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  • 1
    Publication Date: 2015-07-02
    Description: Stem cells present unique regenerative abilities, offering great potential for treatment of prevalent pathologies such as diabetes, neurodegenerative and heart diseases. Various research groups dedicated significant effort to identify sets of genes—so-called stemness signatures —considered essential to define stem cells. However, their usage has been hindered by the lack of comprehensive resources and easy-to-use tools. For this we developed StemChecker , a novel stemness analysis tool, based on the curation of nearly fifty published stemness signatures defined by gene expression, RNAi screens, Transcription Factor (TF) binding sites, literature reviews and computational approaches. StemChecker allows researchers to explore the presence of stemness signatures in user-defined gene sets, without carrying-out lengthy literature curation or data processing. To assist in exploring underlying regulatory mechanisms, we collected over 80 target gene sets of TFs associated with pluri- or multipotency. StemChecker presents an intuitive graphical display, as well as detailed statistical results in table format, which helps revealing transcriptionally regulatory programs, indicating the putative involvement of stemness-associated processes in diseases like cancer. Overall, StemChecker substantially expands the available repertoire of online tools, designed to assist the stem cell biology, developmental biology, regenerative medicine and human disease research community. StemChecker is freely accessible at http://stemchecker.sysbiolab.eu .
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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    Publication Date: 2022-10-27
    Description: © The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in da Fonseca, R. R., Couto, A., Machado, A. M., Brejova, B., Albertin, C. B., Silva, F., Gardner, P., Baril, T., Hayward, A., Campos, A., Ribeiro, A. M., Barrio-Hernandez, I., Hoving, H. J., Tafur-Jimenez, R., Chu, C., Frazao, B., Petersen, B., Penaloza, F., Musacchia, F., Alexander, G. C., Osorio, H., Winkelmann, I., Simakov, O., Rasmussen, S., Rahman, M. Z., Pisani, D., Vinther, J., Jarvis, E., Zhang, G., Strugnell, J. M., Castro, L. F. C., Fedrigo, O., Patricio, M., Li, Q., Rocha, S., Antunes, A., Wu, Y., Ma, B., Sanges, R., Vinar, T., Blagoev, B., Sicheritz-Ponten, T., Nielsen, R., & Gilbert, M. T. P. A draft genome sequence of the elusive giant squid, Architeuthis dux. Gigascience, 9(1), (2020): giz152. doi: 10.1093/gigascience/giz152.
    Description: Background: The giant squid (Architeuthis dux; Steenstrup, 1857) is an enigmatic giant mollusc with a circumglobal distribution in the deep ocean, except in the high Arctic and Antarctic waters. The elusiveness of the species makes it difficult to study. Thus, having a genome assembled for this deep-sea–dwelling species will allow several pending evolutionary questions to be unlocked. Findings: We present a draft genome assembly that includes 200 Gb of Illumina reads, 4 Gb of Moleculo synthetic long reads, and 108 Gb of Chicago libraries, with a final size matching the estimated genome size of 2.7 Gb, and a scaffold N50 of 4.8 Mb. We also present an alternative assembly including 27 Gb raw reads generated using the Pacific Biosciences platform. In addition, we sequenced the proteome of the same individual and RNA from 3 different tissue types from 3 other species of squid (Onychoteuthis banksii, Dosidicus gigas, and Sthenoteuthis oualaniensis) to assist genome annotation. We annotated 33,406 protein-coding genes supported by evidence, and the genome completeness estimated by BUSCO reached 92%. Repetitive regions cover 49.17% of the genome. Conclusions: This annotated draft genome of A. dux provides a critical resource to investigate the unique traits of this species, including its gigantism and key adaptations to deep-sea environments.
