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  • 11
    Publication Date: 2015-12-16
    Description: Ribosome biogenesis is one of the most essential pathways in eukaryotes although it is still not fully characterized. Given the importance of this process in proliferating cells, it is obvious that understanding the macromolecular details of the interactions that take place between the assembly factors, ribosomal proteins and nascent pre-rRNAs is essentially required for the development of new non-genotoxic treatments for cancer. Herein, we have studied the association between the WD40-repeat domains of Erb1 and Ytm1 proteins. These are essential factors for the biogenesis of 60S ribosomal subunits in eukaryotes that form a heterotrimeric complex together with the also essential Nop7 protein. We provide the crystal structure of a dimer formed by the C-terminal part of Erb1 and Ytm1 from Chaetomium thermophilum at 2.1 Å resolution. Using a multidisciplinary approach we show that the β-propeller domains of these proteins interact in a novel manner that leads to a high-affinity binding. We prove that a point mutation within the interface of the complex impairs the interaction between the two proteins and negatively affects growth and ribosome production in yeast. Our study suggests insights into the association of the Erb1-Ytm1 dimer with pre-ribosomal particles.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 12
    Publication Date: 2016-06-16
    Description: Motivation: Developing targeted therapeutics and identifying biomarkers relies on large amounts of research participant data. Beyond human DNA, scientists now investigate the DNA of micro-organisms inhabiting the human body. Recent work shows that an individual’s collection of microbial DNA consistently identifies that person and could be used to link a real-world identity to a sensitive attribute in a research dataset. Unfortunately, the current suite of DNA-specific privacy-preserving analysis tools does not meet the requirements for microbiome sequencing studies. Results: To address privacy concerns around microbiome sequencing, we implement metagenomic analyses using secure computation. Our implementation allows comparative analysis over combined data without revealing the feature counts for any individual sample. We focus on three analyses and perform an evaluation on datasets currently used by the microbiome research community. We use our implementation to simulate sharing data between four policy-domains. Additionally, we describe an application of our implementation for patients to combine data that allows drug developers to query against and compensate patients for the analysis. Availability and implementation: The software is freely available for download at: http://cbcb.umd.edu/~hcorrada/projects/secureseq.html Supplementary information: Supplementary data are available at Bioinformatics online. Contact: hcorrada@umiacs.umd.edu
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 13
    Publication Date: 2016-06-01
    Description: Motivation: DNA methylation aberrations are now known to, almost universally, accompany the initiation and progression of cancers. In particular, the colon cancer epigenome contains specific genomic regions that, along with differences in methylation levels with respect to normal colon tissue, also show increased epigenetic and gene expression heterogeneity at the population level, i.e. across tumor samples, in comparison with other regions in the genome. Tumors are highly heterogeneous at the clonal level as well, and the relationship between clonal and population heterogeneity is poorly understood. Results: We present an approach that uses sequencing reads from high-throughput sequencing of bisulfite-converted DNA to reconstruct heterogeneous cell populations by assembling cell-specific methylation patterns. Our methodology is based on the solution of a specific class of minimum cost network flow problems. We use our methods to analyze the relationship between clonal heterogeneity and population heterogeneity in high-coverage data from multiple samples of colon tumor and matched normal tissues. Availability and implementation : http://github.com/hcorrada/methylFlow . Contact: hcorrada@umiacs.umd.edu Supplementary information: Supplementary information is available at Bioinformatics online .
