„Biosphärenbildung“ : Ein neuer Begriff – Anstoß für eine breitere Diskussion?

Zusammenfassend gesagt hat das Biosphärenbildungskonzept über den Kompetenzbegriff hinaus eine wichtige emphatische Komponente. Es ist: affektiv indem die Menschen innerlich berührt werden, kognitiv indem wissenschaftliche und ethische Grundlagenkenntnisse (auch über Nachhaltigkeit) vermittelt werden, aktiv indem ökologische Orientierungen für Handlungsoptionen und Lebensstile, also Verantwortlichkeiten für nachfolgende Generationen gefördert werden

The Governance of International Nongovernmental Organizations: How Funding and Volunteer Involvement Affect Board Nomination Modes and Stakeholder Representation in International Nongovernmental Organizations

The governance of civil society organizations (CSOs) is a crucial determinant of organizational legitimacy, accountability, and performance. International nongovernmental organizations (INGOs) are a subtype of CSOs and have received a lot of attention as actors in global governance. Research suggests that INGOs can follow a membership model, where the board is elected by the membership, or a board-managed model, where the board is appointed to represent major stakeholders. Following resource dependency theory, we argue that the choice between these two models depends on the INGOs different sources of funding and the degree of volunteer involvement: As donors and volunteers provide important resources, they are in turn granted the right to nominate board members or to sit on the board. In our quantitative study we show that individual members, regional member organizations, and governmental donors hold a stronger position in the governance of INGOs than philanthropists, foundations and volunteers. Our results inform research on CSO governance by highlighting the relevance of board nomination modes and by showing how CSOs can incorporate stakeholders into their governance mechanism

YKL ‐40 genetic polymorphisms and the risk of liver disease progression in patients with advanced fibrosis due to chronic hepatitis C

Background/Aims The aim of this study was to explore the association of a functional YKL ‐40 promoter polymorphism (rs4950928) with baseline disease stage, response to antiviral therapy and risk of liver disease progression in a group of patients with chronic hepatitis C ( CHC ). Methods YKL ‐40 promoter polymorphisms were determined in 456 H epatitis C A ntiviral L ong‐term T reatment against C irrhosis ( HALT ‐C) T rial patients with bridging fibrosis or cirrhosis entering a prerandomization lead‐in peginterferon/ribavirin 24‐week treatment phase and in 462 patients followed for a mean of 3.8 years after randomization to maintenance peginterferon or observation. Results Mean patient age was 49.5 years, 70.4% were men and 71.2% were Caucasian. The 17% frequency of the YKL ‐40 minor allele (T) was similar to that reported in the general population. YKL ‐40 genotype was associated significantly with baseline serum YKL ‐40 levels but was not associated with the likelihood of a virological response following 24–48 weeks of peginterferon/ribavirin therapy. Serum YKL ‐40 levels remained significantly lower during follow‐up in the randomized TT homozygotes compared with CT heterozygotes and CC homozygotes ( P  < 0.001). Despite this association, YKL ‐40 genotype was not associated with the risk of clinical or histological liver disease progression. Conclusions A reduced frequency of the protective YKL ‐40 promoter polymorphism was not observed in the HALT ‐C T rial patient population. The absence of an association between YKL ‐40 promoter polymorphisms and baseline liver disease severity as well as with the risk of liver disease progression over time suggests that this polymorphism is not associated with disease progression in CHC patients with established fibrosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90574/1/liv2686.pd

Update of the FANTOM web resource: from mammalian transcriptional landscape to its dynamic regulation

The international Functional Annotation Of the Mammalian Genomes 4 (FANTOM4) research collaboration set out to better understand the transcriptional network that regulates macrophage differentiation and to uncover novel components of the transcriptome employing a series of high-throughput experiments. The primary and unique technique is cap analysis of gene expression (CAGE), sequencing mRNA 5′-ends with a second-generation sequencer to quantify promoter activities even in the absence of gene annotation. Additional genome-wide experiments complement the setup including short RNA sequencing, microarray gene expression profiling on large-scale perturbation experiments and ChIP-chip for epigenetic marks and transcription factors. All the experiments are performed in a differentiation time course of the THP-1 human leukemic cell line. Furthermore, we performed a large-scale mammalian two-hybrid (M2H) assay between transcription factors and monitored their expression profile across human and mouse tissues with qRT-PCR to address combinatorial effects of regulation by transcription factors. These interdependent data have been analyzed individually and in combination with each other and are published in related but distinct papers. We provide all data together with systematic annotation in an integrated view as resource for the scientific community (http://fantom.gsc.riken.jp/4/). Additionally, we assembled a rich set of derived analysis results including published predicted and validated regulatory interactions. Here we introduce the resource and its update after the initial releas

Gene expression and splicing alterations analyzed by high throughput RNA sequencing of chronic lymphocytic leukemia specimens.

