An ultra-precise microscope that surpasses the limitations of Nobel Prize-winning super-resolution microscopy will let scientists directly measure distances between individual molecules.
The 2014 Nobel Prize in Chemistry was awarded for the development of super-resolution fluorescence microscopy technology that afforded microscopists the first molecular view inside cells, a capability that has provided new molecular perspectives on complex biological systems and processes.
Now the limit of detection of single-molecule microscopes has been smashed again, and the details are published in the current issue of Science Advances.
While individual molecules could be observed and tracked with super-resolution microscopy already, interactions between these molecules occur at a scale at least four times smaller than that resolved by existing single-molecule microscopes.
“The reason why the localisation precision of single-molecule microscopes is around 20-30 nanometres normally is because the microscope actually moves while we’re detecting that signal. This leads to an uncertainty. With the existing super-resolution instruments, we can’t tell whether or not one protein is bound to another protein because the distance between them is shorter than the uncertainty of their positions,” says Scientia Professor Katharina Gaus, research team leader and Head of UNSW Medicine’s EMBL Australia Node in Single Molecule Science.
To circumvent this problem, the team built autonomous feedback loops inside a single-molecule microscope that detects and re-aligns the optical path and stage.
“It doesn’t matter what you do to this microscope, it basically finds its way back with precision under a nanometre. It’s a smart microscope. It does all the things that an operator or a service engineer needs to do, and it does that 12 times per second,” says Professor Gaus.
Measuring the distance between proteins
With the design and methods outlined in the paper, the feedback system designed by the UNSW team is compatible with existing microscopes and affords maximum flexibility for sample preparation.
“It’s a really simple and elegant solution to a major imaging problem. We just built a microscope within a microscope, and all it does is align the main microscope. That the solution we found is simple and practical is a real strength as it would allow easy cloning of the system, and rapid uptake of the new technology,” says Professor Gaus.
To demonstrate the utility of their ultra-precise feedback single-molecule microscope, the researchers used it to perform direct distance measurements between signalling proteins in T cells. A popular hypothesis in cellular immunology is that these immune cells remain in a resting state when the T cell receptor is next to another molecule that acts as a brake.
Their high precision microscope was able to show that these two signalling molecules are in fact further separated from each other in activated T cells, releasing the brake and switching on T cell receptor signalling.
“Conventional microscopy techniques would not be able to accurately measure such a small change as the distance between these signalling molecules in resting T cells and in activated T cells only differed by 4–7 nanometres,” says Professor Gaus.
“This also shows how sensitive these signalling machineries are to spatial segregation. In order to identify regulatory processes like these, we need to perform precise distance measurements, and that is what this microscope enables. These results illustrate the potential of this technology for discoveries that could not be made by any other means.”
Postdoctoral researcher, Dr. Simao Pereira Coelho, together with Ph.D. student Jongho Baek—who has since been awarded his Ph.D. degree—led the design, development, and building of this system. Dr. Baek also received the Dean’s Award for Outstanding Ph.D. Thesis for this work.
Simao Coelho et al. Ultraprecise single-molecule localization microscopy enables in situ distance measurements in intact cells, Science Advances (2020). DOI: 10.1126/sciadv.aay8271
University of New South Wales
Self-aligning microscope smashes limits of super-resolution microscopy (2020, April 20)
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New species of crested dinosaur identified in Mexico
A team of palaeontologists in Mexico have identified a new species of dinosaur after finding its 72 million-year-old fossilized remains almost a decade ago, Mexico’s National Institute of Anthropology and History (INAH) said on Thursday.
The new species, named Tlatolophus galorum, was identified as a crested dinosaur after 80% of its skull was recovered, allowing experts to compare it to other dinosaurs of that type, INAH said.
The investigation, which also included specialists from the National Autonomous University of Mexico, began in 2013 with the discovery of an articulated tail in the north-central Mexican state of Coahuila, where other discoveries have been made.
“Once we recovered the tail, we continued digging below where it was located. The surprise was that we began to find bones such as the femur, the scapula and other elements,” said Alejandro Ramírez, a scientist involved in the discovery.
Later, the scientists were able to collect, clean and analyze other bone fragments from the front part of the dinosaur’s body.
The palaeontologists had in their possession the crest of the dinosaur, which was 1.32 meters long, as well as other parts of the skull: lower and upper jaws, palate and even a part known as the neurocranium, where the brain was housed, INAH said.
The Mexican anthropology body also explained the meaning of the name – Tlatolophus galorum – for the new species of dinosaur.
Tlatolophus is a mixture of two words, putting together a term from the indigenous Mexican language of Nahuatl that means “word” with the Greek term meaning “crest”. Galorum refers to the people linked to the research, INAH said.
(Reporting by Abraham Gonzalez; Writing by Drazen Jorgic; Editing by Ana Nicolaci da Costa)
Alberta family searches for answers in teen's sudden death after COVID exposure, negative tests – CBC.ca
A southern Alberta mother and father are grappling with the sudden, unexplained death of their 17-year-old daughter, and with few answers, they’re left wondering if she could be the province’s youngest victim of COVID-19.
Sarah Strate — a healthy, active Grade 12 student at Magrath High School who loved singing, dancing and being outdoors — died on Monday, less than a week after being notified she’d been exposed to COVID-19.
While two tests came back negative, her parents say other signs point to the coronavirus, and they’re waiting for more answers.
“It was so fast. It’s all still such a shock,” said Sarah’s mother, Kristine Strate. “She never even coughed. She had a sore throat and her ears were sore for a while, and [she had] swollen neck glands.”
Kristine said Sarah developed mild symptoms shortly after her older sister — who later tested positive for COVID-19 — visited from Lethbridge, one of Alberta’s current hot spots for the virus.
