. Scientific Frontline

Monday, June 6, 2022

New nanoparticles aid sepsis treatment in mice

Shaoqin “Sarah” Gong
Source: University of Wisconsin–Madison
Sepsis, the body’s overreaction to an infection, affects more than 1.5 million people and kills at least 270,000 every year in the U.S. alone. The standard treatment of antibiotics and fluids is not effective for many patients, and those who survive face a higher risk of death.

In new research published in the journal Nature Nanotechnology today, the lab of Shaoqin “Sarah” Gong, a professor with the Wisconsin Institute for Discovery at the University of Wisconsin–Madison, reported a new nanoparticle-based treatment that delivers anti-inflammatory molecules and antibiotics.

The new system saved the lives of mice with an induced version of sepsis meant to serve as a model for human infections, and is a promising proof-of-concept for a potential new therapy, pending additional research.

The new nanoparticles delivered the chemical NAD+ or its reduced form NAD(H), a molecule that has an essential role in the biological processes that generate energy, preserve genetic material and help cells adapt to and overcome stress. While NAD(H) is well known for its anti-inflammatory function, clinical application has been hindered because NAD(H) cannot be taken up by cells directly.

“To enable clinical translation, we need to find a way to efficiently deliver NAD(H) to the targeted organs or cells. To achieve this goal, we designed a couple of nanoparticles that can directly transport and release NAD(H) into the cell, while preventing premature drug release and degradation in the bloodstream,” says Gong, who also holds appointments in the Department of Biomedical Engineering and the UW School of Medicine and Public Health’s Department of Ophthalmology and Visual Sciences.

The interdisciplinary work was led by Gong along with Mingzhou Ye and Yi Zhao, two postdoctoral fellows in the Gong lab. John-Demian Sauer, a professor in the Department of Medical Microbiology and Immunology, also collaborated on the project.

An edible QR code takes a shot at fake whiskey

The days of fake whiskey could be numbered, thanks to a team of biomedical engineers from Purdue University and South Korea. The team, led by Young Kim, associate head for research and an associate professor in Purdue’s Weldon School of Biomedical Engineering, has developed an QR code on an edible silk tag that manufacturers can place in bottles of whiskey. Consumers can use a smartphone app to confirm the whiskey’s authenticity. 
Credit: Purdue University photo/John Underwood

In the future, when you order a shot of whiskey, you might ask the bartender to hold an edible fluorescent silk tag that could be found floating inside – even though it is safe to consume.

This little silk tag with a QR code is a security measure that could reveal if the whiskey you’re wanting to buy is fake. Simply using a smartphone to scan the tag, which was developed by biomedical engineers from Purdue University and the National Institute of Agricultural Sciences in South Korea, could confirm the drink’s authenticity.

There are, of course, no tags currently placed in bottles of whiskey. But this new anticounterfeiting technology, published in the journal ACS Central Science, could be a step toward not only finding a solution for the alcohol industry but also addressing fake medications.

“Some liquid medicines contain alcohol. We wanted to test this first in whiskey because of whiskey’s higher alcohol content,” said Young Kim, associate head for research and an associate professor in Purdue’s Weldon School of Biomedical Engineering. “Researchers apply alcohol to silk proteins to make them more durable. Because they tolerate alcohol, the shape of the tag can be maintained for a long time.”

Analysis of huntsman spiders reveals patterns of social behavior

 The Australian huntsman (Delena gloriosa) and her plastered egg sac.
Credit: Linda S. Rayor

A new study of huntsman spiders links evolutionary lineages with life history traits, providing patterns for predicting social behaviors in other less-studied species. Sociality is very rare in spiders – only five out of close to 1,300 huntsman species are known to exhibit social behaviors.

The study, “Huntsman Spider Phylogeny Informs Evolution of Life History, Egg Sacs and Morphology,” published in the journal Molecular Phylogenetics and Evolution, was part of the undergraduate thesis of lead author Jacob Gorneau ’20.

It represents the broadest and most in-depth phylogeny of huntsman spiders – a tree-like diagram showing evolutionary relatedness among groups of organisms – while incorporating extensive biology and life history data for each species. Compared with solitary species, the findings reveal, the social species live in larger permanent family group retreats until the offspring are up to a year old, have egg sacs plastered to surfaces so they can’t be moved and begin foraging later in their development.

“The social species are doing something different than all the other solitary species,” said Linda Rayor, the paper’s senior author and a senior research associate in the Department of Entomology in the College of Agriculture and Life Sciences (CALS).