    Description: R.R.F. thanks the Villum Fonden for grant VKR023446 (Villum Fonden Young Investigator Grant), the Portuguese Science Foundation (FCT) for grant PTDC/MAR/115347/2009; COMPETE-FCOMP-01-012; FEDER-015453, Marie Curie Actions (FP7-PEOPLE-2010-IEF, Proposal 272927), and the Danish National Research Foundation (DNRF96) for its funding of the Center for Macroecology, Evolution, and Climate. H.O. thanks the Rede Nacional de Espectrometria de Massa, ROTEIRO/0028/2013, ref. LISBOA-01-0145-FEDER-022125, supported by COMPETE and North Portugal Regional Operational Programme (Norte2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). A.C. thanks FCT for project UID/Multi/04423/2019. M.P. acknowledges the support from the Wellcome Trust (grant number WT108749/Z/15/Z) and the European Molecular Biology Laboratory. M.P.T.G. thanks the Danish National Research Foundation for its funding of the Center for GeoGenetics (grant DNRF94) and Lundbeck Foundation for grant R52–5062 on Pathogen Palaeogenomics. S.R. was supported by the Novo Nordisk Foundation grant NNF14CC0001. A.H. is supported by a Biotechnology and Biological Sciences Research Council David Phillips Fellowship (fellowship reference: BB/N020146/1). T.B. is supported by the Biotechnology and Biological Sciences Research Council-funded South West Biosciences Doctoral Training Partnership (training grant reference BB/M009122/1). This work was partially funded by the Lundbeck Foundation (R52-A4895 to B.B.). H.J.T.H. was supported by the David and Lucile Packard Foundation, the Netherlands Organization for Scientific Research (#825.09.016), and currently by the Deutsche Forschungsgemeinschaft (DFG) under grant HO 5569/2-1 (Emmy Noether Junior Research Group). T.V. and B. Brejova were supported by grants from the Slovak grant agency VEGA (1/0684/16, 1/0458/18). F.S. was supported by a PhD grant (SFRH/BD/126560/2016) from FCT. A.A. was partly supported by the FCT project PTDC/CTA-AMB/31774/2017. C.C. and Y.W. are partly supported by grant IIS-1526415 from the US National Science Foundation. Computation for the work described in this article was partially supported by the DeiC National Life Science Supercomputer at DTU.
    Keywords: Cephalopod ; Invertebrate ; Genome assembly
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 6
    Publication Date: 2013-09-26
    Description: The p53 core domain binds to response elements (REs) that contain two continuous half-sites as a cooperative tetramer, but how p53 recognizes discontinuous REs is not well understood. Here we describe the crystal structure of the p53 core domain bound to a naturally occurring RE located at the promoter of the Bcl-2-associated X protein (BAX) gene, which contains a one base-pair insertion between the two half-sites. Surprisingly, p53 forms a tetramer on the BAX-RE that is nearly identical to what has been reported on other REs with a 0-bp spacer. Each p53 dimer of the tetramer binds in register to a half-site and maintains the same protein–DNA interactions as previously observed, and the two dimers retain all the protein–protein contacts without undergoing rotation or translation. To accommodate the additional base pair, the DNA is deformed and partially disordered around the spacer region, resulting in an apparent unwinding and compression, such that the interactions between the dimers are maintained. Furthermore, DNA deformation within the p53-bound BAX-RE is confirmed in solution by site-directed spin labeling measurements. Our results provide a structural insight into the mechanism by which p53 binds to discontinuous sites with one base-pair spacer.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 7
    Publication Date: 2015-05-16
    Description: The expected quality of paternal behavior can influence female mating decisions and determine male mating success. We evaluated the importance of oviposition site quality, male body size, parental status (presence vs. absence of eggs under males’ protection), and time invested in care (less vs. more than 1 month) for male mating success in the harvestman Iporangaia pustulosa . The chances of acquiring a clutch are relatively small for noncaring males but increase nearly 4 times once males start caring for eggs. After 1 month of caring, the chances of acquiring an additional clutch show a marked decline, probably because the cumulative energetic costs imposed by paternal care decreases males’ attractiveness or their ability to replenish gametes throughout the caring period. Therefore, male mating success seems to be affected by a combination of presence of eggs and body condition while caring. Because the presence of eggs increases male attractiveness, we also conducted a field experiment removing caring males from their broods and expected that noncaring males would adopt unattended broods as a deceptive strategy to acquire matings. However, noncaring males cannibalized eggs and no brood adoption was recorded. Because well-fed males stay stationary on the vegetation waiting for mating opportunities, unattended broods may have been found more often by vagrant and poorly fed males. We argue that detailed comprehension of the costs and the benefits of paternal activities, as well as the direct benefits of female preference, is fundamental to better understand the interaction between male care and female mate choice.
