edi Our Lady of Grace family page of history : a bookweek bicentennial project / edited by Janeen Brian. By www.catalog.slsa.sa.gov.au Published On :: Our Lady of Grace School (Glengowrie, S.A.) Full Article
edi Calif. Ed-Tech Consortium Seeks Media Repository Solutions; Saint Paul District Needs Background Check Services By marketbrief.edweek.org Published On :: Fri, 08 May 2020 13:52:21 +0000 Saint Paul schools are in the market for a vendor to provide background checks, while the Education Technology Joint Powers Authority is seeking media repositories. A Texas district wants quotes on technology for new campuses. The post Calif. Ed-Tech Consortium Seeks Media Repository Solutions; Saint Paul District Needs Background Check Services appeared first on Market Brief. Full Article Purchasing Alert Background Checks Media Repository Procurement / Purchasing / RFPs Software / Hardware
edi Item 07: A Journal of ye [the] Proceedings of his Majesty's Sloop Swallow, Captain Phillip [Philip] Carteret Commander, Commencing ye [the] 23 of July 1766 and ended [4 July 1767] By feedproxy.google.com Published On :: 5/05/2015 9:51:13 AM Full Article
edi Item 08: A Logg [Log] Book of the proceedings on Board His Majesty's Ship Swallow, Captain Philip Carteret Commander Commencing from the 20th August 1766 and Ending [21st May 1768] By feedproxy.google.com Published On :: 5/05/2015 12:19:15 PM Full Article
edi Item 13: Swallow 1767, A journal of the proceedings on Board His Majesty's Sloop Swallow, commencing the 1st of March 1767 and Ended the 7th of July 1767 By feedproxy.google.com Published On :: 7/05/2015 12:42:02 PM Full Article
edi The accusation against Joe Biden has Democrats rediscovering the value of due process By news.yahoo.com Published On :: Sat, 09 May 2020 08:37:00 -0400 Some Democrats took "Believe Women" literally until Joe Biden was accused. Now they're relearning that guilt-by-accusation doesn't serve justice. Full Article
edi Calibration Procedures for Approximate Bayesian Credible Sets By projecteuclid.org Published On :: Thu, 19 Dec 2019 22:10 EST Jeong Eun Lee, Geoff K. Nicholls, Robin J. Ryder. Source: Bayesian Analysis, Volume 14, Number 4, 1245--1269.Abstract: We develop and apply two calibration procedures for checking the coverage of approximate Bayesian credible sets, including intervals estimated using Monte Carlo methods. The user has an ideal prior and likelihood, but generates a credible set for an approximate posterior based on some approximate prior and likelihood. We estimate the realised posterior coverage achieved by the approximate credible set. This is the coverage of the unknown “true” parameter if the data are a realisation of the user’s ideal observation model conditioned on the parameter, and the parameter is a draw from the user’s ideal prior. In one approach we estimate the posterior coverage at the data by making a semi-parametric logistic regression of binary coverage outcomes on simulated data against summary statistics evaluated on simulated data. In another we use Importance Sampling from the approximate posterior, windowing simulated data to fall close to the observed data. We illustrate our methods on four examples. Full Article
edi Bayesian Effect Fusion for Categorical Predictors By projecteuclid.org Published On :: Wed, 13 Mar 2019 22:00 EDT Daniela Pauger, Helga Wagner. Source: Bayesian Analysis, Volume 14, Number 2, 341--369.Abstract: We propose a Bayesian approach to obtain a sparse representation of the effect of a categorical predictor in regression type models. As this effect is captured by a group of level effects, sparsity cannot only be achieved by excluding single irrelevant level effects or the whole group of effects associated to this predictor but also by fusing levels which have essentially the same effect on the response. To achieve this goal, we propose a prior which allows for almost perfect as well as almost zero dependence between level effects a priori. This prior can alternatively be obtained by specifying spike and slab prior distributions on all effect differences associated to this categorical predictor. We show how restricted fusion can be implemented and develop an efficient MCMC (Markov chain Monte Carlo) method for posterior computation. The performance of the proposed method is investigated on simulated data and we illustrate its application on real data from EU-SILC (European Union Statistics on Income and Living Conditions). Full Article
