Rapid groundwater decline and some cases of recovery in aquifers globally.

Groundwater resources are vital to ecosystems and livelihoods. Excessive groundwater withdrawals can cause groundwater levels to decline1-10, resulting in seawater intrusion11, land subsidence12,13, streamflow depletion14-16 and wells running dry17. However, the global pace and prevalence of local groundwater declines are poorly constrained, because in situ groundwater levels have not been synthesized at the global scale. Here we analyse in situ groundwater-level trends for 170,000 monitoring wells and 1,693 aquifer systems in countries that encompass approximately 75% of global groundwater withdrawals18. We show that rapid groundwater-level declines (>0.5 m year-1) are widespread in the twenty-first century, especially in dry regions with extensive croplands. Critically, we also show that groundwater-level declines have accelerated over the past four decades in 30% of the world's regional aquifers. This widespread acceleration in groundwater-level deepening highlights an urgent need for more effective measures to address groundwater depletion. Our analysis also reveals specific cases in which depletion trends have reversed following policy changes, managed aquifer recharge and surface-water diversions, demonstrating the potential for depleted aquifer systems to recover.

Abyssal ocean overturning slowdown and warming driven by Antarctic meltwater.

The abyssal ocean circulation is a key component of the global meridional overturning circulation, cycling heat, carbon, oxygen and nutrients throughout the world ocean1,2. The strongest historical trend observed in the abyssal ocean is warming at high southern latitudes2-4, yet it is unclear what processes have driven this warming, and whether this warming is linked to a slowdown in the ocean's overturning circulation. Furthermore, attributing change to specific drivers is difficult owing to limited measurements, and because coupled climate models exhibit biases in the region5-7. In addition, future change remains uncertain, with the latest coordinated climate model projections not accounting for dynamic ice-sheet melt. Here we use a transient forced high-resolution coupled ocean-sea-ice model to show that under a high-emissions scenario, abyssal warming is set to accelerate over the next 30 years. We find that meltwater input around Antarctica drives a contraction of Antarctic Bottom Water (AABW), opening a pathway that allows warm Circumpolar Deep Water greater access to the continental shelf. The reduction in AABW formation results in warming and ageing of the abyssal ocean, consistent with recent measurements. In contrast, projected wind and thermal forcing has little impact on the properties, age and volume of AABW. These results highlight the critical importance of Antarctic meltwater in setting the abyssal ocean overturning, with implications for global ocean biogeochemistry and climate that could last for centuries.

Evolving schema representations in orbitofrontal ensembles during learning.

How do we learn about what to learn about? Specifically, how do the neural elements in our brain generalize what has been learned in one situation to recognize the common structure of-and speed learning in-other, similar situations? We know this happens because we become better at solving new problems-learning and deploying schemas1-5-through experience. However, we have little insight into this process. Here we show that using prior knowledge to facilitate learning is accompanied by the evolution of a neural schema in the orbitofrontal cortex. Single units were recorded from rats deploying a schema to learn a succession of odour-sequence problems. With learning, orbitofrontal cortex ensembles converged onto a low-dimensional neural code across both problems and subjects; this neural code represented the common structure of the problems and its evolution accelerated across their learning. These results demonstrate the formation and use of a schema in a prefrontal brain region to support a complex cognitive operation. Our results not only reveal a role for the orbitofrontal cortex in learning but also have implications for using ensemble analyses to tap into complex cognitive functions.

Acceleration of infectious disease drug discovery and development using a humanized model of drug metabolism.

A key step in drug discovery, common to many disease areas, is preclinical demonstration of efficacy in a mouse model of disease. However, this demonstration and its translation to the clinic can be impeded by mouse-specific pathways of drug metabolism. Here, we show that a mouse line extensively humanized for the cytochrome P450 gene superfamily ("8HUM") can circumvent these problems. The pharmacokinetics, metabolite profiles, and magnitude of drug-drug interactions of a test set of approved medicines were in much closer alignment with clinical observations than in wild-type mice. Infection with Mycobacterium tuberculosis, Leishmania donovani, and Trypanosoma cruzi was well tolerated in 8HUM, permitting efficacy assessment. During such assessments, mouse-specific metabolic liabilities were bypassed while the impact of clinically relevant active metabolites and DDI on efficacy were well captured. Removal of species differences in metabolism by replacement of wild-type mice with 8HUM therefore reduces compound attrition while improving clinical translation, accelerating drug discovery.