BackgroundTo determine differentially expressed and spliced RNA transcripts in chronic lymphocytic leukemia specimens a high throughput RNA-sequencing (HTS RNA-seq) analysis was performed.MethodsTen CLL specimens and five normal peripheral blood CD19+ B cells were analyzed by HTS RNA-seq. The library preparation was performed with Illumina TrueSeq RNA kit and analyzed by Illumina HiSeq 2000 sequencing system.ResultsAn average of 48.5 million reads for B cells, and 50.6 million reads for CLL specimens were obtained with 10396 and 10448 assembled transcripts for normal B cells and primary CLL specimens respectively. With the Cuffdiff analysis, 2091 differentially expressed genes (DEG) between B cells and CLL specimens based on FPKM (fragments per kilobase of transcript per million reads and false discovery rate, FDR q &lt; 0.05, fold change &gt;2) were identified. Expression of selected DEGs (n = 32) with up regulated and down regulated expression in CLL from RNA-seq data were also analyzed by qRT-PCR in a test cohort of CLL specimens. Even though there was a variation in fold expression of DEG genes between RNA-seq and qRT-PCR; more than 90 % of analyzed genes were validated by qRT-PCR analysis. Analysis of RNA-seq data for splicing alterations in CLL and B cells was performed by Multivariate Analysis of Transcript Splicing (MATS analysis). Skipped exon was the most frequent splicing alteration in CLL specimens with 128 significant events (P-value &lt;0.05, minimum inclusion level difference &gt;0.1).ConclusionThe RNA-seq analysis of CLL specimens identifies novel DEG and alternatively spliced genes that are potential prognostic markers and therapeutic targets. High level of validation by qRT-PCR for a number of DEG genes supports the accuracy of this analysis. Global comparison of transcriptomes of B cells, IGVH non-mutated CLL (U-CLL) and mutated CLL specimens (M-CLL) with multidimensional scaling analysis was able to segregate CLL and B cell transcriptomes but the M-CLL and U-CLL transcriptomes were indistinguishable. The analysis of HTS RNA-seq data to identify alternative splicing events and other genetic abnormalities specific to CLL is an added advantage of RNA-seq that is not feasible with other genome wide analysis

Molecular basis for the reproductive division of labour in a lower termite

<p>Abstract</p> <p>Background</p> <p>Polyphenism, the expression of different phenotypes with the same genetic background, is well known for social insects. The substantial physiological and morphological differences among the castes generally are the result of differential gene expression. In lower termites, workers are developmentally flexible to become neotenic replacement reproductives via a single moult after the death of the founding reproductives. Thus, both castes (neotenics and workers) are expected to differ mainly in the expression of genes linked to reproductive division of labour, which constitutes the fundamental basis of insect societies.</p> <p>Results</p> <p>Representational difference analysis of cDNAs was used to study differential gene expression between neotenics and workers in the drywood termite <it>Cryptotermes secundus </it>(Kalotermitidae). We identified and, at least partially cloned five novel genes that were highly expressed in female neotenics. Quantitative real-time PCR analysis of all five genes in different castes (neotenics, founding reproductives, winged sexuals and workers of both sexes) confirmed the differential expression patterns. In addition, the relative expression of these genes was determined in three body parts of female neotenics (head, thorax, and abdomen) using quantitative real-time PCR.</p> <p>Conclusion</p> <p>The identified genes could be involved in the control and regulation of reproductive division of labour. Interestingly, this study revealed an expression pattern partly similar to social Hymenoptera indicating both common and species-specific regulatory mechanisms in hemimetabolous and holometabolous social insects.</p

