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Metabolic alterations precede cardiometabolic disease onset. Here we present ceramide- and dihydroceramide-profiling data from a nested case-cohort (type 2 diabetes [T2D, n = 775]; cardiovascular disease [CVD, n = 551]; random subcohort [n = 1137]) in the prospective EPIC-Potsdam study. We apply the novel NetCoupler-algorithm to link a data-driven (dihydro)ceramide network to T2D and CVD risk. Controlling for confounding by other (dihydro)ceramides, ceramides C18:0 and C22:0 and dihydroceramides C20:0 and C22:2 are associated with higher and ceramide C20:0 and dihydroceramide C26:1 with lower T2D risk. Ceramide C16:0 and dihydroceramide C22:2 are associated with higher CVD risk. Genome-wide association studies and Mendelian randomization analyses support a role of ceramide C22:0 in T2D etiology. Our results also suggest that (dh)ceramides partly mediate the putative adverse effect of high red meat consumption and benefits of coffee consumption on T2D risk. Thus, (dihydro)ceramides may play a critical role in linking genetic predisposition and dietary habits to cardiometabolic disease risk.
“Ick bin een Berlina”
(2024)
Background: Robots are increasingly used as interaction partners with humans. Social robots are designed to follow expected behavioral norms when engaging with humans and are available with different voices and even accents. Some studies suggest that people prefer robots to speak in the user’s dialect, while others indicate a preference for different dialects.
Methods: Our study examined the impact of the Berlin dialect on perceived trustworthiness and competence of a robot. One hundred and twenty German native speakers (Mage = 32 years, SD = 12 years) watched an online video featuring a NAO robot speaking either in the Berlin dialect or standard German and assessed its trustworthiness and competence.
Results: We found a positive relationship between participants’ self-reported Berlin dialect proficiency and trustworthiness in the dialect-speaking robot. Only when controlled for demographic factors, there was a positive association between participants’ dialect proficiency, dialect performance and their assessment of robot’s competence for the standard German-speaking robot. Participants’ age, gender, length of residency in Berlin, and device used to respond also influenced assessments. Finally, the robot’s competence positively predicted its trustworthiness.
Discussion: Our results inform the design of social robots and emphasize the importance of device control in online experiments.
Dysfunctional islets of Langerhans are a hallmark of type 2 diabetes (T2D). We hypothesize that differences in islet gene expression alternative splicing which can contribute to altered protein function also participate in islet dysfunction. RNA sequencing (RNAseq) data from islets of obese diabetes-resistant and diabetes-susceptible mice were analyzed for alternative splicing and its putative genetic and epigenetic modulators. We focused on the expression levels of chromatin modifiers and SNPs in regulatory sequences. We identified alternative splicing events in islets of diabetes-susceptible mice amongst others in genes linked to insulin secretion, endocytosis or ubiquitin-mediated proteolysis pathways. The expression pattern of 54 histones and chromatin modifiers, which may modulate splicing, were markedly downregulated in islets of diabetic animals. Furthermore, diabetes-susceptible mice carry SNPs in RNA-binding protein motifs and in splice sites potentially responsible for alternative splicing events. They also exhibit a larger exon skipping rate, e.g., in the diabetes gene Abcc8, which might affect protein function. Expression of the neuronal splicing factor Srrm4 which mediates inclusion of microexons in mRNA transcripts was markedly lower in islets of diabetes-prone compared to diabetes-resistant mice, correlating with a preferential skipping of SRRM4 target exons. The repression of Srrm4 expression is presumably mediated via a higher expression of miR-326-3p and miR-3547-3p in islets of diabetic mice. Thus, our study suggests that an altered splicing pattern in islets of diabetes-susceptible mice may contribute to an elevated T2D risk.
Pedogenic carbonate is widespread at mid latitudes where warm and dry conditions favor soil carbonate growth from spring to fall. The mechanisms and timing of pedogenic carbonate formation are more ambiguous in the tropical domain, where long periods of soil water saturation and high soil respiration enhance calcite dissolution. This paper provides stable carbon, oxygen and clumped isotope values from Quaternary and Miocene pedogenic carbonates in the tropical domain of Myanmar, in areas characterized by warm (>18°C) winters and annual rainfall up to 1,700 mm. We show that carbonate growth in Myanmar is delayed to the driest and coldest months of the year by sustained monsoonal rainfall from mid spring to late fall. The range of isotopic variability in Quaternary pedogenic carbonates can be solely explained by temporal changes of carbonate growth within the dry season, from winter to early spring. We propose that high soil moisture year-round in the tropical domain narrows carbonate growth to the driest months and makes it particularly sensitive to the seasonal distribution of rainfall. This sensitivity is also enabled by high winter temperatures, allowing carbonate growth to occur outside the warmest months of the year. This high sensitivity is expected to be more prominent in the geological record during times with higher temperatures and greater expansion of the tropical realm. Clumped isotope temperatures, δ13C and δ18O values of tropical pedogenic carbonates are impacted by changes of both rainfall seasonality and surface temperatures; this sensitivity can potentially be used to track past tropical rainfall distribution.
