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  • 1
    Publication Date: 2014-12-18
    Description: Author(s): Aurélien Barrau, Carlo Rovelli, and Francesca Vidotto Quantum gravity effects could make a black hole explode in a time shorter than the Hawking radiation time, via local tunneling through a white hole solution. Here we estimate the size of a primordial black hole exploding today via this process, using a simple generic model. Fast radio bursts, strong... [Phys. Rev. D 90, 127503] Published Wed Dec 17, 2014
    Keywords: General relativity, gravitation
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  • 2
    Publication Date: 2014-11-08
    Description: Author(s): Kōji Uryū, Eric Gourgoulhon, Charalampos M. Markakis, Kotaro Fujisawa, Antonios Tsokaros, and Yoshiharu Eriguchi Stationary and axisymmetric solutions of relativistic rotating stars with strong mixed poloidal and toroidal magnetic fields are obtained numerically. Because of the mixed components of the magnetic field, the underlying stationary and axisymmetric spacetimes are no longer circular. These configurat... [Phys. Rev. D 90, 101501] Published Fri Nov 07, 2014
    Keywords: General relativity, gravitation
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  • 3
    Publication Date: 2014-12-04
    Description: Author(s): Antonin Coutant and Renaud Parentani To identify what replaces the key notion of black hole horizon when working with theories which break Lorentz invariance at high energy, we study the modes responsible for the Hawking effect in the presence of high frequency dispersion. We show that they are regularized across the horizon over a sho... [Phys. Rev. D 90, 121501] Published Wed Dec 03, 2014
    Keywords: General relativity, gravitation
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  • 4
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    American Physical Society (APS)
    Publication Date: 2014-01-23
    Description: Author(s): José Luis Jaramillo Black hole horizon sections, modeled as marginally outer trapped surfaces (MOTS), possess a notion of stability admitting a spectral characterization. Specifically, the “principal eigenvalue” λo of the MOTS-stability operator (an elliptic operator on horizon sections) must be nonnegative. We discuss... [Phys. Rev. D 89, 021502] Published Wed Jan 22, 2014
    Keywords: General relativity, gravitation
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  • 5
    Publication Date: 2014-01-23
    Description: Author(s): D. Glavan, T. Prokopec, and V. Prymidis In this paper we study a massless, minimally coupled scalar field in a Friedmann-Lemaître-Robertson-Walker space-time with periods of different constant deceleration parameter. We assume the Bunch-Davies vacuum during inflation and then use a sudden matching approximation to match it onto a radiatio... [Phys. Rev. D 89, 024024] Published Wed Jan 22, 2014
    Keywords: General relativity, gravitation
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  • 6
    Publication Date: 2014-01-23
    Description: Author(s): Anna Heffernan, Adrian Ottewill, and Barry Wardell In a previous paper, we computed expressions for the Detweiler-Whiting singular field of point scalar, electromagnetic and gravitational charges following a geodesic of the Schwarzschild spacetime. We now extend this to the case of equatorial orbits in Kerr spacetime, using coordinate and covariant ... [Phys. Rev. D 89, 024030] Published Wed Jan 22, 2014
    Keywords: General relativity, gravitation
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  • 7
    Publication Date: 2014-03-14
    Description: Author(s): Andrea Taracchini, Alessandra Buonanno, Yi Pan, Tanja Hinderer, Michael Boyle, Daniel A. Hemberger, Lawrence E. Kidder, Geoffrey Lovelace, Abdul H. Mroué, Harald P. Pfeiffer, Mark A. Scheel, Béla Szilágyi, Nicholas W. Taylor, and Anil Zenginoglu Gravitational waves emitted by black-hole binary systems have the highest signal-to-noise ratio in LIGO and Virgo detectors when black-hole spins are aligned with the orbital angular momentum and extremal. For such systems, we extend the effective-one-body inspiral-merger-ringdown waveforms to gener... [Phys. Rev. D 89, 061502] Published Thu Mar 13, 2014
    Keywords: General relativity, gravitation
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  • 8
    Publication Date: 2014-03-21
    Description: Author(s): William E. East, Fethi M. Ramazanoğlu, and Frans Pretorius We study the superradiant scattering of gravitational waves by a nearly extremal black hole (dimensionless spin a=0.99) by numerically solving the full Einstein field equations, thus including backreaction effects. This allows us to study the dynamics of the black hole as it loses energy and angular... [Phys. Rev. D 89, 061503] Published Thu Mar 20, 2014
    Keywords: General relativity, gravitation
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  • 9
    Publication Date: 2014-02-25
    Description: Author(s): Hirotada Okawa, Vitor Cardoso, and Paolo Pani The nonlinear instability of anti-de Sitter spacetime has recently been established with the striking result that generic initial data collapse to form black holes. This outcome suggests that confined matter might generically collapse, and that collapse could only be halted—at most—by nonlinear boun... [Phys. Rev. D 89, 041502] Published Mon Feb 24, 2014
    Keywords: General relativity, gravitation
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  • 10
    Publication Date: 2014-02-25
    Description: Author(s): Raissa F. P. Mendes, George E. A. Matsas, and Daniel A. T. Vanzella General-relativistic stable spacetimes can be made unstable under the presence of certain nonminimally coupled free scalar fields. In this paper, we analyze the evolution of linear scalar-field perturbations in spherically symmetric spacetimes and compare the classical stability analysis with a rece... [Phys. Rev. D 89, 047503] Published Mon Feb 24, 2014
    Keywords: General relativity, gravitation
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  • 11
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    American Physical Society (APS)
    Publication Date: 2014-04-01
    Description: Author(s): Sourav Bhattacharya and Hideki Maeda It is shown that, under the separability assumption for the metric, the slow-rotation approximation for the Bocharova-Bronnikov-Melnikov-Bekenstein black hole in general relativity with a conformally coupled scalar field does not work outside the event horizon. Suggestions indicated by our present a... [Phys. Rev. D 89, 087501] Published Mon Mar 31, 2014
    Keywords: General relativity, gravitation
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  • 12
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    American Physical Society (APS)
    Publication Date: 2014-04-03
    Description: Author(s): Ted Jacobson We show that Hořava gravity can be obtained from Einstein-aether theory in the limit that the twist coupling constant goes to infinity, while holding fixed the expansion, shear and acceleration couplings. This limit helps to clarify the relation between the two theories, and allows Hořava results to... [Phys. Rev. D 89, 081501] Published Wed Apr 02, 2014
    Keywords: General relativity, gravitation
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  • 13
    Publication Date: 2014-04-04
    Description: Author(s): Eugeny Babichev and Alessandro Fabbri We consider the analytic solutions of massive (bi)gravity which can be written in a simple form using advanced Eddington-Finkelstein coordinates. We analyze the stability of these solutions against radial perturbations. First we recover the previously obtained result on the instability of the bidiag... [Phys. Rev. D 89, 081502] Published Thu Apr 03, 2014
    Keywords: General relativity, gravitation
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  • 14
    Publication Date: 2014-08-30
    Description: Author(s): Alexander A. H. Graham and Rahul Jha It has been well known since the 1970s that stationary black holes do not generically support scalar hair. Most of the no-hair theorems which support this depend crucially upon the assumption that the scalar field has no time dependence. Here we fill in this omission by ruling out the existence of s... [Phys. Rev. D 90, 041501] Published Fri Aug 29, 2014
    Keywords: General relativity, gravitation
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  • 15
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    American Physical Society (APS)
    Publication Date: 2014-10-21
    Description: Author(s): Xian Gao A general framework for effective theories propagating two tensor and one scalar degrees of freedom is investigated. Geometrically, it describes dynamical foliation of spacelike hypersurfaces coupled to a general background, in which the scalar mode encodes the fluctuation of the hypersurfaces. With... [Phys. Rev. D 90, 081501] Published Mon Oct 20, 2014
    Keywords: General relativity, gravitation
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  • 16
    Publication Date: 2014-08-29
    Description: Author(s): Kenta Kiuchi, Koutarou Kyutoku, Yuichiro Sekiguchi, Masaru Shibata, and Tomohide Wada We perform high-resolution magnetohydrodynamics simulations of binary neutron star mergers in numerical relativity on the Japanese supercomputer K. The neutron stars and merger remnants are covered by a grid spacing of 70 m, which yields the highest-resolution results among those derived so far. By ... [Phys. Rev. D 90, 041502] Published Thu Aug 28, 2014
    Keywords: General relativity, gravitation
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  • 17
    Publication Date: 2014-11-25
    Description: Author(s): Riccardo Moriconi, Giovanni Montani, and Salvatore Capozziello We study the asymptotic dynamics of the mixmaster universe, near the cosmological singularity, considering f(R) gravity up to a quadratic correction in the Ricci scalar R. The analysis is performed in the scalar-tensor framework and adopting Misner-Chitré-like variables to describe the mixmaster uni... [Phys. Rev. D 90, 101503] Published Mon Nov 24, 2014
    Keywords: General relativity, gravitation
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  • 18
    Publication Date: 2014-11-25
    Description: Author(s): John T. Giblin, Jr. and Eric Thrane The recent claim by BICEP2 of evidence for primordial gravitational waves has focused interest on the potential for early-Universe cosmology using gravitational waves. In addition to cosmic microwave background detectors, efforts are underway to carry out gravitational-wave astronomy with pulsar tim... [Phys. Rev. D 90, 107502] Published Mon Nov 24, 2014
    Keywords: General relativity, gravitation
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  • 19
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    American Physical Society (APS)
    Publication Date: 2014-11-05
    Description: Author(s): J. R. Morris Four-dimensional scalar-tensor theory is considered within two conformal frames, the Jordan frame (JF) and the Einstein frame (EF). The actions for the theory are equivalent and equations of motion can be obtained from each action. It is found that the JF equations of motion, expressed in terms of E... [Phys. Rev. D 90, 107501] Published Tue Nov 04, 2014
    Keywords: General relativity, gravitation
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  • 20
    Publication Date: 2014-11-27
    Description: Author(s): O. B. Zaslavskii If two particles moving towards a black hole collide near the horizon, their energy in the center-of-mass frame can grow unbounded. This is the so-called Bañados-Silk-West effect. Previously, it was shown that in the 3+1 space-time, this effect has a universal nature. We show that for a wide class o... [Phys. Rev. D 90, 107503] Published Wed Nov 26, 2014
    Keywords: General relativity, gravitation
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  • 21
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    American Physical Society (APS)
    Publication Date: 2014-12-03
    Description: Author(s): S. Latifah, A. Sulaksono, and T. Mart By using a simple thermodynamical method, we confirm the finding of Chavanis and Harko that stable Bose-Einstein condensate stars can form. However, by using a thermodynamically consistent boson equation of state, we obtain a less massive Bose-Einstein condensate star compared to the one predicted b... [Phys. Rev. D 90, 127501] Published Tue Dec 02, 2014
    Keywords: General relativity, gravitation
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  • 22
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    American Physical Society (APS)
    Publication Date: 2014-09-04
    Description: Author(s): Richard T. Hammond The probability of spin flip of an electron due to a torsional wave is calculated. It is compared to the electromagnetic case, and ways to detect torsion are discussed. [Phys. Rev. D 90, 067501] Published Wed Sep 03, 2014
    Keywords: General relativity, gravitation
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  • 23
    Publication Date: 2014-09-05
    Description: Author(s): I. V. Tanatarov and O. B. Zaslavskii If two particles collide near a black hole, the energy in their center of mass can, under certain conditions, grow unbounded. This is Bañados-Silk-West effect. We show that this effect retains its validity even if some force acts on a particle, provided some reasonable and weak restrictions are impo... [Phys. Rev. D 90, 067502] Published Thu Sep 04, 2014
    Keywords: General relativity, gravitation
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  • 24
    Publication Date: 2014-09-06
    Description: Author(s): Burkhard Kleihaus, Jutta Kunz, and Sindy Mojica We consider rapidly rotating black holes and neutron stars in dilatonic Einstein-Gauss-Bonnet (EGBd) theory and determine their quadrupole moments, which receive a contribution from the dilaton. The quadrupole moment of EGBd black holes can be considerably larger than the Kerr value. For neutron sta... [Phys. Rev. D 90, 061501] Published Fri Sep 05, 2014
    Keywords: General relativity, gravitation
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  • 25
    Publication Date: 2014-09-12
    Description: Author(s): Amir Ghalee We consider a scalar field with a kinetic term nonminimally coupled to gravity in an anisotropic background. Various potentials for the scalar field are considered. By explicit examples, we show how the anisotropy can change the dynamics of the scalar field compared with the isotropic background. [Phys. Rev. D 90, 067503] Published Thu Sep 11, 2014
    Keywords: General relativity, gravitation
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  • 26
    Publication Date: 2014-09-12
    Description: Author(s): Tolga Birkandan and Mirjam Cvetič We obtained retarded Green’s functions for massless scalar fields in the background of near-extreme, near-horizon rotating charged black hole of five-dimensional minimal gauged supergravity in Phys. Rev. D 84 , 044018 (2011). For general nonextreme black holes, we also derived the radial part of the ... [Phys. Rev. D 90, 067504] Published Thu Sep 11, 2014
    Keywords: General relativity, gravitation
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  • 27
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    American Physical Society (APS)
    Publication Date: 2014-12-10
    Description: Author(s): Matt Visser Event horizons are (generically) not physically observable. In contrast, apparent horizons (and the closely related trapping horizons) are generically physically observable—in the sense that they can be detected by observers working in finite-size regions of spacetime. Consequently event horizons ar... [Phys. Rev. D 90, 127502] Published Fri Dec 05, 2014
    Keywords: General relativity, gravitation
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  • 28
    Publication Date: 2014-10-11
    Description: Author(s): S. Habib Mazharimousavi and M. Halilsoy We reconsider the generalized flare-out conditions in static wormhole throats given by Hochberg and Visser. We show that, due to the presence of matter sources on the throat, these conditions are not applicable to the thin-shell wormholes. [Phys. Rev. D 90, 087501] Published Fri Oct 10, 2014
    Keywords: General relativity, gravitation
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  • 29
    Publication Date: 2014-09-25
    Description: Author(s): J. Fernando Barbero G., Tomasz Pawłowski, and Eduardo J. S. Villaseñor We discuss, within the simplified context provided by the polymeric harmonic oscillator, a construction leading to a separable Hilbert space that preserves some of the most important features of the spectrum of the Hamiltonian operator. This construction may be applied to other polymer quantum mecha... [Phys. Rev. D 90, 067505] Published Wed Sep 24, 2014
    Keywords: General relativity, gravitation
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  • 30
    Publication Date: 2014-05-23
    Description: Author(s): K. A. Bronnikov, J. C. Fabris, R. Silveira, and O. B. Zaslavskii We consider Einstein-Maxwell-dilaton gravity with charged dust and interaction of the form P(χ)F μν F μν , where P(χ) is an arbitrary function of the dilaton field χ that can be normal or phantom. For any regular P(χ), static configurations are possible with arbitrary functions g 00 =exp(2γ(x i )) (i=1, 2, ... [Phys. Rev. D 89, 107501] Published Thu May 22, 2014
    Keywords: General relativity, gravitation
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  • 31
    Publication Date: 2014-06-21
    Description: Author(s): Térence Delsate, Jorge V. Rocha, and Raphael Santarelli We construct exact solutions describing the motion of rotating thin shells in a fully backreacted five-dimensional rotating black hole spacetime. The radial equation of motion follows from the Darmois-Israel junction conditions, where both interior and exterior geometries are taken to be equal angul... [Phys. Rev. D 89, 121501] Published Fri Jun 20, 2014
    Keywords: General relativity, gravitation
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  • 32
