Etude calorimétrique de la réactivité du silicate tricalcique. Influence du mode de broyage et de la dimension des particules

International audienceL'étude concertée du CERILH, de l'Ecole des Mines de Saint-Etienne et de Lafarge Coppée a porté sur le silicate tricalcique C3S. Le silicate tricalcique (C3S) est le minéral prépondérant du clinker et peut s'hydrater en système binaire C3S-eau. La phase comportant le C3S, qu'on appelle l'alite, a été choisie pour l'étude et a dû être synthétisée séparément, dans le but (1) d'observer les différences sur la morphologie des grains et leur réactivité physico-chimique (2) de caractériser les différences de réactivité des grains, en surface et en masse, en étudiant leur hydratation et l'acquisition de la résistance mécanique qui en découle (3) de réaliser ce programme en s'affranchissant de l'effet de finesse et de répartition granulométrique. Ces effets font l'objet d'essais complémentaires permettant de mesurer leur importance relative

A Locked Nucleic Acid Antisense Oligonucleotide (LNA) Silences PCSK9 and Enhances LDLR Expression In Vitro and In Vivo

The proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important factor in the etiology of familial hypercholesterolemia (FH) and is also an attractive therapeutic target to reduce low density lipoprotein (LDL) cholesterol. PCSK9 accelerates the degradation of hepatic low density lipoprotein receptor (LDLR) and low levels of hepatic PCSK9 activity are associated with reduced levels of circulating LDL-cholesterol.The present study presents the first evidence for the efficacy of a locked nucleic acid (LNA) antisense oligonucleotide (LNA ASO) that targets both human and mouse PCSK9. We employed human hepatocytes derived cell lines HepG2 and HuH7 and a pancreatic mouse beta-TC3 cell line known to express high endogenous levels of PCSK9. LNA ASO efficiently reduced the mRNA and protein levels of PCSK9 with a concomitant increase in LDLR protein levels after transfection in these cells. In vivo efficacy of LNA ASO was further investigated in mice by tail vein intravenous administration of LNA ASO in saline solution. The level of PCSK9 mRNA was reduced by approximately 60%, an effect lasting more than 16 days. Hepatic LDLR protein levels were significantly up-regulated by 2.5-3 folds for at least 8 days and approximately 2 fold for 16 days. Finally, measurement of liver alanine aminotransferase (ALT) levels revealed that long term LNA ASO treatment (7 weeks) does not cause hepatotoxicity.LNA-mediated PCSK9 mRNA inhibition displayed potent reduction of PCSK9 in cell lines and mouse liver. Our data clearly revealed the efficacy and safety of LNA ASO in reducing PCSK9 levels, an approach that is now ready for testing in primates. The major significance and take home message of this work is the development of a novel and promising approach for human therapeutic intervention of the PCSK9 pathway and hence for reducing some of the cardiovascular risk factors associated with the metabolic syndrome

The ocean sampling day consortium.

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world's oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

Variants in the GPR146 Gene Are Associated With a Favorable Cardiometabolic Risk Profile

BACKGROUND: In mice, GPR146 (G-protein-coupled receptor 146) deficiency reduces plasma lipids and protects against atherosclerosis. Whether these findings translate to humans is unknown. METHODS: Common and rare genetic variants in the GPR146 gene locus were used as research instruments in the UK-Biobank. The Lifelines, and The Copenhagen-City Heart Study, and a cohort of individuals with familial hypobetalipoproteinemia were used to find and study rare GPR146 variants. RESULTS: In the UK-Biobank, carriers of the common rs2362529-C allele present with lower low-density lipoprotein cholesterol, apo (apolipoprotein) B, high-density lipoprotein cholesterol, apoAI, CRP (C-reactive protein), and plasma liver enzymes compared with noncarriers. Carriers of the common rs1997243-G allele, associated with higher GPR146 expression, present with the exact opposite phenotype. The associations with plasma lipids of the above alleles are allele dose-dependent. Heterozygote carriers of a rare coding variant (p.Pro62Leu; n=2615), predicted to be damaging, show a stronger reductions in the above parameters compared with carriers of the common rs2362529-C allele. The p.Pro62Leu variant is furthermore shown to segregate with low low-density lipoprotein cholesterol in a family with familial hypobetalipoproteinemia. Compared with controls, carriers of the common rs2362529-C allele show a marginally reduced risk of coronary artery disease (P=0.03) concomitant with a small effect size on low-density lipoprotein cholesterol (average decrease of 2.24 mg/dL in homozygotes) of this variant. Finally, mendelian randomization analyses suggest a causal relationship between GPR146 gene expression and plasma lipid and liver enzyme levels. CONCLUSIONS: This study shows that carriers of new genetic GPR146 variants have a beneficial cardiometabolic risk profile, but it remains to be shown whether genetic or pharmaceutical inhibition of GPR146 protects against atherosclerosis in humans