A parallel glycolysis provides a selective advantage through rapid growth acceleration.

Glycolysis is a universal metabolic process that breaks down glucose to produce adenosine triphosphate (ATP) and biomass precursors. The Entner-Doudoroff (ED) pathway is a glycolytic pathway that parallels textbook glycolysis but yields half as much ATP. Accordingly, in organisms that possess both glycolytic pathways (for example, Escherichia coli), its raison d'être remains a mystery. In this study, we found that the ED pathway provides a selective advantage during growth acceleration. Upon carbon and nitrogen upshifts, E. coli accelerates growth faster with than without the ED pathway. Concurrent isotope tracing reveals that the ED pathway flux increases faster than that of textbook glycolysis. We attribute the fast response time of the ED pathway to its strong thermodynamic driving force and streamlining of glucose import. Intermittent nutrient supply manifests the evolutionary advantage of the parallel glycolysis; thus, the dynamic nature of an ostensibly redundant pathway's role in promoting rapid adaptation constitutes a metabolic design principle.

Long-term trends in human body size track regional variation in subsistence transitions and growth acceleration linked to dairying.

Evidence for a reduction in stature between Mesolithic foragers and Neolithic farmers has been interpreted as reflective of declines in health, however, our current understanding of this trend fails to account for the complexity of cultural and dietary transitions or the possible causes of phenotypic change. The agricultural transition was extended in primary centers of domestication and abrupt in regions characterized by demic diffusion. In regions such as Northern Europe where foreign domesticates were difficult to establish, there is strong evidence for natural selection for lactase persistence in relation to dairying. We employ broad-scale analyses of diachronic variation in stature and body mass in the Levant, Europe, the Nile Valley, South Asia, and China, to test three hypotheses about the timing of subsistence shifts and human body size, that: 1) the adoption of agriculture led to a decrease in stature, 2) there were different trajectories in regions of in situ domestication or cultural diffusion of agriculture; and 3) increases in stature and body mass are observed in regions with evidence for selection for lactase persistence. Our results demonstrate that 1) decreases in stature preceded the origins of agriculture in some regions; 2) the Levant and China, regions of in situ domestication of species and an extended period of mixed foraging and agricultural subsistence, had stable stature and body mass over time; and 3) stature and body mass increases in Central and Northern Europe coincide with the timing of selective sweeps for lactase persistence, providing support for the "Lactase Growth Hypothesis."

Epigenetic-based age acceleration in a representative sample of older Americans: Associations with aging-related morbidity and mortality.

Biomarkers developed from DNA methylation (DNAm) data are of growing interest as predictors of health outcomes and mortality in older populations. However, it is unknown how epigenetic aging fits within the context of known socioeconomic and behavioral associations with aging-related health outcomes in a large, population-based, and diverse sample. This study uses data from a representative, panel study of US older adults to examine the relationship between DNAm-based age acceleration measures in the prediction of cross-sectional and longitudinal health outcomes and mortality. We examine whether recent improvements to these scores, using principal component (PC)-based measures designed to remove some of the technical noise and unreliability in measurement, improve the predictive capability of these measures. We also examine how well DNAm-based measures perform against well-known predictors of health outcomes such as demographics, SES, and health behaviors. In our sample, age acceleration calculated using "second and third generation clocks," PhenoAge, GrimAge, and DunedinPACE, is consistently a significant predictor of health outcomes including cross-sectional cognitive dysfunction, functional limitations and chronic conditions assessed 2 y after DNAm measurement, and 4-y mortality. PC-based epigenetic age acceleration measures do not significantly change the relationship of DNAm-based age acceleration measures to health outcomes or mortality compared to earlier versions of these measures. While the usefulness of DNAm-based age acceleration as a predictor of later life health outcomes is quite clear, other factors such as demographics, SES, mental health, and health behaviors remain equally, if not more robust, predictors of later life outcomes.

Self-similar Rayleigh-Taylor mixing with accelerations varying in time and space.