edi Comment: Statistical Inference from a Predictive Perspective By projecteuclid.org Published On :: Wed, 08 Jan 2020 04:00 EST Alessandro Rinaldo, Ryan J. Tibshirani, Larry Wasserman. Source: Statistical Science, Volume 34, Number 4, 599--603.Abstract: What is the meaning of a regression parameter? Why is this the de facto standard object of interest for statistical inference? These are delicate issues, especially when the model is misspecified. We argue that focusing on predictive quantities may be a desirable alternative. Full Article
edi The Joyful Reduction of Uncertainty: Music Perception as a Window to Predictive Neuronal Processing By www.jneurosci.org Published On :: 2020-04-01T09:30:19-07:00 Full Article
edi Editor’s Pick: Gifts for Your Tech-Obsessed Friend By www.health.com Published On :: Tue, 26 Nov 2019 12:49:30 -0500 A guide to the tech gadgets even your hard-to-shop-for friends and family members will love. Full Article
edi Nike Launches Zoom Pulse Sneakers for Medical Workers Who Are On Their Feet All Day By www.health.com Published On :: Fri, 13 Dec 2019 13:45:17 -0500 The new style is available to shop today. Full Article
edi The Phase of Ongoing EEG Oscillations Predicts Visual Perception By www.jneurosci.org Published On :: 2009-06-17 Niko A. BuschJun 17, 2009; 29:7869-7876BehavioralSystemsCognitive Full Article
edi A framework for mesencephalic dopamine systems based on predictive Hebbian learning By www.jneurosci.org Published On :: 1996-03-01 PR MontagueMar 1, 1996; 16:1936-1947Articles Full Article
edi {alpha}-Band Electroencephalographic Activity over Occipital Cortex Indexes Visuospatial Attention Bias and Predicts Visual Target Detection By www.jneurosci.org Published On :: 2006-09-13 Gregor ThutSep 13, 2006; 26:9494-9502BehavioralSystemsCognitive Full Article
edi Pax6, Tbr2, and Tbr1 Are Expressed Sequentially by Radial Glia, Intermediate Progenitor Cells, and Postmitotic Neurons in Developing Neocortex By www.jneurosci.org Published On :: 2005-01-05 Chris EnglundJan 5, 2005; 25:247-251BRIEF COMMUNICATION Full Article
edi Calcium Influx via the NMDA Receptor Induces Immediate Early Gene Transcription by a MAP Kinase/ERK-Dependent Mechanism By www.jneurosci.org Published On :: 1996-09-01 Zhengui XiaSep 1, 1996; 16:5425-5436Articles Full Article
edi BIS Quarterly Review, September 2019 - media briefing By www.bis.org Published On :: 2019-09-22T16:00:00Z On-the-record remarks of the September 2019 Quarterly Review media briefing by Mr Claudio Borio, Head of the Monetary and Economic Department, and Mr Hyun Song Shin, Economic Adviser and Head of Research, 20 September 2019. Full Article
edi BIS Quarterly Review, December 2019 - media briefing By www.bis.org Published On :: 2019-12-08T17:00:00Z On-the-record remarks of the December 2019 Quarterly Review media briefing by Mr Claudio Borio, Head of the Monetary and Economic Department, and Mr Hyun Song Shin, Economic Adviser and Head of Research, 6 December 2019. Full Article
edi BIS Quarterly Review, March 2020 - media remarks By www.bis.org Published On :: 2020-03-01T17:00:00Z On-the-record remarks of the March 2020 Quarterly Review media briefing by Mr Claudio Borio, Head of the Monetary and Economic Department, and Mr Hyun Song Shin, Economic Adviser and Head of Research, 28 February 2020. Full Article
edi Neural Evidence for the Prediction of Animacy Features during Language Comprehension: Evidence from MEG and EEG Representational Similarity Analysis By www.jneurosci.org Published On :: 2020-04-15T09:30:18-07:00 It has been proposed that people can generate probabilistic predictions at multiple levels of representation during language comprehension. We used magnetoencephalography (MEG) and electroencephalography (EEG), in combination with representational similarity analysis, to seek neural evidence for the prediction of animacy features. In two studies, MEG and EEG activity was measured as human participants (both sexes) read three-sentence scenarios. Verbs in the final sentences constrained for either animate or inanimate semantic features of upcoming nouns, and the broader discourse context constrained for either a specific noun or for multiple nouns belonging to the same animacy category. We quantified the similarity between spatial patterns of brain activity following the verbs until just before the presentation of the nouns. The MEG and EEG datasets revealed converging evidence that the similarity between spatial patterns of neural activity following animate-constraining verbs was greater than following inanimate-constraining