. Scientific Frontline

Friday, September 23, 2022

A potential new treatment for brain tumors

Featured photo at top of Pankaj Desai, left, and senior graduate research assistant Aniruddha Karve, right, in the lab.
Photo credit: Andrew Higley | University of Cincinnati

A research question posed in Pankaj Desai’s lab has led to a decade of research, a clinical trial and major national funding to further investigate a potential new treatment for the deadliest form of brain tumors.

Desai, PhD, and his team at the University of Cincinnati recently received a $1.19 million grant from the National Institutes of Health/National Institute of Neurological Disorders and Stroke to continue research into the use of a drug called letrozole to treat glioblastomas (GBM).

Research progression

GBMs are aggressive brain tumors that patients often are unaware of until symptoms emerge and the tumor is substantial. Current treatments include immediate surgery to safely remove as much tumor as possible, radiation and chemotherapy, but the tumor often recurs or becomes resistant to treatments. The average patient survives no more than 15 months after diagnosis.

The medication letrozole was approved by the U.S. Food and Drug Administration as a treatment for postmenopausal women with breast cancer in 2001. The drug works by targeting an enzyme called aromatase that is present in breast cancer cells and helps the cancer grow.

DNA nets capture COVID-19 virus in low-cost rapid-testing platform

Tiny nets woven from DNA strands cover the spike proteins of the virus that causes COVID-19 and give off a glowing signal in this artist’s rendering. 
Image courtesy of Xing Wang

Tiny nets woven from DNA strands can ensnare the spike protein of the virus that causes COVID-19, lighting up the virus for a fast-yet-sensitive diagnostic test – and also impeding the virus from infecting cells, opening a new possible route to antiviral treatment, according to a new study.

Researchers at the University of Illinois Urbana-Champaign and collaborators demonstrated the DNA nets’ ability to detect and impede COVID-19 in human cell cultures in a paper published in the Journal of the American Chemical Society.

“This platform combines the sensitivity of clinical PCR tests and the speed and low cost of antigen tests,” said study leader Xing Wang, a professor of bioengineering and of chemistry at Illinois. “We need tests like this for a couple of reasons. One is to prepare for the next pandemic. The other reason is to track ongoing viral epidemics – not only coronaviruses, but also other deadly and economically impactful viruses like HIV or influenza.”

DNA is best known for its genetic properties, but it also can be folded into custom nanoscale structures that can perform functions or specifically bind to other structures much like proteins do. The DNA nets the Illinois group developed were designed to bind to the coronavirus spike protein – the structure that sticks out from the surface of the virus and binds to receptors on human cells to infect them. Once bound, the nets give off a fluorescent signal that can be read by an inexpensive handheld device in about 10 minutes.

Simple Process Extracts Valuable Magnesium Salt from Seawater

Seawater from the PNNL-Sequim campus fueled this research project.
Photo Credit: Andrea Starr | Pacific Northwest National Laboratory

Since ancient times, humans have extracted salts, like table salt, from the ocean. While table salt is the easiest to obtain, seawater is a rich source of different minerals, and researchers are exploring which ones they can pull from the ocean. One such mineral, magnesium, is abundant in the sea and increasingly useful on the land.

Magnesium has emerging sustainability-related applications, including in carbon capture, low-carbon cement, and potential next-generation batteries. These applications are bringing renewed attention to domestic magnesium production. Currently, magnesium is obtained in the United States through an energy-intensive process from salt lake brines, some of which are in danger due to droughts. The Department of Energy included magnesium on its recently released list of critical materials for domestic production.

A paper published in Environmental Science & Technology Letters shows how researchers at Pacific Northwest National Laboratory (PNNL) and the University of Washington (UW) have found a simple way to isolate a pure magnesium salt, a feedstock for magnesium metal, from seawater. Their new method flows two solutions side-by-side in a long stream. Called the laminar coflow method, the process takes advantage of the fact that the flowing solutions create a constantly reacting boundary. Fresh solutions flow by, never allowing the system to reach a balance.

Air Pollution Can Amplify Negative Effects of Climate Change

Photo credit: Alexei Scutari

The impacts of air pollution on human health, economies and agriculture differ drastically depending on where on the planet the pollutants are emitted, according to a new study that could potentially incentivize certain countries to cut climate-changing emissions.

Led by The University of Texas at Austin and the University of California San Diego, the study is the first to simulate how pollutants affect both climate and air quality for locations around the globe.

The research, which is published in Science Advances, analyzed the climate and air quality impacts of aerosols — tiny solid particles and liquid droplets that contribute to smog and are emitted from industrial factories, power plants and vehicle tailpipes. Aerosols create unique global patterns of impact on human health, agricultural and economic productivity when compared with carbon dioxide (CO2) emissions, which are the focus of efforts to mitigate climate change.

