Abnormal axonal connectivity and hyperactive mTOR complex 1 (mTORC1) are shared features of several neurological disorders. Hyperactive mTORC1 alters axon length and polarity of hippocampal neurons in vitro, but the impact of hyperactive mTORC1 on axon growth in vivo and the mechanisms underlying those effects remain unclear. Using in utero electroporation during corticogenesis, we show that increasing mTORC1 activity accelerates axon growth without multiple axon formation. This was prevented by counteracting mTORC1 signaling through p70S6Ks (S6K1/2) or eukaryotic initiation factor 4E-binding protein (4E-BP1/2), which both regulate translation. In addition to regulating translational targets, S6K1 indirectly signals through GSK3β, a regulator of axogenesis. Although blocking GSK3β activity did not alter axon growth under physiological conditions in vivo, blocking it using a dominant-negative mutant or lithium chloride prevented mTORC1-induced accelerated axon growth. These data reveal the contribution of translational and non-translational downstream effectors such as GSK3β to abnormal axon growth in neurodevelopmental mTORopathies and open new therapeutic options for restoring long-range connectivity.

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Inbred mouse strains have been used preferentially for behavioral testing over outbred counterparts, even though outbred mice reflect the genetic diversity in the human population better. Here, we compare the sociability of widely available outbred CD1 mice with the commonly used inbred C57BL/6J (C57) mice in the one-chamber social interaction test and the three-chamber sociability test. In the one-chamber task, intra-strain pairs of juvenile, non-littermate, male CD1 or C57 mice display a series of social and aggressive behaviors. While CD1 and C57 pairs spend equal amount of time socializing, CD1 pairs spend significantly more time engaged in aggressive behaviors than C57 mice. In the three-chamber task, sociability of C57 mice was less dependent on acclimation paradigms than CD1 mice. Following acclimation to all three chambers, both groups of age-matched male mice spent more time in the chamber containing a stranger mouse than in the empty chamber, suggesting that CD1 mice are sociable like C57 mice. However, the observed power suggests that it is easier to achieve statistical significance with C57 than CD1 mice. Because the stranger mouse could be considered as a novel object, we assessed for a novelty effect by adding an object. CD1 mice spend more time in the chamber with a stranger mouse than that a novel object, suggesting that their preference is social in nature. Thus, outbred CD1 mice are as appropriate as inbred C57 mice for studying social behavior using either the single or the three-chamber test using a specific acclimation paradigm.

Result dissemination is important for scientific progress; however, 25% to 50% of clinical trials are not published. 1,2 To increase dissemination, the National Library of Medicine established an online registry, ClinicalTrials.gov. This database contains over 224 000 trials 3 ; approximately 60% will supply results through the website 4 and 46% will be published in a peer-reviewed journal. 4 This study sought to comprehensively classify neurology trials within ClinicalTrials.gov to compare publication rates as well as time to publication.Methods | An aggregate search was performed on July 19, 2016, through ClinicalTrials.gov, for closed interventional trials conducted within the United States between October 1, 2007, and July 1, 2014. The study was approved by the Yale School of Medicine Institutional Review Board.Using the search term nervous system disease, the search was refined to ensure that trials were conducted within the specified time to allow at least 2 years for potential dissemination. 1,5 Subcategories were subsequently assigned and potential publications were identified. A systematic 3-step process similar to

Introduction: High throughput genotyping technologies and large collaborative consortia have revolutionized the field of medical genetics. Open data access is the final barrier capitalizing fully on the opportunities available in stroke genetics research. The International Stroke Genetics Consortium (ISGC) has created the Cerebrovascular Disease Knowledge Portal (CDKP), a platform to explore and access genetic data related to cerebrovascular diseases. Methods: Funded by the NIH, the CDKP has been developed by the ISGC and the American Heart Association (AHA) Institute for Precision Cardiovascular Medicine. The CDKP seeks to democratize access to genomic data and potentiate stroke genomics research by providing open access to genetic, phenotypic and imaging data on patients with stroke. Within the CDKP, data are aggregated, integrated, and harmonized according to a pre-specified standardized pipeline. Any institution or investigator working with stroke genomic data is welcome to deposit their data or use available data. Results: The CDKP houses two types of data, for different regulatory and analytical needs: summary level data and individual level data. The CDKP offers three main features: (1) a web-based graphical user interphase that allows the exploration of genomic information through a wide menu of integrated tools for analysis and data visualization; (2) a repository of full sets of genome-wide summary statistics produced by published landmark studies in the field; and (3) a repository of individual level data, accessible through a secure cloud working space provided by the AHA Platform for Precision Medicine. The CDKP can be accessed at www.cerebrovascularportal.org . Conclusion: The CDKP advances the ISGC’s goal of liberal data sharing in stroke genomics and other areas of cardiovascular research that may benefit from genomic analyses. In the future, phenotypic datasets can be added to further enrich sharing of non-genetic data as well.