Generational differences in mental health trends in the twenty-first century.

Given the observed deterioration in mental health among Australians over the past decade, this study investigates to what extent this differs in people born in different decades-i.e., possible birth cohort differences in the mental health of Australians. Using 20 y of data from a large, nationally representative panel survey (N = 27,572), we find strong evidence that cohort effects are driving the increase in population-level mental ill-health. Deteriorating mental health is particularly pronounced among people born in the 1990s and seen to a lesser extent among the 1980s cohort. There is little evidence that mental health is worsening with age for people born prior to the 1980s. The findings from this study highlight that it is the poorer mental health of Millennials that is driving the apparent deterioration in population-level mental health. Understanding the context and changes in society that have differentially affected younger people may inform efforts to ameliorate this trend and prevent it continuing for emerging cohorts.

Cell-type-specific optogenetic stimulation of the locus coeruleus induces slow-onset potentiation and enhances everyday memory in rats.

Memory formation is typically divided into phases associated with encoding, storage, consolidation, and retrieval. The neural determinants of these phases are thought to differ. This study first investigated the impact of the experience of novelty in rats incurred at a different time, before or after, the precise moment of memory encoding. Memory retention was enhanced. Optogenetic activation of the locus coeruleus mimicked this enhancement induced by novelty, both when given before and after the moment of encoding. Optogenetic activation of the locus coeruleus also induced a slow-onset potentiation of field potentials in area CA1 of the hippocampus evoked by CA3 stimulation. Despite the locus coeruleus being considered a primarily noradrenergic area, both effects of such stimulation were blocked by the dopamine D1/D5 receptor antagonist SCH 23390. These findings substantiate and enrich the evidence implicating the locus coeruleus in cellular aspects of memory consolidation in hippocampus.

Considering decoupled phenotypic diversification between ontogenetic phases in macroevolution: An example using Triggerfishes (Balistidae).

Across the Tree of Life, most studies of phenotypic disparity and diversification have been restricted to adult organisms. However, many lineages have distinct ontogenetic phases that differ from their adult forms in morphology and ecology. Focusing disproportionately on the evolution of adult forms unnecessarily hinders our understanding of the pressures shaping evolution over time. Non-adult disparity patterns are particularly important to consider for coastal ray-finned fishes, which often have juvenile phases with distinct phenotypes. These juvenile forms are often associated with sheltered nursery environments, with phenotypic shifts between adults and juvenile stages that are readily apparent in locomotor morphology. Whether this ontogenetic variation in locomotor morphology reflects a decoupling of diversification dynamics between life stages remains unknown. Here we investigate the evolutionary dynamics of locomotor morphology between adult and juvenile triggerfishes. We integrate a time-calibrated phylogenetic framework with geometric morphometric approaches and measurement data of fin aspect ratio and incidence, and reveal a mismatch between morphospace occupancy, the evolution of morphological disparity, and the tempo of trait evolution between life stages. Collectively, our results illuminate how the heterogeneity of morpho-functional adaptations can decouple the mode and tempo of morphological diversification between ontogenetic stages.

Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects.

Between 2.5 and 28% of people infected with SARS-CoV-2 suffer Long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear. This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in Long COVID and the potential association between them. To address these objectives, 83 patients with persistent neurological symptoms after COVID-19 were recruited, and 22 now healthy controls chosen because they had suffered COVID-19 but did not experience persistent neurological symptoms. Patients and controls were matched for age, sex and educational level. All participants were assessed by clinical interview, comprehensive standardized neuropsychological tests and structural MRI. The mean global cognitive function of patients with Long COVID assessed by ACE III screening test (Overall Cognitive level - OCLz= -0.39± 0.12) was significantly below the infection recovered-controls (OCLz= +0.32± 0.16, p< 0.01). We observed that 48% of patients with Long COVID had episodic memory deficit, with 27% also impaired overall cognitive function, especially attention, working memory, processing speed and verbal fluency. The MRI examination included grey matter morphometry and whole brain structural connectivity analysis. Compared to infection recovered controls, patients had thinner cortex in a specific cluster centred on the left posterior superior temporal gyrus. In addition, lower fractional anisotropy (FA) and higher radial diffusivity (RD) were observed in widespread areas of the patients' cerebral white matter relative to these controls. Correlations between cognitive status and brain abnormalities revealed a relationship between altered connectivity of white matter regions and impairments of episodic memory, overall cognitive function, attention and verbal fluency. This study shows that patients with neurological Long COVID suffer brain changes, especially in several white matter areas, and these are associated with impairments of specific cognitive functions.

