Statistical indicators of Arctic sea-ice stability-prospects and limitations

This is the final version of the article. Available from the European Geosciences Union via the DOI in this record.We examine the relationship between the mean and the variability of Arctic sea-ice coverage and volume in a large range of climates from globally ice-covered to globally ice-free conditions. Using a hierarchy of two column models and several comprehensive Earth system models, we consolidate the results of earlier studies and show that mechanisms found in simple models also dominate the interannual variability of Arctic sea ice in complex models. In contrast to predictions based on very idealised dynamical systems, we find a consistent and robust decrease of variance and autocorrelation of sea-ice volume before summer sea ice is lost. We attribute this to the fact that thinner ice can adjust more quickly to perturbations. Thereafter, the autocorrelation increases, mainly because it becomes dominated by the ocean water's large heat capacity when the ice-free season becomes longer. We show that these changes are robust to the nature and origin of climate variability in the models and do not depend on whether Arctic sea-ice loss occurs abruptly or irreversibly. We also show that our climate is changing too rapidly to detect reliable changes in autocorrelation of annual time series. Based on these results, the prospects of detecting statistical early warning signals before an abrupt sea-ice loss at a "tipping point" seem very limited. However, the robust relation between state and variability can be useful to build simple stochastic climate models and to make inferences about past and future sea-ice variability from only short observations or reconstructions.This work was carried out under the programme of the Netherlands Earth System Science Centre (NESSC), financially supported by the Ministry of Education, Culture and Science (OCW). We also acknowledge the World Climate Research Programme’s Working Group on Coupled Modelling, which is responsible for CMIP, and we thank the climate modelling groups for producing and making available their model output. We thank Vasilis Dakos for helping to apply his early warnings R package and Chao Li for making available the MPI-ESM model output. S. B. gratefully acknowledges Arie Staal for his fruitful and revealing approaches to savour scientific achievements. We are also indebted to Till Wagner and Ian Eisenman for their valuable comments and their very amiable and cooperative spirit. Finally, we acknowledge two anonymous reviewers who helped us to improve the manuscript

Publisher Correction: Enhanced clay formation key in sustaining the Middle Eocene Climatic Optimum (Nature Geoscience, (2023), 16, 8, (730-738), 10.1038/s41561-023-01234-y)

Correction to: Nature Geoscience, published online 31 July 2023. In the version of the article originally published, a reference was missing from the seventh paragraph of the “A global shift towards enhanced clay formation” section and the first paragraph of the “Further information on the successful model Scenario 8” section (in the latter instance, the reference is cited in the added text “although a global reorganisation of the silicon cycle may have also played a part”). The reference—Dunlea, A. G. et al. Cenozoic global cooling and increased seawater Mg/Ca via reduced reverse weathering. Nat. Commun. 8, 844 (2017)—has now been inserted as new ref. 54. In the “Data treatment and availability section”, the isotopic data, which can be found in the Figshare data repository at , were incorrectly said to be found in the PANGAEA data repository. These corrections have been made in the HTML and PDF versions of the article

Periarticular Bone Changes in Osteoarthritis

Osteoarthritis (OA) can be considered an organ failure with pathological aspects in cartilage, bone, ligaments, and synovium. Altogether, these tissue changes can result in pain and immobilization—a failure of the joint. It is well regarded that OA is a complex multifactorial disease with many risk factors and different etiological pathways that all lead to an apparently similar end stage. Bony changes are clearly observed in advanced OA. However, little understanding exists on the role of these changes, whether they are a consequence of cartilage damage or precede this damage and maybe play an important role in the etiological process. Even more important is the issue of pain. Radiological scores of OA do not match well with pain and mobility scores, which questions the value of these scoring systems. It seems that we do not assess the most relevant parameters. Evaluation of conventional and new radiographic parameters is still an extensive part of the OA research field. We may have overlooked certain (subtle) parameters that can be extracted from x-rays, but other imaging modalities such as MRI, CT, or SPECT might better represent OA in a clinically relevant manner

The Impact of Central and Peripheral Cyclooxygenase Enzyme Inhibition on Exercise-induced Core Body Temperature Elevations.

