Populations of many nearshore marine species are connected through the dispersal of their larvae. In this paper, larval connectivity patterns in the Southern California Bight are explored using 2 ...quantities: potential and realized larval connectivity. Potential connectivity is defined as the probability of larval transport from a source to a destination location and is quantified using Lagrangian particle simulations. Realized connectivity is the product of potential connectivity with larval production and can be used to estimate larval settlement patterns. Potential and realized connectivity patterns are quantified for kelp bassParalabrax clathratus, kelp rockfishSebastes atrovirens, and red abaloneHaliotis rufescens, 3 species with a range of larval dispersal characteristics. Connectivity patterns were found to be both heterogeneous, with locations having different source and destination strengths, and asymmetric, with directionality in larval transport. Both potential and realized connectivity were strongly influenced by the length and timing of the spawning season as well as planktonic larval duration. For kelp bass and kelp rockfish, a strong correspondence was found between realized and potential destination locations, suggesting that circulation processes have a dominant role in shaping the spatial distribution of these 2 species. Strong temporal variability in realized larval connectivity was observed on seasonal and inter-annual time scales (particularly between El Niño and La Niña conditions). These results provide novel information for use in marine fisheries and conservation management.
Diastolic dysfunction is increasingly identified as a key, early onset subclinical condition characterizing cardiopathologies of rising prevalence, including diabetic heart disease and heart failure ...with preserved ejection fraction (HFpEF). Diastolic dysfunction characterization has important prognostic value in management of disease outcomes. Validated tools for in vivo monitoring of diastolic function in rodent models of diabetes are required for progress in pre-clinical cardiology studies. 2D speckle tracking echocardiography has emerged as a powerful tool for evaluating cardiac wall deformation throughout the cardiac cycle. The aim of this study was to examine the applicability of 2D speckle tracking echocardiography for comprehensive global and regional assessment of diastolic function in a pre-clinical murine model of cardio-metabolic disease. Type 2 diabetes (T2D) was induced in C57Bl/6 male mice using a high fat high sugar dietary intervention for 20 weeks. Significant impairment in left ventricle peak diastolic strain rate was evident in longitudinal, radial and circumferential planes in T2D mice. Peak diastolic velocity was similarly impaired in the longitudinal and radial planes. Regional analysis of longitudinal peak diastolic strain rate revealed that the anterior free left ventricular wall is particularly susceptible to T2D-induced diastolic dysfunction. These findings provide a significant advance on characterization of diastolic dysfunction in a pre-clinical mouse model of cardiopathology and offer a comprehensive suite of benchmark values for future pre-clinical cardiology studies.
Aims/hypothesis The role of IL-6 in the development of obesity and hepatic insulin resistance is unclear and still the subject of controversy. We aimed to determine whether global deletion of Il6 in ...mice (Il6 ⁻/⁻) results in standard chow-induced and high-fat diet (HFD)-induced obesity, hepatosteatosis, inflammation and insulin resistance. Methods Male, 8-week-old Il6 ⁻/⁻ and littermate control mice were fed a standard chow or HFD for 12 weeks and phenotyped accordingly. Results Il6 ⁻/⁻ mice displayed obesity, hepatosteatosis, liver inflammation and insulin resistance when compared with control mice on a standard chow diet. When fed a HFD, the Il6 ⁻/⁻ and control mice had marked, equivalent gains in body weight, fat mass and ectopic lipid deposition in the liver relative to chow-fed animals. Despite this normalisation, the greater liver inflammation, damage and insulin resistance observed in chow-fed Il6 ⁻/⁻ mice relative to control persisted when both were fed the HFD. Microarray analysis from livers of mice fed a HFD revealed that genes associated with oxidative phosphorylation, the electron transport chain and tricarboxylic acid cycle were uniformly decreased in Il6 ⁻/⁻ relative to control mice. This coincided with reduced maximal activity of the mitochondrial enzyme β-hydroxyacyl-CoA-dehydrogenase and decreased levels of mitochondrial respiratory chain proteins. Conclusions/interpretation Our data suggest that IL-6 deficiency exacerbates HFD-induced hepatic insulin resistance and inflammation, a process that appears to be related to defects in mitochondrial metabolism.
Pulmonary arterial hypertension (PAH) is a heterogeneous disorder with high mortality.