    Publication Date: 2014-02-21
    Description: Author(s): Shao-Wen Wei and Yu-Xiao Liu Black hole lensing and gravitational waves are, respectively, closely dependent on the property of the lens and radiation source. In this paper, a universal relation between them is established for a rotating, asymptotically flat black hole acting simultaneously as a lens and a gravitational wave so... [Phys. Rev. D 89, 047502] Published Thu Feb 20, 2014
    Keywords: General relativity, gravitation
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  • 33
    Publication Date: 2014-02-21
    Description: Author(s): Lawrence M. Krauss and Frank Wilczek While many aspects of general relativity have been tested, and general principles of quantum dynamics demand its quantization, there is no direct evidence for that. It has been argued that development of detectors sensitive to individual gravitons is unlikely, and perhaps impossible. We argue here, ... [Phys. Rev. D 89, 047501] Published Thu Feb 20, 2014
    Keywords: General relativity, gravitation
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  • 34
    Publication Date: 2014-04-10
    Description: Author(s): Manuel Hohmann We present a static, spherically symmetric, traversable wormhole solution to multimetric gravity which is sustained by only nonexotic matter, i.e., matter which satisfies all energy conditions. The possibility of this solution arises from the fact that under certain conditions the multimetric gravit... [Phys. Rev. D 89, 087503] Published Wed Apr 09, 2014
    Keywords: General relativity, gravitation
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  • 35
    Publication Date: 2014-04-09
    Description: Author(s): Wenbin Lin and Chunhua Jiang We present an exact and close-form harmonic metric for Kerr-Newman black hole, and demonstrate it is unique in the harmonic coordinates. [Phys. Rev. D 89, 087502] Published Tue Apr 08, 2014
    Keywords: General relativity, gravitation
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  • 36
    Publication Date: 2014-04-09
    Description: Author(s): Thibault Damour, Federico Guercilena, Ian Hinder, Seth Hopper, Alessandro Nagar, and Luciano Rezzolla We probe the gravitational interaction of two black holes in the strong-field regime by computing the scattering angle χ of hyperboliclike, close binary-black-hole encounters as a function of the impact parameter. The fully general-relativistic result from numerical relativity is compared to two ana... [Phys. Rev. D 89, 081503] Published Tue Apr 08, 2014
    Keywords: General relativity, gravitation
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  • 37
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    American Physical Society (APS)
    Publication Date: 2014-11-15
    Description: Author(s): Saoussen Mbarek and M. B. Paranjape We study the possibility of the existence of negative mass bubbles within a de Sitter spacetime background with matter content corresponding to a perfect fluid. It is shown that there exist configurations of the perfect fluid that satisfy everywhere the dominant energy condition, the Einstein equati... [Phys. Rev. D 90, 101502] Published Fri Nov 14, 2014
    Keywords: General relativity, gravitation
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  • 38
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    American Physical Society (APS)
    Publication Date: 2014-12-31
    Description: Author(s): Burkhard Kleihaus and Jutta Kunz We present rotating wormhole solutions in general relativity, which are supported by a phantom scalar field. These solutions evolve from the static Ellis wormhole, when the throat is set into rotation. As the rotational velocity increases, the throat deforms until, at a maximal value of the rotation... [Phys. Rev. D 90, 121503] Published Tue Dec 30, 2014
    Keywords: General relativity, gravitation
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  • 39
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    American Physical Society (APS)
    Publication Date: 2014-07-12
    Description: Author(s): Shahar Hod The hydrodynamic vortex, an effective spacetime geometry for propagating sound waves, is studied analytically. In contrast with the familiar Kerr black hole spacetime, the hydrodynamic vortex model is described by an effective acoustic geometry which has no horizons. However, this acoustic spacetime... [Phys. Rev. D 90, 027501] Published Fri Jul 11, 2014
    Keywords: General relativity, gravitation
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  • 40
    Publication Date: 2014-08-13
    Description: Author(s): V. S. Manko and H. García-Compeán The Gaussian curvature of the two-surface r=0, t=const is calculated for the Kerr–de Sitter and Kerr–Newman–de Sitter solutions, yielding nonzero analytical expressions for both cases. The results obtained on the one hand exclude the possibility for that surface to be a disk and, on the other hand, ... [Phys. Rev. D 90, 047501] Published Tue Aug 12, 2014
    Keywords: General relativity, gravitation
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  • 41
    Publication Date: 2014-08-19
    Description: Author(s): Cosimo Bambi The construction of a generic parametrization to describe the spacetime geometry around astrophysical black hole candidates is an important step to test the Kerr black hole hypothesis. In the last few years, the Johannsen-Psaltis metric has been the most common framework to study possible deviations... [Phys. Rev. D 90, 047503] Published Mon Aug 18, 2014
    Keywords: General relativity, gravitation
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  • 42
    Publication Date: 2014-08-14
    Description: Author(s): Prasant Samantray and T. Padmanabhan Field theories in black hole spacetimes undergo dimensional reduction near horizon (in the Rindler limit) to two-dimensional conformal field theories. We investigate this enhancement of symmetries in the context of gauge/gravity duality by considering Rindler space as the boundary of anti-de Sitter ... [Phys. Rev. D 90, 047502] Published Wed Aug 13, 2014
    Keywords: General relativity, gravitation
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  • 43
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    American Physical Society (APS)
    Publication Date: 2014-07-11
    Description: Author(s): José Barrientos O. and Guillermo F. Rubilar In Phys. Rev. D 84 , 024020 (2011) Harko, Lobo, Nojiri and Odintsov presented a modified theory of gravitation, f(R,T) gravity, where the gravitational Lagrangian is given by an arbitrary function of the Ricci scalar and of the trace of the stress-energy tensor. In this Comment we correct the conserv... [Phys. Rev. D 90, 028501] Published Thu Jul 10, 2014
    Keywords: General relativity, gravitation
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  • 44
    Publication Date: 2014-06-17
    Description: Disease tolerance is the ability of the host to reduce the effect of infection on host fitness. Analysis of disease tolerance pathways could provide new approaches for treating infections and other inflammatory diseases. Typically, an initial exposure to bacterial lipopolysaccharide (LPS) induces a state of refractoriness to further LPS challenge (endotoxin tolerance). We found that a first exposure of mice to LPS activated the ligand-operated transcription factor aryl hydrocarbon receptor (AhR) and the hepatic enzyme tryptophan 2,3-dioxygenase, which provided an activating ligand to the former, to downregulate early inflammatory gene expression. However, on LPS rechallenge, AhR engaged in long-term regulation of systemic inflammation only in the presence of indoleamine 2,3-dioxygenase 1 (IDO1). AhR-complex-associated Src kinase activity promoted IDO1 phosphorylation and signalling ability. The resulting endotoxin-tolerant state was found to protect mice against immunopathology in Gram-negative and Gram-positive infections, pointing to a role for AhR in contributing to host fitness.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4098076/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4098076/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bessede, Alban -- Gargaro, Marco -- Pallotta, Maria T -- Matino, Davide -- Servillo, Giuseppe -- Brunacci, Cinzia -- Bicciato, Silvio -- Mazza, Emilia M C -- Macchiarulo, Antonio -- Vacca, Carmine -- Iannitti, Rossana -- Tissi, Luciana -- Volpi, Claudia -- Belladonna, Maria L -- Orabona, Ciriana -- Bianchi, Roberta -- Lanz, Tobias V -- Platten, Michael -- Della Fazia, Maria A -- Piobbico, Danilo -- Zelante, Teresa -- Funakoshi, Hiroshi -- Nakamura, Toshikazu -- Gilot, David -- Denison, Michael S -- Guillemin, Gilles J -- DuHadaway, James B -- Prendergast, George C -- Metz, Richard -- Geffard, Michel -- Boon, Louis -- Pirro, Matteo -- Iorio, Alfonso -- Veyret, Bernard -- Romani, Luigina -- Grohmann, Ursula -- Fallarino, Francesca -- Puccetti, Paolo -- P30 CA056036/CA/NCI NIH HHS/ -- R01 CA109542/CA/NCI NIH HHS/ -- R01 ES007685/ES/NIEHS NIH HHS/ -- R01ES007685/ES/NIEHS NIH HHS/ -- England -- Nature. 2014 Jul 10;511(7508):184-90. doi: 10.1038/nature13323.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy [2] IMS Laboratory, University of Bordeaux, 33607 Pessac, France [3]. ; 1] Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy [2]. ; Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy. ; Center for Genome Research, University of Modena and Reggio Emilia, 41125 Modena, Italy. ; Department of Chemistry and Technology of Drugs, University of Perugia, 06123 Perugia, Italy. ; 1] Experimental Neuroimmunology Unit, German Cancer Research Center, 69120 Heidelberg, Germany [2] Department of Neurooncology, University Hospital, 69120 Heidelberg, Germany. ; Center for Advanced Research and Education, Asahikawa Medical University, 078-8510 Asahikawa, Japan. ; Kringle Pharma Joint Research Division for Regenerative Drug Discovery, Center for Advanced Science and Innovation, Osaka University, 565-0871 Osaka, Japan. ; CNRS UMR6290, Institut de Genetique et Developpement de Rennes, Universite de Rennes 1, 35043 Rennes, France. ; Department of Environmental Toxicology, University of California, Davis, 95616 California, USA. ; Australian School of Advanced Medicine (ASAM), Macquarie University, 2109 New South Wales, Australia. ; Lankenau Institute for Medical Research, Wynnewood, 19096 Pennsylvania, USA. ; New Link Genetics Corporation, Ames, 50010 Iowa, USA. ; IMS Laboratory, University of Bordeaux, 33607 Pessac, France. ; Bioceros, 3584 Utrecht, The Netherlands. ; Department of Medicine, University of Perugia, 06132 Perugia, Italy. ; Department of Clinical Epidemiology & Biostatistics, McMaster University, Ontario L8S 4K1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24930766" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Infections/immunology/metabolism ; Disease Resistance/drug effects/*genetics/*immunology ; Endotoxemia/genetics/immunology/metabolism ; Enzyme Activation/drug effects ; Gene Expression Regulation/drug effects ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Inflammation/enzymology/genetics/metabolism ; Kynurenine/metabolism ; Lipopolysaccharides/pharmacology ; Mice ; Phosphorylation ; Receptors, Aryl Hydrocarbon/genetics/*metabolism ; Signal Transduction ; Tryptophan Oxygenase/metabolism ; src-Family Kinases/metabolism
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  • 45
    Publication Date: 2014-08-15
    Description: The balance between stem cell self-renewal and differentiation is controlled by intrinsic factors and niche signals. In the Drosophila melanogaster ovary, some intrinsic factors promote germline stem cell (GSC) self-renewal, whereas others stimulate differentiation. However, it remains poorly understood how the balance between self-renewal and differentiation is controlled. Here we use D. melanogaster ovarian GSCs to demonstrate that the differentiation factor Bam controls the functional switch of the COP9 complex from self-renewal to differentiation via protein competition. The COP9 complex is composed of eight Csn subunits, Csn1-8, and removes Nedd8 modifications from target proteins. Genetic results indicated that the COP9 complex is required intrinsically for GSC self-renewal, whereas other Csn proteins, with the exception of Csn4, were also required for GSC progeny differentiation. Bam-mediated Csn4 sequestration from the COP9 complex via protein competition inactivated the self-renewing function of COP9 and allowed other Csn proteins to promote GSC differentiation. Therefore, this study reveals a protein-competition-based mechanism for controlling the balance between stem cell self-renewal and differentiation. Because numerous self-renewal factors are ubiquitously expressed throughout the stem cell lineage in various systems, protein competition may function as an important mechanism for controlling the self-renewal-to-differentiation switch.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pan, Lei -- Wang, Su -- Lu, Tinglin -- Weng, Changjiang -- Song, Xiaoqing -- Park, Joseph K -- Sun, Jin -- Yang, Zhi-Hao -- Yu, Junjing -- Tang, Hong -- McKearin, Dennis M -- Chamovitz, Daniel A -- Ni, Jianquan -- Xie, Ting -- GM64428/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Oct 9;514(7521):233-6. doi: 10.1038/nature13562.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA [2] Chinese Academy of Sciences Key Laboratory of Infection and Immunity, Institute of Biophysics, 15 Da Tun Road, Beijing 100101, China [3]. ; 1] Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA [2] Department of Cell Biology and Anatomy, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA [3]. ; 1] Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China [2]. ; Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA. ; 1] Department of Molecular Biology and Graduate School of Biomedical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9148, USA [2] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815-6789, USA. ; Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. ; 1] Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA [2] Chinese Academy of Sciences Key Laboratory of Infection and Immunity, Institute of Biophysics, 15 Da Tun Road, Beijing 100101, China. ; Chinese Academy of Sciences Key Laboratory of Infection and Immunity, Institute of Biophysics, 15 Da Tun Road, Beijing 100101, China. ; Department of Plant Sciences, Tel Aviv University, Tel Aviv 69978, Israel. ; 1] Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA [2] Department of Cell Biology and Anatomy, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119050" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Binding, Competitive ; *Cell Differentiation ; Cell Proliferation ; DNA Helicases/metabolism ; Drosophila Proteins/metabolism ; Drosophila melanogaster/*cytology/*metabolism ; Female ; Intracellular Signaling Peptides and Proteins/metabolism ; Male ; Multiprotein Complexes/*chemistry/*metabolism ; Ovary/cytology ; Peptide Hydrolases/*chemistry/*metabolism ; Protein Binding ; Stem Cells/*cytology/*metabolism ; Ubiquitins/metabolism
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  • 46
    Publication Date: 2014-08-30
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469351/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469351/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geisbert, Thomas W -- UC7 AI070083/AI/NIAID NIH HHS/ -- England -- Nature. 2014 Oct 2;514(7520):41-3. doi: 10.1038/nature13746. Epub 2014 Aug 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Texas Medical Branch at Galveston, Galveston National Laboratory, Galveston, Texas 77550-0610, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25171470" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/*therapeutic use ; Antibodies, Viral/*therapeutic use ; Female ; Hemorrhagic Fever, Ebola/*drug therapy ; *Immunization, Passive ; Male
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  • 47
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    Nature Publishing Group (NPG)
    Publication Date: 2014-02-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cressey, Daniel -- England -- Nature. 2014 Feb 27;506(7489):419-20. doi: 10.1038/506419a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24572404" target="_blank"〉PubMed〈/a〉
    Keywords: Aminobenzoates/administration & dosage/*poisoning ; Anesthesia/ethics/methods ; Anesthetics/administration & dosage/*poisoning ; *Animal Welfare/ethics ; Animals ; Animals, Laboratory/*physiology ; Avoidance Learning/drug effects ; Escape Reaction/drug effects ; Euthanasia, Animal/*ethics/*methods ; Zebrafish/*physiology
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  • 48
    Publication Date: 2014-07-22
    Description: During cap-dependent eukaryotic translation initiation, ribosomes scan messenger RNA from the 5' end to the first AUG start codon with favourable sequence context. For many mRNAs this AUG belongs to a short upstream open reading frame (uORF), and translation of the main downstream ORF requires re-initiation, an incompletely understood process. Re-initiation is thought to involve the same factors as standard initiation. It is unknown whether any factors specifically affect translation re-initiation without affecting standard cap-dependent translation. Here we uncover the non-canonical initiation factors density regulated protein (DENR) and multiple copies in T-cell lymphoma-1 (MCT-1; also called MCTS1 in humans) as the first selective regulators of eukaryotic re-initiation. mRNAs containing upstream ORFs with strong Kozak sequences selectively require DENR-MCT-1 for their proper translation, yielding a novel class of mRNAs that can be co-regulated and that is enriched for regulatory proteins such as oncogenic kinases. Collectively, our data reveal that cells have a previously unappreciated translational control system with a key role in supporting proliferation and tissue growth.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134322/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134322/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schleich, Sibylle -- Strassburger, Katrin -- Janiesch, Philipp Christoph -- Koledachkina, Tatyana -- Miller, Katharine K -- Haneke, Katharina -- Cheng, Yong-Sheng -- Kuchler, Katrin -- Stoecklin, Georg -- Duncan, Kent E -- Teleman, Aurelio A -- 260602/European Research Council/International -- England -- Nature. 2014 Aug 14;512(7513):208-12. doi: 10.1038/nature13401. Epub 2014 Jul 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [2] Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf (UKE), Falkenried 94, 20251 Hamburg, Germany. ; 1] German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [2]. ; 1] Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf (UKE), Falkenried 94, 20251 Hamburg, Germany [2]. ; Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf (UKE), Falkenried 94, 20251 Hamburg, Germany. ; 1] German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [2] Zentrum fur Molekulare Biologie der Universitat Heidelberg (ZMBH), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany. ; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043021" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Proliferation ; Cells, Cultured ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/cytology/genetics/growth & development ; Eukaryotic Initiation Factors/genetics/*metabolism ; Gene Expression Regulation/*genetics ; Open Reading Frames ; Protein Biosynthesis/*genetics ; Signal Transduction
