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Intensive human intervention in the natural drainage system of the Hessische Ried (Upper Rhine Graben, Germany) resulted in the transformation of a large wetland into an intensively used cultural landscape. At least since the first century CE, when Romans conducted early river regulation and water management, the natural water network has experienced extensive anthropogenic re-organisation. The LandGraben project focuses on the reconstruction of the natural and anthropogenic watercourse systems along the river Landgraben, a tributary to the river Rhine in the northern Hessische Ried. Several rivers from the southern Hessische Ried could have fed the river Landgraben during Roman times via the meandering Palaeo-Neckar depression, thus increasing both length and discharge of the Roman waterway. In this study, we present results of our investigations within the southern Hessische Ried to reconstruct the former channel network that was used by Romans for the transportation of troops, wares and border security. Our approach integrates the use of high-resolution digital elevation models (DEMs) as a base for geophysical measurements (electrical resistivity tomography, ERT), direct push sensing and sediment coring in combination with sedimentological and geochemical analyses of the encountered sedimentary units. Local chronostratigraphies were established based on radiocarbon dating. Based on our results, we are able to differentiate a palimpsest of several abandoned fluvial channels throughout the southern Hessische Ried and to reconstruct the spatio-temporal development of the corresponding fluvial systems. Chronostratigraphic data show that the Palaeo-Neckar stopped flowing through the Hessische Ried around 10 000 cal BCE. Moreover, we found that the river Weschnitz, the largest of the possible Landgraben tributaries, stopped flowing through the Palaeo-Neckar depression at ca. 3000 cal BCE. Instead, it took a right-angled shortcut westwards to the river Rhine, north of the city of Lorsch. For the first time, we present geomorphological evidence that the river Weschnitz was not diverted by the Romans as speculated so far. This is corroborated by numerous wooden posts of human-made construction crossing an E–W running water course at the modern Weschnitz knee, with the oldest posts being dendrochronologically dated to the fourth and third millennia BCE. We further argue that the river Winkelbach/Lauter formed its knee towards the river Rhine and thus left the Palaeo-Neckar depression not later than the second century CE but most probably even contemporaneously with the formation of the Weschnitz diversion. In the case of the Winkelbach/Lauter, a high-energy flood event presumably related to strong rainfall and/or meltwater processes in the Odenwald Mountains is assumed to be responsible for the initiation of the new, diverted water course. With regard to the Landgraben and its use as a waterway within the Roman fluvioscape of the Hessische Ried, we therefore conclude that the Romans successfully collected water from several smaller rivers, such as from the rivers Modau and Darmbach and from even smaller tributaries, to make the river Landgraben a navigable waterway. The rivers Weschnitz and Winkelbach/Lauter, however, did not contribute any water to the Landgraben system during Roman times.

Abstract Micro- and nanoplastics (MNPs) are ubiquitous environmental pollutants representing a concern for human health. MNPs have been detected in human placentas, indicating that during pregnancy maternal exposure may lead to placental transfer and foetal exposure, with potential for adverse effects on early-life development. However, a comprehensive risk assessment (RA) framework, specific to early-life is lacking. Here, we propose a novel roadmap to assist the development of an early-life health RA of MNPs. This roadmap is designed based on established chemical, mixture, particle, and MNP assessment strategies aligned with standard RA components (problem formulation, hazard identification, hazard characterisation, exposure assessment, risk characterisation). We systematically work through these stages to identify what is needed to progress a RA for the early-life impacts of MNPs, including what information is missing, and what may be used in the interim. While challenges such as complex physicochemical properties of MNPs, limited toxicity data at relevant exposure levels, and uncertainties related to characterising complex exposures have been described elsewhere, our work discusses how these challenges specifically impact early-life stages such as the significance of MNP presence in biological samples and factors influencing bioaccumulation and placental transfer. Additionally, we introduce the development of new technology readiness levels for methods used in the detection of MNPs in complex matrices. Importantly, this review integrates a broad scope of relevant information into one comprehensive document, providing a unified resource. We highlight specific requirements and areas for targeted research, including the development of dose-response relationships specific to early-life stages and novel strategies for assessing bioaccumulation and placental transfer of MNPs. By addressing these gaps, our roadmap aims to advance the development of a robust framework, ultimately enhancing the understanding and mitigation of risks associated with early-life exposure to MNPs.

The welfare of dairy cows is becoming increasingly important. While diseases like mastitis and lameness are common ailments, injuries to the tail tip go largely unnoticed. This study aimed to investigate whether tail tip lesions, which are mostly described in beef cattle, also occurred on n=5 dairy farms, along with determining what type and at what frequency. The study consisted of two phases. During the first part of the study, tail tips of 78 dairy cows were examined over a period of 6 months; based on these results, we developed a training card on tail tip lesions in dairy cows, which was used in part two of the study to train further examiners to inspect four more flocks. In total, we collected n=3587 tail records from n=513 Holstein and n= 128 Simmental dairy cows. The overall frequency regarding all types of lesions ranged between 84.0 % (±2.0) and 94.1 % (±1.8) in Holstein herds and between 97.0 % (±2.2) and 99.0 % (±2.2) in Simmental herds. To our knowledge, this is the first investigation of tail tip lesions in German dairy cows. We concluded that tail tip lesions might be a frequent yet unnoticed condition in German dairy cows.

Background. Hordeum bulbosum L. is the only wild species of the genus Hordeum, the gene pool of which is successfully used in introgressive hybridization to increase the genetic diversity of H. vulgare L. When creating introgression forms based on hybrids of H. vulgare with H. bulbosum, it is necessary to take into consideration the ploidy of the parent species, and their genetic features that determine the intensity of the process of H. bulbosum chromosomes elimination in embryogenesis. The purpose of our investigation was to study the features associated with the elimination of bulbous barley chromosomes in embryos obtained in various combinations of crosses involving the tetraploid hybrid H. bulbosum with H. vulgare for its effective use in obtaining introgression lines of H. vulgare. Material and methods. The analysis was performed on 9-15 days old embryos obtained in crosses of the tetraploid hybrid F2 (H. bulbosum A17 (4x) × H. vulgare ‘Borwina’ (4x)) (HbHbHvHv) with ‘Igri’ (2x) and ‘Borwina’ (2x) barley varieties, with H. bulbosum A17 (4x), as well as during its self-pollination. The chromosomal composition of embryos of different ages was analyzed on squashed embryo slides using genomic in situ hybridization (GISH). Results. Among the 11-15 days old embryos obtained from self-pollination of the hybrid, approximately half of the studied ones were mixoploids, while in other embryos the majority of cells contained only the genomic material of H. vulgare. The elimination process was very intensive in crosses of the hybrid with the barley varieties ‘Igri’ (2x) and ‘Borwina’ (2x), and by day 10-11 after pollination cells containing only the genomic material of H. vulgare predominated in all embryos, regardless of the direction of crossing and the variety used. Hybrid embryos with a stable chromosomal composition resulted from a cross of a tetraploid hybrid with H. bulbosum A17 (4x). Embryos with recombinant H. vulgare chromosomes carrying alien genetic material of bulbous barley were identified in all types of crosses. Conclusion. The most efficient way for the mass production of introgression lines of cultivated barley varieties based on the partially fertile hybrid F2 (H. bulbosum A17 (4x) × H. vulgare ‘Borwina’ (4x)), is the crossing with varieties of H. vulgare (2x). The progeny from such crosses will contain only cultivated barley plants, among which it is possible to identify forms with the introgression of H. bulbosum and use already the first generation from their self-pollination for selecting H. vulgare lines carrying the genetic material of bulbous barley in both homologs.

