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Abstract Background Limitations of the concept of identity by descent in the presence of stratification within a breeding population may lead to an incomplete formulation of the conventional numerator relationship matrix ( $$\mathbf{A}$$ A ). Combining $$\mathbf{A}$$ A with the genomic relationship matrix ( $$\mathbf{G}$$ G ) in a single-step approach for genetic evaluation may cause inconsistencies that can be a source of bias in the resulting predictions. The objective of this study was to identify stratification using genomic data and to transfer this information to matrix $$\mathbf{A}$$ A , to improve the compatibility of $$\mathbf{A}$$ A and $$\mathbf{G}$$ G . Methods Using software to detect population stratification (ADMIXTURE), we developed an iterative approach. First, we identified 2 to 40 strata ( $$k$$ k ) with ADMIXTURE, which we then introduced in a stepwise manner into matrix $$\mathbf{A}$$ A , to generate matrix $${\mathbf{A}}^{{\varvec{\Gamma}}}$$ A Γ using the metafounder methodology. Improvements in consistency between matrix $$\mathbf{G}$$ G and $${\mathbf{A}}^{{\varvec{\Gamma}}}$$ A Γ were evaluated by regression analysis and through the comparison of the overall mean and mean diagonal values of both matrices. The approach was tested on genotype and pedigree information of European and North American Brown Swiss animals (85,249). Analyses with ADMIXTURE were initially performed on the full set of genotypes (S1). In addition, we used an alternative dataset where we avoided sampling of closely related animals (S2). Results Results of the regression analyses of standard $$\mathbf{A}$$ A on $$\mathbf{G}$$ G were – 0.489, 0.780 and 0.647 for intercept, slope and fit of the regression. When analysing S1 data results of the regression for $${\mathbf{A}}^{{\varvec{\Gamma}}}$$ A Γ on $$\mathbf{G}$$ G corresponding values were – 0.028, 1.087 and 0.807 for $$k$$ k =7, while there was no clear optimum $$k$$ k . Analyses of S2 gave a clear optimal $$k$$ k =24, with − 0.020, 0.998 and 0.817 as results of the regression. For this $$k$$ k differences in mean and mean diagonal values between both matrices were negligible. Conclusions The derivation of hidden stratification information based on genotyped animals and its integration into $$\mathbf{A}$$ A improved compatibility of the resulting $${\mathbf{A}}^{{\varvec{\Gamma}}}$$ A Γ and $$\mathbf{G}$$ G considerably compared to the initial situation. In dairy breeding populations with large half-sib families as sub-structures it is necessary to balance the data when applying population structure analysis to obtain meaningful results.

In this work, the authors determine the crystal structure of a ProQ/FinO RNA chaperone bound to its RNA target. This provides insight into how this family of bacterial proteins recognize transcriptional terminator structures.

Abstract Background Managing beneficial Mendelian characteristics in dairy cattle breeding programs implies that the correlated genetic effects are considered to avoid possible adverse effects in selection processes. The Mendelian trait polledness in cattle is traditionally associated with the belief that the polled locus has unfavorable effects on breeding goal traits. This may be due to the inferior breeding values of former polled bulls and cows in cattle breeds, such as German Simmental, or to pleiotropic or linkage effects of the polled locus. Methods We focused on a variance component estimation approach that uses a marker-based numerator relationship matrix reflecting gametic relationships at the polled locus to test for direct pleiotropic or linked quantitative trait loci (QTL) effects of the polled locus on relevant traits. We applied the approach to performance, health, and female fertility traits in German Simmental cattle. Results Our results showed no evidence for any pleiotropic QTL effects of the polled locus on test-day production traits milk yield and fat percentage, on the mastitis indicator ‘somatic cell score’, and on several female fertility traits, i.e. 56 days non return rate, days open and days to first service. We detected a significant and unfavorable QTL effect accounting for 6.6% of the genetic variance for protein percentage only. Conclusions Pleiotropy does not explain the lower breeding values and phenotypic inferiority of polled German Simmental sires and cows relative to the horned population in the breed. Thus, intensified selection in the polled population will contribute to increased selection response in breeding goal traits and genetic merit and will narrow the deficit in breeding values for production traits.

