New Constraints on Terrestrial and Oceanic Sources of Atmospheric Methanol

We use a global 3-D chemical transport model (GEOS-Chem) to interpret new aircraft, surface, and oceanic observations of methanol in terms of the constraints that they place on the atmospheric methanol budget. Recent measurements of methanol concentrations in the ocean mixed layer (OML) imply that in situ biological production must be the main methanol source in the OML, dominating over uptake from the atmosphere. It follows that oceanic emission and uptake must be viewed as independent terms in the atmospheric methanol budget. We deduce that the marine biosphere is a large primary source (85 Tg a−1) of methanol to the atmosphere and is also a large sink (101 Tg a−1), comparable in magnitude to atmospheric oxidation by OH (88 Tg a−1). The resulting atmospheric lifetime of methanol in the model is 4.7 days. Aircraft measurements in the North American boundary layer imply that terrestrial plants are a much weaker source than presently thought, likely reflecting an overestimate of broadleaf tree emissions, and this is also generally consistent with surface measurements. We deduce a terrestrial plant source of 80 Tg a−1, comparable in magnitude to the ocean source. The aircraft measurements show a strong correlation with CO (R2=0.51−0.61) over North America during summer. We reproduce this correlation and slope in the model with the reduced plant source, which also confirms that the anthropogenic source of methanol must be small. Our reduced plant source also provides a better simulation of methanol observations over tropical South America.Earth and Planetary SciencesEngineering and Applied Science

A new terrestrial palaeoenvironmental record from the Bering Land Bridge and context for human dispersal

Palaeoenvironmental records from the now-submerged Bering Land Bridge (BLB) covering the Last Glacial Maximum (LGM) to the present are needed to document changing environments and connections with the dispersal of humans into North America. Moreover, terrestrially based records of environmental changes are needed in close proximity to the re-establishment of circulation between Pacific and Atlantic Oceans following the end of the last glaciation to test palaeo-climate models for the high latitudes. We present the first terrestrial temperature and hydrologic reconstructions from the LGM to the present from the BLB’s south-central margin. We find that the timing of the earliest unequivocal human dispersals into Alaska, based on archaeological evidence, corresponds with a shift to warmer/wetter conditions on the BLB between 14 700 and 13 500 years ago associated with the early Bølling/Allerød interstadial (BA). These environmental changes could have provided the impetus for eastward human dispersal at that time, from Western or central Beringia after a protracted human population standstill. Our data indicate substantial climate-induced environmental changes on the BLB since the LGM, which would potentially have had significant influences on megafaunal and human biogeography in the region. © 2018 The Authors

Differences in 5'untranslated regions highlight the importance of translational regulation of dosage sensitive genes

Background Untranslated regions (UTRs) are important mediators of post-transcriptional regulation. The length of UTRs and the composition of regulatory elements within them are known to vary substantially across genes, but little is known about the reasons for this variation in humans. Here, we set out to determine whether this variation, specifically in 5’UTRs, correlates with gene dosage sensitivity. Results We investigate 5’UTR length, the number of alternative transcription start sites, the potential for alternative splicing, the number and type of upstream open reading frames (uORFs) and the propensity of 5’UTRs to form secondary structures. We explore how these elements vary by gene tolerance to loss-of-function (LoF; using the LOEUF metric), and in genes where changes in dosage are known to cause disease. We show that LOEUF correlates with 5’UTR length and complexity. Genes that are most intolerant to LoF have longer 5’UTRs, greater TSS diversity, and more upstream regulatory elements than their LoF tolerant counterparts. We show that these differences are evident in disease gene-sets, but not in recessive developmental disorder genes where LoF of a single allele is tolerated. Conclusions Our results confirm the importance of post-transcriptional regulation through 5'UTRs in tight regulation of mRNA and protein levels, particularly for genes where changes in dosage are deleterious and lead to disease. Finally, to support gene-based investigation we release a web-based browser tool, VuTR, that supports exploration of the composition of individual 5'UTRs and the impact of genetic variation within them

An interlaboratory study of TEX86 and BIT analysis of sediments, extracts and standard mixtures.

Two commonly used proxies based on the distribution of glycerol dialkyl glycerol tetraethers (GDGTs) are the TEX86 (TetraEther indeX of 86 carbon atoms) paleothermometer for sea surface temperature reconstructions and the BIT (Branched Isoprenoid Tetraether) index for reconstructing soil organic matter input to the ocean. An initial round-robin study of two sediment extracts, in which 15 laboratories participated, showed relatively consistent TEX86 values (reproducibility ±3-4°C when translated to temperature) but a large spread in BIT measurements (reproducibility ±0.41 on a scale of 0-1). Here we report results of a second round-robin study with 35 laboratories in which three sediments, one sediment extract, and two mixtures of pure, isolated GDGTs were analyzed. The results for TEX86 and BIT index showed improvement compared to the previous round-robin study. The reproducibility, indicating interlaboratory variation, of TEX86 values ranged from 1.3 to 3.0°C when translated to temperature. These results are similar to those of other temperature proxies used in paleoceanography. Comparison of the results obtained from one of the three sediments showed that TEX86 and BIT indices are not significantly affected by interlaboratory differences in sediment extraction techniques. BIT values of the sediments and extracts were at the extremes of the index with values close to 0 or 1, and showed good reproducibility (ranging from 0.013 to 0.042). However, the measured BIT values for the two GDGT mixtures, with known molar ratios of crenarchaeol and branched GDGTs, had intermediate BIT values and showed poor reproducibility and a large overestimation of the "true" (i.e., molar-based) BIT index. The latter is likely due to, among other factors, the higher mass spectrometric response of branched GDGTs compared to crenarchaeol, which also varies among mass spectrometers. Correction for this different mass spectrometric response showed a considerable improvement in the reproducibility of BIT index measurements among laboratories, as well as a substantially improved estimation of molar-based BIT values. This suggests that standard mixtures should be used in order to obtain consistent, and molar-based, BIT values

