Search

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.

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

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.

Extreme-ultraviolet to x-ray free-electron lasers (FELs) in operation for scientific applications are up to now single-user facilities. While most FELs generate around 100 photon pulses per second, FLASH at DESY can deliver almost two orders of magnitude more pulses in this time span due to its superconducting accelerator technology. This makes the facility a prime candidate to realize the next step in FELs—dividing the electron pulse trains into several FEL lines and delivering photon pulses to several users at the same time. Hence, FLASH has been extended with a second undulator line and self-amplified spontaneous emission (SASE) is demonstrated in both FELs simultaneously. FLASH can now deliver MHz pulse trains to two user experiments in parallel with individually selected photon beam characteristics. First results of the capabilities of this extension are shown with emphasis on independent variation of wavelength, repetition rate, and photon pulse length.

We study the structure formation of 1,4,5,8-naphthalene-tetracarboxylicacid-dianhydride (NTCDA) multilayer films on Ag(111) surfaces by energy dispersive near-edge x-ray absorption fine-structure spectroscopy (NEXAFS) and photoelectron spectroscopy. The time resolution of seconds of the method allows us to identify several sub-processes, which occur during the post-growth three-dimensional structural ordering, as well as their characteristic time scales. After deposition at low temperature the NTCDA molecules are preferentially flat lying and the films exhibit no long-range order. Upon annealing the molecules flip into an upright orientation followed by an aggregation in a transient phase which exists for several minutes. Finally, three-dimensional islands are established with bulk-crystalline structure involving substantial mass transport on the surface and morphological roughening. By applying the Kolmogorov–Johnson–Mehl–Avrami model the activation energies of the temperature-driven sub-processes can be derived from the time evolution of the NEXAFS signal.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Research has shown that digestion of A1 β-casein (β-CN) affects gastrointestinal motility and opioid activity through the release of the peptide β-casomorphin-7 (β-CM7). In the case of the A2 variant, the cleavage of β-CM7 does not occur or occurs at a very low rate. Therefore, the aim of the study was to compare the effects of milk containing either homozygote A1 or A2 β-CN on health and growth parameters of dairy calves. Forty-seven neonatal calves (24 females, 23 males) of the breeds German Holstein (GH, n = 9), German Simmental (GS, n = 33) and their crossing (GH × GS, n = 5) were used in a 21-day feeding study. Fecal score (FS), respiratory frequency (RF), and rectal body temperature (BT) were recorded daily, whereas body weight was measured at birth and at day 21 to estimate the average daily weight gain (ADG). Additionally, blood was collected from calves three times during the experimental period and, for the first time, the respective plasma samples were analyzed for intact β-CM7. Consumption of A2-milk led to a lower daily milk intake (dMI) (p < 0.05). Furthermore, fecal consistency was softer for calves fed A2-milk (p < 0.05). Although 44% of A2-calves had diarrhea or revealed a tendency towards it (FS ≥ 3), A1-calves had a prevalence of 21%. Calves with a FS of 4 were offered an electrolyte solution and received a dietary food supplement for the stabilization of the fluid and electrolyte balance. Nevertheless, similar ADG and end weights (EW) of calves fed A1- or A2-milk (p > 0.05) indicate that A2-milk may compensate higher diarrhea rates and lower dMI due to the associated higher protein content. This is the first report of intact β-CM7 in plasma of calves fed milk of either A1 or A2 β-CN. Evidence from this study suggests that due to the change in the amino-acid sequence, A2-milk might be able to prevent or, at least, to minimize the cleavage of β-CM7 in calves.

The objective of this study was to phenotype visceral adipose tissue (VAT) in pigs. In this context, the ability to detect VAT by using the DXA CoreScan mode within the enCORE software, version 17 (GE Healthcare) was evaluated in comparison with MRI measurements (Siemens Magnetom C!) of the same body region. A number of 120 crossbred pigs of the F1 and F2 generation, with the parental breeds Large White, Landrace, Piétrain, and Duroc, were examined at an age of 150 days. A whole-body scan in two different modes (“thick”, “standard”) was carried out by a GE Lunar iDXA scanner. Very strong relationships (R2 = 0.95, RMSE = 175 cm3) were found for VAT between the two DXA modes. The comparison of VAT measured by MRI and DXA shows high linear relationships (“thick”: R2 = 0.76, RMSE = 399.25 cm3/“standard”: R2 = 0.71, RMSE = 443.42 cm3), but is biased, according to the Bland–Altman analysis. A variance analysis of VAT shows significant differences for both DXA modes and for MRI between male and female pigs, as well as between F1 and F2. In conclusion, DXA “CoreScan” has the ability to estimate VAT in pigs with a close relationship to MRI but needs bias correction.