4,171 research outputs found
Transcriptomics modeling of the late-gestation fetal pituitary response to transient hypoxia
Background The late-gestation fetal sheep responds to hypoxia with physiological, neuroendocrine, and cellular responses that aid in fetal survival. The response of the fetus to hypoxia represents a coordinated effort to maximize oxygen transfer from the mother and minimize wasteful oxygen consumption by the fetus. While there have been many studies aimed at investigating the coordinated physiological and endocrine responses to hypoxia, and while immunohistochemical or in situ hybridization studies have revealed pathways supporting the endocrine function of the pituitary, there is little known about the coordinated cellular response of the pituitary to the hypoxia. Results Thirty min hypoxia (from 17.0±1.7 to 8.0±0.8 mm Hg, followed by 30 min normoxia) upregulated 595 and downregulated 790 genes in fetal pituitary (123-132 days' gestation; term = 147 days). Network inference of up- and down- regulated genes revealed a high degree of functional relatedness amongst the gene sets. Gene ontology analysis revealed upregulation of cellular metabolic processes (e.g., RNA synthesis, response to estrogens) and downregulation Conclusions The multiple analytical approaches used in this study suggests that the acute response to 30 min of transient hypoxia in the late-gestation fetus results in reduced cellular metabolism and a pattern of gene expression that is consistent with cellular oxygen and ATP starvation. In this early time point, we see a vigorous gene response. But, like the hypothalamus, the transcriptomic response is not consistent with mediation by HIF-1. If HIF-1 is a significant controller of gene expression in the fetal pituitary after hypoxia, it must be at a later time.Fil: Wood, Charles E.. University of Florida; Estados UnidosFil: Chang, Eileen I.. University of Florida; Estados UnidosFil: Richards, Elaine M.. University of Florida; Estados UnidosFil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Keller Wood, Maureen. University of Florida; Estados Unido
Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex
Transient hypoxia in pregnancy stimulates a physiological reflex response that redistributes blood flow and defends oxygen delivery to the fetal brain. We designed the present experiment to test the hypotheses that transient hypoxia produces damage of the cerebral cortex and that ketamine, an antagonist of NMDA receptors and a known anti-inflammatory agent, reduces the damage. Late gestation, chronically catheterized fetal sheep were subjected to a 30-min period of ventilatory hypoxia that decreased fetal PaO2 from 17 ± 1 to 10 ± 1 mmHg, or normoxia (PaO2 17 ± 1 mmHg), with or without pretreatment (10 min before hypoxia/normoxia) with ketamine (3 mg/kg, i.v.). One day (24 h) after hypoxia/normoxia, fetal cerebral cortex was removed and mRNA extracted for transcriptomics and systems biology analysis (n = 3-5 per group). Hypoxia stimulated a transcriptomic response consistent with a reduction in cellular metabolism and an increase in inflammation. Ketamine pretreatment reduced both of these responses. The inflammation response modeled with transcriptomic systems biology was validated by immunohistochemistry and showed increased abundance of microglia/macrophages after hypoxia in the cerebral cortical tissue that ketamine significantly reduced. We conclude that transient hypoxia produces inflammation of the fetal cerebral cortex and that ketamine, in a standard clinical dose, reduces the inflammation response.Fil: Chang, Eileen I.. University of Florida; Estados UnidosFil: Zárate, Miguel A.. University of Florida; Estados UnidosFil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Richards, Elaine M.. University of Florida; Estados UnidosFil: Arndt, Thomas J.. University of Florida; Estados UnidosFil: Keller Wood, Maureen. University of Florida; Estados UnidosFil: Wood, Charles E.. University of Florida; Estados Unido
Ketamine reduces inflammation pathways in the hypothalamus and hippocampus following transient hypoxia in the late-gestation fetal sheep
