How wiggly spaghetti guard the genome

The image shows an artistic impression of the rocky scaffold structure of the nuclear pore complex filled with intrinsically disordered nucleoporins in the central channel depicted as seaweeds. In this work, the viewer dives into the dark hole of the nuclear pore complex to shine light on the disordered nucleoporins.
Illustration Credit: ©: Sara Mingu

Tiny pores in the cell nucleus play an essential role for healthy aging by protecting and preserving the genetic material. A team from the Department of Theoretical Biophysics at the Max Planck Institute of Biophysics in Frankfurt am Main and the Synthetic Biophysics of Protein Disorder group at Johannes Gutenberg University Mainz (JGU) has literally filled a hole in the understanding of the structure and function of these nuclear pores. The scientists found out how intrinsically disordered proteins in the center of the pore can form a spaghetti-like mobile barrier that is permeable for important cellular factors but blocks viruses or other pathogens.

Human cells shield their genetic material inside the cell nucleus, protected by the nuclear membrane. As the control center of the cell, the nucleus must be able to exchange important messenger molecules, metabolites or proteins with the rest of the cell. About 2,000 pores are therefore built into the nuclear membrane, each consisting of about 1,000 proteins.

Drug for rare form of ALS approved by FDA

A new drug has been approved by the Food and Drug Administration (FDA) for a rare, inherited form of amyotrophic lateral sclerosis (ALS). Called tofersen, the drug — developed by Biogen Inc. and based in part on research conducted at Washington University School of Medicine in St. Louis — slows the progression of the deadly, paralyzing disease. 

Video Credit: Huy Mach and Tamara Bhandari

A new drug has been approved by the Food and Drug Administration (FDA) for a rare, inherited form of amyotrophic lateral sclerosis (ALS), a paralyzing neurological disease. Known as tofersen, the drug has been shown to slow progression of the deadly disease. International clinical trials of tofersen, developed by the global biotechnology company Biogen Inc., were led by a neurologist at Washington University School of Medicine in St. Louis.

Tofersen, also known by the brand name Qalsody, is designed for ALS patients whose disease is caused by mutations in the gene SOD1. In the phase 3 clinical trial, the drug reduced molecular signs of disease and curbed neurodegeneration in the first six months of use. Over longer time frames, some participants experienced a stabilization of muscle strength and control.

The drug is approved under the accelerated approval pathway, under which FDA may approve drugs for serious conditions where there is an unmet medical need and a drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients.

Membrane proteins of cyanobacteria and higher organisms are structurally highly similar

SynDLP, the dynamin-like protein of the cyanobacterium Synechocystis, forms highly ordered oligomeric structures that bind to membranes.
Illustration Credit: ©: Lucas Gewehr, Dirk Schneider

The cells of living organisms are equipped with proteins that are involved in the shaping and remodeling of cellular membranes, thereby performing important tasks. The cell membrane encloses the cell interior, but is constantly remodeled, for example, due to membrane budding, invagination, or fusion processes. This also involves various proteins that were long assumed to be present exclusively or predominantly in higher organisms. In the past 10 to 20 years, however, proteins have been identified or predicted to be present also in simple organisms that do not possess a nucleus. In a research collaboration, a protein involved in membrane remodeling in cyanobacteria has now been described for the first time. The existence of such a bacterial protein was suspected, but proof was still pending. The studied protein is likely a bacterial representative of a similar protein found in higher organisms such as animals and plants.

Chest E-Tattoo Boasts Major Improvements in Heart Monitoring

A new flexible, wearable medical device could provide a major boost in the fight against heart disease, the leading cause of death in the United States.
Photo Credit: University of Texas at Austin / Cockrell School of Engineering

A team led by researchers at The University of Texas at Austin has developed an ultrathin, lightweight electronic tattoo, or e-tattoo, that attaches to the chest for continuous, mobile heart monitoring outside of a clinical setting. It includes two sensors that together provide a clear picture of heart health, giving clinicians a better chance to catch red flags for heart disease early.

“Most heart conditions are not very obvious. The damage is being done in the background and we don’t even know it,” said Nanshu Lu, a professor in the Department of Aerospace and Engineering Mechanics and a lead author of the study. “If we can have continuous, mobile monitoring at home, then we can do early diagnosis and treatment, and if that can be done, 80% of heart disease can be prevented.”

The study is published in Advanced Electronic Materials.

A 'cocktail' of human antibodies shows promise in fighting severe SARS-CoV-2 infections

Antibody 2A10 (yellow shades) and antibody 1H2 (blue shades) were isolated from a vaccinated research volunteer. The LJI team found these two antibodies can neutralize many SARS-CoV-2 variants.
Illustration Credit: Saphire Lab, La Jolla Institute for Immunology.

