Altered cell behavior behind resistance in neuroblastoma

Credit: National Cancer Institute

Researchers at Lund University in Sweden have identified one of the reasons why the childhood cancer neuroblastoma becomes resistant to chemotherapy. The findings are significant for how future treatments should be designed. The results have been published in Science Advances.

Neuroblastoma is an aggressive cancer of the sympathetic nervous system, especially of the adrenal gland. Despite intense treatment with chemotherapy, the disease can be difficult to cure and the prognosis is poor for children who have the aggressive variant. One of the reasons is that the tumor often develops resistance to drugs. In order to understand what happens when the tumor becomes resistant, good disease models are needed that can mimic the complex drug treatment given to patients today:

“Tumors from patients with neuroblastoma look very different, and it is difficult to produce a model that is representative of many patients. This type of challenge often limits medical research”, explains the study's first author, Adriana Mañas, child cancer researcher at Lund University.

Probiotic ‘backpacks’ show promise for treating inflammatory bowel diseases

Probiotic bacteria (teal) coated in a layer of biomaterial as they travel through a human intestine. Attached to the bacteria are reactive oxygen species nano-scavengers.
Image Credit: Quanyin Hu

Like elite firefighters headed into the wilderness to combat an uncontrolled blaze, probiotic bacteria do a better job quelling gut inflammation when they’re equipped with the best gear.

A new study by researchers at the University of Wisconsin–Madison demonstrates just how much promise some well-equipped gut-friendly bacteria hold for improving treatments of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis.

Led by Quanyin Hu, a biomedical engineer and professor in the UW–Madison School of Pharmacy, the research builds on technology the team had previously designed. That prior technology encases beneficial bacteria within a very thin protective shell to help them survive an onslaught of stomach acids and competing microbes long enough to establish and multiply in the guts of mice.

While the technology makes orally administered probiotics more effective, IBD is a complex disease that usually involves more than gut microbial communities that are out of whack.

“IBD is a complicated disease, and you need to attack it at different angles,” says Hu.

So, Hu and his colleagues devised specialized nanoparticles to neutralize molecules implicated in IBD. They’ve also figured out a way of attaching these nanoparticle “backpacks” to beneficial bacteria after encasing them in the protective coating.

Researchers Solve Hundred-Year-Old Botanical Mystery that was Key to the Spread of Plant Life on Land

Plant material from Yale-Myers Forest and YSE greenhouses were used to study how their vascular systems are constructed and how they compare to the extinct plants from the fossil record. Without developing their vascular systems, plants would largely still look like mosses. Shown here: Huperzia lucidula, also known as Shining club-moss.
Photo Credit: courtesy of Craig Brodersen Lab.

The earliest land plants were small — just a few centimeters tall at most — and restricted to moist, boggy habitats around streams and ponds. Around 400 million years ago, however, plants developed vascular systems to extract water more efficiently from the soil and use it for photosynthesis, a transition that would forever alter the Earth’s atmosphere and ecosystems. A team of researchers have now solved a 100-year-old paleontology mystery: How did ancient plants emerge from swamps and riverbanks to new habitats with limited access to water?

In a new paper published in Science, YSE Professor of Plant Physiological Ecology Craig Brodersen and his research team, including lead author Martin Bouda ’17 PhD, ’12 MPhil and Kyra A. Prats ’22 PhD, ’16 MFS, discovered that a simple change in the vascular system of plants made them more drought-resistant, which opened up new landscapes for exploration.

The research was spurred by a century-long debate about why the simple, cylindrical vascular system of the earliest land plants rapidly changed to more complex shapes. In the 1920s, scientists noted this increasing complexity in the fossil record but were not able to pinpoint the reason — if there even was one — for the evolutionary changes.

New pterosaur species found in sub-Saharan Africa

SMU paleontologists helped find a new species of pterosaurs in Angola, where fossils of other large marine animals have been found. E. otyikokolo can be seen flying above the ocean in the ancient picture.
Artwork Credit: Karen Carr Studio.

With wings spanning nearly 16 feet, a new species of pterosaurs has been identified from the Atlantic coast of Angola.

An international team, including two vertebrate paleontologists from SMU, named the new genus and species Epapatelo otyikokolo. This flying reptile of the dinosaur age was found in the same region of Angola as fossils from large marine animals currently on display at the Smithsonian’s National Museum of Natural History.

