474 research outputs found

    Maps of complex motion selectivity in the superior temporal cortex of the alert macaque monkey: a double-label 2-deoxyglucose study

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    The superior temporal sulcus (STS) of the macaque monkey contains multiple visual areas. Many neurons within these regions respond selectively to motion direction and to more complex motion patterns, such as expansion, contraction and rotation. Single-unit recording and optical recording studies in MT/MST suggest that cells with similar tuning properties are clustered into columns extending through multiple cortical layers. In this study, we used a double-label 2-deoxyglucose technique in awake, behaving macaque monkeys to clarify this functional organization. This technique allowed us to label, in a single animal, two populations of neurons responding to two different visual stimuli. In one monkey we compared expansion with contraction; in a second monkey we compared expansion with clockwise rotation. Within the STS we found a patchy arrangement of cortical columns with alternating stimulus selectivity: columns of neurons preferring expansion versus contraction were more widely separated than those selective for expansion versus rotation. This mosaic of interdigitating columns on the floor and posterior bank of the STS included area MT and some neighboring regions of cortex, perhaps including area MST

    Latonduines A and B, New Alkaloids Isolated from the Marine Sponge Stylissa carteri:??? Structure Elucidation, Synthesis, and Biogenetic Implications

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    Part of research collaboration results between Fac Mar Fish UNHAS and EOS UBCLatonduines A (6) and B (7), two new alkaloids with unprecedented heterocyclic skeletons, have been isolated from the Indonesian marine sponge Stylissa carteri. The structures of the latonduines were elucidated by analysis of spectroscopic data and confirmed by the total synthesis of latonduine A (6). It is proposed that ornithine is the biogenetic precursor to the aminopyrimidine fragment of the latonduines

    Fenamates Alter Bilayer Properties

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    Statins Modify Bilayer Mechanical Properties

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    The association between aspects of carer distress and time until nursing home admission in persons with Alzheimer’s disease and dementia with Lewy bodies

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    Objective: The aim of this study was to explore the association between specific aspects of carer distress and time until nursing home admission (NHA) in people with mild dementia. Design: Prospective cohort study. Setting: Participants were recruited from the Dementia Study of Western Norway (DemVest). Participants: This study included 107 participants admitted to a nursing home who were diagnosed with Alzheimer’s disease (AD, n = 64) and dementia with Lewy bodies (DLB, n = 43) and their primary carers. Measurements: The Relative Stress Scale (RSS) was used to assess the level of reported distress in carers. Adjusted partial least square (PLS) prediction analysis of baseline items of the RSS was used to study the associations between individual items of the RSS and time until NHA. Results: Carer distress is an important contributor to early NHA, explaining 19.3% of the total variance of time until NHA in the model without covariates. In the adjusted PLS model, the most important RSS predictors of time until NHA were feeling frustrated (estimate = −137; CI, −209, −64.5), having limitations on social life (estimate = −118; CI, −172, −64), not being able to get away on vacation (estimate −116; CI, −158.3, −73.7), and feeling unable to cope with the situation (estimate = −63; CI, −122.6, −3.4). Conclusions: Preservation of the informal care capacity represents important steps for improving the management of resources in dementia care. This study identifies aspects of carer distress associated with a shorter time until NHA. Looking beyond the sum score of the RSS helps promote the development of flexible and tailored interventions and perhaps delay NHA.publishedVersio

    Characterizing Residue-Bilayer Interactions Using Gramicidin A as a Scaffold and Tryptophan Substitutions as Probes

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Chemical Theory and Computation, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/acs.jctc.7b00400.Previous experiments have shown that the lifetime of a gramicidin A dimer channel (which forms from two non-conducting monomers) in a lipid bilayer is modulated by mutations of the tryptophan (Trp) residues at the bilayer-water interface. We explore this further using extensive molecular dynamics simulations of various gA dimer and monomer mutants at the Trp positions in phosphatidylcholine bilayers with different tail lengths. gA interactions with the surrounding bilayer are strongly modulated by mutating these Trp residues. There are three principal effects: eliminating residue hydrogen bonding ability (i.e., reducing the channel-monolayer coupling strength) reduces the extent of the bilayer deformation caused by the assembled dimeric channel; a residue’s size and geometry affects its orientation, leading to different hydrogen bonding partners; and increasing a residue’s hydrophobicity increases the depth of gA monomer insertion relative to the bilayer center, thereby increasing the lipid bending frustration

