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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 environment 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 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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The Conversation

Nuclear rockets could travel to Mars in half the time − but designing the reactors that would power them isn’t easy

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theconversation.com – Dan Kotlyar, Associate Professor of Nuclear and Radiological Engineering, Georgia Institute of Technology – 2024-10-04 07:23:18

Nuclear-powered rockets could one day enable faster travel.
NASA

Dan Kotlyar, Georgia Institute of Technology

NASA plans to send crewed missions to Mars over the next decade – but the 140 million-mile (225 million-kilometer) journey to the red planet could take several months to years round trip.

This relatively long transit time is a result of the use of traditional chemical rocket fuel. An alternative technology to the chemically propelled rockets the agency develops now is called nuclear thermal propulsion, which uses nuclear fission and could one day power a rocket that makes the in just half the time.

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Nuclear fission involves harvesting the incredible amount of energy released when an atom is split by a neutron. This reaction is known as a fission reaction. Fission technology is well established in power generation and nuclear-powered submarines, and its application to or power a rocket could one day give NASA a faster, more powerful alternative to chemically driven rockets.

NASA and the Defense Advanced Research Projects Agency are jointly developing NTP technology. They plan to deploy and demonstrate the capabilities of a prototype system in space in 2027 – potentially making it one of the first of its kind to be built and operated by the U.S.

Nuclear thermal propulsion could also one day power maneuverable space platforms that would protect American satellites in and beyond Earth’s orbit. But the technology is still in .

I am an associate professor of nuclear engineering at the Georgia Institute of Technology whose research group builds models and simulations to improve and optimize designs for nuclear thermal propulsion . My hope and passion is to assist in designing the nuclear thermal propulsion engine that will take a crewed mission to Mars.

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Nuclear versus chemical propulsion

Conventional chemical propulsion systems use a chemical reaction involving a light propellant, such as hydrogen, and an oxidizer. When mixed together, these two ignite, which results in propellant exiting the nozzle very quickly to propel the rocket.

A diagram showing a nuclear thermal propulsion system, with a chamber for hydrogen connected to several pumps, a reactor chamber and a nozzle that the propellant is ejected from.
Scientists and engineers are working on nuclear thermal propulsion systems that would take hydrogen propellant, pump it into a nuclear reactor to generate energy and expel propellant out the nozzle to lift the rocket.
NASA Glenn Research Center

These systems do not require any sort of ignition system, so they’re reliable. But these rockets must carry oxygen with them into space, which can weigh them down. Unlike chemical propulsion systems, nuclear thermal propulsion systems rely on nuclear fission reactions to heat the propellant that is then expelled from the nozzle to create the driving force or thrust.

In many fission reactions, researchers send a neutron toward a lighter isotope of uranium, uranium-235. The uranium absorbs the neutron, creating uranium-236. The uranium-236 then splits into two fragments – the fission products – and the reaction emits some assorted particles.

Fission reactions create lots of heat energy.

More than 400 nuclear power reactors in operation around the world currently use nuclear fission technology. The majority of these nuclear power reactors in operation are light water reactors. These fission reactors use to slow down the neutrons and to absorb and transfer heat. The water can create steam directly in the core or in a steam generator, which drives a turbine to produce electricity.

Nuclear thermal propulsion systems operate in a similar way, but they use a different nuclear fuel that has more uranium-235. They also operate at a much higher temperature, which makes them extremely powerful and compact. Nuclear thermal propulsion systems have about 10 times more power density than a traditional light water reactor.

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Nuclear propulsion could have a leg up on chemical propulsion for a few reasons.

Nuclear propulsion would expel propellant from the engine’s nozzle very quickly, generating high thrust. This high thrust allows the rocket to accelerate faster.

These systems also have a high specific impulse. Specific impulse measures how efficiently the propellant is used to generate thrust. Nuclear thermal propulsion systems have roughly twice the specific impulse of chemical rockets, which means they could cut the travel time by a factor of 2.

Nuclear thermal propulsion history

For decades, the U.S. has funded the development of nuclear thermal propulsion technology. Between 1955 and 1973, programs at NASA, General Electric and Argonne National Laboratories produced and ground-tested 20 nuclear thermal propulsion engines.

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But these pre-1973 designs relied on highly enriched uranium fuel. This fuel is no longer used because of its proliferation dangers, or dangers that have to do with the spread of nuclear material and technology.

