Correction: Neuropsychopharmacology Volume 50 Issue 2
Related Articles
Mechanochemical bistability of intestinal organoids enables robust morphogenesis
Reproducible pattern and form generation during embryogenesis is poorly understood. Intestinal organoid morphogenesis involves a number of mechanochemical regulators such as cell-type-specific cytoskeletal forces and osmotically driven lumen volume changes. It is unclear how these forces are coordinated in time and space to ensure robust morphogenesis. Here we show how mechanosensitive feedback on cytoskeletal tension gives rise to morphological bistability in a minimal model of organoid morphogenesis. In the model, lumen volume changes can impact the epithelial shape via both direct mechanical and indirect mechanosensitive mechanisms. We find that both bulged and budded crypt states are possible and dependent on the history of volume changes. We test key modelling assumptions via biophysical and pharmacological experiments to demonstrate how bistability can explain experimental observations, such as the importance of the timing of lumen shrinkage and robustness of the final morphogenetic state to mechanical perturbations. This suggests that bistability arising from feedback between cellular tensions and fluid pressure could be a general mechanism that coordinates multicellular shape changes in developing systems.
Increased crevassing across accelerating Greenland Ice Sheet margins
Surface crevassing on the Greenland Ice Sheet is a large source of uncertainty in processes controlling mass loss due to a lack of comprehensive observations of their location and evolution through time. Here we use high-resolution digital elevation models to map the three-dimensional volume of crevasse fields across the Greenland Ice Sheet in 2016 and 2021. We show that, between the two years, large and significant increases in crevasse volume occurred at marine-terminating sectors with accelerating flow (up to +25.3 ± 10.1% in the southeast sector), while the change in total ice-sheet-wide crevasse volume was within measurement error (+4.3 ± 5.9%). The sectoral increases were offset by a reduction in crevasse volume in the central west sector (−14.2 ± 3.2%), particularly at Sermeq Kujalleq (Jakobshavn Isbræ), which exhibited slowdown and thickening over the study period. Changes in crevasse volume correlate strongly with antecedent discharge changes, indicating that the acceleration of ice flow in Greenland forces significant increases in crevassing on a timescale of less than five years. This response provides a mechanism for mass-loss-promoting feedbacks on sub-decadal timescales, including increased calving, faster flow and accelerated water transfer to the bed.
Frequency shift caused by nonuniform field and boundary relaxation in magnetic resonance and comagnetometers
In magnetic resonance experiments, it is widely recognized that a nonuniform magnetic field can lead to an increase in the resonance line width, as well as a reduction in sensitivity and spectral resolution. However, a nonuniform magnetic field can also cause shifts in resonance frequency, which has received far less attention. In this work, we investigate the frequency shift caused by boundary relaxation and nonuniform magnetic field with arbitrary spatial distribution. We find that this frequency shift is spin-species dependent, implying a systematic error in NMR gyroscopes and comagnetometers. The first order correction to this systematic error is proportional to the difference of boundary relaxation rate, and dominates for small cells. In contrast, the third and higher order corrections arise from the difference of gyromagnetic ratios of spin species, and dominates for large cells. This insight helps understanding the unexplained isotope shifts in recent NMR gyroscopes and new physics searching experiments that utilize comagnetometers. Finally, we propose a tool for wall interaction research based on the frequency shift’s dependency on boundary relaxation.
PGRMC2 is a pressure-volume regulator critical for myocardial responses to stress in mice
Progesterone receptors are classified into nuclear and membrane-bound receptor families. Previous unbiased proteomic studies indicate a potential association between cardiac diseases and the progesterone receptor membrane-bound component-2 (PGRMC2); however, the role of PGRMC2 in the heart remains unknown. In this study, we use a heart-specific knockout (KO) mouse model (MyH6•Pgrmc2flox/flox) in which the Pgrmc2 gene was selectively deleted in cardiomyocytes. Here we show that PGRMC2 serves as a mediator of steroid hormones for rapid calcium signaling in cardiomyocytes to maintain cardiac contraction, sufficient stroke volume, and adequate cardiac output by regulating the cardiac pressure-volume relationship. The KO hearts from male and female mice exhibit an impairment in pressure-volume relationship. Under hypoxic conditions, this pressure-volume dysregulation progresses to congestive left and right ventricular failure in the KO hearts. Overall, we propose that PGRMC2 is a cardiac pressure-volume regulator to maintain normal cardiac physiology, especially during hypoxic stress.
Cognitive reserve is associated with education, social determinants, and cognitive outcomes among older American Indians in the Strong Heart Study
Cognitive reserve, a component of resilience, may be conceptualized as the ability to overcome accumulating neuropathology and maintain healthy aging and function. However, research measuring and evaluating it in American Indians is needed. We recruited American Indians from 3 regional centers for longitudinal examinations (2010-13, n = 818; 2017-19, n = 403) including MRI, cognitive, clinical, and questionnaire data. We defined cognitive reserve by measuring the residual from individual regressions of cognitive tests over imaged brain volumes, adjusted for age and sex. Analyses examined three different metrics of cognitive reserve against sociodemographic, clinical, and longitudinal cognitive data in causal mediation models. Better cognitive reserve was significantly associated with more education, higher income, lower prevalence of depression, lower prevalence of diabetes, and lower prevalence of kidney disease, but we found no statistically significant evidence for an association with plasma biomarkers for Alzheimer’s disease and related dementias, APOE e4 carrier status, alcohol use, body mass, or hypertension. Better cognitive reserve was associated with better cognitive function over mean 6.7 years follow-up (range 4-9 years); and the association for education with cognition over time was mediated in part (15-24%) by cognitive reserve. Cognitive reserve, although challenging to measure, appears important for understanding the range of cognitive aging in American Indians.
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