2,696 research outputs found

    Diffusion Tensor Imaging Detects Early Cerebral Cortex Abnormalities in Neuronal Architecture Induced by Bilateral Neonatal Enucleation: An Experimental Model in the Ferret

    Get PDF
    Diffusion tensor imaging (DTI) is a technique that non-invasively provides quantitative measures of water translational diffusion, including fractional anisotropy (FA), that are sensitive to the shape and orientation of cellular elements, such as axons, dendrites and cell somas. For several neurodevelopmental disorders, histopathological investigations have identified abnormalities in the architecture of pyramidal neurons at early stages of cerebral cortex development. To assess the potential capability of DTI to detect neuromorphological abnormalities within the developing cerebral cortex, we compare changes in cortical FA with changes in neuronal architecture and connectivity induced by bilateral enucleation at postnatal day 7 (BEP7) in ferrets. We show here that the visual callosal pattern in BEP7 ferrets is more irregular and occupies a significantly greater cortical area compared to controls at adulthood. To determine whether development of the cerebral cortex is altered in BEP7 ferrets in a manner detectable by DTI, cortical FA was compared in control and BEP7 animals on postnatal day 31. Visual cortex, but not rostrally adjacent non-visual cortex, exhibits higher FA than control animals, consistent with BEP7 animals possessing axonal and dendritic arbors of reduced complexity than age-matched controls. Subsequent to DTI, Golgi-staining and analysis methods were used to identify regions, restricted to visual areas, in which the orientation distribution of neuronal processes is significantly more concentrated than in control ferrets. Together, these findings suggest that DTI can be of utility for detecting abnormalities associated with neurodevelopmental disorders at early stages of cerebral cortical development, and that the neonatally enucleated ferret is a useful animal model system for systematically assessing the potential of this new diagnostic strategy

    Corrections for Racial Disparities in Law Enforcement

    Full text link
    Much empirical analysis has documented racial disparities at the beginning and end stages of criminal cases. However, our understanding about the perpetuation of—and even corrections for—differential outcomes in the process remains less than complete. This Article provides a comprehensive examination of criminal dispositions using all DWI cases in North Carolina from 2001 to 2011, focusing on several major decision points in the process. Starting with pretrial hearings and culminating in sentencing results, we track differences in outcomes by race and gender. Before sentencing, significant gaps emerge in the severity of pretrial release conditions that disadvantage black and Hispanic defendants. Yet when prosecutors decide whether to pursue charges, we observe an initial correction mechanism: Hispanic men are almost two-thirds more likely to have those charges dropped relative to white men. Although few cases survive after the plea bargaining stage, a second correction mechanism arises: Hispanic men are substantially less likely to receive harsher sentences and are sent to jail for significantly less time relative to white men. The first mechanism is based, in part, on prosecutors’ reviewing the strength of the evidence, but much more on declining to invest scarce resources in the pursuit of defendants who fail to appear for trial. The second mechanism seems to follow more directly from judicial discretion to reverse decisions made by law enforcement or prosecutors. We discuss possible explanations for these novel empirical results and review methods for more precisely identifying causal mechanisms in criminal justice

    Investigating the Putative Glycine Hinge in Shaker Potassium Channel

    Get PDF
    The crystal structure of an open potassium channel reveals a kink in the inner helix that lines the pore (Jiang, Y.X., A. Lee, J.Y. Chen, M. Cadene, B.T. Chait, and R. MacKinnon. 2002. Nature 417:523–526). The putative hinge point is a highly conserved glycine residue. We examined the role of the homologous residue (Gly466) in the S6 transmembrane segment of Shaker potassium channels. The nonfunctional alanine mutant G466A will assemble, albeit poorly, with wild-type (WT) subunits, suppressing functional expression. To test if this glycine residue is critical for activation gating, we did a glycine scan along the S6 segment in the background of G466A. Although all of these double mutants lack the higher-level glycosylation that is characteristic of mature Shaker channels, one (G466A/V467G) is able to generate voltage-dependent potassium current. Surface biotinylation shows that functional and nonfunctional constructs containing G466A express at comparable levels in the plasma membrane. Compared with WT channels, the shifted-glycine mutant has impairments in voltage-dependent channel opening, including a right-shifted activation curve and a decreased rate of activation. The double mutant has relatively normal open-channel properties, except for a decreased affinity for intracellular blockers, a consequence of the loss of the side chain of Val467. Control experiments with the double mutants M440A/G466A and G466A/V467A suggest that the flexibility provided by Gly466 is more important for channel function than its small size. Our results support roles for Gly466 both in biogenesis of the channel and as a hinge in activation gating

    The Role of Social Perspective-Taking in Developing Students\u27 Leadership Capacities

