Bioactive coatings of glass-ceramics on metals

To combine the mechanical properties of high-strength base metals with the biological properties of bioactive materials, coatings of BIOVERIT® glasses and glass-ceramics on CoCr alloys and titanium have been produced. Different kinds of coating processes have been used: dipping, sputtering, plasma spraying, sintering and pasting. Dipping and pasting seem not to be suitable to produce layers because of cracks and low adhesion strength of the coatings (dipping) and the limitations in relation to the implant shape and the thickness of the layers (pasting). Using sputter techniques it is possible to produce dense layers ( < 10µim) with a high adhesion strength. Plasma spraying resuhed in layers with a thickness of 50 to 300µim, but during the plasma spraying process there is a partial evaporation of the highly volatile glass components. Sintering processes are very suitable to produce layers with a high adhesion strength; these layers are long term stable in simulated body fluid

Does Animal Personality Affect Movement in Habitat Corridors? Experiments with Common Voles (Microtus arvalis) using Different Corridor Widths.

Kowalski GJ, Grimm V, Herde A, Günther A, Eccard JA. Does Animal Personality Affect Movement in Habitat Corridors? Experiments with Common Voles (Microtus arvalis) using Different Corridor Widths. Animals : an open access journal from MDPI. 2019;9(6): 291.Animal personality may affect an animal's mobility in a given landscape, influencing its propensity to take risks in an unknown environment. We investigated the mobility of translocated common voles in two corridor systems 60 m in length and differing in width (1 m and 3 m). Voles were behaviorally phenotyped in repeated open field and barrier tests. Observed behavioral traits were highly repeatable and described by a continuous personality score. Subsequently, animals were tracked via an automated very high frequency (VHF) telemetry radio tracking system to monitor their movement patterns in the corridor system. Although personality did not explain movement patterns, corridor width determined the amount of time spent in the habitat corridor. Voles in the narrow corridor system entered the corridor faster and spent less time in the corridor than animals in the wide corridor. Thus, landscape features seem to affect movement patterns more strongly than personality. Meanwhile, site characteristics, such as corridor width, could prove to be highly important when designing corridors for conservation, with narrow corridors facilitating faster movement through landscapes than wider corridors

Retinal Layer Separation (ReLayS) method enables the molecular analysis of photoreceptor segments and cell bodies, as well as the inner retina

Understanding the physiology of the retina, and especially of the highly polarized photoreceptors, is essential not only to broaden our knowledge of the processes required for normal vision, but also to develop effective therapies to prevent or slow retinal degenerative diseases. However, the molecular analysis of photoreceptors is a challenge due to the heterogeneity of the retinal tissue and the lack of easy and reliable methods for cell separation. Here we present the ReLayS method—a simple technique for the separation of photoreceptor segments (PS) containing both inner and outer segments, outer nuclear layer (ONL), and inner retina (InR) that contains the remaining retinal layers. The layer-specific material isolated from a mouse half-retina with the ReLayS method was sufficient for protein isolation and Western blotting or RNA isolation and real-time PCR studies. The separation of PS, ONL, and InR was successfully validated by Western blotting and real-time PCR using proteins and genes with known expression profiles within the retina. Furthermore, the separation of the PS from the ONL enabled the detection of light-driven translocation of transducin from the PS to the soma. ReLayS is a simple and useful method to address protein and possibly metabolites distribution in photoreceptor compartments in various situations including development, ageing, and degenerative diseases

Potential Immunocompetence of Proteolytic Fragments Produced by Proteasomes before Evolution of the Vertebrate Immune System

To generate peptides for presentation by major histocompatibility complex (MHC) class I molecules to T lymphocytes, the immune system of vertebrates has recruited the proteasomes, phylogenetically ancient multicatalytic high molecular weight endoproteases. We have previously shown that many of the proteolytic fragments generated by vertebrate proteasomes have structural features in common with peptides eluted from MHC class I molecules, suggesting that many MHC class I ligands are direct products of proteasomal proteolysis. Here, we report that the processing of polypeptides by proteasomes is conserved in evolution, not only among vertebrate species, but including invertebrate eukaryotes such as insects and yeast. Unexpectedly, we found that several high copy ligands of MHC class I molecules, in particular, self-ligands, are major products in digests of source polypeptides by invertebrate proteasomes. Moreover, many major dual cleavage peptides produced by invertebrate proteasomes have the length and the NH2 and COOH termini preferred by MHC class I. Thus, the ability of proteasomes to generate potentially immunocompetent peptides evolved well before the vertebrate immune system. We demonstrate with polypeptide substrates that interferon γ induction in vivo or addition of recombinant proteasome activator 28α in vitro alters proteasomal proteolysis in such a way that the generation of peptides with the structural features of MHC class I ligands is optimized. However, these changes are quantitative and do not confer qualitatively novel characteristics to proteasomal proteolysis. The data suggest that proteasomes may have influenced the evolution of MHC class I molecules

