Single-base substitutions in the CHM promoter as a cause of choroideremia

Although over 150 unique mutations affecting the coding sequence of CHM have been identified in patients with the X-linked chorioretinal disease choroideremia (CHM), no regulatory mutations have been reported, and indeed the promoter has not been defined. Here, we describe two independent families affected by CHM bearing a mutation outside the gene's coding region at position c.-98: C>A and C>T, which segregated with the disease. The male proband of family 1 was found to lack CHM mRNA and its gene product Rab escort protein 1, whereas whole-genome sequencing of an affected male in family 2 excluded the involvement of any other known retinal genes. Both mutations abrogated luciferase activity when inserted into a reporter construct, and by further employing the luciferase reporter system to assay sequences 5′ to the gene, we identified the CHM promoter as the region encompassing nucleotides c.-119 to c.-76. These findings suggest that the CHM promoter region should be examined in patients with CHM who lack coding sequence mutations, and reveals, for the first time, features of the gene's regulation

CHANG-ES XI: Circular Polarization in the Cores of Nearby Galaxies

We detect 5 galaxies in the CHANG-ES (Continuum Halos in Nearby Galaxies -- an EVLA Survey) sample that show circular polarization (CP) at L-band in our high resolution data sets. Two of the galaxies (NGC~4388 and NGC~4845) show strong Stokes $V/I\,\equiv\,m_C\,\sim\,2$\%, two (NGC~660 and NGC~3628) have values of $m_C\sim \,0.3$\%, and NGC~3079 is a marginal detection at $m_C\sim \,0.2$\%. The two strongest $m_C$ galaxies also have the most luminous X-ray cores and the strongest internal absorption in X-rays. We have expanded on our previous Faraday conversion interpretation and analysis and provide analytical expressions for the expected $V$ signal for a general case in which the cosmic ray electron energy spectral index can take on any value. We provide examples as to how such expressions could be used to estimate magnetic field strengths and the lower energy cutoff for CR electrons. Four out of our detections are {\it resolved}, showing unique structures, including a {\it jet} in NGC~4388 and a CP `conversion disk' in NGC~4845. The conversion disk is inclined to the galactic disk but is perpendicular to a possible outflow direction. Such CP structures have never before been seen in any galaxy to our knowledge. None of the galaxy cores show linear polarization at L-band. Thus CP may provide a unique probe of physical conditions deep into radio AGNs.Comment: 30 pages, 4 figures, accepted to MNRA

Target Zones in History and Theory: Lessons from an Austro-Hungarian Experiment (1896-1914)

The first known experiment with an exchange rate band took place in Austria- Hungary between 1896 and 1914. The rationale for introducing this policy rested on precisely those intuitions that the modern literature has emphasized: the band was designed to secure both exchange rate stability and monetary policy autonomy. However, unlike more recent experiences, such as the ERM, this policy was not undermined by credibility problems. The episode provides an ideal testing ground for some important ideas in modern macroeconomics: specifically, can formal rules, when faithfully adhered to, provide policy makers with some advantages such as short term autonomy? First, we find that a credible band has a "microeconomic" influence on exchange rate stability. By reducing uncertainty, a credible fluctuation band improves the quality of expectations, a channel that has been neglected in the modern literature. Second, we show that the standard test of the basic target zone model is flawed and develop an alternative methodology. We believe that these findings shed a new light on the economics of exchange rate bands

Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

BACKGROUND: Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. METHODS: We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. RESULTS: Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1) probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. CONCLUSIONS: Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss

Antiferromagnetic CuMnAs multi-level memory cell with microelectronic compatibility

Antiferromagnets offer a unique combination of properties including the radiation and magnetic field hardness, the absence of stray magnetic fields, and the spin-dynamics frequency scale in terahertz. Recent experiments have demonstrated that relativistic spin-orbit torques can provide the means for an efficient electric control of antiferromagnetic moments. Here we show that elementary-shape memory cells fabricated from a single-layer antiferromagnet CuMnAs deposited on a III–V or Si substrate have deterministic multi-level switching characteristics. They allow for counting and recording thousands of input pulses and responding to pulses of lengths downscaled to hundreds of picoseconds. To demonstrate the compatibility with common microelectronic circuitry, we implemented the antiferromagnetic bit cell in a standard printed circuit board managed and powered at ambient conditions by a computer via a USB interface. Our results open a path towards specialized embedded memory-logic applications and ultra-fast components based on antiferromagnets

miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity

miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP) induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity

A 12.5 GHz-Spaced Optical Frequency Comb Spanning >400 nm for near-Infrared Astronomical Spectrograph Calibration

A 12.5 GHz-spaced optical frequency comb locked to a Global Positioning disciplined oscillator for near-IR spectrograph calibration is presented. The comb is generated via filtering a 250 MHz-spaced comb. Subsequency nonlinear broadening of the 12.5 GHz comb extends the wavelength range to cover 1380 nm to 1820 nm, providing complete coverage over the H-band transmission widow of Earth's atmosphere. Finite suppression of spurious sidemodes, optical linewidth and instability of the comb have been examined to estmiate potential wavelength biases in spectrograph calibration. Sidemode suppression varies between 20 db and 45 dB, and the optical linewidth is ~350 kHz at 1550 nm. The comb frequency uncertainty is bounded by +/- 30 kHz (corresponding to a radial velocity of +/- 5 cm/s), limited by the Global Positioning System disciplined oscillator reference. These results indicate this comb can readily support radial velocity measurements below 1 m/s in the near-IR.Comment: 16 pages, 12 figures, new file fixes some readability problems on Mac

Elevated surface chlorophyll associated with natural oil seeps in the Gulf of Mexico

Natural hydrocarbon seeps occur on the sea floor along continental margins, and account for up to 47% of the oil released into the oceans. Hydrocarbon seeps are known to support local benthic productivity, but little is known about their impact on photosynthetic organisms in the overlying water column. Here we present observations with high temporal and spatial resolution of chlorophyll concentrations in the northern Gulf of Mexico using in situ and shipboard flow-through fluorescence measurements from May to July 2012, as well as an analysis of ocean-colour satellite images from 1997 to 2007. All three methods reveal elevated chlorophyll concentrations in waters influenced by natural hydrocarbon seeps. Temperature and nutrient profiles above seep sites suggest that nutrient-rich water upwells from depth, which may facilitate phytoplankton growth and thus support the higher chlorophyll concentrations observed. Because upwelling occurs at natural seep locations around the world, we conclude that offshore hydrocarbon seeps, and perhaps other types of deep ocean vents and seeps at depths exceeding 1,000 m, may influence biogeochemistry and productivity of the overlying water column