Allograft rejection is associated with development of functional IgE specific for donor MHC antigens.

BACKGROUND: Donor-specific antibodies of the IgG isotype are measured routinely for diagnostic purposes in renal transplant recipients and are associated with antibody-mediated rejection and long-term graft loss. OBJECTIVE: This study aimed to investigate whether MHC-specific antibodies of the IgE isotype are induced during allograft rejection. METHODS: Anti-MHC/HLA IgE levels were measured in sera of mice grafted with skin or heart transplants from various donor strains and in sera of kidney transplant patients with high levels of HLA IgG. Mediator release was triggered in vitro by stimulating basophils that were coated with murine or human IgE-positive serum, respectively, with specific recombinant MHC/HLA antigens. Kidney tissue samples obtained from organ donors were analyzed by using flow cytometry for cells expressing the high-affinity receptor for IgE (FcεRI). RESULTS: Donor MHC class I- and MHC class II-specific IgE was found on acute rejection of skin and heart grafts in several murine strain combinations, as well as during chronic antibody-mediated heart graft rejection. Anti-HLA IgE, including donor HLA class I and II specificities, was identified in a group of sensitized transplant recipients. Murine and human anti-MHC/HLA IgE triggered mediator release in coated basophils on stimulation with specific MHC/HLA antigens. HLA-specific IgE was not linked to atopy, and allergen-specific IgE present in allergic patients did not cross-react with HLA antigens. FcεRI+ cells were found in the human renal cortex and medulla and provide targets for HLA-specific IgE. CONCLUSION: These results demonstrate that MHC/HLA-specific IgE develops during an alloresponse and is functional in mediating effector mechanisms

Infusing Virtual Creatures with Vision

In this paper, we evolve light following behaviours in preevolved virtual creatures. The neural controllers of creatures evolved for movement are augmented with simple visual neurons and neural connections. The resulting neural networks are trained for light following by an evolutionary algorithm. We show that, through this process, we are able to train the neural controllers to follow a light source. Many of the evolved behaviours show stability and adaptiveness to environmental perturbations of body orientation.N

Effects of Traumeel (Tr14) on Exercise-Induced Muscle Damage Response in Healthy Subjects: A Double-Blind RCT

The present double-blind, randomized, placebo-controlled clinical trial intended to test whether ingestion of a natural combination medicine (Tr14 tablets) affects serum muscle damage and inflammatory immune response after downhill running. 96 male subjects received Tr14 tablets, which consist of 14 diluted biological and mineral components, or a placebo for 72 h after the exercise test, respectively. Changes in postexercise levels of various serum muscle damage and immunological markers were investigated. The area under the curve with respect to the increase (AUCi) of perceived pain score and creatine kinase (CK) were defined as primary outcome measures. While for CK the p value of the difference between the two groups is borderline, the pain score and muscle strength were not statistically significant. However, a trend towards lower levels of muscle damage (CK, p=0.05; LDH, p=0.06) in the Tr14 group was shown. Less pronounced lymphopenia (p=0.02), a trend towards a lower expression of CD69 count (p=0.07), and antigen-stimulated ICAM-1 (p=0.01) were found in the verum group. The Tr14 group showed a tendentially lower increase of neutrophils (p=0.10), BDNF (p=0.03), stem cell factor (p=0.09), and GM-CSF (p=0.09) to higher levels. The results of the current study indicate that Tr14 seems to limit exercise-induced muscle damage most likely via attenuation of both innate and adaptive immune responses. This study was registered with ClinicalTrials.gov (NCT01912469)

Effects of Acute Endurance Exercise on Plasma Protein Profiles of Endurance-Trained and Untrained Individuals over Time

