Oxigraf Offices Are Closed November 26, 2020 In Observance of Thanksgiving.
An international crew of astronauts is en route to the International Space Station following a successful launch on the first NASA-certified commercial human spacecraft system in history. NASA’s SpaceX Crew-1 mission lifted off at 7:27 p.m. EST Sunday from Launch Complex 39A at the agency’s Kennedy Space Center in Florida.
The SpaceX Falcon 9 rocket propelled the Crew Dragon spacecraft with NASA astronauts Michael Hopkins, Victor Glover, and Shannon Walker, along with Soichi Noguchi of the Japan Aerospace Exploration Agency (JAXA), into orbit to begin a six-month science mission aboard the space station.
“NASA is delivering on its commitment to the American people and our international partners to provide safe, reliable, and cost-effective missions to the International Space Station using American private industry,” said NASA Administrator Jim Bridenstine. “This is an important mission for NASA, SpaceX and our partners at JAXA, and we look forward to watching this crew arrive at station to carry on our partnership for all of humanity.”
The Crew Dragon spacecraft, named Resilience, will dock autonomously to the forward port of the station’s Harmony module about 11 p.m. Monday, Nov. 16. NASA Television and the agency’s website are providing ongoing live coverage through docking, hatch opening, and the ceremony to welcome the crew aboard the orbiting laboratory.
“I could not be more proud of the work we’ve done here today,” said Gwynne Shotwell, president and chief operating officer of SpaceX. “Falcon 9 looked great, Dragon was dropped off into a beautiful orbit about 12 minutes into the mission, and we’ll get more data as we go.”
The Crew-1 mission is the first of six crewed missions NASA and SpaceX will fly as part of the agency’s Commercial Crew Program. This mission has several firsts, including:
- The first flight of the NASA-certified commercial system designed for crew transportation, which moves the system from development into regular flights;
- The first international crew of four to launch on an American commercial spacecraft;
- The first time the space station’s long duration expedition crew size will increase from six to seven crew members, which will add to the crew time available for research; and
- The first time the Federal Aviation Administration has licensed a human orbital spaceflight launch. The astronauts named the Crew Dragon spacecraft Resilience, highlighting the dedication teams involved with the mission have displayed and to demonstrate that when we work together, there is no limit to what we can achieve. They named it in honor of their families, colleagues, and fellow citizens.
“Watching this mission launch is a special moment for NASA and our SpaceX team,” said Steve Stich, manager of NASA’s Commercial Crew Program. “We are looking forward to getting this crew to station to continue our important work, and I want to thank the teams for the amazing effort to make the next generation of human space transportation possible.”
During flight, SpaceX commands the spacecraft from its mission control center in Hawthorne, California, and NASA teams monitor space station operations throughout the flight from the Mission Control Center at the agency’s Johnson Space Center in Houston.
Hopkins, Glover, Walker, and Noguchi will join the Expedition 64 crew of Commander Sergey Ryzhikov and Flight Engineer Sergey Kud-Sverchkov, both of the Russian space agency Roscosmos, and Flight Engineer Kate Rubins of NASA.
“It is an honor to have our Japanese astronaut launch on this Crew-1 Dragon as the first astronaut of the International Partner participating in the ISS program,” said Hiroshi Sasaki, JAXA vice president. “We look forward to having him conduct lots of science and demonstrate the technology, for here on Earth and for the future. I would also like to thank NASA and SpaceX for their tremendous effort to make this happen.”
Rubins, Hopkins, Glover, Walker, and Noguchi will participate in a live crew news conference from orbit at 9:55 a.m. Thursday, Nov. 19, on NASA TV and the agency’s website.
Michael Hopkins is commander of the Crew Dragon spacecraft and the Crew-1 mission. Hopkins is responsible for all phases of flight, from launch to re-entry. He also will serve as an Expedition 64 flight engineer aboard the station. Selected as a NASA astronaut in 2009, Hopkins spent 166 days in space as a long-duration crew member of Expeditions 37 and 38 and completed two spacewalks totaling 12 hours and 58 minutes. Born in Lebanon, Missouri, Hopkins grew up on a farm outside Richland, Missouri. He has a bachelor’s degree in aerospace engineering from the University of Illinois, and a master’s degree in aerospace engineering from Stanford University. Before joining NASA, Hopkins was a flight test engineer with the U.S. Air Force. Follow Hopkins on Twitter.
Victor Glover is the pilot of the Crew Dragon spacecraft and second-in-command for the mission. Glover is responsible for spacecraft systems and performance. He also will be a long-duration space station crew member. Selected as an astronaut in 2013, this is his first spaceflight.
