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Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (μCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.
Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (μCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.
The number of alien plants escaping from cultivation into native ecosystems is increasing steadily. We provide an overview of the historical, contemporary and potential future roles of ornamental horticulture in plant invasions. We show that currently at least 75% and 93% of the global naturalised alien flora is grown in domestic and botanical gardens, respectively. Species grown in gardens also have a larger naturalised range than those that are not. After the Middle Ages, particularly in the 18th and 19th centuries, a global trade network in plants emerged. Since then, cultivated alien species also started to appear in the wild more frequently than non-cultivated aliens globally, particularly during the 19th century. Horticulture still plays a prominent role in current plant introduction, and the monetary value of live-plant imports in different parts of the world is steadily increasing. Historically, botanical gardens - an important component of horticulture - played a major role in displaying, cultivating and distributing new plant discoveries. While the role of botanical gardens in the horticultural supply chain has declined, they are still a significant link, with one-third of institutions involved in retail-plant sales and horticultural research. However, botanical gardens have also become more dependent on commercial nurseries as plant sources, particularly in North America. Plants selected for ornamental purposes are not a random selection of the global flora, and some of the plant characteristics promoted through horticulture, such as fast growth, also promote invasion. Efforts to breed non-invasive plant cultivars are still rare. Socio-economical, technological, and environmental changes will lead to novel patterns of plant introductions and invasion opportunities for the species that are already cultivated. We describe the role that horticulture could play in mediating these changes. We identify current research challenges, and call for more research efforts on the past and current role of horticulture in plant invasions. This is required to develop science-based regulatory frameworks to prevent further plant invasions.
The concept of bonding and antibonding orbitals is fundamental in chemistry. The population of those orbitals and the energetic difference between the two reflect the strength of the bonding interaction. Weakening the bond is expected to reduce this energetic splitting, but the transient character of bond-activation has so far prohibited direct experimental access. Here we apply time-resolved soft X-ray spectroscopy at a free electron laser to directly observe the decreased bonding antibonding splitting following bond-activation using an ultrashort optical laser pulse.
Empirical ground-motion models used in seismic hazard analysis are commonly derived by regression of observed ground motions against a chosen set of predictor variables. Commonly, the model building process is based on residual analysis and/or expert knowledge and/or opinion, while the quality of the model is assessed by the goodness-of-fit to the data. Such an approach, however, bears no immediate relation to the predictive power of the model and with increasing complexity of the models is increasingly susceptible to the danger of overfitting. Here, a different, primarily data-driven method for the development of ground-motion models is proposed that makes use of the notion of generalization error to counteract the problem of overfitting. Generalization error directly estimates the average prediction error on data not used for the model generation and, thus, is a good criterion to assess the predictive capabilities of a model. The approach taken here makes only few a priori assumptions. At first, peak ground acceleration and response spectrum values are modeled by flexible, nonphysical functions (polynomials) of the predictor variables. The inclusion of a particular predictor and the order of the polynomials are based on minimizing generalization error. The approach is illustrated for the next generation of ground-motion attenuation dataset. The resulting model is rather complex, comprising 48 parameters, but has considerably lower generalization error than functional forms commonly used in ground-motion models. The model parameters have no physical meaning, but a visual interpretation is possible and can reveal relevant characteristics of the data, for example, the Moho bounce in the distance scaling. In a second step, the regression model is approximated by an equivalent stochastic model, making it physically interpretable. The resulting resolvable stochastic model parameters are comparable to published models for western North America. In general, for large datasets generalization error minimization provides a viable method for the development of empirical ground-motion models.
