Endotracheal tube-induced sore throat pain and inflammation is coupled to the release of mitochondrial DNA

In the absence of infection, the pathophysiology of endotracheal tube-induced sore throat pain is unclear. Activated neutrophils release elastase, reactive oxygen species, and inflammatory cytokines known to contribute to neuropathic pain. Sterile tissue injury can cause the release of damage-associated molecular patterns such as mitochondrial DNA that promote neutrophil activation. We hypothesized that endotracheal tube-induced sore throat pain is linked to mitochondrial DNA-mediated neutrophil inflammation. A nonrandomized prospective survey for sore throat pain was conducted in 31 patients who required short-term intubation and had no evidence of upper airway infection. Patterns of neutrophil abundance, activation, and mitochondrial DNA levels were analyzed in tracheal lavage fluid following intubation and prior to extubation. Thirteen of 31 patients reported sore throat pain. Sore throat patients had high neutrophilia with elevated adhesion molecule and TLR9 expression and constitutive reactive oxygen species generation. Tracheal lavage fluid from sore throat patients accumulated mitochondrial DNA and stimulated neutrophils to release mediators associated with pain in a TLR9- and DNAse-dependent fashion. Endotracheal tube-induced sore throat is linked to the release of mitochondrial DNA and can drive TLR9-mediated inflammatory responses by neutrophils reported to cause pain. Mitigating the effects of cell-free mitochondrial DNA may prove beneficial for the prevention of endotracheal tube-mediated sore throat pain

TOWARD TARGET 2 OF THE GLOBAL STRATEGY FOR PLANT CONSERVATION: AN EXPERT ANALYSIS OF THE PUERTO RICAN FLORA TO VALIDATE NEW STREAMLINED METHODS FOR ASSESSING CONSERVATION STATUS

Target 2 of the 2020 Global Strategy for Plant Conservation (GSPC) calls for a comprehensive list of the world\u27s threatened plant species. The lack of such a list is one of the greatest impediments to protecting the full complement of the world\u27s plant species, and work to achieve this has been slow. An efficient system for identifying those species that are at risk of extinction could help to achieve this goal in a time frame sensitive to today\u27s conservation needs. Two systems that efficiently use available data to assess conservation status were tested against a provisional International Union for Conservation of Nature and Natural Resources (IUCN) Red List analysis to evaluate the native seed plant species of Puerto Rico. It was demonstrated that both systems efficiently identify species at risk, which is a step toward both the GSPC Target 2 and a more comprehensive IUCN Red List for plants. Both systems were effective at identifying plant species at risk, with the New York analysis identifying 98% and the Smithsonian analysis 85% of the plant species considered Threatened in the IUCN Red List. Both analyses to some extent overestimated those plants at risk, but the species identified are all range restricted and, thus, of some conservation interest

Carbon Pricing in Climate Policy: Seven Reasons, Complementary Instruments, and Political Economy Considerations

Carbon pricing is a recurrent theme in debates on climate policy. Discarded at the 2009 COP in Copenhagen, it remained part of deliberations for a climate agreement in subsequent years. As there is still much misunderstanding about the many reasons to implement a global carbon price, ideological resistance against it prospers. Here, we present the main arguments for carbon pricing, to stimulate a fair and well-informed discussion about it. These include considerations that have received little attention so far. We stress that a main reason to use carbon pricing is environmental effectiveness at a relatively low cost, which in turn contributes to enhance social and political acceptability of climate policy. This includes the property that corrected prices stimulate rapid environmental innovations. These arguments are underappreciated in the public debate, where pricing is frequently downplayed and the erroneous view that innovation policies are sufficient is widespread. Carbon pricing and technology policies are, though, largely complementary and thus are both needed for effective climate policy. We also comment on the complementarity of other instruments to carbon pricing. We further discuss distributional consequences of carbon pricing and present suggestions on how to address these. Other political economy issues that receive attention are lobbying, co-benefits, international policy coordination, motivational crowding in/out, and long-term commitment. The overview ends with reflections on implementing a global carbon price, whether through a carbon tax or emissions trading. The discussion goes beyond traditional arguments from environmental economics by including relevant insights from energy research and innovation studies as well

Neutrophil extracellular trap fragments stimulate innate immune responses that prevent lung transplant tolerance

