Distinct disorders affecting the brain share common genetic origins

Over the last few years, large cohorts of patients with distinct brain disorders of neuropsychiatric and neurological origin have been analyzed for copy number variation. Surprisingly, the same genetic abnormalities were found in cohorts of patients affected with mental retardation, autism, or schizophrenia

Domain structure of epitaxial Co films with perpendicular anisotropy

Epitaxial hcp Cobalt films with pronounced c-axis texture have been prepared by pulsed lased deposition (PLD) either directly onto Al2O3 (0001) single crystal substrates or with an intermediate Ruthenium buffer layer. The crystal structure and epitaxial growth relation was studied by XRD, pole figure measurements and reciprocal space mapping. Detailed VSM analysis shows that the perpendicular anisotropy of these highly textured Co films reaches the magnetocrystalline anisotropy of hcp-Co single crystal material. Films were prepared with thickness t of 20 nm < t < 100 nm to study the crossover from in-plane magnetization to out-of-plane magnetization in detail. The analysis of the periodic domain pattern observed by magnetic force microscopy allows to determine the critical minimum thickness below which the domains adopt a pure in-plane orientation. Above the critical thickness the width of the stripe domains is evaluated as a function of the film thickness and compared with domain theory. Especially the discrepancies at smallest film thicknesses show that the system is in an intermediate state between in-plane and out-of-plane domains, which is not described by existing analytical domain models

Metabonomics adds a new dimension to fragile X syndrome

Fragile X syndrome is the most common cause of inherited intellectual disability, but the underlying pathophysiology is complex and effective treatments are lacking. In a recent study of fragile X mental retardation 1 (Fmr1) knockout mice, the metabolic profile of the fragile X brain was determined using proton high-resolution magic angle spinning nuclear magnetic resonance spectroscopy. This analysis revealed deficiencies in four metabolic categories: neurotransmission, osmoregulation, energy metabolism and oxidative stress response. Abnormalities in the metabolic phenotype were linked to the fragile X mental retardation protein using an integrated metabolome and interactome mapping approach, allowing a global picture of the disorder to emerge

Frustration Driven Stripe Domain Formation in Co/Pt Multilayer Films

We report microscopic mechanisms for an unusual magnetization reversal behavior in Co/Pt multilayers where some of the first-order reversal curves protrude outside of the major loop. Transmission x-ray microscopy reveals a fragmented stripe domain topography when the magnetic field is reversed prior to saturation, in contrast to an interconnected pattern when reversing from a saturated state. The different domain nucleation and propagation behaviors are due to unannihilated domains from the prior field sweep. These residual domains contribute to random dipole fields that impede the subsequent domain growth and prevent domains from growing as closely together as for the interconnected pattern.Comment: 13 pages, 3 figures, to appear in AP

Vascular endothelial growth factor directly inhibits primitive neural stem cell survival but promotes definitive neural stem cell survival

There are two types of neural stem cells (NSCs). Primitive NSCs [leukemia inhibitory factor (LIF) dependent but exogenous fibroblast growth factor (FGF) 2 independent] can be derived from mouse embryonic stem (ES) cells in vitro and from embryonic day 5.5 (E5.5) to E7.5 epiblast and E7.5-E8.5 neuroectoderm in vivo. Definitive NSCs (LIF independent but FGF2 dependent) first appear in the E8.5 neural plate and persist throughout life. Primitive NSCs give rise to definitive NSCs. Loss and gain of functions were used to study the role of vascular endothelial growth factor (VEGF)-A and its receptor, Flk1, in NSCs. The numbers of Flk1 knock-out mice embryo-derived and ES cell-derived primitive NSCs were increased because of the enhanced survival of primitive NSCs. In contrast, neural precursor-specific, Flk1 conditional knock-out mice-derived, definitive NSCs numbers were decreased because of the enhanced cell death of definitive NSCs. These effects were not observed in cells lacking Flt1, another VEGF receptor. In addition, the cell death stimulated by VEGF-A of primitive NSC and the cell survival stimulated by VEGF-A of definitive NSC were blocked by Flk1/Fc-soluble receptors and VEGF-A function-blocking antibodies. These VEGF-A phenotypes also were blocked by inhibition of the downstream effector nuclear factor kappa B (NF-kappa B). Thus, both the cell death of primitive NSC and the cell survival of definitive NSC induced by VEGF-A stimulation are mediated by bifunctional NF-kappa B effects. In conclusion, VEGF-A function through Flk1 mediates survival (and not proliferative or fate change) effects on NSCs, specifically