The Global Threat Reduction Initiative, launched by the Department of Energy and National Nuclear Security Administration, aims to convert many of the research reactors employing highly enriched uranium fuel to high-assay, low-enriched uranium, or HALEU, fuel.

High-assay, low- enriched uranium fuel has less material capable of undergoing a fission reaction, with highly enriched uranium fuel. So, the rockets needs to have more HALEU fuel loaded on, which makes the engine heavier. To solve this issue, researchers are looking into special materials that would use fuel more efficiently in these reactors.

NASA and the DARPA’s Demonstration Rocket for Agile Cislunar Operations, or DRACO, program intends to use this high-assay, low-enriched uranium fuel in its nuclear thermal propulsion engine. The program plans to launch its rocket in 2027.

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As part of the DRACO program, the aerospace company Lockheed Martin has partnered with BWX Technologies to develop the reactor and fuel designs.

The nuclear thermal propulsion engines in development by these groups will need to comply with specific performance and safety standards. They’ll need to have a core that can operate for the duration of the mission and perform the necessary maneuvers for a fast trip to Mars.

Ideally, the engine should be able to produce high specific impulse, while also satisfying the high thrust and low engine mass requirements.

Ongoing research

Before engineers can design an engine that satisfies all these standards, they need to start with models and simulations. These models researchers, such as those in my group, understand how the engine would handle starting up and shutting down. These are operations that require quick, massive temperature and pressure changes.

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The nuclear thermal propulsion engine will differ from all existing fission power systems, so engineers will need to build software tools that work with this new engine.

My group designs and analyzes nuclear thermal propulsion reactors using models. We model these complex reactor systems to see how things such as temperature changes may affect the reactor and the rocket’s safety. But simulating these effects can take a lot of expensive computing power.

We’ve been working to develop new computational tools that model how these reactors act while they’re starting up and operated without using as much computing power.

My colleagues and I hope this research can one day help develop models that could autonomously control the rocket.The Conversation

Dan Kotlyar, Associate Professor of Nuclear and Radiological Engineering, Georgia Institute of Technology

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Trees’ own beneficial microbiome could lead to discovery of new treatments to fight citrus greening disease

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theconversation.com – Kateel G. Shetty, Assistant Professor of Earth and , Florida International – 2024-10-04 07:23:03

Citrus is still big business in Florida, but the industry has taken a massive hit in recent decades.
Joe Raedle/via Getty Images

Kateel G. Shetty, Florida International University; Jessica Dominguez, Florida International University, and Krishnaswamy Jayachandran, Florida International University

Citrus trees showing natural tolerance to citrus greening disease host bacteria that produce novel antimicrobials that can be used to fight off the disease, our recent study shows. We found the trees at an organic farm in Clermont, Florida.

Citrus greening disease – known more formally as Huanglongbing, or HLB, is caused by the bacterium Candidatus Liberibacter asiaticus. It is spread by an insect called the Asian citrus psyllid. There is no known cure for the disease.

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We are Florida-based researchers who study sustainable farming practices, a discipline also known as agroecology. Our team has isolated these antimicrobial compounds in the lab and is now working to test them with the goal of producing an effective treatment for HLB.

Why it matters

HLB has dealt a massive blow to Florida’s iconic citrus industry.

Since citrus greening disease was first detected in the state in 2005, Florida citrus production is down by more than 92%. The disease is just one factor. Others include hurricanes and freezes.

Infected trees produce fewer fruit. The fruit that does grow is partially green, smaller, shaped irregularly and bitter tasting. It may drop from the trees before ripening. Leaves may show blotchy mottling.

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According to the U.S. Department of Agriculture, the 2022-2023 growing season was the least productive since 1936. Smaller crops to higher prices on oranges, tangerines, grapefruits, lemons and limes.

A few pale lemons growing in spotted foliage
Pomelo tree leaves with symptoms of citrus greening.
Conor Wolfe, CC BY-ND

Management of HLB is daunting. Growers currently rely on pesticides to control the psyllid and antibiotics like oxytetracycline in an attempt to control HLB. These treatments are expensive and may pose health and environmental risks. The need for of effective treatments to control HLB is evident.

How we did our work

Like humans, plants host diverse communities of microorganisms both inside and outside, representing the plant microbiome.

Endophytes – beneficial microorganisms living inside plants – play an important role in nutrient intake, disease and pest resistance, and adaptation to environmental stress.

