Climate change is altering the availability of resources and the conditions that are crucial to plant performance. One way plants will respond to these changes is through environmentally induced ...shifts in phenotype (phenotypic plasticity). Understanding plastic responses is crucial for predicting and managing the effects of climate change on native species as well as crop plants. Here, we provide a toolbox with definitions of key theoretical elements and a synthesis of the current understanding of the molecular and genetic mechanisms underlying plasticity relevant to climate change. By bringing ecological, evolutionary, physiological and molecular perspectives together, we hope to provide clear directives for future research and stimulate cross-disciplinary dialogue on the relevance of phenotypic plasticity under climate change.
Abstract
The Encyclopedia of DNA Elements (ENCODE) Data Coordinating Center has developed the ENCODE Portal database and website as the source for the data and metadata generated by the ENCODE ...Consortium. Two principles have motivated the design. First, experimental protocols, analytical procedures and the data themselves should be made publicly accessible through a coherent, web-based search and download interface. Second, the same interface should serve carefully curated metadata that record the provenance of the data and justify its interpretation in biological terms. Since its initial release in 2013 and in response to recommendations from consortium members and the wider community of scientists who use the Portal to access ENCODE data, the Portal has been regularly updated to better reflect these design principles. Here we report on these updates, including results from new experiments, uniformly-processed data from other projects, new visualization tools and more comprehensive metadata to describe experiments and analyses. Additionally, the Portal is now home to meta(data) from related projects including Genomics of Gene Regulation, Roadmap Epigenome Project, Model organism ENCODE (modENCODE) and modERN. The Portal now makes available over 13000 datasets and their accompanying metadata and can be accessed at: https://www.encodeproject.org/.
The coronary circulation is both culprit and victim of acute myocardial infarction. The rupture of an epicardial atherosclerotic plaque with superimposed thrombosis causes coronary occlusion, and ...this occlusion must be removed to induce reperfusion. However, ischaemia and reperfusion cause damage not only in cardiomyocytes but also in the coronary circulation, including microembolization of debris and release of soluble factors from the culprit lesion, impairment of endothelial integrity with subsequently increased permeability and oedema formation, platelet activation and leucocyte adherence, erythrocyte stasis, a shift from vasodilation to vasoconstriction, and ultimately structural damage to the capillaries with eventual no-reflow, microvascular obstruction (MVO), and intramyocardial haemorrhage (IMH). Therefore, the coronary circulation is a valid target for cardioprotection, beyond protection of the cardiomyocyte. Virtually all of the above deleterious endpoints have been demonstrated to be favourably influenced by one or the other mechanical or pharmacological cardioprotective intervention. However, no-reflow is still a serious complication of reperfused myocardial infarction and carries, independently from infarct size, an unfavourable prognosis. MVO and IMH can be diagnosed by modern imaging technologies, but still await an effective therapy. The current review provides an overview of strategies to protect the coronary circulation from acute myocardial ischaemia/reperfusion injury. This article is part of a Cardiovascular Research Spotlight Issue entitled 'Cardioprotection Beyond the Cardiomyocyte', and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.
Using the context of the 2021 U.S. Capitol riot, an attack on the U.S Congress that was in response to the alleged voter fraud perpetuated by high profile Republicans, this study sought to uncover ...the differences in content memory (i.e., free recall and recognition) scores for both factually correct and disinformation news content. In addition, it also explored how exposure to different message modalities (i.e., text, image, and video) may exacerbate the recall and recollection of news content, especially when presented with purposely misleading information. An online experiment (n = 568) using manipulated mock news articles was conducted to gauge participants' content memory for participants exposed to either factually correct or disinformation news content. Findings showcase that while there is no significant difference in content memory scores between those exposed to disinformation and factually correct news, partisans might be more tempted to purposely remember story details that support their party regardless of whether those details are accurate. Moreover, while modality may help in aiding one's memory for information, other factors such as expectancy-violation should be integrated with existing multimedia learning theories when applying the cognitive processing logic of modality to news consumption.