Sleep deprivation and hippocampal ripple disruption after one-session learning eliminate memory expression the next day.

Memory reactivation during non-rapid-eye-movement ripples is thought to communicate new information to a systems-wide network and thus can be a key player mediating the positive effect of sleep on memory consolidation. Causal experiments disrupting ripples have only been performed in multiday training paradigms, which decrease but do not eliminate memory performance, and no comparison with sleep deprivation has been made. To enable such investigations, we developed a one-session learning paradigm in a Plusmaze and show that disruption of either sleep with gentle handling or hippocampal ripples with electrical stimulation impaired long-term memory. Furthermore, we detected hippocampal ripples and parietal high-frequency oscillations after different behaviors, and a bimodal frequency distribution in the cortical events was observed. Faster cortical high-frequency oscillations increased after normal learning, a change not seen in the hippocampal ripple-disruption condition, consistent with these having a role in memory consolidation.

Neuronal signature of spatial decision-making during navigation by freely moving rats by using calcium imaging.

A challenge in spatial memory is understanding how place cell firing contributes to decision-making in navigation. A spatial recency task was created in which freely moving rats first became familiar with a spatial context over several days and thereafter were required to encode and then selectively recall one of three specific locations within it that was chosen to be rewarded that day. Calcium imaging was used to record from more than 1,000 cells in area CA1 of the hippocampus of five rats during the exploration, sample, and choice phases of the daily task. The key finding was that neural activity in the startbox rose steadily in the short period prior to entry to the arena and that this selective population cell firing was predictive of the daily changing goal on correct trials but not on trials in which the animals made errors. Single-cell and population activity measures converged on the idea that prospective coding of neural activity can be involved in navigational decision-making.

Ca2+ imaging of self and other in medial prefrontal cortex during social dominance interactions in a tube test.

The study of social dominance interactions between animals offers a window onto the decision-making involved in establishing dominance hierarchies and an opportunity to examine changes in social behavior observed in certain neurogenetic disorders. Competitive social interactions, such as in the widely used tube test, reflect this decision-making. Previous studies have focused on the different patterns of behavior seen in the dominant and submissive animal, neural correlates of effortful behavior believed to mediate the outcome of such encounters, and interbrain correlations of neural activity. Using a rigorous mutual information criterion, we now report that neural responses recorded with endoscopic calcium imaging in the prelimbic zone of the medial prefrontal cortex show unique correlations to specific dominance-related behaviors. Interanimal analyses revealed cell/behavior correlations that are primarily with an animal's own behavior or with the other animal's behavior, or the coincident behavior of both animals (such as pushing by one and resisting by the other). The comparison of unique and coincident cells helps to disentangle cell firing that reflects an animal's own or the other's specific behavior from situations reflecting conjoint action. These correlates point to a more cognitive rather than a solely behavioral dimension of social interactions that needs to be considered in the design of neurobiological studies of social behavior. These could prove useful in studies of disorders affecting social recognition and social engagement, and the treatment of disorders of social interaction.

Assaying Effector Cell-to-Cell Mobility in Plant Tissues Identifies Hypermobility and Indirect Manipulation of Plasmodesmata.

