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Orsay virus (OrV) is the first virus known to be able to complete a full infection cycle in the model nematode species Caenorhabditis elegans. OrV is transmitted horizontally and its infection is limited by antiviral RNA interference (RNAi). However, we have no insight into the kinetics of OrV replication in C. elegans. We developed an assay that infects worms in liquid, allowing precise monitoring of the infection. The assay revealed a dual role for the RNAi response in limiting Orsay virus infection in C. elegans. Firstly, it limits the progression of the initial infection at the step of recognition of dsRNA. Secondly, it provides an inherited protection against infection in the offspring. This establishes the heritable RNAi response as anti-viral mechanism during OrV infections in C. elegans. Our results further illustrate that the inheritance of the anti-viral response is important in controlling the infection in the canonical wild type Bristol N2. The OrV replication kinetics were established throughout the worm life-cycle, setting a standard for further quantitative assays with the OrV-C. elegans infection model. [ABSTRACT FROM AUTHOR]

Cover crops (CC) can promote nutrient retention and recycling for main crops yet may also promote soilborne pathogens or suppress beneficial root symbionts such as arbuscular mycorrhizal fungi (AMF). We investigated how root fungal communities of main crop are affected by preceding CC monocultures and mixtures and by main crop identity. We expected that AMF abundance and diversity in main crops are promoted by AM‐host CC, and suppressed by non‐AM‐host CC, and that mixtures of CC species can promote beneficial and suppress pathogenic root fungi. Our full‐factorial field experiment comprised crop rotation in sand soil with different CC treatments (monocultures of radish [AM non‐host], ryegrass, clover, vetch [AM hosts], mixtures of radish + vetch, ryegrass + clover and fallow) and two main crops (oat and endive). At peak crop growth, we investigated the root fungal communities in the main crops using microscopy and high throughput sequencing (Illumina MiSeq). Cover crop identity was of prime importance and CC legacy overruled main crop identity in determining root fungal communities in main crops. Compared with fallow, CC with ryegrass increased AMF colonization and richness in both main crops and of non‐AMF in oat. Legacies of ryegrass, ryegrass + clover and vetch resulted in distinct root fungal communities in the main crops, while the legacy of CC with radish were similar to the legacy of fallow. Root fungal community in crops after clover had highest abundance of representative fungal pathogens in contrast with the other CC treatments that resulted in fungal communities where pathogens were scarce. Oppositely to expected, CC mixtures did not enhance fungal symbionts or suppressed pathogens. Overall, fungal communities in roots of the main crops in our field experiment were determined by the preceding CC species in monoculture, rather than by the CC AMF preference or functional group. This research highlights that the choice of CC determines the root fungal community in main crop which may influence crop quality. [ABSTRACT FROM AUTHOR]

The genotype-by-environment interactions of five parental environments with seed and plant performance are mediated by distinct genetic and molecular pathways, and the selective pressures that have shaped their natural variation.Seed performance after dispersal is highly dependent on parental environmental cues, especially during seed formation and maturation. Here we examine which environmental factors are the most dominant in this respect and whether their effects are dependent on the genotypes under investigation. We studied the influence of light intensity, photoperiod, temperature, nitrate, and phosphate during seed development on five plant attributes and thirteen seed attributes, using 12 Arabidopsis genotypes that have been reported to be affected in seed traits. As expected, the various environments during seed development resulted in changed plant and/or seed performances. Comparative analysis clearly indicated that, overall, temperature plays the most dominant role in both plant and seed performance, whereas light has a prominent impact on plant traits. In comparison to temperature and light, nitrate mildly affected some of the plant and seed traits while phosphate had even less influence on those traits. Moreover, clear genotype-by-environment interactions were identified. This was shown by the fact that individual genotypes responded differentially to the environmental conditions. Low temperature significantly increased seed dormancy and decreased seed longevity of NILDOG1 and cyp707a1-1, whereas low light intensity increased seed dormancy and decreased seed longevity of NILDOG3 and NILDOG6. This also indicates that different genetic and molecular pathways are involved in the plant and seed responses. By identifying environmental conditions that affect the dormancy vs longevity correlation in the same way as previously identified naturally occurring loci, we have identified selective forces that probably shaped evolution for these important seed traits. [ABSTRACT FROM AUTHOR]

Air is a major conduit for the dispersal of organisms at the local and the global scale. Most research has focused on the dispersal of plants, vertebrates and human disease agents. However, the air represents a key dispersal medium also for bacteria, fungi and protists. Many of those represent potential pathogens of animals and plants and have until now gone largely unrecorded. Here we studied the turnover in composition of the entire aerobiome, the collective diversity of airborne microorganisms. For that we performed daily analyses of all prokaryotes and eukaryotes (including plants) using multi-marker high-throughput sequencing for a total of three weeks. We linked the resulting communities to local weather conditions, to assess determinants of aerobiome composition and distribution. We observed hundreds of microbial taxa, mostly belonging to spore-forming organisms including fungi, but also protists. Additionally, we detected many potential human- and plant-pathogens. Community composition fluctuated on a daily basis and was linked to concurrent weather conditions, particularly air pressure and temperature. Using network analyses, we identified taxonomically diverse groups of organisms with correlated temporal dynamics. In part, this was due to co-variation with environmental conditions, while we could also detect specific host-parasite interactions. This study provides the first full inventory of the aerobiome and identifies putative drivers of its dynamics in terms of taxon composition. This knowledge can help develop early warning systems against pathogens and improve our understanding of microbial dispersal.

