Neuromesodermal progenitors are a conserved source of spinal cord with divergent growth dynamics.

During gastrulation, embryonic cells become specified into distinct germ layers. In mouse, this continues throughout somitogenesis from a population of bipotent stem cells called neuromesodermal progenitors (NMps). However, the degree of self-renewal associated with NMps in the fast-developing zebrafish embryo is unclear. Using a genetic clone-tracing method, we labelled early embryonic progenitors and found a strong clonal similarity between spinal cord and mesoderm tissues. We followed individual cell lineages using light-sheet imaging, revealing a common neuromesodermal lineage contribution to a subset of spinal cord tissue across the anterior-posterior body axis. An initial population subdivides at mid-gastrula stages and is directly allocated to neural and mesodermal compartments during gastrulation. A second population in the tailbud undergoes delayed allocation to contribute to the neural and mesodermal compartment only at late somitogenesis. Cell tracking and retrospective cell fate assignment at late somitogenesis stages reveal these cells to be a collection of mono-fated progenitors. Our results suggest that NMps are a conserved population of bipotential progenitors, the lineage of which varies in a species-specific manner due to vastly different rates of differentiation and growth.

"Train-High Sleep-Low" Dietary Periodization Does Not Alter Ventilatory Strategies During Cycling Exercise.

Objective: The purpose of this study was to investigate the effects of "train-high sleep-low" (THSL) dietary periodization on ventilatory strategies during cycling exercise at submaximal and maximal intensities.Method: In a randomized crossover design, 8 trained men [age (mean ± SEM) = 28 ± 1 y; peak oxygen uptake = 56.8 ± 2.4 mL kg-1 min-1] completed two glycogen-depleting protocols on a cycle ergometer on separate days, with the cycling followed by a low carbohydrate (CHO) meal and beverages containing either no additional CHO (THSL) or beverages containing 1.2 g kg-1 CHO [traditional CHO replacement (TRAD)]. The following morning, participants completed 4 minutes of cycling below (Stage 1), at (Stage 2), and above (Stage 3) gas exchange threshold, followed by a 5-km time trial.Results: Timetrial performance was significantly faster in TRAD compared to THSL (8.7 ± 0.3 minutes and 9.0 ± 0.3 minutes, respectively; p = 0.02). No differences in ventilation, tidal volume, or carbon dioxide production occurred between conditions at any exercise intensity (p > 0.05). During Stage 1, oxygen uptake was 37.9 ± 1.5 mL kg-1 min-1 in the TRAD condition and 39.6 ± 1.8 mL kg-1 min-1 in THSL (p = 0.05). During Stage 2, VO2 was 44.6 ± 1.7 mL kg-1 min-1 in the TRAD condition and 47.0 ± 1.9 mL kg-1 min-1 in THSL (p = 0.07). No change in operating lung volume was detected between dietary conditions (p > 0.05).Conclusions: THSL impairs performance following the dietary intervention, but this occurs with no alteration of ventilatory measures.

Attentional focus does not impact locomotor-respiratory coupling in trained runners.

PURPOSE: The purpose of this study was to explore relationships between attentional strategies and LRC, running economy, perceived exertion, and dyspnea. METHODS: 25 endurance-trained males ([Formula: see text]O2max = 68.2 ± 4.7 mL kg-1 min-1) ran for 5 min each at two different submaximal speeds, during which LRC and oxygen consumption ([Formula: see text]O2) were measured. The degree of LRC was calculated as the percentage of breaths occurring during the same decile of the step cycle. Attentional focus was assessed at the end of exercise using an Attentional Focusing Questionnaire, with subscales for association, dissociation, and distress. RESULTS: We found no significant relationships between attentional focus measures and LRC. However, dissociation scores were positively correlated with [Formula: see text]O2 (r = 0.404), as well as  %[Formula: see text]O2max (r = 0.474), at the slower running speed. Distress scores were the only attentional focus subscale related to perceived exertion and dyspnea (r = 0.378 to 0.654). CONCLUSION: These findings suggest attentional focus is not driving the high levels of LRC seen in trained endurance athletes but may relate to running economy and perceptual responses.

