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Overexpression and activation of matrix metalloproteinase-13 (MMP-13) within atheroma increases susceptibility to plaque rupture, a major cause of severe cardiovascular complications. In comparison to pan-MMP targeting [18F]BR-351, we evaluated the potential for [18F]FMBP, a selective PET radiotracer for MMP-13, to detect extracellular matrix (ECM) remodeling in vascular plaques possessing markers of inflammation. [18F]FMBP and [18F]BR-351 were initially assessed in vitro by incubation with en face aortae from 8 month-old atherogenic ApoE−/− mice. Ex vivo biodistributions, plasma metabolite analyses, and ex vivo autoradiography were analogously performed 30 min after intravenous radiotracer administration in age-matched C57Bl/6 and ApoE−/− mice under baseline or homologous blocking conditions. En face aortae were subsequently stained with Oil Red O (ORO), sectioned, and subject to immunofluorescence staining for Mac-2 and MMP-13. High-resolution autoradiographic image analysis demonstrated target specificity and regional concordance to lipid-rich lesions. Biodistribution studies revealed hepatobiliary excretion, low accumulation of radioactivity in non-excretory organs, and few differences between strains and conditions in non-target organs. Plasma metabolite analyses uncovered that [18F]FMBP exhibited excellent in vivo stability (≥74% intact) while [18F]BR-351 was extensively metabolized (≤37% intact). Ex vivo autoradiography and histology of en face aortae revealed that [18F]FMBP, relative to [18F]BR-351, exhibited 2.9-fold greater lesion uptake, substantial specific binding (68%), and improved sensitivity to atherosclerotic tissue (2.9-fold vs 2.1-fold). Immunofluorescent staining of aortic en face cross sections demonstrated elevated Mac-2 and MMP-13-positive areas within atherosclerotic lesions identified by [18F]FMBP ex vivo autoradiography. While both radiotracers successfully identified atherosclerotic plaques, [18F]FMBP showed superior specificity and sensitivity for lesions possessing features of destructive plaque remodeling. The detection of ECM remodeling by selective targeting of MMP-13 may enable characterization of high-risk atherosclerosis featuring elevated collagenase activity.

PET imaging is a continuously developing clinical tool for the imaging of different markers of cardiovascular diseases. In this article, some important PET tracers for several diseases affecting the heart and the vessels are highlighted; these include myocardial blood flow, atherosclerosis, fatty acid metabolism, and pathologies in the cardiac autonomic nervous system.

Exercise induces beneficial responses in the brain, which is accompanied by an increase in BDNF, a trophic factor associated with cognitive improvement and the alleviation of depression and anxiety. However, the exact mechanisms whereby physical exercise produces an induction in brain Bdnf gene expression are not well understood. While pharmacological doses of HDAC inhibitors exert positive effects on Bdnf gene transcription, the inhibitors represent small molecules that do not occur in vivo. Here, we report that an endogenous molecule released after exercise is capable of inducing key promoters of the Mus musculus Bdnf gene. The metabolite β-hydroxybutyrate, which increases after prolonged exercise, induces the activities of Bdnf promoters, particularly promoter I, which is activity-dependent. We have discovered that the action of β-hydroxybutyrate is specifically upon HDAC2 and HDAC3, which act upon selective Bdnf promoters. Moreover, the effects upon hippocampal Bdnf expression were observed after direct ventricular application of β-hydroxybutyrate. Electrophysiological measurements indicate that β-hydroxybutyrate causes an increase in neurotransmitter release, which is dependent upon the TrkB receptor. These results reveal an endogenous mechanism to explain how physical exercise leads to the induction of BDNF. DOI: http://dx.doi.org/10.7554/eLife.15092.001, eLife digest Exercise is not only good for our physical health but it benefits our mental health and abilities too. Physical exercise can affect how much of certain proteins are made in the brain. In particular, the levels of a protein called brain derived neurotrophic factor (or BDNF for short) increase after exercise. BDNF has already been shown to enhance mental abilities at the same time as acting against anxiety and depression in mice, and might act in similar way in humans. Nevertheless, it is currently not clear how exercise increases the production of BDNF by cells in the brain. Sleiman et al. have now investigated this question by comparing mice that were allowed to use a running wheel for 30 days with control mice that did not exercise. The comparison showed that the exercising mice had higher levels of BDNF in their brains than the control mice, which confirms the results of previous studies. Next, biochemical experiments showed that this change occurred when enzymes known as histone deacetylases stopped inhibiting the production of BDNF. Therefore Sleiman et al. hypothesised that exercise might produce a chemical that itself inhibits the histone deacetylases. Indeed, the exercising mice produced more of a molecule called β-hydroxybutyrate in their livers, which travels through the blood into the brain where it could inhibit histone deacetylases. Further experiments showed that injecting β-hydroxybutyrate directly into the brains of mice led to increase in BDNF. These new findings reveal with molecular detail one way in which exercise can affect the expression of proteins in the brain. This new understanding may provide ideas for new therapies to treat psychiatric diseases, such as depression, and neurodegenerative disorders, such as Alzheimer’s disease. DOI: http://dx.doi.org/10.7554/eLife.15092.002

An impedance immunosensor was developed based on interdigitated microelectrode array that had gold-based band electrodes sputter-deposited on borosilicate glass substrate. The digit width and the interdigit space were both 15 µm. Anti-E. coli O157:H7 polyclonal antibodies labeled with biodin were immobilized on the electrode surface with a self assembled monolayer of streptavidin. Electrochemical impedance spectroscopy was used to follow and characterize the stepwise assembly of the chemically modified surface, mobilized antibodies, attached cells and washing steps. Both SEM and AFM were used to visualize the features of the electrode surface during the process of electrode preparation and bacterial detection. The change in the charge-transfer resistance value for an electrolytic redox probe of [Fe(CN)6]3-/4- at the electrode-solution interface was measured and correlated to the cell number of E. coli O157:H7 in a sample. The result showed that the impedance immunosensor could detect as low as 1x104 cells/ml in 1.5 h without any pre-enrichment of the sample and centrifuge of bacterial cells. SEM graphs show that attached bacterial cells only covered approximately 10% of the electrode surface area, indicating a high sensitivity of the biosensor. This biosensor was evaluated for the rapid detection of E. coli O157:H7 using poultry carcass wash water and ground beef samples.