Diffuse Neutron Scattering Study of Magnetic Correlations in half-doped La0.5Ca0.5-xSrxMnO3 (x = 0.1, 0.3 and 0.4) Manganites

The short range ordered magnetic correlations have been studied in half doped La0.5Ca0.5-xSrxMnO3 (x = 0.1, 0.3 and 0.4) compounds by polarized neutron scattering technique. On doping Sr2+ for Ca2+ ion, these compounds with x = 0.1, 0.3, and 0.4 exhibit CE-type, mixture of CE-type and A-type, and A-type antiferromagnetic ordering, respectively. Magnetic diffuse scattering is observed in all the compounds above and below their respective magnetic ordering temperatures and is attributed to magnetic polarons. The correlations are primarily ferromagnetic in nature above T\_N, although a small antiferromagnetic contribution is also evident. Additionally, in samples x = 0.1 and 0.3 with CE-type antiferromagnetic ordering, superlattice diffuse reflections are observed indicating correlations between magnetic polarons. On lowering temperature below T\_N the diffuse scattering corresponding to ferromagnetic correlations is suppressed and the long range ordered antiferromagnetic state is established. However, the short range ordered correlations indicated by enhanced spin flip scattering at low Q coexist with long range ordered state down to 3K. In x = 0.4 sample with A-type antiferromagnetic ordering, superlattice diffuse reflections are absent. Additionally, in comparison to x = 0.1 and 0.3 sample, the enhanced spin flip scattering at low Q is reduced at 310K, and as temperature is reduced below 200K, it becomes negligibly low. The variation of radial correlation function, g(r) with temperature indicates rapid suppression of ferromagnetic correlations at the first nearest neighbor on approaching TN. Sample x = 0.4 exhibits growth of ferromagnetic phase at intermediate temperatures (~ 200K). This has been further explored using SANS and neutron depolarization techniques.Comment: 13 pages, 12 figures, To appear in Physical Review

Absence of Phase Transition for Antiferromagnetic Potts Models via the Dobrushin Uniqueness Theorem

We prove that the $q$-state Potts antiferromagnet on a lattice of maximum coordination number $r$ exhibits exponential decay of correlations uniformly at all temperatures (including zero temperature) whenever $q > 2r$. We also prove slightly better bounds for several two-dimensional lattices: square lattice (exponential decay for $q \ge 7$), triangular lattice ($q \ge 11$), hexagonal lattice ($q \ge 4$), and Kagom\'e lattice ($q \ge 6$). The proofs are based on the Dobrushin uniqueness theorem.Comment: 32 pages including 3 figures. Self-unpacking file containing the tex file, the needed macros (epsf.sty, indent.sty, subeqnarray.sty, and eqsection.sty) and the 3 ps file

Tracking interfacial changes of graphene/Ge(110) during in-vacuum annealing

Graphene quality indicators obtained by Raman spectroscopy have been correlated to the structural changes of the graphene/Germanium interface as a function of in-vacuum thermal annealing. Specifically, it is found that graphene becomes markedly defected at 650 {\deg}C. By combining scanning tunneling microscopy, x-Ray Photoelectron Spectroscopy and Near Edge x-ray Absorption Fine Structure Spectroscopy, we conclude that these defects are due to the release of H_{2} gas trapped at the graphene/Germanium interface. The H_{2} gas was produced following the transition from the as-grown hydrogen-termination of the Ge(110) surface to the emergence of surface reconstructions in the substrate. Interestingly, a complete self-healing process is observed in graphene upon annealing to 800 {\deg}C. The subtle interplay revealed between the microscopic changes occurring at the graphene/Germanium interface and graphene's defect density is valuable for advancing graphene growth, controlled 2D-3D heterogeneous materials interfacing and integrated fabrication technology on semiconductors

Induction of differentiation inhibits the tumorigenic potential of glioblastoma cancer stem cells

The outcome of the patients with newly diagnosed glioblastoma remains dismal, despite the use of surgery, radiotherapy and adjuvant temozolomide and while new agents like anti-angiogenic agents seem to offer some promise, a new approach is needed. Recent studies suggest that cancer stem cells (CSCs) may play an important role in malignant gliomas invasion and proliferation. Therefore, CSCs became new therapeutical targets, and one of the main experimental therapies which could be used against CSCs is the differentiation therapy.The purpose of this study was to characterize the CSCs isolated from glioblastoma samples, to assess in vivo the tumorigenic potential of these cells and to induct the differentiation of the CSCs. The changes in invasive markers (matrixmetalloproteases-MMPs, cadherins and cathenins) expression were assessed. CSCs exposed to differentiation inductor factors have been inoculated in nude mice and their tumorigenic potential has been evaluated. The stemness biological feature was correlated with increased of MMPs, cadherins, catenin expression and with tumour contra-lateral invasion. The expression of MMPs, cadherins and cadherins decreased after exposure of the CSCs cultures to the differentiation inductor factors. In vivo experiments demonstrated the inhibition of tumorigenic potential of differentiated CSCs cultures.In conclusion, differentiated CSCs showed a decreased expression of invasive markers in vitro and lost their tumorigenic potential in vivo

Mechanisms explaining transitions between tonic and phasic firing in neuronal populations as predicted by a low dimensional firing rate model

