878 research outputs found

    A role for the SHANK1 scaffold protein in experience-induced synaptic plasticity and memory consolidation

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    The processes by which the brain acquires, stores, and retrieves external information has been an extensively researched field in psychology. Findings from these studies have overwhelmingly suggested that plasticity of neuroanatomical networks across development and during various experiences provide a critical mechanism mediating learning. Specifically, numerous studies have suggested dendritic spine plasticity across development and during learning as a likely process for memory consolidation. During early postnatal development, dendritic spine density increases in numerous sensory cortices, reaching a peak in adolescence, followed by a subsequent reduction in dendritic spine density to adult levels. In the hippocampus, dendritic spine density steadily increases during postnatal development, and plateaus in adulthood. Similar to the plasticity observed across development, increases in dendritic spine density occur in the neocortex and hippocampus following various learning paradigms, suggesting synaptic remodeling. While the anatomical properties for these forms of plasticity are well investigated, the underlying molecular processes remain largely unknown. Interestingly, recent studies have strongly suggested a role for SHANK1 in normal synaptic development and plasticity. SHANK1 is a scaffolding protein that is concentrated to the postsynaptic density (PSD) of excitatory synapses and is involved in the binding of glutamate receptors to their active zones. Previous developmental studies have demonstrated that SHANK1 is initially localized in the cytoplasm of neurons followed by an increased dendritic spine expression during periods of postnatal dendritic spine proliferation. Likewise, SHANK1 expression is increased across postnatal development in purified postsynaptic fractions, further suggesting a role in developmental properties of dendritic spines. Interestingly, global SHANK1 knockout (SHANK1 -/-) mice have also been shown to exhibit a reduction in dendritic spine density and increased immature dendritic spine phenotype. Consistent with that observed in development, SHANK1 has been hypothesized to play an important role in learning-induced dendritic spine plasticity and cognition. SHANK1-/- mice exhibit marked impairments in contextual fear-conditioning and radial-arm-maze retention. Similarly, mice that overexpress SHANK1 exhibit impairments in both cued and contextual fear conditioning, further suggesting that appropriate SHANK1 regulation is crucial for normal cognition.Collectively, these studies strongly suggest a role for SHANK1 in developmental and learning-induced dendritic spine plasticity; however, a detailed examination of this has never been conducted. Furthermore, many of these studies genetically dysregulated SHANK1 from birth, thus a role for SHANK1 in normal adult learning-induced plasticity has not yet been examined. The studies in the present thesis further explored SHANK1 as an underlying mediator of dendritic spine plasticity in three specific aims. In Aim 1, a detailed examination of layer and cell-specific dendritic spine plasticity in S1 during distinct learning phases for WTEB was conducted. Findings from this study revealed no significant changes in dendritic spine density on layer III or layer V pyramidal cells at the specific time points examined across WTEB. In exploring these findings, we further discussed the implications of these findings, possible explanations as well as potential future studies to explore this research question. Aim 2 explored a role for SHANK1 expression during neuronal development, a well characterized period of dendritic spine plasticity. These studies demonstrated SHANK1 localization to neurons as well as astrocytes and microglia. Furthermore, this study also characterized cell-specific changes in SHANK1 expression during periods of developmental synaptic plasticity. Aim 3 expanded upon these findings to explore a role SHANK1 expression, during learning-induced neocortical dendritic spine plasticity and learning of WTEB. These studies demonstrated a transient increase in SHANK1 levels during periods of neocortical synaptic plasticity across WTEB. Collectively, these studies further support a role of SHANK1 in the organization and remodeling of synaptic networks during development and learning. In so doing these studies also provided additional insight into potential specific mechanisms underlying developmental and experience-induced synaptic remodeling, deepening our understanding of memory consolidation within specific learning networks

    A Comparison of External Loads in Division III Men\u27s Lacrosse Between High Competition Matches and Low Competition Matches

