Distinct respiratory responses of soils to complex organic substrate are governed predominantly by soil architecture and its microbial community

Factors governing the turnover of organic matter (OM) added to soils, including substrate quality, climate, environment and biology, are well known, but their relative importance has been difficult to ascertain due to the interconnected nature of the soil system. This has made their inclusion in mechanistic models of OM turnover or nutrient cycling difficult despite the potential power of these models to unravel complex interactions. Using high temporal-resolution respirometery (6 min measurement intervals), we monitored the respiratory response of 67 soils sampled from across England and Wales over a 5 day period following the addition of a complex organic substrate (green barley powder). Four respiratory response archetypes were observed, characterised by different rates of respiration as well as different time-dependent patterns. We also found that it was possible to predict, with 95% accuracy, which type of respiratory behaviour a soil would exhibit based on certain physical and chemical soil properties combined with the size and phenotypic structure of the microbial community. Bulk density, microbial biomass carbon, water holding capacity and microbial community phenotype were identified as the four most important factors in predicting the soils’ respiratory responses using a Bayesian belief network. These results show that the size and constitution of the microbial community are as important as physico-chemical properties of a soil in governing the respiratory response to OM addition. Such a combination suggests that the 'architecture' of the soil, i.e. the integration of the spatial organisation of the environment and the interactions between the communities living and functioning within the pore networks, is fundamentally important in regulating such processes

Natural selection and the origin and maintenance of standard genetic marker systems

Natural selection has always been assumed to be the major force of evolution, but its presence has been difficult to demonstrate. A review of the evidence for selective differences among genotypes for most human genetic polymorphisms indicates there is little of a direct nature. Indirect theoretical evidence, however, seems to support a major role for natural selection, and it does not seem to support the hypothesis that most amino acid substitutions within the human species are neutral. Among small isolates, most of the gene frequency differences are most likely due to genetic drift or the founder effect, and the principal counterbalancing force is gene flow or migration. But genetic differences among the major human subdivisions do not seem to be due to the same interacting forces. One reason for the inability to detect selection has been an oversimplified view of its operation, which assigns genotypes a constant fitness in every generation. Many recent theoretical developments of more complicated kinds of selection may lead to a resolution of the problem and suggest better interpretations of the enormous amount of data on human genetic variation that is rapidly accumulating.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94241/1/1330230504_ftp.pd

Singularity in polarization:rewiring yeast cells to make two buds

SummaryFor budding yeast to ensure formation of only one bud, cells must polarize toward one, and only one, site. Polarity establishment involves the Rho family GTPase Cdc42, which concentrates at polarization sites via a positive feedback loop. To assess whether singularity is linked to the specific Cdc42 feedback loop, we disabled the yeast cell's endogenous amplification mechanism and synthetically rewired the cells to employ a different positive feedback loop. Rewired cells violated singularity, occasionally making two buds. Even cells that made only one bud sometimes initiated two clusters of Cdc42, but then one cluster became dominant. Mathematical modeling indicated that, given sufficient time, competition between clusters would promote singularity. In rewired cells, competition occurred slowly and sometimes failed to develop a single “winning” cluster before budding. Slowing competition in normal cells also allowed occasional formation of two buds, suggesting that singularity is enforced by rapid competition between Cdc42 clusters

agr-Mediated Dispersal of Staphylococcus aureus Biofilms

The agr quorum-sensing system of Staphylococcus aureus modulates the expression of virulence factors in response to autoinducing peptides (AIPs). Recent studies have suggested a role for the agr system in S. aureus biofilm development, as agr mutants exhibit a high propensity to form biofilms, and cells dispersing from a biofilm have been observed displaying an active agr system. Here, we report that repression of agr is necessary to form a biofilm and that reactivation of agr in established biofilms through AIP addition or glucose depletion triggers detachment. Inhibitory AIP molecules did not induce detachment and an agr mutant was non-responsive, indicating a dependence on a functional, active agr system for dispersal. Biofilm detachment occurred in multiple S. aureus strains possessing divergent agr systems, suggesting it is a general S. aureus phenomenon. Importantly, detachment also restored sensitivity of the dispersed cells to the antibiotic rifampicin. Proteinase K inhibited biofilm formation and dispersed established biofilms, suggesting agr-mediated detachment occurred in an ica-independent manner. Consistent with a protease-mediated mechanism, increased levels of serine proteases were detected in detaching biofilm effluents, and the serine protease inhibitor PMSF reduced the degree of agr-mediated detachment. Through genetic analysis, a double mutant in the agr-regulated Aur metalloprotease and the SplABCDEF serine proteases displayed minimal extracellular protease activity, improved biofilm formation, and a strongly attenuated detachment phenotype. These findings indicate that induction of the agr system in established S. aureus biofilms detaches cells and demonstrate that the dispersal mechanism requires extracellular protease activity

Early integration of bilateral touch in the primary somatosensory cortex

Animal, as well as behavioural and neuroimaging studies in humans have documented integration of bilateral tactile information at the level of primary somatosensory cortex (SI). However, it is still debated whether integration in SI occurs early or late during tactile processing, and whether it is somatotopically organized. To address both the spatial and temporal aspects of bilateral tactile processing we used magnetoencephalography in a tactile repetition-suppression paradigm. We examined somatosensory evoked-responses produced by probe stimuli preceded by an adaptor, as a function of the relative position of adaptor and probe (probe always at the left index finger; adaptor at the index or middle finger of the left or right hand) and as a function of the delay between adaptor and probe (0, 25 or 125 ms). Percentage of response-amplitude suppression was computed by comparing paired (adaptor+probe) with single stimulations of adaptor and probe. Results show that response suppression varies differentially in SI and SII as a function of both spatial and temporal features of the stimuli. Remarkably, repetition suppression of SI activity emerged early in time, regardless of whether the adaptor stimulus was presented on the same and the opposite body side with respect to the probe. These novel findings support the notion of an early and somatotopically organized interhemispheric integration of tactile information in SI

Understanding of Coupled Terrestrial Carbon, Nitrogen and Water Dynamics—An Overview

Coupled terrestrial carbon (C), nitrogen (N) and hydrological processes play a crucial role in the climate system, providing both positive and negative feedbacks to climate change. In this review we summarize published research results to gain an increased understanding of the dynamics between vegetation and atmosphere processes. A variety of methods, including monitoring (e.g., eddy covariance flux tower, remote sensing, etc.) and modeling (i.e., ecosystem, hydrology and atmospheric inversion modeling) the terrestrial carbon and water budgeting, are evaluated and compared. We highlight two major research areas where additional research could be focused: (i) Conceptually, the hydrological and biogeochemical processes are closely linked, however, the coupling processes between terrestrial C, N and hydrological processes are far from well understood; and (ii) there are significant uncertainties in estimates of the components of the C balance, especially at landscape and regional scales. To address these two questions, a synthetic research framework is needed which includes both bottom-up and top-down approaches integrating scalable (footprint and ecosystem) models and a spatially nested hierarchy of observations which include multispectral remote sensing, inventories, existing regional clusters of eddy-covariance flux towers and CO2 mixing ratio towers and chambers

Genetic diversity fuels gene discovery for tobacco and alcohol use

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury(1-4). These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries(5). Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.Peer reviewe

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700