102 research outputs found
Extending the dynamic range of transcription factor action by translational regulation
A crucial step in the regulation of gene expression is binding of
transcription factor (TF) proteins to regulatory sites along the DNA. But
transcription factors act at nanomolar concentrations, and noise due to random
arrival of these molecules at their binding sites can severely limit the
precision of regulation. Recent work on the optimization of information flow
through regulatory networks indicates that the lower end of the dynamic range
of concentrations is simply inaccessible, overwhelmed by the impact of this
noise. Motivated by the behavior of homeodomain proteins, such as the maternal
morphogen Bicoid in the fruit fly embryo, we suggest a scheme in which
transcription factors also act as indirect translational regulators, binding to
the mRNA of other transcription factors. Intuitively, each mRNA molecule acts
as an independent sensor of the TF concentration, and averaging over these
multiple sensors reduces the noise. We analyze information flow through this
new scheme and identify conditions under which it outperforms direct
transcriptional regulation. Our results suggest that the dual role of
homeodomain proteins is not just a historical accident, but a solution to a
crucial physics problem in the regulation of gene expression.Comment: 14 pages, 5 figure
A Tight Upper Bound on Mutual Information
We derive a tight lower bound on equivocation (conditional entropy), or
equivalently a tight upper bound on mutual information between a signal
variable and channel outputs. The bound is in terms of the joint distribution
of the signals and maximum a posteriori decodes (most probable signals given
channel output). As part of our derivation, we describe the key properties of
the distribution of signals, channel outputs and decodes, that minimizes
equivocation and maximizes mutual information. This work addresses a problem in
data analysis, where mutual information between signals and decodes is
sometimes used to lower bound the mutual information between signals and
channel outputs. Our result provides a corresponding upper bound.Comment: 6 pages, 3 figures; proof illustration adde
Mutual Repression enhances the Steepness and Precision of Gene Expression Boundaries
Embryonic development is driven by spatial patterns of gene expression that
determine the fate of each cell in the embryo. While gene expression is often
highly erratic, embryonic development is usually exceedingly precise. In
particular, gene expression boundaries are robust not only against intrinsic
noise from gene expression and protein diffusion, but also against
embryo-to-embryo variations in the morphogen gradients, which provide
positional information to the differentiating cells. How development is robust
against intra- and inter-embryonic variations is not understood. A common motif
in the gene regulation networks that control embryonic development is mutual
repression between pairs of genes. To assess the role of mutual repression in
the robust formation of gene expression patterns, we have performed large-scale
stochastic simulations of a minimal model of two mutually repressing gap genes
in Drosophila, hunchback (hb) and knirps (kni). Our model includes not only
mutual repression between hb and kni, but also the stochastic and cooperative
activation of hb by the anterior morphogen Bicoid (Bcd) and of kni by the
posterior morphogen Caudal (Cad), as well as the diffusion of Hb and Kni. Our
analysis reveals that mutual repression can markedly increase the steepness and
precision of the gap gene expression boundaries. In contrast to spatial
averaging and cooperative gene activation, mutual repression thus allows for
gene-expression boundaries that are both steep and precise. Moreover, mutual
repression dramatically enhances their robustness against embryo-to-embryo
variations in the morphogen levels. Finally, our simulations reveal that gap
protein diffusion plays a critical role not only in reducing the width of gap
gene expression boundaries via spatial averaging, but also in repairing
patterning errors that could arise due to the bistability induced by mutual
repression.Comment: 29 pages, 9 figures, supporting text with 9 supporting figures;
accepted for publication in PLoS Comp. Bio
Stable developmental patterns of gene expression without morphogen gradients
Gene expression patterns are established by cross-regulating target genes
that interpret morphogen gradients. However, as development progresses,
morphogen activity is reduced, leaving the emergent pattern without stabilizing
positional cues. The pattern then can be deteriorated by the intrinsically
noisy biochemical processes acting at the cellular level. But remarkably, the
established gene expression patterns remain spatially and temporally stable in
many biological systems. Here we combine spatial-stochastic simulations with an
enhanced sampling method and a recently developed stability theory to address
how spatiotemporal integrity of a gene expression pattern is maintained in
developing tissue lacking morphogen gradients. Using a minimal embryo model
consisting of spatially coupled biochemical reactor volumes, we study a stripe
pattern in which weak cross-repression between nearest neighbor domians
alternates with strong repression between next-nearest neighbor domains,
inspired by the gap gene system in the Drosophila embryo. We find that
fine-tuning of the weak repressive interactions to an optimal level can
significantly increase temporal stability of the expression patterns, allowing
for stable patterns over developmentally relevant times in the absence of
morphogen gradients. The numerically determined optimal parameters closely
agree with the predictions of the stability theory. By analizing the dynamics
of factors characterizing pattern integrity, we trace back the stability
enhancement to the emergence of restoring forces, maintaining the pattern in a
meta-stable basin. Altogether our results demonstrate that metastable
attractors can emerge as a property of stochastic gene expression patterns even
without system-wide positional cues, provided that the gene regulatory
interactions shaping the pattern are optimally tuned
Black hole solutions in F(R) gravity with conformal anomaly
In this paper, we consider theory instead of Einstein gravity
with conformal anomaly and look for its analytical solutions. Depending on the
free parameters, one may obtain both uncharged and charged solutions for some
classes of models. Calculation of Kretschmann scalar shows that there is
a singularity located at , which the geometry of uncharged (charged)
solution is corresponding to the Schwarzschild (Reissner-Nordstr\"om)
singularity. Further, we discuss the viability of our models in details. We
show that these models can be stable depending on their parameters and in
different epoches of the universe.Comment: 12 pages, one figur
Implementation and testing of the first prompt search for gravitational wave transients with electromagnetic counterparts
Aims. A transient astrophysical event observed in both gravitational wave
(GW) and electromagnetic (EM) channels would yield rich scientific rewards. A
first program initiating EM follow-ups to possible transient GW events has been
developed and exercised by the LIGO and Virgo community in association with
several partners. In this paper, we describe and evaluate the methods used to
promptly identify and localize GW event candidates and to request images of
targeted sky locations.
