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Viruses are doing mysterious things everywhere – AI can help researchers understand what they’re up to in the oceans and in your gut

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theconversation.com – Libusha , Associate Professor of and Computational Biology, Microbiology and Immunology, Albert Einstein College of Medicine – 2024-05-15 07:16:41

Many viral genetic sequences code for proteins that researchers haven't seen before.

KTSDesign/Science Photo Library via Getty Images

Libusha Kelly, Albert Einstein College of Medicine

Viruses are a mysterious and poorly understood force in microbial ecosystems. Researchers know they can infect, kill and manipulate human and bacterial cells in nearly every environment, from the oceans to your gut. But scientists don't yet have a full picture of how viruses affect their surrounding environments in large part because of their extraordinary diversity and ability to rapidly evolve.

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Communities of microbes are difficult to study in a laboratory setting. Many microbes are challenging to cultivate, and their natural has many more features influencing their or failure than scientists can replicate in a lab.

So systems biologists like me often sequence all the DNA present in a sample – for example, a fecal sample from a patient – separate out the viral DNA sequences, then annotate the sections of the viral genome that code for proteins. These notes on the location, structure and other features of genes researchers understand the functions viruses might carry out in the environment and help identify different kinds of viruses. Researchers annotate viruses by matching viral sequences in a sample to previously annotated sequences available in public databases of viral genetic sequences.

However, scientists are identifying viral sequences in DNA collected from the environment at a rate that far outpaces our ability to annotate those genes. This means researchers are publishing findings about viruses in microbial ecosystems using unacceptably small fractions of available data.

To improve researchers' ability to study viruses around the globe, my team and I have developed a novel approach to annotate viral sequences using artificial intelligence. Through protein language models akin to large language models like ChatGPT but specific to proteins, we were able to classify previously unseen viral sequences. This the door for researchers to not only learn more about viruses, but also to address biological questions that are difficult to answer with current techniques.

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Annotating viruses with AI

Large language models use relationships between words in large datasets of text to provide potential answers to questions they are not explicitly “taught” the answer to. When you ask a chatbot “What is the capital of France?” for example, the model is not looking up the answer in a table of capital . Rather, it is using its training on huge datasets of documents and information to infer the answer: “The capital of France is Paris.”

Similarly, protein language models are AI algorithms that are trained to recognize relationships between billions of protein sequences from environments around the world. Through this training, they may be able to infer something about the essence of viral proteins and their functions.

We wondered whether protein language models could answer this question: “Given all annotated viral genetic sequences, what is this new sequence's function?”

In our proof of concept, we trained neural networks on previously annotated viral protein sequences in pre-trained protein language models and then used them to predict the annotation of new viral protein sequences. Our approach allows us to probe what the model is “seeing” in a particular viral sequence that to a particular annotation. This helps identify candidate proteins of interest either based on their specific functions or how their genome is arranged, winnowing down the search of vast datasets.

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Microscopy image of spherical bacteria colored bright green

Prochlorococcus is one of the many species of marine bacteria with proteins that researchers haven't seen before.

Anne Thompson/Chisholm Lab, MIT via Flickr

By identifying more distantly related viral gene functions, protein language models can complement current methods to provide new insights into microbiology. For example, my team and I were able to use our model to discover a previously unrecognized integrase – a type of protein that can move genetic information in and out of cells – in the globally abundant marine picocyanobacteria Prochlorococcus and Synechococcus. Notably, this integrase may be able to move genes in and out of these populations of bacteria in the oceans and enable these microbes to better adapt to changing environments.

Our language model also identified a novel viral capsid protein that is widespread in the global oceans. We produced the first picture of how its genes are arranged, showing it can contain different sets of genes that we believe indicates this virus serves different functions in its environment.

These preliminary findings represent only two of thousands of annotations our approach has provided.

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Analyzing the unknown

Most of the hundreds of thousands of newly discovered viruses remain unclassified. Many viral genetic sequences match protein families with no known function or have never been seen before. Our work shows that similar protein language models could help study the threat and promise of our planet's many uncharacterized viruses.

While our study focused on viruses in the global oceans, improved annotation of viral proteins is critical for better understanding the role viruses play in and disease in the human body. We and other researchers have hypothesized that viral activity in the human gut microbiome might be altered when you're sick. This means that viruses may help identify stress in microbial communities.

