Local Agenda 21 in Germany: an inter- and intranational comparison

"More than ten years after the Rio Earth Summit in 1992, which marked the institutionalization of Agenda 21 and the beginning of Local Agenda 21 processes all over the world, it is time to summarize and evaluate the situation with respect to Local Agenda 21 in Germany. Even in Germany, which can be considered as a latecomer regarding the implementation of Local Agenda 21, the diffusion of this policy innovation seems to have reached its end. This paper starts from an international, comparative perspective and Germany's position as a latecomer regarding Local Agenda 21 initiation however, it focuses primarily on the intranational, comparative standpoint. We analyze the diffusion of Local Agenda 21 in four German states (Länder) (Berlin, North Rhine-Westphalia, Bavaria, and Thuringia). The comparisons between Germany and other countries at international level and between the Länder at national level demonstrate that the diffusion of Local Agenda 21 depends above all on three factors: (1) local authorities' capacities for action(2) financial and political support from national and regional governmental organizations and (3) (trans)national and regional agenda transfer institutions which facilitate the exchange of knowledge and know-how between local authorities, and thus accelerate the diffusion of Local Agenda 21 processes. Local authorities, which have greater capacities for action, which are better supported by the particular German state (Land) where they are located, and which show a higher degree of integration into transfer networks are more active and innovative in the area of Local Agenda 21." (author's abstract)"Mehr als zehn Jahre nach dem Umweltgipfel in Rio 1992, der die Institutionalisierung der Agenda 21 und den Beginn von Lokalen Agenda 21-Prozessen überall in der Welt kennzeichnete, ist es an der Zeit, die Situation der Lokalen Agenda 21 in Deutschland zu bilanzieren und zu evaluieren. Sogar in Deutschland, das als Nachzügler im Bereich der Implementation der Lokalen Agenda 21 betrachtet werden kann, scheint die Diffusion dieser Politikinnovation an ihrem Ende angelangt zu sein. Als Ausgangspunkt dieses Artikels dient die international vergleichende Perspektive und Deutschlands Position als Nachzügler im Hinblick auf die Initiierung der Lokalen Agenda 21. Die Analyse konzentriert sich allerdings vor allem auf die intranational vergleichende Perspektive. Wir analysieren die Diffusion der Lokalen Agenda 21 in vier ausgewählten deutschen Ländern (Berlin, Nordrhein- Westfalen, Bayern und Thüringen). Die Vergleiche zwischen Deutschland und anderen Ländern auf der internationalen Ebene und zwischen den deutschen Ländern auf der nationalen Ebene zeigen, dass die Diffusion der Lokalen Agenda 21 vor allem von drei Faktoren abhängt: (1) den Handlungskapazitäten der Städte und Gemeinden, (2) der finanziellen und politischen Unterstützung durch nationale und regionale Regierungsorganisationen sowie (3) den (trans)nationalen und regionalen Institutionen des Agenda-Transfers, die den Erfahrungsaustausch zwischen den Kommunen verbessern und die Diffusion von Lokalen Agenda 21-Prozessen beschleunigen. Städte und Gemeinden, die über mehr Handlungskapazitäten verfügen, von dem Bundesland, in dem sie liegen, besser unterstützt werden, und einen höheren Grad der Integration in Transfernetzwerke aufweisen, sind im Bereich der Lokalen Agenda 21 aktiver und innovativer." (Autorenreferat

Predictive MGMT status in a homogeneous cohort of IDH wildtype glioblastoma patients

