Elastic properties of 5d transition-metal carbides: An ab initio study

We have systematically studied the mechanical stability of group V transition metal carbides TMC$_2$ (TM = Hf, Ta, W, Re, Os, Ir, Pt, and Au) in the pyrite and fluorite phase, by calculating their elastic constants within the density functional theory scheme. It was found that all but ReC$_2$ and OsC$_2$ are stable in pyrite phase. On the other hand, all metal carbides studied were unstable in the fluorite phase.Comment: 7 pages, 4 figure

Sequential Monte Carlo with transformations

This paper examines methodology for performing Bayesian inference sequentially on a sequence of posteriors on spaces of different dimensions. For this, we use sequential Monte Carlo samplers, introducing the innovation of using deterministic transformations to move particles effectively between target distributions with different dimensions. This approach, combined with adaptive methods, yields an extremely flexible and general algorithm for Bayesian model comparison that is suitable for use in applications where the acceptance rate in reversible jump Markov chain Monte Carlo is low. We use this approach on model comparison for mixture models, and for inferring coalescent trees sequentially, as data arrives

Role of Membrane GM1 on Early Neuronal Membrane Actions of Aβ During Onset of Alzheimer\u27s Disease

The ability of beta-amyloid peptide (Aβ) to disrupt the plasma membrane through formation of pores and membrane breakage has been previously described. However, the molecular determinants for these effects are largely unknown. In this study, we examined if the association and subsequent membrane perforation induced by Aβ was dependent on GM1levels. Pretreatment of hippocampal neurons with D-PDMP decreased GM1 and Aβ clustering at the membrane (Aβ fluorescent-punctas/20 μm, control = 16.2 ± 1.1 vs. D-PDMP = 6.4 ± 0.4, p \u3c 0.001). Interestingly, membrane perforation with Aβ occurred with a slower time course when the GM1 content was diminished (time to establish perforated configuration (TEPC) (min): control = 7.8 ± 2 vs. low GM1 = 12.1 ± 0.5, p \u3c 0.01), suggesting that the presence of GM1 in the membrane can modulate the distribution and the membrane perforation by Aβ. On the other hand, increasing GM1 facilitated the membrane perforation (TEPC: control = 7.8 ± 2 vs. GM1 = 6.2 ± 1 min, p \u3c 0.05). Additionally, using Cholera Toxin Subunit-B (CTB) to block the interaction of Aβ with GM1 attenuated membrane perforation significantly. Furthermore, pretreatment with CTB decreased the membrane association of Aβ (fluorescent-punctas/20 μm, Aβ: control = 14.8 ± 2.5 vs. CTB = 8 ± 1.4, p \u3c 0.05), suggesting that GM1 also plays a role in both association of Aβ with the membrane and in perforation. In addition, blockade of the Aβ association with CTB inhibited synaptotoxicity. Taken together, our results strongly suggest that membrane lipid composition can affect the ability of Aβ to associate and subsequently perforate the plasma membrane thereby modulating its neurotoxicity in hippocampal neurons

The Level of NMDA Receptor in the Membrane Modulates Amyloid-β Association and Perforation

Alzheimer’s disease is a neurodegenerative disorder that affects mostly the elderly. The main histopathological markers are the senile plaques formed by amyloid-β peptide (Aβ) aggregates that can perforate the plasma membrane of cells, increasing the intracellular calcium levels and releasing synaptic vesicles that finally lead to a delayed synaptic failure. Several membrane proteins and lipids interact with Aβ affecting its toxicity in neurons. Here, we focus on NMDA receptors (NMDARs) as proteins that could be modulating the association and neurotoxic perforation induced by Aβ on the plasma membrane. In fact, our results showed that decreasing NMDARs, using enzymatic or siRNA approaches, increased the association of Aβ to the neurons. Furthermore, overexpression of NMDARs also resulted in an enhanced association between NMDA and Aβ. Functionally, the reduction in membrane NMDARs augmented the process of membrane perforation. On the other hand, overexpressing NMDARs had a protective effect because Aβ was now unable to cause membrane perforation, suggesting a complex relationship between Aβ and NMDARs. Because previous studies have recognized that Aβ oligomers are able to increase membrane permeability and produce amyloid pores, the present study supports the conclusion that NMDARs play a critical protective role on Aβ actions in hippocampal neurons. These results could explain the lack of correlation between brain Aβ burden and clinically observed dementia

Observations on the water distribution and extractable sugar content in carrot slices after pulsed electric field treatment

peer-reviewedThe impact of pulsed electric field (PEF) processing conditions on the distribution of water in carrot tissue and extractability of soluble sugars from carrot slices was studied. Time domain NMR relaxometry was used to investigate the water proton mobility in PEF-treated carrot samples. Three distinct transverse relaxation peaks were observed in untreated carrots. After PEF treatment only two slightly-overlapping peaks were found; these were attributed to water present in the cytoplasm and vacuole of carrot xylem and phloem tissues. This post-treatment observation indicated an increase in water permeability of tissues and/or a loss of integrity in the tonoplast. In general, the stronger the electric field applied, the lower the area representing transverse relaxation (T2) values irrespective of treatment duration. Moreover an increase in sucrose, β- and α-glucose and fructose concentrations of carrot slice extracts after PEF treatment suggested increases in both cell wall and vacuole permeability as a result of exposure to pulsed electric fields.The authors acknowledge financial support from the Irish Phytochemical Food Network (IPFN) project funded under the Food Institutional Research Measure (FIRM, 06/TNI/AFRC6) of the Irish Department of Agriculture, Food and Marine. Dr. Aguiló-Aguayo thanks Generalitat of Catalonia for the postdoctoral grant Beatriu de Pinós (BP-DGR2010). E. Balagueró thanks the Lifelong Learning Programme for the internship grant Leonardo da Vinci MOTIVA3 (201 1-1-ES1-LEO02-34225)

