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Abstract Elite athletes are high-performance outliers within their specific sports. Even though science seeks to understand the nature of expertise and elite performance, much knowledge remains compartmentalized within subdisciplines. Despite this multidimensionality being acknowledged, an interdisciplinary approach to understanding elite athletes is still rare. This paper synthesizes insights across scientific domains in order to describe the population and individual characteristics of elite athletes. We analyzed diagnostic data from approximately 300 German squad athletes across eight different sports (e.g., gymnastics, volleyball, ice hockey, 3 × 3 basketball etc., agefemale = 18.95 ± 4.84 years, agemale = 19.32 ± 4.19 years) with expertise values ranging from 2 (low expertise) to 16 (high expertise). Data covered muscular strength, lower-body dynamics, muscle-power genetics, blood micronutrients, basic cognitive function, mental health, social support, and training conditions. Results of logistic regressions identified basic cognitive function (B = 0.89) and well-balanced blood micronutrients (B = 1.22) as critical factors distinguishing elite athletes. Additionally, multiple linear regressions suggested that lower-body dynamics (ß = 0.72) is related to increasing expertise values. We examined interactions between determinants of elite performance, and found that social support is positively associated with mental health and training conditions, whereas muscular strength correlates with lower-body dynamics. Focusing on top elite athletes in contrast to semi-elite athletes, we found higher within-group similarities in basic cognitive function and blood micronutrients. Findings indicate the need for a systemic, individualized, and comprehensive model using individual-based profiles.

Abstract The metabolomic profile of aging is complex. Here, we analyse 325 nuclear magnetic resonance (NMR) biomarkers from 250,341 UK Biobank participants, identifying 54 representative aging-related biomarkers associated with all-cause mortality. We conduct genome-wide association studies (GWAS) for these 325 biomarkers using whole-genome sequencing (WGS) data from 95,372 individuals and perform multivariable Mendelian randomization (MVMR) analyses, discovering 439 candidate “biomarker - disease” causal pairs at the nominal significance level. We develop a metabolomic aging score that outperforms other aging metrics in predicting short-term mortality risk and exhibits strong potential for discriminating aging-accelerated populations and improving disease risk prediction. A longitudinal analysis of 13,263 individuals enables us to calculate a metabolomic aging rate which provides more refined aging assessments and to identify candidate anti-aging and pro-aging NMR biomarkers. Taken together, our study has presented a comprehensive aging-related metabolomic profile and highlighted its potential for personalized aging monitoring and early disease intervention.

Abstract Background Viruses with double-stranded (ds) DNA genomes in the realm Duplodnaviria share a conserved structural gene module but show a broad range of variation in their repertoires of DNA replication proteins. Some of the duplodnaviruses encode (nearly) complete replication systems whereas others lack (almost) all genes required for replication, relying on the host replication machinery. DNA polymerases (DNAPs) comprise the centerpiece of the DNA replication apparatus. The replicative DNAPs are classified into 4 unrelated or distantly related families (A-D), with the protein structures and sequences within each family being, generally, highly conserved. More than half of the duplodnaviruses encode a DNAP of family A, B or C. We showed previously that multiple pairs of closely related viruses in the order Crassvirales encode DNAPs of different families. Methods Groups of phages in which DNAP swapping likely occurred were identified as subtrees of a defined depth in a comprehensive evolutionary tree of tailed bacteriophages that included phages with DNAPs of different families. The DNAP swaps were validated by constrained tree analysis that was performed on phylogenetic tree of large terminase subunits, and the phage genomes encoding swapped DNAPs were aligned using Mauve. The structures of the discovered unusual DNAPs were predicted using AlphaFold2. Results We identified four additional groups of tailed phages in the class Caudoviricetes in which the DNAPs apparently were swapped on multiple occasions, with replacements occurring both between families A and B, or A and C, or between distinct subfamilies within the same family. The DNAP swapping always occurs “in situ”, without changes in the organization of the surrounding genes. In several cases, the DNAP gene is the only region of substantial divergence between closely related phage genomes, whereas in others, the swap apparently involved neighboring genes encoding other proteins involved in phage genome replication. In addition, we identified two previously undetected, highly divergent groups of family A DNAPs that are encoded in some phage genomes along with the main DNAP implicated in genome replication. Conclusions Replacement of the DNAP gene by one encoding a DNAP of a different family occurred on many independent occasions during the evolution of different families of tailed phages, in some cases, resulting in very closely related phages encoding unrelated DNAPs. DNAP swapping was likely driven by selection for avoidance of host antiphage mechanisms targeting the phage DNAP that remain to be identified, and/or by selection against replicon incompatibility.