•Disinformation news content is recalled at a similar rate as content that is factually correct.•Partisans might be more tempted to communicate story details that support their party regardless if it is accurate.•Exposure to text and image articles generated greater recall when compared to video for non-disinformation news.•Exposure to the text article and video generated greater recall when compared to the image article for disinformation news.•Expectancy-violation may explain differentiating rates of recall across modalities and news types.
As climate change challenges organismal fitness by creating a phenotype–environment mismatch, phenotypic plasticity generated by epigenetic mechanisms (e.g., DNA methylation) can provide a temporal ...buffer for genetic adaptation. Epigenetic mechanisms may be crucial for sessile benthic marine organisms, such as reef‐building corals, where ocean acidification (OA) and warming reflect in strong negative responses. We tested the potential for scleractinian corals to exhibit phenotypic plasticity associated with a change in DNA methylation in response to OA. Clonal coral fragments of the environmentally sensitive Pocillopora damicornis and more environmentally robust Montipora capitata were exposed to fluctuating ambient pH (7.9–7.65) and low pH (7.6–7.35) conditions in common garden tanks for ~6 weeks. M. capitata responded weakly, or acclimated more quickly, to OA, with no difference in calcification, minimal separation of metabolomic profiles, and no change in DNA methylation between treatments. Conversely, P. damicornis exhibited diminished calcification at low pH, stronger separation in metabolomic profiles, and responsiveness of DNA methylation to treatment. Our data suggest corals differ in their temporal dynamics and sensitivity for environmentally triggered real‐time epigenetic reprogramming. The generation of potentially heritable plasticity via environmental induction of DNA methylation provides an avenue for assisted evolution applications in corals under rapid climate change.
Localist Administrative Law DAVIDSON, NESTOR M.
The Yale law journal,
01/2017, Letnik:
126, Številka:
3
Journal Article
To read the voluminous literature on administrative law is to inhabit a world focused almost exclusively on federal agencies. This myopic view, however, ignores the wide array of administrative ...bodies that make and implement policy at the local-government level. The administrative law that emerges from the vast subterranean regulatory state operating within cities, suburbs, towns, and counties has gone largely unexamined. Not only are scholars ignoring a key area of governance, but courts have similarly failed to develop an administrative jurisprudence that recognizes what is distinctive about local agencies. The underlying justifications for core administrative law doctrines at the federal level, such as deference to agency expertise and respect for separation of powers, must be adapted for local contexts in which mayors can sit on city councils, agencies may operate with few clear procedural constraints, and ordinary citizens can play a direct role in determining policy. To remedy these gaps in the literature and the doctrine, this Article makes three contributions. First, it offers a detailed descriptive account of local administration, outlining domains of local agency action, the governmental structures that define those agencies, and practical details of local agency operation. The Article then draws from this empirical grounding to identify particularly salient factors that can more transparently inform judicial review of a variety of local agency actions, from statutory interpretation to substantive policymaking to enforcement and licensing. These factors include the particular and varied nature of local-government structures, the tension between informality and procedural legitimacy within local administration, the mottled interplay of public and private spheres in local governance, and local agency expertise that reflects local knowledge. This localist perspective, finally, has direct relevance to core scholarly debates in both localgovernment law and administrative law. An understanding of local administration adds a layer of internal complexity to questions of local-government authority and identity, reorienting discussions about democratic accountability and experimentalism. It likewise holds the promise of deepening administrative jurisprudence with a perspective that reaches across the entire range of our vertical federalism. In short, the world of local agencies opens a window for the study of an important, yet underappreciated, set of institutions. Calling attention to these agencies will ultimately foster a new discourse about administrative law for local-government scholars and a broader understanding of governance for scholars of administrative law.
