Genome wide prediction of HNF4α functional binding sites by the use of local and global sequence context

An application of machine learning algorithms enables prediction of the functional context of transcription factor binding sites in the human genome

Incidence of tuberous sclerosis and age at first diagnosis: new data and emerging trends from a national, prospective surveillance study

Background: Tuberous Sclerosis Complex (TSC) is a rare multisystem disorder. In 2012 diagnostic criteria for TSC were revised. However, data on the incidence of TSC are limited. Methods: Prospective, national surveillance study in Germany over a 2-year-period (03/2015-02/2017) using current revised criteria for TSC. Patients up to the age of 18 years with a new diagnosis of definite or possible TSC (clinical and/or genetic) were included. The aims of this study were 1) to generate up-to-date data on the incidence of definite or possible TSC, 2) to assess age at first diagnosis, and 3) to compare these data with previous epidemiologic data. Results: In total, 86 patients met inclusion criteria (definite or possible TSC) with a median age at diagnosis of 6 months (range: 5 months before birth -197 months of age). Among patients identified with features of TSC, 73.3% met criteria for definite diagnosis (median age: 7 months) and 26.7% met criteria for a possible diagnosis (median age: 3 months). 55.8% of patients were male. When excluding prenatally diagnosed patients, median age at diagnosis was 11 months with a range of 0 to 197 months. The 3 most common clinical features at diagnosis of TSC were central nervous system involvement in 73.3% patients (of these 95.2% experienced seizures), cutaneous involvement in 58.1% patients (with the most common lesion being hypomelanotic macules in 92%) and cardiac rhabdomyoma in half of the patients. Cardiac rhabdomyoma were detected by prenatal ultrasonography in 22.1% of patients. The presence of cardiac rhabdomyoma was associated with cardiac arrhythmias in 25.6% (about 13% of all diagnosed patients) in our cohort. The overall prevalence of seizure disorders was 69.8%. The annual incidence rate of TSC is estimated at a minimum of 1:17.785 live births. However correcting for underreporting, the estimated incidence rate of definite or possible TSC is approximately 1:6.760-1:13.520 live births in Germany. Conclusions: This is the first study that assessed prospectively the incidence rate of TSC in children and adolescents using the updated diagnostic criteria of 2012. This prospective surveillance study demonstrates a low age at first diagnosis (median:6 months), likely due to antenatal detection of cardiac rhabdomyoma. Early diagnosis bears the potential for implementing effective therapies at an earlier stage

Untersuchungen zur genotypischen und phänotypischen Variabilität verschiedener Schilfklone (Phragmites australis)

