Studies on the mechanism of retinoid-induced pattern duplications in the early chick limb bud: temporal and spatial aspects.

All-trans-retinoic acid causes striking digit pattern changes when it is continuously released from a bead implanted in the anterior margin of an early chick wing bud. In addition to the normal set of digits (234), extra digits form in a mirror-symmetrical arrangement, creating digit patterns such as a 432234. These retinoic acid-induced pattern duplications closely mimic those found after grafts of polarizing region cells to the same positions with regard to dose-response, timing, and positional effects. To elucidate the mechanism by which retinoic acid induces these pattern duplications, we have studied the temporal and spatial distribution of all-trans-retinoic acid and its potent analogue TTNPB in these limb buds. We find that the induction process is biphasic: there is an 8-h lag phase followed by a 6-h duplication phase, during which additional digits are irreversibly specified in the sequence digit 2, digit 3, digit 4. On average, formation of each digit seems to require between 1 and 2 h. The tissue concentrations, metabolic pattern, and spatial distribution of all-trans-retinoic acid and TTNPB in the limb rapidly reach a steady state, in which the continuous release of the retinoid is balanced by loss from metabolism and blood circulation. Pulse-chase experiments reveal that the half-time of clearance from the bud is 20 min for all-trans-retinoic acid and 80 min for TTNPB. Manipulations that change the experimentally induced steep concentration gradient of TTNPB suggest that a graded distribution of retinoid concentrations across the limb is required during the duplication phase to induce changes in the digit pattern. The extensive similarities between results obtained with retinoids and with polarizing region grafts raise the possibility that retinoic acid serves as a natural "morphogen" in the limb

Mal-Adaptation of Event-Related EEG Responses Preceding Performance Errors

Recent EEG and fMRI evidence suggests that behavioral errors are foreshadowed by systematic changes in brain activity preceding the outcome by seconds. In order to further characterize this type of error precursor activity, we investigated single-trial event-related EEG activity from 70 participants performing a modified Eriksen flanker task, in particular focusing on the trial-by-trial dynamics of a fronto-central independent component that previously has been associated with error and feedback processing. The stimulus-locked peaks in the N2 and P3 latency range in the event-related averages showed expected compatibility and error-related modulations. In addition, a small pre-stimulus negative slow wave was present at erroneous trials. Significant error-preceding activity was found in local stimulus sequences with decreased conflict in the form of less negativity at the N2 latency (310–350 ms) accumulating across five trials before errors; concomitantly response times were speeding across trials. These results illustrate that error-preceding activity in event-related EEG is associated with the performance monitoring system and we conclude that the dynamics of performance monitoring contribute to the generation of error-prone states in addition to the more remote and indirect effects in ongoing activity such as posterior alpha power in EEG and default mode drifts in fMRI

COMPARISON BETWEEN FREEDOM OF RELIGION IN GERMANY AND IN THE UNITED STATES IN GENERAL AND THE TREATMENT OF THE CHURCH OF SCIENTOLOGY SPECIFICALLY

The thesis first gives background information about the general development of fundamental rights in both Germany and the United States and specifically the freedom of religion. The analysis discusses in particular freedom of religion granted by Article 4 of the Basic Law in Germany and the religious clauses of the First Amendment of the American Constitution. In the first conclusion, the differences in the interpretations of the religious clauses both in Germany and the United States will be stated. These differences will then be illustrated by a discussion on the Church of Scientology through its basic facts, history, ideas, and attitude. The most important German and American court rulings will be provided which confront the issue of whether or not the Church of Scientology is legally defined as a church. Even though the American courts do not provide a definition of religion, the Internal Revenue Service does. The issue arises whether or not Scientology meets these requirements. In an excursus, the thesis examines, whether Scientology theologically is a religion. Finally, there will be a discussion of German constitutional issues regarding the Church of Scientology. The conclusion states that Germany does not neglect the fundamental right of religious freedom in its actions against Scientology but protects its relatively young democracy from the threat of extremism and fundamentalism; whereas the United States is able to grant more freedom due to its better established and secured democracy, it still has some control through the scrutiny of the Internal Revenue Service

Acetylation of BMAL1 by TIP60 controls BRD4-P-TEFb recruitment to circadian promoters.

Many physiological processes exhibit circadian rhythms driven by cellular clocks composed of interlinked activating and repressing elements. To investigate temporal regulation in this molecular oscillator, we combined mouse genetic approaches and analyses of interactions of key circadian proteins with each other and with clock gene promoters. We show that transcriptional activators control BRD4-PTEFb recruitment to E-box-containing circadian promoters. During the activating phase of the circadian cycle, the lysine acetyltransferase TIP60 acetylates the transcriptional activator BMAL1 leading to recruitment of BRD4 and the pause release factor P-TEFb, followed by productive elongation of circadian transcripts. We propose that the control of BRD4-P-TEFb recruitment is a novel temporal checkpoint in the circadian clock cycle

Studie zu einem Sportentwicklungskonzept für die Stadt Hildesheim : Abschlussbericht

