99 research outputs found
Discovery of Human Signaling Systems: Pairing Peptides to G Protein-Coupled Receptors
The peptidergic system is the most abundant network of ligand-receptor-mediated signaling in humans. However, the physiological roles remain elusive for numerous peptides and more than 100 G protein-coupled receptors (GPCRs). Here we report the pairing of cognate peptides and receptors. Integrating comparative genomics across 313 species and bioinformatics on all protein sequences and structures of human class A GPCRs, we identify universal characteristics that uncover additional potential peptidergic signaling systems. Using three orthogonal biochemical assays, we pair 17 proposed endogenous ligands with five orphan GPCRs that are associated with diseases, including genetic, neoplastic, nervous and reproductive system disorders. We also identify additional peptides for nine receptors with recognized ligands and pathophysiological roles. This integrated computational and multifaceted experimental approach expands the peptide-GPCR network and opens the way for studies to elucidate the roles of these signaling systems in human physiology and disease. Video Abstract: Features learned from comparative sequence and structural analyses enabled prediction of peptide ligands for orphan GPCRs that, when coupled with functional validation, expose physiologically relevant signaling systems. © 2019 The Author(s
Low Complexity Regularization of Linear Inverse Problems
Inverse problems and regularization theory is a central theme in contemporary
signal processing, where the goal is to reconstruct an unknown signal from
partial indirect, and possibly noisy, measurements of it. A now standard method
for recovering the unknown signal is to solve a convex optimization problem
that enforces some prior knowledge about its structure. This has proved
efficient in many problems routinely encountered in imaging sciences,
statistics and machine learning. This chapter delivers a review of recent
advances in the field where the regularization prior promotes solutions
conforming to some notion of simplicity/low-complexity. These priors encompass
as popular examples sparsity and group sparsity (to capture the compressibility
of natural signals and images), total variation and analysis sparsity (to
promote piecewise regularity), and low-rank (as natural extension of sparsity
to matrix-valued data). Our aim is to provide a unified treatment of all these
regularizations under a single umbrella, namely the theory of partial
smoothness. This framework is very general and accommodates all low-complexity
regularizers just mentioned, as well as many others. Partial smoothness turns
out to be the canonical way to encode low-dimensional models that can be linear
spaces or more general smooth manifolds. This review is intended to serve as a
one stop shop toward the understanding of the theoretical properties of the
so-regularized solutions. It covers a large spectrum including: (i) recovery
guarantees and stability to noise, both in terms of -stability and
model (manifold) identification; (ii) sensitivity analysis to perturbations of
the parameters involved (in particular the observations), with applications to
unbiased risk estimation ; (iii) convergence properties of the forward-backward
proximal splitting scheme, that is particularly well suited to solve the
corresponding large-scale regularized optimization problem
Planck intermediate results. VIII. Filaments between interacting clusters
About half of the baryons of the Universe are expected to be in the form of
filaments of hot and low density intergalactic medium. Most of these baryons
remain undetected even by the most advanced X-ray observatories which are
limited in sensitivity to the diffuse low density medium. The Planck satellite
has provided hundreds of detections of the hot gas in clusters of galaxies via
the thermal Sunyaev-Zel'dovich (tSZ) effect and is an ideal instrument for
studying extended low density media through the tSZ effect. In this paper we
use the Planck data to search for signatures of a fraction of these missing
baryons between pairs of galaxy clusters. Cluster pairs are good candidates for
searching for the hotter and denser phase of the intergalactic medium (which is
more easily observed through the SZ effect). Using an X-ray catalogue of
clusters and the Planck data, we select physical pairs of clusters as
candidates. Using the Planck data we construct a local map of the tSZ effect
centered on each pair of galaxy clusters. ROSAT data is used to construct X-ray
maps of these pairs. After having modelled and subtracted the tSZ effect and
X-ray emission for each cluster in the pair we study the residuals on both the
SZ and X-ray maps. For the merging cluster pair A399-A401 we observe a
significant tSZ effect signal in the intercluster region beyond the virial
radii of the clusters. A joint X-ray SZ analysis allows us to constrain the
temperature and density of this intercluster medium. We obtain a temperature of
kT = 7.1 +- 0.9, keV (consistent with previous estimates) and a baryon density
of (3.7 +- 0.2)x10^-4, cm^-3. The Planck satellite mission has provided the
first SZ detection of the hot and diffuse intercluster gas.Comment: Accepted by A&
The roles of the formal and informal sectors in the provision of effective science education
For many years, formal school science education has been criticised by students, teachers, parents and employers throughout the world. This article presents an argument that a greater collaboration between the formal and the informal sector could address some of these criticisms. The causes for concern about formal science education are summarised and the major approaches being taken to address them are outlined. The contributions that the informal sector currently makes to science education are identified. It is suggested that the provision of an effective science education entails an enhanced complementarity between the two sectors. Finally, there is a brief discussion of the collaboration and communication still needed if this is to be effective
Planck early results IX : XMM-Newton follow-up for validation of Planck cluster candidates
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