Superconductivity at 43 K in Samarium-arsenide Oxides SmFeAsO1−xFxSmFeAsO_{1-x}F_x

Since the discovery of high-transition temperature ($T_c$) superconductivity in layered copper oxides, extensive efforts have been devoted to explore the higher $T_c$ superconductivity. However, the $T_c$ higher than 40 K can be obtained only in the copper oxide superconductors so far. The highest reported value of $T_c$ for non-copper-oxide bulk superconductivity is 39 K in $MgB_2$.\cite{jun} The $T_c$ of about 40 K is close to or above the theoretical value predicted from BCS theory.\cite{mcmillan} Therefore, it is very significant to search for non-copper oxide superconductor with the transition temperature higher than 40 K to understand the mechanism of high-$T_c$ superconductivity. Here we report the discovery of bulk superconductivity in samarium-arsenide oxides $SmFeAsO_{1-x}F_x$ with ZrCuAiAs type structure. Resistivity and magnetization measurements show strong evidences for transition temperature as high as 43 K. $SmFeAsO_{1-x}F_x$ is the first non-copper oxide superconductor with $T_c$ higher than 40 K. The $T_c$ higher than 40 K may be a strong argument to consider $SmFeAsO_{1-x}F_x$ as an unconventional superconductor.Comment: 8 pages, 4 figure

Cux1 and Cux2 selectively target basal and apical dendritic compartments of layer II-III cortical neurons

© 2014 Wiley Periodicals, Inc. A number of recent reports implicate the differential regulation of apical and basal dendrites in autism disorders and in the higher functions of the human brain. They show that apical and basal dendrites are functionally specialized and that mechanisms regulating their development have important consequences for neuron function. The molecular identity of layer II-III neurons of the cerebral cortex is determined by the overlapping expression of Cux1 and Cux2. We previously showed that both Cux1 and Cux2 are necessary and nonredundant for normal dendrite development of layer II-III neurons. Loss of function of either gene reduced dendrite arbors, while overexpression increased dendritic complexity and suggested additive functions. We herein characterize the function of Cux1 and Cux2 in the development of apical and basal dendrites. By in vivo loss and gain of function analysis, we show that while the expression level of either Cux1 or Cux2 influences both apical and basal dendrites, they have distinct effects. Changes in Cux1 result in a marked effect on the development of the basal compartment whereas modulation of Cux2 has a stronger influence on the apical compartment. These distinct effects of Cux genes might account for the functional diversification of layer II-III neurons into different subpopulations, possibly with distinct connectivity patterns and modes of neuron response. Our data suggest that by their differential effects on basal and apical dendrites, Cux1 and Cux2 can promote the integration of layer II-III neurons in the intracortical networks in highly specific ways.Peer Reviewe

The von Hippel-Lindau Tumor Suppressor Protein Promotes c-Cbl-Independent Poly-Ubiquitylation and Degradation of the Activated EGFR

Somatic mutations or reduced expression of the von Hippel-Lindau (VHL) tumor suppressor occurs in the majority of the clear cell renal cell carcinoma (ccRCC) and is a causal factor for the pathogenesis of ccRCC. pVHL was reported to suppress the oncogenic activity of Epidermal Growth Factor Receptor (EGFR) by reducing the expression of the EGFR agonist TGF-α and by reducing the translation efficiency of EGFR itself. Furthermore, it was reported that pVHL down-regulates activated EGFR by promoting efficient lysosomal degradation of the receptor. These modes of negative regulation of EGFR by pVHL were dependent on Hypoxia Inducible Factor (HIF). In this study, we report that HIF was not the only factor stabilizing the activated EGFR in VHL-deficient ccRCC cells. Down-regulation of endogenous HIF in these cells had little effect on the turnover rates of the activated EGFR. Furthermore, neither pretreatment with lysomomal inhibitors pretreatment nor down-regulation of c-Cbl, a major E3 ubiquitin ligase that targets the activated EGFR for lysosomal degradation, significantly increased the stabilities of EGFR in VHL-expressing ccRCC cells. In contrast, pretreatment with proteasomal inhibitors extended EGFR lifetime and led to similar EGFR half-lives in VHL-expressing and VHL-deficient ccRCC cells. Down-regulation of c-Cbl in VHL-deficient ccRCC cells revealed that the c-Cbl and pVHL collaborated to down-regulate the activated EGFR. Finally, we found that pVHL promoted the poly-ubiquitylation of the activated EGFR, and this function was c-Cbl-independent. Thus these results indicate that pVHL limits EGFR signaling by promoting c-Cbl-independent poly-ubiquitylation of the activated receptor, which likely results in its degradation by proteasome

CdSe Quantum Dot (QD)-Induced Morphological and Functional Impairments to Liver in Mice

