To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Growing evidence suggests that soluble amyloid-beta (Abeta) peptides play a pivotal role in Alzheimer’s disease(AD) pathogenesis by mediating synaptotoxic effects particularly at early disease stages.
We quantified the effects of different order Abeta assemblies on spontaneous firing dynamics ofneuronal networks cultured on multielectrode arrays ('neurochips”) as a read-out. We used naturally secreted, stable and conformationally highly homogenous Abeta monomers, dimers, and a mixture of different low-noligomers, derived from permanently transfected cell lines.
Abeta dimers promoted a dose-dependent suppression of overall activity and network synchrony and altered the burst structure already in the low picomolar dose range. By contrast, Abeta monomers exhibited no effect on overall activity, but only a slight effect on burst structure and a moderate effect on network synchrony. A yet different response pattern was seen for a mixture of various low-n Abeta oligomers. Thus, multiparametric assessment of electrical activity changes on neurochips revealed characteristic signatures of the network response for the different Abeta assemblies. Since alterations of Network function likely occur in initial disease stages, these results confirm the pivotal role of Abeta dimers in early AD pathogenesis.
Neurochip recordings of toxic dimeric Abeta species may serve as a valuable diagnostic read-out in early AD and may also be applicable for future testing of drugs, antibodies, or small molecules aiming at Abeta dimers.
Microelectrode arrays (MEAs) with cultured neuronal networks are highly suitable to quantify neuroactive activity and neurotoxicity of applied substances.
Multiparametric characterization of functional alterations of in vitro-neuronal network activity by different typical and atypical antipsychotics.
To identify differential effects of antipsychotics on spontaneous neuronal network activity as a functional readout.
Cultured networks of dissociated cortical cells of postpartal mice coupled to MEAs were exposed to increasing doses of aripiprazole, clozapine, haloperidol, olanzapine, raclopride, and risperidone.
We found a concentration-dependent inhibition of firing patterns for all substances except olanzapine. All other substances mediated a concomitant irreversible suppression of burst and spike rates, a decrease of the burst duration and the number of spikes in bursts as well as dose-dependent network desynchronization (decrease of Cohen's kappa). The comparison of the different antipsychotics with regard to their half-maximal effective dose values (EC-50) for inhibiting the spike rate yielded an increasing order of EC50 values, i.e. a declining order of toxic potency, of aripiprazole (8.77 μM) < clozapine (9.36 μM) < haloperidol (9.77 μM) < risperidone (15.9 μM) < raclopride (22.7 μM). No significant correlations were identified between EC50 values of the distinct antipsychotics and their binding affinity to the dopamine D(2), the serotonin 5-HT(1A), 5-HT(2A), 5-HT(2C), and the M(1) and M(2) muscarinic acetylcholine receptors.
In MEAs, a dose-dependent neurotoxic effect of typical and atypical antipsychotics alike occurred at supratherapeutic doses via a yet unknown mechanism that did not involve actions on major receptor targets of these compounds.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The search for life in the Universe is a fundamental problem of astrobiology and modern science. The current progress in the detection of terrestrial-type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favourable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of global (astrospheric), and local (atmospheric and surface) environments of exoplanets in the habitable zones (HZs) around G-K-M dwarf stars including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favourable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro)physical, chemical and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the HZ to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field in light of presentations and discussions during the NASA Nexus for Exoplanetary System Science funded workshop ‘Exoplanetary Space Weather, Climate and Habitability’ and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.
Cytomegalovirus (CMV) infection is endemic worldwide but its seroprevalence varies widely. The goal of this study was to estimate the age-specific seroprevalence of CMV infection in Belgium based on two cross-sectional serological datasets from 2002 and 2006. The seroprevalence was estimated relying on diagnostic test results based on cut-off values pre-specified by the manufacturers of the tests as well as relying on mixture models applied to continuous pathogen-specific immunoglobulin G antibody titre concentrations. The age-specific seroprevalence of hepatitis A virus (HAV), based on three Belgian cross-sectional serological datasets from 1993, 2002 and 2006, was used as a comparator since individuals acquire lifelong immunity upon recovery, implying an increasing seroprevalence with age. The age group weighted overall CMV seroprevalence derived from the mixture model was 32% (95% confidence interval (CI) 31–34%) in 2002 and 31% (95% CI 30–32%) in 2006. We demonstrated that CMV epidemiology differs from the immunizing infection HAV. This was the first large-scale study of CMV and HAV serial datasets in Belgium, estimating seroprevalence specified by age and birth cohort.
Early childhood aggressive behaviour is a predictor of future violence. Therefore, identifying risk factors for children’s aggressive behaviour is important in understanding underlying mechanisms. Maternal postpartum depression is a known risk factor. However, little research has focused on the influence of paternal behaviour on early childhood aggression and its interaction with maternal postpartum depression.
This study was performed in two cohorts: the Fathers Project, in the United Kingdom (n = 143) and the Generation R Study, in The Netherlands (n = 549). In both cohorts, we related paternal antisocial personality (ASP) traits and maternal postpartum depressive (PPD) symptoms to childhood aggressive behaviour at age two (Fathers Project) and age three (Generation R Study). We additionally tested whether the presence of paternal ASP traits increased the association between maternal PPD–symptoms and early childhood aggression.
