58 research outputs found

    Concerted loop motion triggers induced fit of FepA to ferric enterobactin

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    Spectroscopic analyses of fluorophore-labeled Escherichia coli FepA described dynamic actions of its surface loops during binding and transport of ferric enterobactin (FeEnt). When FeEnt bound to fluoresceinated FepA, in living cells or outer membrane fragments, quenching of fluorophore emissions reflected conformational motion of the external vestibular loops. We reacted Cys sulfhydryls in seven surface loops (L2, L3, L4, L5, L7 L8, and L11) with fluorophore maleimides. The target residues had different accessibilities, and the labeled loops themselves showed variable extents of quenching and rates of motion during ligand binding. The vestibular loops closed around FeEnt in about a second, in the order L3 > L11 > L7 > L2 > L5 > L8 > L4. This sequence suggested that the loops bind the metal complex like the fingers of two hands closing on an object, by individually adsorbing to the iron chelate. Fluorescence from L3 followed a biphasic exponential decay as FeEnt bound, but fluorescence from all the other loops followed single exponential decay processes. After binding, the restoration of fluorescence intensity (from any of the labeled loops) mirrored cellular uptake that depleted FeEnt from solution. Fluorescence microscopic images also showed FeEnt transport, and demonstrated that ferric siderophore uptake uniformly occurs throughout outer membrane, including at the poles of the cells, despite the fact that TonB, its inner membrane transport partner, was not detectable at the poles

    Cognitive impairments in a Down syndrome model with abnormal hippocampal and prefrontal dynamics and cytoarchitecture

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    The Dp(10)2Yey mouse carries a ∼2.3-Mb intra-chromosomal duplication of mouse chromosome 10 (Mmu10) that has homology to human chromosome 21, making it an essential model for aspects of Down syndrome (DS, trisomy 21). In this study, we investigated neuronal dysfunction in the Dp(10)2Yey mouse and report spatial memory impairment and anxiety-like behavior alongside altered neural activity in the medial prefrontal cortex (mPFC) and hippocampus (HPC). Specifically, Dp(10)2Yey mice showed impaired spatial alternation associated with increased sharp-wave ripple activity in mPFC during a period of memory consolidation, and reduced mobility in a novel environment accompanied by reduced theta-gamma phase-amplitude coupling in HPC. Finally, we found alterations in the number of interneuron subtypes in mPFC and HPC that may contribute to the observed phenotypes and highlight potential approaches to ameliorate the effects of human trisomy 21

    A combined rocket-borne and ground-based study of the sodium layer and charged dust in the upper mesosphere

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    The Hotel Payload 2 rocket was launched on January 31st 2008 at 20.14 LT from the Andøya Rocket Range in northern Norway (69.31° N, 16.01° E). Measurements in the 75–105 km region of atomic O, negatively-charged dust, positive ions and electrons with a suite of instruments on the payload were complemented by lidar measurements of atomic Na and temperature from the nearby ALOMAR observatory. The payload passed within 2.58 km of the lidar at an altitude of 90 km. A series of coupled models is used to explore the observations, leading to two significant conclusions. First, the atomic Na layer and the vertical profiles of negatively-charged dust (assumed to be meteoric smoke particles), electrons and positive ions, can be modelled using a self-consistent meteoric input flux. Second, electronic structure calculations and Rice–Ramsperger–Kassel–Markus theory are used to show that even small Fe–Mg–silicates are able to attach electrons rapidly and form stable negatively-charged particles, compared with electron attachment to O2 and O3. This explains the substantial electron depletion between 80 and 90 km, where the presence of atomic O at concentrations in excess of 1010 cm−3 prevents the formation of stable negative ions

    Outcome Feedback Effects on Risk Propensity in an MCPLP Task

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    In this experimental analysis, the effects of outcome feedback on risk propensity were assessed within the multiple-cue-probability-learning-paradigm (MCPLP). The individual decision maker in this task received outcome feedback on a decision-by-decision basis. It was hypothesized that information on his/her success or lack of success (outcome feedback) on each decision would influence the decision to risk (commit) resources. Hierarchical regression results revealed that after all other performance effects had been partialled out, current outcome feedback explained much of the commitment decision.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

    Consensus recommendations for the use of automated insulin delivery technologies in clinical practice

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    The significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers, and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past 6 years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage

    SEM images, quantitative analysis code of SEM images, and data analysis code for "Grass pollen surface ornamentation is diverse across the phylogeny: evidence from northern South America and the global literature"

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       The grasses are one of the most diverse plant families on Earth, however, their classification and evolutionary history are obscured by their pollen stenopalynous (similar) morphology. A combination of high-resolution imaging of pollen surface ornamentation and computational analysis has previously been proposed as promising tool to classify grass taxonomic boundaries. In this study, we test this hypothesis by studying Poaceae pollen across the phylogeny from plants collected in northern South America, but also from published literature across the globe. We assessed if morphotypes that we establish using descriptive terminology are supported by computational analysis, if they vary along six (a)biotic variables and how vary across the phylogeny. Based on this analysis, we constructed a reference framework for pollen surface ornamentation morphotypes. Our results showed that there is a very wide variation of grass pollen surface ornamentation. We identified nine new and six known morphotypes and established our dataset of 223 species (243 individual plant specimens) from 11 subfamilies. Computational analysis showed that our morphotypes are well-supported by two quantitative features of pollen sculptural elements (size and density). The specific dataset and mapping of the phylogeny confirmed that pollen morphological sculpture is unrelated to (a)biotic variables but is diverse across through the phylogeny.</p
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