A homeo domain protein reveals the metameric nature of the developing chick hindbrain

The segmented embryonic hindbrain of vertebrates develops by sequential constriction of the neural tube into eight metameric units known as rhombomeres. The cellular and molecular basis of this segmentation process is largely unknown. Using an antibody, we analyzed the expression pattern of the chick homeo domain-containing protein Ghox-lab in the developing chick hindbrain. At the neural plate stage, prior to the appearance of rhombomeres, Ghox-lab is expressed within a single domain that extends anteriorly up to the site where rhombomere 4 will later form. After rhombomere 4 has appeared and as hindbrain segmentation progresses, the level of Ghox-lab protein increases significantly within the fourth rhombomere. This intensification, accompanied by the elimination of Ghox-lab protein in rhombomeres 5 and 6, eventually results in the formation of a distinct island of expression in rhombomere 4. All cells in the newly formed rhombomere 4 express Ghox-lab, except for the cells of the floor plate. In addition, neural crest cells migrating from the fourth rhombomere are also Ghox-lab-positive. These data raise the possibility that Ghox-lab protein might be one of the factors involved in the specification of the metameric pattern of the vertebrate hindbrain.     

Functional parcellation of the inferior frontal and midcingulate cortices in a flanker‐stop‐change paradigm

Conflict monitoring and motor inhibition are engaged in the performance of complex tasks. The midcingulate cortex (MCC) has been suggested to detect conflicts, whereas the right inferior frontal cortex (IFC) seems to be of relevance for the inhibition process. The current experiment investigates the neural underpinnings of their interplay via a modified flanker paradigm. Conflict was manipulated by the congruency of flanking stimuli relative to a target (congruent vs. incongruent) and motor inhibition by a within‐trial response change of the initiated response (keep response vs. stop‐change). We used event‐related functional magnetic resonance imaging, decomposition with high model order ICA, and single trial analysis to derive a functional parcellation of the whole‐brain data. Results demonstrate the segmentation of the MCC into anterior and posterior subregions, and of the IFC into the pars opercularis, pars triangularis, and pars orbitalis. The pars opercularis and pars triangularis of the right IFC constituted the foundation of inhibition‐related networks. With high conflict on incongruent trials, activity in the posterior MCC network, as well as in one right IFC network was observed. Stop‐change trials modulated both the MCC as well as networks covering extended parts of the IFC. Whereas conflict processing and inhibition most often are studied separately, this study provides a synopsis of functionally coupled brain regions acting in concert to enable an optimal performance in situations involving interference and inhibition. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Assessing the spatiotemporal evolution of neuronal activation with single-trial event-related potentials and functional MRI

The brain acts as an integrated information processing system, which methods in cognitive neuroscience have so far depicted in a fragmented fashion. Here, we propose a simple and robust way to integrate functional MRI (fMRI) with single trial event-related potentials (ERP) to provide a more complete spatiotemporal characterization of evoked responses in the human brain. The idea behind the approach is to find brain regions whose fMRI responses can be predicted by paradigm-induced amplitude modulations of simultaneously acquired single trial ERPs. The method was used to study a variant of a two-stimulus auditory target detection (odd-ball) paradigm that manipulated predictability through alternations of stimulus sequences with random or regular target-to-target intervals. In addition to electrophysiologic and hemodynamic evoked responses to auditory targets per se, single-trial modulations were expressed during the latencies of the P2 (170-ms), N2 (200-ms), and P3 (320-ms) components and predicted spatially separated fMRI activation patterns. These spatiotemporal matches, i.e., the prediction of hemodynamic activation by time-variant information from single trial ERPs, permit inferences about regional responses using fMRI with the temporal resolution provided by electrophysiology.     

R(+)-Methanandamide-Induced Apoptosis of Human Cervical Carcinoma Cells Involves A Cyclooxygenase-2-Dependent Pathway

Purpose  Cannabinoids have received renewed interest due to their antitumorigenic effects. Using human cervical carcinoma cells (HeLa), this study investigates the role of cyclooxygenase-2 (COX-2) in apoptosis elicited by the endocannabinoid analog R(+)-methanandamide (MA). Methods  COX-2 expression was assessed by RT-PCR and Western blotting. PGE₂/PGD₂ levels in cell culture supernatants and DNA fragmentation were measured by ELISA. Results  MA led to an induction of COX-2 expression, PGD₂ and PGE₂ synthesis. Cells were significantly less sensitive to MA-induced apoptosis when COX-2 was suppressed by siRNA or the selective COX-2 inhibitor NS-398. COX-2 expression and apoptosis by MA was also prevented by the ceramide synthase inhibitor fumonisin B₁, but not by antagonists to cannabinoid receptors and TRPV1. In line with the established role of peroxisome proliferator-activated receptor γ (PPARγ) in the proapoptotic action of PGs of the D and J series, inhibition of MA-induced apoptosis was also achieved by siRNA targeting lipocalin-type PGD synthase (L-PGDS) or PPARγ. A role of COX-2 and PPARγ in MA-induced apoptosis was confirmed in another human cervical cancer cell line (C33A) and in human lung carcinoma cells (A549). Conclusion  This study demonstrates COX-2 induction and synthesis of L-PGDS-derived, PPARγ-activating PGs as a possible mechanism of apoptosis by MA. Karin Eichele and Robert Ramer contributed equally to this work.     

