. Scientific Frontline

Thursday, January 5, 2023

Ludwig Cancer Research study uncovers novel aspect of tumor evolution and potential targets for therapy

 Ping-Chih Ho, Ludwig Lausanne Associate Member
Photo Credit: Ludwig Cancer Research

A Ludwig Cancer Research study has discovered that the immune system’s surveillance of cancer can itself induce metabolic adaptations in the cells of early-stage tumors that simultaneously promote their growth and equip them to suppress lethal immune responses.

Led by Ludwig Lausanne Associate Member Ping-Chih Ho and published in Cell Metabolism, the study details the precise mechanism by which this “immunometabolic editing” of emergent tumors occurs in mouse models of the skin cancer melanoma and identifies a novel biochemical signaling cascade and proteins that orchestrate its effects. Aside from illuminating a previously unknown dimension of tumor evolution, the findings hold significant promise for improving the efficacy of cancer immunotherapy.

“We have uncovered dozens of metabolic enzymes that contribute to immune evasion in melanoma tumors,” said Ho. “These enzymes, as well as some of the individual components of the signaling pathway we’ve identified, represent a rich trove of potential drug targets to undermine the defenses erected by immunometabolic editing. Such drugs could make tumors vulnerable to immune clearance and could also be used in combination with checkpoint blockade and other immunotherapies to overcome the resistance most cancers have to such treatments.”

New approach successfully traces genomic variants back to genetic disorders

Doctors researching DNA and genetics.
Illustration Credit: Julia Fekecs, NHGRI

National Institutes of Health researchers have published an assessment of 13 studies that took a genotype-first approach to patient care. This approach contrasts with the typical phenotype-first approach to clinical research, which starts with clinical findings. A genotype-first approach to patient care involves selecting patients with specific genomic variants and then studying their traits and symptoms; this finding uncovered new relationships between genes and clinical conditions, broadened the traits and symptoms associated with known disorders, and offered insights into newly described disorders. The study was published in the American Journal of Human Genetics.

“We demonstrated that genotype-first research can work, especially for identifying people with rare disorders who otherwise might not have been brought to clinical attention,” says Caralynn Wilczewski, Ph.D., a genetic counselor at the National Human Genome Research Institute’s (NHGRI) Reverse Phenotyping Core and first author of the paper.

Typically, to treat genetic conditions, researchers first identify patients who are experiencing symptoms, then they look for variants in the patients’ genomes that might explain those findings. However, this can lead to bias because the researchers are studying clinical findings based on their understanding of the disorder. The phenotype-first approach limits researchers from understanding the full spectrum of symptoms of the disorders and the associated genomic variants.

New quantum computing architecture could be used to connect large-scale devices

This image shows a module composed of superconducting qubits that can be used to directionally emit microwave photons.
Illustration Credit: Massachusetts Institute of Technology / Courtesy of the researchers

Quantum computers hold the promise of performing certain tasks that are intractable even on the world’s most powerful supercomputers. In the future, scientists anticipate using quantum computing to emulate materials systems, simulate quantum chemistry, and optimize hard tasks, with impacts potentially spanning finance to pharmaceuticals.

However, realizing this promise requires resilient and extensible hardware. One challenge in building a large-scale quantum computer is that researchers must find an effective way to interconnect quantum information nodes — smaller-scale processing nodes separated across a computer chip. Because quantum computers are fundamentally different from classical computers, conventional techniques used to communicate electronic information do not directly translate to quantum devices. However, one requirement is certain: Whether via a classical or a quantum interconnect, the carried information must be transmitted and received.

To this end, MIT researchers have developed a quantum computing architecture that will enable extensible, high-fidelity communication between superconducting quantum processors. In work published today in Nature Physics, MIT researchers demonstrate step one, the deterministic emission of single photons — information carriers — in a user-specified direction. Their method ensures quantum information flows in the correct direction more than 96 percent of the time.

