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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 Kelly, Associate Professor of Systems 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.

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 success 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 help 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 opens 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.

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 cities. 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 leads 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 space of vast datasets.

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.

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 health 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

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

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As the Taurid meteor shower passes by Earth, pseudoscience rains down – and obscures a potential real threat from space

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theconversation.com – Mark Boslough, Research Associate Professor of Earth and Planetary Sciences, University of New Mexico – 2024-11-15 07:31:00

This image of a Taurid fireball was taken in 2014 by NASA’s All Sky Fireball Network in Tullahoma, Tenn.

NASA

Mark Boslough, University of New Mexico

With the Taurid meteor shower now hitting the night skies worldwide, look for what could be a celestial treat – you might see shooting stars, and maybe even fireballs, the biggest and brightest meteors.

As the full moon begins to wane after Nov. 15, the sky will be darker, due to diminishing moonlight, so finding the meteors will get easier. That said, the best visibility for the meteors through the rest of the month will come just before moonrise each night.

Beyond the light show, there is something else that scientists as well as onlookers have long wondered about: the possibility that bigger chunks are in the Taurid meteor streams, chunks the size of boulders, buildings or even mountains.

And if that’s true, could one of those monster-sized Taurid objects collide with Earth? Could they wipe out a city, or worse? Is it possible that’s already happened, sometime in our planet’s past?

This animation simulates the motion of the hypothetical Taurid meteor swarm through space.

As a physicist who researches the risk that comets and asteroids pose to the Earth, I’m aware that this is a subject where pseudoscience often competes with actual science. So let’s try to find the line between fact and fiction.

Pig Pen, glowing tails and shooting stars

Comet Encke is the so-called parent comet of the Taurid meteors. It’s relatively small, just over 3 miles (almost 5 kilometers) in diameter, and crosses inside Earth’s orbit and back out every 3.3 years.

As Encke moves, it sheds dust wherever it goes, like the Peanuts character Pig Pen. A meteor shower occurs when that dust and debris light up while entering Earth’s atmosphere at high speeds. Ultimately, they vanish into an incandescent puff of vapor with a glowing tail, creating the illusion of a “shooting star.”

But dust isn’t all that breaks off the comet. So do bigger chunks, the size of pebbles and stones. When they collide with the air, they create the much brighter fireballs, which sometimes explode.

Against a black and white starscape, a bright spot appears in the center of the photo.

An image of comet Encke, taken by NASA’s MESSENGER spacecraft in November 2013.

NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington/Southwest Research Institute

Doomsday showers

The “coherent catastrophism” hypothesis suggests that comet Encke was created when an even larger comet broke up into pieces; Encke survived as the largest piece. The hypothesis also suggests that other mountain-sized chunks broke off and coalesced into a large swarm of fragments too. If such a swarm exists, there is a possibility that those large chunks could one day hit Earth as it passes through the swarm.

But just because something might be physically possible doesn’t mean that it exists. Mainstream astronomers have rejected this theory’s most catastrophic predictions. Among other reasons, scientists have never observed high concentrations of these mountain-sized objects.

Despite the lack of evidence, researchers on the fringes of science have embraced the idea. They claim the Earth experienced a global catastrophic swarm 12,900 years ago; the impact, they say, caused continent-wide firestorms, floods and abrupt climate change that led to the mass extinction of large mammals, such as woolly mammoths, and the disappearance of early Americans known as the Clovis people.

The evidence for a catastrophic cause of these events, most of which did not happen, is lacking. Nevertheless, the idea has gained a large following and formed the basis for British author Graham Hancock’s popular TV series, “Ancient Apocalypse.”

A black and white photo of a forest of flattened trees.

This photo shows the flattened trees resulting from the Tunguska event.

Universal History Archives/Universal Images Group via Getty Images

The Tunguska event

But even outlandish ideas can have elements of truth, and there are hints that some objects – more than just dust and debris, but less than doomsday size – indeed exist in the Taurid meteor stream, and that the Earth has already encountered them.

One clue comes from an event on June 30, 1908, when an enormous explosion in the sky blew down millions of trees in Siberia. This was the Tunguska event – an airburst from an object that may have been up to 160 feet (about 50 meters) in diameter.

The collision unleashed several megatons of energy, which is roughly the equivalent of a large thermonuclear bomb. What happens is this: The incoming object penetrates deep into Earth’s atmosphere, and the dense air slows it down and heats it up until it vaporizes and explodes.