PurposeHuman OX40 (hOX40/CD134), a member of the TNF receptor superfamily, is mainly expressed on activated T lymphocytes. Triggered by its ligand OX40L (CD252), it provides costimulatory signals that support the differentiation, proliferation and long-term survival of T cells. Besides being a relevant therapeutic target, hOX40 is also an important biomarker for monitoring the presence or infiltration of activated T cells within the tumor microenvironment (TME), the inflammatory microenvironment (IME) in immune-mediated diseases (IMIDs) and the lymphatic organs. Here, we developed novel single domain antibodies (nanobodies, Nbs) targeting hOX40 to monitor the activation status of T cells by in vivo molecular imaging.MethodsNbs against hOX40 (hOX40-Nbs) were selected from an immunized Nb-library by phage display. The identified hOX40-Nbs were characterized in vitro, including determination of their specificity, affinity, stability, epitope recognition and their impact on OX40 signaling and T cell function. A lead candidate was site-specifically conjugated with a fluorophore via sortagging and applied for noninvasive in vivo optical imaging (OI) of hOX40-expressing cells in a xenograft mouse model.ResultsOur selection campaign revealed four unique Nbs that exhibit strong binding affinities and high stabilities under physiological conditions. Epitope binning and domain mapping indicated the targeting of at least two different epitopes on hOX40. When analyzing their impact on OX40 signaling, an agonistic effect was excluded for all validated Nbs. Incubation of activated T cells with hOX40-Nbs did not affect cell viability or proliferation patterns, whereas differences in cytokine release were observed. In vivo OI with a fluorophore-conjugated lead candidate in experimental mice with hOX40-expressing xenografts demonstrated its specificity and functionality as an imaging probe.ConclusionConsidering the need for advanced probes for noninvasive in vivo monitoring of T cell activation dynamics, we propose, that our hOX40-Nbs have a great potential as imaging probes for noninvasive and longitudinal in vivo diagnostics. Quantification of OX40+ T cells in TME or IME will provide crucial insights into the activation state of infiltrating T cells, offering a valuable biomarker for assessing immune responses, predicting treatment efficacy, and guiding personalized immunotherapy strategies in patients with cancer or IMIDs.

BackgroundMicro- and nanoplastics (MNPs) are emerging pollutants of concern with ubiquitous presence in global ecosystems. MNPs pose potential implications for human health; however, the health impacts of MNP exposures are not yet understood. Recent evidence suggests that MNPs can cross the placental barrier, underlying the urgent need to understand their impact on reproductive health and development. ObjectiveThe Actionable eUropean ROadmap for early-life health Risk Assessment of micro- and nanoplastics (AURORA) project will investigate MNP exposures and their biological and health effects during pregnancy and early life, which are critical periods due to heightened vulnerability to environmental stressors. The AURORA project will enhance exposure assessment capabilities for measuring MNPs, MNP-associated chemicals, and plastic additives in human tissues, including placenta and blood. MethodsIn this interdisciplinary project, we will advance methods for in-depth characterization and scalable chemical analytical strategies, enabling high-resolution and large-scale toxicological, exposure assessment, and epidemiological studies. The AURORA project performs observational studies to investigate determinants and health impacts of MNPs by including 800 mother-child pairs from 2 existing birth cohorts and 110 women of reproductive age from a newly established cohort. This will be complemented by toxicological studies using a tiered-testing approach and epidemiological investigations to evaluate associations between maternal and prenatal MNP exposures and health perturbations, such as placental function, immune-inflammatory responses, oxidative stress, accelerated aging, endocrine disruption, and child growth and development. The ultimate goal of the AURORA project is to create an MNP risk assessment framework and identify the remaining knowledge gaps and priorities needed to comprehensively assess the impact of MNPs on early-life health. ResultsIn the first 3 years of this 5-year project (2021-2026), progress was made toward all objectives. This includes completion of recruitment and data collection for new and existing cohorts, development of analytical methodological protocols, and initiation of the toxicological tiered assessments. As of September 2024, data analysis is ongoing and results are expected to be published starting in 2025. ConclusionsAs plastic pollution increases globally, it is imperative to understand the impact of MNPs on human health, particularly during vulnerable developmental stages such as early life. The contributions of the AURORA project will inform future risk assessment. International Registered Report Identifier (IRRID)DERR1-10.2196/63176

Abstract Few studies report the occurrence of microplastics (MP), including tire wear particles (TWP) in the marine atmosphere, and little data is available regarding their size or sources. Here we present active air sampling devices (low- and high-volume samplers) for the evaluation of composition and MP mass loads in the marine atmosphere. Air was sampled during a research cruise along the Norwegian coast up to Bear Island. Samples were analyzed with pyrolysis-gas chromatography-mass spectrometry, generating a mass-based data set for MP in the marine atmosphere. Here we show the ubiquity of MP, even in remote Arctic areas with concentrations up to 37.5 ng m−3. Cluster of polyethylene terephthalate (max. 1.5 ng m−3) were universally present. TWP (max. 35 ng m−3) and cluster of polystyrene, polypropylene, and polyurethane (max. 1.1 ng m−3) were also detected. Atmospheric transport and dispersion models, suggested the introduction of MP into the marine atmosphere equally from sea- and land-based emissions, transforming the ocean from a sink into a source for MP.

Signal-regulatory protein α (SIRPα) expressed by myeloid cells is of particular interest for therapeutic strategies targeting the interaction between SIRPα and the “don’t eat me” ligand CD47 and as a marker to monitor macrophage infiltration into tumor lesions. To address both approaches, we developed a set of novel human SIRPα (hSIRPα)–specific nanobodies (Nbs). We identified high-affinity Nbs targeting the hSIRPα/hCD47 interface, thereby enhancing antibody-dependent cellular phagocytosis. For non-invasive in vivo imaging, we chose S36 Nb as a non-modulating binder. By quantitative positron emission tomography in novel hSIRPα/hCD47 knock-in mice, we demonstrated the applicability of 64Cu-hSIRPα-S36 Nb to visualize tumor infiltration of myeloid cells. We envision that the hSIRPα-Nbs presented in this study have potential as versatile theranostic probes, including novel myeloid-specific checkpoint inhibitors for combinatorial treatment approaches and for in vivo stratification and monitoring of individual responses during cancer immunotherapies.

