A New Cancer Mechanism: Failed Cell Housekeeping

Illustration of single-stranded RNA
Illustration Credit: National Institute of General Medical Sciences

New research pinpoints a gene that, when mutated, causes cancer through a mechanism scientists haven’t seen before: cells lose the ability to dispose of their trash, namely defective strands of RNA.

This mechanism appears to cut across many different malignancies and could present a whole new set of molecules for cancer drugs to target, as reported in the journal Science by a team from Harvard Medical School, Boston Children’s Hospital, and Dana-Farber Cancer Institute.

While studying zebrafish, Megan Insco, HMS instructor in medicine who was a research fellow in the lab of Leonard Zon at HMS and Boston Children’s at the time, identified a tumor-suppressing gene called CDK13. When mutated, it expedited the development of melanoma. 

The same gene was also mutated in many human melanomas, she found.

But what was really surprising was how the CDK13 mutation causes cancer.

Investigating the RNAs made by melanoma cells, Insco saw multiple short, defective RNAs. She immediately shared this odd finding with Zon.

Researchers map the genome of the world’s grumpiest cat

The mighty roar of a grumpy and angry Pallas' cat (Otocolobus manul)
Photo Credit: Johannes Heel

University of Minnesota researchers recently led successful efforts to build the first genome for Pallas’s cat (Otocolobus manul), a small wild cat native to central Asia known for its grumpy facial expression. The cat, which faces growing challenges from climate change, habitat fragmentation, and poaching, had no available genetic resources to help with conservation prior to this study. 

The study, published in NAR Genomics and Bioinformatics, was led by Nicole Flack, a doctoral candidate in the College of Veterinary Medicine, along with Christopher Faulk, a professor in the College of Food, Agricultural, and Natural Resource Sciences. 

The researchers used blood samples from Tater, a 6-year-old Pallas’s cat who lives at the Utica Zoo in New York, to construct a high-quality diploid nuclear genome assembly, a representative map of genes for the species.

The study results include confirmation that the Pallas’s cat is more closely related to certain wild cat species and less related to house cat species than some previous studies have suggested. 

Wild plants can adapt to agricultural propagation

Wild plants for restoration projects are propagated in culture.
Photo Credit: Ute Matthies

Researchers study rapid domestication of plants grown for seed production to restore ecosystems

Wild plants play an important role in the renaturation of degraded landscapes and ecosystems. The seeds for this are mainly propagated in specialized farms, similar to crops. A team of biologists led by researchers from the University of Marburg has now taken a more detailed look at how the farm production of seeds for restoration affects the characteristics of the species. Across as few as three generations, some species evolved signs of a so-called domestication syndrome - a suite of traits typically evolved by crops during domestication from their wild relatives. The observed changes across the first generations were primarily small and unlikely to compromise the quality of the currently produced seeds. Yet, it is the first warning that seeds of wild plants must be produced with caution and only for a limited number of cultivated generations before new seeds are collected from the wild. The results of the study have been published in the Journal PNAS.

The destruction of natural habitats is the greatest threat to biodiversity. More than half of the world's land area is already degraded. However, this dire state can be partially reversed through ecosystem restoration - the restoration of natural habitats on degraded land. Restoration measures include, for example, restoring forests by planting trees or restoring grasslands by sowing seeds. The seeds for these measures are usually produced in specialized seed farms.

Fecal beads to act at the core of the intestinal microbiota

Alginate microparticles containing isolated bacterial strains (white particles) and a fecal transplant (brown particles), with a zoom on the structure of the microparticles by scanning electron microscopy.
 Image Credits: © Adèle Rakotonirina et Nathalie Boulens
(CC BY-NC-ND 4.0)

A UNIGE team, in collaboration with the CHUV, has developed a new method of encapsulating fecal bacteria to treat a serious intestinal infection.

Clostridioides difficile infection causes severe diarrhea and results in the death of nearly 20,000 patients in Europe each year. It is one of the most common hospital-acquired infections. When it relapses, the disease must be treated by fecal microbiota transplantation. This treatment, which is administered via a nasogastric or colorectal tube, is very demanding. Researchers at the University of Geneva (UNIGE), in collaboration with the Lausanne University Hospital (CHUV), have developed small beads to be taken orally, which could radically improve its administration. This work can be found in the International Journal of Pharmaceutics.

