The Protein-Conducting Channel in the Membrane of the Endoplasmic Reticulum Is Open Laterally toward the Lipid Bilayer

Lipids and proteins were found to contact a nascent type II membrane protein, as well as a nascent secretory protein, during their insertion into the membrane of the endoplasmic reticulum. This suggests that the protein-conducting channel is open laterally toward the lipid bilayer during an early stage of protein insertion. Contact to lipids was confined to the hydrophobic core region of the respective signal or signal anchor sequence. Thus, the nascent polypeptide is positioned in the translocation complex such that the signal or signal anchor sequence faces the lipid bilayer, whereas the hydrophilic, translocating portion is in proteinaceous environment

Does d-cycloserine facilitate the effects of homework compliance on social anxiety symptom reduction?

BACKGROUND: Prior studies examining the effect of d-cycloserine (DCS) on homework compliance and outcome in cognitive-behavior therapy (CBT) have yielded mixed results. The aim of this study was to investigate whether DCS facilitates the effects of homework compliance on symptom reduction in a large-scale study for social anxiety disorder (SAD). METHODS: 169 participants with generalized SAD received DCS or pill placebo during 12-session exposure-based group CBT. Improvements in social anxiety were assessed by independent raters at each session using the Liebowitz social anxiety scale (LSAS). RESULTS: Controlling for LSAS at the previous session, and irrespective of treatment condition, greater homework compliance in the week prior related to lower LSAS at the next session. However, DCS did not moderate the effect of homework compliance and LSAS, LSAS on homework compliance, or the overall augmenting effect of DCS on homework compliance. Furthermore, LSAS levels were not predictive of homework compliance in the following week. CONCLUSION: The findings support the general benefits of homework compliance on outcome, but not a DCS-augmenting effect. The comparably small number of DCS-enhanced sessions in this study could be one reason for the failure to find a facilitating effect of DCS

Possible discontinuous evolution of atmospheric xenon suggested by Archean barites

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Almayrac, M. G., Broadley, M. W., Bekaert, D. V., Hofmann, A., & Marty, B. Possible discontinuous evolution of atmospheric xenon suggested by Archean barites. Chemical Geology, 581, (2021): 120405, https://doi.org/10.1016/j.chemgeo.2021.120405.The Earth's atmosphere has continually evolved since its formation through interactions with the mantle as well as through loss of volatile species to space. Atmospheric xenon isotopes show a unique and progressive evolution during the Archean that stopped around the Archean-Proterozoic transition. The Xe isotope composition of the early atmosphere has been previously documented through the analysis of fluid inclusions trapped within quartz and barite. Whether this evolution was continuous or not is unclear, requiring additional analyses of ancient samples, which may potentially retain remnants of the ancient atmosphere. Here we present new argon, krypton and xenon isotopic data from a suite of Archean and Proterozoic barites ranging in age from 3.5 to 1.8 Ga, with the goal of providing further insights in to the evolution of atmospheric Xe, whilst also outlining the potential complications that can arise when using barites as a record of past atmospheres. Xenon released by low temperature pyrolysis and crushing of two samples which presumably formed around 2.8 and 2.6 Ga show Xe isotope mass dependent fractionation (MDF) of 11‰.u−1 and 3.4‰.u−1, respectively, relative to modern atmosphere. If trapped Xe is contemporaneous with the respective formation age, the significant difference in the degree of fractionation between the two samples provides supporting evidence for a plateau in the MDF-Xe evolution between 3.3 Ga and 2.8 Ga, followed by a rapid evolution at 2.8–2.6 Ga. This sharp decrease in MDF-Xe degree suggests the potential for a discontinuous temporal evolution of atmospheric Xe isotopes, which could have far reaching implications regarding current physical models of the early evolution of the Earth's atmosphere.This work was funded by the ERC grant No. 695618 to B.M. We thank the S.A.R.M for providing elemental bulk analyses of the barites. We thank Laurent Zimmerman for technical mentorship and assistance

M. Sediment Collapse Indicators in the 1970 Flathead Lake Seismic Dataset

Draft of article on lake sediment collapse into voids left by the melting of buried glacial ice blocks.https://scholarworks.umt.edu/flathead/1016/thumbnail.jp

Enhancement of the efficiency of non-viral gene delivery by application of pulsed magnetic field

New approaches to increase the efficiency of non-viral gene delivery are still required. Here we report a simple approach that enhances gene delivery using permanent and pulsating magnetic fields. DNA plasmids and novel DNA fragments (PCR products) containing sequence encoding for green fluorescent protein were coupled to polyethylenimine coated superparamagnetic nanoparticles (SPIONs). The complexes were added to cells that were subsequently exposed to permanent and pulsating magnetic fields. Presence of these magnetic fields significantly increased the transfection efficiency 40 times more than in cells not exposed to the magnetic field. The transfection efficiency was highest when the nanoparticles were sedimented on the permanent magnet before the application of the pulsating field, both for small (50 nm) and large (200-250 nm) nanoparticles. The highly efficient gene transfer already within 5 min shows that this technique is a powerful tool for future in vivo studies, where rapid gene delivery is required before systemic clearance or filtration of the gene vectors occur

Enhancement of psychosocial treatment with D-cycloserine: models, moderators, and future directions