Rice with reduced stomatal density conserves water and has improved drought tolerance under future climate conditions.

Much of humanity relies on rice (Oryza sativa) as a food source, but cultivation is water intensive and the crop is vulnerable to drought and high temperatures. Under climate change, periods of reduced water availability and high temperature are expected to become more frequent, leading to detrimental effects on rice yields. We engineered the high-yielding rice cultivar 'IR64' to produce fewer stomata by manipulating the level of a developmental signal. We overexpressed the rice epidermal patterning factor OsEPF1, creating plants with substantially reduced stomatal density and correspondingly low stomatal conductance. Low stomatal density rice lines were more able to conserve water, using c. 60% of the normal amount between weeks 4 and 5 post germination. When grown at elevated atmospheric CO2 , rice plants with low stomatal density were able to maintain their stomatal conductance and survive drought and high temperature (40°C) for longer than control plants. Low stomatal density rice gave equivalent or even improved yields, despite a reduced rate of photosynthesis in some conditions. Rice plants with fewer stomata are drought tolerant and more conservative in their water use, and they should perform better in the future when climate change is expected to threaten food security.

Sex Differences in the Speed-Duration Relationship of Elite Runners across the Lifespan.

PURPOSE: To determine if the speed-duration relationship is altered with age and sex of elite Master's runners. METHODS: The world's top 10 performances for men and women in three events (800, 1500, and 5000 m) across six age groups (18-34 yr, 40-49 yr, 50-59 yr, 60-69 yr, 70-79 yr, and 80-89 yr) were analyzed from public data to establish theoretical models of the speed-duration relationship. Critical speed (CS) and the curvature constant ( D ') were estimated by fitting the average speeds and performance times with a two-parameter hyperbolic model. RESULTS: Critical speed expressed relative to the 18- to 34-yr-olds, declined with age (92.2% [40-49] to 55.2% [80-89]; P < 0.001), and absolute CS was higher in men than women within each age group ( P < 0.001). The percent difference in CS between the men and women progressively increased across age groups (10.8% [18-34] to 15.5% [80-89]). D ' was lower in women than men in the 60-69 yr, 70-79 yr, and 80-89 yr age groups ( P < 0.001), but did not differ in the 18-34 yr, 40-49 yr, or 50-59 yr age groups. CONCLUSIONS: Critical speed progressively decreased with age, likely due to age-related decrements in several physiological systems that cause reduced aerobic capacity. The mechanism for the larger sex difference in CS in the older age groups is unknown but may indicate physiological differences that occur with aging and/or historical sociological factors that have reduced participation opportunities of older female runners resulting in a more limited talent pool.

The unappreciated generative role of cell movements in pattern formation.

The mechanisms underpinning the formation of patterned cellular landscapes has been the subject of extensive study as a fundamental problem of developmental biology. In most cases, attention has been given to situations in which cell movements are negligible, allowing researchers to focus on the cell-extrinsic signalling mechanisms, and intrinsic gene regulatory interactions that lead to pattern emergence at the tissue level. However, in many scenarios during development, cells rapidly change their neighbour relationships in order to drive tissue morphogenesis, while also undergoing patterning. To draw attention to the ubiquity of this problem and propose methodologies that will accommodate morphogenesis into the study of pattern formation, we review the current approaches to studying pattern formation in both static and motile cellular environments. We then consider how the cell movements themselves may contribute to the generation of pattern, rather than hinder it, with both a species specific and evolutionary viewpoint.

World Championship and Olympic Games Experience Influences Future Medal Performance in Track-and-Field Athletes.

