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Drilling down on treatment-resistant fungi with molecular machines

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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 foot, 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 development of new antifungal drugs.

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.

Molecular machines as alternative antifungals

While doctors 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.

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. Compared with conventional drugs, molecular machines killed C. albicans much faster.

Subsequent studies found that molecular machines could also kill other fungi, including 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 remove 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.

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 help 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 health care facilities during the COVID-19 pandemic. According to the Centers for Disease Control and Prevention, strained health care systems, 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

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

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Weight loss plans are less effective for many Black women − because existing ones often don’t meet their unique needs

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theconversation.com – Loneke Blackman Carr, Assistant Professor of Community and Public Health Nutrition, University of Connecticut – 2024-11-13 07:24:00

People who are obese or overweight are at higher risk of developing several chronic diseases.
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Loneke Blackman Carr, University of Connecticut and Jameta Nicole Barlow, George Washington University

The popularity of weight loss drugs such as Ozempic and Mounjaro continue to reflect Americans’ desire to slim down. While these new drugs have offered a solution for people struggling with obesity, many eligible patients – especially Black adults – cannot afford the high price.

These drugs are also not a one-stop solution for better health, as healthy eating and regular exercise are also key to losing weight. But current weight loss interventions based on lifestyle changes largely fail to meet the needs of Black women.

As community health researchers, we wondered why scientists have been unable to craft a lifestyle-based weight loss solution that works for Black women.

So we reviewed 10 years of research on weight loss interventions based on lifestyle changes. We found that only a few studies focused on Black women, and those that did often resulted in only small amounts of weight loss and were inconsistent in how they approached weight loss. Why is that?

Missing the mark for Black women

Obesity increases the risk of developing weight-related conditions such as Type 2 diabetes, heart disease and some types of cancer. Nearly 60% of Black women in the U.S. are obese, placing them at greater risk of developing these conditions.

Lifestyle interventions focusing on healthy diet and increased physical activity are proven to help most people lose weight, typically resulting in a 5% to 10% weight reduction that also reduces the risk of chronic disease. However, these lifestyle interventions usually result in only a 2% to 3% weight loss in Black women.

Our review suggests that lifestyle-based weight loss has been stymied among Black women because they often aren’t included in this research. Because their lived experiences aren’t considered in these studies, these interventions might not meet their specific needs. Of the 138 studies we assessed, Black women made up at least half of the participants in only eight studies.

Research on why lifestyle interventions are often less effective for Black women is lacking. However, some studies highlight the effects of race and gender on their daily lives as potential factors.

Person sitting on couch, pinching skin between eyebrows
The ‘strong’ Black woman is compelled to ignore her physical and emotional needs to take care of others.
PixelsEffect/E+ via Getty Images

The superwoman role

Black women exposed to the persistent stress of navigating everyday racism and sexism face the additional burden of what researchers call the superwoman role. Not only do Black women have to weather their own experiences of race- and gender-based inequalities, they’re also expected to be invulnerable, hyperindependent and suppress their emotions in order to seem strong to their family and community. Many minimize their vulnerabilities and overstress their capabilities in order to fulfill an overwhelming obligation to take care of other people.

Many famous names have spoken about the effects of being the strong superwoman. Actress Taraji P. Henson has pointed to how the need to display strength can lead to ignoring the physical and emotional needs of Black women.

Rapper Megan Thee Stallion spoke about the emotional toll of the superwoman role after being shot by rapper Tory Lanez. “As a Black woman … people expect me to take the punches, take the beating, take the lashings, and handle it with grace. But I’m human.”

The superwoman role levies a heavy tax on Black women, leaving little room to prioritize their health. To cope with the stress, some engage in emotional eating or binge eating. The constant demands of playing multiple caregiver roles can also disrupt physical activity.

Naturally, these challenges make it difficult to adopt healthier eating habits and a consistent exercise routine. Even when working toward weight loss, some Black women continue to gain weight.

Improving weight loss for Black women

Lifestyle interventions that fully integrate the lived experiences of Black women into treatment may be key to improving weight loss. We argue that Black Feminism and Womanism, which focus on the experiences of women of color, can guide researchers to rebuild and reframe weight loss interventions to be more effective for Black women.

