Phylogenetic diversity, antimicrobial susceptibility and virulence gene profiles of Brachyspira hyodysenteriae isolates from pigs in Germany

Swine dysentery (SD) is an economically important diarrheal disease in pigs caused by different strongly hemolytic Brachyspira (B.) species, such as B. hyodysenteriae, B. suanatina and B. hampsonii. Possible associations of epidemiologic data, such as multilocus sequence types (STs) to virulence gene profiles and antimicrobial susceptibility are rather scarce, particularly for B. hyodysenteriae isolates from Germany. In this study, B. hyodysenteriae (n = 116) isolated from diarrheic pigs between 1990 and 2016 in Germany were investigated for their STs, susceptibility to the major drugs used for treatment of SD (tiamulin and valnemulin) and genes that were previously linked with virulence and encode for hemolysins (tlyA, tlyB, tlyC, hlyA, BHWA1_RS02885, BHWA1_RS09085, BHWA1_RS04705, and BHWA1_RS02195), outer membrane proteins (OMPs) (bhlp16, bhlp17.6, bhlp29.7, bhmp39f, and bhmp39h) as well as iron acquisition factors (ftnA and bitC). Multilocus sequence typing (MLST) revealed that 79.4% of the isolates belonged to only three STs, namely ST52 (41.4%), ST8 (12.1%), and ST112 (25.9%) which have been observed in other European countries before. Another 24 isolates belonged to twelve new STs (ST113-118, ST120-123, ST131, and ST193). The temporal distribution of STs revealed the presence of new STs as well as the regular presence of ST52 over three decades (1990s–2000s). The proportion of strains that showed resistance to both tiamulin und valnemulin (39.1%) varied considerably among the most frequent STs ranging from 0% (0/14 isolates resistant) in ST8 isolates to 46.7% (14/30), 52.1% (25/48), and 85.7% (6/7) in isolates belonging to ST112, ST52, and ST114, respectively. All hemolysin genes as well as the iron-related gene ftnA and the OMP gene bhlp29.7 were regularly present in the isolates, while the OMP genes bhlp17.6 and bhmp39h could not be detected. Sequence analysis of hemolysin genes of selected isolates revealed co-evolution of tlyB, BHWA1_RS02885, BHWA1_RS09085, and BHWA1_RS02195 with the core genome and suggested independent evolution of tlyA, tlyC, and hlyA. Our data indicate that in Germany, swine dysentery might be caused by a limited number of B. hyodysenteriae clonal groups. Major STs (ST8, ST52, and ST112) are shared with other countries in Europe suggesting a possible role of the European intra-Community trade of pigs in the dissemination of certain clones. The identification of several novel STs, some of which are single or double locus variants of ST52, may on the other hand hint towards an ongoing diversification of the pathogen in the studied area. The linkage of pleuromutilin susceptibility and sequence type of an isolate might reflect a clonal expansion of the underlying resistance mechanism, namely mutations in the ribosomal RNA genes. A linkage between single virulence-associated genes (VAGs) or even VAG patterns and the phylogenetic background of the isolates could not be established, since almost all VAGs were regularly present in the isolates

All-Polymer Photonic Microcavities Doped with Perylene Bisimide J-Aggregates

Thanks to exciting chemical and optical features, perylene bisimide (PBI) J-aggregates are ideal candidates to be employed for high-performance plastic photonic devices. However, they generally tend to form - stacked H-aggregates that are unsuitable for implementation in polymer resonant cavities. In this work, we demonstrate the efficient compatibilization of a tailored perylene bisimide forming robust J-aggregated supramolecular polymers into amorphous polypropylene. The new nanocomposite was then implemented into an all-polymer planar microcavity which provides strong and directional spectral redistribution of the J-aggregate photoluminescence, owing to a strong modification of the photonic states. A systematic analysis of the photoemitting processes, including photoluminescence decay and quantum yields, shows that the optical confinement in the polymeric microcavity does not introduce any additional nonradiative de-excitation pathways to those already found in the J-aggregate nanocomposite film and pave the way to PBI-based high-performance plastic photonic devices

Comprehensive Life Cycle Support for Access Rules in Information Systems: The CEOSIS Project

