Meisosomes, folded membrane microdomains between the apical extracellular matrix and epidermis

Apical extracellular matrices (aECMs) form a physical barrier to the environment. In Caenorhabditis elegans, the epidermal aECM, the cuticle, is composed mainly of different types of collagen, associated in circumferential ridges separated by furrows. Here, we show that in mutants lacking furrows, the normal intimate connection between the epidermis and the cuticle is lost, specifically at the lateral epidermis, where, in contrast to the dorsal and ventral epidermis, there are no hemidesmosomes. At the ultrastructural level, there is a profound alteration of structures that we term 'meisosomes,' in reference to eisosomes in yeast. We show that meisosomes are composed of stacked parallel folds of the epidermal plasma membrane, alternately filled with cuticle. We propose that just as hemidesmosomes connect the dorsal and ventral epidermis, above the muscles, to the cuticle, meisosomes connect the lateral epidermis to it. Moreover, furrow mutants present marked modifications of the biomechanical properties of their skin and exhibit a constitutive damage response in the epidermis. As meisosomes co-localise to macrodomains enriched in phosphatidylinositol (4,5) bisphosphate, they could conceivably act, like eisosomes, as signalling platforms, to relay tensile information from the aECM to the underlying epidermis, as part of an integrated stress response to damage

Calibration and First light of the Diabolo photometer at the Millimetre and Infrared Testa Grigia Observatory

We have designed and built a large-throughput dual channel photometer, Diabolo. This photometer is dedicated to the observation of millimetre continuum diffuse sources, and in particular, of the Sunyaev-Zel'dovich effect and of anisotropies of the 3K background. We describe the optical layout and filtering system of the instrument, which uses two bolometric detectors for simultaneous observations in two frequency channels at 1.2 and 2.1 mm. The bolometers are cooled to a working temperature of 0.1 K provided by a compact dilution cryostat. The photometric and angular responses of the instrument are measured in the laboratory. First astronomical light was detected in March 1995 at the focus of the new Millimetre and Infrared Testa Grigia Observatory (MITO) Telescope. The established sensitivity of the system is of 7 mK_RJ s^1/2$. For a typical map of at least 10 beams, with one hour of integration per beam, one can achieve the rms values of y_SZ ~ 7 10^-5 and the 3K background anisotropy Delta T/T ~ 7 10^-5, in winter conditions. We also report on a novel bolometer AC readout circuit which allows for the first time total power measurements on the sky. This technique alleviates (but does not forbid) the use of chopping with a secondary mirror. This technique and the dilution fridge concept will be used in future scan--modulated space instrument like the ESA Planck mission project.Comment: 10 pages, LaTeX, 12 figures, accepted for publication in Astronomy and Astrophysics Supplement Serie

An individual patient-data meta-analysis of metronomic oral vinorelbine in metastatic non-small cell lung cancer

MOV is an active and well-tolerated chemotherapy in metastatic NSCLC and is a manageable therapy in frail patients

Default Network Deactivations Are Correlated with Psychopathic Personality Traits

Background: The posteromedial cortex (PMC) and medial prefrontal cortex (mPFC) are part of a network of brain regions that has been found to exhibit decreased activity during goal-oriented tasks. This network is thought to support a baseline of brain activity, and is commonly referred to as the ‘‘default network’’. Although recent reports suggest that the PMC and mPFC are associated with affective, social, and self-referential processes, the relationship between these default network components and personality traits, especially those pertaining to social context, is poorly understood. Methodology/Principal Findings: In the current investigation, we assessed the relationship between PMC and mPFC deactivations and psychopathic personality traits using fMRI and a self-report measure. We found that PMC deactivations predicted traits related to egocentricity and mPFC deactivations predicted traits related to decision-making. Conclusions/Significance: These results suggest that the PMC and mPFC are associated with processes involving selfrelevancy and affective decision-making, consistent with previous reports. More generally, these findings suggest a link between default network activity and personality traits

Archiving primary data: solutions for long-term studies

The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (Pls) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers

The Copernicus Marine Environment Monitoring Service Ocean State Report

The Copernicus Marine Environment Monitoring Service (CMEMS) Ocean State Report (OSR) provides an annual report of the state of the global ocean and European regional seas for policy and decision-makers with the additional aim of increasing general public awareness about the status of, and changes in, the marine environment. The CMEMS OSR draws on expert analysis and provides a 3-D view (through reanalysis systems), a view from above (through remote-sensing data) and a direct view of the interior (through in situ measurements) of the global ocean and the European regional seas. The report is based on the unique CMEMS monitoring capabilities of the blue (hydrography, currents), white (sea ice) and green (e.g. Chlorophyll) marine environment. This first issue of the CMEMS OSR provides guidance on Essential Variables, large-scale changes and specific events related to the physical ocean state over the period 1993–2015. Principal findings of this first CMEMS OSR show a significant increase in global and regional sea levels, thermosteric expansion, ocean heat content, sea surface temperature and Antarctic sea ice extent and conversely a decrease in Arctic sea ice extent during the 1993–2015 period. During the year 2015 exceptionally strong large-scale changes were monitored such as, for example, a strong El Niño Southern Oscillation, a high frequency of extreme storms and sea level events in specific regions in addition to areas of high sea level and harmful algae blooms. At the same time, some areas in the Arctic Ocean experienced exceptionally low sea ice extent and temperatures below average were observed in the North Atlantic Ocean

