- Neuromuscular Function and Blood Flow Occlusion with Dynamic Arm Flexor Contractions. [Journal Article]
- MSMed Sci Sports Exerc 2019 Jul 16
- CONCLUSIONS: Concentric elbow flexions at low-force with BFO causes greater impairments in strength and power than HF and therefore may be a replacement for high-force exercise used in chronic training.
- Characterization of performance fatigability during a self-paced exercise. [Journal Article]
- JAJ Appl Physiol (1985) 2019 Jul 18
- Pacing during a high-intensity cycling time trial (TT) appears to prevent premature task failure, but the performance fatigability during a self-paced exercise is currently unknown. Therefore, the cu…
Pacing during a high-intensity cycling time trial (TT) appears to prevent premature task failure, but the performance fatigability during a self-paced exercise is currently unknown. Therefore, the current study characterized the time-course of performance fatigability during a 4-km TT. Eleven male cyclists performed three separated TTs in a crossover counterbalanced design. The TTs lasted until the end of the fast-start (FS, 600 ± 205 m), even-pace (EP, 3600 ± 190 m) and end-spurt (ES, 4000 m) phases. Performance fatigability was characterized by using isometric maximal voluntary contractions (IMVC), while the muscle activation [i.e., voluntary activation (VA)] and contractile function of knee extensors [i.g., peak torque of potentiated twitches (TwPt)] were evaluated using electrically-evoked contractions performed (PRE) and 1 min after (POST) each specific part of the trial. Gas exchange, power output (PO) and electromyographic activity (EMG) were also recorded. EMG/PO showed an abrupt increase followed by a continuous decrease towards the end of FS resulting in a drop on IMVC (-12%), VA (-8%) and TwPt (-23%). EMG/PO was stable during EP, with no additional drop on IMVC, VA and TwPt (-12%, -6% and -22%, respectively). EMG/PO increased abruptly during the ES, but there was no change on IMVC, VA and TwPt (-13%, -8% and -26%, respectively). These findings demonstrate that the performance fatigability during a self-paced exercise is characterized by a large drop on contractile function and muscle activation at beginning of the trial (i.e., FS), without additional change during the middle and end phases (i.e., EP and ES).
- Myosin IIA-mediated forces regulate multicellular integrity during vascular sprouting. [Journal Article]
- MBMol Biol Cell 2019 Jul 18; :mbcE19020076
- Angiogenic sprouting is a critical process involved in vascular network formation within tissues. During sprouting, tip cells and ensuing stalk cells migrate collectively into the extracellular matri…
Angiogenic sprouting is a critical process involved in vascular network formation within tissues. During sprouting, tip cells and ensuing stalk cells migrate collectively into the extracellular matrix while preserving cell-cell junctions, forming patent structures that support blood flow. Although several signaling pathways have been identified in controlling sprouting, it remains unclear to what extent this process is mechanoregulated. To address this gap, we investigated the role of cellular contractility in sprout morphogenesis using a biomimetic model of angiogenesis. 3D maps of mechanical deformations generated by sprouts revealed that mainly leader cells, not stalk cells, exert contractile forces on the surrounding matrix. Surprisingly, inhibiting cellular contractility with blebbistatin did not affect the extent of cellular invasion but resulted in cell-cell dissociation primarily between tip and stalk cells. Closer examination of cell-cell junctions revealed that blebbistatin impaired adherens junction organization particularly between tip and stalk cells. Using CRISPR/Cas9-mediated gene editing, we further identified NMIIA as the major isoform responsible for regulating multicellularity and cell contractility during sprouting. Together, these studies reveal a critical role for NMIIA-mediated contractile forces in maintaining multicellularity during sprouting and highlight the central role of forces in regulating cell-cell adhesions during collective motility.
- Succinate induces skeletal muscle fiber remodeling via SUNCR1 signaling pathway. [Journal Article]
- EREMBO Rep 2019 Jul 18; :e47892
- The conversion of skeletal muscle fiber from fast twitch to slow-twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Ske…
The conversion of skeletal muscle fiber from fast twitch to slow-twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid (TCA) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber-type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain IIb expression. Further, by using pharmacological or genetic loss-of-function models generated by phospholipase Cβ antagonists, SUNCR1 global knockout, or SUNCR1 gastrocnemius-specific knockdown, we found that the effects of succinate on skeletal muscle fiber-type remodeling are mediated by SUNCR1 and its downstream calcium/NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR1 signaling pathway. These findings suggest the potential beneficial use of succinate-based compounds in both athletic and sedentary populations.
