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.

Researchers Explore Future Climate in Africa, Using Clues from the Past

Severe flooding struck South Africa's Western Cape province in September
Photo Credit: KAMAL IG

In September 2023, extreme rains struck South Africa’s Western Cape province, flooding villages and leaving a trail of destruction. The catastrophic devastation is just one recent example in a string of extreme weather events that are growing more common around the world.

Fueled by rising sea surface temperatures from climate warming, torrential storms are increasing both in frequency and magnitude. Concurrently, global warming is also producing the opposite effect in other instances, as a mega-drought threatened the water supply of Cape Town in southwestern Africa to the point where residents were at risk of running out of water. This one-two punch of weather extremes are devastating habitats, ecosystems, and human infrastructure.

A team of paleoclimatologists from Syracuse University, George Mason University, and the University of Connecticut are studying an ancient source to determine future rainfall and drought patterns: fossilized plants that lived on Earth millions of years ago.

In a study published in Geophysical Research letters led by Claire Rubbelke, a Ph.D. candidate in the Department of Earth and Environmental sciences at Syracuse, and Tripti Bhattacharya, Thonis Family Professor of Earth and Environmental sciences at Syracuse, researchers zeroed in on the Pliocene epoch (~3 million years ago) – a time when conditions were very similar to today. Despite warmer temperatures, many parts of the world, including southwestern Africa, experienced dramatic increases in rainfall over land, likely caused by warmer-than-normal sea surface temperatures. This mimics a modern event called a Benguela Niño, where researchers believe shifting winds cause warm waters to move southward along the coast of Africa causing enhanced rainfall over typically arid regions.

Astronomers Discover First Step Toward Planet Formation

An image of the radio wave strength at a wavelength of 1.3 mm of the disk around the star DG Taurus, observed with ALMA. Unlike older protostellar disks, ring-like structures have not yet formed, suggesting that the disk is at the stage just before planet formation.
Image Credit: ALMA (ESO/NAOJ/NRAO), S. Ohashi et al.

An international research team led by Project Assistant Professor Satoshi Ohashi of the National Astronomical Observatory of Japan (NAOJ) has conducted high-resolution and multi-wavelength observations of a protoplanetary disk around a relatively young protostar, DG Taurus (DG Tau), using ALMA* to study the structure of the disk and the size and amount of dust, the material for planets. Associate Professor Okuzumi from Tokyo Institute of Technology (Tokyo Tech) participated in this research as a team member. As a result, the team succeeded in capturing the conditions on the eve of planet formation, as the disk was smooth with no signature of planets. They also found that the dust had grown significantly in the outer part of the disk and that the dust concentration was higher than normal in the inner part of the disk. With these results, the first step in the process of planet formation has been revealed.

Super-efficient laser light-induced detection of cancer cell-derived nanoparticles

Schematic diagram of light-induced assembly of extracellular vesicles (EV)   Using laser irradiation, the researchers managed to directly detect nanoscale EVs in a cell supernatant within minutes.   
Illustration Credit: Takuya Iida, Osaka Metropolitan University

Can particles as minuscule as viruses be detected accurately within a mere 5 minutes? Osaka Metropolitan University scientists say yes, with their innovative method for ultrafast and ultrasensitive quantitative measurement of biological nanoparticles, opening doors for early diagnosis of a broad range of diseases. 

Nanoscale extracellular vesicles (EVs) including exosomes, with diameters of 50–150 nm, play essential roles in intercellular communication and have garnered attention as biomarkers for various diseases and drug delivery capsules. Consequently, the rapid and sensitive detection of nanoscale EVs from trace samples is of vital importance for early diagnosis of intractable diseases such as cancer and Alzheimer's disease. However, the extraction of nanoscale EVs from cell culture media previously required a complex and time-consuming process involving ultracentrifugation.

How male mosquitoes compensate for having only one X chromosome

Cell nucleus of Anopheles cells: The DNA is colored blue. SOA were verified in orange coloration and the X-chromosomal transcription side in green.
Image Credit: ©Maria Felicia Basilicata

The research group of Dr Claudia Keller Valsecchi (Institute of Molecular Biology, Mainz, Germany) and their collaborators have discovered the master regulator responsible for balancing the expression of X chromosome genes between males and females in the malaria mosquito. This discovery helps scientists to better understand the evolution of the epigenetic mechanisms responsible for equalizing gene expression between the sexes. The findings may contribute to the development of new ways to prevent the spread of malaria.

