314 research outputs found

    Low-temperature dependence of the thermo-magnetic transport properties of the SrTiO3/LaAlO3 interface

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    We report transport measurements, including: Hall, Seebeck and Nernst Effect. All these transport properties exhibit anomalous field and temperature dependences, with a change of behavior observed at about H 1.5T and T 15K. We were able to reconcile the low-temperature-low-field behavior of all transport properties using a simple two band analysis. A more detailed model is required in order to explain the high magnetic field regime.Comment: 6 pages, 7 figure

    On Global Conservation Laws at Null Infinity

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    The ``standard'' expressions for total energy, linear momentum and also angular momentum of asymptotically flat Bondi metrics at null infinity are also obtained from differential conservation laws on asymptotically flat backgrounds, derived from a quadratic Lagrangian density by methods currently used in classical field theory. It is thus a matter of taste and commodity to use or not to use a reference spacetime in defining these globally conserved quantities. Backgrounds lead to N\oe ther conserved currents; the use of backgrounds is in line with classical views on conservation laws. Moreover, the conserved quantities are in principle explicitly related to the sources of gravity through Einstein's equations, while standard definitions are not. The relations depend, however, on a rule for mapping spacetimes on backgrounds

    Kank Is an EB1 Interacting Protein that Localises to Muscle-Tendon Attachment Sites in Drosophila

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    Little is known about how microtubules are regulated in different cell types during development. EB1 plays a central role in the regulation of microtubule plus ends. It directly binds to microtubule plus ends and recruits proteins which regulate microtubule dynamics and behaviour. We report the identification of Kank, the sole Drosophila orthologue of human Kank proteins, as an EB1 interactor that predominantly localises to embryonic attachment sites between muscle and tendon cells. Human Kank1 was identified as a tumour suppressor and has documented roles in actin regulation and cell polarity in cultured mammalian cells. We found that Drosophila Kank binds EB1 directly and this interaction is essential for Kank localisation to microtubule plus ends in cultured cells. Kank protein is expressed throughout fly development and increases during embryogenesis. In late embryos, it accumulates to sites of attachment between muscle and epidermal cells. A kank deletion mutant was generated. We found that the mutant is viable and fertile without noticeable defects. Further analysis showed that Kank is dispensable for muscle function in larvae. This is in sharp contrast to C. elegans in which the Kank orthologue VAB-19 is required for development by stabilising attachment structures between muscle and epidermal cells

    The Functional DRD3 Ser9Gly Polymorphism (rs6280) Is Pleiotropic, Affecting Reward as Well as Movement

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    Abnormalities of motivation and behavior in the context of reward are a fundamental component of addiction and mood disorders. Here we test the effect of a functional missense mutation in the dopamine 3 receptor (DRD3) gene (ser9gly, rs6280) on reward-associated dopamine (DA) release in the striatum. Twenty-six healthy controls (HCs) and 10 unmedicated subjects with major depressive disorder (MDD) completed two positron emission tomography (PET) scans with [11C]raclopride using the bolus plus constant infusion method. On one occasion subjects completed a sensorimotor task (control condition) and on another occasion subjects completed a gambling task (reward condition). A linear regression analysis controlling for age, sex, diagnosis, and self-reported anhedonia indicated that during receipt of unpredictable monetary reward the glycine allele was associated with a greater reduction in D2/3 receptor binding (i.e., increased reward-related DA release) in the middle (anterior) caudate (p<0.01) and the ventral striatum (p<0.05). The possible functional effect of the ser9gly polymorphism on DA release is consistent with previous work demonstrating that the glycine allele yields D3 autoreceptors that have a higher affinity for DA and display more robust intracellular signaling. Preclinical evidence indicates that chronic stress and aversive stimulation induce activation of the DA system, raising the possibility that the glycine allele, by virtue of its facilitatory effect on striatal DA release, increases susceptibility to hyperdopaminergic responses that have previously been associated with stress, addiction, and psychosis

    Covariation of depressive symptoms, parkinsonism, and post-dexamethasone plasma cortisol levels in a bipolar patient: simultaneous response to ECT and lithium carbonate

