This study presents new U–Pb–Hf isotopic data and zircon ages from the Ediacaran to Ordovician Ötztal Complex of the Eastern Alps in Austria to provide new constraints on the evolution of the northern Gondwana active margin in the “proto-Alpine” realm. The multistage tectonic evolution of the complex started with siliciclastic deposition presumably in an accretionary wedge that may have lasted from ca. 600 Ma to ca. 517 Ma. The age spectra are dominated by Neoproterozoic zircon grains indicating that the complex was most likely sourced from the Arabian–Nubian shield, with a contribution of older Proterozoic and Archean grains from the more westerly Saharan metacraton. The deposition was partly overlapping in time with Cambrian to Early Ordovician mafic magmatism that formed either as mafic underplate below the accretionary wedge or outboard, being later accreted as part of the lower plate. The wedge was then intruded by compositionally diverse granitoids from ca. 500 Ma until ca. 440 Ma. By comparing the Ediacaran and Early Paleozoic evolution of the Ötztal Complex with originally more westerly Cadomian-basement terranes (e.g., those now found in the Bohemian Massif), we concluded that the Cenerian orogeny was generally younger in the proto-Alps than elsewhere in the former Cadomian belt. This was possibly due to a significantly curved geometry of the northern Gondwana margin and/or due to an eastward ridge–trench–transform triple point migration. Arrival of a warmer part of the oceanic plate then may have caused mantle melting, mafic underplating, and voluminous granitic plutonism in the forearc, perhaps finally terminated by ridge–trench interaction and slab break-off.
Krypton-81 (81Kr) and chlorine-36 (36Cl) are among the few isotopic tracers capable of constraining groundwater residence times on 105-106 year timescales. In sedimentary aquifer systems bounded by low-permeability units, however, diffusive solute exchange can strongly modify tracer distributions and bias apparent ages derived from concentration ratios. In the transboundary Milk River Aquifer (MRA), progressive chloride enrichment caused by diffusion across shale aquitards complicates the interpretation of 36Cl/Cl as a chronometer. Here, we combine new measurements of 81Kr, 36Cl, stable chlorine isotopes (37Cl/35Cl), and 14C with advection-diffusion transport modeling to quantify the importance of matrix diffusion on tracer systematics and inferred groundwater ages. The simulations reproduce the observed decrease in 36Cl/Cl and concomitant increase in δ37Cl along regional flow paths, demonstrating that diffusive influx of Cl-rich aquitard water dominates the evolution of the chlorine isotope system. In contrast, modeled and observed 81Kr activities show substantially lower sensitivity to diffusive exchange over the timescales considered. A comparison of simulated and measured tracer relationships indicates that, in the MRA, apparent ages derived from 36Cl primarily reflect chloride addition rather than radioactive decay, whereas 81Kr provides a more robust and conservative chronometer for fossil groundwater. These results highlight the value of integrating stable and radioactive chlorine isotopes with noble gas dating and explicit transport modeling to disentangle decay from transport effects. The approach developed here provides a quantitative framework for interpreting multitracer data sets in regional aquifers affected by long-term diffusive exchange and has broader implications for assessing fossil groundwater resources in similar hydrogeological settings.
Global population aging and increased chronic stress due to numerous mass disasters including those related to pandemics, climate change, war, displacement, and political unrest all challenge our collective resilience, with a growing burden of late-life neuropsychiatric and neurodegenerative disorders placing unprecedented demands on health and social systems worldwide. With these considerations in mind, understanding and promoting brain health is becoming a priority for the prevention of neuropsychiatric disorders across the lifespan. Brain health represents a dynamic balance of neural, cognitive, and emotional processes that determine resilience to neuropsychiatric illness. In later life, this balance becomes particularly critical as neurobiological and psychosocial stressors converge to shape trajectories of neuropsychiatric and neurodegenerative disorders. This review synthesizes current evidence on the determinants of brain health in aging, emphasizing resilience as a modifiable pathway linking neuropsychiatric illness risk and prevention. We integrate insights from neuroscience, lifestyle medicine, geroscience, and social determinants of health to emphasize the value of a whole-person, life-course approach. Particular attention is given to the interplay between stress physiology, interoceptive regulation, emotional resilience, and cognitive and brain reserve across the aging continuum. Emerging frameworks including brain clocks, precision biomarkers, digital phenotyping, and artificial intelligence, are considered as tools for risk stratification, early detection, and personalized intervention. By linking resilience mechanisms to measurable biological indices, we argue for the integration of neurobiological, psychological, behavioral, and sociocultural domains to inform next-generation strategies in neuropsychopharmacology, prevention science, and the promotion of healthy brain aging.
ABSTRACT Background Intervertebral disc degeneration (IDD) reflects a poorly characterized shift from anabolic matrix renewal to catabolic breakdown. Fragmentary experimental and modeling efforts leave many signaling routes unresolved; a consolidated map is required to guide hypothesis‐driven studies. Methods A literature‐curated regulatory network model (RNM) for human nucleus pulposus (NP) cells was assembled from PubMed and enriched with interactions from STRING, KEGG and R&D Systems. The static graph was converted to a semi‐quantitative dynamical system. Simulations examined responses to interleukin‐1β (IL‐1β) and the Toll‐like receptor (TLR) and were benchmarked against time‐resolved proteomics from 2D NP monolayers and 3D alginate cultures representing healthy and degenerated discs. Single‐node perturbations assessed the impact of targeted inhibition on catabolic output. Results The final network contains 82 proteins and 193 directed edges; 41.4% of supporting evidence derives from NP‐specific studies, the highest for any cell type. Baseline activity depicts a non‐degenerate disc, with high expression of anabolic mediators and low expression of catabolic enzymes. Both IL‐1β and TLR elicited strong c‐Jun and p65 NF‐κB activation in silico and in vitro. The model simulated IκBα depletion, whereas its increase in the experimental study shows the biological agreement among in silico and in vitro simulations. Conclusions This RNM unifies scattered IDD data into a validated dynamic framework that mirrors NP signaling. The publicly available model provides a foundation for multiscale studies linking molecular events to disc mechanics and for prioritizing therapeutic interventions.
