How Humans Run Faster: The Neuromechanical Contributions of Functional Muscle Groups to Running at Different Speeds.

How the neuromechanics of the lower limb functional muscle groups change with running speed remains to be fully elucidated, with implications for our understanding of human locomotion, conditioning, and injury prevention. This study compared the neuromechanics (ground reaction and joint kinetics, kinematics and muscle activity) of middle-distance athletes running on an instrumented treadmill at six wide-ranging speeds (2.78-8.33 m·s-1). Ground reaction forces and kinematics were analyzed using inverse dynamics to calculate flexor and extensor joint torques, and positive and negative work done by these torques. Contributions of each functional muscle group to the total positive and negative work done by the limb during stance, swing, and the whole stride were quantified. During stance, the ankle plantar flexors were the major energy generator and absorber (>60%) at all speeds, but their contribution to whole stride energy generation and absorption declined with speed. Positive work by the hip extensors rose superlinearly with speed during stance (3-fold) and especially during swing (12-fold), becoming the biggest energy generator across the whole stride at >5 m·s-1. Knee flexor and extensor negative work also rose superlinearly with speed during swing, with the knee flexors becoming the greatest energy absorber over the whole stride at >7.22 m·s-1. Across speeds, plantar flexor peak moment and positive work accounted for 97% and 96% of the variance in step length, and swing hip extension peak moment and positive work accounted for 98% and 99% of the variance in step frequency. There were pronounced speed, phase (stance/swing), and work (positive/negative) dependent contributions of the different functional muscle groups during running, with extensive implications for conditioning and injury prevention.

Results of a nationally representative seroprevalence survey of chikungunya virus in Bangladesh.

There is an increasing global burden from chikungunya virus (CHIKV). Bangladesh reported a major epidemic in 2017, however, it was unclear if there had been prior widespread transmission. We conducted a nationally representative seroprevalence survey in 70 randomly selected communities immediately prior to the epidemic. We found 69/2,938 (2.4%) of sampled individuals were seropositive to CHIKV. Being seropositive to dengue virus (aOR 3.13 [95% CIs: 1.86-5.27]), male sex (aOR 0.59 [95% CIs: 0.36-0.99]), and community presence of Aedes aegypti mosquitoes (aOR: 1.80, 95% CI: 1.05-3.07) were significantly associated with CHIKV seropositivity. Using a spatial prediction model, we estimated that across the country, 4.99 (95% CI: 4.89 - 5.08) million people had been previously infected. These findings highlight high population susceptibility prior to the major outbreak and that previous outbreaks must have been spatially isolated.

Sex differences in muscle morphology between male and female sprinters.

There is a marked difference between males and females in sprint running performance, yet a comprehensive investigation of sex differences in the muscle morphology of sprinters, which could explain the performance differences, remains to be completed. This study compared muscle volumes of 23 individual leg muscles and 5 functional muscle groups, assessed with 3 T magnetic resonance imaging, between male (n = 31) and female (n = 22) sprinters, as well as subgroups of elite males (EM, n = 5), elite females (EF, n = 5), and performance-matched (to elite females) males (PMMEF, n = 6). Differences in muscle volume distribution between EM, EF, and unathletic male (UM) controls were also assessed. For the full cohorts, male sprinters were more muscular than their female counterparts, but the differences were nonuniform and anatomically variable, with the largest differences in the hip extensors and flexors. However, among elite sprinters the sex differences in the volume of the functional muscle groups were almost uniform (absolute volume +47-53%), and the muscle volume distribution of EM was more similar to EF than to UM (P < 0.039). For PMMEF, relative hip extensor volume, but not stature or percent body fat, differentiated for performance (PMMEF and EF < EM) rather than sex. In conclusion, although the full cohorts of sprinters showed a marked sex difference in the amount and distribution of muscle mass, elite sprinters appeared to be selected for a common muscle distribution phenotype that for these elite subgroups was a stronger effect than that of sex. Relative hip extensor muscle volume, rather than stature, percent body fat, or total relative muscle volume, appeared to be the primary determinant of the sex difference in performance.NEW & NOTEWORTHY We present novel evidence suggesting muscle volume, specifically relative hip extensor volume, may be a primary deterministic variable for the sex difference in sprint performance, such that with matched sprint times, male and female sprinters may be expected to have equivalent muscle morphology. We highlight striking similarities in distribution of leg muscle mass between elite male and female sprinters and provide evidence for the existence of a muscular distribution phenotype specific to elite sprinters, irrespective of sex.

