How Do We Ingest MPs? What We Know (and Don’t Know) 5 Ways to Reduce Exposure How Are Industry and Tech Addressing the Problem? Future Developments and Consumer Advocacy Microplastics (MPs) are tiny plastic particles (<5 mm), invisible to the naked eye, which are now widespread contaminants found in food, water, and air due to extensive plastic pollution. Emerging research highlights their presence in human organs, raising concerns about long-term health impacts. While scientists continue to explore these uncertainties, consumers can proactively minimize their exposure. Simple, evidence-backed choices, such as opting for plastic-free tea bags, filtering drinking water, and selecting natural fabrics, significantly lower MP intake. By understanding the sources and practical mitigation methods, individuals can protect both personal health and environmental well-being, driving broader industry shifts toward sustainable practices and innovative, eco-friendly solutions.1 This article provides readers with practical, evidence-based strategies to reduce exposure to MPs. Image Credit: SIVStockStudio/Shutterstock.com How Do We Ingest MPs? Humans unintentionally ingest MPs primarily through contaminated food, beverages, and inhalation. Common dietary sources include shellfish, fish, table salt, beer, bottled water, and even tap water, which absorb MPs from polluted oceans, lakes, rivers, or packaging processes.2 Seafood, especially shellfish, accumulates MPs as marine organisms inadvertently consume or absorb them. Salt harvested from contaminated seawater also introduces MPs into our diet. Additionally, beverages like bottled water and beer frequently contain MPs released from plastic containers or during production. Notably, MPs have been detected at alarmingly high concentrations in bottled mineral water, emphasizing packaging's significant role.2,3 Airborne MPs introduce an additional ingestion pathway, as small particles suspended in indoor and outdoor air can be inhaled or swallowed. Activities such as using synthetic textiles, carpets, or household plastic items further release MPs into our immidiate environment.3 While some estimates alarmingly suggest humans ingest MPs equivalent to one credit card weekly, these numbers may be considerably exaggerated due to inconsistent measurement methods. Nevertheless, consistent ingestion, even in smaller quantities, raises concerns about potential health risks, including inflammation, cellular damage, and toxin exposure.2,3 Why More Young Adults Are Getting Colorectal Cancer What We Know (and Don’t Know) MPs are increasingly detected in food and drinking water, raising significant public health concerns. Originating from various sources like textile fibers, cosmetic products, packaging materials, and degraded plastics, these pollutants have infiltrated the environment widely, including marine life, freshwater sources, soil, and air.3,4 Human exposure to MPs primarily occurs through ingestion, notably via contaminated seafood, bottled water, salt, honey, beer, and even vegetables. Although research confirms MPs can accumulate within human tissues and organs, the precise health consequences remain uncertain. Potential health concerns linked to MP exposure include gastrointestinal disturbances, chronic inflammation, immune system disruption, endocrine and thyroid dysfunction, reproductive disorders, and increased cancer risk. Despite growing evidence of these hazards from animal studies, definitive data on human toxicity levels and long-term impacts remain sparse.3,4 Public awareness about specific health risks is inconsistent, with many individuals still unaware of the potential severity, especially regarding reproductive or hormonal effects. Enhanced education and clearer communication about these risks are essential to inform consumer decisions, guide regulatory policy, and reduce plastic pollution.4 How microplastics affect your health Play 5 Ways to Reduce Exposure Recent research highlights their presence in drinking water, seafood, fruits, vegetables, and everyday additives like salt, sugar, and honey. Although their long-term health effects remain uncertain, studies indicate potential risks, including inflammation, oxidative stress, and disruption of metabolic and immune systems. Here are five ways to reduce your MP intake. 1.Choose Natural Fabrics Synthetic clothing sheds thousands of microfibers during washing, contributing significantly to MP pollution. We should choose natural fibers like cotton, wool, and linen to reduce fiber shedding. A study highlighted that synthetic fabrics like polyester and nylon significantly increase MP release compared to natural materials.5,6 2.Avoid Plastic Tea Bags Tea bags, especially those made of nylon or polyethylene terephthalate (PET), can release billions of MP particles into your cup. Switch to loose-leaf tea or choose biodegradable, plastic-free tea bags made of paper or other natural fibers to reduce MP exposure.5,6 3.Filter Your Tap Water MPs commonly contaminate tap water, entering from sources such as degraded plastic waste and atmospheric deposition. Studies report significant levels of MPs in unfiltered drinking water. Installing an activated carbon or reverse osmosis filter can effectively remove most MPs, providing cleaner and safer water for consumption.5,6 4.Limit Single-Use Plastics Plastic bottles, containers, and utensils degrade over time, releasing MPs into foods and beverages. Reduce single-use plastic consumption by choosing glass, stainless steel, or reusable Bisphenol A (BPA)-free containers and utensils. Recent studies reveal high MP contamination in single-use plastic bottled water, underscoring the benefits of sustainable alternatives.5 5.Be Mindful of Food Packaging Processed foods packaged in plastics often contain MP residues that migrate into the food. Choose fresh or minimally processed foods packaged in paper, glass, or metal. Additionally, storing food in glass or ceramic containers rather than plastic can significantly decrease MP contamination, protecting your health in the long term.6 Adopting these simple strategies can substantially reduce your exposure to MPs, mitigating potential health risks. While scientific understanding of MPs’ health impacts continues to evolve, proactive steps to minimize exposure are a wise choice for overall well-being. Download your PDF copy now! How Are Industry and Tech Addressing the Problem? Industries and technologies are increasingly tackling the issue of MP intake through innovative strategies aimed at reducing exposure and contamination. Industries have been developing filtration and treatment systems that effectively remove MPs from water supplies, significantly reducing the concentration of MPs entering food chains. Advanced filtration methods such as membrane bioreactors, reverse osmosis, and nanofiltration have shown great promise due to their high efficiency in removing MPs.7 Technological innovations are also targeting packaging materials, a major contributor to plastic pollution. Biodegradable and bio-based materials derived from natural resources such as algae and plant-based polymers are being developed as sustainable alternatives. These materials decompose naturally without leaving harmful residues, thus preventing the generation of MPs. Additionally, tech companies are creating detection technologies to monitor and manage MP pollution more effectively. Sophisticated spectroscopic methods and automated imaging systems are employed to detect and quantify MPs, facilitating targeted remediation actions accurately.7 Industries are collaborating with environmental tech startups to enhance recycling processes through chemical recycling methods, which break down plastics at the molecular level, allowing for the complete reuse of materials without degradation into MPs. These innovative recycling technologies significantly limit the amount of MPs released into ecosystems.7 Moreover, consumer-oriented technology, including mobile apps and smart devices, educates the public about sustainable consumption and encourages lifestyle choices that minimize plastic waste generation. By raising awareness, these technologies play a crucial role in reducing the global intake of MPs.7 Through such multifaceted approaches, industry and technology collectively contribute to a substantial decrease in MP pollution, thereby mitigating human and environmental health risks associated with MP exposure. 5 Biohacking Secrets to Help You Live Longer Future Developments and Consumer Advocacy Combating MP pollution requires integrated technological, policy, and consumer advocacy efforts. Future developments focus on advanced filtration methods, biodegradation technologies, and microbial enzyme research to efficiently remove MPs from water. Industries will increasingly adopt biodegradable and eco-friendly materials, reducing reliance on traditional plastics.8 Consumer advocacy remains critical, with awareness campaigns educating about health and environmental impacts. Advocates press for clear product labeling and strict MP guidelines, enabling informed consumer choices.8 Policy advocacy also drives change, with groups lobbying for legislation banning MPs in products like cosmetics and detergents. Emerging laws globally enhance industry accountability and promote sustainable practices.8 Finally, international cooperation is key to consolidating research, standardizing regulations, and accelerating technological advances. Supported by consumer advocacy, these integrated measures promise significant progress toward reducing MP pollution, ensuring healthier ecosystems and safer consumer products.8 References

Living with psoriatic arthritis means that movement can sometimes feel like a battle, but I’ve learned that the right kind of exercise can make all the difference. Over time, I’ve discovered a few low-impact activities that help keep my joints happy while also boosting my mood and overall well-being. If you’re looking for gentle, joint-friendly ways to stay active, here are my favorite exercises and why they work so well for me. 1. Yin Yoga: Deep Stretching and Relaxation Yoga has always been an incredible tool for my body and mind, but yin yoga, in particular, has been a gamechanger. Unlike more active forms of yoga, yin involves holding deep stretches for several minutes, allowing connective tissue to gently release and lengthen. This is especially beneficial for psoriatic arthritis because it: Eases joint stiffness and improves flexibility Promotes relaxation, reducing overall inflammation Helps with mindfulness and stress management, which can lessen flare-ups I love yin yoga because it allows me to move at my own pace and listen to my body without pushing too hard. Yin encourages the use of props like blocks and bolster pillows to help relax the muscles instead of stretching or straining them. My joints always feel safe and supported in these poses compared to other types of yoga. Plus, the meditative aspect helps me process the emotional side of living with a chronic illness. It also gives me a chance to slow down and check in with how my body is feeling, which is crucial for managing my symptoms. The long, slow holds in yin yoga target deep connective tissues, which can be affected by arthritis, helping to keep them supple and healthy over time.

