74,139 research outputs found
N-Cadherin cleavage during activated hepatic stellate cell apoptosis is inhibited by tissue inhibitor of metalloproteinase-1. [In supplement: 11th International Symposium on the Cells of the Hepatic Sinusoid and their Relation to Other Cells]
Apoptosis of hepatic stellate cells (HSC) has previously been shown to occur during spontaneous resolution of experimental liver fibrosis. TIMP-1 has also been shown to have a key role because of its ability to inhibit apoptosis of HSC via matrix metalloproteinase (MMP) inhibition. This has led to further study of novel substrates for MMPs that might impact on HSC survival. N-Cadherin is known to mediate cell-cell contacts in fibroblasts. In this study we demonstrate that N-Cadherin is expressed by activated rat HSC. Furthermore, during apoptosis of HSC, the N-Cadherin is cleaved into smaller fragments. Apoptosis of HSC may be inhibited by TIMP-1. This is associated with reduced fragmentation of N-Cadherin. N-Cadherin may have an important role in supporting HSC survival while N-Cadherin cleavage may play a part in promoting HSC apoptosis in recovery from liver fibrosis
Hepatic fibrogenesis requires sympathetic neurotransmitters
Background and aims: Hepatic stellate cells (HSC) are activated by liver injury to become proliferative fibrogenic myofibroblasts. This process may be regulated by the sympathetic nervous system (SNS) but the mechanisms involved are unclear. Methods: We studied cultured HSC and intact mice with liver injury to test the hypothesis that HSC respond to and produce SNS neurotransmitters to promote fibrogenesis. Results: HSC expressed adrenoceptors, catecholamine biosynthetic enzymes, released norepinephrine (NE), and were growth inhibited by α- and β-adrenoceptor antagonists. HSC from dopamine β-hydroxylase deficient (Dbh(−/−)) mice, which cannot make NE, grew poorly in culture and were rescued by NE. Inhibitor studies demonstrated that this effect was mediated via G protein coupled adrenoceptors, mitogen activated kinases, and phosphatidylinositol 3-kinase. Injury related fibrogenic responses were inhibited in Dbh(−/−) mice, as evidenced by reduced hepatic accumulation of α-smooth muscle actin(+ve) HSC and decreased induction of transforming growth factor β1 (TGF-β1) and collagen. Treatment with isoprenaline rescued HSC activation. HSC were also reduced in leptin deficient ob/ob mice which have reduced NE levels and are resistant to hepatic fibrosis. Treating ob/ob mice with NE induced HSC proliferation, upregulated hepatic TGF-β1 and collagen, and increased liver fibrosis. Conclusions: HSC are hepatic neuroglia that produce and respond to SNS neurotransmitters to promote hepatic fibrosis
The Hyper Suprime-Cam Software Pipeline
In this paper, we describe the optical imaging data processing pipeline
developed for the Subaru Telescope's Hyper Suprime-Cam (HSC) instrument. The
HSC Pipeline builds on the prototype pipeline being developed by the Large
Synoptic Survey Telescope's Data Management system, adding customizations for
HSC, large-scale processing capabilities, and novel algorithms that have since
been reincorporated into the LSST codebase. While designed primarily to reduce
HSC Subaru Strategic Program (SSP) data, it is also the recommended pipeline
for reducing general-observer HSC data. The HSC pipeline includes high level
processing steps that generate coadded images and science-ready catalogs as
well as low-level detrending and image characterizations.Comment: 39 pages, 21 figures, 2 tables. Submitted to Publications of the
Astronomical Society of Japa
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In Vivo Generation of Engraftable Murine Hematopoietic Stem Cells by Gfi1b, c-Fos, and Gata2 Overexpression within Teratoma.
Generation of hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) could potentially provide unlimited HSCs for clinical transplantation, a curative treatment for numerous blood diseases. However, to date, bona fide HSC generation has been largely unsuccessful in vitro. We have previously described proof of concept for in vivo HSC generation from PSCs via teratoma formation. However, our first-generation system was complex and the output low. Here, we further optimize this technology and demonstrate the following: (1) simplified HSC generation using transcription factor overexpression; (2) improved HSC output using c-Kit-deficient host mice, and (3) that teratomas can be transplanted and cryopreserved. We demonstrate that overexpression of Gfi1b, c-Fos, and Gata2, previously reported to transdifferentiate fibroblasts into hematopoietic progenitors in vitro, can induce long-term HSC formation in vivo. Our in vivo system provides a useful platform to investigate new strategies and re-evaluate existing strategies to generate HSCs and study HSC development
Bayesian inference and model choice in a hidden stochastic two-compartment model of hematopoietic stem cell fate decisions
Despite rapid advances in experimental cell biology, the in vivo behavior of
hematopoietic stem cells (HSC) cannot be directly observed and measured.
Previously we modeled feline hematopoiesis using a two-compartment hidden
Markov process that had birth and emigration events in the first compartment.
Here we perform Bayesian statistical inference on models which contain two
additional events in the first compartment in order to determine if HSC fate
decisions are linked to cell division or occur independently. Pareto Optimal
Model Assessment approach is used to cross check the estimates from Bayesian
inference. Our results show that HSC must divide symmetrically (i.e., produce
two HSC daughter cells) in order to maintain hematopoiesis. We then demonstrate
that the augmented model that adds asymmetric division events provides a better
fit to the competitive transplantation data, and we thus provide evidence that
HSC fate determination in vivo occurs both in association with cell division
and at a separate point in time. Last we show that assuming each cat has a
unique set of parameters leads to either a significant decrease or a
nonsignificant increase in model fit, suggesting that the kinetic parameters
for HSC are not unique attributes of individual animals, but shared within a
species.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS269 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
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