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By Pooja Toshniwal Paharia Sep 5 2023

In a recent study posted to the bioRxiv preprint* server, researchers in Sweden investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein amyloid as a potential triggering factor for protein misfolding and amyloid formation in neurodegenerative diseases (NDs).

Neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) and Alzheimer's disease (AD) are accelerated by the conversion of human proteins into misfolded amyloid fibril aggregates. This process is self-perpetuating through seeding from preformed fibril seeds. SARS-CoV-2 S, abundant in the inflammatory response, is a plausible mechanism for amyloid fibril formation.

Study: SARS-CoV-2 Spike amyloid fibrils specifically and selectively accelerates amyloid fibril formation of human prion protein and the amyloid β peptide. Image Credit: Design_Cells / Shutterstock

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information. About the study

In the present study, researchers performed cross-seeding neurodegenerative disease-related proteins with S protein amyloid fibrils.

In the in vitro environment, seeding studies were carried out by cross-seeding human prion protein (HuPrP)- and the Aβ1-42 protein-derived with seven distinct amyloid protein fibrils obtained from SARS-CoV-2 S peptides. The researchers examined whether SARS-CoV-2 S protein-derived amyloid protein accelerates the human A peptide and HuPrP fibril formation. Thus, prefabricated fibrils from seven SARS-CoV-2 Wuhan-Hu-1 strain S amyloidogenic sequences (spike seeds)-derived peptides, each 20 amino-acid long, were added, matching the starting protein sequence of the S glycoprotein.

E. Coli was used to make human PrP. To test seeding effect specificity, 10% seed concentrations of different amyloidogenic proteins such as Aβ1-42, TTR, insulin, and lysozyme were introduced. ThT fluorescence changes with time were used to monitor fibrillation. To slow the fibrillation rate of the unseeded HuPrP reaction and dissolve the S protein peptides, hexafluoro-isopropanol (HFIP) was used. The heterologous seed might be a protein that differs from the substrate by a single point mutation, the same protein from a different species, or another protein related to the same illness.

The seeding effect of S protein amyloids was studied using Aβ1-42 as a substrate. Replicate reaction samples were obtained for inspection using transmission electron microscopy (TEM) while ThT was monitoring Aβ1-42 fibril development. To match the greatest concentration of S protein peptide amyloids, the team added control seeds to HuPrP at 0.010 mg/mL concentration. The positive control was the fibrillar form of HuPrP90-231 at 0.0010 mg/mL concentration. Results

Using an in vitro conversion experiment, the researchers discovered that S protein-amyloid fibril-seeded amyloid production of CJD-associated HuPrP was significantly accelerated. The HuPrP conversion assay was seeded with different in vitro-generated disease-associated amyloid fibrils, and the Aβ1-42 protein was exposed to a panel of control seeds, but no fibril development was accelerated for insulin, lysozyme, or TTR. The findings indicated seeding as a unique property of S protein-amyloid fibrils rather than a universal impact.

Positive controls included Aβ1-42 protein fibrils and an amalgamation of seven fibrillated S glycoprotein peptides, and both controls indicated seeding action. Further, S protein-amyloid fibril seeds enhanced amyloid fibril development in AD-associated Aβ1-42. Spike532 (532NLVKNKCVNFNFNGLTGTGV551) was most successful in seeding HuPrP, whereas Spike601 (601GTNTSNQVAVLYQDVNCTEV620) was most effective in seeding Aβ1-42, demonstrating substrate-dependent selectivity of the cross-seeding activity.

The development of Aβ1-42 fibrils was enhanced by all seven S protein amyloids. However, like with HuPrP seeding, there was a considerable differential in seeding efficiency across the various S protein amyloids, with Aβ1-42 being more responsive to Spike601. The exponential phase of growth was finished for all seeded samples at 120 minutes in the TEM study, whereas the unseeded specimen, lacking fibrillar components but rich in oligomeric structures, continued to be in the beginning nucleation phase. Amyloid fibrils were seen in all S peptide amyloid-seeded samples.

The CJD-linked HuPrP and AD-linked Aβ1-42 peptides showed cross-seeding vulnerability with SARSCoV-2 S glycoprotein amyloids. Spike532 amyloid considerably shortened the lag period of amyloid production for HuPrP by a greater extent than other amyloid peptides, but Spike192 amyloid protein did not significantly reduce the lag period.

