Biomarker test can detect Alzheimer's pathology earlier

 

Years before tau tangles show up in brain scans of patients with Alzheimer's disease, a biomarker test developed at the University of Pittsburgh School of Medicine can detect small amounts of the clumping-prone tau protein and its misfolded pathological forms that litter the brain, cerebrospinal fluid and potentially blood, new research published today in Nature Medicine suggests.

The cerebrospinal fluid biomarker test correlates with the severity of cognitive decline, independent of other factors, including brain amyloid deposition, thereby opening doors for early-stage disease diagnosis and intervention.

Since amyloid-beta pathology often precedes tau abnormalities in Alzheimer's disease, most biomarker efforts have focused on early detection of amyloid-beta changes. However, the clumping of tau protein into well-ordered structures referred to by pathologists as "neurofibrillary tangles" is a more defining event for Alzheimer's disease as it is more strongly associated with the cognitive changes seen in affected people.

"Our test identifies very early stages of tau tangle formation -- up to a decade before any tau clumps can show up on a brain scan," said senior author Thomas Karikari, Ph.D., assistant professor of psychiatry at Pitt. "Early detection is key to more successful therapies for Alzheimer's disease since trials show that patients with little-to-no quantifiable insoluble tau tangles are more likely to benefit from new treatments than those with a significant degree of tau brain deposits."

Since many elderly people who have amyloid-beta plaques in their brains will never go on to develop cognitive symptoms of Alzheimer's disease during their lifetime, the widely adopted diagnostics framework developed by the Alzheimer's Association specifies the three neuropathological pillars necessary to diagnose the disease -- combined presence of tau and amyloid-beta pathology and neurodegeneration. In a quest for early and accessible biomarkers for Alzheimer's disease, Karikari's earlier work showed that a brain-specific form of tau, called BD-tau, can be measured in blood and reliably indicate the presence of Alzheimer's disease-specific neurodegeneration. Several years prior, Karikari showed that specific forms of phosphorylated tau, p-tau181, p-tau217 and p-tau212, in the blood can predict the presence of brain amyloid-beta without the need for costly and time-consuming brain imaging.

But these tools largely detect amyloid pathology, so the issue of early detection of tau still looms large. While tau-PET remains a reliable and accurate predictor of tau burden in the brain, the test's utility is limited by availability, low resolution, high cost, labor and sensitivity. At present, tau-PET scans can pick up the signal from neurofibrillary tangles only when a large number are present in the brain, at which point the degree of brain pathology has become pronounced and is not easily reversible.

In this latest research, using the tools of biochemistry and molecular biology, Karikari and team identified a core region of the tau protein that is necessary for neurofibrillary tangle formation. Detecting sites within that core region of 111 amino acids, a sequence they call tau_258-368,can identify clumping-prone tau proteins and help initiate further diagnostics and early treatment. In particular, the two new phosphorylation sites, p-tau-262 and p-tau-356, can accurately inform the status of early-stage tau aggregation that, with an appropriate intervention, could potentially be reversed.

"Amyloid-beta is a kindling, and tau is a matchstick. A large percentage of people who have brain amyloid-beta deposits will never develop dementia. But once the tau tangles light up on a brain scan, it may be too late to put out the fire and their cognitive health can quickly deteriorate," said Karikari. "Early detection of tangle-prone tau could identify the individuals who are likely to develop Alzheimer's-associated cognitive decline and could be helped with new generation therapies."

Other authors of this research are Eric Abrahamson, Ph.D., Xuemei Zeng, Ph.D., Anuradha Sehrawat, Ph.D., Yijun Chen, M.S., Tharick Pascoal, M.D., Ph.D., and Milos Ikonomovic, M.D., all of Pitt; Tohidul Islam, Ph.D., Przemys?aw Kac, M.S., Hlin Kvartsberg, Ph.D., Maria Olsson, B.S., Emma Sjons, B.S., Fernando Gonzalez-Ortiz, M.D., M.S., Henrik Zetterberg, M.D., Ph.D., and Kaj Blennow, M.D., Ph.D., all of University of Gothenburg, Sweden; Emily Hill, Ph.D., Ivana Del Popolo, M.S., Abbie Richardson, M.S., Victoria Mitchell, M.S., and Mark Wall, Ph.D., all of the University of Warwick, UK; Stijn Servaes, Ph.D., Joseph Therriault, Ph.D., Cécile Tissot, Ph.D., Nesrine Rahmouni, M.S., and Pedro Rosa-Neto, M.D., Ph.D., all of McGill University, Canada; Denis Smirnov, Ph.D., and Douglas Galasko, M.D., both of University of California, San Diego; Tammaryn Lashley, Ph.D., of University College London, UK.

This study was supported by, among others, the National Institute on Aging (grants R01AG083874, U24AG082930, P30AG066468, RF1AG052525-01A1, R01AG053952, R37AG023651, RF1AG025516, R01AG073267, R01AG075336, R01AG072641, P01AG14449, and P01AG025204, among others), the Swedish Research Council (grant 2021-03244), the Alzheimer's Association (grant AARF-21-850325), the Swedish Alzheimer Foundation, the Aina (Ann) Wallströms and Mary-Ann Sjöbloms Foundation, the Emil and Wera Cornells Foundation and a professorial endowment fund from the Department of Psychiatry, University of Pittsburgh.