Black Feminism and Womanism are approaches guiding Black women and girls to surviving and thriving, specifically by always considering the role that gender and race play in different issues. These frameworks focus on multiple areas of health and wellness, including physical, mental and emotional health, arguing that self-care and wellness practices are acts of social change.

Focusing on the full context of Black women’s lives can lead to better overall health. Obesity, specifically, is influenced by multiple factors, and treating obesity requires a focus on holistic health and well-being. This includes addressing Black women’s economic needs, incorporating faith practices central to Black life, attending to emotional and mental health, and building an environment that makes acquiring healthy food and engaging in daily exercise an easy choice.

Three people walking down a tree-lined trail, smiling at each other
Lifestyle changes are easier to incorporate when they’re tailored to your everyday life.
FG Trade/E+ via Getty Images

Current weight loss interventions vary widely in which elements of Black women’s lives they focus on. For example, some emphasize spirituality, while others concentrate on emotional health. Approaches to weight loss that respond to individual needs and move away from one-size-fits-all will be critical to addressing the various aspects of Black women’s lives that affect their wellness.

If health care providers and researchers begin listening to and working with Black women to redesign weight loss interventions, they will likely find that their efforts at addressing obesity among Black women are more effective.The Conversation

Loneke Blackman Carr, Assistant Professor of Community and Public Health Nutrition, University of Connecticut and Jameta Nicole Barlow, Associate Professor of Writing, Health Policy & Management and Women’s, Gender and Sexuality Studies,, George Washington University

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Can AI chatbots boost human creativity?

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theconversation.com – Jaeyeon Chung, Assistant Professor of Business, Rice University – 2024-11-13 07:26:00

AI chatbots can give helpful suggestions.

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Jaeyeon Chung, Rice University

Think back to a time when you needed a quick answer, maybe for a recipe or a DIY project. A few years ago, most people’s first instinct was to “Google it.” Today, however, many people are more likely to reach for ChatGPT, OpenAI’s conversational AI, which is changing the way people look for information.

Rather than simply providing lists of websites, ChatGPT gives more direct, conversational responses. But can ChatGPT do more than just answer straightforward questions? Can it actually help people be more creative?

I study new technologies and consumer interaction with social media. My colleague Byung Lee and I set out to explore this question: Can ChatGPT genuinely assist people in creatively solving problems, and does it perform better at this than traditional search engines like Google?

Across a series of experiments in a study published in the journal Nature Human Behavour, we found that ChatGPT does boost creativity, especially in everyday, practical tasks. Here’s what we learned about how this technology is changing the way people solve problems, brainstorm ideas and think creatively.

ChatGPT and creative tasks

Imagine you’re searching for a creative gift idea for a teenage niece. Previously, you might have googled “creative gifts for teens” and then browsed articles until something clicked. Now, if you ask ChatGPT, it generates a direct response based on its analysis of patterns across the web. It might suggest a custom DIY project or a unique experience, crafting the idea in real time.

To explore whether ChatGPT surpasses Google in creative thinking tasks, we conducted five experiments where participants tackled various creative tasks. For example, we randomly assigned participants to either use ChatGPT for assistance, use Google search, or generate ideas on their own. Once the ideas were collected, external judges, unaware of the participants’ assigned conditions, rated each idea for creativity. We averaged the judges’ scores to provide an overall creativity rating.

One task involved brainstorming ways to repurpose everyday items, such as turning an old tennis racket and a garden hose into something new. Another asked participants to design an innovative dining table. The goal was to test whether ChatGPT could help people come up with more creative solutions compared with using a web search engine or just their own imagination.

two adults and two small children play with an arrangement of cardboard boxes in a brightly lit room with hard flooring

ChatGPT did well with the task of suggesting creative ideas for reusing household items.

Simon Ritzmann/DigitalVision via Getty Images

The results were clear: Judges rated ideas generated with ChatGPT’s assistance as more creative than those generated with Google searches or without any assistance. Interestingly, ideas generated with ChatGPT – even without any human modification – scored higher in creativity than those generated with Google.