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 14
    Publication Date: 2016-07-09
    Description: Motivation: DisGeNET-RDF makes available knowledge on the genetic basis of human diseases in the Semantic Web. Gene-disease associations (GDAs) and their provenance metadata are published as human-readable and machine-processable web resources. The information on GDAs included in DisGeNET-RDF is interlinked to other biomedical databases to support the development of bioinformatics approaches for translational research through evidence-based exploitation of a rich and fully interconnected linked open data. Availability and implementation: http://rdf.disgenet.org/ Contact: support@disgenet.org
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 15
    Publication Date: 2011-11-24
    Description: Nothofagus nitida (Phil.) Krasser (Nothofagaceae) regenerates under the canopy in microsites protected from high light. Nonetheless, it is common to find older saplings in clear areas and adults as emergent trees of the Chilean evergreen forest. We hypothesized that this shade to sun transition in N. nitida is supported by an increase in photochemical and non-photochemical energy dissipation capacities of both photosystems in parallel with the increase in plant size and light availability. To dissect the relative contribution of light environment and plant developmental stage to these physiological responses, the photosynthetic performance of both photosystems was studied from the morpho-anatomical to the biochemical level in current-year leaves of N. nitida plants of different heights (ranging from 0.1 to 7 m) growing under contrasting light environments (integrated quantum flux (IQF) 5–40 mol m –2  day –1 ). Tree height (TH) and light environment (IQF) independently increased the saturated electron transport rates of both photosystems, as well as leaf and palisade thickness, but non-photochemical energy flux, photoinhibition susceptibility, state transition capacity, and the contents of D1 and PsbS proteins were not affected by IQF and TH. Spongy mesophyll thickness and palisade cell diameter decreased with IQF and TH. A max , light compensation and saturation points, Rubisco and nitrogen content (area basis) only increased with light environment (IQF), whereas dark respiration ( R d ) decreased slightly and relative chlorophyll content was higher in taller trees. Overall, the independent effects of more illuminated environment and tree height mainly increased the photochemical instead of the non-photochemical energy flux. Regardless of the photochemical increase with TH, carbon assimilation only significantly improved with higher IQF. Therefore it seems that mainly acclimation to the light environment supports the phenotypic transition of N. nitida from shade to sun.
    Print ISSN: 0829-318X
    Electronic ISSN: 1758-4469
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 16
    Publication Date: 2014-01-22
    Description: Papillomaviruses (PVs) are widespread pathogens. However, the extent of PV infections in bats remains largely unknown. This work represents the first comprehensive study of PVs in Iberian bats. We identified four novel PVs in the mucosa of free-ranging Eptesicus serotinus (EserPV1, EserPV2, and EserPV3) and Rhinolophus ferrumequinum (RferPV1) individuals and analyzed their phylogenetic relationships within the viral family. We further assessed their prevalence in different populations of E. serotinus and its close relative E. isabellinus . Although it is frequent to read that PVs co-evolve with their host, that PVs are highly species-specific, and that PVs do not usually recombine, our results suggest otherwise. First, strict virus–host co-evolution is rejected by the existence of five, distantly related bat PV lineages and by the lack of congruence between bats and bat PVs phylogenies. Second, the ability of EserPV2 and EserPV3 to infect two different bat species ( E. serotinus and E. isabellinus ) argues against strict host specificity. Finally, the description of a second noncoding region in the RferPV1 genome reinforces the view of an increased susceptibility to recombination in the E2-L2 genomic region. These findings prompt the question of whether the prevailing paradigms regarding PVs evolution should be reconsidered.
