A network-based approach for predicting key enzymes explaining metabolite abundance alterations in a disease phenotype

<p>Background The study of metabolism has attracted much attention during the last years due to its relevance in various diseases. The advance in metabolomics platforms allows us to detect an increasing number of metabolites in abnormal high/low concentration in a disease phenotype. Finding a mechanistic interpretation for these alterations is important to understand pathophysiological processes, however it is not an easy task. The availability of genome scale metabolic networks and Systems Biology techniques open new avenues to address this question.</p> <p>Results In this article we present a novel mathematical framework to find enzymes whose malfunction explains the accumulation/depletion of a given metabolite in a disease phenotype. Our approach is based on a recently introduced pathway concept termed Carbon Flux Paths (CFPs), which extends classical topological definition by including network stoichiometry. Using CFPs, we determine the Connectivity Curve of an altered metabolite, which allows us to quantify changes in its pathway structure when a certain enzyme is removed. The influence of enzyme removal is then ranked and used to explain the accumulation/depletion of such metabolite. For illustration, we center our study in the accumulation of two metabolites (L-Cystine and Homocysteine) found in high concentration in the brain of patients with mental disorders. Our results were discussed based on literature and found a good agreement with previously reported mechanisms. In addition, we hypothesize a novel role of several enzymes for the accumulation of these metabolites, which opens new strategies to understand the metabolic processes underlying these diseases.</p> <p>Conclusions With personalized medicine on the horizon, metabolomic platforms are providing us with a vast amount of experimental data for a number of complex diseases. Our approach provides a novel apparatus to rationally investigate and understand metabolite alterations under disease phenotypes. This work contributes to the development of Systems Medicine, whose objective is to answer clinical questions based on theoretical methods and high-throughput “omics” data.</p&gt

The spherical collapse model with shell crossing

In this work, we study the formation and evolution of dark matter halos by means of the spherical infall model with shell-crossing. We present a framework to tackle this effect properly based on the numerical follow-up, with time, of that individual shell of matter that contains always the same fraction of mass with respect to the total mass. In this first step, we do not include angular momentum, velocity dispersion or triaxiality. Within this framework - named as the Spherical Shell Tracker (SST) - we investigate the dependence of the evolution of the halo with virial mass, with the adopted mass fraction of the shell, and for different cosmologies. We find that our results are very sensitive to a variation of the halo virial mass or the mass fraction of the shell that we consider. However, we obtain a negligible dependence on cosmology. Furthermore, we show that the effect of shell-crossing plays a crucial role in the way that the halo reaches the stabilization in radius and the virial equilibrium. We find that the values currently adopted in the literature for the actual density contrast at the moment of virialization, delta_vir, may not be accurate enough. In this context, we stress the problems related to the definition of a virial mass and a virial radius for the halo. The question of whether the results found here may be obtained by tracking the shells with an analytic approximation remains to be explored.Comment: 15 pages, 4 figures, 9 tables, replaced to match the published MNRAS versio

SIDE, a fiber fed spectrograph for the 10.4 m Gran Telescopio Canarias (GTC)

SIDE (Super Ifu Deployable Experiment) will be a second-generation, common-user instrument for the Grantecan (GTC) on La Palma (Canary Islands, Spain). It is being proposed as a spectrograph of low and intermediate resolution, highly efficient in multi-object spectroscopy and 3D spectroscopy. SIDE features the unique possibility of performing simultaneous visible and NIR observations for selected ranges. The SIDE project is leaded by the Instituto de Astrofisica de Andalucia (IAA-CSIC) in Granada (Spain) and the SIDE Consortium is formed by a total of 10 institutions from Spain, Mexico and USA. The SIDE Feasibility Study has been completed and currently the project is under revision by the GTC Project Office.Comment: 9 pages, 6 figures, to appear in "Ground-based and Airborne Instrumentation for Astronomy II" SPIE conference Proc. 7014, Marseille, 23-28 June 200

Non-hermitian topology as a unifying framework for the Andreev versus Majorana states controversy

Zero-energy Andreev levels in hybrid semiconductor-superconductor nanowires mimic all expected Majorana phenomenology, including 2 e2∕ h conductance quantisation, even where band topology predicts trivial phases. This surprising fact has been used to challenge the interpretation of various transport experiments in terms of Majorana zero modes. Here we show that the Andreev versus Majorana controversy is clarified when framed in the language of non-Hermitian topology, the natural description for quantum systems open to the environment. This change of paradigm allows one to understand topological transitions and the emergence of zero modes in more general systems than can be described by band topology. This is achieved by studying exceptional point bifurcations in the complex spectrum of the system’s non-Hermitian Hamiltonian. Within this broader topological classification, Majoranas from both conventional band topology and a large subset of Andreev levels at zero energy are in fact topologically equivalent, which explains why they cannot be distinguishedWe thank J. Cayao for useful discussions in the early stages of this work. Research supported by the Spanish Ministry of Science, Innovation and Universities through Grants PGC2018-097018-B-I00, FIS2015-65706-P, FIS2015-64654-P, FIS2016-80434-P (AEI/FEDER, EU), the FPI programme BES-2016-078122, the Ramón y Cajal programme Grants RYC-2011-09345, RYC-2013-14645, the María de Maeztu Programme for Units of Excellence in R&D (MDM-2014-0377), and the European Union’s Horizon 2020 research and innovation programme under the FETOPEN Grant Agreement No. 828948. We also acknowledge support from CSIC Research Platform on Quantum Technologies PTI-00

Chaotic oscillations in a nearly inviscid, axisymmetric capillary bridge at 2:1 parametric resonance

We consider the 2:1 internal resonances (such that Ω1>0 and Ω2 ≃ 2Ω1 are natural frequencies) that appear in a nearly inviscid, axisymmetric capillary bridge when the slenderness Λ is such that 0<Λ<π (to avoid the Rayleigh instability) and only the first eight capillary modes are considered. A normal form is derived that gives the slow evolution (in the viscous time scale) of the complex amplitudes of the eigenmodes associated with Ω1 and Ω2, and consists of two complex ODEs that are balances of terms accounting for inertia, damping, detuning from resonance, quadratic nonlinearity, and forcing. In order to obtain quantitatively good results, a two-term approximation is used for the damping rate. The coefficients of quadratic terms are seen to be nonzero if and only if the eigenmode associated with Ω2 is even. In that case the quadratic normal form possesses steady states (which correspond to mono- or bichromatic oscillations of the liquid bridge) and more complex periodic or chaotic attractors (corresponding to periodically or chaotically modulated oscillations). For illustration, several bifurcation diagrams are analyzed in some detail for an internal resonance that appears at Λ ≃ 2.23 and involves the fifth and eighth eigenmodes. If, instead, the eigenmode associated with Ω2 is odd, and only one of the eigenmodes associated with Ω1 and Ω2 is directly excited, then quadratic terms are absent in the normal form and the associated dynamics is seen to be fairly simple