Standard information reporting helps to ensure that assay conditions and data are consistently reported and to facilitate inter-laboratory comparisons. Here, we present recommendations on minimum information for reporting on the TEER (trans-epithelial/endothelial electrical resistance) assay (MIRTA). The TEER assay is extensively used to evaluate the health of an epithelial/endothelial cell culture model and as an indicator of the potential toxicity of a test substance. This publication is the result of an international collaboration─called the RespTox (Respiratory Toxicity) Collaborative─through which twelve laboratories shared their protocols for assessing the barrier function of respiratory epithelial cells using the TEER assay following exposure to substances. The protocols from each laboratory were reviewed to identify general steps for performing the TEER assay, interlaboratory differences between steps, the rationale for differences, whether these differences impact results or cross-laboratory comparisons between TEER measurements. While the MIRTA recommendations are focused on respiratory epithelial cell systems, these recommendations can be adapted for other cell systems that form barriers. The use of these recommendations will support data transparency and reproducibility, reduce challenges in data interpretation, enable cross-laboratory comparisons, help assess study quality, and facilitate the incorporation of the TEER assay into national and international testing guidance.

Einleitung

Barrieren beim Zugang zur Schwangerschaftsabbruchversorgung können die Inanspruchnahme von Versorgungsleistungen verzögern, was zu einem zeitlich verzögerten Schwangerschaftsabbruch und gesundheitlichen Risiken führen kann. Zu Barrieren gehören u. a. die räumliche Erreichbarkeit, Geheimhaltung, Wartezeiten, Stigmatisierung, schlechte oder schlecht zugängliche Informationen und Kosten für einen Abbruch. Im Beitrag werden Barrieren beim Zugang zur Schwangerschaftsabbruchversorgung in Deutschland untersucht. Eingeschlossen werden Barrieren in der Verfügbarkeit und Erreichbarkeit von Versorgungsangeboten, im Zugang zu Informationen, den Kosten für einen Abbruch sowie organisatorische Hindernisse.

Methoden

Die Analysen basieren auf den Daten einer Online-Querschnittsbefragung von 594 Frauen mit Schwangerschaftsabbruch in Deutschland, die im Rahmen der ELSA-Studie 2021 und 2022 durchgeführt wurde.

Ergebnisse

Die Ergebnisse zeigen, dass auch in Deutschland der Zugang zu einem Schwangerschaftsabbruch für viele Frauen mit unterschiedlichen Hürden verbunden ist. 80,1 % der Befragten gaben mindestens eine Barriere beim Zugang zum Schwangerschaftsabbruch an, 65,5 % mehr als 2 und 3 und mehr Barrieren wurden von 40,5 % der Befragten angegeben. Besonders die Geheimhaltung des Eingriffs und damit einhergehende Stigmatisierungsängste stellten für viele Teilnehmerinnen Hürden dar.

Diskussion und Fazit

Die Studienergebnisse unterstreichen die Notwendigkeit, den Zugang zu sicheren Schwangerschaftsabbrüchen zu verbessern. Zum Abbau der Zugangsbarrieren gehören daher die Entkriminalisierung, eine flächendeckende Versorgungsstruktur, finanzielle Unterstützungsangebote, verbesserte Informationsangebote sowie der Abbau von Stigmatisierung und Diskriminierung.

Generalized lipodystrophy is a feature of various hereditary disorders, often leading to a progeroid appearance. In the present study we identified a missense and a frameshift variant in a compound heterozygous state in SUPT7L in a boy with intrauterine growth retardation, generalized lipodystrophy, and additional progeroid features. SUPT7L encodes a component of the transcriptional coactivator complex STAGA. By transcriptome sequencing, we showed the predicted missense variant to cause aberrant splicing, leading to exon truncation and thereby to a complete absence of SUPT7L in dermal fibroblasts. In addition, we found altered expression of genes encoding DNA repair pathway components. This pathway was further investigated and an increased rate of DNA damage was detected in proband-derived fibroblasts and genome-edited HeLa cells. Finally, we performed transient overexpression of wildtype SUPT7L in both cellular systems, which normalizes the number of DNA damage events. Our findings suggest SUPT7L as a novel disease gene and underline the link between genome instability and progeroid phenotypes.

