Structural insights into positive and negative allosteric regulation of a G protein-coupled receptor through protein-lipid interactions

Lipids are becoming known as essential allosteric modulators of G protein-coupled receptor (GPCRs). However, how they exert their efects on GPCR conformation at the atomic level is still unclear. In light of recent experimental data, we have performed several long-timescale molecular dynamics (MD) simulations, totalling 24 μs, to rigorously map allosteric modulation and conformational changes in the β2 adrenergic receptor (β2AR) that occur as a result of interactions with three diferent phospholipids. In particular, we identify diferent sequential mechanisms behind receptor activation and deactivation, respectively, mediated by specifc lipid interactions with key receptor regions. We show that net negatively charged lipids stabilize an active-like state of β2AR that is able to dock Gsα protein. Clustering of anionic lipids around the receptor with local distortion of membrane thickness is also apparent. On the other hand, net-neutral zwitterionic lipids inactivate the receptor, generating either fully inactive or intermediate states, with kinetics depending on lipid headgroup charge distribution and hydrophobicity. These chemical diferences alter membrane thickness and density, which diferentially destabilize the β2AR active state through lateral compression efects

LAVICAD (LAboratori VIrtual de Comunicacions Analògiques i Digitals) i Atenea

El Laboratori Virtual de Comunicacions Analògiques i Digitals s’ha desenvolupat dins del projecte comweb com una aplicació integrada en Moodle. Està formada per un conjunt de simuladors (applets de Java) que emulen subsistemes d’alguns sistemes de comunicacions quotidians en la vida diària com per exemple la televisió digital terrestre o les xarxes de comunicació Wifi. Aquestos simuladors s’utilitzen en activitats formatives d’algunes assignatures de comunicacions. Actualment s'està implementant la interfície de les comunicacions bidireccionals entre el servidor (Moodle) en el que es disposin els applets i la interfície d’usuari que utilitzen els estudiants quant executen els simuladors com a activitat d’aprenentatge en el marc d’una assignatura. Així, el professor pot obtenir informació de retorn de les seves propostes.Peer Reviewe

Magnesium phosphate cements formulated with low grade magnesium oxide incorporating phase change materials for thermal energy storage

Magnesium Phosphate Cement (MPC) has become an essential reference for investigators seeking alternatives to the use of Ordinary Portland Cement (OPC) in building sector because of its high environmental impact. The research group developed a MPC formulated with low-grade MgO (LG-MgO) by-product, which could be considered as a sustainable MPC (sust-MPC). This research focuses on the incorporation of different percentages of Microencapsulated Phase Change Materials (MPCM) into sust-MPC, due to their ability to reduce energy consumption of heating, ventilating, and air conditioning (HVAC) systems. The study consists of an exhaustive characterization of thermal sustainable MPC (TS-MPC) dosages which incorporate air-entraining additive (AEA) and MPCM to improve their thermal behaviour. Thus, TS-MPC would reduce the use of HVAC systems contributing to the decrease of CO2 emissions and increasing energy efficiency in buildings. Moreover, properties such as bulk density, porosity, thermal conductivity, modulus of elasticity, compressive strength, and flexural strength are analysed to evaluate the potential use of these cements as a part of a passive conditioning system. Results show the proper behaviour of these cements to reduce thermal oscillation in buildings. Experimental results demonstrated the relation between the amount of the MPCM and the AEA percentage as well as the thermal and mechanical properties of the TS-MPC due to their contribution to increase the porosity. Furthermore, it should be noted the increase of porosity and the reduction of thermal conductivity of the optimal formulation, which are 60% higher and 50% lower than the sust-MPC obtained without MPCM and additive, respectively.Postprint (author's final draft

Depth-sensing indentation applied to polymers: a comparison between standard methods of analysis in relation to the nature of the materials

Mechanical data (hardness and elastic modulus) from instrumented indentation testing are often extracted assuming linear elasticity in the initial portion of the unloading. The method is nowadays widely accepted as a convenient tool to interpret depth-sensing data, however it is a matter of controversy when applied to polymer materials due to their time-dependent behaviour. More recently, Loubet and co-workers applied continuous stiffness measurements (CSM), consisting of superimposing a small oscillation to the quasi-static component of loading, to the study of the mechanical properties of polymers and proposed a new model to account for the apparent increase in the contact area detected at the first stages of contact. The present work offers a comparative study between the Loubet‟s model using CSM and the procedure yielding a single reading from the onset of unloading. A wide range of thermoplastic polymer materials including glassy and semicrystalline polymers have been investigated. The most important equations employed for each method are summarized and the advantages and disadvantages of employing one procedure or the other are discussed. The differences found between the results obtained from both approaches are discussed in relation to the nature of the polymer material. A comparison between mechanical data extracted from indentation measurements and from classical dynamic mechanical analysis is offered

A Conserved Arginine-Rich Motif within the Hypervariable N-Domain of Drosophila Centromeric Histone H3 (CenH3CID) Mediates BubR1 Recruitment

Centromere identity is determined epigenetically by deposition of CenH3, a centromere-specific histone H3 variant that dictates kinetochore assembly. The molecular basis of the contribution of CenH3 to centromere/kinetochore functions is, however, incompletely understood, as its interactions with the rest of centromere/kinetochore components remain largely uncharacterised at the molecular/structural level.Here, we report on the contribution of Drosophila CenH3(CID) to recruitment of BubR1, a conserved kinetochore protein that is a core component of the spindle attachment checkpoint (SAC). This interaction is mediated by the N-terminal domain of CenH3(CID) (NCenH3(CID)), as tethering NCenH3(CID) to an ectopic reporter construct results in BubR1 recruitment and BubR1-dependent silencing of the reporter gene. Here, we also show that this interaction depends on a short arginine (R)-rich motif and that, most remarkably, it appears to be evolutionarily conserved, as tethering constructs carrying the highly divergent NCenH3 of budding yeast and human also induce silencing of the reporter. Interestingly, though NCenH3 shows an exceedingly low degree of conservation, the presence of R-rich motives is a common feature of NCenH3 from distant species. Finally, our results also indicate that two other conserved sequence motives within NCenH3(CID) might also be involved in interactions with kinetochore components.These results unveil an unexpected contribution of the hypervariable N-domain of CenH3 to recruitment of kinetochore components, identifying simple R-rich motives within it as evolutionary conserved structural determinants involved in BubR1 recruitment

Glucose-6-Phosphate Dehydrogenase Protects Escherichia coli from Tellurite-Mediated Oxidative Stress

The tellurium oxyanion tellurite induces oxidative stress in most microorganisms. In Escherichia coli, tellurite exposure results in high levels of oxidized proteins and membrane lipid peroxides, inactivation of oxidation-sensitive enzymes and reduced glutathione content. In this work, we show that tellurite-exposed E. coli exhibits transcriptional activation of the zwf gene, encoding glucose 6-phosphate dehydrogenase (G6PDH), which in turn results in augmented synthesis of reduced nicotinamide adenine dinucleotide phosphate (NADPH). Increased zwf transcription under tellurite stress results mainly from reactive oxygen species (ROS) generation and not from a depletion of cellular glutathione. In addition, the observed increase of G6PDH activity was paralleled by accumulation of glucose-6-phosphate (G6P), suggesting a metabolic flux shift toward the pentose phosphate shunt. Upon zwf overexpression, bacterial cells also show increased levels of antioxidant molecules (NADPH, GSH), better-protected oxidation-sensitive enzymes and decreased amounts of oxidized proteins and membrane lipids. These results suggest that by increasing NADPH content, G6PDH plays an important role in E. coli survival under tellurite stress