Micro‐plastic marine debris is widely distributed in vast regions of the subtropical gyres and has emerged as a major open ocean pollutant. The fate and transport of plastic marine debris is governed ...by poorly understood geophysical processes, such as ocean mixing within the surface boundary layer. Based on profile observations and a one‐dimensional column model, we demonstrate that plastic debris is vertically distributed within the upper water column due to wind‐driven mixing. These results suggest that total oceanic plastics concentrations are significantly underestimated by traditional surface measurements, requiring a reinterpretation of existing plastic marine debris data sets. A geophysical approach must be taken in order to properly quantify and manage this form of marine pollution.
Key Points
Plastic debris is vertically distributed due to wind‐driven upper ocean mixing
Traditional measurements significantly underestimate marine plastic content
A geophysical approach must be taken to quantify marine plastic pollution
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Highlights • Circuit regulation of addiction is complex and dynamic. • The pattern and source of dopamine and glutamate neurotransmission in the striatum are critical for shaping addictive processes. ...• Novel techniques are providing new insights into the neural circuits that regulate addiction.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Through much of the history of metabolism, lactate (La(-)) has been considered merely a dead-end waste product during periods of dysoxia. Congruently, the end product of glycolysis has been viewed ...dichotomously: pyruvate in the presence of adequate oxygenation, La(-) in the absence of adequate oxygenation. In contrast, given the near-equilibrium nature of the lactate dehydrogenase (LDH) reaction and that LDH has a much higher activity than the putative regulatory enzymes of the glycolytic and oxidative pathways, we contend that La(-) is always the end product of glycolysis. Cellular La(-) accumulation, as opposed to flux, is dependent on (1) the rate of glycolysis, (2) oxidative enzyme activity, (3) cellular O2 level, and (4) the net rate of La(-) transport into (influx) or out of (efflux) the cell. For intracellular metabolism, we reintroduce the Cytosol-to-Mitochondria Lactate Shuttle. Our proposition, analogous to the phosphocreatine shuttle, purports that pyruvate, NAD(+), NADH, and La(-) are held uniformly near equilibrium throughout the cell cytosol due to the high activity of LDH. La(-) is always the end product of glycolysis and represents the primary diffusing species capable of spatially linking glycolysis to oxidative phosphorylation.
Cytochrome P450 (CYP) enzymes are responsible for the metabolism of many exogenous and endogenous compounds. CYPs are abundant in the liver and are also expressed in many extra-hepatic tissues ...including the brain. Although total CYP levels in the brain are much lower than in the liver, brain CYPs are concentrated near drug targets in specific regions and cell types, and can potentially have a considerable impact on local metabolism. Individual differences in brain CYP metabolism, due to inducers, inhibitors or genetic variation, can influence sensitivity and response to centrally acting drugs. Brain CYPs may also play a role in modulating brain activity, behavior, susceptibility to central nervous system diseases and treatment outcomes. This review highlights recent progress that has been made in understanding the functional significance of CYPs in the brain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Lactate (La
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) has long been at the center of controversy in research, clinical, and athletic settings. Since its discovery in 1780, La
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has often been erroneously viewed as simply a hypoxic waste ...product with multiple deleterious effects. Not until the 1980s, with the introduction of the cell-to-cell lactate shuttle did a paradigm shift in our understanding of the role of La
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in metabolism begin. The evidence for La
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as a major player in the coordination of whole-body metabolism has since grown rapidly. La
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is a readily combusted fuel that is shuttled throughout the body, and it is a potent signal for angiogenesis irrespective of oxygen tension. Despite this, many fundamental discoveries about La
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are still working their way into mainstream research, clinical care, and practice. The purpose of this review is to synthesize current understanding of La
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metabolism via an appraisal of its robust experimental history, particularly in exercise physiology. That La
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production increases during dysoxia is beyond debate, but this condition is the exception rather than the rule. Fluctuations in blood La
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in health and disease are not typically due to low oxygen tension, a principle first demonstrated with exercise and now understood to varying degrees across disciplines. From its role in coordinating whole-body metabolism as a fuel to its role as a signaling molecule in tumors, the study of La
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metabolism continues to expand and holds potential for multiple clinical applications. This review highlights La
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’s central role in metabolism and amplifies our understanding of past research.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The increasing involvement of pharmacists in public health will require changes in the behaviour of both pharmacists and the general public. A great deal of research has shown that attitudes and ...beliefs are important determinants of behaviour. This review aims to examine the beliefs and attitudes of pharmacists and consumers towards pharmaceutical public health in order to inform how best to support and improve this service.
