A calcineurin-Hoxb13 axis regulates growth mode of mammalian cardiomyocytes.

A major factor in the progression to heart failure in humans is the inability of the adult heart to repair itself after injury. We recently demonstrated that the early postnatal mammalian heart is capable of regeneration following injury through proliferation of preexisting cardiomyocytes1,2 and that Meis1, a three amino acid loop extension (TALE) family homeodomain transcription factor, translocates to cardiomyocyte nuclei shortly after birth and mediates postnatal cell cycle arrest3. Here we report that Hoxb13 acts as a cofactor of Meis1 in postnatal cardiomyocytes. Cardiomyocyte-specific deletion of Hoxb13 can extend the postnatal window of cardiomyocyte proliferation and reactivate the cardiomyocyte cell cycle in the adult heart. Moreover, adult Meis1-Hoxb13 double-knockout hearts display widespread cardiomyocyte mitosis, sarcomere disassembly and improved left ventricular systolic function following myocardial infarction, as demonstrated by echocardiography and magnetic resonance imaging. Chromatin immunoprecipitation with sequencing demonstrates that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and cell cycle. Finally, we show that the calcium-activated protein phosphatase calcineurin dephosphorylates Hoxb13 at serine-204, resulting in its nuclear localization and cell cycle arrest. These results demonstrate that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and proliferation and provide mechanistic insights into the link between hyperplastic and hypertrophic growth of cardiomyocytes.

Noninvasive Estimation of Hydration Status in Athletes Using Wearable Sensors and a Data-Driven Approach Based on Orthostatic Changes.

Dehydration beyond 2% bodyweight loss should be monitored to reduce the risk of heat-related injuries during exercise. However, assessments of hydration in athletic settings can be limited in their accuracy and accessibility. In this study, we sought to develop a data-driven noninvasive approach to measure hydration status, leveraging wearable sensors and normal orthostatic movements. Twenty participants (10 males, 25.0 ± 6.6 years; 10 females, 27.8 ± 4.3 years) completed two exercise sessions in a heated environment: one session was completed without fluid replacement. Before and after exercise, participants performed 12 postural movements that varied in length (up to 2 min). Logistic regression models were trained to estimate dehydration status given their heart rate responses to these postural movements. The area under the receiver operating characteristic curve (AUROC) was used to parameterize the model's discriminative ability. Models achieved an AUROC of 0.79 (IQR: 0.75, 0.91) when discriminating 2% bodyweight loss. The AUROC for the longer supine-to-stand postural movements and shorter toe-touches were similar (0.89, IQR: 0.89, 1.00). Shorter orthostatic tests achieved similar accuracy to clinical tests. The findings suggest that data from wearable sensors can be used to accurately estimate mild dehydration in athletes. In practice, this method may provide an additional measurement for early intervention of severe dehydration.

Post-Drive Standing Balance of Vehicle Passengers Using Wearable Sensors: The Effect of On-Road Driving and Task Performance.

Postural sway has been demonstrated to increase following exposure to different types of motion. However, limited prior studies have investigated the relationship between exposure to normative on-road driving conditions and standing balance following the exposure. The purpose of this on-road study was to quantify the effect of vehicle motion and task performance on passengers' post-drive standing balance performance. In this study, trunk-based kinematic data were captured while participants performed a series of balance exercises before and after an on-road driving session in real-time traffic. Postural sway for all balance exercises increased following the driving session. Performing a series of ecologically relevant visual-based tasks led to increases in most post-drive balance metrics such as sway position and velocity. However, the post-drive changes following the driving session with a task were not significantly different compared to changes observed following the driving session without a task. The post-drive standing balance performance changes observed in this study may increase vulnerable users' risk of falling. Wearable sensors offer an opportunity to monitor postural sway following in-vehicle exposures.

Motion sickness in passenger vehicles during test track operations.

As automation transforms drivers into passengers, the deployment of automated vehicles (AVs) has the potential to greatly increase the incidence of motion sickness. A study was conducted to quantify motion sickness response of front-seat passengers performing ecologically relevant passenger activities during conditions consistent with driving on public roadways. Fifty-two adults with a large range of self-reported levels of motion sickness susceptibility and age participated in data collection on a closed test track in a passenger sedan. Motion sickness ratings increased with task vs. no-task and moderate vs. low acceleration test conditions. Increased motion sickness susceptibility was associated with higher motion sickness ratings. In comparison to older participants (age > 60), younger participants (age < 60) experienced increased motion sickness. This is the first in-vehicle study that systematically compared normative passenger activities and acceleration magnitudes typical of normative driving conditions on motion sickness response for a large, diverse sample of passengers, enabling the exploration of the effects of covariates. Practitioner summary: The data demonstrate that a relatively large range of motion sickness response can be expected to result from passengers performing visual tasks in passenger vehicles. Measurement and modelling efforts should seek to elucidate relationships among the factors contributing to motion sickness for the purpose of informing and prioritising future countermeasures for automated vehicles (AVs). Abbreviations: AV(S): automated vehicles; BMI: body mass index; BVP: blood volume pulse; EDA: electrodermal activity; FMS: fast motion sickness scale; GPS: global positioning system; IMU: inertial measurement unit; ISO: International Organization for Standardization; MISC: misery scale; MSDV: motion sickness dose value; NDS: naturalistic driving study; SAE: Society of Automotive Engineers International; UMTRI: The University of Michigan Transportation Research Institute Key Aspect of Research: Motion sickness may be an important barrier to widespread adoption of automated vehicles @UMTRI.

Muscle stem cells as immunomodulator during regeneration.

The skeletal muscle is well known for its remarkable ability to regenerate after injuries. The regeneration is a complex and dynamic process that involves muscle stem cells (also called muscle satellite cells, MuSCs), fibro-adipogenic progenitors (FAPs), immune cells, and other muscle-resident cell populations. The MuSCs are the myogenic cell populaiton that contribute nuclei directly to the regenerated myofibers, while the other cell types collaboratively establish a microenvironment that facilitates myogenesis of MuSCs. The myogenic process includes activation, proliferation and differentiationof MuSCs, and subsequent fusion their descendent mononuclear myocytes into multinuclear myotubes. While the contributions of FAPs and immune cells to this microenvironment have been well studied, the influence of MuSCs on other cell types remains poorly understood. This review explores recent evidence supporting the potential role of MuSCs as immunomodulators during muscle regeneration, either through cytokine production or ligand-receptor interactions.