An anonymous San Diego resident has become a fascinating example of how the human immune system fights SARS-CoV-2. In a new investigation, scientists from La Jolla Institute for Immunology (LJI) have shown how antibodies, collected from this clinical study volunteer, bind to the SARS-CoV-2 “Spike” protein to neutralize the virus.

Although studies have shown antibodies bound to Spike before, this new research reveals how the original Moderna SARS-CoV-2 vaccine could prompt the body to produce antibodies against the later Omicron variants of SARS-CoV-2. The researchers also captured highly detailed, 3D structures of three promising neutralizing antibodies bound to Spike.

This important work shows exactly where Spike is vulnerable to human antibodies—and how future vaccines and antibody therapeutics might exploit these weaknesses. In fact, studies in mice suggest some of these antibodies may help prevent severe cases of COVID-19.

“To blunt the next pandemic and protect people from seasonal re-emergence of this one, we need antibodies of the broadest possible capacity—ones that are not escaped,” says LJI President and CEO Erica Ollmann Saphire, Ph.D., senior author of the new Cell Reports study. “We found those in a vaccinated San Diegan.”

Toward a Therapy for a Rare Genetic Disease

Researchers have designed a “mini gene” that could eventually be developed into a gene therapy for Usher Syndrome type 1F
Photo Credit: Subin

Usher Syndrome type 1F is a rare but severe genetic disease that causes deafness, lack of balance, and progressive blindness.

Now, a team led by researchers at Harvard Medical School, Massachusetts Eye and Ear, and The Ohio State University has made an important first step toward developing a gene therapy for the disease.

The research, conducted in mice, is described Apr. 26 in Nature Communications.

The scientists designed a “mini gene” — a shortened version of a gene — to replace the gene that is mutated in Usher 1F. The mutation renders hair cells inside the inner ear incapable of producing a key protein involved in sound transmission. In mice, the mini gene increased production of the missing protein, enabling the hair cells to sense sound and restoring hearing.

Because vision loss in Usher 1F involves a slightly different form of the same protein, the researchers say the same approach may be useful for preventing blindness.

“Patients with Usher 1F are born with profound hearing loss and progressive vision loss, and so far, we have been able to offer very few solutions to these families,” said co-senior author Artur Indzhykulian, HMS assistant professor of otolaryngology–head and neck surgery at Mass Eye and Ear.

Brain circuits for locomotion evolved long before appendages and skeletons

The sea slug, Pleurobranchea californica 
Photo Credit: Fred Zwicky

Hundreds of millions of years before the evolution of animals with segmented bodies, jointed skeletons or appendages, soft-bodied invertebrates like sea slugs ruled the seas. A new study finds parallels between the brain architecture that drives locomotion in sea slugs and that of more complex segmented creatures with jointed skeletons and appendages. 

Reported in the Journal of Neuroscience, the study suggests that, rather than developing an entirely new set of neural circuits to govern the movement of segmented body parts, the insects, crustaceans and even vertebrates like mammals adapted a network of neurons, a module, that guided locomotion and posture in much simpler organisms. 

“Sea slugs may still have that module, a smallish network of neurons called the ‘A-cluster,’ with 23 neurons identified so far,” said University of Illinois Urbana-Champaign molecular and integrative physiology professor Rhanor Gillette, who led the new research. 

“The question that we addressed in this study is whether the similarities we see between sea slugs and more complex creatures evolved independently or whether those with segmented body parts and appendages may have inherited their underlying neural circuitry from a soft-bodied, bilaterally symmetrical common ancestor,” he said. 

Predators decrease prey disease levels but also population size

Microscope image showing a phantom midge larva (genus Chaoborus), top left, preying on a Daphnia dentifera water flea, bottom right. Chaoborus is a fierce predator with a complex “catching basket” on its head for quickly trapping small crustaceans like water fleas.
Photo Credit: Meghan Duffy, University of Michigan.

Nature documentaries will tell you that lions, cheetahs, wolves and other top predators target the weakest or slowest animals and that this culling benefits prey herds, whether it’s antelope in Africa or elk in Wyoming.

This idea has been widely accepted by biologists for many years and was formalized in 2003 as the healthy herds hypothesis. It proposes that predators can help prey populations by picking off the sick and injured and leaving healthy, strong animals to reproduce.

