Identification of miRNA signatures associated with radiation-induced late lung injury in mice.

Acute radiation exposure of the thorax can lead to late serious, and even life-threatening, pulmonary and cardiac damage. Sporadic in nature, late complications tend to be difficult to predict, which prompted this investigation into identifying non-invasive, tissue-specific biomarkers for the early detection of late radiation injury. Levels of circulating microRNA (miRNA) were measured in C3H and C57Bl/6 mice after whole thorax irradiation at doses yielding approximately 70% mortality in 120 or 180 days, respectively (LD70/120 or 180). Within the first two weeks after exposure, weight gain slowed compared to sham treated mice along with a temporary drop in white blood cell counts. 52% of C3H (33 of 64) and 72% of C57Bl/6 (46 of 64) irradiated mice died due to late radiation injury. Lung and heart damage, as assessed by computed tomography (CT) and histology at 150 (C3H mice) and 180 (C57Bl/6 mice) days, correlated well with the appearance of a local, miRNA signature in the lung and heart tissue of irradiated animals, consistent with inherent differences in the C3H and C57Bl/6 strains in their propensity for developing radiation-induced pneumonitis or fibrosis, respectively. Radiation-induced changes in the circulating miRNA profile were most prominent within the first 30 days after exposure and included miRNA known to regulate inflammation and fibrosis. Importantly, early changes in plasma miRNA expression predicted survival with reasonable accuracy (88-92%). The miRNA signature that predicted survival in C3H mice, including miR-34a-5p, -100-5p, and -150-5p, were associated with pro-inflammatory NF-κB-mediated signaling pathways, whereas the signature identified in C57Bl/6 mice (miR-34b-3p, -96-5p, and -802-5p) was associated with TGF-β/SMAD signaling. This study supports the hypothesis that plasma miRNA profiles could be used to identify individuals at high risk of organ-specific late radiation damage, with applications for radiation oncology clinical practice or in the context of a radiological incident

Five Kepler target stars that show multiple transiting exoplanet candidates

We present and discuss five candidate exoplanetary systems identified with the Kepler spacecraft. These five systems show transits from multiple exoplanet candidates. Should these objects prove to be planetary in nature, then these five systems open new opportunities for the field of exoplanets and provide new insights into the formation and dynamical evolution of planetary systems. We discuss the methods used to identify multiple transiting objects from the Kepler photometry as well as the false-positive rejection methods that have been applied to these data. One system shows transits from three distinct objects while the remaining four systems show transits from two objects. Three systems have planet candidates that are near mean motion commensurabilities---two near 2:1 and one just outside 5:2. We discuss the implications that multitransiting systems have on the distribution of orbital inclinations in planetary systems, and hence their dynamical histories; as well as their likely masses and chemical compositions. A Monte Carlo study indicates that, with additional data, most of these systems should exhibit detectable transit timing variations (TTV) due to gravitational interactions---though none are apparent in these data. We also discuss new challenges that arise in TTV analyses due to the presence of more than two planets in a system.Comment: Accepted to Ap

Deep Sequencing of B Cell Receptor Repertoires From COVID-19 Patients Reveals Strong Convergent Immune Signatures.

Deep sequencing of B cell receptor (BCR) heavy chains from a cohort of 31 COVID-19 patients from the UK reveals a stereotypical naive immune response to SARS-CoV-2 which is consistent across patients. Clonal expansion of the B cell population is also observed and may be the result of memory bystander effects. There was a strong convergent sequence signature across patients, and we identified 1,254 clonotypes convergent between at least four of the COVID-19 patients, but not present in healthy controls or individuals following seasonal influenza vaccination. A subset of the convergent clonotypes were homologous to known SARS and SARS-CoV-2 spike protein neutralizing antibodies. Convergence was also demonstrated across wide geographies by comparison of data sets between patients from UK, USA, and China, further validating the disease association and consistency of the stereotypical immune response even at the sequence level. These convergent clonotypes provide a resource to identify potential therapeutic and prophylactic antibodies and demonstrate the potential of BCR profiling as a tool to help understand patient responses

