Cell type-specific regulation of ciliary transition zone assembly in vertebrates.

Ciliopathies are life-threatening human diseases caused by defective cilia. They can often be traced back to mutations of genes encoding transition zone (TZ) proteins demonstrating that the understanding of TZ organisation is of paramount importance. The TZ consists of multimeric protein modules that are subject to a stringent assembly hierarchy. Previous reports place Rpgrip1l at the top of the TZ assembly hierarchy in Caenorhabditis elegans By performing quantitative immunofluorescence studies in RPGRIP1L-/- mouse embryos and human embryonic cells, we recognise a different situation in vertebrates in which Rpgrip1l deficiency affects TZ assembly in a cell type-specific manner. In cell types in which the loss of Rpgrip1l alone does not affect all modules, additional truncation or removal of vertebrate-specific Rpgrip1 results in an impairment of all modules. Consequently, Rpgrip1l and Rpgrip1 synergistically ensure the TZ composition in several vertebrate cell types, revealing a higher complexity of TZ assembly in vertebrates than in invertebrates.

FTO is a relevant factor for the development of the metabolic syndrome in mice.

The metabolic syndrome is a worldwide problem mainly caused by obesity. FTO was found to be a obesity-risk gene in humans and FTO deficiency in mice led to reduction in adipose tissue. Thus, FTO is an important factor for the development of obesity. Leptin-deficient mice are a well characterized model for analysing the metabolic syndrome. To determine the relevance of FTO for the development of the metabolic syndrome we analysed different parameters in combined homozygous deficient mice (Lep(ob/ob);Fto(-/-)). Lep(ob/ob);Fto(-/-) mice showed an improvement in analysed hallmarks of the metabolic syndrome in comparison to leptin-deficient mice wild type or heterozygous for Fto. Lep(ob/ob);Fto(-/-) mice did not develop hyperglycaemia and showed an improved glucose tolerance. Furthermore, extension of beta-cell mass was prevented in Lep(ob/ob);Fto(-/-)mice and accumulation of ectopic fat in the liver was reduced. In conclusion this study demonstrates that FTO deficiency has a protective effect not only on the development of obesity but also on the metabolic syndrome. Thus, FTO plays an important role in the development of metabolic disorders and is an interesting target for therapeutic agents.

The ciliary protein Ftm is required for ventricular wall and septal development.

Ventricular septal defects (VSDs) are the most common congenital heart defects in humans. Despite several studies of the molecular mechanisms involved in ventricular septum (VS) development, very little is known about VS-forming signaling. We observed perimembranous and muscular VSDs in Fantom (Ftm)-negative mice. Since Ftm is a ciliary protein, we investigated presence and function of cilia in murine hearts. Primary cilia could be detected at distinct positions in atria and ventricles at embryonic days (E) 10.5-12.5. The loss of Ftm leads to shortened cilia and a reduced proliferation in distinct atrial and ventricular ciliary regions at E11.5. Consequently, wall thickness is diminished in these areas. We suggest that ventricular proliferation is regulated by cilia-mediated Sonic hedgehog (Shh) and platelet-derived growth factor receptor α (Pdgfrα) signaling. Accordingly, we propose that primary cilia govern the cardiac proliferation which is essential for proper atrial and ventricular wall development and hence for the fully outgrowth of the VS. Thus, our study suggests ciliopathy as a cause of VSDs.

Foreign body reaction in vaginally eroded and noneroded polypropylene suburethral slings in the female: a case series.

INTRODUCTION AND HYPOTHESIS: Aim of this study was to investigate the pattern of the foreign body reaction of macroporous polypropylene mesh (MPPM) used in females for the treatment of stress urinary incontinence and to compare this pattern between eroded and noneroded tapes. METHODS: Ten explanted suburethral slings, five eroded and five noneroded, were examined immunohistochemically under light microscopy; the tissue reaction was compared between eroded and noneroded materials. RESULTS: Eroded material showed a significantly higher accumulation of macrophages around the filaments of the mesh. CONCLUSIONS: This is the first study comparing reaction around eroded and noneroded MPPMs and indicates a more intense tissue reaction around eroded mesh, when compared to noneroded material. More studies are needed to prove whether the detected foreign body reaction was the actual trigger for the erosion.

The effect of global versus local processing styles on assimilation versus contrast in social judgment.

The authors propose a global/local processing style model (GLOMO) for assimilation and contrast effects in social judgment. GLOMO is based on Schwarz and Bless' (1992, 2007) inclusion-exclusion model, which suggests that when information is included into a category, assimilation occurs, whereas when information is excluded from a category, contrast occurs. According to GLOMO, inclusion versus exclusion should be influenced by whether people process information globally or locally. In 5 experiments, using both disambiguation and social comparison, the authors induced local versus global processing through perceptual tasks and time perspective and showed that global processing produced assimilation, whereas local processing produced contrast. The experiments showed that processing styles elicited in one task can carry over to other tasks and influence social judgments. Furthermore, they found that hemisphere activation and accessibility of judgment-consistent knowledge partially mediated these effects. Implications for current and classic models of social judgment are discussed.

