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Timely TGFβ signalling inhibition induces notochord

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The work, published today in Nature, marks a significant step forward in our ability to study how the human body takes shape during early development.

The notochord, a rod-shaped tissue, is a crucial part of the scaffold of the developing body. It is a defining feature of all animals with backbones and plays a critical role in organising the tissue in the developing embryo.

Despite its importance, the complexity of the structure has meant it has been missing in previous lab-grown models of human trunk development.

In this research, the scientists first analysed chicken embryos to understand exactly how the notochord forms naturally. By comparing this with existing published information from mouse and monkey embryos, they established the timing and sequence of the molecular signals needed to create notochord tissue.

With this blueprint, they produced a precise sequence of chemical signals and used this to coax human stem cells into forming a notochord.

The stem cells formed a miniature ‘trunk-like’ structure, which spontaneously elongated to 1–2 millimetres in length. It contained developing neural tissue and bone stem cells, arranged in a pattern that mirrors development in human embryos. This suggested that the notochord was encouraging cells to become the right type of tissue at the right place at the right time.

Study Reveals Key Alzheimer’s Pathway — And Blocking It Reverses Symptoms in Mice

A sequence of stress signals among specialized clean-up cells in the brain could at last reveal why some immune responses can cause significant nerve degeneration that results in the loss of memory, judgement, and awareness behind Alzheimer’s disease.

Blocking this pathway in mouse brains modeled on Alzheimer’s prevented damage to their synapse connections and reduced the buildup of potentially toxic tau proteins – both hallmarks of the condition.

The researchers, led by a team from the City University of New York (CUNY), believe this pathway – called the integrated stress response (ISR) – causes brain immune cells called microglia to go ‘dark’ and start damaging rather than benefiting the brain.

Four Clinical Trials We’re Watching That Could Change Medicine in 2025

Meanwhile, scientists dug into how psychedelics and MDMA fight off depression and post-traumatic stress disorders. The year was a relative setback for the psychedelic renaissance, with the FDA rejecting MDMA therapy. But the field is still gaining recognition for its therapeutic potential.

Then there’s lenacapavir, a shot that protects people from HIV. Named “breakthrough of the year” by Science, the shot completely protected African teenage girls and women against HIV infection. Another trial supported the results, showing the drug protected people who have sex with men at nearly 100 percent efficacy. The success stems from a new understanding of the protein “capsule” guarding the virus’ genetic material. Many other viruses have a similar makeup—meaning the strategy could help researchers design new drugs to fight them off too.

So, what’s poised to take the leap from breakthrough to clinical approval in 2025? Here’s what to expect in the year ahead.

‘Aging hotspot’ found in the brain may hold the key to longevity

Researchers at the Allen Institute have identified a specific brain region in mice where aging triggers significant changes in numerous cell types. The study also pinpointed which cell types undergo the most profound transformations.

This new information, published in the journal Nature, points toward potential approaches for slowing or controlling the aging process in the brain.

The research was focused on numerous glial cell types – the brain’s “support cells” – that demonstrated considerable shifts in gene activity with age. Among the cells most affected were microglia, border-associated macrophages, oligodendrocytes, tanycytes, and ependymal cells.

Chinese scientists find common blood pressure drug could cure rare brain tumour

Chinese scientists have found a common hypertension drug could prove potent in treating a rare but highly invasive brain tumour.

Although craniopharyngioma is a benign tumour, it can cause complications due to its growth along the critical nerve structures of the brain close to the hypothalamus and the pituitary gland.

Given its location, the tumour can cause hormone dysfunction and metabolic disorders, like obesity, diabetes and hypothyroidism.

How Altered States of Consciousness Change Time Perception

Summary: Time perception varies depending on context, often slowing in emergencies or unfamiliar settings and speeding up during absorption or as we age. Time expansion experiences (Tees) occur when seconds stretch into minutes, frequently in accidents, sports, or moments of calm. These experiences, often tied to altered states of consciousness, allow people to process more information and act decisively.

While theories link Tees to noradrenaline release or evolutionary adaptation, their occurrence in peaceful states suggests a deeper connection to changes in self-perception and awareness. Understanding Tees could offer insights into human cognition and survival mechanisms.

Sleep microstructure organizes memory replay

How sleep microstructure organizes memory replay.

T occur in isolation; older memories are also replayed during sleep, raising an intriguing challenge: how does the brain avoid interference between fragile new memories and stable old ones?” + To explore this question, researchers developed a groundbreaking method to study both hippocampal activity and sleep dynamics simultaneously in naturally sleeping mice. Using a technique called pupillometry, which measures oscillatory changes in pupil size, they uncovered a previously unknown “microstructure” within non-REM sleep that helps the brain manage memory replay.

They discovered that memory replay is organized into distinct substates of non-REM sleep:

1. Contracted pupil substates: During these phases, the hippocampus predominantly replays new memories. This activity is associated with sharp-wave ripples—brief bursts of electrical activity critical for memory consolidation—and strong excitatory inputs from external sources.

2. Dilated pupil substates: In contrast, older memories are reactivated during these phases, characterized by increased local inhibitory activity, which helps maintain stability and prevent interference.

To test the importance of these substates, the researchers disrupted sharp-wave ripples during contracted pupil substates using a closed-loop system. This interference impaired the recall of recent memories but had no effect when applied during dilated pupil substates, confirming that these phases serve different purposes in memory processing.

This study reveals that the brain uses the microstructure of non-REM sleep to segregate and organize memory replay, ensuring that new and old memories are handled in distinct time windows. By multiplexing these processes, the brain supports continuous learning and prevents the chaos of memory interference. This discovery not only deepens our understanding of sleep but also highlights its pivotal role in making learning and memory seamless.

Fragile X Breakthrough: Study Shows Existing Drug Restores Early Communication

Research reveals distinct mechanisms underlying neonatal and post-pubertal social behaviors, providing valuable insights for developing targeted early interventions.

Researchers from the University of Texas Health Science Center at San Antonio and Hirosaki University have unveiled significant findings on the development of social behaviors in fragile X syndrome, the most common genetic cause of autism spectrum disorder. The study, published in Genomic Psychiatry, highlights the effects of a specific prenatal treatment on social behaviors in mice.

The researchers found that administering bumetanide—a drug that regulates chloride levels in neurons—to pregnant mice restored normal social communication in newborn pups with the fragile X mutation. However, they also discovered an unexpected outcome: the same treatment reduced social interaction after puberty in both fragile X and typical mice. These findings shed light on the complex and developmental-stage-specific effects of interventions for fragile X syndrome.

The Hypothalamic Hotspot: Revealing the Brain’s Secret to Aging

Largest brain aging study points to possible connections between diet, inflammation, and brain health.

Scientists at the Allen Institute have discovered specific types of brain cells in mice that experience significant changes as they age. They also identified a distinct “hotspot” where many of these changes are concentrated. Published today (January 1) in Nature, these findings could lead to the development of therapies aimed at slowing or managing the brain’s aging process.