Why is it so hard? What can we do about it? Do you sometimes have problems making up your mind about things? I do, and apparently many of the members of the WebMD multiple sclerosis (MS) community on Facebook do, too. When I asked how many people had trouble making decisions, I got dozens of replies of “Yes!” “Absolutely!” “100%” etc., along with my favorite answer, from Zach, who commented, “Yes. I mean No.” One commented that choosing what kind of chips to buy could take a half-hour. Julia posted, “Trouble making decisions is definitely a cognitive issue in MS! One of my most challenging issues that drives my husband nuts!” Neuropsychiatrists call decision-making an “executive function (EF).” Other high-level abilities like paying attention; starting, sticking with, and finishing tasks; learning new things; and staying focused at busy times and places are also called executive functions. MS can impair all those important tasks in life. The MS Association of America (MSAA) says that EF impairment is usually not disabling, but it can be embarrassing or annoying. Loss of executive function might cause us to repeat the same actions over and over or to become easily distracted. These impairments, they say, “can affect a person’s ability to plan, prioritize, and solve problems.”

A new USC Schaeffer Center white paper finds expanded access to anti-obesity medications would lead to significant increases in life expectancy and disease-free years while generating a substantial societal return on investment, even after accounting for treatment costs. More than 4 in 10 U.S. adults have obesity, which is linked to increased risk of over 200 diseases - including heart disease, diabetes, cancer and dementia - and costs society $260 billion annually to treat. Highly effective new anti-obesity medications can be a powerful tool against chronic disease, but fewer than one-third of health insurers cover them amid concerns about upfront costs. Expanding access to anti-obesity medications for all adults without diabetes who qualify would generate $10 trillion in social value by enabling people to live longer and healthier lives, Schaeffer Center researchers found. Further, the investment in expanded access would yield returns to society exceeding 13% annually, which is comparable to returns on early childhood education for disadvantaged children and nearly double the U.S. stock market's returns this century - investments widely regarded as valuable. While the costs of anti-obesity medications have grabbed headlines, our analysis shows why it's important to consider the lifetime value of treatment. Expanding access will prevent or delay obesity-related comorbidities, resulting in improved quality and quantity of life for many Americans." Alison Sexton Ward, research scientist at the Schaeffer Center and co-author of the study The analysis comes as federal officials consider a proposal to expand Medicare and Medicaid coverage of anti-obesity medications - a move that, if adopted, could also encourage broader coverage among private insurers. The new study builds on a widely cited 2023 Schaeffer Center white paper that found Medicare coverage of these medications could result in as much as $175 billion in cost offsets to the program over the next decade by reducing demand for care. Expanded access generates value for more than just the sickest patients Schaeffer Center researchers leveraged an economic-demographic microsimulation model known as the Future Adult Model to project the lifetime trajectories of health, medical spending, treatment costs and other economic outcomes for adults 25 and older without diabetes who qualify for anti-obesity medication under clinical guidelines. These findings were broken down by age group, body mass index (BMI) and risk of developing diabetes. Although branded competition typically pushes down net prices of high-cost drugs even before cheaper generics arrive, the researchers conservatively assumed the net price of anti-obesity medication would remain constant before declining substantially when expected generic competition begins in 2032. The net price, which includes rebates and negotiated discounts, is estimated at about 55-65% below the list price and is consistent with net price estimates used by the Congressional Budget Office. Younger and healthier adults who qualify for the medications were found to benefit the most from expanded access, though all age groups would have longer lives and less time with diabetes. As many as 1.8 years would be added to the lives of adults starting treatment at ages 25 to 34, while they would have as much as 5.9 additional years without diabetes. Researchers determined the social value of expanding access by weighing the value of longer, healthier lives and savings from reduced medical costs against treatment costs. Because of the years gained in better health, the greatest social value comes from treating younger and heathier adults. For instance, treating a 25-year-old with low immediate risk of developing diabetes on average generates nearly 30% higher lifetime social value than treating a 35-year-old with similar risk. "Insurers often limit coverage of anti-obesity medications to sicker patients, such as those with prediabetes or diabetes, but our analysis shows they are likely missing out on a chance to prevent worse and more costly outcomes through early treatment," said co-author Darius Lakdawalla, chief scientific officer at the Schaeffer Center and professor at the USC Mann School of Pharmacy and Pharmaceutical Sciences and the USC Price School of Public Policy. It's not just younger and healthier people. The lifetime net social value is positive for nearly every group the researchers analyzed. Strong investment returns found across populations Researchers also estimated the annual return to society for each dollar invested in expanding access to anti-obesity medication, reflecting the long-term health and economic benefits of such treatments. Expanding access would broadly generate compelling rates of return across different groups of patients. This measurement, known as the internal rate of return (IRR), exceeded 13% for all subgroups with obesity (BMI of 30 or higher) over a 30-year period. "Expanding access to anti-obesity medication is probably the single most effective policy to improve Americans' public health," said co-author Dana Goldman, co-director of the Schaeffer Center and founding director of the USC Schaeffer Institute for Public Policy & Government Service. "The challenge will be to do it in a way that rewards innovators but keeps the public costs low."