Objective: This study aimed to demonstrate the superiority of cryocompression over cryotherapy alone in the prevention of chemotherapy-induced peripheral neuropathy (CIPN) grade 2 or above. Methods: This prospective randomized study was conducted between May 2020 and January 2023 in Innsbruck. Eligible patients had a diagnosis of gynecological cancer and received a minimum of 3 cycles of taxane-based CT (neoadjuvant, adjuvant or palliative therapy). Patients were randomized 1:1 to receive either cryotherapy or cryocompression on their upper extremities during chemotherapy (CT). We performed temperature measurements, two QoL questionnaires and neurological tests during CT and at follow-up 3 and 6–9 months after the completion of CT. CIPN was assessed using the CTCAE score. Results: Of 200 patients recruited, both groups showed a lower prevalence of CIPN in this study compared to recent literature. In the group receiving cryotherapy, the prevalence of grade 1 CIPN was 30.1 %, and that of grade 2 CIPN or above was 13.7 %; in the group treated with cryocompression, the prevalence of grade 1 CIPN was 32.8 %, and that of grade 2 or above CIPN was 17.2 %. We found a significant reduction in temperature in the cryotherapy and cryocompression groups. Regarding the two QOL questionnaires as well as the neurological tests no significant differences were found between the two groups. Conclusion: Our study suggests that cryotherapy as well as cryocompression is a safe and effective way to cool patients’ extremities to lower the prevalence of CIPN. Cryocompression was not more effective than cryotherapy alone in the prevention of CIPN.

ABSTRACT The phylum Nucleocytoviricota consists of large and giant viruses that range in genome size from about 100 kilobases (kb) to more than 2.5 megabases. Here, using metagenome mining followed by extensive phylogenomic analysis and protein structure comparison, we delineate a distinct group of viruses with double-stranded (ds) DNA genomes in the range of 35–45 kb that appear to be related to the Nucleocytoviricota. In phylogenetic trees of the conserved double jelly-roll major capsid proteins (MCPs) and DNA packaging ATPases, these viruses do not show affinity to any particular branch of the Nucleocytoviricota and accordingly would comprise a class which we propose to name “Mriyaviricetes” (after Ukrainian “mriya,” dream). Structural comparison of the MCP suggests that, among the extant virus lineages, mriyaviruses are the closest one to the ancestor of the Nucleocytoviricota. In the phylogenetic trees, mriyaviruses split into two well-separated branches, the family Yaraviridae and proposed new family “Gamadviridae.” The previously characterized members of these families, yaravirus and Pleurochrysis sp. endemic viruses, infect amoeba and haptophytes, respectively. The genomes of the rest of the mriyaviruses were assembled from metagenomes from diverse environments, suggesting that mriyaviruses infect various unicellular eukaryotes. Mriyaviruses lack DNA polymerase, which is encoded by all other members of the Nucleocytoviricota, and RNA polymerase subunits encoded by all cytoplasmic viruses among the Nucleocytoviricota, suggesting that they replicate in the host cell nuclei. All mriyaviruses encode a HUH superfamily endonuclease that is likely to be essential for the initiation of virus DNA replication via the rolling circle mechanism.IMPORTANCEThe origin of giant viruses of eukaryotes that belong to the phylum Nucleocytoviricota is not thoroughly understood and remains a matter of major interest and debate. Here, we combine metagenome database searches with extensive protein sequence and structure analysis to describe a distinct group of viruses with comparatively small genomes of 35–45 kilobases that appear to comprise a distinct class within the phylum Nucleocytoviricota that we provisionally named “Mriyaviricetes.” Mriyaviruses appear to be the closest identified relatives of the ancestors of the Nucleocytoviricota. Analysis of proteins encoded in mriyavirus genomes suggests that they replicate their genome via the rolling circle mechanism that is unusual among viruses with double-stranded DNA genomes and so far not described for members of Nucleocytoviricota.