Methylation of the O(6)-Methylguanine-DNA methyltransferase (MGMT) promoter is predictive for treatment response in glioblastoma patients. However, precise predictive cutoff values to distinguish "MGMT methylated" from "MGMT unmethylated" patients remain highly debated in terms of pyrosequencing (PSQ) analysis. We retrospectively analyzed a clinically and molecularly very well-characterized cohort of 111 IDH wildtype glioblastoma patients, who underwent gross total tumor resection and received standard Stupp treatment. Detailed clinical parameters were obtained. Predictive cutoff values for MGMT promoter methylation were determined using ROC curve analysis and survival curve comparison using Log-rank (Mantel-Cox) test. MGMT status was analyzed using pyrosequencing (PSQ), semi-quantitative methylation specific PCR (sqMSP) and direct bisulfite sequencing (dBiSeq). Highly methylated (> 20%) MGMT correlated with significantly improved progression-free survival (PFS) and overall survival (OS) in our cohort. Median PFS was 7.2 months in the unmethylated group (UM, 20% mean methylation). Median OS was 13.4 months for UM, 17.9 months for LM and 29.93 months for HM. Within the LM group, correlation of PSQ and sqMSP or dBiSeq was only conclusive in 51.5% of our cases. ROC curve analysis revealed superior test precision for survival if additional sqMSP results were considered (AUC = 0.76) compared to PSQ (cutoff 10%) alone (AUC = 0.67). We therefore challenge the widely used, strict PSQ cutoff at 10% which might not fully reflect the clinical response to alkylating agents and suggest applying a second method for MGMT testing (e.g. MSP) to confirm PSQ results for patients with LM MGMT levels if therapeutically relevant

The Passive Yet Successful Way of Planktonic Life: Genomic and Experimental Analysis of the Ecology of a Free-Living Polynucleobacter Population

Background: The bacterial taxon Polynucleobacter necessarius subspecies asymbioticus represents a group of planktonic freshwater bacteria with cosmopolitan and ubiquitous distribution in standing freshwater habitats. These bacteria comprise,1 % to 70 % (on average about 20%) of total bacterioplankton cells in various freshwater habitats. The ubiquity of this taxon was recently explained by intra-taxon ecological diversification, i.e. specialization of lineages to specific environmental conditions; however, details on specific adaptations are not known. Here we investigated by means of genomic and experimental analyses the ecological adaptation of a persistent population dwelling in a small acidic pond. Findings: The investigated population (F10 lineage) contributed on average 11 % to total bacterioplankton in the pond during the vegetation periods (ice-free period, usually May to November). Only a low degree of genetic diversification of the population could be revealed. These bacteria are characterized by a small genome size (2.1 Mb), a relatively small number of genes involved in transduction of environmental signals, and the lack of motility and quorum sensing. Experiments indicated that these bacteria live as chemoorganotrophs by mainly utilizing low-molecular-weight substrates derived from photooxidation of humic substances. Conclusions: Evolutionary genome streamlining resulted in a highly passive lifestyle so far only known among free-living bacteria from pelagic marine taxa dwelling in environmentally stable nutrient-poor off-shore systems. Surprisingly, such a lifestyle is also successful in a highly dynamic and nutrient-richer environment such as the water column of the investigate

Optimizing identification of consensus molecular subtypes in muscle-invasive bladder cancer: a comparison of two sequencing methods and gene sets using FFPE specimens

Abstract Background Molecular subtypes predict prognosis in muscle-invasive bladder cancer (MIBC) and are explored as predictive markers. To provide a common base for molecular subtyping and facilitate clinical applications, a consensus classification has been developed. However, methods to determine consensus molecular subtypes require validation, particularly when FFPE specimens are used. Here, we aimed to evaluate two gene expression analysis methods on FFPE samples and to compare reduced gene sets to classify tumors into molecular subtypes. Methods RNA was isolated from FFPE blocks of 15 MIBC patients. Massive analysis of 3’ cDNA ends (MACE) and the HTG transcriptome panel (HTP) were used to retrieve gene expression. We used normalized, log2-transformed data to call consensus and TCGA subtypes with the consensusMIBC package for R using all available genes, a 68-gene panel (ESSEN1), and a 48-gene panel (ESSEN2). Results Fifteen MACE-samples and 14 HTP-samples were available for molecular subtyping. The 14 samples were classified as Ba/Sq in 7 (50%), LumP in 2 (14.3%), LumU in 1 (7.1%), LumNS in 1 (7.1%), stroma-rich in 2 (14.3%) and NE-like in 1 (7.1%) case based on MACE- or HTP-derived transcriptome data. Consensus subtypes were concordant in 71% (10/14) of cases when comparing MACE with HTP data. Four cases with aberrant subtypes had a stroma-rich molecular subtype with either method. The overlap of the molecular consensus subtypes with the reduced ESSEN1 and ESSEN2 panels were 86% and 100%, respectively, with HTP data and 86% with MACE data. Conclusion Determination of consensus molecular subtypes of MIBC from FFPE samples is feasible using various RNA sequencing methods. Inconsistent classification mainly involves the stroma-rich molecular subtype, which may be the consequence of sample heterogeneity with (stroma)-cell sampling bias and highlights the limitations of bulk RNA-based subclassification. Classification is still reliable when analysis is reduced to selected genes