- Development of a bio-MEMS Device for Electrical and Mechanical Conditioning and Characterization of Cell Sheets for Myocardial Repair. [Journal Article]
- BBBiotechnol Bioeng 2019 Jul 18
- Here we propose a bio-MEMS device designed to evaluate contractile force and conduction velocity of cell sheets in response to mechanical and electrical stimulation of the cell source as it grows to …
Here we propose a bio-MEMS device designed to evaluate contractile force and conduction velocity of cell sheets in response to mechanical and electrical stimulation of the cell source as it grows to form a cellular sheet. Moreover, the design allows for incorporation of patient-specific data and cell sources: an optimized device would allow cell sheets to be cultured, characterized, and conditioned to be compatible with a specific patient's cardiac environment in vitro, prior to implantation. This design draws upon existing methods in the literature but makes an important advance by combining the mechanical and electrical stimulation into a single system for optimized cell sheet growth. The device has been designed to achieve cellular alignment, electrical stimulation, mechanical stimulation, conduction velocity readout, contraction force readout, characterization, and eventually cell sheet release. The platform is based on a set of comb electrical contacts consisting of three-dimensional walls made of polydimethylsiloxane and coated with electrically conductive metals on the tops of the walls. Not only do the walls serve as a method for stimulating cells that are sitting on top of them, but their geometry is tailored such that they are flexible enough to be bent by the cells and used to measure force. The platform can be stretched via a linear actuator setup, allowing for simultaneous electrical and mechanical stimulation that can be derived from patient-specific clinical data. This article is protected by copyright. All rights reserved.
- Impact of obesity on central processing time rather than overall reaction time in young adult men. [Journal Article]
- EWEat Weight Disord 2019 Jul 17
- CONCLUSIONS: Although the association between weight status and RT might be elusive in young adults, our results show that higher central adiposity is negatively associated with PMT in young adults. Longitudinal studies are needed to explore the changes in obesity indexes and process speed in longer terms.
- Temporal Association Between Ischemic Muscle Perfusion Recovery and the Restoration of Muscle Contractile Function After Hindlimb Ischemia. [Journal Article]
- FPFront Physiol 2019; 10:804
- During incomplete skeletal muscle recovery from ischemia, such as that occurs with critical limb ischemia, the temporal relationship between recovery of muscle capillary perfusion and contractile fun…
During incomplete skeletal muscle recovery from ischemia, such as that occurs with critical limb ischemia, the temporal relationship between recovery of muscle capillary perfusion and contractile function is poorly defined. We examined this relationship in BALB/cJ mice (N = 24) following unilateral hindlimb ischemia (HLI), which pre-clinically mimics the myopathy observed in critical limb ischemia patients. Specifically, we examined this relationship in two phenotypically distinct muscles (i.e., "oxidative" soleus - Sol and "glycolytic" extensor digitorum longus - EDL) 14- or 56-days after HLI. Although overall limb blood flow (LDPI) reached its' recovery peak (48% of control) by HLI d14, the capillary networks in both the Sol and EDL (whole mount confocal imaging) were disrupted and competent muscle capillary perfusion (perfused lectin+μm2/muscle μm2) remained reduced. Interestingly, both Sol and EDL muscles recovered their distinct capillary structures and perfusion (Con Sol; 0.056 ± 0.02 lectin+μm2/muscle μm2, and Con EDL; 0.039 ± 0.005 lectin+μm2/muscle μm2) by HLI d56 (Sol; 0.062 ± 0.011 lectin+μm2/muscle μm2 and EDL; 0.0035 ± 0.005 lectin+μm2/muscle μm2), despite no further improvement in limb blood flow (LDPI). Both muscles suffered severe myopathy, indicated by loss of dystrophin positive immunostaining and the absence of stimulation induced isometric force production at HLI d14. Dystrophin immunofluorescence returned at HLI d56, although neither myofiber CSA (μm2) nor isometric force production (58 and 28% sustained deficits, Sol and EDL, respectively) recovered completely in either muscle. In summary, we reveal that the temporal relationship between the restoration of muscle capillary perfusion and functional ischemic skeletal muscle regeneration favors competent muscle capillary perfusion recovery in BALB/c mice in a phenotypically non-distinct manner.