Virus discovery by genomics and metagenomics empowered studies of viromes, facilitated characterization of pathogen epidemiology, and redefined our understanding of the natural genetic diversity of viruses with profound functional and structural implications. Here we employed a data-driven virus discovery approach that directly queries unprocessed sequencing data in a highly parallelized way and involves a targeted viral genome assembly strategy in a wide range of sequence similarity. By screening more than 269,000 datasets of numerous authors from the Sequence Read Archive and using two metrics that quantitatively assess assembly quality, we discovered 40 nidoviruses from six virus families whose members infect vertebrate hosts. They form 13 and 32 putative viral subfamilies and genera, respectively, and include 11 coronaviruses with bisegmented genomes from fishes and amphibians, a giant 36.1 kilobase coronavirus genome with a duplicated spike glycoprotein (S) gene, 11 tobaniviruses and 17 additional corona-, arteri-, cremega-, nanhypo- and nangoshaviruses. Genome segmentation emerged in a single evolutionary event in the monophyletic lineage encompassing the subfamily Pitovirinae. We recovered the bisegmented genome sequences of two coronaviruses from RNA samples of 69 infected fishes and validated the presence of poly(A) tails at both segments using 3'RACE PCR and subsequent Sanger sequencing. We report a genetic linkage between accessory and structural proteins whose phylogenetic relationships and evolutionary distances are incongruent with the phylogeny of replicase proteins. We rationalize these observations in a model of inter-family S recombination involving at least five ancestral corona- and tobaniviruses of aquatic hosts. In support of this model, we describe an individual fish co-infected with members from the families Coronaviridae and Tobaniviridae. Our results expand the scale of the known extraordinary evolutionary plasticity in nidoviral genome architecture and call for revisiting fundamentals of genome expression, virus particle biology, host range and ecology of vertebrate nidoviruses.

This study presents the simulated response of regional climate and the oxygen isotopic composition of precipitation (δ18Op) to different along-strike topographic evolution scenarios. These simulations are conducted to determine if the previously hypothesized diachronous surface uplift in the Western and Eastern Alps would produce δ18Op signals in the geologic record that are sufficiently large and distinct to be detected using stable isotope paleoaltimetry. We present a series of topographic sensitivity experiments conducted with the water-isotope-tracking atmospheric general circulation model (GCM) ECHAM5-wiso. The topographic scenarios are created from the variation of two free parameters, (1) the elevation of the Western–Central Alps and (2) the elevation of the Eastern Alps. The results indicate Δδ18Op values (i.e., the difference between δ18Op values at the low- and high-elevation sites) of up to −8 ‰ along the strike of the Alps for the diachronous uplift scenarios, primarily due to changes in orographic precipitation and adiabatic lapse rate driven localized changes in near-surface variables. These simulated magnitudes of Δδ18Op values suggest that the expected isotopic signal would be significant enough to be preserved and measured in geologic archives. Moreover, the simulated slight δ18Op differences of 1 ‰–2 ‰ across the low-elevation sites support the use of the δ–δ paleoaltimetry approach and highlight the importance of sampling far-field low-elevation sites to differentiate between the different surface uplift scenarios. The elevation-dependent rate of change in δ18Op (“isotopic lapse rate”) varies depending on the topographic configuration and the extent of the surface uplift. Most of the changes are significant (e.g., −1.04 ‰ km−1 change with slope error of ±0.09 ‰ km−1), while others were within the range of the statistical uncertainties (e.g., −0.15 ‰ km−1 change with slope error of ±0.13 ‰ km−1). The results also highlight the plausible changes in atmospheric circulation patterns and associated changes in moisture transport pathways in response to changes in the topography of the Alps. These large-scale atmospheric dynamics changes can complicate the underlying assumption of stable isotope paleoaltimetry and therefore require integration with paleoclimate modeling to ensure accurate reconstruction of the paleoelevation of the Alps.