The pollution of the environment with plastics is of growing concern worldwide, including the Arctic region. While larger plastic pieces are a visible pollution issue, smaller microplastics are not visible with the naked eye. These particles are available for interaction by Arctic biota and have become a concern for animal and human health. The determination of microplastic properties includes several methodological steps, i.e., sampling, extraction, quantification, and chemical identification. This review discusses suitable analytical tools for the identification, quantification, and characterization of microplastics in the context of monitoring in the Arctic. It further addresses quality assurance and quality control (QA/QC), which is particularly important for the determination of microplastic in the Arctic, as both contamination and analyte losses can occur. It presents specific QA/QC measures for sampling procedures and for the handling of samples in the laboratory, either on land or on ship, and considering the small size of microplastics as well as the high risk of contamination. The review depicts which data should be mandatory to report, thereby supporting a framework for harmonized data reporting.

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of bovine paratuberculosis, a chronic granulomatous enteritis leading to economic losses and posing a risk to human health due to its zoonotic potential. The pathogen cannot reliably be detected by standard methods, and immunological procedures during the infection are not well understood. Therefore, the aim of our study was to explore host–pathogen interactions in MAP-infected dairy cows and to improve diagnostic tests. Serum proteomics analysis using quantitative label-free LC-MS/MS revealed 60 differentially abundant proteins in MAP-infected dairy cows compared to healthy controls from the same infected herd and 90 differentially abundant proteins in comparison to another control group from an uninfected herd. Pathway enrichment analysis provided new insights into the immune response to MAP and susceptibility to the infection. Furthermore, we found a higher abundance of Cathepsin S (CTSS) in the serum of MAP-infected dairy cows, which is involved in multiple enriched pathways associated with the immune system. Confirmed with Western blotting, we identified CTSS as a potential biomarker for bovine paratuberculosis. This study enabled a better understanding of procedures in the host–pathogen response to MAP and improved detection of paratuberculosis-diseased cattle.

Objectives: The Prospective Randomized On-X Mechanical Prosthesis Versus St Jude Medical Mechanical Prosthesis Evaluation (PROSE) trial purpose was to investigate whether a current-generation mechanical prosthesis (On-X; On-X Life Technologies/Artivion Inc) reduced the incidence of thromboembolic-related complications compared with a previous-generation mechanical prosthesis (St Jude Medical Mechanical Prosthesis; Abbott/St Jude Medical). This second report documents the valve-related complications by individual prostheses and by Western and Developing populations. Methods: The PROSE trial study was conducted in 28 worldwide centers and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The study protocol, and analyses of 10 demographic variables and 24 risk factors were published in detail in 2021. Results: The total patient population (N = 855) included patients receiving an On-X valve (n = 462) and a St Jude Medical valve (n = 393). The overall freedom evaluation showed no differences at 5 years between the prostheses for thromboembolism or for valve thrombosis. There were also no differences in mortality. There were several differences between Developing and Western populations. The freedom relations at 5 years for mortality favored Western over Developing populations. Valve thrombosis was differentiated by position and site: aortic

The mission of WEST (tungsten-W Environment in Steady-state Tokamak) is to explore long pulse operation in a full tungsten (W) environment for preparing next-step fusion devices (ITER and DEMO) with a focus on testing the ITER actively cooled W divertor in tokamak conditions. Following the successful completion of phase 1 (2016-2021), phase 2 started in December 2022 with the lower divertor made entirely of actively cooled ITER-grade tungsten mono-blocks. A boronization prior the first plasma attempt allowed for a smooth startup with the new divertor. Despite the reduced operating window due to tungsten, rapid progress has been made in long pulse operation, resulting in discharges with a pulse length of 100 s and an injected energy of around 300 MJ per discharge. Plasma startup studies were carried out with equatorial boron nitride limiters to compare them with tungsten limiters, while Ion Cyclotron Resonance Heating assisted startup was attempted. High fluence operation in attached regime, which was the main thrust of the first campaigns, already showed the progressive build up of deposits and appearance of dust, impacting the plasma operation as the plasma fluence increased. In total, the cumulated injected energy during the first campaigns reached 43 GJ and the cumulated plasma time exceeded 5 h. Demonstration of controlled X-Point Radiator regime is also reported, opening a promising route for investigating plasma exhaust and plasma-wall interaction issues in more detached regime. This paper summarises the lessons learned from the manufacturing and the first operation of the ITER-grade divertor, describing the progress achieved in optimising operation in a full W environment with a focus on long pulse operation and plasma wall interaction.

The disruption and runaway electron analysis model code was extended to include tungsten impurities in disruption simulations with the aim of studying the runaway electron (RE) generation. This study investigates RE current sensitivity on the following plasma parameters and modelling choices: tungsten concentration, magnetic perturbation strength, electron modelling, thermal quench time and tokamak geometry—ITER-like or ASDEX-like. Our investigation shows that a tungsten concentration below 10 ^−3 does not cause significant RE generation on its own. However, at higher concentrations it is possible to reach a very high RE current. Out of the two tested models of electrons in plasma: fluid and isotropic (kinetic), results from the fluid model are more conservative, which is useful when it comes to safety analysis. However, these results are overly pessimistic when compared to the isotropic model, which is based on a more reliable approach. Our results also show that the hot-tail RE generation mechanism is dominant as a primary source of RE in tungsten induced disruptions, usually providing orders of magnitude higher RE seed than Dreicer generation. We discuss best practices for simulations with tungsten-rich plasma, present the dependence of the safety limits on modelling choices and highlight the biggest shortcoming of the current simulation techniques. The obtained results pave the way for a wider analysis of tungsten impact on the disruption dynamics, including the mitigation techniques for ITER in the case of strong contamination of the plasma with tungsten.

Abstract Objectives The PROSE trial purpose is to investigate whether the incidence of thromboembolic—related complications is reduced with a current generation mechanical prosthesis (On-X Life Technologies/CryoLife Inc.—On-X) compared with a previous generation mechanical prosthesis (St Jude Medical—SJM). The primary purpose of the initial report is to document the preoperative demographics, and the preoperative and operative risk factors by individual prosthesis and by Western and Developing populations. Methods The PROSE study was conducted in 28 worldwide centres and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The preoperative demographics incorporated age, gender, functional class, etiology, prosthetic degeneration, primary rhythm, primary valve lesion, weight, height, BSA and BMI. The preoperative and operative evaluation incorporated 24 risk factors. Results The total patient population (855) incorporated On-X population (462) and the St Jude Medical population (393). There was no significant difference of any of the preoperative demographics between the On-X and SJM groups. The preoperative and operative risk factors evaluation showed there was no significant difference between the On-X and St Jude Medical populations. The preoperative and operative risk factors by valve position (aortic and mitral) also documented no differentiation. The dominant preoperative demographics of the Western world population were older age, male gender, sinus rhythm, aortic stenosis, congenital aortic lesion, and mitral regurgitation. The dominant demographics of the Developing world population were rheumatic etiology, atrial fibrillation, aortic regurgitation, mixed aortic lesions, mitral stenosis and mixed mitral lesions. The Developing world group had only one significant risk factor, congestive heart failure. The majority of the preoperative and operative risk factors were significant in the Western world population. Conclusions The preoperative demographics do not differentiate the prostheses but do differentiate the Western and Developing world populations. The preoperative and operative risk factors do not differentiate the prostheses BUT do differentiate the Western and Developing world populations.