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    Lacrosse is an open field sport with limited knowledge on the demands of gameplay at the Division III level. The purpose of this study was to investigate the external loads on Division III men’s lacrosse players during NCAA season games. Comparisons were made between the external loads placed on the athletes in top competition versus external loads placed on the athletes in low competition matches. Top competition matches were defined as matches against teams that qualified for the NCAA tournament whereas low competition matches included teams that did not meet top competition requirements. The dependent variables measured included total distance, work rate, intensity, 2D load, and 3D load. Defensive players were found to have significantly higher external load values for total distance (m; p=0.003), work rate (m/min; p=0.006 ), intensity (AU; p=0.071), 2D load (AU; p= 0.039 ) and 3D load (AU; p=0.022), while there were no significant differences (p\u3e0.05) for other positions between competition level. Competition level exerts a higher external load for defensive players, but not attack, midfield, or specialists (goalie, face-off, etc), which may indicate the need for specialized conditioning or active load management to deal with potential fatigue

    Microscopic crystallographic analysis of dislocations in molecular crystals

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    Organic molecular crystals encompass a vast range of materials from pharmaceuticals to organic optoelectronics and proteins to waxes in biological and industrial settings. Crystal defects from grain boundaries to dislocations are known to play key roles in mechanisms of growth and also in the functional properties of molecular crystals. In contrast to the precise analysis of individual defects in metals, ceramics, and inorganic semiconductors enabled by electron microscopy, significantly greater ambiguity remains in the experimental determination of individual dislocation character and slip systems in molecular materials. In large part, nanoscale dislocation analysis in molecular crystals has been hindered by the severely constrained electron exposures required to avoid irreversibly degrading these crystals. Here, we present a low-dose, single-exposure approach enabling nanometre-resolved analysis of individual extended dislocations in molecular crystals. We demonstrate the approach for a range of crystal types to reveal dislocation character and operative slip systems unambiguously.Comment: Manuscript (14 pages, 4 figures) and Supplementary Material (32 pages, 19 figures) in a single PDF fil

    Defining the current distribution of the imperiled Black-spotted Newt across south Texas, USA

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    The Black-spotted Newt (Notophthalmus meridionalis) is a chronically understudied salamander species, with many aspects of its natural history, ecology, and distribution poorly known. Previous studies using traditional methodologies have had limited success documenting N. meridionalis on the landscape, detecting individuals at 6% (7 of 114) and 1% (2 of 221) of sites surveyed. A novel environmental DNA (eDNA) assay was designed and implemented with the goals of assessing the current distribution of N. meridionalis across south Texas, USA, and better understanding the conditions for positive eDNA detections. We conducted eDNA sampling and traditional surveys at 80 sites throughout south Texas. Notophthalmus meridionalis was detected at 12 localities in total: four localities using eDNA surveys, four localities using traditional methods, and four localities with both methodologies. eDNA detections were obtained from five counties, including one where N. meridionalis has never been reported and another where N. meridionalis has not been observed since the 1930s. eDNA detections were obtained in all four seasons, generally following moderate to heavy rainfall events. Our results support the increased use of eDNA surveys to detect rare and cryptic amphibians and to better understand the current distribution of this imperiled species

    A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria.

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    To broadly explore mitochondrial structure and function as well as the communication of mitochondria with other cellular pathways, we constructed a quantitative, high-density genetic interaction map (the MITO-MAP) in Saccharomyces cerevisiae. The MITO-MAP provides a comprehensive view of mitochondrial function including insights into the activity of uncharacterized mitochondrial proteins and the functional connection between mitochondria and the ER. The MITO-MAP also reveals a large inner membrane-associated complex, which we term MitOS for mitochondrial organizing structure, comprised of Fcj1/Mitofilin, a conserved inner membrane protein, and five additional components. MitOS physically and functionally interacts with both outer and inner membrane components and localizes to extended structures that wrap around the inner membrane. We show that MitOS acts in concert with ATP synthase dimers to organize the inner membrane and promote normal mitochondrial morphology. We propose that MitOS acts as a conserved mitochondrial skeletal structure that differentiates regions of the inner membrane to establish the normal internal architecture of mitochondria