Abstract During the first wave of the COVID-19 pandemic, we collected over 12,000 responses from a survey of scientists, who were asked to express their opinions on immunity certificates (also called “immunity passports”) as a potential instrument to lessen the impact of the crisis. Overall, we find that scientists perceive immunity certificates as favorable for public health (50.2%) and the state of the economy (54.4%) while one-fifth (19.1%) and one-sixth (15.4%) disagree. Scientists stipulate some concerns about fairness (36.5%) and inequality (22.4%) arising from implementation of immunity certification. We find some smaller differences among scientific fields, particularly between health scientists and social scientists, with the latter being slightly more positive about the effect of immunity certification. Scholars in the United States, including health scientists, are more likely to view the immunity certificates favorably and mention fewer concerns about this policy’s effect on fairness and inequality. Female scholars are significantly less in favor of immunity certificates, while scientists with more conservative political views hold more favorable opinions. Our results reveal that given the uncertainties during an early phase of a pandemic, scientists see scope for immunity certification to lessen the general societal impacts of the crisis.

Abstract Background Seventy percent of patients suffering from birch pollen allergy (BPA) develop a pollen‐related food allergy (prFA), especially to apples, due to a clinically relevant cross‐reactivity between the major allergen in birch Bet v 1 and Mal d 1 in apples. Therefore allergen‐specific immunotherapy with fresh apples (AITA) could be a promising natural treatment of both BPA and prFA. Objective To assess the clinical efficacy of immunotherapy by daily apple consumption for patients with BPA and prFA. Methods A daily defined increasing amount of selected cultivars (Red Moon®, Pink Lady®, Topaz, Golden Delicious) was continuously consumed by 16 patients (12 female; median age; 50; range, 23–68 years), leading to increased intake of allergen over a period of at least 8 months. Specific IgE and IgG4 to Bet v 1 and Mal d 1, conjunctival and oral provocation tests, skin reactivity, and the average daily rhinoconjunctivitis combined symptom and medication score (CSMS) were measured during the peak birch pollen season. Results After 8 months of therapy, patients showed increased tolerance to apples (p

The protein Mal d 1 is responsible for most allergic reactions to apples (Malus domestica) in the northern hemisphere. Mal d 1 contains a cysteine residue on its surface, with its reactive side chain thiol exposed to the surrounding food matrix. We show that, in vitro, this cysteine residue is prone to spontaneous chemical modification by ascorbic acid (vitamin C). Using NMR spectroscopy and mass spectrometry, we characterize the chemical structure of the cysteine adduct and provide a three-dimensional structural model of the modified apple allergen. The S-ascorbylated cysteine partially masks a major IgE antibody binding site on the surface of Mal d 1, which attenuates IgE binding in sera of apple-allergic patients. Our results illustrate, from a structural perspective, the role that chemical modifications of allergens with components of the natural food matrix can play.

PR-10 proteins constitute a major cause of food allergic reactions. Birch-pollen-related food allergies are triggered by the immunologic cross-reactivity of IgE antibodies with structurally homologous PR-10 proteins that are present in birch pollen and various food sources. While the three-dimensional structures of PR-10 food allergens have been characterized in detail, only a few experimental studies have addressed the structural flexibility of these proteins. In this study, we analyze the millisecond-timescale structural flexibility of thirteen PR-10 proteins from prevalent plant food sources by NMR relaxation-dispersion spectroscopy, in a comparative manner. We show that all the allergens in this study have inherently flexible protein backbones in solution, yet the extent of the structural flexibility appears to be strikingly protein-specific (but not food-source-specific). Above-average flexibility is present in the two short helices, α1 and α2, which form a V-shaped support for the long C-terminal helix α3, and shape the internal ligand-binding cavity, which is characteristic for PR-10 proteins. An in-depth analysis of the NMR relaxation-dispersion data for the PR-10 allergen from peanut reveals the presence of at least two subglobal conformational transitions on the millisecond timescale, which may be related to the release of bound low-molecular-weight ligands from the internal cavity.

Electroencephalography (EEG) allows measuring human brain activity for scientific, diagnostic and therapeutic purposes. For scientific purposes, EEG is traditionally used to study the brain-behaviour relationship under well controlled laboratory conditions while the participant sits quietly in a room. Consequently, our knowledge regarding the brain-behaviour relationship was limited to human behaviour under constrained conditions. The development of mobile EEG hardware in the last years allows moving beyond the lab and studying brain activity in everyday life. Most EEG systems record from electrodes that are distributed over the head, kept in place with an elastic cap or net. For long term EEG recordings, to study natural behaviour in public, these systems are not optimal, as they are rather bulky and unpleasant to wear for longer periods. We argue for “transparent”, ear-centered EEG systems instead. Transparent in the sense that both the person wearing the EEG system as well as the people interacting with that person are not disturbed by it. We describe here the integration of a commercially available research-grade mobile EEG amplifier and a commercially available neck speaker as a mounting system to be used in combination with ear electrodes (cEEGrid). This nEEGlace can be used for ear-EEG recordings in public over extended periods of time. The integrated microphone and the integrated speakers provide the possibility to play and record sound. This allows conducting experiments on auditory perception beyond the lab by both studying the brain responses to naturally occurring sounds as well as to experimental auditory stimuli. We describe the general design, present a working prototype, outline a number of use cases and discuss future improvements of the proposed design.

