Recent advances in electronic structure theory and their influence on the accuracy of ab initio potential energy surfaces

Recent advances in electronic structure theory and the availability of high speed vector processors have substantially increased the accuracy of ab initio potential energy surfaces. The recently developed atomic natural orbital approach for basis set contraction has reduced both the basis set incompleteness and superposition errors in molecular calculations. Furthermore, full CI calculations can often be used to calibrate a CASSCF/MRCI approach that quantitatively accounts for the valence correlation energy. These computational advances also provide a vehicle for systematically improving the calculations and for estimating the residual error in the calculations. Calculations on selected diatomic and triatomic systems will be used to illustrate the accuracy that currently can be achieved for molecular systems. In particular, the F+H2 yields HF+H potential energy hypersurface is used to illustrate the impact of these computational advances on the calculation of potential energy surfaces

The school environment and adolescent physical activity and sedentary behaviour : A mixed-studies systematic review

There is increasing academic and policy interest in interventions aiming to promote young people's health by ensuring that the school environment supports healthy behaviours. The purpose of this review was to summarize the current evidence on school-based policy, physical and social-environmental influences on adolescent physical activity and sedentary behaviour. Electronic databases were searched to identify studies that (1) involved healthy adolescents (11-18years old), (2) investigated school-environmental influences and (3) reported a physical activity and/or sedentary behaviour outcome or theme. Findings were synthesized using a non-quantitative synthesis and thematic analysis. Ninety-three papers of mixed methodological quality were included. A range of school-based policy (e.g. break time length), physical (e.g. facilities) and social-environmental (e.g. teacher behaviours) factors were associated with adolescent physical activity, with limited research on sedentary behaviour. The mixed-studies synthesis revealed the importance of specific activity settings (type and location) and intramural sport opportunities for all students. Important physical education-related factors were a mastery-oriented motivational climate and autonomy supportive teaching behaviours. Qualitative evidence highlighted the influence of the wider school climate and shed light on complexities of the associations observed in the quantitative literature. This review identifies future research needs and discusses potential intervention approaches to be considered

Structure-activity relationships of anthraquinone derivatives derived from bromaminic acid as inhibitors of ectonucleoside triphosphate diphosphohydrolases (E-NTPDases)

Reactive blue 2 (RB-2) had been characterized as a relatively potent ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) inhibitor with some selectivity for NTPDase3. In search for the pharmacophore and to analyze structure-activity relationships we synthesized a series of truncated derivatives and analogs of RB-2, including 1-amino-2-sulfo-4-ar(alk)ylaminoanthraquinones, 1-amino-2-methyl-4-arylaminoanthraquinones, 1-amino-4-bromoanthraquinone 2-sulfonic acid esters and sulfonamides, and bis-(1-amino-4-bromoanthraquinone) sulfonamides, and investigated them in preparations of rat NTPDase1, 2, and 3 using a capillary electrophoresis assay. Several 1-amino-2-sulfo-4-ar(alk)ylaminoanthraquinone derivatives inhibited E-NTPDases in a concentration-dependent manner. The 2-sulfonate group was found to be required for inhibitory activity, since 2-methyl-substituted derivatives were inactive. 1-Amino-2-sulfo-4-p-chloroanilinoanthraquinone (18) was identified as a nonselective competitive blocker of NTPDases1, 2, and 3 (Ki 16–18 μM), while 1-amino-2-sulfo-4-(2-naphthylamino)anthraquinone (21) was a potent inhibitor with preference for NTPDase1 (Ki 0.328 μM) and NTPDase3 (Ki 2.22 μM). Its isomer, 1-amino-2-sulfo-4-(1-naphthylamino)anthraquinone (20), was a potent and selective inhibitor of rat NTPDase3 (Ki 1.5 μM)

A capillary electrophoresis method for the characterization of ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) and the analysis of inhibitors by in-capillary enzymatic microreaction

