Aberrant repair and fibrosis development in skeletal muscle

The repair process of damaged tissue involves the coordinated activities of several cell types in response to local and systemic signals. Following acute tissue injury, infiltrating inflammatory cells and resident stem cells orchestrate their activities to restore tissue homeostasis. However, during chronic tissue damage, such as in muscular dystrophies, the inflammatory-cell infiltration and fibroblast activation persists, while the reparative capacity of stem cells (satellite cells) is attenuated. Abnormal dystrophic muscle repair and its end stage, fibrosis, represent the final common pathway of virtually all chronic neurodegenerative muscular diseases. As our understanding of the pathogenesis of muscle fibrosis has progressed, it has become evident that the muscle provides a useful model for the regulation of tissue repair by the local microenvironment, showing interplay among muscle-specific stem cells, inflammatory cells, fibroblasts and extracellular matrix components of the mammalian wound-healing response. This article reviews the emerging findings of the mechanisms that underlie normal versus aberrant muscle-tissue repair

On the molecular origins of the ferroelectric splay nematic phase

Nematic liquid crystals have been known for more than a century, but it was not until the 60s–70s that, with the development of room temperature nematics, they became widely used in applications. Polar nematic phases have been long-time predicted, but have only been experimentally realized recently. Synthesis of materials with nematic polar ordering at room temperature is certainly challenging and requires a deep understanding of its formation mechanisms, presently lacking. Here, we compare two materials of similar chemical structure and demonstrate that just a subtle change in the molecular structure enables denser packing of the molecules when they exhibit polar order, which shows that reduction of excluded volume is in the origin of the polar nematic phase. Additionally, we propose that molecular dynamics simulations are potent tools for molecular design in order to predict, identify and design materials showing the polar nematic phase and its precursor nematic phases

Dielectric spectroscopy of a ferroelectric nematic liquid crystal and the effect of the sample thickness

The recently discovered ferroelectric nematic liquid crystals have been reported to exhibit very large dielectric permittivity values. Here, we report a systematic investigation of the dielectric behavior of a prototypical ferroelectric nematogen by varying the thickness of the parallel capacitor measuring cell. While in the non-polar high temperature nematic phase results show only slight differences due to slight variations of the alignment, the measured permittivity values in the ferroelectric nematic phase show a linear dependence on the cell thickness. It is also shown that the characteristic relaxation frequency decreases inversely proportionally to the thickness. The results are discussed in terms of three different available models based on different underlying mechanisms, accounting for cancellation of the probe electric fields by polarization reorientation or by ionic charges, or based on a recently proposed continuous phenomenological model

P17-23. Enhanced expression of HIV antigens and improved antigen presentation after infection with replication competent attenuated vaccinia virus in vitro

1 página.-- Presentación de póster presentation.-- Este artículo es parte del suplemento: AIDS Vaccine 2009.Peer reviewe

CD38 Defines a Subset of B Cells in Rainbow Trout Kidney With High IgM Secreting Capacities

Funding Information: This work was supported by the European Research Council (ERC Consolidator Grant 2016 725061 TEMUBLYM) and by the Comunidad de Madrid (grant 2016-T1/BIO-1672).Peer reviewedPublisher PD

Dysregulation of B Cell Activity During Proliferative Kidney Disease in Rainbow Trout

This work was supported by the European Research Council (ERC Consolidator Grant 2016 725061 TEMUBLYM) and the European Commission under the H2020 Programme (Grant H2020-634429 ParaFishControl). IE was recipient of APOSTD/2016/037 grant by the “Generalitat Valenciana” and YH was recipient of a PhD Studentship from the Ministry of Education, Republic of China (Taiwan). JWH was supported by BBSRC grant BB/K009125/1 and SNSF grant CRSII3_147649-1. PDR was funded by grant T1-BIO-1672 from the “Comunidad de Madrid”.Peer reviewedPublisher PD

Roles for Treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A

© 2013 Matsumiya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedA better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.This work was funded by the Wellcome Trust. MM has a Wellcome Trust PhD studentship and HM is a Wellcome Trust Senior Fello

3-Deazaadenosine alleviates senescence to promote cellular fitness and cell therapy efficiency in mice

International audienc