Human cachexia induces changes in mitochondria, autophagy and apoptosis in the skeletal muscle

Cachexia is a wasting syndrome characterized by the continuous loss of skeletal muscle mass due to imbalance between protein synthesis and degradation, which is related with poor prognosis and compromised quality of life. Dysfunctional mitochondria are associated with lower muscle strength and muscle atrophy in cancer patients, yet poorly described in human cachexia. We herein investigated mitochondrial morphology, autophagy and apoptosis in the skeletal muscle of patients with gastrointestinal cancer-associated cachexia (CC), as compared with a weight-stable cancer group (WSC). CC showed prominent weight loss and increased circulating levels of serum C-reactive protein, lower body mass index and decreased circulating hemoglobin, when compared to WSC. Electron microscopy analysis revealed an increase in intermyofibrillar mitochondrial area in CC, as compared to WSC. Relative gene expression of Fission 1, a protein related to mitochondrial fission, was increased in CC, as compared to WSC. LC3 II, autophagy-related (ATG) 5 and 7 essential proteins for autophagosome formation, presented higher content in the cachectic group. Protein levels of phosphorylated p53 (Ser46), activated caspase 8 (Asp384) and 9 (Asp315) were also increased in the skeletal muscle of CC. Overall, our results demonstrate that human cancer-associated cachexia leads to exacerbated muscle-stress response that may culminate in muscle loss, which is in part due to disruption of mitochondrial morphology, dysfunctional autophagy and increased apoptosis. To the best of our knowledge, this is the first report showing quantitative morphological alterations in skeletal muscle mitochondria in cachectic patients

Supersymmetric BCS

We implement relativistic BCS superconductivity in N=1 supersymmetric field theories with a U(1)_R symmetry. The simplest model contains two chiral superfields with a Kahler potential modified by quartic terms. We study the phase diagram of the gap as a function of the temperature and the specific heat. The superconducting phase transition turns out to be first order, due to the scalar contribution to the one-loop potential. By virtue of supersymmetry, the critical curves depend logarithmically with the UV cutoff, rather than quadratically as in standard BCS theory. We comment on the difficulties in having fermion condensates when the chemical potential is instead coupled to a baryonic U(1)_B current. We also discuss supersymmetric models of BCS with canonical Kahler potential constructed by "integrating-in" chiral superfields.Comment: 26 pages, 5 figure

Rigidly Supersymmetric Gauge Theories on Curved Superspace

In this note we construct rigidly supersymmetric gauged sigma models and gauge theories on certain Einstein four-manifolds, and discuss constraints on these theories. In work elsewhere, it was recently shown that on some nontrivial Einstein four-manifolds such as AdS$_4$, N=1 rigidly supersymmetric sigma models are constrained to have target spaces with exact K\"ahler forms. Similarly, in gauged sigma models and gauge theories, we find that supersymmetry imposes constraints on Fayet-Iliopoulos parameters, which have the effect of enforcing that K\"ahler forms on quotient spaces be exact. We also discuss general aspects of universality classes of gauged sigma models, as encoded by stacks, and also discuss affine bundle structures implicit in these constructions.Comment: 23 pages; references added; more discussion added; v4: typos fixe

Entanglement Entropy of 3-d Conformal Gauge Theories with Many Flavors

Three-dimensional conformal field theories (CFTs) of deconfined gauge fields coupled to gapless flavors of fermionic and bosonic matter describe quantum critical points of condensed matter systems in two spatial dimensions. An important characteristic of these CFTs is the finite part of the entanglement entropy across a circle. The negative of this quantity is equal to the finite part of the free energy of the Euclidean CFT on the three-sphere, and it has been proposed to satisfy the so called F-theorem, which states that it decreases under RG flow and is stationary at RG fixed points. We calculate the three-sphere free energy of non-supersymmetric gauge theory with a large number N_F of bosonic and/or fermionic flavors to the first subleading order in 1/N_F. We also calculate the exact free energies of the analogous chiral and non-chiral {\cal N} = 2 supersymmetric theories using localization, and find agreement with the 1/N_F expansion. We analyze some RG flows of supersymmetric theories, providing further evidence for the F-theorem.Comment: 31 pages, 2 figures; v2 refs added, minor change

Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grant numbers 11/15682-4, 12/02270-2, 15/18121-4), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Regenera INCT Process Grant 465656/2014-5). JL is funded by the NIH/NIDDK R01DK106210. GDB is funded by the Wellcome Trust and the MRC Centre for Medical Mycology. Open access journalPeer reviewedPublisher PD

Thermalization from gauge/gravity duality: Evolution of singularities in unequal time correlators