Aim Biotic interactions within guilds or across trophic levels have widely been ignored in species distribution models (SDMs). This synthesis outlines the development of species interaction distribution models (SIDMs), which aim to incorporate multispecies interactions at large spatial extents using interaction matrices. Location Local to global. Methods We review recent approaches for extending classical SDMs to incorporate biotic interactions, and identify some methodological and conceptual limitations. To illustrate possible directions for conceptual advancement we explore three principal ways of modelling multispecies interactions using interaction matrices: simple qualitative linkages between species, quantitative interaction coefficients reflecting interaction strengths, and interactions mediated by interaction currencies. We explain methodological advancements for static interaction data and multispecies time series, and outline methods to reduce complexity when modelling multispecies interactions. Results Classical SDMs ignore biotic interactions and recent SDM extensions only include the unidirectional influence of one or a few species. However, novel methods using error matrices in multivariate regression models allow interactions between multiple species to be modelled explicitly with spatial co-occurrence data. If time series are available, multivariate versions of population dynamic models can be applied that account for the effects and relative importance of species interactions and environmental drivers. These methods need to be extended by incorporating the non-stationarity in interaction coefficients across space and time, and are challenged by the limited empirical knowledge on spatio-temporal variation in the existence and strength of species interactions. Model complexity may be reduced by: (1) using prior ecological knowledge to set a subset of interaction coefficients to zero, (2) modelling guilds and functional groups rather than individual species, and (3) modelling interaction currencies and species effect and response traits. Main conclusions There is great potential for developing novel approaches that incorporate multispecies interactions into the projection of species distributions and community structure at large spatial extents. Progress can be made by: (1) developing statistical models with interaction matrices for multispecies co-occurrence datasets across large-scale environmental gradients, (2) testing the potential and limitations of methods for complexity reduction, and (3) sampling and monitoring comprehensive spatio-temporal data on biotic interactions in multispecies communities.
This paper presents a Bayesian non-parametric method based on Gaussian Process (GP) regression to derive ground-motion models for peak-ground parameters and response spectral ordinates. Due to its non-parametric nature there is no need to specify any fixed functional form as in parametric regression models. A GP defines a distribution over functions, which implicitly expresses the uncertainty over the underlying data generating process. An advantage of GP regression is that it is possible to capture the whole uncertainty involved in ground-motion modeling, both in terms of aleatory variability as well as epistemic uncertainty associated with the underlying functional form and data coverage. The distribution over functions is updated in a Bayesian way by computing the posterior distribution of the GP after observing ground-motion data, which in turn can be used to make predictions. The proposed GP regression models is evaluated on a subset of the RESORCE data base for the SIGMA project. The experiments show that GP models have a better generalization error than a simple parametric regression model. A visual assessment of different scenarios demonstrates that the inferred GP models are physically plausible.
A Bayesian ground-motion model is presented that directly estimates the coefficients of the model and the correlation between different ground-motion parameters of interest. The model is developed as a multi-level model with levels for earthquake, station and record terms. This separation allows to estimate residuals for each level and thus the estimation of the associated aleatory variability. In particular, the usually estimated within-event variability is split into a between-station and between-record variability. In addition, the covariance structure between different ground-motion parameters of interest is estimated for each level, i.e. directly the between-event, between-station and between-record correlation coefficients are available. All parameters of the model are estimated via Bayesian inference, which allows to assess their epistemic uncertainty in a principled way. The model is developed using a recently compiled European strong-motion database. The target variables are peak ground velocity, peak ground acceleration and spectral acceleration at eight oscillator periods. The model performs well with respect to its residuals, and is similar to other ground-motion models using the same underlying database. The correlation coefficients are similar to those estimated for other parts of the world, with nearby periods having a high correlation. The between-station, between-event and between-record correlations follow generally a similar trend.
Bayesian networks are a powerful and increasingly popular tool for reasoning under uncertainty, offering intuitive insight into (probabilistic) data-generating processes. They have been successfully applied to many different fields, including bioinformatics. In this paper, Bayesian networks are used to model the joint-probability distribution of selected earthquake, site, and ground-motion parameters. This provides a probabilistic representation of the independencies and dependencies between these variables. In particular, contrary to classical regression, Bayesian networks do not distinguish between target and predictors, treating each variable as random variable. The capability of Bayesian networks to model the ground-motion domain in probabilistic seismic hazard analysis is shown for a generic situation. A Bayesian network is learned based on a subset of the Next Generation Attenuation (NGA) dataset, using 3342 records from 154 earthquakes. Because no prior assumptions about dependencies between particular parameters are made, the learned network displays the most probable model given the data. The learned network shows that the ground-motion parameter (horizontal peak ground acceleration, PGA) is directly connected only to the moment magnitude, Joyner-Boore distance, fault mechanism, source-to-site azimuth, and depth to a shear-wave horizon of 2: 5 km/s (Z2.5). In particular, the effect of V-S30 is mediated by Z2.5. Comparisons of the PGA distributions based on the Bayesian networks with the NGA model of Boore and Atkinson (2008) show a reasonable agreement in ranges of good data coverage.