Safety and efficacy of diaphragm pacing in patients with respiratory insufficiency due to amyotrophic lateral sclerosis (DiPALS): a multicentre, open-label, randomised controlled trial

Background: Non-invasive ventilation is part of the standard of care for treatment of respiratory failure in patients with amyotrophic lateral sclerosis (ALS). The NeuRx RA/4 Diaphragm Pacing System has received Humanitarian Device Exemption approval from the US Food and Drug Administration for treatment of respiratory failure in patients with ALS. We aimed to establish the safety and efficacy of diaphragm pacing with this system in patients with respiratory muscle weakness due to ALS. Methods: We undertook a multicentre, open-label, randomised controlled trial at seven specialist ALS and respiratory centres in the UK. Eligible participants were aged 18 years or older with laboratory supported probable, clinically probable, or clinically definite ALS; stable riluzole treatment for at least 30 days; and respiratory insufficiency. We randomly assigned participants (1:1), via a centralised web-based randomisation system with minimisation that balanced patients for age, sex, forced vital capacity, and bulbar function, to receive either non-invasive ventilation plus pacing with the NeuRx RA/4 Diaphragm Pacing System or non-invasive ventilation alone. Patients, carers, and outcome assessors were not masked to treatment allocation. The primary outcome was overall survival, defined as the time from randomisation to death from any cause. Analysis was by intention to treat. This trial is registered, ISRCTN number 53817913. Findings: Between Dec 5, 2011, and Dec 18, 2013, we randomly assigned 74 participants to receive either non-invasive ventilation alone (n=37) or non-invasive ventilation plus diaphragm pacing (n=37). On Dec 18, 2013, the Data Monitoring and Ethics Committee (DMEC) recommended suspension of recruitment on the basis of overall survival figures. Randomly assigned participants continued as per the study protocol until June 23, 2014, when the DMEC advised discontinuation of pacing in all patients. Follow-up assessments continued until the planned end of the study in December, 2014. Survival was shorter in the non-invasive ventilation plus pacing group than in the non-invasive ventilation alone group (median 11·0 months [95% CI 8·3-13·6] vs 22·5 months [13·6-not reached]; adjusted hazard ratio 2·27, 95% CI 1·22-4·25; p=0·009). 28 (76%) patients died in the pacing group and 19 (51%) patients died in the non-invasive ventilation alone group. We recorded 162 adverse events (5·9 events per person-year) in the pacing group, of which 46 events were serious, compared with 81 events (2·5 events per person-year) in the non-invasive ventilation alone group, of which 31 events were serious. Interpretation: Addition of diaphragm pacing to standard care with non-invasive ventilation was associated with decreased survival in patients with ALS. Our results suggest that diaphragmatic pacing should not be used as a routine treatment for patients with ALS in respiratory failure

Schmidt-hammer exposure ages from periglacial patterned ground (sorted circles) in Jotunheimen, Norway, and their interpretative problems

© 2016 Swedish Society for Anthropology and Geography Periglacial patterned ground (sorted circles and polygons) along an altitudinal profile at Juvflya in central Jotunheimen, southern Norway, is investigated using Schmidt-hammer exposure-age dating (SHD). The patterned ground surfaces exhibit R-value distributions with platycurtic modes, broad plateaus, narrow tails, and a negative skew. Sample sites located between 1500 and 1925 m a.s.l. indicate a distinct altitudinal gradient of increasing mean R-values towards higher altitudes interpreted as a chronological function. An established regional SHD calibration curve for Jotunheimen yielded mean boulder exposure ages in the range 6910 ± 510 to 8240 ± 495 years ago. These SHD ages are indicative of the timing of patterned ground formation, representing minimum ages for active boulder upfreezing and maximum ages for the stabilization of boulders in the encircling gutters. Despite uncertainties associated with the calibration curve and the age distribution of the boulders, the early-Holocene age of the patterned ground surfaces, the apparent cessation of major activity during the Holocene Thermal Maximum (HTM) and continuing lack of late-Holocene activity clarify existing understanding of the process dynamics and palaeoclimatic significance of large-scale sorted patterned ground as an indicator of a permafrost environment. The interpretation of SHD ages from patterned ground surfaces remains challenging, however, owing to their diachronous nature, the potential for a complex history of formation, and the influence of local, non-climatic factors

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of binary black hole coalescences confidently observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include the effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that have already been identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total source-frame mass M > 70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz emitted gravitational-wave frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place a conservative upper limit for the merger rate density of high-mass binaries with eccentricities 0 < e ≤ 0.3 at 16.9 Gpc−3 yr−1 at the 90% confidence level