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  • 1
    Publication Date: 2015-08-08
    Description: The original Kepler mission observed and characterized over 2400 eclipsing binaries (EBs) in addition to its prolific exoplanet detections. Despite the mechanical malfunction and subsequent non-recovery of two reaction wheels used to stabilize the instrument, the Kepler satellite continues collecting data in its repurposed K2 mission surveying a series of fields along the ecliptic plane. Here, we present an analysis of the first full baseline K2 data release: the Campaign 0 data set. In the 7761 light curves we have identified a total of 207 EBs. Of these, 97 are new discoveries that were not previously identified. Our pixel-level analysis of these objects has also resulted in identification of several false positives (observed targets contaminated by neighbouring EBs), as well as the serendipitous discovery of two short-period exoplanet candidates. We provide catalogue cross-matched source identifications, orbital periods, morphologies and ephemerides for these eclipsing systems. We also describe the incorporation of the K2 sample into the Kepler Eclipsing Binary Catalog, § present spectroscopic follow-up observations for a limited selection of nine systems and discuss prospects for upcoming K2 campaigns.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 2
    Publication Date: 2015-09-22
    Description: Zooplankton diel vertical migration (DVM) is often explained as a balance between predator avoidance and resource acquisition. However, recent studies suggest that ultraviolet radiation (UV) may also be important in driving zooplankton DVM in some systems. Williamson et al. ( Williamson et al ., 2011 ) proposed the "transparency-regulator hypothesis," which integrates UV into our current understanding of the drivers of DVM and predicts that the relative roles of UV and visual predation pressure will vary systematically across a gradient of lake transparency. To assess this hypothesis, we conducted in situ mesocosm experiments in five different lakes: two lakes without fish and three lakes with fish that spanned a range of UV and visible light transparency. We used an open-bottomed mesocosm design that allowed for the direct manipulation of UV that did not constrain visual predators or the amplitude or timing of natural migrations. Consistent with the transparency-regulator hypothesis, we found that UV is an important driver of Daphnia DVM in highly UV transparent lakes with and without fish but not in low transparency systems. Our results also suggest that UV and visual predation pressure may interact in systems of intermediate transparency.
    Print ISSN: 0142-7873
    Electronic ISSN: 1464-3774
    Topics: Biology
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  • 3
    Publication Date: 2015-11-24
    Description: Aims The biochemical defense of lichens against herbivores and its relationship to lichen frequency are poorly understood. Therefore, we tested whether chemical compounds in lichens act as feeding defense or rather as stimulus for snail herbivory among lichens and whether experimental feeding by snails is related to lichen frequency in the field. Methods In a no-choice feeding experiment, we fed 24 lichen species to snails of two taxa from the Clausilidae and Enidae families and compared untreated lichens and lichens with compounds removed by acetone rinsing. Then, we related experimental lichen consumption with the frequency of lichen species among 158 forest plots in the field (Schwäbische Alb, Germany), where we had also sampled snail and lichen species. Important findings In five lichen species, snails preferred treated samples over untreated controls, indicating chemical feeding defense, and vice versa in two species, indicating chemical feeding stimulus. Interestingly, compared with less frequent lichen species, snails consumed more of untreated and less of treated samples of more frequent lichen species. Removing one outlier species resulted in the loss of a significant positive relationship when untreated samples were analyzed separately. However, the interaction between treatment and lichen frequency remained significant when excluding single species or including snail genus instead of taxa, indicating that our results were robust and that lumping the species to two taxa was justified. Our results imply lichen-feeding snails to prefer frequent lichens and avoid less frequent ones because of secondary compound recognition. This supports the idea that consumers adapt to the most abundant food source.