We conducted a comprehensive study of plasma metabolites using ultraperformance liquid chromatography mass ...spectrometry to identify patients at high risk of early death, to identify patients who respond well to treatment, and to provide novel molecular insights into disease pathogenesis.
Fifty-three circulating metabolites distinguished well-phenotyped patients with idiopathic or heritable PAH (n=365) from healthy control subjects (n=121) after correction for multiple testing (P<7.3e-5) and confounding factors, including drug therapy, and renal and hepatic impairment. A subset of 20 of 53 metabolites also discriminated patients with PAH from disease control subjects (symptomatic patients without pulmonary hypertension, n=139). Sixty-two metabolites were prognostic in PAH, with 36 of 62 independent of established prognostic markers. Increased levels of tRNA-specific modified nucleosides (N2,N2-dimethylguanosine, N1-methylinosine), tricarboxylic acid cycle intermediates (malate, fumarate), glutamate, fatty acid acylcarnitines, tryptophan, and polyamine metabolites and decreased levels of steroids, sphingomyelins, and phosphatidylcholines distinguished patients from control subjects. The largest differences correlated with increased risk of death, and correction of several metabolites over time was associated with a better outcome. Patients who responded to calcium channel blocker therapy had metabolic profiles similar to those of healthy control subjects.
Metabolic profiles in PAH are strongly related to survival and should be considered part of the deep phenotypic characterization of this disease. Our results support the investigation of targeted therapeutic strategies that seek to address the alterations in translational regulation and energy metabolism that characterize these patients.
A laboratory incubation study was conducted with nine UK soils to determine the effect of soil physical and chemical properties, and temperature, on the efficacy the nitrification inhibitor ...dicyandiamide (DCD). Nitrogen was applied to soil as ammonium chloride at a rate of 100 μg N g−1 dry soil, and incubated at 60% water-filled-pore-space at either 5, 15 or 25 °C. The ammonium (NH4+) pool was enriched with 15N to 60 atom% excess and DCD was applied at a rate of 10 μg g−1 dry soil. The concentrations and enrichments of the NH4+ and nitrate (NO3−) pools, along with nitrous oxide (N2O) flux measurements, were determined regularly for 60 days after N application. Gross soil N transformation rates were quantified with a 15N tracing model. The persistence of DCD was strongly related (P < 0.001) to temperature with the measured half-life across all soils of 89, 37 and 18 days at 5, 15, and 25 °C, respectively. There was wide variation in the half-life of DCD among soils; which was predominantly associated with the soil oxalate extractable Fe concentration. Greater (P < 0.001) inhibition in autotrophic nitrification by DCD occurred at 5 and 15 °C compared to 25 °C. Across all soils and temperatures DCD increased the rate of mineralisation of recalcitrant organic-N and the rate of adsorption of free NH4+, however, effects varied between soils. DCD did not have a significant effect on the rate of oxidation of recalcitrant organic-N to NO3− or on any of the immobilisation processes or mineralisation of labile N to NH4+. The efficacy of DCD in inhibiting net NO3− production best correlated with soil Cu (r = −0.82), % clay (r = −0.71), total N (r = −0.66) and LOI (r = −0.61). Stepwise multiple regression showed that Cu, oxalate extractable Fe and oxalate extractable Al explained 85.0% of the variation in the percentage inhibition of net NO3− production by DCD. The inhibitor also reduced cumulative N2O emissions, with reductions negatively correlated with a range of soil properties associated with organic matter. We provide evidence that the interaction between temperature, soil clay content and soil organic matter governs the efficacy of DCD. The grassland soils had higher native total N concentrations than the arable soils, hence the inhibition of net NO3− production by DCD was lower and this resulted in an overall inhibition in N2O emissions of 58% and 81% for grassland and arable soils respectively.
•DCD's longevity was strongly related to temperature and soil oxalate extractable iron concentration.•Evidence that an interaction among temperature, soil clay content and soil organic matter govern the efficacy of DCD.•The efficacy of DCD in inhibiting net nitrate production and nitrous oxide emissions was lower in grassland soils than in arable soils.
Aim
To evaluate the ability of specific carbohydrates, including commercially available products, to support the growth of representatives of two well‐known groups of gut commensals, namely ...lactobacilli and bifidobacteria.
