The novel adipokine progranulin counteracts IL-1 and TLR4-driven inflammatory response in human and murine chondrocytes via TNFR1

Progranulin (PGRN) is a recently identified adipokine that is supposed to have anti-inflammatory actions. The proinflammatory cytokine interleukin-1β (IL1β) stimulates several mediators of cartilage degradation. Toll like receptor-4 (TLR4) can bind to various damage-associated molecular patterns, leading to inflammatory condition. So far, no data exist of PGRN effects in inflammatory conditions induced by IL1β or lipopolysaccharide (LPS). Here, we investigated the anti-inflammatory potential of PGRN in IL1β-or LPS-induced inflammatory responses of chondrocytes. Human osteoarthritic chondrocytes and ATDC-5 cells were treated with PGRN in presence or not of IL1β or LPS. First, we showed that recombinant PGRN had no effects on cell viability. We present evidence that PGRN expression was increased during the differentiation of ATDC-5 cell line. Moreover, PGRN mRNA and protein expression is increased in cartilage, synovial and infrapatellar fat pad tissue samples from OA patients. PGRN mRNA levels are upregulated under TNFα and IL1β stimulation. Our data showed that PGRN is able to significantly counteract the IL1β-induced expression of NOS2, COX2, MMP13 and VCAM-1. LPS-induced expression of NOS2 is also decreased by PGRN. These effects are mediated, at least in part, through TNFR1. Taken together, our results suggest that PGRN has a clear anti-inflammatory function

A variational approach to strongly damped wave equations

We discuss a Hilbert space method that allows to prove analytical well-posedness of a class of linear strongly damped wave equations. The main technical tool is a perturbation lemma for sesquilinear forms, which seems to be new. In most common linear cases we can furthermore apply a recent result due to Crouzeix--Haase, thus extending several known results and obtaining optimal analyticity angle.Comment: This is an extended version of an article appeared in \emph{Functional Analysis and Evolution Equations -- The G\"unter Lumer Volume}, edited by H. Amann et al., Birkh\"auser, Basel, 2008. In the latest submission to arXiv only some typos have been fixe

Quantum-Aware Software Defined Networks

Software Defined Networks (SDN) represent a major paradigm change in communications networks. It provides a level of abstraction and independence from the traditional networking practice that allows for a fast path of innovation and, specifically, opens new opportunities for Quantum Key Distribution (QKD) networks. In this contribution we explore the implications of this paradigm for the deployment of QKD in practice from the point of view of telecommunications? providers, network equipment manufacturers and applied research and development. We propose a generic quantum-aware SDN architecture and two applications, a generic end to end encryption one and other for the network infrastructure itself

Families of superintegrable Hamiltonians constructed from exceptional polynomials

We introduce a family of exactly-solvable two-dimensional Hamiltonians whose wave functions are given in terms of Laguerre and exceptional Jacobi polynomials. The Hamiltonians contain purely quantum terms which vanish in the classical limit leaving only a previously known family of superintegrable systems. Additional, higher-order integrals of motion are constructed from ladder operators for the considered orthogonal polynomials proving the quantum system to be superintegrable

Cognitive and motivational monitoring during enriched sport activities in a sample of children living in Europe. The ESA program

Enriched Sport Activities (ESA) Program is an Evidence-based Practice Exercise Program cofounded by the Erasmus + Programme of the European Union (Key action: Sport-579661-EPP-1-2016-2-IT-SPO-SCP). It aims to enhance social inclusion, equal opportunities and psycho-physical wellbeing in children with typical development and special needs. This aim will be pursued through two ways: (1) Children and preadolescents’ participation in Enriched Sport Activities (ESA) Program; (2) Parents’ involvement and education on cognitive, motivational and social benefits of Physical Activities (PA) in their children. Recent research showed that high-level cognitive processes, such as inhibition, shifting, working memory and planning, can be improved by aerobic exercise programs following both single bouts of exercise and longer trainings from moderate to vigorous intensity [1]. Nevertheless, in the developmental age, structured sport activities, such as martial arts, basketball, soccer, rowing and dancing, act by delivering both physical and psychological benefits. The former involve physical fitness such as cardiorespiratory fitness, muscular strength, muscular endurance, flexibility and motor skills such as coordination, whilst the latter concern enjoyment, self-confidence and self-esteem, a sense of belonging and social support [2–4]. The effectiveness of PMA (Programma Motorio Arricchito), a structured motor program on coordination and executive functioning in kindergarten children, has been demonstrated [5]