Although CO2 and aerosols are often emitted at the same time during the combustion of fuel, the two substances behave differently in Earth’s atmosphere, said co-lead author Geeta Persad, an assistant professor in UT Austin’s Jackson School of Geosciences.

Fighting fungal infections with metals

A Petri dish with red agar on which grows a fungal strand in the shape of the element symbol for platinum (Pt).
Credit: CO-ADD

An international collaboration led by researchers from the University of Bern and the University of Queensland in Australia has demonstrated that chemical compounds containing special metals are highly effective in fighting dangerous fungal infections. These results could be used to develop innovative drugs which are effective against resistant bacteria and fungi.

Each year, more than one billion people contract a fungal infection. Although they are harmless to most people, over 1.5 million patients die each year as a result of infections of this kind. While more and more fungal strains are being detected that are resistant to one or more of the available drugs, the development of new drugs has come to a virtual standstill in recent years. Today, only around a dozen clinical trials are underway with new active agents for the treatment of fungal infections. “In comparison with more than a thousand cancer drugs that are currently being tested on human subjects, this is an exceptionally small number,” explains Dr. Angelo Frei of the Department of Chemistry, Biochemistry and Pharmacy at the University of Bern, lead author of the study. The results have been published in the journal JACS Au.

Boosting antibiotics research with crowd sourcing

The CO-ADD Team at work in the laboratory.
Credit: CO-ADD

To encourage the development of anti-fungal and antibacterial agents, researchers at the University of Queensland in Australia have founded the Community for Open Antimicrobial Drug Discovery, or CO-ADD. The ambitious goal of the initiative is to find new antimicrobial active agents by offering chemists worldwide the opportunity to test any chemical compound against bacteria and fungi at no cost. As Frei explains, the initial focus of CO-ADD has been on “organic” molecules, which mainly consist of the elements of carbon, hydrogen, oxygen and nitrogen, and do not contain any metals.

However, Frei, who is trying to develop new metal-based antibiotics with his research group at the University of Bern, has found that over 1,000 of the more than 300,000 compounds tested by CO-ADD contained metals. “For most folks, when used in connection with the word ‘people’, the word metal triggers a feeling of unease. The opinion that metals are fundamentally harmful to us is widespread. However, this is only partially true. The decisive factor is which metal is used and in which form,” explains Frei, who is responsible for all the metal compounds in the CO-ADD database.

Low toxicity demonstrated

Dr. Angelo Frei at work in the laboratory.
Credit: Angelo Frei

In their new study, the researchers turned their attention to the metal compounds which showed activity against fungal infections. Here, 21 highly-active metal compounds were tested against various resistant fungal strains. These contained the metals cobalt, nickel, rhodium, palladium, silver, europium, iridium, platinum, molybdenum and gold. “Many of the metal compounds demonstrated a good activity against all fungal strains and were up to 30,000 times more active against fungi than against human cells,” explains Frei. The most active compounds were then tested in a model organism, the larvae of the wax moth. The researchers observed that just one of the eleven tested metal compounds showed signs of toxicity, while the others were well tolerated by the larvae. In the next step, some metal compounds were tested in an infection model, and one compound was effective in reducing the fungal infection in larvae.

Considerable potential for broad application

Metal compounds are not new to the world of medicine: Cisplatin, for example, which contains platinum, is one of the most widely used anti-cancer drugs. Despite this, there is a long way to go before new antimicrobial drugs that contain metals can be approved. “Our hope is that our work will improve the reputation of metals in medical applications and motivate other research groups to further explore this large but relatively unexplored field,” says Frei. “If we exploit the full potential of the periodic table, we may be able to prevent a future where we don’t have any effective antibiotics and active agents to prevent and treat fungal infections.”

The study was supported by the Swiss National Science Foundation, the Wellcome Trust and the University of Queensland, among others.

Source/Credit: University of Bern

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Asteroid that formed Vredefort crater bigger than previously believed

Credits: NASA Earth Observatory Image by Lauren Dauphin / University of Rochester
Illustration by Julia Joshpe

About two billion years ago, an impactor hurtled toward Earth, crashing into the planet in an area near present-day Johannesburg, South Africa. The impactor—most likely an asteroid—formed what is today the biggest crater on our planet. Scientists have widely accepted, based on previous research, that the impact structure, known as the Vredefort crater, was formed by an object about 15 kilometers (approximately 9.3 miles) in diameter that was travelling at a velocity of 15 kilometers per second.

But according to new research from the University of Rochester, the impactor may have been much bigger—and would have had devastating consequences across the planet. This research, published in the Journal of Geophysical Research, provides a more accurate understanding of the large impact and will allow researchers to better simulate impact events on Earth and other planets, both in the past and the future.