A capillary electrophoresis (CE) method for the characterization of recombinant NTPDases 1, 2, and 3, and for assaying NTPDase inhibitors has been developed performing the enzymatic reaction within the capillary. After hydrodynamic injection of plugs of substrate solution with or without inhibitor in reaction buffer, followed by a suspension of an enzyme-containing membrane preparation, and subsequent injection of another plug of substrate solution with or without inhibitor, the reaction took place close to the capillary inlet. After 5 min, the electrophoretic separation of the reaction products was initiated by applying a constant current of  μA. The method employing a polyacrylamide-coated capillary and reverse polarity mode provided baseline resolution of substrates and products within a short separation time of less than 7 min. A 50 mM phosphate buffer (pH 6.5) was used for the separations and the products were detected by their UV absorbance at 210 nm. The Michaelis–Menten constants (Km) for the recombinant rat NTPDases 1, 2, and 3 obtained with this method were consistent with previously reported data. The inhibition studies revealed pronounced differences in the potency of reactive blue 2, pyridoxalphosphate-6-azophenyl-2-4-disulfonic acid (PPADS), suramin, and N6-diethyl-β,γ-dibromomethylene-ATP (ARL67156) towards the NTPDase isoforms. Notably, ARL67156 does not inhibit all NTPDases, having only a minor inhibitory effect on NTPDase2. Dipyridamole is not an inhibitor of the NTPDase isoforms investigated. The new method is fast and accurate, it requires only tiny amounts of material (nanoliter scale), no sample pretreatment and can be fully automated; thus it is clearly superior to the current standard methods

Male × Female Interaction for a Pre-Copulatory Trait, but Not a Post-Copulatory Trait, among Cosmopolitan Populations of Drosophila melanogaster

Sexual coevolution occurs when changes in the phenotype of one sex select for changes in the other sex. We can identify the “footprint” of this coevolution by mating males and females from different populations and testing for a male-female genotype interaction for a trait associated with male (or female) performance. Here we mated male Drosophila melanogaster from five different continents with females from their own and different continents to test for a male-female interaction for mating speed, a pre-copulatory trait, and female reproductive investment, a post-copulatory trait. We found a strong male-female interaction for mating speed, consistent with previous studies using different populations, suggesting that the potential for sexual coevolution for this trait is present in this species. In contrast, we did not detect a male-female interaction for female reproductive investment. Although a male-female interaction for mating speed is compatible with the hypothesis of ongoing sexual coevolution, the nature of our experimental design is unable to exclude alternate explanations. Thus, the evolutionary mechanisms promoting male-female genotype interactions for pre-copulatory mating traits in D. melanogaster warrant further investigation

Judging Time-to-Passage of looming sounds: evidence for the use of distance-based information

Perceptual judgments are an essential mechanism for our everyday interaction with other moving agents or events. For instance, estimation of the time remaining before an object contacts or passes us is essential to act upon or to avoid that object. Previous studies have demonstrated that participants use different cues to estimate the time to contact or the time to passage of approaching visual stimuli. Despite the considerable number of studies on the judgment of approaching auditory stimuli, not much is known about the cues that guide listeners’ performance in an auditory Time-to-Passage (TTP) task. The present study evaluates how accurately participants judge approaching white-noise stimuli in a TTP task that included variable occlusion periods (portion of the presentation time where the stimulus is not audible). Results showed that participants were able to accurately estimate TTP and their performance, in general, was weakly affected by occlusion periods. Moreover, we looked into the psychoacoustic variables provided by the stimuli and analysed how binaural cues related with the performance obtained in the psychophysical task. The binaural temporal difference seems to be the psychoacoustic cue guiding participants’ performance for lower amounts of occlusion, while the binaural loudness difference seems to be the cue guiding performance for higher amounts of occlusion. These results allowed us to explain the perceptual strategies used by participants in a TTP task (maintaining accuracy by shifting the informative cue for TTP estimation), and to demonstrate that the psychoacoustic cue guiding listeners’ performance changes according to the occlusion period.This study was supported by: Bial FoundationGrant 143/14 (https://www.bial.com/en/bial_foundation.11/11th_symposium.219/ fellows_preliminary_results.235/fellows_ preliminary_results.a569.html); FCT PTDC/EEAELC/112137/2009 (https://www.fct.pt/apoios/projectos/consulta/vglobal_projecto?idProjecto=112137&idElemConcurso=3628); and COMPETE: POCI-01-0145-FEDER-007043 and FCT – Fundação para a Ciência e Tecnologia within the Project Scope: UID/CEC/00319/2013.info:eu-repo/semantics/publishedVersio

