Monday, October 31, 2022

A way to snap molecules together like Lego wins 2022 chemistry Nobel

Three chemists are pioneers of 'click chemistry' and 'bioorthogonal chemistry'

A toolkit for snapping together molecules like Lego building blocks has won the 2022 Nobel Prize in chemistry.

Chemists Carolyn Bertozzi of Stanford University, Morten Meldal of the University of Copenhagen and Barry Sharpless of the Scripps Research Institute in La Jolla, Calif., will evenly split the prize for developing click chemistry and bioorthogonal chemistry, the Royal Swedish Academy of Sciences announced October 5 in a news conference in Stockholm. These tools allow scientists to easily construct complex molecules in the lab and inside living organisms.

“The good thing with this discovery is that it can be used for almost everything,” said Olof Ramström, a chemist at the University of Massachusetts Lowell and a member of the Nobel committee for chemistry. Applications include building drug molecules, polymers, new materials and tracking biomolecules among cells.

“We’re kind of at the tip of the iceberg already in terms of applications,” says Angela Wilson, president of the American Chemical Society. “I think this chemistry is going to revolutionize medicine in so many areas.”

Around 20 years ago, Sharpless introduced “click chemistry” — a way to simply and quickly attach two compounds using certain connector molecules. But finding these Lego-like connector molecules that can bond together in a chemical reaction wasn’t easy. Working independently, Sharpless and Meldal discovered a solution.

By adding a smidge of copper to a mixture containing two other small molecules — called an azide and an alkyne — the scientists could rapidly snap the two molecules together into a ring-shaped chemical. Without the copper, the molecules would eventually combine, but sluggishly, Ramström said.

The reaction quickly “gained enormous interest across chemistry and related fields,” he added. Even though scientists would later discover a handful of other molecules that could snap together in the same fashion, that first reaction is considered the “crown jewel of click reactions.”

But while catalyzing reactions with copper may work fine in a glass beaker, the metal can harm living cells. Bertozzi discovered a way to do copper-free click chemistry, so scientists can now design chemical reactions inside of organisms without mucking up their normal cellular functions.

Bertozzi tricked cells into incorporating a click chemical into sugars decorating the cell’s surface. When scientists expose these cells to a different click chemical, a type of alkyne, the two can snap together, just like the molecules in Sharpless’ and Meldal’s reactions. By linking the alkyne to green-glowing molecules, scientists can illuminate the surfaces of cells.

“Imagine you could attach shining molecules to biomolecules in a living cell. Then you could follow them in a microscope and see where they are and how they move. This is what Carolyn Bertozzi did,” said Johan Åqvist, a theoretical chemist at Uppsala University in Sweden and chair of the Nobel committee for chemistry.

Bertozzi’s specialty has been studying sugar molecules, which “are incredibly difficult to work with,” says Leslie Vosshall, a neuroscientist at the Rockefeller University in New York City, who is the vice president and chief scientific officer at the Howard Hughes Medical Institute. Straightforward methods exist for looking at DNA, RNA and proteins, but not so much for sugars, she says. “Sugars are the dark matter of the cell.”

By targeting specific sugars on cell surfaces, scientists can develop new treatments. For instance, Bertozzi and her colleagues were able to target and deactivate sugars that were helping tumor cells hide from T cells in the body (SN: 3/21/17).

Nomination: https://x-i.me/acabha5

https://academicawards.sciencefather.com/awards/

https://www.youtube.com/channel/UChVQEPGlT4VkC-jITRQl9Eg

New study shows that students who participated in ASU's Dreamscape Learn lab course performed better, were more engaged

Students at Arizona State University are learning biology in a unique virtual reality experience, hurtling through space to interact with creatures in an intergalactic wildlife sanctuary the size of a small city and to solve the mystery of why the creatures are dying.

And the data are in to show that the experience is working.

ASU’s Dreamscape Learn biology course debuted in the spring 2022 semester for students who took Biology 181 (introduction to biology for biology majors) and Biology 100 (introduction to biology for non-science majors).

The experience is straight out of Hollywood, created in a collaboration with Dreamscape Immersive, a company co-founded by Walter Parkes, former head of Dreamworks Motion Pictures and the writer or producer of hit movies including “WarGames,” “Gladiator” and the “Men in Black” series.

And while its roots are in Hollywood, the technology is an innovative new way to learn, driven by storytelling and a sense of wonder.

Consider what happened in Biology 181. Initial studies show that students who participated in the Dreamscape Learn version of the course had dramatically higher lab grades and better engagement than their peers who took the conventional lab course.

“We were amazed by the results, which far exceeded our expectations and proved our initial assumptions that the interactivity and compelling storytelling of Dreamscape Learn would indeed lead to better student outcomes,” said Lisa Flesher, chief of Realm 4 Project Acceleration at ASU.

Annie Hale, executive director of the EdPlus Action Lab at ASU, a learning research lab, led a team of research scientists who studied how well the students performed.

