Gene discovery indicates motor neuron diseases caused by abnormal lipid processing in cells

A new genetic discovery adds weight to a theory that motor neuron degenerative diseases are caused by abnormal lipid (fat) processing pathways inside brain cells. This theory will help pave the way for new diagnostic approaches and treatments for this group of conditions. The discovery will provide answers for certain families who have previously had no diagnosis.

Motor neuron degenerative diseases (MNDs) are a large family of neurological disorders. Currently, there are no treatments available to prevent onset or progression of the condition. MNDs are caused by changes in one of numerous different genes. Despite the number of genes known to cause MNDs, many patients remain without a much-needed genetic diagnosis.

The team behind the current work developed a hypothesis to explain a common cause of MNDs stemming from their discovery of 15 genes responsible for MNDs. The genes they identified are all involved in processing lipids - in particular cholesterol – inside brain cells. Their new hypothesis, published in the journal Brain, describes the specific lipid pathways that the team believe are important in the development of MNDs.

Now, the team has identified a further new gene – named TMEM63C – which causes a degenerative disease that affects the upper motor neuron cells in the nervous system. Also published in Brain, their latest discovery is important as the protein encoded by TMEM63C is located in the region of the cell where the lipid processing pathways they identified operate. This further bolster the hypothesis that MNDs are caused by abnormal processing of lipids including cholesterol.

“This new gene finding is consistent with our hypothesis that the correct maintenance of specific lipid processing pathways is crucial for the way brain cells function, and that abnormalities in these pathways are a common linking theme in motor neuron degenerative diseases,” said study co-author Professor Andrew Crosby from the University of Exeter. “It also enables new diagnoses and answers to be readily provided for families affected by some forms of MND”

New imaging technique to find out what happens in the brains of dogs and cats

In a preliminary experiment, Parkkonen held a quantum optical MEG sensor with his hand on his family cat’s, Roosa’s, head while she listened to simple sound sequences.
Credit: Professor Lauri Parkkonen / Aalto University

For years, Professor Lauri Parkkonen's team at Aalto University has been developing quantum optical sensors for measuring the brain's magnetic fields using a technique known as magnetoencephalography (MEG). In traditional MEG, the superconducting sensors operate at very low temperatures and need centimeters of thermal insulation, but the quantum optical sensors work at room temperature, so they can be placed directly on the surface of the head. This allows more accurate measurements of the brain’s magnetic fields.

Parkkonen and his team plan to use the new method to build on their earlier work measuring brain activity in cats and dogs. Now they plan to characterize the complexity of the temporal structures in sensory stimuli that cat and dog brains can track. Similar experiments in humans have found that our brain produces specific responses to deviations in complex structures only when we attend to the stimuli and become aware of the deviations. Once the technique is perfected, Parkkonen and his team plan to use it to make similar measurements in human babies.

The experiments will begin this autumn – though Parkkonen has already done some preliminary tests with his family cat, Roosa – and the project is expected to continue until 2026. The researchers hope that their findings will provide an unprecedented window onto the cognition of cats and dogs, and this could also help bridge the gap between our understanding of human brains and the brains of other mammals.

Rethinking the rabies vaccine

Scientists from La Jolla Institute for Immunology and the Institut Pasteur have shed light on the structure of the rabies virus glycoprotein. 
Credit: Heather Callaway, Ph.D., LJI

Rabies virus kills a shocking 59,000 people each year, many of them children. Some victims, especially kids, don’t realize they’ve been exposed until it is too late. For others, the intense rabies treatment regimen is out of the question: treatment is not widely available and the average $3,800 expense poses unthinkable economic burden for most people around the world.

Rabies vaccines, rather than treatments, are much more affordable and easier to administer. But those vaccines also come with a massive downside:

“Rabies vaccines don’t provide lifelong protection. "You have to get your pets boosted every year to three years,” says LJI Professor Erica Ollmann Saphire, Ph.D. “Right now, rabies vaccines for humans and domestic animals are made from killed virus. But this inactivation process can cause the molecules to become misshapen—so these vaccines aren’t showing the right form to the immune system. If we made a better shaped, better structured vaccine, would immunity last longer?”

Saphire and her team, in collaboration with a team led by Institut Pasteur Professor Hervé Bourhy, DVM, PhD., may have discovered the path to better vaccine design. In a new study, published in Science Advances, the researchers share one of the first high-resolution looks at the rabies virus glycoprotein in its vulnerable “trimeric” form.