Scientists use robots to reveal how predatory fish cope with unpredictable prey


Scientists at the University of Bristol have demonstrated how predators overcome their preys’ erratic behavior by adapting their own during the hunt.

The study, published today in scientific journal PNAS, challenges the well-held theory that behaving unpredictably helps animals survive encounters with predators.

Instead of simply fleeing directly away from a predator, many prey species from across the animal kingdom choose to escape in a surprisingly wide range of directions. Scientists have long suspected that this unpredictability helps them evade capture by keeping predators guessing about the prey’s next move.

By studying how real predatory fish (blue acara cichlids) attack robotic prey, researchers from Bristol’s School of Biological Sciences were able to experimentally test this idea. Rather than confirming that unpredictable escape tactics are beneficial to prey, the new research suggests that predators can neutralize this strategy by flexibly adjusting their own behavior.

Paleontologists Discovered Teeth and Bones of Ancient Animals in the Urals

Credit: Ural Federal University

Paleontologists from the Institute of Plant and Animal Ecology of the Ural Branch of the Russian Academy of Sciences and Ural Federal University Dmitry Gimranov and Anton Kisagulov together with volunteers discovered teeth and bones of ancient Eocene animals in the Sverdlovsk Region (the Sugat River near the village of Talitsa). Most of the finds are 40 million years old. There are also later finds dating back to the Middle or Late Pleistocene (0.75-0.02 million years). The oldest finds were numerous and consisted mainly of shark and ray teeth and fish bones. The "mammoth time" finds were few and include bones of frogs, birds and mammals. Late finds will have to be dated by radiocarbon analysis.

Shark and ray teeth will be transferred for study to Tatyana Malyshkina, a Senior Researcher at the Laboratory of Stratigraphy and Paleontology at the Zavaritsky Institute of Geology and Geochemistry of the Ural Branch of the Russian Academy of Sciences. The finds will enrich her collection with new specimens and possibly serve as a basis for the description of new species. The mammal finds will be studied by Dmitry Gimranov, a Senior Researcher at the Paleoecology Laboratory of the Institute of Plant and Animal Ecology of the Ural Branch of the Russian Academy of Sciences and the Laboratory of Natural Science Methods in Humanities of the UrFU.

Novel Method for Early Disease Detection Using DNA Droplets

Droplet systems such as DNA droplets, which are formed by liquid-liquid phase separation of macromolecules, play an essential role in cellular functions. Now, by combining the technologies of DNA droplets and DNA computing, computational DNA droplets have been developed by scientists at Tokyo Tech, which can recognize specific patterns in tumor biomarker microRNA sequences.

Aqueous droplet formation by liquid-liquid phase separation (or coacervation) in macromolecules is a hot topic in life sciences research. Of these various macromolecules that form droplets, DNA is quite interesting because it is predictable and programmable, which are qualities useful in nanotechnology. Recently, the programmability of DNA was used to construct and regulate DNA droplets formed by coacervation of sequence designed DNAs.

A group of scientists at Tokyo University of Technology (Tokyo Tech) led by Prof. Masahiro Takinoue has developed a computational DNA droplet with the ability to recognize specific combinations of chemically synthesized microRNAs (miRNAs) that act as biomarkers of tumors. Using these miRNAs as molecular input, the droplets can give a DNA logic computing output through physical DNA droplet phase separation. Prof. Takinoue explains the need for such studies, "The applications of DNA droplets have been reported in cell-inspired microcompartments. Even though biological systems regulate their functions by combining biosensing with molecular logical computation, no literature is available on integration of DNA droplet with molecular computing." Their findings were published in Advanced Functional Materials.

Developing this DNA droplet required a series of experiments. First, they designed three types of Y-shaped DNA nanostructures called Y-motifs A, B, and C with 3 sticky ends to make A, B, and C DNA droplets. Typically, similar droplets band together automatically while to join dissimilar droplets a special "linker" molecule is required. So, they used linker molecules to join the A droplet with B and C droplet; these linker molecules were called AB and AC linkers, respectively.

Sunday, June 5, 2022

Red pandas face a fractured future

Red Panda
Credit: Damber Bista

The much-loved red panda is renowned for its tree-climbing ability and adorable nature, but new research shows the endangered mammal is being driven closer to extinction.

University of Queensland PhD candidate Damber Bista, who tracked red pandas in Nepal over a 12-month period from Queensland using GPS telemetry, has found that human impact is causing the mammal to restrict its movements which is further fragmenting their habitat.

Mr Bista said it was a worrying sign.