Neutrophil extracellular traps (NETs) have been shown to worsen acute pulmonary injury including after lung transplantation. The breakdown of NETs by DNAse-1 can help restore lung function, but whether there is an impact on allograft tolerance remains less clear. Using intravital 2-photon microscopy, we analyzed the effects of DNAse-1 on NETs in mouse orthotopic lung allografts damaged by ischemia-reperfusion injury. Although DNAse-1 treatment rapidly degrades intragraft NETs, the consequential release of NET fragments induces prolonged interactions between infiltrating CD4 + T cells and donor-derived antigen presenting cells. DNAse-1 generated NET fragments also promote human alveolar macrophage inflammatory cytokine production and prime dendritic cells for alloantigen-specific CD4 + T cell proliferation through activating toll-like receptor (TLR) — Myeloid Differentiation Primary Response 88 (MyD88) signaling pathways. Furthermore, and in contrast to allograft recipients with a deficiency in NET generation due to a neutrophil-specific ablation of Protein Arginine Deiminase 4 (PAD4), DNAse-1 administration to wild-type recipients promotes the recognition of allo- and self-antigens and prevents immunosuppression-mediated lung allograft acceptance through a MyD88-dependent pathway. Taken together, these data show that the rapid catalytic release of NET fragments promotes innate immune responses that prevent lung transplant tolerance. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeon

Apyrase treatment prevents ischemia–reperfusion injury in rat lung isografts

ObjectiveEndothelial cells express the ectoenzyme ectonucleoside adenosine triphosphate diphosphohydrolase, an apyrase that inhibits vascular inflammation by catalyzing the hydrolysis of adenosine triphosphate and adenosine diphosphate. However, ectonucleoside adenosine triphosphate diphosphohydrolase expression is rapidly lost following oxidative stress, leading to the potential for adenosine triphosphate and related purigenic nucleotides to exacerbate acute solid organ inflammation and injury. We asked if administration of a soluble recombinant apyrase APT102 attenuates lung graft injury in a cold ischemia reperfusion model of rat syngeneic orthotopic lung transplantation.MethodsMale Fisher 344 donor lungs were cold preserved in a low-potassium dextrose solution in the presence or absence of APT102 for 18 hours prior to transplantation into syngeneic male Fisher 344 recipients. Seven minutes after reperfusion, lung transplant recipients received either a bolus of APT102 or vehicle (saline solution). Four hours after reperfusion, APT102- and saline solution–treated groups were evaluated for lung graft function and inflammation.ResultsAPT102 significantly reduced lung graft extracellular pools of adenosine triphosphate and adenosine diphosphate, improved oxygenation, and protected against pulmonary edema. Apyrase treatment was associated with attenuated neutrophil graft sequestration and less evidence of tissue inflammation as assessed by myeloperoxidase activity, expression of proinflammatory mediators, and numbers of apoptotic endothelial cells.ConclusionsAdministration of a soluble recombinant apyrase promotes lung function and limits the tissue damage induced by prolonged cold storage, indicating that extracellular purigenic nucleotides play a key role in promoting ischemia–reperfusion injury following lung transplantation

Distribution and abundance of western gray whales off northeastern Sakhalin Island, Russia, 2001’003

In 2001’003, >60,000 km of aerial surveys and 7,700 km of vessel surveys were conducted during June to November when critically endangered Korean–Okhotsk or western gray whales (Eschrichtius robustus) were present off the northeast coast of Sakhalin Island, Russia. Results of surveys in all years indicated gray whales occurred in predominantly two areas, (1) adjacent to Piltun Bay, and (2) offshore from Chayvo Bay, hereafter referred to as the Piltun and offshore feeding areas. In the Piltun feeding area, the majority of whales were observed in waters shallower than 20 m and were distributed from several hundred meters to ∼ 5 km from the shoreline. In the offshore feeding area during all years, the distribution of gray whales extended from southwest to northeast in waters 30’5 m in depth. During all years, the distribution and abundance of whales changed in both the Piltun and offshore feeding areas, and both north–south and inshore–offshore movements were documented within and between feeding seasons. The discovery of a significant number of whales feeding in the offshore area each year was a substantial finding of this study and raises questions regarding western gray whale abundance and population levels, feeding behavior and ecology, and individual site-fidelity. Fluctuations in the number of whales observed within the Piltun and offshore feeding areas and few sightings outside of these two areas indicate that gray whales move between the Piltun and offshore feeding areas during their summer–fall feeding season. Seasonal shifts in the distribution and abundance of gray whales between and within both the Piltun and offshore feeding areas are thought, in part, to be a response to seasonal changes in the distribution and abundance of prey. However, the mechanism driving the movements of whales along the northeast coast of Sakhalin Island is likely very complex and influenced by a multitude of factors

