fbpx
Connect with us

The Conversation

Drilling down on treatment-resistant fungi with molecular machines

Published

on

Drilling down on treatment-resistant fungi with molecular machines

Newly developed molecular drills may be able to fight treatment-resistant fungal infections like Candida auris.
Dr_Microbe/iStock via Getty Images

Ana L. Santos, Rice University; Jacob Beckham, Rice University, and James Tour, Rice University

Fungi are present on the skin of around 70% of the population, without causing harm or benefit. Some fungal infections, like athlete's , are minor. Others, like Candida albicans, can be deadly – especially for individuals with weakened immune systems.

Fungal infections are on the rise because of an aging population and an increased prevalence of chronic diseases. At the same time, fungi are becoming more resistant to treatment. As a result, fungal infections could soon become a serious public health threat.

In 2022, the World Health Organization released its first-ever “Fungal Priority Pathogen List,” calling for improved surveillance, public health interventions and the of new antifungal .

We are an interdisciplinary team of chemists and biologists charting a new path to tackle drug-resistant infections. We are using tiny nanoscale drills that combat harmful pathogens at the molecular level. As the traditional antimicrobial research pipeline struggles, our approach has the potential to rejuvenate the fight against these stubborn infections.

Advertisement

Molecular machines as alternative antifungals

While urgently need new antifungal drugs, developing them is challenging. First, it is difficult to develop drugs that selectively kill fungi without harming human cells because of their many similarities.

Second, fungi can rapidly develop resistance to multiple antifungal drugs at once when medications are misused or overused. As such, developing antifungal drugs is much less rewarding for drug companies than developing medications for chronic conditions like diabetes and hypertension that require long-term use.

One solution to this problem could lie in a Nobel Prize-winning technology: molecular machines.

Molecular machines are synthetic compounds that rapidly rotate their components at about 3 million times per second when exposed to light. Doctors can use a light-tipped probe to activate these molecular machines to treat internal infections, or a lamp for skin infections. The light starts the machines spinning, and that rotational motion pushes them to drill through and puncture the cell's membranes and organelles, which results in cell death.

Advertisement

Our group first used this technology to kill cancer cells in 2017. To target the right cells, molecular machines can be linked to specific peptides that bind only to the desired cells, allowing, for instance, the targeting of specific cancer types. Since then, we have used these molecules to kill bacteria, destroy tissue and stimulate muscle contraction. These properties make molecular machines an enticing candidate technology to address the growing fungal threat.

A diagram showing the structure of a molecular machine as gray lines connected in the shape of several hexagons
The 3D structure of a molecular machine. The molecular machine consists of rotor (top) and stator (bottom) portions connected by a central axle. Following light activation, molecular machines rotate rapidly, drilling into fungal cells.
Tour Lab, Rice University

Testing antifungal molecular machines

Researchers first tested the ability of light-activated molecular machines to kill fungi in Candida albicans. This yeastlike fungus can cause life-threatening infections in immunocompromised people. with conventional drugs, molecular machines killed C. albicans much faster.

Subsequent studies found that molecular machines could also kill other fungi, molds like Aspergillus fumigatus and species of dermatophytes, the types of fungi that cause skin, scalp and nail infections. Molecular machines even eliminated fungal biofilms, which are slimy, antimicrobial-resistant communities of microorganisms that stick together on surfaces and commonly cause medical device-associated infections.

Unlike conventional antifungals, which target the fungal cell membrane or cell wall, molecular machines localize to the fungal mitochondria. Often referred to as the “powerhouses of the cell,” mitochondria produce energy to power other cellular activities. When activated with visible light, molecular machines destroy the fungal mitochondria. Once the fungal cell's mitochondria stop working, the cell loses its energy supply and dies.

Two black-and-white electron microscopy images of a fungal cell. The left image shows a large, round, healthy cell, while the cell on the right is shrunken following treatment with light-activated molecular machines.
Candida albicans before and after being exposed to light-activated molecular machines. Molecular machines puncture C. albicans‘ cell wall and intracellular organelles, eventually killing the fungal cell.
Matthew Meyer/Rice University.