    Print ISSN: 1752-993X
    Electronic ISSN: 1752-9921
    Topics: Biology
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  • 4
    Publication Date: 2015-11-21
    Description: Assisted reproductive technologies (ART) are associated with several complications including low birth weight, abnormal placentation and increased risk for rare imprinting disorders. Indeed, experimental studies demonstrate ART procedures independent of existing infertility induce epigenetic perturbations in the embryo and extraembryonic tissues. To test the hypothesis that these epigenetic perturbations persist and result in adverse outcomes at term, we assessed placental morphology and methylation profiles in E18.5 mouse concepti generated by in vitro fertilization (IVF) in two different genetic backgrounds. We also examined embryo transfer (ET) and superovulation procedures to ascertain if they contribute to developmental and epigenetic effects. Increased placental weight and reduced fetal-to-placental weight ratio were observed in all ART groups when compared with naturally conceived controls, demonstrating that non-surgical embryo transfer alone can impact placental development. Furthermore, superovulation further induced overgrowth of the placental junctional zone. Embryo transfer and superovulation defects were limited to these morphological changes, as we did not observe any differences in epigenetic profiles. IVF placentae, however, displayed hypomethylation of imprinting control regions of select imprinted genes and a global reduction in DNA methylation levels. Although we did not detect significant differences in DNA methylation in fetal brain or liver samples, rare IVF concepti displayed very low methylation and abnormal gene expression from the normally repressed allele. Our findings suggest that individual ART procedures cumulatively increase placental morphological abnormalities and epigenetic perturbations, potentially causing adverse neonatal and long-term health outcomes in offspring.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 5
    Publication Date: 2016-07-24
    Description: Since more than a decade ago, Saccharomyces cerevisiae has been used as a model to dissect complex traits, revealing the genetic basis of a large number of traits in fine detail. However, to have a more global view of the genetic architecture of traits across species, the examination of the molecular basis of phenotypes within non-conventional species would undoubtedly be valuable. In this respect, the Saccharomycotina yeasts represent ideal and potential non-model organisms. Here we sought to assess the feasibility of genetic mapping by bulk segregant analysis in the protoploid Lachancea kluyveri (formerly S. kluyveri ) yeast species, a distantly related species to S. cerevisiae . For this purpose, we designed a fluorescent mating-type marker, compatible with any mating-competent strains representative of this species, to rapidly create a large population of haploid segregants (〉10 5 cells). Quantitative trait loci can be mapped by selecting and sequencing an enriched pool of progeny with extreme phenotypic values. As a test bed, we applied this strategy and mapped the causal loci underlying halotolerance phenotypes in L. kluyveri . Overall, this study demonstrates that bulk segregant mapping is a powerful way for investigating the genetic basis of natural variations in non-model yeast organisms and more precisely in L. kluyveri .
    Print ISSN: 1567-1356
    Electronic ISSN: 1567-1364
    Topics: Biology
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  • 6
    Publication Date: 2016-07-28
    Description: Cell cycle (CC) and TP53 regulatory networks are frequently deregulated in cancer. While numerous genome-wide studies of TP53 and CC-regulated genes have been performed, significant variation between studies has made it difficult to assess regulation of any given gene of interest. To overcome the limitation of individual studies, we developed a meta-analysis approach to identify high confidence target genes that reflect their frequency of identification in independent datasets. Gene regulatory networks were generated by comparing differential expression of TP53 and CC-regulated genes with chromatin immunoprecipitation studies for TP53, RB1, E2F, DREAM, B-MYB, FOXM1 and MuvB. RNA-seq data from p21-null cells revealed that gene downregulation by TP53 generally requires p21 (CDKN1A). Genes downregulated by TP53 were also identified as CC genes bound by the DREAM complex. The transcription factors RB, E2F1 and E2F7 bind to a subset of DREAM target genes that function in G1/S of the CC while B-MYB, FOXM1 and MuvB control G2/M gene expression. Our approach yields high confidence ranked target gene maps for TP53, DREAM, MMB-FOXM1 and RB-E2F and enables prediction and distinction of CC regulation. A web-based atlas at www.targetgenereg.org enables assessing the regulation of any human gene of interest.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 7
    Publication Date: 2013-09-25
