated from other temporal changes using the surrogate of time since fire? We conducted a 12-yr study of bird and vegetation responses to fire at 124 sites across six vegetation classes in Booderee National Park, Australia. Approximately half of these sites, established in 2002, were burned by a large (>3000 ha) wildfire in 2003. To disentangle collinear effects of temporal changes in vegetation and direct demographic effects on population recovery that are subsumed by time since fire, we incorporated both longitudinal and cross-sectional vegetation effects in addition to time since fire within logistic structural equation models. We identified temporal changes in vegetation structure and richness of plant and bird species that characterized burned and unburned sites in all vegetation classes. For nine bird species, a significant component of the year trend was driven by temporal trends in one of three vegetation variables (number of understory or midstory plant species, or midstory cover). By contrast, we could not separate temporal effects between time since fire and vegetation attributes for bird species richness, reporting rate, and the occurrence of 11 other bird species. Our findings help identify species for which indirect effects of vegetation dominate recovery and thus may benefit from vegetation management where conservation actions are required and, conversely, those species for which direct effects of time since fire drive recovery, where simply leaving a system to recover following the last disturbance will be sufficient. © 2016 by the Ecological Society of America

Rotavirus Infection: A Systemic Illness?

Candy discusses a new study inPLoS Medicine that challenges the view that in children with rotavirus diarrhea, the virus is confined to the upper small intestine

Impulsores Claves para Establecer el Ecosistema Dinámico de Emprendimiento en Ecuador

p>El presente análisis demostrará que el Ecuador se encuentra en un momento oportuno para la implementación de estrategias concretas que fomenten el sistema dinámico de emprendimiento por medio del trabajo conjunto de los cuatro ejes claves de la economía: Academia, y los Sectores Público, Privado y Cívico.El presente análisis demostrará que el Ecuador se encuentra en un momento oportuno para la implementación de estrategias concretas que fomenten el sistema dinámico de emprendimiento por medio del trabajo conjunto de los cuatro ejes claves de la economía: Academia, y los Sectores Público, Privado y Cívico