In der vorliegenden Arbeit werden Wachstum und Entwicklung von 10 Schilfklonen (Phragmites australis) verglichen, um die genotypische Determinierung verschiedener Eigenschaften sowie den Einfluss der Standortfaktoren auf diese Eigenschaften zu untersuchen. Dabei sollen Aussagen zum Bestehen unterschiedlicher Ökotypen beim Schilf abgeleitet werden. Die Untersuchungen erfolgten auf sechs Pflanzfeldern, die im Rahmen von Renaturierungsmaßnahmen an den Ufern der Berliner Gewässer Seddinsee, Langer See und Havel im Frühjahr 1995 angelegt wurden. Die Anpflanzung erfolgt am Land, das Schilf wuchs in das Wasser vor. Die Herkunftsorte der Schilfklone unterschieden sich in der Nährstoffversorgung, der Substratqualität und der Exposition. Die Ergebnisse ließen deutliche Unterschiede in der Morphometrie der Halme (Halmlänge, Halmdurchmesser, Blattfläche pro Halm), der Halmbiomasse und der Balance zwischen Halmdichten und Halmlängen (bzw. Trockenmassen) zwischen den einzelnen Schilfklonen erkennen. Da dies beim Wachstum unter vergleichbaren Standortbedingungen gefunden wurde, kann eine genotypische Determinierung dieser Eigenschaften vermutet werden. Es konnte ebenfalls ein starker Einfluss der Umwelt auf das Wachstum des Schilfs festgestellt werden. Allgemein waren die Wachstumsbedingungen im Wasser deutlich besser als am Land. Die höchsten Halmbiomassen der einzelnen Schilfklone wurden daher im Wasser erreicht (zwischen 0,7 und 2,1 kg Trockenmasse pro m²), während die Werte am Land geringer waren (zwischen 0,6 und 1,0 kg/m²). Obwohl sich die Schilfklone an ihren ursprünglichen Standorten deutlich in den Stickstoffgehalten der Halme unterschieden, ergaben sich auf den Pflanzungen keine Unterschiede zwischen ihnen. Im Gegensatz dazu lagen die N-Werte bei jedem Schilfklon im Wasser erheblich höher als am Land. Dies lässt folgern, dass die Stickstoffgehalte der Halme in erster Linie vom Stickstoff-Angebot am jeweiligen Standort abhängen. Insgesamt deuten die Ergebnisse darauf hin, dass die Schilfklone genotypische Unterschiede in verschiedenen Merkmalen aufweisen können. Eine mögliche Nutzung zu einer Verbesserung des Erfolges von Pflanzmaßnahmen wird diskutiert.In this study, growth and development of 10 reed clones (Phragmites australis) were compared to investigate genetically determined differences in various characteristics as well as the influence of site conditions on these characteristics. In addition, conclusions on the existence of different ecotypes were to be drawn. The study was performed on six experimental fields, established for shore renaturation on the lakes Seddinsee, Langer See and on the river Havel in Berlin in spring 1995. The plantations were established ashore, the reed expanded into the water. The sites of origin of the clones differed in nutrient supply, substrate quality and shore exposition. The results showed distinct differences between the individual reed clones regarding the morphometrics of the shoots (shoot length, culm diameter, leaf area per shoot), standing crop and the trade-off between shoot length (or dry matter) and shoot density. The fact that these results were found with clones that had grown under comparable site conditions seems to suggest a genotypic determination of these characteristics. A strong influence of the environment on the growth of the reed could also be deserved. In general, the conditions for growth were better in water than ashore. The highest standing crops of the individual reed clones were reached in water (between 0.7 and 2.1 kg drymatter pro m²), while the values ashore were lower (between 0.6 and 1.0 kg/m²). Although the reed clones at their original sites were clearly different in the nitrogen content of shoots, no differences were observed on the experimental fields. In contrast, the N-values of each clone were higher in water than ashore. This suggests that the nitrogen content of the shoots depends primarily on the nitrogen availability at the specific site. The results overall suggest that reed clones could exhibit genetically determined differences in various characteristics. A possible practical use to increase the efficiency of further reed plantations is discussed

Plot of the distribution of global and local contexts in the 375 sequences (red squares) selected from the 'positive' set of ChIP-chip results reported by Odom

[11] versus all 10,852 sequences from the 'negative' (not binding; H13K_noHNF4) set (green dots) reported for the same experiment. The selected sequences are characterized by the highest global and local context scores whereas the majority of the 'negative' sequences are characterized by low values for these two scores. The vertical and horizontal lines show two thresholds chosen for the global context score (0.28) and the local context score (0.18).<p><b>Copyright information:</b></p><p>Taken from "Genome wide prediction of HNF4α functional binding sites by the use of local and global sequence context"</p><p>http://genomebiology.com/2008/9/2/R36</p><p>Genome Biology 2008;9(2):R36-R36.</p><p>Published online 21 Feb 2008</p><p>PMCID:PMC2374721.</p><p></p

Research briefings: the 'Effects of transfusion thresholds on neurocognitive outcome of extremely low birth-weight infants (ETTNO)' study: background, aims, and study protocol

Background: Infants with extremely low birth weight uniformly develop anemia of prematurity and frequently require red blood cell transfusions (RBCTs). Although RBCT is widely practiced, the indications remain controversial in the absence of conclusive data on the long-term effects of RBCT. Objectives: To summarize the current equipoise and to outline the study protocol of the 'Effects of Transfusion Thresholds on Neurocognitive Outcome of extremely low birth-weight infants (ETTNO)' study. Methods: Review of the literature and design of a large pragmatic randomized controlled trial of restrictive versus liberal RBCT guidelines enrolling 920 infants with birth weights of 400-999 g with long-term neurodevelopmental follow-up. Results and Conclusions: The results of ETTNO will provide definite data about the efficacy and safety of restrictive versus liberal RBCT guidelines in very preterm infants