Koldingwhitaker5627

A drastic transition at birth, from constant maternal nutrient supply in utero to intermittent postnatal feeding, requires changes in the metabolic system of the neonate. Despite their central role in metabolic homeostasis, little is known about how pancreatic β cells adjust to the new nutritional challenge. Here, we find that after birth β cell function shifts from amino acid- to glucose-stimulated insulin secretion in correlation with the change in the nutritional environment. This adaptation is mediated by a transition in nutrient sensitivity of the mTORC1 pathway, which leads to intermittent mTORC1 activity. Disrupting nutrient sensitivity of mTORC1 in mature β cells reverts insulin secretion to a functionally immature state. Finally, manipulating nutrient sensitivity of mTORC1 in stem cell-derived β cells in vitro strongly enhances their glucose-responsive insulin secretion. AZD5991 These results reveal a mechanism by which nutrients regulate β cell function, thereby enabling a metabolic adaptation for the newborn. Published by Elsevier Inc.Bacteria tumble periodically, following environmental cues. Whether they can tumble near a solid surface is a basic issue for the inception of infection or mineral biofouling. Observing freely swimming Escherichia coli near and parallel to a glass surface imaged at high magnification (×100) and high temporal resolution (500 Hz), we identified tumbles as events starting (or finishing, respectively) in abrupt deceleration (or reacceleration, respectively) of the body motion. Selected events show an equiprobable clockwise (CW) or counterclockwise change in direction that is superimposed on a surface CW path because of persistent propulsion. These tumbles follow a common long (about 300 ± 100 ms, N = 52) deceleration-reorientation-acceleration pattern. A wavelet transform multiscale analysis shows these tumbles cause in-plane diffusive reorientations with 1.5 rad2/s rotational diffusivity, a value that compares with that measured in bulk tumbles. In half of the cases, additional few-millisecond bursts of an almost equiprobable CW or counterclockwise change of direction (12 ± 90°, N = 89) occur within the reorientation stage. The highly dispersed absolute values of change of direction (70 ± 66°, N = 89) of only a few bursts destabilize the cell-swimming direction. These first observations of surface tumbles set a foundation for statistical models of run-and-tumble surface motion different from that in bulk and lend support for chemotaxis near solid surface. We discuss new developments in the nonequilibrium dynamics and thermodynamics of living systems, giving a few examples to demonstrate the importance of nonequilibrium thermodynamics for understanding biological dynamics and functions. We study single-molecule enzyme dynamics, in which the nonequilibrium thermodynamic and dynamic driving forces of chemical potential and flux are crucial for the emergence of non-Michaelis-Menten kinetics. We explore single-gene expression dynamics, in which nonequilibrium dissipation can suppress fluctuations. We investigate the cell cycle and identify the nutrition supply as the energy input that sustains the stability, speed, and coherence of cell cycle oscillation, from which the different vital phases of the cell cycle emerge. We examine neural decision-making processes and find the trade-offs among speed, accuracy, and thermodynamic costs that are important for neural function. Lastly, we consider the thermodynamic cost for specificity in cellular signaling and adaptation.Recent advances in theory and algorithms for atomically detailed simulations open the way to the study of the kinetics of a wide range of molecular processes in biophysics. The theories propose a shift from the traditionally very long molecular dynamic trajectories, which are exact but may not be efficient in the study of kinetics, to the use of a large number of short trajectories. The short trajectories exploit a mapping to a mesh in coarse space and allow for efficient calculations of kinetics and thermodynamics. In this review, I focus on one theory Milestoning is a theory and an algorithm that offers a hierarchical calculation of properties of interest, such as the free energy profile and the mean first passage time. Approximations to the true long-time dynamics can be computed efficiently and assessed at different steps of the investigation. The theory is discussed and illustrated using two biophysical examples ion permeation through a phospholipid membrane and protein translocation through a channel.Determining whether and how a gene is transcribed are two of the central processes of life. The conceptual basis for understanding such gene regulation arose from pioneering biophysical studies in eubacteria. However, eukaryotic genomes exhibit vastly greater complexity, which raises questions not addressed by this bacterial paradigm. First, how is information integrated from many widely separated binding sites to determine how a gene is transcribed? Second, does the presence of multiple energy-expending mechanisms, which are absent from eubacterial genomes, indicate that eukaryotes are capable of improved forms of genetic information processing? An updated biophysical foundation is needed to answer such questions. We describe the linear framework, a graph-based approach to Markov processes, and show that it can accommodate many previous studies in the field. Under the assumption of thermodynamic equilibrium, we introduce a language of higher-order cooperativities and show how it can rigorously quantify gene regulatory properties suggested by experiment. We point out that fundamental limits to information processing arise at thermodynamic equilibrium and can only be bypassed through energy expenditure. Finally, we outline some of the mathematical challenges that must be overcome to construct an improved biophysical understanding of gene regulation.The notion of a U shape in happiness-that well-being is highest for people in their 20s, decreases to its nadir in midlife, and then rises into old age-has captured the attention of the media, which often cite it as evidence for a midlife crisis. We argue that support for the purported U shape is not as robust and generalizable as is often assumed and present our case with the following arguments (a) Cross-sectional studies are inadequate for drawing conclusions about within-person change in happiness across the life span; (b) cross-sectional evidence with respect to the ubiquity and robustness of the U shape in general levels of happiness and life satisfaction is mixed; (c) longitudinal support for the U shape in happiness and life satisfaction is also mixed; (d) longitudinal research on subjective indicators of well-being other than general levels of happiness and life satisfaction challenges the U shape; (e) when asked to reflect on their lives, older adults tend to recall midlife as one of the more positive periods; and (f) a focus on a single trajectory of well-being is of limited scientific and applied value because it obscures the diversity in pathways throughout life as well as its sources.