One Punch Isn’t Enough to Overcome a Common Cancer Mutation

Acute myeloid leukemia as seen under a microscope.
Image Credit: Animalculist
(CC BY-SA 4.0)

Cancer cells are often a mess of mutations. About 20 to 25 percent of cancers involve mutations in a complex of molecules called SWI/SNF. Yet drugs designed to block SWI/SNF activity haven’t always worked as expected.

Researchers at Harvard Medical School have now figured out why.

As reported Nov. 2 in Cell, the team found that when drugs block SWI/SNF, a second molecule steps up to compensate.

Blocking this second molecule alongside SWI/SNF suppressed cancer cell growth in lab dishes, suggesting that a two-drug approach could make treatments more effective in people.

“I am excited about this work because it shows an alternative path forward for treating cancers in which the SWI/SNF complex is mutated,” said senior author Karen Adelman, the Edward S. Harkness Professor of Biological Chemistry and Molecular Pharmacology in the Blavatnik Institute at HMS, whose lab conducted the work.

“What’s interesting and meaningful about this study is it shows that a one-two punch, a double-agent therapy, could be really useful for keeping these cancer cells at bay,” she said.

Study links changes in global water cycle to higher temperatures

Over last 2,000 years, rising and falling temperatures have altered the way water moves around the planet
Photo Credit: Giulia Veneziano

It’s a multibillion-dollar question: What will happen to water as temperatures continue to rise? There will be winners and losers with any change that redistributes where, when and how much water is available for humans to drink and use.

To find answers and make informed predictions, scientists look to the past. Reconstructions of past climate change using geologic data have helped to show the far-reaching influence of human activity on temperatures since the industrial age. But assembling hydroclimate records for the same timeframe has proved to be much harder.

A study from the Past Global Changes (PAGES) Iso2k project team, led by Bronwen Konecky at Washington University in St. Louis, takes an important step toward reconstructing a global history of water over the past 2,000 years. Using geologic and biologic evidence preserved in natural archives — including 759 different paleoclimate records from globally distributed corals, trees, ice, cave formations and sediments — the researchers showed that the global water cycle has changed during periods of higher and lower temperatures in the recent past.

Jurassic worlds might be easier to spot than modern Earth

Modeling by Cornell astronomers finds that telescopes could more easily detect an exoplanet with higher levels of atmospheric oxygen than modern Earth, as existed during the dinosaur age.
Illustration Credit: Rebecca Payne/Carl Sagan Institute

Might a tyrannosaur roam on Trappist-1e, a protoceratops on Proxima Centauri b, or a quetzalcoatlus on Kepler 1047c?

Things may not have ended well for dinosaurs on Earth, but Cornell astronomers say the “light fingerprint” of the conditions that enabled them to emerge here – including abundant atmospheric oxygen – provides a crucial missing piece in our search for signs of life on planets orbiting other stars.

Modeling by Cornell astronomers finds that telescopes could more easily detect an exoplanet with higher levels of atmospheric oxygen than modern Earth, as existed during the dinosaur age.

Their analysis of the most recent 540 million years of Earth’s evolution, known as the Phanerozoic Eon, finds that telescopes could better detect potential chemical signatures of life in the atmosphere of an Earth-like exoplanet more closely resembling the age the dinosaurs inhabited than the one we know today.

Two key biosignature pairs – oxygen and methane, and ozone and methane – appeared stronger in models of Earth roughly 100 million to 300 million years ago, when oxygen levels were significantly higher. The models simulated the transmission spectra, or light fingerprint, generated by an atmosphere that absorbs some colors of starlight and lets others filter through, information scientists use to determine the atmosphere’s composition.

FSU researchers capture high-resolution images of magnesium ions interacting with CRISPR gene-editing enzyme

Hong Li, professor in the Department of Chemistry and Biochemistry and director of the Institute of Molecular Biophysics.
Photo Credit: Devin Bittner/FSU College of Arts and Sciences

The gene-editing technology known as CRISPR has led to revolutionary changes in agriculture, health research and more.