Journal Reference:

1. Tohidul Islam, Emily Hill, Eric E. Abrahamson, Stijn Servaes, Denis S. Smirnov, Xuemei Zeng, Anuradha Sehrawat, Yijun Chen, Przemysław R. Kac, Hlin Kvartsberg, Maria Olsson, Emma Sjons, Fernando Gonzalez-Ortiz, Joseph Therriault, Cécile Tissot, Ivana Del Popolo, Nesrine Rahmouni, Abbie Richardson, Victoria Mitchell, Henrik Zetterberg, Tharick A. Pascoal, Tammaryn Lashley, Mark J. Wall, Douglas Galasko, Pedro Rosa-Neto, Milos D. Ikonomovic, Kaj Blennow, Thomas K. Karikari. Phospho-tau serine-262 and serine-356 as biomarkers of pre-tangle soluble tau assemblies in Alzheimer’s disease. Nature Medicine, 2025; DOI: 10.1038/s41591-024-03400-0 

Courtesy:

University of Pittsburgh. "Biomarker test can detect Alzheimer's pathology earlier." ScienceDaily. ScienceDaily, 10 February 2025. <www.sciencedaily.com/releases/2025/02/250210132601.htm>.

 

 

 

New treatment may offer quick cure for common cause of high blood pressure

 

Doctors at Queen Mary University of London, Barts Health NHS Trust, and University College London have led the development of a simple, minimally invasive Targeted Thermal Therapy (Triple T) that has the potential to transform medical management of a common, but commonly overlooked, cause of high blood pressure.

This breakthrough, published today in The Lancet, could, after further testing, help millions of people worldwide who currently go undiagnosed and untreated.

In the UK, Triple T, known scientifically as endoscopic ultrasound-guided radiofrequency ablation, was rigorously tested, in collaboration with researchers from University College London, University College Hospital NHS Trust, Cambridge University NHS Trust, and the University of Cambridge.

A hidden cause of high blood pressure

High blood pressure affects one in three adults, of whom a hormonal condition called primary aldosteronism accounts for one in twenty cases. However, fewer than one percent of those affected are ever diagnosed.

The condition occurs when tiny benign nodules in one or both adrenal glands produce excess aldosterone, a hormone that raises blood pressure by increasing salt levels in the body. Patients with primary aldosteronism often do not respond well to standard blood pressure medications and face higher risks of heart attacks, strokes, and kidney failure.

A game-changing alternative to surgery

Until now, the only effective cure for primary aldosteronism has been surgical removal of the entire adrenal gland, requiring general anaesthesia, a two-to three-day hospital stay, and weeks of recovery. As a result, many patients go untreated.

Triple T offers a faster, safer alternative to surgery, by selectively destroying the small adrenal nodule without removing the gland. This is made possible by recent advances in diagnostic scans, using molecular dyes that accurately identify and locate even the smallest adrenal nodules. Those in the left adrenal gland are seen to be immediately adjacent to the stomach, from where they can be directly targeted.

The new treatment harnesses the energy of waves, adapting two well-established medical techniques: radiofrequency or microwaves generate heat in a small needle placed into the malfunctioning tissue, causing a controlled burn; ultrasound uses reflected sound waves to create a real-time video of the procedure.

In Triple T, as in routine endoscopy, a tiny internal camera -- in this case using ultrasound as well as light -- is passed by mouth into the stomach. The endoscopist visualises the

adrenal gland and guides a fine needle from the stomach precisely into the nodule. Short bursts of heat destroy the nodule but leave the surrounding healthy tissues unharmed. This minimally invasive approach takes only 20 minutes and eliminates the need for internal or external incisions.

Successful trial shows promise

The study is called FABULAS, the name being an acronym for Feasibility study of radiofrequency endoscopic ABlation, with ULtrasound guidance, as a non-surgical, Adrenal Sparing treatment for aldosterone-producing adenomas.

FABULAS tested Triple T in 28 patients with primary aldosteronism, whose molecular scan had pinpointed a hormone-producing nodule in the left adrenal gland. The new procedure was found to be safe and effective, with most patients having normal hormone levels six months later. Many participants were able to stop all blood pressure medications, with no recurrence of the condition.

Professor Morris Brown, co-senior author of the FABULAS study and Professor of Endocrine Hypertension at Queen Mary University of London, said: "It is 70 years since the discovery in London of the hormone aldosterone, and, a year later, of the first patient in USA with severe hypertension due to an aldosterone-producing tumour. This patient's doctor, Jerome Conn, predicted, with perhaps only minor exaggeration, that 10-20% of all hypertensions might one day be traced to curable nodules in one or both glands. We are now able to realise this prospect, offering 21st-century breakthroughs in diagnosis and treatment."

One of the trial participants, Michelina Alfieri, shared her experience:

"Before the study, I suffered from debilitating headaches for years despite multiple GP visits. As a full-time worker and single parent, my daily life was severely affected. This non-invasive treatment provided an immediate recovery -- I was back to my normal routine straight away. I'm incredibly grateful to the team for giving me this choice."

What's next?

The success of FABULAS has led to a larger randomised trial called 'WAVE', which is comparing Triple T with traditional adrenal surgery. The results are expected in 2027.

Professor Stephen Pereira, Chief Investigator of FABULAS and Professor of Hepatology & Gastroenterology at UCL Institute for Liver and Digestive Health, added: "With appropriate training, this less invasive technique could be widely offered in endoscopy units across the UK and internationally."

Clinical Endocrinology Lead at Addenbrooke's Hospital and Professor of Clinical Endocrinology at the University of Cambridge, Professor Mark Gurnell, said: "This breakthrough was made possible thanks to the collaborative development of novel PET tracer molecules, which enable non-invasive diagnosis by allowing us to precisely locate and treat adrenal nodules for the first time.

"Thanks to this work, we may finally be able to diagnose and treat more people with primary aldosteronism, lowering their risk of developing cardiovascular diseases and other complications, and reducing the number of people dependent on long-term blood pressure medication," he added.

A major step forward for hypertension treatment

For the millions of people suffering from undiagnosed primary aldosteronism, this research offers new hope. Safely targeted thermal therapy, delivered by mouth, could replace major surgery, allowing faster recovery and better outcomes.

