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This Protein Could Boost Brain Function without Exercise

Jacob Scott

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The drumbeat of exercise’s brain benefits may sound familiar. Most of us know that getting our move on can mean a boost to mental and neurological health. But what if, through understanding these biochemical processes, we could get all of that brain gain without going through the exercise pain? Mouse experiments have already demonstrated the feasibility of such a shortcut. And there is a hint that the results in rodents could work in humans as well.

When plasma from well-exercised mice is injected into their idling counterparts, the sedentary rodents have improved memory and reduced brain inflammation. The blood of Olympic athletes is not about to be transfused into the arms of sofa spuds—at least not yet. But people with mild cognitive impairment who exercise for six months show increases in a key protein identified in the runner-mouse plasma. The same protein may be able to whisper its chemical message across the notoriously choosy blood-brain barrier and trigger anti-inflammatory processes in the brain.

These findings, published on December 8 in Nature, offer new details of how exercise benefits the brain and how molecules boosted by physical activity communicate across the organ’s strict gatekeeper. The results also hint at a surprising role for the liver and anticlotting systems in these effects and possibly point the way to a futuristic scenario of exercise in a pill—or perhaps a plasma injection.

“Puzzle pieces are coming together,” says Saul Villeda, an associate professor in the department of anatomy at the University of California, San Francisco, about these hints of multisystem involvement in exercise’s effects on the brain. Villeda, who was not involved in the new study, and his colleagues previously identified a protein in exercised-mouse plasma that refreshed neurons in the aging mouse brain. “We’re starting to identify factors in the blood that can target different facets of decline or pathology, and this one really highlights blood factors affecting inflammation in the brain,” he says. “The word that keeps popping into my head is ‘convergence.’”

On the path to convergence, behavioral scientist Zurine de Miguel, now an assistant professor at California State University, Monterey Bay, and her colleagues at Stanford University and the Department of Veterans Affairs Palo Alto Health Care System first had to let mice exercise. The animals ran their heart out for 28 days, and then their plasma was transferred to mice that had not touched a running wheel during that time. The recipient animals showed improvements in learning and memory after they had received the “runner plasma.” Their brain, in turn, revved up genes that produced proteins that facilitated memory and learning and showed a dampened inflammatory response. When the researchers deliberately induced brain inflammation in the animals, the runner-mouse plasma dialed back that response, too.

The team next looked at what the runner plasma contained. They found increased levels of anticlotting proteins, including one called “clusterin,” which helps to clear cells of debris. Homing in on this protein, the investigators tested the effects of stripping it from the runner plasma. Brains of sedentary mice receiving clusterin-free plasma showing much less anti-inflammatory activity.

The team also found that clusterin readily attached to the cells that form the blood-brain barrier. When they mimicked the effects of physical activity by injecting the protein into the circulation of mice genetically modified to have neurodegenerative disease, the animals’ brain inflammation also declined.

Finally, the researchers wanted to see if exercise causes clusterin elevations in people. They measured the protein in 20 veterans with mild cognitive impairment before and after six months of structure physical activity and found that the levels increased.

De Miguel notes that in her and her colleagues’ study, results differed somewhat between male and female mice. Despite similar anticlotting protein profiles between the sexes, the females showed more variability. The hormones they make can affect anticlotting factors, de Miguel says, and the possibility that female mice were in a sexually receptive stage during the study might explain this greater variation.

The experiment illustrates a growing recognition of the brain’s dependence on assistance from outside the neural no-fly zone. The liver and heart are the most likely sources of clusterin, the authors say. The results implicate both organs as sources of beneficial molecules resulting from physical exercise, de Miguel says. “They all seem to be cross talking to the brain,” she adds.

Villeda says that his group’s work with “runner plasma” in aging mice also implicates the liver. The organ produces an enzyme linked to cognitive improvements in the animals, and the same enzyme was also increased in the blood of older active people. The liver connection “was surprising to us because it wasn’t usually what you focus on when you think about exercise,” he says. With the liver connection, “these mechanisms are starting to converge and come into a similar space.”

Although physical activity is closely linked to good health, it may be possible to overdo exercise. There are hints that some people who engage often in highly strenuous physical activity may have increased risk for amyotrophic lateral sclerosis. “There is some information out there that says that too much exercise can impair some of your immune response and make you susceptible to opportunistic infections,” de Miguel says.

