Peptide-protein microarrays and surface plasmon resonance detection: biosensors for versatile biomolecular interaction analysis.

International audienceBiosensors in microarray format provide promising tools for high-throughput analyses of complex samples. Although they are able to detect, quantify and characterize a multitude of compounds, most of the available devices are specialized in the analysis of one type of interaction, limiting their application to a define area. The aim of our work was to develop and characterize versatile protein (or peptide) microarrays suitable for the simultaneous analysis of a large panel of biological interactions. Our system involved a simple procedure to immobilized proteins or peptides, based on pyrrole electropolymerization, and ligand binding was detected by imaging the surface plasmon resonance. We demonstrated its suitability in three different contexts, i.e. humoral response characterization, ion binding analysis and cell detection. This work evidences the potentiality of this approach which allows multiparametric, high-throughput and label-free analysis of biological samples suitable for the detection of compounds as various as proteins, ions or cells and the characterization of their interaction with peptides or proteins

A prospective study of the evolution of lamivudine resistance mutations in patients with chronic hepatitis B treated with lamivudine

International audienceBackground/Aims. Lamivudine resistance has been described in subjects with chronic hepatitis B infections, associated with mutations in the viral polymerase gene. The objective of this study was to estimate the emergence rate of lamivudine-resistant viral strains and their consequences over a two-year period. Methods. We evaluated 283 lamivudine-naive subjects with chronic hepatitis B. Clinical and virological features were assessed at inclusion and every six months thereafter. Viral DNA was characterised using PCR-based sequencing. Potential risk factors for the emergence of lamivudine resistance mutations were assessed using logistic regression analysis. Results. The annualised incidence rate for viral polymerase mutations was 22%. The only independent risk factor identified was high viral load at inclusion. Detectable viral DNA and elevated transaminases were more frequent in subjects harbouring mutant viral strains, and these underwent a lower rate of HBe seroconversion. All subjects responded favourably to treatment, with no difference in symptoms between the two groups. Conclusions. This prospective cohort study identified lamivudine resistant mutations emerging in 22% of subjects yearly, which were apparently not associated with clinical aggravation over the study period

Arrival angles of teleseismic fundamental mode Rayleigh waves across the AlpArray

The dense AlpArray network allows studying seismic wave propagation with high spatial resolution. Here we introduce an array approach to measure arrival angles of teleseismic Rayleigh waves. The approach combines the advantages of phase correlation as in the two-station method with array beamforming to obtain the phase-velocity vector. 20 earthquakes from the first two years of the AlpArray project are selected, and spatial patterns of arrival-angle deviations across the AlpArray are shown in maps, depending on period and earthquake location. The cause of these intriguing spatial patterns is discussed. A simple wave-propagation modelling example using an isolated anomaly and a Gaussian beam solution suggests that much of the complexity can be explained as a result of wave interference after passing a structural anomaly along the wave paths. This indicates that arrival-angle information constitutes useful additional information on the Earth structure, beyond what is currently used in inversions

Ambient-noise tomography of the wider Vienna Basin region

We present a new 3-D shear-velocity model for the top 30 km of the crust in the wider Vienna Basin region based on surface waves extracted from ambient-noise cross-correlations. We use continuous seismic records of 63 broad-band stations of the AlpArray project to retrieve interstation Green’s functions from ambient-noise cross-correlations in the period range from 5 to 25 s. From these Green’s functions, we measure Rayleigh group traveltimes, utilizing all four components of the cross-correlation tensor, which are associated with Rayleigh waves (ZZ, RR, RZ and ZR), to exploit multiple measurements per station pair. A set of selection criteria is applied to ensure that we use high-quality recordings of fundamental Rayleigh modes. We regionalize the interstation group velocities in a 5 km × 5 km grid with an average path density of ∼20 paths per cell. From the resulting group-velocity maps, we extract local 1-D dispersion curves for each cell and invert all cells independently to retrieve the crustal shear-velocity structure of the study area. The resulting model provides a previously unachieved lateral resolution of seismic velocities in the region of ∼15 km. As major features, we image the Vienna Basin and Little Hungarian Plain as low-velocity anomalies, and the Bohemian Massif with high velocities. The edges of these features are marked with prominent velocity contrasts correlated with faults, such as the Alpine Front and Vienna Basin transfer fault system. The observed structures correlate well with surface geology, gravitational anomalies and the few known crystalline basement depths from boreholes. For depths larger than those reached by boreholes, the new model allows new insight into the complex structure of the Vienna Basin and surrounding areas, including deep low-velocity zones, which we image with previously unachieved detail. This model may be used in the future to interpret the deeper structures and tectonic evolution of the wider Vienna Basin region, evaluate natural resources, model wave propagation and improve earthquake locations, among others