Advances in the understanding of the neurobiology of fear extinction have resulted in the development of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure treatment. We review a decade of research that has focused on the efficacy of DCS for augmenting the mechanisms (e.g., fear extinction) and outcome of exposure treatment across the anxiety disorders. Following a series of small-scale studies offering strong support for this clinical application, more recent larger-scale studies have yielded mixed results, with some showing weak or no effects. We discuss possible explanations for the mixed findings, pointing to both patient and session (i.e., learning experiences) characteristics as possible moderators of efficacy, and offer directions for future research in this area. We also review recent studies that have aimed to extend the work on DCS augmentation of exposure therapy for the anxiety disorders to DCS enhancement of learning-based interventions for addiction, anorexia nervosa, schizophrenia, and depression. Here, we attend to both DCS effects on facilitating therapeutic outcomes and additional therapeutic mechanisms beyond fear extinction (e.g., appetitive extinction, hippocampal-dependent learning).F31 MH103969 - NIMH NIH HHS; K24 DA030443 - NIDA NIH HHS; R34 MH099309 - NIMH NIH HHS; R34 MH086668 - NIMH NIH HHS; R21 MH102646 - NIMH NIH HHS; R34 MH099318 - NIMH NIH HH

Enhancement of the efficiency of non-viral gene delivery by application of pulsed magnetic field

New approaches to increase the efficiency of non-viral gene delivery are still required. Here we report a simple approach that enhances gene delivery using permanent and pulsating magnetic fields. DNA plasmids and novel DNA fragments (PCR products) containing sequence encoding for green fluorescent protein were coupled to polyethylenimine coated superparamagnetic nanoparticles (SPIONs). The complexes were added to cells that were subsequently exposed to permanent and pulsating magnetic fields. Presence of these magnetic fields significantly increased the transfection efficiency 40 times more than in cells not exposed to the magnetic field. The transfection efficiency was highest when the nanoparticles were sedimented on the permanent magnet before the application of the pulsating field, both for small (50 nm) and large (200–250 nm) nanoparticles. The highly efficient gene transfer already within 5 min shows that this technique is a powerful tool for future in vivo studies, where rapid gene delivery is required before systemic clearance or filtration of the gene vectors occurs

Separate Universes Do Not Constrain Primordial Black Hole Formation

Carr and Hawking showed that the proper size of a spherical overdense region surrounded by a flat FRW universe cannot be arbitrarily large as otherwise the region would close up on itself and become a separate universe. From this result they derived a condition connecting size and density of the overdense region ensuring that it is part of our universe. Carr used this condition to obtain an upper bound for the density fluctuation amplitude with the property that for smaller amplitudes the formation of a primordial black hole is possible, while larger ones indicate a separate universe. In contrast, we find that the appearance of a maximum is not a consequence of avoiding separate universes but arises naturally from the geometry of the chosen slicing. Using instead of density a volume fluctuation variable reveals that a fluctuation is a separate universe iff this variable diverges on superhorizon scales. Hence Carr's and Hawking's condition does not pose a physical constraint on density fluctuations. The dynamics of primordial black hole formation with an initial curvature fluctuation amplitude larger than the one corresponding to the maximum density fluctuation amplitude was previously not considered in detail and so we compare it to the well-known case where the amplitude is smaller by presenting embedding and conformal diagrams of both types in dust spacetimes.Comment: Updated version corresponds to the published version 10.1103/PhysRevD.83.124025, 22 pages, 22 figure

Continuity properties of measurable group cohomology

A version of group cohomology for locally compact groups and Polish modules has previously been developed using a bar resolution restricted to measurable cochains. That theory was shown to enjoy analogs of most of the standard algebraic properties of group cohomology, but various analytic features of those cohomology groups were only partially understood. This paper re-examines some of those issues. At its heart is a simple dimension-shifting argument which enables one to `regularize' measurable cocycles, leading to some simplifications in the description of the cohomology groups. A range of consequences are then derived from this argument. First, we prove that for target modules that are Fr\'echet spaces, the cohomology groups agree with those defined using continuous cocycles, and hence they vanish in positive degrees when the acting group is compact. Using this, we then show that for Fr\'echet, discrete or toral modules the cohomology groups are continuous under forming inverse limits of compact base groups, and also under forming direct limits of discrete target modules. Lastly, these results together enable us to establish various circumstances under which the measurable-cochains cohomology groups coincide with others defined using sheaves on a semi-simplicial space associated to the underlying group, or sheaves on a classifying space for that group. We also prove in some cases that the natural quotient topologies on the measurable-cochains cohomology groups are Hausdorff.Comment: 52 pages. [Nov 22, 2011:] Major re-write with Calvin C. Moore as new co-author. Results from previous version strengthened and several new results added. [Nov 25, 2012:] Final version now available at springerlink.co

Diffraction-based determination of single-crystal elastic constants of polycrystalline titanium alloys

Single-crystal elastic constants have been derived by lattice strain measurements using neutron diffraction on polycrystalline Ti-6Al-4V, Ti-6Al-2Sn-4Zr-6Mo and Ti-3Al-8V-6Cr-4Zr-4Mo alloy samples. A variety of model approximations for the grain-to-grain interactions, namely approaches by Voigt, Reuss, Hill, Kroener, de Wit and Matthies, including texture weightings, have been applied and compared. A load-transfer approach for multiphase alloys was also implemented and the results are compared with single-phase data. For the materials under investigation, the results for multiphase alloys agree well with the results for single-phase materials in the corresponding phases. In this respect, all eight elastic constants in the dual-phase Ti-6Al-2Sn-4Zr-6Mo alloy have been derived for the first time