The nature and severity of climate change impacts vary significantly from region to region. Consequently, high-resolution climate information is needed for meaningful impact assessments and the design of mitigation strategies. This demand has led to an increase in the application of empirical-statistical downscaling (ESD) models to general circulation model (GCM) simulations of future climate. In contrast to dynamical downscaling, the perfect prognosis ESD (PP-ESD) approach has several benefits, including low computation costs, the prevention of the propagation of GCM-specific errors, and high compatibility with different GCMs. Despite their advantages, the use of ESD models and the resulting data products is hampered by (1) the lack of accessible and user-friendly downscaling software packages that implement the entire downscaling cycle, (2) difficulties reproducing existing data products and assessing their credibility, and (3) difficulties reconciling different ESD-based predictions for the same region. We address these issues with a new open-source Python PP-ESD modeling framework called pyESD. pyESD implements the entire downscaling cycle, i.e., routines for data preparation, predictor selection and construction, model selection and training, evaluation, utility tools for relevant statistical tests, visualization, and more. The package includes a collection of well-established machine learning algorithms and allows the user to choose a variety of estimators, cross-validation schemes, objective function measures, and hyperparameter optimization in relatively few lines of code. The package is well-documented, highly modular, and flexible. It allows quick and reproducible downscaling of any climate information, such as precipitation, temperature, wind speed, or even short-term glacier length and mass changes. We demonstrate the use and effectiveness of the new PP-ESD framework by generating weather-station-based downscaling products for precipitation and temperature in complex mountainous terrain in southwestern Germany. The application example covers all important steps of the downscaling cycle and different levels of experimental complexity. All scripts and datasets used in the case study are publicly available to (1) ensure the reproducibility and replicability of the modeled results and (2) simplify learning to use the software package.

Organized sports programmes offer manifold opportunities for learning and personal development. Prisoners in organized sports programmes could profit from these educational opportunities, which could eventually support their process of reintegration into society. However, research on the educational experiences of imprisoned individuals during organized sports activities is scarce. Using quantitative survey data (N = 568 adult male prisoners) collected within the scope of the Hessian Prison Sports Study in Hesse, Germany, the present study examines educational experiences that are instigated through participation in five different prison sports programmes (fitness, racket, and team sports, running groups, and strength training). The results show that participants reported few educational experiences. The most common experiences reported were learning to exert effort and acquiring health-related knowledge. The findings reveal distinct patterns for specific sports programmes. For instance, team sports more frequently address cooperation skills and fairness. This paper advocates for more attention to the educational potential of sports in prison settings, where sports outcomes should be better aligned with the desired educational outcomes.

Abstract Background Phenylpropanoids such as p-coumaric acid represent important precursors for the synthesis of a broad range of plant secondary metabolites including stilbenoids, flavonoids, and lignans, which are of pharmacological interest due to their health-promoting properties. Although extraction from plant material or chemical synthesis is possible, microbial synthesis of p-coumaric acid from glucose has the advantage of being less expensive and more resource efficient. In this study, Corynebacterium glutamicum was engineered for the production of the plant polyphenol precursor p-coumaric acid from glucose. Results Heterologous expression of the tyrosine ammonia-lyase encoding gene from Flavobacterium johnsoniae enabled the conversion of endogenously provided tyrosine to p-coumaric acid. Product consumption was avoided by abolishing essential reactions of the phenylpropanoid degradation pathway. Accumulation of anthranilate as a major byproduct was eliminated by reducing the activity of anthranilate synthase through targeted mutagenesis to avoid tryptophan auxotrophy. Subsequently, the carbon flux into the shikimate pathway was increased, phenylalanine biosynthesis was reduced, and phosphoenolpyruvate availability was improved to boost p-coumaric acid accumulation. A maximum titer of 661 mg/L p-coumaric acid (4 mM) in defined mineral medium was reached. Finally, the production strain was utilized in co-cultivations with a C. glutamicum strain previously engineered for the conversion of p-coumaric acid into the polyphenol resveratrol. These co-cultivations enabled the synthesis of 31.2 mg/L (0.14 mM) resveratrol from glucose without any p-coumaric acid supplementation. Conclusions The utilization of a heterologous tyrosine ammonia-lyase in combination with optimization of the shikimate pathway enabled the efficient production of p-coumaric acid with C. glutamicum. Reducing the carbon flux into the phenylalanine and tryptophan branches was the key to success along with the introduction of feedback-resistant enzyme variants.