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  • 49
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Oct 9;514(7521):140. doi: 10.1038/514140a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25297398" target="_blank"〉PubMed〈/a〉
    Keywords: Alaska ; Animals ; Arctic Regions ; Female ; *Global Warming ; Male ; Pacific Ocean ; Walruses/*physiology
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  • 50
    Publication Date: 2014-05-30
    Description: Targeted genome editing by artificial nucleases has brought the goal of site-specific transgene integration and gene correction within the reach of gene therapy. However, its application to long-term repopulating haematopoietic stem cells (HSCs) has remained elusive. Here we show that poor permissiveness to gene transfer and limited proficiency of the homology-directed DNA repair pathway constrain gene targeting in human HSCs. By tailoring delivery platforms and culture conditions we overcame these barriers and provide stringent evidence of targeted integration in human HSCs by long-term multilineage repopulation of transplanted mice. We demonstrate the therapeutic potential of our strategy by targeting a corrective complementary DNA into the IL2RG gene of HSCs from healthy donors and a subject with X-linked severe combined immunodeficiency (SCID-X1). Gene-edited HSCs sustained normal haematopoiesis and gave rise to functional lymphoid cells that possess a selective growth advantage over those carrying disruptive IL2RG mutations. These results open up new avenues for treating SCID-X1 and other diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082311/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082311/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Genovese, Pietro -- Schiroli, Giulia -- Escobar, Giulia -- Di Tomaso, Tiziano -- Firrito, Claudia -- Calabria, Andrea -- Moi, Davide -- Mazzieri, Roberta -- Bonini, Chiara -- Holmes, Michael C -- Gregory, Philip D -- van der Burg, Mirjam -- Gentner, Bernhard -- Montini, Eugenio -- Lombardo, Angelo -- Naldini, Luigi -- 249845/European Research Council/International -- TGT11D02/Telethon/Italy -- England -- Nature. 2014 Jun 12;510(7504):235-40. doi: 10.1038/nature13420. Epub 2014 May 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉TIGET, San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy. ; 1] TIGET, San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy [2] Vita Salute San Raffaele University, 20132 Milan, Italy. ; 1] TIGET, San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy [2] The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland 4102, Australia. ; Experimental Hematology Unit, San Raffaele Scientific Institute, 20132 Milan, Italy. ; Sangamo BioSciences Inc., Richmond, California 94804, USA. ; Department of Immunology Erasmus MC, University Medical Center, 3015 Rotterdam, The Netherlands. ; 1] TIGET, San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy [2] Vita Salute San Raffaele University, 20132 Milan, Italy [3].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870228" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD34/metabolism ; DNA, Complementary/genetics ; Endonucleases/metabolism ; Fetal Blood/cytology/metabolism/transplantation ; Gene Targeting/*methods ; Genome, Human/*genetics ; Hematopoiesis/genetics ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*cytology/*metabolism ; Humans ; Interleukin Receptor Common gamma Subunit/genetics ; Male ; Mice ; Mutation/genetics ; Targeted Gene Repair/*methods ; X-Linked Combined Immunodeficiency Diseases/*genetics/therapy
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  • 51
    Publication Date: 2014-12-04
    Description: The TRIM37 (also known as MUL) gene is located in the 17q23 chromosomal region, which is amplified in up to approximately 40% of breast cancers. TRIM37 contains a RING finger domain, a hallmark of E3 ubiquitin ligases, but its protein substrate(s) is unknown. Here we report that TRIM37 mono-ubiquitinates histone H2A, a chromatin modification associated with transcriptional repression. We find that in human breast cancer cell lines containing amplified 17q23, TRIM37 is upregulated and, reciprocally, the major H2A ubiquitin ligase RNF2 (also known as RING1B) is downregulated. Genome-wide chromatin immunoprecipitation (ChIP)-chip experiments in 17q23-amplified breast cancer cells identified many genes, including multiple tumour suppressors, whose promoters were bound by TRIM37 and enriched for ubiquitinated H2A. However, unlike RNF2, which is a subunit of polycomb repressive complex 1 (PRC1), we find that TRIM37 associates with polycomb repressive complex 2 (PRC2). TRIM37, PRC2 and PRC1 are co-bound to specific target genes, resulting in their transcriptional silencing. RNA-interference-mediated knockdown of TRIM37 results in loss of ubiquitinated H2A, dissociation of PRC1 and PRC2 from target promoters, and transcriptional reactivation of silenced genes. Knockdown of TRIM37 in human breast cancer cells containing amplified 17q23 substantially decreases tumour growth in mouse xenografts. Conversely, ectopic expression of TRIM37 renders non-transformed cells tumorigenic. Collectively, our results reveal TRIM37 as an oncogenic H2A ubiquitin ligase that is overexpressed in a subset of breast cancers and promotes transformation by facilitating silencing of tumour suppressors and other genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269325/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269325/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhatnagar, Sanchita -- Gazin, Claude -- Chamberlain, Lynn -- Ou, Jianhong -- Zhu, Xiaochun -- Tushir, Jogender S -- Virbasius, Ching-Man -- Lin, Ling -- Zhu, Lihua J -- Wajapeyee, Narendra -- Green, Michael R -- R01 GM033977/GM/NIGMS NIH HHS/ -- R01GM033977/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Dec 4;516(7529):116-20. doi: 10.1038/nature13955. Epub 2014 Nov 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA [2] Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. ; CEA/DSV/iRCM/LEFG, Genopole G2, and Universite Paris Diderot, 91057 Evry, France. ; Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. ; Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877, USA. ; 1] Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA [2] Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. ; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470042" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/*enzymology/*genetics ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Gene Silencing ; Heterografts ; Histones/metabolism ; Humans ; MCF-7 Cells ; Mice ; NIH 3T3 Cells ; Nuclear Proteins/*genetics/*metabolism ; Oncogene Proteins/*genetics/metabolism ; Polycomb Repressive Complex 1/*genetics/metabolism
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  • 52
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Oct 2;514(7520):6. doi: 10.1038/514006a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25279880" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biotechnology/economics/*trends ; *Brain/physiology ; Callithrix ; Humans ; National Institutes of Health (U.S.)/organization & administration ; Neurosciences/economics/*trends ; United States
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  • 53
    Publication Date: 2014-09-16
    Description: A defining feature governing head patterning of jawed vertebrates is a highly conserved gene regulatory network that integrates hindbrain segmentation with segmentally restricted domains of Hox gene expression. Although non-vertebrate chordates display nested domains of axial Hox expression, they lack hindbrain segmentation. The sea lamprey, a jawless fish, can provide unique insights into vertebrate origins owing to its phylogenetic position at the base of the vertebrate tree. It has been suggested that lamprey may represent an intermediate state where nested Hox expression has not been coupled to the process of hindbrain segmentation. However, little is known about the regulatory network underlying Hox expression in lamprey or its relationship to hindbrain segmentation. Here, using a novel tool that allows cross-species comparisons of regulatory elements between jawed and jawless vertebrates, we report deep conservation of both upstream regulators and segmental activity of enhancer elements across these distant species. Regulatory regions from diverse gnathostomes drive segmental reporter expression in the lamprey hindbrain and require the same transcriptional inputs (for example, Kreisler (also known as Mafba), Krox20 (also known as Egr2a)) in both lamprey and zebrafish. We find that lamprey hox genes display dynamic segmentally restricted domains of expression; we also isolated a conserved exonic hox2 enhancer from lamprey that drives segmental expression in rhombomeres 2 and 4. Our results show that coupling of Hox gene expression to segmentation of the hindbrain is an ancient trait with origin at the base of vertebrates that probably led to the formation of rhombomeric compartments with an underlying Hox code.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209185/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209185/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parker, Hugo J -- Bronner, Marianne E -- Krumlauf, Robb -- R01 DE017911/DE/NIDCR NIH HHS/ -- R01 NS086907/NS/NINDS NIH HHS/ -- R01DE017911/DE/NIDCR NIH HHS/ -- R01NS086907/NS/NINDS NIH HHS/ -- England -- Nature. 2014 Oct 23;514(7523):490-3. doi: 10.1038/nature13723. Epub 2014 Sep 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA. ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA. ; 1] Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA [2] Department of Anatomy and Cell Biology, Kansas University Medical Center, Kansas City, Kansas 66160, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25219855" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Body Patterning/genetics ; Conserved Sequence/*genetics ; Enhancer Elements, Genetic/genetics ; *Evolution, Molecular ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks/*genetics ; Genes, Homeobox/*genetics ; Lampreys/embryology/genetics ; Molecular Sequence Data ; Phylogeny ; Rhombencephalon/*embryology/*metabolism ; Vertebrates/*embryology/genetics ; Zebrafish/embryology/genetics
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  • 54
    Publication Date: 2014-01-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crooks, Richard M -- England -- Nature. 2014 Jan 9;505(7482):165-6. doi: 10.1038/505165a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712-1224, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24402276" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Aptamers, Nucleotide ; Biosensing Techniques/*methods ; Humans ; Male ; Microfluidics/*methods
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  • 55
    Publication Date: 2014-09-12
    Description: The phylogeny of Allotheria, including Multituberculata and Haramiyida, remains unsolved and has generated contentious views on the origin and earliest evolution of mammals. Here we report three new species of a new clade, Euharamiyida, based on six well-preserved fossils from the Jurassic period of China. These fossils reveal many craniodental and postcranial features of euharamiyidans and clarify several ambiguous structures that are currently the topic of debate. Our phylogenetic analyses recognize Euharamiyida as the sister group of Multituberculata, and place Allotheria within the Mammalia. The phylogeny suggests that allotherian mammals evolved from a Late Triassic (approximately 208 million years ago) Haramiyavia-like ancestor and diversified into euharamiyidans and multituberculates with a cosmopolitan distribution, implying homologous acquisition of many craniodental and postcranial features in the two groups. Our findings also favour a Late Triassic origin of mammals in Laurasia and two independent detachment events of the middle ear bones during mammalian evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bi, Shundong -- Wang, Yuanqing -- Guan, Jian -- Sheng, Xia -- Meng, Jin -- England -- Nature. 2014 Oct 30;514(7524):579-84. doi: 10.1038/nature13718. Epub 2014 Sep 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing 100044, China [2] Department of Biology, Indiana University of Pennsylvania, Indiana, Pennsylvania 15705, USA. ; Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing 100044, China. ; Beijing Natural History Museum, 126 Tianqiao Street, Dongcheng District, Beijing 100050, China. ; Paleontological Museum of Liaoning, Shenyang Normal University, Shenyang, Liaoning 110034, China. ; Division of Paleontology, American Museum of Natural History, Central Park West at 79th Street, New York, New York 10024, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25209669" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; China ; *Fossils ; Mammals/*anatomy & histology/*classification ; Mandible/anatomy & histology ; *Phylogeny ; Skeleton ; Skull/anatomy & histology ; Tooth/anatomy & histology
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  • 56
    Publication Date: 2014-08-28
    Description: Sensory regions of the brain integrate environmental cues with copies of motor-related signals important for imminent and ongoing movements. In mammals, signals propagating from the motor cortex to the auditory cortex are thought to have a critical role in normal hearing and behaviour, yet the synaptic and circuit mechanisms by which these motor-related signals influence auditory cortical activity remain poorly understood. Using in vivo intracellular recordings in behaving mice, we find that excitatory neurons in the auditory cortex are suppressed before and during movement, owing in part to increased activity of local parvalbumin-positive interneurons. Electrophysiology and optogenetic gain- and loss-of-function experiments reveal that motor-related changes in auditory cortical dynamics are driven by a subset of neurons in the secondary motor cortex that innervate the auditory cortex and are active during movement. These findings provide a synaptic and circuit basis for the motor-related corollary discharge hypothesized to facilitate hearing and auditory-guided behaviours.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248668/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248668/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schneider, David M -- Nelson, Anders -- Mooney, Richard -- NS079929/NS/NINDS NIH HHS/ -- R01 DC013826/DC/NIDCD NIH HHS/ -- R21 NS079929/NS/NINDS NIH HHS/ -- T32 GM008441/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Sep 11;513(7517):189-94. doi: 10.1038/nature13724. Epub 2014 Aug 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Neurobiology, Duke University School of Medicine, Durham, North Carolina 27710, USA [2]. ; Department of Neurobiology, Duke University School of Medicine, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25162524" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Auditory Cortex/*physiology ; Electrical Synapses/*physiology ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity/*physiology ; Optogenetics ; Sensory Receptor Cells/metabolism
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  • 57
    Publication Date: 2014-04-18
    Description: Fertilization occurs when sperm and egg recognize each other and fuse to form a new, genetically distinct organism. The molecular basis of sperm-egg recognition is unknown, but is likely to require interactions between receptor proteins displayed on their surface. Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. Here we identify folate receptor 4 (Folr4) as the receptor for Izumo1 on the mouse egg, and propose to rename it Juno. We show that the Izumo1-Juno interaction is conserved within several mammalian species, including humans. Female mice lacking Juno are infertile and Juno-deficient eggs do not fuse with normal sperm. Rapid shedding of Juno from the oolemma after fertilization suggests a mechanism for the membrane block to polyspermy, ensuring eggs normally fuse with just a single sperm. Our discovery of an essential receptor pair at the nexus of conception provides opportunities for the rational development of new fertility treatments and contraceptives.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998876/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998876/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bianchi, Enrica -- Doe, Brendan -- Goulding, David -- Wright, Gavin J -- 098051/Wellcome Trust/United Kingdom -- England -- Nature. 2014 Apr 24;508(7497):483-7. doi: 10.1038/nature13203. Epub 2014 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK. ; Mouse Production Team, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK. ; Electron and Advanced Light Microscopy Suite, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24739963" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conserved Sequence ; Evolution, Molecular ; Female ; Fertility/genetics ; Fertilization/genetics/*physiology ; Genes, Essential ; Glycosylphosphatidylinositols/metabolism ; Humans ; Immunoglobulins/*metabolism ; Infertility, Female/genetics ; Male ; Mammals ; Membrane Proteins/*metabolism ; Mice ; Oocytes/cytology/metabolism ; Ovum/cytology/*metabolism ; Parthenogenesis ; Receptors, Cell Surface/deficiency/genetics/*metabolism ; Sperm Injections, Intracytoplasmic ; Spermatozoa/*metabolism ; Time Factors