Five electronic databases were searched for articles published in English between 2001 and 2010. Titles and abstracts were screened by one researcher according to the inclusion criteria. Papers were included if they assessed pharmacy staff or consumer attitudes towards pharmaceutical public health. Full papers identified for inclusion were assessed by a second researcher and data were extracted by one researcher.
From the 5628 papers identified, 63 studies in 67 papers were included. Pharmacy staff: Most pharmacists viewed public health services as important and part of their role but secondary to medicine related roles. Pharmacists' confidence in providing public health services was on the whole average to low. Time was consistently identified as a barrier to providing public health services. Lack of an adequate counselling space, lack of demand and expectation of a negative reaction from customers were also reported by some pharmacists as barriers. A need for further training was identified in relation to a number of public health services. Consumers: Most pharmacy users had never been offered public health services by their pharmacist and did not expect to be offered. Consumers viewed pharmacists as appropriate providers of public health advice but had mixed views on the pharmacists' ability to do this. Satisfaction was found to be high in those that had experienced pharmaceutical public health
There has been little change in customer and pharmacist attitudes since reviews conducted nearly 10 years previously. In order to improve the public health services provided in community pharmacy, training must aim to increase pharmacists' confidence in providing these services. Confident, well trained pharmacists should be able to offer public health service more proactively which is likely to have a positive impact on customer attitudes and health.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
G protein-coupled receptors (GPCRs) contribute to the regulation of every aspect of human physiology and are therapeutic targets for the treatment of numerous diseases. As a consequence, ...understanding the myriad of mechanisms controlling GPCR signaling and trafficking is essential for the development of new pharmacological strategies for the treatment of human pathologies. Of the many GPCR-interacting proteins, postsynaptic density protein of 95 kilodaltons, disc large, zona occludens-1 (PDZ) domain-containing proteins appear most abundant and have similarly been implicated in disease mechanisms. PDZ proteins play an important role in regulating receptor and channel protein localization within synapses and tight junctions and function to scaffold intracellular signaling protein complexes. In the current study, we review the known functional interactions between PDZ domain-containing proteins and GPCRs and provide insight into the potential mechanisms of action. These PDZ domain-containing proteins include the membrane-associated guanylate-like kinases postsynaptic density protein of 95 kilodaltons; synapse-associated protein of 97 kilodaltons; postsynaptic density protein of 93 kilodaltons; synapse-associated protein of 102 kilodaltons; discs, large homolog 5; caspase activation and recruitment domain and membrane-associated guanylate-like kinase domain-containing protein 3; membrane protein, palmitoylated 3; calcium/calmodulin-dependent serine protein kinase; membrane-associated guanylate kinase protein (MAGI)-1, MAGI-2, and MAGI-3, Na(+)/H(+) exchanger regulatory factor proteins (NHERFs) (NHERF1, NHERF2, PDZ domain-containing kidney protein 1, and PDZ domain-containing kidney protein 2), Golgi-associated PDZ proteins (Gα-binding protein interacting protein, C-terminus and CFTR-associated ligand), PDZ domain-containing guanine nucleotide exchange factors (GEFs) 1 and 2, regulator of G protein signaling (RGS)-homology-RhoGEFs (PDZ domain-containing RhoGEF and leukemia-associated RhoGEF), RGS3 and RGS12, spinophilin and neurabin-1, SRC homology 3 domain and multiple ankyrin repeat domain (Shank) proteins (Shank1, Shank2, and Shank3), partitioning defective proteins 3 and 6, multiple PDZ protein 1, Tamalin, neuronal nitric oxide synthase, syntrophins, protein interacting with protein kinase C α 1, syntenin-1, and sorting nexin 27.
