Further supporting evidence for REEP1 phenotypic and allelic heterogeneity.

Heterozygous mutations in REEP1 (MIM #609139) encoding the receptor expression-enhancing protein 1 (REEP1) are a well-recognized and relatively frequent cause of autosomal dominant hereditary spastic paraplegia (HSP), SPG31.1 REEP1 localizes in the mitochondria and endoplasmic reticulum (ER) and facilitates ER-mitochondria interactions.2 In addition to the HSP phenotype, REEP1 has been associated with an autosomal dominant spinal type of Charcot-Marie-Tooth disease in 2 families.3 More recently, a patient with homozygous REEP1 mutation with a much more severe phenotype akin to spinal muscular atrophy with respiratory distress type 1 (SMARD1) was reported.4 In this report, we present a patient with a homozygous mutation in REEP1 manifesting a severe congenital distal spinal muscular atrophy (SMA) with diaphragmatic paralysis, expanding the phenotype from mild autosomal dominant HSP through to severe recessive distal SMA pattern

Neuroadaptations in the Cellular and Postsynaptic Group 1 Metabotropic Glutamate Receptor mGluR5 and Homer Proteins Following Extinction of Cocaine Self-administration

This study examined the role of group1 metabotropic glutamate receptor mGluR5 and associated postsynaptic scaffolding protein Homer1b/c in behavioral plasticity after three withdrawal treatments from cocaine self-administration. Rats self-administered cocaine or saline for 14 days followed by a withdrawal period during which rats underwent extinction training, remained in their home cages, orwere placed in the self-administration chambers in the absence of extinction. Subsequently, the tissue level and distribution of proteins in the synaptosomal fraction associated with the postsynaptic densitywere examined. Cocaine self-administration followed by home cage exposure reduced the mGluR5 protein in nucleus accumbens (NA) shell and dorsolateral striatum. While extinction training reduced mGluR5 protein in NAshell, NAcore and dorsolateral striatum did not display any change. The scaffolding protein PSD95 increased in NAcore of the extinguished animals. Extinction of drug seeking was associated with a significant decrease in the synaptosomal mGluR5 protein in NAshell and an increase in dorsolateral striatum, while that of NAcore was not modified. Interestingly, both Homer1b/c and PSD95 scaffolding proteins were decreased in the synaptosomal fraction after extinction training in NAshell but not NAcore. Extinguished drug-seeking behavior was also associated with an increase in the synaptosomal actin proteins in dorsolateral striatum. Therefore, extinction of cocaine seeking is associated with neuroadaptations in mGluR5 expression and distribution that are region-specific and consist of extinction-induced reversal of cocaine-induced adaptations aswell as emergent extinction-induced alterations. Concurrent plasticity in the scaffolding proteins further suggests that mGluR5 receptor neuroadaptations may have implications for synaptic function

Glutamatergic Plasticity in Medial Prefrontal Cortex and Ventral Tegmental Area Following Extended-Access Cocaine Self-Administration

Glutamate signaling in prefrontal cortex and ventral tegmental area plays an important role in the molecular and behavioral plasticity associated with addiction to drugs of abuse. The current study investigated the expression and postsynaptic density redistribution of glutamate receptors and synaptic scaffolding proteins in dorsomedial and ventromedial prefrontal cortex and ventral tegmental area after cocaine self-administration. After 14 days of extended-access (6 h/day) cocaine self-administration, rats were exposed to one of three withdrawal regimen for 10 days. Animals either stayed in home cages (Home), returned to self-administration boxes with the levers withdrawn (Box), or underwent extinction training (Extinction). Extinction training was associated with significant glutamatergic plasticity. In dorsomedial prefrontal cortex of the Extinction group, there was an increase in postsynaptic density GluR1, PSD95, and actin proteins; while postsynaptic density mGluR5 protein decreased and there was no change in NMDAR1, Homer1b/c, or PICK1 proteins. These changes were not observed in ventromedial prefrontal cortex or ventral tegmental area. In ventral tegmental area, Extinction training reversed the decreased postsynaptic density NMDAR1 protein in the Home and Box withdrawal groups. These data suggest that extinction of drug seeking is associated with selective glutamatergic plasticity in prefrontal cortex and ventral tegmental area that include modulation of receptor trafficking to postsynaptic density

