1,098 research outputs found
Verwey transition in FeO at high pressure: quantum critical behavior at the onset of metallization
We provide evidence for the existence of a {\em quantum critical point} at
the metallization of magnetite FeO at an applied pressure of GPa. We show that the present ac magnetic susceptibility data
support earlier resistivity data. The Verwey temperature scales with pressure
, with . The resistivity data shows a
temperature dependence , with above and
2.5 at the critical pressure, respectively. This difference in with
pressure is a sign of critical behavior at . The magnetic susceptibility
is smooth near the critical pressure, both at the Verwey transition and near
the ferroelectric anomaly. A comparison with the critical behavior observed in
the Mott-Hubbard and related systems is made.Comment: 5 pages, 5 figure
Pubertal presentation in seven patients with congenital adrenal hyperplasia due to P450 Oxidoreductase deficiency
Context: P450 oxidoreductase (POR) is a crucial electron donor to all microsomal P450 cytochrome (CYP) enzymes including 17α-hydroxylase (CYP17A1), 21-hydroxylase (CYP21A2) and P450 aromatase. Mutant POR causes congenital adrenal hyperplasia with combined glucocorticoid and sex steroid deficiency. P450 oxidoreductase deficiency (ORD) commonly presents neonatally, with disordered sex development in both sexes, skeletal malformations, and glucocorticoid deficiency. \ud
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Objective: The aim of the study was to describe the clinical and biochemical characteristics of ORD during puberty. \ud
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Design: Clinical, biochemical, and genetic assessment of seven ORD patients (five females, two males) presenting during puberty was conducted. \ud
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Results: Predominant findings in females were incomplete pubertal development (four of five) and large ovarian cysts (five of five) prone to spontaneous rupture, in some only resolving after combined treatment with estrogen/progestin, GnRH superagonists, and glucocorticoids. Pubertal development in the two boys was more mildly affected, with some spontaneous progression. Urinary steroid profiling revealed combined CYP17A1 and CYP21A2 deficiencies indicative of ORD in all patients; all but one failed to mount an appropriate cortisol response to ACTH stimulation indicative of adrenal insufficiency. Diagnosis of ORD was confirmed by direct sequencing, demonstrating disease-causing POR mutations. \ud
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Conclusion: Delayed and disordered puberty can be the first sign leading to a diagnosis of ORD. Appropriate testosterone production during puberty in affected boys but manifest primary hypogonadism in girls with ORD may indicate that testicular steroidogenesis is less dependent on POR than adrenal and ovarian steroidogenesis. Ovarian cysts in pubertal girls may be driven not only by high gonadotropins but possibly also by impaired CYP51A1-mediated production of meiosis-activating sterols due to mutant POR
Mamld1 Knockdown Reduces Testosterone Production and Cyp17a1 Expression in Mouse Leydig Tumor Cells
MAMLD1 is known to be a causative gene for hypospadias. Although previous studies have indicated that MAMLD1 mutations result in hypospadias primarily because of compromised testosterone production around the critical period for fetal sex development, the underlying mechanism(s) remains to be clarified. Furthermore, although functional studies have indicated a transactivation function of MAMLD1 for the non-canonical Notch target Hes3, its relevance to testosterone production remains unknown. To examine these matters, we performed Mamld1 knockdown experiments.Mamld1 knockdown was performed with two siRNAs, using mouse Leydig tumor cells (MLTCs). Mamld1 knockdown did not influence the concentrations of pregnenolone and progesterone but significantly reduced those of 17-OH pregnenolone, 17-OH progesterone, dehydroepiandrosterone, androstenedione, and testosterone in the culture media. Furthermore, Mamld1 knockdown significantly decreased Cyp17a1 expression, but did not affect expressions of other genes involved in testosterone biosynthesis as well as in insulin-like 3 production. Hes3 expression was not significantly altered. In addition, while 47 genes were significantly up-regulated (fold change >2.0×) and 38 genes were significantly down-regulated (fold change <0.5×), none of them was known to be involved in testosterone production. Cell proliferation analysis revealed no evidence for compromised proliferation of siRNA-transfected MLTCs.The results, in conjunction with the previous data, imply that Mamld1 enhances Cyp17a1 expression primarily in Leydig cells and permit to produce a sufficient amount of testosterone for male sex development, independently of the Hes3-related non-canonical Notch signaling
The Optical System for the Large Size Telescope of the Cherenkov Telescope Array
The Large Size Telescope (LST) of the Cherenkov Telescope Array (CTA) is
designed to achieve a threshold energy of 20 GeV. The LST optics is composed of
one parabolic primary mirror 23 m in diameter and 28 m focal length. The
reflector dish is segmented in 198 hexagonal, 1.51 m flat to flat mirrors. The
total effective reflective area, taking into account the shadow of the
mechanical structure, is about 368 m. The mirrors have a sandwich structure
consisting of a glass sheet of 2.7 mm thickness, aluminum honeycomb of 60 mm
thickness, and another glass sheet on the rear, and have a total weight about
47 kg. The mirror surface is produced using a sputtering deposition technique
to apply a 5-layer coating, and the mirrors reach a reflectivity of 94%
at peak. The mirror facets are actively aligned during operations by an active
mirror control system, using actuators, CMOS cameras and a reference laser.