Acute physical exercise and repeated exercise stimuli affect whole-body metabolic and immunologic homeostasis. The aim of this study was to determine plasma protein profiles of trained (EET, n=19) and untrained (SED, n=17) individuals at rest and in response to an acute bout of endurance exercise. Participants completed a bicycle exercise test at an intensity corresponding to 80% of their VO2max. Plasma samples were taken before, directly after, and three hours after exercise and analyzed using multiplex immunoassays. Seventy-eight plasma variables were included in the final analysis. Twenty-nine variables displayed significant acute exercise effects in both groups. Seven proteins differed between groups, without being affected by acute exercise. Among these A2Macro and IL-5 were higher in EET individuals while leptin showed elevated levels in SED individuals. Fifteen variables revealed group and time differences with elevated levels for IL-3, IL-7, IL-10, and TNFR2 in EET individuals. An interaction effect could be observed for nine variables including IL-6, MMP-2, MMP-3, and muscle damage markers. The proteins that differ between groups indicate a long-term exercise effect on plasma protein concentrations. These findings might be of importance in the development of exercise-based strategies in the prevention and therapy of chronic metabolic and inflammatory diseases and for training monitoring

Red2Flpe-SCON: a versatile, multicolor strategy for generating mosaic conditional knockout mice

Acknowledgements: We thank present and past members of the Koo, Elling and Urban labs at IMBA for valuable discussions and critical comments, Dr. Rike Zietlow and the Life Science Editors for reading and correcting the manuscript, VBC core facilities (especially the Histopathology facility, BioOptics and the animal caretakers). We thank Single Cell Discoveries for helping us with single cell RNA sequencing and offering technical advice on sample handling. This work was supported by core funding from the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences; ERC starting grant, Troy Stem cells, 639050; Interpark Bio-Convergence Center Grant Program; and fellowship to S.W. (DOC Fellowship of the Austrian Academy of Sciences). G.C. was supported by a Lise Meitner Postdoctoral fellowship M2976, FWF, and by the FWF Standalone (P35694) and ERA PerMed (I 5900) grants. B.-K.K. and his team are supported by the Institute for Basic Science.Funder: This work was supported by core funding from the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences; ERC starting grant, Troy Stem cells, 639050; Interpark Bio-Convergence Center Grant Program; and fellowship to first author Sam Wu (DOC Fellowship of the Austrian Academy of Sciences)Funder: FWF Lise Meitner Postdoctoral fellowship M2976 FWF Standalone P35694 FWF ERA PerMed I 5900AbstractImage-based lineage tracing enables tissue turnover kinetics and lineage potentials of different adult cell populations to be investigated. Previously, we reported a genetic mouse model system, Red2Onco, which ectopically expressed mutated oncogenes together with red fluorescent proteins (RFP). This system enabled the expansion kinetics and neighboring effects of oncogenic clones to be dissected. We now report Red2Flpe-SCON: a mosaic knockout system that uses multicolor reporters to label both mutant and wild-type cells. We develop the Red2Flpe mouse line for red clone-specific Flpe expression, as well as the FRT-based SCON (Short Conditional IntrON) method to facilitate tunable conditional mosaic knockouts in mice. We use the Red2Flpe-SCON method to study Sox2 mutant clonal analysis in the esophageal epithelium of adult mice which reveal that the stem cell gene, Sox2, is less essential for adult stem cell maintenance itself, but rather for stem cell proliferation and differentiation.</jats:p

AstRoMap European Astrobiology Roadmap

The European AstRoMap project (supported by the European Commission Seventh Framework Programme) surveyed the state of the art of astrobiology in Europe and beyond and produced the first European roadmap for astrobiology research. In the context of this roadmap, astrobiology is understood as the study of the origin, evolution, and distribution of life in the context of cosmic evolution; this includes habitability in the Solar System and beyond. The AstRoMap Roadmap identifies five research topics, specifies several key scientific objectives for each topic, and suggests ways to achieve all the objectives. The five AstRoMap Research Topics are: Research Topic 1: Origin and Evolution of Planetary Systems Research Topic 2: Origins of Organic Compounds in Space Research Topic 3: Rock-Water-Carbon Interactions, Organic Synthesis on Earth, and Steps to Life Research Topic 4: Life and Habitability Research Topic 5: Biosignatures as Facilitating Life Detection. It is strongly recommended that steps be taken towards the definition and implementation of a European Astrobiology Platform (or Institute) to streamline and optimize the scientific return by using a coordinated infrastructure and funding system