4,398 research outputs found
Strong Lensing Probabilities in a Cosmological Model with a Running Primordial Power Spectrum
The combination of the first-year Wilkinson Microwave Anisotropy Probe (WMAP)
data with other finer scale cosmic microwave background (CMB) experiments (CBI
and ACBAR) and two structure formation measurements (2dFGRS and Lyman
forest) suggest a CDM cosmological model with a running spectral power
index of primordial density fluctuations. Motivated by this new result on the
index of primordial power spectrum, we present the first study on the predicted
lensing probabilities of image separation in a spatially flat CDM
model with a running spectral index (RSI-CDM model). It is shown that
the RSI-CDM model suppress the predicted lensing probabilities on
small splitting angles of less than about 4 compared with that of
standard power-law CDM (PL-CDM) model.Comment: 11 pages including 1 figures. Accepted for publication in Modern
Physics Letters A (MPLA), minor revision
mGluR5 antagonism inhibits cocaine reinforcement and relapse by elevation of extracellular glutamate in the nucleus accumbens via a CB1 receptor mechanism.
Metabotropic glutamate receptor 5 (mGluR5) antagonism inhibits cocaine self-administration and reinstatement of drug-seeking behavior. However, the cellular and molecular mechanisms underlying this action are poorly understood. Here we report a presynaptic glutamate/cannabinoid mechanism that may underlie this action. Systemic or intra-nucleus accumbens (NAc) administration of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) dose-dependently reduced cocaine (and sucrose) self-administration and cocaine-induced reinstatement of drug-seeking behavior. The reduction in cocaine-taking and cocaine-seeking was associated with a reduction in cocaine-enhanced extracellular glutamate, but not cocaine-enhanced extracellular dopamine (DA) in the NAc. MPEP alone, when administered systemically or locally into the NAc, elevated extracellular glutamate, but not DA. Similarly, the cannabinoid CB1 receptor antagonist, rimonabant, elevated NAc glutamate, not DA. mGluR5s were found mainly in striatal medium-spiny neurons, not in astrocytes, and MPEP-enhanced extracellular glutamate was blocked by a NAc CB1 receptor antagonist or N-type Ca++ channel blocker, suggesting that a retrograde endocannabinoid-signaling mechanism underlies MPEP-induced glutamate release. This interpretation was further supported by our findings that genetic deletion of CB1 receptors in CB1-knockout mice blocked both MPEP-enhanced extracellular glutamate and MPEP-induced reductions in cocaine self-administration. Together, these results indicate that the therapeutic anti-cocaine effects of mGluR5 antagonists are mediated by elevation of extracellular glutamate in the NAc via an endocannabinoid-CB1 receptor disinhibition mechanism
Maternal cocaine administration in mice alters DNA methylation and gene expression in hippocampal neurons of neonatal and prepubertal offspring
Previous studies documented significant behavioral changes in the offspring of cocaine-exposed mothers. We now explore the hypothesis that maternal cocaine exposure could alter the fetal epigenetic machinery sufficiently to cause lasting neurochemical and functional changes in the offspring. Pregnant CD1 mice were administered either saline or 20 mg/kg cocaine twice daily on gestational days 8-19. Male pups from each of ten litters of the cocaine and control groups were analyzed at 3 (P3) or 30 (P30) days postnatum. Global DNA methylation, methylated DNA immunoprecipitation followed by CGI(2) microarray profiling and bisulfite sequencing, as well as quantitative real-time RT-PCR gene expression analysis, were evaluated in hippocampal pyramidal neurons excised by laser capture microdissection. Following maternal cocaine exposure, global DNA methylation was significantly decreased at P3 and increased at P30. Among the 492 CGIs whose methylation was significantly altered by cocaine at P3, 34% were hypermethylated while 66% were hypomethylated. Several of these CGIs contained promoter regions for genes implicated in crucial cellular functions. Endogenous expression of selected genes linked to the abnormally methylated CGIs was correspondingly decreased or increased by as much as 4-19-fold. By P30, some of the cocaine-associated effects at P3 endured, reversed to opposite directions, or disappeared. Further, additional sets of abnormally methylated targets emerged at P30 that were not observed at P3. Taken together, these observations indicate that maternal cocaine exposure during the second and third trimesters of gestation could produce potentially profound structural and functional modifications in the epigenomic programs of neonatal and prepubertal mice
Finding Complex Biological Relationships in Recent PubMed Articles Using Bio-LDA
The overwhelming amount of available scholarly literature in the life
sciences poses significant challenges to scientists wishing to keep up with
important developments related to their research, but also provides a useful
resource for the discovery of recent information concerning genes, diseases,
compounds and the interactions between them. In this paper, we describe an
algorithm called Bio-LDA that uses extracted biological terminology to
automatically identify latent topics, and provides a variety of measures to
uncover putative relations among topics and bio-terms. Relationships identified
using those approaches are combined with existing data in life science datasets
to provide additional insight. Three case studies demonstrate the utility of
the Bio-LDA model, including association predication, association search and
connectivity map generation. This combined approach offers new opportunities
for knowledge discovery in many areas of biology including target
identification, lead hopping and drug repurposing.Comment: 14 pages, 8 figures, 10 table
X-ray Emission of Baryonic Gas in the Universe: Luminosity-Temperature Relationship and Soft-Band Background
We study the X-ray emission of baryon fluid in the universe using the WIGEON
cosmological hydrodynamic simulations. It has been revealed that cosmic baryon
fluid in the nonlinear regime behaves like Burgers turbulence, i.e. the fluid
field consists of shocks. Like turbulence in incompressible fluid, the Burgers
turbulence plays an important role in converting the kinetic energy of the
fluid to thermal energy and heats the gas. We show that the simulation sample
of the CDM model without adding extra heating sources can fit well the
observed distributions of X-ray luminosity versus temperature ( vs.