In plants, plasmodesmata establish cytoplasmic continuity between cells to allow for communication and resource exchange across the cell wall. While plant pathogens use plasmodesmata as a pathway for both molecular and physical invasion, the benefits of molecular invasion (cell-to-cell movement of pathogen effectors) are poorly understood. To establish a methodology for identification and characterization of the cell-to-cell mobility of effectors, we performed a quantitative live imaging-based screen of candidate effectors of the fungal pathogen Colletotrichum higginsianum. We predicted C. higginsianum effectors by their expression profiles, the presence of a secretion signal, and their predicted and in planta localization when fused to green fluorescent protein. We assayed for cell-to-cell mobility of nucleocytosolic effectors and identified 14 that are cell-to-cell mobile. We identified that three of these effectors are "hypermobile," showing cell-to-cell mobility greater than expected for a protein of that size. To explore the mechanism of hypermobility, we chose two hypermobile effectors and measured their impact on plasmodesmata function and found that even though they show no direct association with plasmodesmata, each increases the transport capacity of plasmodesmata. Thus, our methods for quantitative analysis of cell-to-cell mobility of candidate microbe-derived effectors, or any suite of host proteins, can identify cell-to-cell hypermobility and offer greater understanding of how proteins affect plasmodesmal function and intercellular connectivity. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Distinct contributions of ventral CA1/amygdala co-activation to the induction and maintenance of synaptic plasticity.

The amygdala is known to modulate hippocampal synaptic plasticity. One role could be an immediate effect of basolateral amygdala (BLA) in priming synaptic plasticity in the hippocampus. Another role could be through associative synaptic co-operation and competition that triggers events involved in the maintenance of synaptic potentiation. We present evidence that the timing and activity level of BLA stimulation are important factors for the induction and maintenance of long-term potentiation (LTP) in ventral hippocampal area CA1. A 100 Hz BLA co-stimulation facilitated the induction of LTP, whereas 200 Hz co-stimulation attenuated induction. A 100 Hz BLA co-stimulation also caused enhanced persistence, sufficient to prevent synaptic competition. This maintenance effect is likely through translational mechanisms, as mRNA expression of primary response genes was unaffected, whereas protein level of plasticity-related products was increased. Further understanding of the neural mechanisms of amygdala modulation on hippocampus could provide insights into the mechanisms of emotional disorders.

The stability and number of nucleating interactions determine DNA hybridization rates in the absence of secondary structure.

The kinetics of DNA hybridization are fundamental to biological processes and DNA-based technologies. However, the precise physical mechanisms that determine why different DNA sequences hybridize at different rates are not well understood. Secondary structure is one predictable factor that influences hybridization rates but is not sufficient on its own to fully explain the observed sequence-dependent variance. In this context, we measured hybridization rates of 43 different DNA sequences that are not predicted to form secondary structure and present a parsimonious physically justified model to quantify our observations. Accounting only for the combinatorics of complementary nucleating interactions and their sequence-dependent stability, the model achieves good correlation with experiment with only two free parameters. Our results indicate that greater repetition of Watson-Crick pairs increases the number of initial states able to proceed to full hybridization, with the stability of those pairings dictating the likelihood of such progression, thus providing new insight into the physical factors underpinning DNA hybridization rates.

Peer mentoring for people with acquired brain injury - a systematic review.

INTRODUCTION: Over 100 million people worldwide live with disabilities resulting from an acquired brain injury (ABI). ABI survivors experience cognitive and physical problems and require support to resume an active life. They can benefit from support from someone who has been through the same issues (i.e. peer mentor). This review investigated the effectiveness of peer mentoring for ABI survivors. METHOD: Eleven databases, two trial registers, and PROSPERO were searched for published studies. Two reviewers independently screened all titles, abstracts, and full texts, extracted data, and assessed quality. The PRISMA 2020 guidelines were followed to improve transparency in the reporting of the review. RESULTS: The search returned 4,094 results; 2,557 records remained after the removal of duplicates and 2,419 were excluded based on titles and abstracts. Of the remaining 138, 12 studies met the inclusion criteria. Five were conducted in the United States, three in Canada, three in the UK, and one in New Zealand. Meta-analysis was inappropriate due to the heterogeneity of study designs. Therefore, a narrative synthesis of the data was undertaken. CONCLUSION: Although peer mentoring has the potential to positively influence activity and participation among ABI survivors, further research is needed to understand the extent of the benefits.