A total of 486 students’ lab grades were measured. Half of the students were placed in the Dreamscape Learn course, which had three parts — a lecture, the virtual reality experience and a three-hour lab. The other half were placed in the conventional course, which did not include the VR experience.

Students in the Dreamscape Learn course had six VR experiences of about 10 to 15 minutes each across the semester, during which they sat at desks with a headset, hand trackers and desktop controls. They felt vibrations in their chairs as they “traveled” through the sanctuary and used the joystick to control actions such as a creature dissection.

Hale said that engagement was stronger for students who reported that they experienced the sanctuary as a place they visited and not just an image they saw.

“When students reported they felt as though they were present in the VR story, we saw a positive correlation between engagement and lab scores,” she said.

Some of the feedback from students included:

“I loved the aspect of the VR a lot more than I would any form of a worksheet. I feel like I understood the same amount of information without feeling like it was tedious.”
"It was logic and problem-solving, and I love logic and problem-solving. And then just adding the element of story in, that just makes it all the better.”
“I thought it was really nice when you were able to get up close to the creatures that were in the Dreamscape environment. … And I thought it really made it feel as if you were someone there that was actually helping."

Mary Ellen Lewis, a biochemistry major, said the Dreamscape Learn Biology 181 course was very personalized.

“Your name is in there, and you have a character inside the VR world, and it was certainly not like anything I had ever done before,” she said.

Lewis liked being able to “travel” inside of cells.

“When we got to cell biology, the VR program took us inside the cells so we could see that this aberrant protein was infecting the creatures and making them sick,” she said.

“It let us see the issue up front, where in a textbook, it’s very distant and you’re just reading about it.”

Since students were assigned to either the Dreamscape Learn or conventional version of the course, researchers were able to purposefully balance the composition of students within each lab on numerous factors, such as socioeconomic status (as determined by Pell Grant eligibility) and whether they were first-generation college-goers.

Hale sees promising results when it comes to traditionally underserved students.

"We need more data to have predictive power … but when you look at spring 2022 BIO 181 in context, descriptively, nearly every student demographic showed impressive learning gains,” Hale said.

Other major findings from the report included:

Overall, students in the Dreamscape Learn course had higher lab grades than those in the conventional course — 9% higher overall. The median lab grade for students in Dreamscape Learn was 96%, compared with 87% for the other group.
Students enjoyed the experience. The average rating on a scale of 1 to 5 (with 5 being excellent) was 4.4.
Engagement was higher in the Dreamscape Learn group than in the non-Dreamscape Learn group. Students in the Dreamscape Learn labs were observed chatting, working together and helping each other twice as often as those in the non-Dreamscape Learn lab. And the teaching assistants in the Dreamscape Learn lab were more likely to check in and answer questions.

The research team also surveyed 211 students in Biology 100. The Dreamscape Learn experience was offered to all Biology 100 students, and their average enjoyment rating was 4.6 out of 5. Because there was no alternative conventional lab, there was no grade comparison.

The Biology 181 Dreamscape Learn experience was deeply researched, using several different methods.

“There is no one perfect protocol to study this because fundamentally, we’re changing the way that students engage with learning,” Hale said.

“It’s not just one piece in isolation — each component of the entire experience has to be studied with each other. There’s pedagogy, there’s narrative, there’s the VR that transports students into the story, there’s cadence and structure between the lectures and VR and labs.

“And it’s all happening simultaneously.”

In addition to recording the students’ lab grades, the researchers had them complete questionnaires immediately after their virtual reality sessions. Data also was collected through hourlong qualitative interviews with 63 students, from both course types, plus 12 three-hour ethnographic lab observations and additional surveys for both Dreamscape Learn and non-Dreamscape Learn course sections.

“Of the total interviews, 39 hourlong interviews were with 15% of Dreamscape Learn students, which is a huge amount. Typically, with qualitative research, around 2% of a sample is interviewed,” Hale said.

The lab observations tracked engagement.

“For the students in the Dreamscape Learn class, because of the pedagogy and design, they had to work together in an enmeshed way,” she said.

“They were getting up out of their little groups of four to help students at other tables. That sounds silly, but in lab classes, you typically work with your peers at your table and the rest of the class is not usually involved with each other.”

What’s ahead

By spring 2023, all introductory biology courses offered through the School of Life Sciences will include Dreamscape Learn lab courses. Approximately 5,800 students are enrolled in those courses for spring.

Angilletta and VandenBrooks are continuing to create content for Biology 182, which will debut in the spring. And they’ll likely tweak Biology 181, too.

“The quality of the writing, the way we’re developing assets in VR and the storytelling have all really improved, so we plan to go back and revisit our original stories and concepts,” VandenBrooks said.

Crow said a fascinating part of the process was watching faculty navigate completely foreign teaching territories.

“They dove headfirst into learning and understanding a totally different art form and figuring out how to connect it to a learning environment,” Crow said. “I think it’s been an unbelievably transformative process both for our faculty and our students.”

