Shifts in species' distribution and abundance in response to climate change have been well documented, but the underpinning processes are still poorly understood. We present the results of a ...systematic literature review and meta‐analysis investigating the frequency and importance of different mechanisms by which climate has impacted natural populations. Most studies were from temperate latitudes of North America and Europe; almost half investigated bird populations. We found significantly greater support for indirect, biotic mechanisms than direct, abiotic mechanisms as mediators of the impact of climate on populations. In addition, biotic effects tended to have greater support than abiotic factors in studies of species from higher trophic levels. For primary consumers, the impact of climate was equally mediated by biotic and abiotic mechanisms, whereas for higher level consumers the mechanisms were most frequently biotic, such as predation or food availability. Biotic mechanisms were more frequently supported in studies that reported a directional trend in climate than in studies with no such climatic change, although sample sizes for this comparison were small. We call for more mechanistic studies of climate change impacts on populations, particularly in tropical systems.
Highlighting the important role of marketing in encouraging sustainable consumption, the current research presents a review of the academic literature from marketing and behavioral science that ...examines the most effective ways to shift consumer behaviors to be more sustainable. In the process of the review, the authors develop a comprehensive framework for conceptualizing and encouraging sustainable consumer behavior change. The framework is represented by the acronym SHIFT, and it proposes that consumers are more inclined to engage in pro-environmental behaviors when the message or context leverages the following psychological factors: Social influence, Habit formation, Individual self, Feelings and cognition, and Tangibility. The authors also identify five broad challenges to encouraging sustainable behaviors and use these to develop novel theoretical propositions and directions for future research. Finally, the authors outline how practitioners aiming to encourage sustainable consumer behaviors can use this framework.
•Indicators are incorporated to examine the tele-connected sub-regional Water-Energy-Food Nexus.•The impacts and tradeoffs between each subsystem is examined across multiple scale.•Results reveal a ...mismatch between sub-regional resource availability and final consumption.
Population and economic growth pose unique challenges in securing sufficient water, energy, and food to meet demand at the sub-national (regional), national, and supra-national level. An increasing share of this demand is met through trade and imports. The unprecedented rapid growth, extent, and complexity of global value chains (GVCs) since the 1980s have reshaped global trade. The GVCs – and new economic patterns of regionalization – affect the demands on water, energy, and food within countries and across global supply chains. East Asia is of particular interest due to the region’s rapid economic growth, substantial population size, high interdependence of the region’s economies, and varying degree of resource availability. While greater interdependence across the region has increased the efficiency of production and trade, these activities require the input of water-energy-food and generate disturbances in the environment. The transnational inter-regional input-output approach is utilized in a tele-connected Water-Energy-Food Nexus (WEFN) analysis of the East Asia GVC to assess competing demands for these resources and environmental outcomes.
This analysis demonstrates the hidden virtual flows of water, energy, and food embodied in intra-regional and transnational inter-regional trade. China’s current national export oriented economic growth strategy in East Asia is not sustainable from the WEFN perspective. China is a net virtual exporter of nexus resources to Japan and South Korea. China’s prioritization of economic growth and trade in low value added and pollution intensive sectors consumes a great amount of nexus resources within its territory to satisfy consumers’ demands in Japan and South Korea. Japan’s Kanto and Kinki regions and South Korea’s Sudokwon region were the major beneficiaries while China bore the environmental burden associated with the production of exports. For example, net virtual exports from China’s East region included over 1.2billionm3 of scarce water and 61.3million metric (CO2 equivalent) tons of greenhouse gases (i.e. CO2, NH4, and N2O) and 2 million metric tons of SOx emissions.
Trade is an important mechanism for overcoming resource bottlenecks, but, taking into account environmental linkages, regional specialization is not necessarily mutually beneficial. This analysis demonstrates a mismatch between regional water-energy-food availability and final resource consumption and the lack of attention for environmental impacts in national economic growth strategies. Resource scarce countries like China must, therefore, incorporate trade-off decisions between pursuing national economic growth, incurring environmental degradation, and food security into strategic regional development policies.