Some track-and-field national governing bodies send athletes to World Championship and Olympic Games (WC/OG) to gain experience that may positively impact future success, even though athletes may not be expected to place high or medal. However, it is unclear if this strategy is advantageous for future medal attainment. PURPOSE: To determine if participation and/or advancement at a track-and-field athlete's first WC/OG influences the odds of future medaling. METHODS: Performances of US track-and-field athletes who made their first WC/OG team during 2000-2013 were tracked through 2016 to stratify athletes into categories. Athletes who medaled on their first team or never made a subsequent team (ie, no experience) were compared with athletes who did not medal on their first team but made subsequent teams (ie, experience). The experience group was further divided into athletes who advanced or did not advance out of the initial round at their first competition for a secondary analysis. Odds ratios (ORs) were calculated using logistic regression to measure the association between experience level and medaling. RESULTS: A significant OR was obtained for advanced versus did not advance (OR = 2.29, 95% confidence interval, 1.07-4.89, P = .03), but not for experience versus no experience (OR = 1.04, 95% confidence interval, 0.60-1.78, P = .91) group. CONCLUSIONS: Advancing out of the initial round of competition during an athlete's first WC/OG competition is associated with increased odds of future medaling. National governing bodies should consider this "experience threshold" during team selection processes.

High Intraindividual Variability in the Response of Serum Erythropoietin to Multiple Simulated Altitude Exposures.

Baranauskas, Marissa N., Timothy J. Fulton, Alyce D. Fly, Bruce J. Martin, Timothy D. Mickleborough, and Robert F. Chapman. High intraindividual variability in the response of serum erythropoietin to multiple simulated altitude exposures. High Alt Med Biol. 23:85-89, 2022. Purpose: To evaluate within-subject variability in the serum erythropoietin (EPO) response to multiple simulated altitude exposures. Methods: Seven physically active men and women (age 27 ± 3 years, body mass index = 24.6 ± 4.0 kg/m2) were exposed to normobaric hypoxia (fraction of inspired oxygen [FiO2] = 0.14) for 12 hours on three separate occasions. Serum EPO concentrations were measured before exposure (0 hour), after 6 hours, and after 12 hours in hypoxia. The EPO response to hypoxia was calculated as percent change from 0 to 12 hours (ΔEPO0-12). Results: Exposure time had a significant effect on EPO (p < 0.001) with concentrations increasing 3.2 ± 1.3 mIU/ml from 0 to 6 hours (p = 0.034) and 4.7 ± 1.2 mIU/ml from 0 to 12 hours (p = 0.001). Group mean ΔEPO0-12 remained unchanged (p = 0.688) between the three exposures; however, there was considerable intraindividual variability in EPO responses. The intrasubject coefficient of variation for ΔEPO0-12 was 61% ± 28% (range: 17%-103%) with intrasubject associations ranging r = 0.052 to r = 0.651 between repeated exposures. Conclusions: Athletes who routinely supplement training with simulated altitude methods (e.g., hypoxic tents) should expect inconsistent EPO responses to intermittent exposures lasting ≤12 hours.

Respiratory Muscle Fatigue Alters Cycling Performance and Locomotor Muscle Fatigue.

PURPOSE: This study aimed to determine if preexisting respiratory muscle fatigue (RMF) alters motoneuronal output, locomotor muscle fatigue, and cycling performance. METHODS: Eight trained male cyclists performed 5-km cycling time trials after a resistive breathing task that induced RMF and under control conditions (CON). Motoneuronal output was estimated using vastus lateralis surface electromyography, and locomotor muscle fatigue was quantified as the change in potentiated quadriceps twitch force from preexercise to postexercise. RESULTS: Time to complete the time trial was 1.9% ± 0.9% longer in RMF compared with CON (P < 0.001). Estimated motoneuronal output was lower in RMF compared with CON during 1 km (45% ± 11% vs 53% ± 13%, P = 0.004) and 2 km (45% ± 14% vs 51% ± 14%, P = 0.008), but was not different thereafter. Ventilation was lower in RMF compared with CON during 1 km (114 ± 19 vs 135 ± 24 L·min, P = 0.003) and 2 km (136 ± 23 vs 152 ± 31 L·min, P = 0.009); however, ratings of dyspnea were similar. After the 5-km time trial, locomotor muscle fatigue was attenuated in RMF compared with CON (-22% ± 6%, vs -28% ± 7%, P = 0.02). CONCLUSIONS: Alterations to dyspnea for a given ventilation seem to have constrained power output during cycling exercise, thereby limiting the development of locomotor muscle fatigue. These findings indicate that the respiratory system is an integral component in a global feedback loop that regulates exercise performance and the development of locomotor muscle fatigue.