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    : A patient presented with concurrent mood congruent delusions, parkinsonism, and elevated post-dexamethasone plasma cortisol levels. This triad could result from simultaneous development of cholinergic-monoaminergic dysfunction within critical limbic and extrapyramidal loci. The magnitude of each abnormality decreased in concert during a course of electroconvulsive therapy (ECT). Remaining abnormalities disappeared during treatment with lithium. Actions of ECT and lithium on muscarinic systems are reviewed, and a strategy for testing the hypothesis that dysfunction of cholinergic-monoaminergic mechanisms develops in parallel in different neural networks is considered.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66202/1/j.1600-0447.1986.tb06229.x.pd

    Young hands, old books: : Drawings by children in a fourteenth-century manuscript, LJS MS. 361

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    This article scrutinises three marginal drawings in LJS 361, Kislak Center for Special Collections, Rare Books and Manuscripts, University of Pennsylvania Libraries. It first considers the provenance of the manuscript, questioning how it got into the hands of children. Then, it combines developmental psychology with close examination of the material evidence to develop a list of criteria to attribute the drawings to children. There is consideration of the features that help us estimate the age of the artists, and which indicate that one drawing was a collaborative effort between two children. A potential relationship is identified between the doodles and the subject matter of the text, prompting questions about pre-modern child education and literacy. Finally, the article considers the implications of this finding in both codicology and social history since these marginal illustrations demonstrate that children were active in the material life of medieval books

    Transcription Factor SP4 Is a Susceptibility Gene for Bipolar Disorder

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    The Sp4 transcription factor plays a critical role for both development and function of mouse hippocampus. Reduced expression of the mouse Sp4 gene results in a variety of behavioral abnormalities relevant to human psychiatric disorders. The human SP4 gene is therefore examined for its association with both bipolar disorder and schizophrenia in European Caucasian and Chinese populations respectively. Out of ten SNPs selected from human SP4 genomic locus, four displayed significant association with bipolar disorder in European Caucasian families (rs12668354, pā€Š=ā€Š0.022; rs12673091, pā€Š=ā€Š0.0005; rs3735440, pā€Š=ā€Š0.019; rs11974306, pā€Š=ā€Š0.018). To replicate the genetic association, the same set of SNPs was examined in a Chinese bipolar case control sample. Four SNPs displayed significant association (rs40245, pā€Š=ā€Š0.009; rs12673091, pā€Š=ā€Š0.002; rs1018954, pā€Š=ā€Š0.001; rs3735440, pā€Š=ā€Š0.029), and two of them (rs12673091, rs3735440) were shared with positive SNPs from European Caucasian families. Considering the genetic overlap between bipolar disorder and schizophrenia, we extended our studies in Chinese trios families for schizophrenia. The SNP7 (rs12673091, pā€Š=ā€Š0.012) also displayed a significant association. The SNP7 (rs12673091) was therefore significantly associated in all three samples, and shared the same susceptibility allele (A) across all three samples. On the other hand, we found a gene dosage effect for mouse Sp4 gene in the modulation of sensorimotor gating, a putative endophenotype for both schizophrenia and bipolar disorder. The deficient sensorimotor gating in Sp4 hypomorphic mice was partially reversed by the administration of dopamine D2 antagonist or mood stabilizers. Both human genetic and mouse pharmacogenetic studies support Sp4 gene as a susceptibility gene for bipolar disorder or schizophrenia. The studies on the role of Sp4 gene in hippocampal development may provide novel insights for the contribution of hippocampal abnormalities in these psychiatric disorders

    A Universal Critical Density Underlying the Physics of Electrons at the LaAlO3/SrTiO3 Interface

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    The two-dimensional electron system formed at the interface between the insulating oxides LaAlO3 and SrTiO3 exhibits ferromagnetism, superconductivity, and a wide range of unique magnetotransport properties. A key challenge is to find a unified microscopic mechanism that underlies these emergent phenomena. Here we show that a universal Lifshitz transition between d-orbitals lies at the core of the observed transport phenomena in this system. Our measurements find a critical electronic density at which the transport switches from single to multiple carriers. This density has a universal value, independent of the LaAlO3 thickness and electron mobility. The characteristics of the transition, its universality, and its compatibility with spectroscopic measurements establish it as a transition between d-orbitals of different symmetries. A simple band model, allowing for spin-orbit coupling at the atomic level, connects the observed universal transition to a range of reported magnetotransport properties. Interestingly, we also find that the maximum of the superconducting transition temperature occurs at the same critical transition, indicating a possible connection between the two phenomena. Our observations demonstrate that orbital degeneracies play an important role in the fascinating behavior observed so far in these oxides