verbs. This effect could not be explained by lexical-semantic processing of the verbs themselves. We therefore suggest that it reflected the inherent difference in the semantic similarity structure of the predicted animate and inanimate nouns. Moreover, the effect was present regardless of whether a specific word could be predicted, providing strong evidence for the prediction of coarse-grained semantic features that goes beyond the prediction of individual words. SIGNIFICANCE STATEMENT Language inputs unfold very quickly during real-time communication. By predicting ahead, we can give our brains a "head start," so that language comprehension is faster and more efficient. Although most contexts do not constrain strongly for a specific word, they do allow us to predict some upcoming information. For example, following the context of "they cautioned the...," we can predict that the next word will be animate rather than inanimate (we can caution a person, but not an object). Here, we used EEG and MEG techniques to show that the brain is able to use these contextual constraints to predict the animacy of upcoming words during sentence comprehension, and that these predictions are associated with specific spatial patterns of neural activity. Full Article
edi The Effect of Counterfactual Information on Outcome Value Coding in Medial Prefrontal and Cingulate Cortex: From an Absolute to a Relative Neural Code By www.jneurosci.org Published On :: 2020-04-15T09:30:18-07:00 Adaptive coding of stimuli is well documented in perception, where it supports efficient encoding over a broad range of possible percepts. Recently, a similar neural mechanism has been reported also in value-based decision, where it allows optimal encoding of vast ranges of values in PFC: neuronal response to value depends on the choice context (relative coding), rather than being invariant across contexts (absolute coding). Additionally, value learning is sensitive to the amount of feedback information: providing complete feedback (both obtained and forgone outcomes) instead of partial feedback (only obtained outcome) improves learning. However, it is unclear whether relative coding occurs in all PFC regions and how it is affected by feedback information. We systematically investigated univariate and multivariate feedback encoding in various mPFC regions and compared three modes of neural coding: absolute, partially-adaptive and fully-adaptive. Twenty-eight human participants (both sexes) performed a learning task while undergoing fMRI scanning. On each trial, they chose between two symbols associated with a certain outcome. Then, the decision outcome was revealed. Notably, in one-half of the trials participants received partial feedback, whereas in the other half they got complete feedback. We used univariate and multivariate analysis to explore value encoding in different feedback conditions. We found that both obtained and forgone outcomes were encoded in mPFC, but with opposite sign in its ventral and dorsal subdivisions. Moreover, we showed that increasing feedback information induced a switch from absolute to relative coding. Our results suggest that complete feedback information enhances context-dependent outcome encoding. SIGNIFICANCE STATEMENT This study offers a systematic investigation of the effect of the amount of feedback information (partial vs complete) on univariate and multivariate outcome value encoding, within multiple regions in mPFC and cingulate cortex that are critical for value-based decisions and behavioral adaptation. Moreover, we provide the first comparison of three possible models of neural coding (i.e., absolute, partially-adaptive, and fully-adaptive coding) of value signal in these regions, by using commensurable measures of prediction accuracy. Taken together, our results help build a more comprehensive picture of how the human brain encodes and processes outcome value. In particular, our results suggest that simultaneous presentation of obtained and foregone outcomes promotes relative value representation. Full Article
