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This study presents results from the European Centre for Medium-Range Weather Forecasts (ECMWF) carbon dioxide (CO2) analysis system where the atmospheric CO2 is controlled through the assimilation of column-average dry-air mole fractions of CO2 (XCO2) from the Greenhouse gases Observing Satellite (GOSAT). The analysis is compared to a free run simulation and they are both evaluated against XCO2 data from the Total Carbon Column Observing Network (TCCON). We show that the assimilation of the GOSAT XCO2 product from the Bremen Optimal Estimation DOAS (BESD) algorithm during the year 2013 provides XCO2 fields with an improved station-to-station bias deviation of 0.7 parts per million (ppm) compared to the free run (1.4 ppm) and an improved estimated precision of ~ 1 ppm compared to the used GOSAT data (3.4 ppm). We also show that the analysis has skill for synoptic situations in the vicinity of frontal systems where the GOSAT retrievals are sparse due to cloud contamination. We finally computed the 10 day forecast from each analysis at 00:00 UTC. Compared to its own analysis the CO2 forecast shows synoptic skill for the largest scale weather patterns even up to day 5 according to the anomaly correlation coefficient. [ABSTRACT FROM AUTHOR]

MACC-II,III, Monitoring Atmospheric Composition and Climate, is the current pre-operational Copernicus Atmosphere Monitoring Service (CAMS). It provides data records on atmospheric composition for recent years, present conditions and forecasts for a few days ahead. To support the quality assessment of the CAMS products, the EU FP7 project NORS created a server to validate the gridded MACC-II,III/CAMS model data against remote-sensing observations from the Network for the Detection of Atmospheric Composition Change (NDACC), for a selected set of target species and pilot stations. This paper describes in detail the algorithms used in this validation server. [ABSTRACT FROM AUTHOR]

Since the nineties, atmospheric measurement systems have been deployed at Reunion Island, mainly for monitoring the atmospheric composition in the framework of NDSC/NDACC (Network for the Detection of Stratospheric Change/Network for the Detection of Atmospheric Composition Change). The location of Reunion Island presents a great interest because there are very few multi-instrumented stations in the tropics and particularly in the Southern Hemisphere. In 2012, a new observatory was commissioned in Maïdo at 2200ma.s.l.: it hosts various instruments for atmospheric measurements, including LiDAR systems, spectro-radiometers and in situ gases and aerosols measurements. This new high-altitude Maïdo station allows: 1. To improve the performance of the optical instruments above the marine boundary layer, and to open new perspectives on upper troposphere and lower stratosphere studies. 2. To develop in-situ measurements of the atmospheric composition for climate change survey, in a reference site in the tropical/subtropical region of the Southern Hemisphere. 3. To offer trans-national access to host experiments or measurement campaigns for focused process studies. [ABSTRACT FROM AUTHOR]

