Large-scale albuminuria screen for nephropathy models in chemically induced mouse mutants

Background/Aim: Phenotype-driven screening of a great pool of randomly mutant mice and subsequent selection of animals showing symptoms equivalent to human kidney diseases may result in the generation of novel suitable models for the study of the pathomechanisms and the identification of genes involved in kidney dysfunction. Methods: We carried out a large-scale analysis of ethylnitrosourea (ENU)-induced mouse mutants for albuminuria by using qualitative SDS-polyacrylamide gel electrophoresis. Results: The primary albuminuria screen preceded the comprehensive phenotypic mutation analysis in a part of the mice of the Munich ENU project to avoid loss of mutant animals as a consequence of prolonged suffering from severe nephropathy. The primary screen detected six confirmed phenotypic variants in 2,011 G1 animals screened for dominant mutations and no variant in 48 G3 pedigrees screened for recessive mutations. Further breeding experiments resulted in two lines showing a low phenotypic penetrance of albuminuria. The secondary albuminuria screen was carried out in mutant lines which were established in the Munich ENU project without preceding primary albuminuria analysis. Two lines showing increased plasma urea levels were chosen to clarify if severe kidney lesions are involved in the abnormal phenotype. This analysis revealed severe albuminuria in mice which are affected by a recessive mutation leading to increased plasma urea and cholesterol levels. Conclusion: Thus, the phenotypic selection of ENU-induced mutants according to the parameter proteinuria in principle demonstrates the feasibility to identify nephropathy phenotypes in ENU-mutagenized mice. Copyright (C) 2005 S. Karger AG, Basel

Outlaw Community Innovations

Recent studies of outlaw communities provide qualitative evidence of their existence and the organisation of the underlying innovation processes. We provide descriptive results from a large scale survey of two online outlaw communities focussing on Microsoft's XBox. In line with previous findings, we identify two types of participants in outlaw communities - user innovators and adopters. Based on 2,256 responses, we find that users modify their XBox mainly to be able to increase the set of available functions of their XBox. Users are also motivated to modify their XBox for the sake of having fun and to conduct pirate behaviour. Finally, the results from our survey suggest that user innovators are largely intrinsically motivated by fun and the intellectual stimulation of writing code for homebrew software

Comparison of Intravitreal Bevacizumab Upload Followed by a Dexamethasone Implant versus Dexamethasone Implant Monotherapy for Retinal Vein Occlusion with Macular Edema

Purpose: To compare the efficacy and safety of three intravitreal bevacizumab upload injections followed by a dexamethasone implant versus dexamethasone implant monotherapy in eyes with macular edema due to retinal vein occlusion. Methods: Sixty-four eyes of 64 patients were included in this prospective, consecutive, nonrandomized case series: group 1 consisted of 38 patients (22 with central retinal vein occlusion, CRVO, 16 with branch retinal vein occlusion, BRVO) treated using a dexamethasone implant (Ozurdex) alone; group 2 consisted of 26 patients (14 CRVO, 12 BRVO) treated with three consecutive intravitreal bevacizumab injections at monthly intervals followed by a dexamethasone implant. In case of recurrence, both cohorts received further dexamethasone implants. Preoperatively and monthly best corrected visual acuity (BCVA, ETDRS), central retinal thickness (Spectralis-OCT), intraocular pressure, and wide-angle fundus photodocumentation (Optomap) were performed. The primary clinical endpoint was BCVA at 6 months after initiation of therapy. Secondary endpoints were central retinal thickness and safety of the therapy applied. Results: In group 1, an increase in BCVA of 2.5 (+/- 1.6) letters in the CRVO and of 13.0 (+/- 3.2) letters in BRVO patients was seen after 6 months, in group 2 of 5.9 (+/- 0.4) letters (CRVO) and 3.8 (+/- 2.4) letters (BRVO), which was not statistically significant. When comparing the two treatment groups with respect to the type of vein occlusion, there was a significant advantage for BRVO patients for the dexamethasone implant monotherapy (BRVO patients in group 1, p = 0.005). Central retinal thickness showed a significant reduction after 6 months only in patients of group 1, both for CRVO (p = 0.01) and BRVO (p = 0.003). First recurrence after the first dexamethasone implant injection occurred after 3.8 months (mean) in CRVO and 3.5 months in BRVO patients (group 1), versus 3.2 and 3.7 months, respectively, in group 2. In group 1, 63.6% with CRVO and 50% with BRVO showed an increased intraocular pressure after treatment; in group 2, 57.1% with CRVO and 50.0% with BRVO, respectively. Conclusion: In CRVO, there was no difference between the two treatment strategies investigated. However, in BRVO, dexamethasone implant monotherapy was associated with better functional outcome. Copyright (C) 2012 S. Karger AG, Base

Some Aesopic Fables in Byzantium and the Latin West: Tradition, Diffusion, and Survival

published or submitted for publicatio

Impact of the Specific Mutation in KRAS Codon 12 Mutated Tumors on Treatment Efficacy in Patients with Metastatic Colorectal Cancer Receiving Cetuximab-Based First-Line Therapy: A Pooled Analysis of Three Trials

Purpose: This study investigated the impact of specific mutations in codon 12 of the Kirsten-ras (KRAS) gene on treatment efficacy in patients with metastatic colorectal cancer (mCRC). Patients: Overall, 119 patients bearing a KRAS mutation in codon 12 were evaluated. All patients received cetuximab-based first-line chemotherapy within the Central European Cooperative Oncology Group (CECOG), AIO KRK-0104 or AIO KRK-0306 trials. Results: Patients with KRAS codon 12 mutant mCRC showed a broad range of outcome when treated with cetuximab-based first-line regimens. Patients with tumors bearing a KRAS p.G12D mutation showed a strong trend to a more favorable outcome compared to other mutations (overall survival 23.3 vs. 14-18 months; hazard ratio 0.66, range 0.43-1.03). An interaction model illustrated that KRAS p.G12C was associated with unfavorable outcome when treated with oxaliplatin plus cetuximab. Conclusion: The present analysis suggests that KRAS codon 12 mutation may not represent a homogeneous entity in mCRC when treated with cetuximab-based first-line therapy. Copyright (C) 2012 S. Karger AG, Base

High-energy emission from the stellar wind collisions in gamma-2 Velorum

The binary system gamma-2 Velorum (WC8+O7.5) contains the nearest known Wolf-Rayet star to the Sun, at a distance of 258$_{-31}^{+41}$ pc. Its strong radio emission shows evidence for a partially absorbed nonthermal component, which has been interpreted as synchrotron emission from electrons accelerated in the colliding wind region. Inverse Compton cooling of these electrons in the intense UV radiation field from the O-type companion star could produce a significant hard X-ray and gamma-ray emission, whose flux depends on the ratio of the energy densities of magnetic to seed photon fields. The Vela region was observed with the INTEGRAL satellite in 2003, as part of the Core Programme. No signals from gamma-2 Vel are detected in the images obtained with the IBIS/ISGRI coded aperture instrument in the energy ranges 20-40 and 40-80 keV. From the derived 3$\sigma$ upper limits, we show that the average magnetic field near the region of stellar wind collision should be relatively high, greater than about 1 G. The high-energy emission of gamma-2 Vel might be detected with the forthcoming GLAST experiment.Comment: 4 pages, 3 figures. To appear in the Proceedings of the 5th INTEGRAL Workshop: "The INTEGRAL Universe", February 16-20, 2004, Munich, German