Extreme oxygen isotope ratios in the early Solar System

The origins of the building blocks of the Solar System can be studied using the isotopic composition of early planetary and meteoritic material. Oxygen isotopes in planetary materials show variations at the per cent level that are not related to the mass of the isotopes; rather, they result from the mixture of components having different nucleosynthetic or chemical origins. Isotopic variations reaching orders of magnitude in minute meteoritic grains are usually attributed to stellar nucleosynthesis before the birth of the Solar System, whereby different grains were contributed by different stars. Here we report the discovery of abundant silica-rich grains embedded in meteoritic organic matter, having the most extreme 18O/16O and 17O/16O ratios observed (both approximately 10(-1)) together with a solar silicon isotopic composition. Both O and Si isotopes indicate a single nucleosynthetic process. These compositions can be accounted for by one of two processes: a single exotic evolved star seeding the young Solar System, or irradiation of the circumsolar gas by high energy particles accelerated during an active phase of the young Sun. We favour the latter interpretation, because the observed compositions are usually not expected from nucleosynthetic processes in evolved stars, whereas they are predicted by the selective trapping of irradiation products.     

Radioactive 26Al from massive stars in the Galaxy

Gamma-rays from radioactive 26Al (half-life approximately 7.2 x 10(5) years) provide a 'snapshot' view of continuing nucleosynthesis in the Galaxy. The Galaxy is relatively transparent to such gamma-rays, and emission has been found concentrated along its plane. This led to the conclusion that massive stars throughout the Galaxy dominate the production of 26Al. On the other hand, meteoritic data show evidence for locally produced 26Al, perhaps from spallation reactions in the protosolar disk. Furthermore, prominent gamma-ray emission from the Cygnus region suggests that a substantial fraction of Galactic 26Al could originate in localized star-forming regions. Here we report high spectral resolution measurements of 26Al emission at 1808.65 keV, which demonstrate that the 26Al source regions corotate with the Galaxy, supporting its Galaxy-wide origin. We determine a present-day equilibrium mass of 2.8 (+/- 0.8) solar masses of 26Al. We use this to determine that the frequency of core collapse (that is, type Ib/c and type II) supernovae is 1.9 (+/- 1.1) events per century.     

Deciphering the evolution and metabolism of an anammox bacterium from a community genome

Anaerobic ammonium oxidation (anammox) has become a main focus in oceanography and wastewater treatment. It is also the nitrogen cycle's major remaining biochemical enigma. Among its features, the occurrence of hydrazine as a free intermediate of catabolism, the biosynthesis of ladderane lipids and the role of cytoplasm differentiation are unique in biology. Here we use environmental genomics--the reconstruction of genomic data directly from the environment--to assemble the genome of the uncultured anammox bacterium Kuenenia stuttgartiensis from a complex bioreactor community. The genome data illuminate the evolutionary history of the Planctomycetes and allow us to expose the genetic blueprint of the organism's special properties. Most significantly, we identified candidate genes responsible for ladderane biosynthesis and biological hydrazine metabolism, and discovered unexpected metabolic versatility.     

Novel microbial communities of the Haakon Mosby mud volcano and their role as a methane sink

Mud volcanism is an important natural source of the greenhouse gas methane to the hydrosphere and atmosphere. Recent investigations show that the number of active submarine mud volcanoes might be much higher than anticipated (for example, see refs 3-5), and that gas emitted from deep-sea seeps might reach the upper mixed ocean. Unfortunately, global methane emission from active submarine mud volcanoes cannot be quantified because their number and gas release are unknown. It is also unclear how efficiently methane-oxidizing microorganisms remove methane. Here we investigate the methane-emitting Haakon Mosby Mud Volcano (HMMV, Barents Sea, 72 degrees N, 14 degrees 44' E; 1,250 m water depth) to provide quantitative estimates of the in situ composition, distribution and activity of methanotrophs in relation to gas emission. The HMMV hosts three key communities: aerobic methanotrophic bacteria (Methylococcales), anaerobic methanotrophic archaea (ANME-2) thriving below siboglinid tubeworms, and a previously undescribed clade of archaea (ANME-3) associated with bacterial mats. We found that the upward flow of sulphate- and oxygen-free mud volcano fluids restricts the availability of these electron acceptors for methane oxidation, and hence the habitat range of methanotrophs. This mechanism limits the capacity of the microbial methane filter at active marine mud volcanoes to <40% of the total flux.     

Seismic waves increase permeability

Earthquakes have been observed to affect hydrological systems in a variety of ways--water well levels can change dramatically, streams can become fuller and spring discharges can increase at the time of earthquakes. Distant earthquakes may even increase the permeability in faults. Most of these hydrological observations can be explained by some form of permeability increase. Here we use the response of water well levels to solid Earth tides to measure permeability over a 20-year period. At the time of each of seven earthquakes in Southern California, we observe transient changes of up to 24 degrees in the phase of the water level response to the dilatational volumetric strain of the semidiurnal tidal components of wells at the Pi?on Flat Observatory in Southern California. After the earthquakes, the phase gradually returns to the background value at a rate of less than 0.1 degrees per day. We use a model of axisymmetric flow driven by an imposed head oscillation through a single, laterally extensive, confined, homogeneous and isotropic aquifer to relate the phase response to aquifer properties. We interpret the changes in phase response as due to changes in permeability. At the time of the earthquakes, the permeability at the site increases by a factor as high as three. The permeability increase depends roughly linearly on the amplitude of seismic-wave peak ground velocity in the range of 0.21-2.1 cm s(-1). Such permeability increases are of interest to hydrologists and oil reservoir engineers as they affect fluid flow and might determine long-term evolution of hydrological and oil-bearing systems. They may also be interesting to seismologists, as the resulting pore pressure changes can affect earthquakes by changing normal stresses on faults.     