Could this object have been a Taurid? After all, the Taurids cross Earth’s orbit twice a year – not just in autumn, but also in June.

A fireball appears in the night sky.

In a 2015 photo, a glowing Taurid fireball descends over Lake Simcoe in Ontario, Canada.

Orchidpost/iStock via Getty Images Plus

Here’s the evidence: First, the descriptions of the trajectory of the Tunguska airburst, as reported by eyewitness observers, is consistent with that of an object coming from the Taurid stream.

What’s more, the pattern of blast damage on the ground beneath an airburst depends on the trajectory of the exploding object. Supercomputer simulations show that the shape of the surface blast that would be caused by an exploding Taurid object matches the pattern of fallen trees at Tunguska.

Finally, during the Taurid meteor shower in 1975, people observed large fireballs – and seismometers, previously placed on the Moon by Apollo astronauts, detected seismic events on the lunar surface. Scientists interpreted those events as impacts, presumably made by the Taurid meteors.

In 2032 and 2036, the Taurid swarm – assuming it exists – is predicted to be closer to the Earth than any time since 1975. That might mean the Moon, and perhaps the Earth, could be pelted again in those years.

There is time to figure this out. Scientists can expand their astronomical surveys to look for Tunguska-sized objects at the locations where they are predicted to be the next time they are in our vicinity.

Most scientists remain skeptical that such a swarm exists, but it’s the job of planetary defenders to investigate possible threats, even if the risk is small. After all, a Tunguska-sized object could conceivably demolish a major city and kill millions; an accurate count of objects on a potential collision course is essential.

Put doomsday scenarios and ancient apocalypses aside. The real question, and still an open one, is whether a Taurid swarm could deliver more Tunguska-sized objects than would otherwise be expected. This would mean we have underestimated the risk from future airbursts.The Conversation

Mark Boslough, Research Associate Professor of Earth and Planetary Sciences, University of New Mexico

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Knee problems tend to flare up as you age – an orthopedic specialist explains available treatment options

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theconversation.com – Angie Brown, Clinical Associate Professor of Physical Therapy, Quinnipiac University – 2024-11-15 07:32:00

Knee problems can hinder mobility and erode your quality of life.

Witthaya Prasongsin/Moment via Getty Images

Angie Brown, Quinnipiac University

Knee injuries are common in athletes, accounting for 41% of all athletic injuries. But knee injuries aren’t limited to competitive athletes. In our everyday lives, an accident or a quick movement in the wrong direction can injure the knee and require medical treatment. A quarter of the adult population worldwide experiences knee pain each year

As a physical therapist and board-certified orthopedic specialist, I help patients of all ages with knee injuries and degenerative conditions.

Your knees have a huge impact on your mobility and overall quality of life, so it’s important to prevent knee problems whenever possible and address pain in these joints with appropriate treatments.

Healthy knees

The knee joint bones consist of the femur, tibia and patella. As in all healthy joints, smooth cartilage covers the surfaces of the bones, forming the joints and allowing for controlled movement.

diagram of a healthy knee

A healthy knee.

Inna Kharlamova/iStock/Getty Images Plus via Getty Images

Muscles, ligaments and tendons further support the knee joint. The anterior cruciate ligament, commonly known as the ACL, and posterior cruciate ligament, or PCL, provide internal stability to the knee. In addition, two tough pieces of fibrocartilage, called menisci, lie inside the joint, providing further stability and shock absorption.

All these structures work together to enable the knee to move smoothly and painlessly throughout everyday movement, whether bending to pick up the family cat or going for a run.

Causes of knee pain

Two major causes of knee pain are acute injury and osteoarthritis.

Ligaments such as the ACL and PCL can be stressed and torn when a shear force occurs between the femur and tibia. ACL injuries often occur when athletes land awkwardly on the knee or quickly pivot on a planted foot. Depending on the severity of the injury, these patients may undergo physical therapy, or they may require surgery for repair or replacement.

PCL injuries are less common. They occur when the tibia experiences a posterior or backward force. This type of injury is common in car accidents when the knee hits the dashboard, or when patients fall forward when walking up stairs.

The menisci can also experience degeneration and tearing from shear and rotary forces, especially during weight-bearing activities. These types of injuries often require rehabilitation through physical therapy or surgery.

Knee pain can also result from injury or overuse of the muscles and tendons surrounding the knee, including the quadriceps, hamstrings and patella tendon.