edi Contribution of NPY Y5 Receptors to the Reversible Structural Remodeling of Basolateral Amygdala Dendrites in Male Rats Associated with NPY-Mediated Stress Resilience By www.jneurosci.org Published On :: 2020-04-15T09:30:18-07:00 Endogenous neuropeptide Y (NPY) and corticotrophin-releasing factor (CRF) modulate the responses of the basolateral amygdala (BLA) to stress and are associated with the development of stress resilience and vulnerability, respectively. We characterized persistent effects of repeated NPY and CRF treatment on the structure and function of BLA principal neurons in a novel organotypic slice culture (OTC) model of male rat BLA, and examined the contributions of specific NPY receptor subtypes to these neural and behavioral effects. In BLA principal neurons within the OTCs, repeated NPY treatment caused persistent attenuation of excitatory input and induced dendritic hypotrophy via Y5 receptor activation; conversely, CRF increased excitatory input and induced hypertrophy of BLA principal neurons. Repeated treatment of OTCs with NPY followed by an identical treatment with CRF, or vice versa, inhibited or reversed all structural changes in OTCs. These structural responses to NPY or CRF required calcineurin or CaMKII, respectively. Finally, repeated intra-BLA injections of NPY or a Y5 receptor agonist increased social interaction, a validated behavior for anxiety, and recapitulated structural changes in BLA neurons seen in OTCs, while a Y5 receptor antagonist prevented NPY's effects both on behavior and on structure. These results implicate the Y5 receptor in the long-term, anxiolytic-like effects of NPY in the BLA, consistent with an intrinsic role in stress buffering, and highlight a remarkable mechanism by which BLA neurons may adapt to different levels of stress. Moreover, BLA OTCs offer a robust model to study mechanisms associated with resilience and vulnerability to stress in BLA. SIGNIFICANCE STATEMENT Within the basolateral amygdala (BLA), neuropeptide Y (NPY) is associated with buffering the neural stress response induced by corticotropin releasing factor, and promoting stress resilience. We used a novel organotypic slice culture model of BLA, complemented with in vivo studies, to examine the cellular mechanisms associated with the actions of NPY. In organotypic slice cultures, repeated NPY treatment reduces the complexity of the dendritic extent of anxiogenic BLA principal neurons, making them less excitable. NPY, via activation of Y5 receptors, additionally inhibits and reverses the increases in dendritic extent and excitability induced by the stress hormone, corticotropin releasing factor. This NPY-mediated neuroplasticity indicates that resilience or vulnerability to stress may thus involve neuropeptide-mediated dendritic remodeling in BLA principal neurons. Full Article
edi Rapid Release of Ca2+ from Endoplasmic Reticulum Mediated by Na+/Ca2+ Exchange By www.jneurosci.org Published On :: 2020-04-15T09:30:18-07:00 Phototransduction in Drosophila is mediated by phospholipase C (PLC) and Ca2+-permeable TRP channels, but the function of endoplasmic reticulum (ER) Ca2+ stores in this important model for Ca2+ signaling remains obscure. We therefore expressed a low affinity Ca2+ indicator (ER-GCaMP6-150) in the ER, and measured its fluorescence both in dissociated ommatidia and in vivo from intact flies of both sexes. Blue excitation light induced a rapid (tau ~0.8 s), PLC-dependent decrease in fluorescence, representing depletion of ER Ca2+ stores, followed by a slower decay, typically reaching ~50% of initial dark-adapted levels, with significant depletion occurring under natural levels of illumination. The ER stores refilled in the dark within 100–200 s. Both rapid and slow store depletion were largely unaffected in InsP3 receptor mutants, but were much reduced in trp mutants. Strikingly, rapid (but not slow) depletion of ER stores was blocked by removing external Na+ and in mutants of the Na+/Ca2+ exchanger, CalX, which we immuno-localized to ER membranes in addition to its established localization in the plasma membrane. Conversely, overexpression of calx greatly enhanced rapid depletion. These results indicate that rapid store depletion is mediated by Na+/Ca2+ exchange across the ER membrane induced by Na+ influx via the light-sensitive channels. Although too slow to be involved in channel activation, this Na+/Ca2+ exchange-dependent release explains the decades-old observation of a light-induced rise in cytosolic Ca2+ in photoreceptors exposed to Ca2+-free solutions. SIGNIFICANCE STATEMENT Phototransduction in Drosophila is mediated by phospholipase C, which activates TRP cation channels by an unknown mechanism. Despite much speculation, it is unknown whether endoplasmic reticulum (ER) Ca2+ stores play any role. We therefore engineered flies expressing a genetically encoded Ca2+ indicator in the photoreceptor ER. Although NCX Na+/Ca2+ exchangers are classically believed to operate only at the plasma membrane, we demonstrate a rapid light-induced depletion of ER Ca2+ stores mediated by Na+/Ca2+ exchange across the ER membrane. This NCX-dependent release was too slow to be involved in channel activation, but explains the decades-old observation of a light-induced rise in cytosolic Ca2+ in photoreceptors bathed in Ca2+-free solutions. Full Article
