Identifying drivers of non-stationary climate-growth relationships of European beech.

The future performance of the widely abundant European beech (Fagus sylvatica L.) across its ecological amplitude is uncertain. Although beech is considered drought-sensitive and thus negatively affected by drought events, scientific evidence indicating increasing drought vulnerability under climate change on a cross-regional scale remains elusive. While evaluating changes in climate sensitivity of secondary growth offers a promising avenue, studies from productive, closed-canopy forests suffer from knowledge gaps, especially regarding the natural variability of climate sensitivity and how it relates to radial growth as an indicator of tree vitality. Since beech is sensitive to drought, we in this study use a drought index as a climate variable to account for the combined effects of temperature and water availability and explore how the drought sensitivity of secondary growth varies temporally in dependence on growth variability, growth trends, and climatic water availability across the species' ecological amplitude. Our results show that drought sensitivity is highly variable and non-stationary, though consistently higher at dry sites compared to moist sites. Increasing drought sensitivity can largely be explained by increasing climatic aridity, especially as it is exacerbated by climate change and trees' rank progression within forest communities, as (co-)dominant trees are more sensitive to extra-canopy climatic conditions than trees embedded in understories. However, during the driest periods of the 20th century, growth showed clear signs of being decoupled from climate. This may indicate fundamental changes in system behavior and be early-warning signals of decreasing drought tolerance. The multiple significant interaction terms in our model elucidate the complexity of European beech's drought sensitivity, which needs to be taken into consideration when assessing this species' response to climate change.

The German Twin Family Panel (TwinLife).

The German Twin Family Panel (TwinLife) is a German longitudinal study of monozygotic and dizygotic same-sex twin pairs and their families that was designed to investigate the development of social inequalities over the life course. The study covers an observation period from approximately 2014 to 2023. The target population of the sample are reared-together twins of four different age cohorts that were born in 2009/2010 (cohort 1), in 2003/2004 (cohort 2), in 1997/1998 (cohort 3) and between 1990 and 1993 (cohort 4). In the first wave, the study included data on 4097 twin families. Families were recruited in all parts of Germany so that the sample comprises the whole range of the educational, occupational and income structure. As of 2019, two face-to-face, at-home interviews and two telephone interviews have been conducted. Data from the first home and telephone interviews are already available free of charge as a scientific use-file from the GESIS data archive. This report aims to provide an overview of the study sample and design as well as constructs that are unique in TwinLife in comparison with previous twin studies - such as an assessment of cognitive abilities or information based on the children's medical records and report cards. In addition, major findings based on the data already released are displayed, and future directions of the study are presented and discussed.

Cerebral resting state markers of biased perception in social anxiety.

Social anxiety (SA) comprises a multitude of persistent fears around the central element of dreaded negative evaluation and exclusion. This very common anxiety is spectrally distributed among the general population and associated with social perception biases deemed causal in its maintenance. Here, we investigated cerebral resting state markers linking SA and biased social perception. To this end, resting state functional connectivity (RSFC) was assessed as the neurobiological marker in a study population with greatly varying SA using fMRI in the first step of the experiment. One month later the impact of unattended laughter-exemplifying social threat-on a face rating task was evaluated as a measure of biased social perception. Applying a dimensional approach, SA-related cognitive biases tied to the valence, dominance and arousal of the threat signal and their underlying RSFC patterns among central nodes of the cerebral emotion, voice and face processing networks were identified. In particular, the connectivity patterns between the amygdalae and the right temporal voice area met all criteria for a cerebral mediation of the association between SA and the laughter valence-related interpretation bias. Thus, beyond this identification of non-state-dependent cerebral markers of biased perception in SA, this study highlights both a starting point and targets for future research on the causal relationships between cerebral connectivity patterns, SA and biased perception, potentially via neurofeedback methods.

Prefrontal mediation of emotion regulation in social anxiety disorder during laughter perception.

Social anxiety disorder (SAD) is characterized by negatively biased perception of social cues and deficits in emotion regulation. While negatively biased perception is thought to maintain social anxiety, emotion regulation represents an ability necessary to overcome both biased perception and social anxiety. Here, we used laughter as a social threat in a functional magnetic resonance imaging (fMRI) study to identify cerebral mediators linking SAD with attention and interpretation biases and their modification through cognitive emotion regulation in the form of reappraisal. We found that reappraisal abolished the negative laughter interpretation bias in SAD and that this process was directly mediated through activation patterns of the left dorsolateral prefrontal cortex (DLPFC) serving as a cerebral pivot between biased social perception and its normalization through reappraisal. Connectivity analyses revealed reduced prefrontal control over threat-processing sensory cortices (here: the temporal voice area) during cognitive emotion regulation in SAD. Our results indicate a central role for the left DLPFC in SAD which might represent a valuable target for future research on interventions either aiming to directly modulate cognitive emotion regulation in SAD or to evaluate its potential as physiological marker for psychotherapeutic interventions relying on emotion regulation.

Peptide-Boronic Acid Inhibitors of Flaviviral Proteases: Medicinal Chemistry and Structural Biology.

A thousand-fold affinity gain is achieved by introduction of a C-terminal boronic acid moiety into dipeptidic inhibitors of the Zika, West Nile, and dengue virus proteases. The resulting compounds have Ki values in the two-digit nanomolar range, are not cytotoxic, and inhibit virus replication. Structure-activity relationships and a high resolution X-ray cocrystal structure with West Nile virus protease provide a basis for the design of optimized covalent-reversible inhibitors aimed at emerging flaviviral pathogens.

Phenylalanine and Phenylglycine Analogues as Arginine Mimetics in Dengue Protease Inhibitors.

Dengue virus is an increasingly global pathogen. One of the promising targets for antiviral drug discovery against dengue and related flaviviruses such as West Nile virus is the viral serine protease NS2B-NS3. We here report the synthesis and in vitro characterization of potent peptidic inhibitors of dengue virus protease that incorporate phenylalanine and phenylglycine derivatives as arginine-mimicking groups with modulated basicity. The most promising compounds were (4-amidino)-L-phenylalanine-containing inhibitors, which reached nanomolar affinities against dengue virus protease. The type and position of the substituents on the phenylglycine and phenylalanine side chains has a significant effect on the inhibitory activity against dengue virus protease and selectivity against other proteases. In addition, the non-natural, basic amino acids described here may have relevance for the development of other peptidic and peptidomimetic drugs such as inhibitors of the blood clotting cascade.