Logic trees have become the most popular tool for the quantification of epistemic uncertainties in probabilistic seismic hazard assessment (PSHA). In a logic-tree framework, epistemic uncertainty is expressed in a set of branch weights, by which an expert or an expert group assigns degree-of-belief values to the applicability of the corresponding branch models. Despite the popularity of logic-trees, however, one finds surprisingly few clear commitments to what logic-tree branch weights are assumed to be (even by hazard analysts designing logic trees). In the present paper we argue that it is important for hazard analysts to accept the probabilistic framework from the beginning for assigning logic-tree branch weights. In other words, to accept that logic-tree branch weights are probabilities in the axiomatic sense, independent of one's preference for the philosophical interpretation of probabilities. We demonstrate that interpreting logic-tree branch weights merely as a numerical measure of "model quality," which are then subsequently normalized to sum up to unity, will with increasing number of models inevitably lead to an apparent insensitivity of hazard curves on the logic-tree branch weights, which may even be mistaken for robustness of the results. Finally, we argue that assigning logic-tree branch weights in a sequential fashion may improve their logical consistency.
Before GAIA improves the HIPPARCOS survey, direct determination of the distance via parallax is only possible for γ Vel, but the analysis of the cluster or association to which WR stars are associated can give distances with a 50% to a 10% accuracy. The list of Galactic clusters, associations and clusters/association candidates has grown significantly in the last decade with the numerous deep, high resolution surveys of the Milky Way. In this work, we revisit the fundamental parameters of known clusters with WR stars, and we present the search for new ones. All our work is based on the catalogs from the VVV (from the VISTA telescope) and the UKIDS (from the UKIRT telescope) near infrared surveys. Finally, the relations between the fundamental parameters of clusters with WR stars are explored.
Bacteria swim in sequences of straight runs that are interrupted by turning events. They drive their swimming locomotion with the help of rotating helical flagella. Depending on the number of flagella and their arrangement across the cell body, different run-and-turn patterns can be observed. Here, we present fluorescence microscopy recordings showing that cells of the soil bacterium Pseudomonas putida that are decorated with a polar tuft of helical flagella, can alternate between two distinct swimming patterns. On the one hand, they can undergo a classical push-pull-push cycle that is well known from monopolarly flagellated bacteria but has not been reported for species with a polar bundle of multiple flagella. Alternatively, upon leaving the pulling mode, they can enter a third slow swimming phase, where they propel themselves with their helical bundle wrapped around the cell body. A theoretical estimate based on a random-walk model shows that the spreading of a population of swimmers is strongly enhanced when cycling through a sequence of pushing, pulling, and wrapped flagellar configurations as compared to the simple push-pull-push pattern.
We present the first physical characterization of the young open cluster VVVCL041. We spectroscopically observed the cluster main-sequence stellar population and a very-massive star candidate: WR62-2. CMFGEN modelling to our near-infrared spectra indicates that WR62-2 is a very luminous (10^6.4±0.2 L⊙)and massive (∼ 80M⊙) star.
Background:
Epidemiological evidence indicates that diets rich in plant foods are associated with a lower risk of ischaemic heart disease (IHD), but there is sparse information on fruit and vegetable subtypes and sources of dietary fibre. This study examined the associations of major plant foods, their subtypes and dietary fibre with risk of IHD in the European Prospective Investigation into Cancer and Nutrition (EPIC).
Methods:
We conducted a prospective analysis of 490 311 men and women without a history of myocardial infarction or stroke at recruitment (12.6 years of follow-up, n cases = 8504), in 10 European countries. Dietary intake was assessed using validated questionnaires, calibrated with 24-h recalls. Multivariable Cox regressions were used to estimate hazard ratios (HR) of IHD.
Results:
There was a lower risk of IHD with a higher intake of fruit and vegetables combined [HR per 200 g/day higher intake 0.94, 95% confidence interval (CI): 0.90-0.99, P-trend = 0.009], and with total fruits (per 100 g/day 0.97, 0.95-1.00, P-trend = 0.021). There was no evidence for a reduced risk for fruit subtypes, except for bananas. Risk was lower with higher intakes of nuts and seeds (per 10 g/day 0.90, 0.82-0.98, Ptrend = 0.020), total fibre (per 10 g/day 0.91, 0.85-0.98, P-trend = 0.015), fruit and vegetable fibre (per 4 g/day 0.95, 0.91-0.99, P-trend = 0.022) and fruit fibre (per 2 g/day 0.97, 0.95-1.00, P-trend = 0.045). No associations were observed between vegetables, vegetables subtypes, legumes, cereals and IHD risk.
Conclusions:
In this large prospective study, we found some small inverse associations between plant foods and IHD risk, with fruit and vegetables combined being the most strongly inversely associated with risk. Whether these small associations are causal remains unclear.