Significant Oxygen Underestimation When Quantifying Barium-Doped SrTiO Layers by Atom Probe Tomography.

In this paper, the capability for quantifying the composition of Ba-doped SrTiO layers from an atom probe measurement was explored. Rutherford backscattering spectrometry and time-of-flight/energy elastic recoil detection were used to benchmark the composition where the amount of titanium was intentionally varied between samples. The atom probe results showed a significant divergence from the benchmarked composition. The cause was shown to be a significant oxygen underestimation (≳14 at%). The ratio between oxygen and titanium for the samples varied between 2.6 and 12.7, while those measured by atom probe tomography were lower and covered a narrower range between 1.4 and 1.7. This difference was found to be associated with the oxygen and titanium predominantly field evaporating together as a molecular ion. The evaporation fields and bonding chemistries determined showed inconsistencies for explaining the oxygen underestimation and ion species measured. The measured ion charge state was in excellent agreement with that predicted by the Kingham postionization theory. Only by considering the measured ion species, their evaporation fields, the coordination chemistry, the analysis conditions, and some recently reported density functional theory modeling for oxide field emission were we able to postulate a field emission and oxygen neutral desorption process that may explain our results.

The Neural Bases of Action-Outcome Learning in Humans.

From an associative perspective the acquisition of new goal-directed actions requires the encoding of specific action-outcome (AO) associations and, therefore, sensitivity to the validity of an action as a predictor of a specific outcome relative to other events. Although competitive architectures have been proposed within associative learning theory to achieve this kind of identity-based selection, whether and how these architectures are implemented by the brain is still a matter of conjecture. To investigate this issue, we trained human participants to encode various AO associations while undergoing functional neuroimaging (fMRI). We then degraded one AO contingency by increasing the probability of the outcome in the absence of its associated action while keeping other AO contingencies intact. We found that this treatment selectively reduced performance of the degraded action. Furthermore, when a signal predicted the unpaired outcome, performance of the action was restored, suggesting that the degradation effect reflects competition between the action and the context for prediction of the specific outcome. We used a Kalman filter to model the contribution of different causal variables to AO learning and found that activity in the medial prefrontal cortex (mPFC) and the dorsal anterior cingulate cortex (dACC) tracked changes in the association of the action and context, respectively, with regard to the specific outcome. Furthermore, we found the mPFC participated in a network with the striatum and posterior parietal cortex to segregate the influence of the various competing predictors to establish specific AO associations.SIGNIFICANCE STATEMENT Humans and other animals learn the consequences of their actions, allowing them to control their environment in a goal-directed manner. Nevertheless, it is unknown how we parse environmental causes from the effects of our own actions to establish these specific action-outcome (AO) relationships. Here, we show that the brain learns the causal structure of the environment by segregating the unique influence of actions from other causes in the medial prefrontal and anterior cingulate cortices and, through a network of structures, including the caudate nucleus and posterior parietal cortex, establishes the distinct causal relationships from which specific AO associations are formed.

Active flows and deformable surfaces in development.

We review progress in active hydrodynamic descriptions of flowing media on curved and deformable manifolds: the state-of-the-art in continuum descriptions of single-layers of epithelial and/or other tissues during development. First, after a brief overview of activity, flows and hydrodynamic descriptions, we highlight the generic challenge of identifying the dependence on dynamical variables of so-called active kinetic coefficients- active counterparts to dissipative Onsager coefficients. We go on to describe some of the subtleties concerning how curvature and active flows interact, and the issues that arise when surfaces are deformable. We finish with a broad discussion around the utility of such theories in developmental biology. This includes limitations to analytical techniques, challenges associated with numerical integration, fitting-to-data and inference, and potential tools for the future, such as discrete differential geometry.

Intrinsically disordered plant protein PARCL colocalizes with RNA in phase-separated condensates whose formation can be regulated by mutating the PLD.