Methods and Results
Sixty‐eight bacterial strains, representing 29 human‐derived lactobacilli and 39 bifidobacteria (both human‐ and animal‐derived), were tested for their ability to metabolize 10 different carbohydrates. Analysis of growth and metabolic activity was performed using a combination of diagnostic parameters, such as final OD600, final pH, fermentation end products and growth rate.
Conclusions
The data assembled in this study provide significant complementary and comparative information on the growth‐promoting properties of a range of carbohydrates, while also investigating interspecies differences between lactobacilli and/or bifidobacteria with regard to their carbohydrate utilization abilities. Galacto‐oligosaccharides (GOS) and lactulose were shown to support the most favourable growth characteristics, whereas relatively poor growth of lactobacilli and bifidobacteria was observed on inulin, maltodextrin and polydextrose. GOS/inulin (9 : 1) and fructo‐oligosaccharides (FOS)/inulin mixtures supported mostly similar growth abilities to those obtained for GOS and FOS, respectively. Microbial consumption of GOS, as determined by high‐performance anion‐exchange chromatography with pulsed amperometric detection, was evident for both lactobacilli and bifidobacteria.
Significance and Impact of the Study
These results may allow for the rational prediction of lactobacilli and/or bifidobacteria to be used in conjunction with prebiotics, such as GOS, as synbiotics.
Patients with oesophageal/gastro-oesophageal junction adenocarcinoma (EAC) not showing early metabolic response (EMR) to chemotherapy have poorer survival and histological response rates <5%. We ...investigated whether tailoring neoadjuvant therapy can improve outcomes in these patients.
Patients with resectable EAC were enrolled and randomised into two single-arm, multicentre phase II trials. After induction cisplatin and 5-fluorouracil (CF), all were assessed by day 15 positron emission tomography (PET). Patients with an EMR maximum standardised uptake values (SUVmax) ≥35% reduction from baseline to day 15 PET received a second CF cycle then oesophagectomy. Non-responders were randomised 1 : 1 to two cycles of CF and docetaxel (DCF, n = 31) or DCF + 45 Gy radiotherapy (DCFRT, n = 35) then oesophagectomy. The primary end point was major histological response (<10% residual tumour) in the oesophagectomy specimen; secondary end points were overall survival (OS), progression-free survival (PFS), and locoregional recurrence (LR).
Of 124 patients recruited, major histological response was achieved in 3/45 (7%) with EMR, 6/30 (20%) DCF, and 22/35 (63%) DCFRT patients. Grade 3/4 toxicities occurred in 12/45 (27%) EMR (CF), 13/31 (42%) DCF, and 25/35 (71%) DCFRT patients. No treatment-related deaths occurred. LR by 3 years was seen in 5/45 (11%) EMR, 10/31 (32%) DCF, and 4/35 (11%) DCFRT patients. PFS 95% confidence interval (CI) at 36 months was 47% (31% to 61%) for EMR, 29% (15% to 45%) for DCF, and 46% (29% to 61%) for DCFRT patients. OS (95% CI) at 60 months was 53% (37% to 67%) for EMR, 31% (16% to 48%) for DCF, and 46% (29% to 61%) for DCFRT patients.
EMR is associated with favourable OS, PFS, and low LR. For non-responders, the addition of docetaxel augmented histological response rates, but OS, PFS, and LR remained inferior compared with responders. DCFRT improved histological response and PFS/LR outcomes, matching the EMR group. Early PET/CT has the potential to tailor therapy for patients not showing an early response to chemotherapy.
ACTRN12609000665235.
•EMR 5-year survival >50%.•Docetaxel + CF improves histological responses for MNR.•DCF + RT improves survival for MNR.