    Print ISSN: 1045-2249
    Electronic ISSN: 1465-7279
    Topics: Biology
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  • 8
    Publication Date: 2016-06-30
    Description: Thousands of long noncoding RNAs (lncRNAs) have been annotated in eukaryotic genomes, but comparative transcriptomic approaches are necessary to understand their biological impact and evolution. To facilitate such comparative studies in Drosophila , we identified and characterized lncRNAs in a second Drosophilid —the evolutionary model Drosophila pseudoobscura . Using RNA-Seq and computational filtering of protein-coding potential, we identified 1,589 intergenic lncRNA loci in D. pseudoobscura . We surveyed multiple sex-specific developmental stages and found, like in Drosophila melanogaster , increasingly prolific lncRNA expression through male development and an overrepresentation of lncRNAs in the testes. Other trends seen in D. melanogaster , like reduced pupal expression, were not observed. Nonrandom distributions of female-biased and non-testis-specific male-biased lncRNAs between the X chromosome and autosomes are consistent with selection-based models of gene trafficking to optimize genomic location of sex-biased genes. The numerous testis-specific lncRNAs, however, are randomly distributed between the X and autosomes, and we cannot reject the hypothesis that many of these are likely to be spurious transcripts. Finally, using annotated lncRNAs in both species, we identified 134 putative lncRNA homologs between D. pseudoobscura and D. melanogaster and find that many have conserved developmental expression dynamics, making them ideal candidates for future functional analyses.
    Electronic ISSN: 1759-6653
    Topics: Biology
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  • 9
    Publication Date: 2015-10-16
    Description: We present an analysis of the evolving comoving cumulative number density of galaxy populations found in the Illustris simulation. Cumulative number density is commonly used to link galaxy populations across different epochs by assuming that galaxies preserve their number density in time. Our analysis allows us to examine the extent to which this assumption holds in the presence of galaxy mergers or when rank ordering is broken owing to variable stellar growth rates. Our primary results are as follows: (1) the inferred average stellar mass evolution obtained via a constant comoving number density assumption is systematically biased compared to the merger tree results at the factor of ~2(4) level when tracking galaxies from redshift z  = 0 to 2(3); (2) the median number density evolution for galaxy populations tracked forward in time is shallower than for galaxy populations tracked backward; (3) a similar evolution in the median number density of tracked galaxy populations is found regardless of whether number density is assigned via stellar mass, stellar velocity dispersion, or halo mass; (4) explicit tracking reveals a large diversity in the stellar and dark matter assembly histories that cannot be captured by constant number density analyses; (5) the significant scatter in galaxy linking methods is only marginally reduced (~20 per cent) by considering additional physical galaxy properties. We provide fits for the median evolution in number density for use with observational data and discuss the implications of our analysis for interpreting multi-epoch galaxy property observations.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 10
    Publication Date: 2015-04-10
    Description: Asteroseismology is a unique tool to explore the internal structure of stars through both observational and theoretical research. The internal structure of pulsating hydrogen shell white dwarfs (ZZ Ceti stars) detected by asteroseismology is regarded as the representative of all DA white dwarfs. Observations for KUV 08368+4026, which locates in the middle of the ZZ Ceti instability strip, have been carried out in 1999 and from 2009 to 2012 with either single-site runs or multisite campaigns. Time series photometric data of about 300 h were collected in total. Through data reduction and analysis, 30 frequencies were extracted, including four triplets, two doublets, one single mode and further signals. The independent modes are identified as either l = 1 or l = 2 modes. Hence, a rotation period of 5.52 ± 0.22 d was deduced from the period spacing in the multiplets. Theoretical static models were built and a best-fitting model for KUV 08368+4026 was obtained with 0.692 ± 0.002 M , (2.92 ± 0.02) x 10 –3 L and the hydrogen mass fraction of 10 –4 stellar mass.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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