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  • 58
    Publication Date: 2014-03-29
    Description: Huntington's disease is an autosomal dominant disease associated with a mutation in the gene encoding huntingtin (Htt) leading to expanded polyglutamine repeats of mutant Htt (mHtt) that elicit oxidative stress, neurotoxicity, and motor and behavioural changes. Huntington's disease is characterized by highly selective and profound damage to the corpus striatum, which regulates motor function. Striatal selectivity of Huntington's disease may reflect the striatally selective small G protein Rhes binding to mHtt and enhancing its neurotoxicity. Specific molecular mechanisms by which mHtt elicits neurodegeneration have been hard to determine. Here we show a major depletion of cystathionine gamma-lyase (CSE), the biosynthetic enzyme for cysteine, in Huntington's disease tissues, which may mediate Huntington's disease pathophysiology. The defect occurs at the transcriptional level and seems to reflect influences of mHtt on specificity protein 1, a transcriptional activator for CSE. Consistent with the notion of loss of CSE as a pathogenic mechanism, supplementation with cysteine reverses abnormalities in cultures of Huntington's disease tissues and in intact mouse models of Huntington's disease, suggesting therapeutic potential.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349202/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349202/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paul, Bindu D -- Sbodio, Juan I -- Xu, Risheng -- Vandiver, M Scott -- Cha, Jiyoung Y -- Snowman, Adele M -- Snyder, Solomon H -- MH18501/MH/NIMH NIH HHS/ -- R01 MH018501/MH/NIMH NIH HHS/ -- T32 GM007309/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 May 1;509(7498):96-100. doi: 10.1038/nature13136. Epub 2014 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; 1] The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; 1] The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [3] Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670645" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/enzymology ; Corpus Striatum/drug effects/enzymology/metabolism/pathology ; Cystathionine gamma-Lyase/*deficiency/genetics ; Cysteine/administration & dosage/biosynthesis/pharmacology/therapeutic use ; Dietary Supplements ; Disease Models, Animal ; Drinking Water/chemistry ; Gene Deletion ; Gene Expression Regulation, Enzymologic/genetics ; Huntington Disease/drug therapy/*enzymology/genetics/*pathology ; Male ; Mice ; Mutant Proteins/genetics/metabolism ; Nerve Tissue Proteins/genetics/metabolism ; Neuroprotective Agents/administration & ; dosage/metabolism/pharmacology/therapeutic use ; Oxidative Stress/drug effects ; Sp1 Transcription Factor/antagonists & inhibitors/metabolism ; Transcription, Genetic/genetics
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  • 59
    Publication Date: 2014-12-04
    Description: Ryanodine receptors (RyRs) mediate the rapid release of calcium (Ca(2+)) from intracellular stores into the cytosol, which is essential for numerous cellular functions including excitation-contraction coupling in muscle. Lack of sufficient structural detail has impeded understanding of RyR gating and regulation. Here we report the closed-state structure of the 2.3-megadalton complex of the rabbit skeletal muscle type 1 RyR (RyR1), solved by single-particle electron cryomicroscopy at an overall resolution of 4.8 A. We fitted a polyalanine-level model to all 3,757 ordered residues in each protomer, defining the transmembrane pore in unprecedented detail and placing all cytosolic domains as tertiary folds. The cytosolic assembly is built on an extended alpha-solenoid scaffold connecting key regulatory domains to the pore. The RyR1 pore architecture places it in the six-transmembrane ion channel superfamily. A unique domain inserted between the second and third transmembrane helices interacts intimately with paired EF-hands originating from the alpha-solenoid scaffold, suggesting a mechanism for channel gating by Ca(2+).〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300236/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300236/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zalk, Ran -- Clarke, Oliver B -- des Georges, Amedee -- Grassucci, Robert A -- Reiken, Steven -- Mancia, Filippo -- Hendrickson, Wayne A -- Frank, Joachim -- Marks, Andrew R -- P01 HL081172/HL/NHLBI NIH HHS/ -- R01 AR060037/AR/NIAMS NIH HHS/ -- R01 GM029169/GM/NIGMS NIH HHS/ -- R01 HL061503/HL/NHLBI NIH HHS/ -- R01 HL083418/HL/NHLBI NIH HHS/ -- R01AR060037/AR/NIAMS NIH HHS/ -- R01GM29169/GM/NIGMS NIH HHS/ -- R01HL061503/HL/NHLBI NIH HHS/ -- U54GM095315/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Jan 1;517(7532):44-9. doi: 10.1038/nature13950. Epub 2014 Dec 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Cellular Biophysics, Columbia University, New York, New York 10032, USA. ; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA. ; 1] Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA [2] Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA. ; 1] Department of Physiology and Cellular Biophysics, Columbia University, New York, New York 10032, USA [2] Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA. ; 1] Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA [2] Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA [3] Department of Biological Sciences, Columbia University, New York, New York 10027, USA. ; 1] Department of Physiology and Cellular Biophysics, Columbia University, New York, New York 10032, USA [2] Department of Medicine, Columbia University, New York, New York 10032, USA [3] Wu Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470061" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/deficiency/metabolism/pharmacology ; Cell Membrane/metabolism ; Cryoelectron Microscopy ; Cytosol/metabolism ; Ion Channel Gating/drug effects ; Muscle, Skeletal/chemistry ; Protein Structure, Tertiary ; Rabbits ; Ryanodine Receptor Calcium Release Channel/*chemistry/metabolism/*ultrastructure ; Tacrolimus Binding Proteins/chemistry/metabolism
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  • 60
    Publication Date: 2014-12-04
    Description: T-helper type 17 (TH17) cells that produce the cytokines interleukin-17A (IL-17A) and IL-17F are implicated in the pathogenesis of several autoimmune diseases. The differentiation of TH17 cells is regulated by transcription factors such as RORgammat, but post-translational mechanisms preventing the rampant production of pro-inflammatory IL-17A have received less attention. Here we show that the deubiquitylating enzyme DUBA is a negative regulator of IL-17A production in T cells. Mice with DUBA-deficient T cells developed exacerbated inflammation in the small intestine after challenge with anti-CD3 antibodies. DUBA interacted with the ubiquitin ligase UBR5, which suppressed DUBA abundance in naive T cells. DUBA accumulated in activated T cells and stabilized UBR5, which then ubiquitylated RORgammat in response to TGF-beta signalling. Our data identify DUBA as a cell-intrinsic suppressor of IL-17 production.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rutz, Sascha -- Kayagaki, Nobuhiko -- Phung, Qui T -- Eidenschenk, Celine -- Noubade, Rajkumar -- Wang, Xiaoting -- Lesch, Justin -- Lu, Rongze -- Newton, Kim -- Huang, Oscar W -- Cochran, Andrea G -- Vasser, Mark -- Fauber, Benjamin P -- DeVoss, Jason -- Webster, Joshua -- Diehl, Lauri -- Modrusan, Zora -- Kirkpatrick, Donald S -- Lill, Jennie R -- Ouyang, Wenjun -- Dixit, Vishva M -- England -- Nature. 2015 Feb 19;518(7539):417-21. doi: 10.1038/nature13979. Epub 2014 Dec 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Physiological Chemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Protein Chemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Early Discovery Biochemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA. ; Discovery Chemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Pathology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470037" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Enzyme Stability ; Female ; Inflammation/genetics/pathology ; Interleukin-17/*biosynthesis ; Intestine, Small/metabolism/pathology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Protein Binding ; *Protein Biosynthesis ; Signal Transduction ; Substrate Specificity ; Th17 Cells/*metabolism ; Transforming Growth Factor beta/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitin-Specific Proteases/biosynthesis/deficiency/genetics/*metabolism ; Ubiquitination
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  • 61
    Publication Date: 2014-11-20
    Description: Emerging evidence suggests that the ribosome has a regulatory function in directing how the genome is translated in time and space. However, how this regulation is encoded in the messenger RNA sequence remains largely unknown. Here we uncover unique RNA regulons embedded in homeobox (Hox) 5' untranslated regions (UTRs) that confer ribosome-mediated control of gene expression. These structured RNA elements, resembling viral internal ribosome entry sites (IRESs), are found in subsets of Hox mRNAs. They facilitate ribosome recruitment and require the ribosomal protein RPL38 for their activity. Despite numerous layers of Hox gene regulation, these IRES elements are essential for converting Hox transcripts into proteins to pattern the mammalian body plan. This specialized mode of IRES-dependent translation is enabled by an additional regulatory element that we term the translation inhibitory element (TIE), which blocks cap-dependent translation of transcripts. Together, these data uncover a new paradigm for ribosome-mediated control of gene expression and organismal development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353651/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353651/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xue, Shifeng -- Tian, Siqi -- Fujii, Kotaro -- Kladwang, Wipapat -- Das, Rhiju -- Barna, Maria -- 7DP2OD00850902/OD/NIH HHS/ -- DP2 OD008509/OD/NIH HHS/ -- R01 GM102519/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Jan 1;517(7532):33-8. doi: 10.1038/nature14010. Epub 2014 Nov 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Developmental Biology, Stanford University, Stanford, California 94305, USA [2] Department of Genetics, Stanford University, Stanford, California 94305, USA [3] Tetrad Graduate Program, University of California, San Francisco, San Francisco, California 94158, USA. ; Department of Biochemistry, Stanford University, Stanford, California 94305, USA. ; 1] Department of Developmental Biology, Stanford University, Stanford, California 94305, USA [2] Department of Genetics, Stanford University, Stanford, California 94305, USA. ; 1] Department of Biochemistry, Stanford University, Stanford, California 94305, USA [2] Department of Physics, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25409156" target="_blank"〉PubMed〈/a〉
    Keywords: 5' Untranslated Regions/*genetics ; Animals ; Bone and Bones/embryology/metabolism ; Cell Line ; Conserved Sequence ; Evolution, Molecular ; Gene Expression Regulation/*genetics ; Genes, Homeobox/*genetics ; Mice ; Molecular Sequence Data ; Protein Biosynthesis/genetics ; RNA Caps/metabolism ; Regulatory Sequences, Ribonucleic Acid/*genetics ; Ribosomal Proteins/metabolism ; Ribosomes/chemistry/*metabolism ; Substrate Specificity ; Zebrafish/genetics
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  • 62
    Publication Date: 2014-12-04
    Description: The manufacture of geometric engravings is generally interpreted as indicative of modern cognition and behaviour. Key questions in the debate on the origin of such behaviour are whether this innovation is restricted to Homo sapiens, and whether it has a uniquely African origin. Here we report on a fossil freshwater shell assemblage from the Hauptknochenschicht ('main bone layer') of Trinil (Java, Indonesia), the type locality of Homo erectus discovered by Eugene Dubois in 1891 (refs 2 and 3). In the Dubois collection (in the Naturalis museum, Leiden, The Netherlands) we found evidence for freshwater shellfish consumption by hominins, one unambiguous shell tool, and a shell with a geometric engraving. We dated sediment contained in the shells with (40)Ar/(39)Ar and luminescence dating methods, obtaining a maximum age of 0.54 +/- 0.10 million years and a minimum age of 0.43 +/- 0.05 million years. This implies that the Trinil Hauptknochenschicht is younger than previously estimated. Together, our data indicate that the engraving was made by Homo erectus, and that it is considerably older than the oldest geometric engravings described so far. Although it is at present not possible to assess the function or meaning of the engraved shell, this discovery suggests that engraving abstract patterns was in the realm of Asian Homo erectus cognition and neuromotor control.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joordens, Josephine C A -- d'Errico, Francesco -- Wesselingh, Frank P -- Munro, Stephen -- de Vos, John -- Wallinga, Jakob -- Ankjaergaard, Christina -- Reimann, Tony -- Wijbrans, Jan R -- Kuiper, Klaudia F -- Mucher, Herman J -- Coqueugniot, Helene -- Prie, Vincent -- Joosten, Ineke -- van Os, Bertil -- Schulp, Anne S -- Panuel, Michel -- van der Haas, Victoria -- Lustenhouwer, Wim -- Reijmer, John J G -- Roebroeks, Wil -- England -- Nature. 2015 Feb 12;518(7538):228-31. doi: 10.1038/nature13962. Epub 2014 Dec 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Faculty of Archaeology, Leiden University, PO Box 9515, 2300RA, Leiden, The Netherlands [2] Faculty of Earth and Life Sciences, VU University Amsterdam, De Boelelaan 1085, 1081HV, Amsterdam, The Netherlands. ; 1] Universite de Bordeaux, CNRS UMR 5199, Allee Geoffroy Saint-Hilaire, 33615 Pessac, France [2] Institute of Archaeology, History, Cultural Studies and Religion, University of Bergen, Oysteinsgate 3PO Box 7805, Bergen, Norway. ; Naturalis Biodiversity Center, Darwinweg 2, PO Box 9517, 2300RA, Leiden, The Netherlands. ; 1] School of Archaeology and Anthropology, Australian National University, Australian Capital Territory, 0200 Canberra, Australia [2] National Museum of Australia, Australian Capital Territory 2601, Canberra, Australia. ; 1] Wageningen University, Soil Geography and Landscape Group &Netherlands Centre for Luminescence Dating, PO Box 47, 6700AA, Wageningen, The Netherlands [2] Delft University of Technology, Faculty of Applied Sciences, Mekelweg 15, 2629JB, Delft, The Netherlands. ; Faculty of Earth and Life Sciences, VU University Amsterdam, De Boelelaan 1085, 1081HV, Amsterdam, The Netherlands. ; 1] Faculty of Archaeology, Leiden University, PO Box 9515, 2300RA, Leiden, The Netherlands [2] Prinses Beatrixsingel 21, 6301VK, Valkenburg, The Netherlands. ; Universite de Bordeaux, CNRS UMR 5199, Allee Geoffroy Saint-Hilaire, 33615 Pessac, France. ; 1] Museum National d'Histoire Naturelle, UMR 7205, Institut de Systematique, Evolution, Biodiversite, CP51, 55 Rue Buffon, 75005 Paris, France [2] Biotope Recherche et Developpement, 22 Boulevard Marechal Foch, 34140 Meze, France. ; Cultural Heritage Agency of the Netherlands, PO Box 1600, 3800BP, Amersfoort, The Netherlands. ; 1] Faculty of Earth and Life Sciences, VU University Amsterdam, De Boelelaan 1085, 1081HV, Amsterdam, The Netherlands [2] Naturalis Biodiversity Center, Darwinweg 2, PO Box 9517, 2300RA, Leiden, The Netherlands [3] Natuurhistorisch Museum Maastricht, De Bosquetplein 7, 6211KJ, Maastricht, The Netherlands. ; 1] Faculte de Medecine, Universite d'Aix-Marseille, EFS, CNRS UMR 7268, Boulevard Pierre Dramard, 13344 Marseille, France [2] Department of Medical Imaging Hopital Nord, Assistance Publique - Hopitaux de Marseille, Chemin de Bourrellys, 13915 Marseille, France. ; Faculty of Archaeology, Leiden University, PO Box 9515, 2300RA, Leiden, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470048" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Shells ; Animals ; Engraving and Engravings/*history ; Fossils ; History, Ancient ; *Hominidae ; Indonesia ; Mollusca ; *Tool Use Behavior
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  • 63
    Publication Date: 2014-12-24
    Description: The kinetochore is the crucial apparatus regulating chromosome segregation in mitosis and meiosis. Particularly in meiosis I, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation) and centromeric cohesion mediated by cohesin is protected in the following anaphase. Although meiotic kinetochore factors have been identified only in budding and fission yeasts, these molecules and their functions are thought to have diverged earlier. Therefore, a conserved mechanism for meiotic kinetochore regulation remains elusive. Here we have identified in mouse a meiosis-specific kinetochore factor that we termed MEIKIN, which functions in meiosis I but not in meiosis II or mitosis. MEIKIN plays a crucial role in both mono-orientation and centromeric cohesion protection, partly by stabilizing the localization of the cohesin protector shugoshin. These functions are mediated mainly by the activity of Polo-like kinase PLK1, which is enriched to kinetochores in a MEIKIN-dependent manner. Our integrative analysis indicates that the long-awaited key regulator of meiotic kinetochore function is Meikin, which is conserved from yeasts to humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jihye -- Ishiguro, Kei-ichiro -- Nambu, Aya -- Akiyoshi, Bungo -- Yokobayashi, Shihori -- Kagami, Ayano -- Ishiguro, Tadashi -- Pendas, Alberto M -- Takeda, Naoki -- Sakakibara, Yogo -- Kitajima, Tomoya S -- Tanno, Yuji -- Sakuno, Takeshi -- Watanabe, Yoshinori -- England -- Nature. 2015 Jan 22;517(7535):466-71. doi: 10.1038/nature14097. Epub 2014 Dec 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1Yayoi, Tokyo 113-0032, Japan. ; Instituto de Biologia Molecular y Celular del Cancer (CSIC-USAL), 37007 Salamanca, Spain. ; Center for Animal Resources and Development, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 Japan. ; Laboratory for Chromosome Segregation, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533956" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Cycle Proteins/metabolism ; Centromere/metabolism ; Chromosomal Proteins, Non-Histone/deficiency/genetics/*metabolism ; *Conserved Sequence ; Female ; Humans ; Infertility/genetics/metabolism ; Kinetochores/*metabolism ; Male ; *Meiosis ; Mice ; Molecular Sequence Data ; Protein-Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Schizosaccharomyces pombe Proteins/metabolism