Naturally found in 15% of the population, Clostridioides difficile is a bacterium that can become pathogenic when the protective "barriers" of our intestinal flora are weakened. This is particularly the case after prolonged and repeated use of antibiotics. Clostridioides difficile then causes severe diarrhea and can lead to a critical inflammation of the colon, known as pseudomembranous colitis. With more than 124,000 cases per year in Europe, it is one of the most common hospital-acquired infections and is fatal in about 15% of cases.

The bat's ability to convert energy into muscle power is affected by flight speed

Photo Credit: Anders Hedenström

Small bats are bad at converting energy into muscle power. Surprisingly, a new study led by Lund University reveals that this ability increases the faster they fly.

The researchers have studied the efficiency of migratory bats – a species that weighs about eight grams and is found in almost all of Europe. Efficiency, in this case, is the ability to convert supplied energy into something we need. For bats and birds, it’s the energy required to fly. In a new study published in the journal Proceedings of the Royal Society B, a research team in Lund states that the efficiency varies with the bats' flight speed. The faster the bats flew, the more energy they managed to convert into muscle power.

“Previously, we believed that efficiency is a constant. So, this is a bit of a breakthrough”, says Anders Hedenström, biology researcher at Lund University.

Using high-speed cameras, laser and smoke in a wind tunnel, the researchers have measured the bat's kinetic energy. They then compared these results with the animals' metabolism – a methodological breakthrough with technically advanced measurements. In the past, researchers have only measured either kinetic energy or metabolic rate and compared this to theories.

Earth’s first animals had particular taste in real estate

Obamus coronatus.
Photo Credit: Mary Droser/University of California, Riverside

Even without body parts that allowed for movement, new research shows — for the first time — that some of Earth’s earliest animals managed to be picky about where they lived.

These creatures from the Ediacaran Period, roughly 550 million years ago, are strangely shaped soft-bodied animals that lived in the sea. Researchers have long considered them enigmatic. 

“It’s not like studying dinosaurs, which are related to birds that we can observe today,” said Phillip C. Boan, UC Riverside paleontology graduate student and lead author of the new study. “With these animals, because they have no modern descendants, we’re still working out basic questions about how they lived, such as how they reproduced and what they ate.”

For this particular research project, the researchers focused on understanding where in the sea the animals spent their lives. 

The ancient sea was also a largely foreign place compared to today’s marine environments. It was dominated by a mat on the sea floor composed of bacteria and layers of other organic materials. In addition, predatory creatures were uncommon.

The brain reacts differently to touch depending on context

Photo Credit: Thor Balkhed

The touch of another person may increase levels of the “feelgood” hormone oxytocin. But the context really matters. The situation impacts oxytocin levels not only in the moment, but also later, as is shown by researchers at Linköping University and the University of Skövde.

 An embrace from a parent, a warm hand on your shoulder or a caress from a romantic partner are examples of how touch can strengthen social bonds between people and influence emotions. But although touch and the sense of touch have a very important function, knowledge of how this actually works is still lacking.

Studies in animals have shown that the hormone oxytocin is linked to touch and social bonding. However, many questions remain unanswered when it comes to oxytocin’s role in human social interactions and how this hormone can influence and be influenced by the brain. To study this closer, researchers have examined what happens in the body when we feel a soft touch. India Morrison. 

Beetles and their biodiversity in dead wood

The red dots on the map of Europe show the locations where the biodiversity of deadwood beetles was studied in relation to the available energy.
Illustration Credit: Peter Kriegel / Universität Würzburg

Which energy type promotes the biodiversity of beetles living in dead wood in the forest? That depends entirely on where the beetles are in the food chain.

Energy is the key to life. For decades, scientists have been trying to decipher the connection between available energy and biodiversity in ecosystems.

In the process, clear correlations have emerged. For example, ecosystems with higher energy input, for example due to stronger solar radiation near the equator, are endowed with greater biodiversity. But ecosystems do not exclusively draw their energy directly from the sun. Energy can also be stored chemically, for example in resources such as wood.

Which type of energy promotes biodiversity? Does it happen uniformly along the food chain? These questions have remained unanswered until now.

The first answers have now come from researchers at the Julius-Maximilians-Universität (JMU) Würzburg Biocentre. A team led by ecologists Simon Thorn and Peter Kriegel has studied the species diversity of beetles that live in deadwood in forests. Data from all over Europe was collected for this purpose. Simon Thorn initiated and coordinated the project six years ago; he has recently started research at the Hessian Agency for Nature Conservation, Environment and Geology.

