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  • 1
    Electronic Resource
    Electronic Resource
    Immunobiology of CR2, the B Lymphocyte Receptor for Epstein-Barr Virus and the C3d Complement Fragment (1988)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 6 (1988), S. 85-113 
    Details
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.iy.06.040188.000505
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    The Clinical use of Colony Stimulating Factors (1991)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 9 (1991), S. 159-191 
    Details
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.iy.09.040191.001111
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  • 3
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    ASPeak: an abundance sensitive peak detection algorithm for RIP-Seq (2013)
    Oxford University Press
    Details
    Publication Date: 2013-09-20
    Description: : Unlike DNA, RNA abundances can vary over several orders of magnitude. Thus, identification of RNA–protein binding sites from high-throughput sequencing data presents unique challenges. Although peak identification in ChIP-Seq data has been extensively explored, there are few bioinformatics tools tailored for peak calling on analogous datasets for RNA-binding proteins. Here we describe ASPeak (abundance sensitive peak detection algorithm), an implementation of an algorithm that we previously applied to detect peaks in exon junction complex RNA immunoprecipitation in tandem experiments. Our peak detection algorithm yields stringent and robust target sets enabling sensitive motif finding and downstream functional analyses. Availability: ASPeak is implemented in Perl as a complete pipeline that takes bedGraph files as input. ASPeak implementation is freely available at https://sourceforge.net/projects/as-peak under the GNU General Public License. ASPeak can be run on a personal computer, yet is designed to be easily parallelizable. ASPeak can also run on high performance computing clusters providing efficient speedup. The documentation and user manual can be obtained from http://master.dl.sourceforge.net/project/as-peak/manual.pdf . Contact: alper.kucukural@umassmed.edu or ccenik@stanford.edu
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 4
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    Dissecting Molecular Evolution in the Highly Diverse Plant Clade Caryophyllales Using Transcriptome Sequencing (2015)
    Oxford University Press
    Details
    Publication Date: 2015-07-18
    Description: Many phylogenomic studies based on transcriptomes have been limited to "single-copy" genes due to methodological challenges in homology and orthology inferences. Only a relatively small number of studies have explored analyses beyond reconstructing species relationships. We sampled 69 transcriptomes in the hyperdiverse plant clade Caryophyllales and 27 outgroups from annotated genomes across eudicots. Using a combined similarity- and phylogenetic tree-based approach, we recovered 10,960 homolog groups, where each was represented by at least eight ingroup taxa. By decomposing these homolog trees, and taking gene duplications into account, we obtained 17,273 ortholog groups, where each was represented by at least ten ingroup taxa. We reconstructed the species phylogeny using a 1,122-gene data set with a gene occupancy of 92.1%. From the homolog trees, we found that both synonymous and nonsynonymous substitution rates in herbaceous lineages are up to three times as fast as in their woody relatives. This is the first time such a pattern has been shown across thousands of nuclear genes with dense taxon sampling. We also pinpointed regions of the Caryophyllales tree that were characterized by relatively high frequencies of gene duplication, including three previously unrecognized whole-genome duplications. By further combining information from homolog tree topology and synonymous distance between paralog pairs, phylogenetic locations for 13 putative genome duplication events were identified. Genes that experienced the greatest gene family expansion were concentrated among those involved in signal transduction and oxidoreduction, including a cytochrome P450 gene that encodes a key enzyme in the betalain synthesis pathway. Our approach demonstrates a new approach for functional phylogenomic analysis in nonmodel species that is based on homolog groups in addition to inferred ortholog groups.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    piggyBac transposons expressing full-length human dystrophin enable genetic correction of dystrophic mesoangioblasts (2016)
    Oxford University Press
    Details
    Publication Date: 2016-01-30
    Description: Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder caused by the absence of dystrophin. We developed a novel gene therapy approach based on the use of the piggyBac ( PB ) transposon system to deliver the coding DNA sequence ( CDS ) of either full-length human dystrophin ( DYS : 11.1 kb) or truncated microdystrophins ( MD1 : 3.6 kb; MD2 : 4 kb). PB transposons encoding microdystrophins were transfected in C2C12 myoblasts, yielding 65±2% MD1 and 66±2% MD2 expression in differentiated multinucleated myotubes. A hyperactive PB ( hyPB ) transposase was then deployed to enable transposition of the large-size PB transposon (17 kb) encoding the full-length DYS and green fluorescence protein (GFP). Stable GFP expression attaining 78±3% could be achieved in the C2C12 myoblasts that had undergone transposition. Western blot analysis demonstrated expression of the full-length human DYS protein in myotubes. Subsequently, dystrophic mesoangioblasts from a Golden Retriever muscular dystrophy dog were transfected with the large-size PB transposon resulting in 50±5% GFP-expressing cells after stable transposition. This was consistent with correction of the differentiated dystrophic mesoangioblasts following expression of full-length human DYS. These results pave the way toward a novel non-viral gene therapy approach for DMD using PB transposons underscoring their potential to deliver large therapeutic genes.