James Webb Telescope Reveals Milky Way-like Galaxies in Young Universe

The power of JWST to map galaxies at high resolution and at longer infrared wavelengths than Hubble allows it look through dust and unveil the underlying structure and mass of distant galaxies. This can be seen in these two images of the galaxy EGS23205, seen as it was about 11 billion years ago. In the HST image (left, taken in the near-infrared filter), the galaxy is little more than a disk-shaped smudge obscured by dust and impacted by the glare of young stars, but in the corresponding JWST mid-infrared image (taken this past summer), it’s a beautiful spiral galaxy with a clear stellar bar.
Image Credit: NASA/CEERS/University of Texas at Austin

New images from NASA’s James Webb Space Telescope (JWST) reveal for the first-time galaxies with stellar bars — elongated features of stars stretching from the centers of galaxies into their outer disks — at a time when the universe was a mere 25% of its present age. The finding of so-called barred galaxies, similar to our Milky Way, this early in the universe will require astrophysicists to refine their theories of galaxy evolution.

Prior to JWST, images from the Hubble Space Telescope had never detected bars at such young epochs. In a Hubble image, one galaxy, EGS-23205, is little more than a disk-shaped smudge, but in the corresponding JWST image taken this past summer, it’s a beautiful spiral galaxy with a clear stellar bar.

“I took one look at these data, and I said, ‘We are dropping everything else!’” said Shardha Jogee, professor of astronomy at The University of Texas at Austin. “The bars hardly visible in Hubble data just popped out in the JWST image, showing the tremendous power of JWST to see the underlying structure in galaxies,” she said, describing data from the Cosmic Evolution Early Release Science Survey (CEERS), led by UT Austin professor, Steven Finkelstein.

New kind of scissors discovered

Professor Chase Beisel and Dr. Oleg Dmytrenko in the Würzburg HIRI laboratory.
Photo Credit: HIRI

Like a Swiss Army knife: a newly discovered component of bacterial immune defense paralyzes infected cells. He could advance molecular biological diagnostics.

Bacteria can also be infected by viruses, and they have developed their own immune defense strategies in this case. Bacterial defense systems such as CRISPR-Cas have various proteins and functions that help the bacteria protect themselves against intruders.

The defense is based on a common basic mechanism: a CRISPR ribonucleic acid (crRNA), which serves as a "lead RNA", helps to identify regions of a foreign genome, such as the DNA of a virus, in order to make them specifically harmless. The nuclease led by a crRNA can cut its target like scissors. It is a strategy of nature that humans have made use of technologically in a variety of ways.

"When you consider how well different nucleases have been implemented in new and improved technologies, any discovery in this area could bring new benefits to society," Professor Chase Beisel describes a research motivation of his laboratory at the Helmholtz Institute for RNA-based in Würzburg Infection research (HIRI). The facility is a location of the Helmholtz Center for Infection Research in Braunschweig in cooperation with the Julius Maximilians University, to which Chase Beisel is the head of the chair for synthetic RNA biology.

Climate change could cause “disaster” in the world’s oceans

J. Keith Moore, UCI professor of Earth system science, says, “… unchecked global warming could lead to a shutdown of the ocean deep circulation. This would be a climate disaster similar in magnitude to complete melting of the ice sheets on land.”
Photo Credit: Steve Zylius / UCI

Climate-driven heating of seawater is causing a slowdown of deep circulation patterns in the Atlantic and Southern oceans, according to University of California, Irvine Earth system scientists, and if this process continues, the ocean’s ability to remove carbon dioxide from the atmosphere will be severely limited, further exacerbating global warming.

In a recent study published in Nature Climate Change, these researchers analyzed projections from three dozen climate models and found that the Atlantic Meridional Overturning Circulation and the Southern Meridional Overturning Circulation will slow by as much as 42 percent by 2100. The simulations suggest that under worst-case warming, the SMOC could cease entirely by 2300.

“Analysis of the projections from 36 Earth system models over a range of climate scenarios shows that unchecked global warming could lead to a shutdown of the ocean deep circulation,” said co-author J. Keith Moore, UCI professor of Earth system science. “This would be a climate disaster similar in magnitude to complete melting of the ice sheets on land.”

