504 research outputs found

    Novel Space Alters Theta and Gamma Synchrony Across the Longitudinal Axis of the Hippocampus.

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    Hippocampal theta (6–10 Hz) and gamma (25–50 Hz and 65–100 Hz) local field potentials (LFPs) reflect the dynamic synchronization evoked by inputs impinging upon hippocampal neurons. Novel experience is known to engage hippocampal physiology and promote successful encoding. Does novelty synchronize or desynchronize theta and/or gamma frequency inputs across the septotemporal (long) axis of the hippocampus (HPC)? The present study tested the hypothesis that a novel spatial environment would alter theta power and coherence across the long axis. We compared theta and gamma LFP signals at individual (power) and millimeter distant electrode pairs (coherence) within the dentate gyrus (DG) and CA1 region while rats navigated a runway (1) in a familiar environment, (2) with a modified path in the same environment and (3) in a novel space. Locomotion in novel space was related to increases in theta and gamma power at most CA1 and DG sites. The increase in theta and gamma power was concurrent with an increase in theta and gamma coherence across the long axis of CA1; however, there was a significant decrease in theta coherence across the long axis of the DG. These findings illustrate significant shifts in the synchrony of entorhinal, CA3 and/or neuromodulatory afferents conveying novel spatial information to the dendritic fields of CA1 and DG targets across the long axis of the HPC. This shift suggests that the entire theta/gamma-related input to the CA1 network, and likely output, receives and conveys a more coherent message in response to novel sensory experience. Such may contribute to the successful encoding of novel sensory experience

    Texas and Southwestern Cattle Raisers Association Members\u27 Preferred Sources of Animal Health Information

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    The nation’s agriculture and food infrastructure is vulnerable to significant social disruption and economic loss from hazards. Biological hazards, such as animal disease epidemics, have resulted in millions of dollars of economic loss and the death of millions of livestock in the past, and it will happen again unless infrastructure stakeholders adopt proper preventative measures. From farm to plate, defense starts on the farm with producers. With the multitude of potential hazards, many factors influence livestock producers’ protective action decision process. A major factor in the decision to take a protective action is from where or from whom the threat information originates. By identifying preferred sources, perceived credible sources, and preferred formats of animal health information by producers, risk communicators can more effectively develop critical animal health warnings and messages to promote rapid detection of hazards. This study targeted 7,661 members of the Texas and Southwestern Cattle Raisers Association. An online questionnaire developed from previous research with similar populations allowed TSCRA members to respond to questions related to the objectives of this study. A representative sample of TSCRA members from Texas, Oklahoma, and New Mexico responded and identified high levels of perceived trust and reliability in local veterinarians as a source of information along with livestock associations and county extension offices. TSCRA members also indicated they have multiple preferred formats for receiving animal health information. By using this information when communicating possible hazards, protective action from such threats will become more probable in this population

    Recently Discovered Populations of Eastern Woodrats (\u3ci\u3eNeotoma floridana\u3c/i\u3e) in Southern Illinois

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    Until recently it was believed that the population of eastern woodrats (Neotoma floridana) in Pine Hills, Union County, Illinois, represented the only extant population remaining in the state. Trapping at sites formerly occupied by woodrats and in areas with suitable habitat resulted in the documentation of additional populations at Fountain Bluff, Little Grand Canyon, and Horseshoe Bluff, Jackson County. Woodrats currently are more numerous and have a wider distribution in southern Illinois than previously believed

    Dystonia Associated with Idiopathic Slow Orthostatic Tremor

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    Background: We aimed to characterize the clinical and electrophysiological features of patients with slow orthostatic tremor. Case Report: The clinical and neurophysiological data of patients referred for lower limb tremor on standing were reviewed. Patients with symptomatic or primary orthostatic tremor were excluded. Eight patients were identified with idiopathic slow 4–8 Hz orthostatic tremor, which was associated with tremor and dystonia in cervical and upper limb musculature. Coherence analysis in two patients showed findings different to those seen in primary orthostatic tremor. Discussion: Slow orthostatic tremor may be associated with dystonia and dystonic tremor

    The coupling between inner and outer scales in a zero pressure boundary layer evaluated using a Hölder exponent framework

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    This work considers the connectivity between large and small scales in boundary-layer turbulence by formalizing the modulation effect of the small scales by the large in terms of the pointwise Hölder condition for the small scales. We re-investigate a previously published dataset from this perspective and are able to characterize the coupling effectively using the (cross-)correlative relations between the large scale velocity and the small scale Hölder exponents. The nature of this coupling varies as a function of dimensionless distance from the wall based on inner-scaling, y+{y}^{+}, as well as on the boundary-layer height, δ. In terms of the fundamental change in the sign of the coupling between large and small scales, the critical height appears to be y+1000{y}^{+}\sim 1000. Below this height, small scale structures are associated with (and occur earlier than) maxima in the large scale velocity. Above this height, while the lag is similar in magnitude, the small scale structures are associated with minima in the large scale velocity. To consider these results further, we introduce a modified quadrant analysis and show that it is the coupling to the large scale low velocity state that is critical for the dynamics

