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101.
Bernice Wright Trevor Gibson Jeremy Spencer Julie A. Lovegrove Jonathan M. Gibbins 《PloS one》2010,5(3)
Background
Flavonoid metabolites remain in blood for periods of time potentially long enough to allow interactions with cellular components of this tissue. It is well-established that flavonoids are metabolised within the intestine and liver into methylated, sulphated and glucuronidated counterparts, which inhibit platelet function.Methodology/Principal Findings
We demonstrate evidence suggesting platelets which contain metabolic enzymes, as an alternative location for flavonoid metabolism. Quercetin and a plasma metabolite of this compound, 4′-O-methyl quercetin (tamarixetin) were shown to gain access to the cytosolic compartment of platelets, using confocal microscopy. High performance liquid chromatography (HPLC) and mass spectrometry (MS) showed that quercetin was transformed into a compound with a mass identical to tamarixetin, suggesting that the flavonoid was methylated by catechol-O-methyl transferase (COMT) within platelets.Conclusions/Significance
Platelets potentially mediate a third phase of flavonoid metabolism, which may impact on the regulation of the function of these cells by metabolites of these dietary compounds. 相似文献102.
Kyle J. Nakamura Johannes S. Gach Laura Jones Katherine Semrau Jan Walter Frederic Bibollet-Ruche Julie M. Decker Laura Heath William D. Decker Moses Sinkala Chipepo Kankasa Donald Thea James Mullins Louise Kuhn Michael B. Zwick Grace M. Aldrovandi 《PloS one》2010,5(3)
Human antibody 4E10 targets the highly conserved membrane-proximal external region (MPER) of the HIV-1 transmembrane glycoprotein, gp41, and has extraordinarily broad neutralizing activity. It is considered by many to be a prototype for vaccine development. In this study, we describe four subjects infected with viruses carrying rare MPER polymorphisms associated with resistance to 4E10 neutralization. In one case resistant virus carrying a W680G substitution was transmitted from mother to infant. We used site-directed mutagenesis to demonstrate that the W680G substitution is necessary for conferring the 4E10-resistant phenotype, but that it is not sufficient to transfer the phenotype to a 4E10-sensitive Env. Our third subject carried Envs with a W680R substitution causing variable resistance to 4E10, indicating that residues outside the MPER are required to confer the phenotype. A fourth subject possessed a F673L substitution previously associated with 4E10 resistance. For all three subjects with W680 polymorphisms, we observed additional residues in the MPER that co-varied with position 680 and preserved charged distributions across this region. Our data provide important caveats for vaccine development targeting the MPER. Naturally occurring Env variants described in our study also represent unique tools for probing the structure-function of HIV-1 envelope. 相似文献
103.
Liu WM Li R Sun JZ Wang J Tsai J Wen W Kohlmann A Williams PM 《Journal of theoretical biology》2006,243(2):273-278
An ideal expression algorithm should be able to tell truly different expression levels with small false positive errors and be robust to assay changes. We propose two algorithms. PQN is the non-central trimmed mean of perfect match intensities with quantile normalization. DQN is the non-central trimmed mean of differences between perfect match and mismatch intensities with quantile normalization. The quantiles for normalization can be either empirical or theoretical. When array types and/or assay change in a study, the normalization to common quantiles at the probe set level is essential. We compared DQN, PQN, RMA, GCRMA, DCHIP, PLIER and MAS5 for the Affymetrix Latin square data and our data of two sets of experiments using the same bone marrow but different types of microarrays and different assay. We found the computation for AUC of ROC at affycomp.biostat.jhsph.edu can be improved. 相似文献
104.
105.
Dana M. Blumenthal Julie A. Kray William Ortmans Lewis H. Ziska Elise Pendall 《Global Change Biology》2016,22(9):3026-3038
Elevated CO2 and warming may alter terrestrial ecosystems by promoting invasive plants with strong community and ecosystem impacts. Invasive plant responses to elevated CO2 and warming are difficult to predict, however, because of the many mechanisms involved, including modification of phenology, physiology, and cycling of nitrogen and water. Understanding the relative and interactive importance of these processes requires multifactor experiments under realistic field conditions. Here, we test how free‐air CO2 enrichment (to 600 ppmv) and infrared warming (+1.5 °C day/3 °C night) influence a functionally and phenologically distinct invasive plant in semi‐arid mixed‐grass prairie. Bromus tectorum (cheatgrass), a fast‐growing Eurasian winter annual grass, increases fire frequency and reduces biological diversity across millions of hectares in western North America. Across 2 years, we found that warming more than tripled B. tectorum biomass and seed production, due to a combination of increased recruitment and increased growth. These results were observed with and without competition from native species, under wet and dry conditions (corresponding with tenfold differences in B. tectorum biomass), and despite the fact that warming reduced soil water. In contrast, elevated CO2 had little effect on B. tectorum invasion or soil water, while reducing soil and plant nitrogen (N). We conclude that (1) warming may expand B. tectorum's phenological niche, allowing it to more successfully colonize the extensive, invasion‐resistant northern mixed‐grass prairie, and (2) in ecosystems where elevated CO2 decreases N availability, CO2 may have limited effects on B. tectorum and other nitrophilic invasive species. 相似文献
106.
