The Complicated History of Religion and Archaeology


The Temple Mount is one of the most popular destinations in the ancient city of Jerusalem. In Arabic, it’s known as Haram al-Sharif — “the Noble Sanctuary.” Considered the holiest site in Judaism and third holiest in Islam, it is where, according to the Bible, King Solomon built the first temple for the Jews. It’s also said to be the location where Abraham offered his son Isaac as a sacrifice, and where the Prophet Muhammad made his Miraculous Night Journey to the throne of God. The golden Dome of the Rock atop the Temple Mount commemorates that event, which is sacred in Islam.

While visiting such hallowed ground today, it’s easy to forget that the Temple Mount’s significance maybe wouldn’t be known without the archaeological excavations and discoveries that began more than 150 years ago.

Biblical archaeologists have long been motivated by their faith to explore the historicity of biblical events. Today, these researchers are trained in the field, but that wasn’t always the case. “The first archaeological endeavors in the Holy Land were conducted not by archaeologists but by theologians, biblical scholars, and engineers primarily interested in locating places mentioned in the Bible,” writes Eric Cline, in his book Biblical Archaeology: A Very Short Introduction

Cline, an anthropology professor at George Washington University, credits an American minister, Edward Robinson, with many early archaeological discoveries across the Holy Land. Robinson explored Palestine in 1838 with an American missionary who was fluent in Arabic and identified more than 100 sites mentioned in the Bible. Some noteworthy finds included the Siloam Tunnel and Robinson’s Arch at the Temple Mount, which was named in Robinson’s honor. 

Though Cline notes that Robinson’s contributions were religiously motivated, his efforts are still recognized by academic archaeologists today. And Robinson was far from the last to be inspired by religion to explore the ancient world. A surprising number of findings have come to light by religiously-motivated archaeologists and religious organizations. “Interest in the ancient Mediterranean, driven by religious organizations, led to a lot of early descriptive and chronological work that was useful when we knew very little,” says John Henderson, an anthropology professor at Cornell University. 

For instance, the Catholic Church’s Pontifical Commission for Sacred Archaeology was responsible for expansive catacomb excavations in Rome, along with many other endeavors in nearby regions. And this type of work has gone beyond Europe and the Middle East. Scores of historical sites across Central and South America — including digs in San Isidro, El Mirador, Izapa and the Paso de la Amada — have been funded or explored by religious organizations interested in the outcome of excavation. For instance, discoveries of Olmec civilizations across the Gulf of Mexico and the Pacific coastal regions of Chiapas have likewise been funded by religious groups. The Church of Jesus Christ of Latter-day Saints began funding such projects in the mid-20th century in hopes of finding locations mentioned in one of their religious texts, the Book of Mormon.

What started out as an effort to corroborate findings in a book of scripture evolved into an academic organization — the New World Archaeological Foundation (NWAF), which has added a number of contributions to Mesoamerican archaeology. “They made meticulous site maps and carried out competent excavations,” says Norman Hammond, an emeritus professor of archaeology at Boston University and senior fellow at Cambridge University. Hammond says it was the NWAF’s support that helped bring to light many of the lesser-known sites beyond “the spectacular temples that made Maya civilization famous.”  

Fred Valdez, an anthropology professor at the University of Texas also commented on the work of the NWAF. “While I can’t address the reasoning behind the NWAF’s strong archaeological interests,” he says, “there is no doubt that the archaeology undertaken and published by them has been of great significance towards understanding Maya civilization.”

A Dig for Donors 

While some archaeological digs and excavations are funded by government grants, others are still dependent on private funding. Religious organizations sometimes step in as the lone source of financial assistance when it isn’t available anywhere else. “Funding is very competitive and hard to get,” says Susan Gillespie, an anthropology professor at the University of Florida. As a result, she says that “archaeological projects are often funded by religious organizations or just wealthy donors who are religious.”

The cost of excavations and analysis can be enormous. Some digs take months or even years to complete — and experts can be expensive to enlist. There’s also the cost of specialized tools and equipment needed, significant travel expenses, and the arduous process of preserving ancient artifacts. That doesn’t take into account the work that must occur before digging even begins. Preparations include extensive site research, the accumulation of documentary evidence and the process of finding funding sources once these preliminary steps are completed. 

Some religious organizations may fund archaeological projects that go beyond their scope of interest. Hammond says that leaders of the Church of Jesus Christ of Latter-day Saints provided him with generous financial support to cover some of his expenses while he was excavating the early Mayan site of Cuello in northern Belize during the 1970s. Hammond says that the church leaders were aware he was a religious skeptic, but they offered him financial support anyway. “Our work produced no support for LDS beliefs, but no negative feedback ever happened,” he says. 

Clashing Interpretations 

Involvement of religious organizations isn’t always positive, however, and many academic archaeologists are discouraged by the way they can hinder the work. For example, the Temple Mount may never be fully excavated or studied extensively due to its religious importance to multiple faiths and the ongoing Israeli-Palestinian conflicts there. An Islamic trust currently manages the site, and its managers — an organization known as the Jerusalem Islamic Waqf — say the site is too sacred for any further archaeological excavations. 

To add to that, there is also a history of religious believers ignoring or even burying scientific conclusions in an effort to promote unsupported religious beliefs. “In the beginning of archaeology, most interpretations were made in support of the Bible because to do otherwise would be heresy,” Gillespie says. 

But even modern archaeological findings can have devastating consequences when religious interpretations are applied. The city of Beirut, Lebanon — not far from the ancient city of Jerusalem — is one such example. Throughout much of Beirut’s history, Arabic Muslims and Canaanite Phoenicians were thought to be one people. But when French archaeologists started digging in Lebanon, they discovered that there may have been two distinct peoples tied to the region — an idea contested by some scholars but perpetuated by certain religious groups. “Some Christians didn’t want to be seen as Arabs, because to them Arabs were Muslim,” writes Rose Eveleth in an article for Aeon.

While some archaeologists believed there was still more history to uncover, officials authorized most of the ancient city to be bulldozed. The city was rebuilt in favor of modernization, but some are skeptical about the true motivation. Archaeologist Albert Naccache, quoted in Eveleth’s Aeon story, claimed the city’s renovations were motivated by religion to preserve the notion that Beirut is an Arab-only nation.

Beyond that, archaeological work is hindered when religiously-influenced agencies decide which ancient sites should be excavated, and which ones should not. “Archaeologists argue that the Israeli government favors saving ancient Jewish sites, especially in Jerusalem, over ones linked to other religions,” science journalist and Israel native Josie Glausiusz writes for Nature

Religious bias can also complicate interpretations of findings once discoveries are made. “One problem with archaeology stimulated by organized religion is that the funders — and often the practitioners — are fully committed to particular versions of the past,” Henderson says. He adds that “it’s always hard in archaeology to avoid the trap of inevitably finding what you expect and failing to see anything that you expect to be absent; adding religion to the picture makes it even harder.” 

Regardless of whether such devotion has led to disillusion, this much is certain: Religious organizations have made an impact. “My guess is that if organized religions had not been interested in archaeology,” Henderson says, “our view of history would be substantially different.”



Source link

34 Best Cyber Monday Video Game Deals (2020): Switch, Xbox, PlayStation


Well before Cyber Monday, there were tons of gaming deals swirling around the internet, like dust kicked up by the release of two new consoles: the PlayStation 5 and Xbox Series X. Now that the newest iterations are out, previous-gen games are seeing discounts all over the place. It’s good timing with the holiday season upon us, but Covid-19 is still raging around the country, and most of us can’t see family. Video games provide a great way to connect with loved ones at a safe distance. We hope our favorite Cyber Monday video game and accessory deals will help in these trying times.

Note: We strike through items that sell out or are no longer at their deal price as of publishing. Discounts sometimes return, so check for yourself. We will update this guide throughout the weekend.

Special offer for Gear readers: Get a 1-year subscription to WIRED for $5 ($25 off). This includes unlimited access to WIRED.com and our print magazine (if you’d like). Subscriptions help fund the work we do every day.

Updated November 29: We’ve added a Mario game and Civilization VI.

WIRED’s Early Cyber Monday Coverage

If you buy something using links in our stories, we may earn a commission. This helps support our journalism. Learn more.

Nintendo Switch Deals

Photograph: Nintendo

Nintendo’s at-home and on-the-go console has been a popular little guy ever since it first came out in 2017, and it’s only gotten better over time. With a robust library of AAA and indie games to choose from, the Switch is my favorite couch-side companion for these winter months. See our Best Switch Accessories and Best Switch Games guides for more picks.



Source link

Best smartwatch: Five things to consider



What to consider when buying a new smartwatch. (Luke Chesser via Unsplash/)

Current smartwatches offer cutting-edge breakthroughs: Easy-to-use operating systems with responsive touch screens, voice activation, seamless syncing with your smartphone via WiFi and Bluetooth connectivity, along with a myriad of apps and features all with a swipe of your fingertips. The first generations were a bit bulky and sometimes slower than we would’ve liked—but the latest versions are easier to navigate, more stylish, and also combine fitness/heart-rate/oxygen rate tracking along with GPS tracking and navigation. All these features allow you to access information so quickly that you are never out of the loop with the added bonus of managing your health.

