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Health

Inflammatory Trigger a New Clue in Alzheimer’s and PSP

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Summary: An inflammatory trigger like one present during viral infections is elevated in those with Alzheimer’s disease and progressive supranuclear palsy (PSP).

Source: UT San Antonio

Scientists from The University of Texas Health Science Center at San Antonio (UT Health San Antonio) today reported that an inflammatory trigger like one present during viral infections is elevated in Alzheimer’s disease and progressive supranuclear palsy, a rare brain disorder.

“We have identified a new trigger of brain inflammation in these disorders,” said Elizabeth Ochoa, study author from UT Health San Antonio.

The finding published in Science Advances is novel for this reason, she said.

Ochoa, a recent doctoral graduate, and her mentor, Bess Frost, Ph.D., study senior author, are investigators with the Sam and Ann Barshop Institute for Longevity and Aging Studies, the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, and the Department of Cell Systems and Anatomy at UT Health San Antonio. Frost is the Bartell Zachry Distinguished Professor for Research in Neurodegenerative Disorders.

Alzheimer’s disease and progressive supranuclear palsy are marked by toxic deposits of a protein called tau. Their research found that tau-induced “jumping genes”—which can relocate or copy themselves to other locations in the genome—form double-stranded RNA. This abnormal RNA mimics the inflammatory trigger that is also present in viral infections.

“Transposable elements—the so-called jumping genes—are a new area of interest in understanding Alzheimer’s disease. Our study provides new insights into how they can drive the disease process in addition to their ability to jump,” Ochoa said. “These double-stranded RNAs look like a virus to the immune system even though the jumping genes are a part of our normal genome.”

Alzheimer’s disease and progressive supranuclear palsy are marked by toxic deposits of a protein called tau. Image is in the public domain

The researchers detected accumulation of double-stranded RNA in postmortem brain tissue from patients with Alzheimer’s disease and progressive supranuclear palsy and in brains of mouse and fruit fly models of tauopathy.

“We found substantial deposits of double-stranded RNA in astrocytes, which are cells that provide metabolic support for neurons, regulate neurotransmitters and maintain blood-brain barrier integrity,” Frost said. “In aging and disease, astrocytes respond to injury and disruption of the neuronal environment. Our findings open new doors for understanding astrocyte biology and their role in transposable element control.”

Loss of neurons, which are cells of the central nervous system, is progressive in Alzheimer’s and other neurodegenerative diseases.

The researchers conducted experiments in fruit flies to quickly test their questions about double-stranded RNA and inflammation in the brain. “To ensure that what we found in our fruit fly experiments is relevant to mammalian disease, we also studied brain tissue from mouse models and from postmortem human brains affected by tauopathy,” Ochoa said.

“As we are currently targeting jumping gene activation in a local Phase II clinical trial for patients with Alzheimer’s disease, it’s important to understand the full repertoire of toxic molecules, including double-stranded RNAs, that jumping genes produce,” Frost said.

Ochoa recently earned her Ph.D. from the Cell Biology, Genetics and Molecular Medicine Discipline of the Integrated Biomedical Sciences program at UT Health San Antonio. She earned her undergraduate degree from Seattle University.

Frost, associate professor of cell systems and anatomy in the Barshop and Biggs institutes at UT Health San Antonio, received the highly competitive Edith and Peter O’Donnell Award in Medicine in 2020 from TAMEST, the Texas Academy of Medicine, Engineering, Science and Technology. She was also a Gold Medalist in 2022 for the prestigious Oskar Fischer Prize.

About this Alzheimer’s disease and PSP research news

Author: Press Office
Source: UT San Antonio
Contact: Press Office – UT San Antonio
Image: The image is in the public domain

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Original Research: Open access.
“Pathogenic tau–induced transposable element–derived dsRNA drives neuroinflammation” by Elizabeth Ochoa et al. Science Advances

Abstract

Pathogenic tau–induced transposable element–derived dsRNA drives neuroinflammation

Deposition of tau protein aggregates in the brain of affected individuals is a defining feature of “tauopathies,” including Alzheimer’s disease. Studies of human brain tissue and various model systems of tauopathy report that toxic forms of tau negatively affect nuclear and genomic architecture, identifying pathogenic tau–induced heterochromatin decondensation and consequent retrotransposon activation as a causal mediator of neurodegeneration.