The California native holds a Bachelor of Science degree in general engineering from California Polytechnic State University, a Master of Science degree in flight test engineering and a master’s degree military operational art and science from Air University, and a Master of Science degree in systems engineering from Naval Postgraduate School. Glover is a naval aviator and was a test pilot in the F/A‐18 Hornet, Super Hornet, and EA‐18G Growler aircraft. Follow Glover on Twitter and Instagram.
Shannon Walker is a mission specialist for Crew-1. As a mission specialist, she works closely with the commander and pilot to monitor the vehicle during the dynamic launch and re-entry phases of flight. She also is responsible for monitoring timelines, telemetry, and consumables. Once aboard the station, Walker will become a flight engineer for Expedition 64. Selected as a NASA astronaut in 2004, Walker launched to the International Space Station aboard the Russian Soyuz TMA-19 spacecraft as the co-pilot, and spent 161 days aboard the orbiting laboratory. More than 130 microgravity experiments were conducted during her stay in areas such as human research, biology, and materials science. A Houston native, Walker received a Bachelor of Arts degree in physics from Rice University, as well as a Master of Science degree and a doctorate in space physics, both from Rice University, in 1992 and 1993, respectively.
Soichi Noguchi also is a mission specialist for Crew-1, working with the commander and pilot to monitor the vehicle during the dynamic launch and re-entry phases of flight, and keeping watch on timelines, telemetry and consumables. Noguchi also will become a long-duration crew member aboard the space station. He was selected as an astronaut candidate by the National Space Development Agency of Japan (NASDA, currently the Japan Aerospace Exploration Agency) in May 1996. Noguchi is a veteran of two spaceflights. During STS-114 in 2005, Noguchi became the first Japanese astronaut to perform a spacewalk outside the space station. He performed a total of three spacewalks during the mission, accumulating 20 hours and 5 minutes of spacewalking time. He launched aboard a Soyuz spacecraft in 2009, to return to the station as a long-duration crew member. The Crew Dragon will be the third spacecraft Noguchi has flown to the orbiting laboratory. Follow Noguchi on Twitter and Instagram.
The crew will conduct science and maintenance during a six-month stay aboard the orbiting laboratory and will return in spring 2021. It is scheduled to be the longest human space mission launched from the United States. The Crew Dragon spacecraft is capable of staying in orbit for at least 210 days, as a NASA requirement.
Crew Dragon also is delivering more than 500 pounds of cargo, new science hardware and experiments inside, including Food Physiology, a study of the effects of an optimized diet on crew health and, Genes in Space-7, a student-designed experiment that aims to better understand how spaceflight affects brain function, enabling scientists to keep astronauts healthy as they prepare for long-duration missions in low-Earth orbit and beyond.
Among the science and research investigations the crew will support during its six-month mission are a study using chips with tissue that mimics the structure and function of human organs to understand the role of microgravity on human health and diseases and translate those findings to improve human health on Earth, growing radishes in different types of light and soils as part of ongoing efforts to produce food in space, and testing a new system to remove heat from NASA’s next generation spacesuit, the Exploration Extravehicular Mobility Unit (xEMU).
During their stay on the orbiting laboratory, Crew-1 astronauts expect to see a range of uncrewed spacecraft including the next generation of SpaceX cargo Dragon spacecraft, the Northrop Grumman Cygnus, and the Boeing CST-100 Starliner on its uncrewed flight test to the station. They also will conduct a variety of spacewalks and welcome crews of the Russian Soyuz vehicle and the next SpaceX Crew Dragon in 2021.
At the conclusion of the mission, the Crew-1 astronauts will board Crew Dragon, which will then autonomously undock, depart the space station, and re-enter Earth’s atmosphere. Crew Dragon also will return to Earth important and time-sensitive research. NASA and SpaceX are capable of supporting seven splashdown sites located off Florida’s east coast and in the Gulf of Mexico. Upon splashdown, the SpaceX recovery ship will pick up the crew and return to shore.
NASA’s Commercial Crew Program is delivering on its goal of safe, reliable, and cost-effective transportation to and from the International Space Station from the United States through a partnership with American private industry. This partnership is changing the arc of human spaceflight history by opening access to low-Earth orbit and the International Space Station to more people, more science, and more commercial opportunities.
The space station remains the springboard to NASA’s next great leap in space exploration, including future missions to the Moon and, eventually, to Mars. For more than 20 years, humans have lived and worked continuously aboard the International Space Station, advancing scientific knowledge and demonstrating new technologies, making research breakthroughs not possible on Earth. As a global endeavor, 242 people from 19 countries have visited the unique microgravity laboratory that has hosted more than 3,000 research and educational investigations from researchers in 108 countries and areas.
