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Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids.
There is much interest in defining the signals that initiate abnormal proliferation of cells in a variety of states characterized by the presence of mononuclear phagocytes. Since IL-1 is a major secretory product of activated human monocytes we examined whether this cytokine can stimulate the growth of human vascular smooth muscle cells (SMC). Neither recombinant IL-1 (rIL-1) alpha (less than or equal to 5.0 ng/ml) nor beta (less than or equal to 100 ng/ml) stimulated SMC growth during 2-d incubations under usual conditions. IL-1 did stimulate SMC to produce prostanoids such as PGE1 or PGE2 that can inhibit SMC proliferation. When prostaglandin synthesis was inhibited by indomethacin or aspirin both rIL-1 alpha and beta (greater than or equal to 1 ng/ml) markedly increased SMC growth. In longer-term experiments (7-28 d) rIL-1 stimulated the growth of SMC even in the absence of cyclooxygenase inhibitors. The addition of exogenous PGE1 or PGE2 (but not PGF1 alpha, PGF2 alpha, PGI2) to indomethacin-treated SMC blocked their mitogenic response to rIL-1. Antibody to IL-1 (but not to platelet-derived growth factor [PDGF]) abolished the mitogenic response of SMC to rIL-1. Exposure of SMC to rIL-1 or PDGF caused rapid (maximal at 1 h) and transient (baseline by 3 h) expression of the c-fos proto-oncogene, determined by Northern analysis. We conclude that IL-1 is a potent mitogen for human SMC. Endogenous prostanoid production simultaneously induced by IL-1 appears to antagonize this growth-promoting effect in the short term (2 d) but not during more prolonged exposures. IL-1 produced by activated monocytes at sites of tissue inflammation or injury may thus mediate both positive and negative effects on SMC proliferation that are temporally distinct
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Immune interferon inhibits proliferation and induces 2'-5'-oligoadenylate synthetase gene expression in human vascular smooth muscle cells.
Proliferation of vascular smooth muscle cells (SMC) contributes to formation of the complicated human atherosclerotic plaque. These lesions also contain macrophages, known to secrete SMC mitogens, and T lymphocytes. Many of the SMC in the lesions express class II major histocompatibility antigens, an indication that activated T cells secrete immune IFN-gamma locally in the plaque. We therefore studied the effect of IFN-gamma on the proliferation of cultured SMC derived from adult human blood vessels. IFN-gamma (1,000 U/ml) reduced [3H]thymidine (TdR) incorporation into DNA by SMC stimulated with the well-defined mitogens IL 1 (from 15.3 +/- 0.7 to 6.2 +/- 0.7 dpm X 10(-3)/24 h) or platelet-derived growth factor (PDGF) (from 18.5 +/- 1.0 to 7.3 +/- 0.7 dpm X 10(-3)/24 h). Kinetic and nuclear labeling studies indicated that this effect of IFN-gamma was not due to altered thymidine transport or specific radioactivity of TdR in the cell. In longer term experiments (4-16 d) IFN-gamma prevented net DNA accumulation by SMC cultures stimulated by PDGF. IFN-gamma also delayed (from 30 to 60 min) the time to peak level of c-fos RNA in IL 1-treated SMC. It is unlikely that cytotoxicity caused these effects of IFN-gamma, as the inhibition of growth was reversible and we detected no cell death in SMC cultures exposed to this cytokine. Activation of 2'-5' oligoadenylate synthetase gene expression may mediate certain antiproliferative and antiviral effects of interferons. Both IFN-gamma and type I IFNs (IFN-alpha or IFN-beta) induced 2'-5' oligoadenylate synthetase mRNA and enzyme activity in SMC cultures, but with concentration dependence and time course that may not account for all of IFN-gamma's cytostatic effect on SMC. The accumulation of SMC in human atherosclerotic lesions is a long-term process that must involve altered balance between growth stimulatory and inhibitory factors. The cytostatic effect of IFN-gamma on human SMC demonstrated here may influence this balance during human atherogenesis, because T cells present in the complicated atherosclerotic plaque likely produce this cytokine
The Extreme Hosts of Extreme Supernovae
We use GALEX ultraviolet (UV) and optical integrated photometry of the hosts of 17 luminous supernovae (LSNe, having peak M_V 100 M_☉), by appearing in low-SFR hosts, are potential tests for theories of the initial mass function that limit the maximum mass of a star based on the SFR