The definition and management of access rules (e.g., to control access to business documents and business functions) is a fundamental task in any enterprise information system (EIS). While there exists considerable work on how to specify and represent access rules, only little research has been spent on access rule changes. Examples include the evolution of organizational models with need for subsequent adaptation of related access rules as well as direct access rule modifications (e.g., to state a previously defined rule more precisely). This paper presents a comprehensive change framework for the controlled evolution of role-based access rules in EIS. First, we consider changes of organizational models and elaborate how they affect existing access rules. Second, we define change operations which enable direct adaptations of access rules. In the latter context, we define the formal semantics of access rule changes based on operator trees. Particularly, this enables their unambiguous application; i.e., we can precisely determine which effects are caused by respective rule changes. This is important, for example, to be able to efficiently and correctly adapt user worklists in process-aware information systems. Altogether this paper contributes to comprehensive life cycle support for access rules in (adaptive) EIS

Three-dimensional photonic confinement in imprinted liquid crystalline pillar microcavities

Sv.H. acknowledges financial support by the EPSRC ”Hybrid Polaritonics” Grant (EP/M025330/1). F.W. thanks the Deutsche Forschungsgemeinschaft (DFG) for financial support (WU317/18-1).We demonstrate the feasibility of a thermal imprint technology capable of structuring organic thin films with liquid crystalline properties forming feature sizes on a several micrometer scale. The imprint technique can directly be applied onto a variety of substrates including dielectric mirrors. The so fabricated three-dimensional microcavities have lateral extensions up to 20 µm and heights between 1 and 5 µm. Exemplarily, pillar microcavities were produced wherein three-dimensional photonic confinement is observed by the formation of 0D cavity mode patterns. The imprint technique further favors the formation of hemispherical pillar geometries rather than cylindrical pillars resulting in equidistant mode spacings of transversal cavity modes.PostprintPeer reviewe

In Vitro Antibacterial Activity of Microbial Natural Products against Bacterial Pathogens of Veterinary and Zoonotic Relevance

Antimicrobial resistance (AMR) is considered one of the greatest threats to both human and animal health. Efforts to address AMR include implementing antimicrobial stewardship programs and introducing alternative treatment options. Nevertheless, effective treatment of infectious diseases caused by bacteria will still require the identification and development of new antimicrobial agents. Eight different natural products were tested for antimicrobial activity against seven pathogenic bacterial species (Brachyspira sp., Chlamydia sp., Clostridioides sp., Mannheimia sp., Mycobacterium sp., Mycoplasma sp., Pasteurella sp.). In a first pre-screening, most compounds (five out of eight) inhibited bacterial growth only at high concentrations, but three natural products (celastramycin A [CA], closthioamide [CT], maduranic acid [MA]) displayed activity at concentrations 16 µg/mL against Mannheimia for CA, CT, and MA, respectively. CA, CT, and MA exhibited higher MIC50 and MIC90 values against Pasteurella isolates with a known AMR phenotype against commonly used therapeutic antimicrobial agents than against isolates with unknown AMR profiles. This study demonstrates the importance of whole-cell antibacterial screening of natural products to identify promising scaffolds with broad- or narrow-spectrum antimicrobial activity against important Gram-negative veterinary pathogens with zoonotic potentia

Influence of optical material properties on strong coupling in organic semiconductor based microcavities

The optical properties of organic semiconductors are generally characterised by a number of material specific parameters, including absorbance, photoluminescence quantum yield, Stokes shift, and molecular orientation. Here, we study four different organic semiconductors and compare their optical properties to the characteristics of the exciton-polaritons that are formed when these materials are introduced into metal-clad microcavities. We find that the strength of coupling between cavity photons and excitons is clearly correlated with the absorptivity of the material. In addition, we show that anisotropy strongly affects the characteristics of the formed exciton-polaritons

