Role of NINJA in root jasmonate signaling.

Wound responses in plants have to be coordinated between organs so that locally reduced growth in a wounded tissue is balanced by appropriate growth elsewhere in the body. We used a JASMONATE ZIM DOMAIN 10 (JAZ10) reporter to screen for mutants affected in the organ-specific activation of jasmonate (JA) signaling in Arabidopsis thaliana seedlings. Wounding one cotyledon activated the reporter in both aerial and root tissues, and this was either disrupted or restricted to certain organs in mutant alleles of core components of the JA pathway including COI1, OPR3, and JAR1. In contrast, three other mutants showed constitutive activation of the reporter in the roots and hypocotyls of unwounded seedlings. All three lines harbored mutations in Novel Interactor of JAZ (NINJA), which encodes part of a repressor complex that negatively regulates JA signaling. These ninja mutants displayed shorter roots mimicking JA-mediated growth inhibition, and this was due to reduced cell elongation. Remarkably, this phenotype and the constitutive JAZ10 expression were still observed in backgrounds lacking the ability to synthesize JA or the key transcriptional activator MYC2. Therefore, JA-like responses can be recapitulated in specific tissues without changing a plant's ability to make or perceive JA, and MYC2 either has no role or is not the only derepressed transcription factor in ninja mutants. Our results show that the role of NINJA in the root is to repress JA signaling and allow normal cell elongation. Furthermore, the regulation of the JA pathway differs between roots and aerial tissues at all levels, from JA biosynthesis to transcriptional activation.

Physiopathologie de l'hypertrophie ventriculaire gauche. [Physiopathology of left ventricular hypertrophy]

Left ventricular hypertrophy (LVH) is an early complication of hypertension. To a certain degree, this process counteracts the parietal stress induced by high blood pressure. Genetic factors, obesity, high salt diet and different growth factors, notably angiotensin II and noradrenaline, can also predispose to hypertrophic cardiomyopathy. Left ventricular mass is increased on echocardiography in about 20% of hypertensive subjects. LVH is initially associated with a change in myocardial diastolic function and later with abnormal systolic function. It is a major risk factor, a cause of cardiac failure, reduction in coronary reserve and of ventricular arrhythmias. Treatment of hypertension is associated with regression of LVH and preservation or improvement in myocardial diastolic and systolic functions. The decrease in left ventricular mass could reduce the incidence of cardiovascular complications in hypertension.

Fat poetry: a kingdom for PPAR gamma.

Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. In addition to managing the most important energy reserve of the body, it secretes a multitude of soluble proteins called adipokines, which have beneficial or, alternatively, deleterious effects on the homeostasis of the whole body. The expression of these adipokines is an integrated response to various signals received from many organs, which depends heavily on the integrity and physiological status of the adipose tissue. One of the main regulators of gene expression in fat is the transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma), which is a fatty acid- and eicosanoid-dependent nuclear receptor that plays key roles in the development and maintenance of the adipose tissue. Furthermore, synthetic PPARgamma agonists are therapeutic agents used in the treatment of type 2 diabetes.This review discusses recent knowledge on the link between fat physiology and metabolic diseases, and the roles of PPARgamma in this interplay via the regulation of lipid and glucose metabolism. Finally, we assess the putative benefits of targeting this nuclear receptor with still-to-be-identified highly selective PPARgamma modulators.

Ceftriaxone--bilirubin-albumin interactions in the neonate: an in vivo study.

The in vivo bilirubin-albumin binding interaction of ceftriaxone (CRO) was investigated in 14 non-jaundiced newborns, aged 33-42 weeks of gestation, during the first few days of life after they had reached stable clinical condition. CRO (50 mg/kg) was infused intravenously over 30 min. The competitive binding effect of CRO on the bilirubin-albumin complex was estimated by determining the reserve albumin concentration (RAC) at baseline, at the end of CRO infusion, and at 15 and 60 min thereafter. Immediately after the end of drug administration, RAC decreased from 91.9 (+/- 25.1) mumol/l to 38.6 (+/- 10.1) mumol/l (P = 0.0001). At the same time the plasma bilirubin toxicity index (PBTI) increased from 0.64 (+/- 0.40) before drug infusion to 0.96 (+/- 0.44) thereafter (P = 0.0001). The highest displacement factor (DF) was calculated to be 2.8 (+/- 0.6) at the end of drug infusion. Average total serum bilirubin concentrations decreased from a baseline value of 59.6 (+/- 27.0) mumol/l to 55.2 (+/- 27.1) mumol/l (P = 0.026). Sixty minutes after the end of CRO infusion, RAC was 58.3 (+/- 21.7) mumol/l, PBTI regained baseline, but DF was still 1.9 (+/- 0.2). No adverse events were recorded. Our results demonstrate significant competitive interaction of CRO with bilirubin-albumin binding in vivo. Thus, ceftriaxone should not be given to the neonate at risk of developing bilirubin encephalopathy.