Rice lab’s quantum simulator delivers new insight

Rice physicists used ultracold atoms and a 1D channel of light to simulate electrons in 1D wires and study how two of their intrinsic properties — spin and charge — travel at different speeds. They used a laser beam (top left) to produce collective waves that rippled left to right along the wire over time (top to bottom), transporting either spin or charge. A spin wave is illustrated. Spins must point up (blue) or down (red), and atoms with opposite spin naturally arrange in an alternating up-down, up-down pattern (top row). The wave transports spin by sequentially exchanging adjacent up/down spins (shaded ovals). Researchers measured the speed of both spin waves and charge waves (not shown), demonstrating the two traveled at different speeds.
Illustration by Ella Maru Studio, provided courtesy of R. Hulet/Rice University

A quantum simulator at Rice University is giving physicists a clear look at spin-charge separation, the quantum world’s version of the magician’s illusion of sawing a person in half.

Published this week in Science, the research has implications for quantum computing and electronics with atom-scale wires.

Electrons are minuscule, subatomic particles that cannot be divided. Despite this, quantum mechanics dictates that two of their attributes — spin and charge — travel at different speeds in one-dimensional wires.

Rice physicists Randy Hulet, Ruwan Senaratne and Danyel Cavazos built an ultracold venue where they could repeatedly view and photograph a pristine version of this quantum spectacle, and they collaborated with theorists from Rice, China, Australia and Italy on the published results.

Chemical pollution threatens biodiversity

Chemicals threaten biodiversity - not only because they can directly poison animals and plants, but because they affect the living conditions and functions of living things.
Credit: Gabriel Sigmund & Aaron Kintz

Pollution of the environment with chemicals threatens biodiversity. The complexity of this pollution has so far been insufficiently recorded by decision-makers - this is what international researchers around Gabriel Sigmund from the University of Vienna and Ksenia Groh from the Eawag water research institute (Dübendorf, Switzerland) are writing in the current issue of the journal Science. They appeal to decision-makers and researchers to consider more chemicals than previously planned. Your contribution will appear shortly before the international negotiations on a new biodiversity agreement, the "post-2020 Global Biodiversity Framework". These take place from the 21st. June in Nairobi (Kenya).

"Design to the agreement mentions chemical pollution, but it only takes nutrients, pesticides and plastic waste into account and falls short of it," explains environmental scientist Gabriel Sigmund. "Many highly problematic chemicals that pollute the environment and thus threaten the diversity of animal and plant species are simply overlooked," added ecotoxicologist Ksenia Groh. This does not do justice to the immense variety of man-made chemicals. So far not considered in the draft agreement, but from the perspective of the researchers toxic metals, industrial chemicals, chemicals from consumer goods, pharmaceuticals and the often-unknown conversion products of these chemicals are problematic.

Research reveals the northernmost glaciers on the globe are melting at record speed

Coastal glaciers in northern Greenland
image resized using AI by SFLORG
Credit: William Colgan

Greenland's many small glaciers are melting at great speed, and the melting is increasing, especially in the Arctic regions, where the temperature rise is worst.

Now, researchers have studied precisely how much mass these glaciers – not connected to the ice sheet – have lost in recent decades.

In the Arctic, temperatures are rising more than in the rest of the world, and this is causing the northernmost glaciers in Greenland to melt at record speed. This is shown in a new study by researchers led by DTU Space in collaboration with Geological Survey of Denmark and Greenland (GEUS), NASA Goddard Space Flight Center, Utrecht University, University of Bristol, Technical University Munich, and the University of Copenhagen.

The study focuses on smaller glaciers with no connection to the Greenland Ice Sheet. These peripheral glaciers make up only about four percent of Greenland's ice-covered areas, corresponding to approximately the same area as Ireland (72,000 km2), but they contribute as much as 11 percent of the total loss of ice from Greenland's ice-covered areas. Thus, they are a major contributor to global sea level rise.

"The loss of ice from these small glaciers occurs because they are more sensitive to ongoing temperature changes and therefore melt faster than we see in many other places in the Arctic," said Professor Shfaqat Abbas Khan from DTU Space, lead author of the paper published in Geophysical Research Letters.

Heart surgery delays will cost lives

Urgent action is needed to clear the backlog of people with a common heart condition who are waiting for lifesaving treatment, according to research published in the journal BMJ Open. Researchers have warned that a lack of action could result in thousands of people dying while waiting for treatment.

The COVID-19 pandemic has led to thousands of heart procedures being postponed and record waiting lists. Previous work has estimated that 4,989 people in England with severe aortic stenosis missed out on life-saving treatment between March and November 2020.

Aortic stenosis develops when the heart’s aortic valve becomes narrowed, restricting blood flow out of the heart. Prompt treatment is vital for people diagnosed with severe aortic stenosis, as around 50 percent will die within two years of symptoms beginning.