When it comes to haptic feedback, most technologies are limited to simple vibrations. But our skin is loaded with tiny sensors that detect pressure, vibration, stretching and more. Now, Northwestern University engineers have unveiled a new technology that creates precise movements to mimic these complex sensations. The study will be published on March 28 in the journal Science. While sitting on the skin, the compact, lightweight, wireless device applies force in any direction to generate a variety of sensations, including vibrations, stretching, pressure, sliding and twisting. The device also can combine sensations and operate fast or slow to simulate a more nuanced, realistic sense of touch. Powered by a small rechargeable battery, the device uses Bluetooth to wirelessly connect to virtual reality headsets and smartphones. It also is small and efficient, so it could be placed anywhere on the body, combined with other actuators in arrays or integrated into current wearable electronics. The researchers envision their device eventually could enhance virtual experiences, help individuals with visual impairments navigate their surroundings, reproduce the feeling of different textures on flat screens for online shopping, provide tactile feedback for remote health care visits and even enable people with hearing impairments to "feel" music. "Almost all haptic actuators really just poke at the skin," said Northwestern's John A. Rogers, who led the device design. "But skin is receptive to much more sophisticated senses of touch. We wanted to create a device that could apply forces in any direction - not just poking but pushing, twisting and sliding. We built a tiny actuator that can push the skin in any direction and in any combination of directions. With it, we can finely control the complex sensation of touch in a fully programmable way." A pioneer in bioelectronics, Rogers is the Louis A. Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering, and Neurological Surgery, with appointments in the McCormick School of Engineering and Northwestern University Feinberg School of Medicine. He also directs the Querrey Simpson Institute for Bioelectronics. Rogers co-led the work with Northwestern's Yonggang Huang, the Jan and Marcia Achenbach Professor in Mechanical Engineering and professor of civil and environmental engineering at McCormick. Northwestern's Kyoung-Ho Ha, Jaeyoung Yoo and Shupeng Li are the study's co-first authors. The study builds on previous work from Rogers' and Huang's labs, in which they designed a programmable array of miniature vibrating actuators to convey a sense of touch. The haptic hang-up In recent years, visual and auditory technologies have experienced explosive growth, delivering unprecedented immersion through devices like high-fidelity, deeply detailed surround-sound speakers and fully immersive virtual-reality goggles. Haptics technologies, however, mostly have plateaued. Even state-of-the-art systems only offer buzzing patterns of vibrations. This developmental gap stems largely from the extraordinary complexity of human touch. The sense of touch involves different types of mechanoreceptors (or sensors) - each with its own sensitivity and response characteristics - located at varying depths within the skin. When these mechanoreceptors are stimulated, they send signals to the brain, which are translated as touch. Replicating that sophistication and nuance requires precise control over the type, magnitude and timing of stimuli delivered to the skin. This presents a massive challenge, which current technologies have struggled - and failed - to overcome. Part of the reason haptic technology lags video and audio in its richness and realism is that the mechanics of skin deformation are complicated. Skin can be poked in or stretched sideways. Skin stretching can happen slowly or quickly, and it can happen in complex patterns across a full surface, such as the full palm of the hand." Northwestern's J. Edward Colgate, a haptics pioneer and study co-author Actuator unleashed To simulate that complexity, the Northwestern team developed the first actuator with full freedom of motion (FOM). This means the actuator is not constrained to a single type of movement or limited set of movements. Instead, it can move and apply forces in all directions along the skin. These dynamic forces engage all mechanoreceptors in the skin, both individually and in combination with one another. "It's a big step toward managing the complexity of the sense of touch," said Colgate, Walter P. Murphy Professor of Mechanical Engineering at McCormick. "The FOM actuator is the first small, compact haptic device that can poke or stretch skin, operate slow or fast, and be used in arrays. As a result, it can be used to produce a remarkable range of tactile sensations." Measuring just a few millimeters in size, the device harnesses a tiny magnet and set of wire coils, arranged in a nesting configuration. As electricity flows through the coils, it generates a magnetic field. When that magnetic field interacts with the magnet, it produces a force strong enough to move, push, pull or twist the magnet. By combining actuators into arrays, they can reproduce the feeling of pinching, stretching, squeezing and tapping. "Achieving both a compact design and strong force output is crucial," said Huang, who led the theoretical work. "Our team developed computational and analytical models to identify optimal designs, ensuring each mode generates its maximum force component while minimizing unwanted forces or torques." Bringing the virtual world to life On the other side of the device, the team added an accelerometer, which enables it to gauge its orientation in space. With this information, the system can provide haptic feedback based on the user's context. If the actuator is on a hand, for example, the accelerometer can detect if the user's hand is palm up or palm down. The accelerator also can track the actuator's movement, providing information about its speed, acceleration and rotation. Rogers said this motion-tracking capability is especially useful when navigating spaces or touching different textures on a flat screen. "If you run your finger along a piece a silk, it will have less friction and slide faster than when touching corduroy or burlap," he said. "You can imagine shopping for clothes or fabrics online and wanting to feel the texture." Beyond replicating everyday tactile experiences, the platform also can transfer information through the skin. By changing the frequency, intensity and rhythm of haptic feedback, the team converted the sound of music into physical touch, for example. They also were able to alter tones just by changing the direction of the vibrations. Feeling these vibrations enabled users to differentiate between various instruments. "We were able to break down all the characteristics of music and map them into haptic sensations without losing the subtle information associated with specific instruments," Rogers said. "It's just one example of how the sense of touch could be used to complement another sensory experience. We think our system could help further close the gap between the digital and physical worlds. By adding a true sense of touch, digital interactions can feel more natural and engaging." The study title is "Full freedom-of-motion actuators as advanced haptic interfaces."

