. Scientific Frontline

Tuesday, November 7, 2023

Scientists use quantum biology, AI to sharpen genome editing tool

ORNL scientists developed a method that improves the accuracy of the CRISPR Cas9 gene editing tool used to modify microbes for renewable fuels and chemicals production. This research draws on the lab’s expertise in quantum biology, artificial intelligence and synthetic biology.
Illustration Credit: Philip Gray/ORNL, U.S. Dept. of Energy

Scientists at Oak Ridge National Laboratory used their expertise in quantum biology, artificial intelligence and bioengineering to improve how CRISPR Cas9 genome editing tools work on organisms like microbes that can be modified to produce renewable fuels and chemicals.

CRISPR is a powerful tool for bioengineering, used to modify genetic code to improve an organism’s performance or to correct mutations. The CRISPR Cas9 tool relies on a single, unique guide RNA that directs the Cas9 enzyme to bind with and cleave the corresponding targeted site in the genome. Existing models to computationally predict effective guide RNAs for CRISPR tools were built on data from only a few model species, with weak, inconsistent efficiency when applied to microbes.

“A lot of the CRISPR tools have been developed for mammalian cells, fruit flies or other model species. Few have been geared towards microbes where the chromosomal structures and sizes are very different,” said Carrie Eckert, leader of the Synthetic Biology group at ORNL. “We had observed that models for designing the CRISPR Cas9 machinery behave differently when working with microbes, and this research validates what we’d known anecdotally.”

New strategy may halt tumors' aggressive response to glucose deprivation

The figure shows the expression of a differentiation marker in the tumors of mice treated with the glucose inhibitor, the epigenetic inhibitor, or both. Top left image is the placebo, top right is the glucose inhibitor, bottom left is the epigenetic inhibitor and bottom right is the glucose inhibitor and epigenetic inhibitor. The brown signal indicates the presence of the differentiation marker. The treatment with the glucose inhibitor (top right) reduces the brown signal, whereas the addition of the epigenetic inhibitor rescues the expression of the differentiation marker.
Image Credit: Dr. Claudio Scafoglio.

One of the hallmarks of cancer cell development is its dependence on sugar, especially glucose, to grow and divide. Scientists have long been studying how to restrict or block this process that promotes tumor growth, called glycolysis, from happening as a possible effective strategy against cancer.

Previously, researchers from the UCLA Health Jonsson Comprehensive Cancer Center identified a specific protein sodium glucose transporter 2, or SGLT2, as a mechanism that lung cancer cells can utilize to obtain glucose. Drugs that inhibit SGLT2 are already FDA approved for other conditions and the UCLA team found these drugs could also delay the development of lung cancer and improved survival when tested in mice, suggesting these drugs could be repurposed for lung cancer treatment.

However, while inhibiting glycolysis can slow down the growth of tumors, the researchers found it can also make cancer cells more aggressive, making the cancer harder to treat. This led the team to look at other mechanisms of resistance in the tumors that still grow while being treated with SGLT2 inhibition that may link glucose restriction to increases aggression.

‘Neglected’ Dinosaur Had Super Senses

A family of Thescelosaurus emerges from safety to forage in the forests of the Hell Creek Formation, 66 million years ago.
Illustration Credit: Anthony Hutchings.

A CT scan of an often-overlooked, plant-eating dinosaur’s skull reveals that while it may not have been all that “brainy,” it had a unique combination of traits associated with living animals that spend at least part of their time underground, including a super sense of smell and outstanding balance. The work is the first to link a specific sensory fingerprint with this behavior in extinct dinosaurs.

The dinosaur in question, Willo, is a specimen housed at the North Carolina Museum of Natural Sciences. Willo is a Thescelosaurus neglectus – a small (12 feet or 3.6 meters long) but heavy (750 pounds or 340 kilograms) herbivore that lived in what is now North America just before the end-Cretaceous mass extinction event, 66 million years ago.

Willo’s scientific name roughly translates to “wonderful, overlooked lizard.” But David Button, a former Brimley Postdoctoral Scholar at the North Carolina Museum of Natural Sciences and North Carolina State University, decided to look more closely at this “overlooked” dinosaur’s skull. Button is currently a research associate at the University of Bristol in the U.K.

The kids aren't alright: Saplings reveal how changing climate may undermine forests

A University of Arizona-led experiment exposed different species of trees to heat and drought to study how young trees respond to climate change. After 20 weeks of drought and a one-week heat wave, this Douglas fir sapling was dry and brittle.
Photo Credit: Alexandra Lalor

UArizona researchers studied how young trees respond to a hotter, drier climate. Their findings can help shape forest management policy and our understanding of how landscapes will change.

