Evolutionary Patterns in Coiled-Coils

Models of protein evolution are used to describe evolutionary processes, for phylogenetic analyses and homology detection. Widely used general models of protein evolution are biased toward globular domains and lack resolution to describe evolutionary processes for other protein types. As three-dimensional structure is a major constraint to protein evolution, specific models have been proposed for other types of proteins. Here, we consider evolutionary patterns in coiled-coil forming proteins. Coiled-coils are widespread structural domains, formed by a repeated motif of seven amino acids (heptad repeat). Coiled-coil forming proteins are frequently rods and spacers, structuring both the intracellular and the extracellular spaces that often form protein interaction interfaces. We tested the hypothesis that due to their specific structure the associated evolutionary constraints differ from those of globular proteins. We showed that substitution patterns in coiled-coil regions are different than those observed in globular regions, beyond the simple heptad repeat. Based on these substitution patterns we developed a coiled-coil specific (CC) model that in the context of phylogenetic reconstruction outperforms general models in tree likelihood, often leading to different topologies. For multidomain proteins containing both a coiled-coil region and a globular domain, we showed that a combination of the CC model and a general one gives higher likelihoods than a single model. Finally, we showed that the model can be used for homology detection to increase search sensitivity for coiled-coil proteins. The CC model, software, and other supplementary materials are available at http://www.evocell.org/cgl/resources (last accessed January 29, 2015).FCT fellowship: (SFRH/BD/51880/2012)

Rabifier2: an improved bioinformatic classifier of Rab GTPases

SUMMARY: The Rab family of small GTPases regulates and provides specificity to the endomembrane trafficking system; each Rab subfamily is associated with specific pathways. Thus, characterization of Rab repertoires provides functional information about organisms and evolution of the eukaryotic cell. Yet, the complex structure of the Rab family limits the application of existing methods for protein classification. Here, we present a major redesign of the Rabifier, a bioinformatic pipeline for detection and classification of Rab GTPases. It is more accurate, significantly faster than the original version and is now open source, both the code and the data, allowing for community participation. AVAILABILITY AND IMPLEMENTATION: Rabifier and RabDB are freely available through the web at http://rabdb.org. The Rabifier package can be downloaded from the Python Package Index at https://pypi.python.org/pypi/rabifier, the source code is available at Github https://github.com/evocell/rabifier

Long-term risk of complications after mid-urethral sling IVS implantation

Introduction Results of short-term evaluation of multifilament microporous midurethral tape IVS differ a great deal. During the first year of implantation, erosions have been observed in 0%–26% of operated women. Long-term observations are rare. They suggest high risk of extrusion and infection even after years of implantation. Objective The purpose of the study was to evaluate long-term risk of complications after IVS implantation. Material and Methods Between 2001–2005, 72 women were operated on with the use of IVS mid-urethral tape. Results Two women had vaginal erosions during the first 3 months after the operation. Twelve women had vaginal erosions, purulent vaginal discharge, with IVS tape sticking out of the abdominal wall or vagina, and abdominal abscess. These complications were diagnosed between 9 months and 6 years after IVS implantation. The patients were operated on vaginally and open abdominally, 1–5 times because of complications after IVS implantation. Conclusions In the case of post-IVS complication, as much tape as possible should be excised. Long-term follow up on patients with IVS implantation should be recommended to the centres where IVS tape was used, even to patients after removal of the tape. Risk of erosion, extrusion and infection after midurethral multifilament microporous IVS tape implantation is too high – which is the reason it should no longer be used

Standardized modified colposuspension – midterm results of prospective studies in one centre

Introduction Burch colposuspension is still estimated as a ‘gold standard’ by the Cochrane Collaboration Group in the treatment of operative stress urinary incontinence (SUI) Some urogynecologists agree with this statement, some argue that Burch colposuspension should no longer be used. Objective The aim of this study was to evaluate mid-term effects and patient’s satisfaction with standardized modified colposuspension performed in one centre. Material and Methods Modified colposuspension was performed after standardization by 2 trained gynaecologists in 354 women. Data collected from 227 women were added to the final analysis of mid-term results. Average time from the operation to mid-term visit was 19 months (range 9–36 months). Results At mid-term visit, 86.3% of patients were cured. There was no case of post-void urine residual over 100 ml. Pain near the operated region was reported by 1 woman from agricultural region. No one reported negative impact of modified colposuspension on sexual activity or dyspareunia. Conclusions Modified colposuspension according to the E. Petri technique seems to be an operation that is safe and well-tolerated by women with preoperative stress urinary incontinence and paravaginal defect without urodynamic signs of ISD in mid-term observation