Andrew P. Landstrom & team propose a Ca2+-mediated mechanism in ATP1A3-D801N carriers & identify NCX1 as a possible therapeutic target.
1Department of Cell Biology and.
2Department of Pediatrics, Division of Cardiology, Duke University School of Medicine, Durham, North Carolina, USA.
3Department of Biomedical Engineering and.
4Division of Pediatric Neurology and Developmental Medicine, Department of Pediatrics, Duke University, Durham, North Carolina, USA.
For more than a decade, a class of drugs called BET inhibitors has been tested in cancer trials with high expectations. The biology looked promising. Many cancers depend on oncogenes that “Bromo- and Extra-Terminal domain” (BET) proteins help activate, so blocking BET proteins should slow tumor growth.
David J. Silvester, a mathematics professor at the University of Manchester, has developed a novel machine-learning method to detect sudden changes in fluid behavior, improving speed and the cost of identifying these instabilities and overcoming one of the major obstacles faced when using machine learning to simulate physical systems. The findings are published in the Journal of Computational Physics.
Computational simulations of mathematical models of fluid flow are essential for everyday applications ranging from predicting the weather to the assessment of nuclear reactor safety. The advent of this simulation capability over the past 50 years has revolutionized the development of fuel-efficient airplanes, and sail configurations on racing yachts can now be optimized in real time, providing the marginal gains needed to win races in the America’s Cup.
Optimized aerodynamics means that modern day cyclists can ride faster, golf balls fly further and Olympic swimmers consistently set world records. Computational fluid dynamics also enables the modeling of the flow of blood in the human heart, making the provision of patient-specific surgery possible.
How do radicals form in aqueous solutions when exposed to UV light? This question is important for health research and environmental protection. For example, with regard to the overfertilization of water bodies by intensive agriculture. A team at BESSY II has now developed a new method of investigating hydroxyl radicals in solution. By using a clever trick, the scientists gained surprising insights into the reaction pathway. The findings are published in the Journal of the American Chemical Society.
Hydroxyl radicals (OH·) are found everywhere, from the troposphere to the cells of the human body. There, they cause oxidative stress and accelerate the aging process. They are also increasingly present in rivers and lakes, where they are formed by the photolysis of nitrogen oxides that have entered the water from over-fertilized soils. When UV radiation from sunlight strikes nitrogen oxides, hydroxyl radicals and a range of other radicals are generated. The chemistry of these radicals is extremely difficult to characterize accurately, as they react very quickly.
A team led by Professor Alexander Föhlisch of the HZB has investigated the chemistry of hydroxyl radicals formed from nitrogen oxides in water using X-ray absorption spectroscopy at the BESSY II X-ray source.
Muscles are remarkably effective systems for generating controlled force, and engineers developing hardware for robots or prosthetics have long struggled to create analogs that can approach their unique combination of strength, rapid response, scalability, and control. But now, researchers at the MIT Media Lab and Politecnico di Bari in Italy have developed artificial muscle fibers that come closer to matching many of these qualities.
Like the fibers that bundle together to form biological muscles, these fibers can be arranged in different configurations to meet the demands of a given task. Unlike conventional robotic actuation systems, they are compliant enough to interface comfortably with the human body and operate silently without motors, external pumps, or other bulky supporting hardware.
The new electrofluidic fiber muscles—electrically driven actuators built in fiber format—are described in a recent paper published in Science Robotics. The work is led by Media Lab Ph.D. candidate Ozgun Kilic Afsar; Vito Cacucciolo, a professor at the Politecnico di Bari; and four co-authors.
Why can images of things we have seen seem so real when we later recall them from memory? A new study led by Cedars-Sinai Health Sciences University investigators sheds light on the answer. The research shows that the same brain neurons are activated when we imagine something and when we perceive something. The research, led by Cedars-Sinai, is the first to provide a detailed understanding of the shared mechanism that underlies visual perception and creation of mental images in the human brain. It was published in the journal Science.
“We generate a mental image of an object that we have seen before by reactivating the brain cells we used to see it in the first place,” said Ueli Rutishauser, Ph.D., director of the Center for Neural Science and Medicine and professor of Neurosurgery, Neurology and Biomedical Sciences at Cedars-Sinai Health Sciences University, and the study’s joint senior author.
“Our study revealed the code that we use to re-create the images.”
University of Virginia School of Medicine scientists have developed a bold new approach to drug development and discovery that could dramatically accelerate the creation of new medicines. UVA’s Nikolay V. Dokholyan, Ph.D., and colleagues have developed a suite of artificial intelligence-powered tools, called YuelDesign, YuelPocket and YuelBond, that work together to transform how new drugs are created. The centerpiece, YuelDesign, uses a cutting-edge form of AI called diffusion models to design new drug molecules tailored to fit their protein targets exactly, even accounting for the way proteins flex and shift shape during binding.
A companion tool, YuelPocket, identifies exactly where on a protein a drug can attach, while YuelBond ensures the chemical bonds in designed molecules are accurate. Together, the approach is poised to improve both how new drugs are designed and how quickly and efficiently existing drugs can be evaluated for new purposes.
“Think of it this way: Other methods try to design a key for a lock that’s sitting perfectly still, but in your body, that lock is constantly jiggling and changing shape. Our AI designs the key while the lock is moving, so the fit is much more realistic,” said Dokholyan, of UVA’s Department of Neurology. “This could make a real difference for patients with cancer, neurological disorders and many other conditions where we desperately need better drugs targeting these wiggly proteins but keep hitting dead ends.”
Insecticide-treated bed nets remain one of the most effective tools in malaria prevention, acting both as a physical barrier and as an insecticidal surface that kills or disables mosquitoes before they can transmit disease. New research by a multidisciplinary research team from the University of Liverpool and the Liverpool School of Tropical Medicine (LSTM) uses surface science to assess how well malaria nets perform.
Published in Science Advances, the focus of the study was the phasing out of PFAS coatings, a group of synthetic fluorinated coating chemicals that have been valued for stability and performance. However, their environmental persistence and potential health risks have made their removal an important priority. The paper is titled “Multimodal platform for ITN efficacy: Surface chemistry, bioavailability, and mosquito behavior.”
To understand the impact of removing PFAS, the team developed a novel multimodal evaluation platform combining chemical analysis, advanced surface imaging, and mosquito behavioral tracking.
The cells that line the blood vessels in our brains are highly selective. By deciding which molecules are allowed in and out of our most important organ, the barrier these cells form is critical for keeping us alive. But how the brain chooses what passes beyond this barrier has been difficult to decipher.
Now, a team led by Janelia Research Campus Group Leader Jiefu Li has developed a new method to examine the proteins lining the inside surface of blood vessels. The technique enables them to uncover two proteins and pathways that play a role in opening and closing the blood-brain barrier—a first step in starting to understand how this important interface works. The study is published in the journal Science.
Uncovering how the blood-brain barrier functions could help scientists figure out what happens when it goes awry, contributing to conditions like multiple sclerosis, encephalitis, and dementia. It could also help researchers develop better ways to deliver medicines that treat neurodegenerative diseases like Alzheimer’s and Parkinson’s, which are often blocked from entering the brain.