The healthy herds hypothesis has even been used to suggest that manipulating predator numbers to protect prey might be a useful conservation strategy. Even so, hard evidence supporting the hypothesis is scarce, and in recent years many of its assumptions and predictions have been questioned.

In a study published online April 26 in the journal Ecology, a University of Michigan-led research team used a pint-sized predator-prey-parasite system inside 20-gallon water tanks to test the healthy herds hypothesis.

Woodpecker helps managers promote new life in burned forests

A male Black-backed Woodpecker at Silvio O. Conte National Wildlife Refuge, Brunswick, Vermont, USA.
Photo Credit: U.S. Fish and Wildlife Service Northeast Region
(CC BY 2.0)

Scientists have created a tool based on the habitat preferences of the black-backed woodpecker to help forest managers make decisions that promote regrowth and biodiversity following wildfires.

“Wildfire is like a 10,000-piece puzzle, and climate change is rearranging the pieces,” said Andrew Stillman, a postdoctoral researcher at the Cornell Atkinson Center for Sustainability and the Cornell Lab of Ornithology and first author of “Incorporating Pyrodiversity into Wildlife Habitat Assessments for RapidPost-Fire Management: A Woodpecker Case Study,” published April 25 in Ecological Applications.

“Gigantic, severe fires are becoming the new norm in California due to drought, longer burn seasons and dense forests. But birds do really well in landscapes that are ‘pyrodiverse’ – areas where fire results in uneven patches burned at high, medium, and low severity,” Stillman said.

Black-backed woodpeckers love pyrodiversity. They prefer to build their nest cavities in newly burned areas after high severity fires. But they also like to be adjacent to areas that burned at low intensity, where their young can hide from predators among living trees that still provide cover. Because of the species’ unique habitat associations, they are sensitive to the removal of trees after fire, and forest managers use information on the woodpecker to guide their post-fire planning.

This killer protein causes pancreatic cancer

Mouse pancreas cells with high levels of the protein SRSF1; CSHL Professor Adrian Krainer found that mice with high levels of SRFS1 tend to exhibit intraepithelial neoplasia—a known precursor to the most common form of pancreatic cancer.
Image Credit: Cold Spring Harbor Laboratory

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. It’s also one of the deadliest. More than 90% of PDAC patients die within five years of diagnosis. Usually, by the time the cancer is identified, it has already spread.

“PDAC is often found too late for treatments like chemotherapy and surgery to be very effective,” Cold Spring Harbor Laboratory (CSHL) Professor Adrian Krainer says. “But if we can clearly understand the underlying genetic mechanisms of PDAC, this might lead to earlier diagnoses and new types of therapies.”

Krainer and CSHL Postdoc Ledong Wan partnered with CSHL Professor David Tuveson to explore the role of a genetic process called RNA splicing in pancreatic cancer. RNA splicing helps DNA deliver instructions to cells for protein production. The team zeroed in on a splicing-regulator protein called SRSF1. They found that high levels of SRSF1 cause inflammation, or pancreatitis. This jumpstarts PDAC tumor development.

New black hole images reveal a glowing, fluffy ring and a high-speed jet

Scientists observing the compact radio core of M87 have discovered new details about the galaxy’s supermassive black hole. In this artist’s conception, the black hole’s massive jet is seen rising up from the center of the black hole. The observations on which this illustration is based represent the first time that the jet and the black hole shadow have been imaged together, giving scientists new insights into how black holes can launch these powerful jets. 
Illustration Credit: S. Dagnello (NRAO/AUI/NSF)

In 2017, astronomers captured the first image of a black hole by coordinating radio dishes around the world to act as a single, planet-sized telescope. The synchronized network, known collectively as the Event Horizon Telescope (EHT), focused in on M87*, the black hole at the center of the nearby Messier 87 galaxy. The telescope’s laser-focused resolution revealed a very thin glowing ring around a dark center, representing the first visual of a black hole’s shadow. 

Astronomers have now refocused their view to capture a new layer of M87*. The team, including scientists at MIT’s Haystack Observatory, has harnessed another global web of observatories — the Global millimeter VLBI Array (GMVA) — to capture a more zoomed-out view of the black hole.

The new images, taken one year after the EHT’s initial observations, reveal a thicker, fluffier ring that is 50 percent larger than the ring that was first reported. This larger ring is a reflection of the telescope array’s resolution, which was tuned to pick up more of the super-hot, glowing plasma surrounding the black hole. 

Paradoxical quantum phenomenon measured for the first time

Photo Credit: © Thomas Schweigler, TU Wien

How do quantum particles share information? A peculiar conjecture about quantum information has been experimentally confirmed at the TU Wien.