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

Nuclear receptor profile in calvarial bone cells undergoing osteogenic versus adipogenic differentiation

Nuclear receptors (NRs) are key regulators of cell function and differentiation. We examined NR expression during osteogenic versus adipogenic differentiation of primary mouse calvarial osteoblasts (MOBs). MOBs were cultured for 21 days in osteogenic or adipogenic differentiation media. von Kossa and Oil Red O staining, and qRT-PCR of marker genes and 49 NRs were performed. PCR amplicons were subcloned to establish correct sequences and absolute standard curves. Forty-three NRs were detected at days 0–21. Uncentered average linkage hierarchical clustering identified four expression clusters: NRs (1) upregulated during osteogenic, but not adipogenic, differentiation, (2) upregulated in both conditions, with greater upregulation during adipogenic differentiation, (3) upregulated equally in both conditions, (4) downregulated during adipogenic, but not osteogenic, differentiation. One-way ANOVA with contrast revealed 20 NRs upregulated during osteogenic differentiation and 12 NRs upregulated during adipogenic differentiation. Two-way ANOVA demonstrated that 18 NRs were higher in osteogenic media, while 9 NRs were higher in adipogenic media. The time effect revealed 16 upregulated NRs. The interaction of condition with time revealed 6 NRs with higher expression rate during adipogenic differentiation and 3 NRs with higher expression rate during osteogenic differentiation. Relative NR abundance at days 0 and 21 were ranked. Basal ranking changed at least 5 positions for 13 NRs in osteogenic media and 9 NRs in adipogenic media. Osteogenic and adipogenic differentiation significantly altered NR expression in MOBs. These differences offer a fingerprint of cellular commitment and may provide clues to the underlying mechanisms of osteogenic versus adipogenic differentiation. J. Cell. Biochem. 105: 1316–1326, 2008. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61336/1/21931_ftp.pd

Epidemiology and outcome predictors in 450 patients with hanging-induced cardiac arrest: a retrospective study

BackgroundCardiac arrest is the most life-threatening complication of attempted suicide by hanging. However, data are scarce on its characteristics and outcome predictors.MethodsThis retrospective observational multicentre study in 31 hospitals included consecutive adults admitted after cardiac arrest induced by suicidal hanging. Factors associated with in-hospital mortality were identified by multivariate logistic regression with multiple imputations for missing data and adjusted to the temporal trends over the study period.ResultsOf 450 patients (350 men, median age, 43 [34–52] years), 305 (68%) had a psychiatric history, and 31 (6.9%) attempted hanging while hospitalized. The median time from unhanging to cardiopulmonary resuscitation was 0 [0–5] min, and the median time to return of spontaneous circulation (ROSC) was 20 [10–30] min. Seventy-nine (18%) patients survived to hospital discharge. Three variables were independently associated with higher in-hospital mortality: time from collapse or unhanging to ROSC>20 min (odds ratio [OR], 4.71; 95% confidence intervals [95%CIs], 2.02–10.96; p = 0.0004); glycaemia >1.4 g/L at admission (OR, 6.38; 95%CI, 2.60–15.66; p < 0.0001); and lactate >3.5 mmol/L at admission (OR, 6.08; 95%CI, 1.71–21.06; p = 0.005). A Glasgow Coma Scale (GCS) score of >5 at admission was associated with lower in-hospital mortality (OR, 0.009; 95%CI, 0.02–0.37; p = 0.0009).ConclusionIn patients with hanging-induced cardiac arrest, time from collapse or unhanging to return of spontaneous circulation, glycaemia, arterial lactate, and coma depth at admission were independently associated with survival to hospital discharge. Knowledge of these risk factors may help guide treatment decisions in these patients at high risk of hospital mortality