Cyclooxygenase 2: understanding the pathophysiological role through genetically altered mouse models

El pdf del artículo es la versión post-print.Cyclooxygenase (COX) -1 and –2 catalyze the first step in the biosynthesis of prostanoids. COX-1 is constitutively expressed in many tissues and seems to be involved in the house keeping function of prostanoids. COX-2, the inducible isoform, accounts for the elevated production of prostaglandins in response to various inflammatory stimuli, hormones and growth factors. COX-2 expression has been also associated with cell growth regulation, tissue remodelling and carcinogenesis. More of these characteristics have been elucidate through using COX selective inhibitors. Recent advances in transgenic and gene-targeting approaches allow a sophisticated manipulation of the mouse genome by gene addition, gene deletion or gene modifications. The development of COX-2 genetically altered mice has provided models to elucidate the physiological and pathophysiological roles of this enzyme.This work was supported by grants from Instituto de Salud Carlos III (Red de Centros C03/01), Generalitat Valenciana (GRUPOS03/072), Ministerio de Educación y Ciencia (SAF2004-00957) and Comunidad de Madrid (CAM2004-GR/SAL/0388).Peer reviewe

Upgrade of the ALICE Time Projection Chamber

The Time Projection Chamber (TPC) of the ALICE experiment is being upgraded with new readout chambers based on Gas Electron Multiplier (GEM) technology during the second long shutdown of the CERN Large Hadron Collider. The upgraded detector will operate continuously and trigger-less without the use of a gating grid. It will thus be able to read out all minimum bias Pb–Pb events that the LHC will deliver at the anticipated peak interaction rate of 50 kHz for the high-luminosity heavy-ion era. After several years of R&D;, the last two years were devoted to the production of 80 quadruple GEM chambers in several institutes and countries utilizing 640 GEM foils. The chambers underwent a detailed quality control procedure in order to ensure the highest standard as required for the installation in the ALICE TPC. To guarantee optimal operational safety, a careful design of the HV configuration, employing so-called cascaded power supplies, was developed. Continuous readout of the TPC data with rates of 3.28 TByte/s into the online data farm will be accomplished by a new TPC front-end scheme, utilizing the newly developed SAMPA readout ASIC and the GBT readout system developed at CERN

Track Reconstruction in a High-Density Environment with ALICE

ALICE is the dedicated heavy-ion experiment at the CERN Large Hadron Collider (LHC). Its main tracking and particle-identification detector is a large volume Time Projection Chamber (TPC). The TPC has been designed to perform well in the high-track density environment created in high-energy heavy-ion collisions. In this proceeding, we describe the track reconstruction procedure in ALICE. In particular, we focus on the two main challenges that were faced during the Run 2 data-taking period (2015–2018) of the LHC, which were the baseline fluctuations and the local space charge distortions in the TPC. We present the corresponding solutions in detail and describe the software tools that allowed us to circumvent these challenges.ALICE is the dedicated heavy-ion experiment at the CERN Large Hadron Collider (LHC). Its main tracking and particle-identification detector is a large volume Time Projection Chamber (TPC). The TPC has been designed to perform well in the high-track density environment created in high-energy heavy-ion collisions. In this proceeding, we describe the track reconstruction procedure in ALICE. In particular, we focus on the two main challenges that were faced during the Run 2 data-taking period (2015--2018) of the LHC, which were the baseline fluctuations and the local space charge distortions in the TPC. We present the corresponding solutions in detail and describe the software tools that allowed us to circumvent these challenges

Total serum testosterone and WOMAC pain and function among older men and women with severe knee OA

OBJECTIVES: We investigated if serum total testosterone (T)-level is associated with knee pain and function in men and women with severe knee osteoarthritis (OA). METHODS: We enrolled 272 adults ≥60 years (70.4±4.4 years, 53% women) who underwent unilateral total knee replacement (TKR) due to severe knee OA. Serum T-levels and WOMAC pain and function of the operated and contra-lateral knee were measured at 6-8 weeks after surgery. At the non-operated knee, 56% participants had radiographic knee OA with a Kellgren-Lawrence grade ≥2. Cross-sectional analyses were performed by gender and BMI subgroups using multivariable regression adjusted for age, physical activity and BMI. RESULTS: At the operated knee, higher T-levels were associated with less WOMAC pain in men (B = -0.62; P = 0.046) and women (B = -3.79; P = 0.02), and less WOMAC disability scores in women (B = -3.62; P = 0.02) and obese men (B = -1.99; P = 0.02). At the non-operated knee, T-levels were not associated with WOMAC pain in men or women, but higher T-levels were associated with less disability in women (B = -0.95; P = 0.02). T-levels were inconsistently associated with pain and disability in BMI subgroups among men. Only among obese women, T-levels were inversely associated with radiographic knee OA (OR = 0.10; P = 0.003). CONCLUSIONS: Higher total T-levels were associated with less pain in the operated knee in men and women undergoing TKR and less disability in women. At the non-operated knee, higher T-levels were inconsistently associated with less pain and disability

Identification of key lipids critical for platelet activation by comprehensive analysis of the platelet lipidome

Peng B, Geue S, Coman C, et al. Identification of key lipids critical for platelet activation by comprehensive analysis of the platelet lipidome. Blood. 2018;132(5):e1-e12.Platelet integrity and function critically depend on lipid composition. However, the lipid inventory in platelets was hitherto not quantified. Here, we examined the lipidome of murine platelets using lipid-category tailored protocols on a quantitative lipidomics platform. We could show that the platelet lipidome comprises almost 400 lipid species and covers a concentration range of 7 orders of magnitude. A systematic comparison of the lipidomics network in resting and activated murine platelets, validated in human platelets, revealed that <20% of the platelet lipidome is changed upon activation, involving mainly lipids containing arachidonic acid. Sphingomyelin phosphodiesterase-1 (Smpd1) deficiency resulted in a very specific modulation of the platelet lipidome with an order of magnitude upregulation of lysosphingomyelin (SPC), and subsequent modification of platelet activation and thrombus formation. In conclusion, this first comprehensive quantitative lipidomic analysis of platelets sheds light on novel mechanisms important for platelet function, and has therefore the potential to open novel diagnostic and therapeutic opportunities