Integr8 and Genome Reviews: integrated views of complete genomes and proteomes

Integr8 is a new web portal for exploring the biology of organisms with completely deciphered genomes. For over 190 species, Integr8 provides access to general information, recent publications, and a detailed statistical overview of the genome and proteome of the organism. The preparation of this analysis is supported through Genome Reviews, a new database of bacterial and archaeal DNA sequences in which annotation has been upgraded (compared to the original submission) through the integration of data from many sources, including the EMBL Nucleotide Sequence Database, the UniProt Knowledgebase, InterPro, CluSTr, GOA and HOGENOM. Integr8 also allows the users to customize their own interactive analysis, and to download both customized and prepared datasets for their own use. Integr8 is available at http://www.ebi.ac.uk/integr8

Optimierung der statistischen und strukturellen Mustererkennung in Biomolekülen

In der vorliegenden Arbeit wurde eine Methodik zur Analyse von Suchmustern fuer die Vorhersage von Transkriptionsfaktorbindungsstellen in DNA-Sequenzen entwickelt. Fuer die Suchmuster, in diesem Fall Nukleotidverteilungs-Matrizen aus der Datenbank TRANSFAC (http://www.transfac.de), wurden mittels ausgewaehlter positiver und negativer Datensaetze Fehlerraten ermittelt. Fuer die Verwendung mit dem Matrixsuchprogramm MatInspector wurde fuer jede Matrix drei Schwellenwerte definiert - ein Schwellenwert fuer eine minimale Rate an falsch positiven Treffern (sinnvoll fuer die Untersuchung grosser DNA-Sequenzen), ein Schwellenwert fuer eine minimale Rate an falsch negativen Treffern (sinnvoll fuer die umfassende Analyse kurzer Sequenzabschnitte), sowie ein Schwellenwert bei dem beide Fehlerraten zusammen ein Minimum haben. Desweiteren wird eine Methode zum strukturbasierten Datenbankscreening vorgestellt, die es erlaubt ueber attraktive Pseudopotentiale die aktive Site eines Enzyms flexibel zu beschreiben und so das Docken von kleinen Molekuelen aus einer Datenbank zu ermoeglichen und mit Hilfe einer Energiefunktion zu bewerten.This work describes a methodolgy for analysing search patterns for the prediction of transcription factor binding sites in DNA sequences. Search patterns, in this case nucleotide distribution matrices from the database TRANSFAC (http://www.transfac.de) were examined with a positive and a negative data set in order to determine their error rates. For use with the matrix search program MatInspector a set of three thresholds for each matrix was derived which can be used to obtain a minimal rate of false positives (useful for the analysis of long sequences), a minimal rate of false negatives (useful to analyse short sequences comprehensively for putative transcription factor binding sites) and an optimal rate for both errors where the sum of both rates is minimal. Furthermore a methodolgy for a structure based database screening was developed which allows the use of attractive pseudo potentials for the flexible description of an active site of an enzyme in order to dock small molecules from a database. It gives the possibility to score these docked molecules with the help of an energy function

Prenatal tobacco exposure and brain morphology: A prospective study in young children

It is well known that smoking during pregnancy can affect offspring health. Prenatal tobacco exposure has been associated with negative behavioral and cognitive outcomes in childhood, adolescence, and young adulthood. These associations between prenatal tobacco exposure and psychopathology in offspring could possibly be explained by the influence of prenatal tobacco exposure on brain development. In this prospective study, we investigated the association between prenatal tobacco exposure, behavioral and emotional functioning and brain morphology in young children. On the basis of age and gender, we matched 113 children prenatally exposed to tobacco with 113 unexposed controls. These children were part of a population-based study in the Netherlands, the Generation R\ud Study, and were followed from pregnancy onward. Behavioral and emotional functioning was assessed at age 6 with the Child Behavior Checklist. We assessed brain morphology using magnetic resonance imaging techniques in children aged 6–8 years. Children exposed to tobacco throughout pregnancy have smaller total brain volumes and smaller cortical gray matter volumes. Continued prenatal tobacco exposure was associated with cortical thinning, primarily in the superior frontal, superior parietal, and precentral cortices. These children also demonstrated increased scores of affective problems. In addition, thickness of the precentral and superior frontal cortices was associated with affective problems. Importantly, brain development in offspring of mothers who quit smoking during pregnancy resembled that of nonexpose