Galaxy bias from galaxy–galaxy lensing in the DES science verification data

We present a measurement of galaxy–galaxy lensing around a magnitude-limited (iAB < 22.5) sample of galaxies from the dark energy survey science verification (DES-SV) data. We split these lenses into three photometric-redshift bins from 0.2 to 0.8, and determine the product of the galaxy bias b and cross-correlation coefficient between the galaxy and dark matter overdensity fields r in each bin, using scales above 4 h−1 Mpc comoving, where we find the linear bias model to be valid given our current uncertainties. We compare our galaxy bias results from galaxy–galaxy lensing with those obtained from galaxy clustering and CMB lensing for the same sample of galaxies, and find our measurements to be in good agreement with those in Crocce et al., while, in the lowest redshift bin (z ∼ 0.3), they show some tension with the findings in Giannantonio et al. We measure b· r to be 0.87 ± 0.11, 1.12 ± 0.16 and 1.24 ± 0.23, respectively, for the three redshift bins of width Δz = 0.2 in the range 0.2 < z < 0.8, defined with the photometric-redshift algorithm BPZ. Using a different code to split the lens sample, TPZ, leads to changes in the measured biases at the 10–20 per cent level, but it does not alter the main conclusion of this work: when comparing with Crocce et al. we do not find strong evidence for a cross-correlation parameter significantly below one in this galaxy sample, except possibly at the lowest redshift bin (z ∼ 0.3), where we find r = 0.71 ± 0.11 when using TPZ, and 0.83 ± 0.12 with BPZ

Dark energy survey year 1 results: curved-sky weak lensing mass map

We construct the largest curved-sky galaxy weak lensing mass map to date from the DES first-year (DES Y1) data. The map, about 10 times larger than the previous work, is constructed over a contiguous ≈1500 deg2, covering a comoving volume of ≈10 Gpc3. The effects of masking, sampling, and noise are tested using simulations. We generate weak lensing maps from two DES Y1 shear catalogues, METACALIBRATION and IM3SHAPE, with sources at redshift 0.2 < z < 1.3, and in each of four bins in this range. In the highest signal-to-noise map, the ratio between the mean signal to noise in the E-mode map and the B-mode map is ∼1.5 (∼2) when smoothed with a Gaussian filter of σG = 30 (80) arcmin. The second and third moments of the convergence κ in the maps are in agreement with simulations. We also find no significant correlation of κ with maps of potential systematic contaminants. Finally, we demonstrate two applications of the mass maps: (1) cross-correlation with different foreground tracers of mass and (2) exploration of the largest peaks and voids in the maps

Dark Energy Survey Year 1 results: cosmological constraints from galaxy clustering and weak lensing

We present cosmological results from a combined analysis of galaxy clustering and weak gravitational lensing, using 1321 deg 2 of griz imaging data from the first year of the Dark Energy Survey (DES Y1). We combine three two-point functions: (i) the cosmic shear correlation function of 26 million source galaxies in four redshift bins, (ii) the galaxy angular autocorrelation function of 650,000 luminous red galaxies in five redshift bins, and (iii) the galaxy-shear cross-correlation of luminous red galaxy positions and source galaxy shears. To demonstrate the robustness of these results, we use independent pairs of galaxy shape, photometric redshift estimation and validation, and likelihood analysis pipelines. To prevent confirmation bias, the bulk of the analysis was carried out while blind to the true results; we describe an extensive suite of systematics checks performed and passed during this blinded phase. The data are modeled in flat Λ CDM and w CDM cosmologies, marginalizing over 20 nuisance parameters, varying 6 (for Λ CDM) or 7 (for w CDM) cosmological parameters including the neutrino mass density and including the 457 × 457 element analytic covariance matrix. We find consistent cosmological results from these three two-point functions, and from their combination obtain S 8 ≡σ 8 (Ω m /0.3) 0.5 =0.783 +0.021 −0.025 and Ω m =0.264 +0.032 −0.019 for Λ CDM for w CDM, we find S 8 =0.794 +0.029 −0.027, Ω m =0.279 +0.043 −0.022, and w=−0.80 +0.20 −0.22 at 68% CL. The precision of these DES Y1 results rivals that from the Planck cosmic microwave background measurements, allowing a comparison of structure in the very early and late Universe on equal terms. Although the DES Y1 best-fit values for S 8 and Ω m are lower than the central values from Planck

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old