One notable finding was ChatGPT’s ability to generate incrementally creative ideas: those that improve or build on what already exists. While truly radical ideas might still be challenging for AI, ChatGPT excelled at suggesting practical yet innovative approaches. In the toy-design experiment, for example, participants using ChatGPT came up with imaginative designs, such as turning a leftover fan and a paper bag into a wind-powered craft.

Limits of AI creativity

ChatGPT’s strength lies in its ability to combine unrelated concepts into a cohesive response. Unlike Google, which requires users to sift through links and piece together information, ChatGPT offers an integrated answer that helps users articulate and refine ideas in a polished format. This makes ChatGPT promising as a creativity tool, especially for tasks that connect disparate ideas or generate new concepts.

It’s important to note, however, that ChatGPT doesn’t generate truly novel ideas. It recognizes and combines linguistic patterns from its training data, subsequently generating outputs with the most probable sequences based on its training. If you’re looking for a way to make an existing idea better or adapt it in a new way, ChatGPT can be a helpful resource. For something groundbreaking, though, human ingenuity and imagination are still essential.

Additionally, while ChatGPT can generate creative suggestions, these aren’t always practical or scalable without expert input. Steps such as screening, feasibility checks, fact-checking and market validation require human expertise. Given that ChatGPT’s responses may reflect biases in its training data, people should exercise caution in sensitive contexts such as those involving race or gender.

We also tested whether ChatGPT could assist with tasks often seen as requiring empathy, such as repurposing items cherished by a loved one. Surprisingly, ChatGPT enhanced creativity even in these scenarios, generating ideas that users found relevant and thoughtful. This result challenges the belief that AI cannot assist with emotionally driven tasks.

Future of AI and creativity

As ChatGPT and similar AI tools become more accessible, they open up new possibilities for creative tasks. Whether in the workplace or at home, AI could assist in brainstorming, problem-solving and enhancing creative projects. However, our research also points to the need for caution: While ChatGPT can augment human creativity, it doesn’t replace the unique human capacity for truly radical, out-of-the-box thinking.

This shift from Googling to asking ChatGPT represents more than just a new way to access information. It marks a transformation in how people collaborate with technology to think, create and innovate.The Conversation

Jaeyeon Chung, Assistant Professor of Business, Rice University

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Brain-training games remain unproven, but research shows what sorts of activities do benefit cognitive functioning

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theconversation.com – Ian McDonough, Associate Professor of Psychology, Binghamton University, State University of New York – 2024-11-13 07:25:00

Brain-training games sell themselves as a way to maintain cognitive function, but the evidence isn’t there yet.

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Ian McDonough, Binghamton University, State University of New York and Michael Dulas, Binghamton University, State University of New York

Some 2.3 million of U.S. adults over 65 – more than 4% – have a diagnosis of dementia. But even without a diagnosis, a certain amount of cognitive decline is normal as age sets in.

And whether it’s due to fear of cognitive decline or noticing lapses in cognition when we are stressed, many of us have had moments when we thought we could use an extra cognitive boost.

The good news is research has shown that people can make changes throughout adulthood that can help prevent or delay cognitive decline and even reduce their risk of dementia. These include quitting smoking and properly managing blood pressure.

In addition to these lifestyle changes, many people are turning to brain-training games, which claim to optimize your brain’s efficiency and capacity at any age. The makers of brain-training apps and games claim their products can do everything from staving off cognitive decline to improving your IQ.

But so far these claims have been met with mixed evidence.

We are cognitive neuroscientists who focus on brain health across the adult lifespan. We study how the brain informs cognition and the ways we can use brain imaging to understand cognitive and brain-training interventions. We aim to understand how our brains change naturally over time as well as what we can do about it.

Ongoing research shows what actually happens to the brain when it is engaged in new learning, offering a window into how people can sustain their brain health and how brain-training games can play a role. We believe these studies offer some strategies to train your brain the right way.

Brain training fact vs. fiction

Brain training is a set of tasks, often computerized, based on well-known tests to measure a type of cognition, but in a gamified manner.

