2,502 research outputs found

    Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System

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    Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50–100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair

    Enhancing outcomes of low-intensity parenting groups through sufficient exemplar training: a randomized control trial

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    Low-intensity parenting groups, such as the Triple P-Positive Parenting Program Discussion Groups, appear to be a cost-effective intervention for child conduct problems. Several studies evaluating a Triple P Discussion Group on disobedience found promising results for improving child and parent outcomes. However, a sufficient exemplar training approach that incorporates generalization promotion strategies may assist parents to more flexibly apply positive parenting principles to a broader range of child target behaviors and settings, leading to greater change. We compared the effects of sufficient exemplar training to an existing narrowly focused low-intensity intervention. Participants were 78 families with a 5–8 year-old child. Sufficient exemplar training resulted in more robust changes in child behavior and superior outcomes for mothers on measures of parenting behavior, parenting self-efficacy, mental health, and perceptions of partner support at post-intervention and 6-month follow-up. These results indicate that teaching sufficient exemplars may promote generalization leading to enhanced intervention outcomes

    Distinct Pathways Mediate the Sorting of Tail-Anchored Proteins to the Plastid Outer Envelope

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    Background: Tail-anchored (TA) proteins are a distinct class of membrane proteins that are sorted post-translationally to various organelles and function in a number of important cellular processes, including redox reactions, vesicular trafficking and protein translocation. While the molecular targeting signals and pathways responsible for sorting TA proteins to their correct intracellular destinations in yeasts and mammals have begun to be characterized, relatively little is known about TA protein biogenesis in plant cells, especially for those sorted to the plastid outer envelope. Methodology/Principal Findings: Here we investigated the biogenesis of three plastid TA proteins, including the 33-kDa and 34-kDa GTPases of the translocon at the outer envelope of chloroplasts (Toc33 and Toc34) and a novel 9-kDa protein of unknown function that we define here as an outer envelope TA protein (OEP9). Using a combination of in vivo and in vitro assays we show that OEP9 utilizes a different sorting pathway than that used by Toc33 and Toc34. For instance, while all three TA proteins interact with the cytosolic OEP chaperone/receptor, AKR2A, the plastid targeting information within OEP9 is distinct from that within Toc33 and Toc34. Toc33 and Toc34 also appear to differ from OEP9 in that their insertion is dependent on themselves and the unique lipid composition of the plastid outer envelope. By contrast, the insertion of OEP9 into the plastid outer envelope occurs in a proteinaceous-dependent, but Toc33/34-independent manner and membrane lipids appear to serve primarily to facilitate normal thermodynamic integration of this TA protein. Conclusions/Significance: Collectively, the results provide evidence in support of at least two sorting pathways for plastid TA outer envelope proteins and shed light on not only the complex diversity of pathways involved in the targeting and insertion of proteins into plastids, but also the molecular mechanisms that underlie the delivery of TA proteins to their proper intracellular locations in general

    Pore water exchange-driven inorganic carbon export from intertidal salt marshes

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    © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Tamborski, J. J., Eagle, M., Kurylyk, B. L., Kroeger, K. D., Wang, Z. A., Henderson, P., & Charette: 1774-1792, https://doi.org/10.1002/lno.11721.Respiration in intertidal salt marshes generates dissolved inorganic carbon (DIC) that is exported to the coastal ocean by tidal exchange with the marsh platform. Understanding the link between physical drivers of water exchange and chemical flux is a key to constraining coastal wetland contributions to regional carbon budgets. The spatial and temporal (seasonal, annual) variability of marsh pore water exchange and DIC export was assessed from a microtidal salt marsh (Sage Lot Pond, Massachusetts). Spatial variability was constrained from 224Ra : 228Th disequilibria across two hydrologic units within the marsh sediments. Disequilibrium between the more soluble 224Ra and its sediment-bound parent 228Th reveals significant pore water exchange in the upper 5 cm of the marsh surface (0–36 L m−2 d−1) that is most intense in low marsh elevation zones, driven by tidal overtopping. Surficial sediment DIC transport ranges from 0.0 to 0.7 g C m−2 d−1. The sub-surface sediment horizon intersected by mean low tide was disproportionately impacted by tidal pumping (20–80 L m−2 d−1) and supplied a seasonal DIC flux of 1.7–5.4 g C m−2 d−1. Export exceeded 10 g C m−2 d−1 for another marsh unit, demonstrating that fluxes can vary substantially across salt marshes under similar conditions within the same estuary. Seasonal and annual variability in marsh pore water exchange, constrained from tidal time-series of radium isotopes, was driven in part by variability in mean sea level. Rising sea levels will further inundate high marsh elevation zones, which may lead to greater DIC export.This research was undertaken thanks in part to funding from the Canada First Research Excellence Fund, through the Ocean Frontier Institute. Additional funding was provided by the U.S. Geological Survey (USGS) Coastal & Marine Geology Program and the USGS Land Change Science Program's LandCarbon program