Botulinum toxin-A for idiopathic overactivity of the vesical detrusor: a 2-year follow-up.

The aim of this trial was to examine the effects after 2 years of a single intravesical botulinum toxin-A injection (BTX-A). This prospective, observational study was conducted using urodynamic measurements and quality of life (QoL) assessment to document the effect after 2 years of a single 100 I.U. injection of BTX-A into the vesical detrusor muscle. Twenty-six patients were followed up for 2 years after a first intravesical BTX-A injection. Of these 26 patients, one was a primary failure, three were lost to follow-up, and 11 patients had a repeated injection at 5-26 months (one patient had a third injection). Seven of the remaining 11 patients in the single injection group were recommended repeated injection or another treatment, and four required no other treatment. In conclusion, 2 years after a single BTX-A injection statistically significant differences in urodynamics and an improvement in QoL could still be demonstrated.

Results on function and safety of the Safyre-t, a hybrid transobturator vaginal sling for the treatment of stress urinary incontinence.

AIMS: To examine the efficacy and safety of the Safyre-t vaginal sling. METHODS: 108 women with a Safyre-t were invited for a gynecological follow up examination. RESULTS: 79/108 patients showed up for an examination at 20 +/- 4 months 59.5% stated that they were subjectively dry. Vaginal sling erosion was found in 8.8% of the patients and a pre-erosive state in another 13.9%. The lateral silicone column could be palpated medial to the pubic bone in 47% of the patients indicating dislocation. 6/53 sexually active women complained of dyspareunia and one women stated that her partner had felt discomfort during sexual intercourse since her vaginal sling surgery. CONCLUSIONS: This study shows that despite high patient satisfaction and acceptable subjective continence rates, the Safyre-t was associated with a comparatively high rate of vaginal sling erosions and dislocations.

Demands and properties of alloplastic implants for the treatment of stress urinary incontinence.

Surgical treatment of stress urinary incontinence changed dramatically with the introduction of the tension-free vaginal tape. Owing to its high efficacy and minimal patient discomfort this new minimally invasive procedure quickly obtained widespread acceptance and superseded the abdominal colposuspension as the gold standard. In the course of success of the original method a number of tension-free vaginal tapes flooded the market, varying in approach and material. These variations may strongly influence the safety, efficacy and long-term results of tension-free vaginal tape and its major modification, the transobturator technique. Therefore, it is the aim of this review to closely illuminate available materials and complications associated with this procedure. An extensive Medline search of the published literature up until 2006 on the subject of stress urinary incontinence was carried out. All sources identified were reviewed with particular attention to the method applied, the properties of the mesh materials and clinical complications. Apart from several technical variations, there are marked differences between the different vaginal sling materials, ranging from absorbable collagens over polypropylene to allografts. Although performed globally in substantial and increasing numbers, minimally invasive techniques for the surgical treatment of stress urinary incontinence are lacking sufficient safety data.

A disrupted balance between Bmp/Wnt and Fgf signaling underlies the ventralization of the Gli3 mutant telencephalon.

Regionalization of the neural plate and the early neural tube is controlled by several signaling centers that direct the generation of molecularly distinct domains. In the developing telencephalon, the anterior neural ridge (ANR) and the roof and floor plate act as such organizing centers via the production of Fgfs, Bmps/Wnts, and Shh, respectively. It remains largely unknown, however, how the combination of these different signals is used to coordinate the generation of different telencephalic territories. In the present study, we report on telencephalic development in Pdn mutant mice, which carry an integration of a retrotransposon in the Gli3 locus. Homozygous mutant animals are characterized by a partial dorsal-to-ventral transformation of the telencephalon and by an increased size of the septum. On a molecular level, these alterations correlate with a reduction and/or loss of Bmp/Wnt expression and a concomitant expansion of Fgf8 transcription. Finally, we provide evidence that the ectopic activation of Fgf signaling in the dorsal telencephalon provides an explanation for the ventralization of the Gli3 mutant telencephalon as application of Fgf8-soaked beads to dorsal telencephalic explants led to the specific induction and repression of ventral marker and dorsal marker genes, respectively.

Outpatient psychotherapy for mothers--first empirical results.

MOTHERHOOD is a vulnerable phase in the life of any woman, one that may be associated with an increased risk of mental illness. Despite the major clinical significance of this patient group, only a few psychotherapeutic treatment programs are tailored to the needs of mothers of infants. Even when treatment is urgently needed, many mothers of infants reject inpatient psychotherapy so as not to be separated from their children. The outcome may be chronification of disorders, in some cases with a negative impact on their children's development. A new psychotherapeutic outpatient treatment program adapted to the special needs of mothers and offering a substitute to inpatient treatment is presented. First empirical results show that the presented treatment concept led to significant improvements in the symptoms, whose stabilization continued up to the follow-up two years after the start of therapy.