As the sheer number of transgenic mice strains grow and rodent models of pediatric disease increase, there is an expanding need for a comprehensive, standardized battery of neonatal mouse motor ...tests. These tests can validate injury or disease models, determine treatment efficacy and/or assess motor behaviors in new transgenic strains. This paper presents a series of neonatal motor tests to evaluate general motor function, including ambulation, hindlimb foot angle, surface righting, negative geotaxis, front- and hindlimb suspension, grasping reflex, four limb grip strength and cliff aversion. Mice between the ages of post-natal day 2 to 14 can be used. In addition, these tests can be used for a wide range of neurological and neuromuscular pathologies, including cerebral palsy, hypoxic-ischemic encephalopathy, traumatic brain injury, spinal cord injury, neurodegenerative diseases, and neuromuscular disorders. These tests can also be used to determine the effects of pharmacological agents, as well as other types of therapeutic interventions. In this paper, motor deficits were evaluated in a novel neonatal mouse model of cerebral palsy that combines hypoxia, ischemia and inflammation. Forty-eight hours after injury, five tests out of the nine showed significant motor deficits: ambulation, hindlimb angle, hindlimb suspension, four limb grip strength, and grasping reflex. These tests revealed weakness in the hindlimbs, as well as fine motor skills such as grasping, which are similar to the motor deficits seen in human cerebral palsy patients.
To curtail the spread of wildfire, firefighters are often required to work long hours in hot, smoky conditions with little rest between consecutive shifts. In isolation, heat, smoke, and sleep ...disruption can have a detrimental impact on cognitive and physical abilities. Far less is known, however, about the combined impact that heat, smoke, and sleep disruption can have on firefighters' performance during wildfire suppression or on human performance in general. The available literature, though scant, suggests that audio and visual tracking may be degraded after sustained heat exposure following one night of sleep deprivation. Exposure to heat and carbon monoxide, in contrast, appears to have only limited impact on cognitive performance, even after physical exercise. Heat and carbon monoxide exposure does, however, increase physiological exertion to a given work or exercise bout. To the authors' knowledge, there are no published studies that have explored the impacts of heat exposure following sleep disruption on physical work performance, sleep disruption and smoke exposure on physical or cognitive work, or the combined impacts of sleep disruption, smoke and heat exposure on cognitive or physical work. While more integrative research is needed, the current review provides a summary of the available evidence and an indication of the degree of confidence agencies can have in the research. This will allow both the scientific community and agencies to make informed recommendations regarding the management of wildland firefighters' health and safety on the fireground.
► Wildland firefighters face multiple occupational stressors that place them at increased risk. ► Sleep restriction, heat and smoke impact physical and mental performance. ► In combination these stressors are likely to have a bigger impact on health and safety. ► We provide guidance to policy makers managing the OHS risks for firefighters.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Drug addiction is a chronic disease defined by a complex set of characteristics, including loss of control over drug intake and persistent drug craving, which primarily affects a small percentage of ...people who try drugs. Although many models have been developed to study individual aspects of drug use, there is great translational value in having an animal model that encompasses multiple aspects of the human disease, including the variation in severity observed in humans. Here, we describe an intermittent access model of cocaine self-administration that produces a subset of rats that display many of the core features of addiction, including escalation of drug intake, a binge-like pattern of drug use, robust locomotor sensitization, and high levels of drug-seeking during cue-induced reinstatement. This group is compared with rats that have the same drug history but do not develop this pattern of drug-taking and drug-seeking, as well as rats that undergo a traditional continuous access paradigm. Finally, we observe that high levels of cocaine consumption produce long-term changes in intracellular calcium signaling in the dorsomedial striatum.
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DOBA, EMUNI, FIS, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
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