Each mirror facet carries a CMOS camera, which measures the position of the
light spot of the optical axis reference laser on the target of the telescope
camera. The two actuators and the universal joint of each mirror facet are
respectively fixed to three neighboring joints of the dish space frame, via
specially designed interface plate.Comment: In Proceedings of the 34th International Cosmic Ray Conference
(ICRC2015), The Hague, The Netherlands. All CTA contributions at
arXiv:1508.0589
Activation of native TRPC1/C5/C6 channels by endothelin-1 is mediated by both PIP3 and PIP2 in rabbit coronary artery myocytes
We investigate activation mechanisms of native TRPC1/C5/C6 channels (termed TRPC1 channels) by stimulation of endothelin-1 (ET-1) receptor subtypes in freshly dispersed rabbit coronary artery myocytes using single channel recording and immunoprecipitation techniques. ET-1 evoked non-selective cation channel currents with a unitary conductance of 2.6 pS which were not inhibited by either ET(A) or ET(B) receptor antagonists, respectively BQ-123 and BQ788, when administered separately. However, in the presence of both antagonists, ET-1-evoked channel activity was abolished indicating that both ET(A) and ET(B) receptor stimulation activate this conductance. Stimulation of both ET(A) and ET(B) receptors evoked channel activity which was inhibited by the protein kinase C (PKC) inhibitor chelerythrine and by anti-TRPC1 antibodies indicating that activation of both receptor subtypes causes TRPC1 channel activation by a PKC-dependent mechanism. ET(A) receptor-mediated TRPC1 channel activity was selectively inhibited by phosphoinositol-3-kinase (PI-3-kinase) inhibitors wortmannin (50 nm) and PI-828 and by antibodies raised against phosphoinositol-3,4,5-trisphosphate (PIP(3)), the product of PI-3-kinase-mediated phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP(2)). Moreover, exogenous application of diC8-PIP(3) stimulated PKC-dependent TRPC1 channel activity. These results indicate that stimulation of ET(A) receptors evokes PKC-dependent TRPC1 channel activity through activation of PI-3-kinase and generation of PIP(3). In contrast, ET(B) receptor-mediated TRPC1 channel activity was inhibited by the PI-phospholipase C (PI-PLC) inhibitor U73122. 1-Oleoyl-2-acetyl-sn-glycerol (OAG), an analogue of diacylglycerol (DAG), which is a product of PI-PLC, also activated PKC-dependent TRPC1 channel activity. OAG-induced TRPC1 channel activity was inhibited by anti-phosphoinositol-4,5-bisphosphate (PIP(2)) antibodies and high concentrations of wortmannin (20 μm) which depleted tissue PIP(2) levels. In addition exogenous application of diC8-PIP(2) activated PKC-dependent TRPC1 channel activity. These data indicate that stimulation of ET(B) receptors evokes PKC-dependent TRPC1 activity through PI-PLC-mediated generation of DAG and requires a permissive role of PIP(2). In conclusion, we provide the first evidence that stimulation of ET(A) and ET(B) receptors activate native PKC-dependent TRPC1 channels through two distinct phospholipids pathways involving a novel action of PIP(3), in addition to PIP(2), in rabbit coronary artery myocytes
Biochemical and pharmacological profile of a potent and selective endothelin B-receptor antagonist, BQ-788.
Mitochondrial and nuclear genes suggest that stony corals are monophyletic but most families of stony corals are not (Order Scleractinia, Class Anthozoa, Phylum Cnidaria)
Modern hard corals (Class Hexacorallia; Order Scleractinia) are widely studied because of their fundamental role in reef
building and their superb fossil record extending back to the Triassic. Nevertheless, interpretations of their evolutionary
relationships have been in flux for over a decade. Recent analyses undermine the legitimacy of traditional suborders,
families and genera, and suggest that a non-skeletal sister clade (Order Corallimorpharia) might be imbedded within the
stony corals. However, these studies either sampled a relatively limited array of taxa or assembled trees from heterogeneous
data sets. Here we provide a more comprehensive analysis of Scleractinia (127 species, 75 genera, 17 families) and various
outgroups, based on two mitochondrial genes (cytochrome oxidase I, cytochrome b), with analyses of nuclear genes (ßtubulin,
ribosomal DNA) of a subset of taxa to test unexpected relationships. Eleven of 16 families were found to be
polyphyletic. Strikingly, over one third of all families as conventionally defined contain representatives from the highly
divergent "robust" and "complex" clades. However, the recent suggestion that corallimorpharians are true corals that have
lost their skeletons was not upheld. Relationships were supported not only by mitochondrial and nuclear genes, but also
often by morphological characters which had been ignored or never noted previously. The concordance of molecular
characters and more carefully examined morphological characters suggests a future of greater taxonomic stability, as well as
the potential to trace the evolutionary history of this ecologically important group using fossils
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