The family went into isolation at their home in Magrath on Tuesday, April 20. They were swabbed the next day and the results were negative.
‘Everything went south, super-fast’
By Friday night, Sarah had developed fever and chills. On Saturday, she started vomiting and Kristine, a public health nurse, tried to keep her hydrated.
“She woke up feeling a bit more off on Monday morning,” Kristine said. “And everything went south, super-fast.”
Sarah had grown very weak and her parents decided to call 911 when she appeared to become delirious.
“She had her blanket on and I was talking to her and, in an instant, she was unresponsive,” said Kristine, who immediately started performing CPR on her daughter.
When paramedics arrived 20 minutes later, they were able to restore a heartbeat and rushed Sarah to hospital in Lethbridge, where she died.
“I thought there was hope once we got her heart rate back. I really did,” recalled Sarah’s father, Ron.
“He was praying for a miracle, and sometimes miracles don’t come,” said Kristine.
Searching for answers
At the hospital, the family was told Sarah’s lungs were severely infected and that she may have ended up with blood clots in both her heart and lungs, a condition that can be a complication of COVID-19.
But a second test at the hospital came back negative for COVID-19.
“There really is no other answer,” Ron said. “When a healthy 17-year-old girl, who was sitting up in her bed and was able to talk, and within 10 minutes is unconscious on our floor — there was no reason [for it].”
The province currently has no record of any Albertans under the age of 20 who have died of COVID-19.
According to the Strate family, the medical examiner is running additional blood and tissue tests, in an effort to uncover the cause of Sarah’s death.
‘Unusual but not impossible’
University of Alberta infectious disease specialist Dr. Lynora Saxinger, who was not involved in Sarah’s treatment, says it is conceivable that further testing could uncover evidence of a COVID-19 infection, despite two negative test results.
However, she hasn’t seen a similar case in Alberta.
“It would be unusual but not impossible because no test is perfect. We have had cases where an initial test is negative and then if you keep on thinking it’s COVID and you re-test, you then can find COVID,” she said.
According to Saxinger, the rate of false negatives is believed to be very low. But it can happen if there are problems with the testing or specimen collection.
She says people are more likely to test positive after symptoms develop.
“The best sensitivity of the test is around day four or five of having symptoms,” she said. “So you can miss things if you test very, very early. And with new development of symptoms, it’s always a good time to re-test because then the likelihood of getting a positive test is a little higher. But again, no test is perfect.”
Sarah deteriorated so quickly — dying five days after she first developed symptoms — she didn’t live long enough to make it to her follow-up COVID-19 test. Instead, it was done at the hospital.
‘An amazing kid’
The Strate family now faces an agonizing wait for answers — one that will likely take months — about what caused Sarah’s death.
But Ron, who teaches at the school where Sarah attended Grade 12, wants his daughter to be remembered for the life she lived, not her death.
Sarah was one of five children. Ron says she was strong, active and vibrant and had plans to become a massage therapist after graduating from high school.
She played several sports and loved to sing and dance as part of a show choir. She was a leader in the school’s suicide prevention group and would stand up for other students who were facing bullying.
“She’s one of the leaders in our Hope Squad … which goes out and helps kids to not be scared,” he father said.
“She’s an amazing kid.”
Sarah would often spend hours helping struggling classmates, and her parents hope her kindness is not forgotten.
“She’d done so many good things. Honestly, I’ve got so many messages from parents saying, ‘You have no idea how much your daughter helped our kid,'” said Ron.
“This 17-year-old girl probably lived more of a life in 17 years than most adults will live in their whole lives. She was so special. I love her so much.”
China launches key module of space station planned for 2022
BEIJING (Reuters) -China launched an unmanned module on Thursday containing what will become living quarters for three crew on a permanent space station that it plans to complete by the end of 2022, state media reported.
The module, named “Tianhe”, or “Harmony of the Heavens”, was launched on the Long March 5B, China’s largest carrier rocket, at 11:23 a.m. (0323 GMT) from the Wenchang Space Launch Centre on the southern island of Hainan.
Tianhe is one of three main components of what would be China’s first self-developed space station, rivalling the only other station in service – the International Space Station (ISS).
The ISS is backed by the United States, Russia, Europe, Japan and Canada. China was barred from participating by the United States.
“(Tianhe) is an important pilot project in the building of a powerful nation in both technology and in space,” state media quoted President Xi Jinping as saying in a congratulatory speech.
Tianhe forms the main living quarters for three crew members in the Chinese space station, which will have a life span of at least 10 years.
The Tianhe launch was the first of 11 missions needed to complete the space station, which will orbit Earth at an altitude of 340 to 450 km (211-280 miles).
In the later missions, China will launch the two other core modules, four manned spacecraft and four cargo spacecraft.
Work on the space station programme began a decade ago with the launch of a space lab Tiangong-1 in 2011, and later, Tiangong-2 in 2016.
Both helped China test the programme’s space rendezvous and docking capabilities.
China aims to become a major space power by 2030. It has ramped up its space programme with visits to the moon, the launch of an uncrewed probe to Mars and the construction of its own space station.
In contrast, the fate of the ageing ISS – in orbit for more than two decades – remains uncertain.
The project is set to expire in 2024, barring funding from its partners. Russia said this month that it would quit the project from 2025.
Russia is deepening ties with China in space as tensions with Washington rise.
Moscow has slammed the U.S.-led Artemis moon exploration programme and instead chosen to join Beijing in setting up a lunar research outpost in the coming years.
(Reporting by Ryan Woo and Liangping Gao; Editing by Christian Schmollinger, Simon Cameron-Moore and Lincoln Feast.)
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