Intracranial hypertension: what additional information can be derived from ICP waveform after head injury?

OBJECTIVE: Although intracranial hypertension is one of the important prognostic factors after head injury, increased intracranial pressure (ICP) may also be observed in patients with favourable outcome. We have studied whether the value of ICP monitoring can be augmented by indices describing cerebrovascular pressure-reactivity and pressure-volume compensatory reserve derived from ICP and arterial blood pressure (ABP) waveforms. METHOD: 96 patients with intracranial hypertension were studied retrospectively: 57 with fatal outcome and 39 with favourable outcome. ABP and ICP waveforms were recorded. Indices of cerebrovascular reactivity (PRx) and cerebrospinal compensatory reserve (RAP) were calculated as moving correlation coefficients between slow waves of ABP and ICP, and between slow waves of ICP pulse amplitude and mean ICP, respectively. The magnitude of 'slow waves' was derived using ICP low-pass spectral filtration. RESULTS: The most significant difference was found in the magnitude of slow waves that was persistently higher in patients with a favourable outcome (p<0.00004). In patients who died ICP was significantly higher (p<0.0001) and cerebrovascular pressure-reactivity (described by PRx) was compromised (p<0.024). In the same patients, pressure-volume compensatory reserve showed a gradual deterioration over time with a sudden drop of RAP when ICP started to rise, suggesting an overlapping disruption of the vasomotor response. CONCLUSION: Indices derived from ICP waveform analysis can be helpful for the interpretation of progressive intracranial hypertension in patients after brain trauma.

Prognostic value of fractional flow reserve: linking physiologic severity to clinical outcomes.

BACKGROUND: Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear. OBJECTIVES: The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization. METHODS: Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold. RESULTS: A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief. CONCLUSIONS: FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.

Prise en charge des endométriomes et de l'endométriose recto-vaginate et vésicate [Management of endometrioma, recto-vaginal and bladder endometriosis].

Endometriosis is a frequent, benign, chronic disease associated with pain and/or infertility. Classically the lesions are found on the pelvic peritoneum, ovary (endometrioma), rectovaginal septum and bladder. Management of endometrioma has evolved over the last few years to individualised treatment. Indeed endometrioma cystectomy can decrease pain and the risk of recurrence but is also associated with a decrease in ovarian reserve. A multi-disciplinary team should manage recto-vaginal or bladder endometriosis. Surgical resection of these lesions must be as complete as possible and can be complex.

Geomorphological heritage, conservation and promotion in high-alpine protected areas

In recent decades, recognition of both cultural and natural heritage has grown in the Alps. This tendency illustrates a collective identity building (local, national, alpine), but it also highlights, in the current context of global change, a renewed reflection of man's relationship with the environment. Thus, a fundamental and scientific intrinsic value (as a part of wilderness) tends to be recognized in the natural heritage as a whole. However, geoheritage (and geodiversity) is still often perceived as a secondary natural component, compared with bioheritage (and biodiversity). In this context, we study the geomorphological heritage (landforms and the processes that shape them) of Les Contamines-Montjoie Natural Reserve. Indeed, despite the high geomorphological richness (especially glacial) of the reserve, which covers more than 4000 ha of the Mont-Blanc Massif, local recognition of this heritage is still limited. In order to recognize and protect it, and starting with a scientific study, this research identifies the main local richness and assesses the geotourist and educational potentials. Finally, several tools to educate and promote geoheritage (educational paths and website) are proposed.

Local transient myocardial liposomal gene transfer of inducible nitric oxide synthase does not aggravate myocardial function and fibrosis and leads to moderate neovascularization in chronic myocardial ischemia in pigs.

