Symmetric arrangement of mitochondria:plasma membrane contacts between adjacent photoreceptor cells regulated by Opa1

Mitochondria are known to play an essential role in photoreceptor function and survival that enables normal vision. Within photoreceptors, mitochondria are elongated and extend most of the inner-segment length, where they supply energy for protein synthesis and the phototransduction machinery in the outer segment, as well as acting as a calcium store. Here, we examined the arrangement of the mitochondria within the inner segment in detail using three-dimensional (3D) electron microscopy techniques and show they are tethered to the plasma membrane in a highly specialized arrangement. Remarkably, mitochondria and their cristae openings align with those of neighboring inner segments. The pathway by which photoreceptors meet their high energy demands is not fully understood. We propose this to be a mechanism to share metabolites and assist in maintaining homeostasis across the photoreceptor cell layer. In the extracellular space between photoreceptors, Müller glial processes were identified. Due to the often close proximity to the inner-segment mitochondria, they may, too, play a role in the inner-segment mitochondrial arrangement as well as metabolite shuttling. OPA1 is an important factor in mitochondrial homeostasis, including cristae remodeling; therefore, we examined the photoreceptors of a heterozygous Opa1 knockout mouse model. The cristae structure in the Opa1+/− photoreceptors was not greatly affected, but the mitochondria were enlarged and had reduced alignment to neighboring inner-segment mitochondria. This indicates the importance of key regulators in maintaining this specialized photoreceptor mitochondrial arrangement

Atmospheric characterization of Proxima b by coupling the Sphere high-contrast imager to the Espresso spectrograph

Context. The temperate Earth-mass planet Proxima b is the closest exoplanet to Earth and represents what may be our best ever opportunity to search for life outside the Solar System. Aims. We aim at directly detecting Proxima b and characterizing its atmosphere by spatially resolving the planet and obtaining high-resolution reflected-light spectra. Methods. We propose to develop a coupling interface between the SPHERE high-contrast imager and the new ESPRESSO spectrograph, both installed at ESO VLT. The angular separation of 37 mas between Proxima b and its host star requires the use of visible wavelengths to spatially resolve the planet on a 8.2-m telescope. At an estimated planet-to-star contrast of ~10^-7 in reflected light, Proxima b is extremely challenging to detect with SPHERE alone. However, the combination of a ~10^3-10^4 contrast enhancement from SPHERE to the high spectral resolution of ESPRESSO can reveal the planetary spectral features and disentangle them from the stellar ones. Results. We find that significant but realistic upgrades to SPHERE and ESPRESSO would enable a 5-sigma detection of the planet and yield a measurement of its true mass and albedo in 20-40 nights of telescope time, assuming an Earth-like atmospheric composition. Moreover, it will be possible to probe the O2 bands at 627, 686 and 760 nm, the water vapour band at 717 nm, and the methane band at 715 nm. In particular, a 3.6-sigma detection of O2 could be made in about 60 nights of telescope time. Those would need to be spread over 3 years considering optimal observability conditions for the planet. Conclusions. The very existence of Proxima b and the SPHERE-ESPRESSO synergy represent a unique opportunity to detect biosignatures on an exoplanet in the near future. It is also a crucial pathfinder experiment for the development of Extremely Large Telescopes and their instruments (abridged).Comment: 16 pages, 7 figures, revised version accepted to A&

Quantum Dynamics of the Slow Rollover Transition in the Linear Delta Expansion

We apply the linear delta expansion to the quantum mechanical version of the slow rollover transition which is an important feature of inflationary models of the early universe. The method, which goes beyond the Gaussian approximation, gives results which stay close to the exact solution for longer than previous methods. It provides a promising basis for extension to a full field theoretic treatment.Comment: 12 pages, including 4 figure

Thermodynamic and kinetic factors in the hydrothermal synthesis of hybrid frameworks: zinc 4-cyclohexene-1,2-dicarboxylates

Experimental and computational studies indicate that the formation of a series of zinc 4-cyclohexene-1,2-dicarboxylates takes place under thermodynamic rather than kinetic control

Newborn Screening for Primary Congenital Hypothyroidism: Estimating Test Performance at Different TSH Thresholds

