Cancer research: Metabolite drives tumor development

Tumor organoids (green/blue) are used as a model to study the metabolic changes in liver cell cancer.
 Image Credit: Dr. Sandro Nuciforo, Department of Biomedicine, University of Basel

Cancer cells are chameleons. They completely change their metabolism to grow continuously. University of Basel scientists have discovered that high levels of the amino acid arginine drive metabolic reprogramming to promote tumor growth. This study suggests new avenues to improve liver cancer treatment.

The liver is a vital organ with many important functions in the body. It metabolizes nutrients, stores energy, regulates the blood sugar level and plays a crucial role in detoxifying and removing harmful components and drugs. Liver cancer is one of the world’s most lethal types of cancer. Conditions that cause liver cancer include obesity, excessive alcohol consumption and hepatitis C infection. Early diagnosis and appropriate therapeutic strategies are crucial for improving treatments in liver cancer.

Cancer as a metabolic disease

In the past decade, scientists have made much progress in understanding the multiple facets of cancer. Historically, it has long been viewed as a disorder in cell proliferation. However, there is growing evidence that cancer is a metabolic disease. In other words, cancer arises when cells rewire their metabolism to allow uncontrolled cell proliferation. How do cells change their metabolism and how does this change in turn lead to tumorigenicity? With their new study in “Cell”, researchers led by Professor Michael N. Hall at the Biozentrum, University of Basel, have discovered a key driver of metabolic rewiring in liver cancer cells.

Evolutionary history of three-finger snake toxins decoded

Burkhard Rost, a professor of bioinformatics
Photo Credit: Julia Eberle / ediundsepp / TUM

Snakebites cause around 100,000 deaths worldwide every year. Researchers at the Technical University of Munich (TUM) have investigated how the toxin emerged between 50 and 120 million years ago through the modification of a gene that also occurs in mammals and other reptiles. The results could help with the development of better snakebite treatments and lead to new knowledge for the treatment of illnesses such as type 2 diabetes and hypertension.

When venom passes into a snakebite victim, it binds onto receptors on nerve and muscle cells and interrupts communication pathways between them. This initially causes paralysis and, without an antidote, can cause death within a matter of minutes or hours. A team of researchers has studied how the protein structure of snake venoms known as three-finger toxins (3FTxs) has changed over the course of evolution.

Biodiversity in the forest: mixed forests are more productive if they are structurally complex

Photo Credit: Imat Bagja Gumilar

The more tree-rich forests are, the faster the trees grow and the more CO2 they can bind. A joint study by the TU Dresden, Leuphana University of Lüneburg, Martin Luther University Halle-Wittenberg (MLU), University of Leipzig, University of Montpellier and the German Center for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig shows which mechanisms lie behind it. The results have now been published in the journal Science Advances.

If many different tree species live together in mixed stands, this has a positive effect on their growth and thus wood production - many studies have already confirmed this. The greater the variety of tree species in a forest, the more complex the structures are. The species not only grow to different extents in a certain period of time and have very different tree tops, they also have individual demands on light, water and nutrients. It was previously unclear how the structural complexity in mixed stocks is related to productivity and which mechanisms work here.

A mother mouse needs a diverse gut microbiome to form a healthy placenta

“More and more evidence is suggesting that [the gut microbiome] begins to exert its influence even during prenatal life,” said UCLA’s Elaine Hsiao.
Photo Credit: Karsten Paulick

The bacteria found naturally in the digestive tract does a lot more than help digest food.

Scientists have established that these microbial communities are also involved with the immune system and play a role in mental health. Now, they can add helping grow a healthy placenta during pregnancy to the list of unexpected ways the gut microbiome influences health and well-being.

New research led by UCLA scientists and published today in the journal Science Advances shows that mice with depleted gut microbiomes had smaller placentas than normal mice and that the network of blood vessels between the placenta and the fetus was also less developed.

Either of these conditions could deprive a fetus of nutrients, oxygen and other things it needs to grow. But when malnourished pregnant mice that had been fed low-protein diets and had diminished microbiomes were supplemented with short-chain fatty acids, which are produced by gut microbes, their placentas grew to normal size, the researchers said.

The new findings add to mounting evidence that in addition to its many other activities, the gut microbiome plays a role in the formation of new blood vessels, a process known as angiogenesis. They also show that byproducts of microbe metabolism known as metabolites play key roles in feto-placental development.

Researchers catch protons in the act of dissociation with SLAC’s ultrafast 'electron camera'

Irradiating ammonia – which is made up of one nitrogen and three hydrogens – with ultraviolet light causes one hydrogen to dissociate from the ammonia. SLAC researchers used an ultrafast “electron camera” to watch exactly what that hydrogen was doing as it dissociated. The technique had been proposed, but never proven to work, until now. In the future, researchers could use the technique to study hydrogen transfers – critical chemical reactions that drive many biological processes.
Illustration Credit: Nanna H. List/KTH Royal Institute of Technology

Scientists have caught fast-moving hydrogen atoms – the keys to countless biological and chemical reactions – in action.

A team led by researchers at the Department of Energy’s SLAC National Accelerator Laboratory and Stanford University used ultrafast electron diffraction (UED) to record the motion of hydrogen atoms within ammonia molecules. Others had theorized they could track hydrogen atoms with electron diffraction, but until now nobody had done the experiment successfully.

The results, published in Physical Review Letters, leverage the strengths of high-energy Megaelectronvolt (MeV) electrons for studying hydrogen atoms and proton transfers, in which the singular proton that makes up the nucleus of a hydrogen atom moves from one molecule to another.  

