Komatiite Arndt, Nicholas; Lesher, C. Michael; Barnes, Steve J.
07/2008
eBook
Komatiites erupted billions of years ago as pulsating streams of white-hot lava. Their unusual chemical compositions and exceptionally high formation temperatures produced highly fluid lava that ...crystallized as spectacular layered flows. Investigation of the extreme conditions in which komatiites formed provides important evidence about the thermal and chemical evolution of the planet, and the nature of the Precambrian mantle. This monograph, written by three experts with long experience in the field, presents a complete account of the characteristics of komatiites including their volcanic structures, textures, mineralogy and chemical compositions. Models for their formation and eruption are evaluated (including the anhydrous vs. hydrous magmas controversy). A chapter is also devoted to the valuable nickel and copper ore deposits found in komatiites. Komatiite is a key reference for researchers and advanced students interested in petrology, Archaean geology, economic geology, and broader questions about the evolution of the Earth's crust and mantle.
Inflammatory endotypes in COPD Barnes, Peter J.
Allergy (Copenhagen),
July 2019, Letnik:
74, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Chronic obstructive pulmonary disease (COPD) is a major global health problem that is poorly treated by current therapies as it has proved difficult to treat the underlying inflammation, which is ...largely corticosteroid‐resistant in most patients. Although rare genetic endotypes of COPD have been recognized, despite the clinical heterogeneity of COPD, it has proved difficult to identify distinct inflammatory endotypes. Most patients have increased neutrophils and macrophages in sputum, reflecting the increased secretion of neutrophil and monocyte chemotactic mediators in the lungs. However, some patients also have increased eosinophils in sputum and this may be reflected by increased blood eosinophils. Increased blood and sputum eosinophils are associated with more frequent exacerbations and predict a good response to corticosteroids in reducing and treating acute exacerbations. Eosinophilic COPD may represent an overlap with asthma but the mechanism of eosinophilia is uncertain as, although an increase in sputum IL‐5 has been detected, anti‐IL‐5 therapies are not effective in preventing exacerbations. More research is needed to link inflammatory endotypes to clinical manifestations and outcomes in COPD and in particular to predict response to precision medicines.
Oxidative stress is a major driving mechanism in the pathogenesis of COPD. There is increased oxidative stress in the lungs of COPD patients due to exogenous oxidants in cigarette smoke and air ...pollution and due to endogenous generation of reactive oxygen species by inflammatory and structural cells in the lung. Mitochondrial oxidative stress may be particularly important in COPD. There is also a reduction in antioxidant defences, with inactivation of several antioxidant enzymes and the transcription factors Nrf2 and FOXO that regulate multiple antioxidant genes. Increased systemic oxidative stress may exacerbate comorbidities and contribute to skeletal muscle weakness. Oxidative stress amplifies chronic inflammation, stimulates fibrosis and emphysema, causes corticosteroid resistance, accelerates lung aging, causes DNA damage and stimulates formation of autoantibodies. This suggests that treating oxidative stress by antioxidants or enhancing endogenous antioxidants should be an effective strategy to treat the underlying pathogenetic mechanisms of COPD. Most clinical studies in COPD have been conducted using glutathione-generating antioxidants such as N-acetylcysteine, carbocysteine and erdosteine, which reduce exacerbations in COPD patients, but it is not certain whether this is due to their antioxidant or mucolytic properties. Dietary antioxidants have so far not shown to be clinically effective in COPD. There is a search for more effective antioxidants, which include superoxide dismutase mimetics, NADPH oxidase inhibitors, mitochondria-targeted antioxidants and Nrf2 activators.
Our world is awash with plastic. The massive increase in plastics production, combined with a shift to single-use, disposable plastics and widespread mismanagement of plastic waste, has created a ...huge “tragedy of the commons” (Hardin, 1968) in our oceans, seas and waterways. Plastics pollution is now a global externality that damages ecosystems, curtails biodiversity and ultimately has the potential to affect everyone on the planet. Although waste output is often modelled separately from environmental pollution in research, in the case of plastics, the waste problem has become one of global pollution. In this paper, we model the relationship between mismanaged plastic waste1 and income per capita for 151 countries, and for the first time find empirical support for the environmental Kuznets curve using plastics pollution data. Further, we find support for the hypothesis that a key instrument for reducing plastics pollution is investment in scientific and technological research. The paper concludes with a discussion of the results, limitations, and implications for future research and practice.
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•Models the relationship between mismanaged plastic waste and economic development.•Finds original empirical support for the EKC in the context of mismanaged plastic waste.•Plastics pollution reduced in countries through scientific and technical research.•Examines policy implications of research findings in reducing plastics pollution.
Original empirical support for environmental Kuznets curve for plastics pollution and reduction in plastics pollution via research investment, based on data for 151 countries.
Chronic obstructive pulmonary disease (COPD) is regarded as a disease of accelerated lung aging. This affliction shows all of the hallmarks of aging, including telomere shortening, cellular ...senescence, activation of PI3 kinase-mTOR signaling, impaired autophagy, mitochondrial dysfunction, stem cell exhaustion, epigenetic changes, abnormal microRNA profiles, immunosenescence, and a low-grade chronic inflammation (inflammaging). Many of these pathways are driven by chronic exogenous and endogenous oxidative stress. There is also a reduction in antiaging molecules, such as sirtuins and Klotho, which further accelerate the aging process. COPD is associated with several comorbidities (multimorbidity), such as cardiovascular and metabolic diseases, that share the same pathways of accelerated aging. Understanding these mechanisms has helped identify several novel therapeutic targets, and several drugs and dietary interventions are now in development to treat multimorbidity.
Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation of the peripheral airways and lung parenchyma, which leads to progressive obstruction of the airways. Current ...management with long-acting bronchodilators does not reduce disease progression, and there are no treatments that effectively suppress chronic inflammation in COPD. An increased understanding of the inflammatory processes that are involved in the pathophysiology of COPD has identified several new therapeutic targets. This Review discusses some of the most promising of these targets, including new antioxidants, kinase inhibitors and drugs that target cellular senescence, microbial colonization, epigenetic regulation of inflammatory gene expression and corticosteroid resistance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation affecting predominantly the lung parenchyma and peripheral airways that results in largely irreversible and ...progressive airflow limitation. This inflammation is characterized by increased numbers of alveolar macrophages, neutrophils, T lymphocytes (predominantly TC 1, TH 1, and TH 17 cells), and innate lymphoid cells recruited from the circulation. These cells and structural cells, including epithelial and endothelial cells and fibroblasts, secrete a variety of proinflammatory mediators, including cytokines, chemokines, growth factors, and lipid mediators. Although most patients with COPD have a predominantly neutrophilic inflammation, some have an increase in eosinophil counts, which might be orchestrated by TH 2 cells and type 2 innate lymphoid cells though release of IL-33 from epithelial cells. These patients might be more responsive to corticosteroids and bronchodilators. Oxidative stress plays a key role in driving COPD-related inflammation, even in ex-smokers, and might result in activation of the proinflammatory transcription factor nuclear factor κB (NF-κB), impaired antiprotease defenses, DNA damage, cellular senescence, autoantibody generation, and corticosteroid resistance though inactivation of histone deacetylase 2. Systemic inflammation is also found in patients with COPD and can worsen comorbidities, such as cardiovascular diseases, diabetes, and osteoporosis. Accelerated aging in the lungs of patients with COPD can also generate inflammatory protein release from senescent cells in the lung. In the future, it will be important to recognize phenotypes of patients with optimal responses to more specific therapies, and development of biomarkers that identify the therapeutic phenotypes will be important.
The recognition that there are some patients with features of asthma and chronic obstructive pulmonary disease (COPD) has highlighted the need to develop more specific treatments for these clinical ...phenotypes. Some patients with COPD have predominantly eosinophilic inflammation and might respond to high doses of inhaled corticosteroids and newly developed specific antieosinophil therapies, including blocking antibodies against IL-5, IL-13, IL-33, and thymic stromal lymphopoietin, as well as oral chemoattractant receptor-homologous molecule expressed on TH 2 cells antagonists. Other patients have severe asthma or are asthmatic patients who smoke with features of COPD-induced inflammation and might benefit from treatments targeting neutrophils, including macrolides, CXCR2 antagonists, phosphodiesterase 4 inhibitors, p38 mitogen-activating protein kinase inhibitors, and antibodies against IL-1 and IL-17. Other patients appear to have largely fixed obstruction with little inflammation and might respond to long-acting bronchodilators, including long-acting muscarinic antagonists, to reduce hyperinflation. Highly selected patients with severe asthma might benefit from bronchial thermoplasty. Some patients with overlap syndromes can be conveniently treated with triple fixed-dose combination inhaler therapy with an inhaled corticosteroid, long-acting β2 -agonist, and long-acting muscarinic antagonist, several of which are now in development. Corticosteroid resistance is a feature of asthma-COPD overlap syndrome, and understanding the various molecular mechanisms of this resistance has identified novel therapeutic targets and presented the prospect of therapies that can restore corticosteroid responsiveness.
•Exporting plastic waste creates psychological distance from plastic waste pollution.•Exporting plastic waste creates an artificially cleaner local environment.•Artificially cleaner local ...environments encourage plastics consumption.•Level of plastic waste acts as a mediator in the relationship.•Examines policy aimed at reducing future plastics consumption and pollution.
Per capita consumption of plastic continues to increase and remains at high levels in high-income countries, despite obvious contributions to the global problem of plastics pollution. This paper attempts to provide an explanation for this phenomenon based on construal level theory, positing that plastic waste is a problem that is perceived as “out of sight and out of mind” for consumers in high plastic consumption (typically high income) countries and that this is influenced by the export of plastic waste to other (typically lower income and lower consumption) countries for disposal – shifting the burden of mismanaged plastic waste and perceptions of plastics pollution in the countries creating the majority of plastic waste. The apparent lack of plastics pollution in a local environment becomes a mediator, influenced by the export of plastic waste, which may then contribute to further plastics consumption. The theory is tested using structural equation modelling using rare, available matched data for mismanaged plastic waste, plastic waste exports, and plastics consumption at an aggregate country level. All study hypotheses are supported. The paper concludes with recommendations for future research and practice, including potential changes to government policy aimed at reducing future plastics consumption and pollution.
All cells sense and integrate mechanical and biochemical cues from their environment to orchestrate organismal development and maintain tissue homeostasis. Mechanotransduction is the evolutionarily ...conserved process whereby mechanical force is translated into biochemical signals that can influence cell differentiation, survival, proliferation and migration to change tissue behavior. Not surprisingly, disease develops if these mechanical cues are abnormal or are misinterpreted by the cells - for example, when interstitial pressure or compression force aberrantly increases, or the extracellular matrix (ECM) abnormally stiffens. Disease might also develop if the ability of cells to regulate their contractility becomes corrupted. Consistently, disease states, such as cardiovascular disease, fibrosis and cancer, are characterized by dramatic changes in cell and tissue mechanics, and dysregulation of forces at the cell and tissue level can activate mechanosignaling to compromise tissue integrity and function, and promote disease progression. In this Commentary, we discuss the impact of cell and tissue mechanics on tissue homeostasis and disease, focusing on their role in brain development, homeostasis and neural degeneration, as well as in brain cancer.
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