Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance

Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKalpha1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism

From mobile phone data to the spatial structure of cities

Pervasive infrastructures, such as cell phone networks, enable to capture large amounts of human behavioral data but also provide information about the structure of cities and their dynamical properties. In this article, we focus on these last aspects by studying phone data recorded during 55 days in 31 Spanish metropolitan areas. We first define an urban dilatation index which measures how the average distance between individuals evolves during the day, allowing us to highlight different types of city structure. We then focus on hotspots, the most crowded places in the city. We propose a parameter free method to detect them and to test the robustness of our results. The number of these hotspots scales sublinearly with the population size, a result in agreement with previous theoretical arguments and measures on employment datasets. We study the lifetime of these hotspots and show in particular that the hierarchy of permanent ones, which constitute the "heart" of the city, is very stable whatever the size of the city. The spatial structure of these hotspots is also of interest and allows us to distinguish different categories of cities, from monocentric and "segregated" where the spatial distribution is very dependent on land use, to polycentric where the spatial mixing between land uses is much more important. These results point towards the possibility of a new, quantitative classification of cities using high resolution spatio-temporal data.Comment: 14 pages, 15 figure

Uncovering the spatial structure of mobility networks

The extraction of a clear and simple footprint of the structure of large, weighted and directed networks is a general problem that has many applications. An important example is given by origin-destination matrices which contain the complete information on commuting flows, but are difficult to analyze and compare. We propose here a versatile method which extracts a coarse-grained signature of mobility networks, under the form of a $2\times 2$ matrix that separates the flows into four categories. We apply this method to origin-destination matrices extracted from mobile phone data recorded in thirty-one Spanish cities. We show that these cities essentially differ by their proportion of two types of flows: integrated (between residential and employment hotspots) and random flows, whose importance increases with city size. Finally the method allows to determine categories of networks, and in the mobility case to classify cities according to their commuting structure.Comment: 10 pages, 5 figures +Supplementary informatio

Crystallization and preliminary X-ray diffraction analysis of levansucrase (LsdA) from Gluconacetobacter diazotrophicus SRT4

The endophytic bacterium Gluconacetobacter diazotrophicus SRT4 secretes a constitutively expressed levansucrase (LsdA; EC 2.4.1.10), which converts sucrose to fructo-oligosaccharides and levan. Fully active LsdA was purified to high homogeneity by non-denaturing reversed-phase HPLC and was crystallized at room temperature by the hanging-drop vapour-diffusion method using ammonium sulfate and ethanol as precipitants. The crystals are extremely sensitive, but native data have been collected to 2.5 A under cryogenic conditions using synchrotron radiation. LsdA crystals belong to the orthorhombic space group P22(1)2(1) or P2(1)2(1)2, with unit-cell parameters a = 53.80, b = 119.39, c = 215.10 A

Helium-Iron Compounds at Terapascal Pressures.

We investigate the binary phase diagram of helium and iron using first-principles calculations. We find that helium, which is a noble gas and inert at ambient conditions, forms stable crystalline compounds with iron at terapascal pressures. A FeHe compound becomes stable above 4 TPa, and a FeHe_{2} compound above 12 TPa. Melting is investigated using molecular dynamics simulations, and a superionic phase with sublattice melting of the helium atoms is predicted. We discuss the implications of our predicted helium-iron phase diagram for interiors of giant (exo)planets and white dwarf stars

Determinants of the adherence to an "a priori" defined Mediterranean dietary pattern

Background: A prospective cohort study with university level participants was initiated to study the effect of Mediterranean diet on health. Aims: The objective of this study was to identify possible lifestyle and socioeconomic variables associated with the consumption of a Mediterranean dietary pattern (MDP). Method: This analysis includes 1587 males and 2260 females. MDP was defined “a priori” by summing the standardized residuals of nutrients and foods after adjusting a regression model using total energy intake as the independent variable. Multiple regression and non-parametric locally weighted regression models were adjusted with the relative adherence to the MDP as the dependent variable in males and females. Results: Women were more compliant than men with the MDP (Coefficient regression (b) = 4.1; Confidence Interval (CI) 95 % = 3.2 to 4.9). The compliance with the MDP was significantly poorer among younger participants both in men and women (p < 0.001 in men and in women). Participants who were more physically active were more likely to fulfill the traditional MDP (p = 0.01 in men and p < 0.001 in women). Conclusions: Our findings provide evidence supporting the progressive departure from the traditional MDP in younger and highly educated subjects of the Mediterranean area. A more active life-style is associated with a better compliance with the MDP

Breaking the H2 chemical bond in a crystalline environment

Through density functional theory and molecular dynamics calculations, we have analysed various metal polyhydrides to understand whether hydrogen is present in its molecular or atomic form - tetrahydrides of Ba,Sr,Ra, Cs and La; Ba$_8$H$_{46}$ and BaH$_{12}$. We show that, in experimentally reported binary barium hydrides (BaH$_x$), molecular H$_2$ and atomic H$^-$ can coexist with the metallic cations. In this thorough study of differences between BaH$_4$, higher barium hydrides, and other binary tetrahydrides we find the number of atomic hydrogens is equal to the formal charge of the cations. The remaining hydrogen forms molecules in proportions yielding, e.g. BaH$_2$(H$_2)_x$, at pressures as high as 200 GPa. At room temperature these are highly dynamic structures with the hydrogens switching between H$^-$ and H$_2$ while retaining the 2:x ratio. We find some qualitative differences between our static DFT calculations and previously reported structural and spectroscopic experimental results. Two factors allow us to resolve such discrepancies: Firstly, in static relaxation H$_2$ must be regarded as a non-spherical object, which breaks symmetry in a way invisible to X-rays; Secondly the required number of molecules $x$ may be incompatible with the experimental space group (e.g. $BaH_2(H_2)_5$). In molecular dynamics, bond-breaking transitions between various structural symmetry configurations happen on a picosecond timescale via an H$_3^-$ intermediate. Rebonding is slow enough to allow a spectroscopic signal but frequent enough to average out over the lengthscale involved in diffraction

Onto better TRAILs for cancer treatment

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo-2 ligand (Apo2L), is a member of the TNF cytokine superfamily. By cross-linking TRAIL-Receptor (TRAIL-R) 1 or TRAIL-R2, also known as death receptors 4 and 5 (DR4 and DR5), TRAIL has the capability to induce apoptosis in a wide variety of tumor cells while sparing vital normal cells. The discovery of this unique property among TNF superfamily members laid the foundation for testing the clinical potential of TRAIL-R-targeting therapies in the cancer clinic. To date, two of these therapeutic strategies have been tested clinically: (i) recombinant human TRAIL and (ii) antibodies directed against TRAIL-R1 or TRAIL-R2. Unfortunately, however, these TRAIL-R agonists have basically failed as most human tumors are resistant to apoptosis induction by them. It recently emerged that this is largely due to the poor agonistic activity of these agents. Consequently, novel TRAIL-R-targeting agents with increased bioactivity are currently being developed with the aim of rendering TRAIL-based therapies more active. This review summarizes these second-generation novel formulations of TRAIL and other TRAIL-R agonists, which exhibit enhanced cytotoxic capacity toward cancer cells, thereby providing the potential of being more effective when applied clinically than first-generation TRAIL-R agonists