However, our approach is also limited because it requires high-quality annotations. Researchers are developing newer protein language models that incorporate other “tasks” as part of their training, particularly predicting protein structures to detect similar proteins, to make them more powerful.

Making all AI tools available via FAIR Data Principles – data that is findable, accessible, interoperable and reusable – can help researchers at large realize the potential of these new ways of annotating protein sequences leading to discoveries that benefit human health.The Conversation

Libusha Kelly, Associate Professor of Systems and Computational Biology, Microbiology and Immunology, Albert Einstein College of Medicine

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This article is republished from The Conversation under a Creative Commons license. Read the original article.

The Conversation

Even short trips to space can change an astronaut’s biology − a new set of studies offers the most comprehensive look at spaceflight health since NASA’s Twins Study

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theconversation.com – Susan Bailey, Professor of Radiation Cancer Biology and Oncology, Colorado University – 2024-07-03 07:22:56
Crew members from the Inspiration4 mission. New research looks at the biological effects of their short trip to .
SpaceX, CC BY-NC

Susan Bailey, Colorado State University

Only about 600 people have ever traveled to space. The vast majority of astronauts over the past six decades have been middle-aged on short-duration missions of fewer than 20 days.

Today, with private, commercial and multinational spaceflight providers and flyers entering the market, we are witnessing a new era of human spaceflight. Missions have ranged from minutes, hours and days to months.

As humanity looks ahead to returning to the Moon over the coming decade, space exploration missions will be much longer, with many more space travelers and even space tourists. This also means that a wider diversity of people will experience the extreme of space – more women and people of different ethnicities, ages and health status.

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Since people respond differently to the unique stressors and exposures of space, researchers in space health, like me, seek to better understand the human health effects of spaceflight. With such information, we can figure out how to help astronauts stay healthy both while they're in space and once they return to Earth.

As part of the historic NASA Twins Study, in 2019, my colleagues and I published groundbreaking research on how one year on board the International Space Station affects the human body.

I am a radiation cancer biologist in Colorado State University's Department of Environmental and Radiological Health Sciences. I've spent the past few years continuing to build on that earlier research in a series of papers recently published across the portfolio of Nature journals.

These papers are part of the Space Omics and Medical Atlas package of manuscripts, data, protocols and repositories that represent the largest collection ever assembled for aerospace medicine and space biology. Over 100 institutions from 25 countries contributed to the coordinated release of a wide range of spaceflight data.

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The NASA Twins Study

NASA's Twins Study seized on a unique research .

NASA selected astronaut Scott for the agency's first one-year mission, during which he spent a year on board the International Space Station from 2015 into 2016. Over the same time period, his identical twin brother, Mark Kelly, a former astronaut and current U.S. senator representing Arizona, remained on Earth.

Two identical men wearing blue jumpsuits stand next to each other.
NASA astronaut Scott Kelly, left, who went into space during the NASA Twins Study, stands next to his twin brother, Mark Kelly, who stayed on Earth.
AP Photo/Pat Sullivan

My team and I examined blood samples collected from the twin in space and his genetically twin back on Earth before, during and after spaceflight. We found that Scott's telomeres – the protective caps at the ends of chromosomes, much like the plastic tip that keeps a shoelace from fraying – lengthened, quite unexpectedly, during his year in space.

When Scott returned to Earth, however, his telomeres quickly shortened. Over the months, his telomeres recovered but were still shorter after his journey than they had been before he went to space.

As you get older, your telomeres shorten because of a variety of factors, including stress. The length of your telomeres can serve as a biological indicator of your risk for developing age-related conditions such as dementia, cardiovascular disease and cancer.

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In a separate study, my team studied a cohort of 10 astronauts on six-month missions on board the International Space Station. We also had a control group of age- and sex-matched participants who stayed on the ground.

We measured telomere length before, during and after spaceflight and again found that telomeres were longer during spaceflight and then shortened upon return to Earth. Overall, the astronauts had many more short telomeres after spaceflight than they had before.

One of the other Twins Study investigators, Christopher Mason, and I conducted another telomere study – this time with twin high-altitude mountain climbers – a somewhat similar extreme environment on Earth.

We found that while climbing Mount Everest, the climbers' telomeres were longer, and after they descended, their telomeres shortened. Their twins who remained at low altitude didn't experience the same changes in telomere length. These results indicate that it's not the space station's microgravity that led to the telomere length changes we observed in the astronauts – other culprits, such as increased radiation exposure, are more likely.