Neutralino relic density in a Universe with a non-vanishing cosmological constant

We discuss the relic density of the lightest of the supersymmetric particles in view of new cosmological data, which favour the concept of an accelerating Universe with a non-vanishing cosmological constant. Recent astrophysical observations provide us with very precise values of the relevant cosmological parameters. Certain of these parameters have direct implications on particle physics, e.g., the value of matter density, which in conjunction with electroweak precision data put severe constraints on the supersymmetry breaking scale. In the context of the Constrained Minimal Supersymmetric Standard Model (CMSSM) such limits read as: M_{1/2} \simeq 300 \GeV - 340 \GeV, m_0 \simeq 80 \GeV - 130 \GeV. Within the context of the CMSSM a way to avoid these constraints is either to go to the large $\tan \beta$ and $\mu > 0$ region, or make ${\tilde \tau}_R$, the next to lightest supersymmetric particle (LSP), be almost degenerate in mass with LSP.Comment: REVTeX, 50 pages, 35 eps figures; Minor changes, references and a figure added; Better quality figures can be obtained upon request from [email protected]

Subcellular heterogeneity of ryanodine receptor properties in ventricular myocytes with low T-tubule density

Rationale: In ventricular myocytes of large mammals, not all ryanodine receptor (RyR) clusters are associated with T-tubules (TTs); this fraction increases with cellular remodeling after myocardial infarction (MI). Objective: To characterize RyR functional properties in relation to TT proximity, at baseline and after MI. Methods: Myocytes were isolated from left ventricle of healthy pigs (CTRL) or from the area adjacent to a myocardial infarction (MI). Ca2+ transients were measured under whole-cell voltage clamp during confocal linescan imaging (fluo-3) and segmented according to proximity of TTs (sites of early Ca2+ release, F>F50 within 20 ms) or their absence (delayed areas). Spontaneous Ca2+ release events during diastole, Ca2+ sparks, reflecting RyR activity and properties, were subsequently assigned to either category. Results: In CTRL, spark frequency was higher in proximity of TTs, but spark duration was significantly shorter. Block of Na+/Ca2+ exchanger (NCX) prolonged spark duration selectively near TTs, while block of Ca2+ influx via Ca2+ channels did not affect sparks properties. In MI, total spark mass was increased in line with higher SR Ca2+ content. Extremely long sparks (>47.6 ms) occurred more frequently. The fraction of near-TT sparks was reduced; frequency increased mainly in delayed sites. Increased duration was seen in near-TT sparks only; Ca2+ removal by NCX at the membrane was significantly lower in MI. Conclusion: TT proximity modulates RyR cluster properties resulting in intracellular heterogeneity of diastolic spark activity. Remodeling in the area adjacent to MI differentially affects these RyR subpopulations. Reduction of the number of sparks near TTs and reduced local NCX removal limit cellular Ca2+ loss and raise SR Ca2+ content, but may promote Ca2+ waves

Endothelial Progenitor Cells as a Potential Biomarker in Interstitial Lung Disease Associated with Rheumatoid Arthritis

Interstitial lung disease (ILD) increases morbidity and mortality in patients with rheumatoid arthritis (RA). Although the pathogenesis of ILD associated with RA (RA-ILD(+)) remains poorly defined, vascular tissue is crucial in lung physiology. In this context, endothelial progenitor cells (EPC) are involved in endothelial tissue repair. However, little is known about their implication in RA-ILD(+). Accordingly, we aimed to investigate the potential role of EPC related to endothelial damage in RA-ILD(+). EPC quantification in peripheral blood from 80 individuals (20 RA-ILD(+) patients, 25 RA-ILD(-) patients, 21 idiopathic pulmonary fibrosis (IPF) patients, and 14 healthy controls) was performed by flow cytometry. EPC were considered as CD34(+), CD45(low), CD309(+) and CD133(+). A significant increase in EPC frequency in RA-ILD(+) patients, as well as in RA-ILD(-) and IPF patients, was found when compared with controls (p < 0.001, p = 0.02 and p < 0.001, respectively). RA-ILD(+) patients exhibited a higher EPC frequency than the RA-ILD(-) ones (p = 0.003), but lower than IPF patients (p < 0.001). Our results suggest that EPC increase may represent a reparative compensatory mechanism in patients with RA-ILD(+). The degree of EPC frequency may help to identify the presence of ILD in RA patients and to discriminate RA-ILD(+) from IPF