. Scientific Frontline

Thursday, November 2, 2023

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.

Wednesday, November 1, 2023

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.

Study reveals location of starfish’s head

Postdoctoral scholar Laurent Formery (left) and biology Professor Christopher Lowe with starfish on the shore of Stanford’s Hopkins Marine Station, in Monterey, California.
Photo Credit: LiPo Ching / Stanford University

A new study that combines genetic and molecular techniques helps solve the riddle of starfish body plans, and how starfish start life with bilateral body symmetry – just like humans – but grow up to be adults with fivefold “pentaradial” symmetry.

If you put a hat on a starfish, where would you put it? On the center of the starfish? Or on the point of an arm and, if so, which one? The question is silly, but it gets at serious questions in the fields of zoology and developmental biology that have perplexed veteran scientists and schoolchildren in introductory biology classes alike: Where is the head on a starfish? And how does their body layout relate to ours?

Now, a new Stanford study that used genetic and molecular tools to map out the body regions of starfish – by creating a 3D atlas of their gene expression – helps answer this longstanding mystery. The “head” of a starfish, the researchers found, is not in any one place. Instead, the headlike regions are distributed with some in the center of the sea star as well as in the center of each limb of its body.

The Remains of an Ancient Planet Lie Deep Within Earth

Video Credit: California Institute of Technology

In the 1980s, geophysicists made a startling discovery: two continent-sized blobs of unusual material were found deep near the center of the Earth, one beneath the African continent and one beneath the Pacific Ocean. Each blob is twice the size of the Moon and likely composed of different proportions of elements than the mantle surrounding it.

Where did these strange blobs—formally known as large low-velocity provinces (LLVPs)—come from? A new study led by Caltech researchers suggests that they are remnants of an ancient planet that violently collided with Earth billions of years ago in the same giant impact that created our Moon.

The study, published in the journal Nature on November 1, also proposes an answer to another planetary science mystery. Researchers have long hypothesized that the Moon was created in the aftermath of a giant impact between Earth and a smaller planet dubbed Theia, but no trace of Theia has ever been found in the asteroid belt or in meteorites. This new study suggests that most of Theia was absorbed into the young Earth, forming the LLVPs, while residual debris from the impact coalesced into the Moon.

What Happens When We Pass Out? Researchers ID New Brain and Heart Connections

An image of a heart labeled by vagal sensory neurons. In a new study published in the journal Nature, UC San Diego researchers and their colleagues found that these neurons trigger fainting, laying a foundation for addressing fainting-related disorders.
Image Credit: Augustine Lab, UC San Diego

Nearly 40 percent of people experience syncope, or fainting spells, at least once in their lives. These brief losses of consciousness, whether brought by pain, fear, heat, hyperventilation or other causes, account for a significant portion of hospital emergency room visits. Yet the exact root mechanisms at play when people “pass out” largely have remained a mystery.

Publishing a new report in Nature, University of California San Diego researchers, along with colleagues at The Scripps Research Institute and other institutions, have for the first time identified the genetic pathway between the heart and brain tied to fainting.

One of their unique approaches was to think of the heart as a sensory organ rather than the longstanding viewpoint that the brain sends out signals and the heart simply follows directions. School of Biological Sciences Assistant Professor Vineet Augustine, the paper’s senior author, applies a variety of approaches to better understand these neural connections between the heart and brain.

Researchers demonstrate novel technique to observe molten salt intrusion in nuclear-grade graphite

From left, Yuxuan Zhang, James Keiser, Jisue Moon, Cristian Contescu, Erik Stringfellow (back) and Nidia Gallego, with Dino Sulejmanovic (not shown), first visualized molten salt distribution in graphite pores.
Photo Credit: Carlos Jones/ORNL, U.S. Dept. of Energy

In response to a renewed international interest in molten salt reactors, researchers from the Department of Energy’s Oak Ridge National Laboratory have developed a novel technique to visualize molten salt intrusion in graphite.

During ORNL’s revolutionary Molten Salt Reactor Experiment, or MSRE, in the 1960s, scientists first demonstrated the feasibility of nuclear fission reactions with molten fluoride salt used both as a fuel carrier and as a coolant, substituting for the solid fuel and water used in traditional nuclear reactors. Molten salt reactor designs show great promise as a means of carbon-free power generation.

To slow down neutrons so they can easily promote nuclear fission, nuclear reactors use a material called a moderator. To moderate the MSRE, scientists used synthetic graphite, which is resistant to thermal shock and dimensionally stable because of its extensive pore system resulting from the manufacturing process. MSRE graphite was custom-made and specially coated to decrease porosity and defend against detrimental effects that may occur when hydraulic and gas pressures cause molten salt to seep into graphite’s pores. Moreover, preventing molten salt intrusion avoids additional issues with waste management during reactor decommissioning.

Higher risk of cancer following 'all clear' after suspected cancer referral

Photo Credit: National Cancer Institute

Patients who were referred to urgent suspected cancer pathways, but were found not to have cancer at that time, have a higher risk of subsequent cancer in the 1-5 years following the ‘all clear’ than those who haven’t been through the referral pathways.

The study, published today in Lancet Oncology, is the first to examine the risk of cancer in patients in England who entered the urgent suspected cancer pathway but were found not to have cancer at that time. These patients were found to have a higher-than-expected risk of subsequent cancer in the 1-5 years after the initial ‘all clear’.

In England, the urgent suspected cancer referral pathway is the most common route to diagnosis. Of the 3 million patients who are referred for urgent cancer assessments in England each year, 7% are found to have cancer. This leaves a large group of patients who go through these pathways but do not have cancer at the time – a group that is currently understudied and who may be in need of support.

New study: Deep-sea pressure preserves food for microbes in the abyss

A flake of marine snow from the experiment.
Photo Credit: © Peter Stief/SDU

A new study from the Danish Center for Hadal Research reports on a series of experiments with exposing marine snow to increasing pressure - up to 1000 bar, which corresponds to the pressure at the bottom of some of the world's deep-sea trenches, 10 km below the sea surface.

Marine snow is millimeter-sized flakes, created when sticky, dead cells at the sea surface clump together with other dead or dying cells, particles and bacteria and sink to the bottom. The organic material can be dead algae, dead small animals, or their feces. Together, it is called marine snow because the flakes look like snow as they sink through the water column. There can be hundreds of different bacteria in one flake in addition to particles of organic matter.

"Not much is known about how marine snow responds to the increasing pressure when it sinks. But it is known that marine snow is food for an enormous number of microbes and small animals on the seabed. In fact, there are more microbes in the part of the ocean that lies at or below 1000 meters depth than anywhere else on Earth. This habitat is extremely large, and there can be a long distance between the microbes down there, but nevertheless a huge number of Earth's organisms thrive under high pressure, and we don't know how", says biologist Peter Stief, who is the lead author of the study.

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