Pterosaur fossils that date back to the Late Cretaceous are extremely rare in sub-Saharan Africa, said team member Michael J. Polcyn, research associate in the Huffington Department of Earth Sciences and senior research fellow, ISEM at SMU (Southern Methodist University).

“This new discovery gives us a much better understanding of the ecological role of the creatures that were flying above the waves of Bentiaba, on the west coast of Africa, approximately 71.5 million years ago,” Polcyn said.

Renowned paleontologist Louis L. Jacobs, SMU professor emeritus of earth sciences and president of ISEM, an interdisciplinary institute at the university, also collaborated on the research. The team’s findings were published in the journal Diversity.

Alzheimer's disease can be diagnosed before symptoms emerge

Oskar Hansson, Professor of Neurology Lund University 
Photo Credit: Kennet Ruona

A large study led by Lund University in Sweden has shown that people with Alzheimer's disease can now be identified before they experience any symptoms. It is now also possible to predict who will deteriorate within the next few years. The study is published in Nature Medicine, and is very timely in light of the recent development of new drugs for Alzheimer's disease.

It has long been known that there are two proteins linked to Alzheimer’s – beta-amyloid, which forms plaques in the brain, and tau, which at a later stage accumulates inside brain cells. Elevated levels of these proteins in combination with cognitive impairment have previously formed the basis for diagnosing Alzheimer's.

“Changes occur in the brain between ten and twenty years before the patient experiences any clear symptoms, and it is only when tau begins to spread that the nerve cells die and the person in question experiences the first cognitive problems. This is why Alzheimer's is so difficult to diagnose in its early stages”, explains Oskar Hansson, senior physician in neurology at Skåne University Hospital and professor at Lund University.

He has now led a large international research study that was carried out with 1,325 participants from Sweden, the US, the Netherlands and Australia. The participants did not have any cognitive impairment at the beginning of the study. By using PET scans, the presence of tau and amyloid in the participants' brains could be visualized. The people in whom the two proteins were discovered were found to be at a 20-40 times higher risk of developing the disease at follow-up a few years later, compared to the participants who had no biological changes.

Friendly monkeys have friendly microbes

More sociable monkeys have a higher abundance of certain beneficial gut bacteria, and a lower abundance of potentially disease-causing bacteria, new research has found.

The study involved analyzing social network data from a population of non-captive macaques on the island of Cayo Santiago, off Puerto Rico, and combining this with sequencing data to assess their individual gut microbiota.

The researchers found that monkeys that engage in social interactions were more likely to have an abundance of gut microbes that are known to benefit the immune system, and were less likely to have an abundance of potentially harmful bacteria. The analyses controlled for other factors that could affect the microbiome, including age, season, sex and rank within the group’s hierarchy.

The study was conducted by Dr Katerina Johnson at the University of Oxford's Department of Psychiatry, in collaboration with Dr Karli Watson from the University of Colorado Boulder, alongside Oxford professors Robin Dunbar and Philip Burnet.

Linking Mass Extinctions to the Expansion and Radiation of Land Plants

Ymer Island, Greenland, during the collection of the Heintzbjerg sample sequence used in this study. In the foreground looking down the slope is the Zoologdalen Formation. The body of water is the Dusen Fjord, which separates the northern and southern portions of Ymer Island.
Photo Credit: John Marshall, University of Southampton.

The Devonian Period, 419 to 358 million years ago, was one of the most turbulent times in Earth’s past and was marked by at least six significant marine extinctions, including one of the five largest mass extinctions ever to have occurred. Additionally, it was during the Devonian that trees and complex land plants similar to those we know today first evolved and spread across the landscape. This evolutionary advancement included the development of significant and complex root systems capable of affecting soil biogeochemistry on a scale the ancient Earth had yet to experience.

It has been theorized that these two seemingly separate events, marine extinctions and plant evolution and expansion, were intricately linked in the Devonian. Specifically, it has been proposed that plant evolution and root development occurred so rapidly and on such a massive scale that nutrient export from the land to the ancient oceans would have drastically increased. This scenario is seen in modern systems where anthropogenically sourced nutrient export has vastly increased the nutrient load into areas such as the Gulf of Mexico and the Great Lakes, leading to large-scale algal blooms that ultimately deplete the oxygen in the water column. This effect, known as eutrophication, magnified on a global scale, would have been catastrophic to ancient oceans, fueling algal blooms that would have depleted most of the ocean’s oxygen.

