Epilepsy in Dcx Knockout Mice Associated with Discrete Lamination Defects and Enhanced Excitability in the Hippocampus

Patients with Doublecortin (DCX) mutations have severe cortical malformations associated with mental retardation and epilepsy. Dcx knockout (KO) mice show no major isocortical abnormalities, but have discrete hippocampal defects. We questioned the functional consequences of these defects and report here that Dcx KO mice are hyperactive and exhibit spontaneous convulsive seizures. Changes in neuropeptide Y and calbindin expression, consistent with seizure occurrence, were detected in a large proportion of KO animals, and convulsants, including kainate and pentylenetetrazole, also induced seizures more readily in KO mice. We show that the dysplastic CA3 region in KO hippocampal slices generates sharp wave-like activities and possesses a lower threshold for epileptiform events. Video-EEG monitoring also demonstrated that spontaneous seizures were initiated in the hippocampus. Similarly, seizures in human patients mutated for DCX can show a primary involvement of the temporal lobe. In conclusion, seizures in Dcx KO mice are likely to be due to abnormal synaptic transmission involving heterotopic cells in the hippocampus and these mice may therefore provide a useful model to further study how lamination defects underlie the genesis of epileptiform activities

The remnants of restinga habitats in the brazilian Atlantic Forest of Rio de Janeiro state, Brazil: habitat loss and risk of disappearance

"Restingas" (herbaceous/shrubby coastal sand-dune habitats) used to cover most of Rio de Janeiro State coast, and have suffered extensive degradation over the last five centuries. Using satellite images and field work, we identified the remaining restingas in the State, recording the factors that might cause their degradation. We used two mosaics of Landsat 7 scenes (spatial resolution 15 and 30 m) to map and evaluate preliminarly the remaining areas and conservation status. Each remnant area was checked in the field, degraded areas within it were mapped and subtracted from the remnants. We identified 21 restinga remnants totalling 105,285 ha. The largest and smallest restinga remnants were Jurubatiba (25,141 ha) and Itaipu (23 ha), respectively. We identified 14 causes of degradation. The most important were vegetation removal for housing developments, establishment of exotic plant species, change of original substrate, and selective removal of species of economic importance for the horticultural industry. All restingas had disturbed parts under strong pressure due to human activities. Due to intense habitat loss, and occurrence of endemic/threatened vertebrate species in restinga habitats, we strongly indicate the implementation of new conservation units to protect these fragile remnants. This habitat is steadily decreasing and most remnants lack legal protection. Therefore, under the current human pressure most of this unique habitat is likely to be lost from the State within the next few years

Modeling the impact of comorbidity on breast cancer patient outcomes

Nationwide inpatient sample, Breast cancer, Comorbidity, Descriptive statistics, Least squares regression, Survival analysis, Logistic regression, Censoring, Length of stay, Total charges, Mortality,

MCT8 mutation analysis and identification of the first female with Allan-Herndon-Dudley syndrome due to loss of MCT8 expression

Mutations in the thyroid monocarboxylate transporter 8 gene (MCT8/SLC16A2) have been reported to result in X-linked mental retardation (XLMR) in patients with clinical features of the Allan–Herndon–Dudley syndrome (AHDS). We performed MCT8 mutation analysis including 13 XLMR families with LOD scores >2.0, 401 male MR sibships and 47 sporadic male patients with AHDS-like clinical features. One nonsense mutation (c.629insA) and two missense changes (c.1A>T and c.1673G>A) were identified. Consistent with previous reports on MCT8 missense changes, the patient with c.1673G>A showed elevated serum T3 level. The c.1A>T change in another patient affects a putative translation start codon, but the same change was present in his healthy brother. In addition normal serum T3 levels were present, suggesting that the c.1A>T (NM_006517) variation is not responsible for the MR phenotype but indicates that MCT8 translation likely starts with a methionine at position p.75. Moreover, we characterized a de novo translocation t(X;9)(q13.2;p24) in a female patient with full blown AHDS clinical features including elevated serum T3 levels. The MCT8 gene was disrupted at the X-breakpoint. A complete loss of MCT8 expression was observed in a fibroblast cell-line derived from this patient because of unfavorable nonrandom X-inactivation. Taken together, these data indicate that MCT8 mutations are not common in non-AHDS MR patients yet they support that elevated serum T3 levels can be indicative for AHDS and that AHDS clinical features can be present in female MCT8 mutation carriers whenever there is unfavorable nonrandom X-inactivation.Suzanna Gerarda Maria Frints, Steffen Lenzner, Mareike Bauters, Lars Riff Jensen, Hilde Van Esch, Vincent des Portes, Ute Moog, Merryn Victor Erik Macville, Kees van Roozendaa, Constance Theresia Rimbertha Maria Schrander-Stumpel, Andreas Tzschach, Peter Marynen, Jean-Pierre Fryns, Ben Hamel, Hans van Bokhoven, Jamel Chelly, Chérif Beldjord, Gillian Turner, Jozef Gecz, Claude Moraine, Martine Raynaud, Hans Hilger Ropers, Guy Froyen and Andreas Walter Kus

Recurrent Deletion of ZNF630 at Xp11.23 Is Not Associated With Mental Retardation How to Cite this Article

ZNF630 is a member of the primate-specific Xp11 zinc finger gene cluster that consists of six closely related genes, of which ZNF41, ZNF81, and ZNF674 have been shown to be involved in mental retardation. This suggests that mutations of ZNF630 How to Cite this Article: 638 might influence cognitive function. Here, we detected 12 ZNF630 deletions in a total of 1,562 male patients with mental retardation from Brazil, USA, Australia, and Europe. The breakpoints were analyzed in 10 families, and in all cases they were located within two segmental duplications that share more than 99% sequence identity, indicating that the deletions resulted from non-allelic homologous recombination. In 2,121 healthy male controls, 10 ZNF630 deletions were identified. In total, there was a 1.6-fold higher frequency of this deletion in males with mental retardation as compared to controls, but this increase was not statistically significant (P-value ¼ 0.174). Conversely, a 1.9-fold lower frequency of ZNF630 duplications was observed in patients, which was not significant either (P-value ¼ 0.163). These data do not show that ZNF630 deletions or duplications are associated with mental retardation.

PHENIX detector overview

The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved

Beam Energy and Centrality Dependence of Direct-Photon Emission from Ultrarelativistic Heavy-Ion Collisions

International audienceThe PHENIX collaboration presents first measurements of low-momentum (0.41  GeV/c) direct-photon yield dNγdir/dη is a smooth function of dNch/dη and can be well described as proportional to (dNch/dη)α with α≈1.25. This scaling behavior holds for a wide range of beam energies at the Relativistic Heavy Ion Collider and the Large Hadron Collider, for centrality selected samples, as well as for different A+A collision systems. At a given beam energy, the scaling also holds for high pT (>5  GeV/c), but when results from different collision energies are compared, an additional sNN-dependent multiplicative factor is needed to describe the integrated-direct-photon yield