    Benzo-fused Lactams from a Diversity-oriented Synthesis (DOS) Library as Inhibitors of Scavenger Receptor BI (SR-BI)-mediated Lipid Uptake

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    We report a new series of 8-membered benzo-fused lactams that inhibit cellular lipid uptake from HDL particles mediated by Scavenger Receptor, Class B, Type I (SR-BI). The series was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR), measuring the transfer of the fluorescent lipid DiI from HDL particles to CHO cells overexpressing SR-BI. The series is part of a previously reported diversity-oriented synthesis (DOS) library prepared via a build-couple-pair approach. Detailed structure–activity relationship (SAR) studies were performed with a selection of the original library, as well as additional analogs prepared via solution phase synthesis. These studies demonstrate that the orientation of the substituents on the aliphatic ring have a critical effect on activity. Additionally, a lipophilic group is required at the western end of the molecule, and a northern hydroxyl group and a southern sulfonamide substituent also proved to be optimal. Compound 2p was found to possess a superior combination of potency (av IC50 = 0.10 μM) and solubility (79 μM in PBS), and it was designated as probe ML312

    Discovery of Bisamide-heterocycles as Inhibitors of Scavenger Receptor BI (SR-BI)-mediated Lipid Uptake

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    A new series of potent inhibitors of cellular lipid uptake from HDL particles mediated by scavenger receptor, class B, type I (SR-BI) was identified. The series was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR) that measured the transfer of the fluorescent lipid DiI from HDL particles to CHO cells overexpressing SR-BI. The series is characterized by a linear peptidomimetic scaffold with two adjacent amide groups, as well as an aryl-substituted heterocycle. Analogs of the initial hit were rapidly prepared via Ugi 4-component reaction, and select enantiopure compounds were prepared via a stepwise sequence. Structure–activity relationship (SAR) studies suggest an oxygenated arene is preferred at the western end of the molecule, as well as highly lipophilic substituents on the central and eastern nitrogens. Compound 5e, with (R)-stereochemistry at the central carbon, was designated as probe ML279. Mechanistic studies indicate that ML279 stabilizes the interaction of HDL particles with SR-BI, and its effect is reversible. It shows good potency (IC50 = 17 nM), is non-toxic, plasma stable, and has improved solubility over our alternative probe ML278

    Indolinyl-Thiazole Based Inhibitors of Scavenger Receptor-BI (SR-BI)-Mediated Lipid Transport

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    A potent class of indolinyl-thiazole based inhibitors of cellular lipid uptake mediated by scavenger receptor, class B, type I (SR-BI) was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR) in an assay measuring the uptake of the fluorescent lipid DiI from HDL particles. This class of compounds is represented by ML278 (17–11), a potent (average IC50 = 6 nM) and reversible inhibitor of lipid uptake via SR-BI. ML278 is a plasma-stable, noncytotoxic probe that exhibits moderate metabolic stability, thus displaying improved properties for in vitro and in vivo studies. Strikingly, ML278 and previously described inhibitors of lipid transport share the property of increasing the binding of HDL to SR-BI, rather than blocking it, suggesting there may be similarities in their mechanisms of action

    Detailed single crystal EPR lineshape measurements for the single molecule magnets Fe8Br and Mn12-ac

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    It is shown that our multi-high-frequency (40-200 GHz) resonant cavity technique yields distortion-free high field EPR spectra for single crystal samples of the uniaxial and biaxial spin S = 10 single molecule magnets (SMMs) [Mn12O12(CH3COO)16(H2O)4].2CH3COOH.4H2O and [Fe8O2(OH)12(tacn)6]Br8.9H2O. The observed lineshapes exhibit a pronounced dependence on temperature, magnetic field, and the spin quantum numbers (Ms values) associated with the levels involved in the transitions. Measurements at many frequencies allow us to separate various contributions to the EPR linewidths, including significant D-strain, g-strain and broadening due to the random dipolar fields of neighboring molecules. We also identify asymmetry in some of the EPR lineshapes for Fe8, and a previously unobserved fine structure to some of the EPR lines for both the Fe8 and Mn12 systems. These findings prove relevant to the mechanism of quantum tunneling of magnetization in these SMMs.Comment: Phys. Rev. B, accepted with minor revision
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