Measuring the value of air quality: application of the spatial hedonic model

This study applies a hedonic model to assess the economic benefits of air quality improvement following the 1990 Clean Air Act Amendment at the county level in the lower 48 United States. An instrumental variable approach that combines geographically weighted regression and spatial autoregression methods (GWR-SEM) is adopted to simultaneously account for spatial heterogeneity and spatial autocorrelation. SEM mitigates spatial dependency while GWR addresses spatial heterogeneity by allowing response coefficients to vary across observations. Positive amenity values of improved air quality are found in four major clusters: (1) in East Kentucky and most of Georgia around the Southern Appalachian area; (2) in a few counties in Illinois; (3) on the border of Oklahoma and Kansas, on the border of Kansas and Nebraska, and in east Texas; and (4) in a few counties in Montana. Clusters of significant positive amenity values may exist because of a combination of intense air pollution and consumer awareness of diminishing air quality

Internalization Dissociates β2-Adrenergic Receptors

G protein-coupled receptors (GPCRs) self-associate as dimers or higher-order oligomers in living cells. The stability of associated GPCRs has not been extensively studied, but it is generally thought that these receptors move between the plasma membrane and intracellular compartments as intact dimers or oligomers. Here we show that β2-adrenergic receptors (β2ARs) that self-associate at the plasma membrane can dissociate during agonist-induced internalization. We use bioluminescence-resonance energy transfer (BRET) to monitor movement of β2ARs between subcellular compartments. BRET between β2ARs and plasma membrane markers decreases in response to agonist activation, while at the same time BRET between β2ARs and endosome markers increases. Energy transfer between β2ARs is decreased in a similar manner if either the donor- or acceptor-labeled receptor is mutated to impair agonist binding and internalization. These changes take place over the course of 30 minutes, persist after agonist is removed, and are sensitive to several inhibitors of arrestin- and clathrin-mediated endocytosis. The magnitude of the decrease in BRET between donor- and acceptor-labeled β2ARs suggests that at least half of the receptors that contribute to the BRET signal are physically segregated by internalization. These results are consistent with the possibility that β2ARs associate transiently with each other in the plasma membrane, or that β2AR dimers or oligomers are actively disrupted during internalization

Beta-Arrestin Functionally Regulates the Non-Bleaching Pigment Parapinopsin in Lamprey Pineal

The light response of vertebrate visual cells is achieved by light-sensing proteins such as opsin-based pigments as well as signal transduction proteins, including visual arrestin. Previous studies have indicated that the pineal pigment parapinopsin has evolutionally and physiologically important characteristics. Parapinopsin is phylogenetically related to vertebrate visual pigments. However, unlike the photoproduct of the visual pigment rhodopsin, which is unstable, dissociating from its chromophore and bleaching, the parapinopsin photoproduct is stable and does not release its chromophore. Here, we investigated arrestin, which regulates parapinopsin signaling, in the lamprey pineal organ, where parapinopsin and rhodopsin are localized to distinct photoreceptor cells. We found that beta-arrestin, which binds to stimulated G protein-coupled receptors (GPCRs) other than opsin-based pigments, was localized to parapinopsin-containing cells. This result stands in contrast to the localization of visual arrestin in rhodopsin-containing cells. Beta-arrestin bound to cultured cell membranes containing parapinopsin light-dependently and translocated to the outer segments of pineal parapinopsin-containing cells, suggesting that beta-arrestin binds to parapinopsin to arrest parapinopsin signaling. Interestingly, beta-arrestin colocalized with parapinopsin in the granules of the parapinopsin-expressing cell bodies under light illumination. Because beta-arrestin, which is a mediator of clathrin-mediated GPCR internalization, also served as a mediator of parapinopsin internalization in cultured cells, these results suggest that the granules were generated light-dependently by beta-arrestin-mediated internalization of parapinopsins from the outer segments. Therefore, our findings imply that beta-arrestin-mediated internalization is responsible for eliminating the stable photoproduct and restoring cell conditions to the original dark state. Taken together with a previous finding that the bleaching pigment evolved from a non-bleaching pigment, vertebrate visual arrestin may have evolved from a “beta-like” arrestin by losing its clathrin-binding domain and its function as an internalization mediator. Such changes would have followed the evolution of vertebrate visual pigments, which generate unstable photoproducts that independently decay by chromophore dissociation