“Understanding the largest impact structure that we have on Earth is critical,” says Natalie Allen ’20, now a PhD student at John Hopkins University. Allen is the first author of the paper, based on research she conducted as an undergraduate at Rochester with Miki Nakajima, an assistant professor of Earth and environmental sciences. “Having access to the information provided by a structure like the Vredefort crater is a great opportunity to test our model and our understanding of the geologic evidence so we can better understand impacts on Earth and beyond.”

New research reveals the relationship between particular brain circuits and different aspects of mental wellbeing

Brain circuits and wellbeing
Credit: Miriam Klein-Flugge 

Associate Professor Miriam Klein-Fl├╝gge and colleagues looked at brain connectivity and mental health data from nearly 500 people. In particular, they looked at the connectivity of the amygdala – a brain region well known for its importance in emotion and reward processing. The researchers used functional magnetic resonance imaging to consider seven small subdivisions of the amygdala and their associated networks rather than combining the whole region together as previous studies have done.

The team also adopted a more precise approach to the data on mental wellbeing, looking at a large group of healthy people and using questionnaires that captured information about wellbeing in the social, emotional, sleep, and anger domains. This generated more precise data than many investigations which still use broad diagnoses such as depression or anxiety, which involve many different symptoms.

The paper, published in Nature Human Behavior, shows how the improved level of detail about both brain connectivity and wellbeing made it possible to characterize the exact brain networks that relate to these distinct aspects of mental health. The brain connections that mattered most for discerning whether an individual was struggling with sleep problems, for example, looked very different from those that carried information about their social wellbeing.

Robot sleeves for kids with cerebral palsy

Experimental setup for earlier iteration of the proposed robot sleeves.
Credit: Jonathan Realmuto/UCR

UC Riverside engineers are developing low-cost, robotic “clothing” to help children with cerebral palsy gain control over their arm movements.

Cerebral palsy is the most common cause of serious physical disability in childhood, and the devices envisioned for this project are meant to offer long-term daily assistance for those living with it.

However, traditional robots are rigid and not comfortable on the human body. Enabled by a $1.5 million grant from the National Science Foundation, this project is taking the novel approach of building devices from soft textiles, which will also facilitate more natural limb functioning.

“Hard materials don’t interact well with humans,” said Jonathan Realmuto, UCR assistant professor of mechanical engineering and project lead. “What we’re going for by using materials like nylon and elastic are essentially robotic garments.”

These garments will contain sealed, airtight regions that can inflate, making them temporarily rigid, and providing the force for movement.

“Let’s say you want to flex the elbow for a bicep curl. We can inject air into specially designed bladders embedded in the fabric that would propel the arm forward,” Realmuto said.

Mysterious ripples in the Milky Way were caused by a passing dwarf galaxy

Illustration: NASA JPL-Caltech R. Hurt (SSC Caltech)

Using data from the Gaia space telescope, a team led by researchers at Lund University in Sweden has shown that large parts of the Milky Way's outer disk vibrate. The ripples are caused by a dwarf galaxy, now seen in the constellation Sagittarius, that shook our galaxy as it passed by hundreds of millions of years ago.

Our cosmic home, the Milky Way, contains between 100 and 400 billion stars. Astronomers believe that the galaxy was born 13.6 billion years ago, emerging from a rotating cloud of gas composed of hydrogen and helium. Over billions of years, the gas then collected in a rotating disk where the stars, such as our sun, were formed.

In a new study published in Monthly Notices of the Royal Astronomical Society, the research team presents their findings about the stars in the outer regions of the galactic disk.

Thursday, September 22, 2022

Atomic-Scale Imaging Reveals a Facile Route to Crystal Formation

Aluminum hydroxide, depicted here in orange, undergoes fluctuations between structures before forming an ordered crystal. 
Illustration by Nathan Johnson | Pacific Northwest National Laboratory

What do clouds, televisions, pharmaceuticals, and even the dirt under our feet have in common? They all have or use crystals in some way. Crystals are more than just fancy gemstones. Clouds form when water vapor condenses into ice crystals in the atmosphere. Liquid crystal displays are used in a variety of electronics, from televisions to instrument panels. Crystallization is an important step for drug discovery and purification. Crystals also make up rocks and other minerals. Their crucial role in the environment is a focus of materials science and health sciences research.

Scientists have yet to fully understand how crystallization occurs, but the importance of surfaces in promoting the process has long been recognized. Research from Pacific Northwest National Laboratory (PNNL), the University of Washington (UW), and Durham University sheds new light on how crystals form at surfaces. Their results were published in Science Advances.

Previous studies on crystallization led scientists to form the classical nucleation theory—the predominant explanation for why crystals begin to form, or nucleate. When crystals nucleate, they begin as very small ephemeral clusters of just a few atoms. Their small size makes the clusters extremely difficult to detect. Scientists have managed to collect only a few images of such processes.

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