Transgender People Reciving Gender-Affirming Hormone Therapy Have A 37% Lower Chance of Acquiring HIV, and for People Living With HIV, Hormone Therapy Appears To Sacrifice A 44% Lower Chance Of The Virus Remaining Detectable in Blood, According to a University of Michigan Study. Overall, The Research Found That Hormone Therapy for Patients Reciving Medical Care to Align Their Physical Characteristics with Their Gender Identity Improved All HIV-Related Health Outcomes for Transgender, Nonbinary and Gender Miscellaneous People. The Study, Published in the Lancet HIV, Examined Health Records of More Than 8,000 Transgender and Gender Miscellaneous Patients Who Received Primary Care At Community Health Centers In Boston and New York City Between 2013 and 2019. “Trans communities have been hard hit by the hiv epidemic. Research on the Health-Promoting Effects of Hormone Therapy for Trans People is Robust for Mental Health, But Less So For Physical Illnesses Such as HIV. Associate Professor of Epidemiology at the U-M School of Public Health Who Recently Had A Study On Hormone Therapy and Depression Published. Transgender People Are About 13 Times More Likely To Be HIV-Positive Than Other Adults of Reproductive Age, According to the World Health Organization. At the same time, the who reports that transgender individuals have Lower rates of Access to Health Services Than the General Population Due to a Range of Issues, Including Violence, Legal Barriers, Stigma, Discrimination and SocioConomic Marginalization. Likely Those Barriers, The Researchers Found, Contribute to Higher HIV Rates in Black, Hispanic/Latino and Multiracial Transgender People Than Among White Transgender People. The Researchers ALSO Found that Very Few Study Participants -only About 3% of Those Without HIV-Were Taking Pre-Exposure Prophylaxis, OR PrEP, Medication Intended for Individuals at High Risk for HIV Exposure, Suggesting An Important Opportunity to Expand HIV Prevention EFFVIVTS. We have public health tools to reduce HIV, Including Newer Biomedical Prevention Strategies Like Prep and Traditional Behavioral Approaches Such AS Supporting Condom Use. But prevents HIV and Optimizing HIV CARE ARE NOT 'ONE SIZE FITS ALL' IN PUBLIC HEALTH. We Need Tailored Approaches That Address The Lived Experiences and Priorities of Trans People, Such AS Integrated Models of Care That Incorporate Gender Care With HIV Prevention and Care Services. ” Sari Reisner, Study's Lead Author and Associate Professor of Epidemiology at the U-M School of Public Health The Findings Suggest That Gender-Affirming Care Functions As A Public Health Intervention That Addresses Multiple Health Needs Simultaneously. By Providing Gender-Affirming Hormone Therapy, Health Care Providers Can Potential Support A Person's Gender Identity While Also Reduction HIV Transmission and Improving HIV Treatment Outcomes In A Population Facing Significant Health Disparities, The Researchers Found. The Study ALSO REVEALED THAT PATIENTS WHO REMAINED CONSENTLY ENGAGED IN CARE HAD BETTER HEALTH OUTCOMES, AND, MORE SPECIFICALLY, THAT THE NUMBER OF YEARS ENGAGED IN CARE WAS RELATED TO KEEPING THE HIV VIRUS IN CHECK OR VIRAL SUPPEMENT HIGH. Reisner, Who Also Published A Viewpoint Article In The Lancet HIV Examining Why Transgender People Face Higher HIV Rates, Suggests Solutions To Address The Various Social, Economic and Health Care Barriers That Exacerbate HIV INEQUITIES. The Article Emphasizes The Need to Develop Solutions in Partnership with Transgender Communities and Calls for More Research and Funding Into Research for Transgender People Living With HIV. "Trans communities are made vulnerable to HIV. For Trans People, HIV Vulnerabilities and Resiliencies Are Situated Within The MultileVel and Biopsychosocial Contexts in which we Live," Reisner Said. "Public Health Cannot Effectively Mitigate the HIV EPIDEMIC UNLESS WE DISMANTLE THE INTERSECTING SYSTEMS OF POWER AND PRIVILEGE RELATION TO BOTH GENDER AND TO OHER MARGINALIZED IDENTITIES, WHICK HIV INEQUITIES." The Study was Funded by the Patient-Centered Research Outcomes Institute and the National Institutes of Health.

Banning smartphone and social media access alone fails to equip children for healthy use of technology, argues a group of international experts in The BMJ today. They say the focus should shift to a rights based approach, underpinned by age appropriate design and education, that protects children from harm while developing skills to help them participate in a digital society. Bans on smartphone and social media access have been advocated in many countries to protect children from harm despite lack of evidence on their effects, explain Victoria Goodyear and colleagues. For example, a recent evaluation of school smartphone policies in England reported that restricted smartphone use in schools was not associated with benefits to adolescent mental health and wellbeing, physical activity and sleep, educational attainment, or classroom behaviour. That study also found no evidence of school restrictions being associated with lower levels of overall phone or media use or problematic social media use. While technology-free moments and spaces are important for children, the authors argue that blanket restrictions are "stop gap solutions that do little to support children's longer term healthy engagement with digital spaces across school, home, and other contexts, and their successful transition into adolescence and adulthood in a technology filled world." Instead, they call for a rights based approach to smartphone and social media use, in line with the UN Convention on the Rights of the Child, which recommends ways of protecting children from harm while nurturing the healthy development of smartphone and social media use. Recent international legislation, such as the European Union's Digital Services Act and the UK Online Safety Act, also reflect a clear understanding of the need to ensure children's uses of technology are compatible with their wellbeing. Immediate priorities are to improve legislation for the tech industry grounded in children's rights and create professional training and guidance for schools, teachers, and parents to help them be actively involved in the development of children's healthy technology use and in shaping future policies and approaches, they write. They acknowledge several potential challenges, but say in the longer term, this approach is likely to be more beneficial and sustainable as it is focused on building a safe ecosystem in a digital society. "Ultimately, there is a need to shift debates, policies, and practices from a sole focus on restricting smartphone and social media access toward an emphasis on nurturing children's skills for healthy technology use," they conclude.

Research from Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago strongly suggests that Kawasaki disease is caused by a single respiratory virus that is yet to be identified. Findings contradict the theory that many different pathogens or toxins could cause this disease that can lead to serious cardiac complications in young children. "The cause of Kawasaki disease has been a mystery for over 50 years," said Anne Rowley, MD, pediatric infectious diseases expert and scientist at Manne Research Institute at Lurie Children's, who is the lead author on the study published in Laboratory Investigation. "Our compelling data are a huge step forward and provide a clear direction for the field to identify and sequence the virus that causes Kawasaki disease in susceptible children. This will be critical to advancing the diagnosis, treatment and prevention of Kawasaki disease." Kawasaki disease is relatively uncommon, affecting mostly children between 6 months and 5 years of age. Lurie Children's sees 50-60 newly diagnosed Kawasaki disease patients a year. Currently, there is no diagnostic test for Kawasaki disease. Clinical signs include fever, rash, swelling of the hands and feet, irritation and redness of the whites of the eyes, swollen lymph glands in the neck, and irritation and inflammation of the mouth, lips, and throat. Children with Kawasaki disease have a 20 percent chance of developing heart disease, while infants are at higher risk with 50 percent chance of cardiac complications. The standard treatment, intravenous immunoglobulin and aspirin, substantially decreases the risk of heart disease in patients with Kawasaki disease. Steroids may be added for the highest risk patients. In their study, Dr. Rowley and colleagues prepared antibodies from blood cells of children with Kawasaki disease, in order to see what these antibodies will target in tissue samples of patients who died from the disease. They found that the antibodies recognized so-called inclusion bodies, which are by-products of a virus, in all 20 tissue samples that represented cases from the U.S. and Japan over 50 years. We saw the same inclusion bodies targeted in every tissue sample spanning five decades and two continents, which shows that we are dealing with one predominant virus causing Kawasaki disease. It appears to be a respiratory virus since the inclusion bodies were in the medium size airways. Going forward, we need to focus on studies of pathology specimens to gain understanding of what is inside the inclusion bodies so that we can identify the Kawasaki disease virus and finally solve the mystery." Dr. Anne Rowley, MD, pediatric infectious diseases expert and scientist at Manne Research Institute at Lurie Children's This work was supported by the National Institutes of Health grant R01AI150719 to Dr. Rowley, the Max Goldenberg Foundation, the Center for Kawasaki Disease at the Ann & Robert H. Lurie Children's Hospital of Chicago, the Northwestern University NUSeq Core Facility, and the Northwestern University Flow Cytometry Core Facility supported by Cancer Center Support Grant (NCI CA060553). Dr. Rowley is a Professor of Pediatrics and Microbiology-Immunology at Northwestern University Feinberg School of Medicine. She holds the Dorothy M. and Edward E. Burwell Board Designated Professorship in Immunobiology at Lurie Children's.