Axis Specification in Zebrafish Is Robust to Cell Mixing and Reveals a Regulation of Pattern Formation by Morphogenesis.

A fundamental question in developmental biology is how the early embryo establishes the spatial coordinate system that is later important for the organization of the embryonic body plan. Although we know a lot about the signaling and gene-regulatory networks required for this process, much less is understood about how these can operate to pattern tissues in the context of the extensive cell movements that drive gastrulation. In zebrafish, germ layer specification depends on the inheritance of maternal mRNAs [1-3], cortical rotation to generate a dorsal pole of ß-catenin activity [4-8], and the release of Nodal signals from the yolk syncytial layer (YSL) [9-12]. To determine whether germ layer specification is robust to altered cell-to-cell positioning, we separated embryonic cells from the yolk and allowed them to develop as spherical aggregates. These aggregates break symmetry autonomously to form elongated structures with an anterior-posterior pattern. Both forced reaggregation and endogenous cell mixing reveals how robust early axis specification is to spatial disruption of maternal pre-patterning. During these movements, a pole of Nodal signaling emerges that is required for explant elongation via the planar cell polarity (PCP) pathway. Blocking of PCP-dependent elongation disrupts the shaping of opposing poles of BMP and Wnt/TCF activity and the anterior-posterior patterning of neural tissue. These results lead us to suggest that embryo elongation plays a causal role in timing the exposure of cells to changes in BMP and Wnt signal activity during zebrafish gastrulation. VIDEO ABSTRACT.

Effect of carbohydrate ingestion on central fatigue during prolonged running exercise in moderate hypoxia.

To determine whether acute exposure to moderate hypoxia alters central and peripheral fatigue and to test whether carbohydrate ingestion impacts fatigue characteristics, 12 trained runners completed three running trials lasting 1 h each at 65% of normoxic maximum oxygen uptake. The first trial was performed in normoxia [inspired O2 fraction ( FiO2 ) = 0.21], and the last two trials were completed in hypoxia ( FiO2 = 0.15). Participants ingested a placebo drink in normoxia (NORM-PLA), a placebo drink in hypoxia (HYP-PLA), or a carbohydrate solution in hypoxia (HYP-CHO). HYP conditions were randomized. Peripheral [change in potentiated quadriceps twitch force (ΔQtw,pot)] and central [change in voluntary activation (ΔVA)] fatigue were assessed via preexercise-to-postexercise changes in magnetically evoked quadriceps twitch. In HYP, blood was drawn to determine the ratio of free-tryptophan (f-TRP) to branched-chain amino acids (BCAA). After exercise, peripheral fatigue was reduced to a similar degree in normoxia and hypoxia (ΔQtw,pot = -4.5 ± 1.3% and -4.0 ± 1.5% in NORM-PLA and HYP-PLA, respectively; P = 0.61). Central fatigue was present after normoxic and hypoxic exercise but to a greater degree in HYP-PLA compared with NORM-PLA (ΔVA: -4.7 ± 0.9% vs. -1.9 ± 0.7%; P < 0.01). Carbohydrate ingestion did not influence central fatigue (ΔVA in HYP-CHO: -5.7 ± 1.2%; P = 0.51 vs. HYP-PLA). After exercise, no differences were observed in the ratio of f-TRP to BCAA between HYP-PLA and HYP-CHO ( P = 0.67). Central fatigue increased during prolonged running exercise in moderate hypoxia although the ratio of f-TRP to BCAA remained unchanged. Ingesting carbohydrates while running in hypoxia did not influence fatigue development. NEW & NOTEWORTHY Hypoxic exposure influences the origin of exercise-induced fatigue and the rate of fatigue development depending on the severity of hypoxia. Our data suggest that moderate hypoxia increases central, but not peripheral, fatigue in trained runners exercising at 65% of normoxic maximum oxygen uptake. The increase in central fatigue was unaffected by carbohydrate intake and occurred although the ratio of free tryptophan to branched-chain amino acids remained unchanged.