Shear-wave velocity structure beneath the Dinarides from the inversion of Rayleigh-wave dispersion

Highlights • Rayleigh-wave phase velocity in the wider Dinarides region using the two-station method. • Uppermost mantle shear-wave velocity model of the Dinarides-Adriatic Sea region. • Velocity model reveals a robust high-velocity anomaly present under the whole Dinarides. • High-velocity anomaly reaches depth of 160 km in the northern Dinarides to more than 200 km under southern Dinarides. • New structural model incorporating delamination as one of the processes controlling the continental collision in the Dinarides. The interaction between the Adriatic microplate (Adria) and Eurasia is the main driving factor in the central Mediterranean tectonics. Their interplay has shaped the geodynamics of the whole region and formed several mountain belts including Alps, Dinarides and Apennines. Among these, Dinarides are the least investigated and little is known about the underlying geodynamic processes. There are numerous open questions about the current state of interaction between Adria and Eurasia under the Dinaric domain. One of the most interesting is the nature of lithospheric underthrusting of Adriatic plate, e.g. length of the slab or varying slab disposition along the orogen. Previous investigations have found a low-velocity zone in the uppermost mantle under the northern-central Dinarides which was interpreted as a slab gap. Conversely, several newer studies have indicated the presence of the continuous slab under the Dinarides with no trace of the low velocity zone. Thus, to investigate the Dinaric mantle structure further, we use regional-to-teleseismic surface-wave records from 98 seismic stations in the wider Dinarides region to create a 3D shear-wave velocity model. More precisely, a two-station method is used to extract Rayleigh-wave phase velocity while tomography and 1D inversion of the phase velocity are employed to map the depth dependent shear-wave velocity. Resulting velocity model reveals a robust high-velocity anomaly present under the whole Dinarides, reaching the depths of 160 km in the north to more than 200 km under southern Dinarides. These results do not agree with most of the previous investigations and show continuous underthrusting of the Adriatic lithosphere under Europe along the whole Dinaric region. The geometry of the down-going slab varies from the deeper slab in the north and south to the shallower underthrusting in the center. On-top of both north and south slabs there is a low-velocity wedge indicating lithospheric delamination which could explain the 200 km deep high-velocity body existing under the southern Dinarides

Crustal Thinning From Orogen to Back-Arc Basin: The Structure of the Pannonian Basin Region Revealed by P-to-S Converted Seismic Waves