Extended supersymmetric sigma models in AdS_4 from projective superspace

There exist two superspace approaches to describe N=2 supersymmetric nonlinear sigma models in four-dimensional anti-de Sitter (AdS_4) space: (i) in terms of N=1 AdS chiral superfields, as developed in arXiv:1105.3111 and arXiv:1108.5290; and (ii) in terms of N=2 polar supermultiplets using the AdS projective-superspace techniques developed in arXiv:0807.3368. The virtue of the approach (i) is that it makes manifest the geometric properties of the N=2 supersymmetric sigma-models in AdS_4. The target space must be a non-compact hyperkahler manifold endowed with a Killing vector field which generates an SO(2) group of rotations on the two-sphere of complex structures. The power of the approach (ii) is that it allows us, in principle, to generate hyperkahler metrics as well as to address the problem of deformations of such metrics. Here we show how to relate the formulation (ii) to (i) by integrating out an infinite number of N=1 AdS auxiliary superfields and performing a superfield duality transformation. We also develop a novel description of the most general N=2 supersymmetric nonlinear sigma-model in AdS_4 in terms of chiral superfields on three-dimensional N=2 flat superspace without central charge. This superspace naturally originates from a conformally flat realization for the four-dimensional N=2 AdS superspace that makes use of Poincare coordinates for AdS_4. This novel formulation allows us to uncover several interesting geometric results.Comment: 88 pages; v3: typos corrected, version published in JHE

The Statistics of Supersymmetric D-brane Models

We investigate the statistics of the phenomenologically important D-brane sector of string compactifications. In particular for the class of intersecting D-brane models, we generalise methods known from number theory to determine the asymptotic statistical distribution of solutions to the tadpole cancellation conditions. Our approach allows us to compute the statistical distribution of gauge theoretic observables like the rank of the gauge group, the number of chiral generations or the probability of an SU(N) gauge factor. Concretely, we study the statistics of intersecting branes on T^2 and T^4/Z_2 and T^6/Z_2 x Z_2 orientifolds. Intriguingly, we find a statistical correlation between the rank of the gauge group and the number of chiral generations. Finally, we combine the statistics of the gauge theory sector with the statistics of the flux sector and study how distributions of gauge theoretic quantities are affected.Comment: 62 pages, 31 figures, harvmac; v3: sections 3.2. + 3.7. added, figs. 7,28,29 added, figs. 24,25,26 corrected, refs. added, typos correcte

Yukawa couplings and masses of non-chiral states for the Standard Model on D6-branes on T6/Z6'

The perturbative leading order open string three-point couplings for the Standard Model with hidden USp(6) on fractional D6-branes on T6/Z6' from arXiv:0806.3039 [hep-th], arXiv:0910.0843 [hep-th] are computed. Physical Yukawa couplings consisting of holomorphic Wilsonian superpotential terms times a non-holomorphic prefactor involving the corresponding classical open string Kaehler metrics are given, and mass terms for all non-chiral matter states are derived. The lepton Yukawa interactions are at leading order flavour diagonal, while the quark sector displays a more intricate pattern of mixings. While N=2 supersymmetric sectors acquire masses via only two D6-brane displacements - which also provide the hierarchies between up- and down-type Yukawas within one quark or lepton generation -, the remaining vector-like states receive masses via perturbative three-point couplings to some Standard Model singlet fields with vevs along flat directions. Couplings to the hidden sector and messengers for supersymmetry breaking are briefly discussed.Comment: 52 pages (including 8p. appendix); 5 figures; 14 tables; v2: discussion in section 4.1.3 extended, footnote 5 added, typos corrected, accepted by JHE

Six-dimensional Supergravity and Projective Superfields

We propose a superspace formulation of N=(1,0) conformal supergravity in six dimensions. The corresponding superspace constraints are invariant under super-Weyl transformations generated by a real scalar parameter. The known variant Weyl super-multiplet is recovered by coupling the geometry to a super-3-form tensor multiplet. Isotwistor variables are introduced and used to define projective superfields. We formulate a locally supersymmetric and super-Weyl invariant action principle in projective superspace. Some families of dynamical supergravity-matter systems are presented.Comment: 39 pages; v3: some modifications in section 2; equations (2.3), (2.14b), (2.16) and (2.17) correcte

High-throughput screening of caterpillars as a platform to study host-microbe interactions and enteric immunity.

Mammalian models of human disease are expensive and subject to ethical restrictions. Here, we present an independent platform for high-throughput screening, using larvae of the tobacco hornworm Manduca sexta, combining diagnostic imaging modalities for a comprehensive characterization of aberrant phenotypes. For validation, we use bacterial/chemical-induced gut inflammation to generate a colitis-like phenotype and identify significant alterations in morphology, tissue properties, and intermediary metabolism, which aggravate with disease progression and can be rescued by antimicrobial treatment. In independent experiments, activation of the highly conserved NADPH oxidase DUOX, a key mediator of gut inflammation, leads to similar, dose-dependent alterations, which can be attenuated by pharmacological interventions. Furthermore, the developed platform could differentiate pathogens from mutualistic gastrointestinal bacteria broadening the scope of applications also to microbiomics and host-pathogen interactions. Overall, larvae-based screening can complement mammals in preclinical studies to explore innate immunity and host-pathogen interactions, thus representing a substantial contribution to improve mammalian welfare

mRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy

Large genes including several CRISPR-Cas modules like gene activators (CRISPRa) require dual adeno-associated viral (AAV) vectors for an efficient in vivo delivery and expression. Current dual AAV vector approaches have important limitations, e.g., low reconstitution efficiency, production of alien proteins, or low flexibility in split site selection. Here, we present a dual AAV vector technology based on reconstitution via mRNA trans-splicing (REVeRT). REVeRT is flexible in split site selection and can efficiently reconstitute different split genes in numerous in vitro models, in human organoids, and in vivo. Furthermore, REVeRT can functionally reconstitute a CRISPRa module targeting genes in various mouse tissues and organs in single or multiplexed approaches upon different routes of administration. Finally, REVeRT enabled the reconstitution of full-length ABCA4 after intravitreal injection in a mouse model of Stargardt disease. Due to its flexibility and efficiency REVeRT harbors great potential for basic research and clinical applications