As a ubiquitous paradigm of instabilities and mixing that occur in instances as diverse as supernovae, plasma fusion, oil recovery, and nanofabrication, the Rayleigh-Taylor (RT) problem is rightly regarded as important. The acceleration of the fluid medium in these instances often depends on time and space, whereas most past studies assume it to be constant or impulsive. Here, we analyze the symmetries of RT mixing for variable accelerations and obtain the scaling of correlations and spectra for classes of self-similar dynamics. RT mixing is shown to retain the memory of deterministic conditions for all accelerations, with the dynamics ranging from superballistic to subdiffusive. These results contribute to our understanding and control of the RT phenomena and reveal specific conditions under which Kolmogorov turbulence might be realized in RT mixing.

Distributed propulsion enables fast and efficient swimming modes in physonect siphonophores.

Many fishes employ distinct swimming modes for routine swimming and predator escape. These steady and escape swimming modes are characterized by dramatically differing body kinematics that lead to context-adaptive differences in swimming performance. Physonect siphonophores, such as Nanomia bijuga, are colonial cnidarians that produce multiple jets for propulsion using swimming subunits called nectophores. Physonect siphonophores employ distinct routine and steady escape behaviors but-in contrast to fishes-do so using a decentralized propulsion system that allows them to alter the timing of thrust production, producing thrust either synchronously (simultaneously) for escape swimming or asynchronously (in sequence) for routine swimming. The swimming performance of these two swimming modes has not been investigated in siphonophores. In this study, we compare the performances of asynchronous and synchronous swimming in N. bijuga over a range of colony lengths (i.e., numbers of nectophores) by combining experimentally derived swimming parameters with a mechanistic swimming model. We show that synchronous swimming produces higher mean swimming speeds and greater accelerations at the expense of higher costs of transport. High speeds and accelerations during synchronous swimming aid in escaping predators, whereas low energy consumption during asynchronous swimming may benefit N. bijuga during vertical migrations over hundreds of meters depth. Our results also suggest that when designing underwater vehicles with multiple propulsors, varying the timing of thrust production could provide distinct modes directed toward speed, efficiency, or acceleration.

The 103,200-arm acceleration dataset in the UK Biobank revealed a landscape of human sleep phenotypes.

SignificanceHuman sleep phenotypes are diversified by genetic and environmental factors, and a quantitative classification of sleep phenotypes would lead to the advancement of biomedical mechanisms underlying human sleep diversity. To achieve that, a pipeline of data analysis, including a state-of-the-art sleep/wake classification algorithm, the uniform manifold approximation and projection (UMAP) dimension reduction method, and the density-based spatial clustering of applications with noise (DBSCAN) clustering method, was applied to the 100,000-arm acceleration dataset. This revealed 16 clusters, including seven different insomnia-like phenotypes. This kind of quantitative pipeline of sleep analysis is expected to promote data-based diagnosis of sleep disorders and psychiatric disorders that tend to be complicated by sleep disorders.

Spiral Large-Dimension Microfluidic Channel for Flow-Rate- and Particle-Size-Insensitive Focusing by the Stabilization and Acceleration of Secondary Flow.

Inertial microfluidics has demonstrated its ability to focus particles in a passive and straightforward manner. However, achieving flow-rate- and particle-size-insensitive focusing in large-dimension channels with a simple design remains challenging. In this study, we developed a spiral microfluidic with a large-dimension channel to achieve inertial focusing. By designing a unique "big buffering area" and a "small buffering area" in the spiral microchannel, we observed the stabilization and acceleration of secondary flow. Our optimized design allowed for efficient (>99.9%) focusing of 15 µm particles within a wide range of flow rates (0.5-4.5 mL/min) during a long operation duration (0-60 min). Additionally, we achieved effective (>95%) focusing of different-sized particles (7, 10, 15, and 30 µm) and three types of tumor cells (K562, HeLa, and MCF-7) near the inner wall of the 1 mm wide outlet when applying different flow rates (1-3 mL/min). Finally, successful 3D cell focusing was achieved within an optimized device, with the cells positioned at a distance of 50 µm from the wall. Our strategy of stabilizing and accelerating Dean-like secondary flow through the unique configuration of a "big buffering area" and a "small buffering area" proved to be highly effective in achieving inertial focusing that is insensitive to the flow rate and particle size, particularly in large-dimension channels. Consequently, it shows great potential for use in hand-operated microfluidic tools for flow cytometry.