Now that Angiletta and VandenBrooks have navigated the process, the two will work with other ASU units on creating Dreamscape Learn content, including in chemistry and the climate crisis.

Dreamscape Learn will also debut in K–12 classrooms and work will continue on the Dreamscape Immersive Classroom, a VR-enabled environment that enables students to interact in real-time as fully rendered life-like avatars, where they can also be networked with other immersive classrooms anywhere in the world.

Protons may be stretchier than physics predicts

Quarks inside the particles seem to move more than they should in an electric field

A proton (illustrated) contains three particles called quarks (red, green and blue blobs). In electric fields, those quarks seem to move more than theory predicts, making the proton stretchier than imagined.

The subatomic particles are built of smaller particles called quarks, which are bound together by a powerful interaction known as the strong force. New experiments seem to show that the quarks respond more than expected to an electric field pulling on them, physicist Nikolaos Sparveris and colleagues report October 19 in Nature. The result suggests that the strong force isn’t quite as strong as theory predicts.

It’s a finding at odds with the standard model of particle physics, which describes the particles and forces that combine to make up us and everything around us. The result has some physicists stumped about how to explain it — or whether to even try.

“It is certainly puzzling for the physics of the strong interaction, if this thing persists,” says Sparveris, of Temple University in Philadelphia.

Such stretchiness has turned up in other labs’ experiments, but wasn’t as convincing, Sparveris says. The stretchiness that he and his colleagues measured was less extreme than in previous experiments, but also came with less experimental uncertainty. That increases the researchers’ confidence that protons are indeed stretchier than theory says they should be.

At the Thomas Jefferson National Accelerator Facility in Newport News, Va., the team probed protons by firing electrons at a target of ultracold liquid hydrogen. Electrons scattering off protons in the hydrogen revealed how the protons’ quarks respond to electric fields (SN: 9/13/22). The higher the electron energy, the deeper the researchers could see into the protons, and the more the electrons revealed about how the strong force works inside protons.

For the most part, the quarks moved as expected when electric interactions pulled the particles in opposite directions. But at one point, as the electron energy was ramped up, the quarks appeared to respond more strongly to an electric field than theory predicted they would.

But it only happened for a small range of electron energies, leading to a bump in a plot of the proton’s stretch.

“Usually, behaviors of these things are quite, let’s say, smooth and there are no bumps,” says physicist Vladimir Pascalutsa of the Johannes Gutenberg University Mainz in Germany.

Pascalutsa says he’s often eager to dive into puzzling problems, but the odd stretchiness of protons is too sketchy for him to put pencil to paper at this time. “You need to be very, very inventive to come up with a whole framework which somehow finds you a new effect” to explain the bump, he says. “I don’t want to kill the buzz, but yeah, I’m quite skeptical as a theorist that this thing is going to stay.”

It will take more experiments to get theorists like him excited about unusually stretchy protons, Pascalutsa says. He could get his wish if Sparveris’ hopes are fulfilled to try the experiment again with positrons, the antimatter version of electrons, scattered from protons instead.

A different type of experiment altogether might make stretchy protons more compelling, Pascalutsa says. A forthcoming study from the Paul Scherrer Institute in Villigen, Switzerland, could do the trick. It will use hydrogen atoms that have muons in place of the electrons that usually orbit atoms’ nuclei. Muons are about 200 times as heavy as electrons, and orbit much closer to the nucleus of an atom than do electrons — offering a closer look at the proton inside (SN: 10/5/17). The experiment would involve stimulating the “muonic hydrogen” with lasers rather than scattering other electrons or positrons from them.

“The precision in the muonic hydrogen experiments will be much higher than whatever can be achieved in scattering experiments,” Pascalutsa says. If the stretchiness turns up there as well, “then I would start to look at this right away.”

Nomination: https://x-i.me/acabha5

https://academicawards.sciencefather.com/awards/

https://www.youtube.com/channel/UChVQEPGlT4VkC-jITRQl9Eg

Microsoft OneDrive crashes because of recent Windows 10 updates

Microsoft is investigating a known issue causing OneDrive and OneDrive for Business crashes on Windows 10 systems where customers have installed updates released earlier this month.

"After installing KB5018410 or later updates, OneDrive might unexpectedly close," the company explained in a Windows health dashboard update.

On affected devices, this issue will prevent users from signing out or unlinking their OneDrive accounts or their sites and folders from Microsoft Teams and SharePoint.

As Redmond further explained, affected users might receive errors when trying to:

Sign out or unlink your account in the Microsoft OneDrive sync app.
Unlink sites or folders from syncing to your device from Microsoft SharePoint or Microsoft Teams sites.
Uninstalling the OneDrive sync app might fail.

The complete list of impacted platforms includes Windows 10, version 22H2; Windows 10, version 21H2; Windows 10, version 21H1; Windows 10, version 20H2.