There are so many brands and features to choose from—so we’re here to help you understand the latest products and features at a glance, so you can pick the best one for your budget and lifestyle.

  • <b>BEST SMARTWATCH FOR BATTERY LIFE:</b><a href=”https://www.amazon.com/Protectors-PlayBetter-Portable-Charging-ClimbPro/dp/B08BHZVZHJ/ref=as_li_ss_tl?dchild=1&keywords=garmin+fenix+6+pro+solar&qid=1605223494&sr=8-4&linkCode=ll1&tag=popularscience-best-smartwatch-pcr-20&linkId=ca7a516c85973b4c8b88c8655ead5a05&language=en_US” target=_blank> Garmin Fenix 6 Pro Solar</a>
  • <b>BEST ANDROID AND IPHONE-COMPATIBLE SMARTWATCH:</b><a href=”https://www.amazon.com/Samsung-Bluetooth-Unlocked-Advanced-monitoring/dp/B089DQ33QW/ref=sr_1_3?dchild=1&keywords=samsung+galaxy+3+smartwatch&qid=1605224216&sr=8-3″> </a><a href=”https://www.amazon.com/Samsung-Bluetooth-Unlocked-Advanced-monitoring/dp/B089DQ33QW/ref=as_li_ss_tl?dchild=1&keywords=samsung+galaxy+3+smartwatch&qid=1605224216&sr=8-3&th=1&linkCode=ll1&tag=popularscience-best-smartwatch-pcr-20&linkId=a7aa52a21f14b4a3d4e84096493d98ae&language=en_US” target=_blank>Samsung Galaxy Watch 3</a>
  • <b>BEST SMARTWATCH DISPLAY:</b><a href=”https://www.amazon.com/New-Apple-Watch-GPS-Cellular-40mm/dp/B08J5W9PX1/ref=sr_1_4?crid=60A2TDO57IW8&dchild=1&keywords=apple%2Bwatch%2Bseries%2B6&qid=1605223612&sprefix=Apple%2B%2Caps%2C1448&sr=8-4&th=1″><b> </b></a><a href=”https://www.amazon.com/New-Apple-Watch-GPS-Cellular-40mm/dp/B08J5W9PX1/ref=as_li_ss_tl?crid=60A2TDO57IW8&dchild=1&keywords=apple+watch+series+6&qid=1605223612&sprefix=Apple+,aps,1448&sr=8-4&th=1&linkCode=ll1&tag=popularscience-best-smartwatch-pcr-20&linkId=bea0d6c1c95ffc1622207d0b2a03fc7a&language=en_US” target=_blank>Apple Watch Series 6</a>
  • <b>BEST HEALTH AND FITNESS SMARTWATCH:</b><a href=”https://www.amazon.com/Fitbit-Advanced-Smartwatch-Management-Temperature/dp/B08DFLG5SP/ref=sr_1_4?dchild=1&keywords=fitbit+smart+watch&qid=1605223835&sr=8-4″><b> </b></a><a href=”https://bestbuy.7tiv.net/WWqeP” target=_blank>Fitbit Sense</a>
  • <b>BEST “SMART HOME” SMARTWATCH:</b><a href=”https://www.amazon.com/Samsung-Sport-Smartwatch-Bluetooth-SM-R600NZKAXAR/dp/B075X35D8M/ref=sr_1_5_mod_primary_new?dchild=1&keywords=Samsung+Gear+smartwatch&qid=1605237382&refinements=p_72%3A1248879011&rnid=1248877011&s=electronics&sbo=RZvfv%2F%2FHxDF%2BO5021pAnSA%3D%3D&sr=1-5″> </a><a href=”https://www.amazon.com/Samsung-Sport-Smartwatch-Bluetooth-SM-R600NZKAXAR/dp/B075X4RQHZ/ref=as_li_ss_tl?dchild=1&keywords=Samsung+Gear+smartwatch&qid=1605237382&refinements=p_72:1248879011&rnid=1248877011&s=electronics&sbo=RZvfv//HxDF+O5021pAnSA&sr=1-5&th=1&linkCode=ll1&tag=popularscience-best-smartwatch-pcr-20&linkId=315c7ffb2892d0dc18afde8f27d734b7&language=en_US” target=_blank>Samsung Gear Sport Smartwatch</a>
  • <b>BEST BUDGET SMARTWATCH: </b><a href=”https://www.amazon.com/Apple-Watch-GPS-38mm-Silver-Aluminium/dp/B07K3HG6T9/ref=as_li_ss_tl?dchild=1&keywords=apple+series+3&qid=1605229065&sr=8-1&th=1&linkCode=ll1&tag=popularscience-best-smartwatch-pcr-20&linkId=293a02251c80397b6810f2a6c44ee27d&language=en_US” target=_blank>Apple Watch Series 3</a>

Things to consider when buying a smartwatch

Smartwatches are essentially lightweight wrist-sized mini-computers that sync via connections with your smartphone or via their own cellular hookups. In addition to time telling, smartwatches offer apps to control music, maps, weather, schedules, calendars, email, shopping, voice activation, reminders, and fitness, and heart rate tracking. Let’s walk through a few key features such as battery life, compatibility of operating systems, display size, ease of use, and sensors for fitness/health tracking.

How often will you need to charge it?

Most smartwatches have an average battery life of only 1 to 2 days, and the more smart features your watch has and that you use, the faster the battery will drain. However, if your desired uses for your smartwatch are more fitness and GPS only, there are batteries that can last with limited use up to 120 days. Smartwatch batteries started as liquid lithium batteries, but most commonly now use rechargeable batteries of lithium-ion polymer technology. These newer batteries are lightweight and safer as they have a lower chance of leaking electrolytes. The battery in your smartwatch is designed with a magnetic charging cable and can take anywhere from one hour to overnight to fully charge. Some options on the market even utilize a hybrid charge harnessing solar power.

There is a great deal of variability in charging speed and battery life between models and brands. As we mentioned earlier, a user with a smartwatch loaded with apps, who uses the watch very frequently will see a faster battery drain. The smartwatch configuration, cellular network, signal strength, and streaming quality are among some of the factors that affect battery life. Bells and whistles are cool but It’s important to consider which features you want and use on your smartwatch and turn the rest off to receive the most optimal battery life.

Best smartwatch for battery life: Garmin Fenix 6 Pro Solar

Rugged, premium quality pick with emphasis on sports and navigation.

Rugged, premium quality pick with emphasis on sports and navigation. (Amazon/)

This smartwatch is a great choice when long battery life is an important consideration (and when outdoor sports or wilderness adventures are a lifestyle consideration). With a power manager feature and solar-charged battery, allow for up to 14 days of battery use without plugging in the charging cord. Battery can support GPS Activity up to 28/36 days with solar charging. Able to withstand water pressures of up to 100 meters, it makes rain, snorkeling, or just aggressive puddle splashes no problem.

Which operating system is best?

Operating systems and their subsequent compatibility are important to consider with your smartwatch purchase. A popular operating system offered in various smartwatch brands is Google’s Wear OS, brands that use this include Huawei, Fossil, TicWatch and Misfit. Wear OS syncs with your smartphone and aligns with physical sensors that track your fitness and health goals. GPS tracking is possible with Wear OS but not offered in every smartwatch – sometimes you might have to take your phone along for this feature.

Custom operating systems that are developed specifically for certain brands are found in many big brand smartwatches and often are most compatible with specific smartphones. For example, Samsung uses Tizen OS, most recently updated and rebranded as One UI. This custom operating system is open-source, which means that developers can use it and build on it for free, although it’s predominantly found in Samsung smartwatches, fitness trackers, and TVs. While it can be used with both Android and Apple smartphones, it has the most options when paired with Android and Samsung smartphone devices.

Apple is another major brand with its own unique operating system, the watchOS. As is typical with Apple devices, this operating system is designed solely to be used with iOS Apple Smartphones. A plus for iPhone owners is this smartwatch operating system is designed to work seamlessly with that device.

The popular fitness tracker company Fitbit, uses their own FitbitOS for their smartwatches, which works with either Android or Apple smartphones and must be updated and managed through an app installation. Similarly, Garmin smartwatches use their own Garmin OS, which is managed through an app installed on either your Android or iPhone.

Best Android and iPhone-compatible smartwatch: Samsung Galaxy Watch 3

For those who don’t want to look like they have a computer on their wrist.

For those who don’t want to look like they have a computer on their wrist. (Amazon/)

One of the first big pros for the Samsung Galaxy Watch 3 is simply how stylish it looks. It doesn’t initially scream “smartwatch,” so it works no matter your overall aesthetic. But it’s real power comes from the fact that, although designed to work with Samsung phones, it’s actually iOS and Android compatible. That flexibility makes infinitely more functional than a watch that is only compatible with a single OS.

How big is the watch face?

Typically, a larger display makes the watch easier to read and use, and feel easier to control. That being said, we are inherently limited by the size of our individual wrists! In addition to literal size, the quality of display is affected by the quality of the screen. Brightness, retina display, graphics, and font choices, and the user interface all make for a more satisfying user experience, even in a tiny watch face. New features designed to make these small screens more accessible include easy to use zoom features for quicker font and graphic recognition.