How will “runner plasma” be used as a therapy if these effects in mice bear out in people? “I have more hope now than when I started my lab because it was difficult to think about identifying all of these factors,” Villeda says. “But now we have candidates, and when you have those, you can start thinking about small molecule development.”

De Miguel says that a possible first step might be testing which exercise protocols trigger the biggest increases in proteins that carry a brain benefit. As with mice, someone in need of the brain-boosting power of physical exercise could simply receive an injection of “runner plasma,” getting a runner’s gain without the ensuing pain.

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‘Moon Knight’ Took Marvel in a Different Orbit, but It Didn’t Rise to the Occasion

Jacob Scott

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Before anyone writes that off as an anomaly, “Eternals” tackled a similar introduction of a dense mythology on the bigger screen, with equally mixed results. It’s a reminder that while film-goers have had more than a decade to get to know characters like Iron Man, Captain America and Thor, introducing some of these lesser-known heroes can pose a more formidable challenge beyond catering to the most ardent fans.
For Marvel, there are warning signs in that, since “Moon Knight” will be followed by several series based on second-tier characters, although the next two on the horizon, “Ms. Marvel” (which is due in June) and “She-Hulk,” at least have the benefit of sharing franchises and name recognition with existing Avengers.
Ultimately, “Moon Knight’s” murky storytelling appeared to squander its principal assets, which included the cool look of the character — a costume that was too seldom used — and the presence of Isaac, who possesses additional genre credentials via the “Star Wars” sequels.

Taking its time in peeling back the layers of the character’s complicated backstory, “Moon Knight” took a weird plunge into the Egyptian mythology behind it, in ways that became increasingly confounding and surreal.

By the time the protagonist’s two halves, Steven Grant and Marc Spector, wound up in a psychiatric hospital talking to an anthropomorphic hippo in the penultimate chapter, the question wasn’t so much being able to keep up with the story as whether bothering to do so was worth the effort.

The sixth and final episode brought the plot to a messy close, seeking to stop the goddess Ammit from proceeding to “purify the souls of Cairo, and then the world.” In the customary credit sequence, the producers capped that off by introducing a third personality, Jake Lockley, also rooted in the comics. While that seemingly spelled the end for the show’s villain (Ethan Hawke), the finish — giving the god Khonshu the protégé he sought — paved the way for further adventures should Marvel so choose.

That last twist might be cause for celebration in narrower confines of the Marvel fan universe, but “Moon Knight” too often felt like it was one long Easter-egg sequence, conspicuously preaching to that choir.

Granted, Marvel has made clear that Disney+ offers the chance to explore different kinds of stories, but “Moon Knight” feels at best like a quirky showcase for Isaac and at worst a failed experiment in terms of execution and tone.

That doesn’t mean this “Moon” won’t somehow rise again, if the closely held streaming data justifies it. But the promise that surrounded this property has faded, providing further evidence that even Marvel isn’t immune from setbacks as it moves into its next phase.

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Start-up Pony.ai says it’s the first self-driving company to get a taxi license in China

Jacob Scott

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Autonomous driving start-up Pony.ai can collect fares for robotaxi rides in parts of two major Chinese cities as of Sunday.

Pony.ai handout

BEIJING — Self-driving start-up Pony.ai announced Sunday it received a taxi license, the first of its kind in China.

The license allows Pony.ai to operate 100 self-driving cars as traditional taxis in the Nansha district of the southern city of Guangzhou, the company said.

The Chinese start-up, which is backed by Toyota, received approval from Beijing city late last year to charge fees to operate a commercial robotaxi business in a suburban district of the city. It is not the same as a taxi licence.

Baidu’s Apollo Go also received approval in the same Beijing district last year.

Pony.ai was valued at $8.5 billion in early March. The company said its Nansha taxi license required 24 months of autonomous driving testing in China and/or other countries, and no involvement in any active liability traffic accidents, among other factors.

The start-up said it plans to launch commercial robotaxi businesses in two other large Chinese cities next year. The company is already testing self-driving cars in those cities and in California. 

Robotaxis in China currently have a human driver present for safety.

— CNBC’s Arjun Kharpal contributed to this report.