Mitophagy for cardioprotection.

Mitochondrial function is maintained by several strictly coordinated mechanisms, collectively termed mitochondrial quality control mechanisms, including fusion and fission, degradation, and biogenesis. As the primary source of energy in cardiomyocytes, mitochondria are the central organelle for maintaining cardiac function. Since adult cardiomyocytes in humans rarely divide, the number of dysfunctional mitochondria cannot easily be diluted through cell division. Thus, efficient degradation of dysfunctional mitochondria is crucial to maintaining cellular function. Mitophagy, a mitochondria specific form of autophagy, is a major mechanism by which damaged or unnecessary mitochondria are targeted and eliminated. Mitophagy is active in cardiomyocytes at baseline and in response to stress, and plays an essential role in maintaining the quality of mitochondria in cardiomyocytes. Mitophagy is mediated through multiple mechanisms in the heart, and each of these mechanisms can partially compensate for the loss of another mechanism. However, insufficient levels of mitophagy eventually lead to mitochondrial dysfunction and the development of heart failure. In this review, we discuss the molecular mechanisms of mitophagy in the heart and the role of mitophagy in cardiac pathophysiology, with the focus on recent findings in the field.

Molecular properties and regulation of NAD+ kinase (NADK).

Nicotinamide adenine dinucleotide (NAD+) kinase (NADK) phosphorylates NAD+, thereby producing nicotinamide adenine dinucleotide phosphate (NADP). Both NADK genes and the NADP(H)-producing mechanism are evolutionarily conserved among archaea, bacteria, plants and mammals. In mammals, NADK is activated by phosphorylation and protein-protein interaction. Recent studies conducted using genetically altered models validate the essential role of NADK in cellular redox homeostasis and metabolism in multicellular organisms. Here, we describe the evolutionary conservation, molecular properties, and signaling mechanisms and discuss the pathophysiological significance of NADK.

Thioredoxin 1 promotes autophagy through transnitrosylation of Atg7 during myocardial ischemia.

Modification of cysteine residues by oxidative and nitrosative stress affects structure and function of proteins, thereby contributing to the pathogenesis of cardiovascular disease. Although the major function of thioredoxin 1 (Trx1) is to reduce disulfide bonds, it can also act as either a denitrosylase or transnitrosylase in a context-dependent manner. Here we show that Trx1 transnitrosylates Atg7, an E1-like enzyme, thereby stimulating autophagy. During ischemia, Trx1 was oxidized at Cys32-Cys35 of the oxidoreductase catalytic center and S-nitrosylated at Cys73. Unexpectedly, Atg7 Cys545-Cys548 reduced the disulfide bond in Trx1 at Cys32-Cys35 through thiol-disulfide exchange and this then allowed NO to be released from Cys73 in Trx1 and transferred to Atg7 at Cys402. Experiments conducted with Atg7 C402S-knockin mice showed that S-nitrosylation of Atg7 at Cys402 promotes autophagy by stimulating E1-like activity, thereby protecting the heart against ischemia. These results suggest that the thiol-disulfide exchange and the NO transfer are functionally coupled, allowing oxidized Trx1 to mediate a salutary effect during myocardial ischemia through transnitrosylation of Atg7 and stimulation of autophagy.

The Muscle Morphology of Elite Female Sprint Running.