Microcirculation (2010) 17, 69-78. doi: 10.1111/j.1549-8719.2010.00002.x Abstract Background: This study was designed to explore the effect of transient inducible nitric oxide synthase (iNOS) overexpression via cationic liposome-mediated gene transfer on cardiac function, fibrosis, and microvascular perfusion in a porcine model of chronic ischemia. Methods and Results: Chronic myocardial ischemia was induced using a minimally invasive model in 23 landrace pigs. Upon demonstration of heart failure, 10 animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection and 13 animals received a sham procedure to serve as control. The efficacy of this iNOS-gene-transfer was demonstrated for up to 7 days by reverse transcriptase-polymerase chain reaction in preliminary studies. Four weeks after iNOS transfer, magnetic resonance imaging showed no effect of iNOS overexpression on cardiac contractility at rest and during dobutamine stress (resting ejection fraction: control 27%, iNOS 26%; P = ns). Late enhancement, infarct size, and the amount of fibrosis were similar between groups. Although perfusion and perfusion reserve in response to adenosine and dobutamine were not significantly modified by iNOS-transfer, both vessel number and diameter were significantly increased in the ischemic area in the iNOS-treated group versus control (point score: control 15.3, iNOS 34.7; P < 0.05). Conclusions: Our findings demonstrate that transient iNOS overexpression does not aggravate cardiac dysfunction or postischemic fibrosis, while potentially contributing to neovascularization in the chronically ischemic heart.

Added prognostic value of myocardial blood flow quantitation in rubidium-82 positron emission tomography imaging.

AIMS: We studied the respective added value of the quantitative myocardial blood flow (MBF) and the myocardial flow reserve (MFR) as assessed with (82)Rb positron emission tomography (PET)/CT in predicting major adverse cardiovascular events (MACEs) in patients with suspected myocardial ischaemia. METHODS AND RESULTS: Myocardial perfusion images were analysed semi-quantitatively (SDS, summed difference score) and quantitatively (MBF, MFR) in 351 patients. Follow-up was completed in 335 patients and annualized MACE (cardiac death, myocardial infarction, revascularization, or hospitalization for congestive heart failure or de novo stable angor) rates were analysed with the Kaplan-Meier method in 318 patients after excluding 17 patients with early revascularizations (<60 days). Independent predictors of MACEs were identified by multivariate analysis. During a median follow-up of 624 days (inter-quartile range 540-697), 35 MACEs occurred. An annualized MACE rate was higher in patients with ischaemia (SDS >2) (n = 105) than those without [14% (95% CI = 9.1-22%) vs. 4.5% (2.7-7.4%), P < 0.0001]. The lowest MFR tertile group (MFR <1.8) had the highest MACE rate [16% (11-25%) vs. 2.9% (1.2-7.0%) and 4.3% (2.1-9.0%), P < 0.0001]. Similarly, the lowest stress MBF tertile group (MBF <1.8 mL/min/g) had the highest MACE rate [14% (9.2-22%) vs. 7.3% (4.2-13%) and 1.8% (0.6-5.5%), P = 0.0005]. Quantitation with stress MBF or MFR had a significant independent prognostic power in addition to semi-quantitative findings. The largest added value was conferred by combining stress MBF to SDS. This holds true even for patients without ischaemia. CONCLUSION: Perfusion findings in (82)Rb PET/CT are strong MACE outcome predictors. MBF quantification has an added value allowing further risk stratification in patients with normal and abnormal perfusion images.

Impact of brain aging and neurodegeneration on cognition: evidence from MRI.

PURPOSE OF REVIEW: We present an overview of recent concepts in mechanisms underlying cognitive decline associated with brain aging and neurodegeneration from the perspective of MRI. RECENT FINDINGS: Recent findings challenge the established link between neuroimaging biomarkers of neurodegeneration and age-related or disease-related cognitive decline. Amyloid burden, white matter hyperintensities and local patterns of brain atrophy seem to have differential impact on cognition, particularly on episodic and working memory - the most vulnerable domains in 'normal aging' and Alzheimer's disease. Studies suggesting that imaging biomarkers of neurodegeneration are independent of amyloid-β give rise to new hypothesis regarding the pathological cascade in Alzheimer's disease. Findings in patients with autosomal-dominant Alzheimer's disease confirm the notion of differential temporal trajectory of amyloid deposition and brain atrophy to add another layer of complexity on the basic mechanisms of cognitive aging and neurodegeneration. Finally, the concept of cognitive reserve in 'supernormal aging' is questioned by evidence for the preservation of neurochemical, structural and functional brain integrity in old age rather than recruitment of 'reserves' for maintaining cognitive abilities. SUMMARY: Recent advances in clinical neuroscience, brain imaging and genetics challenge pathophysiological hypothesis of neurodegeneration and cognitive aging dominating the field in the last decade and call for reconsidering the choice of therapeutic window for early intervention.