With further studies underway, this breakthrough treatment could soon become a standard procedure worldwide, transforming care for patients with this curable form of hypertension.

The research was primarily supported by Barts Charity, National Institute for Health and Care Research (NIHR) through the Barts and Cambridge Biomedical Research Centres (BRCs), and the British Heart Foundation.

It is being followed by a larger randomised trial, called 'WAVE', which will compare TTT to traditional surgery in 120 patients. The results are expected in 2027.

Journal Reference:

1. Giulia Argentesi, Xilin Wu, Alexander Ney, Emily Goodchild, Kate Laycock, Yun-Ni Lee, Russell Senanayake, James MacFarlane, Elisabeth Ng, Jessica Kearney, Sam O'Toole, Jackie Salsbury, Nick Carroll, Daniel Gillett, John A Tadross, Alison Marker, Edmund M Godfrey, George Goodchild, Jonathan P Bestwick, Mark Gurnell, Heok Cheow, Stephen P Pereira, William M Drake, Morris J Brown, Jose Bastos, Elena D Benu, Elizabeth Cervi, Patrizia Ebano, Razeen Mahroof, Iulia Munteanu, August Palma, Patrick Wilson. Endoscopic, ultrasound-guided, radiofrequency ablation of aldosterone-producing adenomas (FABULAS): a UK, multicentre, prospective, proof-of-concept trial. The Lancet, 2025; DOI: 10.1016/S0140-6736(24)02755-7 

Courtesy:

Queen Mary University of London. "New treatment may offer quick cure for common cause of high blood pressure." ScienceDaily. ScienceDaily, 10 February 2025. <www.sciencedaily.com/releases/2025/02/250210132401.htm>.

 

 

Novel 'living' biomaterial aims to advance regenerative medicine

A biomaterial that can mimic certain behaviors within biological tissues could advance regenerative medicine, disease modeling, soft robotics and more, according to researchers at Penn State.

Materials created up to this point to mimic tissues and extracellular matrices (ECMs) -- the body's biological scaffolding of proteins and molecules that surrounds and supports tissues and cells -- have all had limitations that hamper their practical applications, according to the team. To overcome some of those limitations, the researchers developed a bio-based, "living" material that encompasses self-healing properties and mimics the biological response of ECMs to mechanical stress.

They published their results in Materials Horizons, where the research was also featured on the cover of the journal.

"We developed a cell-free -- or acellular -- material that dynamically mimics the behavior of ECMs, which are key building blocks of mammalian tissues that are crucial for tissue structure and cell functions," said corresponding author Amir Sheikhi, associate professor of chemical engineering and the Dorothy Foehr Huck and J. Lloyd Huck Early Career Chair in Biomaterials and Regenerative Engineering.

According to the researchers, previous iterations of their material -- a hydrogel, or water-rich polymer network -- were synthetic and lacked the desired combination of mechanical responsiveness and biological mimicry of ECMs.

"Specifically, these materials need to replicate nonlinear strain-stiffening, which is when ECM networks stiffen under strain caused by physical forces exerted by cells or external stimuli," Sheikhi said, explaining nonlinear strain-stiffening is important for providing structural support and facilitating cell signaling. "The materials also need to replicate the self-healing properties necessary for tissue structure and survival. Prior synthetic hydrogels had difficulties in balancing material complexity, biocompatibility and mechanical mimicry of ECMs."

The team addressed these limitations by developing acellular nanocomposite living hydrogels (LivGels) made from "hairy" nanoparticles. The nanoparticles are composed of nanocrystals, or "nLinkers," with disordered cellulose chains, or "hairs," at the ends. These hairs introduce anisotropy, meaning the nLinkers have different properties depending on their directional orientation and allow dynamic bonding with biopolymer networks. In this case, the nanoparticles bonded with a biopolymeric matrix of modified alginate, which is a natural polysaccharide found in brown algae.

"These nLinkers form dynamic bonds within the matrix that enable strain-stiffening behavior, that is, mimicking ECM's response to mechanical stress; and self-healing properties, which restore integrity after damage," Sheikhi said, noting that the researchers used rheological testing, which measures how material behaves under various stressors, to measure how rapidly the LivGels recovered their structure after high strain. "This design approach allowed fine-tuning of the material's mechanical properties to match those of natural ECMs."

Critically, Sheikhi said, this material is entirely made of biological materials and avoids synthetic polymers with potential biocompatibility issues. Beyond mitigating the limitations of previously developed materials, LivGels achieve the dual traits of nonlinear mechanics and self-healing without sacrificing structural integrity. The nLinkers specifically facilitate dynamic interactions that allow precise control of stiffness and strain-stiffening properties. Taken together, the design approach converts bulk, static hydrogels to dynamic hydrogels that closely mimic ECMs.

The potential applications include scaffolding for tissue repair and regeneration within regenerative medicine, simulating tissue behavior for drug testing and creating realistic environments for studying disease progression. The researchers said it could also be used for 3D bioprinting customizable hydrogels or for developing soft robotics with adaptable mechanical properties.

"Our next steps include optimizing LivGels for specific tissue types, exploring in vivo applications for regenerative medicine, integrating LivGels with 3D bioprinting platforms and investigating potential in dynamic wearable or implantable devices," Sheikhi said.

Roya Koshani, a chemical engineering post-doctoral scholar at Penn State, and Sina Kheirabadi, a doctoral candidate in chemical engineering at Penn State, were co-authors on the paper. Sheikhi is also affiliated with the Departments of Biomedical Engineering, of Chemistry and of Neurosurgery, and with the Huck Institutes of the Life Sciences.