    Get PDF
    This study examined relationships between social perspective-taking (SPT) and the individual, group, and societal domains of socially responsible leadership. SPT is a higher-order cognitive skill linked to moral development and social coordination, but never empirically connected to leadership development. Analyses determined SPT has a strong direct effect on group-level leadership values and an indirect effect on societallevel leadership values. Results offer critical new insights into directionality in the social change model

    Xenopus tropicalis allurin: Expression, purification, and characterization of a sperm chemoattractant that exhibits cross-species activity

    Get PDF
    AbstractPreviously we reported the identification of the first vertebrate sperm chemoattractant, allurin, in the frog Xenopus laevis (Xl) and demonstrated that it was a member of the CRISP family of proteins. Here we report identification, purification, and characterization of Xenopus tropicalis (Xt) allurin, a homologous protein in X. tropicalis. “Egg water” as well as purified allurin from both species exhibit efficient cross-species sperm chemoattractant activity. Western blots show that Xt egg water contains a single anti-allurin cross-reactive protein whose molecular weight (20,497 Da by MALDI MS) agrees well with the molecular weight of the hypothetical gene product for a newly recognized “Crisp A” gene in the X. tropicalis genome. A recombinant form of the protein, expressed in 3T3 cells, exhibits chemoattraction for both Xt and Xl sperm and cross reacts with anti-allurin antibodies. Examination of Crisp protein expression in the Xt oviduct using RT-PCR showed that of five documented Xt Crisp genes (Crisps 2, 3, LD1, LD2 and A) only Crisp A was expressed. In contrast, Crisp 2, Crisp 3, Crisp LD1, and Crisp LD2, but not Crisp A, were all found to be expressed in the Xt testes while subsets of Crisp proteins where expressed in the Xt ovary. These data suggest that Crisp proteins in amphibians may play multiple roles in sperm production, maturation and guidance just as they are thought to in mammals indicating that Crisp protein involvement in reproduction may not be limited to mammals

    Src phosphorylation converts Mdm2 from a ubiquitinating to a neddylating E3 ligase

    Get PDF
    Murine double minute-2 protein (Mdm2) is a multifaceted phosphorylated protein that plays a role in regulating numerous proteins including the tumor suppressor protein p53. Mdm2 binds to and is involved in conjugating either ubiquitin or Nedd8 (Neural precursor cell expressed, developmentally down-regulated 8) to p53. Although regulation of the E3 ubiquitin activity of Mdm2 has been investigated, regulation of the neddylating activity of Mdm2 remains to be defined. Here we show that activated c-Src kinase phosphorylates Y281 and Y302 of Mdm2, resulting in an increase in Mdm2 stability and its association with Ubc12, the E2 enzyme of the neddylating complex. Mdm2-dependent Nedd8 conjugation of p53 results in transcriptionally inactive p53, a process that is reversed with a small molecule inhibitor to either Src or Ubc12. Thus, our studies reveal how Mdm2 may neutralize and elevate p53 in actively proliferating cells and also provides a rationale for using therapies that target the Nedd8 pathway in wild-type p53 tumors

    Velocity Segregation and Systematic Biases In Velocity Dispersion Estimates With the SPT-GMOS Spectroscopic Survey

    Get PDF
    The velocity distribution of galaxies in clusters is not universal; rather, galaxies are segregated according to their spectral type and relative luminosity. We examine the velocity distributions of different populations of galaxies within 89 Sunyaev Zel'dovich (SZ) selected galaxy clusters spanning 0.28<z<1.08 0.28 < z < 1.08. Our sample is primarily draw from the SPT-GMOS spectroscopic survey, supplemented by additional published spectroscopy, resulting in a final spectroscopic sample of 4148 galaxy spectra---2868 cluster members. The velocity dispersion of star-forming cluster galaxies is 17±417\pm4% greater than that of passive cluster galaxies, and the velocity dispersion of bright (m<m0.5m < m^{*}-0.5) cluster galaxies is 11±411\pm4% lower than the velocity dispersion of our total member population. We find good agreement with simulations regarding the shape of the relationship between the measured velocity dispersion and the fraction of passive vs. star-forming galaxies used to measure it, but we find a small offset between this relationship as measured in data and simulations in which suggests that our dispersions are systematically low by as much as 3\% relative to simulations. We argue that this offset could be interpreted as a measurement of the effective velocity bias that describes the ratio of our observed velocity dispersions and the intrinsic velocity dispersion of dark matter particles in a published simulation result. Measuring velocity bias in this way suggests that large spectroscopic surveys can improve dispersion-based mass-observable scaling relations for cosmology even in the face of velocity biases, by quantifying and ultimately calibrating them out.Comment: Accepted to ApJ; 21 pages, 11 figures, 5 table
    corecore