Host-pathogen interactions play a major role in evolutionary selection and shape natural genetic variation. The genetically distinct Caenorhabditis elegans strains, Bristol N2 and Hawaiian CB4856, are differentially susceptible to the Orsay virus (OrV). Here, we report the dissection of the genetic architecture of susceptibility to OrV infection. We compare OrV infection in the relatively resistant wild-type CB4856 strain to the more susceptible canonical N2 strain. To gain insight into the genetic architecture of viral susceptibility, 52 fully sequenced recombinant inbred lines (CB4856xN2 RILs) were exposed to OrV. This led to the identification of two loci on chromosome IV associated with OrV resistance. To verify the two loci and gain additional insight into the genetic architecture controlling virus infection, introgression lines (ILs) that together cover chromosome IV, were exposed to OrV. Of the 27 ILs used, 17 had an CB4856 introgression in an N2 background, and 10 had an N2 introgression in a CB4856 background. Infection of the ILs confirmed and finemapped the locus underlying variation in OrV susceptibility, and we found that a single nucleotide polymorphism in cul-6 may contribute to the difference in OrV susceptibility between N2 and CB4856. An allele swap experiment showed the strain CB4856 became as susceptible as the N2 strain by having an N2 cul-6 allele, although having the CB4856 cul-6 allele did not increase resistance in N2. In addition, we found that multiple strains with nonoverlapping introgressions showed a distinct infection phenotype from the parental strain, indicating that there are punctuated locations on chromosome IV determining OrV susceptibility. Thus, our findings reveal the genetic complexity of OrV susceptibility in C. elegans and suggest that viral susceptibility is governed by multiple genes. [ABSTRACT FROM AUTHOR]

The mycobiome (fungal microbiome) influences plants—from seed germination to full maturation. While many studies on fungal‐plant interaction studies have focused on known mutualistic and pathogenic fungi, the functional role of ubiquitous endophytic fungi remains little explored.We examined how root‐inhabiting fungi (endophytes) influence range‐expanding plant species. We isolated endophytes from three European intra‐continental range‐expanders and three congenerics that are native both in the range expander's original (southern Europe) and new (northern Europe) range. To standardize our collection, endophytes were obtained from all six plant species growing under controlled conditions in northern (new range of the range expander) and southern (native range of the range expander) soils. We cultivated, molecularly identified and tested the effects of all isolates on seed germination, and growth of seedlings and older plants.Most of the 34 isolates could not be functionally characterized based on their taxonomic identity and literature information on functions. Endophytes affected plant growth in a plant species–endophyte‐specific manner, but overall differed between range‐expanders and natives. While endophytes reduced germination and growth of range‐expanders compared to natives, they reduced seedling growth of natives more than of range‐expanders.Synthesis. We conclude that endophytic fungi have a direct effect on plant growth in a plant growth stage‐dependent manner. While these effects differed between range expanders and natives, the effect strength and significance varied among the plant genera included in the present study. Nevertheless, endophytes likely influence the establishment of newly arriving plants and influence vegetation dynamics. [ABSTRACT FROM AUTHOR]

Effects of habitat restoration on belowground organisms and ecosystem processes are poorly understood. Morriën and colleagues show that changes in the composition and network interactions of soil biota lead to improved carbon uptake efficiency when formerly cultivated land is restored.

Introduced exotic plant species that originate from other continents are known to alter soil microbial community composition and nutrient cycling. Plant species that expand range to higher latitudes and altitudes as a consequence of current climate warming might as well affect the composition and functioning of native soil communities in their new range. However, the functional consequences of plant origin have been poorly studied in the case of plant range shifts. Here, we determined rhizosphere bacterial communities of four intracontinental range-expanding plant species in comparison with their four congeneric natives grown in soils collected from underneath those plant species in the field and in soils that are novel to them. We show that, when controlling for both species relatedness and soil characteristics, range-expanding plant species in higher latitude ecosystems will influence soil bacterial community composition and nutrient cycling in a manner similar to congeneric related native species. Our results highlight the importance to include phylogenetically controlled comparisons to disentangle the effect of origin from the effect of contrasting plant traits in the context of exotic plant species.

Current climate change has led to latitudinal and altitudinal range expansions of numerous species. During such range expansions, plant species are expected to experience changes in interactions with other organisms, especially with belowground biota that have a limited dispersal capacity. Nematodes form a key component of the belowground food web as they include bacterivores, fungivores, omnivores and root herbivores. However, their community composition under climate change‐driven intracontinental range‐expanding plants has been studied almost exclusively under controlled conditions, whereas little is known about actual patterns in the field. Here, we use novel molecular sequencing techniques combined with morphological quantification in order to examine nematode communities in the rhizospheres of four range‐expanding and four congeneric native species along a 2,000 km latitudinal transect from South‐Eastern to North‐Western Europe. We tested the hypotheses that latitudinal shifts in nematode community composition are stronger in range‐expanding plant species than in congeneric natives and that in their new range, range‐expanding plant species accumulate fewest root‐feeding nematodes. Our results show latitudinal variation in nematode community composition of both range expanders and native plant species, while operational taxonomic unit richness remained the same across ranges. Therefore, range‐expanding plant species face different nematode communities at higher latitudes, but this is also the case for widespread native plant species. Only one of the four range‐expanding plant species showed a stronger shift in nematode community composition than its congeneric native and accumulated fewer root‐feeding nematodes in its new range. We conclude that variation in nematode community composition with increasing latitude occurs for both range‐expanding and native plant species and that some range‐expanding plant species may become released from root‐feeding nematodes in the new range. [ABSTRACT FROM AUTHOR]