edi Somatostatin-Expressing Interneurons in the Auditory Cortex Mediate Sustained Suppression by Spectral Surround By www.jneurosci.org Published On :: 2020-04-29T09:30:19-07:00 Sensory systems integrate multiple stimulus features to generate coherent percepts. Spectral surround suppression, the phenomenon by which sound-evoked responses of auditory neurons are suppressed by stimuli outside their receptive field, is an example of this integration taking place in the auditory system. While this form of global integration is commonly observed in auditory cortical neurons, and potentially used by the nervous system to separate signals from noise, the mechanisms that underlie this suppression of activity are not well understood. We evaluated the contributions to spectral surround suppression of the two most common inhibitory cell types in the cortex, parvalbumin-expressing (PV+) and somatostatin-expressing (SOM+) interneurons, in mice of both sexes. We found that inactivating SOM+ cells, but not PV+ cells, significantly reduces sustained spectral surround suppression in excitatory cells, indicating a dominant causal role for SOM+ cells in the integration of information across multiple frequencies. The similarity of these results to those from other sensory cortices provides evidence of common mechanisms across the cerebral cortex for generating global percepts from separate features. SIGNIFICANCE STATEMENT To generate coherent percepts, sensory systems integrate simultaneously occurring features of a stimulus, yet the mechanisms by which this integration occurs are not fully understood. Our results show that neurochemically distinct neuronal subtypes in the primary auditory cortex have different contributions to the integration of different frequency components of an acoustic stimulus. Together with findings from other sensory cortices, our results provide evidence of a common mechanism for cortical computations used for global integration of stimulus features. Full Article
edi Neurog2 Acts as a Classical Proneural Gene in the Ventromedial Hypothalamus and Is Required for the Early Phase of Neurogenesis By www.jneurosci.org Published On :: 2020-04-29T09:30:19-07:00 The tuberal hypothalamus is comprised of the dorsomedial, ventromedial, and arcuate nuclei, as well as parts of the lateral hypothalamic area, and it governs a wide range of physiologies. During neurogenesis, tuberal hypothalamic neurons are thought to be born in a dorsal-to-ventral and outside-in pattern, although the accuracy of this description has been questioned over the years. Moreover, the intrinsic factors that control the timing of neurogenesis in this region are poorly characterized. Proneural genes, including Achate-scute-like 1 (Ascl1) and Neurogenin 3 (Neurog3) are widely expressed in hypothalamic progenitors and contribute to lineage commitment and subtype-specific neuronal identifies, but the potential role of Neurogenin 2 (Neurog2) remains unexplored. Birthdating in male and female mice showed that tuberal hypothalamic neurogenesis begins as early as E9.5 in the lateral hypothalamic and arcuate and rapidly expands to dorsomedial and ventromedial neurons by E10.5, peaking throughout the region by E11.5. We confirmed an outside-in trend, except for neurons born at E9.5, and uncovered a rostrocaudal progression but did not confirm a dorsal-ventral patterning to tuberal hypothalamic neuronal birth. In the absence of Neurog2, neurogenesis stalls, with a significant reduction in early-born BrdU+ cells but no change at later time points. Further, the loss of Ascl1 yielded a similar delay in neuronal birth, suggesting that Ascl1 cannot rescue the loss of Neurog2 and that these proneural genes act independently in the tuberal hypothalamus. Together, our findings show that Neurog2 functions as a classical proneural gene to regulate the temporal progression of tuberal hypothalamic neurogenesis. SIGNIFICANCE STATEMENT Here, we investigated the general timing and pattern of neurogenesis within the tuberal hypothalamus. Our results confirmed an outside-in trend of neurogenesis and uncovered a rostrocaudal progression. We also showed that Neurog2 acts as a classical proneural gene and is responsible for regulating the birth of early-born neurons within the ventromedial hypothalamus, acting independently of Ascl1. In addition, we revealed a role for Neurog2 in cell fate specification and differentiation of ventromedial -specific neurons. Last, Neurog2 does not have cross-inhibitory effects on Neurog1, Neurog3, and Ascl1. These findings are the first to reveal a role for Neurog2 in hypothalamic development. Full Article