Both injuries to and overuse of the knee can lead to degenerative changes in the joint surfaces, known as osteoarthritis. Osteoarthritis is a progressive disease that can lead to pain, swelling and stiffness. This disease affects the knees of over 300 million people worldwide, most often those 50 years of age and up. American adults have a 40% chance of developing osteoarthritis that affects their daily lives, with the knee being the most commonly affected joint.

Age is also a factor in knee pain. The structure and function of your joints change as you age. Cartilage starts to break down, your body produces less synovial fluid to lubricate your joints, and muscle strength and flexibility decrease. This can lead to painful, restricted movement in the joint.

Risk factors

There are some risk factors for knee osteoarthritis that you cannot control, such as genetics, age, sex and your history of prior injuries.

Fortunately, there are several risk factors you can control that can predispose you to knee pain and osteoarthritis specifically. The first is excessive weight. Based on studies between 2017 and 2020, nearly 42% of all adult Americans are obese. This obesity is a significant risk factor for diabetes and osteoarthritis and can also play a role in other knee injuries.

A lack of physical activity is another risk, with 1 in 5 U.S. adults reporting that they’re inactive outside of work duties. This can result in less muscular support for the knee and more pressure on the joint itself.

An inflammatory diet also adds to the risk of knee pain from osteoarthritis. Research shows that the average American diet, often high in sugar and fat and low in fiber, can lead to changes to the gut microbiome that contribute to osteoarthritis pain and inflammation.

Preventing knee pain

Increasing physical activity is one of the key elements to preventing knee pain. Often physical therapy intervention for patients with knee osteoarthritis focuses on strengthening the knee to decrease pain and support the joint during movement.

The U.S. Department of Health and Human Services recommends that adults spend at least 150 to 300 minutes per week on moderate-intensity, or 75 to 150 minutes per week on vigorous-intensity aerobic physical activity. These guidelines do not change for adults who already have osteoarthritis, although their exercise may require less weight-bearing activities, such as swimming, biking or walking.

The agency also recommends that all adults do some form of resistance training at least two or more days a week. Adults with knee osteoarthritis particularly benefit from quadriceps-strengthening exercises, such as straight leg raises.

Treatments for knee pain

Conservative treatment of knee pain includes anti-inflammatory and pain medications and physical therapy.

Medical treatment for knee osteoarthritis may include cortisone injections to decrease inflammation or hyaluronic acid injections, which help lubricate the joint. The relief from these interventions is often temporary, as they do not stop the progression of the disease. But they can delay the need for surgery by one to three years on average, depending on the number of injections.

Physical therapy is generally a longer-lasting treatment option for knee pain. Physical therapy treatment leads to more sustained pain reduction and functional improvements when compared with cortisone injections treatment and some meniscal repairs.

Patients with osteoarthritis often benefit from total knee replacement, a surgery with a high success rate and lasting results.

Surgical interventions for knee pain include the repair, replacement or removal of the ACL, PCL, menisci or cartilage. When more conservative approaches fail, patients with osteoarthritis may benefit from a partial or total knee replacement to allow more pain-free movement. In these procedures, one or both sides of the knee joint are replaced by either plastic or metal components. Afterward, patients attend physical therapy to aid in the return of range of motion.

Although there are risks with any surgery, most patients who undergo knee replacement benefit from decreased pain and increased function, with 90% of all replacements lasting more than 15 years. But not all patients are candidates for such surgeries, as a successful outcome depends on the patient’s overall health and well-being.

New treatments on the horizon

New developments for knee osteoarthritis are focused on less invasive therapies. Recently, the U.S. Food and Drug Administration approved a new implant that acts as a shock absorber. This requires a much simpler procedure than a total knee replacement.

Other promising interventions include knee embolization, a procedure in which tiny particles are injected into the arteries near the knee to decrease blood flow to the area and reduce inflammation near the joint. Researchers are also looking into injectable solutions derived from human bodies, such as plasma-rich protein and fat cells, to decrease inflammation and pain from osteoarthritis. Human stem cells and their growth factors also show potential in treating knee osteoarthritis by potentially improving muscle atrophy and repairing cartilage.

Further research is needed on these novel interventions. However, any intervention that holds promise to stop or delay osteoarthritis is certainly encouraging for the millions of people afflicted with this disease.The Conversation

Angie Brown, Clinical Associate Professor of Physical Therapy, Quinnipiac University

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Get chronic UTIs? Future treatments may add more bacteria to your bladder to beat back harmful microbes

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theconversation.com – Sarguru Subash, Assistant Professor of Veterinary Pathobiology, Texas A&M University – 2024-11-15 07:31:00

Certain strains of E. coli can outcompete disease-causing microbes for resources.