Natural floodplains are ecosystems with a diverse mosaic of habitats and site conditions, but also highly threatened due to anthropogenic pressures. Plant species occur in all habitat types and can indicate their value for nature conservation. To improve sustainable management of rivers and floodplains, several indices such as the River Ecosystem Service Index (RESI) have been developed. However, there are so far no assessment schemes for the entire range of floodplain plants. The common assessment approaches like biological integrity, achievement rates or threatened species (Red list), applying to other species groups or other ecosystems, are not appropriate in floodplains. Legal obligations and the need to restore floodplains clearly call for an index assessing the ecological value in a reference area which can be combined with a 5-scale assessment in accordance to established assessments like RESI or the Water Framework Directive.Five typical characteristics describing vascular plants’ adaptation to floodplain habitats were identified. These can be derived from published data sets available for all species in Germany. We checked these indicators for multicollinearity and selected three of them: species number, hydrodynamic indicators, nature conservation indicators. Species number highly correlate with habitat indicators and geographic occurrence. For the selected three indicators we determined thresholds to group habitats and their indicator rate to five classes (very low to very high value for nature conservation). These thresholds are valid for the river Danube and for the habitat types scrutinized in this study.The Florix approach was sensitive in data sets testing active against former floodplains and protected against unprotected areas: For the entire reference region ‘Danube floodplain’, Florix values were higher in the active floodplain and in the protected areas. Only the habitat type ‘water bodies’ showed better scores for habitats in the former floodplain, for ‘softwood forests’ the status of being part of a protected area had no effect. Florix results were validated in two case studies differing in land use intensity. The region with dominant agricultural use showed significantly lower values than that with a higher portion of forests and grasslands.Florix can be used for a floristic conservation status assessment at single habitat level or for the entity of a study region in comparison to a reference region. It allows to identify main pressures and to complement a habitat-type based evaluation. To achieve higher comparability, we should strive for a generalized monitoring in Europe like it is common in aquatic ecosystem monitoring.

Forecasting models have been used extensively to inform decision making during the COVID-19 pandemic. In this preregistered and prospective study, the authors evaluated 14 short-term models for Germany and Poland, finding considerable heterogeneity in predictions and highlighting the benefits of combined forecasts.

Palos Verdes Reef (PVR) is an artificial reef designed to restore rocky-reef associated marine species by directly restoring rocky-reef habitat that has been impacted by scour, sedimentation, and burial in the shallow subtidal portion of the Palos Verdes Peninsula in Los Angeles County, California, USA. The restoration reef provides high-quality habitat that is contiguous with the natural reef and allows for rapid succession. This project is a unique endeavor as restoring lost habitat in situ and has not been attempted in a temperate rocky reef and kelp forest community. While the primary design criteria for PVR is fish production in an area where already-limited hard substrate had been lost, it is also designed to be resilient to ongoing sedimentation and turbidity challenges on the peninsula. Following over a decade of design, planning, outreach, site surveying, and permitting, PVR was built in 2020 as 18 discrete modules using 52,729 tons of quarry rock placed approximately 8–80 m from existing, unburied rocky-reef habitat. There was no significant accumulation or scouring of sediment due to the placement of the reef and temperature data shows that internal tides regularly inundate the reef with cool, nutrient rich water. Rocky-reef associated taxa rapidly recruited to the restoration site, with visible changes occurring within just a few months post-construction. PVR modules showed rapid, significantly positive responses in fish density, fish biomass, kelp density, and biotic benthic cover less than 18 months after reef placement with a general pattern of succession in giant kelp growth from nearshore to offshore resulting in an established, thick canopy, in the nearshore, shallow modules. The newly available, high-quality habitat was quickly colonized and already shows late successional patterns with respect to fish and benthic communities. This restoration reef will produce large amounts of biomass over the long-term, though future surveys of multiple restored, adjacent, and reference sites will determine if high biomass at PVR is a result of new secondary production or attraction from nearby reefs.

Cavitation bubbles show many nonlinear characteristics of liquid and gas phase. Here the authors demonstrate coherent diffractive imaging of cavitation bubble using infrared pump and XFEL probe and discuss the formation and evolution of the bubbles.

Background. One of the ways to use the genetic potential of bulbous barley, which is characterized by a number of valuable traits, is interspecific hybridization. In crosses of H. vulgare (2x) × H. bulbosum (2x) and H. vulgare (4x) × H. bulbosum (4x) with a genome ratio of 1Hv: 1Hb in a hybrid embryo, elimination of bulbous barley chromosomes is observed in many cases, and the intensity of the process and the result of the crossing depend on the genotypes of the parental forms. This limits the possibility of including a significant variety of parental forms in crosses. Сrossing of diploid forms of H. vulgare with tetraploid accessions of H. bulbosum (4x) results in the formation of triploid hybrids (HvHbHb) with stable chromosomal composition in pollen mother cells (PMCs) at metaphase I (MI) of meiosis. These triploid hybrids can serve as a basis for obtaining series of introgressive lines of cultivated barley. One of the tasks of this type of work is to estimate the involvement of various chromosomes and their arms in homoeologous associations. The aim of this work was to study the possibility of homoeologous pairing of chromosomes of parental species at MI of meiosis in triploid hybrids using GISH and FISH with chromosome-specific markers, as well as to register the participation of individual arms of the cultivated barley chromosomes in homoeologous associations with the chromosomes of bulbous barley in triploid hybrids (HvHbHb).Materials and methods. Seven triploid hybrids of H. vulgare × H.bulbosum (HvHbHb) obtained in four combinations of crosses with the participation of three diploid cultivars of cultivated barley and two tetraploid accession of bulbous barley were used in this study. The features of homoeologous pairing of chromosomes at MI were studied using the method of fluorescent in situ hybridization (GISH and FISH) with chromosome-specific markers.Results All the studied hybrid plants are characterized by a stable chromosomal composition in PMCs at the MI stage of meiosis. Meiotic configurations formed by homoeologous chromosomes of the parental species, ranging from 0.87 to 1.40 on average per cell, were identified in all the studied plants. Among them, vbb trivalents prevailed. Analysis of chromosome pairing at MI in triploid hybrids revealed the participation of all chromosome arms of H. vulgare in homoeologous Hv-Hb associations, except for the short arm of chromosome 1H. In all the studied triploid hybrids, there is a tendency for a higher frequency of involvement of the long arms of chromosomes in the formation of homoeologous associations; this feature is most clearly manifested in case of chromosome 5H.Conclusions Intergenomic associations with the participation of all arms of H. vulgare chromosomes, except for the short arm of chromosome 1H, were revealed at MI in H. vulgare × H. bulbosum triploid hybrids (HvHbHb). Chromosome 5H, as well as any other cultivated barley chromosome, is characterized by a higher involvement of its long arm in homoeologous associations Hv-Hb, as compared to the short arm.