A University of Arizona-led experiment exposed different species of trees to heat and drought to study how young trees respond to climate change. After 20 weeks of drought and a one-week heat wave, this Douglas fir sapling was dry and brittle. Alexandra Lalor

As climate scientist Don Falk was hiking through a forest, the old, green pines stretched overhead. But he had the feeling that something was missing. Then his eyes found it: a seedling, brittle and brown, overlooked because of its lifelessness. Once Falk's eyes found one, the others quickly fell into his awareness. An entire generation of young trees had died.

Falk – a professor in the UArizona School of Natural Resources and the Environment, with joint appointments in the Laboratory of Tree-Ring Research and the Arizona Institute for Resilience – refers to this large-scale die-off of the younger generation of trees as a recruitment failure. This is particularly devastating for a population of trees because the youngest are essential for forest recovery following massive die-off events, such as severe wildfires and insect outbreaks, both of which will become more frequent as the climate continues to change, he said.

People with prior illness more likely to report longer symptoms after COVID-19 infection

Photo Credit: Kelly Sikkema

The study from King’s College London, which is published on the pre-print server MedRxiv and has not been peer-reviewed, shows that while two thirds of individuals with post-COVID illness were healthy before infection, individuals with long illness duration were significantly more likely to have similar symptoms 1-2 months before developing COVID-19.

Most people with COVID-19 recover completely within a few days or weeks. However, some report ongoing symptoms including fatigue, ‘brain fog’, sneezing, a runny nose and headache long after infection. For some individuals, this may manifest as long COVID.

In this study, researchers first analyzed data from over 23,000 ZOE Symptom Study app users, who reported their health (whether healthy or unhealthy) at least once weekly, both before and after they had COVID-19. They found that individuals who had symptoms before they caught SARS-CoV-2 infection were significantly more likely to have a longer illness duration.

The researchers then assessed 1350 adults who reported long-term symptoms after COVID-19 (at least eight weeks, with nearly a thousand having symptoms for more than 12 weeks), matched with 1350 individuals whose symptoms had resolved within four weeks.

Warmer, wetter winters bring risks to river insects

Professor Steve Ormerod, School of Biosciences
Photo Credit: Courtesy of Cardiff University

Research by Cardiff University has shown that the warmer, wetter winters in the UK caused by climate change are likely to impact the stability of insect populations in streams.

The research, spanning four decades, has demonstrated that stream insects are affected by warmer, wetter winters caused by fluctuating climate over the Atlantic Ocean. The consequences are felt by insect populations even in the smallest Welsh river sources.

“UK winters are becoming warmer and wetter on average, and we wanted to understand how this might impact our rivers. Streams and rivers are profoundly affected by climate through changes in global air temperatures and precipitation which affect flow patterns and water temperature.

“Over the years, we’ve noticed increasingly that changes in our rivers also track global climatic patterns over the Atlantic and these provide important clues about climate change” said Professor Steve Ormerod, the Water Research Institute at Cardiff University.

Predatory Bacteria

Predatory bacteria such as B. bacteriovorus attack and neutralize other types of bacteria.
Illustration Credit:: Benjamin Güdel

Antibiotic resistance is increasingly becoming a challenge for treating bacterial infections. Microbiologist Simona Huwiler is researching whether predatory bacteria — that is, bacteria that eat other bacteria — can be used as a new kind of antibiotic and whether this approach also leads to the development of resistance.

The spread of antibiotic-resistant bacteria is an enormous challenge for the healthcare system. It is almost impossible to stop the development of antimicrobial resistance, and there are almost no new kinds of antibiotics being developed that can be used against drug-resistant bacteria. Researchers are therefore looking to nature to find alternatives. They have set their sights on the natural enemies of pathogenic bacteria such as bacteriophages – viruses that kill bacteria – as well as predatory bacteria that attack, consume and eliminate other types of bacteria. Bdellovibrio bacteriovorus is one type of predatory bacteria that is of interest to researchers. It’s an ideal candidate because it likes to dine on gram-negative bacteria with antibiotic resistance. Experiments in the lab have shown that Bdellovibrio bacteriovorus is capable of killing and eating many kinds of pathogenic bacteria, including Escherichia coli, Enterobacter, Proteus, Serratia, Citrobacter, Yersinia, Shigellen, Salmonella and Vibrio. This varied meal plan is an advantage compared to bacteriophages, which usually prefer to eat one specific kind of bacteria.