In research published in Nature Catalysis, scientists at Florida State University produced the first high-resolution, time-lapsed images showing magnesium ions interacting with the CRISPR-Cas9 enzyme while it cut strands of DNA, providing clear evidence that magnesium plays a role in both chemical bond breakage and near-simultaneous DNA cutting.

“If you are cutting genes, you don’t want to have only one strand of DNA broken, because the cell can repair it easily without editing. You want both strands to be broken,” said Hong Li, professor in the Department of Chemistry and Biochemistry and director of the Institute of Molecular Biophysics. “You need two cuts firing close together. Magnesium plays a role in that, and we saw exactly how that works.”

Brain health in over 50s deteriorated more rapidly during the pandemic

Photo Credit: Gabriel Porras

Brain health in over 50s deteriorated more rapidly during the pandemic, even if they didn’t have COVID-19, according to major new research linking the pandemic to sustained cognitive decline.

Researchers looked at results from computerized brain function tests from more than 3,000 participants of the online PROTECT study, who were aged between 50 and 90 and based in the UK. The remote study, led by teams at the University of Exeter and the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, and part-funded by NIHR Maudsley BRC, tested participants’ short-term memory and ability to complete complex tasks.

Through analyzing the results from this big dataset, researchers found that cognitive decline quickened significantly in the first year of the pandemic, when they found a 50 per cent change to the rate of decline across the study group. This figure was higher in those who already had mild cognitive decline before the pandemic, according to the research published in The Lancet Healthy Longevity.

Atherosclerosis: RNA fragment creates prospect for new therapies

Image Credit: © Weber Lab, IPEK

Atherosclerosis is considered a frequent cause of cardiovascular diseases and strokes. Despite medical progress, case numbers are constantly rising. Targeted new therapeutic approaches are therefore more important than ever. An international team led by Professor Christian Weber, Director of the Institute for Cardiovascular Prevention (IPEK) at the University Hospital of Munich, and Professor Donato Santovito, leader of the Translational Vascular Therapy research group at IPEK, has now identified a specific microRNA molecule as a promising starting point for the investigation of new therapies.

Some time ago, the researchers had already demonstrated that the transmembrane protein CXCR4 plays a significant role in the development of atherosclerosis. The protein transmits signals to the cell interior. If CXCR4 is specifically silenced in arterial endothelial cells or in smooth muscle cells, it results in more severe atherosclerotic lesions. At the same time, there is increased leukocyte ingress into the cell, which leads to inflammatory processes. With regard to leukocytes, however, the presence of CXCR4 can also promote the development of inflammatory processes. “It made sense, therefore, to only boost the expression of CXCR4 on the cells of the vascular wall in order to counteract the atherosclerosis,” says Santovito. “The challenge, however, is not to influence any biological processes, as the protein occurs in all cells and exercises various important functions.”

New antibodies neutralize resistant bacteria

Cryo-electron microscopic reconstruction of the binding of a human anti-PcrV Fab antibody (yellow) to a PcrV pentamer (blue) of the type III secretion system (T3SS) of Pseudomonas aeruginosa. The antibody binding leads to an inhibition of the T3SS, which is an important virulence factor of P. aeruginosa.
Image Credits: CSSB/Biao Yuan

A research team has discovered antibodies that could lead to a new approach to treating acute and chronic infections with the bacterium Pseudomonas aeruginosa. Due to its numerous resistance mechanisms, P. aeruginosa is associated with high morbidity and mortality and can cause complicated infections and dangerous cases of sepsis in severely ill patients. The team of scientists from the University of Cologne, University Hospital Cologne, the Helmholtz Centre for Infection Research in Braunschweig and University Hospital Hamburg-Eppendorf isolated the antibodies from immune cells of chronically ill patients and described their binding mechanisms. The study ‘Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa’ was published in the renowned scientific journal Cell.

Antibiotic-resistant bacteria are a crucial health concern worldwide not only to infected people, but also to our healthcare systems in general. Infections with the bacterium P. aeruginosa in particular are a threat due to numerous resistance mechanisms, often leading to complicated infections of the lungs and dangerous sepsis, especially in severely ill patients. In addition, the pathogen can permanently colonize organs such as the lungs, where it promotes progressive tissue damage. Often, so-called last-resort antibiotics must be used to treat infected patients, as the standard treatments no longer work. New therapeutic approaches are therefore urgently needed to ensure effective treatment for infections with multi-resistant pathogens such as P. aeruginosa in the future.