Antibiotic residues in water a threat to human health

Photo Credit: Thomas Hoang

Antibiotic residues in wastewater and wastewater treatment plants in regions around China and India risk contributing to antibiotic resistance, and the drinking water may pose a threat to human health, according to an analysis from Karolinska Institutet published in The Lancet Planetary Health. The researchers also determined the relative contribution of various sources of antibiotic contamination in waterways, such as hospitals, municipals, livestock, and pharmaceutical manufacturing.

” Our results can help decision-makers to target risk reduction measures against environmental residues of priority antibiotics and in high-risk sites, to protect human health and the environment,” says Nada Hanna, researcher at the Department of Global Public Health at Karolinska Institutet, and the study’s first author. “Allocating these resources efficiently is especially vital for resource-poor countries that produce large amounts of antibiotics.”

Bacteria that become resistant to antibiotics are a global threat that can lead to untreatable bacterial infections in animals and humans.

Antibiotics can enter the environment during their production, consumption and disposal. Antibiotic residues in the environment, such as in wastewater and drinking water, can contribute to the emergence and spread of resistance.

Effects of highly pathogenic avian influenza on canids investigated

When the H5N1 HPAI virus (orange) affected a flock of crows in a public garden, it caused a mass die-off of crows. An Ezo red fox and a Japanese raccoon dog were also infected by the H5N1 HPAI virus, the former likely by consuming corpses of the crows, and the latter due to close contact with crow corpses
Illustration Credit: Takahiro Hiono

Researchers at Hokkaido University have revealed the effects of high pathogenicity avian influenza virus infection on an Ezo red fox and a Japanese raccoon dog, linking their infection to a recorded die-off of crows.

High Pathogenicity Avian Influenza (HPAI), commonly known as a type of bird flu, is caused by a group of influenza viruses that affect birds. Humans are very rarely infected by this virus. The most well-known HPAI viral subtype is H5N1, first reported in 1996 for its infection in geese, and then found in humans since 1997. A great amount of time and resources are devoted to monitoring and tracking the spread of HPAI across the globe, due to its disruptive potential on poultry farming—outbreaks are contained by culling exposed and infected flocks.

How to turn a tentacle into a foot

Hydra with reduced Zic4 content. The red arrowheads indicate the tentacles that have been transformed into feet, the asterisk indicates the animal's mouth.
Illustration Credit:  Galliot, Brigitte CC-BY-NC

By identifying a key cell identity regulator, a team from UNIGE and the IMF has managed to modify the structure and function of tentacle cells in the hydra.

Humans, animals, plants: all multicellular organisms consist of so-called differentiated specialized cells. Thus, the cells that make up the epidermis do not have the same identity - nor the same function - as those that line the digestive system, for example. However, the mechanisms allowing these cells to maintain their identity are still poorly understood. Working on hydra, a team from the University of Geneva (UNIGE), in collaboration with the Friedrich Miescher Institute for Biomedical Research (IMF) in Basel, discovered one of the key regulators: the factor of transcription Zic4. After reducing its expression, researchers have found that the tentacle cells of the hydra change their identity and turn into foot cells, forming functional feet in the animal's head. These results are to be discovered in the journal Science Advances.

Wednesday, January 4, 2023

Reef fish must relearn 'rules of engagement' after coral bleaching

butterfly fish
Photo Credit: Светлана

Mass coral bleaching events are making it harder for some species of reef fish to identify competitors, new research reveals.

Scientists studying reefs across five Indo-Pacific regions found that the ability of butterfly fish individuals to identify competitor species and respond appropriately was compromised after widespread loss of coral caused by bleaching.

This change means they make poorer decisions that leave them less able to avoid unnecessary fights, using up precious limited energy. The scientists behind the study believe these changes could have implications for species survival as further global warming increases the likelihood of coral loss.

“By recognizing a competitor, individual fish can make decisions about whether to escalate, or retreat from, a contest—conserving valuable energy and avoiding injuries,” said Sally Keith, a senior lecturer in marine biology at Lancaster University and lead author of the study.

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