Myocardial aging as a T-cell–mediated phenomenon

In recent years, the myocardium has been rediscovered under the lenses of immunology, and lymphocytes have been implicated in the pathogenesis of cardiomyopathies with different etiologies. Aging is an important risk factor for heart diseases, and it also has impact on the immune system. Thus, we sought to determine whether immunological activity would influence myocardial structure and function in elderly mice. Morphological, functional, and molecular analyses revealed that the age-related myocardial impairment occurs in parallel with shifts in the composition of tissue-resident leukocytes and with an accumulation of activated CD4+ Foxp3- (forkhead box P3) IFN-γ+ T cells in the heart-draining lymph nodes. A comprehensive characterization of different aged immune-deficient mouse strains revealed that T cells significantly contribute to age-related myocardial inflammation and functional decline. Upon adoptive cell transfer, the T cells isolated from the mediastinal lymph node (med-LN) of aged animals exhibited increased cardiotropism, compared with cells purified from young donors or from other irrelevant sites. Nevertheless, these cells caused rather mild effects on cardiac functionality, indicating that myocardial aging might stem from a combination of intrinsic and extrinsic (immunological) factors. Taken together, the data herein presented indicate that heart-directed immune responses may spontaneously arise in the elderly, even in the absence of a clear tissue damage or concomitant infection. These observations might shed new light on the emerging role of T cells in myocardial diseases, which primarily affect the elderly population.info:eu-repo/semantics/publishedVersio

Oxidation state governs structural transitions in peroxiredoxin II that correlate with cell cycle arrest and recovery

Inactivation of eukaryotic 2-Cys peroxiredoxins (Prxs) by hyperoxidation has been proposed to promote accumulation of hydrogen peroxide (H2O2) for redox-dependent signaling events. We examined the oxidation and oligomeric states of PrxI and -II in epithelial cells during mitogenic signaling and in response to fluxes of H2O2. During normal mitogenic signaling, hyperoxidation of PrxI and -II was not detected. In contrast, H2O2-dependent cell cycle arrest was correlated with hyperoxidation of PrxII, which resulted in quantitative recruitment of ∼66- and ∼140-kD PrxII complexes into large filamentous oligomers. Expression of cyclin D1 and cell proliferation did not resume until PrxII-SO2H was reduced and native PrxII complexes were regenerated. Ectopic expression of PrxI or -II increased Prx-SO2H levels in response to oxidant exposure and failed to protect cells from arrest. We propose a model in which Prxs function as peroxide dosimeters in subcellular processes that involve redox cycling, with hyperoxidation controlling structural transitions that alert cells of perturbations in peroxide homeostasis

The structure and formation of functional hard coatings: a short review

Turning tools come in different shapes and sizes, geometry, base material and coating, according to their destination. They are widely used both for obtaining parts and for machinability tests. In this paper a short review about high-speed steel (HSS) turning tools and their coatings is presented. Hard coatings formed on the tool material should be functional depending on the tool final application. Requirements for hard coatings and technological problems for layer formation on the real cutting tool are discussed

Objective review of de novo stand-alone error correction methods for NGS data

[EN] The sequencing market has increased steadily over the last few years, with different approaches to read DNA information prone to different types of errors. Multiple studies demonstrated the impact of sequencing errors on different applications of next-generation sequencing (NGS), making error correction a fundamental initial step. Different methods in the literature use different approaches and fit different types of problems. We analyzed 50 methods divided into five main approaches (k-spectrum, suffix arrays, multiple-sequence alignment, read clustering, and probabilistic models). They are not published as a part of a suite (stand-alone), and target raw, unprocessed data without an existing reference genome (de novo). These correctors handle one or more sequencing technologies using the same or different approaches. They face general challenges (sometimes with specific traits for specific technologies) such as repetitive regions, uncalled bases, and ploidy. Even assessing their performance is a challenge in itself because of the approach taken by various authors, the unknown factor (de novo), and the behavior of the third-party tools employed in the benchmarks. This study aims to help the researcher in the field to advance the field of error correction, the educator to have a brief but comprehensive companion, and the bioinformatician to choose the right tool for the right job. © 2016 John Wiley & Sons, LtdWe want to thank our colleague Eloy Romero Alcale who has provided valuable advice regarding the structure of the document. This work was supported by Generalitat Valenciana [GRISOLIA/2013/013 to A.A.].Alic, AS.; Ruzafa, D.; Dopazo, J.; Blanquer Espert, I. (2016). Objective review of de novo stand-alone error correction methods for NGS data. Wiley Interdisciplinary Reviews: Computational Molecular Science. 6(2):111-146. https://doi.org/10.1002/wcms.1239S1111466

Regulatory T cells promote myelin regeneration in the central nervous system

Regeneration of CNS myelin involves differentiation of oligodendrocytes from oligodendrocyte progenitor cells. In multiple sclerosis, remyelination can fail despite abundant oligodendrocyte progenitor cells, suggesting impairment of oligodendrocyte differentiation. T cells infiltrate the CNS in multiple sclerosis, yet little is known about T cell functions in remyelination. We report that regulatory T cells (T$_{reg}$) promote oligodendrocyte differentiation and (re)myelination. T$_{reg}$-deficient mice exhibited substantially impaired remyelination and oligodendrocyte differentiation, which was rescued by adoptive transfer of T$_{reg}$. In brain slice cultures, T$_{reg}$ accelerated developmental myelination and remyelination, even in the absence of overt inflammation. T$_{reg}$ directly promoted oligodendrocyte progenitor cell differentiation and myelination in vitro. We identified CCN3 as a T$_{reg}$-derived mediator of oligodendrocyte differentiation and myelination in vitro. These findings reveal a new regenerative function of T$_{reg}$ in the CNS, distinct from immunomodulation. Although the cells were originally named 'T$_{reg}$' to reflect immunoregulatory roles, this also captures emerging, regenerative T$_{reg}$ functions.This work was supported by the Biotechnology and Biological Sciences Research Council (BB/J01026X/1 and BB/N003721/1, to D.C.F.), The Leverhulme Trust (ECF-2014-390, to Y.D.), QUB (QUB - Lucy McGuigan Bequest, to D.C.F.), The UK Multiple Sclerosis Society (941 and 50, to R.J.M.F. and C.Z.), MRC UK Regenerative Medicine platform (MR/KO26666/1, to A.C.W.), University of Edinburgh Wellcome Trust Multi User Equipment Grant (WT104915MA, to A.C.W.), by a core support grant from the Wellcome Trust and MRC to the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute (097922/Z/11/Z to R.J.M.F.), studentship support from Dept. for the Economy (Northern Ireland) and British Pathological Society, US National Multiple Sclerosis Society (RG5203A4, to J.R.C.), NIH/NINDS (NS095889, to J.R.C.), NIH/NIGMS IRACDA Postdoctoral Fellowship (K12GM081266, to S.R.M.) and Wellcome Trust (110138/Z/15/Z, to D.C.F.)