Abstract Background Post-operative delirium is an important, yet under-researched complication of surgery. Patients undergoing urological surgery may be at especially high risk of POD, as they are often older, and interventions can be associated with conditions that trigger delirium. The main aim of this systematic review was to evaluate the available evidence for risk factors in this patient group. Methods Five databases were searched (MEDLINE, Web of Science, EMBASE, CINAHL and PsychInfo) between January 1987 and June 2019. The Newcastle–Ottawa Scale was used to assess for risk of bias. Pooled odds ratio or mean difference (MD) for individual risk factors were estimated using the Mantel–Haenzel and inverse variance methods. Results Seven articles met the inclusion criteria, giving a total population of 1937. The incidence of POD ranged from 5 to 29%. Three studies were deemed low risk of bias and four at a high risk of bias. Nine risk factors were suitable for meta-analysis, with age (MD 4.314 95% CI 1.597, 7.032 p = 0.002) and the clock drawing test (MD − 2.443 95% CI − 3.029, − 1.857 p

Abstract/summary Background As in other countries, there is concern and some fragmentary evidence that GPs’ central role in the Swiss healthcare system as the primary provider of care might be changing or even be in decline. Our study gives a systematic account of GPs’ involvement in accident care from 2008 to 2016 and identifies changes in GPs’ involvement in this typical field of primary care: how frequently GPs were involved along the care pathway, to what extent they figured as initial care provider, and what their role in the care pathway was. Methods Using a claims dataset from the largest Swiss accident insurer with two million accident cases, we constructed individual care pathways, i.e., when and from which providers patients received care. We calculated probabilities for the involvement of various care provider groups, for initial care provision, and for the role of GPs in patients’ care pathways, adjusted for injury and patient characteristics using multinomial regression. Results In 2014, GPs were involved in 70% of all accident cases requiring outpatient care but no inpatient stay, and provided initial care in 56%. While involvement stayed at about the same level for accidents occurring from 2008 to 2014, the share of accidents where GPs provided initial care decreased by 4 percentage points. The share of cases where GPs acted as sole care provider decreased by 7 percentage points down to 44%. At the same time, accident cases involving care from an ED at any point in time increased from 38 to 46% and the share receiving initial care from an ED from 30 to 35 percentage points – apparently substituting for the declining involvement of GPs in initial care. GPs’ involvement in accident care is higher in rural compared to urban regions, among elderly compared to younger patients, and among Swiss compared to non-Swiss citizens. Conclusions GPs play a key role in accident care with considerable variation depending on region and patient profile. From 2008 to 2014, there is a remarkable decline in GPs’ provision of initial care after an accident. This is a strong indication that the GPs’ role in the Swiss healthcare system is changing.

Lameness in pigs is one of the major reasons for culling and early losses in pigs. This can be linked to osteoporosis due to pathologic alterations in bone mineral density (BMD) or bone mineral content (BMC) and may also be linked to the sex. Dealing with the ban on piglet castration without anaesthesia in Germany 2021, we have three male “sex” types: entire boars (EB), immunocastrated boars (IB), and surgically castrated boars (SB). The hypothesis of the present study is that BMC or BMD varies between different male sex types. If sex has an effect on bone mineralization (BMC or BMD) and if this affects leg health, it could result in more lameness and problems during fattening in the negatively affected sex type. The present study evaluated bone mineralization (in terms of BMD and BMC) and body composition traits using dual-energy X-ray absorptiometry (DXA) three times during growth at 30, 50, and 90 kg live body weight. Nine body regions were analysed for bone mineral traits and compared for different male sex types and the fattening season. Significant differences were found regarding BMD (and BMC) among EB, IB, and SB for whole-body BMD (BMC). Additionally significant differences were found in the front and lower hind limbs, where SB showed a significantly higher BMD compared to EB, with IB in between. Additionally regional differences were detected among the groups. Further studies are needed to evaluate the effect of these differences in bone mineralization on leg health.

Most realistic kinetic calculations for tokamak plasmas are now required to incorporate the effect of partially ionized high-Z elements arising either from uncontrolled influxes of metallic impurities, such as tungsten in high input power regimes or from mitigation of runaway electrons generated after possible major disruptions by massive gas injection. The usual electron–ion Fokker–Planck collision operator must therefore be modified, because all plasma atoms are not entirely ionized, as is the case for light elements. This represents a challenge, in order to perform fast but also accurate calculations, regardless of the type of element present in the plasma, but also their local levels of ionization while covering a wide range of electron energies in a consistent way, from a few keV to tens of MeV in plasmas whose electron temperature may itself vary from 10 eV to several keV. In this context, a unified description of the atomic models is proposed, based on a multi-Yukawa representation of the electrostatic potential calibrated against results obtained by advanced quantum calculations. Besides the possibility to improve the description of inner and outer atomic shells in the determination of the atomic form factor, this model allows one to derive analytical formulations for both elastic and inelastic scattering, which can then be easily incorporated in kinetic calculations. The impact of the number of exponentials in the description of the atomic potential is discussed, and a comparison with simple and advanced atomic models is also performed.

The advancement of new immunotherapies necessitates appropriate probes to monitor the presence and distribution of distinct immune cell populations. Considering the key role of CD4+ cells in regulating immunological processes, we generated novel single-domain antibodies [nanobodies (Nbs)] that specifically recognize human CD4. After in-depth analysis of their binding properties, recognized epitopes, and effects on T-cell proliferation, activation, and cytokine release, we selected CD4-specific Nbs that did not interfere with crucial T-cell processes in vitro and converted them into immune tracers for noninvasive molecular imaging. By optical imaging, we demonstrated the ability of a high-affinity CD4-Nb to specifically visualize CD4+ cells in vivo using a xenograft model. Furthermore, quantitative high-resolution immune positron emission tomography (immunoPET)/MR of a human CD4 knock-in mouse model showed rapid accumulation of 64Cu-radiolabeled CD4-Nb1 in CD4+ T cell-rich tissues. We propose that the CD4-Nbs presented here could serve as versatile probes for stratifying patients and monitoring individual immune responses during personalized immunotherapy in both cancer and inflammatory diseases.

