Abstract
Concern over plastic pollution of the marine environment is severe. The mass-imbalance between the plastic litter supplied to and observed in the ocean currently suggests a missing sink. ...However, here we show that the ocean interior conceals high loads of small-sized plastic debris which can balance and even exceed the estimated plastic inputs into the ocean since 1950. The combined mass of just the three most-littered plastics (polyethylene, polypropylene, and polystyrene) of 32–651 µm size-class suspended in the top 200 m of the Atlantic Ocean is 11.6–21.1 Million Tonnes. Considering that plastics of other sizes and polymer types will be found in the deeper ocean and in the sediments, our results indicate that both inputs and stocks of ocean plastics are much higher than determined previously. It is thus critical to assess these terms across all size categories and polymer groups to determine the fate and danger of plastic contamination.
In this short paper, I assess how COVID‐19‐related disruptions in transportation services, as well as new demands for transportation services, could impact Canadian agricultural supply chains. The ...brief analysis reveals that agricultural access to bulk ocean freight, rail movement, and trucking has generally improved in the pandemic, bolstered by the reduced demand for these transportation services by other sectors of the economy. The intermodal containerized movement of grains and food products has seen some disruption from the lack of empty containers in North America. The widespread consumer adoption of physical distancing measures has vastly increased the demand for retail food pickup and delivery services to the point where these services are being rationed by long wait times. From a policy perspective, there is an apparent need for (a) continued supply chain monitoring and industry engagement, (b) the proactive development of strategies to deal with absenteeism and other potential threats to the supply chain, and (c) an assessment of the economic and health merits of providing additional public resources to provide greater access to grocery pickup and delivery services.
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Dans ce court article, j'évalue comment les perturbations des services de transport liées au COVID‐19, ainsi que les nouvelles demandes de services de transport, pourraient avoir une incidence sur les chaînes d'approvisionnement agricole du Canada. La brève analyse révèle que l'accès des agriculteurs au fret maritime en vrac, au transport ferroviaire et au camionnage s'est généralement amélioré au cours de la pandémie, soutenu par la réduction de la demande de ces services de transport par d'autres secteurs de l'économie. Le mouvement intermodal conteneurisé de céréales et de produits alimentaires a été perturbé par le manque de conteneurs vides en Amérique du Nord. L'adoption généralisée par les consommateurs de mesures physiques de distanciation a considérablement accru la demande de services de collecte et de livraison de produits alimentaires au détail, au point que ces services sont rationnés par de longs délais d'attente. D'un point de vue politique, il existe un besoin apparent de: 1) une surveillance continue de la chaîne d'approvisionnement et un engagement de l'industrie, 2) l'élaboration proactive de stratégies pour lutter contre l'absentéisme et d'autres menaces potentielles pour la chaîne d'approvisionnement, et 3) une évaluation de la conjoncture économique. et les avantages pour la santé de fournir des ressources publiques supplémentaires pour offrir un meilleur accès aux services de cueillette et de livraison d'épicerie.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
This article reviews the economic impacts of climate change and the policy implications of the results. Current estimates indicate that climate change will likely have a limited impact on ...the economy and human welfare in the twenty-first century. In fact, the initial impacts of climate change may well be positive. However, in the long run the negative impacts dominate the positive ones. Negative impacts will be substantially greater in poorer, hotter, and lower-lying countries. Poverty reduction complements greenhouse gas emissions reduction as a means to reduce climate change impacts. Although climate change may affect the growth rate of the global economy and may trap more people in poverty, quantification of these impacts remains difficult. The optimal carbon tax in the near term is somewhere between a few tens and a few hundreds of dollars per ton of carbon.
Plants have evolved sophisticated mechanisms to recycle intracellular constituents, which are essential for developmental and metabolic transitions; for efficient nutrient reuse; and for the proper ...disposal of proteins, protein complexes, and even entire organelles that become obsolete or dysfunctional. One major route is autophagy, which employs specialized vesicles to encapsulate and deliver cytoplasmic material to the vacuole for breakdown. In the past decade, the mechanics of autophagy and the scores of components involved in autophagic vesicle assembly have been documented. Now emerging is the importance of dedicated receptors that help recruit appropriate cargo, which in many cases exploit ubiquitylation as a signal. Although operating at a low constitutive level in all plant cells, autophagy is upregulated during senescence and various environmental challenges and is essential for proper nutrient allocation. Its importance to plant metabolism and energy balance in particular places autophagy at the nexus of robust crop performance, especially under suboptimal conditions.
Store-Operated Calcium Channels Prakriya, Murali; Lewis, Richard S
Physiological reviews,
10/2015, Volume:
95, Issue:
4
Journal Article
Peer reviewed
Open access
Store-operated calcium channels (SOCs) are a major pathway for calcium signaling in virtually all metozoan cells and serve a wide variety of functions ranging from gene expression, motility, and ...secretion to tissue and organ development and the immune response. SOCs are activated by the depletion of Ca(2+) from the endoplasmic reticulum (ER), triggered physiologically through stimulation of a diverse set of surface receptors. Over 15 years after the first characterization of SOCs through electrophysiology, the identification of the STIM proteins as ER Ca(2+) sensors and the Orai proteins as store-operated channels has enabled rapid progress in understanding the unique mechanism of store-operate calcium entry (SOCE). Depletion of Ca(2+) from the ER causes STIM to accumulate at ER-plasma membrane (PM) junctions where it traps and activates Orai channels diffusing in the closely apposed PM. Mutagenesis studies combined with recent structural insights about STIM and Orai proteins are now beginning to reveal the molecular underpinnings of these choreographic events. This review describes the major experimental advances underlying our current understanding of how ER Ca(2+) depletion is coupled to the activation of SOCs. Particular emphasis is placed on the molecular mechanisms of STIM and Orai activation, Orai channel properties, modulation of STIM and Orai function, pharmacological inhibitors of SOCE, and the functions of STIM and Orai in physiology and disease.
