Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle

Cannabinoid CB1 receptors peripherally modulate energy metabolism. Here, we investigated the role of CB1 receptors in the expression of glucose/pyruvate/tricarboxylic acid (TCA) metabolism in rat abdominal muscle. Dihydrolipoamide dehydrogenase (DLD), a flavoprotein component (E3) of alpha-ketoacid dehydrogenase complexes with diaphorase activity in mitochondria, was specifically analyzed. After assessing the effectiveness of the CB1 receptor antagonist AM251 (3 mg kg(-1), 14 days) on food intake and body weight, we could identified seven key enzymes from either glycolytic pathway or TCA cycle-regulated by both diet and CB1 receptor activity-through comprehensive proteomic approaches involving two-dimensional electrophoresis and MALDI-TOF/LC-ESI trap mass spectrometry. These enzymes were glucose 6-phosphate isomerase (GPI), triosephosphate isomerase (TPI), enolase (Eno3), lactate dehydrogenase (LDHa), glyoxalase-1 (Glo1) and the mitochondrial DLD, whose expressions were modified by AM251 in hypercaloric diet-induced obesity. Specifically, AM251 blocked high-carbohydrate diet (HCD)-induced expression of GPI, TPI, Eno3 and LDHa, suggesting a down-regulation of glucose/pyruvate/lactate pathways under glucose availability. AM251 reversed the HCD-inhibited expression of Glo1 and DLD in the muscle, and the DLD and CB1 receptor expression in the mitochondrial fraction. Interestingly, we identified the presence of CB1 receptors at the membrane of striate muscle mitochondria. DLD over-expression was confirmed in muscle of CB1-/- mice. AM251 increased the pyruvate dehydrogenase and glutathione reductase activity in C2C12 myotubes, and the diaphorase/oxidative activity in the mitochondria fraction. These results indicated an up-regulation of methylglyoxal and TCA cycle activity. Findings suggest that CB1 receptors in muscle modulate glucose/pyruvate/lactate pathways and mitochondrial oxidative activity by targeting DLD.

Two Nuclear Localization Signals in USP1 Mediate Nuclear Import of the USP1/UAF1 Complex

9 p. : il.

Communities in complex networks

The study of complex networks has attracted the attention of the scientific community for many obvious reasons. A vast number of systems, from the brain to ecosystems, power grid, and the Internet, can be represented as large complex networks, i.e, assemblies of many interacting components with nontrivial topological properties. The link between these components can describe a global behaviour such as the Internet traffic, electricity supply service, market trend, etc. One of the most relevant topological feature of graphs representing these complex systems is community structure which aims to identify the modules and, possibly, their hierarchical organization, by only using the information encoded in the graph topology. Deciphering network community structure is not only important in order to characterize the graph topologically, but gives some information both on the formation of the network and on its functionality.

The Cryo-EM Structure of a Complete 30S Translation Initiation Complex from Escherichia coli

11 p.

Synthetic scope and DFT analysis of the chiral binap-gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

he 1,3-dipolar cycloaddition between glycine-derived azlactones with maleimides is efficiently catalyzed by the dimeric chiral complex [(S-a)-Binap.AuTFA](2). The alanine-derived oxazolone only reacts with tert-butyl acrylate giving anomalous regiochemistry, which is explained and supported by Natural Resonance Theory and Nucleus Independent Chemical Shifts calculations. The origin of the high enantiodiscrimination observed with maleimides and tert-butyl acrylate is analyzed using DFT computed at M06/Lanl2dz//ONIOM(b3lyp/Lanl2dz:UFF) level. Several applications of these cycloadducts in the synthesis of new proline derivatives with a 2,5-trans-arrangement and in the preparation of complex fused polycyclic molecules are described.

Analysis of Spanish text-thesaurus as a complex network

[EN]Based on the theoretical tools of Complex Networks, this work provides a basic descriptive study of a synonyms dictionary, the Spanish Open Thesaurus represented as a graph. We study the main structural measures of the network compared with those of a random graph. Numerical results show that Open-Thesaurus is a graph whose topological properties approximate a scale-free network, but seems not to present the small-world property because of its sparse structure. We also found that the words of highest betweenness centrality are terms that suggest the vocabulary of psychoanalysis: placer (pleasure), ayudante (in the sense of assistant or worker), and regular (to regulate).