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Civilians in space

In our latest study, we studied telomeres from the crew on board SpaceX's 2021 Inspiration4 mission. This mission had the first all-civilian crew, whose ages spanned four decades. All of the crew members' telomeres lengthened during the mission, and three of the four astronauts also exhibited telomere shortening once they were back on Earth.

Four people wearing black jumpsuits wave their hands in the air.
The crew members from SpaceX's 2021 Inspiration4 mission.
SpaceX, CC BY-NC

What's particularly interesting about these findings is that the Inspiration4 mission lasted only three days. So, not only do scientists now have consistent and reproducible data on telomeres' response to spaceflight, but we also know it happens quickly. These results suggest that even short trips, like a getaway to space, will be associated with changes in telomere length.

Scientists still don't totally understand the health impacts of such changes in telomere length. We'll need more research to figure out how both long and short telomeres might affect an astronaut's long-term health.

Telomeric RNA

In another paper, we showed that the Inspiration4 crew – as well as Scott Kelly and the high-altitude mountain climbers – exhibited increased levels of telomeric RNA, termed TERRA.

Telomeres consist of lots of repetitive DNA sequences. These are transcribed into TERRA, which contributes to telomere structure and helps them do their job.

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Together with laboratory studies, these findings tell us that telomeres are being damaged during spaceflight. While there is still a lot we don't know, we do know that telomeres are especially sensitive to oxidative stress. So, the chronic oxidative damage that astronauts experience when exposed to space radiation around the clock likely contributes to the telomeric responses we observe.

We also wrote a review article with a more futuristic perspective of how better understanding telomeres and aging might begin to inform the ability of humans to not only survive long-duration space travel but also to thrive and even colonize other planets. Doing so would require humans to reproduce in space and future generations to grow up in space. We don't know if that's even possible – yet.

Plant telomeres in space

My colleagues and I contributed other work to the Space Omics and Medical Atlas package, as well, including a paper published in Nature Communications. The study team, led by A&M biologist Dorothy Shippen and Ohio University biologist Sarah Wyatt, found that, unlike people, plants flown in space did not have longer telomeres during their time on board the International Space Station.

The plants did, however, ramp up their production of telomerase, the enzyme that helps maintain telomere length.

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As anyone who's seen “The Martian” knows, plants will play an essential role in long-term human survival in space. This finding suggests that plants are perhaps more naturally suited to withstand the stressors of space than humans.The Conversation

Susan Bailey, Professor of Radiation Cancer Biology and Oncology, Colorado State University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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From diagnosing brain disorders to cognitive enhancement, 100 years of EEG have transformed neuroscience

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theconversation.com – Erika Nyhus, Associate Professor of Psychology and Neuroscience, Bowdoin College – 2024-07-02 07:28:40
The electroencephalogram scientists to record and read brain activity.
Kateryna Kon/Science Photo Library via Getty Images

Erika Nyhus, Bowdoin College

Electroencephalography, or EEG, was invented 100 years ago. In the years since the invention of this device to monitor brain electricity, it has had an incredible impact on how scientists study the human brain.

Since its first use, the EEG has shaped researchers' understanding of cognition, from perception to memory. It has also been important for diagnosing and guiding treatment of multiple brain disorders, epilepsy.

I am a cognitive neuroscientist who uses EEG to study how people remember from their past. The EEG's 100-year anniversary is an to reflect on this discovery's significance in neuroscience and medicine.

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Discovery of EEG

On July 6, 1924, psychiatrist Hans Berger performed the first EEG recording on a human, a 17-year-old boy undergoing neurosurgery. At the time, Berger and other researchers were performing electrical recordings on the brains of animals.

What set Berger apart was his obsession with finding the physical basis of what he called psychic energy, or mental effort, in people. Through a series of experiments spanning his early career, Berger measured brain volume and temperature to study changes in mental processes such as intellectual work, attention and desire.

He then turned to recording electrical activity. Though he recorded the first traces of EEG in the human brain in 1924, he did not publish the results until 1929. Those five intervening years were a tortuous phase of self-doubt about the source of the EEG signal in the brain and refining the experimental setup. Berger recorded hundreds of EEGs on multiple subjects, including his own , with both experimental successes and setbacks.