Mastophorus muris (Gmelin, 1790) is a globally distributed parasitic nematode of broad range mammals. The taxonomy within the genus Mastophorus and the cryptic diversity among the genus are controversial among taxonomists. This study provides a detailed morphological description of M. muris from Mus musculus combined with a molecular phylogenetic approach. Moreover, descriptions and molecular data of M. muris from non- Mus rodents and wildcats complement our findings and together provide new insights into their taxonomy. The analysis of M. muris was based on light microscopy and scanning electron microscopy. The morphological description focused on the dentition pattern of the two trilobed pseudolabia. Additionally, we described the position of the vulva, arrangement of caudal pairs of papillae, spicules and measured specimens from both sexes and the eggs. For the molecular phylogenetic approach, we amplified the small subunit ribosomal RNA gene and the internal transcribed spacer, and the cytochrome c oxidase subunit 1. Mastophorus morphotypes based on dentition patterns and phylogenetic clustering indicate a subdivision of the genus in agreement with their host. We recognize two groups without a change to formal taxonomy: One group including those specimens infecting Mus musculus , and the second group including organisms infecting non- Mus rodents. Our genetic and morphological data shed light into the cryptic diversity within the genus Mastopohorus. We identified two host-associated groups of M. muris. The described morphotypes and genotypes of M. muris allow a consistent distinction between host-associated parasites.

Sclerostin (SOST) is produced by osteocytes and is known as a negative regulator of bone homeostasis. Parathyroid hormone (PTH) regulates calcium, phosphate as well as vitamin D metabolism, and is a strong inhibitor of SOST synthesis in vitro and in vivo. PTH has two methionine amino acids (positions 8 and 18) which can be oxidized. PTH oxidized at Met18 (Met18(ox)-PTH) continues to be bioactive, whereas PTH oxidized at Met8 (Met8(ox)-PTH) or PTH oxidized at Met8 and Met18 (Met8, Met18(di-ox)-PTH) has minor bioactivity. How non-oxidized PTH (n-oxPTH) and oxidized forms of PTH act on sclerostin synthesis is unknown. The effects of n-oxPTH and oxidized forms of PTH on SOST gene expression were evaluated in UMR106 osteoblast-like cells. Moreover, we analyzed the relationship of SOST with n-oxPTH and all forms of oxPTH in 516 stable kidney transplant recipients using an assay system that can distinguish in clinical samples between n-oxPTH and the sum of all oxidized PTH forms (Met8(ox)-PTH, Met18(ox)-PTH, and Met8, Met18(di-ox)-PTH). We found that both n-oxPTH and Met18(ox)-PTH at doses of 1, 3, 20, and 30 nmol/L significantly inhibit SOST gene expression in vitro, whereas Met8(ox)-PTH and Met8, Met18(di-ox)-PTH only have a weak inhibitory effect on SOST gene expression. In the clinical cohort, multivariate linear regression showed that only n-oxPTH, but not intact PTH (iPTH) nor oxPTH, is independently associated with circulating SOST after adjusting for known confounding factors. In conclusion, only bioactive PTH forms such as n-oxPTH and Met18(ox)-PTH, inhibit SOST synthesis.

