Eu0.5_{0.5}Sr1.5_{1.5}MnO4_4: a three-dimensional XY spin glass

The frequency, temperature, and dc-bias dependence of the ac-susceptibility of a high quality single crystal of the Eu$_{0.5}$Sr$_{1.5}$MnO$_4$ layered manganite is investigated. Eu$_{0.5}$Sr$_{1.5}$MnO$_4$ behaves like a XY spin glass with a strong basal anisotropy. Dynamical and static scalings reveal a three-dimensional phase transition near $T_g$ = 18 K, and yield critical exponent values between those of Heisenberg- and Ising-like systems, albeit slightly closer to the Ising case. Interestingly, as in the latter system, the here observed rejuvenation effects are rather weak. The origin and nature of the low temperature XY spin glass state is discussed.Comment: REVTeX 4 style; 5 pages, 4 figure

Signatures of Spin Glass Freezing in NiO Nanoparticles

We present a detailed study of the magnetic properties of sol-gel prepared nickel oxide nanoparticles of different sizes. We report various measurements such as frequency, field and temperature dependence of ac susceptibility, temperature and field dependence of dc magnetization and time decay of thermoremanent magnetization. Our results and analysis show that the system behaves as a spin glass.Comment: 8 pages, 9 figure

Intrathecal B-cell activation in LGI1 antibody encephalitis.

ObjectiveTo study intrathecal B-cell activity in leucine-rich, glioma-inactivated 1 (LGI1) antibody encephalitis. In patients with LGI1 antibodies, the lack of CSF lymphocytosis or oligoclonal bands and serum-predominant LGI1 antibodies suggests a peripherally initiated immune response. However, it is unknown whether B cells within the CNS contribute to the ongoing pathogenesis of LGI1 antibody encephalitis.MethodsPaired CSF and peripheral blood (PB) mononuclear cells were collected from 6 patients with LGI1 antibody encephalitis and 2 patients with other neurologic diseases. Deep B-cell immune repertoire sequencing was performed on immunoglobulin heavy chain transcripts from CSF B cells and sorted PB B-cell subsets. In addition, LGI1 antibody levels were determined in CSF and PB.ResultsSerum LGI1 antibody titers were on average 127-fold higher than CSF LGI1 antibody titers. Yet, deep B-cell repertoire analysis demonstrated a restricted CSF repertoire with frequent extensive clusters of clonally related B cells connected to mature PB B cells. These clusters showed intensive mutational activity of CSF B cells, providing strong evidence for an independent CNS-based antigen-driven response in patients with LGI1 antibody encephalitis but not in controls.ConclusionsOur results demonstrate that intrathecal immunoglobulin repertoire expansion is a feature of LGI1 antibody encephalitis and suggests a need for CNS-penetrant therapies

Threshold electronic structure at the oxygen K edge of 3d transition metal oxides: a configuration interaction approach

It has been generally accepted that the threshold structure observed in the oxygen K edge X-ray absorption spectrum in 3d transition metal oxides represents the electronic structure of the 3d transition metal. There is, however, no consensus about the correct description. We present an interpretation, which includes both ground state hybridization and electron correlation. It is based on a configuration interaction cluster calculation using a MO6 cluster. The oxygen K edge spectrum is calculated by annihilating a ligand hole in the ground state and is compared to calculations representing inverse photoemission experiments in which a 3d transition metal electron is added. Clear differences are observed related to the amount of ligand hole created in the ground state. Two "rules" connected to this are discussed. Comparison with experimental data of some early transition metal compounds is made and shows that this simple cluster approach explains the experimental features quite well.Comment: 10 pages, submitted to Phys. Rev. B, tried to make a better PS file

Maternal embryonic leucine zipper kinase (MELK) regulates multipotent neural progenitor proliferation.