This is among the first EEG readings published in Hans Berger's study. The top trace is the EGG while the bottom is a reference trace of 10 Hz.
Two EEG traces, the top more irregular in rhythm than the bottom.
Hans Berger/Über das Elektrenkephalogramm des Menchen. Archives für Psychiatrie. 1929; 87:527-70 via Wikimedia Commons

Finally convinced of his results, he published a series of papers in the journal Archiv für Psychiatrie and had hopes of winning a Nobel Prize. Unfortunately, the research community doubted his results, and years passed before anyone else started using EEG in their own research.

Berger was eventually nominated for a Nobel Prize in 1940. But Nobels were not awarded that year in any category due to World War II and Germany's occupation of Norway.

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Neural oscillations

When many neurons are active at the same time, they produce an electrical signal strong enough to spread instantaneously through the conductive tissue of the brain, skull and scalp. EEG electrodes placed on the head can record these electrical .

Since the discovery of EEG, researchers have shown that neural activity oscillates at specific frequencies. In his initial EEG recordings in 1924, Berger noted the predominance of oscillatory activity that cycled eight to 12 times per second, or 8 to 12 hertz, named alpha oscillations. Since the discovery of alpha rhythms, there have been many attempts to understand how and why neurons oscillate.

Neural oscillations are thought to be important for effective communication between specialized brain regions. For example, theta oscillations that cycle at 4 to 8 hertz are important for communication between brain regions involved in memory encoding and retrieval in animals and humans.

Finger pointing at EEG reading
Different frequencies of neural oscillations indicate different types of brain activity.
undefined undefined/iStock via Getty Images Plus

Researchers then examined whether they could alter neural oscillations and therefore affect how neurons to each other. Studies have shown that many behavioral and noninvasive methods can alter neural oscillations and to changes in cognitive performance. Engaging in specific mental activities can induce neural oscillations in the frequencies those mental activities use. For example, my team's research found that mindfulness meditation can increase theta frequency oscillations and improve memory retrieval.

Noninvasive brain stimulation methods can target frequencies of interest. For example, my team's ongoing research found that brain stimulation at theta frequency can lead to improved memory retrieval.

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EEG has also led to major discoveries about how the brain processes information in many other cognitive domains, including how people perceive the world around them, how they focus their attention, how they communicate through language and how they emotions.

Diagnosing and treating brain disorders

EEG is commonly used today to diagnose sleep disorders and epilepsy and to guide brain disorder treatments.

Scientists are using EEG to see whether memory can be improved with noninvasive brain stimulation. Although the research is still in its infancy, there have been some promising results. For example, one study found that noninvasive brain stimulation at gamma frequency – 25 hertz – improved memory and neurotransmitter transmission in Alzheimer's disease.

Back of person's head enveloped by the many, small round electrodes of an EEG cap
Researchers and clinicians use EEG to diagnose conditions like epilepsy.
BSIP/Collection Mix: Subjects via Getty Images

A new type of noninvasive brain stimulation called temporal interference uses two high frequencies to cause neural activity equal to the difference between the stimulation frequencies. The high frequencies can better penetrate the brain and reach the targeted area. Researchers recently tested this method in people using 2,000 hertz and 2,005 hertz to send 5 hertz theta frequency at a key brain region for memory, the hippocampus. This led to improvements in remembering the name associated with a face.

Although these results are promising, more research is needed to understand the exact role neural oscillations play in cognition and whether altering them can lead to long-lasting cognitive enhancement.

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The future of EEG

The 100-year anniversary of the EEG provides an opportunity to consider what it has taught us about brain function and what this technique can do in the future.

In a survey commissioned by the journal Nature Human Behaviour, over 500 researchers who use EEG in their work were asked to make predictions on the future of the technique. What will be possible in the next 100 years of EEG?

Some researchers, including myself, predict that we'll use EEG to diagnose and create targeted treatments for brain disorders. Others anticipate that an affordable, wearable EEG will be widely used to enhance cognitive function at home or will be seamlessly integrated into virtual reality applications. The possibilities are vast.The Conversation

Erika Nyhus, Associate Professor of Psychology and Neuroscience, Bowdoin College

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Supreme Court kicks cases about tech companies’ First Amendment rights back to lower courts − but appears poised to block states from hampering online content moderation

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theconversation.com – Lynn Greenky, Professor Emeritus of Communication and Rhetorical Studies, Syracuse University – 2024-07-01 15:26:42
How much power do social companies have over what users post?
Midnight Studio/iStock/Getty Images Plus

Lynn Greenky, Syracuse University

The U.S. Supreme Court has sent back to lower courts the about whether states can block social media companies such as Facebook and X, formerly Twitter, from regulating and controlling what users can post on their platforms.