- Molecular determinants of homo- and heteromeric interactions of Junctophilin-1 at triads in adult skeletal muscle fibers. [Journal Article]
- PNProc Natl Acad Sci U S A 2019 Jul 17
- In adult skeletal muscles, 2 junctophilin isoforms (JPH1 and JPH2) tether the sarcoplasmic reticulum (SR) to transverse tubule (T-tubule) membranes, generating stable membrane contact sites known as …
In adult skeletal muscles, 2 junctophilin isoforms (JPH1 and JPH2) tether the sarcoplasmic reticulum (SR) to transverse tubule (T-tubule) membranes, generating stable membrane contact sites known as triads. JPHs are anchored to the membrane of the SR by a C-terminal transmembrane domain (TMD) and bind the T-tubule membrane through their cytosolic N-terminal region, which contains 8 lipid-binding (MORN) motifs. By combining expression of GFP-JPH1 deletion mutants in skeletal muscle fibers with in vitro biochemical experiments, we investigated the molecular determinants of JPH1 recruitment at triads in adult skeletal muscle fibers. We found that MORN motifs bind PI(4,5)P2 in the sarcolemma, but do not mediate the selective localization of JPH1 at the T-tubule compartment of triads. On the contrary, fusion proteins containing only the TMD of JPH1 were able to localize at the junctional SR compartment of the triad. Bimolecular fluorescence complementation experiments indicated that the TMD of JPH1 can form dimers, suggesting that the observed localization at triads may result from dimerization with the TMDs of resident JPH1. A second domain, capable of mediating homo- and heterodimeric interactions between JPH1 and JPH2 was identified in the cytosolic region. FRAP experiments revealed that removal of either one of these 2 domains in JPH1 decreases the association of the resulting mutant proteins with triads. Altogether, these results suggest that the ability to establish homo- and heterodimeric interactions with resident JPHs may support the recruitment and stability of newly synthesized JPHs at triads in adult skeletal muscle fibers.
- Zombie ant death grip due to hypercontracted mandibular muscles. [Journal Article]
- JEJ Exp Biol 2019 Jul 17; 222(Pt 14)
- There are numerous examples of parasites that manipulate the behavior of the hosts that they infect. One such host-pathogen relationship occurs between the 'zombie-ant fungus' Ophiocordyceps unilater…
There are numerous examples of parasites that manipulate the behavior of the hosts that they infect. One such host-pathogen relationship occurs between the 'zombie-ant fungus' Ophiocordyceps unilateralis sensu lato and its carpenter ant host. Infected ants climb to elevated locations and bite onto vegetation where they remain permanently affixed well after death. The mandibular muscles, but not the brain, of infected ants are extensively colonized by the fungus. We sought to investigate the mechanisms by which O. unilateralis s.l. may be able to influence mandibular muscle contraction despite widespread muscle damage. We found that infected muscles show evidence of hypercontraction. Despite the extensive colonization, both motor neurons and neuromuscular junctions appear to be maintained. Infection results in sarcolemmal damage, but this is not specific to the death grip. We found evidence of precise penetration of muscles by fungal structures and the presence of extracellular vesicle-like particles, both of which may contribute to mandibular hypercontraction.
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- A direct interaction between survivin and myosin II is required for cytokinesis. [Journal Article]
- JCJ Cell Sci 2019 Jul 17; 132(14)
- An acto-myosin contractile ring, which forms after anaphase onset and is highly regulated in time and space, mediates cytokinesis, the final step of mitosis. The chromosomal passenger complex (CPC), …
An acto-myosin contractile ring, which forms after anaphase onset and is highly regulated in time and space, mediates cytokinesis, the final step of mitosis. The chromosomal passenger complex (CPC), composed of Aurora-B kinase, INCENP, borealin and survivin (also known as BIRC5), regulates various processes during mitosis, including cytokinesis. It is not understood, however, how CPC regulates cytokinesis. We show that survivin binds to non-muscle myosin II (NMII), regulating its filament assembly. Survivin and NMII interact mainly in telophase, and Cdk1 regulates their interaction in a mitotic-phase-specific manner, revealing the mechanism for the specific timing of survivin-NMII interaction during mitosis. The survivin-NMII interaction is indispensable for cytokinesis, and its disruption leads to multiple mitotic defects. We further show that only the survivin homodimer binds to NMII, attesting to the biological importance for survivin homodimerization. We suggest a novel function for survivin in regulating the spatio-temporal formation of the acto-NMII contractile ring during cytokinesis and we elucidate the role of Cdk1 in regulating this process.This article has an associated First Person interview with the first author of the paper.