On the basis of their similarity to retroviruses, retrotransposons drive neuroinflammation via toxic intermediates, including double-stranded RNA (dsRNA). We find that dsRNA and dsRNA sensing machinery are elevated in astrocytes of postmortem brain tissue from patients with Alzheimer’s disease and progressive supranuclear palsy and in brains of tau transgenic mice.

Using a Drosophila model of tauopathy, we identify specific tau-induced retrotransposons that form dsRNA and find that pathogenic tau and heterochromatin decondensation causally drive dsRNA-mediated neurodegeneration and neuroinflammation.

Our study suggests that pathogenic tau–induced heterochromatin decondensation and retrotransposon activation cause elevation of inflammatory, transposable element–derived dsRNA in the adult brain.

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Health

Experts find clue as to how Alzheimer’s disease starts and say mutations may starve brain

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Alzheimer’s breakthrough as experts find clue to how memory-robbing disease starts and say hallmark mutations may starve brain of crucial energy

  • Australian researchers examined zebrafish with genes connected to Alzheimer’s
  • They found brain cells of fish with the genes had disrupted oxygen generation
  • This means the brain had less energy to function, impacting its performance
  • Researchers are confident they have found a driver of the disease in humans

By John Ely Senior Health Reporter For Mailonline

Published: | Updated:










Hopes of stopping Alzheimer’s in its tracks were raised today as scientists said they may have found what drives the memory-robbing disease.

Australian researchers believe their discovery — if proven true in human trials — may ‘enormously benefit our ageing population’.

Genes thought to raise the risk of the condition disrupt the way brain cells produce energy and could contribute to the deterioration of the brain, their study suggests.

University of Adelaide academics examined how genetic mutations linked to early-onset Alzheimer’s affected zebrafish.

Brain cells of the fish with the telltale DNA changes used less oxygen, meaning their brains were unable to produce enough energy to function correctly.  

Similar data on mice backed-up their theory. 

Lead researcher Dr Karissa Barthelson said the team are confident they have found a ‘fundamental, early driver of Alzheimer’s in humans’.

‘Energy production is the most fundamentally important cellular activity supporting all other functions, particularly in highly active organs such as brains,’ she said.

‘If we can understand what is going wrong with oxygen use and energy production, we may see ways of stopping the disease before it starts.’

Australian researchers have found what could be a key driving factor in the memory-robbing disease Alzheimer’s finding genes associated with the condition disrupt how brain cells use oxygen

The scientists used zebrafish for their study due to their ability produce a huge number of offspring which makes it easier to detect subtle genetic differences

She added: ‘That would enormously benefit our ageing population.’  

Dr Barthelson and colleagues published their findings in the journal Disease Models and Mechanisms. 

Alzheimer’s is a degenerative brain disease, in which the build-up of abnormal proteins causes nerve cells to die.

This disrupts the transmitters that carry messages, and causes the brain to shrink. 

Dr Barthelson also said the disease that ‘people’s brains become severely deficient in energy production’.

The disease, the most common type of dementia, usually strikes over-65s but one in 20 cases are among younger adults.

Dr Barthelson’s team studied zebrafish because they have very large families, which makes it easier to detect subtle effects.

The experts also examined a different team’s similar research on mice and found the same result.  

Dr Barthelson said: ‘This reinforces our confidence that we’ve found a fundamental, early driver of Alzheimer’s in humans. 

‘It is very satisfying to have found this important common, early factor driving the development of Alzheimer’s disease.’ 

The team of researchers now plan to examine how the genes associated with Alzheimer’s impact the the energy generation of different types of brain cells. 

About 1million people in the UK have Alzheimer’s disease, with the condition being responsible for the majority of dementia cases in the country,

In the US an estimated 5million people have Alzheimer’s and it is the officially sixth leading cause of death in the country, though more recent estimates have suggested it should now be bumped up to third. 

WHAT IS ALZHEIMER’S?

Alzheimer’s disease is a progressive, degenerative disease of the brain, in which build-up of abnormal proteins causes nerve cells to die.

This disrupts the transmitters that carry messages, and causes the brain to shrink. 

More than 5 million people suffer from the disease in the US, where it is the 6th leading cause of death, and more than 1 million Britons have it.

WHAT HAPPENS?

As brain cells die, the functions they provide are lost. 

That includes memory, orientation and the ability to think and reason. 

The progress of the disease is slow and gradual. 

On average, patients live five to seven years after diagnosis, but some may live for ten to 15 years.