INTRODUCTION: A paucity of research exists examining the importance of muscle morphological and functional characteristics for elite female sprint performance. PURPOSE: This study aimed to compare lower body muscle volumes and vertical jumping power between elite and subelite female sprinters and assess the relationships of these characteristics with sprint race and acceleration performance. METHODS: Five elite (100 m seasons best [SBE 100 ], 11.16 ± 0.06 s) and 17 subelite (SBE 100 , 11.84 ± 0.42 s) female sprinters underwent: 3T magnetic resonance imaging to determine the volume of 23 individual leg muscles/compartments and five functional muscle groups; countermovement jump and 30 m acceleration tests. RESULTS: Total absolute lower body muscle volume was higher in elite versus subelite sprinters (+15%). Elite females exhibited greater muscle volume of the hip flexors (absolute, +28%; relative [to body mass], +19%), hip extensors (absolute, +22%; relative, +14%), and knee extensors (absolute, +21%), demonstrating pronounced anatomically specific muscularity, with relative hip flexor volume alone explaining 48% of sprint performance variability. The relative volume of five individual muscles (sartorius, gluteus maximus, adductor magnus, vastus lateralis, illiopsoas) were both distinct between groups (elite > subelite) and related to SBE 100 ( r = 0.553-0.639), with the combination of the sartorius (41%) and the adductor magnus (17%) explaining 58% of the variance in SBE 100 . Elite female sprinters demonstrated greater absolute countermovement jump power versus subelite, and absolute and relative power were related to both SBE 100 ( r = -0.520 to -0.741) and acceleration performance ( r = 0.569 to 0.808). CONCLUSIONS: This investigation illustrates the distinctive, anatomically specific muscle volume distribution that facilitates elite sprint running in females, and emphasizes the importance of hip flexor and extensor relative muscle volume.

Metformin Attenuates Hyperglycaemia-Stimulated Pro-Fibrotic Gene Expression in Adventitial Fibroblasts via Inhibition of Discoidin Domain Receptor 2.

Molecular mechanisms underlying the diverse therapeutic effects of anti-diabetic metformin, beyond its anti-hyperglycaemic effects, remain largely unclear. Metformin is reported to reduce the long-term complications of diabetes, including cardiovascular fibrosis and remodelling. Our recent investigations show that Discoidin Domain Receptor 2 (DDR2), a Collagen receptor tyrosine kinase, has an obligate regulatory role in Collagen type I gene expression in cardiac and vascular adventitial fibroblasts, and that it may be a molecular link between arterial fibrosis and metabolic syndrome in rhesus monkeys. Using gene knockdown and overexpression approaches, the present study examined whether DDR2 is a target of metformin and whether, by targeting DDR2, it inhibits Fibronectin and Collagen type I expression in rat aortic adventitial fibroblasts exposed to hyperglycaemic conditions. Metformin was found to attenuate hyperglycaemia-induced increase in DDR2 mRNA and protein expression by inhibiting TGF-ß1/SMAD2/3 signalling that mediates the stimulatory effect of hyperglycaemia on DDR2 expression. Metformin also inhibited DDR2-dependent expression of Fibronectin and Collagen type I, indicating that it regulates these matrix proteins via DDR2 inhibition. The findings identify DDR2, a mediator of cardiovascular remodelling, as a molecular target of metformin, thereby uncovering the molecular basis of its protective role in vascular fibrosis and possibly cardiac fibrosis associated with diabetic cardiomyopathy.

Discoidin Domain Receptor 2 Regulates AT1R Expression in Angiotensin II-Stimulated Cardiac Fibroblasts via Fibronectin-Dependent Integrin-ß1 Signaling.

This study probed the largely unexplored regulation and role of fibronectin in Angiotensin II-stimulated cardiac fibroblasts. Using gene knockdown and overexpression approaches, Western blotting, and promoter pull-down assay, we show that collagen type I-activated Discoidin Domain Receptor 2 (DDR2) mediates Angiotensin II-dependent transcriptional upregulation of fibronectin by Yes-activated Protein in cardiac fibroblasts. Furthermore, siRNA-mediated fibronectin knockdown attenuated Angiotensin II-stimulated expression of collagen type I and anti-apoptotic cIAP2, and enhanced cardiac fibroblast susceptibility to apoptosis. Importantly, an obligate role for fibronectin was observed in Angiotensin II-stimulated expression of AT1R, the Angiotensin II receptor, which would link extracellular matrix (ECM) signaling and Angiotensin II signaling in cardiac fibroblasts. The role of fibronectin in Angiotensin II-stimulated cIAP2, collagen type I, and AT1R expression was mediated by Integrin-ß1-integrin-linked kinase signaling. In vivo, we observed modestly reduced basal levels of AT1R in DDR2-null mouse myocardium, which were associated with the previously reported reduction in myocardial Integrin-ß1 levels. The role of fibronectin, downstream of DDR2, could be a critical determinant of cardiac fibroblast-mediated wound healing following myocardial injury. In summary, our findings suggest a complex mechanism of regulation of cardiac fibroblast function involving two major ECM proteins, collagen type I and fibronectin, and their receptors, DDR2 and Integrin-ß1.