Global warming has begun to have a major impact on the species composition and functioning of plant and soil communities. However, long-term community and ecosystem responses to increased temperature are still poorly understood. In this study, we used a well-established elevational gradient in northern Sweden to elucidate how plant, microbial and nematode communities shift with elevation and associated changes in temperature in three highly contrasting vegetation types (i.e. heath, meadow and Salix vegetation). We found that responses of both the abundance and composition of microbial and nematode communities to elevation differed greatly among the vegetation types. Within vegetation types, changes with elevation of plant, microbial and nematode communities were mostly linked at fine levels of taxonomic resolution, but this pattern disappeared when coarser functional group levels were considered. Further, nematode communities shifted towards more conservative nutrient cycling strategies with increasing elevation in heath and meadow vegetation. Conversely, in Salix vegetation microbial communities with conservative strategies were most pronounced at the mid-elevation. These results provide limited support for increasing conservative nutrient cycling strategies at higher elevation (i.e. with a harsher climate). Our findings indicate that climate-induced changes in plant community composition may greatly modify or counteract the impact of climate change on soil communities. Therefore, to better understand and predict ecosystem responses to climate change, it will be crucial to consider vegetation type and its specific interactions with soil communities. [ABSTRACT FROM AUTHOR]

Summary Attenuation of RAS-mediated signalling is a conserved process essential to control cell proliferation, differentiation, and apoptosis. Cooperative interactions between histone modifications such as acetylation, methylation and sumoylation are crucial for proper attenuation in C. elegans, implying that the proteins recognising these histone modifications could also play an important role in attenuation of RAS-mediated signalling. We sought to systematically identify these proteins and found BET-1. BET-1 is a conserved double bromodomain protein that recognises acetyl-lysines on histone tails and maintains the stable fate of various lineages. Unexpectedly, adults lacking both BET-1 and SUMO-1 are depleted of muscle myosin, an essential component of myofibrils. We also show that this muscle myosin depletion does not occur in all animals at a specific time, but rather that the penetrance of the phenotype increases with age. To gain mechanistic insights into this process, we sought to delay the occurrence of the muscle myosin depletion phenotype and found that it requires caspase activity and MEK-dependent signalling. We also performed transcription profiling on these mutants and found an up-regulation of the FGF receptor, egl-15, a tyrosine kinase receptor acting upstream of MEK. Consistent with a MEK requirement, we could delay the muscle phenotype by systemic or hypodermal knock down of egl-15. Thus, this work uncovered a caspase- and MEK-dependent mechanism that acts specifically on ageing adults to maintain the appropriate net level of muscle myosin.

One of the major goals of quantitative genetics is to unravel the complex interactions between molecular genetic factors and the environment. The effects of these genotype-by-environment interactions also affect and cause variation in gene expression. The regulatory loci responsible for this variation can be found by genetical genomics that involves the mapping of quantitative trait loci (QTLs) for gene expression traits also called expression QTL (eQTLs). Most genetical genomics experiments published so far, are performed in a single environment and hence do not allow investigation of the role of genotype-by-environment interactions. Furthermore, most studies have been done in a steady state environment leading to acclimated expression patterns. However a response to the environment or change therein can be highly plastic and possibly lead to more and larger differences between genotypes. Here we present a genetical genomics study on 120 Arabidopsis thaliana, Landsberg erecta x Cape Verde Islands, recombinant inbred lines (RILs) in active response to the environment by treating them with 3 hours of shade. The results of this experiment are compared to a previous study on seedlings of the same RILs from a steady state environment. The combination of two highly different conditions but exactly the same RILs with a fixed genetic variation showed the large role of genotype-by-environment interactions on gene expression levels.We found environment-dependent hotspots of transcript regulation. The major hotspot was confirmed by the expression profile of a near isogenic line. Our combined analysis leads us to propose CSN5A, a COP9 signalosome component, as a candidate regulator for the gene expression response to shade.

• First complete aerial microbiome inventory through multi-primer metabarcoding. • Huge diversity of bacteria, fungi, protists and plant material in the air. • Microbiome contains many potential pathogens of plants and animals. • Many co-occuring taxa such as obligate insect parasites with host insects. • Predictable patterns of microbiome and pathogens depending on weather conditions. Air is a major conduit for the dispersal of organisms at the local and the global scale. Most research has focused on the dispersal of plants, vertebrates and human disease agents. However, the air represents a key dispersal medium also for bacteria, fungi and protists. Many of those represent potential pathogens of animals and plants and have until now gone largely unrecorded. Here we studied the turnover in composition of the entire aerobiome, the collective diversity of airborne microorganisms. For that we performed daily analyses of all prokaryotes and eukaryotes (including plants) using multi-marker high-throughput sequencing for a total of three weeks. We linked the resulting communities to local weather conditions, to assess determinants of aerobiome composition and distribution. We observed hundreds of microbial taxa, mostly belonging to spore-forming organisms including fungi, but also protists. Additionally, we detected many potential human- and plant-pathogens. Community composition fluctuated on a daily basis and was linked to concurrent weather conditions, particularly air pressure and temperature. Using network analyses, we identified taxonomically diverse groups of organisms with correlated temporal dynamics. In part, this was due to co-variation with environmental conditions, while we could also detect specific host-parasite interactions. This study provides the first full inventory of the aerobiome and identifies putative drivers of its dynamics in terms of taxon composition. This knowledge can help develop early warning systems against pathogens and improve our understanding of microbial dispersal. [ABSTRACT FROM AUTHOR]