Okadaic acid (OA), a prevalent marine biotoxin found in shellfish, is known for causing acute gastrointestinal symptoms. Despite its potential to reach the bloodstream and the liver, the hepatic effects of OA are not well understood, highlighting a significant research gap. This study aims to comprehensively elucidate the impact of OA on the liver by examining the transcriptome, proteome, and phosphoproteome alterations in human HepaRG liver cells exposed to non-cytotoxic OA concentrations. We employed an integrative multi-omics approach, encompassing RNA sequencing, shotgun proteomics, phosphoproteomics, and targeted DigiWest analysis. This enabled a detailed exploration of gene and protein expression changes, alongside phosphorylation patterns under OA treatment. The study reveals concentration- and time-dependent deregulation in gene and protein expression, with a significant down-regulation of xenobiotic and lipid metabolism pathways. Up-regulated pathways include actin crosslink formation and a deregulation of apoptotic pathways. Notably, our results revealed that OA, as a potent phosphatase inhibitor, induces alterations in actin filament organization. Phosphoproteomics data highlighted the importance of phosphorylation in enzyme activity regulation, particularly affecting proteins involved in the regulation of the cytoskeleton. OA's inhibition of PP2A further leads to various downstream effects, including alterations in protein translation and energy metabolism. This research expands the understanding of OA's systemic impact, emphasizing its role in modulating the phosphorylation landscape, which influences crucial cellular processes. The results underscore OA's multifaceted effects on the liver, particularly through PP2A inhibition, impacting xenobiotic metabolism, cytoskeletal dynamics, and energy homeostasis. These insights enhance our comprehension of OA's biological significance and potential health risks.

Loss-of-function variants in ATP6V0A2 , encoding the trans Golgi V-ATPase subunit V0a2, cause wrinkly skin syndrome (WSS), a connective tissue disorder with glycosylation defects and aberrant cortical neuron migration. We used knock-out ( Atp6v0a2 −/− ) and knock-in ( Atp6v0a2 RQ/RQ ) mice harboring the R755Q missense mutation selectively abolishing V0a2-mediated proton transport to investigate the WSS pathomechanism. Homozygous mutants from both strains displayed a reduction of growth, dermis thickness, and elastic fiber formation compatible with WSS. A hitherto unrecognized male infertility due to globozoospermia was evident in both mouse lines with impaired Golgi-derived acrosome formation and abolished mucin-type O-glycosylation in spermatids. Atp6v0a2 −/− mutants showed enhanced fucosylation and glycosaminoglycan modification, but reduced levels of glycanated decorin and sialylation in skin and/or fibroblasts, which were absent or milder in Atp6v0a2 RQ/RQ . Atp6v0a2 RQ/RQ mutants displayed more abnormal migration of cortical neurons, correlating with seizures and a reduced O-mannosylation of α-dystroglycan. While anterograde transport within the secretory pathway was similarly delayed in both mutants the brefeldin A-induced retrograde fusion of Golgi membranes with the endoplasmic reticulum was less impaired in Atp6v0a2 RQ/RQ . Measurement of the pH in the trans Golgi compartment revealed a shift from 5.80 in wildtype to 6.52 in Atp6v0a2 −/− and 6.25 in Atp6v0a2 RQ/RQ . Our findings suggest that altered O-glycosylation is more relevant for the WSS pathomechanism than N-glycosylation and leads to a secondary dystroglycanopathy. Most phenotypic and cellular properties correlate with the different degrees of trans Golgi pH elevation in both mutants underlining the fundamental relevance of pH regulation in the secretory pathway.

As the performance of weather and climate forecasting systems and their benchmark systems are generally not homogeneous in time and space and may vary in specific situations, improvements in certain situations or subsets have different effects on overall skill. We present a decomposition of skill scores for the conditional verification of such systems. The aim is to evaluate the performance of a system individually for predefined subsets with respect to the overall performance. The overall skill score is decomposed into a weighted sum representing subset contributions , where each individual contribution is the product of the following: (1) the subset skill score , assessing the performance of a forecast system compared to a reference system for a particular subset; (2) the frequency weighting , accounting for varying subset size; and (3) the reference weighting , relating the performance of the reference system in the individual subsets to the performance of the full data set. The decomposition and its interpretation are exemplified using synthetic data. Subsequently, we use it for a practical example from the field of decadal climate prediction: an evaluation of the Atlantic European near-surface temperature forecast from the German “Mittelfristige Klimaprognosen” (MiKlip) initiative decadal prediction system that is conditional on different Atlantic Multidecadal Oscillation (AMO) phases during initialization. With respect to the chosen western European North Atlantic sector, the decadal prediction system “preop-dcpp-HR” performs better than the uninitialized simulations mostly due to contributions during the positive AMO phase driven by the subset skill score. Compared to the low-resolution system (preop-LR), no overall performance benefits are made in this region, but positive contributions are achieved for initialization in neutral AMO phases. Additionally, the decomposition reveals a strong imbalance among the subsets (defined by AMO phases) in terms of reference weighting, allowing for insightful interpretation and conclusions. This skill score decomposition framework for conditional verification is a valuable tool to analyze the effect of physical processes on forecast performance and, consequently, supports model development and the improvement of operational forecasts.