NIAID/Flickr, CC BY-SA

Sarguru Subash, Texas A&M University

Millions of people in the U.S. and around the world suffer from urinary tract infections every year. Some groups are especially prone to chronic UTIs, including women, older adults and some veterans.

These infections are typically treated with antibiotics, but overusing these drugs can make the microbes they target become resistant and reduce the medicines’ effectiveness.

To solve this problem of chronic UTIs and antibiotic resistance, we combined our expertise in microbiology and engineering to create a living material that houses a specific strain of beneficial E. coli. Our research shows that the “good” bacteria released from this biomaterial can compete with “bad” bacteria for nutrients and win, dramatically reducing the number of disease-causing microbes.

With further development, we believe this technique could help manage recurring UTIs that do not respond to antibiotics.

Bringing bacteria to the bladder

For the microbes living in people, nutrients are limited their presence varies between different parts of the body. Bacteria have to compete with other microbes and the host to acquire essential nutrients. By taking up available nutrients, beneficial bacteria can stop or slow the growth of harmful bacteria. When harmful bacteria are starved of important nutrients, they aren’t able to reach high enough numbers to cause disease.

Delivering beneficial bacteria to the bladder to prevent UTIs in challenging, though. For one, these helpful bacteria can naturally colonize only in people who are unable to fully empty their bladder, a condition called urinary retention. Even among these patients, how long these bacteria can colonize their bladders varies widely.

Current methods to deliver bacteria to the bladder are invasive and require repeated catheter insertion. Even when bacteria are successfully released into the bladder, urine will flush out these microbes because they cannot stick to the bladder wall.

Micrograph of clusters of pink rods scattered across a blue textured wall, while yellow blobs extend thin tendrils across the clumps

This microscopy image shows the bladder of a mouse (blue) covered with E. coli (pink) and the white blood cells (yellow) attacking them.

Valerie O’Brien, Matthew Joens, Scott J. Hultgren, James A.J. Fitzpatrick, Washington University, St. Louis/NIH via Flickr, CC BY-NC

Biomaterials to treat UTIs

Since beneficial bacteria cannot attach to and survive in the bladder for long, we developed a biomaterial that could slowly release bacteria in the bladder over time.

Our biomaterial is composed of living E. coli embedded in a matrix structure made of gel. It resembles a piece of jelly about 500 times smaller than a drop of water and can release bacteria for up to two weeks in the bladder. By delivering the bacteria via biomaterial, we overcome the need for the bacteria to attach to the bladder to persist in the organ.

We tested our biomaterial by placing it in human urine in petri dishes and exposing it to bacterial pathogens that cause UTIs. Our results showed that when mixed in a 50:50 ratio, the E. coli outcompeted the UTI-causing bacteria by increasing to around 85% of the total population. When we added more E. coli than UTI-causing bacteria, which is what we envision for future development and testing, the proportion of E. coli increased to over 99% of the population, essentially wiping out the UTI-causing bacteria. Moreoever, the biomaterial continued releasing E. coli for up to two weeks in human urine.

Our findings suggest that E.coli could stick around and survive in the bladder for extended periods of time and successfully decrease the growth of many types of bacteria that cause UTIs.

Person pressing hands against stomach

UTIs can be painful.

Images we create and what actually happens are always beautiful when we have imagination/iStock via Getty Images Plus

Improving biomaterials

Our findings show that E. coli can not only control harmful bacteria it’s closely related to but also a broad range of disease-causing bacteria in humans and animals. This means scientists might not need to identify different types of beneficial bacteria to control each pathogen – and there are many – that can cause a UTI.

Our team is currently evaluating how effectively our biomaterial can cure UTIs in mice. We are also working to identify the specific nutrients that beneficial and harmful bacteria compete over and what factors may help beneficial bacteria win. We could add these nutrients to our biomaterial to be released or withheld.

This research is still at an early stage, and clinical uses are not in development yet, so if it does reach patients it will be well in the future. We hope that our technology could be refined and applied to control other bacterial infections and some cancers caused by bacteria.The Conversation

Sarguru Subash, Assistant Professor of Veterinary Pathobiology, Texas A&M University

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

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