The growing demand for alternative sources of non-animal proteins has stimulated research in this area. Mushrooms show potential in the innovation of plant-based food products. In this study, the aim was to develop prototype fish fillets analogues from Pleurotus ostreatus mushrooms applying enzymatic treatment (β-glucanase and transglutaminase-TG). A Plackett–Burman 20 experimental design was used to optimize forty variables. Oat flour (OF) exerted a positive effect on the hardness and gumminess texture parameters but a negative effect on cohesiveness and resilience. Soy protein isolate (SPI) exhibited a positive effect on elasticity, gumminess and chewiness, while acacia gum had a negative effect on elasticity, cohesiveness and resilience. After sensory analysis the assay with 1% cassava starch, 5% OF, 5% SPI, 0.1% transglutaminase (240 min/5 °C), 1% coconut oil, 1% soybean oil, 0.2% sodium tripolyphosphate, 0.6% β-glucanase (80 °C/10 min) and without β-glucanase inactivation was found to exhibit greater similarity to fish fillet. The classes hydrocarbons, alcohols and aldehydes are the predominant ones in aromatic profile analysis by chromatography and electronic nose. It is concluded that a mushroom-based analogue of fish fillet can be prepared using enzymatic treatment with TG.

Abstract Background Previous studies about health in prisons conclude that incarceration has detrimental consequences for physical and mental health. It is associated with weight gain, decreased fitness, increased cardiovascular risks, and increased risks for mental illnesses, like depression and anxiety. This article examines the relationships between sports activity and health developments among prisoners. We analyze data from the Hessian Prison Sports Study, conducted in 12 prisons of the federal state of Hesse, Germany. Results Based on quantitative survey data of 568 prisoners in regular custody, our empirical findings show that inmates perceive substantial health declines since incarceration. They report substantial decreases in general health (d=-0.52) and life satisfaction (d=-0.84) as well as an increased number of health problems (d = 0.71). However, sport has a potential to buffer this decline of health. Prisoners engaged in sports report a less negative development of their health compared to inactive prisoners. The greater the amount of time spent with sports activities, the better are the health trajectories found. Conclusion Findings add to the public health and prison sport literature by demonstrating health benefits of sporting activities in a vulnerable population group that almost inevitably is exposed to manifold strains and burdens.

Abstract Anthranilate and its derivatives are important basic chemicals for the synthesis of polyurethanes as well as various dyes and food additives. Today, anthranilate is mainly chemically produced from petroleum‐derived xylene, but this shikimate pathway intermediate could be also obtained biotechnologically. In this study, Corynebacterium glutamicum was engineered for the microbial production of anthranilate from a carbon source mixture of glucose and xylose. First, a feedback‐resistant 3‐deoxy‐arabinoheptulosonate‐7‐phosphate synthase from Escherichia coli, catalysing the first step of the shikimate pathway, was functionally introduced into C. glutamicum to enable anthranilate production. Modulation of the translation efficiency of the genes for the shikimate kinase (aroK) and the anthranilate phosphoribosyltransferase (trpD) improved product formation. Deletion of two genes, one for a putative phosphatase (nagD) and one for a quinate/shikimate dehydrogenase (qsuD), abolished by‐product formation of glycerol and quinate. However, the introduction of an engineered anthranilate synthase (TrpEG) unresponsive to feedback inhibition by tryptophan had the most pronounced effect on anthranilate production. Component I of this enzyme (TrpE) was engineered using a biosensor‐based in vivo screening strategy for identifying variants with increased feedback resistance in a semi‐rational library of TrpE muteins. The final strain accumulated up to 5.9 g/L (43 mM) anthranilate in a defined CGXII medium from a mixture of glucose and xylose in bioreactor cultivations. We believe that the constructed C. glutamicum variants are not only limited to anthranilate production but could also be suitable for the synthesis of other biotechnologically interesting shikimate pathway intermediates or any other aromatic compound derived thereof.