Multi-color Optical and NIR Light Curves of 64 Stripped-Envelope Core-Collapse Supernovae
We present a densely-sampled, homogeneous set of light curves of 64 low
redshift (z < 0.05) stripped-envelope supernovae (SN of type IIb, Ib, Ic and
Ic-bl). These data were obtained between 2001 and 2009 at the Fred L. Whipple
Observatory (FLWO) on Mt. Hopkins in Arizona, with the optical FLWO 1.2-m and
the near-infrared PAIRITEL 1.3-m telescopes. Our dataset consists of 4543
optical photometric measurements on 61 SN, including a combination of UBVRI,
UBVr'i', and u'BVr'i', and 2142 JHKs near-infrared measurements on 25 SN. This
sample constitutes the most extensive multi-color data set of stripped-envelope
SN to date. Our photometry is based on template-subtracted images to eliminate
any potential host galaxy light contamination. This work presents these
photometric data, compares them with data in the literature, and estimates
basic statistical quantities: date of maximum, color, and photometric
properties. We identify promising color trends that may permit the
identification of stripped-envelope SN subtypes from their photometry alone.
Many of these SN were observed spectroscopically by the CfA SN group, and the
spectra are presented in a companion paper (Modjaz et al. 2014). A thorough
exploration that combines the CfA photometry and spectroscopy of
stripped-envelope core-collapse SN will be presented in a follow-up paper.Comment: 26 pages, 17 figures, 8 tables. Revised version resubmitted to ApJ
Supplements after referee report. Additional online material is available
through http://cosmo.nyu.edu/SNYU
Creativity and the computer nerd: an exploration of attitudes
This study arises from our concern that many of our best art and design students are failing to make the most of the opportunities provided by IT because of their fear or dislike of computers. This not only deprives them of useful skills, but, even more importantly, deprives many IT based developments of their input. In this paper we investigate the relationship between attitudes to creativity and to computers among students. We quickly discard an approach based on theories of personality types as philosophically and educationally problematic. An approach based on the self-concept of artists and designers, in relation to their own creativity and to their feelings about computers, offers more hope of progress. This means that we do not try to define the attributes of "creative people". Rather, we ask what creativity means to students of art and design and relate these responses to their attitudes to computers. Self-concept depends on how the subjects see themselves within society and culture, and is liable to change as culture changes. One major instrument of cultural change at the present time is the growth of IT itself. We then describe a first attempt at using a psychological method - Kelly's Repertory Grids - to investigate the self-concept of artists and designers. It is hoped to continue with this approach in further studies over the next few years
High Density Circumstellar Interaction in the Luminous Type IIn SN 2010jl: The first 1100 days
HST and ground based observations of the Type IIn SN 2010jl are analyzed,
including photometry, spectroscopy in the ultraviolet, optical and NIR bands,
26-1128 days after first detection. At maximum the bolometric luminosity was
erg/s and even at 850 days exceeds erg/s. A NIR
excess, dominating after 400 days, probably originates in dust in the
circumstellar medium (CSM). The total radiated energy is
ergs, excluding the dust component. The spectral lines can be separated into
one broad component due to electron scattering, and one narrow with expansion
velocity km/s from the CSM. The broad component is initially
symmetric around zero velocity but becomes blueshifted after days,
while remaining symmetric about a shifted centroid velocity. Dust absorption in
the ejecta is unlikely to explain the line shifts, and we attribute the shift
instead to acceleration by the SN radiation. From the optical lines and the
X-ray and dust properties, there is strong evidence for large scale asymmetries
in the CSM. The ultraviolet lines indicate CNO processing in the progenitor,
while the optical shows a number of narrow coronal lines excited by the X-rays.