Über basisch substituierte Tryptamine und Tryptophole. 3. Mitt.: Pharmakologische Prüfung in 1- und 2-Stellung basisch substituierter Derivate

Basic Substituted Tryptamines and Tryptophols The pharmacological examination of derivatives of 1-(dialkylaminomethyl)-tryptamine and -tryptophol and of 2-(piperidinomethyl)-tryptophol is described. 1-(piperidinomethyl)-benzoyltryptophol-methiodide is the most effective compound of this series; on the ileum of the rat stimulated with Doryl® it shows an effect four times higher than scopolamine-n-butylbromide (Buscopan®), and on the ileum of the guinea-pig stimulated with histamine good antihistaminic properties are observed. The positive inotropic effect of this compound on the isolated auricle of the guinea-pig has been characterized as an indirect sympathomimetic one.     

Multimodal imaging of functional networks and event-related potentials in performance monitoring

The stop-signal task is a prototypical experiment to study cognitive processes that mediate successful performance in a rapidly changing environment. By means of simultaneous recording and combined analysis of electroencephalography and functional magnetic resonance imaging on single trial level, we provide a comprehensive view on brain responses related to performance monitoring in this task. Three types of event-related EEG components were analyzed: a go-related N2/P3-complex devoid of motor-inhibition, the stop-related N2/P3-complex and the error-related negativity with its consecutive error positivity. Relevant functional networks were identified by crossmodal correlation analyses in a parallel independent component analysis framework. Go-related potentials were associated with a midcingulate network known to participate in the processing of conflicts, a left-dominant somatosensory-motor network, and deactivations in visual cortices. Stop-related brain responses in association with the N2/P3-complex were seen with networks known to support motor and cognitive inhibition, including parts of the basal ganglia, the anterior midcingulate cortex and pre-supplementary motor area as well as the anterior insula. Error-related brain responses showed a similar constellation with additional recruitment of the posterior insula and the inferior frontal cortex. Our data clearly indicate that the pre-supplementary motor area is involved in inhibitory mechanisms but not in the processing of conflicts per se.     

Adrenal glucocorticoids have a key role in circadian resynchronization in a mouse model of jet lag

Jet lag encompasses a range of psycho- and physiopathological symptoms that arise from temporal misalignment of the endogenous circadian clock with external time. Repeated jet lag exposure, encountered by business travelers and airline personnel as well as shift workers, has been correlated with immune deficiency, mood disorders, elevated cancer risk, and anatomical anomalies of the forebrain. Here, we have characterized the molecular response of the mouse circadian system in an established experimental paradigm for jet lag whereby mice entrained to a 12-hour light/12-hour dark cycle undergo light phase advancement by 6 hours. Unexpectedly, strong heterogeneity of entrainment kinetics was found not only between different organs, but also within the molecular clockwork of each tissue. Manipulation of the adrenal circadian clock, in particular phase-shifting of adrenal glucocorticoid rhythms, regulated the speed of behavioral reentrainment. Blocking adrenal corticosterone either prolonged or shortened jet lag, depending on the time of administration. This key role of adrenal glucocorticoid phasing for resetting of the circadian system provides what we believe to be a novel mechanism-based approach for possible therapies for jet lag and jet lag–associated diseases.     

Neurophysiological evidence of impaired musical sound perception in cochlear-implant users

Objective

Music perception with a cochlear implant (CI) can be unsatisfactory because current-day implants are primarily designed to enable speech discrimination. The present study aimed at evaluating electrophysiological correlates of musical sound perception in CI users to help achieve the long-term goal of improved restoration of hearing in those individuals.

Methods

Auditory discrimination accuracy in adult CI users (n = 12) and matched normal-hearing controls (n = 12) was measured by behavioral discrimination tasks and mismatch negativity (MMN) recordings. Discrimination profiles were obtained by using a set of clarinet sounds (original/vocoded) varying along different acoustic dimensions (frequency/intensity/duration) and deviation magnitudes (four levels).

Results

Behavioral results and MMN recordings revealed reduced auditory discrimination accuracy in CI users. An inverse relationship was found between MMN amplitudes and duration of profound deafness.

Conclusions

CI users have difficulties in discriminating small changes in the acoustic properties of musical sounds. The recently developed multi-feature MMN paradigm (Pakarinen et al., 2007) can be used to objectively evaluate discrimination abilities of CI users for musical sounds.

Significance

Measuring auditory discrimination functions by means of a multi-feature MMN paradigm could be of substantial clinical value by providing a comprehensive profile of the extent of restored hearing in CI users.     

3D volume reconstruction of a mouse brain from histological sections using warp filtering

Sectioning tissues for optical microscopy often introduces upon the resulting sections distortions that make 3D reconstruction difficult. Here we present an automatic method for producing a smooth 3D volume from distorted 2D sections in the absence of any undistorted references. The method is based on pairwise elastic image warps between successive tissue sections, which can be computed by 2D image registration. Using a Gaussian filter, an average warp is computed for each section from the pairwise warps in a group of its neighboring sections. The average warps deform each section to match its neighboring sections, thus creating a smooth volume where corresponding features on successive sections lie close to each other. The proposed method can be used with any existing 2D image registration method for 3D reconstruction. In particular, we present a novel image warping algorithm based on dynamic programming that extends Dynamic Time Warping in 1D speech recognition to compute pairwise warps between high-resolution 2D images. The warping algorithm efficiently computes a restricted class of 2D local deformations that are characteristic between successive tissue sections. Finally, a validation framework is proposed and applied to evaluate the quality of reconstruction using both real sections and a synthetic volume.