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Cambridge University Press, Cambridge, UK, 2022, 180 pp, £14.99 (paperback), ISBN: 9781009090865
No full textOligoclonal bands and kappa free light chains: Competing parameters or complementary biomarkers?
No full textPerspective: Time irreversibility in systems observed at coarse resolution
No full textA broken time-reversal symmetry, i.e., broken detailed balance, is central to non-equilibrium physics and is a prerequisite for life. However, it turns out to be quite challenging to unambiguously define and quantify time-reversal symmetry (and violations thereof) in practice, that is, from observations. Measurements on complex systems have a finite resolution and generally probe low-dimensional projections of the underlying dynamics, which are well known to introduce memory. In situations where many microscopic states become “lumped” onto the same observable “state” or when introducing “reaction coordinates” to reduce the dimensionality of data, signatures of a broken time-reversal symmetry in the microscopic dynamics become distorted or masked. In this Perspective, we highlight why, in defining and discussing time-reversal symmetry and quantifying its violations, the precise underlying assumptions on the microscopic dynamics, the coarse graining, and further reductions are not a technical detail. These assumptions decide whether the conclusions that are drawn are physically sound or inconsistent. We summarize recent findings in the field and reflect upon key challenges.HORIZON EUROPE European Research Council 10.13039/10001918
Fragility and thermal expansion control crystal melting and the glass transition
No full textAnalytical relations for the glass transition temperature, Tg, and the crystal melting temperature, Tm, are developed on the basis of nonaffine lattice dynamics. The proposed relations explain the following: (i) the seemingly universal factor of ≈2/3 difference between the glass transition temperature and the melting temperature of the corresponding crystal, and (ii) the recent empirical discovery that both Tg and Tm are proportional to the liquid fragility m divided by the thermal expansion coefficient α of the solid.HORIZON EUROPE European Research Council 10.13039/100019180Army Research Office 10.13039/10000018
Opportunities and challenges for the use of human samples in translational cardiovascular research: a scientific statement of the ESC Working Group on Cellular Biology of the Heart, the ESC Working Group on Cardiovascular Surgery, the ESC Council on Basic Cardiovascular Science, the ESC Scientists of Tomorrow, the European Association of Percutaneous Cardiovascular Interventions of the ESC, and the Heart Failure Association of the ESC
No full textAbstract Animal models offer invaluable insights into disease mechanisms but cannot entirely mimic the variability and heterogeneity of human populations, nor the increasing prevalence of multi-morbidity. Consequently, employing human samples—such as whole blood or fractions, valvular and vascular tissues, myocardium, pericardium, or human-derived cells—is essential for enhancing the translational relevance of cardiovascular research. For instance, myocardial tissue slices, which preserve crucial structural and functional characteristics of the human heart, can be used in vitro to examine drug responses. Human blood serves as a rich source of biomarkers, including extracellular vesicles, various types of RNA (miRNA, lncRNA, and circRNAs), circulating inflammatory cells, and endothelial colony-forming cells, facilitating detailed studies of cardiovascular diseases. Primary cardiomyocytes and vascular cells isolated from human tissues are invaluable for mechanistic investigations in vitro. In cases where these are unavailable, human induced pluripotent stem cells serve as effective substitutes, albeit with specific limitations. However, the use of human samples presents challenges such as ethical approvals, tissue procurement and storage, variability in patient genetics and treatment regimens, and the selection of appropriate control samples. Biobanks are central to the efficient use of these scarce and valuable resources. This scientific statement discusses opportunities to implement the use of human samples for cardiovascular research within specific clinical contexts, offers a practical framework for acquiring and utilizing different human materials, and presents examples of human sample applications for specific cardiovascular diseases, providing a valuable resource for clinicians, translational and basic scientists engaged in cardiovascular research
Evolution and co-evolution of the suck behaviour, a postcopulatory female resistance trait that manipulates received ejaculate
No full textAbstract Background Sexual conflicts over the post-mating fate of received ejaculate can favour traits in one sex that are costly to the other. Reciprocally mating hermaphrodites face unique challenges as they mate simultaneously in both the male and female role, potentially leading to receipt of unwanted ejaculate. Reciprocal mating can then give rise to postcopulatory female resistance traits that allow manipulation of received ejaculate. A putative example is the suck behaviour, observed in the flatworm genus Macrostomum . It involves the sperm recipient placing its pharynx over its own female genital opening and appearing to suck, likely removing received ejaculate after mating. The genus also contains hypodermically inseminating species that presumably exhibit unilateral mating and have not been observed to suck. Results Here, we examine the evolution of the suck behaviour in the Macrostomum genus, aiming to document the mating behaviour in 64 species. First, we provide videographic evidence that ejaculate is indeed removed during the suck behaviour in a reciprocally mating species, Macrostomum hamatum . Next, we show positive evolutionary correlations between the presence, duration and frequency of reciprocal mating behaviour and the suck behaviour, providing clear evidence that the suck behaviour co-evolves with reciprocal mating behaviour. Finally, we show an association between reproductive behaviour and reproductive morphology, suggesting that the reproductive morphology can be used to infer a species’ mating behaviour. Conclusions Together, our study demonstrates sexually antagonistic coevolution leading to the evolution of a postcopulatory behavioural trait that functions as a female counter-adaptation allowing individuals to gain control over received ejaculate in a hermaphroditic sexual system