    Keywords: Targeted gene modification, DNA-Mediated Cell Transformation and Nucleic Acids Transfer
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    Heating up a cold subject: prospects for under-ice plankton research in lakes (2015)
    Oxford University Press
    Details
    Publication Date: 2015-03-25
    Description: Long-term patterns and drivers of ecosystem structure may be misunderstood if knowledge of an ecosystem is derived primarily from a single season, a situation common in many temperate lakes where the role of winter has been less studied. In lakes, avoidance of winter research has been especially pronounced for those that experience winter ice, but critical ecological processes can take place under ice. Even when obscured by snow, ice transmitting as little as 2% incident light can allow relatively high rates of photosynthesis, and winter trophic interactions may have year-round repercussions. Here, we offer a suite of research questions that require attention, in order to build a mature understanding of seasonal plankton dynamics in lakes. Specifically, we ask freshwater ecologists to consider the extent to which abundance and nutrition of winter primary productivity supports consumers under the ice, reorganizes food webs, and how long the effects of winter trophic dynamics extend throughout the year. In addition, we recognize some critical gaps in knowledge about physical and biogeochemical conditions at the time of ice-off. Worldwide shortening in ice duration lends imperative to under-ice studies, in order to more fully understand changes in ecosystem structure and function that may already be underway.
    Print ISSN: 0142-7873
    Electronic ISSN: 1464-3774
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    An optimized kit-free method for making strand-specific deep sequencing libraries from RNA fragments (2015)
    Oxford University Press
    Details
    Publication Date: 2015-01-10
    Description: Deep sequencing of strand-specific cDNA libraries is now a ubiquitous tool for identifying and quantifying RNAs in diverse sample types. The accuracy of conclusions drawn from these analyses depends on precise and quantitative conversion of the RNA sample into a DNA library suitable for sequencing. Here, we describe an optimized method of preparing strand-specific RNA deep sequencing libraries from small RNAs and variably sized RNA fragments obtained from ribonucleoprotein particle footprinting experiments or fragmentation of long RNAs. Our approach works across a wide range of input amounts (400 pg to 200 ng), is easy to follow and produces a library in 2–3 days at relatively low reagent cost, all while giving the user complete control over every step. Because all enzymatic reactions were optimized and driven to apparent completion, sequence diversity and species abundance in the input sample are well preserved.
    Keywords: Massively Parallel (Deep) Sequencing
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    Quantitative analysis of the relative mutagenicity of five chemical constituents of tobacco smoke in the mouse lymphoma assay (2016)
    Oxford University Press
    Details
    Publication Date: 2016-04-23
    Description: Quantifying health-related biological effects, like genotoxicity, could provide a way of distinguishing between tobacco products. In order to develop tools for using genotoxicty data to quantitatively evaluate the risk of tobacco products, we tested five carcinogens found in cigarette smoke, 4-aminobiphenyl (4-ABP), benzo[ a ]pyrene (BaP), cadmium (in the form of CdCl 2 ), 2-amino-3,4-dimethyl-3H-imidazo[4,5-f]quinoline (MeIQ) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), in the mouse lymphoma assay (MLA). The resulting mutagenicity dose responses were analyzed by various quantitative approaches and their strengths and weaknesses for distinguishing responses in the MLA were evaluated. L5178Y/ Tk +/– 3.7.2C mouse lymphoma cells were treated with four to seven concentrations of each chemical for 4h. Only CdCl 2 produced a positive response without metabolic activation (S9); all five chemicals produced dose-dependent increases in cytotoxicity and mutagenicity with S9. The lowest dose exceeding the global evaluation factor, the benchmark dose producing a 10%, 50%, 100% or 200% increase in the background frequency (BMD 10 , BMD 50 , BMD 100 and BMD 200 ), the no observed genotoxic effect level (NOGEL), the lowest observed genotoxic effect level (LOGEL) and the mutagenic potency expressed as a mutant frequency per micromole of chemical, were calculated for all the positive responses. All the quantitative metrics had similar rank orders for the agents’ ability to induce mutation, from the most to least potent as CdCl 2 (–S9) 〉 BaP(+S9) 〉 CdCl 2 (+S9) 〉 MeIQ(+S9) 〉 4-ABP(+S9) 〉 NNK(+S9). However, the metric values for the different chemical responses (i.e. the ratio of the greatest value to the least value) for the different chemicals ranged from 16-fold (BMD 10 ) to 572-fold (mutagenic potency). These results suggest that data from the MLA are capable of discriminating the mutagenicity of various constituents of cigarette smoke, and that quantitative analyses are available that can be useful in distinguishing between the exposure responses.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 9
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    Air-cushioning in impact problems (2013)
    Oxford University Press
    Details
    Publication Date: 2013-07-18
    Description: This paper concerns the displacement potential formulation of the post-impact influence of an air-cushioning layer on the 2D impact of a liquid half-space by a rigid body. The liquid and air are both ideal and incompressible and attention is focussed on cases when the density ratio between the air and liquid is small. In particular, the correction to classical Wagner theory is analysed in detail for the impact of circular cylinders and wedges.
    Print ISSN: 0272-4960
    Electronic ISSN: 1464-3634
    Topics: Mathematics
    Published by Oxford University Press
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  • 10
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    How we all kill whales (2014)
    Oxford University Press
    Details
    Publication Date: 2014-05-20
    Description: Today there is enormous popular interest in marine mammals. Western media tend to dwell on the ongoing debate about commercial whaling by Japan, Norway and Iceland. There is, however, relative silence as to how the shipping and fishing industries of many if not all maritime countries are also catching and sometimes killing whales, albeit unintentionally. Thus, western countries have, through the development and increase in fishing and shipping in continental shelf waters, essentially resumed whaling as vessel speeds and fishing gear strength have increased in recent decades. The ways in which these animals die, especially in fixed fishing gear that they become entangled in and swim off with, would raise substantial concern with consumers of seafood were they to be aware of what they were enabling.
    Print ISSN: 1054-3139
    Electronic ISSN: 1095-9289
    Topics: Biology , Geosciences , Physics
    Published by Oxford University Press
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