The current frontline symptomatic treatment for Alzheimer's disease (AD) is whole-body upregulation of cholinergic transmission via inhibition of acetylcholinesterase. This approach leads to profound ...dose-related adverse effects. An alternative strategy is to selectively target muscarinic acetylcholine receptors, particularly the M1 muscarinic acetylcholine receptor (M1 mAChR), which was previously shown to have procognitive activity. However, developing M1 mAChR-selective orthosteric ligands has proven challenging. Here, we have shown that mouse prion disease shows many of the hallmarks of human AD, including progressive terminal neurodegeneration and memory deficits due to a disruption of hippocampal cholinergic innervation. The fact that we also show that muscarinic signaling is maintained in both AD and mouse prion disease points to the latter as an excellent model for testing the efficacy of muscarinic pharmacological entities. The memory deficits we observed in mouse prion disease were completely restored by treatment with benzyl quinolone carboxylic acid (BQCA) and benzoquinazoline-12 (BQZ-12), two highly selective positive allosteric modulators (PAMs) of M1 mAChRs. Furthermore, prolonged exposure to BQCA markedly extended the lifespan of diseased mice. Thus, enhancing hippocampal muscarinic signaling using M1 mAChR PAMs restored memory loss and slowed the progression of mouse prion disease, indicating that this ligand type may have clinical benefit in diseases showing defective cholinergic transmission, such as AD.
Many subsurface microorganisms couple their metabolism to the reduction or oxidation of extracellular substrates. For example, anaerobic mineral-respiring bacteria can use external metal oxides as ...terminal electron acceptors during respiration. Porin–cytochrome complexes facilitate the movement of electrons generated through intracellular catabolic processes across the bacterial outer membrane to these terminal electron acceptors. In the mineral-reducing model bacterium Shewanella oneidensis MR-1, this complex is composed of two decaheme cytochromes (MtrA and MtrC) and an outer-membrane β-barrel (MtrB). However, the structures and mechanisms by which porin–cytochrome complexes transfer electrons are unknown. Here, we used small-angle neutron scattering (SANS) to study the molecular structure of the transmembrane complexes MtrAB and MtrCAB. Ab initio modeling of the scattering data yielded a molecular envelope with dimensions of ∼105 × 60 × 35 Å for MtrAB and ∼170 × 60 × 45 Å for MtrCAB. The shapes of these molecular envelopes suggested that MtrC interacts with the surface of MtrAB, extending ∼70 Å from the membrane surface and allowing the terminal hemes to interact with both MtrAB and an extracellular acceptor. The data also reveal that MtrA fully extends through the length of MtrB, with ∼30 Å being exposed into the periplasm. Proteoliposome models containing membrane-associated MtrCAB and internalized small tetraheme cytochrome (STC) indicate that MtrCAB could reduce Fe(III) citrate with STC as an electron donor, disclosing a direct interaction between MtrCAB and STC. Taken together, both structural and proteoliposome experiments support porin–cytochrome–mediated electron transfer via periplasmic cytochromes such as STC.
Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation.
In this multinational, double-blind, randomized trial, we compared ...vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization.
Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval CI, 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups.
In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).
A growing number of bacteria are recognized to conduct electrons across their cell envelope, and yet molecular details of the mechanisms supporting this process remain unknown. Here, we report the ...atomic structure of an outer membrane spanning protein complex, MtrAB, that is representative of a protein family known to transport electrons between the interior and exterior environments of phylogenetically and metabolically diverse microorganisms. The structure is revealed as a naturally insulated biomolecular wire possessing a 10-heme cytochrome, MtrA, insulated from the membrane lipidic environment by embedding within a 26 strand β-barrel formed by MtrB. MtrAB forms an intimate connection with an extracellular 10-heme cytochrome, MtrC, which presents its hemes across a large surface area for electrical contact with extracellular redox partners, including transition metals and electrodes.