Towards complex system design and management in the engineering domain – the smart grid challenge

This is an Author's Accepted Manuscript of an article published in “Emergence: Complexity and Organization”, 15 (2), pp. 14-22 (2013), copyright Taylor & Francis.

Modeling smart grids as complex systems through the implementation of intelligent hubs

ICINCO 2010

A complex systems modelling approach for decentralized simulation of electrical microgrids

ICECCS 2010

Aspects of quality control of wind profiler measurements in complex topography

It is well known in the scientific community that some remote sensing instruments assume that sample volumes present homogeneous conditions within a defined meteorological profile. At complex topographic sites and under extreme meteorological conditions, this assumption may be fallible depending on the site, and it is more likely to fail in the lower layers of the atmosphere. This piece of work tests the homogeneity of the wind field over a boundary layer wind profiler radar located in complex terrain on the coast under different meteorological conditions. The results reveal the qualitative importance of being aware of deviations in this homogeneity assumption and evaluate its effect on the final product. Patterns of behavior in data have been identified in order to simplify the analysis of the complex signal registered. The quality information obtained from the homogeneity study under different meteorological conditions provides useful indicators for the best alternatives the system can offer to build wind profiles. Finally, the results are also to be considered in order to integrate them in a quality algorithm implemented at the product level.

Complex systems in quantum technologies

124 p.

Pivoting between Calmodulin Lobes Triggered by Calcium in the Kv7.2/Calmodulin Complex

Kv7.2 (KCNQ2) is the principal molecular component of the slow voltage gated M-channel, which strongly influences neuronal excitability. Calmodulin (CaM) binds to two intracellular C-terminal segments of Kv7.2 channels, helices A and B, and it is required for exit from the endoplasmic reticulum. However, the molecular mechanisms by which CaM controls channel trafficking are currently unknown. Here we used two complementary approaches to explore the molecular events underlying the association between CaM and Kv7.2 and their regulation by Ca2+. First, we performed a fluorometric assay using dansylated calmodulin (D-CaM) to characterize the interaction of its individual lobes to the Kv7.2 CaM binding site (Q2AB). Second, we explored the association of Q2AB with CaM by NMR spectroscopy, using N-15-labeled CaM as a reporter. The combined data highlight the interdependency of the N- and C-lobes of CaM in the interaction with Q2AB, suggesting that when CaM binds Ca2+ the binding interface pivots between the N-lobe whose interactions are dominated by helix B and the C-lobe where the predominant interaction is with helix A. In addition, Ca2+ makes CaM binding to Q2AB more difficult and, reciprocally, the channel weakens the association of CaM with Ca2+.

Aspects of quality control of wind profiler measurements in complex topography

It is well known in the scientific community that some remote sensing instruments assume that sample volumes present homogeneous conditions within a defined meteorological profile. At complex topographic sites and under extreme meteorological conditions, this assumption may be fallible depending on the site, and it is more likely to fail in the lower layers of the atmosphere. This piece of work tests the homogeneity of the wind field over a boundary layer wind profiler radar located in complex terrain on the coast under different meteorological conditions. The results reveal the qualitative importance of being aware of deviations in this homogeneity assumption and evaluate its effect on the final product. Patterns of behavior in data have been identified in order to simplify the analysis of the complex signal registered. The quality information obtained from the homogeneity study under different meteorological conditions provides useful indicators for the best alternatives the system can offer to build wind profiles. Finally, the results are also to be considered in order to integrate them in a quality algorithm implemented at the product level.

Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-beta 3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.

Hydrothermal Synthesis and Study of Inorganic-Organic Hybrid Vanadate of Nickel(II) Coordination Complex with Pyrazine, Ni3(C4H4N2)3(V8O23)

Artículo científico: postprint