Multiparametric Immunoimaging Maps Inflammatory Signatures in Murine Myocardial Infarction Models

In the past 2 decades, research on atherosclerotic cardiovascular disease has uncovered inflammation to be a key driver of the pathophysiological process. A pressing need therefore exists to quantitatively and longitudinally probe inflammation, in preclinical models and in cardiovascular disease patients, ideally using non-invasive methods and at multiple levels. Here, we developed and employed in vivo multiparametric imaging approaches to investigate the immune response following myocardial infarction. The myocardial infarction models encompassed either transient or permanent left anterior descending coronary artery occlusion in C57BL/6 and Apoe−/−mice. We performed nanotracer-based fluorine magnetic resonance imaging and positron emission tomography (PET) imaging using a CD11b-specific nanobody and a C-C motif chemokine receptor 2-binding probe. We found that immune cell influx in the infarct was more pronounced in the permanent occlusion model. Further, using 18F-fluorothymidine and 18F-fluorodeoxyglucose PET, we detected increased hematopoietic activity after myocardial infarction, with no difference between the models. Finally, we observed persistent systemic inflammation and exacerbated atherosclerosis in Apoe−/− mice, regardless of which infarction model was used. Taken together, we showed the strengths and capabilities of multiparametric imaging in detecting inflammatory activity in cardiovascular disease, which augments the development of clinical readouts

Strategies for Controlled Placement of Nanoscale Building Blocks

The capability of placing individual nanoscale building blocks on exact substrate locations in a controlled manner is one of the key requirements to realize future electronic, optical, and magnetic devices and sensors that are composed of such blocks. This article reviews some important advances in the strategies for controlled placement of nanoscale building blocks. In particular, we will overview template assisted placement that utilizes physical, molecular, or electrostatic templates, DNA-programmed assembly, placement using dielectrophoresis, approaches for non-close-packed assembly of spherical particles, and recent development of focused placement schemes including electrostatic funneling, focused placement via molecular gradient patterns, electrodynamic focusing of charged aerosols, and others

Simvastatin treatment reduces the cholesterol content of membrane/lipid rafts, implicating the N -methyl-D-aspartate receptor in anxiety: a literature review

ABSTRACT Membrane/lipid rafts (MLRs) are plasmalemmal microdomains that are essential for neuronal signaling and synaptic development/stabilization. Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (statins) can disable the N-methyl-D-aspartate (NMDA) receptor through disruption of MLRs and, in turn, decrease NMDA-mediated anxiety. This hypothesis will contribute to understanding the critical roles of simvastatin in treating anxiety via the NMDA receptor

What should be considered in using standard knee radiographs to estimate mechanical alignment of the knee?

Objective: Anatomical tibiofemoral angle (anatomical TFA) of the knee measured on standard knee radiographs is still widely used as proxy for mechanical tibiofemoral angle (mechanical TFA), because of the practical and economic limitations in using full-limb radiographs. However, reported differences between anatomical and mechanical TFAs show wide variations. The first aim of this study was to determine whether gender, the presence of advanced osteoarthritis (OA), and history of total knee arthroplasty (TKA) influence the differences between anatomical and mechanical TFAs. The second aim was to identify anatomical features that cause divergences between anatomical and mechanical TFAs, and the final aim was to determine whether anatomical TFA measured using reference points more distant from the knee provides more accurate estimates of mechanical TFA. Design: In 102 knees with advanced OA before and after TKAs and 99 control knees with no/minimal OA, we assessed the differences between two anatomical TFAs, namely, anatomical TFA1 and anatomical TFA2, which were based on conventional or more distant proximal and distal reference points on standard knee radiographs, respectively, and the mechanical TFA measured on full-limb radiographs. These differences were investigated for women vs men, no/minimal OA vs advanced OA, and for knees before vs after TKA. Regression analyses were performed to determine associations between femoral and tibial anatomical characteristics and the differences between mechanical and anatomical TFAs. Results: The OA group showed significantly greater differences between mechanical and anatomical TFAs than the control group for both genders. In OA and TKA group, women were more likely to have greater mean differences between mechanical and anatomical TFAs than men. However, TKA did not significantly affect these differences. Femoral and tibial bowing angles, particularly of the femur, were found to be the major contributors to divergences between mechanical and two anatomical TFAs. Furthermore, anatomical TFA2 was found to provide more accurate estimates of mechanical TFA. Conclusions: We found that the differences between mechanical and anatomical TFAs depend on gender and the presence of advanced OA, but not on a history of TKA. These findings indicate that prediction of mechanical TFA based on anatomical TFA is dependent on study population characteristics. This study also shows that the presence of lateral bowing of the femur is a major cause of mechanical TFA to anatomical TFA variations associated with gender and advanced OA. To reduce the adverse effects of anatomical variations on estimations of mechanical TFA based on an anatomical TFA method, more distant proximal and distal reference points are recommended to determine anatomical TFA value on standard knee radiographs. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. 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Sez-6 proteins affect dendritic arborization patterns and excitability of cortical pyramidal neurons

Development of appropriate dendritic arbors is crucial for neuronal information transfer. We show, using seizure-related gene 6 (sez-6) null mutant mice, that Sez-6 is required for normal dendritic arborization of cortical neurons. Deep-layer pyramidal neurons in the somatosensory cortex of sez-6 null mice exhibit an excess of short dendrites, and cultured cortical neurons lacking Sez-6 display excessive neurite branching. Overexpression of individual Sez-6 isoforms in knockout neurons reveals opposing actions of membrane-bound and secreted Sez-6 proteins, with membrane-bound Sez-6 exerting an antibranching effect under both basal and depolarizing conditions. Layer V pyramidal neurons in knockout brain slices show reduced excitatory postsynaptic responses and a reduced dendritic spine density, reflected by diminished punctate staining for postsynaptic density 95 (PSD-95). In behavioral tests, the sez-6 null mice display specific exploratory, motor, and cognitive deficits. In conclusion, cell-surface protein complexes involving Sez-6 help to sculpt the dendritic arbor, in turn enhancing synaptic connectivity