    Electronic ISSN: 1759-6653
    Topics: Biology
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  • 17
    Publication Date: 2014-04-29
    Description: Crown dynamics affect tree cross-sectional growth by responding to individual traits and stand history and features, i.e. species, stocking, thinning, site quality or climatic conditions. Under this assumption we analysed two simple models that relate cross-sectional growth to the growth of stem length above the cross section in four species of Mediterranean pines. Cross-sectional growth was measured at breast height. The first model (Model 0) has no parameters, and specifies an isometric relationship between cross-sectional area and stem length. The second model (Model α), which was formulated to analyse Model 0, has one parameter. Neither of the two simple models requires knowledge of crown length, though Model 0 derives – under an assumption of constant crown length – from a more general model that relates cross-sectional growth to crown length dynamics. A mixed-effects modelling strategy was selected to fit Model α in order to incorporate fixed effects of species, and random effects to account for factors like ontogeny (tree effect), stand history (plot effect) and climatic conditions (growth period). Results indicate that Model α predicts better than Model 0 when the single parameter is expanded to take into account all these effects and indicate that the constant ratio between cross-sectional area and the length of stem predicted by Model 0 is one possible value within a ratio that changes over time as function of ontogeny, stand history and climatic conditions. On average the ratio is positive, indicating greater cross-sectional growth than height growth showing greater variation in stem formation. Inter-specific analysis indicated a less asymmetric behaviour in competition for pine species growing in water-stress environment
    Print ISSN: 0015-752X
    Electronic ISSN: 1464-3626
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 18
    Publication Date: 2013-12-12
    Description: In this paper, we study conditions for the vanishing of Abelian integrals on families of zero-dimensional cycles. That is, for any rational function f ( z ), characterize all rational functions g ( z ) and zero-sum integers { n i } such that the function t ↦ n i g ( z i ( t )) vanishes identically. Here z i ( t ) are continuously depending roots of f ( z )– t . We introduce a notion of (un)balanced cycles. Our main result is an inductive solution of the problem of vanishing of Abelian integrals when f , g are polynomials on a family of zero-dimensional cycles under the assumption that the family of cycles we consider as well as all the cycles encountered in the inductive process is unbalanced. We also solve the problem on some balanced cycles. The main motivation for our study is the problem of the vanishing of Abelian integrals on single families of one-dimensional cycles. We show that our problem and our main result are sufficiently rich to include some related problems, such as hyper-elliptic integrals on one-cycles, some applications to slow-fast planar systems and the polynomial (and trigonometric) moment problem for the Abel equation. This last problem was recently solved by Pakovich [ Bull. Sci. Math. 133 (2009) 693–732] and Pakovich and Muzychuk [ Proc. London Math. Soc. 99 (2009) 633–657]. Our approach is largely inspired by their work, thought we provide examples of vanishing Abelian integrals on zero-cycles that are not given as a sum of composition terms in contrast to the situation in the solution of the polynomial moment problem.
    Print ISSN: 0024-6115
    Electronic ISSN: 1460-244X
    Topics: Mathematics
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  • 19
    Publication Date: 2014-04-03
    Description: The amount of tissue-specific expression variability (EV) across individuals is an essential characteristic of a gene and believed to have evolved, in part, under functional constraints. However, the determinants and functional implications of EV are only beginning to be investigated. Our analyses based on multiple expression profiles in 41 primary human tissues show that a gene’s EV is significantly correlated with a number of features pertaining to the genomic, epigenomic, regulatory, polymorphic, functional, structural and network characteristics of the gene. We found that (i) EV of a gene is encoded, in part, by its genomic context and is further influenced by the epigenome; (ii) strong promoters induce less variable expression; (iii) less variable gene loci evolve under purifying selection against copy number polymorphisms; (iv) genes that encode inherently disordered or highly interacting proteins exhibit lower variability; and (v) genes with less variable expression are enriched for house-keeping functions, while genes with highly variable expression tend to function in development and extra-cellular response and are associated with human diseases. Thus, our analysis reveals a number of potential mediators as well as functional and evolutionary correlates of EV, and provides new insights into the inherent variability in eukaryotic gene expression.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 20
    Publication Date: 2014-04-25
    Description: Motivation: Base-calling of sequencing data produced by high-throughput sequencing platforms is a fundamental process in current bioinformatics analysis. However, existing third-party probabilistic or machine-learning methods that significantly improve the accuracy of base-calls on these platforms are impractical for production use due to their computational inefficiency. Results: We directly formulate base-calling as a blind deconvolution problem and implemented BlindCall as an efficient solver to this inverse problem. BlindCall produced base-calls at accuracy comparable to state-of-the-art probabilistic methods while processing data at rates 10 times faster in most cases. The computational complexity of BlindCall scales linearly with read length making it better suited for new long-read sequencing technologies. Availability and Implementation: BlindCall is implemented as a set of Matlab scripts available for download at http://cbcb.umd.edu/~hcorrada/secgen . Contact: hcorrada@umiacs.umd.edu
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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