Simultaneous measurements of atmospheric organic and elemental carbon (OC and EC) were taken during winter and summer seasons at 2003 in 14 cities in China. Daily PM2.5 samples were analyzed for OC ...and EC by the Interagency Monitoring of Protected Visual Environments (IMPROVE) thermal/optical reflectance protocol. Average PM2.5 OC concentrations in the 14 cities were 38.1 μg m−3 and 13.8 μg m−3 for winter and summer periods, and the corresponding EC were 9.9 μg m−3 and 3.6 μg m−3, respectively. OC and EC concentrations had summer minima and winter maxima in all the cities. Carbonaceous matter (CM), the sum of organic matter (OM = 1.6 × OC) and EC, contributed 44.2% to PM2.5 in winter and 38.8% in summer. OC was correlated with EC (R2: 0.56–0.99) in winter, but correlation coefficients were lower in summer (R2: 0.003–0.90). Using OC/EC enrichment factors, the primary OC, secondary OC and EC accounted for 47.5%, 31.7% and 20.8%, respectively, of total carbon in Chinese urban environments. More than two thirds of China's urban carbon is derived from directly emitted particles. Average OC/EC ratios ranged from 2.0 to 4.7 among 14 cities during winter and from 2.1 to 5.9 during summer. OC/EC ratios in this study were consistent with a possible cooling effect of carbonaceous aerosols over China.
There is general agreement among scientists that biodiversity is under assault on a global basis and that species are being lost at a greatly enhanced rate. This article examines the role played by ...biogeographical science in the emergence of conservation guidance and makes the case for the recognition of Conservation Biogeography as a key subfield of conservation biology delimited as: the application of biogeographical principles, theories, and analyses, being those concerned with the distributional dynamics of taxa individually and collectively, to problems concerning the conservation of biodiversity. Conservation biogeography thus encompasses both a substantial body of theory and analysis, and some of the most prominent planning frameworks used in conservation. Considerable advances in conservation guidelines have been made over the last few decades by applying biogeographical methods and principles. Herein we provide a critical review focussed on the sensitivity to assumptions inherent in the applications we examine. In particular, we focus on four inter-related factors: (i) scale dependency (both spatial and temporal); (ii) inadequacies in taxonomic and distributional data (the so-called Linnean and Wallacean shortfalls); (iii) effects of model structure and parameterisation; and (iv) inadequacies of theory. These generic problems are illustrated by reference to studies ranging from the application of historical biogeography, through island biogeography, and complementarity analyses to bioclimatic envelope modelling. There is a great deal of uncertainty inherent in predictive analyses in conservation biogeography and this area in particular presents considerable challenges. Protected area planning frameworks and their resulting map outputs are amongst the most powerful and influential applications within conservation biogeography, and at the global scale are characterised by the production, by a small number of prominent NGOs, of bespoke schemes, which serve both to mobilise funds and channel efforts in a highly targeted fashion. We provide a simple typology of protected area planning frameworks, with particular reference to the global scale, and provide a brief critique of some of their strengths and weaknesses. Finally, we discuss the importance, especially at regional scales, of developing more responsive analyses and models that integrate pattern (the compositionalist approach) and processes (the functionalist approach) such as range collapse and climate change, again noting the sensitivity of outcomes to starting assumptions. We make the case for the greater engagement of the biogeographical community in a programme of evaluation and refinement of all such schemes to test their robustness and their sensitivity to alternative conservation priorities and goals.
Different climate drivers influence precipitation in different ways. Here we use radiative kernels to understand the influence of rapid adjustment processes on precipitation in climate models. Rapid ...adjustments are generally triggered by the initial heating or cooling of the atmosphere from an external climate driver. For precipitation changes, rapid adjustments due to changes in temperature, water vapor, and clouds are most important. In this study we have investigated five climate drivers (CO2, CH4, solar irradiance, black carbon, and sulfate aerosols). The fast precipitation responses to a doubling of CO2 and a 10‐fold increase in black carbon are found to be similar, despite very different instantaneous changes in the radiative cooling, individual rapid adjustments, and sensible heating. The model diversity in rapid adjustments is smaller for the experiment involving an increase in the solar irradiance compared to the other climate driver perturbations, and this is also seen in the precipitation changes.
Plain Language Summary
Future projections of precipitation changes are uncertain, both on regional and global scales. Understanding the climate models' diversity of precipitation change and how these models respond to various climate drivers, such as greenhouse gases and aerosols, is a key topic in climate research. Using sophisticated techniques, we quantify the processes altering precipitation changes on a short time scale and show that changes in the vertical profile of temperature, water vapor, and clouds contribute very differently to precipitation changes for various climate drivers. Our results show that model diversity in precipitation changes varies strongly between the climate drivers.
Key Points
Separation of instantaneous and rapid adjustment contributions to precipitation changes
Contributions of rapid adjustments to precipitation changes differ substantially between climate drivers
Radiative kernels are applied to understand individual rapid adjustment terms
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