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  • 64
    Publication Date: 2014-10-23
    Description: The gastrointestinal tracts of mammals are colonized by hundreds of microbial species that contribute to health, including colonization resistance against intestinal pathogens. Many antibiotics destroy intestinal microbial communities and increase susceptibility to intestinal pathogens. Among these, Clostridium difficile, a major cause of antibiotic-induced diarrhoea, greatly increases morbidity and mortality in hospitalized patients. Which intestinal bacteria provide resistance to C. difficile infection and their in vivo inhibitory mechanisms remain unclear. Here we correlate loss of specific bacterial taxa with development of infection, by treating mice with different antibiotics that result in distinct microbiota changes and lead to varied susceptibility to C. difficile. Mathematical modelling augmented by analyses of the microbiota of hospitalized patients identifies resistance-associated bacteria common to mice and humans. Using these platforms, we determine that Clostridium scindens, a bile acid 7alpha-dehydroxylating intestinal bacterium, is associated with resistance to C. difficile infection and, upon administration, enhances resistance to infection in a secondary bile acid dependent fashion. Using a workflow involving mouse models, clinical studies, metagenomic analyses, and mathematical modelling, we identify a probiotic candidate that corrects a clinically relevant microbiome deficiency. These findings have implications for the rational design of targeted antimicrobials as well as microbiome-based diagnostics and therapeutics for individuals at risk of C. difficile infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354891/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354891/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buffie, Charlie G -- Bucci, Vanni -- Stein, Richard R -- McKenney, Peter T -- Ling, Lilan -- Gobourne, Asia -- No, Daniel -- Liu, Hui -- Kinnebrew, Melissa -- Viale, Agnes -- Littmann, Eric -- van den Brink, Marcel R M -- Jenq, Robert R -- Taur, Ying -- Sander, Chris -- Cross, Justin R -- Toussaint, Nora C -- Xavier, Joao B -- Pamer, Eric G -- AI95706/AI/NIAID NIH HHS/ -- DP2 OD008440/OD/NIH HHS/ -- DP2OD008440/OD/NIH HHS/ -- K23 AI095398/AI/NIAID NIH HHS/ -- P01 CA023766/CA/NCI NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- R01 AI042135/AI/NIAID NIH HHS/ -- R01 AI095706/AI/NIAID NIH HHS/ -- R01 AI42135/AI/NIAID NIH HHS/ -- T32 CA009149/CA/NCI NIH HHS/ -- T32 GM007739/GM/NIGMS NIH HHS/ -- T32GM07739/GM/NIGMS NIH HHS/ -- U54 CA148967/CA/NCI NIH HHS/ -- England -- Nature. 2015 Jan 8;517(7533):205-8. doi: 10.1038/nature13828. Epub 2014 Oct 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA [2] Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; 1] Computational Biology Program, Sloan-Kettering Institute, New York, New York 10065, USA [2] Department of Biology, University of Massachusetts Dartmouth, North Dartmouth, Massachusetts 02747, USA. ; Computational Biology Program, Sloan-Kettering Institute, New York, New York 10065, USA. ; Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Donald B. and Catherine C. Marron Cancer Metabolism Center, Sloan-Kettering Institute, New York, New York 10065, USA. ; Genomics Core Laboratory, Sloan-Kettering Institute, New York, New York 10065, USA. ; 1] Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA [2] Immunology Program, Sloan-Kettering Institute, New York, New York 10065, USA. ; Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; 1] Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA [2] Computational Biology Program, Sloan-Kettering Institute, New York, New York 10065, USA. ; 1] Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA [2] Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA [3] Immunology Program, Sloan-Kettering Institute, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25337874" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/pharmacology ; Bile Acids and Salts/*metabolism ; Biological Evolution ; Clostridium/metabolism ; Clostridium difficile/drug effects/*physiology ; Colitis/metabolism/microbiology/prevention & control/therapy ; Disease Susceptibility/*microbiology ; Feces/microbiology ; Female ; Humans ; Intestines/drug effects/*metabolism/*microbiology ; Metagenome/genetics ; Mice ; Mice, Inbred C57BL ; Microbiota/drug effects/genetics/*physiology ; Symbiosis
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  • 65
    Publication Date: 2014-11-20
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358788/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358788/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dinman, Jonathan D -- R01 HL119439/HL/NHLBI NIH HHS/ -- England -- Nature. 2015 Jan 1;517(7532):24-5. doi: 10.1038/nature14069. Epub 2014 Nov 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25409148" target="_blank"〉PubMed〈/a〉
    Keywords: 5' Untranslated Regions/*genetics ; Animals ; Gene Expression Regulation/*genetics ; Genes, Homeobox/*genetics ; Regulatory Sequences, Ribonucleic Acid/*genetics ; Ribosomes/*metabolism
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  • 66
    Publication Date: 2014-12-24
    Description: Broadly, tissue regeneration is achieved in two ways: by proliferation of common differentiated cells and/or by deployment of specialized stem/progenitor cells. Which of these pathways applies is both organ- and injury-specific. Current models in the lung posit that epithelial repair can be attributed to cells expressing mature lineage markers. By contrast, here we define the regenerative role of previously uncharacterized, rare lineage-negative epithelial stem/progenitor (LNEP) cells present within normal distal lung. Quiescent LNEPs activate a DeltaNp63 (a p63 splice variant) and cytokeratin 5 remodelling program after influenza or bleomycin injury in mice. Activated cells proliferate and migrate widely to occupy heavily injured areas depleted of mature lineages, at which point they differentiate towards mature epithelium. Lineage tracing revealed scant contribution of pre-existing mature epithelial cells in such repair, whereas orthotopic transplantation of LNEPs, isolated by a definitive surface profile identified through single-cell sequencing, directly demonstrated the proliferative capacity and multipotency of this population. LNEPs require Notch signalling to activate the DeltaNp63 and cytokeratin 5 program, and subsequent Notch blockade promotes an alveolar cell fate. Persistent Notch signalling after injury led to parenchymal 'micro-honeycombing' (alveolar cysts), indicative of failed regeneration. Lungs from patients with fibrosis show analogous honeycomb cysts with evidence of hyperactive Notch signalling. Our findings indicate that distinct stem/progenitor cell pools repopulate injured tissue depending on the extent of the injury, and the outcomes of regeneration or fibrosis may depend in part on the dynamics of LNEP Notch signalling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312207/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312207/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vaughan, Andrew E -- Brumwell, Alexis N -- Xi, Ying -- Gotts, Jeffrey E -- Brownfield, Doug G -- Treutlein, Barbara -- Tan, Kevin -- Tan, Victor -- Liu, Feng Chun -- Looney, Mark R -- Matthay, Michael A -- Rock, Jason R -- Chapman, Harold A -- F32 HL117600-01/HL/NHLBI NIH HHS/ -- R01 HL44712/HL/NHLBI NIH HHS/ -- U01 HL099995/HL/NHLBI NIH HHS/ -- U01 HL099999/HL/NHLBI NIH HHS/ -- U01 HL111054/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Jan 29;517(7536):621-5. doi: 10.1038/nature14112. Epub 2014 Dec 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco (UCSF), San Francisco, California 94143, USA. ; Department of Biochemistry, Stanford University School of Medicine and Howard Hughes Medical Institute, Stanford, California 94305, USA. ; Max Planck Institute for Evolutionary Anthropology, Department of Evolutionary Genetics, Deutscher Platz 6, 04103 Leipzig, Germany. ; Department of Anatomy, School of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533958" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bleomycin ; Cell Lineage ; Cell Proliferation ; Cell Separation ; Cysts/metabolism/pathology ; Epithelial Cells/*cytology/metabolism/*pathology ; Female ; Humans ; Keratin-5/metabolism ; Lung/*cytology/*pathology/physiology ; Lung Injury/chemically induced/*pathology/virology ; Male ; Mice ; Orthomyxoviridae Infections/pathology/virology ; Phosphoproteins/genetics/metabolism ; *Re-Epithelialization ; Receptors, Notch/metabolism ; Signal Transduction ; Stem Cell Transplantation ; Stem Cells/*cytology/metabolism ; Trans-Activators/genetics/metabolism
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  • 67
    Publication Date: 2014-12-24
    Description: Despite three decades of successful, predominantly phenotype-driven discovery of the genetic causes of monogenic disorders, up to half of children with severe developmental disorders of probable genetic origin remain without a genetic diagnosis. Particularly challenging are those disorders rare enough to have eluded recognition as a discrete clinical entity, those with highly variable clinical manifestations, and those that are difficult to distinguish from other, very similar, disorders. Here we demonstrate the power of using an unbiased genotype-driven approach to identify subsets of patients with similar disorders. By studying 1,133 children with severe, undiagnosed developmental disorders, and their parents, using a combination of exome sequencing and array-based detection of chromosomal rearrangements, we discovered 12 novel genes associated with developmental disorders. These newly implicated genes increase by 10% (from 28% to 31%) the proportion of children that could be diagnosed. Clustering of missense mutations in six of these newly implicated genes suggests that normal development is being perturbed by an activating or dominant-negative mechanism. Our findings demonstrate the value of adopting a comprehensive strategy, both genome-wide and nationwide, to elucidate the underlying causes of rare genetic disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deciphering Developmental Disorders Study -- 098395/Wellcome Trust/United Kingdom -- 100140/Wellcome Trust/United Kingdom -- CZD/16/6/Chief Scientist Office/United Kingdom -- WT098051/Wellcome Trust/United Kingdom -- Department of Health/United Kingdom -- England -- Nature. 2015 Mar 12;519(7542):223-8. doi: 10.1038/nature14135. Epub 2014 Dec 24.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533962" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Animals ; Carrier Proteins/genetics ; Child ; Child, Preschool ; Chromosomal Proteins, Non-Histone/genetics ; Chromosome Aberrations ; DEAD-box RNA Helicases/genetics ; DNA-Binding Proteins/genetics ; Developmental Disabilities/*diagnosis/*genetics ; Dynamin I/genetics ; Exome/genetics ; Female ; Gene Expression Regulation, Developmental ; Genes, Dominant/genetics ; Genome, Human/genetics ; Great Britain ; Guanine Nucleotide Exchange Factors/genetics ; Homeodomain Proteins/genetics ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation, Missense/genetics ; Nerve Tissue Proteins/genetics ; Nuclear Proteins/genetics ; Parents ; Phosphoproteins/genetics ; Polycomb Repressive Complex 1/genetics ; Protein Phosphatase 2/genetics ; Protein-Serine-Threonine Kinases/genetics ; Rare Diseases/genetics ; Transcription Factors/genetics ; Transposases/genetics ; Zebrafish/genetics
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  • 68
    Publication Date: 2014-11-20
    Description: TP53 is commonly altered in human cancer, and Tp53 reactivation suppresses tumours in vivo in mice (TP53 and Tp53 are also known as p53). This strategy has proven difficult to implement therapeutically, and here we examine an alternative strategy by manipulating the p53 family members, Tp63 and Tp73 (also known as p63 and p73, respectively). The acidic transactivation-domain-bearing (TA) isoforms of p63 and p73 structurally and functionally resemble p53, whereas the DeltaN isoforms (lacking the acidic transactivation domain) of p63 and p73 are frequently overexpressed in cancer and act primarily in a dominant-negative fashion against p53, TAp63 and TAp73 to inhibit their tumour-suppressive functions. The p53 family interacts extensively in cellular processes that promote tumour suppression, such as apoptosis and autophagy, thus a clear understanding of this interplay in cancer is needed to treat tumours with alterations in the p53 pathway. Here we show that deletion of the DeltaN isoforms of p63 or p73 leads to metabolic reprogramming and regression of p53-deficient tumours through upregulation of IAPP, the gene that encodes amylin, a 37-amino-acid peptide co-secreted with insulin by the beta cells of the pancreas. We found that IAPP is causally involved in this tumour regression and that amylin functions through the calcitonin receptor (CalcR) and receptor activity modifying protein 3 (RAMP3) to inhibit glycolysis and induce reactive oxygen species and apoptosis. Pramlintide, a synthetic analogue of amylin that is currently used to treat type 1 and type 2 diabetes, caused rapid tumour regression in p53-deficient thymic lymphomas, representing a novel strategy to target p53-deficient cancers.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312210/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312210/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Venkatanarayan, Avinashnarayan -- Raulji, Payal -- Norton, William -- Chakravarti, Deepavali -- Coarfa, Cristian -- Su, Xiaohua -- Sandur, Santosh K -- Ramirez, Marc S -- Lee, Jaehuk -- Kingsley, Charles V -- Sananikone, Eliot F -- Rajapakshe, Kimal -- Naff, Katherine -- Parker-Thornburg, Jan -- Bankson, James A -- Tsai, Kenneth Y -- Gunaratne, Preethi H -- Flores, Elsa R -- CA-16672/CA/NCI NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- P50CA136411/CA/NCI NIH HHS/ -- R01 CA134796/CA/NCI NIH HHS/ -- R01 CA160394/CA/NCI NIH HHS/ -- R01CA134796/CA/NCI NIH HHS/ -- R01CA160394/CA/NCI NIH HHS/ -- England -- Nature. 2015 Jan 29;517(7536):626-30. doi: 10.1038/nature13910. Epub 2014 Nov 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] Department of Translational Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [3] Graduate School of Biomedical Sciences, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [4] Metastasis Research Center, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. ; 1] Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] Department of Translational Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. ; Department of Veterinary Medicine and Surgery, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. ; Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA. ; 1] Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] Department of Translational Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [3] Metastasis Research Center, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. ; 1] Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] Department of Translational Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [3] Metastasis Research Center, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [4] Radiation Biology &Health Sciences Division, Bhabha Atomic Research Center, Mumbai 400085, India. ; Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. ; Department of Genetics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. ; 1] Department of Translational Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] Department of Dermatology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. ; Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25409149" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics/pathology ; DNA-Binding Proteins/genetics/metabolism ; Female ; Genes, Tumor Suppressor ; Humans ; Islet Amyloid Polypeptide/*metabolism/pharmacology/secretion/therapeutic use ; Lymphoma/drug therapy/genetics/*metabolism/*pathology ; Male ; Mice ; Nuclear Proteins/genetics/metabolism ; Phosphoproteins/genetics/metabolism ; Receptor Activity-Modifying Protein 3/metabolism ; Receptors, Calcitonin/metabolism ; Thymus Gland/metabolism/pathology ; Trans-Activators/genetics/metabolism ; Tumor Suppressor Protein p53/*deficiency/genetics ; Tumor Suppressor Proteins/genetics/metabolism
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  • 69
    Publication Date: 2014-11-11