Rapid and sensitive detection of CpG-methylation using methyl-binding (MB)-PCR

Methylation of CpG islands is associated with transcriptional repression and, in cancer, leads to the abnormal silencing of tumor suppressor genes. We have developed a novel technique for detecting CpG-methylated DNA termed methyl-binding (MB)-PCR. This technique utilizes a recombinant protein with high affinity for CpG-methylated DNA that is coated onto the walls of a PCR vessel and selectively captures methylated DNA fragments from a mixture of genomic DNA. The retention and, hence, the degree of methylation of a specific DNA fragment (e.g. a CpG island promoter of a specific gene) is detected in the same tube by gene-specific PCR. MB-PCR does not require bisulfite treatment or methylation-sensitive restriction and provides a quick, simple and extremely sensitive technique allowing the detection of methylated DNA, in particular in tumor tissue or tumor cells from limited samples. Using this novel approach, we determined the methylation status of several established and candidate tumor suppressor genes and identified the ICSBP gene, encoding the myeloid and B-cell-specific transcription factor interferon consensus sequence-binding protein, as a target for aberrant hypermethylation in acute myeloid leukemia

Active DNA demethylation in human postmitotic cells correlates with activating histone modifications, but not transcription levels

Background: In mammals, the dynamics of DNA methylation, in particular the regulated, active removal of cytosine methylation, has remained a mystery, partly due to the lack of appropriate model systems to study DNA demethylation. Previous work has largely focused on proliferating cell types that are mitotically arrested using pharmacological inhibitors to distinguish between active and passive mechanisms of DNA demethylation. Results: We explored this epigenetic phenomenon in a natural setting of post-mitotic cells: the differentiation of human peripheral blood monocytes into macrophages or dendritic cells, which proceeds without cell division. Using a global, comparative CpG methylation profiling approach, we identified many novel examples of active DNA demethylation and characterized accompanying transcriptional and epigenetic events at these sites during monocytic differentiation. We show that active DNA demethylation is not restricted to proximal promoters and that the time-course of demethylation varies for individual CpGs. Irrespective of their location, the removal of methylated cytosines always coincided with the appearance of activating histone marks. Conclusions: Demethylation events are highly reproducible in monocyte-derived dendritic cells from different individuals. Our data suggest that active DNA demethylation is a precisely targeted event that parallels or follows the modification of histones, but is not necessarily coupled to alterations in transcriptional activity

Transcriptional regulation and macrophage differentiation

Monocytes and macrophages are professional phagocytes that occupy specific niches in every tissue of the body. Their survival, proliferation, and differentiation are controlled by signals from the macrophage colony-stimulating factor receptor (CSF-1R) and its two ligands, CSF-1 and interleukin-34. In this review, we address the developmental and transcriptional relationships between hematopoietic progenitor cells, blood monocytes, and tissue macrophages as well as the distinctions from dendritic cells. A huge repertoire of receptors allows monocytes, tissue-resident macrophages, or pathology-associated macrophages to adapt to specific microenvironments. These processes create a broad spectrum of macrophages with different functions and individual effector capacities. The production of large transcriptomic data sets in mouse, human, and other species provides new insights into the mechanisms that underlie macrophage functional plasticity

The epigenetic pioneer EGR2 initiates DNA demethylation in differentiating monocytes at both stable and transient binding sites

The differentiation of human blood monocytes (MO), the post-mitotic precursors of macrophages (MAC) and dendritic cells (moDC), is accompanied by the active turnover of DNA methylation, but the extent, consequences and mechanisms of DNA methylation changes remain unclear. Here, we profile and compare epigenetic landscapes during IL-4/GM-CSF-driven MO differentiation across the genome and detect several thousand regions that are actively demethylated during culture, both with or without accompanying changes in chromatin accessibility or transcription factor (TF) binding. We further identify TF that are globally associated with DNA demethylation processes. While interferon regulatory factor 4 (IRF4) is found to control hallmark dendritic cell functions with less impact on DNA methylation, early growth response 2 (EGR2) proves essential for MO differentiation as well as DNA methylation turnover at its binding sites. We also show that ERG2 interacts with the 5mC hydroxylase TET2, and its consensus binding sequences show a characteristic DNA methylation footprint at demethylated sites with or without detectable protein binding. Our findings reveal an essential role for EGR2 as epigenetic pioneer in human MO and suggest that active DNA demethylation can be initiated by the TET2-recruiting TF both at stable and transient binding sites.info:eu-repo/semantics/publishedVersio