Background: The optimal ventilation modalities to manage out-of-hospital cardiac arrest (OHCA) remain debated. A specific pressure mode called cardio-pulmonary ventilation (CPV) may be used instead of manual bag ventilation (MBV). We sought to analyse the association between mechanical CPV and return of spontaneous circulation (ROSC) in non-traumatic OHCA., Methods: MBV and CPV were retrospectively identified in patients with non-traumatic OHCA from the Belgian Cardiac Arrest Registry. We used a two-level mixed-effects multivariable logistic regression analysis to determine the association between the ventilation modalities and outcomes. The primary and secondary study criteria were ROSC and survival with a Cerebral Performance Category (CPC) score of 1 or 2 at 30 days. Age, sex, initial rhythm, no-flow duration, low-flow duration, OHCA location, use of a mechanical chest compression device and Rankin status before arrest were used as covariables., Results: Between January 2017 and December 2021, 2566 patients with OHCA who fulfilled the inclusion criteria were included. 298 (11.6%) patients were mechanically ventilated with CPV whereas 2268 were manually ventilated. The use of CPV was associated with greater probability of ROSC both in the unadjusted (odds ratio: 1.28, 95% confidence interval [CI]: 1.01-1.63; p = 0.043) and adjusted analyses (adjusted odds ratio [aOR]: 2.16, 95%CI 1.37-3.41; p = 0.001) but not with a lower CPC score (aOR: 1.44, 95%CI 0.72-2.89; p = 0.31)., Conclusions: Compared with MBV, CPV was associated with an increased risk of ROSC but not with improved an CPC score in patients with OHCA. Prospective randomised trials are needed to challenge these results., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Jean-Christophe Richard declares receiving a part time salary from Air Liquide Medical Systems (ALMS) as Scientific Director of the Med2 Lab in complement of the Angers University Hospital. Moreover, he declares patents from ALMS, GE and COVIDIEN. All other authors state that they have no financial or personal relationships with other people or organisations that could inappropriately influence their work.’., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Given the limited efficacy of pharmacological treatments, the use of musical intervention as a non-drug treatment for patients with Alzheimer's disease is strongly recommended. Musical interventions appear to improve the socio-emotional and cognitive functioning of these patients, and benefits increase when patients' motor skills are engaged. Our study evaluates the factors that may influence patients' socio-emotional and motor engagement during musical activities and measures their sensorimotor synchronisation (SMS) abilities. Participants were asked to tap in time to a metronomic or musical rhythm, in the presence of a musician who performed the task with them. The musician's presence was either physical (live condition) or virtual (video condition). Two tempos were tested: a slow tempo (inter-onset interval of 800 ms) and a fast tempo (inter-onset interval of 667 ms). The results showed that patients spontaneously produced more rhythmic movements in response to the music than to the metronome. However, the consistency and accuracy of sensorimotor synchronisation was better with the metronome than with the music and was also better when the musician was present through the video rather than in person. These effects were modulated by the tempo of the auditory sequences. These results confirm the importance of the musical context and social interactions on these different performances. By simultaneously evaluating the sensorimotor synchronisation of the hands, spontaneous motor behaviours, and socio-emotional behaviours using quantitative and controlled measurements, this study validates a multimodal approach to evaluating patients' engagement in a musical task. These initial results provide promising prospects in terms of application while providing clinicians and researchers with a rigorous methodology for understanding the factors that are at the origin of the therapeutic benefits of musical activities on the behaviour and well-being of patients and their caregivers.

Artemisinin and two of its derivatives, dihydroartemisinin and artesunate, which are front line drugs against malaria, were investigated using Raman optical activity (ROA) and vibrational circular dichroism (VCD) experiments, both supported by density functional theory (DFT) level calculations. The experimental techniques combined with DFT calculations could show that dihydroartemisinin was present as an epimeric mixture in solution. In addition, an approximation of the epimeric ratio could be extracted which was in agreement with the ratio obtained by 1H-NMR spectroscopy. The current study also demonstrates that both ROA and VCD are able to assign the correct absolute configuration (AC) of artemisinin and artesunate out of all their possible diastereomers without any explicit knowledge on their correct stereochemistry and accentuates the synergetic effect between ROA and VCD in AC determination.

Background: Considering the limited efficacy of pharmacological treatments, the use of musical interventions as non-drug treatment for patients with Alzheimer's disease are strongly recommended. Musical interventions seem to improve the socio-emotional and cognitive functioning of these patients, with benefits increasing when patients are engaged at the motor level., Objective: Our study evaluates the factors that may influence patients' socio-emotional and motor engagement during musical activities, and measures their sensorimotor synchronization (SMS) abilities., Methods: Each participant was asked to tap with a metronomic or a musical rhythm, in the presence of a musician who performed the task with them. The presence of the musician was real (live condition) or virtual (video condition). Two tempi were tested: a slow tempo (inter-onset interval of 800 ms) and a fast tempo (inter-onset interval of 667 ms)., Results: Patients spontaneously produced more rhythmic movements in response to the music than to the metronome. However, the consistency and accuracy of sensorimotor synchronization were better with the metronome than with the music, and also better in video than in live condition. These effects were modulated by the tempo of the auditory sequences., Conclusion: These results confirm the importance of the musical context and social interactions on these different performances. By evaluating in parallel the hand sensorimotor synchronization, spontaneous motor and socio-emotional behaviors with quantitative and controlled measurements, this study validates a multimodal approach to evaluate the patients' engagement in a musical task. These initial results open up promising application prospects while providing clinicians and researchers a rigorous methodology for understanding the factors that are at the origin of the therapeutic benefits of musical activities on the behavior and well-being of patients and their caregivers.