Background. Involving alien genetic material Hordeum bulbosum in the genome for the expansion of the genetic diversity of barley is a cultural important task because this species is characterized by a number of valuable traits. One way of using the genetic potential of bulbous barley is interspecies hybridization and the production of fertile introgressive lines of H. vulgare on the base of interspecies hybrids. The purpose of our investigation was to study introgressive lines of cultural barley obtained on the basis of the triploid hybrid H.vulgare cv 'Igri' (2x) × H. bulbosum (4x) in compare to the original Igri variety in the field conditions.Materials and methods. In the field conditions the barley lines with intro-gressions of the genetic material of bulbous barley in the different arms of chromosomes H. vulgare (1HL, 2HL, 3HL, 5HL, 7HL, 2HS, 1HL + 5HL) were studied. Methods. In situ hybridization (FISH, GISH) was used to identify the introgressions and to analyze their saving in line karyotypes after field reproduction. For cultivated in field conditions plants the estimation of winter survival and graininess were estimated. Structural analysis of plants was carried out on tillers of the main spike after maturation. The quality of the grain was determined by the non-destructive method of monitoring - near infrared spectroscopy, using the Infralum FT-10 BIC analyzer.Results. Closed flowering and self-pollination were observed for plants of the studied lines same as for parent variety. The introgressions were saved in the offspring when the plants cultivated in a field conditions without isolation of spike. The analysis showed that small fragments of chromosomes of H. bulbosum in chromosomes 1HL, 2HL, 3HL, 5HL,7HL, 1HL + 5HL of the studied lines do not significantly affect on characteristics (of fertility, productivity and grain quality) of the variety. Differences from the initial variety were observed at line 14.10 with the introgression of genetic material in the chromosome 2HS. It is characterized by lower fertility and productivity, and protein content in the grain is higher than that of the original variety.Conclusions. The studied lines are highfertile forms of barley. The introgression of the genetic material of H. bulbosum into the terminal region of the short arm of the chromosome 2H causes changes in some characteristics of the Igri variety.

We recently identified a deviant bovine immune phenotype characterized by hyperproliferation of lymphocytes after polyclonal stimulation. This phenotype was first discovered in dams that responded to PregSure BVD vaccination by producing pathological antibodies, triggering the fatal disease “bovine neonatal pancytopenia” in calves. The aim of the study was to gain deeper insights into molecular processes occurring in lymphocytes of immune phenotypes and the effect on their secretome after immune stimulation. Two discovery proteomic experiments were performed with unstimulated and Pokeweed Mitogen (PWM) stimulated lymphocytes, using label-free LC-MS/MS. In lymphocytes, 2447 proteins were quantified, and 1204 proteins were quantified in the secretome. Quantitative proteome analysis of immune deviant and control samples after PWM stimulation revealed clear differences. The increase in abundance of IL17A, IL17F, IL8, CCL5, LRRC59, and CLIC4 was higher in controls through mitogenic stimulation. In contrast, the abundance of IFNγ, IL2, IL2RA, CD83, and CD200 increased significantly more in immune deviant lymphocytes. Additional pathway enrichment analysis of differentially secreted proteins also yielded fundamental differences between the immune phenotypes. Our study provides a comprehensive dataset, which gives novel insights into proteome changes of lymphocytes from different bovine immune phenotypes. These differences point to the development of diverse immune responses of bovine immune phenotypes after immune stimulation.

BACKGROUND AND AIM Frozen shoulder is a poorly understood pathological entity that is characterised by a painful and stiff shoulder. To analyse the socioeconomic impact of frozen shoulder in terms of cost generation and prolonged absence from work, we conducted a retrospective cohort study based on shoulder injuries through accidents in Switzerland. METHODS Data were obtained from the comprehensive database of the Statistical Service for the Swiss National Accident Insurances (SSUV). Cases with shoulder injuries (ICD-10 codes S4* and M84.3*) and/or an additional code of adhesive capsulitis (M75.0) were extracted. Outcomes were work incapacity, with long-term work incapacity defined as absence from work for >90 days and very-long-term cases with >360 days lost. Healthcare and treatment costs as well as total insurance expenses were measured over a 5-year follow-up. Multivariate statistical analyses were used to quantify the effect of the frozen shoulder complication. RESULTS Among all 456,926 patients with a shoulder injury, 5% or a total of 22,228 posttraumatic frozen shoulder cases were observed over the 8-year period. Patients suffering from a frozen shoulder after shoulder injury showed significantly longer sick leave periods with 30.8% long-term and 9.7% very-long-term cases compared with 9.4% and 1.3%, respectively, in the non-frozen shoulder cohort. Overall costs per case for an injured shoulder without developing a frozen shoulder was roughly CHF 8000, whereas expenses for cases with posttraumatic and postoperative frozen shoulder were CHF 34,000 per case. CONCLUSION Developing a frozen shoulder after a shoulder injury is associated with significant longer work incapacities (3.3–7.5 times) and is responsible for costs of CHF 78 million every year. The presented numbers are for cases covered by the compulsory accident insurance only and do not include the even more frequent idiopathic frozen shoulder cases.

Objective: The worldwide prevalence of obesity has increased to 10% in men and 15% in women and is associated with severe comorbidities such as diabetes, cancer, and cardiovascular disease. Animal models of obesity are central to experimental studies of disease mechanisms and therapeutic strategies. Diet-induced obesity (DIO) models in rodents have provided important insights into the pathophysiology of obesity and, in most instances, are the first in line for exploratory pharmacology studies. To deepen the relevance towards translation to human patients, we established a corresponding DIO model in Göttingen minipigs (GM). Methods: Young adult female ovariectomized GM were fed a high-fat/high-energy diet for a period of 70 weeks. The ration was calculated to meet the requirements and maintain body weight (BW) of lean adult minipigs (L-GM group) or increased stepwise to achieve an obese state (DIO-GM group). Body composition, blood parameters and intravenous glucose tolerance were determined at regular intervals. A pilot chronic treatment trial with a GLP1 receptor agonist was conducted in DIO-GM. At the end of the study, the animals were necropsied and a biobank of selected tissues was established. Results: DIO-GM developed severe subcutaneous and visceral adiposity (body fat >50% of body mass vs. 22% in L-GM), increased plasma cholesterol, triglyceride, and free fatty acid levels, insulin resistance (HOMA-IR >5 vs. 2 in L-GM), impaired glucose tolerance and increased heart rate when resting and active. However, fasting glucose concentrations stayed within normal range throughout the study. Treatment with a long-acting GLP1 receptor agonist revealed substantial reduction of food intake and body weight within four weeks, with increased drug sensitivity relative to observations in other DIO animal models. Extensive adipose tissue inflammation and adipocyte necrosis was observed in visceral, but not subcutaneous, adipose tissue of DIO-GM. Conclusions: The Munich DIO-GM model resembles hallmarks of the human metabolic syndrome with extensive adipose tissue inflammation and adipocyte necrosis reported for the first time. DIO-GM may be used for evaluating novel treatments of obesity and associated comorbidities. They may help to identify triggers and mechanisms of fat tissue inflammation and mechanisms preventing complete metabolic decompensation despite morbid obesity. Keywords: Pig, High fat diet, Obesity, Diabetes, Metabolic syndrome, Adipose tissue inflammation