Introduction: The adaptability of intertidal gastropods to their environmental niches is a critical aspect of their survival. Littorina brevicula, a common intertidal snail, exhibits phenotypic plasticity in response to varying tidal conditions. This study investigates the phenotypic plasticity and shell structure of L. brevicula across two disparate tidal zones to understand how these factors influence shell morphology and growth.

Methods: A total of 254 specimens of L. brevicula were collected from the intertidal expanse. The analytical approach was tripartite, including traditional morphometric techniques, geometric morphometric methods (GM), and three-dimensional (3D) model simulation analyses. This comprehensive methodology allowed for a detailed examination of shell morphology and growth patterns.

Results: The results demonstrated that shell growth in the high tidal zone was slower compared to the mid tidal zone. Morphological disparities were evident, with high tidal zone specimens showing lower spires and a more spherical shell conformation, while mid tidal zone specimens had elongated spires and a tower-like shell shape. 3D model simulation analyses revealed different stress distributions; the mid-tide zone simulation showed concentrated stress in a circumscribed region, whereas the high-tide zone simulation showed a more expansive stress distribution across the entire shell.

Discussion: The distinct morphological adaptations observed in L. brevicula across tidal zones suggest a strong influence of environmental factors on shell morphology. The slower growth and different stress distribution patterns in the high tidal zone may be indicative of the snails' response to more challenging environmental conditions. These findings provide essential evidence for understanding the adaptability of intertidal gastropods to their environmental niches.

Scene recognition is a core sensory capacity that enables humans to adaptively interact with their environment. Despite substantial progress in the understanding of the neural representations underlying scene recognition, the relevance of these representations for behavior given varying task demands remains unknown. To address this, we aimed to identify behaviorally relevant scene representations, to characterize them in terms of their underlying visual features, and to reveal how they vary across different tasks. We recorded fMRI data while human participants viewed scenes and linked brain responses to behavior in three tasks acquired in separate sessions: man-made/natural categorization, basic-level categorization, and fixation color discrimination. We found correlations between categorization response times and scene-specific brain responses, quantified as the distance to a hyperplane derived from a multivariate classifier. Across tasks, these effects were found in largely distinct parts of the ventral visual stream. This suggests that different scene representations are relevant for behavior depending on the task. Next, using deep neural networks as a proxy for visual feature representations, we found that intermediate layers mediated the relationship between scene representations and behavior for both categorization tasks, indicating a contribution of mid-level visual features to these representations. Finally, we observed opposite patterns of brain-behavior correlations in the man-made/natural and the fixation task, indicating interference of representations with behavior for task demands that do not align with the content of representations. Together, these results reveal the spatial extent, content, and task-dependence of the visual representations that mediate behavior in complex scenes.

Regional regime complexity has long been on the rise and carries a series of potential negative effects, such as waste of resources or reduced effectiveness of regional governance. This article investigates a specific strategy of how states cope with regime complexity, namely by exiting regional international organizations (RIOs). We develop hypotheses on how different types of regional regime complexity influence the chances for exits to occur and theorize interaction effects. The analysis reveals that higher levels of membership- and competency-based regime complexity as well as RIO incompatibility increase the likelihood of state withdrawals. In addition, state characteristics moderate this effect and influence who leaves which organization. Most importantly, smaller rather are less able to shape RIO policies and activities and have fewer capacities to implement them and are thus more likely to exit one of the organizations when being member in many overlapping RIOs. By contrast, powerful states can better navigate regime complexity and avoid negative side-effects and are therefore less inclined to withdraw from RIOs in situations of high regional regime complexity.

