. Scientific Frontline

Monday, May 15, 2023

Most species, including humans, who experience early life adversity suffer as adults. How are gorillas different?

Experienced the loss of her mother and father and the disintegration of her family group before the age of 5. Now 20, she has become a successful mother, raising three offspring.
Photo Credit: Dian Fossey Gorilla Fund

There’s something most species—from baboons to humans to horses—have in common: When they suffer serious adversity early in life, they’re more likely to experience hardship later on in life.

When researchers from the Dian Fossey Gorilla Fund and the University of Michigan decided to look at this question in gorillas, they weren’t sure what they would find.

Previous studies by the Fossey Fund revealed that young gorillas are surprisingly resilient to losing their mothers, in contrast to what has been found in many other species. But losing your mother is only one of many potential bad things that can happen to young animals.

“Assuming that you survive something that we consider early life adversity, it’s often still the case that you will be less healthy or you will have fewer kids or your lifespan will be shorter—no matter what species you are,” said Stacy Rosenbaum, U-M assistant professor of anthropology and senior author of the study. “There’s this whole range of things that happens to you that seems to just make your life worse in adulthood.”

Phage structure captured for the first time, to benefit biotech applications

Phage image
Image Credit: Dr Vicki Gold et al, Nature Communications

New insights into the structure of phages will enable researchers to develop new uses for viruses in biotechnology.

Phages are viruses that infect bacteria, which enables them to be exploited as tools in biotechnology and medicine. Now, for the first time, researchers at the University of Exeter, in collaboration with Massey University and Nanophage Technologies, New Zealand, have mapped out what a commonly-used form of phage looks like, which will help researchers design better uses in future.

One common use for phage is phage display, which is a useful tool in drug discovery. Phage display works by linking a gene fragment of interest to a phage gene that makes one of the phage coat proteins. The new coat protein with the linked protein of interest appears on the surface of the phage, where it can be assayed and tested for biological activity.

Billions of types of phages exist. Phage display often uses a type of phage known as filamentous, so called because they are long and thin, making the display of many proteins across its surface possible. Although phage display and other applications have proved successful, until now, scientists have not known what this type of phage looks like.

Combined delivery of engineered virus with immunotherapy is safe and improves outcomes in subset of patients with glioblastoma

From left to right: Frederick Lang, M.D., Juan Fueyo, M.D., and Candelaria Gomez-Manzano, M.D.
Image Credit: Courtesy of MD Anderson Cancer Center

Intratumoral delivery of an engineered oncolytic virus (DNX-2401) targeting glioblastoma (GBM) cells combined with subsequent immunotherapy was safe and improved survival outcomes in a subset of patients with recurrent GBM, according to results from a multi-institutional Phase I/II clinical trial co-led by researchers at The University of Texas MD Anderson Cancer Center and the University of Toronto.

The study, published today in Nature Medicine, met its primary safety endpoint and demonstrated the combination was well tolerated overall with no dose-limiting toxicities. The study did not meet its primary efficacy endpoint of objective response rate, but the combination achieved a 12-month overall survival (OS) rate of 52.7%, which is greater than the prespecified efficacy threshold of 20%. Three patients remained alive at 45, 48 and 60 months after treatment.

“This viral therapy is a different approach to the current standard of care,” said co-corresponding author Frederick Lang, M.D., chair of Neurosurgery. “Our previous trial demonstrated that not only does the virus act by killing cancer cells directly, it also effectively activates the innate immune system to convert these immunologically cold tumors into hot tumors. This led us to evaluate a combination with checkpoint inhibitors, which we now see can improve survival outcomes in a subset of patients.”

New priming method improves battery life, efficiency

Quan Nguyen (left), Sibani Lisa Biswal and collaborators developed a prelithiation technique that helps improve the performance of lithium-ion batteries with silicon anodes.
Photo Credit: Jeff Fitlow/Rice University

Silicon anode batteries have the potential to revolutionize energy storage capabilities, which is key to meeting climate goals and unlocking the full potential of electric vehicles.