The physiological response to hypoxia in the fetus has been extensively studied with regard to redistribution of fetal combined ventricular output and sparing of oxygen delivery to fetal brain and heart. Previously, we have shown that the fetal brain is capable of mounting changes in gene expression that are consistent with tissue inflammation. The present study was designed to use transcriptomics and systems biology modeling to test the hypothesis that ketamine reduces or prevents the upregulation of inflammation-related pathways in hypothalamus and hippocampus after transient hypoxic hypoxia. Chronically catheterized fetal sheep (122 ± 5 days gestation) were subjected to 30 min hypoxia (relative reduction in PaO2∼50%) caused by infusion of nitrogen into the inspired gas of the pregnant ewe. RNA was isolated from fetal hypothalamus and hippocampus collected 24 h after hypoxia, and was analyzed for gene expression using the Agilent 15.5 k ovine microarray. Ketamine, injected 10 min prior to hypoxia, reduced the cerebral immune response activation to the hypoxia in both brain regions. Genes both upregulated by hypoxia and downregulated by ketamine after hypoxia were significantly associated with gene ontology terms and KEGG pathways that are, themselves, associated with the tissue response to exposure to bacteria. We conclude that the results are consistent with interruption of the cellular response to bacteria by ketamine.Fil: Chang, Eileen I.. University of Florida; Estados UnidosFil: Zarate, Miguel A.. University of Florida; Estados UnidosFil: Arndt, Thomas J.. University of Florida; Estados UnidosFil: Richards, Elaine M.. University of Florida; Estados UnidosFil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Keller Wood, Maureen. University of Florida; Estados UnidosFil: Wood, Charles E.. University of Florida; Estados Unido
How Gibbs distributions may naturally arise from synaptic adaptation mechanisms. A model-based argumentation
This paper addresses two questions in the context of neuronal networks
dynamics, using methods from dynamical systems theory and statistical physics:
(i) How to characterize the statistical properties of sequences of action
potentials ("spike trains") produced by neuronal networks ? and; (ii) what are
the effects of synaptic plasticity on these statistics ? We introduce a
framework in which spike trains are associated to a coding of membrane
potential trajectories, and actually, constitute a symbolic coding in important
explicit examples (the so-called gIF models). On this basis, we use the
thermodynamic formalism from ergodic theory to show how Gibbs distributions are
natural probability measures to describe the statistics of spike trains, given
the empirical averages of prescribed quantities. As a second result, we show
that Gibbs distributions naturally arise when considering "slow" synaptic
plasticity rules where the characteristic time for synapse adaptation is quite
longer than the characteristic time for neurons dynamics.Comment: 39 pages, 3 figure
Photoproduction of K+K− meson pairs on the proton
The exclusive reaction γp→pK+K− was studied in the photon energy range 3.0–3.8 GeV and momentum transfer range 0.6<−t<1.3 GeV2. Data were collected with the CLAS detector at the Thomas Jefferson National Accelerator Facility. In this kinematic range the integrated luminosity was approximately 20 pb−1. The reaction was isolated by detecting the K+ and the proton in CLAS, and reconstructing the K− via the missing-mass technique. Moments of the dikaon decay angular distributions were extracted from the experimental data. Besides the dominant contribution of the ϕ meson in the P wave, evidence for S−P interference was found. The differential production cross sections dσ/dt for individual waves in the mass range of the ϕ resonance were extracted and compared to predictions of a Regge-inspired model. This is the first time the t-dependent cross section of the S-wave contribution to the elastic K+K− photoproduction has been measured
Differential cross section and recoil polarization measurements for the gamma p to K+ Lambda reaction using CLAS at Jefferson Lab
We present measurements of the differential cross section and Lambda recoil
polarization for the gamma p to K+ Lambda reaction made using the CLAS detector
at Jefferson Lab. These measurements cover the center-of-mass energy range from
1.62 to 2.84 GeV and a wide range of center-of-mass K+ production angles.