    Causality and defect formation in the dynamics of an engineered quantum phase transition in a coupled binary Bose-Einstein condensate

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    Continuous phase transitions occur in a wide range of physical systems, and provide a context for the study of non-equilibrium dynamics and the formation of topological defects. The Kibble-Zurek (KZ) mechanism predicts the scaling of the resulting density of defects as a function of the quench rate through a critical point, and this can provide an estimate of the critical exponents of a phase transition. In this work we extend our previous study of the miscible-immiscible phase transition of a binary Bose-Einstein condensate (BEC) composed of two hyperfine states in which the spin dynamics are confined to one dimension [J. Sabbatini et al., Phys. Rev. Lett. 107, 230402 (2011)]. The transition is engineered by controlling a Hamiltonian quench of the coupling amplitude of the two hyperfine states, and results in the formation of a random pattern of spatial domains. Using the numerical truncated Wigner phase space method, we show that in a ring BEC the number of domains formed in the phase transitions scales as predicted by the KZ theory. We also consider the same experiment performed with a harmonically trapped BEC, and investigate how the density inhomogeneity modifies the dynamics of the phase transition and the KZ scaling law for the number of domains. We then make use of the symmetry between inhomogeneous phase transitions in anisotropic systems, and an inhomogeneous quench in a homogeneous system, to engineer coupling quenches that allow us to quantify several aspects of inhomogeneous phase transitions. In particular, we quantify the effect of causality in the propagation of the phase transition front on the resulting formation of domain walls, and find indications that the density of defects is determined during the impulse to adiabatic transition after the crossing of the critical point.Comment: 23 pages, 10 figures. Minor corrections, typos, additional referenc

    Using AVIRIS In The NASA BAA Project To Evaluate The Impact Of Natural Acid Drainage On Colorado Watersheds

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    The Colorado Geological Survey and the co-authors of this paper were awarded one of 15 NASA Broad Agency Announcement (BAA) grants in 2001. The project focuses on the use of hyperspectral remote sensing to map acid-generating minerals that affect water quality within a watershed, and to identify the relative contributions of natural and anthropogenic sources to that drainage. A further objective is to define the most cost-effective remote sensing instrument configuration for this application

    The Holy Grail: A road map for unlocking the climate record stored within Mars' polar layered deposits

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    In its polar layered deposits (PLD), Mars possesses a record of its recent climate, analogous to terrestrial ice sheets containing climate records on Earth. Each PLD is greater than 2 ​km thick and contains thousands of layers, each containing information on the climatic and atmospheric state during its deposition, creating a climate archive. With detailed measurements of layer composition, it may be possible to extract age, accumulation rates, atmospheric conditions, and surface activity at the time of deposition, among other important parameters; gaining the information would allow us to “read” the climate record. Because Mars has fewer complicating factors than Earth (e.g. oceans, biology, and human-modified climate), the planet offers a unique opportunity to study the history of a terrestrial planet’s climate, which in turn can teach us about our own planet and the thousands of terrestrial exoplanets waiting to be discovered. During a two-part workshop, the Keck Institute for Space Studies (KISS) hosted 38 Mars scientists and engineers who focused on determining the measurements needed to extract the climate record contained in the PLD. The group converged on four fundamental questions that must be answered with the goal of interpreting the climate record and finding its history based on the climate drivers. The group then proposed numerous measurements in order to answer these questions and detailed a sequence of missions and architecture to complete the measurements. In all, several missions are required, including an orbiter that can characterize the present climate and volatile reservoirs; a static reconnaissance lander capable of characterizing near surface atmospheric processes, annual accumulation, surface properties, and layer formation mechanism in the upper 50 ​cm of the PLD; a network of SmallSat landers focused on meteorology for ground truth of the low-altitude orbiter data; and finally, a second landed platform to access ~500 ​m of layers to measure layer variability through time. This mission architecture, with two landers, would meet the science goals and is designed to save costs compared to a single very capable landed mission. The rationale for this plan is presented below. In this paper we discuss numerous aspects, including our motivation, background of polar science, the climate science that drives polar layer formation, modeling of the atmosphere and climate to create hypotheses for what the layers mean, and terrestrial analogs to climatological studies. Finally, we present a list of measurements and missions required to answer the four major questions and read the climate record. 1. What are present and past fluxes of volatiles, dust, and other materials into and out of the polar regions? 2. How do orbital forcing and exchange with other reservoirs affect those fluxes? 3. What chemical and physical processes form and modify layers? 4. What is the timespan, completeness, and temporal resolution of the climate history recorded in the PLD