    Description: microRNAs (miRNAs) are dysregulated in a variety of disease states, suggesting that this newly discovered class of gene expression repressors may be viable therapeutic targets. A microarray of miRNA changes in ALS-model superoxide dismutase 1 (SOD1) G93A rodents identified 12 miRNAs as significantly changed. Six miRNAs tested in human ALS tissues were confirmed increased. Specifically, miR-155 was increased 5-fold in mice and 2-fold in human spinal cords. To test miRNA inhibition in the central nervous system (CNS) as a potential novel therapeutic, we developed oligonucleotide-based miRNA inhibitors (anti-miRs) that could inhibit miRNAs throughout the CNS and in the periphery. Anti-miR-155 caused global derepression of targets in peritoneal macrophages and, following intraventricular delivery, demonstrated widespread functional distribution in the brain and spinal cord. After treating SOD1 G93A mice with anti-miR-155, we significantly extended survival by 10 days and disease duration by 15 days (38%) while a scrambled control anti-miR did not significantly improve survival or disease duration. Therefore, antisense oligonucleotides may be used to successfully inhibit miRNAs throughout the brain and spinal cord, and miR-155 is a promising new therapeutic target for human ALS.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 8
    Publication Date: 2013-06-06
    Description: : High-throughput microscopy data require a diversity of analytical approaches. However, the construction of workflows that use algorithms from different software packages is difficult owing to a lack of interoperability. To overcome this limitation, we present CellH5, an HDF5 data format for cell-based assays in high-throughput microscopy, which stores high-dimensional image data along with inter-object relations in graphs. CellH5Browser, an interactive gallery image browser, demonstrates the versatility and performance of the file format on live imaging data of dividing human cells. CellH5 provides new opportunities for integrated data analysis by multiple software platforms. Availability: Source code is freely available at www.github.com/cellh5 under the GPL license and at www.bioconductor.org/packages/release/bioc/html/rhdf5.html under the Artistic-2.0 license. Demo datasets and the CellH5Browser are available at www.cellh5.org . A Fiji importer for cellh5 will be released soon. Contact: daniel.gerlich@imba.oeaw.ac.at or christoph.sommer@imba.oeaw.ac.at Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 9
    Publication Date: 2013-04-02
    Description: Increased physiological levels of oxysterols are major risk factors for developing atherosclerosis and cardiovascular disease. Lipid-loaded macrophages, termed foam cells, are important during the early development of atherosclerotic plaques. To pursue the hypothesis that ligand-based modulation of the nuclear receptor LXRα is crucial for cell homeostasis during atherosclerotic processes, we analysed genome-wide the action of LXRα in foam cells and macrophages. By integrating chromatin immunoprecipitation-sequencing (ChIP-seq) and gene expression profile analyses, we generated a highly stringent set of 186 LXRα target genes. Treatment with the nanomolar-binding ligand T0901317 and subsequent auto-regulatory LXRα activation resulted in sequence-dependent sharpening of the genome-binding patterns of LXRα. LXRα-binding loci that correlated with differential gene expression revealed 32 novel target genes with potential beneficial effects, which in part explained the implications of disease-associated genetic variation data. These observations identified highly integrated LXRα ligand-dependent transcriptional networks, including the APOE/C1/C4/C2 -gene cluster, which contribute to the reversal of cholesterol efflux and the dampening of inflammation processes in foam cells to prevent atherogenesis.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 10
    Publication Date: 2013-04-02
    Description: The TP53 tumor suppressor pathway is abrogated by TP53 mutations in the majority of human cancers. Increased levels of wild-type TP53 in aggressive neuroblastomas appear paradox but are tolerated by tumor cells due to co-activation of the TP53 ubiquitin ligase, MDM2. The role of the MDM2 antagonist, p14 ARF , in controlling the TP53-MDM2 balance in neuroblastoma is unresolved. In the present study, we show that conditional p14 ARF expression substantially suppresses viability, clonogenicity and anchorage-independent growth in p14 ARF -deficient or MYCN -amplified neuroblastoma cell lines. Furthermore, ectopic 14 ARF expression induced accumulation of cells in the G1 phase and apoptosis, which was paralleled by accumulation of TP53 and its targets. Comparative genomic hybridization analysis of 193 primary neuroblastomas detected one homozygous deletion of CDKN2A (encoding both p14 ARF and p16 INK4A ) and heterozygous loss of CDKN2A in 22% of tumors. Co-expression analysis of p14 ARF and its transactivator, E2F1, in a set of 68 primary tumors revealed only a weak correlation, suggesting that further regulatory mechanisms govern p14 ARF expression in neuroblastomas. Intriguingly, analyses utilizing chromatin immunoprecipitation revealed different histone mark-defined epigenetic activity states of p14 ARF in neuroblastoma cell lines that correlated with endogenous p14 ARF expression but not with episomal p14 ARF promoter reporter activity, indicating that the native chromatin context serves to epigenetically repress p14 ARF in neuroblastoma cells. Collectively, the data pinpoint p14 ARF as a critical factor for efficient TP53 response in neuroblastoma cells and assign p14 ARF as a neuroblastoma suppressor candidate that is impaired by genomic loss and epigenetic repression.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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