We present the results of P-to-S receiver function analysis to improve the 3D image of the sedimentary layer, the upper crust, and lower crust in the Pannonian Basin area. The Pannonian Basin hosts deep sedimentary depocentres superimposed on a complex basement structure and it is surrounded by mountain belts. We processed waveforms from 221 three-component broadband seismological stations. As a result of the dense station coverage, we were able to achieve so far unprecedented spatial resolution in determining the velocity structure of the crust. We applied a three-fold quality control process; the first two being applied to the observed waveforms and the third to the calculated radial receiver functions. This work is the first comprehensive receiver function study of the entire region. To prepare the inversions, we performed station-wise H-Vp/Vs grid search, as well as Common Conversion Point migration. Our main focus was then the S-wave velocity structure of the area, which we determined by the Neighborhood Algorithm inversion method at each station, where data were sub-divided into back-azimuthal bundles based on similar Ps delay times. The 1D, nonlinear inversions provided the depth of the discontinuities, shear-wave velocities and Vp/Vs ratios of each layer per bundle, and we calculated uncertainty values for each of these parameters. We then developed a 3D interpolation method based on natural neighbor interpolation to obtain the 3D crustal structure from the local inversion results. We present the sedimentary thickness map, the first Conrad depth map and an improved, detailed Moho map, as well as the first upper and lower crustal thickness maps obtained from receiver function analysis. The velocity jump across the Conrad discontinuity is estimated at less than 0.2 km/s over most of the investigated area. We also compare the new Moho map from our approach to simple grid search results and prior knowledge from other techniques. Our Moho depth map presents local variations in the investigated area: the crust-mantle boundary is at 20–26 km beneath the sedimentary basins, while it is situated deeper below the Apuseni Mountains, Transdanubian and North Hungarian Ranges (28–33 km), and it is the deepest beneath the Eastern Alps and the Southern Carpathians (40–45 km). These values reflect well the Neogene evolution of the region, such as crustal thinning of the Pannonian Basin and orogenic thickening in the neighboring mountain belts

Demographic, clinical, and service-use characteristics related to the clinician’s recommendation to transition from child to adult mental health services

Purpose: The service configuration with distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) may be a barrier to continuity of care. Because of a lack of transition policy, CAMHS clinicians have to decide whether and when a young person should transition to AMHS. This study describes which characteristics are associated with the clinicians’ advice to continue treatment at AMHS. Methods: Demographic, family, clinical, treatment, and service-use characteristics of the MILESTONE cohort of 763 young people from 39 CAMHS in Europe were assessed using multi-informant and standardized assessment tools. Logistic mixed models were fitted to assess the relationship between these characteristics and clinicians’ transition recommendations. Results: Young people with higher clinician-rated severity of psychopathology scores, with self- and parent-reported need for ongoing treatment, with lower everyday functional skills and without self-reported psychotic experiences were more likely to be recommended to continue treatment. Among those who had been recommended to continue treatment, young people who used psychotropic medication, who had been in CAMHS for more than a year, and for whom appropriate AMHS were available were more likely to be recommended to continue treatment at AMHS. Young people whose parents indicated a need for ongoing treatment were more likely to be recommended to stay in CAMHS. Conclusion: Although the decision regarding continuity of treatment was mostly determined by a small set of clinical characteristics, the recommendation to continue treatment at AMHS was mostly affected by service-use related characteristics, such as the availability of appropriate services

Cohort profile : demographic and clinical characteristics of the MILESTONE longitudinal cohort of young people approaching the upper age limit of their child mental health care service in Europe

Purpose: The presence of distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) impacts continuity of mental health treatment for young people. However, we do not know the extent of discontinuity of care in Europe nor the effects of discontinuity on the mental health of young people. Current research is limited, as the majority of existing studies are retrospective, based on small samples or used non-standardised information from medical records. The MILESTONE prospective cohort study aims to examine associations between service use, mental health and other outcomes over 24 months, using information from self, parent and clinician reports. Participants: Seven hundred sixty-three young people from 39 CAMHS in 8 European countries, their parents and CAMHS clinicians who completed interviews and online questionnaires and were followed up for 2 years after reaching the upper age limit of the CAMHS they receive treatment at. Findings to date: This cohort profile describes the baseline characteristics of the MILESTONE cohort. The mental health of young people reaching the upper age limit of their CAMHS varied greatly in type and severity: 32.8% of young people reported clinical levels of self-reported problems and 18.6% were rated to be ‘markedly ill’, ‘severely ill’ or ‘among the most extremely ill’ by their clinician. Fifty-seven per cent of young people reported psychotropic medication use in the previous half year. Future plans: Analysis of longitudinal data from the MILESTONE cohort will be used to assess relationships between the demographic and clinical characteristics of young people reaching the upper age limit of their CAMHS and the type of care the young person uses over the next 2 years, such as whether the young person transitions to AMHS. At 2 years follow-up, the mental health outcomes of young people following different care pathways will be compared. Trial registration number: NCT03013595