Ural Scientists Have Modernized the Process of Nuclear Fuel Reprocessing

The uranium obtained after reprocessing spent nuclear fuel can be reused.
Photo Credit: Lukas Lehotsk

UrFU scientists have discovered that the use of gallium and indium can make the process of pyrochemical reprocessing of nuclear fuel cheaper while maintaining its efficiency. This technology uses molten salts and liquid gallium to separate components of spent nuclear fuel (SNF). To make the process cheaper, the physicists added indium: the technology remained as effective, but the cost of reprocessing itself decreased. The results of the study will help modernize current SNF reprocessing methods and make them more efficient. Full details of the study are published in Alloys.

"This method has many advantages, in particular it focuses on the reprocessing of high-activity, low-life nuclear fuel with a high burn-up depth, which cannot be achieved by other methods such as water technology. It is also environmentally safer, as the amount of radioactive waste after reprocessing is reduced. Gallium can be used in fuel reprocessing by this method, but we have found that by adding indium, the reprocessing efficiency remains as high, but the cost of the process is reduced," explains Alexander Dedyukhin, senior engineer at the Department of Rare Metals and Nanomaterials at UrFU.

World’s first smart breathing tube for mechanically ventilated patients set for human trials

Professor Steve Morgan
Photo Credit: Courtesy of University of Nottingham

The University of Nottingham has secured £1.1 million in funding from the Medical Research Council to undertake human trials for the world’s first optical fiber sensor-equipped endotracheal tube (iTraXS).

Seriously ill or anaesthetized patients are unable to breathe naturally, so clinicians often use endotracheal tubes (ETTs), which are placed in the trachea (windpipe) to maintain an open airway and allow the patient to breathe through a mechanical ventilator. To do this, the tube is placed into the airway and a cuff (balloon) is inflated at the trachea to create a gas seal that allows air to be delivered to the lungs effectively. However, incorrect cuff inflation pressure can cause two main problems.

If pressure is too low, it can risk fluid getting past the cuff and causing ventilator-associate pneumonia (VAP). VAP increases the likelihood of death, affecting up to 20% of people in intensive care, and costs the NHS between £10,000 and £20,000 per patient. Conversely, if pressure is too high it can cause a pressure injury in the trachea, ranging from moderate to severe sore throats through to permanent scarring and narrowing of the windpipe.

The fascinating relationship between mice and a plant that flowers once a century in terms of seed dispersal

Researchers revealed unexpected dispersal behavior of field mice, which influences the forest ecosystem.
Illustration Credit: Reiko Matsushita

Researchers at Nagoya University in Japan have revealed new insights into the interaction between mast seeding plants and the animals that eat their seeds. Hanami Suzuki and Professor Hisashi Kajimura examined the behavior of field mice using seeds from once-in-a-century flowering sasa bamboo plants in central Japan.

The researchers found that the seed use patterns of field mice differed by species (large Japanese field mouse Apodemus speciosus and small Japanese field mouse A. argenteus), the presence or absence of understory vegetation, forest tree species (broadleaf forest or coniferous forest), and season (summer or fall). Their findings underscore the importance of understanding the needs of both plants and animals to ensure the health of local ecosystems. They also overturn a previously held belief about how mice store seeds. 

Dwarf bamboo (Sasa borealis) exhibits masting behavior in wide areas. Masting behavior means a plant collectively flowers and seeds at regular intervals to overwhelm predators and maximize pollination rates. Masting events are rare, however, with intervals up to 120 years. But when they occur, the resulting abundance of seeds in the forest provides easily available food for various animals, especially rodents such as field mice.  

Monday, November 6, 2023

Detecting nuclear materials using light

Sandia National Laboratories researcher Patrick Feng, left, and Former Sandian Joey Carlson, right, hold Organic Glass Scintillators they helped create to detect radioactive materials.
Photo Credit: Randy Wong

Blueshift Optics, owned by former Sandia employee Joey Carlson, is working to shift the way radioactive materials are detected, using technology that he helped create at Sandia National Laboratories.

Radiation detection has long been a critical aspect of national security and efforts to make the world safer.

“Agencies are trying to cast this wide net to catch nuclear smuggling, and this is one aspect of that effort,” said Sandia materials scientist Patrick Feng. “You could use this technology at a border crossing, in a handheld detector as someone enters a facility or fly it on a drone to map an area.”

However, the uses of this technology extend far beyond border security.

“It has the potential to provide us with better data from nuclear physics experiments, enhance national security applications both at home and abroad and has applications in fusion energy,” Carlson said.