By simulation and asymptotic theory, we investigate the transition-path time of a one-dimensional finite-mass reaction coordinate crossing a double-well potential in the presence of non-Markovian friction. First, we consider single-exponential memory kernels and demonstrate that memory accelerates transition paths compared to the Markovian case, especially in the low-mass/high-friction limit. Then, we generalize to multi-exponential kernels and construct an asymptotic formula for the transition-path time that compares well with simulation data.

In molecular physics, it is often necessary to average over the orientation of molecules when calculating observables, in particular when modeling experiments in the liquid or gas phase. Evaluated in terms of Euler angles, this is closely related to integration over two- or three-dimensional unit spheres, a common problem discussed in numerical analysis. The computational cost of the integration depends significantly on the quadrature method, making the selection of an appropriate method crucial for the feasibility of simulations. After reviewing several classes of spherical quadrature methods in terms of their efficiency and error distribution, we derive guidelines for choosing the best quadrature method for orientation averages and illustrate these with three examples from chiral molecule physics. While Gauss quadratures allow for achieving numerically exact integration for a wide range of applications, other methods offer advantages in specific circumstances. Our guidelines can also be applied to higher-dimensional spherical domains and other geometries. We also present a Python package providing a flexible interface to a variety of quadrature methods.

We investigate the anisotropic frequency-dependent dielectric, THz and IR response of liquid water confined between two planar graphene sheets with force-field- and density-functional-theory-based molecular dynamics simulations. Using spatially resolved anisotropic spectra, we demonstrate the critical role of the volume over which the spectral response is integrated when reporting spatially averaged electric susceptibilities. To analyze the spectra, we introduce a unique decomposition into bulk, interfacial, and confinement contributions, which reveals that confinement effects on the spectra occur only for systems with graphene separation below 1.4 nm, for all frequencies. Based on this decomposition, we discuss the molecular origin of the main absorption features of nanoconfined water from the GHz to the IR regime. We show that, at low frequencies, the 15 GHz Debye peak of interfacial water is redshifted due to a slowdown of collective water reorientations. At high frequencies, the OH stretch at 100 THz blue shifts and a signature of free OH groups emerges, while the HOH bend mode at 50 THz is redshifted. Strikingly, in nanoconfinement, the 20 THz libration band shifts to below 15 THz and broadens drastically, spanning two orders of magnitude in frequency. These results are rationalized by the collective water motion and the structure of the hydrogen-bond network at the water–graphene interface and in two-dimensional water layers, which reveals the intricate behavior of nanoconfined water and its spectral properties.

A dichloromethane (DCM) extract of carrot roots was found to stimulate insulin-dependent glucose uptake (GU) in adipocytes in a dose dependent manner. Bioassay-guided fractionation of the DCM extract resulted in the isolation of the polyacetylenes falcarinol and falcarindiol. Both polyacetylenes were able to significantly stimulate basal and/or insulin-dependent GU in 3T3-L1 adipocytes and porcine myotube cell cultures in a dose-dependent manner. Falcarindiol increased peroxisome proliferator-activated receptor (PPAR)γ-mediated transactivation significantly at concentrations of 3, 10 and 30 μM, while PPARγ-mediated transactivation by falcarinol was only observed at 10 μM. Docking studies accordingly indicated that falcarindiol binds to the ligand binding domain of PPARγ with higher affinity than falcarinol and that both polyacetylenes exhibit characteristics of PPARγ partial agonists. Falcarinol was shown to inhibit adipocyte differentiation as evident by gene expression studies and Oil Red O staining, whereas falcarindiol did not inhibit adipocyte differentiation, which indicates that these polyacetylenes have distinct modes of action. The results of the present study suggest that falcarinol and falcarindiol may represent scaffolds for novel partial PPARγ agonists with possible antidiabetic properties.