Quantum dots (QDs), as unique nanoparticle probes, have been used in in vivo fluorescence imaging such as cancers. Due to the novel characteristics in fluorescence, QDs represent a family of promising substances to be used in experimental and clinical imaging. Thus far, the toxicity and harmful health effects from exposure (including environmental exposure) to QDs are not recognized, but are largely concerned by the public. To assess the biological effects of QDs, we established a mouse model of acute and chronic exposure to QDs. Results from the present study suggested that QD particles could readily spread into various organs, and liver was the major organ for QD accumulation in mice from both the acute and chronic exposure. QDs caused significant impairments to livers from mice with both acute and chronic QD exposure as reflected by morphological alternation to the hepatic lobules and increased oxidative stress. Moreover, QDs remarkably induced the production of intracellular reactive oxygen species (ROS) along with cytotoxicity, as characterized by a significant increase of the malondialdehyde (MDA) level within hepatocytes. However, the increase of the MDA level in response to QD treatment could be partially blunted by the pre-treatment of cells with beta-mercaptoethanol (β-ME). These data suggested ROS played a crucial role in causing oxidative stress-associated cellular damage from QD exposure; nevertheless other unidentified mediators might also be involved in QD-mediated cellular impairments. Importantly, we demonstrated that the hepatoxicity caused by QDs in vivo and in vitro was much greater than that induced by cadmium ions at a similar or even a higher dose. Taken together, the mechanism underlying QD-mediated biological influences might derive from the toxicity of QD particles themselves, and from free cadmium ions liberated from QDs as well

Principles of chromosomal organization: lessons from yeast

The spatial organization of genes and chromosomes plays an important role in the regulation of several DNA processes. However, the principles and forces underlying this nonrandom organization are mostly unknown. Despite its small dimension, and thanks to new imaging and biochemical techniques, studies of the budding yeast nucleus have led to significant insights into chromosome arrangement and dynamics. The dynamic organization of the yeast genome during interphase argues for both the physical properties of the chromatin fiber and specific molecular interactions as drivers of nuclear order

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Reduced parahippocampal and lateral temporal GABA(A)-[C-11]flumazenil binding in major depression: preliminary results

Purpose: Major depressive disorder (MDD) has been related to both a dysfunctional γ-amino butyric acid (GABA) system and to hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA). Although GABA has been suggested to inhibit HPA axis activity, their relationship has never been studied at the level of the central GAB

Current technical approaches to brain energy metabolism

Neuroscience is a technology‐driven discipline and brain energy metabolism is no exception. Once satisfied with mapping metabolic pathways at organ level, we are now looking to learn what it is exactly that metabolic enzymes and transporters do and when, where do they reside, how are they regulated, and how do they relate to the specific functions of neurons, glial cells, and their subcellular domains and organelles, in different areas of the brain. Moreover, we aim to quantify the fluxes of metabolites within and between cells. Energy metabolism is not just a necessity for proper cell function and viability but plays specific roles in higher brain functions such as memory processing and behavior, whose mechanisms need to be understood at all hierarchical levels, from isolated proteins to whole subjects, in both health and disease. To this aim, the field takes advantage of diverse disciplines including anatomy, histology, physiology, biochemistry, bioenergetics, cellular biology, molecular biology, developmental biology, neurology, and mathematical modeling. This article presents a well‐referenced synopsis of the technical side of brain energy metabolism research. Detail and jargon are avoided whenever possible and emphasis is given to comparative strengths, limitations, and weaknesses, information that is often not available in regular articles.Fondecyt, Grant Number: 1160317; MINECO, Grant Numbers: SAF2016‐78114‐R and RTC‐2015‐3237‐1; CIBERFES, Grant Numer: CB16/10/00282; SP3‐People‐MC‐ITN program, Grant Number: 608381; EU BATCure, Grant Number: 666918; FEDER (European regional development fund); Investissement d'Avenir, Grant Number: ANR‐11‐INBS‐0011; French State in the context of the “Investments for the future” Program IdEx and the LabEx TRAIL, Grant Numbers: ANR‐10‐IDEX and ANR‐10‐LABX‐57; French–Swiss ANR‐FNS, Grant Numer: ANR‐15‐ CE37‐0012. University of Nottingham; BBSRC, Grant Numers: BB/L019396/1 and BB/K009192/1; MRC, Grant Number: MR/L020661/1; Deutsche Forschungsgemeinschaft, Grant Numers: DFG SPP 1757, SFB 894, and FOR 2289; European Commission, Grant Number: H2020‐FETPROACT 732344; Neurofibres, Grant Number: H2020‐MSCA‐ITN‐722053 EU‐GliaPhD; US National Institutes of Health, Grant Number: R01NS087611; Teva Pharmaceuticals; Agilent Technologies. IdEx, Grant Number: ANR‐10‐IDEX‐03‐02; French–Swiss ANR‐FNS, Grant number: 310030E‐164271; National Institutes of Neurologic Disease and Stroke at the National Institutes of Health, Grant Numer: R01 NS077773; University of Zurich and the Swiss National Science Foundation; Comisión Nacional de Investigación Científica y Tecnológica, Grant Numer: PB 01; Fondo Nacional de Desarrollo Científico y Tecnológico, Grant Numer: 1160317; Ministerio de Economía y Competitividad, Grant Numer: RTC‐2015‐3237‐1,SAF2016‐78114‐R; Agence Nationale de la Recherche, Grant Numers: ANR‐10‐IDEX, ANR‐10‐IDEX‐03‐02, ANR‐10‐LABX‐57, ANR‐11‐INBS‐0011, and ANR‐15‐ CE37‐0012; Biotechnology and Biological Sciences Research Council, Grant Numers: BB/L019396/1 and BB/K009192/1; Medical Research Council, Grant Numer: MR/L020661/1.Peer reviewe