The genus Microhyla Tschudi, 1838 includes 52 species and is one of the most diverse genera of the family Microhylidae, being the most species-rich taxon of the Asian subfamily Microhylinae. The recent, rapid description of numerous new species of Microhyla with complex phylogenetic relationships has made the taxonomy of the group especially challenging. Several recent phylogenetic studies suggested paraphyly of Microhyla with respect to Glyphoglossus Gunther, 1869, and revealed three major phylogenetic lineages of mid-Eocene origin within this assemblage. However, comprehensive works assessing morphological variation among and within these lineages are absent. In the present study we investigate the generic taxonomy of Microhyla-Glyphoglossus assemblage based on a new phylogeny including 57 species, comparative morphological analysis of skeletons from cleared-and-stained specimens for 23 species, and detailed descriptions of generalized osteology based on volume-rendered micro-CT scans for five speciesal-together representing all major lineages within the group. The results confirm three highly divergent and well-supported clades that correspond with external and osteological morphological characteristics, as well as respective geographic distribution. Accordingly, acknowledging ancient divergence between these lineages and their significant morphological differentiation, we propose to consider these three lineages as distinct genera: Microhyla sensu stricto, Glyphoglossus, and a newly described genus, Nanohyla gen. nov.
Mastery is a psychological resource that is defined as the extent to which individuals perceive having control over important circumstances of their lives. Although mastery has been associated with various physical and psychological health outcomes, studies assessing its relationship with weight status and dietary behavior are lacking. The aim of this cross-sectional study was to assess the relationship between mastery and weight status, food intake, snacking, and eating disorder (ED) symptoms in the NutriNet-Sante cohort study. Mastery was measured with the Pearlin Mastery Scale (PMS) in 32,588 adults (77.45% female), the mean age was 50.04 (14.53) years. Height and weight were self-reported. Overall diet quality and food group consumption were evaluated with >= 3 self-reported 24-h dietary records (range: 3-27). Snacking was assessed with an ad-hoc question. ED symptoms were assessed with the Sick-Control-One-Fat-Food Questionnaire (SCOFF). Linear and logistic regression analyses were conducted to assess the relationship between mastery and weight status, food intake, snacking, and ED symptoms, controlling for sociodemographic and lifestyle characteristics. Females with a higher level of mastery were less likely to be underweight (OR: 0.88; 95%CI: 0.84, 0.93), overweight [OR: 0.94 (0.91, 0.97)], or obese [class I: OR: 0.86 (0.82, 0.90); class II: OR: 0.76 (0.71, 0.82); class III: OR: 0.77 (0.69, 0.86)]. Males with a higher level of mastery were less likely to be obese [class III: OR: 0.75 (0.57, 0.99)]. Mastery was associated with better diet quality overall, a higher consumption of fruit and vegetables, seafood, wholegrain foods, legumes, non-salted oleaginous fruits, and alcoholic beverages and with a lower consumption of meat and poultry, dairy products, sugary and fatty products, milk-based desserts, and sweetened beverages. Mastery was also associated with lower snacking frequency [OR: 0.89 (0.86, 0.91)] and less ED symptoms [OR: 0.73 (0.71, 0.75)]. As mastery was associated with favorable dietary behavior and weight status, targeting mastery might be a promising approach in promoting healthy behaviors.
Tula orthohantavirus (TULV) is a rodent-borne hantavirus with broad geographical distribution in Europe. Its major reservoir is the common vole (Microtus arvalis), but TULV has also been detected in closely related vole species. Given the large distributional range and high amplitude population dynamics of common voles, this host-pathogen complex presents an ideal system to study the complex mechanisms of pathogen transmission in a wild rodent reservoir. We investigated the dynamics of TULV prevalence and the subsequent potential effects on the molecular evolution of TULV in common voles of the Central evolutionary lineage. Rodents were trapped for three years in four regions of Germany and samples were analyzed for the presence of TULV-reactive antibodies and TULV RNA with subsequent sequence determination. The results show that individual (sex) and population-level factors (abundance) of hosts were significant predictors of local TULV dynamics. At the large geographic scale, different phylogenetic TULV clades and an overall isolation-by-distance pattern in virus sequences were detected, while at the small scale (<4 km) this depended on the study area. In combination with an overall delayed density dependence, our results highlight that frequent, localized bottleneck events for the common vole and TULV do occur and can be offset by local recolonization dynamics.