Structure–properties relationships in fibre drawing of bioactive phosphate glasses

New bioactive phosphate glasses suitable for continuous fibre production are investigated in this work. The structure of both bulk and fibres from Na2O–CaO–MgO–P2O5 glasses has been studied by means of Raman and 31P and 23Na nuclear magnetic resonance spectroscopies, and the structural results have been correlated with the mechanical properties of the fibres and the dissolution rate of the bulk glasses. It has been observed that the mechanical properties of the phosphate glass fibres are influenced by the glass network connectivity, while the dissolution rates are governed by the Qi speciation of the PO4 units. As seen in previous studies, molar volume seems to play an important role in the fragility behaviour of phosphate glasses. Here, a lower molar volume resulting from the increase in the oxygen packing density hinders the cooperative flow of the PO4 units throughout the glass network and, therefore, causes a reduction in the kinetic fragility

Suppression of Adenosine-Activated Chloride Transport by Ethanol in Airway Epithelia

Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM) for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (ISC) in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A2B adenosine receptor (A2BAR), largely abolished the adenosine-stimulated chloride transport, suggesting that A2BAR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A2BAR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections

Prognostic impact of reduced connexin43 expression and gap junction coupling of neoplastic stromal cells in giant cell tumor of bone

Missense mutations of the GJA1 gene encoding the gap junction channel protein connexin43 (Cx43) cause bone malformations resulting in oculodentodigital dysplasia (ODDD), while GJA1 null and ODDD mutant mice develop osteopenia. In this study we investigated Cx43 expression and channel functions in giant cell tumor of bone (GCTB), a locally aggressive osteolytic lesion with uncertain progression. Cx43 protein levels assessed by immunohistochemistry were correlated with GCTB cell types, clinico-radiological stages and progression free survival in tissue microarrays of 89 primary and 34 recurrent GCTB cases. Cx43 expression, phosphorylation, subcellular distribution and gap junction coupling was also investigated and compared between cultured neoplastic GCTB stromal cells and bone marow stromal cells or HDFa fibroblasts as a control. In GCTB tissues, most Cx43 was produced by CD163 negative neoplastic stromal cells and less by CD163 positive reactive monocytes/macrophages or by giant cells. Significantly less Cx43 was detected in alpha-smooth muscle actin positive than alpha-smooth muscle actin negative stromal cells and in osteoclast-rich tumor nests than in the adjacent reactive stroma. Progressively reduced Cx43 production in GCTB was significantly linked to advanced clinico-radiological stages and worse progression free survival. In neoplastic GCTB stromal cell cultures most Cx43 protein was localized in the paranuclear-Golgi region, while it was concentrated in the cell membranes both in bone marrow stromal cells and HDFa fibroblasts. In Western blots, alkaline phosphatase sensitive bands, linked to serine residues (Ser369, Ser372 or Ser373) detected in control cells, were missing in GCTB stromal cells. Defective cell membrane localization of Cx43 channels was in line with the significantly reduced transfer of the 622 Da fluorescing calcein dye between GCTB stromal cells. Our results show that significant downregulation of Cx43 expression and gap junction coupling in neoplastic stromal cells are associated with the clinical progression and worse prognosis in GCTB