Cell membrane proteins hide secret gateways that can be used to modify cell behavior. This has been demonstrated in a study led by the Hospital del Mar Research Institute and published in Nature Communications, with participation from research centers in Spain, Switzerland, the United Kingdom, Germany, France, Poland, the Netherlands, Denmark, Hungary, Italy, Sweden, China, and the United States. The findings may facilitate the creation of new medications or improve the mechanisms of existing ones. The study's findings are based on computer simulations that achieved an unprecedented level of detail. Researchers were able to observe, at atomic scale and in real time, how membrane lipids interact with G protein-coupled receptors (GPCRs) in their natural environment. These interactions reveal new ways to modulate cellular functions that would otherwise remain invisible. "We have discovered new gateways for drugs to modulate proteins that regulate cellular activity," explains Dr. Jana Selent, coordinator of the GPCR Drug Discovery Research Group within the Biomedical Informatics Research Program (GRIB) at the Hospital del Mar Research Institute, a joint group with Pompeu Fabra University. GPCRs are important because a significant portion of existing drugs target them to act on cells. In fact, 34% of FDA-approved drugs are based on these receptors. "Having detailed information about the specific site where these drugs act within the cell will accelerate the development of targeted therapies," adds Dr. Selent. Work in progress Although the study published is based on data from 190 experiments covering 60% of known GPCRs, the work continues to uncover the mechanisms used by these proteins to regulate cell function. So far, researchers have confirmed that beyond the known access points, there are others only visible through computer simulations. These newly identified pathways could be leveraged to develop innovative therapeutic treatments. According to Dr. David Aranda, postdoctoral researcher at GRIB and lead author of the study, these are "more specific gateways for each receptor-a more direct way to modulate cell behavior." In many cases, it was known that a drug acted on cells, but not how. These results shed light on this aspect of cellular dynamics, making it possible to identify "targets that help create more selective, more precise medications, thereby reducing possible side effects. This could allow us to go beyond current methods used in treating multiple conditions," he adds. This information, along with future findings, is freely available for use by any laboratory working on developing or improving medications.

Thought Leader Prof. Dr. Kristina Kusche-Vihrog Head of Department, Institute of Physiology University of Lübeck In this interview with News Medical Life Sciences, Prof. Dr. Kristina Kusche-Vihrog, head of the Institute of Physiology at the University of Lübeck, speaks about the nanomechanics of living cells and their implications for cardiovascular disease. Could you start by introducing our readers to your research into endothelial cells and what role these cells play? I started a research project as a postdoc, looking into the role of epithelial cells. As this work developed, we recognized that the endothelial cells lining the inside of blood vessels also greatly impact the vascular system. These cells carry a lot of ion channels in their plasma membranes and are highly flexible, meaning that they can react to the force of the streaming blood. Their position inside of the blood vessel is important because endothelial cells can sense everything that comes with the blood, allowing them to react accordingly. For example, endothelial cells could sense vasoactive factors and provide signals to the vascular smooth muscle cells surrounding them. These cells can also be deformed by forces exerted by streaming blood. When deformed, they react in a certain manner, resulting in vasodilating or vasoconstrictory factors that help regulate the vasculature. We recognized that this cell behavior is especially important in terms of passive physiology. Because they are flexible and deformable, endothelial cells can switch between different mechanical states. They typically exhibit normal and healthy behavior, but when something happens in the body, like disease or inflammation, the cells change their behavior and mechanical properties. This is known as endothelial dysfunction. Image Credit: Jose Luis Calvo/Shutterstock.com What impact do cell stiffness and cells’ mechanical properties have on the body? How do we measure these characteristics? An enzyme called the eNOS (endothelial nitric oxide synthase) is found underneath the plasma membrane. This enzyme was discovered many years ago. When cells are soft and deformable, their cytoskeleton is depolymerized. Streaming blood can activate this enzyme, prompting a cascade of arginine and other substances. NO is produced by endothelial cells as a response to this deformation from the bloodstream, causing an increase in vessel diameter and, in turn, a decrease in blood pressure. This important mechanism is connected to the cell’s surface, which is 150 to 200 nanometers of the outer cell layer. The glycocalyx is located on top of the plasma membrane; the layer underneath the plasma membrane is called the cortical cytoskeleton. What role does the glycocalyx play in endothelial cells and cell stiffness? How is this typically measured? The glycocalyx is a fascinating structure, and one of the most important factors in endothelial function is the integrity of the glycocalyx. An AFM is the perfect instrument for measuring the glycocalyx. We can use the AFM to measure this by touching the glycocalyx with a small, 1-micrometer spherical tip and with very low loading force in the range of 0.5 nanonewtons. The glycocalyx structure is highly flexible and vulnerable, so we cannot use high-loading forces. The first few nanometers of the indented cell make up the glycocalyx; as we indent more, we touch the surface of the endothelial cell, the plasma membrane, and the underlying cortical cytoskeleton. The resulting AFM curve features several slopes and can take weeks to analyze. We were able to use enzymes like heparinase to remove the glycocalyx enzymatically, allowing us to quantify the height and mechanical properties of the glycocalyx and the mechanical properties of the cell cortex. The glycocalyx has a mesh-like structure built on many factors of glycoproteins and proteoglycans. For example, heparan sulfate is an important compound of the glycocalyx. the glycocalyx builds a vascular protective structure on top of the cells. Quantifying this can be challenging, but the AFM is ideally suited to this task. Conversations on AFM #3: Insights of a Scientist, NanoMechanics in Living Cells Play Video Credit: Bruker BioAFM Are your experiments performed in cell culture, and what types of cells do you normally work with? We use several different models. HUVECs are our gold standard, and we freshly isolate these from the umbilical vein here, after sourcing cells from the hospital at the University of Lübeck. These cells pose a challenge when transfected; for example, we may use CRISPR-Cas to knock out specific channels in the cell. I prefer to work ex vivo, using blood vessels from mice or patients and splitting them open so that the endothelial cells face upwards. This allows us to measure these endothelial cells in ex vivo blood vessels. This is ideal because we can use patient vessels or different mouse models, including transgenic mouse cells. Glycocalyx preparation takes time when culturing the endothelial cells. This is often a problem at other labs that culture their endothelial cells for only two days, for example, because this is not long enough for proper glycocalyx preparation. Cells in culture and ex vivo preparation patches need time, at least three to four times until the glycocalyx is recovered and can be measured. High blood pressure is probably the most well-known vascular disease, with around 50% of adults thought to have hypertension, according to the CDC. Hypertension causes increased cell stiffness in blood vessels, which can lead to inflammation and secondary issues. How do you see your work directly translating to medical research, for example, with hypertension? Endothelial stiffness can be directly correlated to arterial stiffness. We determined this via a project where we worked with different patient cohorts. To measure this, we used standardized HUVECs and incubated these with patient serum, including pathologic compounds. We found that factors in the patient serum seriously damaged the glycocalyx and stiffened the cell cortex. This stiff cell cortex could be correlated to arterial stiffness measured as pulse wave velocity. Our findings at the single-cell level were also true for significant parts of the arterial system. We found local vasoconstriction, for example, but in the case of inflammatory disease, I am convinced that endothelial cell behavior impacts the arterial system. Could you also share some insight from your research on systemic sclerosis and cell stiffness and the global components that you think play a role in these? This work is an ongoing project, and we currently have preliminary data, particularly on autoantibodies like those associated with SARS‑CoV‑2. Inflammatory disease results in the body producing more autoantibodies, though this process can be a ‘black box.’ These autoantibodies bind against, for example, G protein-coupled receptors like angiotensin II receptors, completely changing the endothelial surface. As part of this process, the glycocalyx is damaged, with its height flattened completely. This is essentially a shedding of the glycocalyx and a stiffer cortex. Our working hypothesis is that in inflammatory diseases like systemic sclerosis, we see the body's self-reaction, and when these autoantibodies bind to these receptors, we see specific cascades leading to inflammatory processes. These receptors are all linked to the cortical cytoskeleton. This is a specific cytoskeleton underneath the plasma membrane. This is not the stress fibers inside the cell; rather, it is a very narrow compartment at around 200 nanometers from the top of the cell surface. This actin-myosin mesh features linker proteins and receptors, with the glycocalyx linked to actin via syndecan or perlecan. Inflammatory diseases lead to shedding of the glycocalyx or cortical stiffening, caused by polymerization of the cortical actin and an intrinsic signal, which leads to collapse of the glycocalyx. We can manipulate the actin cytoskeleton to investigate this, using fluorescence microscopy to focus on the cortical cytoskeleton. My research is focused on this cortical actin, so a confocal microscope is useful. Manipulating the cortical cytoskeleton involves using jasplakinolide to polymerize the actin mesh, or we can use cytochalasin D to depolymerize it. Manipulating actin fibers underneath the plasma membrane results in reactions from the glycocalyx, with a stiff cortex leading to a collapse of the glycocalyx and a soft cortex giving an upright and proper glycocalyx. What are some of the current challenges for this type of research? My first AFM measurements using early instruments were challenging, but modern AFMs are much more user-friendly. The real challenge is working with these types of cells. It is imperative that we handle cells in a physiological way because they are living cells, and only a living cell in a perfect environment can properly act like a living cell. For example, factors such as pH and salt content must be optimal, with appropriate growth time in every case. It is important to study the morphology and behavior of the endothelial cells before the experiment. A lot of experience working with cell culture experiments is needed to confirm that the cells are in good shape before experimenting. Where do you think the future of AFM will lead, and what role will it play for scientists in the future? AFM is one of the best methods for quantifying cell mechanics reliably. It allows me to view online how a living cell reacts when I apply substances. I would like to see more standardized measurements, meaning that we can use AFM as a diagnostic tool. For example, chronic kidney disease patients often require biopsies in the kidney, which are painful. From my group's research, I know that when we use patient serum and incubate standardized HUVECs with this, we can differentiate between stage three, four, and five chronic kidney disease. Using patient serum, we can see significant differences in cortical stiffness and glycocalyx height. This method is noninvasive, and while it takes time to create the necessary force curves, it would be useful to integrate the AFM as a diagnostic tool in translational projects and clinics. We are not far from this reality. In our current project, for example, we can measure endothelial dysfunction. A stiff cell or a cell with a damaged glycocalyx are hallmarks of a dysfunctional cell. We can perform these diagnostics in lab projects, but clinicians are reluctant to use this approach at the moment because of the complexity of the machine involved. I am trying to convince different groups to try this approach, with clinicians giving us serum and my team providing details on detected endothelial dysfunction. About Prof. Dr. Kristina Kusche-Vihrog Prof. Dr. Kristina Kusche-Vihrog is director of the Lübeck Institute of Physiology in Germany and on the board of the German Hypertension Foundation. In 2018, she received the German Society of Nephrology award for research into hypertension. Her research focuses, in particular, on the influence of inflammatory processes on endothelial dysfunction as a precursor to the development of cardiovascular diseases.

It's been five years since COVID-19 was declared a global pandemic. As SARS-CoV-2 shifts to endemic status, questions about its future evolution remain. New variants of the virus will likely emerge, driven by positive selection for traits such as increased transmissibility, longer infection duration and the ability to evade immune defenses. These changes could allow the virus to spread among previously immunized populations, potentially triggering new waves of infection. Predicting new mutations in viruses is crucial for advancing life science research, particularly when trying to understand how viruses evolve, spread and affect public health. Traditionally, researchers rely on wet-lab experiments to study mutations. However, these experiments can be costly and time-consuming. Researchers from the College of Engineering and Computer Science at Florida Atlantic University have developed a new method to predict mutations in protein sequences called Deep Novel Mutation Search (DNMS), a type of artificial intelligence model that uses deep neural networks. For the study, they focused on the SARS-CoV-2 spike protein – the part of the virus responsible for helping it enter human cells – and used a protein language model to predict potential new mutations in this protein never seen before. To do this, researchers used a language model, ProtBERT, which was specifically fine-tuned to understand the "dialect" of SARS-CoV-2 spike proteins. The model works by looking at potential mutations and ranking them based on several factors. These include grammaticality, which refers to how likely or "correct" a mutation is according to the grammatical rules learned by the model, as well as how similar the mutated sequence is to the original protein, which is measured by semantic change and attention change. Results of the study, published in the journal Communications Biology, show that the DNMS language model can separate sequences into groups based on their similarities. The model can predict which mutations are likely to occur by looking for mutations that cause only small changes in the protein's structure and function. This is important because, in most cases, viruses like SARS-CoV-2 evolve through small changes that allow them to adapt without drastically altering their overall function. The DNMS method uses all available information about the sequence and the mutations to create a more accurate prediction of which mutations are likely to occur. Unlike prior research, which typically looks at changes to a reference protein sequence, DNMS introduces a parent-child mutation prediction model. The parent sequence (an existing protein sequence) is used to predict mutations, and these mutations are analyzed based on how they might evolve over time. Our model ranks all possible mutations to find the ones that are most likely to occur in the future. Our study shows that mutations following the protein's grammars, with minimal changes compared to the original sequence and low attention differences, are considered the most likely future mutations." Xingquan "Hill" Zhu, Ph.D., senior author and professor in FAU's Department of Electrical Engineering and Computer Science The method first takes a given SARS-CoV-2 spike protein sequence and simulates all possible single-point mutations. For each mutated version of the protein, DNMS uses the ProtBERT model to calculate how likely each mutation is to follow the "grammar" of the protein (grammaticality) and how similar the mutated sequence is to the original sequence (semantic change). Additionally, the model looks at attention, a measure that has been used to study protein structure and function, but never before applied to mutation prediction. "The key to our method lies in using the context provided by the parent sequence. This context is crucial for evaluating whether a potential mutation aligns with the 'grammar' of the protein," said Zhu. "DNMS works by selecting a parent sequence from a phylogenetic tree – basically a family tree of viral strains – and simulating all possible mutations." The study also looked at the relationship between the predicted mutations and the virus' fitness, or how well it can replicate and survive. Findings show that mutations with high grammaticality, small semantic change, and low attention change were associated with higher viral fitness. This suggests that mutations which fit well within the biological "rules" of the protein and cause minimal disruption to the protein's structure or function are more likely to be beneficial for the virus. "We believe that using sequence data alone can help make these predictions, as proteins follow certain biological rules," said Zhu. The researchers tested the effectiveness of DNMS through statistical analysis. Their results show that DNMS outperforms other methods in predicting novel mutations because it combines all the relevant factors into a single, more accurate prediction model. "The fine-tuned, pre-trained language model developed by our researchers can predict which SARS-CoV-2 mutations are more likely to occur in the future," said Stella Batalama, Ph.D., dean of the College of Engineering and Computer Science. "This method can be useful for guiding experimental research, as it provides predictions about mutations before they are observed in the population, helping public health officials track and prepare for new mutations before they spread widely." Study co-author is Magdalyn E. Elkin, a doctoral student in FAU's Department of Electrical Engineering and Computer Science. The research was sponsored by the United States National Science Foundation.