Genetic removal of tri-unsaturated fatty acids suppresses developmental and molecular phenotypes of an Arabidopsis tocopherol-deficient mutant. Whole-body mapping of malondialdehyde pools in a complex eukaryote.

Malondialdehyde (MDA) is a small, ubiquitous, and potentially toxic aldehyde that is produced in vivo by lipid oxidation and that is able to affect gene expression. Tocopherol deficiency in the vitamin E2 mutant vte2-1 of Arabidopsis thaliana leads to massive lipid oxidation and MDA accumulation shortly after germination. MDA accumulation correlates with a strong visual phenotype (growth reduction, cotyledon bleaching) and aberrant GST1 (glutathione S-transferase 1) expression. We suppressed MDA accumulation in the vte2-1 background by genetically removing tri-unsaturated fatty acids. The resulting quadruple mutant, fad3-2 fad7-2 fad8 vte2-1, did not display the visual phenotype or the aberrant GST1 expression observed in vte2-1. Moreover, cotyledon bleaching in vte2-1 was chemically phenocopied by treatment of wild-type plants with MDA. These data suggest that products of tri-unsaturated fatty acid oxidation underlie the vte2-1 seedling phenotype, including cellular toxicity and gene regulation properties. Generation of the quadruple mutant facilitated the development of an in situ fluorescence assay based on the formation of adducts of MDA with 2-thiobarbituric acid at 37 degrees C. Specificity was verified by measuring pentafluorophenylhydrazine derivatives of MDA and by liquid chromatography analysis of MDA-2-thiobarbituric acid adducts. Potentially applicable to other organisms, this method allowed the localization of MDA pools throughout the body of Arabidopsis and revealed an undiscovered pool of the compound unlikely to be derived from trienoic fatty acids in the vicinity of the root tip quiescent center.

On the problematic of reserving and stochastic loss models

Abstract Traditionally, the common reserving methods used by the non-life actuaries are based on the assumption that future claims are going to behave in the same way as they did in the past. There are two main sources of variability in the processus of development of the claims: the variability of the speed with which the claims are settled and the variability between the severity of the claims from different accident years. High changes in these processes will generate distortions in the estimation of the claims reserves. The main objective of this thesis is to provide an indicator which firstly identifies and quantifies these two influences and secondly to determine which model is adequate for a specific situation. Two stochastic models were analysed and the predictive distributions of the future claims were obtained. The main advantage of the stochastic models is that they provide measures of variability of the reserves estimates. The first model (PDM) combines one conjugate family Dirichlet - Multinomial with the Poisson distribution. The second model (NBDM) improves the first one by combining two conjugate families Poisson -Gamma (for distribution of the ultimate amounts) and Dirichlet Multinomial (for distribution of the incremental claims payments). It was found that the second model allows to find the speed variability in the reporting process and development of the claims severity as function of two above mentioned distributions' parameters. These are the shape parameter of the Gamma distribution and the Dirichlet parameter. Depending on the relation between them we can decide on the adequacy of the claims reserve estimation method. The parameters have been estimated by the Methods of Moments and Maximum Likelihood. The results were tested using chosen simulation data and then using real data originating from the three lines of business: Property/Casualty, General Liability, and Accident Insurance. These data include different developments and specificities. The outcome of the thesis shows that when the Dirichlet parameter is greater than the shape parameter of the Gamma, resulting in a model with positive correlation between the past and future claims payments, suggests the Chain-Ladder method as appropriate for the claims reserve estimation. In terms of claims reserves, if the cumulated payments are high the positive correlation will imply high expectations for the future payments resulting in high claims reserves estimates. The negative correlation appears when the Dirichlet parameter is lower than the shape parameter of the Gamma, meaning low expected future payments for the same high observed cumulated payments. This corresponds to the situation when claims are reported rapidly and fewer claims remain expected subsequently. The extreme case appears in the situation when all claims are reported at the same time leading to expectations for the future payments of zero or equal to the aggregated amount of the ultimate paid claims. For this latter case, the Chain-Ladder is not recommended.