The bolometric light curve is consistent with a radiative shock in an
CSM with a mass loss rate of M_sun/yr. The total mass lost is
M_sun. These properties are consistent with the SN expanding into a CSM
characteristic of an LBV progenitor with a bipolar geometry. The apparent
absence of nuclear processing is attributed to a CSM still opaque to electron
scattering.Comment: ApJ in press. Updated and changed after referees comment
Ongoing Formation of Bulges and Black Holes in the Local Universe: New Insights from GALEX
We analyze a volume-limited sample of massive bulge-dominated galaxies with
data from both the Sloan Digital Sky Survey and the Galaxy Evolution Explorer
(GALEX) satellite. The galaxies have central velocity dispersions greater than
100 km/s and stellar surface mass densities that lie above the value where
galaxies transition from actively star forming to passive systems. The sample
is limited to redshifts 0.03<z<0.07. At these distances, the SDSS spectra
sample the light from the bulge-dominated central regions of the galaxies. The
GALEX NUV data provide high sensitivity to low rates of global star formation
in these systems. Our sample of bulge-dominated galaxies exhibits a much larger
dispersion in NUV-r colour than in optical g-r colour. Nearly all of the
galaxies with bluer NUV-r colours are AGN. Both GALEX images and SDSS colour
profiles demonstrate that the excess UV light is associated with an extended
disk. We find that galaxies with red outer regions almost never have a young
bulge or a strong AGN. Galaxies with blue outer regions have bulges and black
holes that span a wide range in age and accretion rate. Galaxies with young
bulges and strongly accreting black holes almost always have blue outer disks.
Our suggested scenario is one in which the source of gas that builds the bulge
and black hole is a low mass reservoir of cold gas in the disk.The presence of
this gas is a necessary, but not sufficient condition for bulge and black hole
growth. Some mechanism must transport this gas inwards in a time variable way.
As the gas in the disk is converted into stars, the galaxies will turn red, but
further gas infall can bring them back into the blue NUV-r sequence.(Abridged)Comment: 34 pages, 16 figures. Accepted for the GALEX special issue of ApJ
The identification of informative genes from multiple datasets with increasing complexity
Background
In microarray data analysis, factors such as data quality, biological variation, and the increasingly multi-layered nature of more complex biological systems complicates the modelling of regulatory networks that can represent and capture the interactions among genes. We believe that the use of multiple datasets derived from related biological systems leads to more robust models. Therefore, we developed a novel framework for modelling regulatory networks that involves training and evaluation on independent datasets. Our approach includes the following steps: (1) ordering the datasets based on their level of noise and informativeness; (2) selection of a Bayesian classifier with an appropriate level of complexity by evaluation of predictive performance on independent data sets; (3) comparing the different gene selections and the influence of increasing the model complexity; (4) functional analysis of the informative genes.
Results
In this paper, we identify the most appropriate model complexity using cross-validation and independent test set validation for predicting gene expression in three published datasets related to myogenesis and muscle differentiation. Furthermore, we demonstrate that models trained on simpler datasets can be used to identify interactions among genes and select the most informative. We also show that these models can explain the myogenesis-related genes (genes of interest) significantly better than others (P < 0.004) since the improvement in their rankings is much more pronounced. Finally, after further evaluating our results on synthetic datasets, we show that our approach outperforms a concordance method by Lai et al. in identifying informative genes from multiple datasets with increasing complexity whilst additionally modelling the interaction between genes.
Conclusions
We show that Bayesian networks derived from simpler controlled systems have better performance than those trained on datasets from more complex biological systems. Further, we present that highly predictive and consistent genes, from the pool of differentially expressed genes, across independent datasets are more likely to be fundamentally involved in the biological process under study. We conclude that networks trained on simpler controlled systems, such as in vitro experiments, can be used to model and capture interactions among genes in more complex datasets, such as in vivo experiments, where these interactions would otherwise be concealed by a multitude of other ongoing events
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