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n this paper we report on the investigation of baryonic resonance production in proton-proton collisions at the kinetic energies of 1.25 GeV and 3.5 GeV, based on data measured with HADES. Exclusive channels npπ+ and ppπ0 as well as ppe+e− were studied simultaneously in the framework of a one-boson exchange model. The resonance cross sections were determined from the one-pion channels for Δ(1232) and N(1440) (1.25 GeV) as well as further Δ and N* resonances up to 2 GeV/c2 for the 3.5 GeV data. The data at 1.25 GeV energy were also analysed within the framework of the partial wave analysis together with the set of several other measurements at lower energies. The obtained solutions provided the evolution of resonance production with the beam energy, showing a sizeable non-resonant contribution but with still dominating contribution of Δ(1232)P33. In the case of 3.5 GeV data, the study of the ppe+e− channel gave the insight on the Dalitz decays of the baryon resonances and, in particular, on the electromagnetic transition form-factors in the time-like region. We show that the assumption of a constant electromagnetic transition form-factors leads to underestimation of the yield in the dielectron invariant mass spectrum below the vector mesons pole. On the other hand, a comparison with various transport models shows the important role of intermediate ρ production, though with a large model dependency. The exclusive channels analysis done by the HADES collaboration provides new stringent restrictions on the parameterizations used in the models.
The knowledge of baryonic resonance properties and production cross sections plays an important role for the extraction and understanding of medium modifications of mesons in hot and/or dense nuclear matter. We present and discuss systematics on dielectron and strangeness production obtained with HADES on p+p, p+A and A+A collisions in the few GeV energy regime with respect to these resonances.
his contribution aims to give a basic overview of the latest results regarding the production of resonances in different collision systems. The results were extracted from experimental data collected with HADES that is a multipurpose detector located at the GSI Helmholtzzentrum, Darmstadt. The main points discussed here are: the properties of the strange resonances Λ(1405) and Σ(1385), the role of Δ’s as a source of pions in the final state, the production dynamics reflected in form of differential cross sections, and the role of the ϕ meson as a source for K− particles.
The extinction of conditioned fear depends on an efficient interplay between the amygdala and the medial prefrontal cortex (mPFC). In rats, high-frequency electrical mPFC stimulation has been shown to improve extinction by means of a reduction of amygdala activity. However, so far it is unclear whether stimulation of homologues regions in humans might have similar beneficial effects. Healthy volunteers received one session of either active or sham repetitive transcranial magnetic stimulation (rTMS) covering the mPFC while undergoing a 2-day fear conditioning and extinction paradigm. Repetitive TMS was applied offline after fear acquisition in which one of two faces (CS+ but not CS−) was associated with an aversive scream (UCS). Immediate extinction learning (day 1) and extinction recall (day 2) were conducted without UCS delivery. Conditioned responses (CR) were assessed in a multimodal approach using fear-potentiated startle (FPS), skin conductance responses (SCR), functional near-infrared spectroscopy (fNIRS), and self-report scales. Consistent with the hypothesis of a modulated processing of conditioned fear after high-frequency rTMS, the active group showed a reduced CS+/CS− discrimination during extinction learning as evident in FPS as well as in SCR and arousal ratings. FPS responses to CS+ further showed a linear decrement throughout both extinction sessions. This study describes the first experimental approach of influencing conditioned fear by using rTMS and can thus be a basis for future studies investigating a complementation of mPFC stimulation to cognitive behavioral therapy (CBT).
EUSOBI and 30 national breast radiology bodies support mammography for population-based screening, demonstrated to reduce breast cancer (BC) mortality and treatment impact. According to the International Agency for Research on Cancer, the reduction in mortality is 40 % for women aged 50–69 years taking up the invitation while the probability of false-positive needle biopsy is <1 % per round and overdiagnosis is only 1–10 % for a 20-year screening. Mortality reduction was also observed for the age groups 40–49 years and 70–74 years, although with “limited evidence”. Thus, we firstly recommend biennial screening mammography for average-risk women aged 50–69 years; extension up to 73 or 75 years, biennially, is a second priority, from 40–45 to 49 years, annually, a third priority. Screening with thermography or other optical tools as alternatives to mammography is discouraged. Preference should be given to population screening programmes on a territorial basis, with double reading. Adoption of digital mammography (not film-screen or phosphor-plate computer radiography) is a priority, which also improves sensitivity in dense breasts. Radiologists qualified as screening readers should be involved in programmes. Digital breast tomosynthesis is also set to become “routine mammography” in the screening setting in the next future. Dedicated pathways for high-risk women offering breast MRI according to national or international guidelines and recommendations are encouraged.
HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
(2021)
Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
We present measurements of exclusive ensuremathπ+,0 and η production in pp reactions at 1.25GeV and 2.2GeV beam kinetic energy in hadron and dielectron channels. In the case of π+ and π0 , high-statistics invariant-mass and angular distributions are obtained within the HADES acceptance as well as acceptance-corrected distributions, which are compared to a resonance model. The sensitivity of the data to the yield and production angular distribution of Δ (1232) and higher-lying baryon resonances is shown, and an improved parameterization is proposed. The extracted cross-sections are of special interest in the case of pp → pp η , since controversial data exist at 2.0GeV; we find \ensuremathσ=0.142±0.022 mb. Using the dielectron channels, the π0 and η Dalitz decay signals are reconstructed with yields fully consistent with the hadronic channels. The electron invariant masses and acceptance-corrected helicity angle distributions are found in good agreement with model predictions.
Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 22 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, YWHAE, DPH1, GSDMB, MED24, THRA, EEF1A2, and KCNQ2 in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).
Biodiversity post-2020: Closing the gap between global targets and national-level implementation
(2021)
National and local governments need to step up efforts to effectively implement the post-2020 global biodiversity framework of the Convention on Biological Diversity to halt and reverse worsening biodiversity trends. Drawing on recent advances in interdisciplinary biodiversity science, we propose a framework for improved implementation by national and subnational governments. First, the identification of actions and the promotion of ownership across stakeholders need to recognize the multiple values of biodiversity and account for remote responsibility. Second, cross-sectorial implementation and mainstreaming should adopt scalable and multifunctional ecosystem restoration approaches and target positive futures for nature and people. Third, assessment of progress and adaptive management can be informed by novel biodiversity monitoring and modeling approaches handling the multidimensionality of biodiversity change.
Um zu überprüfen, ob sich die Artenzusammensetzung alpiner Kalk-Magerrasen (Blaugras-Horstseggenrasen, Polsterseggenrasen) im Nationalpark Berchtesgaden während der letzten drei Jahrzehnte geändert hat, wurden Vegetationsaufnahmen aus den 1980er Jahren 2013/14 zum zweiten Mal wiederholt vegetationskundlich erfasst.
Ziel der Arbeit war es, durch den Vergleich der Aufnahmenkollektive Vegetationsveränderungen während der letzten drei Jahrzehnte aufzuzeigen und diese als allogene oder autogene Prozesse zu interpretieren. Dabei wurde insbesondere der Frage nachgegangen, ob anthropogene Stickstoff-Einträge als Hauptursache für mögliche Veränderungen angesehen werden können.
Tatsächlich konnten ausgeprägte floristische Veränderungen im Vergleichszeitraum aufgezeigt werden. So hat sich seit den 1980er Jahre die mittlere Artenzahl sowohl im Polsterseggenrasen als auch im Horstseggenrasen um mehr als 10 Arten pro Aufnahmefläche erhöht. Im Polsterseggenrasen wurde ferner eine signifikante Abnahme der mittleren Kontinentalitätszahlen nachgewiesen.
Die dokumentierten floristischen Veränderungen könnten auf die globale Erwärmung und die damit verbundenen Klimaeffekte zurückzuführen sein. Auch natürlich ablaufende Sukzessionsprozesse könnten die aufgezeigten Änderungen in der Artenzusammensetzung erklären, allerdings ist die Zeitspanne von 30 Jahren zu kurz, als dass eine autogene Sukzession als der Hauptfaktor angesehen werden kann. Denkbar ist aber, dass Sukzessionsprozesse durch die globale Erwärmung heutzutage beschleunigt ablaufen. Stickstoffeinträge oder Landnutzungsänderungen spielen als Erklärungsmodell für die Vegetationsveränderungen dagegen wohl eher eine untergeordnete Rolle.
Seit 11 Jahren werden von Mitgliedern der Eurasian Dry Gassland Group (EDDG) und deren Vorgängerorganisationen Grasland-Sonderteile in Tuexenia herausgegeben. Der diesjährige Sonderteil präsentiert sechs Artikel mit unterschiedlichen Fragestellungen zu Trockenrasen und verwandten Graslandtypen aus sechs europäischen Ländern: Belgien, Bosnien-Herzegowina, Deutschland, Italien, Serbien und Ungarn. Ein Artikel behandelt syntaxonomische Aspekte der Serpentin-Steppenrasen des Balkans (s. auch Umschlagfoto). Zwei Beiträge untersuchen funktionelle Eigenschaften von Pflanzenarten im Grasland, der eine (in belgischen Trockenrasen) die Variationen funktioneller Merkmale in Abhängigkeit von den Umweltbedingungen und der andere die Mengenverhältnisse von funktionellen Merkmalen entlang eines Höhengradienten in den italienischen Alpen. Ein Artikel zeigt mithilfe eines experimentellen Ansatzes, dass artenarmes ungarisches Grasland durch Diasporenzufuhr in artenreiche Wiesen überführt werden kann, während ein anderer Beitrag ökologische Theorien am Grasland in einer ungarischen Stadt überprüft. Der sechste Artikel behandelt schließlich Vegetationsveränderungen von Steppenrasen in Nordostdeutschland nach 20 Jahren.