Independent analyses were performed using the K+ p pi- and K+ p (missing pi -)
final-state topologies; results from these analyses were found to exhibit good
agreement. These differential cross section measurements show excellent
agreement with previous CLAS and LEPS results and offer increased precision and
a 300 MeV increase in energy coverage. The recoil polarization data agree well
with previous results and offer a large increase in precision and a 500 MeV
extension in energy range. The increased center-of-mass energy range that these
data represent will allow for independent study of non-resonant K+ Lambda
photoproduction mechanisms at all production angles.Comment: 22 pages, 16 figure
The radial distribution of dust species in young brown dwarf disks
We present a study of the radial distribution of dust species in young brown
dwarf disks. Our work is based on a compositional analysis of the 10 and 20
micron silicate emission features for brown dwarfs in the Taurus-Auriga
star-forming region. A fundamental finding of our work is that brown dwarfs
exhibit stronger signs of dust processing in the cold component of the disk,
compared to the higher mass T Tauri stars in Taurus. For nearly all of our
targets, we find a flat disk structure, which is consistent with the stronger
signs of dust processing observed in these disks. For the case of one brown
dwarf, 2M04230607, we find the forsterite mass fraction to be a factor of ~3
higher in the outer disk compared to the inner disk region. Simple large-scale
radial mixing cannot account for this gradient in the dust chemical
composition, and some local crystalline formation mechanism may be effective in
this disk. The relatively high abundance of crystalline silicates in the outer
cold regions of brown dwarf disks provides an interesting analogy to comets. In
this context, we have discussed the applicability of the various mechanisms
that have been proposed for comets on the formation and the outward transport
of high-temperature material. We also present Chandra X-ray observations for
two Taurus brown dwarfs, 2M04414825 and CFHT-BD-Tau 9. We find 2M04414825,
which has a ~12% crystalline mass fraction, to be more than an order of
magnitude brighter in X-ray than CFHT-BD-Tau 9, which has a ~35% crystalline
mass fraction. Combining with previous X-ray data, we find the inner disk
crystalline mass fractions to be anti-correlated with the X-ray strength.Comment: Accepted in MNRA
Absorption of the and Mesons in Nuclei
Due to their long lifetimes, the and mesons are the ideal
candidates for the study of possible modifications of the in-medium
meson-nucleon interaction through their absorption inside the nucleus. During
the E01-112 experiment at the Thomas Jefferson National Accelerator Facility,
the mesons were photoproduced from H, C, Ti, Fe, and Pb targets. This
paper reports the first measurement of the ratio of nuclear transparencies for
the channel. The ratios indicate larger in-medium widths compared
with what have been reported in other reaction channels.Comment: 6 pages, 4 figure
Near-threshold Photoproduction of Phi Mesons from Deuterium
We report the first measurement of the differential cross section on
-meson photoproduction from deuterium near the production threshold for a
proton using the CLAS detector and a tagged-photon beam in Hall B at Jefferson
Lab. The measurement was carried out by a triple coincidence detection of a
proton, and near the theoretical production threshold of 1.57 GeV.
The extracted differential cross sections for the initial
photon energy from 1.65-1.75 GeV are consistent with predictions based on a
quasifree mechanism. This experiment establishes a baseline for a future
experimental search for an exotic -N bound state from heavier nuclear
targets utilizing subthreshold/near-threshold production of mesons
Differential cross sections and recoil polarizations for the reaction gamma p -> K+ Sigma0
High-statistics measurements of differential cross sections and recoil
polarizations for the reaction have been
obtained using the CLAS detector at Jefferson Lab. We cover center-of-mass
energies () from 1.69 to 2.84 GeV, with an extensive coverage in the
production angle. Independent measurements were made using the
() and () final-state topologies,
and were found to exhibit good agreement. Our differential cross sections show
good agreement with earlier CLAS, SAPHIR and LEPS results, while offering
better statistical precision and a 300-MeV increase in coverage.
Above GeV, - and -channel Regge scaling behavior
can be seen at forward- and backward-angles, respectively. Our recoil
polarization () measurements represent a substantial increase in
kinematic coverage and enhanced precision over previous world data. At forward
angles we find that is of the same magnitude but opposite sign as
, in agreement with the static SU(6) quark model prediction of
. This expectation is violated in some mid- and
backward-angle kinematic regimes, where and are of
similar magnitudes but also have the same signs. In conjunction with several
other meson photoproduction results recently published by CLAS, the present
data will help constrain the partial wave analyses being performed to search
for missing baryon resonances.Comment: 23 pages, 17 figure
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