Tunable light-matter hybridization in open organic microcavities

Sv.H. acknowledges funding by the EPSRC ”Hybrid Polaritonics” Grant (EP/M025330/1), F.W. further thanks the Deutsche Forschungsgemeinschaft (DFG) for financial support (WU317/18-1). J.S. and A.A.P.T. thank the Leverhulme Trust (RPG-2012-526) and the UK Engineering and Physical Sciences Research Council (EP/M013243/1) for financial support.Open microcavities represent a versatile cavity design that allows the external control of internal properties such as cavity thickness and mode detuning without changing the key parameters of the cavity itself, rendering them particularly interesting for light-matter interaction experiments. Here, we demonstrate the tunability of an open microcavity with an embedded active organic layer providing parallel alignment of molecular transition dipole moments as well as strong self-absorption inside the cavity. By decreasing the cavity thickness, we observe a transition from the weak coupling regime into the strong coupling regime evidenced by the onset of avoided crossing behavior between involved modes. This change of coupling mechanism is shown for 2D (planar) as well as 0D (hemispherical) cavities.PostprintPeer reviewe

Recruiting young pre-symptomatic children for a clinical trial in type 1 diabetes: insights from the Fr1da insulin intervention study

Background: Although detection of children at high risk of developing type 1 diabetes and diagnosis of early stages is possible, up to now there exists no approved therapy to delay or prevent type 1 diabetes. Thus it is vital to develop evidence-based interventions. For this a sufficient number of trial participants is crucial but difficult to obtain especially in asymptomatic children. Aim: Identifying family characteristics that lead to or impede trial participation and analyze reasons stated by families for non-participation. Methods: Participants for the Fr1da Insulin Intervention study are recruited from the Fr1da study, a population based screening for early stage type 1 diabetes in Bavaria. Families with eligible children were invited to enroll. We analyzed sex and age of the child, distance of the family to the study center in Munich and the existence of a first degree family member with type 1 as possible influential factors for study participation. We also analyzed reasons stated by families who declined study participation in a phone interview. Results: Of 146 eligible children 77 (53%) were enrolled into the trial. None of the tested family characteristics differed significantly between the enrolling and the families not participating, but in general enrolling families lived closer to the study site than families not participating. This is also reflected in the reasons given by non-participating families. The most frequent reason stated were time restrictions. The second most frequent reason was the venous blood draw. Conclusion: The factors for non-participation identified in this project need be taken into account for the design of future trials in young children to ensure proper recruitment and thus to generate valid results for medical treatment of children. More research on the reason of participation and non-participation in clinical trials is needed. Keywords: Type 1 diabetes, Trial recruitment, Trial enrollment, Infants, Children, Asymptomati

Mixed Th1 and Th2 Mycobacterium tuberculosis-specific CD4 T cell responses in patients with active pulmonary tuberculosis from Tanzania.

Mycobacterium tuberculosis (Mtb) and helminth infections elicit antagonistic immune effector functions and are co-endemic in several regions of the world. We therefore hypothesized that helminth infection may influence Mtb-specific T-cell immune responses. We evaluated the cytokine profile of Mtb-specific T cells in 72 individuals with pulmonary TB disease recruited from two Sub-Saharan regions with high and moderate helminth burden i.e. 55 from Tanzania (TZ) and 17 from South Africa (SA), respectively. We showed that Mtb-specific CD4 T-cell functional profile of TB patients from Tanzania are primarily composed of polyfunctional Th1 and Th2 cells, associated with increased expression of Gata-3 and reduced expression of T-bet in memory CD4 T cells. In contrast, the cytokine profile of Mtb-specific CD4 T cells of TB patients from SA was dominated by single IFN-γ and dual IFN-γ/TNF-α and associated with TB-induced systemic inflammation and elevated serum levels of type I IFNs. Of note, the proportion of patients with Mtb-specific CD8 T cells was significantly reduced in Mtb/helminth co-infected patients from TZ. It is likely that the underlying helminth infection and possibly genetic and other unknown environmental factors may have caused the induction of mixed Th1/Th2 Mtb-specific CD4 T cell responses in patients from TZ. Taken together, these results indicate that the generation of Mtb-specific CD4 and CD8 T cell responses may be substantially influenced by environmental factors in vivo. These observations may have major impact in the identification of immune biomarkers of disease status and correlates of protection

Software for the frontiers of quantum chemistry:An overview of developments in the Q-Chem 5 package

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange–correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear–electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an “open teamware” model and an increasingly modular design