A glycinergic projection from the ventromedial lower brainstem to spinal motoneurons. An ultrastructural double labeling study in rat

__Abstract__ In the present study it was determined whether glycine was present in the descending brainstem projections to spinal motoneurons in the rat. For this purpose injections of wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) were made in the ventromedial part of the lower brainstem at the levels of the rostral inferior olive and the caudal facial nucleus. After perfusion, WGA-HRP histochemistry was performed, followed by the postembedding immunogold tehncque with an antbody against glycine. Electron microscopical examination of the lumbar motoneuronal cell groups showed that 15% of the WGA-HRP labeled terminals, derived from the ventromedial reticular formation, were also labeled for glycine. The majority (91%) of these double labeled terminal were of the F-type (containing many flattened vesicles), while the remaining 9% were of the S-type (containing mostly sphetical vesicles). Many of the double labeled terminals established a synapse, mostly with proximal and distal dendrites. The present data, combined with our previous findings that 40% of the projections from the same ventromedial brainstem area to lumbar motoneurons contained γ-aminobutyric acid (GABA), indicate that over 50% of these brainstem projections contain GABA and/or glycine, exerting a direct inhibition effect on spinal motoneurons. The possibility that the glycinergic fibers within these projections play an important role in producing muscle atonia during rapid eye movement (REM) sleep is discussed

Multifunctional genes

In this paper a sensor fusion for pose estimation using optical and inertial data is presented. The proposed algorithm is based on extended Kalman filtering and fuses data from an optical tracking system and an inertial measurement unit. These two redundant sensor systems complement each other well, with the tracking providing absolute position accuracy and the inertial measurements giving low latency information of derivatives. Models for both sensors are given respecting the different sampling times and latencies. Another key issue is to use information about every landmark, i.e. marker, visible for the tracking system, by coupling the two sensor systems tightly together. The algorithms are evaluated in simulation and tested with an experimental hardware platform. The combined sensor system provides robust pose estimation in case of short time marker occlusion and effectively compensates for latencies the pose measurements

KC-SMARTR: An R package for detection of statistically significant aberrations in multi-experiment aCGH data

Background: Most approaches used to find recurrent or differential DNA Copy Number Alterations (CNA) in array Comparative Genomic Hybridization (aCGH) data from groups of tumour samples depend on the discretization of the aCGH data to gain, loss or no-change states. This causes loss of valuable biological information in tumour samples, which are frequently heterogeneous. We have previously developed an algorithm, KC-SMART, that bases its estimate of the magnitude of the CNA at a given genomic location on kernel convolution (Klijn et al., 2008). This accounts for the intensity of the probe signal, its local genomic environment and the signal distribution across multiple samples. Results: Here we extend the approach to allow comparative analyses of two groups of samples and introduce the R implementation of these two approaches. The comparative module allows for a supervised analysis to be performed, to enable the identification of regions that are differentially aberrated between two user-defined classes. We analyzed data from a series of B- and T-cell lymphomas and were able to retrieve all positive control regions (VDJ regions) in addition to a number of new regions. A t-test employing segmented data, that we implemented, was also able to locate all the positive control regions and a number of new regions but these regions were highly fragmented. Conclusions: KC-SMARTR offers recurrent CNA and class specific CNA detection, at different genomic scales, in a single package without the need for additional segmentation. It is memory efficient and runs on a wide range of machines. Most importantly, it does not rely on data discretization and therefore maximally exploits the biological information in the aCGH data.MediamaticsElectrical Engineering, Mathematics and Computer Scienc

Global transcriptional responses of fission and budding yeast to changes in copper and iron levels: a comparative study

Analysis of genome-wide responses to changing copper and iron levels in budding and fission yeast reveals conservation of only a small core set of genes and remarkable differences in the responses of the two yeasts to excess copper

2,3-cis-2R,3R-(−)-epiafzelechin-3-O-p-coumarate, a novel flavan-3-ol isolated from Fallopia convolvulus seed, is an estrogen receptor agonist in human cell lines