Background. Clostridium difficile infection (CDI) is a common complication of antibiotic therapy that is treated with antibiotics, contributing to ongoing disruption of the colonic microbiota and CDI ...recurrence. Two multinational trials were conducted to compare the efficacy of tolevamer, a nonantibiotic, toxin-binding polymer, with vancomycin and metronidazole. Methods. Patients with CDI were randomly assigned in a 2:1:1 ratio to oral tolevamer 9 g (loading dose) followed by 3 g every 8 hours for 14 days, vancomycin 125 mg every 6 hours for 10 days, or metronidazole 375 mg every 6 hours for 10 days. The primary endpoint was clinical success, defined as resolution of diarrhea and absence of severe abdominal discomfort for more than 2 consecutive days including day 10. Results. In a pooled analysis, 563 patients received tolevamer, 289 received metronidazole, and 266 received vancomycin. Clinical success of tolevamer was inferior to both metronidazole and vancomycin (P < .001), and metronidazole was inferior to vancomycin (P = .02; 44.2% n = 534, 72.7% n = 278, and 81.1% n = 259, respectively). Clinical success in patients with severe CDI who received metronidazole was 66.3% compared with vancomycin, which was 78.5%. (P = .059). A post-hoc multivariate analysis that excluded tolevamer found 3 factors that were strongly associated with clinical success: vancomycin treatment, treatment-naive status, and mild or moderate CDI severity. Adverse events were similar among the treatment groups. Conclusions. Tolevamer was inferior to antibiotic treatment of CDI, and metronidazole was inferior to vancomycin. Trial Registration. clinicaltrials.gov NCT00106509 and NCT00196794.
ABSTRACT
Here, we define dynamic reciprocity (DR) as an ongoing, bidirectional interaction among cells and their surrounding microenvironment. In this review, we posit that DR is especially ...meaningful during wound healing as the DR‐driven biochemical, biophysical, and cellular responses to injury play pivotal roles in regulating tissue regenerative responses. Such cell–extracellular matrix interactions not only guide and regulate cellular morphology, but also cellular differentiation, migration, proliferation, and survival during tissue development, including, e.g., embryogenesis, angiogenesis, as well as during pathologic processes including cancer, diabetes, hypertension, and chronic wound healing. Herein, we examine DR within the wound microenvironment while considering specific examples across acute and chronic wound healing. This review also considers how a number of hypotheses that attempt to explain chronic wound pathophysiology may be understood within the DR framework. The implications of applying the principles of DR to optimize wound care practice and future development of innovative wound healing therapeutics are also briefly considered.
Macropinocytosis is a highly conserved endocytic process by which extracellular fluid and its contents are internalized into cells through large, heterogeneous vesicles known as macropinosomes. ...Oncogenic Ras proteins have been shown to stimulate macropinocytosis but the functional contribution of this uptake mechanism to the transformed phenotype remains unknown. Here we show that Ras-transformed cells use macropinocytosis to transport extracellular protein into the cell. The internalized protein undergoes proteolytic degradation, yielding amino acids including glutamine that can enter central carbon metabolism. Accordingly, the dependence of Ras-transformed cells on free extracellular glutamine for growth can be suppressed by the macropinocytic uptake of protein. Consistent with macropinocytosis representing an important route of nutrient uptake in tumours, its pharmacological inhibition compromises the growth of Ras-transformed pancreatic tumour xenografts. These results identify macropinocytosis as a mechanism by which cancer cells support their unique metabolic needs and point to the possible exploitation of this process in the design of anticancer therapies.
Ischaemia-reperfusion injury occurs when the blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic ...tissue is essential for survival, it also initiates oxidative damage, cell death and aberrant immune responses through the generation of mitochondrial reactive oxygen species (ROS). Although mitochondrial ROS production in ischaemia reperfusion is established, it has generally been considered a nonspecific response to reperfusion. Here we develop a comparative in vivo metabolomic analysis, and unexpectedly identify widely conserved metabolic pathways responsible for mitochondrial ROS production during ischaemia reperfusion. We show that selective accumulation of the citric acid cycle intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase, which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. After reperfusion, the accumulated succinate is rapidly re-oxidized by succinate dehydrogenase, driving extensive ROS generation by reverse electron transport at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo ischaemia-reperfusion injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of ischaemia-reperfusion injury. Furthermore, these findings reveal a new pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation after subsequent reperfusion is a potential therapeutic target to decrease ischaemia-reperfusion injury in a range of pathologies.
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