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•The 20 hemes of a 3-component complex are arranged to move electrons across 185 Å•A β-barrel and 10-heme cytochrome form an insulated transmembrane nanowire•An extracellular 10-heme cytochrome has a large surface area for electron exchange•The hemes of both cytochromes are packed with a maximum inter-heme distance of 8 Å
Structural analysis shows how a naturally insulated molecular “wire” conducts electrons across lipid membranes in bacteria while protecting the membrane from redox damage and facilitating extracellular electron exchange
Substantial research over the past two decades has established that extracellular matrix (ECM) elasticity, or stiffness, affects fundamental cellular processes, including spreading, growth, ...proliferation, migration, differentiation and organoid formation. Linearly elastic polyacrylamide hydrogels and polydimethylsiloxane (PDMS) elastomers coated with ECM proteins are widely used to assess the role of stiffness, and results from such experiments are often assumed to reproduce the effect of the mechanical environment experienced by cells in vivo. However, tissues and ECMs are not linearly elastic materials-they exhibit far more complex mechanical behaviours, including viscoelasticity (a time-dependent response to loading or deformation), as well as mechanical plasticity and nonlinear elasticity. Here we review the complex mechanical behaviours of tissues and ECMs, discuss the effect of ECM viscoelasticity on cells, and describe the potential use of viscoelastic biomaterials in regenerative medicine. Recent work has revealed that matrix viscoelasticity regulates these same fundamental cell processes, and can promote behaviours that are not observed with elastic hydrogels in both two- and three-dimensional culture microenvironments. These findings have provided insights into cell-matrix interactions and how these interactions differentially modulate mechano-sensitive molecular pathways in cells. Moreover, these results suggest design guidelines for the next generation of biomaterials, with the goal of matching tissue and ECM mechanics for in vitro tissue models and applications in regenerative medicine.
Previously, we have shown that radiofrequency (RF) renal denervation (RDN) reduces myocardial infarct size in a rat model of acute myocardial infarction (MI) and improves left ventricular (LV) ...function and vascular reactivity in the setting of heart failure following MI.
The authors investigated the therapeutic efficacy of RF-RDN in a clinically relevant normotensive swine model of heart failure with reduced ejection fraction (HFrEF).
Yucatan miniswine underwent 75 min of left anterior descending coronary artery balloon occlusion to induce MI followed by reperfusion (R) for 18 weeks. Cardiac function was assessed pre- and post-MI/R by transthoracic echocardiography and every 3 weeks for 18 weeks. HFrEF was classified by an LV ejection fraction <40%. Animals who met inclusion criteria were randomized to receive bilateral RF-RDN (n = 10) treatment or sham-RDN (n = 11) at 6 weeks post-MI/R using an RF-RDN catheter.
RF-RDN therapy resulted in significant reductions in renal norepinephrine content and circulating angiotensin I and II. RF-RDN significantly increased circulating B-type natriuretic peptide levels. Following RF-RDN, LV end-systolic volume was significantly reduced when compared with sham-treated animals, leading to a marked and sustained improvement in LV ejection fraction. Furthermore, RF-RDN improved LV longitudinal strain. Simultaneously, RF-RDN reduced LV fibrosis and improved coronary artery responses to vasodilators.
RF-RDN provides a novel therapeutic strategy to reduce renal sympathetic activity, inhibit the renin-angiotensin system, increase circulating B-type natriuretic peptide levels, attenuate LV fibrosis, and improve left ventricular performance and coronary vascular function. These cardioprotective mechanisms synergize to halt the progression of HFrEF following MI/R in a clinically relevant model system.
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A
bstract
We perform an up-to-date global fit of top quark effective theory to experimental data from the Tevatron, and from LHC Runs I and II. Experimental data includes total cross-sections up to ...13 TeV, as well as differential distributions, for both single top and pair production. We also include the top quark width, charge asymmetries, and polarisation information from top decay products. We present bounds on the coefficients of dimension six operators, and examine the interplay between inclusive and differential measurements, and Tevatron/LHC data. All results are currently in good agreement with the Standard Model.
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