The herbivorous sauropod dinosaurs of the Jurassic and Cretaceous periods were the largest terrestrial animals ever, surpassing the largest herbivorous mammals by an order of magnitude in body mass. Several evolutionary lineages among Sauropoda produced giants with body masses in excess of 50 metric tonnes by conservative estimates. With body mass increase driven by the selective advantages of large body size, animal lineages will increase in body size until they reach the limit determined by the interplay of bauplan, biology, and resource availability. There is no evidence, however, that resource availability and global physicochemical parameters were different enough in the Mesozoic to have led to sauropod gigantism.We review the biology of sauropod dinosaurs in detail and posit that sauropod gigantism was made possible by a specific combination of plesiomorphic characters (phylogenetic heritage) and evolutionary innovations at different levels which triggered a remarkable evolutionary cascade. Of these key innovations, the most important probably was the very long neck, the most conspicuous feature of the sauropod bauplan. Compared to other herbivores, the long neck allowed more efficient food uptake than in other large herbivores by covering a much larger feeding envelope and making food accessible that was out of the reach of other herbivores. Sauropods thus must have been able to take up more energy from their environment than other herbivores.The long neck, in turn, could only evolve because of the small head and the extensive pneumatization of the sauropod axial skeleton, lightening the neck. The small head was possible because food was ingested without mastication. Both mastication and a gastric mill would have limited food uptake rate. Scaling relationships between gastrointestinal tract size and basal metabolic rate (BMR) suggest that sauropods compensated for the lack of particle reduction with long retention times, even at high uptake rates.The extensive pneumatization of the axial skeleton resulted from the evolution of an avian-style respiratory system, presumably at the base of Saurischia. An avian-style respiratory system would also have lowered the cost of breathing, reduced specific gravity, and may have been important in removing excess body heat. Another crucial innovation inherited from basal dinosaurs was a high BMR. This is required for fueling the high growth rate necessary for a multi-tonne animal to survive to reproductive maturity.The retention of the plesiomorphic oviparous mode of reproduction appears to have been critical as well, allowing much faster population recovery than in megaherbivore mammals. Sauropods produced numerous but small offspring each season while land mammals show a negative correlation of reproductive output to body size. This permitted lower population densities in sauropods than in megaherbivore mammals but larger individuals.Our work on sauropod dinosaurs thus informs us about evolutionary limits to body size in other groups of herbivorous terrestrial tetrapo...

Adaptive changes of major body systems in astronauts during spaceflight can be simulated by strict anti-orthostatic head-down tilt (HDT) bed rest (BR), a ground-based microgravity (microG) model that provides a meaningful opportunity to study atrophy mechanisms and possible countermeasures under controlled experimental conditions. As nitric oxide (NO) signaling is linked to muscle activity, we investigated altered expression of the three major isoforms of nitric oxide synthase (NOS 1-3) at cellular compartments during prolonged HDT BR without (control group) and with resistance exercise interventions (exercise group) using a flywheel ergometer (FWE). Atrophy detected in mixed (fast-slow) m. vastus lateralis (VL) and slow-type m. soleus (SOL) myofiber Types I and II (minus 35-40% of myofiber cross-sectional area) was prevented by FWE training. Concomitant to muscle atrophy, reduced NOS 1 protein and immunostaining was found in VL not in SOL biopsies. In trained VL, NOS 1 protein and immunostaining at myofibers II were significantly increased at the end of BR. Exercise altered NOS 2/caveolin 3 co-immunostaining patterns of subsarcolemmal focal accumulations in VL or SOL myofibers, which suggests reorganization of sarcolemmal microdomains. In trained VL, increased capillary-to-fiber (C/F) ratio and NOS 3 protein content were documented. Activity-linked NO signaling may be widespread in skeletal muscle cellular compartments that may be directly or indirectly impacted by adequate exercise countermeasure protocols to offset the negative effects induced by disuse, immobilization, or extended exposure to microgravity.

