The sticking probability of D2O-water on ice: Isotope effects and the influence of vibrational excitation

International audienceThe present study measures the sticking probability of heavy water (D2O) on H2O- and on D2O-ice and probes the influence of selective OD-stretch excitation on D2O sticking on these ices. Molecular beam techniques are combined with infrared laser excitation to allow for precise control of incident angle, translational energy, and vibrational state of the incident molecules. For a translational energy of 69 kJ/mol and large incident angles (θ ≥ 45°), the sticking probability of D2O on H2O-ice was found to be 1% lower than on D2O-ice. OD-stretch excitation by IR laser pumping of the incident D2O molecules produces no detectable change of the D2O sticking probability (<10−3). The results are compared with other gas/surface systems for which the effect of vibrational excitation on trapping has been probed experimentally

Disseminating and implementing evidence-based practice

The inconsistent implementation of evidence-based practice has become a significant concern in the traumatic stress field. The European Society for Traumatic Stress Studies (ESTSS) has played a major role in highlighting this issue and has contributed to a number of European initiatives to improve dissemination and implementation. Key initiatives include the introduction of the ESTSS General Certificate in Psychotrauma Psychotraumatology and the European Network for Traumatic Stress (TENTS); these are discussed in this paper

Impact of diet and nutraceutical supplementation on inflammation in elderly people. Results from the RISTOMED study, an open-label randomized control trial.

BACKGROUND & AIMS: Eating habits may influence the life span and the quality of ageing process by modulating inflammation. The RISTOMED project was developed to provide a personalized and balanced diet, enriched with or without nutraceutical compounds, to decrease and prevent inflammageing, oxidative stress and gut microbiota alteration in healthy elderly people. This paper focused on the effect on inflammation and metabolism markers after 56 days of RISTOMED diet alone or supplementation with three nutraceutical compounds. METHODS:A cohort of 125 healthy elderly subjects was recruited and randomized into 4 arms (Arm A, RISTOMED diet; Arm B, RISTOMED diet plus VSL#3 probiotic blend; Arm C, RISTOMED diet plus AISA d-Limonene; Arm D, RISTOMED diet plus Argan oil). Inflammatory and metabolism parameters as well as the ratio between Clostridium cluster IV and Bifidobacteria (CL/B) were collected before and after 56 days of dietary intervention, and their evolution compared among the arms. Moreover, participants were subdivided according to their baseline inflammatory parameters (erythrocytes sedimentation rate (ESR), C-Reactive Protein, fibrinogen, Tumor Necrosis Factor-alfa (TNF-α), and Interleukin 6) in two clusters with low or medium-high level of inflammation. The evolution of the measured parameters was then examined separately in each cluster. RESULTS:Overall, RISTOMED diet alone or with each nutraceutical supplementation significantly decreased ESR. RISTOMED diet supplemented with d-Limonene resulted in a decrease in fibrinogen, glucose, insulin levels and HOMA-IR. The most beneficial effects were observed in subjects with a medium-high inflammatory status who received RISTOMED diet with AISA d-Limonene supplementation. Moreover, RISTOMED diet associated with VSL#3 probiotic blend induced a decrease in the CL/B ratio. CONCLUSIONS:Overall, this study emphasizes the beneficial anti-inflammageing effect of RISTOMED diet supplemented with nutraceuticals to control the inflammatory status of elderly individuals

Quantum state-resolved gas/surface reaction dynamics probed by reflection absorption infrared spectroscopy

International audienceWe report the design and characterization of a new molecular-beam/surface-science apparatus for quantum state-resolved studies of gas/surface reaction dynamics combining optical state-specific reactant preparation in a molecular beam by rapid adiabatic passage with detection of surface-bound reaction products by reflection absorption infrared spectroscopy (RAIRS). RAIRS is a non-invasive infrared spectroscopic detection technique that enables online monitoring of the buildup of reaction products on the target surface during reactant deposition by a molecular beam. The product uptake rate obtained by calibrated RAIRS detection yields the coverage dependent state-resolved reaction probability S(θ). Furthermore, the infrared absorption spectra of the adsorbed products obtained by the RAIRS technique provide structural information, which help to identify nascent reaction products, investigate reaction pathways, and determine branching ratios for different pathways of a chemisorption reaction. Measurements of the dissociative chemisorption of methane on Pt(111) with this new apparatus are presented to illustrate the utility of RAIRS detection for highly detailed studies of chemical reactions at the gas/surface interface