Support for this research was provided by Penn State, including from: the Dorothy Foehr Huck and J. Lloyd Huck Early Career Chair; the Convergence Center for Living Multifunctional Material Systems and the Cluster of Excellence Living, Adaptive and Energy-autonomous Materials Systems Living Multifunctional Materials Collaborative Research Seed Grant Program; the Materials Research Institute; and the College of Engineering Materials Matter at the Human Level seed grants.

Journal Reference:

1. Roya Koshani, Sina Kheirabadi, Amir Sheikhi. Nano-enabled dynamically responsive living acellular hydrogels. Materials Horizons, 2025; 12 (1): 103 DOI: 10.1039/D4MH00922C

Courtesy:

 Penn State. "Novel 'living' biomaterial aims to advance regenerative medicine." ScienceDaily. ScienceDaily, 6 February 2025. <www.sciencedaily.com/releases/2025/02/250206155347.htm>.

Cancer mortality continues to drop despite rising incidence in women

The American Cancer Society (ACS) today released Cancer Statistics, 2025, the organization's annual report on cancer facts and trends. The new findings show the cancer mortality rate declined by 34% from 1991 to 2022 in the United States, averting approximately 4.5 million deaths. However, this steady progress is jeopardized by increasing incidence for many cancer types, especially among women and younger adults, shifting the burden of disease. For example, incidence rates in women 50-64 years of age have surpassed those in men, and rates in women under 50 are now 82% higher than their male counterparts, up from 51% in 2002. This pattern includes lung cancer, which is now higher in women than in men among people younger than 65 years. These important findings are published today in CA: A Cancer Journal for Clinicians, alongside its consumer-friendly companion, Cancer Facts & Figures 2025, available on cancer.org.

"Continued reductions in cancer mortality because of drops in smoking, better treatment, and earlier detection is certainly great news," said Rebecca Siegel, senior scientific director, surveillance research at the American Cancer Society and lead author of the report. "However, this progress is tempered by rising incidence in young and middle-aged women, who are often the family caregivers, and a shifting cancer burden from men to women, harkening back to the early 1900s when cancer was more common in women."

Overall, in 2025, there will be an estimated 2,041,910 new cancer diagnoses in the U.S. (5,600 each day) and 618,120 cancer deaths. In addition to projecting the contemporary cancer burden,ACS researchers compiled the most recent findings on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries (through 2021) and mortality data collected by the National Center for Health Statistics (through 2022).

The report also highlights lagging progress against pancreatic cancer, which is the third leading cause of cancer death in the U.S. Both incidence and mortality rates are increasing, and the five-year survival rate is just 8% for the 9 out of 10 people diagnosed with pancreatic exocrine tumors.

"With a critical need to do better, ACS is constantly working to help advance efforts to aid in the discovery of new treatments for cancer patients and care for survivors," explained Dr. William Dahut, chief scientific officer at the American Cancer Society. "As the largest non-government, non-profit funding source of cancer research in the U.S., we are currently financing more than $450 million in grants to scientists. Our goal is to find answers that help save lives."

Other highlights from the report include:

• Despite overall declines in cancer mortality, death rates are increasing in both men and women for cancers of the oral cavity and pancreas, but just for women for uterine corpus (also known as endometrial) and liver cancers.
• Additionally, alarming inequalities in cancer mortality persist, with rates in Native American people 2-3 times higher than White people for kidney, liver, stomach, and cervical cancers. Black people are twice as likely to die of prostate, stomach, and uterine corpus cancers compared to White people and 50% more likely to die from cervical cancer, which is preventable.
• Incidence rates continue to climb for common cancers, including breast (female), prostate (steepest increase at 3% per year from 2014-2021), pancreatic, uterine corpus, melanoma (female), liver (female), and oral cancers associated with the human papillomavirus.
• The rate of new diagnoses of colorectal cancer in men and women younger than 65 years of age and cervical cancer in women (30-44 years of age) has also increased.
• Cancer incidence in children (14 years of age and younger) declined in recent years after decades of increase but continued to rise among adolescents (ages 15-19 years). Mortality rates have dropped by 70% in children and by 63% in adolescents since 1970, largely because of improved treatment for leukemia.

"Progress against cancer continues to be hampered by striking, wide static disparities for many racial and ethnic groups," said Dr. Ahmedin Jemal, senior vice president, surveillance and health equity science at the American Cancer Society and senior author of the study. "It's essential to help end discrimination and inequality in cancer care for all populations. Taking this step is vital to closing this persistent gap and moving us closer to ending cancer as we know it, for everyone."

"This report underscores the need to increase investment in both cancer treatment and care, including equitable screening programs, especially for underserved groups of patients and survivors. Screening programs are a critical component of early detection, and expanding access to these services will save countless lives," said Dr. Wayne A. I. Frederick, interim chief executive officer of the American Cancer Society and the American Cancer Society Cancer Action Network (ACS CAN). "We also must address these shifts in cancer incidence, mainly among women. A concerted effort between healthcare providers, policymakers and communities needs to be prioritized to assess where and why mortality rates are rising."

Other ACS authors participating in this study include Tyler Kratzer, Angela Giaquinto, and Dr. Hyuna Sung.

Journal Reference:

1. Rebecca L. Siegel, Tyler B. Kratzer, Angela N. Giaquinto, Hyuna Sung, Ahmedin Jemal. Cancer statistics, 2025. CA: A Cancer Journal for Clinicians, 2025; DOI: 10.3322/caac.21871 

Courtesy:

American Cancer Society. "Cancer mortality continues to drop despite rising incidence in women." ScienceDaily. ScienceDaily, 16 January 2025. <www.sciencedaily.com/releases/2025/01/250116133445.htm>.

 

 

 

 

Polymer research shows potential replacement for common superglues with a reusable and biodegradable alternative

Researchers at Colorado State University and their partners have developed an adhesive polymer that is stronger than current commercially available options while also being biodegradable and reusable. The findings -- described in Science - show how the common, naturally occurring polymer P3HB can be chemically re-engineered for use as a strong yet sustainable bonding agent.