Percent duration of heart rate acceleration within the respiratory cycle: a novel approach to assess heart rate asymmetry.

Accelerations and decelerations of heart rate are nonsymmetrical in the magnitude and number of beat-to-beat changes. The asymmetric features of heart rate variability are related to respiratory durations. To explore the link between respiration and heart rate asymmetry (HRA), we evaluated 14 seated, healthy young adults who breathed with nine combinations of inspiration duration (TI) and expiration duration (TE), chosen respectively from 2, 4, and 6 s. A 5-min R-R interval (RRI) time series was obtained from each study period to construct an averaged pattern waveform relative to the respiratory cycle. We observed that the time interval between inspiration onset and RRI minimum progressively lengthened as TI and TE increased. The time interval between expiration onset and RRI maximum also lengthened when TE increased but shortened when TI increased. Consequently, TI and TE had different effects on the acceleration time (AT; from RRI maximum to RRI minimum) and deceleration time (DT; from RRI minimum to RRI maximum). The percentage of AT within the respiratory cycle showed a strong correlation with traditional Guzik's (r = 0.862, P < 0.001) and Porta's (r = 0.878, P < 0.001) indexes of HRA assessed in a Poincaré plot analysis. These findings suggest that, in addition to considering the magnitude and number of beat-to-beat changes, HRA can also be assessed based on another aspect: the duration of consecutive changes. The stepwise link between the duration of heart rate change and respiratory duration provides insight into the mechanisms connecting respiration to HRA.NEW & NOTEWORTHY In healthy adults who regulated their breathing across nine combinations of inspiration and expiration durations, we used averaged pattern waveform technique to quantify the durations of heart rate acceleration and deceleration within the respiratory cycle. The percent duration of acceleration showed a strong correlation with traditional heart rate asymmetry indexes, which evaluate the magnitude and number of beat-to-beat changes. This new approach opens a window to explore the asymmetric features of heart rate variability.

A mathematical model for velocity-selective arterial spin labeling.

PURPOSE: To present a theoretical framework that rigorously defines and analyzes key concepts and quantities for velocity selective arterial spin labeling (VSASL). THEORY AND METHODS: An expression for the VSASL arterial delivery function is derived based on (1) labeling and saturation profiles as a function of velocity and (2) physiologically plausible approximations of changes in acceleration and velocity across the vascular system. The dependence of labeling efficiency on the amplitude and effective bolus width of the arterial delivery function is defined. Factors that affect the effective bolus width are examined, and timing requirements to minimize quantitation errors are derived. RESULTS: The model predicts that a flow-dependent negative bias in the effective bolus width can occur when velocity selective inversion (VSI) is used for the labeling module and velocity selective saturation (VSS) is used for the vascular crushing module. The bias can be minimized by choosing a nominal labeling cutoff velocity that is lower than the nominal cutoff velocity of the vascular crushing module. CONCLUSION: The elements of the model are specified in a general fashion such that future advances can be readily integrated. The model can facilitate further efforts to understand and characterize the performance of VSASL and provide critical theoretical insights that can be used to design future experiments and develop novel VSASL approaches.

Movienet: Deep space-time-coil reconstruction network without k-space data consistency for fast motion-resolved 4D MRI.