However, the irreversible depletion of lithium ions in silicon anodes puts a major constraint on the development of next-generation lithium-ion batteries.

Scientists at Rice University’s George R. Brown School of Engineering have developed a readily scalable method to optimize prelithiation, a process that helps mitigate lithium loss and improves battery life cycles by coating silicon anodes with stabilized lithium metal particles (SLMPs).

The Rice lab of chemical and biomolecular engineer Sibani Lisa Biswal found that spray-coating the anodes with a mixture of the particles and a surfactant improves battery life by 22% to 44%. Battery cells with a greater amount of the coating initially achieved a higher stability and cycle life. However, there was a drawback: When cycled at full capacity, a larger amount of the particle coating led to more lithium trapping, causing the battery to fade more rapidly in subsequent cycles.

Gene-edited calf may reduce reliance on antimicrobials against cattle disease

 Brian Vander Ley, associate professor in the University of Nebraska–Lincoln’s School of Veterinary Medicine and Biomedical Sciences, works with Ginger, a Gir cow gene-edited with resistance to bovine viral diarrhea virus.
Photo Credit: Craig Chandler | University Communication and Marketing

Cattle worldwide face major health threats from a highly infectious viral disease that decades of vaccinations and other precautions have failed to contain. Federal, private-sector and Husker scientists are collaborating on a new line of defense, by producing a gene-edited calf resistant to the virus.

If follow-up research confirms its efficacy, the gene-editing approach offers long-term potential to reduce antimicrobial and antibiotic use in the cattle industry.

The bovine viral diarrhea virus devastates the bovine immune system and can cause severe respiratory and intestinal harm to infected beef and dairy cattle, said veterinary epidemiologist Brian Vander Ley, an associate professor in the University of Nebraska–Lincoln’s School of Veterinary Medicine and Biomedical Sciences.

In utero calves are especially vulnerable to infection. If they survive, they can remain infected for life, repeatedly spreading the virus to other cattle.

“They show up as normal cattle but really, they’re shedding a tremendous amount of virus. They’re the ‘Typhoid Marys’ of BVDV spread,” said Vander Ley, assistant director of UNL’s Great Plains Veterinary Educational Center in Clay Center.

Cost-effective and Non-toxic Substance Helps in the Extraction of Noble Metals

The new technology will help extract valuable components from complex raw materials.
Photo Credit: Rodion Narudinov

Scientists of the Ural Federal University have found a "solvent" (surfactant), lignosulfonate, which facilitates the transfer of noble metals into solution. Lignosulfonate is a waste product of pulp and paper industry, which is cheap and non-toxic. The scientists have effectively solved two serious problems at once: using a waste product along with processing ores and concentrates. The researchers published a description of the solvent's mechanism of action in the scientific journal Langmuir.

"We investigated the mechanism of action of a very complex surfactant that is at the same time a humectant, dispersant and stabilizer in terms of the surface of the ore concentrate. Lignosulfonate has been used in autoclave metal extraction technologies since the 1970s. However, its efficiency has not been sufficiently studied and the mechanism of action has not been subjectively investigated. Taking into account the fact that today different types of ores are processed, the use of lignosulfonate for processing becomes even more important," says Tatyana Lugovitskaya, co-author of the research, Assistant Professor Researcher of the UrFU Department of Non-Ferrous Metallurgy.

Clinically relevant deficiency of the “bonding hormone” oxytocin demonstrated

The hormones oxytocin and vasopressin are produced in the same area of the brain and are also very similar in structure. This is why disorders that cause vasopressin deficiency could also affect the neurons that produce oxytocin
Image Credit: Colin Behrens

The hormone oxytocin is important for social interaction and to control emotions. A deficiency of this hormone has previously been assumed, for example, in people with autism, but has never been proven. Now, for the first time, researchers from the University of Basel and the University Hospital of Basel have succeeded in demonstrating a deficiency of oxytocin in patients with a deficiency of vasopressin caused by a disease of the pituitary gland. This finding could be key to developing new therapeutic approaches.