Adhesives are commonly used in automotives, packaging, electronics, solar cells and construction, among many other areas. Together they make up a roughly $50 billion industry that supports much of our modern life but also contributes to the mounting issue of plastic waste. The paper describes the team's work using experimental, simulation and process modeling to develop a replacement polymer.

The project was led by University Distinguished Professor Eugene Chen in the Department of Chemistry. Other partners on the paper include Gregg Beckham at the National Renewable Energy Laboratory and Professor Ting Xu at the University of California, Berkley and researchers from their groups.

Chen said that poly(3-hydroxybutyrate), or P3HB, is a natural, biobased and biodegradable polymer that can be produced by microbes under the right biological conditions. While the polymer is not adhesive when made that way, his lab was able to chemically re-engineer its structure to now deliver stronger adhesion than the common petroleum-derived, nonbiodegradable options when used on various substrates or surfaces such as aluminum, glass and wood. The adhesion strength of the re-engineered P3HB can also be tuned to accommodate different application needs.

The findings are part of a larger goal by Chen's group to improve and expand our ability to tackle the global plastics pollution crisis. His team is involved in many efforts to develop chemically recyclable, biodegradable and, overall, more sustainable alternatives to today's plastic materials. He said that while many people inherently recognize the life cycle issues that come with a disposable water bottle, adhesives present more daunting issues with fewer potential solutions.

"Petroleum-based thermoset adhesives such as Gorilla Glue and J-B Weld, along with thermoplastic hot melts, can be very difficult or even impossible to recycle or recover -- primarily because of their strong bonds to other materials," he said. "Our approach instead offers a biodegradable material that can be used in a variety of industries with tunable or even higher strength compared to those options."

Ethan Quinn is a Ph.D. student at CSU and served as a co-lead author on the paper with postdoctoral researcher Zhen Zhang. Quinn said he and Zhang led work around the creation and testing of the material.

"We developed a sample P3HB glue stick and were able to use it with a commercially available glue gun to test its application in sealing cardboard boxes and other properties on steel plates," Quinn said. "I knew the data supported it being stronger than other options, but I was shocked that we were able to show that it far out-performs typical hot-melt options -- holding up to 20 pounds in place compared to the 15 pounds an existing adhesive could not manage."

Chen said P3HB is biodegradable under a variety of instances, including managed and unmanaged environments. That means it will biodegrade naturally in landfills just as well as salty ocean water or soils, for example. That expands the range of possible options for dealing with the material at the end of its life cycle. The P3HB adhesive can also be recovered, reprocessed and reused.

The CSU team will now start work on ways to commercialize the polymer for broad use.

"We are working on two different approaches aiming for mass production, including ways to lower the overall cost and environmental impacts," Chen said. "The analysis performed by the NREL team has identified key areas where we could make improvements, and we will continue to work with the BOTTLE Consortium on those scaling efforts."

Journal Reference:

1. Zhen Zhang, Ethan C. Quinn, Jacob K. Kenny, Alexandra Grigoropoulos, Jason S. DesVeaux, Tiffany Chen, Li Zhou, Ting Xu, Gregg T. Beckham, Eugene Y.-X. Chen. Stereomicrostructure-regulated biodegradable adhesives. Science, 2025; 387 (6731): 297 DOI: 10.1126/science.adr7175 

Courtesy:

Colorado State University. "Polymer research shows potential replacement for common superglues with a reusable and biodegradable alternative." ScienceDaily. ScienceDaily, 16 January 2025. <www.sciencedaily.com/releases/2025/01/250116161241.htm>.

 

 

 

 

Three million years ago, our ancestors were vegetarian

Human ancestors like Australopithecus -- which lived around 3.5 million years ago in southern Africa -- ate very little to no meat, according to new research published in the scientific journal Science. This conclusion comes from an analysis of nitrogen isotope isotopes in the fossilized tooth enamel of seven Australopithecus individuals. The data revealed that these early hominins primarily relied on plant-based diets, with little to no evidence of meat consumption.

The consumption of animal resources, especially meat, is considered a crucial turning point in human evolution. This protein-rich food has been linked to the increase in brain volume and the ability to develop tools. However, direct evidence of when meat emerged among our early ancestors, and of how its consumption developed though time, has been elusive. A team of researchers from the Max Planck Institute for Chemistry in Germany and the University of the Witwatersrand in South Africa (Wits University) now provide evidence that human ancestors of the genus Australopithecus that lived in southern Africa between 3.7 and 3.3 million years ago subsisted mostly on plants.

The research team analyzed stable isotope data from tooth enamel of Australopithecus individuals found in the Sterkfontein cave near Johannesburg, part of South Africa's "Cradle of Humankind," an area known for its rich collection of early hominins fossils. They compared the isotopic data of Australopithecus with that from tooth samples of coexisting animals, including monkeys, antelopes, and large predators such as hyenas, jackals, and big cats.

Tooth enamel preserved dietary signatures

"Tooth enamel is the hardest tissue of the mammalian body and can preserve the isotopic fingerprint of an animal's diet for millions of years," says geochemist Tina Lüdecke, lead author of the study. Lüdecke has led the "Emmy-Noether Junior Research Group for Hominin Meat Consumption" at the Mainz-based Max Planck Institute for Chemistry since 2021 and is an Honorary Research Fellow at the Evolutionary Studies Institute of the University of the Witwatersrand in Johannesburg. She regularly travels to Africa to sample fossilized teeth for her analysis. Wits University owns the Sterkfontein Caves and is the custodian of the Australopithecus fossils.