Treatment at the end of life in patients with advanced melanoma. A multicenter DeCOG study of 1067 patients from the prospective skin cancer registry ADOReg
No full textBackground Although systemic therapies have improved considerably over the last decade, up to 50% of patients with metastatic melanoma still die due to disease progression. Oncological treatment at the end-of-life phase is challenging. The aim of this study was to investigate the frequency and type of systemic therapy received by melanoma patients in their end-of-life phase. Methods Patients with metastatic melanoma who had died between January 1, 2018 and October 31, 2022 were identified from the prospective multicenter skin cancer registry ADOReg. Study endpoints were percentage of patients who had been treated with systemic therapy within the last three months of life, timepoint of initiation of the last-line therapy, overall survival, treatment benefit and the incidence of treatment-related adverse events. Results In total, 1067 patients from 46 skin cancer centers were included. Most of the patients (63%) had received immune checkpoint inhibitors (ICI) as last-line therapy, 22% targeted therapies (TT) and 12% chemotherapy (CTX). Comparing last-line ICI and TT, patients with TT were significantly more likely to benefit from treatment and had significantly fewer and milder treatment-related AE than patients with ICI. Even though two thirds of patients had received ICI as a last-line therapy, the majority of these patients (61%) had stopped therapy within the last 30 days of life, whereas the majority of patients with TT (66%) still continued their treatment to the end of life. We found markedly fewer patients with initiation of ICI within 30 days before their death (19%) compared to a historic cohort including patients who died in 2016 or 2017 (39%). Conclusion Treatment approaches near the end of life have markedly changed in skin cancer centers in Germany over recent years, with ICI prescribed less frequently in the end-of-life phase. In contrast, TT are frequently administered, even within the last 30 days of life. It should also be considered that discontinuation of TT can result in rapid tumor progression. Due to the oral administration and a low rate of severe toxicity, TT appear to be a suitable treatment option, even in the end-of-life situation of melanoma patients
Recommendations on how to proceed in case of suspected allergy to penicillin/β-lactam antibiotics. Position paper of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Society for Pediatric Allergology (
No full textRegulation of tocopherol (vitamin E) biosynthesis by abscisic acid-dependent and -independent pathways during abiotic stress in Arabidopsis
No full textAbstract Main conclusion The increase in tocopherol (vitamin E) biosynthesis in Arabidopsis during drought and osmotic stress, but not during high light or nitrogen deprivation, is mediated by abscisic acid. Abstract Plants increase the production of antioxidants including tocochromanols (vitamin E) during stress. To study the regulation of tocochromanol synthesis, Arabidopsis plants were exposed to drought, osmotic stress stimulated by polyethylene glycol, abscisic acid (ABA), nitrogen deprivation, and high light. ABA treatment resulted in increased contents of tocochromanols, and expression of the key tocopherol biosynthesis genes VTE2 and HPPD was upregulated, indicating that tocochromanol accumulation was regulated by ABA. Under drought and osmotic stress, the ABA and tocochromanol contents as well as VTE2 and HPPD expression were also increased. ABA levels did not change during nitrogen deprivation or high light treatment, indicating that tocochromanol accumulation under these conditions was ABA-independent. Tocochromanol accumulation during drought or osmotic stress was not compromised in the ABA-deficient aba1-6 , aba2-1 and aba3-2 mutants, suggesting that tocochromanol synthesis under these conditions was mostly regulated in an ABA-independent way. Therefore, the accumulation of tocochromanols in Arabidopsis can be regulated by ABA-dependent and ABA-independent signaling pathways, based on the specific conditions.Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Rheinische Friedrich-Wilhelms-Universität Bonn http://dx.doi.org/10.13039/50110000813
Modelling microclimatic variability in Andean forests of northern Patagonia
No full textAbstract Information on microclimatic conditions beneath canopies is key to understanding small-scale ecological processes, especially concerning the response of biodiversity to climate change. In north-western Patagonia, where data on climate-driven species distribution are scarce, our study provides valuable insights by providing microclimatic models covering spatiotemporal dynamics at 30 × 30 m resolution. Applying in-situ data from 2022 to 2024, we employed a random forest-based regression to assess the impact of several biophysical predictor variables describing terrain and vegetation properties on four microclimatic response variables at three vertical levels within forests. We also interpolated this data spatiotemporally, using statistical downscaling of ERA5 data. Our analysis reveals that the influence of the predictor variables varies strongly by month and response variable. Moreover, significant variability was observed between the models and months regarding their explanatory power and error range. For instance, the model predicting maximum air temperature at a 2 m height achieved an R² of 0.88 and an RMSE of 1.5 °C, while the model for minimum air temperature resulted in an R² of 0.73 and an RMSE of 1.8 °C. Our model approach provides a benchmark for spatiotemporal projections in this data-scarce region, aligned with the climate normal from 1981 to 2010. Future refinement could benefit from data on snow cover, land use and land cover, soil, as well as structural information on vegetation over an extended period, to enhance the dynamical aspects of microclimatic modelling. We are confident that our present model will substantially enhance possibilities to analyse species distribution across vegetation types and terrain-related features within the area