Scientists at Auburn University have uncovered a fundamental principle of how brain cells stay connected, and their discovery could change how we understand Alzheimer's disease. Published in Cell Reports, this groundbreaking study reveals that neurons-the cells that make up our brain-use simple physics to maintain their connections, and that these processes change in Alzheimer's patients. For decades, scientists have wondered how brain cells keep in touch with each other even when they're not actively sending signals. Dr. Michael W. Gramlich and his team at Auburn University have now provided an answer, using physics to explain this process for the first time. We've found that neurons use a type of natural force based on entropy - like an invisible glue - to keep their connections strong. And when this process stops working correctly, it may be an early sign of Alzheimer's disease." Dr. Michael W. Gramlich, Auburn University Why this matters Imagine a city where all the traffic lights are always working, keeping cars moving efficiently. Now imagine what happens when some of those lights malfunction-cars pile up, traffic slows, and chaos ensues. This is similar to what happens in the brain when neurons fail to maintain their connections during the early stages of AD. In a healthy brain, neurons stay connected using specific molecular rules even when they're at rest. But in Alzheimer's disease, these connections start breaking down, leading to memory loss and cognitive decline. Dr. Gramlich's team discovered that neurons maintain a specific density of objects, called vesicles, to preserve these crucial connections. Using advanced microscopes and computer models, they found that the denser these vesicles are, the stronger the connection between neurons. The results also suggest that neurons use vesicle density as a way to increase or decrease the connections as well. A breakthrough in understanding Alzheimer's disease One of the most exciting findings of this study is that changes in these neuronal connections could be an early warning sign of Alzheimer's Disease. The research team found that in brains affected by Alzheimer's Disease, the density of vesicles is significantly altered, disrupting the brain's ability to communicate. While past research teams have focused on the biological basis for Alzheimer's Disease, this study shows that using fundamental physics in combination with biology can provide a new path forward toward solving the problem of Alzheimer's Disease. "This discovery gives us a new way to think about Alzheimer's Disease," said Dr. Gramlich. "If we can find ways to restore these connections, we might be able to slow down or even prevent some of the damage caused by the disease." A team effort with lasting impact This study was the result of a collaborative effort at Auburn University, with contributions from Dr. Miranda Reed and graduate student Paxton Wilson, along with three undergraduate students. Their work not only advances our understanding of brain function but also opens the door for new treatments that could help millions of people worldwide. The findings of this research could have far-reaching implications, potentially influencing future treatments for neurodegenerative diseases. By uncovering how neurons maintain their connections, scientists now have a new target for therapies aimed at keeping the brain healthy as we age. This work builds upon the collaboration's previous successful studies on the underlying molecular and physical processes that lead to Alzheimer's Disease and dementia. Auburn University's research is making waves in the scientific community, proving once again that cutting-edge discoveries can come from unexpected places. This breakthrough in neuroscience could change how we fight Alzheimer's Disease and protect brain function for generations to come.

A new study from Queen Mary University of London found that 9% of all reported adverse drug reactions (ADRs) reported to the UK medicines regulator are associated with medications where side effect risk is partly dependent on patient's genes. Of this subset of ADRs, 75% were associated with only three genes that impact how the body processes medication. Genetic testing before prescribing could therefore help avoid ADRs in these cases. Over the past 60 years, The Medicines and Healthcare products Regulatory Agency (MHRA)'s Yellow Card scheme recorded over one million reports of side effects – also known as adverse drug reactions (ADRs) – to medications. Previous studies have indicated that more than 99% of individuals have genetic variants which could lead to an adverse response to certain drugs. In some cases, these reactions can be serious and lead to further health problems, longer hospital stays, or even death. The cost of ADRs to the NHS is estimated to be more than £2 billion a year. A new study, published today in PLOS Medicine, led by Dr. Emma Magavern from Queen Mary University of London analysed over 1.3 million ADR reports submitted to the MHRA Yellow Card scheme. It found that 115,789 (9%) were associated with drugs for which side effect risk can be modified using pharmacogenomics (PGx) information to guide prescribing. Of these, 75% were associated with three genes that affect the way an individual processes medication (CYP2C19, CYP2D6, SLCO1B1). The type of medications that showed the highest volume of ADRs that could be prevented by personalising prescribing with genetic information were treatments for psychiatric disorders (47%) and cardiovascular problems (24%). The study also found that patients who had ADRs which were able to be mitigated by PGx were more likely to be male, older, and to experience side-effects that were severe but non-fatal. Clinical trials have shown that using genetic information to guide prescribing pre-emptively, such as adjusting the dose or choosing different medication, can avoid ADRs and improve patient outcomes. This research highlights the potential of integrating pharmacogenomic testing into clinical practice to make medicines safer and more effective for patients. Dr. Emma Magavern, NIHR Clinical Academic Lecturer in Queen Mary's Centre for Clinical Pharmacology and Precision Medicine who led the study, said: "It is important to understand the landscape of side effects reported nationally over the past half century to elucidate the impact that prospective use of genetic testing to personalise prescribing may have in the UK." Professor Sir Mark Caulfield, Vice-Principal (Health) at Queen Mary and co-author, said: "This is the largest analysis of the potential role of pharmacogenomics in adverse reactions from a national spontaneous reporting system. It suggests that 9% of these reports may relate to our genetic make-up. This could be avoidable if we had measured the genetic make-up of the person before prescribing these medicines. It is time for the NHS to consider adopting pre-emptive testing for known genes that interact with medications." This study shows how reports of suspected side effects to the Yellow Card scheme can help us better understand and prevent serious side effects, including those linked to genetic factors. The MHRA Yellow Card scheme collects reports of suspected side effects from patients, the public and healthcare professionals and plays an important role in monitoring the safety of medicines in the UK. This research also reinforces the importance of our pioneering Yellow Card Biobank with Genomics England, which will help us take a more personalised, proactive approach to patient safety and make medicines safer for everyone." June Raine, MHRA Chief Executive

Lariocidin hits drug-resistant bacteria where others fail — by hijacking the ribosome at a new site, bypassing defences, and opening the door to a new generation of antibiotics. Lariocidin, a lasso-shaped peptide with promising antibiotic properties. (Graphic: Dmitrii Travin and Yury Polikanov). Research: A broad-spectrum lasso peptide antibiotic targeting the bacterial ribosome Researchers at McMaster University, in collaboration with researchers from the University of Illinois at Chicago, have discovered a powerful candidate antibiotic that can kill a broad range of bacteria, including those resistant to existing antibiotics. They have published the findings in the journal Nature. Background Antibiotic resistance occurs when bacteria evolve and develop resistance against existing antibiotics. It is a major public health crisis worldwide that makes the treatment of bacterial infections challenging. More than 4.5 million deaths occurred due to antibiotic resistance in 2019. The World Health Organization (WHO) has designated Gram-negative bacteria as a critical threat because of their ability to develop and spread antibiotic resistance, making it a top priority to discover novel antibacterial drugs. Various peptide-based antibiotics produced by microbes have shown high efficacy in treating bacterial infections. Most of these antibiotics are produced outside the ribosome, the cellular structure responsible for protein synthesis, by specialized peptide synthetases encoded in the genomes of antibiotic-producing microbes. Ribosomally synthesized and post-translationally modified peptides are rapidly gaining popularity as a novel class of antibiotics. The post-translational modifications set the three-dimensional shape of these peptides, facilitating their