When animals digest food, biochemical reactions favor the "light" isotope of nitrogen (¹⁴N). Consequently, the degradation products that are produced in their body contain high proportions of ¹⁴N. The excretion of these "light" nitrogen compounds in urine, feces, or sweat increases the ratio of "heavy" nitrogen (¹⁵N) to this "light" nitrogen the body in comparison to the food it eats. This means that herbivores have a higher nitrogen isotope ratio than the plants they consume, while carnivores in turn have a higher nitrogen isotope ratio than their prey. Therefore, the higher the ¹⁵N to ¹⁴N ratio in a tissue sample, the higher is the trophic position of the organism in the food web.

Nitrogen isotope ratios have long been used to study the diets of modern animals and humans in hair, claws, bones and many other organic materials. However, in fossil material, these measurements have previously been limited to samples that are only a few tens of thousands of years old due to the degradation of organic material over time. In this study, Tina Lüdecke used a novel technique developed in Alfredo Martínez-García's laboratory at the Max Planck Institute for Chemistry, to measure nitrogen isotopes ratios in fossilized tooth enamel that is millions of years old.

Evidence of mostly plant-based food

The team of researchers found that the nitrogen isotope ratios in the tooth enamel of Australopithecus varied, but were consistently low, similar to those of herbivores, and much lower than those of contemporary carnivores. They conclude that the diet of these hominins was variable but consisted largely or exclusively of plant-based food. Therefore,Australopithecus did not regularly hunt large mammals like, for example, the Neanderthals did a few million years later. While the researchers cannot completely rule out the possibility of occasional consumption of animal protein sources like eggs or termites, the evidence indicates a diet that was predominantly vegetarian.

Further research on fossilized tooth enamel

Lüdecke's team plans to expand their research, collecting more data from different hominin species and time periods. They aim to examine fossils from other key sites in eastern and southern Africa as well as southeast Asia to explore when meat consumption began, how it evolved, and whether it provided an evolutionary advantage for our ancestors.

"This method opens up exciting possibilities for understanding human evolution, and it has the potential to answer crucial questions, for example, when did our ancestors begin to incorporate meat in their diet? And was the onset of meat consumption linked to an increase in brain volume?" says Alfredo Martínez-García, from the Max Planck institute for Chemistry.

"This work represents a huge step in extending our ability to better understand diets and trophic level of all animals back into the scale of millions of years. The research provides clear evidence that its diet did not contain significant amounts of meat. We are honoured that the pioneering application of this new method was spearheaded at Sterkfontein, a site that continues to make fundamental contributions to science even 89 years after the first hominin fossils were discovered there by Robert Broom," says Professor Dominic Stratford, Director of Research at the Sterkfontein Caves and co-author of the paper.

The study was funded by the Max Planck Society. Tina Lüdecke's research group is supported by the Emmy Noether program of the German Research Foundation (DFG).

Journal Reference:

1. Tina Lüdecke, Jennifer N. Leichliter, Dominic Stratford, Daniel M. Sigman, Hubert Vonhof, Gerald H. Haug, Marion K. Bamford, Alfredo Martínez-García. Australopithecus at Sterkfontein did not consume substantial mammalian meat. Science, 2025; 387 (6731): 309 DOI: 10.1126/science.adq7315 

Courtesy:

University of the Witwatersrand. "Three million years ago, our ancestors were vegetarian." ScienceDaily. ScienceDaily, 17 January 2025. <www.sciencedaily.com/releases/2025/01/250117112232.htm>.

 

 

 

 

 

Drug-resistant hookworms put pets and people at risk

 

Canine hookworms are becoming increasingly resistant to drugs across Australia, according to new research.

Scientists at The University of Queensland and The University of Sydney have identified widespread resistance to benzimidazole-based dewormers which are commonly used to treat gastrointestinal parasites in dogs.

Dr Swaid Abdullah from UQ's School of Veterinary Science said almost 70 per cent of the hookworm samples studied showed genetic mutations that can cause drug resistance.

"This is a big problem, as hookworm infections can be dangerous for both humans and animals," Dr Abdullah said.

"In dogs, hookworm infections primarily affect the small intestine leading to anaemia, diarrhea, and malnutrition.

"But worse still, the parasites can spread to humans through the skin.

"In people, hookworms from dogs can cause cutaneous larva migrans (CLM) disease -- or 'creeping eruption' -- which is a winding, snake-like rash with blisters and itching."

Dr Abdullah said the best weapons against canine hookworms have been benzimidazole-based dewormers, but they are starting to fail.

"This level of resistance is an urgent issue for pet and public health," he said.

The study team used advanced parasitological diagnostics to examine samples from more than 100 animals in Australia and New Zealand.

The results showed resistance was spreading through hookworm species including the northern hookworm, which had previously been thought to be unaffected.

Professor Jan Šlapeta from The University of Sydney said routine reliance on deworming drugs is likely fuelling the development of resistance

"Responsible parasite management by veterinarians is going to be vital moving forward," Professor Šlapeta said.

"We're calling for a shift toward targeted, risk-based treatment to curb the spread of resistant hookworm.

"Responsible doctors don't give blanket antibiotics to any and all of their patients, and deworming should be approached in the same way if we're to limit drug resistance.

"As resistance spreads, we need ongoing monitoring and the development of new control strategies to protect animal and human health.

"This study is a wake-up call for both pet owners and veterinarians alike -- the era of effortless parasite control may be coming to an end."

Journal Reference:

1. Swaid Abdullah, Thomas Stocker, Hyungsuk Kang, Ian Scott, Douglas Hayward, Susan Jaensch, Michael P. Ward, Malcolm K. Jones, Andrew C. Kotze, Jan Šlapeta. Widespread occurrence of benzimidazole resistance single nucleotide polymorphisms in the canine hookworm, Ancylostoma caninum, in Australia. International Journal for Parasitology, 2024; DOI: 10.1016/j.ijpara.2024.12.001 

Courtesy:

University of Queensland. "Drug-resistant hookworms put pets and people at risk." ScienceDaily. ScienceDaily, 6 January 2025. <www.sciencedaily.com/releases/2025/01/250106221710.htm>.