Aim: To evaluate if real-time dose visualisation during computed tomography (CT)-guided interventions leads to a reduction in radiation dose to participating radiologists., Materials and Methods: The individual radiation dose radiologists are exposed to during CT interventions was measured using dedicated dosimeters (RaySafe i2-system, Unfors RaySafe GmbH, Billdal, Sweden) worn over the usual radiation protective apron. Initially, only the total radiation dose was measured, without visualisation (control group). In the following study period, the radiation dose was shown to participants on a live screen in real-time (experimental group). In both groups, the dose was recorded in 1-second intervals. The results collected were evaluated by comparison using descriptive statistics and mixed-effect models. In particular, the variables experience, gender, role, and position during the intervention were analysed., Results: In total, 517 measurements of 304 interventions (n=249 with and n=268 without live screen) performed by 29 radiologists acting as interventionalists or assistants were analysed. All CT-guided interventions were performed percutaneously, the majority of which (n=280) were microwave ablations (MWA). Radiation doses in the group without visualisation were comparable with usual dose rates for the corresponding intervention type. The mean total radiation dose was reduced by 58.1% (11.6 versus 4.86 μSv) in the experimental group (p=0.034). The highest reduction of 78.5% (15.55 versus 3.35 μSv) was observed in radiologists with the role of assistant (p=0.002). Sub-analysis showed significant dose reduction (p<0.0001) for the use of live screen in general; considering all variables, the role "assistant" alone had a statistically significant influence (p=0.002)., Conclusion: The real-time visualisation of active radiation dose during CT interventions leads to a relevant reduction in radiation dose to participating radiologists., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To investigate the potential of combining Compressed Sensing (CS) and a newly developed AI-based super resolution reconstruction prototype consisting of a series of convolutional neural networks (CNN) for a complete five-minute 2D knee MRI protocol., Methods: In this prospective study, 20 volunteers were examined using a 3T-MRI-scanner (Ingenia Elition X, Philips). Similar to clinical practice, the protocol consists of a fat-saturated 2D-proton-density-sequence in coronal, sagittal and transversal orientation as well as a sagittal T1-weighted sequence. The sequences were acquired with two different resolutions (standard and low resolution) and the raw data reconstructed with two different reconstruction algorithms: a conventional Compressed SENSE (CS) and a new CNN-based algorithm for denoising and subsequently to interpolate and therewith increase the sharpness of the image (CS-SuperRes). Subjective image quality was evaluated by two blinded radiologists reviewing 8 criteria on a 5-point Likert scale and signal-to-noise ratio calculated as an objective parameter., Results: The protocol reconstructed with CS-SuperRes received higher ratings than the time-equivalent CS reconstructions, statistically significant especially for low resolution acquisitions (e.g., overall image impression: 4.3 ± 0.4 vs. 3.4 ± 0.4, p < 0.05). CS-SuperRes reconstructions for the low resolution acquisition were comparable to traditional CS reconstructions with standard resolution for all parameters, achieving a scan time reduction from 11:01 min to 4:46 min (57 %) for the complete protocol (e.g. overall image impression: 4.3 ± 0.4 vs. 4.0 ± 0.5, p < 0.05)., Conclusion: The newly-developed AI-based reconstruction algorithm CS-SuperRes allows to reduce scan time by 57% while maintaining unchanged image quality compared to the conventional CS reconstruction., Competing Interests: Declaration of competing interest David Maintz is part of the speakers bureau at Philips Healthcare; all other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aspergilli can be used to produce food but can spoil it as well. Both food production and spoilage are initiated by germination of the conidia of these fungi that have been introduced by inoculation and contamination, respectively. Germination of these spores includes activation, swelling, establishment of cell polarity, and formation of a germ tube. So far, only quantitative single-species germination studies of fungal spores have been performed. Here, spore germination of the food spoilage fungus Aspergillus niger was studied quantitatively in mono-culture or when mixed with other food-relevant aspergilli (Aspergillus nidulans, Aspergillus terreus, Aspergillus clavatus, and Aspergillus oryzae). In the presence of the germination inducing amino acids proline or alanine, but not in the case of the lowly inducing amino acid arginine, the incidence of swelling and germ tube formation was reduced when 35,000 extra conidia of Aspergillus niger were added to wells containing 5000 of these spores. Adding 35,000 spores of one of the other aspergilli also did not have an effect on germination in the presence of arginine, but the germination inhibition was stronger when compared to the extra A. niger spores in the case of alanine. A similar effect was obtained with proline. Together, results show that the germination of A. niger conidia is impacted by the density of its own spores and that of other aspergilli under favorable nutritional conditions. These results increase our understanding of food spoilage by fungi and can be used to optimize food production with fungi., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluate the overall survival (OS), local progression-free survival (PFS) and prognostic factors of patients with colorectal cancer liver metastases (CRLM) undergoing microwave ablation (MWA)., Method: A total of 132 patients were retrospectively enrolled who had been treated between 2010 and 2018. For the evaluation of survival rates, all patients were divided according to their indications (curative n  = 57 and debulking (patients with additional non-target extrahepatic metastases) n  = 75). In total, 257 ablations were evaluated for prognostic factors: number of liver metastases, primary tumor origin (PTO), diameter and volume of metastases, duration and energy of ablation., Results: The OS was 32.1 months with 93.2% of patients free from recurrence at 28.3 months (median follow-up time). The one- year and three-year OS were 82.72% and 41.66%, respectively. The OS and recurrence-free survival of the curative group were statistically significantly higher than the debulking group ( p  < .001). Statistically significant prognostic factors for OS included the location of the primary tumor ( p  < .038) and the number of metastases (all p  < .017). Metastasis diameter and volume and ablation duration and energy had no significant correlation with survival ( p  > .05)., Conclusions: Satisfactory OS and local tumor PFS can be achieved in patients with CRLM using MWA with the number of metastases and the location of the primary tumor influencing the outcome of patients. The metastasis's size and the duration and energy used for ablation were not of significant prognostic value.