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How to watch Timberwolves vs. Grizzlies: TV channel, NBA live stream info, start time

Jacob Scott

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Who’s Playing

Memphis @ Minnesota

Current Records: Memphis 2-1; Minnesota 1-2

What to Know

The Memphis Grizzlies’ road trip will continue as they head to Target Center at 10 p.m. ET this past Saturday to face off against the Minnesota Timberwolves. Memphis will be strutting in after a win while Minnesota will be stumbling in from a loss.

The Grizzlies are hoping for another victory. They beat the Timberwolves 104-95 this past Thursday. The victory came about thanks to a strong surge after the first quarter to overcome a 39-21 deficit. Memphis’ success was spearheaded by the efforts of power forward Brandon Clarke, who had 20 points in addition to eight rebounds, and shooting guard Desmond Bane, who shot 7-for-15 from beyond the arc and finished with 26 points and six boards.

Barring any buzzer beaters, Memphis is expected to win a tight contest. They might be worth taking a chance on against the spread as they are currently on a two-game streak of ATS wins.

Memphis’ win brought them up to 2-1 while the Timberwolves’ defeat pulled them down to a reciprocal 1-2. A couple offensive stats to keep in the back of your head while watching: The Grizzlies come into the game boasting the second most points per game in the league at 115.6. But Minnesota is even better: they rank first in the league when it comes to points per game, with 115.9 on average. Tune in for what’s sure to be a high-scoring contest.

How To Watch

When: Saturday at 10 p.m. ET Where: Target Center — Minneapolis, Minnesota TV: ESPN Online streaming: fuboTV (Try for free. Regional restrictions may apply.) Follow: CBS Sports App Ticket Cost: $76.96

Odds

The Grizzlies are a slight 2.5-point favorite against the Timberwolves, according to the latest NBA odds.

The oddsmakers had a good feel for the line for this one, as the game opened with the Grizzlies as a 3-point favorite.

Over/Under: -110

See NBA picks for every single game, including this one, from SportsLine’s advanced computer model. Get picks now.

Series History

Memphis have won 19 out of their last 28 games against Minnesota.

Apr 21, 2022 – Memphis 104 vs. Minnesota 95 Apr 19, 2022 – Memphis 124 vs. Minnesota 96 Apr 16, 2022 – Minnesota 130 vs. Memphis 117 Feb 24, 2022 – Minnesota 119 vs. Memphis 114 Jan 13, 2022 – Memphis 116 vs. Minnesota 108 Nov 20, 2021 – Minnesota 138 vs. Memphis 95 Nov 08, 2021 – Memphis 125 vs. Minnesota 118 May 05, 2021 – Memphis 139 vs. Minnesota 135 Apr 02, 2021 – Memphis 120 vs. Minnesota 108 Jan 13, 2021 – Memphis 118 vs. Minnesota 107 Jan 07, 2020 – Memphis 119 vs. Minnesota 112 Dec 01, 2019 – Memphis 115 vs. Minnesota 107 Nov 06, 2019 – Memphis 137 vs. Minnesota 121 Mar 23, 2019 – Minnesota 112 vs. Memphis 99 Feb 05, 2019 – Memphis 108 vs. Minnesota 106 Jan 30, 2019 – Minnesota 99 vs. Memphis 97 Nov 18, 2018 – Memphis 100 vs. Minnesota 87 Apr 09, 2018 – Minnesota 113 vs. Memphis 94 Mar 26, 2018 – Memphis 101 vs. Minnesota 93 Dec 04, 2017 – Memphis 95 vs. Minnesota 92 Feb 04, 2017 – Memphis 107 vs. Minnesota 99 Nov 19, 2016 – Memphis 93 vs. Minnesota 71 Nov 01, 2016 – Minnesota 116 vs. Memphis 80 Oct 26, 2016 – Memphis 102 vs. Minnesota 98 Mar 16, 2016 – Minnesota 114 vs. Memphis 108 Feb 19, 2016 – Memphis 109 vs. Minnesota 104 Jan 23, 2016 – Minnesota 106 vs. Memphis 101 Nov 15, 2015 – Memphis 114 vs. Minnesota 106

Injury Report for Minnesota

No Injury Information

Injury Report for Memphis

Dillon Brooks: Game-Time Decision (Foot) Santi Aldama: Out (Knee) Killian Tillie: Out (Knee)

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