In higher plants, long-distance RNA transport via the phloem is crucial for communication between distant plant tissues to align development with stress responses and reproduction. Several recent studies suggest that specific RNAs are among the potential long-distance information transmitters. However, it is yet not well understood how these RNAs enter the phloem stream, how they are transported, and how they are released at their destination. It was proposed that phloem RNA-binding proteins facilitate RNA translocation. In the present study, we characterized two orthologs of the phloem-associated RNA chaperone-like (PARCL) protein from Arabidopsis thaliana and Brassica napus at functional and structural levels. Microscale thermophoresis showed that these phloem-abundant proteins can bind a broad spectrum of RNAs and show RNA chaperone activity in FRET-based in vitro assays. Our SAXS experiments revealed a high degree of disorder, typical for RNA-binding proteins. In agroinfiltrated tobacco plants, eYFP-PARCL proteins mainly accumulated in nuclei and nucleoli and formed cytosolic and nuclear condensates. We found that formation of these condensates was impaired by tyrosine-to-glutamate mutations in the predicted prion-like domain (PLD), while C-terminal serine-to-glutamate mutations did not affect condensation but reduced RNA binding and chaperone activity. Furthermore, our in vitro experiments confirmed phase separation of PARCL and colocalization of RNA with the condensates, while mutation as well as phosphorylation of the PLD reduced phase separation. Together, our results suggest that RNA binding and condensate formation of PARCL can be regulated independently by modification of the C-terminus and/or the PLD.

Execution of new trajectories toward a stable goal without a functional hippocampus.

The hippocampus is a critical component of a mammalian spatial navigation system, with the firing sequences of hippocampal place cells during sleep or immobility constituting a "replay" of an animal's past trajectories. A novel spatial navigation task recently revealed that such "replay" sequences of place fields can also prospectively map onto imminent new paths to a goal that occupies a stable location during each session. It was hypothesized that such "prospective replay" sequences may play a causal role in goal-directed navigation. In the present study, we query this putative causal role in finding only minimal effects of muscimol-induced inactivation of the dorsal and intermediate hippocampus on the same spatial navigation task. The concentration of muscimol used demonstrably inhibited hippocampal cell firing in vivo and caused a severe deficit in a hippocampal-dependent "episodic-like" spatial memory task in a watermaze. These findings call into question whether "prospective replay" of an imminent and direct path is actually necessary for its execution in certain navigational tasks.

Bayesian network modelling to identify on-ramps to childhood obesity.

BACKGROUND: When tackling complex public health challenges such as childhood obesity, interventions focused on immediate causes, such as poor diet and physical inactivity, have had limited success, largely because upstream root causes remain unresolved. A priority is to develop new modelling frameworks to infer the causal structure of complex chronic disease networks, allowing disease "on-ramps" to be identified and targeted. METHODS: The system surrounding childhood obesity was modelled as a Bayesian network, using data from The Longitudinal Study of Australian Children. The existence and directions of the dependencies between factors represent possible causal pathways for childhood obesity and were encoded in directed acyclic graphs (DAGs). The posterior distribution of the DAGs was estimated using the Partition Markov chain Monte Carlo. RESULTS: We have implemented structure learning for each dataset at a single time point. For each wave and cohort, socio-economic status was central to the DAGs, implying that socio-economic status drives the system regarding childhood obesity. Furthermore, the causal pathway socio-economic status and/or parental high school levels → parental body mass index (BMI) → child's BMI existed in over 99.99% of posterior DAG samples across all waves and cohorts. For children under the age of 8 years, the most influential proximate causal factors explaining child BMI were birth weight and parents' BMI. After age 8 years, free time activity became an important driver of obesity, while the upstream factors influencing free time activity for boys compared with girls were different. CONCLUSIONS: Childhood obesity is largely a function of socio-economic status, which is manifest through numerous downstream factors. Parental high school levels entangle with socio-economic status, and hence, are on-ramp to childhood obesity. The strong and independent causal relationship between birth weight and childhood BMI suggests a biological link. Our study implies that interventions that improve the socio-economic status, including through increasing high school completion rates, may be effective in reducing childhood obesity prevalence.

