The current model of necroptosis assumes that MLKL’s N-terminal cytotoxic domain is unleashed from autoinhibition concurrent with phosphorylation by RIPK3. Here, Pan and Abbott show that inhibition of MLKL’s N terminus abolishes phosphorylation by RIPK3 whereas removal or relieving autoinhibition between the N-terminal and intermediate domains promotes its phosphorylation.
Daniel J. Drucker & team identify the vascular smooth muscle GLP-1 receptor as a key cellular target for the actions of GLP-1 medicines to lower blood pressure.
The figure: Renal GLP1R/Glp1r is expressed in human and murine vascular smooth muscle cells (VSMCs) and Glp1rVSM-/- mice have reduced Glp1r transcripts in renal tissues.
1Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
2Section of Nephrology, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
Address correspondence to: Daniel J. Drucker, Mt. Sinai Hospital, 600 University Ave. Mailbox 39, Toronto, Ontario, Canada, M5G1X5. Phone: 416.361.2661; Email: drucker@lunenfeld.ca.
Scientists build an atlas of the blood vessel in diabetes and decipher crosstalk between “foamy” phagocytes and endothelial cells, showing that TREM2 drives vessel dysfunction in peripheral artery disease.
Read more in Science TranslationalMedicine.
Diabetes-driven TREM2-endothelial cross-talk impairs vascular repair in peripheral arterial disease.
New research suggests that plasma phosphorylated tau 217 (pTau217) can detect Alzheimer’s disease pathology years before it appears on traditional PET scans. In longitudinal studies, elevated pTau217 levels accurately predicted future amyloid accumulation and cognitive decline in currently asymptomatic, healthy older adults. While not yet recommended for routine clinical screening, this biomarker offers a potential “clock” for estimating the onset of symptoms within a three to four year margin.
Participants who were amyloid-beta-negative and had very low pTau217 (below ~2.6% in this cohort) rarely became amyloid-beta-positive, suggesting this subgroup may be low risk and might not require amyloid-beta PET until pTau217 rises, the researchers said.
Higher baseline plasma %pTau217 also predicted tau accumulation in the brain — even when amyloid levels were still low, suggesting it captures very early disease processes.
In terms of cognition, across the full cohort, higher plasma pTau217 was associated with faster decline on a composite cognitive score. However, this relationship was largely driven by individuals who already had elevated amyloid; among amyloid-negative participants, pTau217 did not significantly predict cognitive decline over the follow-up period.
A new international study co-led by investigators from Mass General Brigham and the Eye & ENT Hospital of Fudan University shows that a gene therapy for a rare form of genetic deafness successfully restored hearing in most participants, with results lasting up to 2.5 years. The results, the largest clinical trial of gene therapy for inherited hearing loss to date and the longest follow-up reported so far, are published in Nature. According to the authors, these latest findings reinforce earlier trials that show gene therapy can be used to treat some forms of inherited deafness, helping guide future research and care.
“It’s remarkable to see patients go from complete deafness to being able to hear,” said the study’s corresponding author, Zheng-Yi Chen, DPhil, the Ines and Fredrick Yeatts Chair in Otolaryngology and an associate scientist at Mass Eye and Ear, a member of the Mass General Brigham healthcare system. “For many patients, that also means the ability to develop and use speech.”
Genetic mutations account for up to 60% of hearing loss present at birth. In this study, researchers used a gene therapy they developed to treat autosomal recessive deafness 9 (DFNB9), caused by mutations in the OTOF gene. The OTOF gene provides the body with instructions to make a protein called otoferlin, which is essential for hearing function. Without it, hair cells in the inner ear cannot pass sound signals to the brain, causing severe-to-complete deafness at birth. OTOF mutations account for about 2 to 8 in every 100 cases.
Gene therapies are designed to add a working version of mutated genes that lead to disease. Since a single faulty gene causes DFNB9, it is well-suited for gene therapy research. The treatment is a single injection into the inner ear that uses a harmless virus (AAV) to deliver a working copy of the OTOF gene to the cells needed for hearing.
This latest trial enrolled 42 participants across eight sites in China, ranging in age from infants to adults (0.8 to 32.3 years). Each participant received one of three doses of a single gene therapy treatment: 36 in one ear and six in both ears. The research team then followed participants for up to 2.5 years, to see if treatment remained safe, affected their hearing and speech recognition. The researchers also sought to better understand why some participants may respond better than others.
“These multicenter trial results validate the effectiveness of our OTOF gene therapy,” said Yilai Shu, MD, PhD, a professor from Eye & ENT Hospital of Fudan University, who led the study. “The procedure can be broadly implemented in hospital settings, ensuring consistent delivery for a larger patient population.”
Abstract: Multicentre gene therapy for OTOF-related deafness followed up to 2.5 years https://www.nature.com/articles/s41586-026-10393-y.
Recently, a growing body of research suggests that the brain fog one experiences as they grow older is linked to a tide of inflammation deep within the brain’s memory centre. Scientists call this “neuroinflammaging” – thought to be the inevitable price of growing older.
But now, a new mice study suggests that this inflammation behind brain ageing and brain fog can actually be reversed with a simple nasal spray. This spray could reshape the future of therapies for conditions like Alzheimer’s disease, and may even change what is known about brain ageing itself, say researchers from Texas A&M University.