Microgravity exposure as well as chronic disuse are two main causes of skeletal muscle atrophy in animals and humans. The antigravity calf soleus is a reference postural muscle to investigate the mechanism of disuse-induced maladaptation and plasticity of human and rodent (rats or mice) skeletal musculature. Here, we report microgravity-induced global gene expression changes in space-flown mouse skeletal muscle and the identification of yet unknown disuse susceptible transcripts found in soleus (a mainly slow phenotype) but not in extensor digitorum longus (a mainly fast phenotype dorsiflexor as functional counterpart to soleus). Adult C57Bl/N6 male mice (n = 5) flew aboard a biosatellite for 30 days on orbit (BION-M1 mission, 2013), a sex and age-matched cohort were housed in standard vivarium cages (n = 5), or in a replicate flight habitat as ground control (n = 5). Next to disuse atrophy signs (reduced size and myofiber phenotype I to II type shift) as much as 680 differentially expressed genes were found in the space-flown soleus, and only 72 in extensor digitorum longus (only 24 genes in common) compared to ground controls. Altered expression of gene transcripts matched key biological processes (contractile machinery, calcium homeostasis, muscle development, cell metabolism, inflammatory and oxidative stress response). Some transcripts (Fzd9, Casq2, Kcnma1, Ppara, Myf6) were further validated by quantitative real-time PCR (qRT-PCR). Besides previous reports on other leg muscle types we put forth for the first time a complete set of microgravity susceptible gene transcripts in soleus of mice as promising new biomarkers or targets for optimization of physical countermeasures and rehabilitation protocols to overcome disuse atrophy conditions in different clinical settings, rehabilitation and spaceflight.

We investigated the changes in the cardiovascular system [resting blood pressure (BP) and heart rate (HR), measured by means of a 24-h ambulatory BP and a holter-electrocardiogram (ECG)], glycemic parameters, and lipid metabolism of subjects suffering from metabolic syndrome during a 3-week sojourn at 1,700 m in the Austrian Alps. A total of 22 male subjects with metabolic syndrome were selected. Baseline investigations were performed at Innsbruck (500 m above sea level). During the 3-week altitude stay the participants simulated a holiday with moderate sports activities. Examinations were performed on days 1, 4, 9, and 19. After returning to Innsbruck, post-altitude examinations were conducted after 7-10 days and 6-7 weeks, respectively. The 24-h ambulatory BP and holter ECG revealed a decrease in average HR, BP, and rate pressure product (RPP: systolic blood pressure x HR) after 3 weeks of altitude exposure. In some patients, an increase in premature ventricular beats was observed at the end compared to the beginning of the exposure to moderate altitude. The ECG revealed no ischemic ST-segment changes. Maximal physical capacity as measured by symptom-limited maximal cycle ergometry tests remained unchanged during the study. Six weeks after the altitude exposure the blood pressure increased again and returned to pretest levels. The Homeostasis Model Assessment index, which is a measure of insulin resistance, decreased significantly and glucose concentrations obtained after an oral glucose tolerance test were significantly lower after the stay at altitude compared to the basal values. We conclude that after a 3-week exposure to moderate altitude, patients with metabolic syndrome (1) tolerated their sojourn without any physical problems, (2) exhibited short-term favorable effects on the cardiovascular system, and (3) had significant improvements in glycemic parameters that were paralleled by a significant increase in high-density-lipoprotein-cholesterol.

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Allometric equations are often used to extrapolate traits in animals for which only body mass estimates are known, such as dinosaurs. One important decision can be whether these equations should be based on mammal, bird or reptile data. To address whether this choice will have a relevant influence on reconstructions, we compared allometric equations for birds and mammals from the literature to those for reptiles derived from both published and hitherto unpublished data. Organs studied included the heart, kidneys, liver and gut, as well as gut contents. While the available data indicate that gut content mass does not differ between the clades, the organ masses for reptiles are generally lower than those for mammals and birds. In particular, gut tissue mass is significantly lower in reptiles. When applying the results in the reconstruction of a sauropod dinosaur, the estimated volume of the coelomic cavity greatly exceeds the estimated volume of the combined organ masses, irrespective of the allometric equation used. Therefore, substantial deviation of sauropod organ allometry from that of the extant vertebrates can be allowed conceptually. Extrapolations of retention times from estimated gut contents mass and food intake do not suggest digestive constraints on sauropod dinosaur body size.

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