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Category: biotech/medical

Aging human breast atlas reveals cancer susceptibility

The team used advanced imagining techniques to analyse breast tissue from more than 500 women aged 15 to 86 years old. The tissue included biopsies taken from women for non-cancer-related reasons.

Combining these images with details of the hormone receptors and immune cells present, as well as the tissue architecture, the researchers were able to map how breast tissue changes over time in unprecedented detail. Their findings point to reasons why breast cancer risk increases with age and why tumors in younger women differ biologically.

The author added: “Our map revealed that as women age, their breast tissue goes through major changes, with the most dramatic changes occurring at menopause. There are changes, too, during their twenties, possibly linked to pregnancy and childbirth, but these are far less pronounced.”

The map revealed that all types of cells become fewer in number and divide far less often. Milk-producing structures known as lobules shrink or disappear, while the ducts that that carry milk become relatively more common, with the supporting layer around them becoming thicker. Fat cells increase while blood vessels decrease.

Meanwhile, changes occur in the immune environment. Younger breasts have more B cells and active T cells, which helps them identify and kill cancer cells. As tissue ages, these types of cells decline in number, replaced by other types of immune cell that indicate a more inflammatory and potentially less protective immune environment. ScienceMission sciencenewshighlights.

Scientists have created the most detailed map to date, comprised of over 3 million cells, showing how breast tissue changes as women age – including dramatic changes during menopause.

Continue reading “Aging human breast atlas reveals cancer susceptibility” | >

Tau mutation drives autophagy-lysosome dysfunction

The researchers studied a specific mutation in a brain protein called tau that causes the protein to become misfolded and alter its normal function. In general, when tau proteins become misfolded, they build up inside neurons and contribute to various forms of dementia, including Alzheimer’s dementia and frontotemporal dementia, a neurodegenerative disease similar to Alzheimer’s that often strikes earlier — in middle age — and typically involves significant changes in personality and behavior that precede cognitive decline.

In this new study, the researchers studied neurons that had been reprogrammed from skin cells sampled from patients with frontotemporal dementia who carried the tau mutation. In the neurons, the mutated tau proteins caused waste-recycling centers called lysosomes, which are involved in autophagy, to become dysfunctional, allowing cellular waste to accumulate in the lysosomes, which may contribute to neuronal death. The researchers found that enhancing autophagy with an analog of the chemical compound G2 improved clearance of the garbage, reduced tau levels in the lysosomes and prevented cellular toxicity and death.

G2 was discovered in 2019 via screening experiments seeking drugs that could reduce the accumulation of an aggregation-prone protein in a C. elegans model of alpha-1-antitrypsin deficiency, which can cause severe liver disease. The compound was later shown to boost autophagy function in mammalian cell model systems.

The researchers also have shown that G2 can protect brain cells from death in cells modeling Huntington’s disease, a fatal inherited neurodegenerative disease caused by a genetic mutation present at birth. In the cellular model of Huntington’s disease, the compound prevented the buildup of a harmful RNA molecule. ScienceMission sciencenewshighlights.

New research adds to growing evidence that helping brain cells break down and eliminate their own cellular waste is a promising treatment strategy for a variety of neurodegenerative diseases. In lab experiments, the researchers found that exposure to a novel compound can clear a harmful protein from human neurons modeling frontotemporal dementia — a devastating and ultimately fatal condition — and prevent those neurons from dying.

The study is published in the journal Nature Communications.

Continue reading “Tau mutation drives autophagy-lysosome dysfunction” | >

Body-focused mind-wandering associated with better mental health outcomes, finds new study

Most of us have experienced that when our body is still and resting, the mind doesn’t stop. Instead, it takes off on its own journey of generating thoughts about our past, our plans, and the people around us, a process known as mind-wandering. While researchers have learned a lot about these kinds of thoughts, there aren’t many studies that explore how often our attention turns inward, toward sensations in our bodies, such as our breathing, heartbeat, or physical feelings.

This lesser-known side of our inner experience, called body-wandering, is what a recent study by a brain research team with collaborators from Denmark, Canada and Germany set out to explore.

To understand how the mind focuses on the physical self, researchers conducted a large-scale study with 536 participants who were asked to stay still in the MRI machine during a brain scan while looking at a cross on the screen above them.

How does the most common cause of Alternating Hemiplegia of Childhood (AHC) lead to abnormal repolarization and arrhythmogenesis?

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.

Lamin A/C safeguards replication initiation by orchestrating chromatin accessibility and PCNA recruitment

Zhang et al. reveal lamin A/C as a gatekeeper of replication initiation through effects on chromatin organization and PCNA availability in early S phase. Lamin A/C deficiency disrupts these controls, increasing initiation density and replication-dependent DNA damage.

Why anti-cancer drugs do not always live up to expectations

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.

New AI method flags fluid flow tipping points before simulations break down

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.

Hydroxyl radicals in UV-exposed water reveal surprising reaction pathway

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.

Electrofluidic fiber muscles could enable silent robotic systems

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.

People use the same neurons to see and imagine objects, study shows

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.”

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