This Special Feature is the tenth in a series devoted to dry grasslands and edited by members of the European Dry Grassland Group (EDGG; http://www.edgg.org) or its prede-cessor Arbeitsgruppe Trockenrasen that have been published in Tuexenia since 2005 (GAL-VÁNEK et al. 2012). With this issue we celebrate our tenth anniversary of the Tuexenia Dry Grassland Special Features.
Nitrate is an abundant nutrient and electron acceptor throughout Earth’s biosphere. Virtually all nitrate in nature is produced by the oxidation of nitrite by the nitrite oxidoreductase (NXR) multiprotein complex. NXR is a crucial enzyme in the global biological nitrogen cycle, and is found in nitrite-oxidizing bacteria (including comammox organisms), which generate the bulk of the nitrate in the environment, and in anaerobic ammonium-oxidizing (anammox) bacteria which produce half of the dinitrogen gas in our atmosphere. However, despite its central role in biology and decades of intense study, no structural information on NXR is available. Here, we present a structural and biochemical analysis of the NXR from the anammox bacterium Kuenenia stuttgartiensis, integrating X-ray crystallography, cryo-electron tomography, helical reconstruction cryo-electron microscopy, interaction and reconstitution studies and enzyme kinetics. We find that NXR catalyses both nitrite oxidation and nitrate reduction, and show that in the cell, NXR is arranged in tubules several hundred nanometres long. We reveal the tubule architecture and show that tubule formation is induced by a previously unidentified, haem-containing subunit, NXR-T. The results also reveal unexpected features in the active site of the enzyme, an unusual cofactor coordination in the protein’s electron transport chain, and elucidate the electron transfer pathways within the complex.
Resistance to CD19-directed immunotherapies in lymphoblastic leukemia has been attributed, among other factors, to several aberrant CD19 pre-mRNA splicing events, including recently reported excision of a cryptic intron embedded within CD19 exon 2. While “exitrons” are known to exist in hundreds of human transcripts, we discovered, using reporter assays and direct long-read RNA sequencing (dRNA-seq), that the CD19 exitron is an artifact of reverse transcription. Extending our analysis to publicly available datasets, we identified dozens of questionable exitrons, dubbed “falsitrons,” that appear only in cDNA-seq, but never in dRNA-seq. Our results highlight the importance of dRNA-seq for transcript isoform validation.
Purpose: Despite the high number of patients with phalangeal fractures, evidence-based recommendations for the treatment of specific phalangeal fractures could not be concluded from the literature. The purpose of the present study was to assess current epidemiological data, classification of the fracture type, and mode of treatment.
Methods: This study presents a retrospective review of 261 patients with 283 phalangeal fractures ≥ 18 years of age who were treated in our level I trauma centre between 2017 and 2018. The data were obtained by the analysis of the institution’s database, and radiological examinations.
Results: The average age of the patients was 40.4 years (range 18–98). The ratio of male to female patients was 2.7:1. The two most typical injury mechanisms were crush injuries (33%) and falls (23%). Most phalangeal fractures occurred in the distal phalanx (P3 43%). The 4th ray (D4 29%) was most frequently affected. The P3 tuft fractures, and the middle phalanx (P2) base fractures each accounted for 25% of fracture types. A total of 74% of fractures were treated conservatively, and 26% required surgery, with Kirschner wire(s) (37%) as the preferred surgical treatment. The decision for surgical treatment correlated with the degree of angular and/or rotational deformity, intraarticular step, and sub-/luxation of specific phalangeal fractures, but not with age and gender.
Conclusions: Our findings demonstrated the popularity of conservative treatment of phalangeal fractures, while surgery was only required in properly selected cases. The correct definition of precise fracture pattern in addition to topography is essential to facilitate treatment decision-making.