“Our research findings show that current patterns of habitat fragmentation and forest exploitation, from infrastructure projects such as new roads, are placing the red panda under increased threat,” Mr Bista said.

“Because of this, red pandas are changing their activity to minimize their interactions with disturbances, such as humans, dogs, or livestock, and this is drastically interfering with natural interactions between the animals, resulting in population isolation.”

Friday, June 3, 2022

This parasite will self-destruct

Diagrammatic representation of the target of the antimalarial compound ML901 (colored structure), showing highly specific and potent inhibition of the malaria parasite. ML901 finds a particular chink in an enzyme called tyrosine tRNA synthetase (depicted in pink), part of the machinery that the malaria parasite uses to generate the proteins needed to reproduce itself. The parasite rapidly grinds to a halt and can’t cause disease or be transmitted to other people via mosquitoes (purple).
Image: Leann Tilley and Riley Metcalfe

A new method to combat malaria which sees the disease turn against itself could offer an effective treatment for the hundreds of millions of people infected globally each year, as the efficacy of current antimalarial drugs weakens.

The University of Melbourne-led research published today in Science has identified an anti-malarial compound, ML901, which inhibits the malaria parasite but does not harm mammalian – human or other mammals’ – cells.

Co-lead author Professor Leann Tilley, from the University's Bio21 Institute, said the ML901 compound effectively made the parasite the agent of its own demise, underpinning it potency and selectivity.

“ML901 works by an unusual reaction-hijacking mechanism,” Professor Tilley said.

Lung Cancer Therapy Could Help Patients Live Longer

Karen L. Reckamp, MD, director of Medical Oncology at Cedars-Sinai Cancer, presents new data suggesting an immunotherapy drug combination can extend the lives of those diagnosed with advanced non-small cell lung cancer.
Photo by Cedars-Sinai.

Late-Breaking Research from Cedars-Sinai Cancer Finds an Immunotherapy Drug Combination Improves Survival for Patients with Immunotherapy-Resistant, Non-Small Cell Lung Cancer

Results of a Phase II clinical trial led by Cedars-Sinai Cancer investigators indicate that an immunotherapy drug combination could extend the lives of those diagnosed with advanced non-small cell lung cancer, one of the most common forms of lung cancer. The research was presented today during the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, with simultaneous publication in the peer-reviewed Journal of Clinical Oncology.

Currently, people diagnosed with advanced non-small cell lung cancer have limited treatment options. Therapies for the disease have improved over the past five years—including advances in immunotherapy—although even after initial tumor response, resistance develops in most tumors.

“This clinical trial shows promise in extending the lives of patients who have lung cancer that has become resistant to immunotherapy treatments,” said Karen L. Reckamp, MD, director of Medical Oncology at Cedars-Sinai Cancer, associate director of Clinical Research at Cedars-Sinai and lead author of the ASCO abstract and simultaneous publication. “This is a game changer for the field, and more importantly, for the patients who may benefit from the treatment.”

The study, known as S1800A, was part of Lung-MAP, a lung cancer precision medicine trial supported by the National Cancer Institute, part of the National Institutes of Health.

Great timing, supercomputer upgrade led to successful forecast of volcanic eruption

Former Illinois graduate student Yan Zhan, left, professor Patricia Gregg and research professor Seid Koric led a team that produced the fortuitous forecast of the 2018 Sierra Negra volcanic eruption five months before it occurred. 
Photo by Michelle Hassel

In the fall of 2017, geology professor Patricia Gregg and her team had just set up a new volcanic forecasting modeling program on the Blue Waters and iForge supercomputers. Simultaneously, another team was monitoring activity at the Sierra Negra volcano in the Galapagos Islands, Ecuador. One of the scientists on the Ecuador project, Dennis Geist of Colgate University, contacted Gregg, and what happened next was the fortuitous forecast of the June 2018 Sierra Negra eruption five months before it occurred.

Initially developed on an iMac computer, the new modeling approach had already garnered attention for successfully recreating the unexpected eruption of Alaska’s Okmok volcano in 2008. Gregg’s team, based out of the University of Illinois Urbana-Champaign and the National Center for Supercomputing Applications, wanted to test the model’s new high-performance computing upgrade, and Geist’s Sierra Negra observations showed signs of an imminent eruption.

“Sierra Negra is a well-behaved volcano,” said Gregg, the lead author of a new report of the successful effort. “Meaning that, before eruptions in the past, the volcano has shown all the telltale signs of an eruption that we would expect to see like groundswell, gas release and increased seismic activity. This characteristic made Sierra Negra a great test case for our upgraded model.”

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