The influence of swing leg technique on maximum running speed.

The motion of the swing leg of elite sprinters at maximum speed is markedly different from that of slower sprinters, but the mechanisms by which this difference influences performance are unknown. The aim of this study was to establish whether and, if so, how the motion of the swing leg influences maximum achievable running speed using computer simulation. A seven-segment planar computer model was constructed to simulate the stance phase of sprinting. Optimisation was used to maximise the running speed of the model using two different swing leg techniques, one representative of an elite sprint athlete, and the other of a sub-elite athlete. The maximum speed of the model increased when using the swing leg technique of the elite athlete compared with the technique of the sub-elite athlete (10.2 m s-1 vs 9.3 m s-1). This improvement in performance was due to greater horizontal displacement of the mass centre during stance (0.861 m vs 0.814 m), and an increase in average vertical ground force of 51 N (0.06 bodyweights). The increase in vertical force was due to a larger impact peak caused by more negative vertical momentum of the stance leg at touchdown, and subsequently greater torques in the joints of the stance leg which were placed in faster eccentric conditions and at angles closer to optimum during the first half of stance. It is likely that force increases in early stance associated with swing leg technique contribute to the asymmetrical vertical ground reaction force traces observed in elite sprinters.

The correlation of force-velocity-power relationship of a whole-body movement with 20 m and 60 m sprint performance.

Sprinting ability is important for successful performance in sports. The aim of this study was to examine the correlation between force-velocity-power relationship of a whole-body movement and sprint performance. Twelve male participants performed maximal squat jumps with additional loads ranging from 0% to 100% body weight to obtain force-velocity profiles. The mean force and velocity were calculated during the push-off phase for each jump, which resulted in a force-velocity curve. The theoretical maximal force (F0), theoretical maximal velocity (V0) and theoretical maximum power (P0) were computed via extrapolation of the force and velocity data. In the second session, participants performed two 60 m sprints and the time to cover 20 m (t20), time to cover 60 m (t60), and maximum sprint velocity (Vmax) were calculated from the best 60 m trial. Correlation analyses revealed strong and significant correlations between V0 and t20 (r = -0.60), V0 and t60 (r = -0.60), P0 and t20 (r = -0.75) and P0 and t60 (r = -0.78). Multiple linear regression indicated that P0 explained 56%, 61% and 60% of the variability in t20, t60 and Vmax, respectively. Our results emphasise the importance of developing power production capabilities to improve sprint performance.

Neuromechanics of Middle-Distance Running Fatigue: A Key Role of the Plantarflexors?

PURPOSE: This study aimed to investigate the changes in lower limb kinematics, kinetics, and muscle activation during a high-intensity run to fatigue (HIRF). METHODS: Eighteen male and female competitive middle-distance runners performed a HIRF on an instrumented treadmill at a constant but unsustainable middle-distance speed (~3 min) based on a preceding maximum oxygen uptake (V˙O2max) test. Three-dimensional kinematics and kinetics were collected and compared between the start, 33%, 67%, and the end of the HIRF. In addition, the activation of eight lower limb muscles of each leg was measured with surface EMG (sEMG). RESULTS: Time to exhaustion was 181 ± 42 s. By the end of the HIRF (i.e., vs the start), ground contact time increased (+4.0%), whereas flight time (-3.2%), peak vertical ground reaction force (-6.1%), and vertical impulse (-4.1%) decreased (all P < 0.05), and joint angles at initial contact became more (dorsi)flexed (ankle, +1.9°; knee, +2.1°; hip, +3.6°; all P < 0.05). During stance, by the end of the HIRF: peak ankle plantarflexion moment decreased by 0.4 N·m·kg-1 (-9.0%), whereas peak knee extension moment increased by 0.24 N·m·kg-1 (+10.3%); similarly, positive ankle plantarflexion work decreased by 0.19 J·kg-1 (-13.9%), whereas positive knee extension work increased by 0.09 J·kg-1 (+33.3%; both P < 0.05) with no change in positive hip extension work. Hip extensor surface EMG amplitude increased during the late swing phase (+20.9-37.3%; P < 0.05). CONCLUSION: Running at a constant middle-distance pace led primarily to the fatigue of the plantarflexors with a compensatory increase in positive work done at the knee. Improving the fatigue resistance of the plantarflexors might be beneficial for middle-distance running performance.