edi The Frog Motor Nerve Terminal Has Very Brief Action Potentials and Three Electrical Regions Predicted to Differentially Control Transmitter Release By www.jneurosci.org Published On :: 2020-04-29T09:30:19-07:00 The action potential (AP) waveform controls the opening of voltage-gated calcium channels and contributes to the driving force for calcium ion flux that triggers neurotransmission at presynaptic nerve terminals. Although the frog neuromuscular junction (NMJ) has long been a model synapse for the study of neurotransmission, its presynaptic AP waveform has never been directly studied, and thus the AP waveform shape and propagation through this long presynaptic nerve terminal are unknown. Using a fast voltage-sensitive dye, we have imaged the AP waveform from the presynaptic terminal of male and female frog NMJs and shown that the AP is very brief in duration and actively propagated along the entire length of the terminal. Furthermore, based on measured AP waveforms at different regions along the length of the nerve terminal, we show that the terminal is divided into three distinct electrical regions: A beginning region immediately after the last node of Ranvier where the AP is broadest, a middle region with a relatively consistent AP duration, and an end region near the tip of nerve terminal branches where the AP is briefer. We hypothesize that these measured changes in the AP waveform along the length of the motor nerve terminal may explain the proximal-distal gradient in transmitter release previously reported at the frog NMJ. SIGNIFICANCE STATEMENT The AP waveform plays an essential role in determining the behavior of neurotransmission at the presynaptic terminal. Although the frog NMJ is a model synapse for the study of synaptic transmission, there are many unknowns centered around the shape and propagation of its presynaptic AP waveform. Here, we demonstrate that the presynaptic terminal of the frog NMJ has a very brief AP waveform and that the motor nerve terminal contains three distinct electrical regions. We propose that the changes in the AP waveform as it propagates along the terminal can explain the proximal-distal gradient in transmitter release seen in electrophysiological studies. Full Article
edi Modulations of Insular Projections by Prior Belief Mediate the Precision of Prediction Error during Tactile Learning By www.jneurosci.org Published On :: 2020-05-06T09:30:22-07:00 Awareness for surprising sensory events is shaped by prior belief inferred from past experience. Here, we combined hierarchical Bayesian modeling with fMRI on an associative learning task in 28 male human participants to characterize the effect of the prior belief of tactile events on connections mediating the outcome of perceptual decisions. Activity in anterior insular cortex (AIC), premotor cortex (PMd), and inferior parietal lobule (IPL) were modulated by prior belief on unexpected targets compared with expected targets. On expected targets, prior belief decreased the connection strength from AIC to IPL, whereas it increased the connection strength from AIC to PMd when targets were unexpected. Individual differences in the modulatory strength of prior belief on insular projections correlated with the precision that increases the influence of prediction errors on belief updating. These results suggest complementary effects of prior belief on insular-frontoparietal projections mediating the precision of prediction during probabilistic tactile learning. SIGNIFICANCE STATEMENT In a probabilistic environment, the prior belief of sensory events can be inferred from past experiences. How this prior belief modulates effective brain connectivity for updating expectations for future decision-making remains unexplored. Combining hierarchical Bayesian modeling with fMRI, we show that during tactile associative learning, prior expectations modulate connections originating in the anterior insula cortex and targeting salience-related and attention-related frontoparietal areas (i.e., parietal and premotor cortex). These connections seem to be involved in updating evidence based on the precision of ascending inputs to guide future decision-making. Full Article