Best smartwatch display: Apple Watch Series 6

Is swim-proof, with faster access to information, and new health monitoring sensors.

Is swim-proof, with faster access to information, and new health monitoring sensors. (Amazon/)

The newest in the series of Apple smartwatches, the Series 6 is offered in two sizes, the 44mm being the larger option. The addition of an always-on retina display adjusts to become 2.5x brighter when you and your wrist are outdoors—which makes for easier use in direct sun. In addition, the accessibility feature allows for zooming in on font and graphics making displays and text messages easier to read. As with most Apple products the user interface is clean and easy to navigate. Drawbacks include compatibility with only Apple brand smartphones and an approximately 1 day of battery charge with moderate use.

Will you be tracking health and fitness?

When fitness is your main intended use for your smartwatch, we suggest going with a smartwatch designed specifically with this in mind. The most advanced technology available today can do some amazing things! Some smartwatches can now track electrodermal activity and anticipate stress, as well as track your skin temperature, heart rate, blood oxygen levels as well as track steps, stairs, workouts and use GPS technology to analyze your pace and distance traveled. Apps can help suggest workouts, motivate your goals, manage stress, and promote sleep.

While some other smartwatches offer some kind of nod to fitness tech, their offerings are likely OK for the casual fitness enthusiast but won’t satisfy the hardcore. The focus and versatility that comes with a dedicated fitness device will make sure you’re getting the most out of both your smartwatch and your workout.

Best health and fitness smartwatch: Fitbit Sense

The first name in wearable exercise technology delivers a powerful pick to consider.

The first name in wearable exercise technology delivers a powerful pick to consider. (Amazon/)

Built around a holistic health program, the Fitbit Sense performs the expected functions such as heart rate and body temperature monitoring, but it also adds sleep pattern regulation and stress management. It allows you to access saved data, and track patterns and irregularities in addition to setting fitness goals.

What level of connectivity do you want?

It may seem like the most basic thing to ask yourself when it comes to a smartwatch, but how easily and reliably it connects to either a base phone or WiFi can mean the difference between a functional device and an expensive accessory. Consider the smartwatch as part of a larger, interconnected system. You’d rather have a device that can seamlessly integrate and play nicely with your existing devices, rather than one that runs independently.

It’s increasingly important as smartwatches themselves become more and more sophisticated. Rather than simply pairing with a phone and mimicking the phone’s functionality, smartwatches can interact with other WiFi- or Bluetooth-connected devices such as external speakers and even your television. The ability to use your smartwatch as a remote control or even as a hub to steam app-based media is fun and unique, and requires a device that has the flexibility and capability to pull it off smoothly.

Eventually, your smart home—and its smart appliances—will all be able to communicate with each other, and many can already be controlled by a smartwatch. New doors are opening in terms of total control being literally an arm’s length away, so you may want to find a watch that gives you a step up.

Best “smart home” smartwatch: Samsung Gear Sport Smartwatch

Your first step into a larger world of watch-controlled appliances, media centers, and home amenities.

Your first step into a larger world of watch-controlled appliances, media centers, and home amenities. (Amazon/)

Not only is the Gear Sport surprisingly swim-ready and water-resistant up to 50 meters, but it also features a Samsung Connect app that allows you to control door locks, lights, and other smart home functions with the press of a button. It features some limited fitness tracking apps and allows you to set up a quick-pay feature through Samsung Pay. Versatile, stylish, and unusually rugged for a smartwatch, it may well never leave your side (or, rather, your wrist).

Brands to know

Although smartwatches generally struggled to get the kind of foothold in popular culture that the iPhone or portable music devices enjoyed, the technology Is still powered by some of the biggest names in tech and innovation. As the product category expands and matures, more adoption is almost certainly likely—in either case, it’s good to know that some of the big guns still feel strongly about its potential.

Apple

A name so synonymous with intuitive, sleek tech, the word “iPhone” has almost reached the ubiquity of “Band-Aid” to describe an entire product category. Founded in 1976 as Apple Computers by Steve Jobs, Steve Wozniak, and Ronald Wayne, it has grown from PCs to handheld devices to, now, music platforms, streaming TV channels, and voice-activated personal assistants. You know the name, you know the logo.

Garmin

As you can gauge from its original name, ProNav, Garmin staked its claim by creating GPS devices for cars, boats, aircraft, and outdoor activities. It was founded in 1983 by Gary Burrell and Min H. Kao (the company is a portmanteau of their first names – “Gar” + “Min”) and the first customer for their GPS devices was none other than the U.S. military. They have since expanded into wearable tech and other activity-based devices.

Samsung

A South Korean tech conglomerate powerhouse, Samsung has been manufacturing consumer electronics for decades. In fact, Samsung itself can trace its origins all the way back to 1938, when it was a trading company. They produce everything from Blu-ray players to smart speakers to televisions to smartphones and beyond.

Best budget smartwatch: What You Get for Under $200

There are a lot of choices under $200 in this category, and as a rule of thumb if you only want GPS without cellular the price point goes down. Another cost-saving trick when looking for a deal is to find an older version when newer versions have been released. For example, the Apple Watch version 3 with GPS is a great option for a perfectly good (albeit slightly older model) at a much more reasonable price. The series 3 includes an optical heart sensor, retina display, altimeter, 8GB of storage as well as Bluetooth 4.2 connection.

Conclusion

The smartwatch may not have reached the level of absolute necessity like some other handheld and wearable devices, but its ability to enhance and interact with those must-haves make it an intriguing and, well, fun addition to your tech. Finding one that suits your lifestyle goes beyond just aesthetics. Knowing how and why you want one will help you narrow down your field and ensure you find the right one. For example, if you’re looking to make it a part of your active, daily fitness lifestyle, you’ll want one that can handle it. If you’re looking to eventually control your entire house with a flick of the wrist, you’ll be looking for completely different functionality. The category is also still growing and just testing its limits, so getting used to using one now is never a bad idea.



Source link

Tesla may offer remote access to your car’s Autopilot cameras


As helpful as Tesla’s Sentry Mode may be, it doesn’t provide much insight from the car’s cameras until there’s an incident. What if you could take a peek at any moment? You just might. Electrek reports that code sleuth Green has discovered hints at remote live access to your EV’s Autopilot cameras. You could track suspicious behavior before anything happens, or simply check conditions around your car before you walk to your driveway.

It’s not certain just how this would work, although you’d likely use for periodic drop-ins rather than non-stop viewing. Green noted that an Autopilot camera stream demands 30 megabytes per minute — it wouldn’t seriously strain a phone with an LTE or 5G connection. The data use might be enough to require a premium data subscription, although that’s not guaranteed.





Source link

What We’re Thankful for at Scientific American



At a lot of Thanksgiving dinners, people go around the table and take turns talking about something they’re thankful for. It’s nice! This Thanksgiving season, we’d like to share some of the things that people at Scientific American are thankful for. And we’d love to know what you’re thankful for. If you share this story or tag us on Facebook, Twitter, Instagram, TikTok or wherever you’re celebrating with your virtual communities, we’ll highlight the responses to help everyone appreciate what’s right in the world, even in 2020.

Happy Thanksgiving, and thank you to everyone who is trying to stop the spread of the COVID pandemic this year so it’ll be safe to celebrate with more people around the table next year. Here’s what else we’re grateful for:

Xanthophylls, carotenoids and anthocyanins, the pigments that give us beautiful fall foliage. —Sophie Bushwick, technology editor.

Health care workers, essential workers, all the scientists working on COVID. —Tanya Lewis, health and medicine editor.

For black holes and glowing nebulae and swirling galaxies that remind me that we humans are just a small part of a vast universe much more fascinating and mysterious than the one we see in our everyday lives. And for having the scientific tools to peer out into this cosmos and begin to understand it. —Clara Moskowitz, space and physics editor.

Four Seasons Total Landscaping. —Seth Fletcher, features editor.

The EPA’s approval of nootkatone, a chemical found in cedar trees and grapefruit that appears to repel mosquitos and ticks more effectively than nasty DEET. —Jen Schwartz, technology and mind editor.

All the birds that have come to visit my yard—50 species since I started keeping track in May. The first one I logged was a rose-breasted grosbeak; number 50 was a golden-crowned kinglet. The birds don’t know there’s a pandemic. In a year of social distancing and staying at home, it’s been a balm to watch them nest and fledge and flock and, now, fly south to warmer climes. —Kate Wong, evolution and ecology editor.

That we’ll soon have a Madam Vice President and our president will no longer call climate change a “hoax.” —Jess Ramirez, Web producer.

Indigenous peoples around the world who are putting their lives on the line to defend nature. —Madhusree Mukerjee, science and society editor.

Health care workers who cared for my sister and new nephew (both now home and healthy!) after a complicated birth, and advocates who are working to improve outcomes for birthing folks and their babies. —Amanda Montañez, graphics editor.

That I got to take my daughter to vote in her first presidential election. She’d been waiting four years—already so much more socially conscious than I was at 18! And my “Because Science” PopSocket and my “Vote for Science” T-shirt. —Maya Harty, executive assistant supervisor.

Election workers doing their job despite all the BS. —Tanya Lewis, health and medicine editor.