CK5/6 and GATA3 defined phenotypes of muscle-invasive bladder cancer: impact in adjuvant chemotherapy and molecular subtyping of negative cases

Introduction and Objective: Identifying patients that benefit from cisplatin-based adjuvant chemotherapy is a major issue in the management of muscle-invasive bladder cancer (MIBC). The purpose of this study is to correlate “luminal” and “basal” type protein expression with histological subtypes, to investigate the prognostic impact on survival after adjuvant chemotherapy and to define molecular consensus subtypes of “double negative” patients (i.e., without expression of CK5/6 or GATA3). Materials and Methods: We performed immunohistochemical (IHC) analysis of CK5/6 and GATA3 for surrogate molecular subtyping in 181 MIBC samples. The mRNA expression profiles for molecular consensus classification were determined in CK5/6 and GATA3 (double) negative cases using a transcriptome panel with 19.398 mRNA targets (HTG Molecular Diagnostics). Data of 110 patients undergoing radical cystectomy were available for survival analysis. Results: The expression of CK5/6 correlated with squamous histological subtype (96%) and expression of GATA3 was associated with micropapillary histology (100%). In the multivariate Cox-regression model, patients receiving adjuvant chemotherapy had a significant survival benefit (hazard ratio [HR]: 0.19 95% confidence interval [CI]: 0.1–0.4, p < 0.001) and double-negative cases had decreased OS (HR: 4.07; 95% CI: 1.5–10.9, p = 0.005). Double negative cases were classified as NE-like (30%), stroma-rich (30%), and Ba/Sq (40%) consensus molecular subtypes and displaying different histological subtypes

Overexpression of KMT9α Is Associated with Aggressive Basal-like Muscle-Invasive Bladder Cancer

Muscle-invasive bladder cancer (MIBC) is associated with limited response rates to systemic therapy leading to a significant risk of recurrence and death. A recently discovered histone methyltransferase KMT9, acts as an epigenetic regulator of carcinogenesis in different tumor entities. In this study, we investigated the presence and association of histological and molecular subtypes and their impact on the survival of KMT9α in MIBC. We performed an immunohistochemical (IHC) analysis of KMT9α in 135 MIBC patients undergoing radical cystectomy. KMT9α was significantly overexpressed in the nucleus in MIBC compared to normal urothelium and low-grade urothelial cancer. Using the HTG transcriptome panel, we assessed mRNA expression profiles to determine molecular subtypes and identify differentially expressed genes. Patients with higher nuclear and nucleolar KMT9α expression showed basal/squamous urothelial cancer characteristics confirmed by IHC and differentially upregulated KRT14 expression. We identified a subset of patients with nucleolar expression of KMT9α, which was associated with an increased risk of death in uni- and multivariate analyses (HR 2.28, 95%CI 1.28–4.03, p = 0.005). In conclusion, basal-like MIBC and the squamous histological subtype are associated with high nuclear KMT9α expression. The association with poor survival makes it a potential target for the treatment of bladder cancer

Variability of genomic traits among genome-sequenced members of the family <i>Burkholderiaceae</i>.

<p>The depicted traits are the total number of ORFs, G+C content of the genomes, percentage of CDS encoding signal peptides, transmembrane domains, genes assigned to Enzyme Commission (EC) number classes, proteins assigned to protein families (Pfam), proteins assigned to KEGG categories, and proteins involved in signal transduction. For most traits, 78 genomes of strains affiliated with the family were analyzed using the IMG system <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032772#pone.0032772-Markowitz1" target="_blank">[24]</a>. The sole exception is the analysis of signal transduction genes, which was performed using the MIST2 database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032772#pone.0032772-Ulrich1" target="_blank">[69]</a>, which provided data on 37 strains affiliated with the <i>Burkholderiaceae</i>. For all depicted parameters, all available genomes of family members were considered but not the genome of the endosymbiotic <i>Polynucleobacter</i> strain STIR1. Data of strain QLW-P1DMWA-1 are indicated as red dots.</p