Spike532 seeding significantly reduced the lag period of HuPrP protein fibrillation by 80%, from 712 to 135 minutes on average. The 10-fold spike seed dilution nearly eliminated the seeding abilities of the S protein amyloids. Nevertheless, Spike532 amyloid almost retained its ability to reduce the lag period, with only a 10% reduction in the ability by the dilution.

The 0.010 mg/mL SARS-CoV-2 S protein mixture reduced lag duration from 6.75 hours to 5.1 hours (25%). Insulin fibrils reduced the lag period of HuPrP protein fibrillation considerably, while TTR, lysozyme, and the Aβ1-42 protein fibrils did not. The authors did not propose a mechanistic explanation for the lower Aβ1-42/40 ratio among SARS-CoV-2-positive individuals, but Aβ1-42 accumulation might be one. All seven investigated SARS-CoV-2 S peptide amyloids significantly reduced the duration of fibril generation, especially in an already swift, unseeded response. Spike532 was the most efficient at HuPrP seeding, while Spike601 was the most efficient for Aβ1-42 seeding.

Overall, the study findings showed that SARS-CoV-2 S glycoprotein amyloid fibrils preferentially and specifically enhanced the production of HuPrP and amyloid peptide amyloid fibrils. The findings, albeit solely in vitro, indicated that S protein-amyloid fibril cross-seeding may be involved in the growing number of cases of CJD, AD, and perhaps other NDs in the aftermath of COVID-19.

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information. Journal reference: Preliminary scientific report. Johan Larsson, Ebba Hellstrand, Per Hammarström, Sofie Nyström. SARS-CoV-2 Spike amyloid fibrils specifically and selectively accelerates amyloid fibril formation of human prion protein and the amyloid β peptide. bioRxiv preprint 2023, DOI: https://doi.org/10.1101/2023.09.01.555834, https://www.biorxiv.org/content/10.1101/2023.09.01.555834v1

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It’s MLB Home Run Derby Day! Predictions, live updates and takeaways

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It's MLB Home Run Derby Day! Predictions, live updates and takeaways

It’s 2025 MLB All-Star Home Run Derby day in Atlanta!

Some of the most dynamic home run hitters in baseball will be taking aim at the Truist Park stands on Monday (8 p.m. ET on ESPN) in one of the most anticipated events of the summer.

While the prospect of a back-to-back champion is out of the picture — 2024 winner Teoscar Hernandez is not a part of this year’s field — a number of exciting stars will be taking the field, including Atlanta’s own Matt Olson, who replaced Ronald Acuna Jr. just three days before the event. Will Olson make a run in front of his home crowd? Will Cal Raleigh show off the power that led to 38 home runs in the first half? Or will one of the younger participants take the title?

We have your one-stop shop for everything Derby related, from predictions to live updates once we get underway to analysis and takeaways at the night’s end.


MLB Home Run Derby field

Cal Raleigh, Seattle Mariners (38 home runs in 2025)
James Wood, Washington Nationals (24)
Junior Caminero, Tampa Bay Rays (23)
Byron Buxton, Minnesota Twins (21)
Brent Rooker, Athletics (20)
Matt Olson, Atlanta Braves (17)
Jazz Chisholm Jr., New York Yankees (17)
Oneil Cruz, Pittsburgh Pirates (16)


Live updates


Who is going to win the Derby and who will be the runner-up?

Jeff Passan: Raleigh. His swing is perfect for the Derby: He leads MLB this season in both pull percentage and fly ball percentage, so it’s not as if he needs to recalibrate it to succeed. He has also become a prolific hitter from the right side this season — 16 home runs in 102 at-bats — and his ability to switch between right- and left-handed pitching offers a potential advantage. No switch-hitter (or catcher for that matter) has won a Home Run Derby. The Big Dumper is primed to be the first, beating Buxton in the finals.

Alden Gonzalez: Cruz. He might be wildly inconsistent at this point in his career, but he is perfect for the Derby — young enough to possess the stamina required for a taxing event that could become exhausting in the Atlanta heat; left-handed, in a ballpark where the ball carries out better to right field; and, most importantly, capable of hitting balls at incomprehensible velocities. Raleigh will put on a good show from both sides of the plate but will come in second.