 

 

 

 

Hornwort genomes provide clues on how plants conquered the land

 

Over 450 million years ago, plants began the epic transition from water to dry land. Among the first pioneers were the ancestors of humble hornworts, a group of small, unassuming plants that have persisted to this day. New research reveals insights into the genetic blueprints of hornworts, uncovering fascinating details about plant evolution and the early days of life on land.

"We began by decoding the genomes of ten hornwort species, representing all known families within this unique plant group," said Peter Schafran, a postdoctoral scientist at the Boyce Thompson Institute (BTI) and first author of the study. "What we found was unexpected: hornworts have maintained remarkably stable chromosomes despite evolving separately for over 300 million years."

Unlike many plants, hornworts have not experienced whole-genome duplication (where an organism's entire genetic material is duplicated). This absence of duplication has resulted in stable "autosomes" -- the chromosomes that hold most of an organism's genetic material -- which have remained relatively unchanged across hornworts despite their deep evolutionary history.

However, not all parts of the hornwort genome are so static. The study revealed the presence of "accessory chromosomes" -- extra genetic material that isn't essential for survival but can provide additional benefits. These accessory chromosomes are much more dynamic, evolving rapidly and varying even within individual plants. Additionally, the international team of researchers identified potential sex chromosomes in some species, shedding light on the evolution of plant reproductive strategies.

The study, recently published in Nature Plants, also provided insights into specific plant traits. For example, the researchers uncovered new information about genes involved in flavonoid production (pigments that protect against UV radiation), stomata formation (tiny pores that regulate gas exchange), and hormone signaling. These findings help refine our understanding of how early land plants adapted to their new, challenging environment.

The research project's extensive genetic investigation of hornworts makes them the most thoroughly sequenced plant group relative to their total number of species.

By creating a comprehensive "pan-phylum" dataset for hornworts, the research team has developed a resource to help scientists comprehend how life on Earth has evolved. It provides insights into how plants might adapt to future environmental challenges and could inform efforts to engineer more resilient crops.

"Our research demonstrates the importance of studying diverse organisms, not just well-known model species," said Fay-Wei Li, associate professor at BTI and lead author. "By expanding our knowledge of hornworts, we gain a more complete picture of plant evolution and the incredible diversity of life on our planet."

Journal Reference:

1. Peter Schafran, Duncan A. Hauser, Jessica M. Nelson, Xia Xu, Lukas A. Mueller, Samarth Kulshrestha, Isabel Smalley, Sophie de Vries, Iker Irisarri, Jan de Vries, Kevin Davies, Juan Carlos A. Villarreal, Fay-Wei Li. Pan-phylum genomes of hornworts reveal conserved autosomes but dynamic accessory and sex chromosomes. Nature Plants, 2025; DOI: 10.1038/s41477-024-01883-w

Courtesy:

Boyce Thompson Institute. "Hornwort genomes provide clues on how plants conquered the land." ScienceDaily. ScienceDaily, 6 January 2025. <www.sciencedaily.com/releases/2025/01/250106132143.htm>.

 

 

 

 

Breakthrough for 'smart cell' design

 

Rice University bioengineers have developed a new construction kit for building custom sense-and-respond circuits in human cells. The research, published in the journal Science, represents a major breakthrough in the field of synthetic biology that could revolutionize therapies for complex conditions like autoimmune disease and cancer.

"Imagine tiny processors inside cells made of proteins that can 'decide' how to respond to specific signals like inflammation, tumor growth markers or blood sugar levels," said Xiaoyu Yang, a graduate student in the Systems, Synthetic and Physical Biology Ph.D. program at Rice who is the lead author on the study. "This work brings us a whole lot closer to being able to build 'smart cells' that can detect signs of disease and immediately release customizable treatments in response."

The new approach to artificial cellular circuit design relies on phosphorylation -- a natural process cells use to respond to their environment that features the addition of a phosphate group to a protein. Phosphorylation is involved in a wide range of cellular functions, including the conversion of extracellular signals into intracellular responses -- e.g., moving, secreting a substance, reacting to a pathogen or expressing a gene.

In multicellular organisms, phosphorylation-based signaling often involves a multistage, cascading effect like falling dominoes. Previous attempts at harnessing this mechanism for therapeutic purposes in human cells have focused on re-engineering native, existing signaling pathways. However, the complexity of the pathways makes them difficult to work with, so applications have remained fairly limited.

Thanks to Rice researchers' new findings, however, phosphorylation-based innovations in "smart cell" engineering could see a significant uptick in the coming years. What enabled this breakthrough was a shift in perspective:

Phosphorylation is a sequential process that unfolds as a series of interconnected cycles leading from cellular input (i.e. something the cell encounters or senses in its environment) to output (what the cell does in response). What the research team realized -- and set out to prove -- was that each cycle in a cascade can be treated as an elementary unit, and these units can be linked together in new ways to construct entirely novel pathways that link cellular inputs and outputs.

"This opens up the signaling circuit design space dramatically," said Caleb Bashor, an assistant professor of bioengineering and biosciences and corresponding author on the study. "It turns out, phosphorylation cycles are not just interconnected but interconnectable -- this is something that we were not sure could be done with this level of sophistication before.

"Our design strategy enabled us to engineer synthetic phosphorylation circuits that are not only highly tunable but that can also function in parallel with cells' own processes without impacting their viability or growth rate."

While this may sound straightforward, figuring out the rules for how to build, connect and tune the units -- including the design of intra- and extracellular outputs -- was anything but. Moreover, the fact that synthetic circuits could be built and implemented in living cells was not a given.

"We didn't necessarily expect that our synthetic signaling circuits, which are composed entirely of engineered protein parts, would perform with a similar speed and efficiency as natural signaling pathways found in human cells," Yang said. "Needless to say, we were pleasantly surprised to find that to be the case. It took a lot of effort and collaboration to pull it off."

The do-it-yourself, modular approach to cellular circuit design proved capable of reproducing an important systems-level ability of native phosphorylation cascades, namely amplifying weak input signals into macroscopic outputs. Experimental observations of this effect verified the team's quantitative modelling predictions, reinforcing the new framework's value as a foundational tool for synthetic biology.

Another distinct advantage of the new approach to sense-and-respond cellular circuit design is that phosphorylation occurs rapidly in only seconds or minutes, so the new synthetic phospho-signaling circuits could potentially be programmed to respond to physiological events that occur on a similar timescale. In contrast, many previous synthetic circuit designs were based on different molecular processes such as transcription, which can take many hours to activate.

The researchers also tested the circuits for sensitivity and ability to respond to external signals like inflammatory factors. To prove its translational potential, the team used the framework to engineer a cellular circuit that can detect these factors and could be used to control autoimmune flare-ups and reduce immunotherapy-associated toxicity.

"Our research proves that it is possible to build programmable circuits in human cells that respond to signals quickly and accurately, and it is the first report of a construction kit for engineering synthetic phosphorylation circuits," said Bashor, who also serves as deputy director for the Rice Synthetic Biology Institute, which was launched earlier this year in order to capitalize on Rice's deep expertise in the field and catalyze collaborative research.

Caroline Ajo-Franklin, who serves as institute director, said the study's findings are an example of the transformative work Rice researchers are doing in synthetic biology.

"If in the last 20 years synthetic biologists have learned how to manipulate the way bacteria gradually respond to environmental cues, the Bashor lab's work vaults us forward to a new frontier -- controlling mammalian cells' immediate response to change," said Ajo-Franklin, a professor of biosciences, bioengineering, chemical and biomolecular engineering and a Cancer Prevention and Research Institute of Texas Scholar.

 

Journal Reference:

1. Xiaoyu Yang, Jason W. Rocks, Kaiyi Jiang, Andrew J. Walters, Kshitij Rai, Jing Liu, Jason Nguyen, Scott D. Olson, Pankaj Mehta, James J. Collins, Nichole M. Daringer, Caleb J. Bashor. Engineering synthetic phosphorylation signaling networks in human cells. Science, 2025; 387 (6729): 74 DOI: 10.1126/science.adm8485 

Courtesy:

Rice University. "Breakthrough for 'smart cell' design." ScienceDaily. ScienceDaily, 3 January 2025. <www.sciencedaily.com/releases/2025/01/250103124934.htm>.

 

 

 

Virus that threatened humanity opens the future

 Professor Sangmin Lee from POSTECH's Department of Chemical Engineering, in collaboration with 2024 Nobel Chemistry Laureate Professor David Baker from the University of Washington, has developed an innovative therapeutic platform by mimicking the intricate structures of viruses using artificial intelligence (AI). Their pioneering research was published in Nature on December 18.

Viruses are uniquely designed to encapsulate genetic material within spherical protein shells, enabling them to replicate and invade host cells, often causing disease. Inspired by these complex structures, researchers have been exploring artificial proteins modeled after viruses. These "nanocages" mimic viral behavior, effectively delivering therapeutic genes to target cells. However, existing nanocages face significant challenges: their small size restricts the amount of genetic material they can carry, and their simple designs fall short of replicating the multifunctionality of natural viral proteins.

To address these limitations, the research team used AI-driven computational design. While most viruses display symmetrical structures, they also feature subtle asymmetries. Leveraging AI, the team recreated these nuanced characteristics and successfully designed nanocages in tetrahedral, octahedral, and icosahedral shapes for the first time.

The resulting nanostructures are composed of four types of artificial proteins, forming intricate architectures with six distinct protein-protein interfaces. Among these, the icosahedral structure, measuring up to 75 nanometers in diameter, stands out for its ability to hold three times more genetic material than conventional gene delivery vectors, such as adeno-associated viruses (AAV), marking a significant advancement in gene therapy.

Electron microscopy confirmed the AI-designed nanocages achieved precise symmetrical structures as intended. Functional experiments further demonstrated their ability to effectively deliver therapeutic payloads to target cells, paving the way for practical medical applications.

"Advancements in AI have opened the door to a new era where we can design and assemble artificial proteins to meet humanity's needs," said Professor Sangmin Lee. "We hope this research not only accelerates the development of gene therapies but also drives breakthroughs in next-generation vaccines and other biomedical innovations."

Professor Lee previously worked as a postdoctoral researcher in Professor Baker's laboratory at the University of Washington for nearly three years, from February 2021 to late 2023, before joining POSTECH in January 2024.

This study was supported by the Republic of Korea's Ministry of Science and ICT under the Outstanding Young Scientist Program, the Nano and Material Technology Development Program, and the Global Frontier Research Program, with additional funding provided by the Howard Hughes Medical Institute (HHMI) in the United States.

Journal Reference:

1. Sangmin Lee, Ryan D. Kibler, Green Ahn, Yang Hsia, Andrew J. Borst, Annika Philomin, Madison A. Kennedy, Buwei Huang, Barry Stoddard, David Baker. Four-component protein nanocages designed by programmed symmetry breaking. Nature, 2024; DOI: 10.1038/s41586-024-07814-1 

Courtesy:

Pohang University of Science & Technology (POSTECH). "Virus that threatened humanity opens the future." ScienceDaily. ScienceDaily, 27 December 2024. <www.sciencedaily.com/releases/2024/12/241225145516.htm>.