Lymphoid gene expression supports neuroprotective microglia function
NatureTL;DR
Brain immune cells called microglia can either protect against or worsen Alzheimer's disease, and scientists found that a specific protein called CD28 helps these cells stay in "protective mode" by reducing harmful brain inflammation. This discovery could lead to new treatments that boost the brain's natural defenses against Alzheimer's.
Abstract Microglia, the innate immune cells of the brain, play a defining role in the progression of Alzheimer’s disease (AD) 1 . The microglial response to amyloid plaques in AD can range from neuroprotective to neurotoxic 2 . Here we show that the protective function of microglia is governed by the transcription factor PU.1, which becomes downregulated following microglial contact with plaques. Lowering PU.1 expression in microglia reduces the severity of amyloid disease pathology in mice and is linked to the expression of immunoregulatory lymphoid receptor proteins, particularly CD28, a surface receptor that is critical for T cell activation 3,4 . Microglia-specific deficiency in CD28, which is expressed by a small subset of plaque-associated PU.1 low microglia, promotes a broad inflammatory microglial state that is associated with increased amyloid plaque load. Our findings indicate that PU.1 low CD28-expressing microglia may operate as suppressive microglia that mitigate the progression of AD by reducing the severity of neuroinflammation. This role of CD28 and potentially other lymphoid co-stimulatory and co-inhibitory receptor proteins in governing microglial responses in AD points to possible immunotherapy approaches for treating the disease by promoting protective microglial functions.
- 1Microglia brain immune cells have both protective and harmful responses to amyloid plaques in Alzheimer's disease
- 2The transcription factor PU.1 controls protective microglial function but gets turned down when microglia encounter amyloid plaques
- 3CD28, a receptor protein normally found on immune T cells, is expressed by a small subset of protective microglia near plaques
- 4Mice lacking CD28 in their microglia showed increased brain inflammation and more amyloid plaque buildup
- 5PU.1-low, CD28-expressing microglia act as suppressive cells that reduce neuroinflammation and slow Alzheimer's progression
Baby chicks pass the bouba-kiki test challenging a theory of language
Imagine you hear the made-up words "bouba" and "kiki" - which one sounds round and soft, and which sounds sharp and spiky? Most people say "bouba" sounds round and "kiki" sounds sharp. This is called the bouba-kiki effect, and scientists thought it might be special to humans and related to how we developed language. But this study found that baby chickens, just hours after hatching, make the same connections! When they heard "bouba-like" sounds, 80% of the chicks walked toward round, curved shapes rather than spiky ones. This suggests that connecting sounds with shapes isn't learned or uniquely human - it might be a basic way that many animals' brains work, going back hundreds of millions of years in evolution.
Single-minus gluon tree amplitudes are nonzero
Imagine tiny particles called gluons are like spinning tops. Their spin can be in one of two directions, which physicists call 'plus' or 'minus'. For decades, the rulebook seemed to say that you could never have a situation where just one gluon was spinning 'minus' and all the others were spinning 'plus' — that outcome was thought to be zero. This paper found a loophole. Under very specific, purely mathematical conditions that don't exist in our physical reality but are useful for calculations, this interaction can happen. The researchers wrote down the exact recipe for it, fixing a small but important detail in our fundamental rulebook for how the universe works.
Sub-part-per-trillion test of the Standard Model with atomic hydrogen
Scientists made an incredibly precise measurement of light emitted by hydrogen atoms that tested one of physics' most fundamental theories - the Standard Model - to an accuracy of 0.7 parts per trillion. This measurement also resolved a long-standing disagreement about the size of protons by confirming the smaller value found in previous experiments with exotic atoms.
Liver exerkine reverses aging- and Alzheimer’s-related memory loss via vasculature
This discovery could lead to new treatments for age-related memory loss and Alzheimer's disease that don't require physical exercise. Instead of just telling people to exercise more, doctors might eventually be able to give patients the specific liver protein (GPLD1) or drugs that block TNAP to achieve the brain benefits of exercise. This is especially important for elderly or disabled people who cannot exercise regularly but still want to protect their memory and cognitive function.