The hormones oxytocin and vasopressin are produced in the same area of the brain and are also very similar in structure. Patients with a rare deficiency of vasopressin cannot concentrate their urine and lose liters of water as a result. In order to compensate for this loss, they are obliged to drink up to 10 liters or more per day.

With a nasal spray or a tablet containing synthetically produced vasopressin, these symptoms can usually be treated without any problems. However, even with this treatment, many patients report anxiety, have trouble with social interactions or demonstrate impaired emotional awareness.

Saturday, May 13, 2023

Putting the STING into cancer immunotherapy

Belcher and Hammond Lab researchers developed a cancer vaccine that could make checkpoint blockade therapies more effective for more patients.
Illustration Credit: Bendta Schroeder

Immune checkpoint blockade therapies have been revolutionary in the treatment of some cancer types, emerging as one of the most promising treatments for diseases such as melanoma, colon cancer, and non-small cell lung cancer.  

While in some cases checkpoint blockade therapies elicit a strong immune response that clears tumors, checkpoint inhibitors do not work for all tumor types or all patients. Moreover, some patients who do experience an initial benefit from these therapies see their cancers recur. Only a small minority of patients treated with checkpoint blockade therapies see lasting benefits. Researchers have developed various combination therapy strategies to overcome resistance to checkpoint blockade therapies, with the STING pathway emerging as one of the most attractive lines of inquiry.  

In a study appearing in Advanced Healthcare Materials, a team of MIT researchers engineered a therapeutic cancer vaccine capable of restoring STING signaling and eliminating the majority of tumors in mouse models of colon cancer and melanoma, with minimal side effects. The vaccine also inhibited metastasis in a breast cancer mouse model and prevented the recurrence of tumors in cured mice. 

More research is needed to spread the benefits of electric vehicles equitably

Researchers should focus on equity issues surrounding the spread of electrical vehicles, according to a study by Penn State researchers
Photo Credit: Michael Fousert

Electric vehicles, or EVs, promise to reduce carbon emissions and serve as a tool to help mitigate climate change, but a team of Penn State researchers report there has been little research to determine how equitable the benefits of EVs are and, in fact, whether the technology may unfairly harm some areas and populations.

In a study, the researchers only found 48 papers out of a pool of 9,838 studies that explicitly addressed equity issues of EVs, said Wei Peng, assistant professor of international affairs and civil and environmental engineering, Peng added that the small percentage of papers that addressed equity was telling in itself.

“During that screening process, we began to learn what is over-studied and what is understudied,” said Peng, who is also an associate of the Institute for Computational and Data Sciences. “We highlighted in our paper what we saw as the most understudied: making equity more explicit as research and, second, we saw a need to focus on those emerging markets and parts of the developing world where EVs are going to be more important.”

Unlike vehicles powered by gasoline or diesel fuel, which produce carbon and other chemicals during the combustion process, the electric motors that drive the wheels of an EV do not produce tailpipe emissions. EV owners charge the batteries that are stored on board the EV, rather than add fuel.

New Sensors with the HOTS for Extreme Missions

High Operational Temperature Sensors (HOTS)
Graphic Credit: Defense Advanced Research Projects Agency

Modern technologies are laden with sensors – a now-customary fact of life in much of the world. On smart watches and phones, and in cars and homes, sensors help monitor health, adjust various settings for comfort, and warn of potential dangers. More widely, sensors are deployed across countless commercial and defense systems, including in the oil and gas sector, the automotive industry, alternative energy sources, geothermal applications, and aviation and aerospace.

In these broader industrial contexts, the capabilities of sensors can be inhibited by thermal limitations. A sensor may theoretically be able to process inputs such as speed, pressure, or the integrity of a mechanical component, but inside a turbine engine, temperatures far exceed what any existing sensor can withstand.

DARPA’s new High Operational Temperature Sensors (HOTS) program will work toward developing microelectronic sensor technologies capable of high-bandwidth, high-dynamic-range sensing at extreme temperatures.

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