Feng and Carlson collaborated to develop the state-of-the-art technology known as Organic Glass Scintillators for radiation detection. Sandia recently licensed the technology to Blueshift Optics, paving the way for potential commercial production.

European wildcats avoided introduced domestic cats for 2000 years

A wildcat which is part of the Saving Wildcats conservation breeding for release program which conducted the first release of wildcats to the Cairngorms National Park, Scotland in 2023
Photo Credit: Saving Wildcats

Domestic cats introduced from the Near East and wildcats native to Europe did not mix until the 1960s, despite being exposed to each other for two thousand years.

Two studies published today in Current Biology involving new archaeological and genetic evidence rewrites the history of cats in Europe.

The international team of researchers sequenced and analyzed both wildcats and domestic cats including 48 modern individuals and 258 ancient samples excavated from 85 archaeological sites over the last 8,500 years. They then assessed the patterns of hybridization (or interbreeding) after domestic cats were introduced to Europe over 2,000 years ago, and came into contact with native European wildcats.

The results of the studies demonstrate that, since their introduction, domestic cats and European wildcats generally avoided mating with each other. About 50 years ago in Scotland, however, that all changed and rates of interbreeding between wildcats and domestic cats rose rapidly. This may have happened as a result of dwindling wildcat populations and a lack of opportunity to mate with other wildcats.

Success of Wolbachia-infected mosquitoes in fighting dengue may be underestimated

Alex Perkins, associate professor of biological science
Photo Credit: Courtesy of University of Notre Dame

The fight against dengue fever has a new weapon: a mosquito infected with the bacteria Wolbachia, which prevents the spread of the virus. These mosquitoes have now been deployed in several trials demonstrating their potential in preventing disease transmission.

Now, researchers at the University of Notre Dame have conducted an analysis of the World Mosquito Program’s randomized control trial of Wolbachia-infected mosquitoes in Indonesia, looking at how excluding transmission dynamics impacted the original interpretation of the trial’s results.

“Randomized controlled trials are the gold standard for evaluating the efficacy of any medical or public health intervention. That is very difficult for vector interventions against dengue because incidence of the disease can be somewhat unpredictable and sporadic, requiring very large-scale trials,” said Alex Perkins, associate professor of biological sciences at Notre Dame and senior author on the study.

Improving the efficacy of cancer immunotherapy with modified CAR-T cells

Water color art illustrates the publication by Velasco et al. The authors systematically engineered novel Chimeric Antigen Receptors (CARs), each containing one of the signaling chains of the natural T cell receptor: epsilon, gamma, delta and zeta (from left to right, from top to bottom) to create innovative CAR T cells. The work demonstrated that each signaling chain imprints the functioning of the CAR T cells (represented by the different colors) impacting thus their anti-tumor activity.
Illustration Credit: Sara Wossning Minguet

CAR-T cell therapy is a last hope for many patients with blood, bone marrow or lymph gland cancer when other treatments such as chemotherapy are unsuccessful. A limiting factor of this otherwise very effective and safe therapy is that the cells used in the process quickly reach a state of exhaustion. Researchers at the University of Freiburg have now been able to prevent this exhaustion and thus significantly improve the effect of the therapy in a preclinical animal model. The new results have been published in the journal Nature Immunology.

Using the body’s own defenses against cancer

CAR-T cells are one of the personalized cancer therapies and have been used in specialized centers in Europe since 2018. In this complex treatment, immune cells, or more precisely T cells, are taken from the blood of cancer patients, genetically engineered in the laboratory with a chimeric antigen receptor (CAR) and then re-administered. The receptor helps the T cells to identify and kill cancer cells. As a result, the therapy utilizes the body’s own cells to permanently eradicate the cancer.

Parkinson's: New hope when treatment options seem exhausted

Prof. Paul Lingor
Photo Credit: Courtesy of Technical University of Munich

As Parkinson's progresses, more invasive therapies are used that require brain surgery, for example. When these no longer deliver the desired results, physicians often conclude that treatment options are exhausted. A study led by researchers at the Technical University of Munich (TUM) now shows that such patients can still benefit from a change in treatment. So far, however, this option has only been used very rarely.

A team led by Prof. Paul Lingor has examined data from 22 German Parkinson's centers. The result: although there are several options for therapies in the late stages of the disease, rarely is more than one used - although those affected often benefit from them.

Parkinson's disease is the world’s second-most common neurodegenerative disease after Alzheimer's. So far it has proved incurable. Only the symptoms can be treated. In the early stages, tablets can generally provide relief from complaints. As the disease progresses, this is often no longer enough.

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