Several firing patterns experimentally observed in neural populations have been successfully correlated to animal behavior. Population bursting, hereby regarded as a period of high firing rate followed by a period of quiescence, is typically observed in groups of neurons during behavior. Biophysical membrane-potential models of single cell bursting involve at least three equations. Extending such models to study the collective behavior of neural populations involves thousands of equations and can be very expensive computationally. For this reason, low dimensional population models that capture biophysical aspects of networks are needed. \noindent The present paper uses a firing-rate model to study mechanisms that trigger and stop transitions between tonic and phasic population firing. These mechanisms are captured through a two-dimensional system, which can potentially be extended to include interactions between different areas of the nervous system with a small number of equations. The typical behavior of midbrain dopaminergic neurons in the rodent is used as an example to illustrate and interpret our results. \noindent The model presented here can be used as a building block to study interactions between networks of neurons. This theoretical approach may help contextualize and understand the factors involved in regulating burst firing in populations and how it may modulate distinct aspects of behavior.Comment: 25 pages (including references and appendices); 12 figures uploaded as separate file

Metabolome-wide association study on ABCA7 indicates a role of ceramide metabolism in Alzheimer's disease.

Genome-wide association studies (GWASs) have identified genetic loci associated with the risk of Alzheimer's disease (AD), but the molecular mechanisms by which they confer risk are largely unknown. We conducted a metabolome-wide association study (MWAS) of AD-associated loci from GWASs using untargeted metabolic profiling (metabolomics) by ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). We identified an association of lactosylceramides (LacCer) with AD-related single-nucleotide polymorphisms (SNPs) in ABCA7 (P = 5.0 × 10-5 to 1.3 × 10-44). We showed that plasma LacCer concentrations are associated with cognitive performance and genetically modified levels of LacCer are associated with AD risk. We then showed that concentrations of sphingomyelins, ceramides, and hexosylceramides were altered in brain tissue from Abca7 knockout mice, compared with wild type (WT) (P = 0.049-1.4 × 10-5), but not in a mouse model of amyloidosis. Furthermore, activation of microglia increases intracellular concentrations of hexosylceramides in part through induction in the expression of sphingosine kinase, an enzyme with a high control coefficient for sphingolipid and ceramide synthesis. Our work suggests that the risk for AD arising from functional variations in ABCA7 is mediated at least in part through ceramides. Modulation of their metabolism or downstream signaling may offer new therapeutic opportunities for AD

Metabolome-wide association study on ABCA7 indicates a role of ceramide metabolism in Alzheimer’s disease

Genome-wide association studies (GWASs) have identified genetic loci associated with the risk of Alzheimer’s disease (AD), but the molecular mechanisms by which they confer risk are largely unknown. We conducted a metabolome-wide association study (MWAS) of AD-associated loci from GWASs using untargeted metabolic profiling (metabolomics) by ultraperformance liquid chromatography–mass spectrometry (UPLC-MS). We identified an association of lactosylceramides (LacCer) with AD-related single-nucleotide polymorphisms (SNPs) in ABCA7 (P = 5.0 × 10−5 to 1.3 × 10−44). We showed that plasma LacCer concentrations are associated with cognitive performance and genetically modified levels of LacCer are associated with AD risk. We then showed that concentrations of sphingomyelins, ceramides, and hexosylceramides were altered in brain tissue from Abca7 knockout mice, compared with wild type (WT) (P = 0.049–1.4 × 10−5), but not in a mouse model of amyloidosis. Furthermore, activation of microglia increases intracellular concentrations of hexosylceramides in part through induction in the expression of sphingosine kinase, an enzyme with a high control coefficient for sphingolipid and ceramide synthesis. Our work suggests that the risk for AD arising from functional variations in ABCA7 is mediated at least in part through ceramides. Modulation of their metabolism or downstream signaling may offer new therapeutic opportunities for AD

Integrative analysis identifies key molecular signatures underlying neurodevelopmental deficits in fragile X syndrome

BACKGROUND: Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by epigenetic silencing of FMR1 and loss of FMRP expression. Efforts to understand the molecular underpinnings of the disease have been largely performed in rodent or nonisogenic settings. A detailed examination of the impact of FMRP loss on cellular processes and neuronal properties in the context of isogenic human neurons remains lacking. METHODS: Using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 to introduce indels in exon 3 of FMR1, we generated an isogenic human pluripotent stem cell model of FXS that shows complete loss of FMRP expression. We generated neuronal cultures and performed genome-wide transcriptome and proteome profiling followed by functional validation of key dysregulated processes. We further analyzed neurodevelopmental and neuronal properties, including neurite length and neuronal activity, using multielectrode arrays and patch clamp electrophysiology. RESULTS: We showed that the transcriptome and proteome profiles of isogenic FMRP-deficient neurons demonstrate perturbations in synaptic transmission, neuron differentiation, cell proliferation and ion transmembrane transporter activity pathways, and autism spectrum disorder-associated gene sets. We uncovered key deficits in FMRP-deficient cells demonstrating abnormal neural rosette formation and neural progenitor cell proliferation. We further showed that FMRP-deficient neurons exhibit a number of additional phenotypic abnormalities, including neurite outgrowth and branching deficits and impaired electrophysiological network activity. These FMRP-deficient related impairments have also been validated in additional FXS patient-derived human-induced pluripotent stem cell neural cells. CONCLUSIONS: Using isogenic human pluripotent stem cells as a model to investigate the pathophysiology of FXS in human neurons, we reveal key neural abnormalities arising from the loss of FMRP.Peer reviewe