PURPOSE: To develop a novel deep learning approach for 4D-MRI reconstruction, named Movienet, which exploits space-time-coil correlations and motion preservation instead of k-space data consistency, to accelerate the acquisition of golden-angle radial data and enable subsecond reconstruction times in dynamic MRI. METHODS: Movienet uses a U-net architecture with modified residual learning blocks that operate entirely in the image domain to remove aliasing artifacts and reconstruct an unaliased motion-resolved 4D image. Motion preservation is enforced by sorting the input image and reference for training in a linear motion order from expiration to inspiration. The input image was collected with a lower scan time than the reference XD-GRASP image used for training. Movienet is demonstrated for motion-resolved 4D MRI and motion-resistant 3D MRI of abdominal tumors on a therapeutic 1.5T MR-Linac (1.5-fold acquisition acceleration) and diagnostic 3T MRI scanners (2-fold and 2.25-fold acquisition acceleration for 4D and 3D, respectively). Image quality was evaluated quantitatively and qualitatively by expert clinical readers. RESULTS: The reconstruction time of Movienet was 0.69 s (4 motion states) and 0.75 s (10 motion states), which is substantially lower than iterative XD-GRASP and unrolled reconstruction networks. Movienet enables faster acquisition than XD-GRASP with similar overall image quality and improved suppression of streaking artifacts. CONCLUSION: Movienet accelerates data acquisition with respect to compressed sensing and reconstructs 4D images in less than 1 s, which would enable an efficient implementation of 4D MRI in a clinical setting for fast motion-resistant 3D anatomical imaging or motion-resolved 4D imaging.

Assessing the association of epigenetic age acceleration with osteoarthritis in the Multicenter Osteoarthritis Study (MOST).

PURPOSE: Advancing age is one of the strongest risk factors for osteoarthritis (OA). DNA methylation-based measures of epigenetic age acceleration may provide insights into mechanisms underlying OA. METHODS: We analyzed data from the Multicenter Osteoarthritis Study in a subset of 671 participants ages 45-69 years with no or mild radiographic knee OA. DNA methylation was assessed with the Illumina Infinium MethylationEPIC 850K array. We calculated predicted epigenetic age according to Hannum, Horvath, PhenoAge, and GrimAge epigenetic clocks, then regressed epigenetic age on chronological age to obtain the residuals. Associations between the residuals and knee, hand, and multi-joint OA were assessed using logistic regression, adjusted for chronological age, sex, clinical site, smoking status, and race. RESULTS: Twenty-three percent met criteria for radiographic hand OA, 25% met criteria for radiographic knee OA, and 8% met criteria for multi-joint OA. Mean chronological age (SD) was 58.4 (6.7) years. Mean predicted epigenetic age (SD) according to Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks was 64.9 (6.4), 68.6 (5.9), 50.5 (7.7), and 67.0 (6.2), respectively. Horvath epigenetic age acceleration was not associated with an increased odds of hand OA, odds ratio (95% confidence intervals) = 1.03 (0.99-1.08), with similar findings for knee and multi-joint OA. We found similar magnitudes of associations for Hannum epigenetic age, PhenoAge, and GrimAge acceleration compared to Horvath epigenetic age acceleration. CONCLUSIONS: Epigenetic age acceleration as measured by various well-validated epigenetic clocks based on DNA methylation was not associated with increased risk of knee, hand, or multi-joint OA independent of chronological age.

Solar-induced chlorophyll fluorescence captures the effects of elevated ozone on canopy structure and acceleration of senescence in soybean.

Solar-induced chlorophyll fluorescence (SIF) provides an opportunity to rapidly and non-destructively investigate how plants respond to stress. Here, we explored the potential of SIF to detect the effects of elevated O3 on soybean in the field where soybean was subjected to ambient and elevated O3 throughout the growing season in 2021. Exposure to elevated O3 resulted in a significant decrease in canopy SIF at 760 nm (SIF760), with a larger decrease in the late growing season (36%) compared with the middle growing season (13%). Elevated O3 significantly decreased the fraction of absorbed photosynthetically active radiation by 8-15% in the middle growing season and by 35% in the late growing stage. SIF760 escape ratio (fesc) was significantly increased under elevated O3 by 5-12% in the late growth stage due to a decrease of leaf chlorophyll content and leaf area index. Fluorescence yield of the canopy was reduced by 5-11% in the late growing season depending on the fesc estimation method, during which leaf maximum carboxylation rate and maximum electron transport were significantly reduced by 29% and 20% under elevated O3. These results demonstrated that SIF could capture the elevated O3 effect on canopy structure and acceleration of senescence in soybean and provide empirical support for using SIF for soybean stress detection and phenotyping.

Heart rate reduction during voluntary deep diving in free-ranging loggerhead sea turtles.