Most people would agree that mosquitoes are among the most annoying species on the planet. They keep us up all night with their whining, whirring wings, all while seeking a way to bite us and suck our blood. Yet mosquitoes are more than just a nuisance – they can also carry a whole host of serious, sometimes deadly diseases.

One of the most dangerous diseases that mosquitoes can carry is malaria, a disease that affects millions of people and causes hundreds of thousands of deaths every year, primarily in African countries. Malaria is caused by Plasmodium parasites, which are spread through mosquito bites – specifically those of marsh mosquitoes (Anopheles).

Consistent Metabolism May Prove Costly for Insects in Saltier Water

Clockwise from upper right: scud, mayfly and snail
Photo Credit: Courtesy of North Carolina State University

Increased salinity usually spells trouble for freshwater insects like mayflies. A new study from North Carolina State University finds that the lack of metabolic responses to salinity may explain why some freshwater insects often struggle in higher salinity, while other freshwater invertebrates (like mollusks and crustaceans) thrive. Salinity in this case refers to the concentrations of all the salts in an aquatic environment, not just sodium.

“Freshwater habitats in general are getting saltier for a number of reasons, including road salt and agricultural runoff, extraction of coal and natural gas, drought, and sea level rise,” says David Buchwalter, professor of toxicology at NC State and corresponding author of the research. “Freshwater insects and other organisms that live in these systems are used as indicators of the ecosystem’s health. When these systems get saltier, we see that insect diversity decreases, but we aren’t sure why.”

Aquatic animals (including insects and crustaceans) must constantly maintain the correct balance of water and salts within their body – a process called osmoregulation. Theoretically, the most favorable environment for aquatic animals would be one where external salinity levels are close to those inside the animal. That way the animal doesn’t have to work as hard to maintain osmoregulation.

Scorpius images to test nuclear stockpile simulations

Two cathode inductive voltage-adder cells on the electrical test stand are aligned at Sandia National Laboratories. After thousands of tests, each holding 50 kilovolts across the insulating gap, they are ready to be mounted on seven-cell modules.
Photo Credit: Craig Fritz

One thousand feet below the ground, three national defense labs and a remote test site are building Scorpius — a machine as long as a football field — to create images of plutonium as it is compressed with high explosives, creating conditions that exist just prior to a nuclear explosion.

These nanosecond portraits will be compared with visuals of the same events generated by supercomputer codes to check how accurately the computed images replicate the real thing.

“It’s clear we need to know that the stockpile will work if required,” said Jon Custer, Sandia National Laboratories project lead. “Before President Bush’s testing moratorium in 1992, we knew it did since we were physically testing. Now we have computer codes. How well do they predict what really happens? Do we have accurate data we put into the codes? To answer these questions with higher fidelity, we need better experimental tools, and Scorpius is a major new experimental tool.”

The $1.8 billion project, combining the expertise of researchers from Sandia, Los Alamos and Lawrence Livermore national labs with support from the Nevada National Security Site — a test area bigger than the state of Rhode Island — is expected to be up and running by late 2027.

Physicists Find Evidence for Magnetically Bound Excitons

In materials known as antiferromagnetic Mott insulators, electrons (orbs) are organized in a lattice structure of atoms such that their spins point up (blue) or down (pink) in an alternating pattern. This is a stable state in which the energy is minimized. When the material is hit with light, an electron will hop to a neighboring atomic site, leaving a positively charged hole where it once resided (dark orb). If the electron and hole move further apart from each other, the spin arrangement between them becomes disturbed—the spins are no longer pointing in opposite directions to their neighbors as seen in the second panel—and this costs energy. To avoid this energy penalty, the electron and hole prefer to remain close to each other. This is the magnetic binding mechanism underlying the Hubbard exciton.
Illustration Credit: Caltech

In art, the negative space in a painting can be just as important as the painting itself. Something similar is true in insulating materials, where the empty spaces left behind by missing electrons play a crucial role in determining the material's properties. When a negatively charged electron is excited by light, it leaves behind a positive hole. Because the hole and the electron are oppositely charged, they are attracted to each other and form a bond. The resulting pair, which is short lived, is known as an exciton [pronounced exit-tawn].

Excitons are a key part of many technologies, including solar panels, photodetectors and sensors, as well as light-emitting diodes found in televisions and digital display screens. In most cases, the exciton pairs are bound by electrical, or electrostatic, forces, also known as Coulomb interactions. Now, in a new study in Nature Physics, Caltech researchers report detecting excitons that are not bound via Coulomb forces but rather by magnetism. This is the first experiment to detect how these so-called Hubbard excitons, named after the late physicist John Hubbard, form in real-time.