CONTEXT: Active surveillance of primary congenital hypothyroidism (CH) in a multi-ethnic population with established newborn bloodspot screening. OBJECTIVE: To estimate performance of newborn screening for CH at different test thresholds; to calculate incidence of primary CH. DESIGN: Prospective surveillance undertaken from June 2011 to June 2012 with three-year follow-up of outcomes. Relative likelihood ratios (rLRs) estimated to compare bloodspot thyroid-stimulating hormone (TSH) test thresholds of 6mU/L and 8mU/L, with the nationally recommended standard of 10mU/L for a presumptive positive result. SETTING: UK National Health Service. PATIENTS: Clinician notification of children aged under five years investigated following clinical presentation or presumptive positive screening result. MAIN OUTCOME MEASURE(S): Permanent primary CH status determined by clinician report of continuing thyroxine requirement at three-year follow-up. RESULTS: 629 newborns (58.3% girls; 58.7% white ethnicity) were investigated following presumptive positive screening result and 21 children (52.4% girls; 52.4% white) after clinical presentation; 432 remained on treatment at three-year follow-up. Permanent CH incidence was 5.3 (95%CI 4.8, 5.8) per 10,000 infants. Using locally-applied thresholds, sensitivity, specificity and positive predictive value were 96.76%, 99.97% and 66.88% respectively. Compared with TSH threshold of 10mU/L, positive rLRs for 8mU/L and 6mU/L were 1.20 (95%CI 0.82, 1.75) and 0.52 (95%CI 0.38, 0.72), and negative rLRs 0.11 (95%CI 0.03, 0.36) and 0.11 (95%CI 0.06, 0.20) respectively. CONCLUSIONS: Screening programme performance is good, however a TSH threshold of 8mU/L appears superior to the current national standard (10mU/L) and requires further evaluation. Further research should explore the implications of transient CH for screening policy

A narrow, edge-on disk resolved around HD 106906 with SPHERE

HD~106906AB is so far the only young binary system around which a planet has been imaged and a debris disk evidenced thanks to a strong IR excess. As such, it represents a unique opportunity to study the dynamics of young planetary systems. We aim at further investigating the close (tens of au scales) environment of the HD~106906AB system. We used the extreme AO fed, high contrast imager SPHERE recently installed on the VLT to observe HD~106906. Both the IRDIS imager and the Integral Field Spectrometer were used. We discovered a very inclined, ring-like disk at a distance of 65~au from the star. The disk shows a strong brightness asymmetry with respect to its semi-major axis. It shows a smooth outer edge, compatible with ejection of small grains by the stellar radiation pressure. We show furthermore that the planet's projected position is significantly above the disk's PA. Given the determined disk inclination, it is not excluded though that the planet could still orbit within the disk plane if at a large separation (2000--3000 au). We identified several additional point sources in the SPHERE/IRDIS field-of-view, that appear to be background objects. We compare this system with other debris disks sharing similarities, and we briefly discuss the present results in the framework of dynamical evolution.Comment: 7 pages, 6 figures, accepted by Astronomy & Astrophysic

REEP6 Deficiency Leads to Retinal Degeneration through Disruption of ER Homeostasis and Protein Trafficking

Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy. We recently identified mutations in REEP6, which encodes the receptor expression enhancing protein 6, in several families with autosomal recessive RP. REEP6 is related to the REEP and Yop1p family of ER shaping proteins and potential receptor accessory proteins, but the role of REEP6 in the retina is unknown. Here we characterise the disease mechanisms associated with loss of REEP6 function using a Reep6 knockout mouse generated by CRISPR/Cas9 gene editing. In control mice REEP6 was localised to the inner segment and outer plexiform layer of rod photoreceptors. The Reep6-/- mice exhibited progressive photoreceptor degeneration from P20 onwards. Ultrastructural analyses at P20 by transmission electron microscopy and 3View serial block face scanning EM revealed an expansion of the distal ER in the Reep6-/- rods and an increase in their number of mitochondria. Electroretinograms revealed photoreceptor dysfunction preceded degeneration, suggesting potential defects in phototransduction. There was no effect on the traffic of rhodopsin, Rom1 or peripherin/rds; however, the retinal guanylate cyclases GC1 and GC2 were severely affected in the Reep6 knockout animals, with almost undetectable expression. These changes correlated with an increase in C/EBP homologous protein (CHOP) expression and the activation of caspase 12, suggesting that ER stress contributes to cell death. Collectively, these data suggest that REEP6 plays an essential role in maintaining cGMP homeostasis though facilitating the stability and/or trafficking of guanylate cyclases and maintaining ER and mitochondrial homeostasis

Unquenched large orbital magnetic moment in NiO

Magnetic properties of NiO are investigated by incorporating the spin-orbit interaction in the LSDA+U scheme. It is found that the large part of orbital moment remains unquenched in NiO. The orbital moment contributes about mu_L = 0.29 mu_B to the total magnetic moment of M = 1.93 mu_B, as leads to the orbital-to-spin angular momentum ratio of L/S = 0.36. The theoretical values are in good agreement with recent magnetic X-ray scattering measurements.Comment: 4 pages, 2 figure