EARLY SYMPTOMS:

  • Loss of short-term memory
  • Disorientation
  • Behavioral changes
  • Mood swings
  • Difficulties dealing with money or making a phone call 

LATER SYMPTOMS:

  • Severe memory loss, forgetting close family members, familiar objects or places
  • Becoming anxious and frustrated over inability to make sense of the world, leading to aggressive behavior 
  • Eventually lose ability to walk
  • May have problems eating 
  • The majority will eventually need 24-hour care   

 Source: Alzheimer’s Association

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Science

New Clue From Mysterious Clouds Circling Spinning Black Holes

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Gravitational waves are cosmic ripples in the fabric of space and time that emanate from catastrophic events in space, like collisions of black holes and neutron stars — the collapsed cores of massive supergiant stars. Extremely sensitive gravitational-wave detectors on Earth, like the Advanced

Dr. Lilli Sun is on the hunt for boson clouds – a key contender for dark matter. Credit: Tracey Nearmy/ANU

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Science

Simulations provide clue to missing planets mystery

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A protoplanetary disk as observed by ALMA (left), and a protoplanetary disk during planetary migration, as obtained from the ATERUI II simulation (right). The dashed line in the simulation represents the orbit of a planet, and the gray area indicates a region not covered by the computational domain of the simulation. Credit: Kazuhiro Kanagawa, ALMA(ESO/NAOJ/NRAO)

Forming planets are one possible explanation for the rings and gaps observed in disks of gas and dust around young stars. But this theory has trouble explaining why it is rare to find planets associated with rings. New supercomputer simulations show that after creating a ring, a planet can move away and leave the ring behind. Not only does this bolster the planet theory for ring formation, the simulations show that a migrating planet can produce a variety of patterns matching those actually observed in disks.

Young stars are encircled by protoplanetary disks of gas and dust. One of the world’s most powerful radio telescope arrays, ALMA (Atacama Large Millimeter/submillimeter Array), has observed a variety of patterns of denser and less dense rings and gaps in these protoplanetary disks. Gravitational effects from planets forming in the disk are one theory to explain these structures, but follow-up observations looking for planets near the rings have largely been unsuccessful.

In this research a team from Ibaraki University, Kogakuin University, and Tohoku University in Japan used the world’s most powerful supercomputer dedicated to astronomy, ATERUI II at the National Astronomical Observatory of Japan, to simulate the case of a planet moving away from its initial formation site. Their results showed that in a low viscosity disk, a ring formed at the initial location of a planet doesn’t move as the planet migrates inwards. The team identified three distinct phases. In Phase I, the initial ring remains intact as the planet moves inwards. In Phase II, the initial ring begins to deform and a second ring starts forming at the new location of the planet. In Phase III, the initial ring disappears and only the latter ring remains.

A comparison of the three phases of ring formation and deformation found in these simulations by ATERUI II (top) with real examples observed by ALMA (bottom). The dotted lines in the simulation represent the orbits of the planets, and the gray areas indicate regions not covered by the computational domain of the simulation. In the upper row, the simulated protoplanetary disks are shown from left to right at the start of planetary migration (Phase I), during planetary migration (Phase II), and at the end of planetary migration (Phase III). Credit: Kazuhiro Kanagawa, ALMA (ESO/NAOJ/NRAO)

These results help explain why planets are rarely observed near the outer rings, and the three phases identified in the simulations match well with the patterns observed in actual rings. Higher resolution observations from next-generation telescopes, which will be better able to search for planets close to the central star, will help determine how well these simulations match reality.

These results appeared as K.D. Kanagawa et al. “Dust rings as a footprint of planet formation in a protoplanetary disk” in The Astrophysical Journal on November 12, 2021.

Planet formation may start earlier than previously thought

More information:
K.D. Kanagawa et al, Dust rings as a footprint of planet formation in a protoplanetary disk, The Astrophysical Journal (2021). arXiv:2109.09579 [astro-ph.EP] arxiv.org/abs/2109.09579
Provided by
National Institutes of Natural Sciences

Citation:
Simulations provide clue to missing planets mystery (2021, November 12)
retrieved 13 November 2021
from https://phys.org/news/2021-11-simulations-clue-planets-mystery.html

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Science

Denisovan discoveries: New clue to human evolution’s biggest mystery emerges

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The fragments are so tiny that they can all fit in the palm of one person’s hand.

Now, DNA from 3,000 miles (4,828 kilometers) away in the Philippines is shedding more light on human evolution’s biggest mystery.