    Description: Lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis involve the progressive and inexorable destruction of oxygen exchange surfaces and airways, and have emerged as a leading cause of death worldwide. Mitigating therapies, aside from impractical organ transplantation, remain limited and the possibility of regenerative medicine has lacked empirical support. However, it is clinically known that patients who survive sudden, massive loss of lung tissue from necrotizing pneumonia or acute respiratory distress syndrome often recover full pulmonary function within six months. Correspondingly, we recently demonstrated lung regeneration in mice following H1N1 influenza virus infection, and linked distal airway stem cells expressing Trp63 (p63) and keratin 5, called DASC(p63/Krt5), to this process. Here we show that pre-existing, intrinsically committed DASC(p63/Krt5) undergo a proliferative expansion in response to influenza-induced lung damage, and assemble into nascent alveoli at sites of interstitial lung inflammation. We also show that the selective ablation of DASC(p63/Krt5) in vivo prevents this regeneration, leading to pre-fibrotic lesions and deficient oxygen exchange. Finally, we demonstrate that single DASC(p63/Krt5)-derived pedigrees differentiate to type I and type II pneumocytes as well as bronchiolar secretory cells following transplantation to infected lung and also minimize the structural consequences of endogenous stem cell loss on this process. The ability to propagate these cells in culture while maintaining their intrinsic lineage commitment suggests their potential in stem cell-based therapies for acute and chronic lung diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zuo, Wei -- Zhang, Ting -- Wu, Daniel Zheng'An -- Guan, Shou Ping -- Liew, Audrey-Ann -- Yamamoto, Yusuke -- Wang, Xia -- Lim, Siew Joo -- Vincent, Matthew -- Lessard, Mark -- Crum, Christopher P -- Xian, Wa -- McKeon, Frank -- England -- Nature. 2015 Jan 29;517(7536):616-20. doi: 10.1038/nature13903. Epub 2014 Nov 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Institute of Singapore, A-STAR, 138672 Singapore. ; The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA. ; Advanced Cell Technologies, Marlborough, Massachusetts 01752, USA. ; The Jackson Laboratory, Bar Harbor, Maine 04609, USA. ; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Genome Institute of Singapore, A-STAR, 138672 Singapore [2] The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA [3] Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [4] Department of Medicine, National University Health System, 119228 Singapore [5] Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA. ; 1] Genome Institute of Singapore, A-STAR, 138672 Singapore [2] The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA [3] Department of Medicine, National University Health System, 119228 Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383540" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bronchioles/cytology/virology ; Cell Differentiation ; Cell Lineage ; Cell Proliferation ; Dogs ; Humans ; Influenza A Virus, H1N1 Subtype/pathogenicity ; Keratin-5/*metabolism ; Lung/*cytology/pathology/*physiology/virology ; Madin Darby Canine Kidney Cells ; Mice ; Orthomyxoviridae Infections/metabolism/pathology/virology ; Oxygen/metabolism ; Pedigree ; Phosphoproteins/*metabolism ; Pneumonia/metabolism/pathology/virology ; Pulmonary Alveoli/cytology/pathology/virology ; Re-Epithelialization ; *Regeneration ; Stem Cell Transplantation ; Stem Cells/*cytology/*metabolism ; Trans-Activators/*metabolism
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  • 70
    Publication Date: 2014-11-11
    Description: DNA methylation is an important epigenetic modification that is essential for various developmental processes through regulating gene expression, genomic imprinting, and epigenetic inheritance. Mammalian genomic DNA methylation is established during embryogenesis by de novo DNA methyltransferases, DNMT3A and DNMT3B, and the methylation patterns vary with developmental stages and cell types. DNA methyltransferase 3-like protein (DNMT3L) is a catalytically inactive paralogue of DNMT3 enzymes, which stimulates the enzymatic activity of Dnmt3a. Recent studies have established a connection between DNA methylation and histone modifications, and revealed a histone-guided mechanism for the establishment of DNA methylation. The ATRX-DNMT3-DNMT3L (ADD) domain of Dnmt3a recognizes unmethylated histone H3 (H3K4me0). The histone H3 tail stimulates the enzymatic activity of Dnmt3a in vitro, whereas the molecular mechanism remains elusive. Here we show that DNMT3A exists in an autoinhibitory form and that the histone H3 tail stimulates its activity in a DNMT3L-independent manner. We determine the crystal structures of DNMT3A-DNMT3L (autoinhibitory form) and DNMT3A-DNMT3L-H3 (active form) complexes at 3.82 and 2.90 A resolution, respectively. Structural and biochemical analyses indicate that the ADD domain of DNMT3A interacts with and inhibits enzymatic activity of the catalytic domain (CD) through blocking its DNA-binding affinity. Histone H3 (but not H3K4me3) disrupts ADD-CD interaction, induces a large movement of the ADD domain, and thus releases the autoinhibition of DNMT3A. The finding adds another layer of regulation of DNA methylation to ensure that the enzyme is mainly activated at proper targeting loci when unmethylated H3K4 is present, and strongly supports a negative correlation between H3K4me3 and DNA methylation across the mammalian genome. Our study provides a new insight into an unexpected autoinhibition and histone H3-induced activation of the de novo DNA methyltransferase after its initial genomic positioning.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, Xue -- Wang, Ling -- Li, Jie -- Ding, Zhanyu -- Xiao, Jianxiong -- Yin, Xiaotong -- He, Shuang -- Shi, Pan -- Dong, Liping -- Li, Guohong -- Tian, Changlin -- Wang, Jiawei -- Cong, Yao -- Xu, Yanhui -- England -- Nature. 2015 Jan 29;517(7536):640-4. doi: 10.1038/nature13899. Epub 2014 Nov 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Fudan University Shanghai Cancer Center, Institute of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China [2] State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China. ; Fudan University Shanghai Cancer Center, Institute of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China. ; National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. ; 1] High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China [2] National Laboratory for Physical Science at the Microscale, University of Science and Technology of China, Hefei 230026, China [3] School of Life Sciences, University of Science and Technology of China, Hefei 230026, China. ; 1] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China [2] University of Chinese Academy of Science, Beijing 100049, China. ; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China. ; State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383530" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Catalytic Domain ; Crystallography, X-Ray ; DNA/metabolism ; DNA (Cytosine-5-)-Methyltransferase/*antagonists & ; inhibitors/*chemistry/*metabolism ; DNA Methylation ; Enzyme Activation ; Histones/*chemistry/*metabolism ; Humans ; Mice ; Models, Molecular ; Protein Structure, Tertiary ; Xenopus laevis
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  • 71
    Publication Date: 2014-12-04
    Description: Filamentous actin (F-actin) is the major protein of muscle thin filaments, and actin microfilaments are the main component of the eukaryotic cytoskeleton. Mutations in different actin isoforms lead to early-onset autosomal dominant non-syndromic hearing loss, familial thoracic aortic aneurysms and dissections, and multiple variations of myopathies. In striated muscle fibres, the binding of myosin motors to actin filaments is mainly regulated by tropomyosin and troponin. Tropomyosin also binds to F-actin in smooth muscle and in non-muscle cells and stabilizes and regulates the filaments there in the absence of troponin. Although crystal structures for monomeric actin (G-actin) are available, a high-resolution structure of F-actin is still missing, hampering our understanding of how disease-causing mutations affect the function of thin muscle filaments and microfilaments. Here we report the three-dimensional structure of F-actin at a resolution of 3.7 A in complex with tropomyosin at a resolution of 6.5 A, determined by electron cryomicroscopy. The structure reveals that the D-loop is ordered and acts as a central region for hydrophobic and electrostatic interactions that stabilize the F-actin filament. We clearly identify map density corresponding to ADP and Mg(2+) and explain the possible effect of prominent disease-causing mutants. A comparison of F-actin with G-actin reveals the conformational changes during filament formation and identifies the D-loop as their key mediator. We also confirm that negatively charged tropomyosin interacts with a positively charged groove on F-actin. Comparison of the position of tropomyosin in F-actin-tropomyosin with its position in our previously determined F-actin-tropomyosin-myosin structure reveals a myosin-induced transition of tropomyosin. Our results allow us to understand the role of individual mutations in the genesis of actin- and tropomyosin-related diseases and will serve as a strong foundation for the targeted development of drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477711/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477711/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉von der Ecken, Julian -- Muller, Mirco -- Lehman, William -- Manstein, Dietmar J -- Penczek, Pawel A -- Raunser, Stefan -- R01 60635/PHS HHS/ -- R01 GM060635/GM/NIGMS NIH HHS/ -- R37HL036153/HL/NHLBI NIH HHS/ -- U54 094598/PHS HHS/ -- U54 GM094598/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Mar 5;519(7541):114-7. doi: 10.1038/nature14033. Epub 2014 Dec 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany. ; Institute for Biophysical Chemistry, Hannover Medical School, 30625 Hannover, Germany. ; Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118, USA. ; Department of Biochemistry and Molecular Biology, The University of Texas, Houston Medical School, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470062" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*chemistry/genetics/*metabolism ; Adenosine Diphosphate/metabolism ; Animals ; Cryoelectron Microscopy ; Magnesium/metabolism ; Mice ; Models, Molecular ; Mutation/genetics ; Protein Conformation ; Rabbits ; Static Electricity ; Tropomyosin/*chemistry/genetics/*metabolism
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  • 72
    Publication Date: 2014-11-05
    Description: Establishing the hippocampal cellular ensemble that represents an animal's environment involves the emergence and disappearance of place fields in specific CA1 pyramidal neurons, and the acquisition of different spatial firing properties across the active population. While such firing flexibility and diversity have been linked to spatial memory, attention and task performance, the cellular and network origin of these place cell features is unknown. Basic integrate-and-fire models of place firing propose that such features result solely from varying inputs to place cells, but recent studies suggest instead that place cells themselves may play an active role through regenerative dendritic events. However, owing to the difficulty of performing functional recordings from place cell dendrites, no direct evidence of regenerative dendritic events exists, leaving any possible connection to place coding unknown. Using multi-plane two-photon calcium imaging of CA1 place cell somata, axons and dendrites in mice navigating a virtual environment, here we show that regenerative dendritic events do exist in place cells of behaving mice, and, surprisingly, their prevalence throughout the arbour is highly spatiotemporally variable. Furthermore, we show that the prevalence of such events predicts the spatial precision and persistence or disappearance of place fields. This suggests that the dynamics of spiking throughout the dendritic arbour may play a key role in forming the hippocampal representation of space.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289090/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289090/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sheffield, Mark E J -- Dombeck, Daniel A -- 1R01MH101297/MH/NIMH NIH HHS/ -- R01 MH101297/MH/NIMH NIH HHS/ -- England -- Nature. 2015 Jan 8;517(7533):200-4. doi: 10.1038/nature13871. Epub 2014 Oct 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Northwestern University, Evanston, Illinois 60208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25363782" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Axons/metabolism ; Calcium/*metabolism ; *Calcium Signaling ; Dendrites/*metabolism ; Hippocampus/*cytology/*physiology ; Male ; Memory, Long-Term/physiology ; Mice ; Mice, Inbred C57BL ; Neuronal Plasticity/physiology ; Space Perception/*physiology ; Time Factors
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  • 73
    Publication Date: 2014-12-04
    Description: Cytotoxic chemotherapy is effective in debulking tumour masses initially; however, in some patients tumours become progressively unresponsive after multiple treatment cycles. Previous studies have demonstrated that cancer stem cells (CSCs) are selectively enriched after chemotherapy through enhanced survival. Here we reveal a new mechanism by which bladder CSCs actively contribute to therapeutic resistance via an unexpected proliferative response to repopulate residual tumours between chemotherapy cycles, using human bladder cancer xenografts. Further analyses demonstrate the recruitment of a quiescent label-retaining pool of CSCs into cell division in response to chemotherapy-induced damages, similar to mobilization of normal stem cells during wound repair. While chemotherapy effectively induces apoptosis, associated prostaglandin E2 (PGE2) release paradoxically promotes neighbouring CSC repopulation. This repopulation can be abrogated by a PGE2-neutralizing antibody and celecoxib drug-mediated blockade of PGE2 signalling. In vivo administration of the cyclooxygenase-2 (COX2) inhibitor celecoxib effectively abolishes a PGE2- and COX2-mediated wound response gene signature, and attenuates progressive manifestation of chemoresistance in xenograft tumours, including primary xenografts derived from a patient who was resistant to chemotherapy. Collectively, these findings uncover a new underlying mechanism that models the progressive development of clinical chemoresistance, and implicate an adjunctive therapy to enhance chemotherapeutic response of bladder urothelial carcinomas by abrogating early tumour repopulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465385/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465385/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kurtova, Antonina V -- Xiao, Jing -- Mo, Qianxing -- Pazhanisamy, Senthil -- Krasnow, Ross -- Lerner, Seth P -- Chen, Fengju -- Roh, Terrence T -- Lay, Erica -- Ho, Philip Levy -- Chan, Keith Syson -- AI036211/AI/NIAID NIH HHS/ -- CA125123/CA/NCI NIH HHS/ -- CA129640/CA/NCI NIH HHS/ -- CA175397/CA/NCI NIH HHS/ -- R00 CA129640/CA/NCI NIH HHS/ -- R01 CA175397/CA/NCI NIH HHS/ -- RR024574/RR/NCRR NIH HHS/ -- England -- Nature. 2015 Jan 8;517(7533):209-13. doi: 10.1038/nature14034. Epub 2014 Dec 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Molecular &Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA [2] Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; Department of Molecular &Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; Dan L Duncan Cancer Center and Center for Cell Gene &Therapy, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; Scott Department of Urology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; 1] Department of Molecular &Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA [2] Summer Medical and Research Training (SMART) Program, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; 1] Department of Molecular &Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA [2] Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA [3] Dan L Duncan Cancer Center and Center for Cell Gene &Therapy, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA [4] Scott Department of Urology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470039" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Neutralizing/immunology/pharmacology ; Apoptosis/drug effects ; Celecoxib ; Cell Proliferation/drug effects ; Cyclooxygenase 2/metabolism ; Cyclooxygenase 2 Inhibitors/pharmacology ; Dinoprostone/*antagonists & inhibitors/immunology/metabolism/secretion ; Drug Resistance, Neoplasm/*drug effects ; Female ; Humans ; Male ; Mice ; Neoplastic Stem Cells/*drug effects/metabolism/*pathology ; Pyrazoles/pharmacology ; Signal Transduction/drug effects ; Sulfonamides/pharmacology ; Urinary Bladder Neoplasms/*drug therapy/*pathology ; Wound Healing/genetics ; Xenograft Model Antitumor Assays
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  • 74
    Publication Date: 2014-12-04
    Description: Muscle contraction is initiated by the release of calcium (Ca(2+)) from the sarcoplasmic reticulum into the cytoplasm of myocytes through ryanodine receptors (RyRs). RyRs are homotetrameric channels with a molecular mass of more than 2.2 megadaltons that are regulated by several factors, including ions, small molecules and proteins. Numerous mutations in RyRs have been associated with human diseases. The molecular mechanism underlying the complex regulation of RyRs is poorly understood. Using electron cryomicroscopy, here we determine the architecture of rabbit RyR1 at a resolution of 6.1 A. We show that the cytoplasmic moiety of RyR1 contains two large alpha-solenoid domains and several smaller domains, with folds suggestive of participation in protein-protein interactions. The transmembrane domain represents a chimaera of voltage-gated sodium and pH-activated ion channels. We identify the calcium-binding EF-hand domain and show that it functions as a conformational switch allosterically gating the channel.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Efremov, Rouslan G -- Leitner, Alexander -- Aebersold, Ruedi -- Raunser, Stefan -- England -- Nature. 2015 Jan 1;517(7532):39-43. doi: 10.1038/nature13916. Epub 2014 Dec 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany [2] Structural Biology Research Center, Vlaams Instituut voor Biotechnologie (VIB), 1050 Brussels, Belgium [3] Structural Biology Brussels, Vrije Universiteit Brussel (VUB), 1050 Brussels, Belgium. ; Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland. ; 1] Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland [2] Faculty of Science, University of Zurich, 8057 Zurich, Switzerland. ; Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470059" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation/drug effects ; Animals ; Calcium/deficiency/metabolism/pharmacology ; Cryoelectron Microscopy ; Cytoplasm/metabolism ; Hydrogen-Ion Concentration ; Inositol 1,4,5-Trisphosphate Receptors/chemistry ; Ion Channel Gating/drug effects ; Models, Molecular ; Protein Binding ; Protein Structure, Tertiary/drug effects ; Rabbits ; Ryanodine Receptor Calcium Release Channel/chemistry/*metabolism/*ultrastructure ; Tacrolimus Binding Protein 1A/chemistry/metabolism/ultrastructure