Sport und Bewegung sind im ständigen Wandel befindlich. Die Sportnachfrage spiegelt die zunehmende Vielfalt von Sportausübung, Motiven, Anbietern, Sport- und Bewegungsräumen sowie von Zielgruppen und Akteuren wider. Darauf möchte auch die Stadt Hildesheim reagieren und bestehende Strukturen des Sports analysieren sowie zukünftige Bedarfe und entsprechende Weiterentwicklungen und Veränderungen in einem Sportentwicklungskonzept thematisieren. An der Sportentwicklungsplanung der Stadt Hildesheim wirkt das Institut für Sportwissenschaft der Universität Hildesheim durch eine entsprechende Studie mit, in der insbesondere das Sportverhalten der Bürger/innen sowie der Ist-Zustand der Sporträume erfasst werden sollen. Inhaltliche Schwerpunkte dieser Erhebung sollen sowohl der institutionelle als auch der informelle Sport sein. Zur Datenerhebung sind quantitative Fragebogendesigns zur Befragung der Bürger und der Vereine sowie die Beobachtung von Sporträumen vorgesehen. Ergänzt werden die Daten durch qualitative Interviews. Auf diese Weise sollen Entwicklungspotentiale für die Stadt Hildesheim hervorgebracht werden, die durch sportwissenschaftliche Erkenntnisse zu innovativen Sport- und Bewegungsangeboten ergänzt werden können

Meiotic sex chromosome cohesion and autosomal synapsis are supported by Esco2.

In mitotic cells, establishment of sister chromatid cohesion requires acetylation of the cohesin subunit SMC3 (acSMC3) by ESCO1 and/or ESCO2. Meiotic cohesin plays additional but poorly understood roles in the formation of chromosome axial elements (AEs) and synaptonemal complexes. Here, we show that levels of ESCO2, acSMC3, and the pro-cohesion factor sororin increase on meiotic chromosomes as homologs synapse. These proteins are less abundant on the largely unsynapsed sex chromosomes, whose sister chromatid cohesion appears weaker throughout the meiotic prophase. Using three distinct conditional Esco2 knockout mouse strains, we demonstrate that ESCO2 is essential for male gametogenesis. Partial depletion of ESCO2 in prophase I spermatocytes delays chromosome synapsis and further weakens cohesion along sex chromosomes, which show extensive separation of AEs into single chromatids. Unsynapsed regions of autosomes are associated with the sex chromatin and also display split AEs. This study provides the first evidence for a specific role of ESCO2 in mammalian meiosis, identifies a particular ESCO2 dependence of sex chromosome cohesion and suggests support of autosomal synapsis by acSMC3-stabilized cohesion

Neural plasticity in functional and anatomical MRI studies of children with Tourette syndrome

Background: Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by chronic motor and vocal tics. The typical clinical course of an attenuation of symptoms during adolescence in parallel with the emerging self-regulatory control during development suggests that plastic processes may play an important role in the development of tic symptoms. Methods: We conducted a systematic search to identify existing imaging studies (both anatomical and functional magnetic resonance imaging [fMRI]) in young persons under the age of 19 years with TS. Results: The final search resulted in 13 original studies, which were reviewed with a focus on findings suggesting adaptive processes (using fMRI) and plasticity (using anatomical MRI). Differences in brain activation compared to healthy controls during tasks that require overriding of prepotent responses help to understand compensatory pathways in children with TS. Along with alterations in regions putatively representing the origin of tics, deviations in several other regions most likely represent an activity-dependent neural plasticity that help to modulate tic severity, such as the prefrontal cortex, but also in the corpus callosum and the limbic system. Discussion: Factors that potentially influence the development of adaptive changes in the brain of children with TS are age, comorbidity with other developmental disorders, medication use, IQ along with study-design or MRI techniques for acquisition, and analysis of data. The most prominent limitation of all studies is their cross-sectional design. Longitudinal studies extending to younger age groups and to children at risk for developing TS hopefully will confirm findings of neural plasticity in future investigations.publishedVersio

Extracellular vesicles derived from the choroid plexus trigger the differentiation of neural stem cells

The choroid plexus secrets cerebrospinal fluid (CSF) composed of electrolytes, cytokines, growth factors, metabolites and extracellular vesicles (EVs) that flow through the interconnected brain ventricles. On their course, CSF components can act as signals that affect, for example, neural stem cells (NSCs) residing in niches of the ventricular wall. We studied EV-born CSF signals in an in vitro culture system. We purified EVs from the secretome of a choroid plexus cell line (Z310 cells), and from primary choroid plexus cultures and co-cultured those EVs with NSCs isolated from the niche of the lateral and the third ventricle. EVsZ310 and EVsCHP were purified by differential centrifugation. This yielded fractions of EVs of 50–150-nm diameter that induced a complex multicellular network formation and NSC differentiation. Both types of EV converted the round NSCs to cells that extended long processes that contacted nearby, alike-shaped cells. Mass spectrometry showed that the differentiation-inducing EVZ310 were enriched for membrane and membrane-associated proteins involved in cell differentiation, membrane trafficking, and membrane organization. We hypothesize that this type of EV Z310 cargo causes changes of stem cell morphology that leads to multicellular networks in the niches. This cell-shape transition may represent an initial step in NSC differentiation