At the same time, molecular machines also disrupt the tiny pumps that antifungal agents from the cell, thus preventing the cell from fighting back. Because these molecular machines act by a mechanical instead of a chemical mechanism, fungi are unlikely to develop defenses against this treatment.

In lab experiments, combining light-activated molecular machines with conventional antifungal drugs also reduced the amount of fungi in C. albicans-infected worms and in pig nails infected with Trichophyton rubrum, the most common cause of athlete's foot.

Advertisement

New frontiers for fighting fungal infections

These results suggest that combining molecular machines with conventional antifungals can improve existing therapies and provide new options for treating resistant fungal strains. This strategy could also reduce the side effects of traditional antifungals, such as gastrointestinal upset and skin reactions.

Fungal infection rates will likely continue to rise. As such, the need for new treatments will only become more urgent. Climate change is already causing new human pathogenic fungi to emerge and spread, including Candida auris. C. auris is often resistant to treatment and spread rapidly in facilities during the COVID-19 pandemic. According to the Centers for Disease Control and Prevention, strained health care , overuse of immunosuppressants and misuse of antibiotics have all been implicated in outbreaks of C. auris.

In the future, researchers could use artificial intelligence to create better antifungal molecular machines. By using AI to predict how different molecular machines will interact with fungi and human cells, we can develop safer and more effective antifungal molecules that specifically kill fungi without harming healthy cells.

Antifungal molecular machines are still in the early stages of development and are not yet available for routine clinical use. However, continuing research gives hope that these machines could one day provide better treatments for fungal infections and other infectious diseases.The Conversation

Ana L. Santos, Postdoctoral Fellow in Microbiology, Rice University; Jacob Beckham, Graduate Student in Chemistry, Rice University, and James Tour, Professor of Chemistry, Rice University

Advertisement

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

The Conversation

Animal behavior research is getting better at keeping observer bias from sneaking in – but there’s still room to improve

Published

on

theconversation.com – Todd M. Freeberg, Professor and Associate Head of Psychology, of Tennessee – 2024-05-03 07:16:49

What you expect can influence what you think you see.

Auscape/Universal Images Group via Getty Images

Todd M. Freeberg, University of Tennessee

Animal behavior research relies on careful observation of animals. Researchers might spend months in a jungle habitat watching tropical birds mate and raise their young. They might track the rates of physical contact in cattle herds of different densities. Or they could record the sounds whales make as they migrate through the ocean.

Advertisement

Animal behavior research can fundamental insights into the natural processes that affect ecosystems around the globe, as well as into our own human minds and behavior.

I study animal behavior – and also the research reported by scientists in my field. One of the challenges of this kind of science is making sure our own assumptions don't influence what we think we see in animal subjects. Like all people, how scientists see the world is shaped by biases and expectations, which can affect how data is recorded and reported. For instance, scientists who in a society with strict gender roles for women and might interpret things they see animals doing as reflecting those same divisions.

The scientific corrects for such mistakes over time, but scientists have quicker methods at their disposal to minimize potential observer bias. Animal behavior scientists haven't always used these methods – but that's changing. A new study confirms that, over the past decade, studies increasingly adhere to the rigorous best practices that can minimize potential biases in animal behavior research.

Black and white photo of a horse with a man and a small table between them displaying three upright cards.

Adding up?

Karl Krall/Wikimedia Commons

Advertisement

Biases and self-fulfilling prophecies

A German horse named Clever Hans is widely known in the history of animal behavior as a classic example of unconscious bias leading to a false result.

Around the turn of the 20th century, Clever Hans was purported to be able to do math. For example, in response to his owner's prompt “3 + 5,” Clever Hans would tap his hoof eight times. His owner would then reward him with his favorite vegetables. Initial observers reported that the horse's abilities were legitimate and that his owner was not being deceptive.