Objectives: To evaluate the potential of a fully automatic artificial intelligence (AI)-driven computed tomography (CT) software prototype to quantify severity of COVID-19 infection on chest CT in relationship with clinical and laboratory data., Methods: We retrospectively analyzed 50 patients with laboratory confirmed COVID-19 infection who had received chest CT between March and July 2020. Pulmonary opacifications were automatically evaluated by an AI-driven software and correlated with clinical and laboratory parameters using Spearman-Rho and linear regression analysis. We divided the patients into sub cohorts with or without necessity of intensive care unit (ICU) treatment. Sub cohort differences were evaluated employing Wilcoxon-Mann-Whitney-Test., Results: We included 50 CT examinations (mean age, 57.24 years), of whom 24 (48%) had an ICU stay. Extent of COVID-19 like opacities on chest CT showed correlations (all p < 0.001 if not otherwise stated) with occurrence of ICU stay (R = 0.74), length of ICU stay (R = 0.81), lethal outcome (R = 0.56) and length of hospital stay (R = 0.33, p < 0.05). The opacities extent was correlated with laboratory parameters: neutrophil count (NEU) (R = 0.60), lactate dehydrogenase (LDH) (R = 0.60), troponin (TNTHS) (R = 0.55) and c-reactive protein (CRP) (R = 0.51). Differences (p < 0.001) between ICU group and non-ICU group concerned longer length of hospital stay (24.04 vs. 10.92 days), higher opacity score (12.50 vs. 4.96) and severity of laboratory data changes such as c-reactive protein (11.64 vs. 5.07 mg/dl, p < 0.01)., Conclusions: Automatically AI-driven quantification of opacities on chest CT correlates with laboratory and clinical data in patients with confirmed COVID-19 infection and may serve as non-invasive predictive marker for clinical course of COVID-19., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

The influence of biological maturity status (BMS) on talent identification and development within elite youth soccer is critically debated. During adolescence, maturity-related performance differences within the same age group may cause greater chances of being selected for early maturing players. Therefore, coaches need to consider players' BMS. While standard methods for assessing BMS in adolescents are expensive and time-consuming imaging techniques (i.e., X-ray and MRI), there also exist more pragmatic procedures. This study aimed to evaluate commonly used methods to assess BMS within a highly selected sample of youth soccer players. A total of N = 63 elite male soccer players (U12 and U14) within the German Soccer Association's talent promotion program completed a test battery assessing BMS outcomes. Utilizing MRI diagnostics, players' skeletal age (SA MRI ) was determined by radiologists and served as the reference method. Further commonly used methods included skeletal age measured by an ultrasound device (SA US ), the maturity offset (MO MIR ), and the percentage of adult height (PAH KR ). The relation of these alternative BMS outcomes to SA MRI was examined using different perspectives: performing bivariate correlation analyses (1), modeling BMS as a latent variable (BMS lat ) based on the multiple alternative diagnostics (2), and investigating individual differences in agreement (3). (1) Correlations of SA MRI and the further BMS variables ranked from r = 0.80 to r = 0.84 for the total sample and were lower for U12 (0.56 ≤ r ≤ 0.66), and U14 (0.61 ≤ r ≤ 0.74) (2). The latent structural equation modeling (SEM) ( R 2 = 51%) revealed a significant influence on BMS lat for MO MIR (β = 0.51, p <0.05). The additional contribution of PAH KR (β = 0.27, p = 0.06) and SA US (β = -0.03, p = 0.90) was rather small (3). The investigation of individual differences between the reference method and alternative diagnostics indicated a significant bias for MO MIR ( p <0.01). The results support the use of economical and time-efficient methods for assessing BMS within elite youth soccer. Bivariate correlation analyses as well as the multivariate latent variable approach highlight the measures' usefulness. However, the observed individual level differences for some of the utilized procedures led to the recommendation for practitioners to use at least two alternative assessment methods in order to receive more reliable information about players' BMS within the talent promotion process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Leyhr, Murr, Basten, Eichler, Hauser, Lüdin, Romann, Sardo and Höner.)