We consider a gauge/gravity dual model of thermalization which consists of a collapsing thin matter shell in asymptotically Anti-de Sitter space. A central aspect of our model is to consider a shell moving at finite velocity as determined by its equation of motion, rather than a quasi-static approximation as considered previously in the literature. By applying a divergence matching method, we obtain the evolution of singularities in the retarded unequal time correlator $G^R(t,t')$, which probes different stages of the thermalization. We find that the number of singularities decreases from a finite number to zero as the gauge theory thermalizes. This may be interpreted as a sign of decoherence. Moreover, in a second part of the paper, we show explicitly that the thermal correlator is characterized by the existence of singularities in the complex time plane. By studying a quasi-static state, we show the singularities at real times originate from contributions of normal modes. We also investigate the possibility of obtaining complex singularities from contributions of quasi-normal modes.Comment: 35 pages, 4 figure

Three form potential in (special) minimal supergravity superspace and supermembrane supercurrent

This contribution begins the study of the complete superfield Lagrangian description of the interacting system of D=4 N=1 supergravity (SUGRA) and supermembrane. Firstly, we review a 'three form supergravity' by Ovrut and Waldram, which we prefer to call 'special minimal supergravity'. This off-shell formulation of simple SUGRA is appropriate for our purposes as the supermembrane action contains the so-called Wess-Zumino term given by the integral over a three form potential in superspace, C3. We describe this formulation in the frame of Wess--Zumino superfield approach, showing how the basic variations of minimal SUGRA are restricted by the conditions of the existence of a three-form potential C3 in its superspace. In this language the effect of dynamical generation of cosmological constant, known to be characteristic for this formulation of SUGRA, appears in its superfield form, first described by Ogievetsky and Sokatchev in their formulation of SUGRA as a theory of axial vector superfield. Secondly, we vary the supermembrane action with respect to the special minimal SUGRA superfields (basic variations) and obtain the supercurrent superfields as well as the supergravity superfield equations with the supermembrane contributions.Comment: 18 pages, no figures. V2: Important references added. The abstract and presentation have been changed to reflect the overloop with that. Submitted to the QTS7 Proceedings. J. Phys. style use

Black hole determinants and quasinormal modes

We derive an expression for functional determinants in thermal spacetimes as a product over the corresponding quasinormal modes. As simple applications we give efficient computations of scalar determinants in thermal AdS, BTZ black hole and de Sitter spacetimes. We emphasize the conceptual utility of our formula for discussing `1/N' corrections to strongly coupled field theories via the holographic correspondence.Comment: 28 pages. v2: slightly improved exposition, references adde

Non-equilibrium Dynamics of O(N) Nonlinear Sigma models: a Large-N approach

We study the time evolution of the mass gap of the O(N) non-linear sigma model in 2+1 dimensions due to a time-dependent coupling in the large-$N$ limit. Using the Schwinger-Keldysh approach, we derive a set of equations at large $N$ which determine the time dependent gap in terms of the coupling. These equations lead to a criterion for the breakdown of adiabaticity for slow variation of the coupling leading to a Kibble-Zurek scaling law. We describe a self-consistent numerical procedure to solve these large-$N$ equations and provide explicit numerical solutions for a coupling which starts deep in the gapped phase at early times and approaches the zero temperature equilibrium critical point $g_c$ in a linear fashion. We demonstrate that for such a protocol there is a value of the coupling $g= g_c^{\rm dyn}> g_c$ where the gap function vanishes, possibly indicating a dynamical instability. We study the dependence of $g_c^{\rm dyn}$ on both the rate of change of the coupling and the initial temperature. We also verify, by studying the evolution of the mass gap subsequent to a sudden change in $g$, that the model does not display thermalization within a finite time interval $t_0$ and discuss the implications of this observation for its conjectured gravitational dual as a higher spin theory in $AdS_4$.Comment: 22 pages, 9 figures. Typos corrected, references rearranged and added.v3 : sections rearranged, abstract modified, comment about Kibble-Zurek scaling correcte

Quivers, YBE and 3-manifolds

We study 4d superconformal indices for a large class of N=1 superconformal quiver gauge theories realized combinatorially as a bipartite graph or a set of "zig-zag paths" on a two-dimensional torus T^2. An exchange of loops, which we call a "double Yang-Baxter move", gives the Seiberg duality of the gauge theory, and the invariance of the index under the duality is translated into the Yang-Baxter-type equation of a spin system defined on a "Z-invariant" lattice on T^2. When we compactify the gauge theory to 3d, Higgs the theory and then compactify further to 2d, the superconformal index reduces to an integral of quantum/classical dilogarithm functions. The saddle point of this integral unexpectedly reproduces the hyperbolic volume of a hyperbolic 3-manifold. The 3-manifold is obtained by gluing hyperbolic ideal polyhedra in H^3, each of which could be thought of as a 3d lift of the faces of the 2d bipartite graph.The same quantity is also related with the thermodynamic limit of the BPS partition function, or equivalently the genus 0 topological string partition function, on a toric Calabi-Yau manifold dual to quiver gauge theories. We also comment on brane realization of our theories. This paper is a companion to another paper summarizing the results.Comment: 61 pages, 16 figures; v2: typos correcte