HDAC6 is a bruchpilot deacetylase that facilitates neurotransmitter release

Presynaptic densities are specialized structures involved in synaptic vesicle tethering and neurotransmission; however, the mechanisms regulating their function remain understudied. In Drosophila, Bruchpilot is a major constituent of the presynaptic density that tethers vesicles. Here, we show that HDAC6 is necessary and sufficient for deacetylation of Bruchpilot. HDAC6 expression is also controlled by TDP-43, an RNA-binding protein deregulated in amyotrophic lateral sclerosis (ALS). Animals expressing TDP-43 harboring pathogenic mutations show increased HDAC6 expression, decreased Bruchpilot acetylation, larger vesicle-tethering sites, and increased neurotransmission, defects similar to those seen upon expression of HDAC6 and opposite to hdac6 null mutants. Consequently, reduced levels of HDAC6 or increased levels of ELP3, a Bruchpilot acetyltransferase, rescue the presynaptic density defects in TDP-43-expressing flies as well as the decreased adult locomotion. Our work identifies HDAC6 as a Bruchpilot deacetylase and indicates that regulating acetylation of a presynaptic release-site protein is critical for maintaining normal neurotransmission

The method of detection of ductal carcinoma in situ has no therapeutic implications: results of a population-based cohort study

Multivariable-adjusted Cox regression analysis of ipsilateral and contralateral invasive breast cancer in women aged 49–75 years at DCIS diagnosis (DCIS diagnostic period 1989–2004). Age was the primary time scale, time since DCIS diagnosis (0–5, 5–10, and ≥10 years) the secondary time scale, and DCIS treatment a time-varying covariable (DOCX 22 kb

Motion Robust Magnetic Susceptibility and Field Inhomogeneity Estimation Using Regularized Image Restoration Techniques for fMRI

In functional MRI, head motion may cause dynamic nonlinear field-inhomogeneity changes, especially with large out-of-plane rotations. This may lead to dynamic geometric distortion or blurring in the time series, which may reduce activation detection accuracy. The use of image registration to estimate dynamic field inhomogeneity maps from a static field map is not sufficient in the presence of such rotations. This paper introduces a retrospective approach to estimate magnetic susceptibility induced field maps of an object in motion, given a static susceptibility induced field map and the associated object motion parameters. It estimates a susceptibility map from a static field map using regularized image restoration techniques, and applies rigid body motion to the former. The dynamic field map is then computed using susceptibility voxel convolution. The method addresses field map changes due to out-of-plane rotations during time series acquisition and does not involve real time field map acquisitions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85944/1/Fessler233.pd

Spherical harmonic decomposition applied to spatial-temporal analysis of human high-density EEG

We demonstrate an application of spherical harmonic decomposition to analysis of the human electroencephalogram (EEG). We implement two methods and discuss issues specific to analysis of hemispherical, irregularly sampled data. Performance of the methods and spatial sampling requirements are quantified using simulated data. The analysis is applied to experimental EEG data, confirming earlier reports of an approximate frequency-wavenumber relationship in some bands.Comment: 12 pages, 8 figures, submitted to Phys. Rev. E, uses APS RevTeX style

Spontaneous focusing on numerosity in preschool as a predictor of mathematical skills and knowledge in the fifth grade

Previous studies in a variety of countries have shown that there are substantial individual differences in children’s spontaneous focusing on numerosity (SFON), and these differences are positively related to the development of early numerical skills in preschool and primary school. A total of 74 5-year-olds participated in a 7-year follow-up study, in which we explored whether SFON measured with very small numerosities at 5 years of age predicts mathematical skills and knowledge, math motivation, and reading in fifth grade at 11 years of age. Results show that preschool SFON is a unique predictor of arithmetic fluency and number line estimation but not of rational number knowledge, mathematical achievement, math motivation, or reading. These results hold even after taking into account age, IQ, working memory, digit naming, and cardinality skills. The results of the current study further the understanding of how preschool SFON tendency plays a role in the development of different formal mathematical skills over an extended period of time.</p

Axonal Odorant Receptors Mediate Axon Targeting

In mammals, odorant receptors not only detect odors but also define the target in the olfactory bulb, where sensory neurons project to give rise to the sensory map. The odorant receptor is expressed at the cilia, where it binds odorants, and at the axon terminal. The mechanism of activation and function of the odorant receptor at the axon terminal is, however, still unknown. Here, we identify phosphatidylethanolamine- binding protein 1 as a putative ligand that activates the odorant receptor at the axon terminal and affects the turning behavior of sensory axons.Genetic ablation of phosphatidylethanolamine-binding protein 1 in mice results in a strongly disturbed olfactory sensory map. Our data suggest that the odorant receptor at the axon terminal of olfactory neurons acts as an axon guidance cue that responds to molecules originating in the olfactory bulb. The dual function of the odorant receptor links specificity of odor perception and axon targeting