Source: NASA – November 15, 2020; RELEASE 20-114:
Caffeine is one of the most used ergogenic aid for physical exercise and sports. However, its mechanism of action is still controversial. The adenosinergic hypothesis is promising due to the pharmacology of caffeine, a nonselective antagonist of adenosine A1 and A2A receptors. We now investigated A2AR as a possible ergogenic mechanism through pharmacological and genetic inactivation. Forty-two adult females (20.0 ± 0.2 g) and 40 male mice (23.9 ± 0.4 g) from a global and forebrain A2AR knockout (KO) colony ran an incremental exercise test with indirect calorimetry (V̇O2 and RER). We administered caffeine (15 mg/kg, i.p., nonselective) and SCH 58261 (1 mg/kg, i.p., selective A2AR antagonist) 15 min before the open field and exercise tests. We also evaluated the estrous cycle and infrared temperature immediately at the end of the exercise test. Caffeine and SCH 58621 were psychostimulant. Moreover, Caffeine and SCH 58621 were ergogenic, that is, they increased V̇O2max, running power, and critical power, showing that A2AR antagonism is ergogenic. Furthermore, the ergogenic effects of caffeine were abrogated in global and forebrain A2AR KO mice, showing that the antagonism of A2AR in forebrain neurons is responsible for the ergogenic action of caffeine. Furthermore, caffeine modified the exercising metabolism in an A2AR-dependent manner, and A2AR was paramount for exercise thermoregulation.
The natural plant alkaloid caffeine (1,3,7-trimethylxantine) is one of the most common ergogenic substances for physical activity practitioners and athletes1,2,3,4,5,6,7,8,9,10. Caffeine increases endurance1,8,9,10,11,12, intermittent7,13,14 and resistance4,15 exercise in humans. In rodents, its ergogenic effects are conserved because caffeine increases running time on the treadmill at constant16,17 and accelerated speeds18,19. Sports sciences promote nonselective phosphodiesterase (PDE) inhibition7,8 and increased calcium mobilization2,7,8 as mechanisms for these ergogenic effects. However, the primary pharmacological effect of caffeine is the nonselective antagonism of adenosine A1 and A2A receptors (A1R, A2AR)20,21,22,23.
Adenosine can act as an inhibitory modulator of the Central Nervous System (CNS) associated with tiredness and drowsiness24,25,26,27,28,29. During exercise, circulating ADP/AMP/adenosine levels increase due to ATP hydrolysis30,31. However, there is still no substantial evidence on the role of adenosine in exercise-induced fatigue. It is just known that the nonselective A1R and A2AR agonist 5′-(N-ethylcarboxamido)adenosine (NECA), injected into the rat brain, abolishes the ergogenic effects of caffeine16.
Since there is increasing evidence that the adenosine modulation system critically controls allostasis29 and A2AR have a crucial role in the ability of caffeine to normalize brain function30, we hypothesized that caffeine decreases fatigue during exercise through antagonism of A2AR in the CNS. We combined the use of pharmacology (SCH 58261 and caffeine) and transgenic mice with tissue-selective deletion of A2AR, to test this hypothesis in an incremental running test with indirect calorimetry (or ergospirometry). A2AR knockout (KO) mice allow assessing if the ergogenic effect of caffeine persists in the absence of A2AR; the use of SCH 58261, the current reference for A2AR antagonists32,33, allows directly assessing the ergogenic role of A2AR. SCH 58261 has excellent selectivity and affinity for A2AR32,33, and affords motor benefits in animal models of Parkinson’s disease as does caffeine, supporting the recent FDA approval of the A2AR antagonist Istradefylline for PD treatment33. Our goal is to assess the ergogenicity of A2AR using the pharmacological and genetic tools described above.
SCH 58261: pharmacological inactivation of A2AR is ergogenic
SCH 58261 was psychostimulant for males, but not for females, since SCH 58261 only increased male locomotion in the open field (F1,39 = 4.5, η2 = 0.1, β = 0.54, 95% CI 58.8–72.1, P < 0.05, Fig. 1A).
