133 research outputs found
Mouse Cofactor of BRCA1 (Cobra1) Is Required for Early Embryogenesis
Negative elongation factor (NELF) is a four-subunit protein complex conserved from Drosophila to humans. In vitro biochemical and tissue culture-based studies have demonstrated an important role of NELF in controlling RNA polymerase II (Pol II) pausing in transcription. However, the physiological significance of NELF function is not clear due to the lack of any genetic systems for studying NELF.Here we show that disruption of the mouse B subunit of NELF (NELF-B), also known as cofactor of BRCA1 (Cobra1), causes inner cell mass (ICM) deficiency and embryonic lethality at the time of implantation. Consistent with the phenotype of the Cobra1 knockout (KO) embryos, knockdown of Cobra1 in mouse embryonic stem cells (ESCs) reduces the efficiency of colony formation and increases spontaneous differentiation. Cobra1-depleted ESCs maintain normal levels of Oct4, Nanog, and Sox2, master regulators of pluripotency in ESCs. However, knockdown of Cobra1 leads to precocious expression of developmental regulators including lymphoid enhancer-binding factor 1 (Lef1). Chromatin immunoprecipitation (ChIP) indicates that Cobra1 binds to the Lef1 promoter and modulates the abundance of promoter-bound RNA polymerase.Cobra1 is essential for early embryogenesis. Our findings also indicate that Cobra1 helps maintain the undifferentiated state of mESCs by preventing unscheduled expression of developmental genes
Neuroanatomical Variability of Religiosity
We hypothesized that religiosity, a set of traits variably expressed in the population, is modulated by neuroanatomical variability. We tested this idea by determining whether aspects of religiosity were predicted by variability in regional cortical volume. We performed structural magnetic resonance imaging of the brain in 40 healthy adult participants who reported different degrees and patterns of religiosity on a survey. We identified four Principal Components of religiosity by Factor Analysis of the survey items and associated them with regional cortical volumes measured by voxel-based morphometry. Experiencing an intimate relationship with God and engaging in religious behavior was associated with increased volume of R middle temporal cortex, BA 21. Experiencing fear of God was associated with decreased volume of L precuneus and L orbitofrontal cortex BA 11. A cluster of traits related with pragmatism and doubting God's existence was associated with increased volume of the R precuneus. Variability in religiosity of upbringing was not associated with variability in cortical volume of any region. Therefore, key aspects of religiosity are associated with cortical volume differences. This conclusion complements our prior functional neuroimaging findings in elucidating the proximate causes of religion in the brain
Two-pion Bose-Einstein correlations in central Pb-Pb collisions at = 2.76 TeV
The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb
collisions at TeV at the Large Hadron Collider is
presented. We observe a growing trend with energy now not only for the
longitudinal and the outward but also for the sideward pion source radius. The
pion homogeneity volume and the decoupling time are significantly larger than
those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/388
P2 receptors in atherosclerosis and postangioplasty restenosis
Atherosclerosis is an immunoinflammatory process that involves complex interactions between the vessel wall and blood components and is thought to be initiated by endothelial dysfunction [Ross (Nature 362:801–09, 1993); Fuster et al. (N Engl J Med 326:242–50, 1992); Davies and Woolf (Br Heart J 69:S3–S11, 1993)]. Extracellular nucleotides that are released from a variety of arterial and blood cells [Di Virgilio and Solini (Br J Pharmacol 135:831–42, 2002)] can bind to P2 receptors and modulate proliferation and migration of smooth muscle cells (SMC), which are known to be involved in intimal hyperplasia that accompanies atherosclerosis and postangioplasty restenosis [Lafont et al. (Circ Res 76:996–002, 1995)]. In addition, P2 receptors mediate many other functions including