Grateful to hear that a friend’s mother turned 101 during this pandemic and still plays online bridge and discusses politics with her children once a week. Grateful for hope. —Christi Keller, copy director.

Bald eagles, peregrine falcons, California condors, red-cockaded woodpeckers, whooping cranes, black-footed ferrets, and all the other species that could have gone extinct but didn’t—thanks to science, environmental protection policies, endless conservation efforts, and people who care. —Laura Helmuth, editor in chief.

Fact checkers and copy editors. —Jen Christiansen, graphics editor.

Our colleagues, not just here at Scientific American but also journalists around the world for holding the powerful accountable and providing critical information during the pandemic. —Sunya Bhutta, audience engagement editor.

Anthony Fauci, not just because he’s been a calm, clear, evidence-based voice in the swirling world of COVID-19 information, but because he bravely speaks truth to power despite criticism, mockery and death threats. It’s also fun (and telling?) that as a kid he was a Yankees fan even though he lived in Brooklyn when the borough’s hometown Dodgers were the rage. —Mark Fischetti, sustainability editor.

For having the technology to be able to video chat, call and text family and friends even when we can’t see each other in person. —Clara Moskowitz, space and physics editor.

For being able to witness, sometimes at consciousness-sapping proximity on account of lockdowns and social distancing, the dual neuronal marvels of my five-year-old’s developing theory of mind and my one-year-old’s first steps. —Jeff DelViscio, multimedia editor.

With news from planet Earth being incredibly troubling this year, I am thankful for all the amazing astronomy stories such as the news that researchers detected a group of lakes hidden under Mars’s icy surface. —Rachel Scheer, head of communications.

The Chesapeake Bay and its ospreys and crabs and eelgrass, and the wind and boat that lets me see them, and the #cuteanimals Slack channel. —Josh Fischman, chemistry, policy and biology editor.

The ergonomic desk chair I found abandoned in my apartment stairwell. —Sarah Lewin Frasier, news editor.

All the intimate concerts my favorite musicians are now livestreaming from their homes. Every ticket now guarantees a front row seat. —Liz Tormes, photo editor.

That my family and the people around me at work didn’t get sick and, when I got sick, it was a mild COVID-19 case. —Gary Stix, mind and brain editor.

All essential workers, from doctors and nurses to bus drivers and grocery store clerks. The Black Lives Matter movement, and everyone who is taking action to end police brutality and systemic racism in America. —Sunya Bhutta, audience engagement editor.

Grateful for my family working together to keep those around us safe and healthy, colleagues who love what they do and keep the magazine going strong, time home to spend with my kids and watch them grow every day, and unexpected sightings of hawks and falcons that visited our 5th floor fire escape entertaining us while we quarantined! —Silvia De Santis, prepress and quality manager.  

That the pandemic has led me and my family to take many more walks in the woods and fields that have been available to us all along, but which we never seemed to find time to explore. —Mike Lemonick, opinions editor.

Adulkt Life’s debut album Book of Curses: not only the most invigorating record I’ve heard this year, but the singer is 55 (!) and hadn’t been in a band for 25 years, which, as an aging artistic type myself, is incredibly inspiring. —Ryan Reid, online art director.

Ribbons of honking cranes overhead as they fly south. —Madhusree Mukerjee, science and society editor.

For vaccines, frontline and essential workers, leaders who value and listen to scientific evidence and expertise, the privilege to be able to work from home … and for my dog who likes to cuddle next to me while I work. —Andrea Thompson, sustainability editor.

Working for a magazine that has a real impact on the conversations in our society, whether about public health, racism or evidence-based thinking. We are old, scrappy and hungry. —Andrea Gawrylewski, collections editor.

Thankful for my friends, family and work colleagues. —Chris Monello, marketing manager.

For vaccines! And all the people who work so hard to make and distribute them. —Clara Moskowitz, space and physics editor.

One thing that I’m thankful for is the varied set of folks in space doing science. In a recent tweet from NASA: “‘The amount of scientific output that you’re going to see from this mission I think is absolutely incredible.’ – Kate Rubins of @NASA_Astronauts shares how a larger crew means more @ISS_Research on the @Space_Station” —Rich Hunt, production editor.

Where does one start? Definitely thankful to work with such a great and creative group of people, it is inspiring every day. I am especially thankful for my family and, despite the virus this year, we have been able to spend quality time that we hadn’t in years. Lastly, for the many people who, around the world, have stepped up to help others. Their service is truly remarkable and I am very thankful for it. —Mike Mrak, creative director.

Knowing that we, as a 175-year-old magazine for and about science, still exist at a moment when knowledge and truth could not be more critical to humanity’s continued happy existence on this planet. —Jeff DelViscio, multimedia editor.

All of the researchers who study, track, and contextualize media manipulation, digital disinformation, the spread of false ideas—and then educate policymakers, journalists and the public on how to save reality. They must be so, so tired. —Jen Schwartz, technology and mind editor.





Source link

Animals with more genetic variation are more likely to survive relocation — ScienceDaily


In Nevada’s dry Ivanpah Valley, just southeast of Las Vegas, a massive unintended experiment in animal conservation has revealed an unexpected result.

From 1997 to 2014, the U.S. Fish and Wildlife Service moved more than 9,100 Mojave desert tortoises to the 100-square-kilometer (about 39 miles square) Large Scale Translocation Site. The newcomers, many of which were abandoned pets or had been displaced by development, joined nearly 1,500 desert tortoises already living there.

Conventional wisdom would suggest that tortoises from areas closest to the translocation site would fare best. But a new UCLA study, published today in Science, found no connection between the tortoises’ place of origin and their chances of survival. It did, however, uncover a far better predictor.

Tortoises with lots of genetic variation were much more likely to survive after their relocation, said UCLA conservation ecologist Brad Shaffer, the study’s senior author. Like most organisms, tortoises have two copies of their entire genome, with one copy from each parent. The more those copies differ from each other, the higher the organism’s heterozygosity.

The researchers compared translocated tortoises that lived or died over the same time period after being relocated to the site. They found that survivors averaged 23% greater heterozygosity than those that perished. Simply put, tortoises with more genetic variation had higher survival rates.

“It flies in the face of what we know from other translocation studies, but lots of genetic variation was hands-down the best predictor of whether a tortoise lived or died,” said Shaffer, a professor of ecology and evolutionary biology and director of the UCLA La Kretz Center for California Conservation Science. “Relocating endangered plants and animals is increasingly necessary to counteract the effects of climate change, and this gives us a new tool to increase survival rates.”

Although the relationship between heterozygosity and survival was well supported by the study, it’s unclear why greater genetic variation is linked to survival rates, said former UCLA postdoctoral scholar Peter Scott, the study’s lead author.

“Potentially, individuals with higher heterozygosity have more genomic flexibility,” said Scott, who is now an assistant professor at West Texas A&M University. “It’s likely that tortoises with more variation have a better chance of having one copy of a gene that works really well in stressful or new environments compared to those individuals with two identical copies that only work really well in their environment of origin.”

The researchers wanted to make tortoise conservation efforts more effective, and uncover trends that would help other species as well, Scott said.

“Oftentimes, the chances of success for relocating plants or animals is pretty dismal,” he said. “We wanted to understand why, and use that understanding to increase survival.”

Over the years, tortoises that were given up as pets, or removed from places like developments in suburban Las Vegas and solar farms in the desert, were surrendered to the U.S. Fish and Wildlife Service.

The agency took blood samples to screen for diseases and marked each animal before releasing them into the Ivanpah Valley site, which enabled the animals to be tracked in later surveys. The UCLA researchers sequenced blood samples drawn from 79 tortoises that were released to the site and were known to be alive in 2015, and from another 87 known to have died after they were released at the site.

Although the Large Scale Translocation Site provided an intriguing dataset, it’s not the same as a controlled experiment. Additional studies would be needed to understand why more heterozygous tortoises had a higher survival probability and precisely how much of an increase in genetic variation improves a tortoise’s odds of surviving.

“The only reason we could do this study was because the U.S. Fish and Wildlife Service was incredibly forward-thinking when they set up the translocation site and tracked who lived and died,” Shaffer said. “Many died, and no one was happy about that. But we can learn a lot from that unfortunate result to help conservation management improve.

“When thinking about moving animals or plants out of danger, or repopulating an area emptied by wildfire, now we can easily and economically measure genetic variability to better gauge the survival probability of those translocated individuals. It’s not the only criteria, but it’s an important piece of the puzzle.”



Source link

Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate


Structure of a vaccine candidate

Much effort is being targeted at developing vaccines that will provide protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A trimeric spike protein that decorates the virus is a primary target of the host immune system and the focus of vaccine development. Bangaru et al. present the structure of a leading vaccine candidate: a full-length spike protein with some modifications aimed at enhancing stability that is formulated in polysorbate 80 detergent. The study confirms that the full-length immunogen is in a stable prefusion conformation and provides a basis for understanding immune responses to the vaccine.