However, careful analysis by a young scientist named Oskar Pfungst revealed that if the horse could not see his owner, he couldn't answer correctly. So while Clever Hans was not good at math, he was incredibly good at observing his owner's subtle and unconscious cues that gave the math answers away.

In the 1960s, researchers asked human study participants to code the learning ability of rats. Participants were told their rats had been artificially selected over many generations to be either “bright” or “dull” learners. Over several weeks, the participants ran their rats through eight different learning experiments.

Advertisement

In seven out of the eight experiments, the human participants ranked the “bright” rats as being better learners than the “dull” rats when, in reality, the researchers had randomly picked rats from their breeding colony. Bias led the human participants to see what they thought they should see.

Eliminating bias

Given the clear potential for human biases to skew scientific results, textbooks on animal behavior research methods from the 1980s onward have implored researchers to verify their work using at least one of two commonsense methods.

One is making sure the researcher observing the behavior does not know if the subject from one study group or the other. For example, a researcher would measure a cricket's behavior without knowing if it came from the experimental or control group.

The other best practice is utilizing a second researcher, who has fresh eyes and no knowledge of the data, to observe the behavior and code the data. For example, while analyzing a file, I count chickadees taking seeds from a feeder 15 times. Later, a second independent observer counts the same number.

Advertisement

Yet these methods to minimize possible biases are often not employed by researchers in animal behavior, perhaps because these best practices take more time and effort.

In 2012, my colleagues and I reviewed nearly 1,000 articles published in five leading animal behavior journals between 1970 and 2010 to see how many reported these methods to minimize potential bias. Less than 10% did so. By contrast, the journal Infancy, which focuses on human infant behavior, was far more rigorous: Over 80% of its articles reported using methods to avoid bias.

It's a problem not just confined to my field. A 2015 of published articles in the sciences found that blind protocols are uncommon. It also found that studies using blind methods detected smaller differences between the key groups being observed to studies that didn't use blind methods, suggesting potential biases led to more notable results.

In the years after we published our article, it was cited regularly and we wondered if there had been any improvement in the field. So, we recently reviewed 40 articles from each of the same five journals for the year 2020.

Advertisement

We found the rate of papers that reported controlling for bias improved in all five journals, from under 10% in our 2012 article to just over 50% in our new review. These rates of reporting still lag behind the journal Infancy, however, which was 95% in 2020.

All in all, things are looking up, but the animal behavior field can still do better. Practically, with increasingly more portable and affordable audio and video recording technology, it's getting easier to carry out methods that minimize potential biases. The more the field of animal behavior sticks with these best practices, the stronger the foundation of knowledge and public trust in this science will become.The Conversation

Todd M. Freeberg, Professor and Associate Head of Psychology, University of Tennessee

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

Advertisement
Continue Reading

The Conversation

A look inside the cyberwar between Israel and Hamas reveals the civilian toll

Published

on

theconversation.com – Ryan Shandler, Professor of Cybersecurity and International Relations, Georgia Institute of Technology – 2024-05-03 07:16:12
The conflict between Israel and Hamas is happening online as well as on the ground.
Gwengoat/iStock / Getty Images Plus

Ryan Shandler, Georgia Institute of Technology; Daphna Canetti, University of Haifa, and Tal Mimran, Zefat Academic College

The about the Israel-Hamas war is filled with reports of Israeli families huddling in fear from relentless rocket attacks, Israeli tanks and artillery flattening buildings in the Gaza Strip, hundreds of kidnapped hostages imprisoned in subterranean tunnels, and millions of people driven from their homes by fighting.

But beyond the visceral violence lies a hidden layer of the war – an online conflict. We are scholars of cyberwarfare who have cataloged and analyzed the various cyber operations conducted during the war by Hamas, Israel and other nations and hacking groups supporting one side or the other. The data paints a picture of an unseen facet of the conflict, and it offers insights about the nature of cyber conflict more broadly.