Buster Olney: Olson. He is effectively pinch-hitting for Acuna, and because he received word in the past 72 hours of his participation, he hasn’t had the practice rounds that the other competitors have been going through. But he’s the only person in this group who has done the Derby before, which means he has experienced the accelerated pace, adrenaline and push of the crowd.

His pitcher, Eddie Perez, knows something about performing in a full stadium in Atlanta. And, as Olson acknowledged in a conversation Sunday, the park generally favors left-handed hitters because of the larger distances that right-handed hitters must cover in left field.

Jesse Rogers: Olson. Home-field advantage will mean something this year as hitting in 90-plus degree heat and humidity will be an extra challenge in Atlanta. Olson understands that and can pace himself accordingly. Plus, he was a late addition. He has got nothing to lose. He’ll outlast the young bucks in the field. And I’m not putting Raleigh any lower than second — his first half screams that he’ll be in the finals against Olson.

Jorge Castillo: Wood. His mammoth power isn’t disputed — he can jack baseballs to all fields. But the slight defect in his power package is that he doesn’t hit the ball in the air nearly as often as a typical slugger. Wood ranks 126th out of 155 qualified hitters across the majors in fly ball percentage. And he still has swatted 24 home runs this season. So, in an event where he’s going to do everything he can to lift baseballs, hitting fly balls won’t be an issue, and Wood is going to show off that gigantic power en route to a victory over Cruz in the finals.


Who will hit the longest home run of the night — and how far?

Passan: Cruz hits the ball harder than anyone in baseball history. He’s the choice here, at 493 feet.

Gonzalez: If you exclude the Coors Field version, there have been just six Statcast-era Derby home runs that have traveled 497-plus feet. They were compiled by two men: Aaron Judge and Giancarlo Stanton. James Wood — all 6-foot-7, 234 pounds of him — will become the third.

Olney: James Wood has the easy Stanton- and Judge-type power, and he will clear the Chophouse with the longest homer. Let’s say 497 feet.

Rogers: Hopefully he doesn’t injure himself doing it, but Buxton will break out his massive strength and crush a ball at least 505 feet. I don’t see him advancing far in the event, but for one swing, he’ll own the night.

Castillo: Cruz hits baseballs hard and far. He’ll crush a few bombs, and one will reach an even 500 feet.


Who is the one slugger fans will know much better after the Derby?

Passan: Buxton capped his first half with a cycle on Saturday, and he’ll carry that into the Derby, where he will remind the world why he was baseball’s No. 1 prospect in 2015. Buxton’s talent has never been in question, just his health. And with his body feeling right, he has the opportunity to put on a show fans won’t soon forget.

Olney: Caminero isn’t a big name and wasn’t a high-end prospect like Wood was earlier in his career. Just 3½ years ago, Caminero was dealt to the Rays by the Cleveland Guardians in a relatively minor November trade for pitcher Tobias Myers. But since then, he has refined his ability to cover inside pitches and is blossoming this year into a player with ridiculous power. He won’t win the Derby, but he’ll open some eyes.


What’s the one moment we’ll all be talking about long after this Derby ends?

Gonzalez: The incredible distances and velocities that will be reached, particularly by Wood, Cruz, Caminero, Raleigh and Buxton. The hot, humid weather at Truist Park will only aid the mind-blowing power that will be on display Monday night.

Rogers: The exhaustion on the hitter’s faces, swinging for home run after home run in the heat and humidity of Hot-lanta!

Castillo: Cruz’s 500-foot blast and a bunch of other lasers he hits in the first two rounds before running out of gas in the finals.

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Report: Sternberg to sell Rays for $1.7 billion

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Report: Sternberg to sell Rays for .7 billion

Tampa Bay Rays owner Stu Sternberg has agreed in principle to a $1.7 billion deal to sell the franchise to a group led by a Florida-based developer Patrick Zalupski, according to a report from The Athletic.

The deal is reportedly expected to be closed as early as September and will keep the franchise in the area, with Zalupski, a homebuilder in Jacksonville, having a strong preference to land in Tampa rather than St. Petersburg.