PURPOSE: Exercise increases core body temperature (TC) due to metabolic heat production. However, the exercise-induced release of inflammatory cytokines including interleukin-6 may also contribute to the rise in TC by increasing the hypothalamic temperature setpoint. We aimed to investigate whether the exercise-induced increase in TC is partly caused by an altered hypothalamic temperature setpoint. METHODS: 15 healthy, active male subjects aged 36±14 years were recruited. Subjects performed submaximal treadmill exercise in 3 randomized test conditions: (1) ibuprofen 400mg and acetaminophen 1000mg (IBU/APAP), (2) acetaminophen 1000mg (APAP) and (3) a control condition (CTRL). Acetaminophen and ibuprofen were used to block the effect of interleukin-6 at a central and peripheral level, respectively. TC, skin temperature and heart rate were measured continuously during the submaximal exercise tests. RESULTS: Baseline values of TC, skin temperature and heart rate did not differ across conditions. Serum interleukin-6 concentrations increased in all three conditions. A significantly lower peak TC was observed in IBU/APAP (38.8±0.4°C) versus CTRL (39.2±0.5°C, p=0.02), but not in APAP (38.9±0.4°C) versus CTRL. Similarly, a lower ΔTC was observed in IBU/APAP (1.7±0.3°C) versus CTRL (2.0±0.5°C, p<0.02), but not in APAP (1.7±0.5°C) versus CTRL. No differences were observed in skin temperature and heart rate responses across conditions. CONCLUSIONS: The combined administration of acetaminophen and ibuprofen resulted in an attenuated increase in TC during exercise when compared to a control condition. This observation suggests that a prostaglandin E2 induced elevated hypothalamic temperature setpoint may contribute to the exercise-induced rise in TC

A novel chemogenomics analysis of G protein-coupled receptors (GPCRs) and their ligands: a potential strategy for receptor de-orphanization.

BACKGROUND: G protein-coupled receptors (GPCRs) represent a family of well-characterized drug targets with significant therapeutic value. Phylogenetic classifications may help to understand the characteristics of individual GPCRs and their subtypes. Previous phylogenetic classifications were all based on the sequences of receptors, adding only minor information about the ligand binding properties of the receptors. In this work, we compare a sequence-based classification of receptors to a ligand-based classification of the same group of receptors, and evaluate the potential to use sequence relatedness as a predictor for ligand interactions thus aiding the quest for ligands of orphan receptors. RESULTS: We present a classification of GPCRs that is purely based on their ligands, complementing sequence-based phylogenetic classifications of these receptors. Targets were hierarchically classified into phylogenetic trees, for both sequence space and ligand (substructure) space. The overall organization of the sequence-based tree and substructure-based tree was similar; in particular, the adenosine receptors cluster together as well as most peptide receptor subtypes (e.g. opioid, somatostatin) and adrenoceptor subtypes. In ligand space, the prostanoid and cannabinoid receptors are more distant from the other targets, whereas the tachykinin receptors, the oxytocin receptor, and serotonin receptors are closer to the other targets, which is indicative for ligand promiscuity. In 93% of the receptors studied, de-orphanization of a simulated orphan receptor using the ligands of related receptors performed better than random (AUC > 0.5) and for 35% of receptors de-orphanization performance was good (AUC > 0.7). CONCLUSIONS: We constructed a phylogenetic classification of GPCRs that is solely based on the ligands of these receptors. The similarities and differences with traditional sequence-based classifications were investigated: our ligand-based classification uncovers relationships among GPCRs that are not apparent from the sequence-based classification. This will shed light on potential cross-reactivity of GPCR ligands and will aid the design of new ligands with the desired activity profiles. In addition, we linked the ligand-based classification with a ligand-focused sequence-based classification described in literature and proved the potential of this method for de-orphanization of GPCRs.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are