Background: Population-specificity of exploratory dietary patterns limits their generalizability in investigations with type 2 diabetes incidence.
Objective: The aim of this study was to derive country-specific exploratory dietary patterns, investigate their association with type 2 diabetes incidence, and replicate diabetes-associated dietary patterns in other countries.
Methods: Dietary intake data were used, assessed by country-specific questionnaires at baseline of 11,183 incident diabetes cases and 14,694 subcohort members (mean age 52.9 y) from 8 countries, nested within the European Prospective Investigation into Cancer and Nutrition study (mean follow-up time 6.9 y). Exploratory dietary patterns were derived by principal component analysis. HRs for incident type 2 diabetes were calculated by Prentice-weighted Cox proportional hazard regression models. Diabetes-associated dietary patterns were simplified or replicated to be applicable in other countries. A meta-analysis across all countries evaluated the generalizability of the diabetes-association.
Results: Two dietary patterns per country/UK-center, of which overall 3 dietary patterns were diabetes-associated, were identified. A risk-lowering French dietary pattern was not confirmed across other countries: pooled HRFrance per 1 SD: 1.00; 95% CI: 0.90, 1.10. Risk-increasing dietary patterns, derived in Spain and UK-Norfolk, were confirmed, but only the latter statistically significantly: HRSpain: 1.09; 95% CI: 0.97, 1.22 and HRUK-Norfolk: 1.12; 95% CI: 1.04, 1.20. Respectively, this dietary pattern was characterized by relatively high intakes of potatoes, processed meat, vegetable oils, sugar, cake and cookies, and tea. Conclusions: Only few country/center-specific dietary patterns (3 of 18) were statistically significantly associated with diabetes incidence in this multicountry European study population. One pattern, whose association with diabetes was confirmed across other countries, showed overlaps in the food groups potatoes and processed meat with identified diabetes-associated dietary patterns from other studies. The study demonstrates that replication of associations of exploratory patterns with health outcomes is feasible and a necessary step to overcome population-specificity in associations from such analyses.
Background:
Epidemiological evidence indicates that diets rich in plant foods are associated with a lower risk of ischaemic heart disease (IHD), but there is sparse information on fruit and vegetable subtypes and sources of dietary fibre. This study examined the associations of major plant foods, their subtypes and dietary fibre with risk of IHD in the European Prospective Investigation into Cancer and Nutrition (EPIC).
Methods:
We conducted a prospective analysis of 490 311 men and women without a history of myocardial infarction or stroke at recruitment (12.6 years of follow-up, n cases = 8504), in 10 European countries. Dietary intake was assessed using validated questionnaires, calibrated with 24-h recalls. Multivariable Cox regressions were used to estimate hazard ratios (HR) of IHD.
Results:
There was a lower risk of IHD with a higher intake of fruit and vegetables combined [HR per 200 g/day higher intake 0.94, 95% confidence interval (CI): 0.90-0.99, P-trend = 0.009], and with total fruits (per 100 g/day 0.97, 0.95-1.00, P-trend = 0.021). There was no evidence for a reduced risk for fruit subtypes, except for bananas. Risk was lower with higher intakes of nuts and seeds (per 10 g/day 0.90, 0.82-0.98, Ptrend = 0.020), total fibre (per 10 g/day 0.91, 0.85-0.98, P-trend = 0.015), fruit and vegetable fibre (per 4 g/day 0.95, 0.91-0.99, P-trend = 0.022) and fruit fibre (per 2 g/day 0.97, 0.95-1.00, P-trend = 0.045). No associations were observed between vegetables, vegetables subtypes, legumes, cereals and IHD risk.
Conclusions:
In this large prospective study, we found some small inverse associations between plant foods and IHD risk, with fruit and vegetables combined being the most strongly inversely associated with risk. Whether these small associations are causal remains unclear.
Metabolic signatures of healthy lifestyle patterns and colorectal cancer risk in a European cohort
(2020)
BACKGROUND & AIMS: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.
METHODS: Scores reflecting adherence to the WCRF/AICR recommendations (scale, 1-5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer and Nutrition participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression.
RESULTS: Higher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95% CI, 0.29-0.90; endogenous metabolites: OR, 0.62 per unit change; 95% CI, 0.50-0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95% CI, 0.86-1.00) overall. Signature associations were stronger in male compared with female participants.
CONCLUSIONS: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.