The Muscle Morphology of Elite Sprint Running.

PURPOSE: This study aimed to investigate the differences in muscle volumes and strength between male elite sprinters, sub-elite sprinters, and untrained controls and to assess the relationships of muscle volumes and strength with sprint performance. METHODS: Five elite sprinters (100-m season's best equivalent [SBE100], 10.10 ± 0.07 s), 26 sub-elite sprinters (SBE100, 10.80 ± 0.30 s), and 11 untrained control participants underwent 1) 3-T magnetic resonance imaging scans to determine the volume of 23 individual lower limb muscles/compartments and 5 functional muscle groups and 2) isometric strength assessment of lower body muscle groups. RESULTS: Total lower body muscularity was distinct between the groups (controls < sub-elite +20% < elite +48%). The hip extensors exhibited the largest muscle group differences/relationships (elite, +32% absolute and +15% relative [per kg] volume, vs sub-elite explaining 31%-48% of the variability in SBE100), whereas the plantarflexors showed no differences between sprint groups. Individual muscle differences showed pronounced anatomical specificity (elite vs sub-elite absolute volume range, +57% to -9%). Three hip muscles were consistently larger in elite vs sub-elite (tensor fasciae latae, sartorius, and gluteus maximus; absolute, +45%-57%; relative volume, +25%-37%), and gluteus maximus volume alone explained 34%-44% of the variance in SBE100. The isometric strength of several muscle groups was greater in both sprint groups than controls but similar for the sprint groups and not related to SBE100. CONCLUSIONS: These findings demonstrate the pronounced inhomogeneity and anatomically specific muscularity required for fast sprinting and provides novel, robust evidence that greater hip extensor and gluteus maximus volumes discriminate between elite and sub-elite sprinters and are strongly associated with sprinting performance.

Coordinated regulation of cell survival and cell cycle pathways by DDR2-dependent SRF transcription factor in cardiac fibroblasts.

Relative resistance to apoptosis and the ability to proliferate and produce a collagen-rich scar determine the critical role of cardiac fibroblasts in wound healing and tissue remodeling following myocardial injury. Identification of cardiac fibroblast-specific factors and mechanisms underlying these aspects of cardiac fibroblast function is therefore of considerable scientific and clinical interest. In the present study, gene knockdown and overexpression approaches and promoter binding assays showed that discoidin domain receptor 2 (DDR2), a mesenchymal cell-specific collagen receptor tyrosine kinase localized predominantly in fibroblasts in the heart, acts via ERK1/2 MAPK-activated serum response factor (SRF) transcription factor to enhance the expression of antiapoptotic cIAP2 in cardiac fibroblasts, conferring resistance against oxidative injury. Furthermore, DDR2 was found to act via ERK1/2 MAPK-activated SRF to transcriptionally upregulate Skp2 that in turn facilitated post-translational degradation of p27, the cyclin-dependent kinase inhibitor that causes cell cycle arrest, to promote G1-S transition, as evidenced by Rb phosphorylation, increased proliferating cell nuclear antigen (PCNA) levels, and flow cytometry. DDR2-dependent ERK1/2 MAPK activation also suppressed forkhead box O 3a (FoxO3a)-mediated transcriptional induction of p27. Inhibition of the binding of collagen type I to DDR2 using WRG-28 indicated the obligate role of collagen type I in the activation of DDR2 and its regulatory role in cell survival and cell cycle protein expression. Notably, DDR2 levels positively correlated with SRF, cIAP2, and PCNA levels in cardiac fibroblasts from spontaneously hypertensive rats. To conclude, DDR2-mediated ERK1/2 MAPK activation facilitates coordinated regulation of cell survival and cell cycle progression in cardiac fibroblasts via SRF.NEW & NOTEWORTHY Relative resistance to apoptosis and the ability to proliferate and produce a collagen-rich scar enable cardiac fibroblasts to play a central role in myocardial response to injury. This study reports novel findings that mitogen-stimulated cardiac fibroblasts exploit a common regulatory mechanism involving collagen receptor (DDR2)-dependent activation of ERK1/2 MAPK and serum response factor to achieve coordinated regulation of apoptosis resistance and cell cycle progression, which could facilitate their survival and function in the injured myocardium.