New research published Thursday has found that a Philippine ethnic group known as the Ayta Magbukon has the highest known level of Denisovan ancestry in the world.

Denisovan DNA lives on in some humans today because, once our Homo sapien ancestors encountered the Denisovans, they had sex with them and gave birth to babies — something geneticists call admixture. By analyzing current-day genetic data, we can look back into human history.

The “admixing” happened more than 50,000 years ago, as modern humans moved out of Africa and likely crossed paths with both Neanderthals and Denisovans. But pinning down exactly where it happened has proven difficult — particularly in the case of Denisovans.

It’s especially puzzling that the only Denisovan fossils were found in Siberia (with the potential exception of a jaw bone on the Tibetan plateau). Genetic evidence has tied the archaic humans most closely to places much farther south.

“The fact that Ayta Magbukon have the highest amount of Denisovan ancestry of anywhere in the world is unexpected, and I am intrigued, as previous studies did not report such high amounts in other Philippines populations,” said João Teixeira, a visiting fellow at the Australian Centre for Ancient DNA at The University of Adelaide. He was not involved in the study.

Researchers from the Philippines and Sweden stumbled on the new findings as part of a wider study on human history in the Philippines that involved studying the genetic makeup of 118 different groups in the country. The study was published in the journal Current Biology on Thursday.

The study found that the Ayta Magbukon had around 5% Denisovan ancestry, more than Aboriginal Australians and Papuans, whom previous research found to have around 4%, said Mattias Jakobsson, a geneticist at Uppsala University in Sweden and an author of the study.

Denisovan ancestory is also present in many East Asian people — although at a much lower level, other studies have found.

Ayta Magbukon belong to a wider group of people in the Philippines that identify as Negritos, Jakobsson said.

The findings are further evidence that Denisovans once lived all throughout Asia and were likely living in the Philippines long before any Homo sapiens arrived, the authors said. It also suggests that different Denisovan populations mixed and intermingled with Homo sapiens in multiple locations and various points in time.

“If the results are accurate, then human colonizations of the Philippines and surrounding regions were even more complex than we thought up to now,” said Chris Stringer, a professor and research leader in Human Origins at The Natural History Museum in London. He was not involved in research.

It also appears that our ancestors may have interacted more widely with Denisovans than Neanderthals — a much more deeply studied early human who lived in Europe and some parts of Asia until about 40,000 years ago, Stringer said.

“Relatively small groups of early modern humans interbred with Neanderthals in western Eurasia and then spread across Eurasia and beyond, passing on that level of acquired Neanderthal DNA to descendant populations,” he said.

“In the case of the Denisovans, it looks like they were genetically much more diverse, and they intermixed separately in different locations with differentiating early modern populations, hence the more varied patterns we see today.”

Why so few Denisovan fossils?

Denisovan DNA, along with Neanderthal DNA, was sequenced completely for the first time in 2010, which led to the initial discovery that they were interbreeding with our Homo sapien ancestors.

DNA sequenced from the few fossilized bones found in the Siberian cave they were named after has allowed us to learn more about the Denisovans. But we still don’t know what these extinct hominins looked like.

It’s not clear why we have so few fossilized remains of Denisovans, but several factors could be at play. Unlike Europe, southeast Asia isn’t a region that’s been well studied by archaeologists. Also, some locations in the region that might harbor a rich fossil record are now submerged under the sea.

Tantalizingly, the fossils could also be hiding in plain sight — in museum or university collections — but misidentified because we know so little about Denisovan morphology. There are remains in China, Taiwan and other places that could be Denisovan, but it has not yet been possible to extract any DNA, which does not preserve well in tropical heat, from those fossils.

“What if we have been looking at them all along and calling them something else? The recognized fossil evidence for Denisovans includes fossils for which DNA or proteins have confirmed it to be the case. But how can we tell for sure what a Denisovan is supposed to look like?” Teixeira said.

This finding — along with the recent discoveries of new types of archaic humans in the Philippines and Indonesia — suggest that Southeast Asia may play a key role in untangling the human story.

“Island Southeast Asia is still relatively underrepresented. However this may change in the future given the increased interest in the region. Our study, together with the recent discoveries on Homo luzonensis and Homo floresiensis, brings Island Southeast Asia at the forefront of research in human evolutionary history,” said Maximilian Larena, study author and researcher at Uppsala University.