The association between paternal ASP traits and early childhood aggressive behaviour, corrected for maternal PPD-symptoms, was similar in magnitude between the cohorts (Fathers Project: standardized β = 0.12, p = 0.146; Generation R: β = 0.14, p = 0.001), although the association was not statistically significant in the Fathers Project. Strikingly, and in contrast to our expectations, there was evidence of a negative interaction between paternal ASP traits and maternal PPD-symptoms on childhood aggressive behaviour (Fathers Project: β = −0.20, p = 0.020; Generation R: β = −0.09, p = 0.043) in both studies. This meant that with higher levels of paternal ASP traits the association between maternal PPD-symptoms and childhood aggressive behaviour was less and vice versa.
Our findings stress the importance of including both maternal and paternal psychopathology in future studies and interventions focusing on early childhood aggressive behaviour.
The parent–child attachment relationship plays an important role in the development of the infant's stress regulation system. However, genetic and epigenetic factors such as FK506 binding protein 51 (FKBP5) genotype and DNA methylation have also been associated with hypothalamus–pituitary–adrenal axis functioning. In the current study, we examined how parent–child dyadic regulation works in concert with genetic and epigenetic aspects of stress regulation. We study the associations of attachment, extreme maternal insensitivity, FKBP5 single nucleotide polymorphism 1360780, and FKBP5 methylation, with cortisol reactivity to the Strange Situation Procedure in 298 14-month-old infants. The results indicate that FKBP5 methylation moderates the associations of FKBP5 genotype and resistant attachment with cortisol reactivity. We conclude that the inclusion of epigenetics in the field of developmental psychopathology may lead to a more precise picture of the interplay between genetic makeup and parenting in shaping stress reactivity.
We use the TGAS proper motions and parallaxes as well as published and new radial velocities to study the dynamics of nearby moving groups. In particular we try to determine their age using backtracing of the individual members to a common origin. We find that the current data, probably the radial velocities, do not allow to reach a successful conclusion.
Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
We present our approach of visibility modeling of disks around low-mass (< 2 M⊙) young stellar objects (YSOs). We compiled an atlas based on mid-infrared interferometric observations from the MIDI instrument at the VLTI. We use three different models to fit the data. These models allow us to determine overall sizes (and the extent of the inner gaps) of the modeled circumstellar disks.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
For over a decade, the structure of the inner “hole” in the transition disk around TW Hydrae has been a subject of debate. To probe the innermost regions of the protoplanetary disk, observations at the highest possible spatial resolution are required. We present new interferometric data of TW Hya from near-infrared to millimeter wavelengths. We confront existing models of the disk structure with the complete data set and develop a new, detailed radiative-transfer model. This model is characterized by: 1) a spatial separation of the largest grains from the small disk grains; and 2) a smooth inner rim structure, rather than a sharp disk edge.
Over the past decade, a growing number of deep imaging surveys have started to provide meaningful constraints on the population of extrasolar giant planets at large orbital separation. Primary targets for these surveys have been carefully selected based on their age, distance and spectral type, and often on their membership to young nearby associations where all stars share common kinematics, photometric and spectroscopic properties. The next step is a wider statistical analysis of the frequency and properties of low mass companions as a function of stellar mass and orbital separation. In late 2009, we initiated a coordinated European Large Program using angular differential imaging in the H band (1.66 μm) with NaCo at the VLT. Our aim is to provide a comprehensive and statistically significant study of the occurrence of extrasolar giant planets and brown dwarfs at large (5-500 AU) orbital separation around ~150 young, nearby stars, a large fraction of which have never been observed at very deep contrast. The survey has now been completed and we present the data analysis and detection limits for the observed sample, for which we reach the planetary-mass domain at separations of ≳50 AU on average. We also present the results of the statistical analysis that has been performed over the 75 targets newly observed at high-contrast. We discuss the details of the statistical analysis and the physical constraints that our survey provides for the frequency and formation scenario of planetary mass companions at large separation.
Dissimilarities in the spatial distribution of small (μm–size) and large (mm–size) dust grains at the cavity edge of transition disks have been recently pointed out and are now under debate. We obtained VLT/NACO near-IR polarimetric observations of SAO 206462 (HD 135344B). The disk around the star shows very complex structures, such as dips and spirals. We also find an inner cavity much smaller than what is inferred from sub-mm images. The interaction between disk and orbiting companion(s) may explain this discrepancy.
In the regions of highest optical obscuration and infrared confusion, only 21-cm emission can be used to find galaxies in the Zone of Avoidance. A feasibility study conducted with the 300-ft telescope successfully uncovered galaxies which seem to be consistent with populations of optically-selected low surface brightness galaxies. A complete survey is currently being conducted in the north with the Dwingeloo telescope. The big breakthrough should come in the south, however, with the advent of the Parkes telescope multibeam system.
The Dwingeloo Obscured Galaxies Survey (DOGS) is a 21-cm blind survey for galaxies hidden in the northern ‘Zone of Avoidance’ (ZOA): the portion of the optical extragalactic sky which is obscured by dust in the Milky Way. Like the Parkes southern hemisphere ZOA survey, the DOGS project is designed to reveal hidden dynamically important nearby galaxies and to help ‘fill in the blanks’ in the local large scale structure. To date, 36 galaxies have been detected by the Dwingeloo survey; 23 of these were previously unknown [no corresponding sources recorded in the NASA Extragalactic Database (NED)]. Among the interesting detections are three nearby galaxies in the vicinity of NGC 6946 and 11 detections in the Supergalactic plane crossing region. VLA follow-up observations have been conducted for several of the DOGS detections.