In a search for treatments against HLB, we looked to endophytes of survivor citrus trees – in other words, trees that are HLB positive but showed only mild symptoms and continue to bear fruit. By studying 342 endophytes of survivor trees, we discovered five bacterial endophytes capable of producing novel antimicrobials.

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The HLB bacteria cannot be grown on laboratory culture media like agar or broth. So, we used bacterial cells present in the ground tissue samples of infected psyllids to test the antimicrobial compounds in the lab. These studies revealed that the antimicrobial compounds were highly effective at killing the live cells of citrus greening pathogen in this controlled environment. The antimicrobials can be mixed with and were found to be effective at low concentrations.

What’s still not known

Preliminary results from our ongoing work indicate that multiple antimicrobial compounds are present in the bacterial culture extract. This is a positive sign because the antimicrobial compounds may be found to attack pathogenic bacteria in several different ways. If that’s the case, it will minimize the development of resistance in the same way a variety of antibiotics are useful to human .

One of our next steps will be to evaluate selected compounds against HLB, using infected citrus roots under laboratory conditions and infected citrus plants under greenhouse conditions, to test whether the plants will absorb these antimicrobial compounds through their leaves or roots. This work will be conducted in collaboration with scientists from A&M University and the University of Florida.

What’s next

Further research will focus on methods to increase the production of purified antimicrobial compound in order for it to be evaluated in the field. To help get the technology to growers faster, we may look for partnerships with interested commercial biopesticide companies to help with product development.

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Our work has taken on new urgency due to emerging psyllid-transmitted diseases that infect potato, tomato and carrot crops in the U.S. that are caused by closely related bacterial pathogens.

The Research Brief is a short take on interesting academic work.The Conversation

Kateel G. Shetty, Assistant Professor of Earth and Environment, Florida International University; Jessica Dominguez, PhD Candidate in Agroecology, Florida International University, and Krishnaswamy Jayachandran, Professor of Agroecology, Florida International University

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Up against Hank Greenberg, baseball’s first Jewish superstar, antisemitism struck out

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theconversation.com – Robert Gudmestad, Professor and Chair of History Department, Colorado University – 2024-10-03 11:23:23

Hank Greenberg hit 331 home runs with a batting average of .313 during his career.

Sporting News via Getty Images

Robert Gudmestad, Colorado State University

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Hank Greenberg might be the best baseball player you’ve never heard of.

Greenberg was the first baseman for the Detroit Tigers during the 1930s and 1940s. His career was relatively short – 13 years – and interrupted by two stints of service in World War II.

Yet outside the war years, there were glorious seasons.

Greenberg led the American League in home runs four times, played in five All-Star , twice won the American League’s Most Valuable Player Award and, in 1938, nearly broke what was then the game’s most hallowed record: Babe Ruth’s 60 home runs in one season. In 1956, Greenberg was elected to the Baseball Hall of Fame.

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Greenberg was also Jewish, and he is often called America’s first Jewish sports superstar. As Greenberg wrote in his autobiography, that was not an easy honor to bear. Greenberg played during a time of rising antisemitism, and the cruel taunts he suffered from players and fans lasted throughout his career. Vile remarks and bigoted slurs – “kike,” “sheenie” and “Jew bastard” were typical – left a mark on him and the sport he loved.

Along the way, Greenberg also faced a crisis of conscience: his struggle on whether to play during Rosh Hashanah and Yom Kippur, the Jewish High Holidays. He resolved the conflict with a Solomon-like choice, more than 30 years before baseball legend Sandy Koufax pondered the same dilemma during the 1965 World Series.

Today, nearly 80 years after Greenberg retired from baseball, antisemitism is once again on the rise both in the U.S. and worldwide. As a historian of American sport, I suggest there are lessons to be learned on how Greenberg handled the hate.

Wearing a Detroit Tigers uniform, Hank Greenberg poses for a photo holding his baseball bat.

Hank Greenberg was the first major league player to sign up for military service in World War II. He was in for nearly four years.

Bettmann via Getty Images

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Horns like the devil

Greenberg signed a contract with the Tigers in 1930 and played in the minor leagues for the next three years. For many of his teammates, he was the first Jewish person they’d ever met. One told Greenberg, quite seriously, that he thought Jewish people had horns, like the devil.

Once brought up to the major leagues, Greenberg was generally accepted by his teammates. The same could not be said of opposing players and fans, who hounded him throughout his career. The fans insulting Greenberg were in the distinct minority, but they were loud, nonstop and got virtually no resistance from other fans or the .