The Transylvanian Plateau in Romania is well known to host large areas of a variety of dry grassland types, still traditionally managed by low-intensity mowing or grazing. While this natural heritage is now under threat from changes in agricultural practices, the diversity of Transylvanian dry grasslands is still little understood. There is a lack of both field data sampled with standardised methods and a syntaxonomic treatment with modern statistical methods and supra-regional perspective. Therefore, the European Dry Grassland Group (EDGG) carried out its first international Research Expedition in Transylvania 2009 to study syntaxonomy, vegetation-environment relationships, and biodiversity patterns of these communities. In various locations across Transylvania, we sampled 10-m² vegetation plots (n = 82) and nested-plot series from 0.0001 m² to 100 m² (n = 20), including all vascular plant, bryophyte, and lichen species, as well as structural and soil data. The vegetation classification was carried out with modified TWINSPAN, followed by determination of diagnostic species with phi values and a small-scale re-assignment of relevés with the aim of crispness maximisation. Both TWINSPAN and ordination revealed three major groups of syntaxa, which were matched to three orders from the class of basiphilous dry grasslands, Festuco-Brometea, represented by one alliance each: rocky dry grasslands (Stipo pulcherrimae-Festucetalia pallentis: Seslerion rigidae); xeric grasslands on deep soils (Festucetalia valesiacae: Stipion lessingianae) and meso-xeric grasslands on deep soils (Brachypodietalia pinnati: Cirsio-Brachypodion pinnati). We accepted nine association-level units plus two that potentially merit association status but were only represented by one relevé each. Most of the units could be identified with one or several previously described associations. To support nomenclatural stability, we provide a nomenclatural revision and designate nomenclatural types where previously there were none. Further, we used DCA ordination and analysis of variance to determine the main environmental drivers of floristic differentiation and to determine ecological and structural differences between the vegetation types. The strongest differentiation occurred along the aridity gradient with the dense, particularly diverse stands on more or less level sites on the one hand (Brachypodietalia pinnati) and the more open, less diverse stands on steep south-facing slopes on the other end of the gradient (Stipo pulcherrimae- Festucetalia pallentis, Festucetalia valesiacae). The two xeric orders were then separated along the second DCA axis, with the Stipo pulcherrimae-Festucetalia pallentis inhabiting the stone-rich sites at higher altitudes while the Festucetalia valesiacae occur on soft, deep substrata at lower altitudes. The analysed dry grassland communities have extraordinarily high -diversity at all spatial scales for all plants and for vascular plants, but are relatively poor in bryophytes and lichens. Some formerly mown stands of the Festuco sulcatae-Brachypodietum pinnati (Brachypodietalia pinnati) are even richer in vascular plant species than any other recorded vegetation type worldwide on the spatial scales of 0.1 m² (43) and 10 m² (98); the respective relevés are documented here for the first time. Also, the b-diversity of the grasslands was unexpectedly high, with a mean z-value of 0.275. Despite its limited extent, the methodological thoroughness of this study allows us to shed new light on the syntaxonomy of dry grasslands in Romania and to raise the awareness that Transylvania still hosts High Nature Value grasslands that are bio - diversity hotspots at a global scale but at the same time are highly endangered through changes in agricultural practices.
Artificial Intelligence (AI) has the potential to greatly improve the delivery of healthcare and other services that advance population health and wellbeing. However, the use of AI in healthcare also brings potential risks that may cause unintended harm. To guide future developments in AI, the High-Level Expert Group on AI set up by the European Commission (EC), recently published ethics guidelines for what it terms “trustworthy” AI. These guidelines are aimed at a variety of stakeholders, especially guiding practitioners toward more ethical and more robust applications of AI. In line with efforts of the EC, AI ethics scholarship focuses increasingly on converting abstract principles into actionable recommendations. However, the interpretation, relevance, and implementation of trustworthy AI depend on the domain and the context in which the AI system is used. The main contribution of this paper is to demonstrate how to use the general AI HLEG trustworthy AI guidelines in practice in the healthcare domain. To this end, we present a best practice of assessing the use of machine learning as a supportive tool to recognize cardiac arrest in emergency calls. The AI system under assessment is currently in use in the city of Copenhagen in Denmark. The assessment is accomplished by an independent team composed of philosophers, policy makers, social scientists, technical, legal, and medical experts. By leveraging an interdisciplinary team, we aim to expose the complex trade-offs and the necessity for such thorough human review when tackling socio-technical applications of AI in healthcare. For the assessment, we use a process to assess trustworthy AI, called 1Z-Inspection® to identify specific challenges and potential ethical trade-offs when we consider AI in practice.
Pathogens possess the ability to adapt and survive in some host species but not in others–an ecological trait known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. Three main causative agents of LD, Borrelia burgdorferi, B. afzelii, and B. garinii, vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different Borrelia species, utilizing feeding chambers and live mice and quail, we found species-level differences in bacterial transmission. These differences localize on the tick blood meal, and specifically complement, a defense in vertebrate blood, and a polymorphic bacterial protein, CspA, which inactivates complement by binding to a host complement inhibitor, Factor H (FH). CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. CspA is the only member of the Pfam54 gene family to exhibit host-specific FH-binding. Phylogenetic analyses revealed convergent evolution as the driver of such uniqueness, and that FH-binding likely emerged during the last glacial maximum. Our results identify a determinant of host tropism in Lyme disease infection, thus defining an evolutionary mechanism that shapes host-pathogen associations.