    Spin-wave spectrum in La2CuO4 -- double occupancy and competing interaction effects

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    The recently observed spin-wave energy dispersion along the AF zone boundary in La2CuO4 is discussed in terms of double occupancy and competing interaction effects in the ttt-t' Hubbard model on a square lattice.Comment: 4 pages, 2 figure

    Population assessment of future trajectories in coronary heart disease mortality.

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    Background: Coronary heart disease (CHD) mortality rates have been decreasing in Iceland since the 1980s, largely reflecting improvements in cardiovascular risk factors. The purpose of this study was to predict future CHD mortality in Iceland based on potential risk factor trends. Methods and findings: The previously validated IMPACT model was used to predict changes in CHD mortality between 2010 and 2040 among the projected population of Iceland aged 25–74. Calculations were based on combining: i) data on population numbers and projections (Statistics Iceland), ii) population risk factor levels and projections (Refine Reykjavik study), and iii) effectiveness of specific risk factor reductions (published meta-analyses). Projections for three contrasting scenarios were compared: 1) If the historical risk factor trends of past 30 years were to continue, the declining death rates of past decades would level off, reflecting population ageing. 2) If recent trends in risk factors (past 5 years) continue, this would result in a death rate increasing from 49 to 70 per 100,000. This would reflect a recent plateau in previously falling cholesterol levels and recent rapid increases in obesity and diabetes prevalence. 3) Assuming that in 2040 the entire population enjoys optimal risk factor levels observed in low risk cohorts, this would prevent almost all premature CHD deaths before 2040. Conclusions: The potential increase in CHD deaths with recent trends in risk factor levels is alarming both for Iceland and probably for comparable Western populations. However, our results show considerable room for reducing CHD mortality. Achieving the best case scenario could eradicate premature CHD deaths by 2040. Public health policy interventions based on these predictions may provide a cost effective means of reducing CHD mortality in the future

    Regulation of Sodium Channel Function by Bilayer Elasticity: The Importance of Hydrophobic Coupling. Effects of Micelle-forming Amphiphiles and Cholesterol

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    Membrane proteins are regulated by the lipid bilayer composition. Specific lipid–protein interactions rarely are involved, which suggests that the regulation is due to changes in some general bilayer property (or properties). The hydrophobic coupling between a membrane-spanning protein and the surrounding bilayer means that protein conformational changes may be associated with a reversible, local bilayer deformation. Lipid bilayers are elastic bodies, and the energetic cost of the bilayer deformation contributes to the total energetic cost of the protein conformational change. The energetics and kinetics of the protein conformational changes therefore will be regulated by the bilayer elasticity, which is determined by the lipid composition. This hydrophobic coupling mechanism has been studied extensively in gramicidin channels, where the channel–bilayer hydrophobic interactions link a “conformational” change (the monomer↔dimer transition) to an elastic bilayer deformation. Gramicidin channels thus are regulated by the lipid bilayer elastic properties (thickness, monolayer equilibrium curvature, and compression and bending moduli). To investigate whether this hydrophobic coupling mechanism could be a general mechanism regulating membrane protein function, we examined whether voltage-dependent skeletal-muscle sodium channels, expressed in HEK293 cells, are regulated by bilayer elasticity, as monitored using gramicidin A (gA) channels. Nonphysiological amphiphiles (β-octyl-glucoside, Genapol X-100, Triton X-100, and reduced Triton X-100) that make lipid bilayers less “stiff”, as measured using gA channels, shift the voltage dependence of sodium channel inactivation toward more hyperpolarized potentials. At low amphiphile concentration, the magnitude of the shift is linearly correlated to the change in gA channel lifetime. Cholesterol-depletion, which also reduces bilayer stiffness, causes a similar shift in sodium channel inactivation. These results provide strong support for the notion that bilayer–protein hydrophobic coupling allows the bilayer elastic properties to regulate membrane protein function
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