Laws in Florida and Texas sought to impose restrictions on the internal policies and algorithms of social media platforms in ways that influence which posts will be promoted and spread widely and which will be made less visible or even removed.

In the unanimous decision, issued on July 1, 2024, the high court remanded the two cases, Moody v. NetChoice and NetChoice v. Paxton, to the 11th and 5th U.S. Circuit Courts of Appeals, respectively. The court admonished the lower courts for their failure to consider the full force of the laws' applications. It also warned the lower courts to consider the boundaries imposed by the Constitution against government interference with private speech.

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Contrasting views of social media sites

In their arguments before the court in February 2024, the two sides described competing visions of how social media fits into the often overwhelming flood of information that defines modern digital society.

The states said the platforms were mere conduits of communication, or “speech hosts,” similar to legacy telephone companies that were required to carry all calls and prohibited from discriminating against users. The states said that the platforms should have to carry all posts from users without discrimination among them based on what they were saying.

The states argued that the content moderation rules the social media companies imposed were not examples of the platforms themselves speaking – or choosing not to speak. Rather, the states said, the rules affected the platforms' behavior and caused them to censor certain views by allowing them to determine whom to allow to speak on which topics, which is outside First Amendment protections.

By contrast, the social media platforms, represented by NetChoice, a tech industry trade group, argued that the platforms' guidelines about what is acceptable on their sites are protected by the First Amendment's guarantee of speech free from government interference. The companies say their platforms are not public forums that may be subject to government regulation but rather private services that can exercise their own editorial judgment about what does or does not appear on their sites.

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They argued that their policies were aspects of their own speech and that they should be to develop and implement guidelines about what is acceptable speech on their platforms based on their own First Amendment rights.

Here's what the First Amendment says and what it means.

A reframe by the Supreme Court

All the litigants – NetChoice, and Florida – framed the issue around the effect of the laws on the content moderation policies of the platforms, specifically whether the platforms were engaged in protected speech. The 11th U.S. Circuit Court of Appeals upheld a lower court preliminary injunction against the Florida , holding the content moderation policies of the platforms were speech and the law was unconstitutional.

The 5th U.S. Circuit Court of Appeals came to the opposite conclusion and held that the platforms were not engaged in speech, but rather the platform's algorithms controlled platform behavior unprotected by the First Amendment. The 5th Circuit determined the behavior was censorship and reversed a lower court injunction against the Texas law.

The Supreme Court, however, reframed the inquiry. The court noted that the lower courts failed to consider the full range of activities the laws covered. Thus, while a First Amendment inquiry was in order, the decisions of the lower courts and the arguments by the parties were incomplete. The court added that neither the parties nor the lower courts engaged in a thorough analysis of whether and how the states' laws affected other elements of the platforms' products, such as Facebook's direct messaging applications, or even whether the laws have any impact on email providers or online marketplaces.

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The Supreme Court directed the lower courts to engage in a much more exacting analysis of the laws and their implications and provided some guidelines.

First Amendment principles

The court held that content moderation policies reflect the constitutionally protected editorial choices of the platforms, at least regarding what the court as “heartland applications” of the laws – such as Facebook's News Feed and YouTube's homepage.

The Supreme Court required the lower courts to consider two core constitutional principles of the First Amendment. One is that the amendment protects speakers from being compelled to communicate messages they would prefer to exclude. Editorial discretion by entities, including social media companies, that compile and curate the speech of others is a protected First Amendment activity.

The other principle that the amendment precludes the government from controlling private speech, even for the purpose of balancing the marketplace of ideas. Neither nor federal government may manipulate that marketplace for the purposes of presenting a more balanced array of viewpoints.

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The court also affirmed that these principles apply to digital media in the same way they apply to traditional or legacy media.

In the 96-page opinion, Justice Elena Kagan wrote: “The First Amendment … does not go on when social media are involved.” For now, it appears the social media platforms will continue to control their content.The Conversation

Lynn Greenky, Professor Emeritus of Communication and Rhetorical Studies, Syracuse University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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