The Anthropometry of Economical Running.

The influence of anthropometry and body composition on running economy is unclear, with previous investigations involving small relatively homogeneous groups of runners and limited anthropometric/composition measurements. PURPOSE: To comprehensively investigate the relationships of anthropometry and body composition with running economy within a large heterogeneous sample of runners. METHODS: Eighty-five runners (males [M], n = 45; females [F], n = 40), of diverse competitive standard, performed a discontinuous protocol of incremental treadmill running (4-min stages, 1 km·h increments) to establish locomotory energy cost (LEc) of running at submaximal speeds (averaged across 10-12 km·h; the highest common speed < lactate turnpoint). Measurements of anthropometry, including segment lengths, perimeters, masses and moments of inertia, and body composition were obtained using tape-based measurements and dual-energy x-ray absorptiometry. RESULTS: Absolute LEc (ABSLEc, kcal·km) was positively correlated with 21 (of 27) absolute anthropometric variables in both male and female cohorts. Multiple-regression analyses revealed that one variable (mean perimeter z score) explained 49.4% (M) and 68.9% (F) of the variance in ABSLEc. Relative LEc (RELLEc, kcal·kg·km) was also correlated with five (M) and seven (F) normalized anthropometric variables, and regression analyses explained 31.6% (M; percentage bone mass and normalized hip perimeter) and 33.3% (F, normalized forearm perimeter) of the variance in RELLEc. CONCLUSIONS: These findings provide novel and robust evidence that anthropometry and body composition variables, predominantly indicative of relative slenderness, explain a considerable proportion of the variance in running economy (i.e., more slender, lower energy cost). We, therefore, recommend that runners and coaches are attentive to relative slenderness in selecting and training athletes with the aim of enhancing running economy, and improving distance running performance.

Discoidin domain Receptor 2: A determinant of metabolic syndrome-associated arterial fibrosis in non-human primates.

Collagen accumulation and remodeling in the vascular wall is a cardinal feature of vascular fibrosis that exacerbates the complications of hypertension, aging, diabetes and atherosclerosis. With no specific therapy available to date, identification of mechanisms underlying vascular fibrogenesis is an important clinical goal. Here, we tested the hypothesis that Discoidin Domain Receptor 2 (DDR2), a collagen-specific receptor tyrosine kinase, is a determinant of arterial fibrosis. We report a significant increase in collagen type 1 levels along with collagen and ECM remodeling, degradation of elastic laminae, enhanced fat deposition and calcification in the abdominal aorta in a non-human primate model of high-fat, high-sucrose diet (HFS)-induced metabolic syndrome. These changes were associated with a marked increase in DDR2. Resveratrol attenuated collagen type I deposition and remodeling induced by the HFS diet, with a concomintant reduction in DDR2. Further, in isolated rat vascular adventitial fibroblasts and VSMCs, hyperglycemia increased DDR2 and collagen type I expression via TGF-ß1/SMAD2/3, which was attenuated by resveratrol. Notably, gene knockdown and overexpression approaches demonstrated an obligate role for DDR2 in hyperglycemia-induced increase in collagen type I expression in these cells. Together, our observations point to DDR2 as a hitherto unrecognized molecular link between metabolic syndrome and arterial fibrosis, and hence a therapeutic target.

Collagen receptor cross-talk determines α-smooth muscle actin-dependent collagen gene expression in angiotensin II-stimulated cardiac fibroblasts.

