Contrast-enhanced whole-heart coronary MRA at 3.0T for the evaluation of cardiac venous anatomy

This study was designed to evaluate the value of contrast-enhanced whole-heart coronary MRA (CMRA) at 3.0T in depicting the cardiac venous anatomy. In cardiac resynchronization therapy (CRT), left ventricular (LV) pacing is achieved by positioning the LV lead in one of the tributaries of the coronary sinus (CS). Pre-implantation knowledge of the venous anatomy may help determine whether transvenous LV lead placement for CRT is feasible. Images of 51 subjects undergoing contrast-enhanced whole-heart CMRA at 3.0T were retrospectively analyzed. Data acquisition was performed using electrocardiography-triggered, navigator-gated, inversion-recovery prepared, segmented gradient-echo sequence. A 32-element cardiac coil was used for data acquisition. The visibility of the cardiac veins was graded visually using a 4-point scale (1: poor–4: excellent). The paired Student t test was used to evaluate differences in diameters of the ostium of the CS in anteroposterior and superoinferior direction. The cardiac veins were finally evaluated in 48 subjects with three anatomic variations. The diameter of the CS ostium in the superoinferior direction (1.13 ± 0.26 cm) was larger than in the anteroposterior direction (0.82 ± 0.19 cm) (P < 0.05). The mean visibility score of CS, posterior interventricular vein, posterior vein of the left ventricle, left marginal vein, and anterior interventricular vein was 4.0 ± 0.0, 3.4 ± 0.5, 3.4 ± 0.5, 3.0 ± 0.8, and 3.3 ± 0.5, respectively. In conclusion, contrast-enhanced whole-heart CMRA at 3.0T can depict the normal and variant cardiac venous anatomy

Silencing and Un-silencing of Tetracycline-Controlled Genes in Neurons

To identify the underlying reason for the controversial performance of tetracycline (Tet)-controlled regulated gene expression in mammalian neurons, we investigated each of the three components that comprise the Tet inducible systems, namely tetracyclines as inducers, tetracycline-transactivator (tTA) and reverse tTA (rtTA), and tTA-responsive promoters (Ptets). We have discovered that stably integrated Ptet becomes functionally silenced in the majority of neurons when it is inactive during development. Ptet silencing can be avoided when it is either not integrated in the genome or stably-integrated with basal activity. Moreover, long-term, high transactivator levels in neurons can often overcome integration-induced Ptet gene silencing, possibly by inducing promoter accessibility

Synthèse et caractérisation spectroscopique d hétéro-composés fonctionnalisés (thiols, sélénols, tellurols et phosphine-boranes)

Des thiols, sélénols et tellurols fonctionnalisés et cinétiquement non-stabilisés ont été préparés dans des conditions particulières de réaction sous vide. De façon plus précise, le 3-mercapto-2-propènenitrile, des allényl- et alcynylsélénols, des alcényl- ou cyclopropyl-tellurols ont ainsi pu être isolés et caractérisés par spectroscopie. Les synthèses ont ensuite été adaptées à diverses études spectroscopiques. Les spectres Infrarouge de l éthènetellurol et l éthènylphosphine-borane ont été enregistrés. Les spectres de photoélectron des sélénols et tellurols insaturés ont permis de rationaliser les interactions existant entre la paire libre d électrons de l hétéroatome et l insaturation en fonction de leur éloignement relatif. La complexation des systèmes réactifs a été abordée par la complexation des phosphines primaires par le borane. Une étude générale a été menée sur ces phosphine-boranes en phase gazeuse par diffraction électronique. L influence de la complexation sur les paramètres géométriques (longueurs de liaisons, angles) par rapport aux systèmes libres correspondants a ainsi été précisée.Primary heterocompounds (Thiols, Selenols, Tellurols and Phosphine-boranes) have been prepared in particular conditions on a preparative scale and with a high purity. Allenyl- and alkynylselenols, cyclopropyl- and alkenyltellurols as well as primary , -unsaturated phosphines-boranes have thus been isolated and characterized by spectroscopy. The microwave, infrared or photoelectron spectra of several of these kinetically unstable compounds have been recorded. Thus, by photoelectron spectroscopy and quantum calculations, the type and extent of the interaction between the SeH or TeH group and the unsaturated moiety has been clarified for compounds with gradual increasing distance between the heteroatom and the unsaturated group. On the other hand, a general study was undertaken on the primary phosphine-boranes in gas phase by electronic diffraction. The modification of the interatomic lengths and angles by complexation with borane has been precised.RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF

Impaired NMDA receptor function in mouse olfactory bulb neurons by tetracycline-sensitive NR1(N598R) expression

High Ca2+ permeability and its control by voltage-dependent Mg2+ block are defining features of NMDA receptors. These features are lost if the principal NR1 subunit carries an asparagine (N) to arginine (R) substitution in a critical channel site at NR1 position 598. NR1(R) expression from a single allele in gene-targeted NR1+/R mice is lethal soon after birth, precluding analysis of altered synaptic functions later in life. We therefore employed the forebrain specific small alpha, GreekCaMKII promoter to drive tTA-mediated tetracyclin sensitive transcription of transgenes for NR1(R) and for lacZ as reporter. Transgene expression was observed in cortex, striatum, hippocampus, amygdala and olfactory bulb and was mosaic in all these forebrain regions. It was highest in olfactory bulb granule cells, in most of which Ca2+ permeability and voltage-dependent Mg2+ block of NMDA receptors were reduced to different extents. This indicates significant impairment of NMDA receptor function by NR1(R) in presence of the wild-type NR1 complement. Indeed, even though NR1(R) mRNA constituted only 18% of the entire NR1 mRNA population in forebrain, the transgenic mice died during adolescence unless transgene expression was suppressed by doxycycline. Thus, glutamate receptor function can be altered in the mouse by regulated NR1(R) transgene expression

Studies on conditional gene expression in the brain

This manuscript summarizes our recent attempts to regulate in vitro and in vivo the expression of genes encoding components and regulators of the postsynaptic machinery along with marker genes such as lacZ and GFP. In particular, we studied tTA-dependent regulation and utilized Cre in combination with reversible silencing by intron engineering of dominant negative alleles. We further present a "knockin" approach for on-site artificial regulation of chromosomal genes

A highly sensitive novel immunoassay specifically detects low levels of soluble Aβ oligomers in human cerebrospinal fluid

Introduction: Amyloid β-protein oligomers play a key role in Alzheimer’s disease (AD), but well-validated assays that routinely detect them in cerebrospinal fluid (CSF) are just emerging. We sought to confirm and extend a recent study using the Singulex Erenna platform that reported increased mean CSF oligomer levels in AD. Methods: We tested four antibody pairs and chose one pair that was particularly sensitive, using 1C22, our new oligomer-selective monoclonal antibody, for capture. We applied this new assay to extracts of human brain and CSF. Results: A combination of 1C22 for capture and 3D6 for detection yielded an Erenna immunoassay with a lower limit of quantification of approximately 0.15 pg/ml that was highly selective for oligomers over monomers and detected a wide size-range of oligomers. Most CSFs we tested had detectable oligomer levels but with a large overlap between AD and controls and a trend for higher mean levels in mild cognitive impairment (MCI) than controls. Conclusion: Aβ oligomers are detectable in most human CSFs, but AD and controls overlap. MCI CSFs may have a modest elevation in mean value by this assay. Electronic supplementary material The online version of this article (doi:10.1186/s13195-015-0100-y) contains supplementary material, which is available to authorized users

Respiration and parturition affected by conditional overexpression of the Ca2+-activated K+ channel subunit, SK3.

In excitable cells, small-conductance Ca2+-activated potassium channels (SK channels) are responsible for the slow after-hyperpolarization that often follows an action potential. Three SK channel subunits have been molecularly characterized. The SK3 gene was targeted by homologous recombination for the insertion of a gene switch that permitted experimental regulation of SK3 expression while retaining normal SK3 promoter function. An absence of SK3 did not present overt phenotypic consequences. However, SK3 overexpression induced abnormal respiratory responses to hypoxia and compromised parturition. Both conditions were corrected by silencing the gene. The results implicate SK3 channels as potential therapeutic targets for disorders such as sleep apnea or sudden infant death syndrome and for regulating uterine contractions during labor