The main conclusion we've drawn is that the consequences of cyber conflict are primarily felt by civilians, not the soldiers or militants actively engaged in the fighting. We find that the cyberattacks inflict on digital systems is far less significant than the resulting harm to humans, and the resulting upward spiral of violence.

Advertisement

Hamas' cyberwarfare activities

The cyberattacks hitting Israeli and civilian systems have had mixed effects. Some technically simple attacks succeeded in obtaining crucial intelligence that assisted Hamas fighters' incursion into Israel. Other attacks employed a scattershot approach, targeting anything within digital reach – hospitals, universities, and newspapers. These attacks didn't serve any military purpose, but simply aimed to disrupt Israeli and terrorize the public.

The quantity and sophistication of the attacks have made clear that hackers working for the government of Iran, a key Hamas funder and supplier, are supporting Hamas' online warfare. Other “hacktivists” and private hacking groups based in countries as varied as , Pakistan and Russia have also joined the fray.

Before the deadly Oct. 7, 2023 terror attack on Israel that sparked the current war, Hamas cyber operatives were working to support the attack planning. A Hamas hacking unit called Gaza Cybergang spied on Israel in search of sensitive information about Israeli military installations. The information they gleaned was instrumental during the attack.

Hamas hackers also conducted phishing attacks, relatively simple attacks in which fake email or text messages resemble legitimate ones and encourage a user to either reply with sensitive information or click on a link that downloads malicious software to their computer or mobile phone.

Advertisement

As the Oct. 7 attack unfolded, the pro-Palestinian hacktivist group AnonGhost released a mobile app with the same name as a prominent reputable app that gives Israeli citizens warnings about impending attacks from Hamas into Israel. AnonGhost issued false alerts – including, reportedly, one about a nuclear attack – and collected users' data, including their contacts, call logs and text messages.

However, since full-fledged hostilities erupted, Hamas has been largely unable to carry out effective cyberattacks that aid its war efforts. As a result, the group turned to information warfare, seeking to evoke panic and shift public opinion.

The most common type of attack that Hamas' cyberwarriors and their allies use now is a distributed denial-of-service, when a barrage of nonsense internet traffic is aimed at one or more websites, email servers or other internet-connected systems. They get overwhelmed by the nonsense traffic and either shut down or cease to function properly.

Denial-of-service attacks have hit websites for news media outlets, banks, financial institutions and government agencies. One attack took the Jerusalem Post website offline for two days. The group that claimed responsibility for that attack was a religious hacktivist group called Anonymous Sudan, with known connections to Russian hacking groups.

Advertisement

Hamas and its online allies are also using wiper malware, which infects a computer and destroys its data. This kind of attack does not serve a purpose such as extortion or surveillance – it just aims to destroy everything in its wake.

We also recorded several attacks that infiltrated databases and released their contents, such as one where the private data of at Ono Academic College was published online.

Another of attacks took control of digital billboards to display the Palestinian in sites around Israel, along with false news about military defeats. These attacks are part of a broader misinformation effort designed to shape domestic debate and terrorize Israeli civilians.

A billboard reads 'Hacked' and contains a pro-Palestinian message.
Electronic billboards have been hacked to display pro-Palestinian messages around the world, including this one in Spain.
Horacio Villalobos/Corbis via Getty Images

Israel's activities

By contrast with Hamas, Israel is a global cyber power whose military possesses some of the strongest cyber warfare capabilities in the world.

Yet the effectiveness of Israel's cyber arsenal is limited because Hamas doesn't depend on the internet very much. Without any targets to strike on a digital battlefield, Israel's primary strategy has been to turn on or off internet connectivity in Gaza. It can do this because Israel controls the electricity and internet cables that serve Gaza.

Advertisement

On Oct. 27, 2023, Israel imposed a near-total telecommunications blackout that lasted for approximately 34 hours. The telecommunications blackout was condemned by international organizations, including the World Organization, whose director general posted that the blackout made it “impossible for ambulances to reach the injured.” Without internet or telephone connections, injured Palestinians in Gaza can't call an ambulance, nor can medical staff stay connected with their dispatch centers.