Excessive collagen deposition by myofibroblasts during adverse cardiac remodeling leads to myocardial fibrosis that can compromise cardiac function. Unraveling the mechanisms underlying collagen gene expression in cardiac myofibroblasts is therefore an important clinical goal. The collagen receptors, discoidin domain receptor 2 (DDR2), a collagen-specific receptor tyrosine kinase, and integrin-ß1, are reported to mediate tissue fibrosis. Here, we probed the role of DDR2-integrin-ß1 cross-talk in the regulation of collagen α1(I) gene expression in angiotensin II (Ang II)-stimulated cardiac fibroblasts. Results from gene silencing/overexpression approaches, electrophoretic mobility shift assays, and ChIP revealed that DDR2 acts via extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (ERK1/2 MAPK)-dependent transforming growth factor-ß1 (TGF-ß1) signaling to activate activator protein-1 (AP-1) that in turn transcriptionally enhances the expression of collagen-binding integrin-ß1 in Ang II-stimulated cardiac fibroblasts. The DDR2-integrin-ß1 link was also evident in spontaneously hypertensive rats and DDR2-knockout mice. Further, DDR2 acted via integrin-ß1 to regulate α-smooth muscle actin (α-SMA) and collagen type I expression in Ang II-exposed cardiac fibroblasts. Downstream of the DDR2-integrin-ß1 axis, α-SMA was found to regulate collagen α1(I) gene expression via the Ca2+ channel, transient receptor potential cation channel subfamily C member 6 (TRPC6), and the profibrotic transcription factor, Yes-associated protein (YAP). This finding indicated that fibroblast-to-myofibroblast conversion is mechanistically coupled to collagen expression. The observation that collagen receptor cross-talk underlies α-SMA-dependent collagen type I expression in cardiac fibroblasts expands our understanding of the complex mechanisms involved in collagen gene expression in the heart and may be relevant to cardiac fibrogenesis.

Is There an Optimal Speed for Economical Running?

The influence of running speed and sex on running economy is unclear and may have been confounded by measurements of oxygen cost that do not account for known differences in substrate metabolism, across a limited range of speeds, and differences in performance standard. Therefore, this study assessed the energy cost of running over a wide range of speeds in high-level and recreational runners to investigate the effect of speed (in absolute and relative terms) and sex (men vs women of equivalent performance standard) on running economy. To determine the energy cost (kcal · kg-1 · km-1) of submaximal running, speed at lactate turn point (sLTP), and maximal rate of oxygen uptake, 92 healthy runners (high-level men, n = 14; high-level women, n = 10; recreational men, n = 35; recreational women, n = 33) completed a discontinuous incremental treadmill test. There were no sex-specific differences in the energy cost of running for the recreational or high-level runners when compared at absolute or relative running speeds (P > .05). The absolute and relative speed-energy cost relationships for the high-level runners demonstrated a curvilinear U shape with a nadir reflecting the most economical speed at 13 km/h or 70% sLTP. The high-level runners were more economical than the recreational runners at all absolute and relative running speeds (P < .05). These findings demonstrate that there is an optimal speed for economical running, there is no sex-specific difference, and high-level endurance runners exhibit better running economy than recreational endurance runners.

Running Technique is an Important Component of Running Economy and Performance.

Despite an intuitive relationship between technique and both running economy (RE) and performance, and the diverse techniques used by runners to achieve forward locomotion, the objective importance of overall technique and the key components therein remain to be elucidated. PURPOSE: This study aimed to determine the relationship between individual and combined kinematic measures of technique with both RE and performance. METHODS: Ninety-seven endurance runners (47 females) of diverse competitive standards performed a discontinuous protocol of incremental treadmill running (4-min stages, 1-km·h increments). Measurements included three-dimensional full-body kinematics, respiratory gases to determine energy cost, and velocity of lactate turn point. Five categories of kinematic measures (vertical oscillation, braking, posture, stride parameters, and lower limb angles) and locomotory energy cost (LEc) were averaged across 10-12 km·h (the highest common velocity < velocity of lactate turn point). Performance was measured as season's best (SB) time converted to a sex-specific z-score. RESULTS: Numerous kinematic variables were correlated with RE and performance (LEc, 19 variables; SB time, 11 variables). Regression analysis found three variables (pelvis vertical oscillation during ground contact normalized to height, minimum knee joint angle during ground contact, and minimum horizontal pelvis velocity) explained 39% of LEc variability. In addition, four variables (minimum horizontal pelvis velocity, shank touchdown angle, duty factor, and trunk forward lean) combined to explain 31% of the variability in performance (SB time). CONCLUSIONS: This study provides novel and robust evidence that technique explains a substantial proportion of the variance in RE and performance. We recommend that runners and coaches are attentive to specific aspects of stride parameters and lower limb angles in part to optimize pelvis movement, and ultimately enhance performance.