    Convergent Evidence from Mouse and Human Studies Suggests the Involvement of Zinc Finger Protein 326 Gene in Antidepressant Treatment Response

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    OBJECTIVES: The forced swim test (FST) is a commonly used model to predict antidepressant efficacy. Uncovering the genetic basis of the model may unravel the mechanism of antidepressant treatment. METHODS: FVB/NJ (FVB) and C57BL/6J (B6) were first identified as the response and non-response strains to fluoxetine (a serotonin-specific reuptake inhibitor antidepressant) treatment in the mouse FST. Simple-interval (SIM) and composite-interval (CIM) mappings were applied to map the quantitative trait loci (QTLs) of the anti-immobility effect of fluoxetine in FST (FST(FLX)) in 865 male B6ƗFVB-F2 mice. The brain mRNA expressions of the gene with the maximum QTL-linkage signal for FST(FLX) after the FST were compared between B6 and FVB mice and also compared between fluoxetine and saline treatment. The association of the variants in the human homologue of the mouse FST(FLX)-QTL gene with major depressive disorder (MDD) and antidepressant response were investigated in 1080 human subjects (MDD/control = 582/498). RESULTS: One linkage signal for FST(FLX)-QTL was detected at an intronic SNP (rs6215396) of the mouse Zfp326 gene (maximal CIM-LOD = 9.36). The Zfp326 mRNA expression in the FVB thalamus was significantly down-regulated by fluoxetine in the FST, and the higher FVB-to-B6 Zfp326 mRNA expressions in the frontal cortex, striatum and hypothalamus diminished after fluoxetine treatment. Two coding-synonymous SNPs (rs2816881 and rs10922744) in the human homologue of Zfp326, ZNF326, were significantly associated with the 8-week antidepressant treatment response in the MDD patients (Bonferroni-corrected p = 0.004-0.028). CONCLUSIONS: The findings suggest the involvement of the Zfp326 and ZNF326 genes in antidepressant treatment response

    Nicotinic acetylcholine receptor Ī²2 subunit gene implicated in a systems-based candidate gene study of smoking cessation

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    Although the efficacy of pharmacotherapy for tobacco dependence has been previously demonstrated, there is substantial variability among individuals in treatment response. We performed a systems-based candidate gene study of 1295 single nucleotide polymorphisms (SNPs) in 58 genes within the neuronal nicotinic receptor and dopamine systems to investigate their role in smoking cessation in a bupropion placebo-controlled randomized clinical trial. Putative functional variants were supplemented with tagSNPs within each gene. We used global tests of main effects and treatment interactions, adjusting the P-values for multiple correlated tests. An SNP (rs2072661) in the 3ā€² UTR region of the Ī²2 nicotinic acetylcholine receptor subunit (CHRNB2) has an impact on abstinence rates at the end of treatment (adjusted P = 0.01) and after a 6-month follow-up period (adjusted P = 0.0002). This latter P-value is also significant with adjustment for the number of genes tested. Independent of treatment at 6-month follow-up, individuals carrying the minor allele have substantially decreased the odds of quitting (OR = 0.31; 95% CI 0.18ā€“0.55). Effect of estimates indicate that the treatment is more effective for individuals with the wild-type (OR = 2.14, 95% CI 1.20ā€“3.81) compared with individuals carrying the minor allele (OR = 0.83, 95% CI 0.32ā€“2.19), although this difference is only suggestive (P = 0.10). Furthermore, this SNP demonstrated a role in the time to relapse (P = 0.0002) and an impact on withdrawal symptoms at target quit date (TQD) (P = 0.0009). Overall, while our results indicate strong evidence for CHRNB2 in ability to quit smoking, these results require replication in an independent sample
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