Elucidating the structural basis for differing enzyme inhibitor potency by cryo-EM

Histidine biosynthesis is an essential process in plants and microorganisms, making it an attractive target for the development of herbicides and antibacterial agents. Imidazoleglycerol-phosphate dehydratase (IGPD), a key enzyme within this pathway, has been biochemically characterized in both Saccharomyces cerevisiae (Sc_IGPD) and Arabidopsis thaliana (At_IGPD). The plant enzyme, having been the focus of in-depth structural analysis as part of an inhibitor development program, has revealed details about the reaction mechanism of IGPD, whereas the yeast enzyme has proven intractable to crystallography studies. The structure–activity relationship of potent triazole-phosphonate inhibitors of IGPD has been determined in both homologs, revealing that the lead inhibitor (C348) is an order of magnitude more potent against Sc_IGPD than At_IGPD; however, the molecular basis of this difference has not been established. Here we have used single-particle electron microscopy (EM) to study structural differences between the At and Sc_IGPD homologs, which could influence the difference in inhibitor potency. The resulting EM maps at ∼3 Å are sufficient to de novo build the protein structure and identify the inhibitor binding site, which has been validated against the crystal structure of the At_IGPD/C348 complex. The structure of Sc_IGPD reveals that a 24-amino acid insertion forms an extended loop region on the enzyme surface that lies adjacent to the active site, forming interactions with the substrate/inhibitor binding loop that may influence inhibitor potency. Overall, this study provides insights into the IGPD family and demonstrates the power of using an EM approach to study inhibitor binding

Statistics of electromagnetic transitions as a signature of chaos in many-electron atoms

Using a configuration interaction approach we study statistics of the dipole matrix elements (E1 amplitudes) between the 14 lower odd states with J=4 and 21st to 100th even states with J=4 in the Ce atom (1120 lines). We show that the distribution of the matrix elements is close to Gaussian, although the width of the Gaussian distribution, i.e. the root-mean-square matrix element, changes with the excitation energy. The corresponding line strengths are distributed according to the Porter-Thomas law which describes statistics of transition strengths between chaotic states in compound nuclei. We also show how to use a statistical theory to calculate mean squared values of the matrix elements or transition amplitudes between chaotic many-body states. We draw some support for our conclusions from the analysis of the 228 experimental line strengths in Ce [J. Opt. Soc. Am. v. 8, p. 1545 (1991)], although direct comparison with the calculations is impeded by incompleteness of the experimental data. Nevertheless, the statistics observed evidence that highly excited many-electron states in atoms are indeed chaotic.Comment: 16 pages, REVTEX, 4 PostScript figures (submitted to Phys Rev A

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer

Exogenous WNT5A and WNT11 proteins rescue CITED2 dysfunction in mouse embryonic stem cells and zebrafish morphants

Mutations and inadequate methylation profiles of CITED2 are associated with human congenital heart disease (CHD). In mouse, Cited2 is necessary for embryogenesis, particularly for heart development, and its depletion in embryonic stem cells (ESC) impairs cardiac differentiation. We have now determined that Cited2 depletion in ESC affects the expression of transcription factors and cardiopoietic genes involved in early mesoderm and cardiac specification. Interestingly, the supplementation of the secretome prepared from ESC overexpressing CITED2, during the onset of differentiation, rescued the cardiogenic defects of Cited2-depleted ESC. In addition, we demonstrate that the proteins WNT5A and WNT11 held the potential for rescue. We also validated the zebrafish as a model to investigate cited2 function during development. Indeed, the microinjection of morpholinos targeting cited2 transcripts caused developmental defects recapitulating those of mice knockout models, including the increased propensity for cardiac defects and severe death rate. Importantly, the co-injection of anti-cited2 morpholinos with either CITED2 or WNT5A and WNT11 recombinant proteins corrected the developmental defects of Cited2-morphants. This study argues that defects caused by the dysfunction of Cited2 at early stages of development, including heart anomalies, may be remediable by supplementation of exogenous molecules, offering the opportunity to develop novel therapeutic strategies aiming to prevent CHD.Agência financiadora: Fundação para a Ciência e a Tecnologia (FCT) Comissão de Coordenação e Desenvolvimento Regional do Algarve (CCDR Algarve) ALG-01-0145-FEDER-28044; DFG 568/17-2 Algarve Biomedical Center (ABC) Municipio de Louléinfo:eu-repo/semantics/publishedVersio