Structural investigation of nucleophosmin interaction with the tumor suppressor Fbw7γ

Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts. Among NPM1 protein partners, a pivotal role is played by the tumor suppressor Fbw7γ, an E3-ubiquitin ligase that degrades oncoproteins like c-MYC, cyclin E, Notch and c-jun. In AML with NPM1 mutations, Fbw7γ is degraded following its abnormal cytosolic delocalization by mutated NPM1. This mechanism also applies to other tumor suppressors and it has been suggested that it may play a key role in leukemogenesis. Here we analyse the interaction between NPM1 and Fbw7γ, by identifying the protein surfaces implicated in recognition and key aminoacids involved. Based on the results of computational methods, we propose a structural model for the interaction, which is substantiated by experimental findings on several site-directed mutants. We also extend the analysis to two other NPM1 partners (HIV Tat and CENP-W) and conclude that NPM1 uses the same molecular surface as a platform for recognizing different protein partners. We suggest that this region of NPM1 may be targeted for cancer treatment

Violation of area-law scaling for the entanglement entropy in spin 1/2 chains

Entanglement entropy obeys area law scaling for typical physical quantum systems. This may naively be argued to follow from locality of interactions. We show that this is not the case by constructing an explicit simple spin chain Hamiltonian with nearest neighbor interactions that presents an entanglement volume scaling law. This non-translational model is contrived to have couplings that force the accumulation of singlet bonds across the half chain. Our result is complementary to the known relation between non-translational invariant, nearest neighbor interacting Hamiltonians and QMA complete problems.Comment: 9 pages, 4 figure

Higher-order Mechanics: Variational Principles and other topics

After reviewing the Lagrangian-Hamiltonian unified formalism (i.e, the Skinner-Rusk formalism) for higher-order (non-autonomous) dynamical systems, we state a unified geometrical version of the Variational Principles which allows us to derive the Lagrangian and Hamiltonian equations for these kinds of systems. Then, the standard Lagrangian and Hamiltonian formulations of these principles and the corresponding dynamical equations are recovered from this unified framework.Comment: New version of the paper "Variational principles for higher-order dynamical systems", which was presented in the "III Iberoamerican Meeting on Geometry, Mechanics and Control" (Salamanca, 2012). The title is changed. A detailed review is added. Sections containing results about variational principles are enlarged with additional comments, diagrams and summarizing results. Bibliography is update

Spin-Nematic Squeezed Vacuum in a Quantum Gas

Using squeezed states it is possible to surpass the standard quantum limit of measurement uncertainty by reducing the measurement uncertainty of one property at the expense of another complementary property. Squeezed states were first demonstrated in optical fields and later with ensembles of pseudo spin-1/2 atoms using non-linear atom-light interactions. Recently, collisional interactions in ultracold atomic gases have been used to generate a large degree of quadrature spin squeezing in two-component Bose condensates. For pseudo spin-1/2 systems, the complementary properties are the different components of the total spin vector , which fully characterize the state on an SU(2) Bloch sphere. Here, we measure squeezing in a spin-1 Bose condensate, an SU(3) system, which requires measurement of the rank-2 nematic or quadrupole tensor as well to fully characterize the state. Following a quench through a nematic to ferromagnetic quantum phase transition, squeezing is observed in the variance of the quadratures up to -8.3(-0.7 +0.6) dB (-10.3(-0.9 +0.7) dB corrected for detection noise) below the standard quantum limit. This spin-nematic squeezing is observed for negligible occupation of the squeezed modes and is analogous to optical two-mode vacuum squeezing. This work has potential applications to continuous variable quantum information and quantum-enhanced magnetometry

Parametrization for the Scale Dependent Growth in Modified Gravity

We propose a scale dependent analytic approximation to the exact linear growth of density perturbations in Scalar-Tensor (ST) cosmologies. In particular, we show that on large subhorizon scales, in the Newtonian gauge, the usual scale independent subhorizon growth equation does not describe the growth of perturbations accurately, as a result of scale-dependent relativistic corrections to the Poisson equation. A comparison with exact linear numerical analysis indicates that our approximation is a significant improvement over the standard subhorizon scale independent result on large subhorizon scales. A comparison with the corresponding results in the Synchronous gauge demonstrates the validity and consistency of our analysis.Comment: 10 pages, 5 figures. Minor modifications and references added to match published versio

From Atiyah Classes to Homotopy Leibniz Algebras

A celebrated theorem of Kapranov states that the Atiyah class of the tangent bundle of a complex manifold $X$ makes $T_X[-1]$ into a Lie algebra object in $D^+(X)$, the bounded below derived category of coherent sheaves on $X$. Furthermore Kapranov proved that, for a K\"ahler manifold $X$, the Dolbeault resolution $\Omega^{\bullet-1}(T_X^{1,0})$ of $T_X[-1]$ is an $L_\infty$ algebra. In this paper, we prove that Kapranov's theorem holds in much wider generality for vector bundles over Lie pairs. Given a Lie pair $(L,A)$, i.e. a Lie algebroid $L$ together with a Lie subalgebroid $A$, we define the Atiyah class $\alpha_E$ of an $A$-module $E$ (relative to $L$) as the obstruction to the existence of an $A$-compatible $L$-connection on $E$. We prove that the Atiyah classes $\alpha_{L/A}$ and $\alpha_E$ respectively make $L/A[-1]$ and $E[-1]$ into a Lie algebra and a Lie algebra module in the bounded below derived category $D^+(\mathcal{A})$, where $\mathcal{A}$ is the abelian category of left $\mathcal{U}(A)$-modules and $\mathcal{U}(A)$ is the universal enveloping algebra of $A$. Moreover, we produce a homotopy Leibniz algebra and a homotopy Leibniz module stemming from the Atiyah classes of $L/A$ and $E$, and inducing the aforesaid Lie structures in $D^+(\mathcal{A})$.Comment: 36 page

Averaging inhomogeneities in scalar-tensor cosmology

The backreaction of inhomogeneities on the cosmic dynamics is studied in the context of scalar-tensor gravity. Due to terms of indefinite sign in the non-canonical effective energy tensor of the Brans-Dicke-like scalar field, extra contributions to the cosmic acceleration can arise. Brans-Dicke and metric f(R) gravity are presented as specific examples. Certain representation problems of the formalism peculiar to these theories are pointed out.Comment: Comments and references added. 14 page

The correlation of RNase A enzymatic activity with the changes in the distance between Nepsilon2-His12 and N delta1-His119 upon addition of stabilizing and destabilizing salts.

The effect of stabilizing and destabilizing salts on the catalytic behavior of ribonuclease A (RNase A) was investigated at pH 7.5 and 25 degrees C, using spectrophotometric, viscometric and molecular dynamic methods. The changes in the distance between N(epsilon2) of His(12) and N(delta1) of His(119) at the catalytic center of RNase A upon the addition of sodium sulfate, sodium hydrogen sulfate and sodium thiocyanate were evaluated by molecular dynamic methods. The compactness and expansion in terms of Stokes radius of RNase A upon the addition of sulfate ions as kosmotropic salts, and thiocyanate ion as a chaotropic salt, were estimated by viscometric measurements. Enzyme activity was measured using cytidine 2', 3'-cyclic monophosphate as a substrate. The results from the measurements of distances between N(epsilon2) of His(12) and N(delta1) of His(119) and Stokes radius suggest (i) that the presence of sulfate ions decreases the distance between the catalytic His residues and increases the globular compactness, and (ii) that there is an expansion of the enzyme surface as well as elongation of the catalytic center in the presence of thiocyanate ion. These findings are in agreement with activity measurements