Neuronal Heterotopias in the Developing Cerebral Cortex Produced by Neurotrophin-4

AbstractThe marginal zone (MZ) of embryonic neocortex is crucial to its normal development. We report that neurotrophin-4 (but not NT3 or NGF), applied to embryonic rodent cortex in vitro or in vivo, produces heterotopic accumulations of neurons in the MZ. Although heterotopia production is TrkB mediated, BDNF is >10-fold less effective than NT4. Heterotopic neurons have the same birth date and phenotype as normal MZ neurons; they are not the result of NT4-induced proliferation or rescue from apoptosis. We suggest that NT4 causes excess neurons to migrate into the MZ and thus may play a role in normal MZ formation as well as in the pathogenesis of certain human cortical dysplasias

Benzo[a]Pyrene Diol Epoxide Perturbation of Cell Cycle Kinetics of Synchronized Mouse Liver Epithelial Cells

A cell cycle synchronization system is described for the analysis of the perturbation of cell cycle kinetics and the cycle-phase specificity of chemicals and other agents. We used the system to study the effects of ({+-})r-7, t-8-dihydroxy-t-9, 10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaP diol epoxide) upon the cell cycle of mouse liver epithelial cells(NMuLi). BaP diol epoxide(0.6 uM) was added to replated cultures of NMuLi cells that had been synchronized in various stages of the cell cycle by centrifugal elutriation. DNA histograms were obtained by flow cytometry as a function of time after replating. The data were analyzed by a computer modeling routine and reduced to a few graphs illustrating the 'net effects' of the BaP diol epoxide relative to controls. BaP diol epoxide slowed S-phase traversal in all samples relative to their respective control. Traversal through G{sub 2}M was also slowed by at least 50%. BaP diol epoxide had no apparent effect upon G{sub 1} traversal by cycling cells, but delayed the recruitment of quiescent G{sub 0} cells by about 2 hrs. The methods described constitute a powerful new approach for probing the cell cycle effects of a wide variety of agents. The present system appears to be extremely sensitive and capable of characterizing the action of agents on each phase of the cell cycle. The methods are automatable and would allow for the assay and possible differential characterization of mutagens and carcinogens

National Geodetic Satellite Program, Part II: Smithsonian Astrophysical Observatory

A sequence of advances in the determination of geodetic parameters presented by the Smithsonian Astrophysical Observatory are described. A Baker-Nunn photographic system was used in addition to a ruby-laser ranging system to obtain data for refinement of geodetic parameters. A summary of the data employed to: (1) derive coordinates for the locations of various tracking stations; and (2) determine the gravitational potential of the earth, is presented

Peripheral Innate Immune Activation Correlates With Disease Severity in GRN Haploinsufficiency.

Objective: To investigate associations between peripheral innate immune activation and frontotemporal lobar degeneration (FTLD) in progranulin gene (GRN) haploinsufficiency. Methods: In this cross-sectional study, ELISA was used to measure six markers of innate immunity (sCD163, CCL18, LBP, sCD14, IL-18, and CRP) in plasma from 30 GRN mutation carriers (17 asymptomatic, 13 symptomatic) and 29 controls. Voxel based morphometry was used to model associations between marker levels and brain atrophy in mutation carriers relative to controls. Linear regression was used to model relationships between plasma marker levels with mean frontal white matter integrity [fractional anisotropy (FA)] and the FTLD modified Clinical Dementia Rating Scale sum of boxes score (FTLD-CDR SB). Results: Plasma sCD163 was higher in symptomatic GRN carriers [mean 321 ng/ml (SD 125)] compared to controls [mean 248 ng/ml (SD 58); p < 0.05]. Plasma CCL18 was higher in symptomatic GRN carriers [mean 56.9 pg/ml (SD 19)] compared to controls [mean 40.5 pg/ml (SD 14); p < 0.05]. Elevation of plasma LBP was associated with white matter atrophy in the right frontal pole and left inferior frontal gyrus (p FWE corrected <0.05) in all mutation carriers relative to controls. Plasma LBP levels inversely correlated with bilateral frontal white matter FA (R2 = 0.59, p = 0.009) in mutation carriers. Elevation in plasma was positively correlated with CDR-FTLD SB (b = 2.27 CDR units/μg LBP/ml plasma, R2 = 0.76, p = 0.003) in symptomatic carriers. Conclusion: FTLD-GRN is associated with elevations in peripheral biomarkers of macrophage-mediated innate immunity, including sCD163 and CCL18. Clinical disease severity and white matter integrity are correlated with blood LBP, suggesting a role for peripheral immune activation in FTLD-GRN

Beings in their own right? Exploring Children and young people's sibling and twin relationships in the Minority World

This paper examines the contributions that the sociological study of sibship and twinship in the Minority World can make to childhood studies. It argues that, in providing one forum within which to explore children and young people's social relationships, we can add to our understanding of children and young people's interdependence and develop a more nuanced understanding of agency. As emergent subjects, children, young people and adults are in a process of ‘becoming’. However, this does not mean that they can ‘become’ anything they choose to. The notion of negotiated interdependence (Punch 2002) is useful in helping us to grasp the contingent nature of children and young people's agency