Objectives: To analyze the performance of radiological assessment categories and quantitative computational analysis of apparent diffusion coefficient (ADC) maps using variant machine learning algorithms to differentiate clinically significant versus insignificant prostate cancer (PCa)., Methods: Retrospectively, 73 patients were included in the study. The patients (mean age, 66.3 ± 7.6 years) were examined with multiparametric MRI (mpMRI) prior to radical prostatectomy (n = 33) or targeted biopsy (n = 40). The index lesion was annotated in MRI ADC and the equivalent histologic slides according to the highest Gleason Grade Group (GrG). Volumes of interest (VOIs) were determined for each lesion and normal-appearing peripheral zone. VOIs were processed by radiomic analysis. For the classification of lesions according to their clinical significance (GrG ≥ 3), principal component (PC) analysis, univariate analysis (UA) with consecutive support vector machines, neural networks, and random forest analysis were performed., Results: PC analysis discriminated between benign and malignant prostate tissue. PC evaluation yielded no stratification of PCa lesions according to their clinical significance, but UA revealed differences in clinical assessment categories and radiomic features. We trained three classification models with fifteen feature subsets. We identified a subset of shape features which improved the diagnostic accuracy of the clinical assessment categories (maximum increase in diagnostic accuracy ΔAUC = + 0.05, p < 0.001) while also identifying combinations of features and models which reduced overall accuracy., Conclusions: The impact of radiomic features to differentiate PCa lesions according to their clinical significance remains controversial. It depends on feature selection and the employed machine learning algorithms. It can result in improvement or reduction of diagnostic performance., Key Points: • Quantitative imaging features differ between normal and malignant tissue of the peripheral zone in prostate cancer. • Radiomic feature analysis of clinical routine multiparametric MRI has the potential to improve the stratification of clinically significant versus insignificant prostate cancer lesions in the peripheral zone. • Certain combinations of standard multiparametric MRI reporting and assessment categories with feature subsets and machine learning algorithms reduced the diagnostic performance over standard clinical assessment categories alone.

Purpose: To examine predictive value of apparent diffusion coefficient (ADC) in diffusion-weighted imaging (DWI) for response of patients with primary and secondary lung neoplasms undergoing transpulmonary chemoembolization (TPCE) and transarterial chemoperfusion (TACP) treatment., Materials and Methods: Thirty-one patients (mean age ± SD 64 ± 12.4 y) with 42 lung target lesions (13 primary and 29 secondary) underwent DWI and subsequent ADC analysis on a 1.5T MR imaging scanner before and 30.3 days ± 6.4 after first session of TPCE or TACP. After 3.1 treatment sessions ± 1.4 performed in 2- to 4-week intervals, morphologic response was analyzed by comparing tumor diameter and volume before and after treatment on unenhanced T1-weighted MR images. On a per-lesion basis, response was classified according to Response Evaluation Criteria In Solid Tumors., Results: Threshold ADC increase of 20.7% indicated volume response with 88% sensitivity and 78% specificity (area under the curve [AUC] = 0.84). Differences between ADC changes in volume response groups were significant (P = .002). AUC for volume response predicted by ADC before treatment was 0.77. Median ADC before treatment and mean ADC change were 1.09 × 10 -3 mm 2 /second and 0.36 × 10 -3 mm 2 /second ± 0.23, 1.45 × 10 -3 mm 2 /second and 0.14 × 10 -3 mm 2 /second ± 0.16, and 1.30 × 10 -3 mm 2 /second and 0.06 × 10 -3 mm 2 /second ± 0.19 in partial response, stable disease, and progressive disease groups. In primary lung cancer lesions, strong negative correlation of ADC change with change in diameter (ρ = -.87, P < .001) and volume (ρ = -.66, P = .016) was found. In metastases, respective correlation coefficients were ρ = -.18 (P = .356) and ρ = -.35 (P = .061)., Conclusions: ADC quantification shows considerable diagnostic value for predicting response and monitoring TPCE and TACP treatment of patients with primary and secondary lung neoplasms., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Plant range expansion is occurring at a rapid pace, largely in response to human-induced climate warming. Although the movement of plants along latitudinal and altitudinal gradients is well-documented, effects on belowground microbial communities remain largely unknown. Furthermore, for range expansion, not all plant species are equal: in a new range, the relatedness between range-expanding plant species and native flora can influence plant-microorganism interactions. Here we use a latitudinal gradient spanning 3,000 km across Europe to examine bacterial and fungal communities in the rhizosphere and surrounding soils of range-expanding plant species. We selected range-expanding plants with and without congeneric native species in the new range and, as a control, the congeneric native species, totalling 382 plant individuals collected across Europe. In general, the status of a plant as a range-expanding plant was a weak predictor of the composition of bacterial and fungal communities. However, microbial communities of range-expanding plant species became more similar to each other further from their original range. Range-expanding plants that were unrelated to the native community also experienced a decrease in the ratio of plant pathogens to symbionts, giving weak support to the enemy release hypothesis. Even at a continental scale, the effects of plant range expansion on the belowground microbiome are detectable, although changes to specific taxa remain difficult to decipher.