Some things are related, others are not. Suppose you randomly select a person from a crowd who is significantly taller than the average. In that case, there is a good chance that they will also weigh more than the average. Statistically, one quantity also contains some information about the other.

Quantum physics allows for even stronger links between different quantities: different particles or parts of an extensive quantum system can "share" a certain amount of information. There are curious theoretical predictions about this: surprisingly, the measure of this "mutual information" does not depend on the size of the system but only on its surface. This surprising result has been confirmed experimentally at the TU Wien and published in "Nature Physics". Theoretical input to the experiment and its interpretation came from the Max-Planck-Institut für Quantenoptik in Garching, FU Berlin, ETH Zürich and New York University.

Prolonged droughts likely spelled the end for Indus megacities

A section through the Dharamjali stalagmite that the authors studied. 
Photo Credit: Alena Giesche

The beginning of this arid period — starting at around 4,200 years ago and lasting for over two centuries — coincides with the reorganization of the metropolis-building Indus Civilization, which spanned present-day Pakistan and India.

The research identified three protracted droughts — each lasting between 25 and 90 years — during this arid period. “We find clear evidence that this interval was not a short-term crisis but a progressive transformation of the environmental conditions in which Indus people lived,” said study co-author Prof Cameron Petrie, from Cambridge’s Department of Archaeology.

The researchers charted historic rainfall by examining growth layers in a stalagmite collected from a cave near Pithoragarh, India. By measuring a range of environmental tracers — including oxygen, carbon and calcium isotopes — they obtained a reconstruction showing relative rainfall at seasonal resolution. They also used high-precision Uranium-series dating to get a handle on the age and duration of the droughts.

“Multiple lines of evidence allow us to piece together the nature of these droughts from different angles — and confirm they are in agreement,” said lead author of the research Alena Giesche, who conducted the research as part of her PhD in Cambridge’s Department of Earth Sciences.

Near-universal T cell immunity towards a broad range of bacteria

Neutralizing the bacterially derived cytotoxic bomb: the pneumococci lie in the background, an array of macrophages and dendritic cells are arranged around the central image of a T cell. Rows of TCRs interacting with the identified pneumolysin epitope bound to HLA (white) cross the length and breadth of the artwork, emphasizing their centrality in the immune response.
Illustration Credit: Dr. Erica Tandori.

Typically, T cells of the immune system respond to a specific feature (antigen) of a microbe, thereby generating protective immunity. As reported in the journal Immunity, an international team of scientists have discovered an exception to this rule. Namely, a group of divergent bacterial pathogens, including pneumococci, all share a small highly conserved protein sequence, which is both presented and recognized by human T cells in a conserved population-wide manner.

The study set out to understand immune mechanisms that protect against pneumococcus, a bacterial pathobiont that can reside harmlessly in the upper respiratory mucosae but can also cause infectious disease, especially in infants and older adults, which can range from middle ear and sinus infections to pneumococcal pneumonia and invasive bloodstream infections.

Most currently used pneumococcal polysaccharide-based conjugate vaccines (PCVs) are effective against 10–13 serotypes, but growing serotype replacement becomes a problem.

Versatile, High-Speed, and Efficient Crystal Actuation with Photothermally Resonated Natural Vibrations

Mechanically responsive molecular crystals are extremely useful in soft robotics, which requires a versatile actuation technology. Crystals driven by the photothermal effect are particularly promising for achieving high-speed actuation. However, the response (bending) observed in these crystals is usually small. Now, scientists from Japan address this issue by inducing large resonated natural vibrations in anisole crystals with UV light illumination at the natural vibration frequency of the crystal.

Every material possesses a unique natural vibration frequency such that when an external periodic force is applied to this material close to this frequency, the vibrations are greatly amplified. In the parlance of physics, this phenomenon is known as "resonance." Resonance is ubiquitous in our daily life, and, depending on the context, could be deemed desirable or undesirable. For instance, musical instruments like the guitar relies on resonance for sound amplification. On the other hand, buildings and bridges are more likely to collapse under an earthquake if the ground vibration frequency matches their natural frequency.

Interestingly, natural vibration has not received much attention in material actuation, which relies on the action of mechanically responsive crystals. Versatile actuation technologies are highly desirable in the field of soft robotics. Although crystal actuation based on processes like photoisomerization and phase transitions have been widely studied, these processes lack versatility since they require specific crystals to work. One way to improve versatility is by employing photothermal crystals, which show bending due to light-induced heating. While promising for achieving high-speed actuation, the bending angle is usually small (<0.5°), making the actuation inefficient.