Vanessa Julie Roden Imelda M. Hausmann Alexander Nützel Barbara Seuss Mike Reich Max Urlichs Hans Hagdorn Wolfgang Kiessling 《Palaeontology》2020,63(1):85-102
With 1429 animal species, the Triassic Cassian Formation in the Dolomites, Southern Alps (Italy), yields the highest species richness reported from any spatially constrained pre-Quaternary formation known to science. The high preserved diversity is partly attributable to a high primary diversity governed by the tropical setting, increasing alpha diversity, and the breadth of habitats spurring beta diversity. More important is the excellent preservation of fossils and the ease with which they can be extracted from the poorly lithified sediments. We propose the term ‘liberation Lagerstätten’ to capture this preservational window. In contrast to conservation Lagerstätten, liberation Lagerstätten like the Cassian Formation originate from normal marine conditions but low-grade diagenesis. Molluscs contribute substantially to species richness, comprising 67% of all invertebrate species in the Cassian Formation. The gastropod dominance (39% of all species) is nearly as great as in Recent tropical settings, contradicting the concept of a substantial Cenozoic rise. 相似文献
107.
108.
An obligate intermediate along the slow folding pathway of a group II intron ribozyme 总被引:4,自引:1,他引:4
Most RNA molecules collapse rapidly and reach the native state through a pathway that contains numerous traps and unproductive intermediates. The D135 group II intron ribozyme is unusual in that it can fold slowly and directly to the native state, despite its large size and structural complexity. Here we use hydroxyl radical footprinting and native gel analysis to monitor the timescale of tertiary structure collapse and to detect the presence of obligate intermediates along the folding pathway of D135. We find that structural collapse and native folding of Domain 1 precede assembly of the entire ribozyme, indicating that D1 contains an on-pathway intermediate to folding of the D135 ribozyme. Subsequent docking of Domains 3 and 5, for which D1 provides a preorganized scaffold, appears to be very fast and independent of one another. In contrast to other RNAs, the D135 ribozyme undergoes slow tertiary collapse to a compacted state, with a rate constant that is also limited by the formation D1. These findings provide a new paradigm for RNA folding and they underscore the diversity of RNA biophysical behaviors. 相似文献
109.
110.
Ayres DL Darling A Zwickl DJ Beerli P Holder MT Lewis PO Huelsenbeck JP Ronquist F Swofford DL Cummings MP Rambaut A Suchard MA 《Systematic biology》2012,61(1):170-173
Phylogenetic inference is fundamental to our understanding of most aspects of the origin and evolution of life, and in recent years, there has been a concentration of interest in statistical approaches such as Bayesian inference and maximum likelihood estimation. Yet, for large data sets and realistic or interesting models of evolution, these approaches remain computationally demanding. High-throughput sequencing can yield data for thousands of taxa, but scaling to such problems using serial computing often necessitates the use of nonstatistical or approximate approaches. The recent emergence of graphics processing units (GPUs) provides an opportunity to leverage their excellent floating-point computational performance to accelerate statistical phylogenetic inference. A specialized library for phylogenetic calculation would allow existing software packages to make more effective use of available computer hardware, including GPUs. Adoption of a common library would also make it easier for other emerging computing architectures, such as field programmable gate arrays, to be used in the future. We present BEAGLE, an application programming interface (API) and library for high-performance statistical phylogenetic inference. The API provides a uniform interface for performing phylogenetic likelihood calculations on a variety of compute hardware platforms. The library includes a set of efficient implementations and can currently exploit hardware including GPUs using NVIDIA CUDA, central processing units (CPUs) with Streaming SIMD Extensions and related processor supplementary instruction sets, and multicore CPUs via OpenMP. To demonstrate the advantages of a common API, we have incorporated the library into several popular phylogenetic software packages. The BEAGLE library is free open source software licensed under the Lesser GPL and available from http://beagle-lib.googlecode.com. An example client program is available as public domain software. 相似文献