Objectives The correlation between quartz dust concentrations in the Swiss enterprises and the incidence of silicosis and other related diseases acknowledged as occupational diseases (OD) was investigated. Material and Methods Quartz dust concentrations were obtained from Suva’s databases of occupational health surveillance measurements between 2005 and 2014. Information on quartz dust-related diseases was from medical dossiers of workers with OD acknowledged by Suva between 2005 and 2014. Results The median quartz dust concentration of the 2579 measurements between 2005 and 2014 was 0.09 mg/m 3 (alveolar fraction). Out of all measurements, 28% were above the Swiss occupational exposure limit (OEL) of 0.15 mg/m 3 (alveolar fraction). One hundred eighty-one individuals suffered from acknowledged quartz dust-related disease (179 silicosis and 2 chronic obstructive pulmonary disease (COPD)). Additionally, 8 out of these workers were diagnosed with lung cancer and 55 with COPD of a non-specified cause. Out of all workers, 46% were exposed to silica dust for the first time before 1975 when the current Swiss OEL was introduced. Out of the foreign workers, 63% began to work abroad, during which they could have at least partly acquired their silicosis. Out of all workers, 75% were ever-smokers. Conclusions The incidence of silicosis decreased drastically from approximately 300 cases/year in the 1970s to fewer than 20 cases/year 20 years ago. Several findings of this study that could help to interpret the ongoing occurrence of the disease include excessive exposure in or outside of Switzerland in former or current times, vulnerability to the development of silicosis due to cigarette smoke, or poor compliance with wearing breathing masks. Int J Occup Med Environ Health 2018;31(5):659–676

AIMS OF THE STUDY Given the lack of information on the relation between baseline patient, injury and treatment data and longer-term outcomes for survivors of significant trauma, the objective of this evaluation was to examine the degree to which these characteristics might predict working constraints and expenses. METHODS 1183 significantly injured patients (New Injury Severity Score >8) of working age were treated at a Swiss trauma centre. Only patients insured by the largest national accident insurer, Suva, were included. Their sociodemographic, trauma, treatment and early clinical status data were evaluated against insurance variables for 4 years post-injury (uni- and multivariate analysis, R2). RESULTS 346 out of 363 surviving Suva-insured patients were eligible for analysis, constituting a 95% complete 4-year longitudinal follow-up. Overall, 121 (35%) presented with a reduced capacity to work (RCW) 1 to 4 years after the trauma. Patients experienced a mean percentage RCW (PRCW) of 27% 1 year after injury and of 14% at 4 years. In multivariate analysis all investigated parameters together explained 40% of the adjusted variance of patients’ mean PRCW over the 4-year surveillance period, with the highest association found for the block of injury-related variables (17%). Sixty percent of variance was explained for total insurance costs, found to be on average CHF 417,000 per case in patients with a RCW compared with CHF 47,000 per case without RCW (p

Mycobacterium avium subsp. paratuberculosis (MAP) is a pathogen causing paratuberculosis in cattle and small ruminants. During the long asymptomatic subclinical stage, high numbers of MAP are excreted and can be transmitted to food for human consumption, where they survive many of the standard techniques of food decontamination. Whether MAP is a human pathogen is currently under debate. The aim of this study was a better understanding of the host-pathogen response by analyzing the interaction of peripheral blood lymphocytes (PBL) from cattle with MAP in their exoproteomes/secretomes to gain more information about the pathogenic mechanisms of MAP. Because in other mycobacterial infections, the immune phenotype correlates with susceptibility, we additionally tested the interaction of MAP with recently detected cattle with a different immune capacity referred as immune deviant (ID) cows. In PBL, different biological pathways were enhanced in response to MAP dependent on the immune phenotype of the host. PBL of control cows activated members of cell activation and chemotaxis of leukocytes pathway as well as IL-12 mediated signaling. In contrast, in ID cows CNOT1 was detected as highly abundant protein, pointing to a different immune response, which could be favorable for MAP. Additionally, MAP exoproteomes differed in either GroEL1 or DnaK abundance, depending on the interacting host immune response. These finding point to an interdependent, tightly regulated response of the bovine immune system to MAP and vise versa.

Objective: Laron syndrome (LS) is a rare, autosomal recessive disorder in humans caused by loss-of-function mutations of the growth hormone receptor (GHR) gene. To establish a large animal model for LS, pigs with GHR knockout (KO) mutations were generated and characterized. Methods: CRISPR/Cas9 technology was applied to mutate exon 3 of the GHR gene in porcine zygotes. Two heterozygous founder sows with a 1-bp or 7-bp insertion in GHR exon 3 were obtained, and their heterozygous F1 offspring were intercrossed to produce GHR-KO, heterozygous GHR mutant, and wild-type pigs. Since the latter two groups were not significantly different in any parameter investigated, they were pooled as the GHR expressing control group. The characterization program included body and organ growth, body composition, endocrine and clinical-chemical parameters, as well as signaling studies in liver tissue. Results: GHR-KO pigs lacked GHR and had markedly reduced serum insulin-like growth factor 1 (IGF1) levels and reduced IGF-binding protein 3 (IGFBP3) activity but increased IGFBP2 levels. Serum GH concentrations were significantly elevated compared with control pigs. GHR-KO pigs had a normal birth weight. Growth retardation became significant at the age of five weeks. At the age of six months, the body weight of GHR-KO pigs was reduced by 60% compared with controls. Most organ weights of GHR-KO pigs were reduced proportionally to body weight. However, the weights of liver, kidneys, and heart were disproportionately reduced, while the relative brain weight was almost doubled. GHR-KO pigs had a markedly increased percentage of total body fat relative to body weight and displayed transient juvenile hypoglycemia along with decreased serum triglyceride and cholesterol levels. Analysis of insulin receptor related signaling in the liver of adult fasted pigs revealed increased phosphorylation of IRS1 and PI3K. In agreement with the loss of GHR, phosphorylation of STAT5 was significantly reduced. In contrast, phosphorylation of JAK2 was significantly increased, possibly due to the increased serum leptin levels and increased hepatic leptin receptor expression and activation in GHR-KO pigs. In addition, increased mTOR phosphorylation was observed in GHR-KO liver samples, and phosphorylation studies of downstream substrates suggested the activation of mainly mTOR complex 2. Conclusion: GHR-KO pigs resemble the pathophysiology of LS and are an interesting model for mechanistic studies and treatment trials. Keywords: Growth hormone receptor, Laron syndrome, Pig model, Dwarfism, Hypoglycemia, Insulin-like growth factor 1, Signaling

A pesar del reciente auge de la digitalización, las organizaciones todavía tienen dificultades con el uso de equipos virtuales internacionales, que aún tienden a seguir el concepto de planificación top-down (de arriba abajo) y, por consiguiente, son controladas por algún tipo de sede. Sin embargo, en el contexto de los juegos de multijugadores, observamos una manera más auto-organizada de formar equipos, lo que comúnmente se conoce como pugging: se forman los equipos, se establece un objetivo común y luego se disuelven. Siguen el concepto de autonomía ascendente. El pugging es altamente beneficioso para el mundo del juego, razón por la cual seguiremos el marco de la transducción cultural para transferir este concepto de equipo del juego al contexto corporativo. Puesto que el contexto corporativo y el juego están fuertemente entrelazados y se influyen mutuamente en gran medida, expandiremos este marco con el concepto de transtracción.

