Thoughts on the alveolar phase of COVID-19 Mason, Robert J
American journal of physiology. Lung cellular and molecular physiology,
07/2020, Letnik:
319, Številka:
1
Journal Article
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COVID-19 can be divided into three clinical stages, and one can speculate that these stages correlate with where the infection resides. For the asymptomatic phase, the infection mostly resides in the ...nose, where it elicits a minimal innate immune response. For the mildly symptomatic phase, the infection is mostly in the pseudostratified epithelium of the larger airways and is accompanied by a more vigorous innate immune response. In the conducting airways, the epithelium can recover from the infection, because the keratin 5 basal cells are spared and they are the progenitor cells for the bronchial epithelium. There may be more severe disease in the bronchioles, where the club cells are likely infected. The devastating third phase is in the gas exchange units of the lung, where ACE2-expressing alveolar type II cells and perhaps type I cells are infected. The loss of type II cells results in respiratory insufficiency due to the loss of pulmonary surfactant, alveolar flooding, and possible loss of normal repair, since type II cells are the progenitors of type I cells. The loss of type I and type II cells will also block normal active resorption of alveolar fluid. Subsequent endothelial damage leads to transudation of plasma proteins, formation of hyaline membranes, and an inflammatory exudate, characteristic of ARDS. Repair might be normal, but if the type II cells are severely damaged alternative pathways for epithelial repair may be activated, which would result in some residual lung disease.
An ideal primer on contemporary Middle East Politics,
covering the entire MENA region from an interdisciplinary
perspective
This compelling volume examines important and
cross-cutting themes in the ...study of contemporary Middle East and
North African politics and international relations in the current
climate. Drawing together contributions from scholars based within
the region and beyond, it weaves together essential
interdisciplinary, conceptually rich, and forward-looking content.
Chapters cover population and youth, civil-military relations, soft
power and geopolitical competition, regionalization and
internationalization of conflict, the role of oil in reconstruction
efforts, extra-regional actors, environmental politics, and
specifically, the Israel-Palestine conflict. Students are supported
with an extended and innovative glossary, including key concepts,
actors and abbreviations. New Perspectives on Middle East
Politics serves as an ideal primer and companion volume for
scholars of contemporary Middle East Studies, as well as for policy
professionals, journalists and the general reader engaging and
re-engaging with the region. Contributor
affiliations: Mohamed Abdelraouf, Gulf Research Centre,
Jeddah, United Arab Emirates Dina Arakji, Carnegie Middle East
Center, Beirut, Lebanon Eyad AlRefai, Lancaster University,
Lancashire, England and King Abdulaziz University, Saudi Arabia
Philipp Casula, University of Basel, Switzerland Ishac Diwan, Paris
Sciences et Lettres and Ecole Normale Superieure, Paris, France
Seif Hendy, American University in Cairo, Egypt Simon Mabon,
Lancaster University, Lancashire, England Robert Mason, Lancaster
University, Lancashire, England Neil Partrick, freelance
consultant, UK
Mercury (Hg) is a global pollutant that affects human and ecosystem health. We synthesize understanding of sources, atmosphere-land-ocean Hg dynamics and health effects, and consider the implications ...of Hg-control policies. Primary anthropogenic Hg emissions greatly exceed natural geogenic sources, resulting in increases in Hg reservoirs and subsequent secondary Hg emissions that facilitate its global distribution. The ultimate fate of emitted Hg is primarily recalcitrant soil pools and deep ocean waters and sediments. Transfers of Hg emissions to largely unavailable reservoirs occur over the time scale of centuries, and are primarily mediated through atmospheric exchanges of wet/dry deposition and evasion from vegetation, soil organic matter and ocean surfaces. A key link between inorganic Hg inputs and exposure of humans and wildlife is the net production of methylmercury, which occurs mainly in reducing zones in freshwater, terrestrial, and coastal environments, and the subsurface ocean. Elevated human exposure to methylmercury primarily results from consumption of estuarine and marine fish. Developing fetuses are most at risk from this neurotoxin but health effects of highly exposed populations and wildlife are also a concern. Integration of Hg science with national and international policy efforts is needed to target efforts and evaluate efficacy.
The Minamata Convention to reduce anthropogenic mercury (Hg) emissions entered into force in 2017, and attention is now focused on how to best monitor its effectiveness at reducing Hg exposure to ...humans. A key question is how closely Hg concentrations in the human food chain, especially in fish and other aquatic wildlife, will track the changes in atmospheric Hg that are expected to occur following anthropogenic emission reductions. We investigated this question by evaluating several regional groups of case studies where Hg concentrations in aquatic biota have been monitored continuously or intermittently for several decades. Our analysis shows that in most cases Hg time trends in biota did not agree with concurrent Hg trends in atmospheric deposition or concentrations, and the divergence between the two trends has become more apparent over the past two decades. An over-arching general explanation for these results is that the impact of changing atmospheric inputs on biotic Hg is masked by two factors: 1) The aquatic environment contains a large inventory of legacy emitted Hg that remains available for bio-uptake leading to a substantial lag in biotic response time to a change in external inputs; and 2) Biotic Hg trends reflect the dominant effects of changes in multi-causal, local and regional processes (e.g., aquatic or terrestrial biogeochemical processes, feeding ecology, climate) that control the speciation, bioavailability, and bio-uptake of both present-day and legacy emitted Hg. Globally, climate change has become the most prevalent contributor to the divergence. A wide range of biotic Hg outcomes can thus be expected as anthropogenic atmospheric Hg emissions decline, depending on how these processes operate on specific regions and specific organisms. Therefore, evaluating the effectiveness of the Minamata Convention will require biomonitoring of multiple species that represent different trophic and ecological niches in multiple regions of the world.