interactions with the target proteins and protecting them from degradation by cellular peptidases. Lasso peptides are biologically active molecules with a distinct, structurally constrained knotted fold that belong to the class of ribosomally synthesized and post-translationally modified peptides. Lasso peptides act on several bacterial targets; however, none of them has been identified as targeting the bacterial ribosome. In this Nature article, Professor Gerry Wright from McMaster University and his team reported the identification of a new lasso peptide named lariocidin that acts as a broad-spectrum antibiotic by targeting the bacterial ribosome at a unique site. Importantly, lariocidin not only inhibits protein synthesis by interfering with translocation but also induces translation errors (miscoding), giving it a dual mechanism of action. The researchers note that lariocidin meets three key criteria for a next-generation antibiotic: a novel structure, a new binding site, and a distinct mechanism of action. Lasso-shaped antibiotic co-developed by UIC evades standard drug resistance Play The study Researchers generated a collection of environmental bacterial strains by culturing them in the laboratory for approximately one year. Such a long-term culture allowed the growth of even the slowest-growing bacteria that could have otherwise been missed. They prepared methanolic extracts of individual bacterial colonies and tested them against a multidrug-resistant bacterium. This led to the identification of a novel lasso peptide, lariocidin, which was produced by a type of soil bacterium called Paenibacillus. By conducting a series of biochemical and structural experiments, they found that lariocidin is capable of killing a wide range of bacteria, including multidrug-resistant strains, by inhibiting ribosomal protein synthesis. They also found that lariocidin binds to a unique site in the small ribosomal subunit of bacteria, which is clearly distinct from the sites of action of existing antibiotics that target the small ribosomal subunit. This unique binding site enabled lariocidin to circumvent the defense mechanisms that bacteria have evolved to resist other drugs. This ribosomal binding mode relies primarily on interactions with the RNA backbone rather than the nucleobases, making it less susceptible to resistance caused by mutations at the binding site. In lab-adapted bacterial strains with a single ribosomal RNA operon, researchers identified rare spontaneous mutations in the 16S rRNA that reduced lariocidin susceptibility—further validating the ribosome as its target. The team emphasized that developing antibiotics that act at previously untapped ribosomal sites offers a way to bypass common resistance mechanisms. As observed by researchers, the unique structure of lariocidin enabled it to overcome the challenges that other antibiotics typically face when targeting the bacterial ribosome. Mechanistically, antibiotics initially enter the bacterial cell through transporters in order to inhibit protein synthesis, specifically the ribosome. However, bacteria can change or remove these transporters to block the entry of antibiotics. The strong positive charge of lariocidin, on the other hand, enabled it to enter the bacterial cell directly through the membrane without the need for transporters. This specific feature made lariocidin a broad-spectrum antibiotic. Because lariocidin bypasses the need for specific transporters, it can enter a wide range of bacterial species, reducing the likelihood of resistance developing through transporter-related mechanisms. Using a mouse model of Acinetobacter baumannii infection, researchers demonstrated that lariocidin is capable of significantly reducing the bacterial burden in various organs. They further found that the peptide has a low propensity for generating spontaneous resistance and has no cytotoxic effects on human cells. Its antimicrobial activity was even stronger in nutrient-limited media that mimic host environments, suggesting improved clinical potential compared to standard susceptibility tests in rich media. This enhanced potency was linked in part to the presence of bicarbonate, which increases bacterial membrane potential and promotes uptake of the positively charged lariocidin. All these features made lariocidin a promising candidate for further development into a clinical antibiotic for the treatment of serious bacterial multidrug-resistant infections. The study also identified a structurally related isoform, lariocidin B (LAR-B), which contains an additional isopeptide bond, forming a double-lariat structure. This may improve the stability of the molecule and marks LAR-B as the founder of a proposed new class (class V) of lasso peptides. By conducting bioinformatic analysis of available bacterial genomes, researchers suggested that there could be other ribosome-targeting lasso peptides still to be discovered in nature. They identified dozens of lariocidin-like biosynthetic gene clusters (BGCs) across multiple bacterial phyla, including Actinomycetota, Bacilliota, and Proteobacteria, suggesting a wide evolutionary distribution of this antibiotic scaffold. The researchers describe lariocidin as the first member of a previously unrecognized family of ribosome-targeting lasso peptides, with the potential for even more potent analogs to be discovered. The researchers are now working on developing strategies to modify the lasso peptide and produce it in large quantities for clinical development.

A new study led by researchers at the Earth-Life Science Institute (ELSI) at Institute of Science Tokyo has uncovered a surprising role for calcium in shaping life's earliest molecular structures. Their findings suggest that calcium ions can selectively influence how primitive polymers form, shedding light on a long-standing mystery: how life's molecules came to prefer a single "handedness" (chirality). Like our left and right hands, many molecules exist in two mirror-image forms. Yet life on Earth has a striking preference: DNA's sugars are right-handed, while proteins are built from left-handed amino acids. This phenomenon, called homochirality, is essential for life as we know it-but how it first emerged remains a major puzzle in origins of life research. The team investigated tartaric acid (TA), a simple molecule with two chiral centers, to explore how early Earth's environment might have influenced the formation of homochiral polymers. They discovered that calcium dramatically alters how TA molecules link together. Without calcium, pure left- or right-handed TA readily polymerises into polyesters, but mixtures containing equal amounts of both forms fail to form polymers readily. However, in the presence of calcium, this pattern reverses-calcium slows down the polymerisation of pure TA while enabling mixed solutions to polymerise. "This suggests that calcium availability could have created environments on early Earth where homochiral polymers were favoured or disfavoured," says Chen Chen, Special Postdoctoral Researcher at RIKEN Center for Sustainable Resource Science (CSRS), who co-led the study. The researchers propose that calcium drives this effect through two mechanisms: first, by binding with TA to form calcium tartrate crystals, which selectively remove equal amounts of both left- and right-handed molecules from the solution; and second, by altering the polymerisation chemistry of the remaining TA molecules. This process could have amplified small imbalances in chirality, ultimately leading to the uniform handedness seen in modern biomolecules. What makes this study especially intriguing is its suggestion that polyesters-simple polymers formed from molecules like tartaric acid-could have been among life's earliest homochiral molecules, even before RNA, DNA, or proteins. "The origin of life is often discussed in terms of biomolecules like nucleic acids and amino acids," ELSI's Specially Appointed Associate Professor Tony Z. Jia, who co-led the study, explains. "However, our work introduces an alternative perspective: that 'non-biomolecules' like polyesters may have played a critical role in the earliest steps toward life." The findings also highlight how different environments on early Earth could have influenced which types of polymers formed. Calcium-poor settings, such as some lakes or ponds, may have promoted homochiral polymers, while calcium-rich environments might have favoured mixed-chirality polymers. Beyond chemistry, this research bridges multiple scientific fields-biophysics, geology, and materials science-to explore how simple molecules interacted in dynamic prebiotic environments. The study is also the result of years of interdisciplinary collaboration, bringing together researchers from seven countries across Asia, Europe, Australia, and North America. We faced significant challenges in integrating all of the complex chemical, biophysical, and physical analyses in a clear and logical way. But thanks to the hard work and dedication of our team, we've uncovered a compelling new piece of the origins of life puzzle." Ruiqin Yi, project co-leader of the Guangzhou Institute of Geochemistry, Chinese Academy of Sciences This research not only deepens our understanding of life's beginnings on Earth but also suggests that similar processes could be at play on other planets, helping scientists search for life beyond our world.