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  • 75
    Publication Date: 2014-12-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tannock, Ian F -- England -- Nature. 2015 Jan 8;517(7533):152-3. doi: 10.1038/nature14075. Epub 2014 Dec 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario M5G 2M9, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470047" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dinoprostone/*antagonists & inhibitors ; Drug Resistance, Neoplasm/*drug effects ; Female ; Humans ; Male ; Neoplastic Stem Cells/*drug effects/*pathology ; Urinary Bladder Neoplasms/*drug therapy/*pathology
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  • 76
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-11-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kintisch, Eli -- New York, N.Y. -- Science. 2014 Nov 7;346(6210):685. doi: 10.1126/science.346.6210.685.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25378600" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Carnivory ; *Conservation of Natural Resources ; Food Chain ; Lynx ; Mustelidae ; Norway ; Population Dynamics ; *Reindeer
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    Electronic ISSN: 1095-9203
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  • 77
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-11-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stokstad, Erik -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):530-1. doi: 10.1126/science.346.6209.530.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25359941" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Chytridiomycota ; Communicable Diseases, Emerging/*veterinary ; *Endangered Species ; Mycoses/*veterinary ; Urodela/*microbiology
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  • 78
    Publication Date: 2014-08-26
    Description: Aging-associated cognitive decline is affected by factors produced inside and outside the brain. By using multiorgan genome-wide analysis of aged mice, we found that the choroid plexus, an interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent gene expression profile that was also found in aged human brains. In aged mice, this response was induced by brain-derived signals, present in the cerebrospinal fluid. Blocking IFN-I signaling within the aged brain partially restored cognitive function and hippocampal neurogenesis and reestablished IFN-II-dependent choroid plexus activity, which is lost in aging. Our data identify a chronic aging-induced IFN-I signature, often associated with antiviral response, at the brain's choroid plexus and demonstrate its negative influence on brain function, thereby suggesting a target for ameliorating cognitive decline in aging.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baruch, Kuti -- Deczkowska, Aleksandra -- David, Eyal -- Castellano, Joseph M -- Miller, Omer -- Kertser, Alexander -- Berkutzki, Tamara -- Barnett-Itzhaki, Zohar -- Bezalel, Dana -- Wyss-Coray, Tony -- Amit, Ido -- Schwartz, Michal -- AG045034/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 3;346(6205):89-93. doi: 10.1126/science.1252945. Epub 2014 Aug 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel. ; Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. ; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. michal.schwartz@weizmann.ac.il ido.amit@weizmann.ac.il. ; Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel. michal.schwartz@weizmann.ac.il ido.amit@weizmann.ac.il.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25147279" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/genetics/*pathology ; Animals ; Brain/*physiology ; Choroid Plexus/*metabolism ; *Cognition ; *Gene Expression Regulation ; Hippocampus/cytology ; Interferon Regulatory Factors/*genetics ; Interferon Type I/*physiology ; Mice ; Mice, Transgenic ; Neurogenesis ; Receptors, Interferon/genetics
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  • 79
    Publication Date: 2014-05-17
    Description: A switchlike response in nuclear factor-kappaB (NF-kappaB) activity implies the existence of a threshold in the NF-kappaB signaling module. We show that the CARD-containing MAGUK protein 1 (CARMA1, also called CARD11)-TAK1 (MAP3K7)-inhibitor of NF-kappaB (IkappaB) kinase-beta (IKKbeta) module is a switch mechanism for NF-kappaB activation in B cell receptor (BCR) signaling. Experimental and mathematical modeling analyses showed that IKK activity is regulated by positive feedback from IKKbeta to TAK1, generating a steep dose response to BCR stimulation. Mutation of the scaffolding protein CARMA1 at serine-578, an IKKbeta target, abrogated not only late TAK1 activity, but also the switchlike activation of NF-kappaB in single cells, suggesting that phosphorylation of this residue accounts for the feedback.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shinohara, Hisaaki -- Behar, Marcelo -- Inoue, Kentaro -- Hiroshima, Michio -- Yasuda, Tomoharu -- Nagashima, Takeshi -- Kimura, Shuhei -- Sanjo, Hideki -- Maeda, Shiori -- Yumoto, Noriko -- Ki, Sewon -- Akira, Shizuo -- Sako, Yasushi -- Hoffmann, Alexander -- Kurosaki, Tomohiro -- Okada-Hatakeyama, Mariko -- 5R01CA141722/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 May 16;344(6185):760-4. doi: 10.1126/science.1250020.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ; Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Institute for Quantitative and Computational Biosciences (QC Bio) and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90025, USA. ; Laboratory for Cell Signaling Dynamics, RIKEN Quantitative Biology Center (QBiC), 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan. Cellular Informatics Laboratory, RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan. ; Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ; Graduate School of Engineering, Tottori University 4-101, Koyama-minami, Tottori 680-8552, Japan. ; Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. ; Cellular Informatics Laboratory, RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan. ; Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Institute for Quantitative and Computational Biosciences (QC Bio) and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90025, USA. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp. ; Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp. ; Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833394" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/metabolism ; CARD Signaling Adaptor Proteins/genetics/*metabolism ; Cell Line ; Chickens ; Feedback, Physiological ; Guanylate Cyclase/genetics/*metabolism ; I-kappa B Kinase/*metabolism ; MAP Kinase Kinase Kinases/genetics/*metabolism ; Mice ; Mice, Knockout ; Mutation ; NF-kappa B/*agonists ; Phosphorylation ; Receptors, Antigen, B-Cell/genetics/*metabolism ; Serine/genetics/metabolism ; Signal Transduction
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  • 80
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-10-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibbons, Ann -- New York, N.Y. -- Science. 2014 Oct 24;346(6208):405-6. doi: 10.1126/science.346.6208.405.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25342776" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Domestic/*psychology ; *Biological Evolution ; *Cooperative Behavior ; Female ; Hominidae/anatomy & histology/psychology ; Humans ; Male ; Skull/*anatomy & histology ; Testosterone/metabolism ; Tooth/anatomy & histology
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  • 81
    Publication Date: 2014-06-14
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340075/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340075/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Churcher, Thomas S -- Cohen, Justin M -- Novotny, Joseph -- Ntshalintshali, Nyasatu -- Kunene, Simon -- Cauchemez, Simon -- MR/K010174/1/Medical Research Council/United Kingdom -- U54 GM088491/GM/NIGMS NIH HHS/ -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Jun 13;344(6189):1230-2. doi: 10.1126/science.1251449.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Infectious Disease Epidemiology, Imperial College London, London, UK. ; Clinton Health Access Initiative, Boston, MA 02127, USA. ; Clinton Health Access Initiative, Boston, MA 02127, USA. Global Health Group, University of California, San Francisco, CA 94143, USA. ; National Malaria Control Program, Manzini, Swaziland. ; Department of Infectious Disease Epidemiology, Imperial College London, London, UK. Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, Paris, France. simon.cauchemez@pasteur.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24926005" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Culicidae/parasitology ; Disease Eradication/*methods/*trends ; Endemic Diseases/*prevention & control ; Female ; *Global Health ; Humans ; Insect Vectors/parasitology ; Malaria/epidemiology/*prevention & control/transmission ; Mosquito Control/methods ; Seasons
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 82
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-03-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pegau, W Scott -- New York, N.Y. -- Science. 2014 Mar 28;343(6178):1416. doi: 10.1126/science.343.6178.1416.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24675929" target="_blank"〉PubMed〈/a〉
    Keywords: Alaska ; Animals ; *Disasters ; *Fishes ; *Petroleum Pollution
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  • 83
    Publication Date: 2014-03-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shlomai, Amir -- Rice, Charles M -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1212-3. doi: 10.1126/science.1252186.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24626921" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiviral Agents/*pharmacology ; DNA, Circular/*metabolism ; DNA, Viral/*metabolism ; Hepatitis B/*drug therapy ; Hepatitis B virus/*drug effects ; Hepatocytes/*drug effects ; Humans ; Interferon-alpha/*pharmacology ; Lymphotoxin beta Receptor/*agonists
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  • 84
    Publication Date: 2014-09-23
    Description: The neuromuscular junction (NMJ) is the synapse between a motor neuron and skeletal muscle. Defects in NMJ transmission cause muscle weakness, termed myasthenia. The muscle protein Dok-7 is essential for activation of the receptor kinase MuSK, which governs NMJ formation, and DOK7 mutations underlie familial limb-girdle myasthenia (DOK7 myasthenia), a neuromuscular disease characterized by small NMJs. Here, we show in a mouse model of DOK7 myasthenia that therapeutic administration of an adeno-associated virus (AAV) vector encoding the human DOK7 gene resulted in an enlargement of NMJs and substantial increases in muscle strength and life span. When applied to model mice of another neuromuscular disorder, autosomal dominant Emery-Dreifuss muscular dystrophy, DOK7 gene therapy likewise resulted in enlargement of NMJs as well as positive effects on motor activity and life span. These results suggest that therapies aimed at enlarging the NMJ may be useful for a range of neuromuscular disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arimura, Sumimasa -- Okada, Takashi -- Tezuka, Tohru -- Chiyo, Tomoko -- Kasahara, Yuko -- Yoshimura, Toshiro -- Motomura, Masakatsu -- Yoshida, Nobuaki -- Beeson, David -- Takeda, Shin'ichi -- Yamanashi, Yuji -- G0701521/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1505-8. doi: 10.1126/science.1250744.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan. ; Department of Occupational Therapy, Nagasaki University School of Health Sciences, Nagasaki, Japan. ; Department of Electrical and Electronics Engineering, Faculty of Engineering, Nagasaki Institute of Applied Science, Nagasaki, Japan. ; Laboratory of Developmental Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. ; Division of Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. yyamanas@ims.u-tokyo.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25237101" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dependovirus ; Disease Models, Animal ; Female ; Genetic Therapy/*methods ; Genetic Vectors/administration & dosage ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle Proteins/*genetics ; Muscle, Skeletal/*innervation/physiopathology ; Muscular Dystrophies, Limb-Girdle/genetics/*pathology/*therapy ; Neuromuscular Junction/*pathology
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  • 85
    Publication Date: 2014-05-31
    Description: Synaptic vesicle recycling has long served as a model for the general mechanisms of cellular trafficking. We used an integrative approach, combining quantitative immunoblotting and mass spectrometry to determine protein numbers; electron microscopy to measure organelle numbers, sizes, and positions; and super-resolution fluorescence microscopy to localize the proteins. Using these data, we generated a three-dimensional model of an "average" synapse, displaying 300,000 proteins in atomic detail. The copy numbers of proteins involved in the same step of synaptic vesicle recycling correlated closely. In contrast, copy numbers varied over more than three orders of magnitude between steps, from about 150 copies for the endosomal fusion proteins to more than 20,000 for the exocytotic ones.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilhelm, Benjamin G -- Mandad, Sunit -- Truckenbrodt, Sven -- Krohnert, Katharina -- Schafer, Christina -- Rammner, Burkhard -- Koo, Seong Joo -- Classen, Gala A -- Krauss, Michael -- Haucke, Volker -- Urlaub, Henning -- Rizzoli, Silvio O -- New York, N.Y. -- Science. 2014 May 30;344(6187):1023-8. doi: 10.1126/science.1252884.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. International Max Planck Research School Neurosciences, 37077 Gottingen, Germany. ; Bioanalytical Mass Spectrometry Group, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. ; Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. International Max Planck Research School Molecular Biology, 37077 Gottingen, Germany. ; Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. ; Leibniz Institut fur Molekulare Pharmakologie, Department of Molecular Pharmacology and Cell Biology, Robert-Rossle-Strasse 10, 13125 Berlin, Germany. ; Bioanalytical Mass Spectrometry Group, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. Bioanalytics, Department of Clinical Chemistry, University Medical Center Gottingen, 37075 Gottingen, Germany. ; Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. srizzol@gwdg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876496" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*metabolism/ultrastructure ; Exocytosis ; Imaging, Three-Dimensional ; Immunoblotting/methods ; Mass Spectrometry/methods ; Microscopy, Electron/methods ; Models, Neurological ; Presynaptic Terminals/chemistry/*metabolism/ultrastructure ; Protein Transport ; Rats ; Rats, Wistar ; Synaptic Vesicles/chemistry/*metabolism ; Synaptosomes/chemistry/*metabolism/ultrastructure ; Vesicular Transport Proteins/analysis/*metabolism
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  • 86
    Publication Date: 2014-03-29
    Description: The field of optogenetics uses channelrhodopsins (ChRs) for light-induced neuronal activation. However, optimized tools for cellular inhibition at moderate light levels are lacking. We found that replacement of E90 in the central gate of ChR with positively charged residues produces chloride-conducting ChRs (ChloCs) with only negligible cation conductance. Molecular dynamics modeling unveiled that a high-affinity Cl(-)-binding site had been generated near the gate. Stabilizing the open state dramatically increased the operational light sensitivity of expressing cells (slow ChloC). In CA1 pyramidal cells, ChloCs completely inhibited action potentials triggered by depolarizing current injections or synaptic stimulation. Thus, by inverting the charge of the selectivity filter, we have created a class of directly light-gated anion channels that can be used to block neuronal output in a fully reversible fashion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wietek, Jonas -- Wiegert, J Simon -- Adeishvili, Nona -- Schneider, Franziska -- Watanabe, Hiroshi -- Tsunoda, Satoshi P -- Vogt, Arend -- Elstner, Marcus -- Oertner, Thomas G -- Hegemann, Peter -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):409-12. doi: 10.1126/science.1249375. Epub 2014 Mar 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Biology, Experimental Biophysics, Humboldt Universitat zu Berlin, D-10115 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24674867" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Binding Sites ; CA1 Region, Hippocampal/cytology ; Chloride Channels/*chemistry/*metabolism ; Chlorides/*metabolism ; HEK293 Cells ; Humans ; Hydrogen Bonding ; Ion Channel Gating ; Light ; Models, Molecular ; Molecular Dynamics Simulation ; Mutation ; Patch-Clamp Techniques ; Protein Conformation ; Protein Engineering ; Pyramidal Cells/metabolism ; Rats ; Recombinant Fusion Proteins/chemistry ; Rhodopsin/*chemistry/genetics/*metabolism ; Transfection
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  • 87