Maternal embryonic leucine zipper kinase (MELK) was previously identified in a screen for genes enriched in neural progenitors. Here, we demonstrate expression of MELK by progenitors in developing and adult brain and that MELK serves as a marker for self-renewing multipotent neural progenitors (MNPs) in cultures derived from the developing forebrain and in transgenic mice. Overexpression of MELK enhances (whereas knockdown diminishes) the ability to generate neurospheres from MNPs, indicating a function in self-renewal. MELK down-regulation disrupts the production of neurogenic MNP from glial fibrillary acidic protein (GFAP)-positive progenitors in vitro. MELK expression in MNP is cell cycle regulated and inhibition of MELK expression down-regulates the expression of B-myb, which is shown to also mediate MNP proliferation. These findings indicate that MELK is necessary for proliferation of embryonic and postnatal MNP and suggest that it regulates the transition from GFAP-expressing progenitors to rapid amplifying progenitors in the postnatal brain

Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.

One fundamental but understudied mechanism of gene regulation in disease is allele-specific expression (ASE), the preferential expression of one allele. We leveraged RNA-sequencing data from human brain to assess ASE in autism spectrum disorder (ASD). When ASE is observed in ASD, the allele with lower population frequency (minor allele) is preferentially more highly expressed than the major allele, opposite to the canonical pattern. Importantly, genes showing ASE in ASD are enriched in those downregulated in ASD postmortem brains and in genes harboring de novo mutations in ASD. Two regions, 14q32 and 15q11, containing all known orphan C/D box small nucleolar RNAs (snoRNAs), are particularly enriched in shifts to higher minor allele expression. We demonstrate that this allele shifting enhances snoRNA-targeted splicing changes in ASD-related target genes in idiopathic ASD and 15q11-q13 duplication syndrome. Together, these results implicate allelic imbalance and dysregulation of orphan C/D box snoRNAs in ASD pathogenesis

Strong Association of De Novo Copy Number Mutations with Autism

We tested the hypothesis that de novo copy number variation (CNV) is associated with autism spectrum disorders (ASDs). We performed comparative genomic hybridization (CGH) on the genomic DNA of patients and unaffected subjects to detect copy number variants not present in their respective parents. Candidate genomic regions were validated by higher-resolution CGH, paternity testing, cytogenetics, fluorescence in situ hybridization, and microsatellite genotyping. Confirmed de novo CNVs were significantly associated with autism (P = 0.0005). Such CNVs were identified in 12 out of 118 (10%) of patients with sporadic autism, in 2 out of 77 (3%) of patients with an affected first-degree relative, and in 2 out of 196 (1%) of controls. Most de novo CNVs were smaller than microscopic resolution. Affected genomic regions were highly heterogeneous and included mutations of single genes. These findings establish de novo germline mutation as a more significant risk factor for ASD than previously recognized

Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; a prospective observational study

Background: All spinocerebellar ataxias (SCAs) are rare diseases. SCA1, 2, 3 and 6 are the four most common SCAs, all caused by expanded polyglutamine-coding CAG repeats. Their pathomechanisms are becoming increasingly clear and well-designed clinical trials will be needed. Methods: To characterize the clinical manifestations of spinocerebellar ataxia (SCA) 1, 2, 3 and 6 and their natural histories in the United States (US), we conducted a prospective multicenter study utilized a protocol identical to the European consortium study, using the Scale for the Assessment and Rating of Ataxia (SARA) score as the primary outcome, with follow-ups every 6 months up to 2 years. Results: We enrolled 345 patients (60 SCA1, 75 SCA2, 138 SCA3 and 72 SCA6) at 12 US centers. SCA6 patients had a significantly later onset, and SCA2 patients showed greater upper-body ataxia than patients with the remaining SCAs. The annual increase of SARA score was greater in SCA1 patients (mean ± SE: 1.61 ± 0.41) than in SCA2 (0.71 ± 0.31), SCA3 (0.65 ± 0.24) and SCA6 (0.87 ± 0.28) patients (p = 0.049). The functional stage also worsened faster in SCA1 than in SCA2, 3 and 6 (p = 0.002). Conclusions: The proportions of different SCA patients in US differ from those in the European consortium study, but as in the European patients, SCA1 progress faster than those with SCA2, 3 and 6. Later onset in SCA6 and greater upper body ataxia in SCA2 were noted. We conclude that progression rates of these SCAs were comparable between US and Europe cohorts, suggesting the feasibility of international collaborative clinical studies