platelet aggregation, leukocyte adherence, and arterial vasomotricity. A direct pathological role of P2 receptors is reinforced by recent evidence showing that upregulation and activation of P2Y2 receptors in rabbit arteries mediates intimal hyperplasia [Seye et al. (Circulation 106:2720–726, 2002)]. In addition, upregulation of functional P2Y receptors also has been demonstrated in the basilar artery of the rat double-hemorrhage model [Carpenter et al. (Stroke 32:516–22, 2001)] and in coronary artery of diabetic dyslipidemic pigs [Hill et al. (J Vasc Res 38:432–43, 2001)]. It has been proposed that upregulation of P2Y receptors may be a potential diagnostic indicator for the early stages of atherosclerosis [Elmaleh et al. (Proc Natl Acad Sci U S A 95:691–95, 1998)]. Therefore, particular effort must be made to understand the consequences of nucleotide release from cells in the cardiovascular system and the subsequent effects of P2 nucleotide receptor activation in blood vessels, which may reveal novel therapeutic strategies for atherosclerosis and restenosis after angioplasty
The Epistemic Status of Processing Fluency as Source for Judgments of Truth
This article combines findings from cognitive psychology on the role of processing fluency in truth judgments with epistemological theory on justification of belief. We first review evidence that repeated exposure to a statement increases the subjective ease with which that statement is processed. This increased processing fluency, in turn, increases the probability that the statement is judged to be true. The basic question discussed here is whether the use of processing fluency as a cue to truth is epistemically justified. In the present analysis, based on Bayes’ Theorem, we adopt the reliable-process account of justification presented by Goldman (1986) and show that fluency is a reliable cue to truth, under the assumption that the majority of statements one has been exposed to are true. In the final section, we broaden the scope of this analysis and discuss how processing fluency as a potentially universal cue to judged truth may contribute to cultural differences in commonsense beliefs
Conserved Regulation of p53 Network Dosage by MicroRNA–125b Occurs through Evolving miRNA–Target Gene Pairs
MicroRNAs regulate networks of genes to orchestrate cellular functions. MiR-125b, the vertebrate homologue of the Caenorhabditis elegans microRNA lin-4, has been implicated in the regulation of neural and hematopoietic stem cell homeostasis, analogous to how lin-4 regulates stem cells in C. elegans. Depending on the cell context, miR-125b has been proposed to regulate both apoptosis and proliferation. Because the p53 network is a central regulator of both apoptosis and proliferation, the dual roles of miR-125b raise the question of what genes in the p53 network might be regulated by miR-125b. By using a gain- and loss-of-function screen for miR-125b targets in humans, mice, and zebrafish and by validating these targets with the luciferase assay and a novel miRNA pull-down assay, we demonstrate that miR-125b directly represses 20 novel targets in the p53 network. These targets include both apoptosis regulators like Bak1, Igfbp3, Itch, Puma, Prkra, Tp53inp1, Tp53, Zac1, and also cell-cycle regulators like cyclin C, Cdc25c, Cdkn2c, Edn1, Ppp1ca, Sel1l, in the p53 network. We found that, although each miRNA–target pair was seldom conserved, miR-125b regulation of the p53 pathway is conserved at the network level. Our results lead us to propose that miR-125b buffers and fine-tunes p53 network activity by regulating the dose of both proliferative and apoptotic regulators, with implications for tissue stem cell homeostasis and oncogenesis
Effects of salinity and drought on growth, ionic relations, compatible solutes and activation of antioxidant systems in oleander (Nerium oleander L.)
[EN] Nerium
oleander
is an
ornamental
species
of high
aesthetic
value,
grown
in arid
and
semi-
arid
regions
because
of its
drought
tolerance,
which
is also
considered
as
relatively
resistant
to salt;
yet
the
biochemical
and
molecular
mechanisms
underlying
oleander¿s
stress
toler-
ance
remain
largely
unknown.