Preoperative percutaneous portal vein embolization: evaluation of adverse events in 188 patients.

PURPOSE: To retrospectively assess the frequency of adverse events related to percutaneous preoperative portal vein embolization (PPVE). MATERIALS AND METHODS: Institutional review board did not require its approval or patient informed consent for this study. The adverse events that occurred during PPVE or until planned hepatic surgery was performed or cancelled were retrospectively obtained from clinical, imaging, and laboratory data files in 188 patients (109 male and 79 female patients; mean age, 60 years; range, 16-78 years). Liver resection was planned for metastases (n = 137), hepatocarcinoma (n = 31), cholangiocarcinoma (n = 15), fibrolamellar hepatoma (n = 1), and benign disease (n = 4). PPVE was performed with a single-lumen 5-F catheter and a contralateral approach with n-butyl cyanoacrylate mixed with iodized oil as the main embolic agent. The rate of complications in patients with cirrhosis was compared with that in patients without cirrhosis by using the chi(2) test. RESULTS: Adverse events occurred in 24 (12.8%) of 188 patients, including 12 complications and 12 incidental imaging findings. Complications included thrombosis of the portal vein feeding the future remnant liver (n = 1); migration of emboli in the portal vein feeding the future remnant liver, which necessitated angioplasty (n = 2); hemoperitoneum (n = 1); rupture of a metastasis in the gallbladder (n = 1); transitory hemobilia (n = 1); and transient liver failure (n = 6). Incidental findings were migration of small emboli in nontargeted portal branches (n = 10) and subcapsular hematoma (n = 2). Among the 187 patients in whom PPVE was technically successful, there was a significant difference (P < .001) between the occurrence of liver failure after PPVE in patients with cirrhosis (five of 30) and those without (one of 157). Sixteen liver resections were cancelled due to cancer progression (n = 12), insufficient hypertrophy of the nonembolized liver (n = 3), and complete portal thrombosis (n = 1). CONCLUSION: PPVE is a safe adjuvant technique for hypertrophy of the initially insufficient liver reserve. Post-PPVE transient liver failure is more common in patients with cirrhosis than in those without cirrhosis.

Pericardial fat volume correlates with coronary vasomotion

Purpose: Recent studies showed that pericardial fat was independently correlated with the development of coronary artery disease (CAD). The mechanism remains unclear. We aimed at assessing a possible relationship between pericardial fat volume and endothelium-dependent coronary vasomotion, a surrogate of future cardiovascular events.Methods: Fifty healthy volunteers without known CAD or cardiovascular risk factors (CRF) were enrolled. They all underwent a dynamic Rb- 82 cardiac PET/CT to quantify myocardial blood flow (MBF) at rest, during MBF response to cold pressure test (CPT-MBF) and adenosine stress. Pericardial fat volume (PFV) was measured using a 3D volumetric CT method and common biological CRF (glucose and insulin levels, HOMA-IR, cholesterol, triglyceride, hs-CRP). Relationships between MBF response to CPT, PFV and other CRF were assessed using non-parametric Spearman correlation and multivariate regression analysis of variables with significant correlation on univariate analysis (Stata 11.0).Results: All of the 50 participants had normal MBF response to adenosine (2.7±0.6 mL/min/g; 95%CI: 2.6−2.9) and myocardial flow reserve (2.8±0.8; 95%CI: 2.6−3.0) excluding underlying CAD. Simple regression analysis revealed a significant correlation between absolute CPTMBF and triglyceride level (rho = −0.32, p = 0.024) fasting blood insulin (rho = −0.43, p = 0.0024), HOMA-IR (rho = −0.39, p = 0.007) and PFV (rho = −0.52, p = 0.0001). MBF response to adenosine was only correlated with PFV (rho = −0.32, p = 0.026). On multivariate regression analysis PFV emerged as the only significant predictor of MBF response to CPT (p = 0.002).Conclusion: PFV is significantly correlated with endothelium-dependent coronary vasomotion. High PF burden might negatively influence MBF response to CPT, as well as to adenosine stress, even in persons with normal hyperemic myocardial perfusion imaging, suggesting a link between PF and future cardiovascular events. While outside-to-inside adipokines secretion through the arterial wall has been described, our results might suggest an effect upon NO-dependent and -independent vasodilatation. Further studies are needed to elucidate this mechanism.