Science, this issue p. 1089

Abstract

Vaccine efforts to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, are focused on SARS-CoV-2 spike glycoprotein, the primary target for neutralizing antibodies. We performed cryo–election microscopy and site-specific glycan analysis of one of the leading subunit vaccine candidates from Novavax, which is based on a full-length spike protein formulated in polysorbate 80 detergent. Our studies reveal a stable prefusion conformation of the spike immunogen with slight differences in the S1 subunit compared with published spike ectodomain structures. We also observed interactions between the spike trimers, allowing formation of higher-order spike complexes. This study confirms the structural integrity of the full-length spike protein immunogen and provides a basis for interpreting immune responses to this multivalent nanoparticle immunogen.

Severe acute respiratory syndrome coronavirus (SARS-CoV) caused a global outbreak from 2002 to 2003 (1). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from the same lineage of the β-CoV genus as SARS-CoV, recently emerged in China and spread rapidly, infecting more than 28 million people worldwide by September 2020 (2). Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, was declared a pandemic by the World Health Organization (WHO). In response, several SARS-CoV-2 vaccine candidates are being developed and tested at various stages of clinical trials (35). The SARS-CoV-2 spike (S) trimeric glycoprotein is a focus of vaccine development because it is the primary target of host immune defenses (5, 6).

Like other type 1 fusion proteins, the SARS-CoV-2 S prefusion trimer is metastable and undergoes structural rearrangement from a prefusion to a postfusion conformation upon S-protein receptor binding and cleavage (7, 8). The structure of the stabilized SARS-CoV-2 spike ectodomain has been solved in its prefusion conformation and resembles the SARS-CoV spike (911). Here, we describe the structure of a leading SARS-CoV-2 S vaccine candidate (NVAX-CoV2373) based on a full-length (FL) S, residues 1 to 1273, which includes the transmembrane (TM) and the cytoplasmic tail (CT) (Fig. 1A). The final construct, SARS-CoV-2-3Q-2P, was also modified at the S1/S2 polybasic cleavage site from RRAR to QQAQ to render it protease resistant, along with two proline substitutions at residues K986 and V987 in the S2 fusion machinery core for enhanced stability (Fig. 1A). The FL spikes, expressed and purified from insect cells, were formulated in 0.01% (v/v) polysorbate 80 (PS 80) detergent. To characterize the structural integrity of the 3Q-2P-FL immunogen, we performed negative-stain electron microscopy of the FL spike constituted in PS 80 in the presence of Matrix-M adjuvant, recapitulating the vaccine formulation being tested in humans. Imaging revealed trimeric spike proteins present as free trimers or as multitrimer rosettes, containing as many as 14 trimers with their TM domains enclosed in micellar cores of PS 80 detergent (Fig. 1B). Tight clustering of the spikes in the NVAX-CoV2373 nanoparticle formulation may lead to stronger immune responses over soluble trimers alone, similar to other viral glycoprotein immunogens (hemagglutinin and respiratory syncytial virus F) (12, 13).

Fig. 1 Evaluation of SARS-CoV-2 3Q-2P-FL spike glycoprotein.

(A) Linear diagram of the sequence and structure elements of the FL SARS-CoV-2 spike protein showing the S1 and S2 ectodomain. Structural elements include a cleavable signal sequence (SS, white), NTD (blue), RBD (green), SD1 and SD2 (light blue), protease cleavage site 2′ (S2′, arrow), fusion peptide (FP, red), heptad repeat 1 (HR1, yellow), central helix (CH, brown), heptad repeat 2 (HR2, purple), TM domain (black), and CT (white). The native furin cleavage site was mutated (RRAR→QQAQ) to be protease resistant and stabilized by introducing two proline (2P) substitutions at positions K986P and V987P to produce SARS-CoV-2 3Q-2P-FL spike. A, Ala; D, Asp; E, Glu; K, Lys; L, Leu; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; V, Val. (B) Representative negative-stain EM images and 2D classes of SARS-CoV-2 3Q-2P-FL, formulated in PS 80 detergent in the presence of Matrix-M adjuvant. In the raw micrograph, spike rosettes are circled in yellow and Matrix-M adjuvant cages are circled in white. 2D classes showing individual spikes, higher-order spike nanoparticles, and Matrix-M cages of different sizes. Matrix-M does not appear to interact with the spike nanoparticles.

We next performed single-particle cryo–electron microscopy (cryo-EM) on the spike formulated in PS 80 detergent (Fig. 2A). Initial two-dimensional (2D) classification revealed the presence of two distinct classes: free spike trimers and dimers of trimers (Fig. 2A). The threefold symmetric (C3) reconstruction of the free spike trimer resulted in a 3.6 Å–resolution map, whereas the asymmetric reconstruction (C1) was refined to 3.8-Å resolution (Fig. 2B and fig. S1, A and B). In previous structures, receptor binding domains (RBDs) exist in either a closed (RBD-down) or an open (RBD-up) conformation that can engage in ACE2 binding (9, 10, 14). By contrast, we observed that all three RBDs on the 3Q-2P-FL spike trimer were in the closed conformation in our reconstructions (Fig. 2B and fig. S1C). Despite the RBD-down conformation, binding analysis of the 3Q-2P-FL immunogen to ACE2 by both biolayer interferometry and enzyme-linked immunosorbent assay clearly shows binding to ACE2, indicating that the RBD is dynamic and the receptor binding site accessible (15). Another study on the prefusion structure of an FL spike protein reported similar findings with RBDs clamped down as a consequence of potential clashes between S2 residues 828 to 853 and subdomain 1 (SD1) when RBD is in open conformation (16). Recent reports by Henderson et al. have revealed that introducing mutations and removing N-linked glycosylation at certain positions can alter the propensity toward “up” and “down” states of the RBD (17, 18).

Fig. 2 Cryo-EM analysis of SARS-CoV-2 3Q-2P-FL spikes.

(A) Representative electron micrograph and 2D class averages of 3Q-2P-FL spikes showing free trimers and complexes of trimers. (B) Side and top views of the B factor–sharpened cryo-EM map of 3Q-2P-FL free trimers showing the spike in prefusion state, with the RBDs in closed conformation. The protomers are colored in blue, green, and coral for clarity. (C) Side and top view of the atomic model of free trimer represented as a ribbon diagram fit into the map density. The protomers are colored in blue, green, and coral, and the map is shown as a transparent gray density. (D) Comparison of 3Q-2P-FL spike with published structures (PDB IDs 6VXX and 6VSB) on a subunit level. PDB 6VXX is shown in cyan, PDB 6VSB in blue, and 3Q-2P-FL spike in coral.

Overall, our cryo-EM map was well resolved in both S1 and S2 subunits (fig. S1D), enabling us to model the full S1 N-terminal domain (NTD) and C-terminal domain (CTD) that were less resolved in previous structures (9, 10). Our final atomic model contains residues 14 to 1146 with breaks only in the flexible loop (619 to 631) and the cleavage site (678 to 688) (Fig. 2C). Superimposition of the coordinate models of 3Q-2P-FL spike with published spike structures [Protein Data Bank (PDB) IDs: 6VXX and 6VSB] revealed substantial domain rearrangements in the S1 subunit of 3Q-2P-FL spike (Fig. 2D). The S1 NTD rotated ~14° relative to published models, whereas the CTD and subdomains showed minor local rearrangements (Fig. 2D). Another recent study also observed differences in NTD conformations at lower pH, although our cryo-EM studies were carried out at neutral pH (19). In our 3Q-2P-FL structure, we observed a shift in residues flanking the 615 to 635 loop, resulting in a salt bridge between residue D614 on one protomer and K854 on a neighboring protomer (Fig. 3A). This observation is particularly notable given the increased prevalence of D614→G (D614G) mutation in the emerging SARS-CoV-2 strains and its potential role in viral transmission and pathogenesis (20). The 615 to 635 loop that is generally disordered in spike trimer structures, including ours, was recently modeled as a helix (PDB ID: 6X6P) (Fig. 3B), although the cryo-EM density (EMD-22078) does not support this assignment (fig. S1E) (11).

Fig. 3 Structural features of the SARS-CoV-2 3Q-2P-FL spike trimer.

(A) Interprotomeric salt-bridge interaction between D614 and K854 in 3Q-2P-FL spike trimer. (B) Comparison of the 615 to 635 loop between 3Q-2P-FL spike shown in coral and PDB 6X6P shown in blue. The residues that were built in 6X6P model but not in our model are shown in dark blue. Threonines at positions 618 and 632 flanking the gap in the 3Q-2P-FL trimer model are shown on both models to highlight their relative positions. T, Thr. (C) Linoleic acid (dark blue) binding within a hydrophobic pocket of one RBD where the fatty acid head group reaches out to interact with the closed RBD of the adjacent protomer. The interacting residues are shown in pink. F, Phe; I, Ile; Y, Tyr. (D) PS 80 detergent (blue) binding within the NTD with potential hydrogen bonding with R190 and H207. The interacting residues are shown in orange. Adjacent protomers are shown in yellow and gray in (A), (C), and (D). H, His.