The expressive features of music can influence the velocity of walking. So far, studies used instructed (and intended) synchronization. But is this velocity effect still present with non-instructed (spontaneous) synchronization? To figure that out, participants were instructed to walk in their own comfort tempo on an indoor track, first in silence and then with tempo-matched music. We compared velocities of silence and music conditions. The results show that some music has an activating influence, increasing velocity and motivation, while other music has a relaxing influence, decreasing velocity and motivation. The influence of musical expression on the velocity of self-paced walking can be predicted with a regression model using only three sonic features explaining 56% of the variance. Phase-coherence between footfall and beat did not contribute to the velocity effect, due to its implied fixed pacing. The findings suggest that the velocity effect depends on vigor entrainment that influences both stride length and pacing. Our findings are relevant for preventing injuries, for gait improvement in walking rehabilitation, and for improving performance in sports activities.

Studies of CO ligand binding revealed that two protein states with different ligand affinities exist in the protoglobin from Methanosarcina acetivorans (in MaPgb*, residue Cys(E20)101 was mutated to Ser). The switch between the two states occurs upon the ligation of MaPgb*. In this work, site-directed mutagenesis was used to explore the role of selected amino acids in ligand sensing and stabilization and in affecting the equilibrium between the "more reactive" and "less reactive" conformational states of MaPgb*. A combination of experimental data obtained from electronic and resonance Raman absorption spectra, CO ligand-binding kinetics, and X-ray crystallography was employed. Three amino acids were assigned a critical role: Trp(60)B9, Tyr(61)B10, and Phe(93)E11. Trp(60)B9 and Tyr(61)B10 are involved in ligand stabilization in the distal heme pocket; the strength of their interaction was reflected by the spectra of the CO-ligated MaPgb* and by the CO dissociation rate constants. In contrast, Phe(93)E11 is a key player in sensing the heme-bound ligand and promotes the rotation of the Trp(60)B9 side chain, thus favoring ligand stabilization. Although the structural bases of the fast CO binding rate constant of MaPgb* are still unclear, Trp(60)B9, Tyr(61)B10, and Phe(93)E11 play a role in regulating heme/ligand affinity.