Similar internet shutdowns have occurred frequently since then. Due to damage, displacement and power and internet disruptions, internet connectivity in Gaza has been reduced to 15% of the typical rate.

During periods when there was internet service in Gaza, pro-Israeli hacktivists got involved. For example, the group WeRedEvils crashed the Gaza Now news site. As hostilities intensified, up to 60% of all traffic to Palestinian websites was made up of denial-of-service attack traffic, according to Cloudflare, a U.S.-based data-transfer and tracking company. The bulk of the attacks were aimed at banks and technology companies.

The U.S. is involved, too. The federal Cybersecurity and Infrastructure Security Agency is working with the Israelis to help thwart some cyberattacks.

Advertisement

A few observations about online conflict

In contrast to Hollywood depictions of cyber warfare, where unstoppable hackers can cripple entire armies and countries with the push of a button, the reality of cyber power is more constrained. Digital battles cannot win wars. Most of the online operations in the Israel-Hamas war have little effect on the actual battlefield. They involve spying or propaganda, not wholesale destruction.

Our data shows that cyber warfare doesn't necessarily give terror groups the ability to face major powers on more equal terms. Hamas' online operations have not been able to offset Israel's military superiority. But Israel's online capabilities are not a significant advantage against a largely offline opponent.

Perhaps most importantly, though, is our recurring finding that civilians are the foremost victims of cyberattacks during war. In our experiments, conducted among more than 10,000 people over 10 years, we have seen that cyberattacks arouse severe psychological distress – akin even to the harm generated by physical terrorism. When confronted with cyberattacks, people feel trapped and anxious, and their sense of safety plummets. As a result, victims lash out and demand strong retaliation in a way that fuels cycles of violence.

As Israel and Hamas volley cyberattacks back and forth, innocent people are caught in the crossfire. This human dimension of cyber warfare is the threat that worries us.The Conversation

Ryan Shandler, Professor of Cybersecurity and International Relations, Georgia Institute of Technology; Daphna Canetti, Professor of Political Science, University of Haifa, and Tal Mimran, Associate Professor of International Law, Zefat Academic College

Advertisement

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

Continue Reading

The Conversation

Boeing’s Starliner is about to launch − if successful, the test represents an important milestone for commercial spaceflight

Published

on

theconversation.com – Wendy Whitman Cobb, Professor of Strategy and Security Studies, University – 2024-05-02 07:24:25

Boeing's Starliner spacecraft on approach to the International Station during an uncrewed test in 2022.

Bob Hines/NASA

Wendy Whitman Cobb, Air University

If all goes well late on May 6, 2024, NASA astronauts Butch Wilmore and Suni Williams will blast off into space on Boeing's Starliner spacecraft. Launching from the Kennedy Space Center, this last crucial test for Starliner will test out the new spacecraft and take the pair to the International Space Station for about a .

Advertisement

Part of NASA's commercial crew program, this long-delayed mission will represent the vehicle's first crewed launch. If successful, it will give NASA – and in the future, space tourists – more options for getting to low Earth orbit.

Two people wearing blue jumpsuits hug in front of a plane.

Suni Williams, right, and Butch Wilmore, the two astronauts who will crew the Starliner test.

AP Photo/Terry Renna

From my perspective as a space policy expert, Starliner's launch represents another significant milestone in the of the commercial space industry. But the mission's troubled history also shows just how difficult the path to space can be, even for an experienced company like Boeing.

Origins and development

the retirement of NASA's space shuttle in 2011, NASA invited commercial space companies to help the agency transport cargo and crew to the International Space Station.

Advertisement

In 2014, NASA selected Boeing and SpaceX to build their respective crew vehicles: Starliner and Dragon.

Boeing's vehicle, Starliner, was built to carry up to seven crew members to and from low Earth orbit. For NASA missions to the International Space Station, it will carry up to four at a time, and it's designed to remain docked to the station for up to seven months. At 15 feet, the capsule where the crew will sit is slightly bigger than an Apollo command module or a SpaceX Dragon.