Now, an international team of researchers, including those from the University of Cambridge, has modelled the impact that increasing treatment capacity and using a quicker, less invasive treatment option would have on waiting lists. Even in the best-case scenario, they found that the waiting list would take nearly a year to clear and over 700 people would die while waiting for treatment. The research was funded by the British Heart Foundation and the EPSRC Cambridge Centre for Mathematics of Information in Healthcare.

An Experimental Treatment Failed in Mice, and Researchers Did the Right Thing: They Published About It

Treatment of FOP mice with an antibody to ACVR1 greatly exacerbates abnormal bone formation (heterotopic ossification) following muscle injury. This is a 3D-rendered microCT image in which the heterotopic bone has been colorized green.
Source: University of Connecticut

Blocking the mutant protein with an antibody didn’t stop the strange, abnormal bone growths in mice. But the knowledge gained could steer scientists toward more promising approaches, report researchers from UConn and Alexion Pharmaceuticals in the The Journal of Clinical Investigation.

Fewer than 4,000 people worldwide are afflicted with fibrodysplasia ossificans progressiva (FOP), an inherited disease in which small injuries or bruises to skeletal muscle provoke the growth of massive, abnormal bone and cartilage. Gradually much of the body’s soft tissue turns to bone. Now, researchers at UConn and Alexion Pharmaceuticals who were investigating a potential cure instead found a concerning surprise–blocking the protein responsible for the disease with a monoclonal antibody made the abnormal bone growth worse in mice.

Normally, stem cells help repair muscle damaged by injury or disease. But in people with FOP, certain stem cells get the wrong message from a mutant receptor on their surface. Instead of promoting muscle regeneration, the stem cells develop into bone.

UConn Professor of Molecular and Cell Biology David Goldhamer, Alexion Pharmaceuticals researcher Jeffrey Hunter, and colleagues worked for years to discover a potential antibody therapy for FOP using accurate genetic mouse models of the disease developed by the two groups. The idea was that the antibody would block the mutant receptor and prevent the responsible stem cells from making new bone. But the results were exactly the opposite.

A new hope for a therapy against retinitis pigmentosa

Retinitis pigmentosa is the most common hereditary retinal disease in humans, with a prevalence of one in every 4,000 people worldwide.
Photo by Danish Ahmad

Retinitis pigmentosa, a degenerative genetic disease of the eye, is characterized by progressive vision loss, usually leading to blindness. In some patients, structural defects in the photoreceptor cells have been observed, but the molecular mechanisms involved are not understood. A team from the University of Geneva (UNIGE), in collaboration with the University of Lausanne (UNIL), has identified the essential role played by a molecular zipper formed by four proteins. The absence of this zipper leads to cell death in retinal cells. This discovery could lead to the development of therapeutic approaches for retinitis pigmentosa. This work can be read in the journal PLOS Biology.

Retinitis pigmentosa is the most common hereditary retinal disease in humans, with a prevalence of one in every 4,000 people worldwide. The first symptoms usually appear between the ages of 10 and 20 with a loss of night vision. Thereafter, the visual field narrows into a “tunnel vision” to finally lead to blindness around the age of 40. This disease is characterized by a degeneration of the light sensitive cells, the photoreceptors.

These specialized neuronal cells of the retina are responsible for the conversion of light into a nerve signal. The outer segment of the cell is made up of stacks of discs on which the light-sensitive pigments are located. The inner segment contains all the metabolic machinery essential to the functioning of the cell and is linked to the outer segment by the connecting cilium.

Flawed research not retracted fast enough to prevent spread of misinformation

People who engage with research critically on Twitter may contribute to valuable conservations about science, new research suggests.
Illustration by ijmaki via Pixabay

A new analysis by Northwestern University and University of Michigan researchers suggests retracting academic papers does not dampen the reach of problematic research as intended. Instead, papers that are later retracted are often widely circulated online, both by news outlets and social media, and the cycle of attention that they receive typically dies away before the retraction even happens.

The finding has concerning implications for the spread of misinformation and public trust in science. However, retracted papers included in the analysis were often the subject of more critical discourse on Twitter before their retraction, suggesting that while Twitter should not be an official judge of science, it’s possible that in some communities, it could provide early signals of dubious research.

When a paper is retracted, the goal is to officially discredit it and acknowledge the research as flawed, thereby maintaining the overall integrity of the research enterprise. However, many people who hear about the initial finding may never learn of the retraction.

“Social media and even top news outlets — the most prestigious venues that cover science — are more prone to talk about papers that end up being retracted,” said Ágnes Horvát, an assistant professor of communication and computer science at Northwestern who was an author on the paper, published in the Proceedings of the National Academy of Sciences.