On particles in the Arctic stratosphere

Soon after the discovery of the Antarctic ozone hole it became clear that particles in the polar stratosphere had an infl uence on the destruction of the ozone layer. Two major types of particles, sulphate aerosols and Polar Stratospheric Clouds (PSCs), provide the surfaces where fast heterogeneous chemical reactions convert inactive halogen reservoir species into potentially ozone-destroying radicals. Lidar measurements have been used to classify the PSCs. Following the Mt. Pinatubo eruption in June 1991 it was found that the Arctic stratosphere was loaded with aerosols, and that aerosols observed with lidar and ozone observed with ozone sondes displayed a layered structure, and that the aerosol and ozone contents in the layers frequently appeared to be negatively correlated. The layered structure was probably due to modulation induced by the dynamics at the edge of the polar vortex. Lidar observations of the Mt. Pinatubo aerosols were in several cases accompanied by balloon-borne backscatter soundings, whereby backscatter measurements in three different wavelengths made it possible to obtain information about the particle sizes. An investigation of the infl uence of synoptic temperature histories on the physical properties of PSC particles has shown that most of the liquid type 1b particles were observed in the process of an ongoing, relatively fast, and continuous cooling from temperatures clearly above the nitric acid trihydrate condensation temperature (TNAT). On the other hand, it appeared that a relatively long period, with a duration of at least 1-2 days, at temperatures below TNAT provide the conditions which may lead to the production of solid type 1a PSCs

Corticosteroid Administration to Prevent Complications of Anterior Cervical Spine Fusion: A Systematic Review.

Study Design: Systematic review. Objectives: Anterior cervical approach is associated with complications such as dysphagia and airway compromise. In this study, we aimed to systematically review the literature on the efficacy and safety of corticosteroid administration as a preventive measure of such complications in anterior cervical spine surgery with fusion. Methods: Following a systematic literature search of MEDLINE, Embase, and Cochrane databases in July 2016, all comparative human studies that evaluated the effect of steroids for prevention of complications in anterior cervical spine surgery with fusion were included, irrespective of number of levels and language. Risk of bias was assessed using MINORS (Methodological Index for Non-Randomized Studies) checklist and Cochrane Back and Neck group recommendations, for nonrandomized and randomized studies, respectively. Results: Our search yielded 556 articles, of which 9 studies (7 randomized controlled trials and 2 non-randomized controlled trials) were included in the final review. Dysphagia was the most commonly evaluated complication, and in most studies, its severity or incidence was significantly lower in the steroid group. Although prevertebral soft tissue swelling was less commonly assessed, the results were generally in favor of steroid use. The evidence for airway compromise and length of hospitalization was inconclusive. Steroid-related complications were rare, and in both studies that evaluated the fusion rate, it was comparable between steroid and control groups in long-term follow-up. Conclusions: Current literature supports the use of steroids for prevention of complications in anterior cervical spine surgery with fusion. However, evidence is limited by substantial risk of bias and small number of studies reporting key outcomes

Effect of travelling fire on structural response of a generic steel fire protected moment resisting frame

To simulate a fire inside large compartments, there is a pioneering method called ‘traveling fire’. As steel structures are vulnerable to high temperatures, they are normally fireproofed by insulation materials appropriate for a specific duration of time. An investigation is performed here to examine the robustness of a generic fourstory moment-resisting steel structure, fireproofed to comply with the one-hour standard curve, when it is subjected to traveling fire. The results show that while no collapse occurs during the 12.5%, 50% and 100%, the structure collapses under the 25% fire size at 75 min. This seems to be in contradiction with traditional belief, where it is assumed that taking into consideration a larger-scale fire in a compartment would increase the safety margin. The investigation performed also underlines that the fireproofing of structures does not necessarily provide adequate resistance under traveling fires

An automated pipeline for the discovery of conspiracy and conspiracy theory narrative frameworks: Bridgegate, Pizzagate and storytelling on the web

Although a great deal of attention has been paid to how conspiracy theories circulate on social media and their factual counterpart conspiracies, there has been little computational work done on describing their narrative structures. We present an automated pipeline for the discovery and description of the generative narrative frameworks of conspiracy theories on social media, and actual conspiracies reported in the news media. We base this work on two separate repositories of posts and news articles describing the well-known conspiracy theory Pizzagate from 2016, and the New Jersey conspiracy Bridgegate from 2013. We formulate a graphical generative machine learning model where nodes represent actors/actants, and multi-edges and self-loops among nodes capture context-specific relationships. Posts and news items are viewed as samples of subgraphs of the hidden narrative network. The problem of reconstructing the underlying structure is posed as a latent model estimation problem. We automatically extract and aggregate the actants and their relationships from the posts and articles. We capture context specific actants and interactant relationships by developing a system of supernodes and subnodes. We use these to construct a network, which constitutes the underlying narrative framework. We show how the Pizzagate framework relies on the conspiracy theorists' interpretation of "hidden knowledge" to link otherwise unlinked domains of human interaction, and hypothesize that this multi-domain focus is an important feature of conspiracy theories. While Pizzagate relies on the alignment of multiple domains, Bridgegate remains firmly rooted in the single domain of New Jersey politics. We hypothesize that the narrative framework of a conspiracy theory might stabilize quickly in contrast to the narrative framework of an actual one, which may develop more slowly as revelations come to light.Comment: conspiracy theory, narrative structur