To
investigate
these
mechanisms,
one-year-old
oleander
seedlings
were
exposed
to 15
and
30
days
of treatment
with
increasing
salt
concentratio
ns,
up
to 800
mM
NaCl,
and
to complete
withholding
of irrigation;
growth
parameters
and
bio-
chemical
markers
characteristic
of conserved
stress-response
pathways
were
then
deter-
mined
in stressed
and
control
plants.
Strong
water
deficit
and
salt
stress
both
caused
inhibition
of growth,
degradation
of photosynthetic
pigments,
a slight
(but
statistically
signifi-
cant)
increase
in the
leaf
levels
of specific
osmolytes,
and
induction
of oxidative
stress¿as
indicated
by
the
accumulation
of malondialdehyde
(MDA),
a reliable
oxidative
stress
marker
¿accompanied
by
increases
in the
levels
of total
phenolic
compounds
and
antioxidant
fla-
vonoids
and
in the
specific
activities
of ascorbate
peroxidase
(APX)
and
glutathione
reduc-
tase
(GR).
High
salinity,
in addition,
induced
accumulation
of Na
+
and
Cl
-
in roots
and
leaves
and
the
activation
of superoxide
dismutase
(SOD)
and
catalase
(CAT)
activities.
Apart
from
anatomical
adaptations
that
protect
oleander
from
leaf
dehydration
at moderate
levels
of
stress,
our
results
indicate
that
tolerance
of this
species
to salinity
and
water
deficit
is based
on
the
constitutive
accumulation
in leaves
of high
concentratio
ns
of soluble
carbohydrates
and,
to a lesser
extent,
of glycine
betaine,
and
in the
activation
of the
aforementioned
antiox-
idant
systems.
Moreover,
regarding
specifically
salt
stress,
mechanisms
efficiently
blocking
transport
of toxic
ions
from
the
roots
to the
aerial
parts
of the
plant
appear
to contribute
to a
large
extent
to tolerance
in
Nerium
oleanderThis work was financed by internal funds of the Polytechnic University of Valencia to Monica Boscaiu and Oscar Vicente. Dinesh Kumar’s stay in Valencia was financed by a NAMASTE fellowship from the European Union, and Mohamad Al Hassan was a recipient of an Erasmus Mundus pre-doctoral scholarship financed by the European Commission (Welcome Consortium).Kumar, D.; Al Hassan, M.; Naranjo Olivero, MA.; Agrawal, V.; Boscaiu, M.; Vicente, O. (2017). Effects of salinity and drought on growth, ionic relations, compatible solutes and activation of antioxidant systems in oleander (Nerium oleander L.). PLoS ONE. 12(9). doi:10.1371/journal.pone.0185017Se018501712
Effects of Inorganic Mercury and Methylmercury on Osteoclasts and Osteoblasts in the Scales of the Marine Teleost as a Model System of Bone
Integration of P2Y receptor-activated signal transduction pathways in G protein-dependent signalling networks
The role of nucleotides in intracellular energy provision and nucleic acid synthesis has been known for a long time. In the past decade, evidence has been presented that, in addition to these functions, nucleotides are also autocrine and paracrine messenger molecules that initiate and regulate a large number of biological processes. The actions of extracellular nucleotides are mediated by ionotropic P2X and metabotropic P2Y receptors, while hydrolysis by ecto-enzymes modulates the initial signal. An increasing number of studies have been performed to obtain information on the signal transduction pathways activated by nucleotide receptors. The development of specific and stable purinergic receptor agonists and antagonists with therapeutical potential largely contributed to the identification of receptors responsible for nucleotide-activated pathways. This article reviews the signal transduction pathways activated by P2Y receptors, the involved second messenger systems, GTPases and protein kinases, as well as recent findings concerning P2Y receptor signalling in C6 glioma cells. Besides vertical signal transduction, lateral cross-talks with pathways activated by other G protein-coupled receptors and growth factor receptors are discussed
Toxicity and quality of life report of a phase II study of stereotactic body radiotherapy (SBRT) for low and intermediate risk prostate cancer
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