Breathing may measurably modulate neural responses across brain

Wenyu Tu, co-author on the eLife paper and doctoral student in neuroscience in the Huck Institutes of the Life Sciences, sets up a functional MRI experiment. Functional MRI was used in conjunction with neuronal electrophysiology to identify a link between respiration and neural activity changes.
Photo Credit: Kelby Hochreither/Penn State

Mental health practitioners and meditation gurus have long credited intentional breathing with the ability to induce inner calm, but scientists do not fully understand how the brain is involved in the process. Using functional magnetic resonance imaging (fMRI) and electrophysiology, researchers in the Penn State College of Engineering identified a potential link between respiration and neural activity changes in rats.

Their results were made available online ahead of publication in eLife. The researchers used simultaneous multi-modal techniques to clear the noise typically associated with brain imaging and pinpoint where breathing regulated neural activity.

“There are roughly a million papers published on fMRI — a non-invasive imaging technique that allows researchers to examine brain activity in real time,” said Nanyin Zhang, founding director of the Penn State Center for Neurotechnology in Mental Health Research and professor of biomedical engineering. “Imaging researchers used to believe that respiration is a non-neural physiological artifact, like a heartbeat or body movement, in fMRI imaging. Our paper introduces the idea that respiration has a neural component: It affects the fMRI signal by modulating neural activity.”

By scanning the brainwaves of rodents in a resting state under anesthesia using fMRI, researchers revealed a network of brain regions involved in respiration.

Scientists Created Model to Determine Risks of Sudden Cardiac Arrest

According to Maksim Kashtanov, Sverdlovsk doctors perform 20-30 operations a year for this genetic disease.
Photo Credit: from Maksim Kashtanov's personal archive

European and Russian scientists have developed a model for predicting the risks of sudden cardiac arrest after alcohol septal ablation (ASA) for hypertrophic obstructive cardiomyopathy (HOCM). In other words, after surgery to remove a hypertrophic fragment of the left ventricular septum, which prevents normal blood flow to the aorta. The created model is a new word in science: before that the regularities of sudden cardiac arrest after ASA have not been investigated, the modern system of risk assessment for postoperative patients was absent. Meanwhile, HOCM is the cause of 30% of cases of sudden cardiac arrest.

The researchers' recommendations will contribute to the timely identification of patients at risk of sudden cardiac arrest after alcohol septal ablation and to the most effective treatment of hypertrophic obstructive cardiomyopathy. An article about the research was published in the American Journal of Cardiology.

The researchers analyzed the medical histories of more than 1,830 patients seen in clinics in Germany, the Czech Republic, Denmark, the Netherlands, Great Britain, and Russia. The analysis covered the period from 1996 to 2021. The study is the most extensive and in-depth to date. In developing the model, the authors used Russian statistics that have been forming since 2001. Data from Russia - Ekaterinburg and St. Petersburg - accounted for one-third of the statistical base of the study.

Rejuvenated immune cells can improve clearance of toxic waste from brain

Alzheimer’s, Parkinson’s and many other neurodegenerative diseases are marked by damaging clusters of proteins in the brain. Scientists have expended enormous effort searching for ways to treat such conditions by clearing these toxic clusters but have had limited success.

Now, researchers at Washington University School of Medicine in St. Louis has found an innovative way to improve waste clearance from the brain, and thereby possibly treat or even prevent neurodegenerative conditions. They showed that immune cells surrounding the brain influence how efficiently waste is swept out of the brain, and that such immune cells are impaired in old mice, and in people and mice with Alzheimer’s disease. Further, they found that treating old mice with an immune-stimulating compound rejuvenates immune cells and improves waste clearance from the brain.

The findings, published Nov. 9 in Nature, suggest a new approach to halting some of the effects of aging on the brain.

“Alzheimer’s has been studied for many years from the perspective of how neurons die, but there are other cells, such as immune cells on the periphery of the brain, that also may play a role in Alzheimer’s,” said senior author Jonathan Kipnis, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology & Immunology and a BJC Investigator. “It doesn’t look likely that we will be able to revive dead or dying neurons, but the immune cells that sit on the borders of the brain are a feasible target for treating age-related brain diseases. They’re more accessible, and could be drugged or replaced. In this study, we treated aged mice with a molecule that can activate aged immune cells, and it worked in improving fluid flow and waste clearance from the brain. This holds promise as an approach to treating neurodegenerative diseases.”