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The matricellular protein TSP1 promotes human and mouse endothelial cell senescence through CD47 and Nox1.
Senescent cells withdraw from the cell cycle and do not proliferate. The prevalence of senescent compared to normally functioning parenchymal cells increases with age, impairing tissue and organ homeostasis. A contentious principle governing this process has been the redox theory of aging. We linked matricellular protein thrombospondin 1 (TSP1) and its receptor CD47 to the activation of NADPH oxidase 1 (Nox1), but not of the other closely related Nox isoforms, and associated oxidative stress, and to senescence in human cells and aged tissue. In human endothelial cells, TSP1 promoted senescence and attenuated cell cycle progression and proliferation. At the molecular level, TSP1 increased Nox1-dependent generation of reactive oxygen species (ROS), leading to the increased abundance of the transcription factor p53. p53 mediated a DNA damage response that led to senescence through Rb and p21cip, both of which inhibit cell cycle progression. Nox1 inhibition blocked the ability of TSP1 to increase p53 nuclear localization and p21cip abundance and its ability to promote senescence. Mice lacking TSP1 showed decreases in ROS production, p21cip expression, p53 activity, and aging-induced senescence. Conversely, lung tissue from aging humans displayed increases in the abundance of vascular TSP1, Nox1, p53, and p21cip Finally, genetic ablation or pharmacological blockade of Nox1 in human endothelial cells attenuated TSP1-mediated ROS generation, restored cell cycle progression, and protected against senescence. Together, our results provide insights into the functional interplay between TSP1 and Nox1 in the regulation of endothelial senescence and suggest potential targets for controlling the aging process at the molecular level
Microbiome profiling by Illumina sequencing of combinatorial sequence-tagged PCR products
We developed a low-cost, high-throughput microbiome profiling method that
uses combinatorial sequence tags attached to PCR primers that amplify the rRNA
V6 region. Amplified PCR products are sequenced using an Illumina paired-end
protocol to generate millions of overlapping reads. Combinatorial sequence
tagging can be used to examine hundreds of samples with far fewer primers than
is required when sequence tags are incorporated at only a single end. The
number of reads generated permitted saturating or near-saturating analysis of
samples of the vaginal microbiome. The large number of reads al- lowed an
in-depth analysis of errors, and we found that PCR-induced errors composed the
vast majority of non-organism derived species variants, an ob- servation that
has significant implications for sequence clustering of similar high-throughput
data. We show that the short reads are sufficient to assign organisms to the
genus or species level in most cases. We suggest that this method will be
useful for the deep sequencing of any short nucleotide region that is
taxonomically informative; these include the V3, V5 regions of the bac- terial
16S rRNA genes and the eukaryotic V9 region that is gaining popularity for
sampling protist diversity.Comment: 28 pages, 13 figure
A method for studying protistan diversity using massively parallel sequencing of V9 hypervariable regions of small-subunit ribosomal RNA genes
© 2009 The Authors. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS ONE 4 (2009): e6372, doi:10.1371/journal.pone.0006372.Massively parallel pyrosequencing of amplicons from the V6 hypervariable regions of small-subunit (SSU) ribosomal RNA (rRNA) genes is commonly used to assess diversity and richness in bacterial and archaeal populations. Recent advances in pyrosequencing technology provide read lengths of up to 240 nucleotides. Amplicon pyrosequencing can now be applied to longer variable regions of the SSU rRNA gene including the V9 region in eukaryotes. We present a protocol for the amplicon pyrosequencing of V9 regions for eukaryotic environmental samples for biodiversity inventories and species richness estimation. The International Census of Marine Microbes (ICoMM) and the Microbial Inventory Research Across Diverse Aquatic Long Term Ecological Research Sites (MIRADA-LTERs) projects are already employing this protocol for tag sequencing of eukaryotic samples in a wide diversity of both marine and freshwater environments. Massively parallel pyrosequencing of eukaryotic V9 hypervariable regions of SSU rRNA genes provides a means of estimating species richness from deeply-sampled populations and for discovering novel species from the environment.This work was supported by grants from the W.M. Keck Foundation and the Woods Hole Center for Oceans and Human Health from the National
Institutes of Health and National Science Foundation (NIH/NIEHS 1 P50 ES012742-01 and NSF/OCE 0430724-J) (LAZ and SH)
Estimates of self-reported dietary behavior related to oral health among adolescents according to the type of food
Minimally invasive scoliosis surgery: an innovative technique in patients with adolescent idiopathic scoliosis
Minimally invasive spine surgery is becoming more common in the treatment of adult lumbar degenerative disorders. Minimally invasive techniques have been utilized for multilevel pathology, including adult lumbar degenerative scoliosis. The next logical step is to apply minimally invasive surgical techniques to the treatment of adolescent idiopathic scoliosis (AIS). However, there are significant technical challenges of performing minimally invasive surgery on this patient population. For more than two years, we have been utilizing minimally invasive spine surgery techniques in patients with adolescent idiopathic scoliosis. We have developed the present technique to allow for utilization of all standard reduction maneuvers through three small midline skin incisions. Our technique allows easy passage of contoured rods, placement of pedicle screws without image guidance, and allows adequate facet osteotomy to enable fusion. There are multiple potential advantages of this technique, including: less blood loss, shorter hospital stay, earlier mobilization, and relatively less pain and need for pain medication. The operative time needed to complete this surgery is longer. We feel that a minimally invasive approach, although technically challenging, is a feasible option in patients with adolescent idiopathic scoliosis. Although there are multiple perceived benefits, long term data is needed before it can be recommended for routine use
A new approach to bad news effects on volatilit y: the multiple-sign-volume sensitive regime EGARCH model (MSV-EGARCH)
In this paper, using daily data for six major international stock market indexes and a modified EGARCH specification, the links between stock market returns, volatility and trading volume are investigated in a new nonlinear conditional variance framework with multiple regimes and volume eff ects. Volatility forecast comparisons, using the Harvey-Newbold test for multiple forecasts encompassing, seem to demonstrate that the MSV- EGARCH complex threshold structure is able to correctly fit GARCH- type dynamics of the series under study and dominates competing standard asymmetric models in several of the considered stock indexes.info:eu-repo/semantics/publishedVersio
DNA prime-protein boost based vaccination with a conserved region of leptospiral immunoglobulin-like A and B proteins enhances protection against leptospirosis
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