BACKGROUND: The plant genus Fallopia is well-known in Chinese traditional medicine and includes many species that contain bioactive compounds, namely phytoestrogens. Consumption of phytoestrogens may be linked to decreased incidence of breast and prostate cancers therefore discovery of novel phytoestrogens and novel sources of phytoestrogens is of interest. Although phytoestrogen content has been analyzed in the rhizomes of various Fallopia sp., seeds of a Fallopia sp. have never been examined for phytoestrogen presence. METHODS: Analytical chemistry techniques were used with guidance from an in vitro estrogen receptor bioassay (a stably transfected human ovarian carcinoma cell line) to isolate and identify estrogenic components from seeds of Fallopia convolvulus. A transiently transfected human breast carcinoma cell line was used to characterize the biological activity of the isolated compounds on estrogen receptors (ER) α and β. RESULTS: Two compounds, emodin and the novel flavan-3-ol, (−)-epiafzelechin-3-O-p-coumarate (rhodoeosein), were identified to be responsible for estrogenic activity of F. convolvulus seed extract. Absolute stereochemistry of rhodoeosein was determined by 1 and 2D NMR, optical rotation and circular dichroism. Emodin was identified by HPLC/DAD, LC/MS/MS, and FT/ICR-MS. When characterizing the ER specificity in biological activity of rhodoeosein and emodin, rhodoeosein was able to exhibit a four-fold greater relative estrogenic potency (REP) in breast cells transiently-transfected with ERβ as compared to those transfected with ERα, and emodin exhibited a six-fold greater REP in ERβ-transfected breast cells. Cell type-specific differences were observed with rhodoeosein but not emodin; rhodoeosein produced superinduction of reporter gene activity in the human ovarian cell line (> 400% of maximum estradiol [E2] induction) but not in the breast cell line. CONCLUSION: This study is the first to characterize the novel flavan-3-ol compound, rhodoeosein, and its ability to induce estrogenic activity in human cell lines. Rhodoeosein and emodin may have potential therapeutic applications as natural products activating ERβ, and further characterization of rhodoeosein is necessary to evaluate its selectivity as a cell type-specific ER agonist

Estimating translational selection in Eukaryotic Genomes

Natural selection on codon usage is a pervasive force that acts on a large variety of prokaryotic and eukaryotic genomes. Despite this, obtaining reliable estimates of selection on codon usage has proved complicated, perhaps due to the fact that the selection coefficients involved are very small. In this work, a population genetics model is used to measure the strength of selected codon usage bias, S, in 10 eukaryotic genomes. It is shown that the strength of selection is closely linked to expression and that reliable estimates of selection coefficients can only be obtained for genes with very similar expression levels. We compare the strength of selected codon usage for orthologous genes across all 10 genomes classified according to expression categories. Fungi genomes present the largest S values (2.24–2.56), whereas multicellular invertebrate and plant genomes present more moderate values (0.61–1.91). The large mammalian genomes (human and mouse) show low S values (0.22–0.51) for the most highly expressed genes. This might not be evidence for selection in these organisms as the technique used here to estimate S does not properly account for nucleotide composition heterogeneity along such genomes. The relationship between estimated S values and empirical estimates of population size is presented here for the first time. It is shown, as theoretically expected, that population size has an important role in the operativity of translational selection

Single subject and group whole-brain fMRI mapping of male genital sensation at 7 Tesla

Processing of genital sensations in the central nervous system of humans is still poorly understood. Current knowledge is mainly based on neuroimaging studies using electroencephalography (EEG), magneto-encephalography (MEG), and 1.5- or 3- Tesla (T) functional magnetic resonance imaging (fMRI), all of which suffer from limited spatial resolution and sensitivity, thereby relying on group analyses to reveal significant data. Here, we studied the impact of passive, yet non-arousing, tactile stimulation o