    Rivastigmine for gait stability in patients with Parkinson's disease (ReSPonD): a randomised, double-blind, placebo-controlled, phase 2 trial

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    Background Falls are a frequent and serious complication of Parkinson's disease and are related partly to an underlying cholinergic deficit that contributes to gait and cognitive dysfunction in these patients. Gait dysfunction can lead to an increased variability of gait from one step to another, raising the likelihood of falls. In the ReSPonD trial we aimed to assess whether ameliorating this cholinergic deficit with the acetylcholinesterase inhibitor rivastigmine would reduce gait variability. Methods We did this randomised, double-blind, placebo-controlled, phase 2 trial at the North Bristol NHS Trust Hospital, Bristol, UK, in patients with Parkinson's disease recruited from community and hospital settings in the UK. We included patients who had fallen at least once in the year before enrolment, were able to walk 18 m without an aid, had no previous exposure to an acetylcholinesterase inhibitor, and did not have dementia. Our clinical trials unit randomly assigned (1:1) patients to oral rivastigmine or placebo capsules (both taken twice a day) using a computer-generated randomisation sequence and web-based allocation. Rivastigmine was uptitrated from 3 mg per day to the target dose of 12 mg per day over 12 weeks. Both the trial team and patients were masked to treatment allocation. Masking was achieved with matched placebo capsules and a dummy uptitration schedule. The primary endpoint was difference in step time variability between the two groups at 32 weeks, adjusted for baseline age, cognition, step time variability, and number of falls in the previous year. We measured step time variability with a triaxial accelerometer during an 18 m walking task in three conditions: normal walking, simple dual task with phonemic verbal fluency (walking while naming words beginning with a single letter), and complex dual task switching with phonemic verbal fluency (walking while naming words, alternating between two letters of the alphabet). Analysis was by modified intention to treat; we excluded from the primary analysis patients who withdrew, died, or did not attend the 32 week assessment. This trial is registered with ISRCTN, number 19880883. Findings Between Oct 4, 2012 and March 28, 2013, we enrolled 130 patients and randomly assigned 65 to the rivastigmine group and 65 to the placebo group. At week 32, compared with patients assigned to placebo (59 assessed), those assigned to rivastigmine (55 assessed) had improved step time variability for normal walking (ratio of geometric means 0·72, 95% CI 0·58–0·88; p=0·002) and the simple dual task (0·79; 0·62–0·99; p=0·045). Improvements in step time variability for the complex dual task did not differ between groups (0·81, 0·60–1·09; p=0·17). Gastrointestinal side-effects were more common in the rivastigmine group than in the placebo group (p<0·0001); 20 (31%) patients in the rivastigmine group versus three (5%) in the placebo group had nausea and 15 (17%) versus three (5%) had vomiting

    Optical modeling and polarization calibration for CMB measurements with ACTPol and Advanced ACTPol

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    The Atacama Cosmology Telescope Polarimeter (ACTPol) is a polarization sensitive upgrade to the Atacama Cosmology Telescope. Located at an elevation of 5190 m, ACTPol measures the Cosmic Microwave Background (CMB) temperature and polarization with arcminute-scale angular resolution. Calibration of the detector angles is a critical step in producing maps of the CMB polarization. Polarization angle offsets in the detector calibration can cause leakage in polarization from E to B modes and induce a spurious signal in the EB and TB cross correlations, which eliminates our ability to measure potential cosmological sources of EB and TB signals, such as cosmic birefringence. We present our optical modeling and measurements associated with calibrating the detector angles in ACTPol.Comment: 12 pages, 8 figures, conference proceedings submitted to Proceedings of SPIE; added reference in section 2 and merged repeated referenc
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