The shift in the torque- and force-fascicle length curves during submaximal voluntary contraction have potential implications for human locomotion (e.g. walking) as the operating range of fascicles shifts to the ascending limb, where muscle force capacity is reduced by at least 15%. These data demonstrate the need to match activity levels during construction of the torque- and force-fascicle length curves to activity levels achieved during movement to better characterize the lengths that muscles operate at relative to their optimum during a specific task.Among the many factors that influence the cardiovascular adjustments of marine mammals is the act of respiration at the surface, which facilitates rapid gas exchange and tissue re-perfusion between dives. selleck products We measured heart rate (fH) in six adult male bottlenose dolphins (Tursiops truncatus) spontaneously breathing at the surface to quantify the relationship between respiration and fH, and compared this with fH during submerged breath-holds. We found that dolphins exhibit a pronounced respiratory sinus arrhythmia (RSA) during surface breathing, resulting in a rapid increase in fH after a breath followed by a gradual decrease over the following 15-20 s to a steady fH that is maintained until the following breath. RSA resulted in a maximum instantaneous fH (ifH) of 87.4±13.6 beats min-1 and a minimum ifH of 56.8±14.8 beats min-1, and the degree of RSA was positively correlated with the inter-breath interval (IBI). The minimum ifH during 2 min submerged breath-holds where dolphins exhibited submersion bradycardia (36.4±9.0 beats min-1) was lower than the minimum ifH observed during an average IBI; however, during IBIs longer than 30 s, the minimum ifH (38.7±10.6 beats min-1) was not significantly different from that during 2 min breath-holds. These results demonstrate that the fH patterns observed during submerged breath-holds are similar to those resulting from RSA during an extended IBI. Here, we highlight the importance of RSA in influencing fH variability and emphasize the need to understand its relationship to submersion bradycardia.The role of trunk orientation during uneven running is not well understood. This study compared the running mechanics during the approach step to and the step down for a 10 cm expected drop, positioned halfway through a 15 m runway, with that of the level step in 12 participants at a speed of 3.5 m s-1 while maintaining self-selected (17.7±4.2 deg; mean±s.d.), posterior (1.8±7.4 deg) and anterior (26.6±5.6 deg) trunk leans from the vertical. Our findings reveal that the global (i.e. the spring-mass model dynamics and centre-of-mass height) and local (i.e. knee and ankle kinematics and kinetics) biomechanical adjustments during uneven running are specific to the step nature and trunk posture. Unlike the anterior-leaning posture, running with a posterior trunk lean is characterized by increases in leg angle, leg compression, knee flexion angle and moment, resulting in a stiffer knee and a more compliant spring-leg compared with the self-selected condition. In the approach step versus the level step, reductions in leg length and stiffness through the ankle stiffness yield lower leg force and centre-of-mass position. Contrariwise, significant increases in leg length, angle and force, and ankle moment, reflect in a higher centre-of-mass position during the step down. Plus, ankle stiffness significantly decreases, owing to a substantially increased leg compression. Overall, the step down appears to be dominated by centre-of-mass height changes, regardless of having a trunk lean. Observed adjustments during uneven running can be attributed to anticipation of changes to running posture and height. These findings highlight the role of trunk posture in human perturbed locomotion relevant for the design and development of exoskeleton or humanoid bipedal robots.Some marine birds and mammals can perform dives of extraordinary duration and depth. Such dive performance is dependent on many factors, including total body oxygen (O2) stores. For diving penguins, the respiratory system (air sacs and lungs) constitutes 30-50% of the total body O2 store. To better understand the role and mechanism of parabronchial ventilation and O2 utilization in penguins both on the surface and during the dive, we examined air sac partial pressures of O2 (PO2 ) in emperor penguins (Aptenodytes forsteri) equipped with backpack PO2 recorders. Cervical air sac PO2 values at rest were lower than in other birds, while the cervical air sac to posterior thoracic air sac PO2 difference was larger. Pre-dive cervical air sac PO2 values were often greater than those at rest, but had a wide range and were not significantly different from those at rest. The maximum respiratory O2 store and total body O2 stores calculated with representative anterior and posterior air sac PO2 data did not differ from prior estimates. The mean calculated anterior air sac O2 depletion rate for dives up to 11 min was approximately one-tenth that of the posterior air sacs. Low cervical air sac PO2 values at rest may be secondary to a low ratio of parabronchial ventilation to parabronchial blood O2 extraction. During dives, overlap of simultaneously recorded cervical and posterior thoracic air sac PO2 profiles supported the concept of maintenance of parabronchial ventilation during a dive by air movement through the lungs.

Extracellular matrix (ECM) component hyaluronan (HA) facilitates malignant phenotypes of glioblastoma (GBM), however, whether HA impacts response to GBM immunotherapies is not known. Herein, we investigated whether degradation of HA enhances oncolytic virus immunotherapy for GBM.

Presence of HA was examined in patient and murine GBM. Hyaluronidase-expressing oncolytic adenovirus, ICOVIR17, and its parental virus, ICOVIR15, without transgene, were tested to determine if they increased animal survival and modulated the immune tumor microenvironment (TME) in orthotopic GBM. HA regulation of NF-κB signaling was examined in virus-infected murine macrophages. We combined ICOVIR17 with PD-1 checkpoint blockade and assessed efficacy and determined mechanistic contributions of tumor-infiltrating myeloid and T cells.

Treatment of murine orthotopic GBM with ICOVIR17 increased tumor-infiltrating CD8

T cells and macrophages, and upregulated PD-L1 on GBM cells and macrophages, leading to prolonged animal survival, compared with control virus ICOVIR15.