Proton transfers drive countless reactions in biology and chemistry – think enzymes, which help catalyze biochemical reactions, and proton pumps, which are essential to mitochondria, the powerhouses of cells – so it would be helpful to know exactly how its structure evolves during those reactions. But proton transfers happen super-fast – within a few femtoseconds, one millionth of one billionth of one second. It’s challenging to catch them in action.

Identifying biosecurity to prevent CWD transmission

Photo Credit: Minnesota Board of Animal Health

As chronic wasting disease (CWD) ravaged deer populations across the country in recent years, studies have primarily focused on how CWD can jump from farmed herds to wild deer, with little attention given to how transmission may occur from wild deer to those living on farms. University of Minnesota researchers recently assessed the risks associated with the introduction of CWD to farmed deer herds in Minnesota, Pennsylvania and Wisconsin. Because CWD is highly infectious and sometimes fatal disease for deer with no treatment or vaccination available, strategies to prevent its spread are primary tools available to keep these animals healthy.

The study, published in Preventive Veterinary Medicine, examined various transmission pathways and their associated risk factors for farmed deer herds. The researchers collected data from 71 herds in three states, including both CWD-infected and disease-free herds. The data included deer movements, regulatory violations, CWD test results and distances to infected wild deer. They also interviewed deer farmers about their management practices.

Calculation of the proton radius significantly improved

The radius of the proton was calculated using supercomputers such as the high-performance computer MOGON II at JGU.
Photo Credit: Stefan F. Sämmer

Theoretical physicists at Johannes Gutenberg University Mainz (JGU) have once again succeeded in significantly improving their calculations of the electric charge radius of the proton published in 2021. For the first time, they obtained a sufficiently precise result completely without the use of experimental data. With respect to the size of the proton, these new calculations also favor the smaller value. Concurrently, the physicists have published a stable theory prediction for the magnetic charge radius of the proton. All new findings can be found in three preprints published on the arXiv server.

All known atomic nuclei consist of protons and neutrons, yet many of the characteristics of these ubiquitous nucleons remain to be understood. Specifically, despite several years of effort, scientists have been unable to pin down the radius of the proton. In 2010, the result of a new proton radius measurement technique involving laser spectroscopy of muonic hydrogen caused a stir. In this 'special' kind of hydrogen, the electron in the shell of the atom was replaced by its heavier relative, the muon, which is a much more sensitive probe for the proton's size. The experimentalists came up with a significantly smaller value than that found following corresponding measurements of normal hydrogen as well as the traditional method of determining the proton radius using electron-proton scattering. The big question that physicists have been asking ever since is whether this deviation could be evidence for new physics beyond the Standard Model or simply reflects systematic uncertainties inherent to the different measuring methods.

Strep Molecule Illuminates Cancer Immune Therapies

Colorized electron microscopy shows a chain of Streptococcus pyogenes bacteria between two immune cells.
Image Credit: National Institute of Allergy and Infectious Diseases

Researchers at Harvard Medical School have discovered that a molecule made by Streptococcus pyogenes — the bacterium that causes strep throat and other infections — could help explain several long-standing medical mysteries:

• Why strep sometimes leads to serious immune complications, including rheumatic fever.
• How the immune system's recognition of the molecule may contribute to diseases like lupus.
• Why one of the first cancer immunotherapies showed promise more than 100 years ago.
• How current immune therapies for cancer could be more effective.

The findings also contradict a long-standing belief that the immune system ignores this bacterial molecule and could propel efforts to tame or activate the immune system to treat a range of diseases.

The team, led by the lab of HMS biochemist Jon Clardy, published its findings in the Journal of the American Chemical Society.

“We were very surprised by the results, but the data were compelling,” said Clardy, the Christopher T. Walsh PhD Professor of Biological Chemistry and Molecular Pharmacology in the Blavatnik Institute at HMS.

SARS-CoV-2 Caused More, Deadlier Cases of Sepsis Than Thought

Life-threatening systemic inflammation known as sepsis can follow infection with SARS-CoV-2 (shown in green in this colorized electron micrograph), the virus that causes COVID-19.
Image Credit: National Institute of Allergy and Infectious Diseases

New research suggests that the virus responsible for COVID-19 was a more common and deadly cause of sepsis early in the pandemic than previously assumed — accounting for about one in six cases of sepsis from March 2020 to November 2022.

The results, published online in JAMA Network Open, suggest that clinicians should rethink how they treat sepsis while also providing a framework for future surveillance of viral sepsis.

Sepsis is a serious, sometimes fatal overreaction of the immune system to an infection. Doctors and researchers don’t know as much about sepsis that occurs in response to viral infection as they do about sepsis that arises from bacterial infection.

“Most people, including medical professionals, equate sepsis with bacterial infections,” said first author Claire Shappell, HMS instructor in medicine at Brigham and Women’s Hospital. “This is reflected in treatment guidelines and quality measures that require immediate antibiotics for patients with suspected sepsis.”

Vulnerability to different COVID-19 mutations depends on previous infections and vaccination, study suggests

Image Credit: Alexandra Koch

A new study has found that people differ in how vulnerable they are to different mutations in emerging variants of SARS-CoV-2.

This is because the variant of SARS-CoV-2 a person was first exposed to determines how well their immune system responds to different parts of the virus, and how protected they are against other variants.

It also means that the same COVID-19 vaccine might work differently for different people, depending on which variants of SARS-CoV-2 they have previously been exposed to and where their immune response has focused.

The discovery underlies the importance of continuing surveillance programs to detect the emergence of new variants, and to understand differences in immunity to SARS-CoV-2 across the population.

It will also be important for future vaccination strategies, which must consider both the virus variant a vaccine contains and how immune responses of the population may differ in their response to it.