edi Calcineurin Inhibition Causes {alpha}2{delta}-1-Mediated Tonic Activation of Synaptic NMDA Receptors and Pain Hypersensitivity By www.jneurosci.org Published On :: 2020-05-06T09:30:22-07:00 Calcineurin inhibitors, such as tacrolimus (FK506) and cyclosporine, are widely used as standard immunosuppressants in organ transplantation recipients. However, these drugs can cause severe pain in patients, commonly referred to as calcineurin inhibitor-induced pain syndrome (CIPS). Although calcineurin inhibition increases NMDAR activity in the spinal cord, the underlying mechanism remains enigmatic. Using an animal model of CIPS, we found that systemic administration of FK506 in male and female mice significantly increased the amount of α2-1–GluN1 complexes in the spinal cord and the level of α2-1–bound GluN1 proteins in spinal synaptosomes. Treatment with FK506 significantly increased the frequency of mEPSCs and the amplitudes of monosynaptic EPSCs evoked from the dorsal root and puff NMDAR currents in spinal dorsal horn neurons. Inhibiting α2-1 with gabapentin or disrupting the α2-1–NMDAR interaction with α2-1Tat peptide completely reversed the effects of FK506. In α2-1 gene KO mice, treatment with FK506 failed to increase the frequency of NMDAR-mediated mEPSCs and the amplitudes of evoked EPSCs and puff NMDAR currents in spinal dorsal horn neurons. Furthermore, systemic administration of gabapentin or intrathecal injection of α2-1Tat peptide reversed thermal and mechanical hypersensitivity in FK506-treated mice. In addition, genetically deleting GluN1 in dorsal root ganglion neurons or α2-1 genetic KO similarly attenuated FK506-induced thermal and mechanical hypersensitivity. Together, our findings indicate that α2-1–bound NMDARs mediate calcineurin inhibitor-induced tonic activation of presynaptic and postsynaptic NMDARs at the spinal cord level and that presynaptic NMDARs play a prominent role in the development of CIPS. SIGNIFICANCE STATEMENT Calcineurin inhibitors are immunosuppressants used to prevent rejection of transplanted organs and tissues. However, these drugs can cause severe, unexplained pain. We showed that calcineurin inhibition enhances physical interaction between α2-1 and NMDARs and their synaptic trafficking in the spinal cord. α2-1 is essential for calcineurin inhibitor-induced aberrant activation of presynaptic and postsynaptic NMDARs in the spinal cord. Furthermore, inhibiting α2-1 or disrupting α2-1–NMDAR interaction reduces calcineurin inhibitor-induced pain hypersensitivity. Eliminating NMDARs in primary sensory neurons or α2-1 KO also attenuates calcineurin inhibitor-induced pain hypersensitivity. This new information extends our mechanistic understanding of the role of endogenous calcineurin in regulating synaptic plasticity and nociceptive transmission and suggests new strategies for treating this painful condition. Full Article
edi The growing role of fish in feeding the world By www.fao.org Published On :: Mon, 09 Jun 2014 00:00:00 GMT People have never consumed so much fish or depended so greatly on the sector for their well-being as they do today. Did you know? Fish is one of the most-traded food commodities worldwide, worth almost US$130 billion in 2012 – a figure that will probably continue to increase. World per capita apparent fish consumption increased from an average of 9.9 kg in the [...] Full Article
edi 6 incredible plants you might not have heard of By www.fao.org Published On :: Wed, 04 Feb 2015 00:00:00 GMT All over the world local varieties of fruit, vegetables and grain are grown. Many are seemingly forgotten or are underutilized despite having outstanding nutritional or taste qualities. Some have good commercial potential and could be an excellent cash crop for a smallscale or family farmers, aimed at the local, regional or international market. Here are six traditional crops and six facts [...] Full Article
edi New edition of the Farmer's Market at FAO Headquarters By www.fao.org Published On :: Mon, 16 Dec 2019 00:00:00 GMT The farmers will offer seasonal fresh fruits and vegetables to around 3000 people - including employees, contractors, delegates and visitors - that enter the FAO headquarters every day. Centro Agroalimentare [...] Full Article
edi OK Go - Needing/Getting [3m56s] By www.youtube.com Published On :: Music video by OK Go performing Needing/Getting. Full Article