Air-breathing vertebrates exhibit cardiovascular responses to diving including heart rate reduction (diving bradycardia). Field studies on aquatic mammals and birds have shown that the intensity of bradycardia can vary depending on diving behaviour, such as the depth of dives and dive duration. However, in aquatic reptiles, the variation in heart rate during deep dives under natural conditions has not been fully investigated. In this study, we released five loggerhead sea turtles (Caretta caretta) outfitted with recorders into the sea and recorded their electrocardiogram, depth, water temperature and longitudinal acceleration. After 3 days, the recorders automatically detached from the turtles. The heart rate signals were detected from the electrodes placed on the surface of the plastron. The mean (±s.d.) heart rate of 12.8±4.1 beats min-1 during dives was significantly lower than that of 20.9±4.1 beats min-1 during surface periods. Heart rate during dives varied with dive depth, although it remained lower than that at the surface. When the turtle dived deeper than 140 m, despite the relatively high flipper stroke rate (approximately 19 strokes min-1), the heart rate dropped rapidly to approximately 2 beats min-1 temporarily. The minimum instantaneous heart rate during dives was lower at deeper dive depths. Our results indicate that loggerhead sea turtles show variations in the intensity of diving bradycardia depending on their diving behaviour, similar to that shown by marine mammals and birds.

Hepatobiliary phase imaging in cirrhotic patients using compressed sensing and controlled aliasing in parallel imaging results in higher acceleration.

OBJECTIVE: We aimed to compare the image quality and focal lesion detection ability of hepatobiliary phase (HBP) images obtained using compressed sensing (CS) and controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) in patients with liver cirrhosis. MATERIALS AND METHODS: We retrospectively included 244 gadoxetic acid-enhanced liver MRI from 244 patients with cirrhosis obtained by two HBP images using CS and CAIPIRINHA from July 2020 to December 2020. The optimized resolution and scan time for CS-HBP and CAIPIRINHA-HBP were 0.9 × 0.9 × 1.5 mm3 and 15 s and 1.3 × 1.3 × 3 mm3 and 16 s, respectively. We compared the image quality between the two sets of images in 244 patients and focal lesion (n = 294) analyses for 112 patients. RESULTS: CS-HBP showed comparable overall image quality (3.7 ± 0.9 vs. 3.6 ± 0.8, p = 0.680), superior liver edge sharpness (3.9 ± 0.6 vs. 3.6 ± 0.5, p < 0.001), and fewer respiratory motion artifacts (4.0 ± 0.7 vs. 3.8 ± 0.5, p < 0.001), but higher non-respiratory artifacts (3.4 ± 0.7 vs. 3.6 ± 0.6, p < 0.001) and subjective image noise (3.5 ± 0.8 vs. 3.6 ± 0.7, p = 0.014) than CAIPIRINHA-HBP. CS-HBP showed a higher signal-to-noise ratio in the liver than CAIPIRINHA-HBP (20.9 ± 9.0 vs. 18.9 ± 7.1, p = 0.008). The pooled sensitivity, specificity, and AUC were 90.0%, 77.5%, and 0.84 for CS-HBP and 73.5%, 82.4%, and 0.78 for CAIPIRINHA-HBP, respectively. CONCLUSIONS: CS-HBP showed better focal lesion detection ability, comparable overall image quality, and fewer respiratory motion artifacts, but higher non-respiratory artifacts and noise compared to CAIPIRINHA-HBP. Thus, CS-HBP could be recommended for liver MRI in patients with cirrhosis to improve diagnostic performance. CLINICAL RELEVANCE STATEMENT: Thin-slice CS-HBP may be useful for detecting sub-centimeter hepatocellular carcinoma in cirrhotic patients with Child-Pugh classification A while maintaining comparable subjective image quality. KEY POINTS: • Compared with controlled aliasing in parallel imaging results in higher acceleration, compressed sensing hepatobiliary phase yielded thinner slices and shorter scan time at a higher accelerating factor. • Compressed sensing hepatobiliary phase showed comparable overall image quality, superior liver edge sharpness, and fewer respiratory motion artifacts, but higher non-respiratory artifacts and subjective image noise than controlled aliasing in parallel imaging results in higher acceleration-hepatobiliary phase. • Compressed sensing hepatobiliary phase can detect sub-centimeter hepatocellular carcinoma in cirrhotic patients with Child-Pugh classification A.