Stronger, stretchier, self-healing plastic

The complex shape of an origami crane that was restored using heat after being flattened.
Image Credit: ©2023, Shota Ando

An innovative plastic, stronger and stretchier than the current standard type and which can be healed with heat, remembers its shape and partially biodegradable, has been developed by researchers at the University of Tokyo. They created it by adding the molecule polyrotaxane to an epoxy resin vitrimer, a type of plastic. Named VPR, the material can hold its form and has strong internal chemical bonds at low temperatures. However, at temperatures above 150 degrees Celsius, those bonds recombine and the material can be reformed into different shapes. Applying heat and a solvent breaks VPR down into its raw components. Submerging it in seawater for 30 days also resulted in 25% biodegradation, with the polyrotaxane breaking down into a food source for marine life. This new material could have wide-reaching applications for a more circular economy to recirculate resources and reduce waste, from engineering and manufacturing, to medicine and sustainable fashion.

Despite global campaigns to curb plastic use and waste, it is difficult to avoid the ubiquitous material. From toys and clothes, homeware and electronics, to vehicles and infrastructure, nowadays it may seem like it is in almost everything we use. Although useful, there are many issues associated with plastic’s life cycle and disposal. Developing alternatives which last longer, can be reused and recycled more easily, or which are made from environmentally friendly sources, is key to helping solve these problems and realize several of the United Nations’ Sustainable Development Goals.

Preventing the Exhaustion of T Cells

Healthy (red) and exhausted (green) T cells in the spleen of chronically infected mouse.
Image Credit: Ana Maria Mansilla / Institut für Systemimmunologie, Universität Würzburg

In the immune system's fight against cancer and infections, the T cells often lose their power. The team of Würzburg immunologist Martin Vaeth has found a possible explanation for this phenomenon.

In the immune system, chronic infections and the defense against tumors often lead to the phenomenon of T cell exhaustion: In this process, the T lymphocytes gradually lose their function, which impairs their responses against cancer and infections. The molecular mechanisms that control this loss of function have not been fully unraveled.

It is now certain that the exhaustion process is significantly influenced by the “powerhouses of the cells”, the mitochondria.

When mitochondrial respiration fails, a cascade of reactions is triggered, culminating in the genetic and metabolic reprogramming of T cells – a process that drives their functional exhaustion. But this "burnout" of the T cells can be counteracted: pharmacological or genetic optimization of cellular metabolism increases the longevity and functionality of T cells. This can be achieved, for example, by overexpressing a mitochondrial phosphate transporter that drives the production of the energy-providing molecule adenosine-triphosphate.

The Unraveling of a Protist Genome Could Unlock the Mystery of Marine Viruses

Light-microscopy image of clusters of Aurantiochytrium limacinum cells. The marine protist is prevalent in the world’s oceans.
Image Credits: Laura Halligan, Joshua Rest and Jackie Collier

Viruses are the most prevalent biological entities in the world’s oceans and play essential roles in its ecological and biogeochemical balance. Yet, they are the least understood elements of marine life. By unraveling the entire genome of a certain marine protist that may act as a host for many viruses, an international research team led by scientists from Stony Brook University sets the stage for future investigations of marine protist genomes, marine microbial dynamics and the evolutionary interplay between host organisms and their viruses — work that may open doors to a better understanding of the “invisible” world of marine viruses and offers a key to the ecology and health of oceans worldwide. The research is published early online in Current Biology.

Food webs of the oceans provide humanity with essential food sources as well as the wonderment of sea creatures from polar bears to penguins. This wellspring of life is supported mainly by microscopic organisms, including the wide presence of viruses. Learning more about the viruses through DNA research and other forms of investigation is essential to scientists’ understanding of the sea. Novel groups of viruses are still being discovered, such as the recently discovered “mirusvirues” featured in a Nature paper earlier this year.