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REFERENCES
How black holes may be responsible for Dark Energy • How BLACK HOLES May be Responsible for DAR…
Is Dark Energy made of particles? • Is Dark ENERGY made of PARTICLES? The Quin…
What is Dark Energy made of? • What is Dark Energy made of? Quintessence?… CHAPTERS 0:00 The 70% mystery 0:58 How Dark Energy was discovered? 4:26 What could be causing Dark Energy? 6:58 Repulsive Gravity? 10:16 What is the energy made of? 11:56 Evolving Dark energy? Quintesssence 14:18 Could Dark Energy be a particle? 16:43 Could Black Holes cause Dark Energy? SUMMARY Dark energy is one of the greatest mysteries in modern physics. It appears to make up nearly 70% of the universe, yet scientists still do not know what it is. Unlike matter, it does not clump together. Unlike radiation, it does not dilute as space expands. Instead, it causes the expansion of the universe to accelerate, pushing galaxies apart faster over time. The discovery of this acceleration came in the late 1990s when astronomers measured distant Type Ia supernovae, which act as reliable “standard candles.” By comparing their brightness and redshift, researchers could determine how fast the universe expanded at different points in cosmic history. Instead of finding that gravity slowed expansion—as expected—they discovered the opposite: the universe was expanding faster and faster. This unexpected result led to the concept of dark energy, the unknown driver behind cosmic acceleration. One possible explanation is that dark energy is a cosmological constant, represented by the Greek letter lambda in Einstein’s equations. In this model, empty space itself contains a constant energy density known as vacuum energy. Quantum mechanics predicts that empty space is not truly empty; quantum fields constantly fluctuate, producing short-lived “virtual particles.” These fluctuations create energy even in a vacuum. Experiments like the Casimir effect provide evidence that vacuum energy is real. However, this explanation has a major problem. When physicists calculate vacuum energy using quantum theory, the predicted value is about 10¹²⁰ times larger than what observations of the universe allow. This enormous mismatch is widely considered the worst prediction in physics. In general relativity, cosmic acceleration can occur if the universe contains energy with negative pressure. In the Friedmann equation, expansion accelerates when pressure is sufficiently negative relative to energy density. Dark energy appears to have exactly this property, effectively producing a form of repulsive gravity that stretches spacetime. Another possibility is that dark energy is not constant but comes from a dynamic field known as quintessence. In quantum theory, fields can have particle-like excitations, meaning dark energy might correspond to extremely weakly interacting particles. If the strength of this field changes over time, the acceleration of the universe could grow stronger. In extreme scenarios, this could eventually lead to a catastrophic future known as the Big Rip, where galaxies, stars, atoms, and even spacetime itself are torn apart. A more speculative idea suggests a connection between supermassive black holes and dark energy. Some recent studies have observed that black holes appear to grow more massive over billions of years than expected from normal matter accretion alone. Researchers have proposed that black holes might somehow be linked to dark energy, though current evidence only shows a correlation and not a confirmed causal explanation. #darkenergy For now, dark energy remains an observed phenomenon with multiple possible explanations. Whether it is a property of empty space, a new field of physics, or something even deeper, it stands as one of the most profound open questions in cosmology.
CHAPTERS
0:00 The 70% mystery
0:58 How Dark Energy was discovered?
4:26 What could be causing Dark Energy?
6:58 Repulsive Gravity?
10:16 What is the energy made of?
11:56 Evolving Dark energy? Quintesssence
14:18 Could Dark Energy be a particle?
16:43 Could Black Holes cause Dark Energy?
SUMMARY
Dark energy is one of the greatest mysteries in modern physics. It appears to make up nearly 70% of the universe, yet scientists still do not know what it is. Unlike matter, it does not clump together. Unlike radiation, it does not dilute as space expands. Instead, it causes the expansion of the universe to accelerate, pushing galaxies apart faster over time.
The discovery of this acceleration came in the late 1990s when astronomers measured distant Type Ia supernovae, which act as reliable “standard candles.” By comparing their brightness and redshift, researchers could determine how fast the universe expanded at different points in cosmic history. Instead of finding that gravity slowed expansion—as expected—they discovered the opposite: the universe was expanding faster and faster. This unexpected result led to the concept of dark energy, the unknown driver behind cosmic acceleration.
One possible explanation is that dark energy is a cosmological constant, represented by the Greek letter lambda in Einstein’s equations. In this model, empty space itself contains a constant energy density known as vacuum energy. Quantum mechanics predicts that empty space is not truly empty; quantum fields constantly fluctuate, producing short-lived “virtual particles.” These fluctuations create energy even in a vacuum. Experiments like the Casimir effect provide evidence that vacuum energy is real.
Magnetic monopoles are hypothetical particles with a single magnetic charge — north without south. Predicted by grand unified theories, they may be incredibly massive and could bind together into “magmatter,” an ultra-dense material stronger than anything known in nature.
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/ discord Credits: Magnetic Monopoles & Magmatter — The Strongest Material That Might Exist Written, Produced & Narrated by: Isaac Arthur Select imagery/video supplied by Getty Images Chapters 0:00 Intro 4:52 What Magnetic Monopoles Would Do 10:30 Magmatter: Matter Without Atoms 18:48 Nokia 3,310 19:55 What You Could Build — and What It Would Cost.
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Credits:
Magnetic Monopoles & Magmatter — The Strongest Material That Might Exist.
Written, Produced & Narrated by: Isaac Arthur.
Select imagery/video supplied by Getty Images.
Chapters.
0:00 Intro.
4:52 What Magnetic Monopoles Would Do.
10:30 Magmatter: Matter Without Atoms.
18:48 Nokia 3310
19:55 What You Could Build — and What It Would Cost.