Allosteric modulation of retinal GABA receptors by ascorbic acid

Ionotropic GABA receptors (GABAA and GABAC) belong to the Cys-loop receptor family of ligand-gated ion channels. GABAC receptors are highly expressed in the retina, mainly localized at the axon terminals of bipolar cells. Ascorbic acid, an endogenous redox agent, modulates the function of diverse proteins, and basal levels of ascorbic acid in the retina are very high. However, the effect of ascorbic acid on retinal GABA receptors has not been studied. Here we show that the function of GABAC and GABAA receptors is regulated by ascorbic acid. Patch-clamp recordings from bipolar cell terminals in goldfish retinal slices revealed that GABAC receptor-mediated currents activated by tonic background levels of extracellular GABA, and GABAC currents elicited by local GABA puffs, are both significantly enhanced by ascorbic acid. In addition, a significant rundown of GABA puff-evoked currents was observed in the absence of ascorbic acid. GABA-evoked Cl- currents mediated by homomeric ρ1 GABAC receptors expressed in Xenopus laevis oocytes were also potentiated by ascorbic acid in a concentration-dependent, stereo-specific, reversible, and voltage-independent manner. Studies involving the chemical modification of sulfhydryl groups showed that the two Cys-loop cysteines and histidine 141, all located in the ρ1 subunit extracellular domain, each play a key role in the modulation of GABAC receptors by ascorbic acid. Additionally, we show that retinal GABAA IPSCs and heterologously expressed GABAA receptor currents are similarly augmented by ascorbic acid. Our results suggest that ascorbic acid may act as an endogenous agent capable of potentiating GABAergic neurotransmission in the CNS.Fil: Calero, Cecilia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Vickers, Evan. Oregon Health and Science University; Estados UnidosFil: Cid, Gustavo Moraga. Universidad de Concepción; ChileFil: Aguayo, Luis G.. Universidad de Concepción; ChileFil: von Gersdorff, Henrique. Oregon Health and Science University; Estados UnidosFil: Calvo, Daniel Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

Molecular Requirements for Ethanol Differential Allosteric Modulation of Ligand-Gated Ion Channels Based on Selective G Beta Gamma Modulation

It is now believed that the allosteric modulation produced by ethanol in glycine receptors (GlyRs) depends on alcohol binding to discrete sites within the protein structure. Thus, the differential ethanol sensitivity of diverse GlyR isoforms and mutants was explained by the presence of specific residues in putative alcohol pockets. Here, we demonstrate that ethanol sensitivity in two LGIC members, the GlyR adult alpha1 and embryonic alpha2 subunits, can be modified through selective mutations that rescued or impaired Gbetagamma modulation. Even though that both isoforms were able to physically interact with Gbetagamma, only the alpha1 GlyR was functionally modulated by Gbetagamma and pharmacological ethanol concentrations. Remarkably, the simultaneous switching of two transmembrane and a single extracellular residue in alpha2 GlyRs was enough to generate GlyRs modulated by Gbetagamma and low ethanol concentrations. Interestingly, while we found that these TM residues were different to those in the alcohol binding site, the extracellular residue was recently implicated in conformational changes important to generate a pre-open activated state that precedes ion channel gating. Thus, these results support the idea that the differential ethanol sensitivity of these two GlyR isoforms rests on conformational changes in transmembrane and extracellular residues within the ion channel structure rather than in differences in alcohol binding pockets. Our results describe the molecular basis for the differential ethanol sensitivity of two LGIC members based on selective Gbetagamma modulation and provide a new mechanistic framework for allosteric modulations of abuse drugs

Utility of heavy minerals distribution and granulometric analyses in the study of coastal dynamics: Application to the littoral between Sanlúcar de Barrameda and Rota (Cadiz, southwest Iberian Peninsula)

The present paper deals with grain size and heavy minerals distribution in the sandy coastal sediments of the littoral between the cities of Sanlúcar de Barrameda and Rota. We have related these distributions to the predominant southward littoral drift and the possible source contributions, mostly represented by the Guadalquivir and Guadalete Rivers. The littoral studied is composed of fine sand in the northern sector and medium sand in its central and southern sectors. Heavy minerals were identified using X-ray analysis: the most abundant in the study area are epidote and garnet. We found that their concentrations and sizes decrease from north to south according to the coastal drift, whereas the grain morphology and the mineralogical component generally remain constant.Este trabajo trata de las distribuciones granulométrica y de minerales pesados de los sedimentos arenosos del tramo de litoral comprendido entre las ciudades de Sanlúcar de Barrameda y Rota (suroeste de la península Ibérica). Se han relacionado dichas distribuciones con la deriva litoral predominante hacia el Sur y con las fuentes de aporte de sedimentos constituidas por los ríos Guadalquivir y Guadalete. El litoral estudiado se caracteriza por arena fina en su parte norte y arena media en su parte central y meridional. Los minerales pesados se han identificado mediante rayos X: los más abundantes en el área estudiada son epidota y granate. Se ha deducido cómo sus concentraciones y tamaños disminuyen de norte a sur de acuerdo con la deriva litoral, manteniéndose el conjunto mineralógico y la morfología de los granos constante.Instituto Español de Oceanografí