Boeing designed Starliner to be partially reusable to reduce the cost of getting to space. Though the Atlas V rocket it will take to space and the service module that supports the craft are both expendable, Starliner's crew capsule can be reused up to 10 times, with a six-month turnaround. Boeing has built two flightworthy Starliners to date.

A conical vehicle sitting on a flat vehicle.

The Starliner capsule in transit.

AP Photo/John Raoux

Advertisement

Starliner's development has come with setbacks. Though Boeing received US$4.2 billion from NASA, compared with $2.6 billion for SpaceX, Boeing spent more than $1.5 billion extra in developing the spacecraft.

On Starliner's first uncrewed test flight in 2019, a series of software and hardware failures prevented it from getting to its planned orbit as well as docking with the International Space Station. After testing out some of its systems, it landed successfully at White Sands Missile Range in New Mexico.

In 2022, after identifying and making more than 80 fixes, Starliner conducted a second uncrewed test flight. This time, the vehicle did successfully dock with the International Space Station and landed six days later in New Mexico.

The inside of a Starliner holds a few astronauts. Crew members first trained for the launch in a simulator.

Still, Boeing delayed the first crewed launch for Starliner from 2023 to 2024 because of additional problems. One involved Starliner's parachutes, which help to slow the vehicle as it returns to Earth. Tests found that some links in those parachute lines were weaker than expected, which could have caused them to break. A second problem was the use of flammable tape that could pose a fire hazard.

Advertisement

A major question stemming from these delays concerns why Starliner has been so difficult to develop. For one, NASA officials admitted that it did not as much oversight for Starliner as it did for SpaceX's Dragon because of the agency's familiarity with Boeing.

And Boeing has experienced several problems recently, most visibly with the safety of its airplanes. Astronaut Butch Wilmore has denied that Starliner's problems reflect these troubles.

But several of Boeing's other space activities beyond Starliner have also experienced mechanical failures and budget pressure, including the Space Launch System. This system is planned to be the main rocket for NASA's Artemis program, which plans to return humans to the Moon for the first time since the Apollo era.

Significance for NASA and commercial spaceflight

Given these difficulties, Starliner's will be important for Boeing's future space efforts. Even if SpaceX's Dragon can successfully transport NASA astronauts to the International Space Station, the agency needs a backup. And that's where Starliner comes in.

Advertisement

Following the Challenger explosion in 1986 and the Columbia shuttle accident in 2003, NASA retired the space shuttle in 2011. The agency was left with few options to get astronauts to and from space. a second commercial crew vehicle provider means that NASA will not have to depend on one company or vehicle for space launches as it previously had to.

Perhaps more importantly, if Starliner is successful, it could compete with SpaceX. Though there's no crushing demand for space right now, and Boeing has no plans to market Starliner for tourism anytime soon, competition is important in any market to down costs and increase innovation.

More such competition is likely coming. Sierra Space's Dream Chaser is planning to launch later this year to transport cargo for NASA to the International Space Station. A crewed version of the space plane is also being developed for the next round of NASA's commercial crew program. Blue Origin is working with NASA in this latest round of commercial crew contracts and developing a lunar lander for the Artemis program.

A conical white spacecraft with two rectangular solar panels in space, with the Earth in the background.

SpaceX's dragon capsule.

NASA TV via AP

Advertisement

Though SpaceX has made commercial spaceflight look relatively easy, Boeing's rocky experience with Starliner shows just how hard spaceflight continues to be, even for an experienced company.

Starliner is important not just for NASA and Boeing, but to demonstrate that more than one company can find success in the commercial space industry. A successful launch would also give NASA more confidence in the industry's ability to support operations in Earth's orbit while the agency focuses on future missions to the Moon and beyond.The Conversation

Wendy Whitman Cobb, Professor of Strategy and Security Studies, Air University

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

Advertisement
Continue Reading

News from the South

Trending