Noncell-autonomous HSC70.1 chaperone displays homeostatic feedback regulation by binding its own mRNA.

The HSC70/HSP70 family of heat shock proteins are evolutionarily conserved chaperones involved in protein folding, protein transport, and RNA binding. Arabidopsis HSC70 chaperones are thought to act as housekeeping chaperones and as such are involved in many growth-related pathways. Whether Arabidopsis HSC70 binds RNA and whether this interaction is functional has remained an open question. We provide evidence that the HSC70.1 chaperone binds its own mRNA via its C-terminal short variable region (SVR) and inhibits its own translation. The SVR encoding mRNA region is necessary for HSC70.1 transcript mobility to distant tissues and that HSC70.1 transcript and not protein mobility is required to rescue root growth and flowering time of hsc70 mutants. We propose that this negative protein-transcript feedback loop may establish an on-demand chaperone pool that allows for a rapid response to stress. In summary, our data suggest that the Arabidopsis HSC70.1 chaperone can form a complex with its own transcript to regulate its translation and that both protein and transcript can act in a noncell-autonomous manner, potentially maintaining chaperone homeostasis between tissues.

High expression of the MADS-box gene VRT2 increases the number of rudimentary basal spikelets in wheat.

Spikelets are the fundamental building blocks of Poaceae inflorescences, and their development and branching patterns determine the various inflorescence architectures and grain yield of grasses. In wheat (Triticum aestivum), the central spikelets produce the most and largest grains, while spikelet size gradually decreases acropetally and basipetally, giving rise to the characteristic lanceolate shape of wheat spikes. The acropetal gradient corresponds with the developmental age of spikelets; however, the basal spikelets are developed first, and the cause of their small size and rudimentary development is unclear. Here, we adapted G&T-seq, a low-input transcriptomics approach, to characterize gene expression profiles within spatial sections of individual spikes before and after the establishment of the lanceolate shape. We observed larger differences in gene expression profiles between the apical, central, and basal sections of a single spike than between any section belonging to consecutive developmental time points. We found that SHORT VEGETATIVE PHASE MADS-box transcription factors, including VEGETATIVE TO REPRODUCTIVE TRANSITION 2 (VRT-A2), are expressed highest in the basal section of the wheat spike and display the opposite expression gradient to flowering E-class SEPALLATA1 genes. Based on multi-year field trials and transgenic lines, we show that higher expression of VRT-A2 in the basal sections of the spike is associated with increased numbers of rudimentary basal spikelets. Our results, supported by computational modeling, suggest that the delayed transition of basal spikelets from vegetative to floral developmental programs results in the lanceolate shape of wheat spikes. This study highlights the value of spatially resolved transcriptomics to gain insights into developmental genetics pathways of grass inflorescences.

Delayed development of basal spikelets in wheat explains their increased floret abortion and rudimentary nature.

Large differences exist in the number of grains per spikelet across an individual wheat (Triticum aestivum L.) spike. The central spikelets produce the highest number of grains, while apical and basal spikelets are less productive, and the most basal spikelets are commonly only developed in rudimentary form. Basal spikelets are delayed in initiation, yet they continue to develop and produce florets. The precise timing or the cause of their abortion remains largely unknown. Here, we investigated the underlying causes of basal spikelet abortion using shading applications in the field. We found that basal spikelet abortion is likely to be the consequence of complete floret abortion, as both occur concurrently and have the same response to shading treatments. We detected no differences in assimilate availability across the spike. Instead, we show that the reduced developmental age of basal florets pre-anthesis is strongly associated with their increased abortion. Using the developmental age pre-abortion, we were able to predict final grain set per spikelet across the spike, alongside the characteristic gradient in the number of grains from basal to central spikelets. Future efforts to improve spikelet homogeneity across the spike could thus focus on improving basal spikelet establishment and increasing floret development rates pre-abortion.