Investigations of toothbrushing habits are an important vector to understand their influence on brushing effectiveness. User compliance in toothbrushing is known to deviate from professional recommendations in brushing time, evenness across all areas of the dentition, and brushing force [1,2]. Despite the recent development of tools designed to guide users to optimised brushing habits [3,4], research on habit evaluation and tracking is limited and typically relies on labour-intensive video observation (VO) [5]. Here we present raw data on toothbrush position as determined by an automated motion tracking (MT) capability and by human VO and provide a technical description of the MT capability. The MT system described in this article was developed in collaboration with Soft2Tec GmbH (Rüsselsheim, Germany) as a potential substitute for the VO tool. The MT system consists of a monocular vision module and a target module with active infrared LED trackers. The MT system determined the position and orientation of a toothbrush relative to the jaw while subjects brushed under realistic conditions. For VO, a trained assessor coded video recording data from toothbrushing sessions. The data presented here describes a clinical study (103 subjects; 46 completed two sessions, 57 completed one session, altogether 149 events) comparing toothbrushing behaviour recorded with the MT system and with VO simultaneously. The raw data was deposited in Mendeley Data, under data identification number doi:10.17632/4f384xrbhm.1 [https://data.mendeley.com/datasets/4f384xrbhm/1].

For motor imagery (MI) to be effective, an internal representation of the to-be-imagined movement may be required. A representation can be achieved through prior motor execution (ME), but the neural correlates of MI that are primed by ME practice are currently unknown. In this study, young healthy adults performed MI practice of a unimanual visuo-motor task (Group MI, n = 19) or ME practice combined with subsequent MI practice (Group ME&MI, n = 18) while electroencephalography (EEG) was recorded. Data analysis focused on the MI-induced event-related desynchronization (ERD). Specifically, changes in the ERD and movement times (MT) between a short familiarization block of ME (Block pre-ME), conducted before the MI or the ME combined with MI practice phase, and a short block of ME conducted after the practice phase (Block post-ME) were analyzed. Neither priming effects of ME practice on MI-induced ERD were found nor performance-enhancing effects of MI practice in general. We found enhancements of the ERD and MT in Block post-ME compared to Block pre-ME, but only for Group ME&MI. A comparison of ME performance measures before and after the MI phase indicated however that these changes could not be attributed to the combination of ME and MI practice. The mixed results of this study may be a consequence of the considerable intra- and inter-individual differences in the ERD, introduced by specifics of the experimental setup, in particular the individual and variable task duration, and suggest that task and experimental setup can affect the interplay of ME and MI.

The long-term performance of different selection strategies was evaluated via simulation using the example of a local cattle breed, German Angler cattle. Different optimum contribution selection (OCS) approaches to maximize genetic gain were compared to a reference scenario without selection and truncation selection. The kinships and migrant contribution (MC) were estimated from genomic data. Truncation selection achieved the highest genetic gain but decreased diversity considerably at native alleles. It also caused the highest increase in MCs. Traditional OCS, which only constrains kinship, achieved almost the same genetic gain but also caused a small increase of MC and remarkably reduced the diversity of native alleles. When MC was required not to increase and the increase of kinship at native alleles was restricted, the MC levels and the diversity at native alleles were well managed, and the genetic gain was only slightly reduced. However, genetic progress was substantially lower in the scenario that aimed to recover the original genetic background. Truncation selection and traditional OCS selection both reduce the genetic originality of breeds with historical introgression. The inclusion of MC and kinship at native alleles as additional constraints in OCS showed great potential for conservation. Recovery of the original genetic background is possible but requires many generations of selection and reduces the genetic progress in performance traits. Hence, constraining MCs at their current values can be recommended to avoid further reduction of genetic originality.

Abstract Background Genotyping and whole-genome sequencing data have been generated for hundreds of thousands of cattle. International consortia used these data to compile imputation reference panels that facilitate the imputation of sequence variant genotypes for animals that have been genotyped using dense microarrays. Association studies with imputed sequence variant genotypes allow for the characterization of quantitative trait loci (QTL) at nucleotide resolution particularly when individuals from several breeds are included in the mapping populations. Results We imputed genotypes for 28 million sequence variants in 17,229 cattle of the Braunvieh, Fleckvieh and Holstein breeds in order to compile large mapping populations that provide high power to identify QTL for milk production traits. Association tests between imputed sequence variant genotypes and fat and protein percentages in milk uncovered between six and thirteen QTL (P