We observed two additional densities in the S1 subunit that did not correspond to peptide or glycans within the spike (fig. S2A). The first density was buried within a hydrophobic pocket of the CTD (Fig. 3C). We have previously showed palmitoleic acid occupying a similar pocket in the structure of porcine epidemic diarrhea virus (21). This density in SARS-CoV-2 S corresponded to linoleic acid, a polyunsaturated fatty acid; the presence of this ligand was confirmed by mass spectrometry of 3Q-2P-FL spike (fig. S2, B and C). The main chain carboxyl group of linoleic acid interacts with the R408 and Q409 residues of the RBD from the adjacent protomer, potentially stabilizing the observed RBD-down state (Fig. 3C) and consistent with a recent report (22). The second unassigned density, present in the NTD, was larger and more surface exposed than the first (Fig. 3D and fig. S2D). The aliphatic tail of PS 80 fit well into this hydrophobic pocket, whereas the carbonyl and hydroxyl groups were in proximity to residues R190 and H207 with potential for multiple hydrogen bonds between them (Fig. 3D and fig. S2D). The location of the PS 80 ligand provides a possible explanation for the S1 shift seen in our FL trimer density. PS 80 is specific to the formulation of the Novavax 3Q-2P-FL immunogen, but other ligands may also bind this pocket and provide a potential target for drug design against SARS-CoV-2.

Classification of multimeric spike trimer particles yielded two separate classes: a dimer-of-trimers class that reconstructed to a final resolution of 4.5 Å with twofold symmetry and a trimer-of-trimers class that was resolved to 8.0-Å resolution (Fig. 4, A and B, and fig. S3A). In both reconstructions, the interaction between each pair of trimers involved the SD2 of one protomer from each trimer engaging with the NTD of the adjacent trimer (Fig. 4C), with trimer axes tilted 44.5° relative to each other. The dimer-of-trimer interaction was mainly coordinated by the 615 to 635 loop, which, in contrast to the free-trimer structure, was now fully resolved (Fig. 4D). The loop reaches into and induces subtle changes to a pocket on the adjacent NTD compared with the free-trimer model (Fig. 4D). Residues Y145 and H146 in the binding pocket appear to switch positions in the loop-bound state, resulting in a salt-bridge interaction between H146 and D627 and potential stacking between W152 and H146 (Fig. 4E). We also observed minor displacement of residues 68 to 75 and 248 to 250 surrounding the pocket. In the dimer-of-trimers, we also observed N282 glycans at the dimer interface (fig. S3B). As a control, we also performed cryo-EM studies of the SARS-CoV-2-3Q-FL (without 2P). Notably, the structures of the trimers were identical, and we also observed dimers of trimers (fig. S3, C to E)

Fig. 4 Trimer-trimer interactions and glycan analysis.

(A) Side and top views of the sharpened cryo-EM map of 3Q-2P-FL dimers of spike trimers. Individual spike trimers are shown in blue and coral along a twofold axis of symmetry (dotted line). (B) Top view of the B factor–sharpened cryo-EM map of trimer-of-trimers complex with individual trimers colored in blue, coral, and green. (C) Ribbon representation of a protomer from one trimer (blue) interacting with the protomer from the adjacent trimer (coral) docked into the dimers-of-trimers density. (D) A close-up view of the interaction between the protomers of adjacent trimers. One protomer is shown as a ribbon diagram in blue, and its binding partner is shown as surface in gray. Residues 621-PVAIHADQ-628 in the loop with potential interactions to the neighboring NTD are colored yellow, and the residues in the NTD binding pocket are highlighted in coral. Residue D614 at the start of the loop is highlighted in dark blue. Glycosylation at residue 616 is not shown for clarity. G, Gly. (E) Changes occurring in the binding pocket in the bound state (gray) versus the free trimer (pink). Y145 and H146 switch positions to accommodate the loop better, also resulting in salt-bridge formation between H146 and D627. It also results in stacking between W152 and H146. W, Trp. (F) Pseudoviruses expressing SARS-CoV-2 WT or mutant spikes were used to infect HeLa or HeLa-ACE2 cells for 42 to 48 hours. Infection was measured by luciferase intensity RLU (relative light unit) in the lysed cells after infection. (G) Correlation between pseudovirus infection (RLU) and surface expression of SARS-CoV-2 spike variants in 293T cells measured by MFI (mean fluorescence intensity). (H) Site-specific glycan analysis of 3Q-2P-FL spike protein expressed in Sf9 insect cell line. Proportions shown for no occupancy, oligomannose, and complex or paucimannose potential N-linked glycosylation sites (PNGS) are the average and SEM of 3 to 32 distinctive peptides for each glycosite except for sites 17, 709, and 717, where only a single peptide was observed.

Sequence alignment of residues in the 615 to 635 loop and corresponding NTD binding pocket across representative CoV strains belonging to lineage B of betacoronaviruses revealed residues 621-PVAIHADQ-628 are well conserved, but there are notable differences in the binding pocket residues (fig. S4A). Substantial gaps in the interacting NTD loops along with the absence of H146 at the corresponding site on SARS-CoV make it unlikely that SARS-CoV participates in similar intertrimeric interactions. Although the residues in the NTD pocket were almost identical between SARS-CoV-2 and its closely related bat strain Bat-SL-RatG13, we observed some residue differences and one to three amino acid deletions in the loops comprising the NTD binding pocket of representative strains Bat-SL-CoVZC45, BetaCoV/pangolin/Guangdong/1/2019, and BetaCoV/pangolin/Guangxi/P4L/2007 (fig. S4A).

Some human CoVs, including OC43, exclusively use NTD–sialic acid (SA) interactions as their receptor engagement, whereas others such as Middle East respiratory syndrome (MERS) CoV that use the CTD-RBD for primary receptor binding have also been reported to bind SA receptors through their NTD to aid initial attachment to the host cells (2325). Structural comparisons of the SARS-CoV-2 NTD dimerization pocket with that of the SA binding site on MERS spike revealed that they did not coincide with each other (PDB ID: 6Q04) (25) (fig. S4B). Computational and structural studies have proposed residues on SARS-CoV-2 spike that may be involved in SA binding (26, 27). Structural comparison of this putative glycan binding site to the dimerization site revealed them situated adjacent to one another with residues in loop 70 contributing to both the binding pockets (fig. S4C).

We next performed cell surface expression and pseudovirus replication assays with SARS-CoV-2 wild-type (WT) spike and spikes containing mutations in the 615 to 635 loop and NTD pocket. Each residue in the loop 621-PVAIHADQ-628 and residue H146 in the binding pocket were individually mutated to either alanine or glycine. Additionally, we made a spike construct with all eight residues 621-PVAIHADQ-628 replaced with a glycine-serine (GS) linker to completely abrogate binding. Compared with the WT, the mutants generally exhibited lower levels of infectivity (Fig. 4F). Cell surface expression of these mutants in 293T cells revealed that these mutations also disrupted surface expression of the spike protein, with linear correlation between surface expression and pseudovirus replication (Fig. 4G).

Glycans on viral glycoproteins play a wide role in protein folding, stability, and immune recognition and also in facilitating immune evasion. We therefore conducted site-specific glycosylation analysis of the SARS-CoV-2 prefusion spike protein produced in Sf9 insect cells as previously described (28) to assess the extent of glycosylation and the degree of glycan processing from high-mannose or hybrid type to complex type. The analysis detected glycosylation at all 22 N-linked glycan sequons present on SARS-CoV-2 spike (Fig. 4H). Overall, there was high glycan occupancy of >98%, with only two sites (603 and 657) >5% unoccupied. We did not see clear glycan density at either 603 or 657 in the cryo-EM reconstruction of the 3Q-2P-FL spike. Most sites showed extensive glycan processing to complex or paucimannose-type glycans, with only four sites exhibiting ≥40% oligomannose. The glycan analysis also confirmed the presence of glycans at sites 1158, 1173, and 1194 present in the membrane-proximal region of the spike not resolved by cryo-EM. By comparison with site-specific glycan processing of the spike protein produced in mammalian human embryonic kidney (HEK) 293F cells, both mammalian cells and insect cells exhibit extensive processing at most sites. In general, however processing of glycans on the 2019 CoV prefusion spike protein from insect cells was somewhat greater, particularly at sites 709 and 717, which were predominately oligomannose in spike from HEK293 cells but exclusively complex or paucimannose in spike from Sf9 cells (29).

Our structural work is consistent with the burgeoning body of spike structures, albeit with notable differences in the rearrangement of S1 domains and formation of intertrimer interactions (9, 10). Both these findings were seen in the FL spike immunogens assembled into compact and dense nanoparticles. Cryo–electron tomographic reconstructions of intact SARS-CoV-2 virions showed a relatively dispersed distribution of spike protein trimers on the viral surface and no evidence of higher-order aggregates (30). However, another study showed that the D614G mutation present in close proximity to the dimerization loop results in a several-fold increase of spike numbers on the viral surface, resulting in higher spike protein density and a more infectious virion (20). The greater density may be aided by the ability to form such higher-order multimers. Alternatively, the loop that mediates interspike interactions may play a role in viral viability, consistent with our loop mutant data.

Analysis of safety and immunogenicity of the Novavax SARS-CoV-2-3Q-2P-FL immunogen in mice and baboons revealed strong B and T cell responses to the vaccine with no evidence of vaccine-associated enhanced respiratory disease (15). Phase 1 and 2 clinical trial results showed that the vaccine induced immune responses exceeding levels seen in COVID-19 patients (31). Overall, we found that NVAX-CoV2372 is stable, homogeneous, and locked in the antigenically preferred prefusion conformation. With structural, biophysical, and antigenic characterization now complete, ongoing evaluation in humans will provide the true proof-of-principle for this vaccine concept.