We report the structural and biochemical characterization of GLB-33, a putative neuropeptide receptor that is exclusively expressed in the nervous system of the nematode Caenorhabditis elegans. This unique chimeric protein is composed of a 7-transmembrane domain (7TM), GLB-33 7TM, typical of a G-protein-coupled receptor, and of a globin domain (GD), GLB-33 GD. Comprehensive sequence similarity searches in the genome of the parasitic nematode, Ascaris suum, revealed a chimeric protein that is similar to a Phe-Met-Arg-Phe-amide neuropeptide receptor. The three-dimensional structures of the separate domains of both species and of the full-length proteins were modeled. The 7TM domains of both proteins appeared very similar, but the globin domain of the A. suum receptor surprisingly seemed to lack several helices, suggesting a novel truncated globin fold. The globin domain of C. elegans GLB-33, however, was very similar to a genuine myoglobin-type molecule. Spectroscopic analysis of the recombinant GLB-33 GD showed that the heme is pentacoordinate when ferrous and in the hydroxide-ligated form when ferric, even at neutral pH. Flash-photolysis experiments showed overall fast biphasic CO rebinding kinetics. In its ferrous deoxy form, GLB-33 GD is capable of reversibly binding O2 with a very high affinity and of reducing nitrite to nitric oxide faster than other globins. Collectively, these properties suggest that the globin domain of GLB-33 may serve as a highly sensitive oxygen sensor and/or as a nitrite reductase. Both properties are potentially able to modulate the neuropeptide sensitivity of the neuronal transmembrane receptor., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Neuroglobin, a globin characterized by a bis-histidine ligation of the heme iron, has been identified in mammalian and non-mammalian vertebrates, including fish, amphibians and reptiles. In human neuroglobin, the presence of an internal disulfide bond in the CD loop (CD7-D5) is found to modulate the ligand binding through a change in the heme pocket structure. Although the neuroglobin sequences mostly display conserved Cys at positions CD7, D5 and G18/19, a number of exceptions are known. In this study, neuroglobins from amphibian (Xenopus tropicalis) and fish (Chaenocephalus aceratus, Dissostichus mawsoni and Danio rerio) are investigated using electron paramagnetic resonance and optical absorption spectroscopy. All these neuroglobins differ from human neuroglobin in their Cys-positions. It is demonstrated that if disulfide bonds are formed in fish and amphibian neuroglobins, the reduction of these bonds does not result in alteration of the heme pocket in these globins. Furthermore, it is shown that mutagenesis of the Cys residues of X. tropicalis neuroglobin influences the protein structure. The amphibian neuroglobin is also found to be more resistant to H2O2-induced denaturation than the other neuroglobins under study, although all show an overall large stability in high concentrations of this oxidant. This article is part of a Special Issue entitled: Oxygen Binding and Sensing Proteins., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Electron paramagnetic resonance experiments reveal a significant difference between the principal g values (and hence ligand-field parameters) of the ferric cyanide-ligated form of different variants of the protoglobin of Methanosarcina acetivorans (MaPgb) and of horse heart myoglobin (hhMb). The largest principal g value of the ferric cyanide-ligated MaPgb variants is found to be significantly lower than for any of the other globins reported so far. This is at least partially caused by the strong heme distortions as proven by the determination of the hyperfine interaction of the heme nitrogens and mesoprotons. Furthermore, the experiments confirm recent theoretical predictions [Forti, F.; Boechi, L., Bikiel, D., Martí, M.A.; Nardini, M.; Bolognesi, M.; Viappiani, C.; Estrin, D.; Luque, F. J. J. Phys. Chem. B 2011, 115, 13771-13780] that Phe(G8)145 plays a crucial role in the ligand modulation in MaPgb. Finally, the influence of the N-terminal 20 amino-acid chain on the heme pocket in these protoglobins is also proven.

Our knowledge about human genes and the consequences of mutations leading to human genetic diseases has drastically improved over the last few years. It has been recognized that many mutations are indeed pathogenic because they impact the mRNA rather than the protein itself. With our better understanding of the very complex mechanism of splicing, various bioinformatics tools have been developed. They are now frequently used not only to search for sequence motifs corresponding to splicing signals (splice sites, branch points, ESE, and ESS) but also to predict the impact of mutations on these signals. We now need to address the impact of mutations that affect the splicing process, as their consequences could vary from the activation of cryptic signals to the skipping of one or multiple exons. Despite the major developments of the bioinformatics field coupled to experimental data generated on splicing, it is today still not possible to efficiently predict the consequences of mutations impacting splicing signals, especially to predict if they will lead to exon skipping or to cryptic splice site activation.

Protoglobin from Methanosarcina acetivorans (MaPgb) is a dimeric globin with peculiar structural properties such as a completely buried haem and two orthogonal tunnels connecting the distal cavity to the solvent. CO binding to and dissociation from MaPgb occur through a biphasic kinetics. We show that the heterogenous kinetics arises from binding to (and dissociation from) two tertiary conformations in ligation-dependent equilibrium. Ligation favours the species with high binding rate (and low dissociation rate). The equilibrium is shifted towards the species with low binding (and high dissociation) rates for the unliganded molecules. A quantitative model is proposed to describe the observed carbonylation kinetics.