The running power of females (F7,77 = 221, P < 0.05, Fig. 1B) and males (F7,84 = 183, P < 0.05, Fig. 1B’) increased at each stage of the exercise test. Submaximal V̇O2 also increased to the maximum (V̇O2max, dotted line) of females (F8,77 = 168, P < 0.05, Fig. 1B) and males (F7,84 = 14.3, P < 0.05, Fig. 1B’). Female (F8,70 = 180, P < 0.05, Fig.S2A) and male (F8,70 = 164, P < 0.05, Fig.S2B) submaximal V̇CO2 kinetics was similar to V̇O2. SCH 58261 had no effect on these submaximal values.
We demonstrated for the first time that SCH 58261 is ergogenic since SCH 58261 increased V̇O2max (F1,36 = 27.7, η2 = 0.44, β = 0.99, 95% CI 0.16–0.2, P < 0.5, Fig. 1C) and running power (F1,35 = 55, η2 = 0.61, β = 1.0, 95% CI 1.0–1.3, P < 0.05, Fig. 1D) in both sexes.
SCH 58261 had no effect on increasing RER of females (F7,70 = 6.9, P < 0.5, η2 = 0.43, β = 0.99, Fig. 1E) and males (F7,84 = 9.4, η2 = 0.57, β = 0.99, P < 0.5, Fig. 1E’). Exercise test raised the animals’ core (F1,26 = 5.5, η2 = 0.17, β = 0.62, 95% CI 28.7–29.39, P < 0.05, Fig. 1F) and tail temperature (F1,22 = 81, η2 = 0.78, β = 0.99, 95% CI 24.2–25.6, P < 0.05, Fig. 1G), with no effect of SCH 58261. Figure 1 shows the heating of the mouse’s tail in post-exercise recovery (rec) in relation to rest. Three females at estrus (Fig.S3C) were excluded from temperature experiments due to large exercise-induced tail hyperthermia40. The previous results refer to females in diestrus (Fig.S3A), proestrus (Fig.S3B), and metestrus (Fig.S3D).
Neuronal A2AR antagonism is ergogenic
Caffeine increases exercise performance in rodents16,17,19,26,40 and humans1,4,8,9,10,11,12,13,14,15,24,28,51,52. Our results show the key role of A2AR in the ergogenic effects of caffeine using pharmacological and genetic tools. Thus, the potent and selective A2AR antagonist SCH 58261 displayed an ergogenic effect similar to that of caffeine, and the ergogenic effect of caffeine was abrogated in A2AR KO mice.
SCH 58261 and caffeine improved V̇O2max, running and critical power of wild type mice. These results are in line with the improved running time observed in caffeine-treated rats16,26,53 and mice19. Further evidence for the ergogenic effect of caffeine is based on its ability to increase muscle power and endurance output in rodents54,55,56,57,58. For the first time, we demonstrated that the selective antagonism of A2AR is ergogenic. Also, for the first time, we demonstrated that the genetic inactivation of A2AR impaired the ergogenic effects of caffeine. Tissue-specific A2AR KO selectively in forebrain neurons further allowed showing that these ergogenic effects of caffeine are due to the antagonism of A2AR in forebrain neurons. Thus, we suggest that caffeine decreases central fatigue during exercise. Moreover, caffeine decreased RER in the submaximal stages of the exercise test, an effect also abrogated in A2AR KO mice. However, exercise-induced core and tail hyperthermia were similar among animals treated with SCH 58261 or caffeine, except for A2AR KO mice, suggesting possible A1R-A2AR-mediated interactions56,57 in the temperature control51.
In summary, we have now demonstrated that A2AR antagonism is a mechanism of action for ergogenicity, as SCH 58261 was ergogenic. Furthermore, we showed that the antagonism of forebrain A2AR was the mechanism underlying the ergogenic effect of caffeine since caffeine was not ergogenic in fb-A2AR KO. The use of selective A2AR KO in forebrain neurons further reinforces the ergogenic role of caffeine in decreasing central fatigue, with possible involvement of decreased perceived exertion, pain, and mental fatigue in humans. Despite methodological limitations, our data further suggest that caffeine modified the exercising metabolism in an A2AR-dependent manner and that A2AR is essential for exercise thermoregulation.
Authors: Aderbal S.Aguiar Jr1,2*; Ana Elisa Speck1,2; Paula M. Canas1; RodrigoA. Cunha1,3
1 CNC‑Center for Neuroscience and Cell Biology, University of Coimbra, 3004‑504 Coimbra, Portugal.
2 Biology of Exercise Lab, Department of Health Sciences, UFSC-Federal University of Santa Catarina, Araranguá, SC 88905‑120, Brazil.
3 FMUC – Faculty of Medicine, University of Coimbra, 3004‑504 Coimbra, Portugal.
published in: Nature Scientific Reports 10, 13414 (2020).