The mechanisms by which sister chromatids maintain biorientation on the metaphase spindle are critical to the fidelity of chromosome segregation. Active force interplay exists between predominantly extensional microtubule-based spindle forces and restoring forces from chromatin. These forces regulate tension at the kinetochore that silences the spindle assembly checkpoint to ensure faithful chromosome segregation. Depletion of pericentric cohesin or condensin has been shown to increase the mean and variance of spindle length, which have been attributed to a softening of the linear chromatin spring. Models of the spindle apparatus with linear chromatin springs that match spindle dynamics fail to predict the behavior of pericentromeric chromatin in wild-type and mutant spindles. We demonstrate that a nonlinear spring with a threshold extension to switch between spring states predicts asymmetric chromatin stretching observed in vivo. The addition of cross-links between adjacent springs recapitulates coordination between pericentromeres of neighboring chromosomes.
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http://dx.doi.org/10.1083/jcb.201208163 | DOI Listing |
Clin Pharmacokinet
December 2024
Department of Anesthesiology, University of Groningen, University Medical Center Groningen, P. O. Box 30001, 9700 RB, Groningen, The Netherlands.
Background And Objectives: The pharmacokinetics (PK) of piperacillin/tazobactam (PIP/TAZ) is highly variable across different patient populations and there are controversies regarding non-linear elimination as well as the fraction unbound of PIP (f). This has led to a plethora of subgroup-specific models, increasing the risk of misusing published models when optimising dosing regimens. In this study, we aimed to develop a single model to simultaneously describe the PK of PIP/TAZ in diverse patient populations and evaluate the current dosing recommendations by predicting the PK/pharmacodynamics (PD) target attainment throughout life.
View Article and Find Full Text PDFJ Math Biol
December 2024
School of Mathematics and Statistics, The University of Melbourne, Parkville, Australia.
The epidemiological behavior of Plasmodium vivax malaria occurs across spatial scales including within-host, population, and metapopulation levels. On the within-host scale, P. vivax sporozoites inoculated in a host may form latent hypnozoites, the activation of which drives secondary infections and accounts for a large proportion of P.
View Article and Find Full Text PDFJ Multidiscip Healthc
December 2024
Department of Pediatrics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People's Republic of China.
Purpose: To assess seasonal variations in infant colic (IC) prevalence and explore the association between climate factors, including temperature, air pollutants, and their interactions, with IC.
Methods: Medical records of 1955 infants aged 0-3 months from October 2021 to September 2022 were analyzed, with IC diagnosed according to Rome IV criteria. Seasonal differences in IC prevalence were compared using chi-square tests.
Am J Ind Med
December 2024
Zenith American Solutions, Oak Ridge, Tennessee, USA.
Compr Physiol
December 2024
School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USA.
The evolution of mechanisms for terrestrial locomotion has resulted in multi-segmented limbs that allow navigation on irregular terrains, changing of direction, manipulation of external objects, and control over the mechanical properties of limbs important for interaction with the environment, with corresponding changes in neural pathways in the spinal cord. This article is focused on the organization of these pathways, their interactions with the musculoskeletal system, and the integration of these neuromechanical circuits with supraspinal mechanisms to control limb impedance. It is argued that neural pathways from muscle spindles and Golgi tendon organs form a distributive impedance controller in the spinal cord that controls limb impedance and coordination during responses to external disturbances.
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