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Churchill, Gary A -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):370. doi: 10.1126/science.343.6169.370-a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Jackson Laboratory, Bar Harbor, ME 04609, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24458625" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Experimentation/*standards/*statistics & numerical data ; Animals ; Humans
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  • 88
    Publication Date: 2014-02-15
    Description: Evolutionary changes in traits involved in both ecological divergence and mate choice may produce reproductive isolation and speciation. However, there are few examples of such dual traits, and the genetic and molecular bases of their evolution have not been identified. We show that methyl-branched cuticular hydrocarbons (mbCHCs) are a dual trait that affects both desiccation resistance and mate choice in Drosophila serrata. We identify a fatty acid synthase mFAS (CG3524) responsible for mbCHC production in Drosophila and find that expression of mFAS is undetectable in oenocytes (cells that produce CHCs) of a closely related, desiccation-sensitive species, D. birchii, due in part to multiple changes in cis-regulatory sequences of mFAS. We suggest that ecologically influenced changes in the production of mbCHCs have contributed to reproductive isolation between the two species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chung, Henry -- Loehlin, David W -- Dufour, Heloise D -- Vaccarro, Kathy -- Millar, Jocelyn G -- Carroll, Sean B -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Mar 7;343(6175):1148-51. doi: 10.1126/science.1249998. Epub 2014 Feb 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24526311" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Desiccation ; Drosophila/*genetics/physiology ; Ecosystem ; Evolution, Molecular ; Fatty Acid Synthases/*genetics/physiology ; *Genes, Insect ; *Genetic Variation ; Hydrocarbons/*metabolism ; *Mating Preference, Animal ; Molecular Sequence Data ; *Reproductive Isolation
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  • 89
    Publication Date: 2014-05-31
    Description: The most prominent pattern in global marine biogeography is the biodiversity peak in the Indo-Australian Archipelago. Yet the processes that underpin this pattern are still actively debated. By reconstructing global marine paleoenvironments over the past 3 million years on the basis of sediment cores, we assessed the extent to which Quaternary climate fluctuations can explain global variation in current reef fish richness. Comparing global historical coral reef habitat availability with the present-day distribution of 6316 reef fish species, we find that distance from stable coral reef habitats during historical periods of habitat loss explains 62% of the variation in fish richness, outweighing present-day environmental factors. Our results highlight the importance of habitat persistence during periods of climate change for preserving marine biodiversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pellissier, Loic -- Leprieur, Fabien -- Parravicini, Valeriano -- Cowman, Peter F -- Kulbicki, Michel -- Litsios, Glenn -- Olsen, Steffen M -- Wisz, Mary S -- Bellwood, David R -- Mouillot, David -- New York, N.Y. -- Science. 2014 May 30;344(6187):1016-9. doi: 10.1126/science.1249853.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Fribourg, Department of Biology, Chemin du Musee 10, CH-1700 Fribourg, Switzerland. Department of Bioscience, Aarhus University, 8000 C Aarhus, Denmark. ; Laboratoire Ecologie des Systemes Marins Cotiers UMR 5119, CNRS, Institut de Recherche pour le Developpement (IRD), Institut Francais de Recherche pour l'Exploitation de la Mer, UM2, UM1, cc 093, Place E. Bataillon, FR-34095 Montpellier Cedex 5, France. ; IRD, UR 227 CoReUs, LABEX (Laboratoire d'Excellence) Corail, Laboratoire Arago, Boite Postale 44, FR-66651 Banyuls/mer, France. CESAB (Centre de Synthese et d'Analyse sur la Biodiversite)-FRB (Fondation pour la Recherche sur la Biodiversite), Immeuble Henri Poincare, Domaine du Petit Arbois, FR-13857 Aix-en-Provence cedex 3, France. ; Centre for Macroevolution and Macroecology, Research School of Biology, Australian National University, Canberra, ACT 0200, Australia. ; IRD, UR 227 CoReUs, LABEX (Laboratoire d'Excellence) Corail, Laboratoire Arago, Boite Postale 44, FR-66651 Banyuls/mer, France. ; Department of Ecology and Evolution, Biophore Building, University of Lausanne, 1015 Lausanne, Switzerland. Swiss Institute of Bioinformatics, Quartier Sorge, 1015 Lausanne, Switzerland. ; Center for Ocean and Ice, Danish Meteorological Institute, Lyngbyvej 100, 2100 Copenhagen, Denmark. ; Department of Bioscience, Aarhus University, 8000 C Aarhus, Denmark. Department of Ecology and Environment, DHI Water and Environment, 2970 Horsholm, Denmark. ; Australian Research Council Centre of Excellence for Coral Reef Studies, and School of Marine and Tropical Biology, James Cook University, Townsville, QLD 4811, Australia. ; Laboratoire Ecologie des Systemes Marins Cotiers UMR 5119, CNRS, Institut de Recherche pour le Developpement (IRD), Institut Francais de Recherche pour l'Exploitation de la Mer, UM2, UM1, cc 093, Place E. Bataillon, FR-34095 Montpellier Cedex 5, France. Australian Research Council Centre of Excellence for Coral Reef Studies, and School of Marine and Tropical Biology, James Cook University, Townsville, QLD 4811, Australia. david.mouillot@univ-montp2.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876495" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Australia ; *Biodiversity ; *Climate Change ; *Conservation of Natural Resources ; *Coral Reefs ; *Fishes
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  • 90
    Publication Date: 2014-10-04
    Description: After an infection, pathogen-specific tissue-resident memory T cells (T(RM) cells) persist in nonlymphoid tissues to provide rapid control upon reinfection, and vaccination strategies that create T(RM) cell pools at sites of pathogen entry are therefore attractive. However, it is not well understood how T(RM) cells provide such pathogen protection. Here, we demonstrate that activated T(RM) cells in mouse skin profoundly alter the local tissue environment by inducing a number of broadly active antiviral and antibacterial genes. This "pathogen alert" allows skin T(RM) cells to protect against an antigenically unrelated virus. These data describe a mechanism by which tissue-resident memory CD8(+) T cells protect previously infected sites that is rapid, amplifies the activation of a small number of cells into an organ-wide response, and has the capacity to control escape variants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ariotti, Silvia -- Hogenbirk, Marc A -- Dijkgraaf, Feline E -- Visser, Lindy L -- Hoekstra, Mirjam E -- Song, Ji-Ying -- Jacobs, Heinz -- Haanen, John B -- Schumacher, Ton N -- New York, N.Y. -- Science. 2014 Oct 3;346(6205):101-5. doi: 10.1126/science.1254803. Epub 2014 Aug 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands. ; Division of Biological Stress Response, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands. ; Experimental Animal Pathology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands. ; Division of Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands. t.schumacher@nki.nl.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278612" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD8-Positive T-Lymphocytes/*immunology ; Female ; Immunologic Memory/genetics/*immunology ; Male ; Mice ; Skin/*immunology/microbiology/virology ; Transcriptome
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  • 91
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-04-05
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143233/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143233/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mann, Richard S -- R01 NS070644/NS/NINDS NIH HHS/ -- R01NS070644/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):48-9. doi: 10.1126/science.1252431.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700848" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Drosophila/*physiology ; Female ; Male ; Neurons/*physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 92
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-06-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibbons, Ann -- New York, N.Y. -- Science. 2014 Jun 13;344(6189):1213-4. doi: 10.1126/science.344.6189.1213.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24925995" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Horses/*genetics/*physiology ; *Inbreeding ; Male ; *Physical Conditioning, Animal ; *Running ; Selection, Genetic
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 93
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-02-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2014 Jan 31;343(6170):477. doi: 10.1126/science.343.6170.477.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24482460" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcysteine/administration & dosage/*adverse effects ; Animals ; Antioxidants/administration & dosage/*adverse effects ; Carcinogens/toxicity ; DNA Damage ; Dietary Supplements/adverse effects ; Genes, Neoplasm/*drug effects ; Humans ; Lung Neoplasms/*chemically induced/prevention & control ; Mice ; Smoking/adverse effects ; Tumor Suppressor Protein p53/genetics/metabolism ; Vitamin E/administration & dosage/*adverse effects ; Vitamins/administration & dosage/*adverse effects
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 94
    Publication Date: 2014-03-15
    Description: Vertebrate limbs first emerge as small buds at specific locations along the trunk. Although a fair amount is known about the molecular regulation of limb initiation and outgrowth, the cellular events underlying these processes have remained less clear. We show that the mesenchymal limb progenitors arise through localized epithelial-to-mesenchymal transition (EMT) of the coelomic epithelium specifically within the presumptive limb fields. This EMT is regulated at least in part by Tbx5 and Fgf10, two genes known to control limb initiation. This work shows that limb buds initiate earlier than previously thought, as a result of localized EMT rather than differential proliferation rates.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4097009/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4097009/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gros, Jerome -- Tabin, Clifford J -- R01 HD045499/HD/NICHD NIH HHS/ -- R01-HD045499/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1253-6. doi: 10.1126/science.1248228.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24626928" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cadherins/metabolism ; Chick Embryo ; *Epithelial-Mesenchymal Transition ; Extremities/*embryology ; Fibroblast Growth Factor 10/genetics/metabolism ; Limb Buds/*cytology/metabolism ; Mice ; Mice, Mutant Strains ; Protein Kinase C/metabolism ; T-Box Domain Proteins/genetics/metabolism ; Vimentin/metabolism ; beta Catenin/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 95
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stokstad, Erik -- New York, N.Y. -- Science. 2014 Jan 17;343(6168):238. doi: 10.1126/science.343.6168.238.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436398" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture ; Air Pollutants/*adverse effects/analysis ; Air Pollution/*adverse effects/prevention & control ; Ammonia/*adverse effects/analysis ; Animals ; Fertilizers/*adverse effects ; Health/*economics ; Heart Diseases/chemically induced ; Humans ; Livestock ; Models, Biological ; North Carolina ; Particulate Matter/*adverse effects/analysis ; Respiratory Tract Diseases/chemically induced ; United States ; United States Environmental Protection Agency
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 96
    Publication Date: 2014-05-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2014 May 16;344(6185):679. doi: 10.1126/science.344.6185.679.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833367" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Experimentation/*standards ; Animals ; Biomedical Research/*standards ; Cells ; Female ; Male ; Mice ; National Institutes of Health (U.S.) ; Sex Factors ; United States ; X Chromosome ; Y Chromosome
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  • 97
    Publication Date: 2014-11-08
    Description: Nearly all mitochondrial proteins are nuclear-encoded and are targeted to their mitochondrial destination from the cytosol. Here, we used proximity-specific ribosome profiling to comprehensively measure translation at the mitochondrial surface in yeast. Most inner-membrane proteins were cotranslationally targeted to mitochondria, reminiscent of proteins entering the endoplasmic reticulum (ER). Comparison between mitochondrial and ER localization demonstrated that the vast majority of proteins were targeted to a specific organelle. A prominent exception was the fumarate reductase Osm1, known to reside in mitochondria. We identified a conserved ER isoform of Osm1, which contributes to the oxidative protein-folding capacity of the organelle. This dual localization was enabled by alternative translation initiation sites encoding distinct targeting signals. These findings highlight the exquisite in vivo specificity of organellar targeting mechanisms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263316/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263316/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williams, Christopher C -- Jan, Calvin H -- Weissman, Jonathan S -- P50 GM102706/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Nov 7;346(6210):748-51. doi: 10.1126/science.1257522.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉These authors contributed equally to this work. ; Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, California Institute for Quantitative Biosciences, Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA. These authors contributed equally to this work. jonathan.weissman@ucsf.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25378625" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Endoplasmic Reticulum/metabolism ; Mitochondria/*metabolism ; Mitochondrial Proteins/biosynthesis/chemistry/*metabolism ; *Peptide Chain Initiation, Translational ; Protein Folding ; Ribosomes/*metabolism ; Saccharomyces cerevisiae/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Succinate Dehydrogenase/metabolism
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  • 98
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-02-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibbons, Ann -- New York, N.Y. -- Science. 2014 Jan 31;343(6170):471-2. doi: 10.1126/science.343.6170.471.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24482455" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Crohn Disease/genetics ; DNA/genetics ; Diabetes Mellitus, Type 2/genetics ; Disease/*genetics ; *Evolution, Molecular ; Female ; Genome, Human/*genetics ; Humans ; Interleukin-18/genetics ; Keratins/genetics ; Liver Cirrhosis, Biliary/genetics ; Male ; Neanderthals/*genetics ; Optic Disk/anatomy & histology ; Sequence Analysis, DNA ; Smoking/genetics
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-10-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clery, Daniel -- New York, N.Y. -- Science. 2014 Oct 17;346(6207):290-1. doi: 10.1126/science.346.6207.290.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25324365" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Chemistry ; Mice ; Microscopy, Fluorescence/*methods ; *Nobel Prize ; Organelles/ultrastructure ; United States
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  • 100
    Publication Date: 2014-04-15
    Description: Myelination of the central nervous system requires the generation of functionally mature oligodendrocytes from oligodendrocyte precursor cells (OPCs). Electrically active neurons may influence OPC function and selectively instruct myelination of an active neural circuit. In this work, we use optogenetic stimulation of the premotor cortex in awake, behaving mice to demonstrate that neuronal activity elicits a mitogenic response of neural progenitor cells and OPCs, promotes oligodendrogenesis, and increases myelination within the deep layers of the premotor cortex and subcortical white matter. We further show that this neuronal activity-regulated oligodendrogenesis and myelination is associated with improved motor function of the corresponding limb. Oligodendrogenesis and myelination appear necessary for the observed functional improvement, as epigenetic blockade of oligodendrocyte differentiation and myelin changes prevents the activity-regulated behavioral improvement.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096908/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096908/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibson, Erin M -- Purger, David -- Mount, Christopher W -- Goldstein, Andrea K -- Lin, Grant L -- Wood, Lauren S -- Inema, Ingrid -- Miller, Sarah E -- Bieri, Gregor -- Zuchero, J Bradley -- Barres, Ben A -- Woo, Pamelyn J -- Vogel, Hannes -- Monje, Michelle -- 1S10RR02678001/RR/NCRR NIH HHS/ -- K08 NS070926/NS/NINDS NIH HHS/ -- K08NS070926/NS/NINDS NIH HHS/ -- R01 EY10257/EY/NEI NIH HHS/ -- T32 MH020016/MH/NIMH NIH HHS/ -- UL1 RR025744/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 May 2;344(6183):1252304. doi: 10.1126/science.1252304. Epub 2014 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Neurology, Neurosurgery, and Pediatrics, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24727982" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Thy-1/genetics ; Behavior, Animal/physiology ; *Cell Differentiation ; Cell Lineage ; Cell Proliferation ; Corpus Callosum/cytology/physiology ; Mice ; Mice, Mutant Strains ; Motor Activity/physiology ; Motor Cortex/cytology/*physiology ; Myelin Sheath/*metabolism ; Nerve Fibers, Myelinated/*metabolism ; Neural Stem Cells/*physiology ; Neurons/*physiology ; Oligodendroglia/*cytology ; Rhodopsin/genetics
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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