Reading the biomineralized book of life: expanding otolith biogeochemical research and applications for fisheries and ecosystem-based management

Chemical analysis of calcified structures continues to flourish, as analytical and technological advances enable researchers to tap into trace elements and isotopes taken up in otoliths and other archival tissues at ever greater resolution. Increasingly, these tracers are applied to refine age estimation and interpretation, and to chronicle responses to environmental stressors, linking these to ecological, physiological, and life-history processes. Here, we review emerging approaches and innovative research directions in otolith chemistry, as well as in the chemistry of other archival tissues, outlining their value for fisheries and ecosystem-based management, turning the spotlight on areas where such biomarkers can support decision making. We summarise recent milestones and the challenges that lie ahead to using otoliths and archival tissues as biomarkers, grouped into seven, rapidly expanding and application-oriented research areas that apply chemical analysis in a variety of contexts, namely: (1) supporting fish age estimation; (2) evaluating environmental stress, ecophysiology and individual performance; (3) confirming seafood provenance; (4) resolving connectivity and movement pathways; (5) characterising food webs and trophic interactions; (6) reconstructing reproductive life histories; and (7) tracing stock enhancement efforts. Emerging research directions that apply hard part chemistry to combat seafood fraud, quantify past food webs, as well as to reconcile growth, movement, thermal, metabolic, stress and reproductive life-histories provide opportunities to examine how harvesting and global change impact fish health and fisheries productivity. Ultimately, improved appreciation of the many practical benefits of archival tissue chemistry to fisheries and ecosystem-based management will support their increased implementation into routine monitoring.[GRAPHICS]

Circulating Mitochondrial DNA in Patients in the ICU as a Marker of Mortality: Derivation and Validation

Background: Mitochondrial DNA (mtDNA) is a critical activator of inflammation and the innate immune system. However, mtDNA level has not been tested for its role as a biomarker in the intensive care unit (ICU). We hypothesized that circulating cell-free mtDNA levels would be associated with mortality and improve risk prediction in ICU patients. Methods and Findings: Analyses of mtDNA levels were performed on blood samples obtained from two prospective observational cohort studies of ICU patients (the Brigham and Women's Hospital Registry of Critical Illness [BWH RoCI, n = 200] and Molecular Epidemiology of Acute Respiratory Distress Syndrome [ME ARDS, n = 243]). mtDNA levels in plasma were assessed by measuring the copy number of the NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical ICU patients with an elevated mtDNA level (≥3,200 copies/µl plasma) had increased odds of dying within 28 d of ICU admission in both the BWH RoCI (odds ratio [OR] 7.5, 95% CI 3.6–15.8, p = 1×10−7) and ME ARDS (OR 8.4, 95% CI 2.9–24.2, p = 9×10−5) cohorts, while no evidence for association was noted in non-medical ICU patients. The addition of an elevated mtDNA level improved the net reclassification index (NRI) of 28-d mortality among medical ICU patients when added to clinical models in both the BWH RoCI (NRI 79%, standard error 14%, p<1×10−4) and ME ARDS (NRI 55%, standard error 20%, p = 0.007) cohorts. In the BWH RoCI cohort, those with an elevated mtDNA level had an increased risk of death, even in analyses limited to patients with sepsis or acute respiratory distress syndrome. Study limitations include the lack of data elucidating the concise pathological roles of mtDNA in the patients, and the limited numbers of measurements for some of biomarkers. Conclusions: Increased mtDNA levels are associated with ICU mortality, and inclusion of mtDNA level improves risk prediction in medical ICU patients. Our data suggest that mtDNA could serve as a viable plasma biomarker in medical ICU patients. Please see later in the article for the Editors' Summar

A View of Tropical Cyclones from Above: The Tropical Cyclone Intensity Experiment