References and Notes

  1. N. G. Herrera, N. C. Morano, A. Celikgil, G. I. Georgiev, R. J. Malonis, J. H. Lee, K. Tong, O. Vergnolle, A. B. Massimi, L. Y. Yen, A. J. Noble, M. Kopylov, J. B. Bonanno, S. C. Garrett-Thomson, D. B. Hayes, R. H. Bortz, A. S. Wirchnianski, C. Florez, E. Laudermilch, D. Haslwanter, J. M. Fels, M. E. Dieterle, R. K. Jangra, J. Barnhill, A. Mengotto, D. Kimmel, J. P. Daily, L. A. Pirofski, K. Chandran, M. Brenowitz, S. J. Garforth, E. T. Eng, J. R. Lai, S. C. Almo, Characterization of the SARS-CoV-2 S protein: Biophysical, biochemical, structural, and antigenic analysis. bioRxiv 2020.06.14.150607 [Preprint]. 17 June 2020; .doi:10.1101/2020.06.14.150607

  2. R. Henderson, R. J. Edwards, K. Mansouri, K. Janowska, V. Stalls, M. Kopp, B. F. Haynes, P. Acharya, Glycans on the SARS-CoV-2 spike control the receptor binding domain conformation. bioRxiv 2020.06.26.173765 [Preprint]. 26 June 2020; .doi:10.1101/2020.06.26.173765

  3. T. Zhou, Y. Tsybovsky, A. S. Olia, J. Gorman, M. A. Rapp, G. Cerutti, P. S. Katsamba, A. Nazzari, A. Schon, P. D. Wang, J. Bimela, W. Shi, I. T. Teng, B. Zhang, J. C. Boyington, G. Y. Chuang, J. M. Sampson, M. Sastry, T. Stephens, J. Stuckey, S. Wang, R. A. Friesner, D. D. Ho, J. R. Mascola, L. Shapiro, P. D. Kwong, A pH-dependent switch mediates conformational masking of SARS-CoV-2 spike. bioRxiv 2020.07.04.187989 [Preprint]. 4 July 2020; .doi:10.1101/2020.07.04.187989

  4. L. Zhang, C. B. Jackson, H. Mou, A. Ojha, E. S. Rangarajan, T. Izard, M. Farzan, H. Choe, The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity. bioRxiv 2020.06.12.148726 [Preprint]. 12 June 2020; .doi:10.1101/2020.06.12.148726

  5. R. N. Kirchdoerfer, M. Bhandari, O. Martini, L. M. Sewall, S. Bangaru, K.-J. Yoon, A. B. Ward, Structure and immune recognition of the porcine epidemic diarrhea virus spike protein. bioRxiv 2020.02.18.955195 [Preprint]. 19 February 2020; .doi:10.1101/2020.02.18.955195

Acknowledgments: We thank B. Anderson, H. L. Turner, and C. A. Bowman for their help with electron microscopy, data acquisition, and data processing. We thank B. Webb and L. T. Hoang for their assistance with mass spectrometry and data processing. We thank L. Holden for her assistance with the manuscript. We also thank A. M. Greene at Novavax, Inc., for editing the manuscript. Funding: This work was supported by grants from the National Institute of Allergy and Infectious Diseases Center for HIV/AIDS Vaccine Development (UM1 AI144462 to J.C.P. and A.B.W., R01 AI113867 to J.C.P., R01 AI132317 to D.N., and P01 AI110657 to A.B.W.), the Bill and Melinda Gates Foundation (OPP1170236 to A.B.W.), and Novavax, Inc., Molecular graphics and analyses were performed with UCSF Chimera developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from National Institutes of Health (R01-GM129325 and P41-GM103311) and the Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases. Author contributions: S.B. and A.B.W. conceived and designed the study. S.B., H.L.T., G.O., and A.A. performed cryo-EM data collection, data processing, and model building. X.W., J.K.D., J.R.Y., and J.C.P. performed site-specific glycan analysis and data interpretation. J.L.T., D.H., and D.N. performed mutagenesis and pseudovirus assays. S.B., G.O., and A.B.W. analyzed and interpreted data. S.B. and A.B.W. wrote the paper, and all authors reviewed and edited the paper. J.H.T., A.D.P., N.P., M.J.M., G.G., and G.S. contributed NVX-CoV2373 and Matrix-M adjuvant and provided advice for sample handling. J.H.T., A.D.P., N.P., M.J.M., G.G., and G.S. also contributed to drafting of the manuscript. Competing interests: Authors J.H.T., A.D.P., N.P., M.J.M., G.G., and G.S. are current employees of Novavax, Inc., a for-profit organization, and these authors own stock or hold stock options. These interests do not alter the authors’ adherence to policies on sharing data and materials. Authors H.L.T. and A.B.W. are inventors on U.S. patent application no. 62/412,703 (“Prefusion Coronavirus Spike Proteins and Their Use”). All other authors have no competing interests to declare. Data and materials availability: The EM maps have been deposited at the Electron Microscopy Data Bank (EMDB) with accession codes EMD-22352 (SARS-CoV-2 3Q-2P-FL spike trimer with C3 symmetry), EMD-22353 (SARS-CoV-2 3Q-2P-FL spike trimer with C1 symmetry), EMD-22354 (SARS-CoV-2 3Q-2P-FL spike dimer-of-trimers with C2 symmetry), EMD-22355 (SARS-CoV-2 3Q-2P-FL spike trimer-of-trimers with C1 symmetry), and EMD-22356 (SARS-CoV-2 3Q-FL spike trimer with C3 symmetry). The atomic models have been deposited at the Protein Data Bank with PDB IDs 7JJI (SARS-CoV-2 3Q-2P-FL spike trimer with C3 symmetry) and 7JJJ (SARS-CoV-2 3Q-2P-FL spike dimer-of-trimers with C2 symmetry). The vaccine construct was provided to the Scripps Research Institute under a Material Transfer Agreement with Novavax, Requests for this material should be addressed to Gale Smith at Novavax. Other materials are available from A.B.W. under a Material Transfer Agreement with the Scripps Research Institute. This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures, photos, artwork, or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material.



Source link

The ‘hidden flower’ pollinated by lizards


Hello Nature readers, would you like to get this Briefing in your inbox free every day? Sign up here


A Drakensberg crag lizard noshes on nectar from the ‘hidden flowers’ of Guthriea capensis in a terrarium.Ruth Cozien & Steve Johnson

Late one night, while downloading data from camera traps over beers, researchers in South Africa saw a Drakensberg crag lizard (Pseudocordylus subviridis) visiting a Guthriea capensis flower, commonly known as ‘the hidden flower’. Over the next few days, they captured more footage of the lizards sticking their snouts deep into the flowers for nectar. The scientists had discovered the second known plant to use reptiles as its primary pollinator, and the first to do so in Africa. “A lot of science is a slog. But moments like this make it all worthwhile,” says plant scientist Sandy-Lynn Steenhuisen.

The Guardian | 7 min read

Reference: Ecology paper

Machine-learning systems are chipping in to help archaeologists to pinpoint possible finds and thwart illegal trade in artefacts. Among their tasks are trawling satellite images for the circular stone tombs left by ancient Scythians across the vast Eurasian steppes, classifying countless Roman pottery fragments and searching the Internet for unlawful sales of human bones.

The New York Times | 7 min read

Features & opinion

As COVID-19 restrictions continue to upend plans for data collection, scientists stuck at home are finding innovative ways to adapt their research questions. Seven junior researchers share how they modified their field-based research projects during the pandemic and offer their advice. “Although COVID-19 has been a big blow to researchers and academic work, it’s prompted me to develop different approaches and to think more broadly about my research,” says microbiologist Alexander Kwarteng.

Nature | 13 min read

Scientists at the Borexino solar neutrino experiment, located underground at the Gran Sasso National Laboratory in Italy, have blasted past a milestone in neutrino physics. They have detected, for the first time, neutrinos produced by one of the two types of fusion that power the Sun — the carbon–nitrogen–oxygen (CNO) cycle. (The other is the proton–proton (pp) chain.) Produced deep in the core, neutrinos emitted by the CNO cycle are the only direct probe of the deep interior of the Sun. Physicists spent 20 years perfecting the experiment, which had to be painstakingly purified to remove any natural radiation that could interfere with its measurements, spokesperson Marco Pallavicini tells the Nature Podcast. “The core of Borexino is probably the least radioactive piece of matter on the planet — maybe in the Universe actually,” he says.

Nature Podcast | 35 min listen

Go deeper with expert analysis from physicist Gabriel Orebi Gann in the Nature News & Views article.

Reference: Nature paper

Subscribe to the Nature Podcast on Apple Podcasts, Google Podcasts or Spotify.

Books & culture

Photos of sunsets are already a human obsession — ‘sunset’ is the single most common tag on the photo-sharing website Flickr, notes author Lauren Ring on her inspiration for the latest short story for Nature’s Futures series. What would be the value of such images in an underground future in which we never see the Sun for real? Prompted by her experience of lockdown, Ring explores our ability to find beauty and hope in a difficult present.

