Datenbankenunterstützung für das Protein-Protein-Docking: ein effizienter und robuster Feature-Index

In der vorliegenden Arbeit schlagen wir eine Architektur für ein Dockingsystem vor, das zu einem gegebenen Anfrageprotein alle möglichen Dockingpartner und deren zugehörige Konstellationen in einer Proteindatenbank sucht. Die einzelnen Filter- und Bewertungsschritte dieses Dockingsystems sollen durch den Einsatz räumlicher Zugriffsstrukturen unterstützt werden. Hier behandeln wir insbesondere die Verwendung eines effizienten und robusten Feature-Index. Dieser dient dazu, aus dem Raum aller möglichen Konstellationen von Partnerproteinen aus der Datenbank gute Kandidatenvorschläge zu ermitteln. Dazu werden im Vorfeld die Proteinoberflächen regionalisiert, in einem k-dimensionalen Raum von Kennzahlen beschrieben und in einer k-dimensionalen räumlichen Indexstruktur verwaltet. Für die Docking-Suche wird das Anfrageprotein analog regionalisiert, und zusätzlich werden seine Kennzahlen komplementiert, so daß zum Komplement ähnliche Regionen als mögliche Docking-Stellen im Index gefunden werden können. In den nachfolgenden Filterschritten des Dockingsystems wird unter anderem das räumliche Passen genauer überprüft

High Variability of Acetabular Offset in Primary Hip Osteoarthritis Influences Acetabular Reaming—A Computed Tomography–Based Anatomic Study

Background: The objectives of the present study were to (1) evaluate the accuracy and reliability of native acetabular offset (AO) measurements performed on conventional supine anterior-posterior (ap) pelvis radiographs with reference to computed tomography (CT) in patients with end-stage hip osteoarthritis (OA); (2) determine the minimum and maximum amount of medialization of the center of rotation (COR) simulating different reaming techniques; and (3) identify patients at increased risk of excessive medialization of the COR.Methods: A consecutive series of corresponding 131 CT scans and radiographs of patients with primary hip OA was evaluated using validated software for three-dimensional acetabular and femoral measurements. We simulated the implantation of a hemispherical press-fit cup comparing anatomic and conventional reaming techniques and assessed corresponding changes in AO.Results: Standardized ap pelvis radiographs allowed for an accurate and reliable assessment of AO compared with CT. Cup placement in the most lateral position (anatomic reaming technique) resulted in a mean implant-related medialization of 5.9 ± 3.4 mm. Anatomic cup placement did not require reaming to the true floor in 64 hips (49%). With the conventional reaming technique, the total medialization of the COR (implant-related and reaming-related) was 6.8 ± 2.9, with 34% of cases having a medialization ≥8 mm.Conclusion: The present study highlights the variability of acetabular anatomy in patients with primary OA. AO can be accurately and reliably determined on conventional radiographs and appears to be independent of femoral shape and geometry. Depending on the preferred reaming technique a substantial number of patients appear at risk for excessive cup medialization

Custom stems for femoral deformity in patients less than 40 years of age: 70 hips followed for an average of 14 years

Background and purpose Femoral deformity associated with osteoarthritis is a challenge for both the surgeon and the implant. Many of the patients with these deformities are young. Standard implants can be difficult to fit into these femurs. We prospectively evaluated the outcome of custom uncemented femoral stems in young patients

Influence of surgical approach on component positioning in primary total hip arthroplasty

Background: Minimal invasive surgery (MIS) has gained growing popularity in total hip arthroplasty (THA) but concerns exist regarding component malpositioning. The aim of the present study was to evaluate femoral and acetabular component positioning in primary cementless THA comparing a lateral to a MIS anterolateral approach. Methods: We evaluated 6 week postoperative radiographs of 52 hips with a minimal invasive anterolateral approach compared to 54 hips with a standard lateral approach. All hips had received the same type of implant for primary cementless unilateral THA and had a healthy hip contralaterally. Results: Hip offset was equally restored comparing both approaches. No influence of the approach was observed with regard to reconstruction of acetabular offset, femoral offset, vertical placement of the center of rotation, stem alignment and leg length discrepancy. However, with the MIS approach, a significantly higher percentage of cups (38.5 %) was malpositioned compared to the standard approach (16.7 %) (p = 0.022). Conclusions: The MIS anterolateral approach allows for comparable reconstruction of stem position, offset and center of rotation compared to the lateral approach. However, surgeons must be aware of a higher risk of cup malpositioning for inclination and anteversion using the MIS anterolateral approach

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

Purpose We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. Methods We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. Results These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. Conclusion These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis