The team has found that a class of protective proteins known as MANF plays a role in the process that keep cells efficient and working well.

The findings appear in the journal Proceedings of the National Academy of Sciences.

Our cells make proteins and discard them after they perform their jobs. This efficient, continuous maintenance process is known as cellular homeostasis. However, as we age, our cells’ ability to keep up declines.

Cells can create proteins incorrectly, and the cleanup process can become faulty or overwhelmed. As a result, proteins can clump together, leading to a harmful buildup that has been linked to such diseases as Alzheimer’s and Parkinson’s.

“If the cells are experiencing stress because this protein aggregation has started, the endoplasmic reticulum, which is where proteins are made and then released, gets the signal to stop making these proteins,” explains biology professor Bhagwati Gupta, who supervised the research.

“If it can’t correct the problem, the cell will die, which ultimately leads to degeneration of the neurons and then neurodegenerative diseases that we see.”

Previous studies, including one from McMaster, had shown that MANF protects against increased cellular stress. The team set out to understand how this happens by studying microscopic worms known as C. elegans. They created a system to manipulate the amount of MANF in C. elegans.

“We could literally see where MANF was expressed in the worms because they are translucent. We could see it in all different tissues. Within these tissues, MANF was present in structures known as lysosomes which are associated with lifespan and protein aggregation,” said Shane Taylor, now a post-doctoral fellow at the University of British Columbia who worked on the project for his PhD while at McMaster.

The team discovered that MANF plays a key role in the cell’s disposal process by helping to break down the accumulated proteins, keeping cells healthier and clutter-free.

Increasing MANF levels also activates a natural clean-up system within cells, helping them function better for longer.

“Although our research focused on worms, the findings uncover universal processes. MANF is present in all animals, including humans. We are learning fundamental and mechanistic details that could then be tested in higher systems,” said Taylor.

To develop MANF as a potential therapy, researchers want to understand what other players MANF interacts with.

“Discovering MANF’s role in cellular homeostasis suggests that it could be used to develop treatments for diseases that affect the brain and other parts of the body by targeting cellular processes, clearing out these toxic clumps in cells and maintaining their health,” said Gupta.

“The central idea of aging research is basically can we make the processes better and more efficient. By understanding how MANF works and targeting its function, we could develop new treatments for age-related diseases. We want to live longer and healthier. These kinds of players could help that.”

Published in the journal Aging Cell on October 18, 2024, in collaboration with researchers from the National Institutes of Health (NIH) and Duke University, the study identified a protein linked to the cardiovascular health of animal models with progeria that could translate to human treatments. Heart failure and stroke are the most common causes of death for people with HGPS, who typically have a life expectancy between 6 and 20 years old.

These new findings from the lab of UMD Cell Biology and Molecular Genetics Professor Kan Cao are “highly promising,” according to lead author and biological sciences Ph.D. student Sahar Vakili.

“This could pave the way for new treatments targeting cardiovascular complications in HGPS, which are currently a major cause of mortality in the affected children,” Vakili said. “Beyond progeria, insights gained from this research might also be applicable to other age-related diseases where endothelial dysfunction plays a role.”

Sometimes called the “Benjamin Button disease,” HGPS causes a variety of symptoms associated with aging, including skin wrinkling, joint stiffness, and the loss of hair and body fat. The disease stems from a mutation in the LMNA(lamin A) gene, which produces a protein that helps to keep cells healthy.

To better understand how progeria causes cardiovascular complications, the research team looked at endothelial cells. These cells line the body’s vascular system — including the heart — and control substances moving in and out of the bloodstream. When endothelial cells malfunction, it can lead to an array of conditions, including cardiovascular disease, stroke, blood clots and atherosclerosis (buildup of plaque inside the arteries).

More specifically, the researchers wanted to understand the signals sent by endothelial cells that ultimately lead to HGPS-related cardiovascular disease. For the first time, the team discovered that Angiopoietin-2 (Ang2) — a protein that regulates the formation of new blood vessels and the flow of substances through blood vessel walls — is significantly impaired in individuals with progeria, affecting the overall function of their endothelial cells.

The researchers discovered they could use Ang2 to “rescue” endothelial cells, improving their health despite dysfunction stemming from HGPS. It enhanced the formation of blood vessels, normalized cell migration and even restored nitric oxide levels, which are crucial for a healthy vascular system.

“Ang2 treatment also improves endothelial cell signaling to vascular smooth muscle cells, suggesting it could be a potential therapy for vascular dysfunctions in HGPS,” Vakili said.

Current treatments for HGPS can help reduce the risk of fatal complications like heart attack and stroke, but they do not target the underlying disease. Cao explained that their research is unlikely to offer a definitive progeria cure, but it could buy patients more time by improving their health in other ways.

“While Ang2 only has receptors on the endothelial cells, it may have a broader beneficial impact on additional tissue types beyond cardiovascular systems, such as bone and fat tissues, since blood vessels are essential for our body to transport nutrients, oxygen and waste,” said Cao, who started studying progeria during her postdoc in 2005, just two years after the cause of progeria was discovered.

As a next step, Cao plans to conduct a follow-up study in collaboration with a group at the NIH to explore different methods of administering Ang2 to animal models with progeria.

While the work is ongoing, Cao is confident that each new study will bring researchers closer to identifying a cure.

“We are getting really close to a cure for progeria,” she said. “Research-wise, we are pushing hard, and I can see the light at the end of the tunnel.”

Breast canceris a significant global public health challenge, with 2.3 million new cases and 700,000 deaths every year. Approximately 80% of patients with primary breast cancer can be cured, if they are diagnosed and treated promptly. However, in many cases, the cancer has already spread to other parts of the body, or metastasized, at the time of diagnosis.

Metastatic cancer is incurable and accounts for more than 90% of cancer-related deaths. Currently, there are no reliable in vitro models to study how breast cancer spreads to secondary organs such as bone, lung, liver or brain. Now, researchers from the Precision Nanomaterials Group at Tampere University and the Cancer Molecular Biology Lab at Izmir Institute of Technology have used lab-on-a-chip platforms to create a physiologically relevant metastasis model to study the factors controlling breast cancer bone metastasis.

“Breast cancer most frequently spreads to bone, with an estimated rate of 53%, resulting in severe symptoms such as pain, pathological bone fractures, and spinal cord compressions. Our research provides a laboratory model that estimates the likelihood and mechanism of bone metastasis occurring within a living organism. This advances the understanding of molecular mechanisms in breast cancer bone metastasis and provides the groundwork for developing preclinical tools for predicting bone metastasis risk,” says Burcu Firatligil-Yildirir, postdoctoral researcher at Tampere University and the first author of the paper.

According to Nonappa, Associate Professor and leader of the Precision Nanomaterials Group at Tampere University, developing sustainable in vitro models that mimic the complexity of the native breast and bone microenvironment is a multidisciplinary challenge.

“Our work shows that physiologically relevant in vitro models can be generated by combining cancer biology, microfluidics and soft materials. The results open new possibilities for developing predictive disease, diagnostic and treatment models,” he says.

The Precision Nanomaterials Group at Tampere University develops various in vitro cancer metastasis disease and diagnostic models.

Earlier this week, the new research was published in the journal Physical Review X. The paper is a follow-up to previous work, in which the authors also studied axions and neutron stars, but from a completely different point of view. While in their previous work they investigated the axions that escape the neutron star, now the researchers focus on the ones that are left behind — the axions that get captured by the star’s gravity. As time goes by, these particles should gradually form a hazy cloud around the neutron star, and it turns out that such axion clouds may well be observable in our telescopes. But why would astronomers and physicists be so interested in hazy clouds around far away stars?

Axions: from soap to dark matter

Protons, neutrons, electrons, photons — most of us are familiar with the names of at least some of these tiny particles. The axion is lesser known, and for a good reason: at the moment it is only a hypothetical type of particle — one that nobody has yet detected. Named after a brand of soap, its existence was first postulated in the 1970s, to clean up a problem — hence the soap reference — in our understanding of one of the particles we could observe very well: the neutron. However, while theoretically very nice, if these axions existed they would be extremely light, making them very hard to detect in experiments or observations.

Today, axions are also known as a frontrunning candidate to explain dark matter, one of the biggest mysteries in contemporary physics. Many different pieces of evidence suggest that approximately 85% of the matter content in our Universe is ‘dark’, which simply means that it is not made up of any type of matter that we know and can currently observe. Instead, the existence of dark matter is only inferred indirectly through the gravitational influence it exerts on visible matter. Fortunately, this does not automatically mean that dark matter has no other interactions with visible matter at all, but if such interactions exist their strength is necessarily tiny. As the name suggests, any viable dark matter candidate is thus incredibly difficult to directly observe.

Putting one and one together, physicists have realized that the axion may be exactly what they are looking for to solve the dark matter problem. A particle that has not yet been observed, which would be extremely light, and have very weak interactions with other particles… could axions be at least part of the explanation for dark matter?

Neutron stars as magnifying glasses

The idea of the axion as a dark matter particle is nice, but in physics an idea is only truly nice if it has observable consequences. Would there be a way to observe axions after all, fifty years after their possible existence was first proposed?

When exposed to electric and magnetic fields, axions are expected to be able to convert into photons — particles of light — and vice versa. Light is something we know how to observe, but as mentioned, the corresponding interaction strength should be very small, and therefore so is the amount of light that axions generally produce. That is, unless one considers an environment containing a truly massive amount of axions, ideally in very strong electromagnetic fields.

This led the researchers to consider neutron stars, the densest known stars in our Universe. These objects have masses similar to that of our Sun but compressed into stars of 12 to 15 kilometres in size. Such extreme densities create an equally extreme environment that, notably, also contains enormous magnetic fields, billions of times stronger than any we find on Earth. Recent research has shown that if axions exist, these magnetic fields allow for neutron stars to mass-produce these particles near their surface.

The ones that stay behind

In their previous work, the authors focused on the axions that after production escaped the star — they computed the amounts in which these axions would be produced, which trajectories they would follow, and how their conversion into light could lead to a weak but potentially observable signal. This time, they consider the axions that do not manage to escape — the ones that, despite their tiny mass, get caught by the neutron star’s immense gravity.

Due to the axion’s very feeble interactions, these particles will stay around, and on timescales up to millions of years they will accumulate around the neutron star. This can result in the formation of very dense clouds of axions around neutron stars, which provide some incredible new opportunities for axion research. In their paper, the researchers study the formation, as well as the properties and further evolution, of these axion clouds, pointing out that they should, and in many cases must, exist. In fact, the authors argue that if axions exist, axion clouds should be generic (for a wide range of axion properties they should form around most, perhaps even all, neutron stars), they should in general be very dense (forming a density possibly twenty orders of magnitude larger than local dark matter densities), and because of this they should lead to powerful observational signatures. The latter potentially come in many types, of which the authors discuss two: a continuous signal emitted during large parts of a neutron star’s lifetime, but also a one-time burst of light at the end of a neutron star’s life, when it stops producing its electromagnetic radiation. Both of these signatures could be observed and used to probe the interaction between axions and photons beyond current limits, even using existing radio telescopes.

What’s next?

While so far, no axion clouds have been observed, with the new results we know very precisely what to look for, making a thorough search for axions much more feasible. While the main point on the to do-list is therefore ‘search for axion clouds’, the work also opens up several new theoretical avenues to explore.

For one thing, one of the authors is already involved in follow-up work that studies how the axion clouds can change the dynamics of neutron stars themselves. Another important future research direction is the numerical modelling of axion clouds: the present paper shows great discovery potential, but there is more numerical modelling needed to know even more precisely what to look for and where. Finally, the present results are all for single neutron stars, but many of these stars appear as components of binaries — sometimes together with another neutron star, sometimes together with a black hole. Understanding the physics of axion clouds in such systems, and potentially understanding their observational signals, would be very valuable.

Thus, the present work is an important step in a new and exciting research direction. A full understanding of axion clouds will require complementary efforts from multiple branches of science, including particle (astro)physics, plasma physics, and observational radio astronomy. This work opens up this new, cross-disciplinary field with lots of opportunities for future research.

The study, published today in Current Biology, investigates the neural foundations of behavioural innovation in Heliconius butterflies, the only genus known to feed on both nectar and pollen. As part of this behaviour, they demonstrate a remarkable ability to learn and remember spatial information about their food sources — skills previously connected to the expansion of a brain structure called the mushroom bodies, responsible for learning and memory.

Lead author Dr Max Farnworth from the University of Bristol’s School of Biological Sciences explained: “There is huge interest in how bigger brains may support enhanced cognition, behavioural precision or flexibility. But during brain expansion, it’s often difficult to disentangle effects of increases in overall size from changes in internal structure.”

To answer this question, the study authors delved deeper into the changes that occurred in the neural circuits that support learning and memory in Heliconius butterflies. Neural circuits are quite similar to electrical circuits as each cell has specific targets that they connect with, and assembles a net with its connections. This net then elicits specific functions by constructing a circuitry.

Through a detailed analysis of the butterfly brain, the team discovered that certain groups of cells, known as Kenyon cells, expanded at different rates. This variation led to a pattern called mosaic brain evolution, where some parts of the brain expand while others remain unchanged, analogous to mosaic tiles all being very different from each other.

Dr Farnworth explained: “We predict that because we see these mosaic patterns of neural changes, these will relate to specific shifts in behavioural performance — in line with the range of learning experiments which show that Heliconius outperform their closest relatives in only very specific contexts, such as long-term visual memory and pattern learning.”

To feed on pollen, Heliconius butterflies need to have efficient routes of feeding, as pollen plants are quite rare.

Project supervisor and co-author, Dr Stephen Montgomery said: “Rather than having a random route of foraging, these butterflies apparently choose fixed routes between floral resources — akin to a bus route. The planning and memory processes needed for this behaviour are fulfilled by the assemblies of neurons inside the mushroom bodies, hence why we’re fascinated by the internal circuitry throughout. Our results suggest that specific aspects of these circuits have been tweaked to bring about the enhanced capacities of Heliconius butterflies.”

This study contributes to the understanding on how neural circuits change to reflect cognitive innovation and change. Examining neural circuits in tractable model systems such as insects promises to reveal genetic and cellular mechanisms common to all neural circuits, thus potentially bridging the gap, at least on a mechanistic level, to other organisms such as humans.

Looking ahead, the team plans to explore neural circuits beyond the learning and memory centres of the butterfly brain. They also aim to increase the resolution of their brain mapping to visualise how individual neurons connect at an even more granular level.

Dr Farnworth said: “I was really fascinated by the fact that we see such high degrees of conservation in brain anatomy and evolution, but then very prominent but distinct changes.”

“This is a really fascinating and beautiful example of a layer of biodiversity we don’t usually see, the diversity of brain and sensory systems, and the ways in which animals are processing and using the information provided by the environment around them” concluded Dr Montgomery.

Researchers found 10 ‘target’ PFAS (perfluoroalkyl substances) — chemicals which do not break down in nature — in tap and bottled water available for consumption in major cities in the UK and China. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were detected in over 99% of samples of bottled water sourced from 15 countries around the world.

They observed significant differences in PFAS concentrations between tap water samples from Birmingham, UK, and Shenzhen, China, with Chinese tap water found to have higher concentrations of PFAS compared to UK tap water.

However, the study demonstrates that measures such as boiling and/or activated carbon filtration — typically using a ‘jug’ water filter — can substantially reduce PFAS concentrations in drinking water, with removal rates ranging from 50% to 90% depending on the PFAS and treatment type.

Publishing their findings today (17 October) in ACS ES&T Water, researchers from the University of Birmingham, Southern University of Science and Technology, Shenzhen, and Hainan University, Haikou, reveal a wide range of PFAS contamination for target PFAS, starting at 63% of bottled waters tested.

Co-author Professor Stuart Harrad, from the University of Birmingham, commented: “Our findings highlight the widespread presence of PFAS in drinking water and the effectiveness of simple treatment methods to reduce their levels. Either using a simple water filtration jug or boiling the water removes a substantial proportion of these substances.

“While current PFAS levels in most water samples are not a major health concern, ongoing monitoring and regulation are crucial to protect public health. We provide valuable data on the presence of PFAS in drinking water alongside practical solutions to mitigate consumer exposure via drinking water. This is a significant step towards ensuring safer drinking water for communities worldwide.”

Bottled water from various countries showed varying levels of PFAS, with natural mineral water containing higher concentrations than purified water, but the concentrations were generally below health advisory levels set by regulatory agencies.

Co-author Professor Yi Zheng, from Southern University of Science and Technology, commented: “Increased awareness about the presence of PFAS in both tap and bottled water can lead to more informed choices by consumers, encouraging the use of water purification methods.

Our findings also suggest that the potential health risks of PFAS in drinking water may be influenced by lifestyle and economic conditions, highlighting the need for future research to further explore these factors from a socio-economic perspective.”

Except for comparisons between natural mineral and purified water, the researchers observed no significant difference in target PFAS concentrations between glass and plastic or still and sparkling bottled water.

While concentrations of most individual PFAS were well below corresponding health-based reference values, average PFOS concentrations in tap water samples from Shenzhen, China exceeded the maximum contaminant level (MCL) of 4 ng/L newly promulgated by the US Environmental Protection Agency (USEPA) in 2024.

Researchers purchased 112 bottled water samples from local shops and online supermarkets in the UK and China including 89 still and 23 sparkling waters in either plastic or glass bottles. The samples covered 87 brands with water sources originating from 15 countries in Asia, Europe, North America, and Oceania

They collected 41 tap water samples from homes in Birmingham and the nearby cities of Worcester, Coventry, and Derby — provided by two suppliers: South Staffordshire Water and Seven Trent Water, with a further 14 tap water samples collected from homes in Shenzhen, China.

PFAS are used widely in industry, in fire-fighting foams, and consumer products from waterproof clothing and school uniforms to personal care products because of their water and stain repellent properties. While some have been banned by government regulation, others are still widely used and their toxic effects not yet fully investigated.

The chemicals are already known to enter the body in different ways, for example being breathed in, ingested via food or drinking water, or absorbed through the skin. They are known to cause adverse health effects such as a lowered immune response to vaccination, impaired liver function, decreased birth weight, and increased risk of some cancers.