Sternberg bought the Rays in 2004 for $200 million.

According to Zalupski’s online bio, he is the founder, president and CEO of Dream Finders Homes. The company was founded in December 2008 and closed on 27 homes in Jacksonville the following year. Now, with an expanded footprint to many parts of the United States, Dream Finders has closed on more than 31,100 homes since its founding.

He also is a member of the board of trustees at the University of Florida.

The new ownership group also reportedly includes Bill Cosgrove, the CEO of Union Home Mortgage, and Ken Babby, owner of the Akron RubberDucks and Jacksonville Jumbo Shrimp, both minor-league teams.

A year ago, Sternberg had a deal in place to build a new stadium in the Historic Gas Plant District, a reimagined recreational, retail and residential district in St. Petersburg to replace Tropicana Field.

However, after Hurricane Milton shredded the roof of the stadium last October, forcing the Rays into temporary quarters, Sternberg changed his tune, saying the team would have to bear excess costs that were not in the budget.

“After careful deliberation, we have concluded we cannot move forward with the new ballpark and development project at this moment,” Sternberg said in a statement in March. “A series of events beginning in October that no one could have anticipated led to this difficult decision.”

MLB commissioner Rob Manfred and some other owners began in March to privately push Sternberg to sell the franchise, The Athletic reported.

It is unclear what Zalupski’s group, if it ultimately goes through with the purchase and is approved by MLB owners, will do for a permanent stadium.

The Rays are playing at George M. Steinbrenner Field in Tampa, located at the site of the New York Yankees‘ spring training facility and home of their Single-A Tampa Tarpons.

Field Level Media contributed to this report.

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Ohtani hits leadoff for NL; Raleigh cleanup for AL

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Ohtani hits leadoff for NL; Raleigh cleanup for AL

ATLANTA — Shohei Ohtani will bat leadoff as the designated hitter for the National League in Tuesday night’s All-Star Game at Truist Park, and the Los Angeles Dodgers star will be followed in the batting order by left fielder Ronald Acuna Jr. of the host Atlanta Braves.

Arizona second baseman Ketel Marte will hit third in the batting order announced Monday by Dodgers manager Dave Roberts, followed by Los Angeles first baseman Freddie Freeman, San Diego Padres third baseman Manny Machado, Dodgers catcher Will Smith, Chicago Cubs right fielder Kyle Tucker, New York Mets shortstop Francisco Lindor and Cubs center fielder Pete Crow-Armstrong.

Pittsburgh Pirates right-hander Paul Skenes will start his second straight All-Star Game, Major League Baseball announced last week. Detroit Tigers left-hander Tarik Skubal will make his first All-Star start for the American League.

“I think when you’re talking about the game, where it’s at, these two guys … are guys that you can root for, are super talented, are going to be faces of this game for years to come,” Roberts said.

Detroit second baseman Gleyber Torres will lead off for the AL, followed by Tigers left fielder Riley Greene, New York Yankees right fielder Aaron Judge, Seattle Mariners catcher Cal Raleigh, Toronto Blue Jays first baseman Vladimir Guerrero Jr., Baltimore Orioles designated hitter Ryan O’Hearn, Tampa Bay Rays third baseman Junior Caminero, Tigers center fielder Javy Báez and Athletics shortstop Jacob Wilson.

Ohtani led off for the AL in the 2021 All-Star Game, when the two-way sensation also was the AL’s starting pitcher. He hit leadoff in 2022, then was the No. 2 hitter for the AL in 2023 and for the NL last year after leaving the Los Angeles Angels for the Dodgers.

Skenes and Skubal are Nos. 1-2 in average four-seam fastball velocity among those with 1,500 or more pitches this season, Skenes at 98.2 mph and Skubal at 97.6 mph, according to MLB Statcast.

A 23-year-old right-hander, Skenes is 4-8 despite a major league-best 2.01 ERA for the Pirates, who are last in the NL Central. The 2024 NL Rookie of the Year has 131 strikeouts and 30 walks in 131 innings.

Skubal, a 28-year-old left-hander, is the reigning AL Cy Young Award winner. He is 10-3 with a 2.23 ERA, striking out 153 and walking 16 in 121 innings.

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