Cardiorenal ketone metabolism: a positron emission tomography study in healthy humans

Ketones are alternative energy substrates for the heart and kidney but no studies have investigated their metabolism simultaneously in both organs in humans. The present double tracer positron emission tomography (PET) study evaluated the organ distribution and basal kinetic rates of the radiolabeled ketone, 11C-acetoacetate (11C-AcAc), in the heart and kidney compared to 11C-acetate (11C-Ac), which is a well-validated metabolic radiotracer. Both tracers were highly metabolized by the left ventricle and the renal cortex. In the heart, kinetic rates were similar for both tracers. But in the renal cortex, uptake of 11C-Ac was higher compared to 11C-AcAc, while the reverse was observed for the clearance. Interestingly, infusion of 11C-AcAc led to a significantly delayed release of radioactivity in the renal medulla and pelvis, a phenomenon not observed with 11C-Ac. This suggests an equilibrium of 11C-AcAc with the other ketone, 11C-D-beta-hydroxybutyrate, and a different clearance profile. Overall, this suggests that in the kidney, the absorption and metabolism of 11C-AcAc is different compared to 11C-Ac. This dual tracer PET protocol provides the opportunity to explore the relative importance of ketone metabolism in cardiac and renal diseases, and to improve our mechanistic understanding of new metabolic interventions targeting these two organs

Ecosysème entrepreneurial local et finance participative : enjeux d’une coopération

Many academic works recount the relationship between entrepreneurship, territory and collective dynamics. Similarly, different conceptual territorial innovation models are attached to represent the link between geographic proximity, innovation and competitiveness. In France, many crowdfunding platforms have seen since 2010 to meet the difficulties of financing of innovative projects. These new players challenge existing devices to aid in the creation, development and support of innovative companies in the territories. This work seeks to understand the issues of cooperation brought about by this participatory finance in the constitution of’communities’ digital. How do the territories seek to capitalize these dynamics in a process for capturing these communities around a will of territorialized economic development ? Through an approach focused on the actors in the social economy and solidarity who, historically, organized locally to meet the diversity of the issues of territories, this research aims to answer the following question : how to organize the cooperation by stakeholders in the SSE, via participatory finance, in an entrepreneurial ecosystem ? On the one hand it’s question on how to consider cooperation in funding decisions between different actors of the entrepreneurial ecosystem in a territory, and, on the other hand, imagine how to switch from a virtual community to a community approach by the digital revolution in geographically delimited areas

Extreme current measurements using a fibre optics current sensor

We demonstrate that an optical fibre current sensor can measure current over 500 kA with an accuracy of 0.2%. This level of accuracy has never previously been achieved using a traditional non-optical senso

Pulmonary sequestration: a review of 26 cases

OBJECTIVES: Pulmonary sequestration is a continuum of lung anomalies for which no single embryonic hypothesis is yet available. The aim of this study was to assess the diagnostic tools and treatment for the rare condition, pulmonary sequestration, in an unspecialised centre. METHODS: We performed an analysis of 26 cases of pulmonary sequestration (paediatric and adult) operated at the Centre Hospitalier Universitaire Vaudois between May 1959 and May 1997. A review of the extralobar and intralobar types of sequestrations is discussed. Angiography is compared to other diagnostic tools in this condition, and treatment is discussed. RESULTS: Twenty-six cases of pulmonary sequestrations, a rare congenital pulmonary malformation, were operated on in the defined time period. Seventy-three percent (19) of the cases were intralobar and 27% (seven) extralobar. Extralobar localisation was basal in 71% and situated between the upper and the lower lobe in 29%. In six cases, the diagnosis was made by exploratory thoracotomy. In the other 20 cases, diagnosis was evoked on chest X-ray and confirmed by angiography. Lobectomy (46%) was the most common treatment procedure. Segmental resection was performed in 30% of the cases and bilobectomy in 4%. Post-operative morbidity was low. The most significant complications were pleural empyema, haemothorax and haemopneumoperitoneum in case of extralobar sequestration. There was no evidence of metaplasia or pre-neoplastic changes. CONCLUSIONS: Despite its rarity, some radiological features are sufficiently suggestive of diagnosis of pulmonary sequestration. Investigations are necessary in order to avoid unexpected pathology at the time of operation. Resection of the involved lung leads to excellent results and the long-term outcome is highly favourabl

Sequence-selective DNA recognition and enhanced cellular up-take by peptide–steroid conjugates

Several GCN4 bZIP TF models have previously been designed and synthesized. However, the synthetic routes towards these constructs are typically tedious and difficult. We here describe the substitution of the Leucine zipper domain of the protein by a deoxycholic acid derivative appending the two GCN4 binding region peptides through an optimized double azide–alkyne cycloaddition click reaction. In addition to achieving sequence specific dsDNA binding, we have investigated the potential of these compounds to enter cells. Confocal microscopy and flow cytometry show the beneficial influence of the steroid on cell uptake. This unique synthetic model of the bZIP TF thus combines sequence specific dsDNA binding properties with enhanced cell-uptake. Given the unique properties of deoxycholic acid and the convergent nature of the synthesis, we believe this work represents a key achievement in the field of TF mimicry