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Health

Clue gets FDA clearance for digital birth control

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Clue, best known for its period tracking app, announced that it received clearance from the Food and Drug Administration for a digital birth control function, which it says can help users prevent pregnancy based only on the start date of a user’s period. It calculates the window where someone could get pregnant based on statistical modeling.

“It personalizes over time. So as the individual puts in their cycle day one then we’re able to personalize the window of their high risk days vs their low risk days,” Clue’s chief medical officer Lynae Brayboy told TechCrunch.

The company plans to launch its digital birth control some time this year.

Clue says that its digital birth control is 92 percent effective at preventing unwanted pregnancy when it’s used the way most people do (accounting for some errors) and 97 percent effective under perfect use. The statistical method it uses was originally developed and tested by researchers at the Institute for Reproductive Health at Georgetown University and a company called Cycle Technologies, and acquired by Clue in 2019.

This is the second form of digital birth control to get clearance from the FDA to market itself as birth control. The first, Natural Cycles, requires users to take their body temperature each morning. Its 2018 clearance was controversial — it came just after the app was blamed for unwanted pregnancies in Sweden.

Clue’s digital birth control was cleared by the FDA under its “substantially equivalent” designation, meaning that the agency determined that it was safe and effective because it’s similar to a product already on the market. In this case, Clue’s product was considered similar enough to Natural Cycles. Elina Berglund, the CEO of Natural Cycles, said in a statement that the company will be doing its own analysis of Clue. “Our initial findings based on the FDA filing indicate a significant difference between Natural Cycles and this other product — including that this product is solely based on menstrual data and no other biomarker such as temperature,” she said.

The idea behind digital birth control is related to fertility awareness methods of birth control, where people track metrics like the dates of their periods, their temperature, and changes to their cervical mucus to predict when they’re ovulating and could become pregnant. These methods can be highly effective when used correctly, but they typically take rigorous, hands-on tracking. They can be good options for people who can’t or don’t want to use hormonal birth control or other methods, but some experts worry that the principles can’t translate into apps.

Only people who are between 18 and 45 years old and who have regular periods should use Clue’s birth control, the company told TechCrunch. If someone is ineligible or their cycle becomes too irregular, the app will lock them out, said CEO Audrey Tsang.

Clue’s period tracker previously had a feature that predicted if users were in a fertile window — the day of and days leading up to ovulation. The app said that the fertile window feature should not be used as birth control but could help users who are trying to become pregnant. The company removed that feature last week, saying that it could be inaccurate. “We determined that it could be misleading to those who wish to use the fertile window to avoid pregnancy,” it said in a blog post. “We hope to offer a solution to this problem in the near future.”

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Entertainment

‘Jeopardy!’ ends in a rare two-way tie, forcing a winner-take-all clue

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CLOSE

“Jeopardy!” stars Ken Jennings, James Holzhauer and Brad Rutter plus Sara Haines talk with USA TODAY’s Erin Jensen about their new game show.

USA TODAY

“Jeopardy!” promised “something crazy” would happen during Friday’s “Final Jeopardy!” And the game show didn’t disappoint. 

Friday’s episode of “Jeopardy!” ended in a rare two-way tie between contestants Jack Weller and Brian Chang, the returning three-day champion.

“In all the years I’ve watched #Jeopardy, I don’t remember ever seeing a tie,” tweeted  user @meghansmith55.

Both contestants went into Final Jeopardy with $18,800. 

“A lot hinges on this final category… a very pivotal ‘Final Jeopardy’ coming up in the category of ‘statues,'” said Ken Jennings, the guest host who took over the helm following Alex Trebek’s November death at 80 of pancreatic cancer.

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The question: “Statues honoring this man who was killed in 1779 can be found in Waimea, Kauai & In Whitby, England.”

Weller and Chang both correctly guessed, “Who is Cook?” And both contestants wagered everything they had, resulting in $37,600 and a tie. 

To determine a champion, both contestants faced off during a winner-take-all, one-question tie breaker round on “History”: “In October 1961, Stalin’s body was removed from display in this other man’s tomb.”

Chang buzzed in with the correct answer of “Lenin” first. 

“Brian Chang, you just won $37,600, and you are our four-time ‘Jeopardy!’ Champion with a total of $88,102,” Jennings said. “What a fantastic game.”

Weller won a $2,000 consolation prize for his second-place finish. 

Viewer @EmersonLotzia referred to the tiebreaker as “one of the most rare and intense spectacles of competition.” A tiebreaker last happened during a regular, non-tournament game on March 1, 2018. 

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