Context. The increased brightness temperature of young rocky protoplanets during their magma ocean epoch makes them potentially amenable to atmospheric characterization at distances from the Solar System far greater than thermally equilibrated terrestrial exoplanets, offering observational opportunities for unique insights into the origin of secondary atmospheres and the near surface conditions of prebiotic environments.

Aims. The Large Interferometer For Exoplanets (LIFE) mission will employ a space-based midinfrared nulling interferometer to directly measure the thermal emission of terrestrial exoplanets. In this work, we seek to assess the capabilities of various instrumental design choices of the LIFE mission concept for the detection of cooling protoplanets with transient high-temperature magma ocean atmospheres at the tail end of planetary accretion. In particular, we investigate the minimum integration times necessary to detect transient magma ocean exoplanets in young stellar associations in the Solar neighborhood.

Methods. Using the LIFE mission instrument simulator (LIFEsim), we assessed how specific instrumental parameters and design choices, such as wavelength coverage, aperture diameter, and photon throughput, facilitate or disadvantage the detection of protoplan-ets. We focused on the observational sensitivities of distance to the observed planetary system, protoplanet brightness temperature (using a blackbody assumption), and orbital distance of the potential protoplanets around both G- and M-dwarf stars.

Results. Our simulations suggest that LIFE will be able to detect (S/N ≥ 7) hot protoplanets in young stellar associations up to distances of 100 pc from the Solar System for reasonable integration times (up to a few hours). Detection of an Earth-sized protoplanet orbiting a Solar-sized host star at 1 AU requires less than 30 minutes of integration time. M-dwarfs generally need shorter integration times. The contribution from wavelength regions smaller than 6 µm is important for decreasing the detection threshold and discriminating emission temperatures.

Conclusions. The LIFE mission is capable of detecting cooling terrestrial protoplanets within minutes to hours in several local young stellar associations hosting potential targets. The anticipated compositional range of magma ocean atmospheres motivates further architectural design studies to characterize the crucial transition from primary to secondary atmospheres.

Context. Hot Jupiters are giant planets subject to intense stellar radiation. The physical and chemical properties of their atmosphere make them the most amenable targets for atmospheric characterization.

Aims. In this paper we analyze the photometry collected during the secondary eclipses of the hot Jupiter WASP-3 b by CHEOPS, TESS, and Spitzer. Our aim is to characterize the atmosphere of the planet by measuring the secondary eclipse depth in several passbands and constrain the planetary dayside spectrum.

Methods. We updated the radius and the ephemeris of WASP-3 b by analyzing the transit photometry collected by CHEOPS and TESS. We also analyzed the CHEOPS, TESS, and Spitzer photometry of the occultations of the planet, measuring the eclipse depth at different wavelengths.

Results. Our update of the stellar and planetary properties is consistent with previous works. The analysis of the occultations returns an eclipse depth of 92±21 ppm in the CHEOPS passband, 83±27 ppm for TESS, and >2000 ppm in the IRAC 1-2-4 Spitzer passbands. Using the eclipse depths in the Spitzer bands, we propose a set of likely emission spectra that constrain the emission contribution in the CHEOPS and TESS passbands to approximately a few dozen parts per million. This allowed us to measure a geometric albedo of 0.21±0.07 in the CHEOPS passband, while the TESS data lead to a 95% upper limit of ∼0.2.

Conclusions. WASP-3 b belongs to the group of ultra-hot Jupiters that are characterized by a low Bond albedo (<0.3±0.1), as predicted by different atmospheric models. On the other hand, it seems to efficiently recirculate the absorbed stellar energy, which is not typical for similar, highly irradiated planets. To explain this inconsistency, we propose that other energy recirculation mechanisms are at play besides advection (for example, the dissociation and recombination of H2). Another possibility is that the observations in different bandpasses probe different atmospheric layers; this would make the atmospheric analysis difficult without an appropriate modeling of the thermal emission spectrum of WASP-3 b, which is not feasible with the limited spectroscopic data available to date.