    J/Psi Production from Electromagnetic Fragmentation in Z decay

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    The rate for Z0J/ψ++ Z^{0}\to J/ \psi + \ell^{+}\ell^{-} is suprisingly large with about one event for every million Z0Z^{0} decays. The reason for this is that there is a fragmentation contribution that is not suppressed by a factor of Mψ2/MZ2M^{2}_{\psi}/M^{2}_{Z}. In the fragmentation limit MZ M_{Z}\to\infty with Eψ/MZE_{\psi}/M_{Z} fixed, the differential decay rate for Z0J/ψ++ Z^{0}\to J/ \psi + \ell^{+}\ell^{-} factors into electromagnetic decay rates and universal fragmentation functions. The fragmentation functions for lepton fragmentation and photon fragmentation into J/ψJ/\psi are calculated to lowest order in α\alpha. The fragmentation approximation to the rate is shown to match the full calculation for EψE_{\psi} greater than about 3Mψ3 M_{\psi}.Comment: 16 pages and 8 figure

    Expression of endogenous Mkp1 in 6-OHDA rat models of Parkinson's disease.

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    We have previously demonstrated that mitogen-activated protein kinase phosphatase 1, Mkp1, is expressed in the developing and rat adult substantia nigra and striatum, where it promotes the growth of nigral dopaminergic neurons. Mkp1 may therefore have therapeutic potential for Parkinson's disease. In the present study, we have assessed the expression of Mkp1 and TH in the substantia nigra and striatum of parkinsonian rat models. Expression was measured at 4 and 10 days post-lesion in the 6-hydroxydopamine (6-OHDA) medial forebrain bundle lesion model and after 4, 10 and 28 days in the 6-OHDA striatal lesion model. Our results show that Mkp1 expression was transiently up-regulated in the substantia nigra at 4 days post-6-OHDA administration in the two models while TH expression was decreased at the later time-points examined. These data suggest that Mkp1 may play a role in counteracting the neurotoxic effects of 6-OHDA in nigral dopaminergic neurons

    Decoration of plasmonic Mg nanoparticles by partial galvanic replacement.

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    Plasmonic structures have attracted much interest in science and engineering disciplines, exploring a myriad of potential applications owing to their strong light-matter interactions. Recently, the plasmonic concentration of energy in subwavelength volumes has been used to initiate chemical reactions, for instance by combining plasmonic materials with catalytic metals. In this work, we demonstrate that plasmonic nanoparticles of earth-abundant Mg can undergo galvanic replacement in a nonaqueous solvent to produce decorated structures. This method yields bimetallic architectures where partially oxidized 200-300 nm Mg nanoplates and nanorods support many smaller Au, Ag, Pd, or Fe nanoparticles, with potential for a stepwise process introducing multiple decoration compositions on a single Mg particle. We investigated this mechanism by electron-beam imaging and local composition mapping with energy-dispersive X-ray spectroscopy as well as, at the ensemble level, by inductively coupled plasma mass spectrometry. High-resolution scanning transmission electron microscopy further supported the bimetallic nature of the particles and provided details of the interface geometry, which includes a Mg oxide separation layer between Mg and the other metal. Depending on the composition of the metallic decorations, strong plasmonic optical signals characteristic of plasmon resonances were observed in the bulk with ultraviolet-visible spectrometry and at the single particle level with darkfield scattering. These novel bimetallic and multimetallic designs open up an exciting array of applications where one or multiple plasmonic structures could interact in the near-field of earth-abundant Mg and couple with catalytic nanoparticles for applications in sensing and plasmon-assisted catalysis.Support for this project was provided by the EU Framework Programme for Research and Innovation Horizon 2020 (Starting Grant SPECs 804523). J.A. wishes to acknowledge financial support from Natural Sciences and Engineering Research Council of Canada and “Fonds de Recherche Québec – Nature et Technologies” postdoctoral fellowships (BP and B3X programs). C.B. is thankful for funding from the Engineering and Physical Sciences Research Council (Standard Research Studentship (DTP) EP/R513180/1), and E.R.H. for support from the EPSRC NanoDTC Cambridge (EP/L015978/1). S.M.C. acknowledges support from the Henslow Research Fellowship at Girton College, Cambridge. We acknowledge access and support in the use of the electron Physical Sciences Imaging Centre (MG21980) at the Diamond Light Source, U.K
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