edi Mercury’s Messy Surface May Have Once Had Crucial Ingredients for Life By www.smithsonianmag.com Published On :: Tue, 24 Mar 2020 20:15:38 +0000 A new theory suggests the hot, harsh planet’s interior could have contained volatiles like water Full Article
edi Shuttered Museums Use Social Media to Share Bouquets of Floral Artwork By www.smithsonianmag.com Published On :: Mon, 30 Mar 2020 20:55:47 +0000 Hundreds of museums are participating in an online attempt to spread joy as COVID-19 keeps their galleries empty Full Article
edi Watch Seven Medieval Castles' Digital Reconstruction By www.smithsonianmag.com Published On :: Tue, 31 Mar 2020 11:00:00 +0000 Architects and designers restored royal ruins across Europe to their former glory Full Article
edi New Tool for Biomedical Research Was Invented in Ancient Egypt By www.smithsonianmag.com Published On :: Wed, 01 Apr 2020 20:04:42 +0000 The bright blue pigment that adorns the Bust of Nefertiti’s crown can now be used to study molecular biology Full Article
edi The Fallout of a Medieval Archbishop's Murder Is Recorded in Alpine Ice By www.smithsonianmag.com Published On :: Thu, 02 Apr 2020 15:09:14 +0000 Traces of lead pollution frozen in a glacier confirm that British lead production waned just before the death of Thomas Becket Full Article
edi Ten Apple Varieties Once Thought Extinct Rediscovered in Pacific Northwest By www.smithsonianmag.com Published On :: Fri, 17 Apr 2020 15:26:42 +0000 The "lost" apples will help restore genetic, culinary diversity to a crop North America once produced in astonishing variety Full Article
edi Researchers Follow a 15th-Century Recipe to Recreate Medieval Blue Ink By www.smithsonianmag.com Published On :: Tue, 21 Apr 2020 15:34:41 +0000 The purplish-blue pigment, derived from a Portuguese fruit, fell out of use by the 19th century Full Article
edi Unwind With These Free, Museum-Led Meditation and Mindfulness Sessions By www.smithsonianmag.com Published On :: Wed, 22 Apr 2020 13:59:20 +0000 The Rubin Museum of Art and the Smithsonian's National Museum of Asian Art offer an array of relaxing experiences Full Article
edi Taxis no longer accepting Medicaid vouchers: In Bethel By www.ketchikandailynews.com Published On :: Full Article
edi Scammers target residents posing as credit union By www.ketchikandailynews.com Published On :: Full Article
edi Feeding Baby By www.smithsonianmag.com Published On :: Tue, 14 Apr 2020 13:43:50 +0000 feeding baby 1 Full Article
edi How the Medieval Longbow Cut Down a French Army in 1346 By www.smithsonianmag.com Published On :: Wed, 08 Apr 2020 00:00:00 -0000 The medieval English longbow first came to prominence during the Hundred Years War. In 1346, English forces used it to devastating effect to cut down a superior French army. Full Article
edi What Kind of Damage Can a Medieval War Hammer Do? By www.smithsonianmag.com Published On :: Mon, 27 Apr 2020 00:00:00 -0000 A contemporary weapons expert is about to test a medieval war hammer on a steel breastplate from that era. The aim is to find out how much damage this fearsome instrument of death could deal. Full Article
edi Comment on Tamil flick Endhiran slated to hit theatres on 1st October by Media Wettbewerbe By rss-newsfeed.india-meets-classic.net Published On :: Sat, 25 Sep 2010 21:38:48 +0000 <span class="topsy_trackback_comment"><span class="topsy_twitter_username"><span class="topsy_trackback_content">Tamil flick Endhiran slated to hit theatres on 1st October | RSS ...: Mumbai (Bollypatrika News): Tamil flick “End... http://bit.ly/dxOe6H</span></span> Full Article
edi Comment on Hrithik Roshan still under medication by Vishal Jalore By rss-newsfeed.india-meets-classic.net Published On :: Sat, 27 Nov 2010 17:33:57 +0000 <span class="topsy_trackback_comment"><span class="topsy_twitter_username"><span class="topsy_trackback_content">RT @imconair: Hrithik Roshan still under medication http://bit.ly/gFyC3O #IMCRadio.net</span></span> Full Article
edi Comment on Whistleblower-Alternativen, Anonymous-Portrait, Jugendmedienschutz-Schluss und das Beste aus 2010 by Medien im Mainstream By rss-newsfeed.india-meets-classic.net Published On :: Fri, 17 Dec 2010 18:59:27 +0000 <span class="topsy_trackback_comment"><span class="topsy_twitter_username"><span class="topsy_trackback_content">Whistleblower-Alternativen, Anonymous-Portrait, Jugendmedienschutz ...: Diese Woche wollen wir pr... http://bit.ly/fed0Um #Whistleblower</span></span> Full Article