Methods. During two observing periods (Dec 17 2009 to Jan 8 2010 and Sep 2 to
Oct 20 2010), a low-latency analysis pipeline was used to identify GW event
candidates and to reconstruct maps of possible sky locations. A catalog of
nearby galaxies and Milky Way globular clusters was used to select the most
promising sky positions to be imaged, and this directional information was
delivered to EM observatories with time lags of about thirty minutes. A Monte
Carlo simulation has been used to evaluate the low-latency GW pipeline's
ability to reconstruct source positions correctly.
Results. For signals near the detection threshold, our low-latency algorithms
often localized simulated GW burst signals to tens of square degrees, while
neutron star/neutron star inspirals and neutron star/black hole inspirals were
localized to a few hundred square degrees. Localization precision improves for
moderately stronger signals. The correct sky location of signals well above
threshold and originating from nearby galaxies may be observed with ~50% or
better probability with a few pointings of wide-field telescopes.Comment: 17 pages. This version (v2) includes two tables and 1 section not
included in v1. Accepted for publication in Astronomy & Astrophysic
The caudo-ventral pallium is a novel pallial domain expressing Gdf10 and generating Ebf3-positive neurons of the medial amygdala
In rodents, the medial nucleus of the amygdala receives direct inputs from the accessory olfactory bulbs and is mainly implicated in pheromone-mediated reproductive and defensive behaviors. The principal neurons of the medial amygdala are GABAergic neurons generated principally in the caudo-ventral medial ganglionic eminence and preoptic area. Beside GABAergic neurons, the medial amygdala also contains glutamatergic Otp-expressing neurons cells generated in the lateral hypothalamic neuroepithelium and a non-well characterized Pax6-positive population. In the present work, we describe a novel glutamatergic Ebf3-expressing neuronal subpopulation distributed within the periphery of the postero-ventral medial amygdala. These neurons are generated in a pallial domain characterized by high expression of Gdf10. This territory is topologically the most caudal tier of the ventral pallium and accordingly, we named it Caudo-Ventral Pallium (CVP). In the absence of Pax6, the CVP is disrupted and Ebf3-expressing neurons fail to be generated. Overall, this work proposes a novel model of the neuronal composition of the medial amygdala and unravels for the first time a new novel pallial subpopulation originating from the CVP and expressing the transcription factor Ebf3.This work was supported by Grants of the French National Research Agency (Agence Nationale de la Recherche; ANR) [ANR-13-BSV4-0011] and by the French Government through the ‘Investments for the Future’ LABEX SIGNALIFE [ANR-11-LABX-0028-01] to M.S., by the Spanish Government (BFU2007-60263 and BFU2010-17305) to A.F, and by the Medical Research Council (MR/K013750/1) to T.T. N.R.-R. is funded by a postdoctoral fellowship from the Ville de Nice, France (“Aide Individuelle aux Jeunes Chercheurs 2016”).Peer reviewe
The mammals of Angola
Scientific investigations on the mammals of Angola started over 150 years
ago, but information remains scarce and scattered, with only one recent published
account. Here we provide a synthesis of the mammals of Angola based on a thorough
survey of primary and grey literature, as well as recent unpublished records. We present
a short history of mammal research, and provide brief information on each species
known to occur in the country. Particular attention is given to endemic and near endemic
species. We also provide a zoogeographic outline and information on the conservation
of Angolan mammals. We found confirmed records for 291 native species, most of
which from the orders Rodentia (85), Chiroptera (73), Carnivora (39), and
Cetartiodactyla (33). There is a large number of endemic and near endemic species,
most of which are rodents or bats. The large diversity of species is favoured by the wide range of habitats with contrasting environmental conditions, while endemism tends to
be associated with unique physiographic settings such as the Angolan Escarpment. The
mammal fauna of Angola includes 2 Critically Endangered, 2 Endangered, 11
Vulnerable, and 14 Near-Threatened species at the global scale. There are also 12 data
deficient species, most of which are endemics or near endemics to the countryinfo:eu-repo/semantics/publishedVersio
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