AI Predicts Future Pancreatic Cancer

Pancreatic cancer cells
Image Credit: National Cancer Institute

An artificial intelligence tool has successfully identified people at the highest risk for pancreatic cancer up to three years before diagnosis using solely the patients’ medical records, according to new research led by investigators at Harvard Medical School and the University of Copenhagen, in collaboration with VA Boston Healthcare System, Dana-Farber Cancer Institute, and the Harvard T.H. Chan School of Public Health.

The findings, published May 8 in Nature Medicine, suggest that AI-based population screening could be valuable in finding those at elevated risk for the disease and could expedite the diagnosis of a condition found all too often at advanced stages when treatment is less effective and outcomes are dismal, the researchers said. Pancreatic cancer is one of the deadliest cancers in the world, and its toll projected to increase.

Currently, there are no population-based tools to screen broadly for pancreatic cancer. Those with a family history and certain genetic mutations that predispose them to pancreatic cancer are screened in a targeted fashion. But such targeted screenings can miss other cases that fall outside of those categories, the researchers said.

“One of the most important decisions clinicians face day to day is who is at high risk for a disease, and who would benefit from further testing, which can also mean more invasive and more expensive procedures that carry their own risks,” said study co-senior investigator Chris Sander, faculty member in the Department of Systems Biology in the Blavatnik Institute at HMS. “An AI tool that can zero in on those at highest risk for pancreatic cancer who stand to benefit most from further tests could go a long way toward improving clinical decision-making.”

An unprecedented view of gene regulation

Caption:“Using this method, we generate the highest-resolution maps of the 3D genome that have ever been generated, and what we see are a lot of interactions between enhancers and promoters that haven't been seen previously,” says Anders Sejr Hansen, the Underwood-Prescott Career Development Assistant Professor of Biological Engineering at MIT. 

Video Credit: Melanie Gonick/MIT

Much of the human genome is made of regulatory regions that control which genes are expressed at a given time within a cell. Those regulatory elements can be located near a target gene or up to 2 million base pairs away from the target.

To enable those interactions, the genome loops itself in a 3D structure that brings distant regions close together. Using a new technique, MIT researchers have shown that they can map these interactions with 100 times higher resolution than has previously been possible.

“Using this method, we generate the highest-resolution maps of the 3D genome that have ever been generated, and what we see are a lot of interactions between enhancers and promoters that haven't been seen previously,” says Anders Sejr Hansen, the Underwood-Prescott Career Development Assistant Professor of Biological Engineering at MIT and the senior author of the study. “We are excited to be able to reveal a new layer of 3D structure with our high resolution.”

The researchers’ findings suggest that many genes interact with dozens of different regulatory elements, although further study is needed to determine which of those interactions are the most important to the regulation of a given gene.

T Cells Can Activate Themselves to Fight Tumors

T cells are a type of white blood cell and play a central role in the immune response.
Photo Credit: NIAID.

When you need a bit of motivation, it often has to come from within. New research suggests cancer-fighting immune cells have found a way to do just that.

Scientists at University of California San Diego have discovered a property of T cells that could inspire new anti-tumor therapeutics. Through a previously undescribed form of cell auto-signaling, T cells were shown to activate themselves in peripheral tissues, fueling their ability to attack tumors.

The study, published May 8, 2023 in Immunity, was led by study first author and postdoctoral fellow Yunlong Zhao, PhD, and co-senior authors Enfu Hui, PhD, professor in the School of Biological Sciences at UC San Diego and Jack D. Bui, MD, PhD, professor of pathology at UC San Diego School of Medicine.

T cells are a type of white blood cell that protect against infection and help fight cancer. In the lymph organs, T cells are trained by antigen-presenting cells, which, as their name suggests, present an antigen (a piece of tumor or pathogen) to T cells, stimulating an immune response. 

A new at­las il­lus­trates how the hu­man ret­ina is de­vel­op­ing.

De­tail of a cross-​section of a ret­inal or­ganoid. Dif­fer­ent tis­sue struc­tures are made vis­ible with dif­fer­ent colors.
Pho­to­ Credit: Wahle et al. Nature Bi­o­tech­no­logy 2023

What cell types are found in which hu­man tis­sue, and where? Which genes are act­ive in the in­di­vidual cells, and which pro­teins are found there? An­swers to these ques­tions and more are to be provided by a specialized at­las – in par­tic­u­lar how the dif­fer­ent tis­sues form dur­ing em­bryonic de­vel­op­ment and what causes dis­eases. In cre­at­ing this at­las, re­search­ers aim to map not only tis­sue dir­ectly isol­ated from hu­mans, but also struc­tures called or­ganoids. These are three-​dimensional clumps of tis­sue that are cul­tiv­ated in the labor­at­ory and de­velop in a way sim­ilar to hu­man or­gans, but on a small scale.