Domain wall structure in magnetic bilayers with perpendicular anisotropy

We study the magnetic domain wall structure in magnetic bilayers (two ultrathin ferromagnetic layers separated by a non magnetic spacer) with perpendicular magnetization. Combining magnetic force and ballistic electron emission microscopies, we are able to reveal the details of the magnetic structure of the wall with a high spatial accuracy. In these layers, we show that the classical Bloch wall observed in single layers transforms into superposed N\'eel walls due to the magnetic coupling between the ferromagnetic layers. Quantitative agreement with micromagnetic calculations is achieved.Comment: Author adresses AB, SR, JM and AT: Laboratoire de Physique des Solides, CNRS, Universit\'e Paris Sud, UMR 8502, 91405 Orsay Cedex, France ML : Laboratoire PMTM, Institut Galil\'ee, CNRS, Universit\'e Paris-13, UPR 9001, 93430 Villetaneuse, Franc

Correlation between magnetic interactions and domain structure in A1 FePt ferromagnetic thin films

We have investigated the relationship between the domain structure and the magnetic interactions in a series of FePt ferromagnetic thin films of varying thickness. As-made films grow in the magnetically soft and chemically disordered A1 phase that may have two distinct domain structures. Above a critical thickness $d_{cr}\sim 30$ nm the presence of an out of plane anisotropy induces the formation of stripes, while for $d<d_{cr}$ planar domains occur. Magnetic interactions have been characterized using the well known DCD-IRM remanence protocols, $\delta M$ plots, and magnetic viscosity measurements. We have observed a strong correlation between the domain configuration and the sign of the magnetic interactions. Planar domains are associated with positive exchange-like interactions, while stripe domains have a strong negative dipolar-like contribution. In this last case we have found a close correlation between the interaction parameter and the surface dipolar energy of the stripe domain structure. Using time dependent magnetic viscosity measurements, we have also estimated an average activation volume for magnetic reversal, $\langle V_{ac}\rangle \sim 1.37\times 10^{4}$ nm$^{3},$ which is approximately independent of the film thickness or the stripe period.Comment: 25 pages, 11 figure

CNV-WebStore: Online CNV Analysis, Storage and Interpretation

<p>Abstract</p> <p>Background</p> <p>Microarray technology allows the analysis of genomic aberrations at an ever increasing resolution, making functional interpretation of these vast amounts of data the main bottleneck in routine implementation of high resolution array platforms, and emphasising the need for a centralised and easy to use CNV data management and interpretation system.</p> <p>Results</p> <p>We present CNV-WebStore, an online platform to streamline the processing and downstream interpretation of microarray data in a clinical context, tailored towards but not limited to the Illumina BeadArray platform. Provided analysis tools include CNV analsyis, parent of origin and uniparental disomy detection. Interpretation tools include data visualisation, gene prioritisation, automated PubMed searching, linking data to several genome browsers and annotation of CNVs based on several public databases. Finally a module is provided for uniform reporting of results.</p> <p>Conclusion</p> <p>CNV-WebStore is able to present copy number data in an intuitive way to both lab technicians and clinicians, making it a useful tool in daily clinical practice.</p

In vitro antischistosomal activity of Artemisia annua and Artemisia afra extracts

Background Schistosomiasis, a neglected tropical disease, imposes substantial health and economic burdens on impoverished groups living in predominantly rural areas. Praziquantel (PZQ) is the only drug available for treatment, and it is not completely efficacious. Artemisia annua and Artemisia afra infusions were proposed to possess antischistosomal activities in a recently retracted publication of a clinical trial, leading to our investigation in vitro. Objective The objective was to identify the main components of the infusions and evaluate the in vitro antischistosomal activities of traditionally prepared infusions as well as hexane and dichloromethane (DCM) extracts of the infusions of A. afra and A. annua. Methods Infusions of A. afra and A. annua were submitted to liquid-liquid partitioning with n-hexane and DCM to provide samples for in vitro bioassays using newly transformed schistosomulas (NTS) and adult Schistosoma mansoni worms obtained from infected mice. The viability of the NTS and adult S. mansoni was visually scored via microscopic readout. Results Nine phytochemicals comprising coumarins and organic acids were identified. A. afra and A. annua infusions and extracts possess potent in vitro antischistosomal activities against NTS, at 100 μg/ml. However, the A. afra infusions exhibited better activities against NTS than the A. annua infusion. The A. afra hexane- and DCM extracts presented IC50 values that are similar to PZQ (1.5 μg/ml) and approximately five times lower than the comparison drug artesunate (11.6 μg/ml) against NTS. Low IC50 values for both these extracts were also obtained in phenotypic assays with adult S. mansoni. Conclusion A. afra shows greater antischistosomal potential than A. annua. Thus, further studies are necessary to identify the active molecule(s) responsible for the notable antischistosomal activity of A. afra