L’Évolution biologique, un superbe bricolage

Quand François Jacob (prix Nobel de médecine 1965) s’inspire pour la biologie de la notion de « bricolage » développée par Claude Lévi-Strauss en anthropologie dans La Pensée sauvage (1962) … ou la rencontre de deux géants. Dans ce texte mêlant épistémologie et théorie de l’évolution, F. Jacob émet l’idée que la connaissance scientifique est faite de milliers d’observations parcellaires qui convergent pour être à l’origine d’une découverte ou d’une innovation, tout comme le fait l’évolution biologique pour aboutir à un nouveau trait ou à une nouvelle espèce vivante. Il donne à cet égard l’exemple tout à fait éclairant de la formation progressive (et bricolée ?) du globe oculaire chez les animaux

Le désastre écologique selon… Saint François d’Assise

Ce texte de 1967 du médiéviste américain, volontiers provocateur, rend la civilisation chrétienne responsable du désastre écologique actuel (déjà perceptible… il y a 50 ans). Il nous paraît important de le présenter ici, sous la plume elle aussi acérée du biologiste B. Swynghedauw

Genomics in cardiac metabolism

Cell biology is in transition from reductionism to a more integrated science. Large-scale analysis of genome structure, gene expression, and metabolites are new technologies available for studying cardiac metabolism in diseases known to modify cardiac function. These technologies have several limitations and this review aims both to assess and take a critical look at some important results obtained in genomics restricted to molecular genetics, transcriptomics and metabolomics of cardiac metabolism in pathophysiological processes known to alter myocardial function. Therefore, our goal was to delineate new signalling pathways and new areas of research from the vast amount of data already published on genomics as applied to cardiac metabolism in diseases such as coronary heart disease, heart failure, and ischaemic reperfusio

Statistical Modelling of Cardiovascular Data. An Introduction to Linear Mixed Models

Most of statistical approaches in cardiovascular research were based on variance analysis (ANOVA). However, most of the time, the assumption that data are independent is violated since several measures are performed on the same subject (repeated measures). In addition, the presence of intra- and inter-observers variability can potentially obscure significant differences. The linear mixed model (LMM) is an extended multivariate linear regression method of analysis that accounts for both fixed and random effects. LMM allows for addressing incomplete design cases. In this paper, LMM was applied to two sets of cardiovascular research data and compared to ANOVA. The first example is an analysis of heart rate in mice after atropine and propranolol injections. LMM shows an important mouse random effects that depends on pharmacological treatment and provides with accurate estimates for each significant experimental factors. When randomly suppressing observations from the data sets (20-30%) the time factor of Anova model becomes non significant while LMM still remains significant. The second example is the analysis of isolated coronary-perfused pressure of transgenic mice hearts. LMM evidenced a significant transgenic effect in both male and female animals, while, with ANOVA, the transgenic effects was limited to male mice only. In both cases, as compared to ANOVA, the LMM separately accounts for fixed and random effects, allowing thus for studying more adequately incomplete designs on repeated measures

Changes in Gene Expression During the Formation of Bioengineered Heart Muscle

A three-dimensional bioengineered heart muscle (BEHM) construct model had been previously developed, exhibiting contractile forces up to 800 µN. The interest of this study was to determine gene expression levels of biologic markers involved in calcium-handling between BEHM, cell monolayer, and neonatal heart. Cardiac cells were isolated from one litter of F344 rats and organized into groups ( n  = 5): 4-, 7-, 10-day BEHM and cell monolayer; BEHM was evaluated for cell viability and contractility. Groups were then analyzed for mRNA expression of calcium-handling proteins: myosin heavy chain (MHC) α and β, Sarcoplasmic reticulum Ca++ ATPase (SERCA) 2, phospholamban (PBL), and ryanodine receptor. BEHM exhibited electrically stimulated active force (208 ± 12 µN day 4, 361 ± 22 µN day 7, and 344 ± 29 µN day 10) and no decrease in cell number. Real-time polymerase chain reaction (PCR) showed an increase in gene expression of all calcium-handling proteins in BEHM at 7 and 10 days compared with monolayers, for example, comparing BEHM to monolayer (7 and 10 days, respectively), MHC-α: 2600-fold increase and a 100-fold increase; MHC-β: 70-fold increase at 10 days; ryanodine receptor: 74-fold increase at 10 days; SERCA: 19-fold increase and sixfold increase; PBL: 158-fold increase and 24-fold increase. It was concluded that a three-dimensional environment is a better culturing condition of cardiac cells than a monolayer. Also, BEHM constructs demonstrated a high similarity to a native myocardium, and is, thus, a good starting foundation for engineered heart muscle. Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72077/1/j.1525-1594.2008.00669.x.pd

Late Gadolinium Enhancement Amount as an Independent Risk Factor for the Incidence of Adverse Cardiovascular Events in Patients with Stage C or D Heart Failure

Background: Myocardial fibrosis (MF) is a risk factor for poor prognosis in dilated cardiomyopathy (DCM). Late gadolinium enhancement (LGE) of the myocardium on cardiac magnetic resonance (CMR) represents MF. We examined whether the LGE amount increases the incidence of adverse cardiovascular events in patients with stage C or D heart failure (HF). Methods: Eighty-four consecutive patients with stage C or D HF, either ischemic or non-ischemic, were enrolled. Comprehensive clinical and CMR evaluations were performed. All patients were followed up for a composite endpoint of cardiovascular death, heart transplantation, and cardiac resynchronization therapy with defibrillator (CRT-D).Results: LGE was present in 79.7% of the end-stage HF patients. LGE distribution patterns were mid-wall, epi-myocardial, endo-myocardial, and the morphological patterns were patchy, transmural, and diffuse. During the average follow-up of 544 days, 13 (15.5%) patients had endpoint events: 7 patients cardiac death, 2 patients heart transplantation, and 4 patients underwent CRT-D implantation. On univariate analysis, LGE quantification on cardiac magnetic resonance, blood urine nitrogen, QRS duration on electrocardiogram, left ventricular end-diastolic diameter (LVEDD), and left ventricular end-diastolic volume (LVEDV) on CMR had the strongest associations with the composite endpoint events. However, on multivariate analysis for both Model I (after adjusting for age, sex, and body mass index) and Model II (after adjusting for age, sex, BMI, renal function, QRS duration, and atrial fibrillation on electrocardiogram, the etiology of HF, LVEF, CMR-LVEDD, and CMR-LVEDV), LGE amount was a significant risk factor for composite endpoint events (Model I 6SD HR 1.037, 95%CI 1.005–1.071, p = 0.022; Model II 6SD HR 1.045, 95%CI 1.001–1.084, p = 0.022). Conclusion: LGE amount from high-scale threshold on CMR increased the incidence of adverse cardiovascular events for patients in either stage C or D HF

Glucocorticoid receptor alters isovolumetric contraction and restrains cardiac fibrosis

Corticosteroids directly affect the heart and vasculature and are implicated in the pathogenesis of heart failure. Attention is focussed upon the role of the mineralocorticoid receptor (MR) in mediating pro-fibrotic and other adverse effects of corticosteroids upon the heart. In contrast, the role of the glucocorticoid receptor (GR) in the heart and vasculature is less well understood. We addressed this in mice with cardiomyocyte and vascular smooth muscle deletion of GR (SMGRKO mice). Survival of SMGRKO mice to weaning was reduced compared with that of littermate controls. Doppler measurements of blood flow across the mitral valve showed an elongated isovolumetric contraction time in surviving adult SMGRKO mice, indicating impairment of the initial left ventricular contractile phase. Although heart weight was elevated in both genders, only male SMGRKO mice showed evidence of pathological cardiomyocyte hypertrophy, associated with increased myosin heavy chain-β expression. Left ventricular fibrosis, evident in both genders, was associated with elevated levels of mRNA encoding MR as well as proteins involved in cardiac remodelling and fibrosis. However, MR antagonism with spironolactone from birth only modestly attenuated the increase in pro-fibrotic gene expression in SMGRKO mice, suggesting that elevated MR signalling is not the primary driver of cardiac fibrosis in SMGRKO mice, and cardiac fibrosis can be dissociated from MR activation. Thus, GR contributes to systolic function and restrains normal cardiac growth, the latter through gender-specific mechanisms. Our findings suggest the GR:MR balance is critical in corticosteroid signalling in specific cardiac cell types

Search for the glueball candidates f0(1500) and fJ(1710) in gamma gamma collisions

Data taken with the ALEPH detector at LEP1 have been used to search for gamma gamma production of the glueball candidates f0(1500) and fJ(1710) via their decay to pi+pi-. No signal is observed and upper limits to the product of gamma gamma width and pi+pi- branching ratio of the f0(1500) and the fJ(1710) have been measured to be Gamma_(gamma gamma -> f0(1500)). BR(f0(1500)->pi+pi-) < 0.31 keV and Gamma_(gamma gamma -> fJ(1710)). BR(fJ(1710)->pi+pi-) < 0.55 keV at 95% confidence level.Comment: 10 pages, 3 figure