45 research outputs found
Primary structure and evolutionary relationship between the adult alpha-globin genes and their 5'-flanking regions of Xenopus laevis and Xenopus tropicalis
To investigate the evolution of globin genes in the genus Xenopus, we have determined the primary structure of the related adult alpha I- and alpha II-globin genes of X. laevis and of the adult alpha-globin gene of X. tropicalis, including their 5'-flanking regions. All three genes are comprised of three exons and two introns at homologous positions. The exons are highly conserved and code for 141 amino acids. By contrast, the corresponding introns vary in length and show considerable divergence. Comparison of 900 bp of the 5'-flanking region revealed that the X. tropicalis gene contains a conserved proximal 310-bp promoter sequence, comprised of the canonical TATA and CCAAT motifs at homologous positions, and five conserved elements in the same order and at similar positions as previously shown for the corresponding genes of X. laevis. We therefore conclude that these conserved upstream elements may represent regulatory sequences for cell-specific regulation of the adult Xenopus globin genes
Widespread white matter microstructural differences in schizophrenia across 4322 individuals:Results from the ENIGMA Schizophrenia DTI Working Group
The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.Molecular Psychiatry advance online publication, 17 October 2017; doi:10.1038/mp.2017.170
Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
BACKGROUND Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia (N = 11,095), using a single image analysis protocol. METHODS We included T1-weighted data from 46 datasets (5,080 affected individuals and 6,015 controls) from the ENIGMA Consortium. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Analyses were also performed with respect to the use of antipsychotic medication and other clinical variables, as well as age and sex. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029). RESULTS Small average differences between cases and controls were observed for asymmetries in cortical thickness, specifically of the rostral anterior cingulate (d = −0.08, pFDR = 0.047) and the middle temporal gyrus (d = −0.07, pFDR = 0.048), both driven primarily by thinner cortices in the left hemisphere in schizophrenia. These asymmetries were not significantly associated with the use of antipsychotic medication or other clinical variables. Older individuals with schizophrenia showed a stronger average leftward asymmetry of pallidum volume than older controls (d = 0.08, pFDR = 9.0 × 10−3). The multivariate analysis revealed that 7% of the variance across all structural asymmetries was explained by case-control status (F = 1.87, p = 1.25 × 10−5). CONCLUSIONS Altered trajectories of asymmetrical brain development and/or lifespan asymmetry may contribute to schizophrenia pathophysiology. Small case-control differences of brain macro-structural asymmetry may manifest due to more substantial differences at the molecular, cytoarchitectonic or circuit levels, with functional relevance for lateralized cognitive processes
Verifikation nachrichtentechnischer Systeme mit Systemsimulation und HW/SW-Cosimulation
Der Beitrag zeigt die Erfahrungen beim praktischen Entwurf und bei der Verifikation eines Algorithmus zur Echokompensation und beschreibt dessen Abbildung auf eine Zielarchitektur. Neben der Überprüfung der funktionellen Richtigkeit des Algorithmus stehen bei der Verifikation vor allem Untersuchungen zur benötigten Zahlengenauigkeit und zur erreichbaren Grenzfrequenz im Mittelpunkt. Um einen durchgängigen Designflow zu gewährleisten, haben wir uns bereits bei der Systemverifikation für eine VHDL-Umgebung entschieden. Eine Bibliothek nachrichtentechnischer Standardbaugruppen vereinfachte den Einsatz eines VHDL-Simulators zur Systemsimulation. Zur deutlichen Erhöhung der Effizienz der verwendeten kommerziellen Tools wurden Ergänzungstools entwickelt. Dazu zählen vor allem das Interface des OAK-Debuggers zu VHDL-Simulatoren und das Waveformdisplay ADDA zur Darstellung analoger und digitaler Signalverläufe in einer Simulationsumgebung
Ein kompaktes Radioteleskop für Schulen
Industrie und Forschung benötigen qualifizierten Nachwuchs. Wie aber kann man junge Menschen für eine wissenschaftlich-technische Ausbildung begeistern? Bei der Europäischen Weltraumagentur ESA entstand die Idee, einen Bausatz für ein einfaches Radioteleskop zu entwickeln, das an Schulen aufgestellt werden kann. Das Dresdner Fraunhofer-Institut für Integrierte Schaltungen entwickelte den Prototyp. Der Artikel informiert über Aufbau und Inbetriebnahme des Teleskops, über die Funktionsweise und Beobachtungsmöglichkeiten. Außerdem wird über das Pilotprojekt zum Einsatz des kleinen Radioteleskops an europäischen Schulen informiert und es werden Kontaktadressen bei Interesse zur Teilnahme an diesem Projekt angegeben
Reducing systems biology models to derive mechanism-based drug effect models: blood coagulation as illustrative example
An integrated co-simulation interface for mixed-level system-on-chip design: Presentation held at CDNLive!, 10.-11. September 2007, San Jose, USA, Silicon Valley 2007
The continuously increasing complexity of today's embedded electronic systems strongly requires including system level into design and verification. An ideal top-down design flow would use a system-level model as the executable specification and testbench within which analog or mixed-signal blocks can be developed and verified. This paper describes the co-simulation link between the system-level simulator, Matlab-Simulink, and a mixed-signal simulation environment, AMS Designer. After a detailed description of the implementation and the two synchronization algorithms for framed and unframed data, the co-simulation is demonstrated using the design of a wireless LAN system. Simulating such a complex system-design at the transistor level is not even possible within the design cycle time and simulating the entire design at the system level is not as accurate as transistor-level simulations. This session will demonstrate that performance and accuracy tradeoffs can easily be made using this approach and will demonstrate how to reduce interface problems and increase design efficiency and quality by allowing the different blocks to be revised and tested within the overall system
The Drosophila fork head domain protein crocodile is required for the establishment of head structures.
The fork head (fkh) domain defines the DNA-binding region of a family of transcription factors which has been implicated in regulating cell fate decisions across species lines. We have cloned and molecularly characterized the crocodile (croc) gene which encodes a new family member from Drosophila. croc is expressed in the head anlagen of the blastoderm embryo under the control of the anterior, the dorsoventral and the terminal maternal organizer systems. The croc mutant phenotype indicates that the croc wild-type gene is required to function as an early patterning gene in the anterior-most blastoderm head segment anlage and for the establishment of a specific head skeletal structure that derives from the non-adjacent intercalary segment at a later stage of embryogenesis. As an early patterning gene, croc exerts unusual properties which do not allow it to be grouped among the established segmentation genes. A single-site mutation within the croc fkh domain, which causes a replacement of the first out of four conserved amino acid residues thought to be involved in the coordinate binding of Mg2+, abolishes the DNA binding of the protein in vitro. In view of the resulting lack-of-function mutant phenotype, it appears likely that metal binding by the affected region of the fkh domain is crucial for proper folding of the DNA-binding structure