Greenberg’s response to the abuse: ignore it. But he reacted at least once, during a game against the Chicago White Sox. One Chicago player tried to injure Greenberg – his autobiography does not how – and another called him a “yellow Jew son of a bitch.” After the game, Greenberg visited the opposing team’s locker room and demanded to know who the name caller was. At 6 feet, 3 inches tall and 200-plus pounds, Greenberg was intimidating. The room fell silent. The White Sox players never antagonized him again.

Other pressures bore down on Greenberg. Detroit was a hotbed of antisemitism in the 1930s. The Dearborn Independent, a newspaper owned by the industrialist Henry Ford, described Jews as “the world’s foremost problem,” an echo of Ford’s antisemitic beliefs. The city was also home to Father Charles Coughlin, a Catholic priest who reviled Jews and spread antisemitic rhetoric during his radio show – which at its height was heard by perhaps 40 million people. Overseas, Adolf Hitler was the fuhrer of Germany, and his persecution of Jews became even more apparent after Kristallnacht, in November 1938, when the Nazi regime went on an antisemitic rampage.

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“I came to feel,” Greenberg wrote later, “that if I, as a Jew, hit a home , I was hitting one against Hitler.”

Hank Greenberg posing for a photo with dozens of youngsters.

Although many fans admired Hank Greenberg, particularly youngsters, others relentlessly shouted antisemitic remarks from the stands.

Bettmann via Getty Images

Playing on Jewish holidays

In 1934, when he was 23, Greenberg decided he would not play on the Jewish New Year, Rosh Hashanah, a when observant Jews were supposed to pray and not work. But the Tigers were in a close race for the American League pennant. The team needed Greenberg, their star player.

A local newspaper reporter interviewed a Detroit rabbi and asked if it was acceptable for Greenberg to play. The rabbi said it was OK. Deciding at the last minute, Greenberg played and hit two home runs. Detroit won the game, 2-1. The Detroit Free Press ran a headline in Yiddish, with an English translation: “Happy New Year, Hank.”

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Ten days later came Yom Kippur, the most sacred of all Jewish holidays. Also known as the Day of Atonement, observant Jews are to spend the day in prayer and self-reflection; baseball was not on the agenda. This time, Greenberg did not play, and attended services instead. When he entered the synagogue, the congregation applauded.

The Tigers lost 5-2 to the New York Yankees that day. But Detroit won the pennant anyway.

“I used to resent being singled out as a Jewish ballplayer, period,” Greenberg said in his autobiography. “I’m not sure why or when it changed, because I’m still not a particularly religious person. Lately, though, I find myself wanting to be remembered not only as a great ballplayer, but even more as a great Jewish ballplayer.”

Meeting Robinson

1947 was Jackie Robinson’s rookie year and Greenberg’s last. Robinson, the first baseman for the Brooklyn Dodgers, had broken the color line and was baseball’s first Black player of the modern era; he was enduring enormous abuse, something Greenberg, now with the Pittsburgh Pirates, clearly understood. They played against each other for the first time at Forbes Field in Pittsburgh in May.

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A baseball player at home plate, being congratulated by teammates.

Hank Greenberg is congratulated by teammates after a grand slam.

Bruce Bennett via Getty Images

In the fourth inning, Greenberg got to first on a walk, and according to newspaper accounts, he had a few words for Robinson: “I know it’s plenty tough,” he said. “You’re a good ballplayer, and you’ll do all right.”

Greenberg also publicly supported Robinson, one of the few opposing players to do so.

Nearly a half-century later, Supreme Court justices Ruth Bader Ginsburg and Stephen Breyer were considering whether the Supreme Court should meet on Yom Kippur. They too found inspiration from Greenberg; Ginsburg noted that Greenberg did not “betray his conscience.” The Supreme Court did not meet on Yom Kippur that year, and it hasn’t since.

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Although there has been tremendous progress, racial and ethnic slurs persist in American . In 2024, some fans directed racially abusive comments at two Black players on the U.S. men’s national soccer team. In English football – known as soccer in the U.S. – Muslim players reported widespread discrimination and abuse. Things have changed, but not enough.

Although not a devout Jew, Greenberg understood that to endure the abuse, he had to embrace his identity. Those athletes of today, recently stung by the vitriol of bigots and trolls, may wish to take heed of the lessons learned by this reticent from the previous century, a man whose quiet dignity spoke volumes.The Conversation

Robert Gudmestad, Professor and Chair of History Department, Colorado State University

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