Nature | 5 min read

Andrew Robinson’s pick of the top five science books to read this week includes book-burning through the ages, the Arctic laid bare, and capitalism under scrutiny.

Nature | 3 min read

Where I work

Luke Bisby stands in his lab at University of Edinburgh.

Luke Bisby is a structural engineer and fire-safety researcher at the University of Edinburgh, UK. Credit: Kieran Dodds for Nature

Structural engineer and fire-safety researcher Luke Bisby stands behind a ‘fire sword’ — a stainless-steel pipe with holes to vent propane gas. It allows his team to wield fire in a controlled way to study the properties of engineered-timber buildings. “Ultimately, we’re studying fire to prevent tragedy,” says Bisby. “That image of a kid holding a stick in a campfire until it catches, pulling it out until it stops burning and then plunging it in again? That’s fundamentally the question we’re studying in timber buildings: how much heat is too much?” (Nature | 3 min read)

Quote of the day

Physicist Roger Penrose reflects on his twistor theory, which has yet to catch on in the physics community. (The TLS)



Source link

Amazon’s cloud service back up after widespread outage



FILE PHOTO: The logo of Amazon Web Services (AWS) is seen during the 4th annual America Digital Latin American Congress of Business and Technology in Santiago, Chile, September 5, 2018. REUTERS/Ivan Alvarado

November 26, 2020

(Reuters) – Amazon.com Inc’s widely used cloud service, Amazon Web Services (AWS) was back up on Thursday following an outage that affected several users ranging from websites to software providers.

“We have restored all traffic to Kinesis Data Streams via all endpoints and it is now operating normally,” the company said in a status update.

Amazon Kinesis, a part of AWS’ cloud offerings, collects, processes and analyzes real-time data and offers insights.

Video-streaming device maker Roku Inc, Adobe’s Spark platform, video-hosting website Flickr and the Baltimore Sun newspaper were among those hit by the outage, according to their posts on Twitter.

AWS said it had identified the cause of the outage and taken action to prevent a recurrence, according to the status update.

The company did not immediately respond to a Reuters request for comment on the cause of the outage.

(Reporting by Radhika Anilkumar in Bengaluru; Editing by Shounak Dasgupta)





Source link

The Crown season 4: What it gets right (and wrong) about Princess Diana


The tiara is too spread out, but this replica of Princess Diana’s wedding gown is amazingly well done.


Netflix

For obsessive followers of British royalty like me, Netflix drama The Crown is a royal joy. Now in its fourth season, the series doesn’t get everything right, but it usually comes very close. It’s easy to see creator Peter Morgan and his crew have done their research with all the energy of Sarah Ferguson cheering on rocker Meat Loaf at the It’s a Royal Knockout tournament back in 1987.

Accuracy has been a hallmark of the show all along, but the creators knew the spotlight would be more intense than ever on the latest season, streaming now. Not only does 1980s British Prime Minister Margaret Thatcher (played by X-Files star Gillian Anderson) have a major role, but the show had to cast and then dress and style an actress to look like perhaps the most famous woman of the 20th century: Diana, Princess of Wales. Get it wrong, and this high-class show risks looking like a hastily made Hallmark movie. 

Charles and Diana, Prince and Princess of Wales, smile to the crowd in Jakarta  during an official visit to Indonesia in November 1989. 


Georges De Keerle/Getty Images

There are some wonderful accuracies royal watchers will appreciate. Actress Emma Corrin could never look perfectly like Diana up close — that famous face is too familiar — but from a distance, she resembles her more than most actresses who’ve tried. Diana’s pre-wedding car is right, a small red hatchback. The paparazzi flooding around her as she tries to go to and from her Earl’s Court apartment are right. 

Her ironic “bluebird of happiness” engagement suit is perfect, as is Charles’ blunder of “whatever ‘in love’ means” when quizzed by a journalist. They use baby Prince William’s real nickname of “The Basher.” Even Diana’s bubbly, teenlike handwriting gets it right.

That said, half the fun of a series based on real life is poring over it to see where it nails the details and where things go awry. 

Warning: Small spoilers ahead for season 4 of The Crown.

Meet cute, but not that cute

In the series, Prince Charles is dating Diana’s sister, Sarah, before he gets together with Diana, which is really how it happened. But the show sets it up so that while waiting one day for Sarah, Charles runs into 16-year-old Diana while she’s costumed as a “mad tree” for a school production of A Midsummer Night’s Dream. That scene feels pure Hollywood. While the two probably did meet when Sarah and Charles were dating, Diana probably wasn’t wrapped in leaves, bragging about her love for the play.

Sympathy for the prince

In the series, Diana runs into Charles while he’s stopped in traffic in his convertible, and simply walks up (no bodyguards in sight!) to tell him how sorry she is about the murder of Lord Mountbatten, Charles’ mentor and father figure. It’s part of Diana legend that she did sympathize with him over Mountbatten’s death, but Diana herself reported that it happened at the home of mutual friends in Sussex, England. According to Tatler, she also said, “He leapt upon me and started kissing me and I thought, ‘Urgh, this is not what people do.'” 

diana-charles-traffic-crop

Diana and Charles definitely bonded when she sympathized with him over the death of his father figure, Lord Mountbatten, even if it didn’t happen while Charles was stuck in traffic.


Netflix

Dear deer me

It also seems unlikely Diana cozied up to Prince Philip at Balmoral and they shot a stag together, as depicted in the season’s second episode. Although reports are Diana did present herself as a more outdoorsy, horsey sort than she turned out to be, she probably wasn’t this good of an actress, proclaiming “the muckier the better” and “I’m a country girl at heart.” 

But this does convince her future father-in-law she’s the right woman for the heir to the throne, so the scene works. And the pink sweater that actress Emma Corrin is wearing when she leaves Charles is an exact replica of a famed one from Diana’s early years. The costumer re-creates famed outfits repeatedly, and for those who know Diana’s closet as well as their own, it’s rewarding and fun.

diana-tree-crop

Was Diana dressed as a “mad tree” the first time she met Charles?


Netflix

Ring me up

Diana is seen choosing her famed sapphire engagement ring, which was indeed not custom made, but in the catalog of crown jeweler Garrard. That fact is supposed to be somewhat shocking, because any commoner with enough money could wear the same model of ring. (But if that was scandalous, why did Charles even offer catalog rings as a choice? As an American, I’ll never get that.) Anyway, it is true Diana reportedly thought the ring looked like that of her mother, Frances Shand Kydd, and also true some say it was because it had the biggest stone. Prince William gave the ring to the Duchess of Cambridge when he proposed to her, and modern photos of the duchess make it easy to see how huge it is.

diana-ring-crop

Princess Diana’s gigantic sapphire engagement ring is almost as famous as her wedding gown, so it’s fitting that The Crown shows her selecting it.


Netflix

They see me rolling

Did Diana really roller skate through the royal hallways while listening to Duran Duran on her Walkman? Corrin tells Tatler she thinks so, but I’m kinda doubting it. Update: After the show aired, the show’s head of research and a producer told Vogue the roller skating was true, and that Diana also bicycled through the palace. But none of them cited sources, so I still wonder.

diana-skating-crop

Whether Diana really roller-skated through royal halls, she definitely wore this outfit.


Netflix

Ironic eats

Apparently, some time before the wedding Diana and Camilla did really dine together at a Knightsbridge restaurant called Ménage à Trois. That name seems a little too on the nose, no? But it was a real place, and according to The Daily Mail, its menu indeed was designed specifically to appeal to women diners, offering no main courses (because, um, women don’t like those?), just appetizers and desserts.

diana-camilla-crop

Camilla Parker Bowles and Diana really did dine at a restaurant called Ménage à Trois. Oof, the irony.


Netflix

Here comes the bride

Perhaps no wedding gown is as famous as Diana’s 1981 enormous marshmallow of a dress. The show didn’t set out to copy it completely, costume designer Amy Roberts told WWD, but the lace, the bows, the weirdly flat front, the gonzo train — those all match up with most people’s memories. The veil doesn’t look fitted around her face, though, and another mistake seems more glaring. 

Diana wore her own family’s Spencer tiara, so legendary you can now buy replicas of it. But the tiara made for The Crown lacks the elegant simplicity of the Spencer tiara. Instead it’s enormous and sprawling, more like a cardboard Burger King crown. No big deal, perhaps, to many viewers, but to royal-watchers, it’s like watching a movie about the New York Yankees in which the famed “NY” symbol appears in Comic Sans.

Dance, ballerina, dance

Diana famously loved dancing, and it is true that in 1985 she pulled off a surprise for Charles, dancing on stage to Billy Joel’s Uptown Girl at London’s Royal Opera House. The Crown nails this one — Diana’s slinky white dress looks just like the one she wore, and the dancer she’s paired with strongly resembles ballet star Wayne Sleep, her partner for the performance. Just as in the episode, Charles reportedly wasn’t impressed and thought his wife was showing off. Further proof, perhaps, that ballet-loving Di had to always be on her toes with her husband.

diana-purple-gown-crop

Diana wears this gown to the Royal Opera House, but slips out and changes into a slinky white number to perform a surprise dance onstage to Billy Joel’s Uptown Girl.


Netflix


Now playing:
Watch this:

What’s new to stream for November 2020



4:34



Source link