“The ad­vant­age of or­ganoids is that we can in­ter­vene in their de­vel­op­ment and test act­ive sub­stances on them, which al­lows us to learn more about healthy tis­sue as well as dis­eases,” ex­plains Bar­bara Treut­lein, Pro­fessor of Quant­it­at­ive De­vel­op­mental Bio­logy at the De­part­ment of Biosys­tems Sci­ence and En­gin­eer­ing at ETH Zurich in Basel.

To help pro­duce such an at­las, Treut­lein, to­gether with re­search­ers from the Uni­ver­sit­ies of Zurich and Basel, has now de­veloped an ap­proach to gather and com­pile a great deal of in­form­a­tion about or­ganoids and their de­vel­op­ment. The re­search team ap­plied this ap­proach to the or­ganoids of the hu­man ret­ina, which they de­rived from stem cells.

Researchers develop model for how the brain acquires essential omega-3 fatty acids

Step-by-step process of lipid transport across blood-brain barrier.
Illustration Credit: Ethan Tyler from NIH Medical Arts

Researchers at the UCLA David Geffen School of Medicine, the Howard Hughes Medical Institute at UCLA and the National Institutes of Health have developed a zebrafish model that provides new insight into how the brain acquires essential omega-3 fatty acids, including docosahexaenoic acid (DHA) and linolenic acid (ALA). Their findings, published in Nature Communications, have the potential to improve understanding of lipid transport across the blood-brain barrier and of disruptions in this process that can lead to birth defects or neurological conditions. The model may also enable researchers to design drug molecules that are capable of directly reaching the brain.

Omega-3 fatty acids are considered essential because the body cannot make them and must obtain them through foods, such as fish, nuts and seeds. DHA levels are especially high in the brain and important for a healthy nervous system. Infants obtain DHA from breastmilk or formula, and deficiencies of this fatty acid have been linked to problems with learning and memory. To get to the brain, omega-3 fatty acids must pass through the blood-brain barrier via the lipid transporter Mfsd2a, which is essential for normal brain development. Despite its importance, scientists did not know precisely how Mfsd2a transports DHA and other omega-3 fatty acids.

X-ray beams help researchers learn new tricks from old metals

 

An intense X-ray beam (in pink) is focused into a small spot on a single nanoscale grain of a platinum electrode (highlighted within the droplet). Diffraction interference patterns from that grain were collected on an X-ray detector (the black screen).
Illustration Credit: Dina Sheyfer, Argonne National Laboratory.

A research team led by the U.S. Department of Energy’s (DOE) Argonne National Laboratory used powerful X-ray beams to unlock a new understanding of materials important to the production and use of hydrogen. The goal is to make hydrogen production and usage more efficient and less expensive, offering a better fuel for transportation and industry.

“Efficient hydrogen production is key,” said Hoydoo You, an Argonne senior physicist. ​“Hydrogen is the lightest energy storage material. Hydrogen can be produced from water using renewable energy or excess energy, transported as a fuel, and converted back to water to produce energy for consumers. Platinum and its alloys are best in catalyzing and boosting the water-splitting process by accelerating the exchange of electrons.”

Understanding and developing materials enabling efficient production and usage of hydrogen are key to the hydrogen economy. The researchers made a first step in developing a tool that enables them to characterize the materials with a new level of detail, ultimately producing the best materials for hydrogen production and use.

Study sheds light on how the immune system protects the body

Photo Credit: RDNE Stock project

Researchers explore how patients with a rare and severe immunodeficiency were still able to defend themselves normally against viruses, including COVID-19

The first study of humans with a rare immunodeficiency reveals how the immune system protects the body against pathogens known to cause serious diseases, such as tuberculosis and COVID-19. The research involving McGill University, paves the way for new therapies to treat autoimmune diseases, chronic inflammatory diseases, and new approaches to vaccine development.

The immune system responds differently to various types of pathogens, like bacteria, parasites, and viruses. However, scientists are still trying to uncover how this complex network functions together and the processes that can go wrong with immunodeficiencies.

“The immune system plays a vital role in protecting the body from harmful germs that make people ill. It’s made up of a complex network of organs, cells, and proteins – like IRF1 or regulatory factor 1, which is key in the regulation of an early immune response to pathogens,” says co-author of the study David Langlais, an Assistant Professor in the Departments of Human Genetics and Microbiology and Immunology at McGill University.