) of galaxy groups and is also consistent with the distributions of X-ray
luminosity versus velocity dispersion ( vs. ). Because the
baryonic gas is multiphase, the and
distributions are significantly scattered. If we describe the relationships by
power laws and , we find and . The
X-ray background in the soft keV band emitted by the baryonic gas in
the temperature range K has also been calculated. We show that of
the total background, (1) no more than 2% comes from the region with
temperature less than K, and (2) no more than 7% is from the region
of dark matter with mass density . The
region of is generally clustered and
discretely distributed. Therefore, almost all of the soft X-ray background
comes from clustered sources, and the contribution from truly diffuse gas is
probably negligible. This point agrees with current X-ray observations.Comment: 32 pages including 14 figures and 2 tables. Final version for
publication in Ap
Plasma deposition of Ultrathin polymer films on carbon nanotubes
Ultrathin films of pyrrole were deposited on the surfaces of carbon nanotubes using a plasma polymerization treatment. High-resolution electron transmission microscopy images revealed that an extremely thin film of the polymer layer (2 ∼ 7 nm)(2∼7nm) was uniformly deposited on the outer and inner surfaces of the nanotubes. The nanotubes of all sizes exhibited equally uniform ultrathin films, indicating well-dispersed nanotubes in the fluidized bed reactor during the plasma treatment. In particular, the inner wall of the nanotube was also coated with a uniform ultrathin film of only ∼1–3 nm. Time-of-flight secondary ion mass spectroscopy experiments confirmed the highly branched and cross-linked polymer thin films on the carbon nanotubes. The plasma deposition mechanism is discussed in this letter. © 2002 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71075/2/APPLAB-81-27-5216-1.pd
Plasma coating of carbon nanofibers for enhanced dispersion and interfacial bonding in polymer composites
Ultrathin films of polystyrene were deposited on the surfaces of carbon nanofibers using a plasma polymerization treatment. A small percent by weight of these surface-coated nanofibers were incorporated into polystyrene to form a polymer nanocomposite. The plasma coating greatly enhanced the dispersion of the nanofibers in the polymer matrix. High-resolution transmission-electron-microscopy (HRTEM) images revealed an extremely thin film of the polymer layer (∼3 nm) at the interface between the nanofiber and matrix. Tensile test results showed considerably increased strength in the coated nanofiber composite while an adverse effect was observed in the uncoated composites; the former exhibited shear yielding due to enhanced interfacial bonding while the latter fractured in a brittle fashion. © 2003 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71001/2/APPLAB-83-25-5301-1.pd
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Shear stress regulation of miR-93 and miR-484 maturation through nucleolin.
Pulsatile shear (PS) and oscillatory shear (OS) elicit distinct mechanotransduction signals that maintain endothelial homeostasis or induce endothelial dysfunction, respectively. A subset of microRNAs (miRs) in vascular endothelial cells (ECs) are differentially regulated by PS and OS, but the regulation of the miR processing and its implications in EC biology by shear stress are poorly understood. From a systematic in silico analysis for RNA binding proteins that regulate miR processing, we found that nucleolin (NCL) is a major regulator of miR processing in response to OS and essential for the maturation of miR-93 and miR-484 that target mRNAs encoding Krüppel-like factor 2 (KLF2) and endothelial nitric oxide synthase (eNOS). Additionally, anti-miR-93 and anti-miR-484 restore KLF2 and eNOS expression and NO bioavailability in ECs under OS. Analysis of posttranslational modifications of NCL identified that serine 328 (S328) phosphorylation by AMP-activated protein kinase (AMPK) was a major PS-activated event. AMPK phosphorylation of NCL sequesters it in the nucleus, thereby inhibiting miR-93 and miR-484 processing and their subsequent targeting of KLF2 and eNOS mRNA. Elevated levels of miR-93 and miR-484 were found in sera collected from individuals afflicted with coronary artery disease in two cohorts. These findings provide translational relevance of the AMPK-NCL-miR-93/miR-484 axis in miRNA processing in EC health and coronary artery disease
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