The SH3-binding domain of Cx43 participates in loop/tail interactions critical for Cx43-hemichannel activity

Connexin 43 (Cx43) hemichannels establish local signaling networks via the release of ATP and other molecules, but their excessive opening may result in cell death. Hence, the activity of Cx43-hemichannels ought to be critically controlled. This involves interactions between the C-terminal tail (CT) and the cytoplasmic loop (CL), more particularly the L2 domain within CL. Previous work revealed an important role for the last nine amino acids of the Cx43 CT by targeting the L2 domain, as these nine amino acids were sufficient to restore the activity of CT-truncated Cx43-hemichannels. However, we discovered that deletion of the last 19 amino acids of the CT only partially lowered the binding to the L2 domain, indicating that a second L2-binding region is present in the CT. We here provide evidence that the SH3-binding domain is another CT region that targets the L2 domain. At the functional level, the SH3-binding domain was able to restore the activity of CT-truncated Cx43-hemichannels and alleviate the inhibition of full-length Cx43-hemichannels by high intracellular Ca²⁺ concentration ([Ca²⁺]_i) as demonstrated by various approaches including patch clamp studies of unitary Cx43-hemichannel activity. Finally, we show that in full-length Cx43-hemichannels, deletion of either the SH3-binding domain or the CT9 region suppresses the hemichannel activity, while deletion of both domains completely annihilates the hemichannel activity. These results demonstrate that the Cx43 SH3-binding domain, in addition to the CT9 region, critically controls hemichannel activity at high [Ca²⁺]_i, which may be involved in pathological hemichannel opening.     

Forecasting Mixed‐Frequency Time Series with ECM‐MIDAS Models

This paper proposes a mixed‐frequency error correction model for possibly cointegrated non‐stationary time series sampled at different frequencies. We highlight the impact, in terms of model specification, of the choice of the particular high‐frequency explanatory variable to be included in the cointegrating relationship, which we call a dynamic mixed‐frequency cointegrating relationship. The forecasting performance of aggregated models and several mixed‐frequency regressions are compared in a set of Monte Carlo experiments. In particular, we look at both the unrestricted mixed‐frequency model and at a more parsimonious MIDAS regression. Whereas the existing literature has only investigated the potential improvements of the MIDAS framework for stationary time series, our study emphasizes the need to include the relevant cointegrating vectors in the non‐stationary case. Furthermore, it is illustrated that the choice of dynamic mixed‐frequency cointegrating relationship does not matter as long as the short‐run dynamics are adapted accordingly. Finally, the unrestricted model is shown to suffer from parameter proliferation for samples of relatively small size, whereas MIDAS forecasts are robust to over‐parameterization. We illustrate our results for the US inflation rate. Copyright © 2014 John Wiley & Sons, Ltd.     

Evolution of human BCR-ABL1 lymphoblastic leukaemia-initiating cells

Many tumours are composed of genetically diverse cells; however, little is known about how diversity evolves or the impact that diversity has on functional properties. Here, using xenografting and DNA copy number alteration (CNA) profiling of human BCR-ABL1 lymphoblastic leukaemia, we demonstrate that genetic diversity occurs in functionally defined leukaemia-initiating cells and that many diagnostic patient samples contain multiple genetically distinct leukaemia-initiating cell subclones. Reconstructing the subclonal genetic ancestry of several samples by CNA profiling demonstrated a branching multi-clonal evolution model of leukaemogenesis, rather than linear succession. For some patient samples, the predominant diagnostic clone repopulated xenografts, whereas in others it was outcompeted by minor subclones. Reconstitution with the predominant diagnosis clone was associated with more aggressive growth properties in xenografts, deletion of CDKN2A and CDKN2B, and a trend towards poorer patient outcome. Our findings link clonal diversity with leukaemia-initiating-cell function and underscore the importance of developing therapies that eradicate all intratumoral subclones.     

Fungal lipochitooligosaccharide symbiotic signals in arbuscular mycorrhiza

Arbuscular mycorrhiza (AM) is a root endosymbiosis between plants and glomeromycete fungi. It is the most widespread terrestrial plant symbiosis, improving plant uptake of water and mineral nutrients. Yet, despite its crucial role in land ecosystems, molecular mechanisms leading to its formation are just beginning to be unravelled. Recent evidence suggests that AM fungi produce diffusible symbiotic signals. Here we show that Glomus intraradices secretes symbiotic signals that are a mixture of sulphated and non-sulphated simple lipochitooligosaccharides (LCOs), which stimulate formation of AM in plant species of diverse families (Fabaceae, Asteraceae and Umbelliferae). In the legume Medicago truncatula these signals stimulate root growth and branching by the symbiotic DMI signalling pathway. These findings provide a better understanding of the evolution of signalling mechanisms involved in plant root endosymbioses and will greatly facilitate their molecular dissection. They also open the way to using these natural and very active molecules in agriculture.     

A high-resolution map of human evolutionary constraint using 29 mammals

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ～4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ～60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.