Tropical cyclone (TC) outflow and its relationship to TC intensity change and structure were investigated in the Office of Naval Research Tropical Cyclone Intensity (TCI) field program during 2015 using dropsondes deployed from the innovative new High-Definition Sounding System (HDSS) and remotely sensed observations from the Hurricane Imaging Radiometer (HIRAD), both on board the NASA WB-57 that flew in the lower stratosphere. Three noteworthy hurricanes were intensively observed with unprecedented horizontal resolution: Joaquin in the Atlantic and Marty and Patricia in the eastern North Pacific. Nearly 800 dropsondes were deployed from the WB-57 flight level of ∼60,000 ft (∼18 km), recording atmospheric conditions from the lower stratosphere to the surface, while HIRAD measured the surface winds in a 50-km-wide swath with a horizontal resolution of 2 km. Dropsonde transects with 4–10-km spacing through the inner cores of Hurricanes Patricia, Joaquin, and Marty depict the large horizontal and vertical gradients in winds and thermodynamic properties. An innovative technique utilizing GPS positions of the HDSS reveals the vortex tilt in detail not possible before. In four TCI flights over Joaquin, systematic measurements of a major hurricane’s outflow layer were made at high spatial resolution for the first time. Dropsondes deployed at 4-km intervals as the WB-57 flew over the center of Hurricane Patricia reveal in unprecedented detail the inner-core structure and upper-tropospheric outflow associated with this historic hurricane. Analyses and numerical modeling studies are in progress to understand and predict the complex factors that influenced Joaquin’s and Patricia’s unusual intensity changes

Galaxy Evolution Probe: a concept for a mid and far-infrared space observatory

The Galaxy Evolution Probe (GEP) is a concept for a mid and far-infrared space observatory designed to survey sky for star-forming galaxies from redshifts of z = 0 to beyond z = 4. Furthering our knowledge of galaxy formation requires uniform surveys of star-forming galaxies over a large range of redshifts and environments to accurately describe star formation, supermassive black hole growth, and interactions between these processes in galaxies. The GEP design includes a 2 m diameter SiC telescope actively cooled to 4 K and two instruments: (1) An imager to detect star-forming galaxies and measure their redshifts photometrically using emission features of polycyclic aromatic hydrocarbons. It will cover wavelengths from 10 to 400 μm, with 23 spectral resolution R = 8 filter-defined bands from 10 to 95 μm and five R = 3.5 bands from 95 to 400 μm. (2) A 24 – 193 μm, R = 200 dispersive spectrometer for redshift confirmation, identification of active galactic nuclei, and interstellar astrophysics using atomic fine-structure lines. The GEP will observe from a Sun-Earth L2 orbit, with a design lifetime of four years, devoted first to galaxy surveys with the imager and second to follow-up spectroscopy. The focal planes of the imager and the spectrometer will utilize KIDs, with the spectrometer comprised of four slit-coupled diffraction gratings feeding the KIDs. Cooling for the telescope, optics, and KID amplifiers will be provided by solar-powered cryocoolers, with a multi-stage adiabatic demagnetization refrigerator providing 100 mK cooling for the KIDs

Smartwatch games: Encouraging privacy-protective behaviour in a longitudinal study

While the public claim concern for their privacy, they frequently appear to overlook it. This disparity between concern and behaviour is known as the Privacy Paradox. Such issues are particularly prevalent on wearable devices. These products can store personal data, such as text messages and contact details. However, owners rarely use protective features. Educational games can be effective in encouraging changes in behaviour. Therefore, we developed the first privacy game for (Android) Wear OS watches. 10 participants used smartwatches for two months, allowing their high-level settings to be monitored. Five individuals were randomly assigned to our treatment group, and they played a dynamically-customised privacy-themed game. To minimise confounding variables, the other five received the same app but lacking the privacy topic. The treatment group improved their protection, with their usage of screen locks significantly increasing (p = 0.043). In contrast, 80% of the control group continued to never restrict their settings. After the posttest phase, we evaluated behavioural rationale through semi-structured interviews. Privacy concerns became more nuanced in the treatment group, with opinions aligning with behaviour. Actions appeared influenced primarily by three factors: convenience, privacy salience and data sensitivity. This is the first smartwatch game to encourage privacy-protective behaviour