Background: The lactic acid bacterium Lactobacillus rhamnosus GG is the most studied probiotic bacterium with proven health benefits upon oral intake, including the alleviation of diarrhea. The mission of the Yoba for Life foundation is to provide impoverished communities in Africa increased access to Lactobacillus rhamnosus GG under the name Lactobacillus rhamnosus yoba 2012, world's first generic probiotic strain. We have been able to overcome the strain's limitations to grow in food matrices like milk, by formulating a dried starter consortium with Streptococcus thermophilus that enables the propagation of both strains in milk and other food matrices. The affordable seed culture is used by people in resource-poor communities., Results: We used S. thermophilus C106 as an adjuvant culture for the propagation of L. rhamnosus yoba 2012 in a variety of fermented foods up to concentrations, because of its endogenous proteolytic activity, ability to degrade lactose and other synergistic effects. Subsequently, L. rhamnosus could reach final titers of 1E+09 CFU ml(-1), which is sufficient to comply with the recommended daily dose for probiotics. The specific metabolic interactions between the two strains were derived from the full genome sequences of L. rhamnosus GG and S. thermophilus C106. The piliation of the L. rhamnosus yoba 2012, required for epithelial adhesion and inflammatory signaling in the human host, was stable during growth in milk for two rounds of fermentation. Sachets prepared with the two strains, yoba 2012 and C106, retained viability for at least 2 years., Conclusions: A stable dried seed culture has been developed which facilitates local and low-cost production of a wide range of fermented foods that subsequently act as delivery vehicles for beneficial bacteria to communities in east Africa.

The Hawaiian strain (CB4856) of Caenorhabditis elegans is one of the most divergent from the canonical laboratory strain N2 and has been widely used in developmental, population, and evolutionary studies. To enhance the utility of the strain, we have generated a draft sequence of the CB4856 genome, exploiting a variety of resources and strategies. When compared against the N2 reference, the CB4856 genome has 327,050 single nucleotide variants (SNVs) and 79,529 insertion-deletion events that result in a total of 3.3 Mb of N2 sequence missing from CB4856 and 1.4 Mb of sequence present in CB4856 but not present in N2. As previously reported, the density of SNVs varies along the chromosomes, with the arms of chromosomes showing greater average variation than the centers. In addition, we find 61 regions totaling 2.8 Mb, distributed across all six chromosomes, which have a greatly elevated SNV density, ranging from 2 to 16% SNVs. A survey of other wild isolates show that the two alternative haplotypes for each region are widely distributed, suggesting they have been maintained by balancing selection over long evolutionary times. These divergent regions contain an abundance of genes from large rapidly evolving families encoding F-box, MATH, BATH, seven-transmembrane G-coupled receptors, and nuclear hormone receptors, suggesting that they provide selective advantages in natural environments. The draft sequence makes available a comprehensive catalog of sequence differences between the CB4856 and N2 strains that will facilitate the molecular dissection of their phenotypic differences. Our work also emphasizes the importance of going beyond simple alignment of reads to a reference genome when assessing differences between genomes., (Copyright © 2015 by the Genetics Society of America.)

In the Bateson-Dobzhansky-Muller (BDM) model of speciation, incompatibilities emerge from the deleterious interactions between alleles that are neutral or advantageous in the original genetic backgrounds, i.e., negative epistatic effects. Within species such interactions are responsible for outbreeding depression and F2 (hybrid) breakdown. We sought to identify BDM incompatibilities in the nematode Caenorhabditis elegans by looking for genomic regions that disrupt egg laying; a complex, highly regulated, and coordinated phenotype. Investigation of introgression lines and recombinant inbred lines derived from the isolates CB4856 and N2 uncovered multiple incompatibility quantitative trait loci (QTL). These QTL produce a synthetic egg-laying defective phenotype not seen in CB4856 and N2 nor in other wild isolates. For two of the QTL regions, results are inconsistent with a model of pairwise interaction between two loci, suggesting that the incompatibilities are a consequence of complex interactions between multiple loci. Analysis of additional life history traits indicates that the QTL regions identified in these screens are associated with effects on other traits such as lifespan and reproduction, suggesting that the incompatibilities are likely to be deleterious. Taken together, these results indicate that numerous BDM incompatibilities that could contribute to reproductive isolation can be detected and mapped within C. elegans., (Copyright © 2014 Snoek et al.)