Arabidopsis has four putative, di-heme cytochrome b561 proteins, including one localized in the tonoplast (TCytb). From a comparative electron paramagnetic resonance (EPR), UV-Vis absorption and resonance Raman study, on wild type, H83A/H156A-TCytb and H83L/H156L-TCytb double mutants, it follows that the H83 and H156 residues are binding one of the two hemes. These measurements show that the high-potential heme site is situated at the cytoplasmic side of the membrane and allow the unambiguous differentiation between two models on the heme localization in cytochrome b561 proteins., (Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

New technologies, which constantly become available for mutation detection and gene analysis, have contributed to an exponential rate of discovery of disease genes and variation in the human genome. The task of collecting and documenting this enormous amount of data in genetic databases represents a major challenge for the future of biological and medical science. The Locus Specific Databases (LSDBs) are so far the most efficient mutation databases. This review presents the main types of databases available for the analysis of mutations responsible for genetic disorders, as well as open perspectives for new therapeutic research or challenges for future medicine. Accurate and exhaustive collection of variations in human genomes will be crucial for research and personalized delivery of healthcare., (Copyright © 2009 Elsevier Masson SAS. All rights reserved.)

The globin-coupled sensor (GCS) of Geobacter sulfurreducens is unique amongst GCSs in that its signalling domain is a transmembrane domain with yet unknown function. In the present work we use X-band continuous-wave and pulsed electron paramagnetic resonance (EPR) to investigate the ferric form of the globin domain of the G. sulfurreducens GCS (GsGCS(162)) at pH 8.5. This form shows a unique bis-histidine coordination of the heme with the F8His and E11His. In contrast with previous crystal structure data, where three conformers of the heme structure were identified, ferric GsGCS(162) assumes only one conformation in frozen solution. The EPR data of ferric GsGCS162 are compared in detail with those of other bis-histidine coordinated globins, including other GCS systems., (Copyright 2010 Elsevier Inc. All rights reserved.)

Tumor suppressor protein 101F6, a gene product of the 3p21.3 (human) and 9F1 (mouse) chromosomal region, has recently been identified as a member of the cytochrome b561 (Cyt-b561) protein family by sequence homology. The His(6)-tagged recombinant mouse tumor suppressor Cyt-b561 protein (TSCytb) was recently expressed in yeast and purified, and the ascorbate reducibility was determined. TSCytb is auto-oxidizable and has two distinct heme b centers with redox potentials of approximately 40 and approximately 140 mV. Its split alpha-band in the dithionite-reduced spectrum at both 295 and 77 K is well resolved, and the separation between the two alpha-peaks is approximately 7 nm (approximately 222 cm(-1)). Singular value decomposition analysis of the split alpha-band in the ascorbate-reduced spectra revealed the presence of two major spectral components, each of them with split alpha-band but with different peak separations (6 and 8 nm). Similar minor differences in peak separation were obtained when the split alpha-bands in ascorbate-reduced difference spectra at low (<1 mM) and high (>10 mM) ascorbate concentrations were analysed. According to low-temperature electron paramagnetic resonance (EPR) spectroscopy, the two heme b centers are in the low-spin ferric state with maximum principal g values of 3.61 and 2.96, respectively. These values differ from the ones observed for other members of the Cyt-b561 family. According to resonance Raman spectroscopy, the porphyrin rings are in a relaxed state. The spectroscopic results are only partially in agreement with those obtained earlier for the native chromaffin granule Cyt-b561.

A very sensitive experimental setup for accurate wavelength-dependent hyper-Rayleigh scattering (HRS) measurements of the molecular first hyperpolarizability beta in the broad fundamental wavelength range of 600 to 1800 nm is presented. The setup makes use of a stable continuously tunable picosecond optical parametric amplifier with kilohertz repetition rate. To correct for multi-photon fluorescence, a small spectral range around the second harmonic wavelength is detected in parallel using a spectrograph coupled to an intensified charge-coupled device. Reliable calibration against the pure solvent is possible over the full accessible spectral range. An extensive set of wavelength-dependent HRS calibration data for a wide range of solvents is presented, and very accurate measurements of the beta dispersion of the well-known nonlinear optical chromophore Disperse Red 1 are demonstrated., ((c) 2009 Optical Society of America)