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•Mercury time-trends in aquatic biota often do not agree with atmospheric trends.•Divergence between the two trends has become more apparent in the past two decades.•The divergence is due to legacy mercury and changing biogeochemical processes.•Globally climate change has become the most prevalent contributor to the divergence.•Thus, the efforts of the Minamata Convention may be countered by climate change.
COVID-19 has different clinical stages, and effective therapy depends on the location and extent of the infection. The purpose of this review is to provide a background for understanding the ...progression of the disease throughout the pulmonary epithelium and discuss therapeutic options. The prime sites for infection that will be contrasted in this review are the conducting airways and the gas exchange portions of the lung. These two sites are characterised by distinct cellular composition and innate immune responses, which suggests the use of distinct therapeutic agents. In the nose, ciliated cells are the primary target cells for SARS-CoV-2 viral infection, replication and release. Infected cells shed their cilia, which disables mucociliary clearance. Evidence further points to a suppressed or incompletely activated innate immune response to SARS-CoV-2 infection in the upper airways. Asymptomatic individuals can still have a productive viral infection and infect others. In the gas exchange portion of the lung, the alveolar type II epithelial cell is the main target cell type. Cell death and marked innate immune response during infection likely contribute to alveolar damage and resultant acute respiratory distress syndrome. Alveolar infection can precipitate a hyperinflammatory state, which is the target of many therapies in severe COVID-19. Disease resolution in the lung is variable and may include scaring and long-term sequalae because the alveolar type II cells are also progenitor cells for the alveolar epithelium.
Cigarette smoke (CS) is a highly complex mixture and many of its components are known carcinogens, mutagens, and other toxic substances. CS induces oxidative stress and cell death, and this cell ...toxicity plays a key role in the pathogenesis of several pulmonary diseases.
We studied the effect of cigarette smoke extract (CSE) in human alveolar epithelial type I-like (ATI-like) cells. These are isolated type II cells that are differentiating toward the type I cell phenotype in vitro and have lost many type II cell markers and express type I cell markers. ATI-like cells were more sensitive to CSE than alveolar type II cells, which maintained their differentiated phenotype in vitro. We observed disruption of mitochondrial membrane potential, apoptosis and necrosis that were detected by double staining with acridine orange and ethidium bromide or Hoechst 33342 and propidium iodide and TUNEL assay after treatment with CSE. We also detected caspase 3 and caspase 7 activities and lipid peroxidation. CSE induced nuclear translocation of Nrf2 and increased expression of Nrf2, HO-1, Hsp70 and Fra1. Moreover, we found that Nrf2 knockdown sensitized ATI-like cells to CSE and Nrf2 overexpression provided protection against CSE-induced cell death. We also observed that two antioxidant compounds N-acetylcysteine and trolox protected ATI-like cells against injury by CSE.
Our study indicates that Nrf2 activation is a major factor in cellular defense of the human alveolar epithelium against CSE-induced toxicity and oxidative stress. Therefore, antioxidant agents that modulate Nrf2 would be expected to restore antioxidant and detoxifying enzymes and to prevent CS-related lung injury and perhaps lessen the development of emphysema.
We used functional MRI (fMRI) to assess neural representations of physics concepts (momentum, energy, etc.) in juniors, seniors, and graduate students majoring in physics or engineering. Our goal was ...to identify the underlying neural dimensions of these representations. Using factor analysis to reduce the number of dimensions of activation, we obtained four physics-related factors that were mapped to sets of voxels. The four factors were interpretable as causal motion visualization, periodicity, algebraic form, and energy flow. The individual concepts were identifiable from their fMRI signatures with a mean rank accuracy of .75 using a machine-learning (multivoxel) classifier. Furthermore, there was commonality in participants' neural representation of physics; a classifier trained on data from all but one participant identified the concepts in the left-out participant (mean accuracy = .71 across all nine participant samples). The findings indicate that abstract scientific concepts acquired in an educational setting evoke activation patterns that are identifiable and common, indicating that science education builds abstract knowledge using inherent, repurposed brain systems.
Methylmercury (MeHg) is a contaminant of global concern that bioaccumulates and bioamagnifies in marine food webs. Lower trophic level fauna are important conduits of MeHg from sediment and water to ...estuarine and coastal fish harvested for human consumption. However, the sources and pathways of MeHg to these coastal fisheries are poorly known particularly the potential for transfer of MeHg from the sediment to biotic compartments. Across a broad gradient of human land impacts, we analyzed MeHg concentrations in food webs at ten estuarine sites in the Northeast US (from the Hackensack Meadowlands, NJ to the Gulf of Maine). MeHg concentrations in water column particulate material, but not in sediments, were predictive of MeHg concentrations in fish (killifish and Atlantic silversides). Moreover, MeHg concentrations were higher in pelagic fauna than in benthic-feeding fauna suggesting that MeHg delivery to the water column from methylation sites from within or outside of the estuary may be an important driver of MeHg bioaccumulation in estuarine pelagic food webs. In contrast, bulk sediment MeHg concentrations were only predictive of concentrations of MeHg in the infaunal worms. Our results across a broad gradient of sites demonstrate that the pathways of MeHg to lower trophic level estuarine organisms are distinctly different between benthic deposit feeders and forage fish. Thus, even in systems with contaminated sediments, transfer of MeHg into estuarine food webs maybe driven more by the efficiency of processes that determine MeHg input and bioavailability in the water column.
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