ABSTRACT During its intraerythrocytic development, the malaria parasite Plasmodium falciparum exposes variant surface antigens (VSAs) on infected erythrocytes to establish and maintain an infection. One family of small VSAs is the polymorphic STEVOR proteins, which are marked for export to the host cell surface through their PEXEL signal peptide. Interestingly, some STEVORs have also been reported to localize to the parasite plasma membrane and apical organelles, pointing toward a putative function in host cell egress or invasion. Using deep RNA sequencing analysis, we characterized P. falciparum stevor gene expression across the intraerythrocytic development cycle, including free merozoites, in detail and used the resulting stevor expression profiles for hierarchical clustering. We found that most stevor genes show biphasic expression oscillation, with maximum expression during trophozoite stages and a second peak in late schizonts. We selected four STEVOR variants, confirmed the expected export of these proteins to the host cell membrane, and tracked them to a secondary location, either to the parasite plasma membrane or the secretory organelles of merozoites in late schizont stages. We investigated the function of a particular STEVOR that showed rhoptry localization and demonstrated its role at the parasite-host interface during host cell invasion by specific antisera and targeted gene disruption. Experimentally determined membrane topology of this STEVOR revealed a single transmembrane domain exposing the semiconserved as well as variable protein regions to the cell surface. IMPORTANCE Malaria claims about half a million lives each year. Plasmodium falciparum, the causative agent of the most severe form of the disease, uses proteins that are translocated to the surface of infected erythrocytes for immune evasion. To circumvent the detection of these gene products by the immune system, the parasite evolved a complex strategy that includes gene duplications and elaborate sequence polymorphism. STEVORs are one family of these variant surface antigens and are encoded by about 40 genes. Using deep RNA sequencing of blood-stage parasites, including free merozoites, we first established stevor expression of the cultured isolate and compared it with published transcriptomes. We reveal a biphasic expression of most stevor genes and confirm this for individual STEVORs at the protein level. The membrane topology of a rhoptry-associated variant was experimentally elucidated and linked to host cell invasion, underlining the importance of this multifunctional protein family for parasite proliferation.

A novel vaccine against bovine viral diarrhea (BVD) induced pathogenic antibody production in 5–10% of BVD-vaccinated cows. Transfer of these antibodies via colostrum caused Bovine neonatal pancytopenia (BNP) in calves, with a lethality rate of 90%. The exact immunological mechanisms behind the onset of BNP are not fully understood to date. To gain further insight into these mechanisms, we analyzed the immune proteome from alloreactive antibody producers (BNP cows) and non-responders. After in vitro stimulation of peripheral blood derived lymphocytes (PBL), we detected distinctly deviant expression levels of several master regulators of immune responses in BNP cells, pointing to a changed immune phenotype with severe dysregulation of immune response in BNP cows. Interestingly, we also found this response pattern in 22% of non-BVD-vaccinated cows, indicating a genetic predisposition of this immune deviant (ID) phenotype in cattle. We additionally analyzed the functional correlation of the ID phenotype with 10 health parameters and 6 diseases in a retrospective study over 38 months. The significantly increased prevalence of mastitis among ID cows emphasizes the clinical relevance of this deviant immune response and its potential impact on the ability to fight infections.

Harmonic lasing provides an opportunity to extend the photon energy range of existing and planned x-ray free electron laser (FEL) user facilities. Contrary to nonlinear harmonic generation, harmonic lasing can generate a much more intense, stable, and narrow-band FEL beam. Another interesting application is harmonic lasing self-seeding that allows to improve the longitudinal coherence and spectral power of a self-amplified spontaneous emission FEL. This concept was tested at the soft x-ray FEL user facility FLASH in the range of 4.5–15 nm and at Pohang accelerator laboratory X-ray Free Electron Laser (XFEL) at 1 nm. In this paper we present recent results from the European XFEL where we successfully demonstrated harmonic lasing at 5.9 Angstrom and 2.8 Angstrom. In the latter case we obtained both third and fifth harmonic lasing and, for the first time, operated a harmonic lasing cascade (fifth-third-first harmonics of the undulator). These results pave the way for reaching very high photon energies, up to 100 keV.

Crossbreeding in dairy cattle has been used to improve functional traits, milk composition, and efficiency of Holstein herds. The objective of the study was to compare indicators of the metabolic energy balance, nonesterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), glucose, body condition score (BCS) back fat thickness (BFT), as well as milk yield and milk composition of Holstein and Simmental cows, and their crosses from the prepartum period until the 100th day of lactation at the Livestock Center of the Ludwig Maximilians University (Munich, Germany). In total, 164 cows formed five genetic groups according to their theoretic proportion of Holstein and Simmental genes as follows: Holstein (100% Holstein; n = 9), R1-Hol (51–99% Holstein; n = 30), first generation (F1) crossbreds (50% Holstein, 50% Simmental; n = 17), R1-Sim (1–49% Holstein; n = 81) and Simmental (100% Simmental; n = 27). The study took place between April 2018 and August 2019. BCS, BFT blood parameters, such as BHBA, glucose, and NEFA were recorded weekly. A mixed model analysis with fixed effects breed, week (relative to calving), the interaction of breed and week, parity, calving year, calving season, milking season, and the repeated measure effect of cow was used. BCS increased with the Simmental proportion. All genetic groups lost BCS and BFT after calving. Simmental cows showed lower NEFA values. BHBA and glucose did not differ among genetic groups, but they differed depending on the week relative to calving. Simmental and R1-Sim cows showed a smaller effect than the other genetic groups regarding changes in body weight, BCS, or back fat thickness after a period of a negative energy balance after calving. There was no significant difference for milk yield among genetic groups, although Simmental cows showed a lower milk yield after the third week after calving. Generally, Simmental and R1-Simmental cows seemed to deal better with a negative energy balance after calving than purebred Holstein and the other crossbred lines. Based on a positive heterosis effect of 10.06% for energy corrected milk (ECM), the F1, however, was the most efficient crossbred line.