Simple Summary Gliomas are heterogenous types of cancer, therefore the therapy should be personalized and targeted toward specific pathways. We developed a methodology that corrected strong batch effects from The Cancer Genome Atlas datasets and estimated glioma grade-specific co-enrichment mechanisms using machine learning. Our findings created hypotheses for annotations, e.g., pathways, that should be considered as therapeutic targets. Gliomas develop and grow in the brain and central nervous system. Examining glioma grading processes is valuable for improving therapeutic challenges. One of the most extensive repositories storing transcriptomics data for gliomas is The Cancer Genome Atlas (TCGA). However, such big cohorts should be processed with caution and evaluated thoroughly as they can contain batch and other effects. Furthermore, biological mechanisms of cancer contain interactions among biomarkers. Thus, we applied an interpretable machine learning approach to discover such relationships. This type of transparent learning provides not only good predictability, but also reveals co-predictive mechanisms among features. In this study, we corrected the strong and confounded batch effect in the TCGA glioma data. We further used the corrected datasets to perform comprehensive machine learning analysis applied on single-sample gene set enrichment scores using collections from the Molecular Signature Database. Furthermore, using rule-based classifiers, we displayed networks of co-enrichment related to glioma grades. Moreover, we validated our results using the external glioma cohorts. We believe that utilizing corrected glioma cohorts from TCGA may improve the application and validation of any future studies. Finally, the co-enrichment and survival analysis provided detailed explanations for glioma progression and consequently, it should support the targeted treatment.
We present the discovery of a new double-detonation progenitor system consisting of a hot subdwarf B (sdB) binary with a white dwarf companion with a P (orb) = 76.34179(2) minutes orbital period. Spectroscopic observations are consistent with an sdB star during helium core burning residing on the extreme horizontal branch. Chimera light curves are dominated by ellipsoidal deformation of the sdB star and a weak eclipse of the companion white dwarf. Combining spectroscopic and light curve fits, we find a low-mass sdB star, M (sdB) = 0.383 +/- 0.028 M (circle dot) with a massive white dwarf companion, M (WD) = 0.725 +/- 0.026 M (circle dot). From the eclipses we find a blackbody temperature for the white dwarf of 26,800 K resulting in a cooling age of approximate to 25 Myr whereas our MESA model predicts an sdB age of approximate to 170 Myr. We conclude that the sdB formed first through stable mass transfer followed by a common envelope which led to the formation of the white dwarf companion approximate to 25 Myr ago. Using the MESA stellar evolutionary code we find that the sdB star will start mass transfer in approximate to 6 Myr and in approximate to 60 Myr the white dwarf will reach a total mass of 0.92 M (circle dot) with a thick helium layer of 0.17 M (circle dot). This will lead to a detonation that will likely destroy the white dwarf in a peculiar thermonuclear supernova. PTF1 J2238+7430 is only the second confirmed candidate for a double-detonation thermonuclear supernova. Using both systems we estimate that at least approximate to 1% of white dwarf thermonuclear supernovae originate from sdB+WD binaries with thick helium layers, consistent with the small number of observed peculiar thermonuclear explosions.
This study focuses on three key aspects: (a) crude throat swab samples in a viral transport medium (VTM) as templates for RT-LAMP reactions; (b) a biotinylated DNA probe with enhanced specificity for LFA readouts; and (c) a digital semi-quantification of LFA readouts. Throat swab samples from SARS-CoV-2 positive and negative patients were used in their crude (no cleaning or pre-treatment) forms for the RT-LAMP reaction. The samples were heat-inactivated but not treated for any kind of nucleic acid extraction or purification. The RT-LAMP (20 min processing time) product was read out by an LFA approach using two labels: FITC and biotin. FITC was enzymatically incorporated into the RT-LAMP amplicon with the LF-LAMP primer, and biotin was introduced using biotinylated DNA probes, specifically for the amplicon region after RT-LAMP amplification. This assay setup with biotinylated DNA probe-based LFA readouts of the RT-LAMP amplicon was 98.11% sensitive and 96.15% specific. The LFA result was further analysed by a smartphone-based IVD device, wherein the T-line intensity was recorded. The LFA T-line intensity was then correlated with the qRT-PCR Ct value of the positive swab samples. A digital semi-quantification of RT-LAMP-LFA was reported with a correlation coefficient of R2 = 0.702. The overall RT-LAMP-LFA assay time was recorded to be 35 min with a LoD of three RNA copies/µL (Ct-33). With these three advancements, the nucleic acid testing-point of care technique (NAT-POCT) is exemplified as a versatile biosensor platform with great potential and applicability for the detection of pathogens without the need for sample storage, transportation, or pre-processing.