Takeout proteins are found across a diverse range of insect species and are thought to be involved in important aspects of insect physiology and behavior. These proteins act as ligand carriers, but the nature of their endogenous ligands remains unknown. The crystal structure of Epiphyas postvittana Takeout 1 (EpTo1), the only structure for any Takeout protein to date, revealed an α/β-wrap fold with a purely hydrophobic internal cavity of tubular shape. When recombinantly expressed in Escherichia coli, we previously showed that a surrogate ubiquinone-8 ligand binds within the internal cavity of EpTo1 with excellent shape complementarity. We have now expressed EpTo1 in an insect cell expression system devoid of ubiquinone-8, and solved its crystal structure at 2.2Å resolution. Using combined information from crystallography and mass spectrometry, we identify a mixture of fatty acid moieties, mostly myristic and palmitic acid, bound inside the EpTo1 cavity, mimicking the structure of the longer ubiquinone-8 compound. No significant alteration of the internal cavity was observed regardless of the bound ligands, ubiquinone-8 or fatty acids, suggesting that the internal cavity of EpTo1 forms a rigid scaffold that imposes strict structural constraints for selectivity and specificity of ligand(s) in vivo., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Increased lifespan can be associated with greater resistance to many different stressors, most notably thermal stress. Such hormetic effects have also been found in C. elegans where short-term exposure to heat lengthens the lifespan. Genetic investigations have been carried out using mutation perturbations in a single genotype, the wild type Bristol N2. Yet, induced mutations do not yield insight regarding the natural genetic variation of thermal tolerance and lifespan. We investigated the genetic variation of heat-shock recovery, i.e. hormetic effects on lifespan and associated quantitative trait loci (QTL) in C. elegans. Heat-shock resulted in an 18% lifespan increase in wild type CB4856 whereas N2 did not show a lifespan elongation. Using recombinant inbred lines (RILs) derived from a cross between wild types N2 and CB4856 we found natural variation in stress-response hormesis in lifespan. Approx. 28% of the RILs displayed a hormesis effect in lifespan. We did not find any hormesis effects for total offspring. Across the RILs there was no relation between lifespan and offspring. The ability to recover from heat-shock mapped to a significant QTL on chromosome II which overlapped with a QTL for offspring under heat-shock conditions. The QTL was confirmed by introgressing relatively small CB4856 regions into chromosome II of N2. Our observations show that there is natural variation in hormetic effects on C. elegans lifespan for heat-shock and that this variation is genetically determined., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The number and distribution of gene expression QTL (eQTL) represent the genetic architecture of many complex traits, including common human diseases. We previously reported that the heritable eQTL patterns are highly dynamic with age in an N2 × CB4856 recombinant inbred population of the nematode Caenorhabditis elegans. In particular, we showed that the number of eQTL decreased with age. Here, we investigated the reason for this decrease by combining gene expression profiles at three ages in the wild types N2 and CB4856 with the reported expression profiles of the RIL population. We determined heritability and transgression (when gene expression levels in the RILs are more extreme than the parents) and investigated their relation with eQTL changes with age. Transgressive segregation was widespread but depended on physiological age. The percentage of genes with an eQTL increased with a higher heritability in young worms. However, for old worms this percentage hardly increased. Using a single marker approach, we found that almost 20% of genes with heritability >0.9 had an eQTL in developing worms. Surprisingly, only 10% was found in old worms. Using a multimarker approach, this percentage increased to almost 30% for both age groups. Comparison of the single marker to a multiple marker eQTL mapping indicated that heritable regulation of gene expression becomes more polygenic in aging worms due to multiple loci and possible epistatic interactions. We conclude that linkage studies should account for the relation between increased polygenic regulation and diminished effects at older ages.

Gene expression differences between individuals within a species can be largely explained by differences in genetic background. The effect of genetic variants (alleles) of genes on expression can be studied in a multifactorial way by the application of genetical genomics or expression quantitative trait locus mapping. In this paper, we present a strategy to construct regulatory networks by the application of genetical genomics in combination with transcript profiling of mutants that are disrupted in single genes. We describe the network identification downstream of the receptor-like kinase ERECTA in Arabidopsis (Arabidopsis thaliana). Extending genetical genomics on the Landsberg erecta/Cape Verde Islands (Ler/Cvi) recombinant inbred population with expression profiling of monogenic mutants enabled the identification of regulatory networks in the so far elusive ERECTA signal transduction cascade. We provide evidence that ERECTA is the causal gene for the major hotspot for transcript regulation in the Arabidopsis Ler/Cvi recombinant inbred population. We further propose additional genetic variation between Ler and Cvi in loci of the signaling pathway downstream of ERECTA and suggest candidate genes underlying these loci. Integration of publicly available microarray expression data of other monogenic mutants allowed us to link ERECTA to a downstream mitogen-activated protein kinase signaling cascade. Our study shows that microarray data of monogenic mutants can be effectively used in combination with genetical genomics data to enhance the identification of genetic regulatory networks.

Plants can respond quickly and profoundly to detrimental changes in their environment. For example, Arabidopsis thaliana can induce an upward leaf movement response through differential petiole growth (hyponastic growth) to outgrow complete submergence. This response is induced by accumulation of the phytohormone ethylene in the plant. Currently, only limited information is available on how this response is molecularly controlled. In this study, we utilized quantitative trait loci (QTL) analysis of natural genetic variation among Arabidopsis accessions to isolate novel factors controlling constitutive petiole angles and ethylene-induced hyponastic growth. Analysis of mutants in various backgrounds and complementation analysis of naturally occurring mutant accessions provided evidence that the leucin-rich repeat receptor-like Ser/Thr kinase gene, ERECTA, controls ethylene-induced hyponastic growth. Moreover, ERECTA controls leaf positioning in the absence of ethylene treatment. Our data demonstrate that this is not due to altered ethylene production or sensitivity.

Accessions of a plant species can show considerable genetic differences that are analyzed effectively by using recombinant inbred line (RIL) populations. Here we describe the results of genome-wide expression variation analysis in an RIL population of Arabidopsis thaliana. For many genes, variation in expression could be explained by expression quantitative trait loci (eQTLs). The nature and consequences of this variation are discussed based on additional genetic parameters, such as heritability and transgression and by examining the genomic position of eQTLs versus gene position, polymorphism frequency, and gene ontology. Furthermore, we developed an approach for genetic regulatory network construction by combining eQTL mapping and regulator candidate gene selection. The power of our method was shown in a case study of genes associated with flowering time, a well studied regulatory network in Arabidopsis. Results that revealed clusters of coregulated genes and their most likely regulators were in agreement with published data, and unknown relationships could be predicted.