Locomotor-respiratory coupling is maintained in simulated moderate altitude in trained distance runners.

To determine whether acute exposure to simulated moderate altitude alters locomotor-respiratory coupling (LRC) patterns in runners, 13 trained male distance runners performed a running economy and maximal oxygen uptake (V̇o2max) test in normoxia (NORM) and hypoxia (HYP) ([Formula: see text]= 15.8%; ~2,400 m/8,000 ft) on separate days. Running economy (RE), the degree of LRC, stride frequency-to-breathing frequency quotients (SF/fb), ratings of perceived exertion (RPE), and dyspnea were assessed at three common submaximal speeds and V̇o2max. SF/fb were significantly lower at each submaximal speed in HYP (12.9 km/h: 2.91 ± 0.20 vs. 2.45 ± 0.17, 14.3 km/h: 2.53 ± 0.17 vs. 2.21 ± 0.14, 16.1 km/h: 2.22 ± 0.14 vs. 1.95 ± 0.09; P < 0.05). The degree of LRC (range: 36-99%) in HYP was not significantly different than NORM at any of the three common submaximal speeds. However, the degree of LRC was significantly higher at V̇o2max in HYP than NORM (43.8 ± 3.4% vs. 57.1 ± 3.8%; P < 0.05). RE and RPE were similar at all running speeds. Dyspnea was significantly greater in HYP compared with NORM at 16.1 km/h ( P < 0.05). Trained distance runners are able to maintain LRC in HYP, despite increases in breathing frequency. Within this unique population, years of training may enhance and optimize the ability to maintain LRC to minimize metabolic costs and dyspnea. NEW & NOTEWORTHY Exposure to acute altitude causes increases in ventilation at rest and any submaximal exercising workload, which may alter locomotor-respiratory coupling (LRC). Our data suggest that trained distance runners can maintain LRC during acute exposure to simulated moderate altitude, even when breathing frequency is increased at any submaximal pace.

Altered stored calcium release in skeletal myotubes deficient of triadin and junctin.

Triadin and junctin are integral sarcoplasmic reticulum membrane proteins that form a macromolecular complex with the skeletal muscle ryanodine receptor (RyR1) but their roles in skeletal muscle calcium homeostasis remain incompletely understood. Here we report that delivery of siRNAs specific for triadin or junctin into C2C12 skeletal myoblasts reduced the expression of triadin and junctin in 8-day-old myotubes by 80 and 100%, respectively. Knocking down either triadin or junctin in these cells reduced Ca2+ release induced by depolarization (10mM KCl) by 20-25%. Unlike triadin knockdown myotubes, junctin knockdown and junctin/triadin double knockdown myotubes also had reduced Ca2+ release induced by 400 microM 4-chloro-m-cresol, 10mM caffeine, 400 microM UTP, or 1 microM thapsigargin. Thus, knocking down junctin compromised the Ca2+ stores in the sarcoplasmic reticulum of these cells. Our subsequent studies showed that in junctin knockdown myotubes at least two sarcoplasmic reticulum proteins (RyR1 and skeletal muscle calsequestrin) were down-regulated while these proteins' mRNA expression was not affected. The results suggest that triadin has a role in facilitating KCl depolarization-induced Ca2+ release in contrast to junctin which has a role in maintaining sarcoplasmic reticulum Ca2+ store size in C2C12 myotubes.