Zoonotic diseases are infectious diseases of humans caused by pathogens that are shared between humans and other vertebrate animals. Previously, pristine natural areas with high biodiversity were ...seen as likely sources of new zoonotic pathogens, suggesting that biodiversity could have negative impacts on human health. At the same time, biodiversity has been recognized as potentially benefiting human health by reducing the transmission of some pathogens that have already established themselves in human populations. These apparently opposing effects of biodiversity in human health may now be reconcilable. Recent research demonstrates that some taxa are much more likely to be zoonotic hosts than others are, and that these animals often proliferate in human-dominated landscapes, increasing the likelihood of spillover. In less-disturbed areas, however, these zoonotic reservoir hosts are less abundant and nonreservoirs predominate. Thus, biodiversity loss appears to increase the risk of human exposure to both new and established zoonotic pathogens. This new synthesis of the effects of biodiversity on zoonotic diseases presents an opportunity to articulate the next generation of research questions that can inform management and policy. Future studies should focus on collecting and analyzing data on the diversity, abundance, and capacity to transmit of the taxa that actually share zoonotic pathogens with us. To predict and prevent future epidemics, researchers should also focus on how these metrics change in response to human impacts on the environment, and how human behaviors can mitigate these effects. Restoration of biodiversity is an important frontier in the management of zoonotic disease risk.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Over the past decade, sorafenib has been the only systemic agent with proven clinical efficacy for patients with unresectable hepatocellular carcinoma (HCC). Recently, lenvatinib was shown to be ...non-inferior to sorafenib, while regorafenib, cabozantinib, and ramucirumab were shown to be superior to placebo in patients failing sorafenib. In addition, trials of immune checkpoint inhibitors reported encouraging efficacy signals. However, apart from alpha-fetoprotein, which is used to select patients for ramucirumab, no biomarkers are available to identify patients that may respond to a specific treatment. Different synergisms have been postulated based on the potential interplay between antiangiogenic drugs and immunotherapy, with several clinical trials currently testing this hypothesis. Indeed, encouraging preliminary results of phase I studies of bevacizumab plus atezolizumab and lenvatinib plus pembrolizumab have led to the design of ongoing phase III trials, including both antiangiogenics and immune checkpoint inhibitors in the front-line setting. Other important phase II studies have tested molecular therapies directed against different novel targets, such as transforming growth factor-beta, MET (hepatocyte growth factor receptor), and fibroblast growth factor receptor 4. These studies integrated translational research with the aim of better defining the biological tumour profile and identifying tumour and blood biomarkers that select patients who may really benefit from a specific molecular therapy. Importantly, good safety profiles make these drugs suitable for future combinations. In this review, we discuss the most recent data on novel combination strategies and targets, as well as looking ahead to the future role of molecular therapies in the treatment of patients with advanced HCC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This paper uses imputed national climate change impact functions to estimate national social costs of carbon, which are largest in poor countries with large populations. The national social costs of ...carbon of faster growing economies are less sensitive to the pure rate of time preference and more sensitive to the rate of risk aversion. The pattern of national social costs of carbon is not sensitive to the assumed impact function, climate sensitivity, and scenario, although the global social cost of carbon is. Income convergence raises the national social costs of carbon of poorer countries, and lowers them for richer countries. Both global and national social costs of carbon are most sensitive to the income elasticity of climate change impacts, a parameter about which we know little.
•Estimates of the national social cost of carbon•Large, poor countries show the highest estimates.•Income elasticity of impact is key parameter.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sepsis - which is a severe life-threatening infection with organ dysfunction - initiates a complex interplay of host pro-inflammatory and anti-inflammatory processes. Sepsis can be considered a race ...to the death between the pathogens and the host immune system, and it is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses provides a novel approach for treating this highly lethal condition. Biomarker-guided immunotherapy that is administered to patients at the proper immune phase of sepsis is potentially a major advance in the treatment of sepsis and in the field of infectious disease.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Store-operated calcium (Ca
) entry (SOCE) occurs through a widely distributed family of ion channels activated by the loss of Ca
from the endoplasmic reticulum (ER). The best understood of these is ...the Ca
release-activated Ca
(CRAC) channel, which is notable for its unique activation mechanism as well as its many essential physiological functions and the diverse pathologies that result from dysregulation. In response to ER Ca
depletion, CRAC channels are formed through a diffusion trap mechanism at ER-plasma membrane (PM) junctions, where the ER Ca
-sensing stromal interaction molecule (STIM) proteins bind and activate hexamers of Orai pore-forming proteins to trigger Ca
entry. Cell biological studies are clarifying the architecture of ER-PM junctions, their roles in Ca
and lipid transport, and functional interactions with cytoskeletal proteins. Molecular structures of STIM and Orai have inspired a multitude of mutagenesis and electrophysiological studies that reveal potential mechanisms for how STIM is toggled between inactive and active states, how it binds and activates Orai, and the importance of STIM-binding stoichiometry for opening the channel and establishing its signature characteristics of extremely high Ca
selectivity and low Ca
conductance.
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