Most brain-training games were designed to help participants master one or more specific skills. One example is a game that shows you a letter and number combination, where sometimes you must quickly identify whether the letter is even or odd, while other times you must switch to deciding whether the letter is a consonant or vowel. The game may increase in difficulty by requiring you to accomplish the task within a set time limit.

Such games are designed to require a high level of attention, fast processing speed and a flexible mind to alternate between the rules, known as executive functioning.

But it turns out that the specific skills learned in these games often do not translate to more general, real-world applications. Whether brain games meet their end goal of lasting cognitive improvement across a number of areas is still highly debated among psychologists. To make such claims requires rigorous evidence that playing a specific game improves cognitive or brain performance.

In 2016, in fact, the Federal Trade Commission issued a US$50 million penalty to one of the most popular brain-training games at the time, Lumosity, for misleading consumers into thinking that they could achieve higher levels of mental performance at work or at school and prevent or delay cognitive decline by using its product.

If improving on a brain game helps the player get better only at that or highly similar games, maybe game developers need a different approach.

Improving our brain function is possible, even if many of the claims made by developers of brain-training games are unsupported by scientific evidence.

Put some challenge into it

In a study dubbed the Synapse Project, in which one of us, Ian McDonough, helped assess the final outcomes, one group of participants were tasked with engaging in a new activity with which they had little experience. They were assigned to either digital photography or quilting. Though these activities were not games, they were meant to be engaging, challenging and done in a social environment.

Another group was assigned activities that involved little active learning, such as engaging in themed activities related to travel or cooking, or more solitary activities such as solving crossword puzzles, listening to music or watching classic movies. These groups met for 15 hours a week over 14 weeks. All participants were tested at the beginning and end of the study on various cognitive abilities.

Those assigned to the new, challenging activities showed significant gains in their memory, processing speed and reasoning abilities relative to those assigned to the less challenging activities. None of the participants were directly trained on these cognitive tests, which means that the challenging activities enhanced skills that transferred to new situations, such as remembering a list of words or solving abstract problems.

Brain scans of participants showed that over the course of the study, those engaged in the more challenging activities increased their neural efficiency. In other words, their brains didn’t have to work as hard to solve problems or recall information.

The study also showed that the more time participants spent on their projects, the bigger their brain gains and the better their memory was at the end of the 14 weeks.

One difference between the types of activities engaged in the Synapse Project and traditional brain training is whether activities are done in a group or alone. Although other studies have found a benefit to social interaction, the Synapse Project found no difference between the social and solitary activities in the low-challenge group. So, challenge rather than the social components seems to be the driver of maintaining cognitive and brain health.

What you can do to maintain a healthy brain

You might be thinking it’s time to take up digital photography or quilting. But in the end, it’s not about those specific tasks. What matters most is that you challenge yourself, which often comes naturally when doing something new.

The new learning that often is accompanied by a sense of effort – and sometimes frustration – requires accessing the resources in the frontal lobe, which manages thinking and judgment, and the parietal lobe, which processes attention and combines different sensory inputs. These regions constantly talk to each other to keep the mind adaptable in all kinds of situations and prevent the brain from going into “habit mode.”

Where does this leave us? Well, on the one hand, games touted as “training your brain” may not be the best solution compared with other routes to improving cognition.

Ironically, you might already be training your brain by playing effortful games that are not marketed as “brain training.” For example, games such as Tetris or real-time strategy games such as Rise of Nations have shown improvements in players’ cognition. Research has even shown that playing Super Mario 64 can result in increases in brain volume in regions such as the hippocampus, the memory center of the brain.

While little evidence suggests that any brain-training game or program globally improves cognition, some may improve specific aspects of it. As with other activities, challenge is key.

If you’re a word person, try a numbers-based game. If you love math, consider a word game or puzzle. Choosing a task that makes you feel uncomfortable gives you the best shot at maintaining and even improving your cognition. Once you start feeling a sense of ease and familiarity, that’s a sign that it’s time to switch tasks, change the game or at least add some challenge by advancing to a new level of difficulty that feels just beyond your reach.The Conversation

Ian McDonough, Associate Professor of Psychology, Binghamton University, State University of New York and Michael Dulas, Assistant Professor of Psychology, Binghamton University, State University of New York

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