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Cis-regulatory elements (CREs) control gene expression and are dynamic in their structure and function, reflecting changes in the composition of diverse effector proteins over time¹. However, methods for measuring the organization of effector proteins at CREs across the genome are limited, hampering efforts to connect CRE structure to their function in cell fate and disease. Here we developed PRINT, a computational method that identifies footprints of DNA-protein interactions from bulk and...

Female mammalian cells have two X chromosomes, one of maternal origin and one of paternal origin. During development, one X chromosome randomly becomes inactivated^(1-4). This renders either the maternal X (X(m)) chromosome or the paternal X (X(p)) chromosome inactive, causing X mosaicism that varies between female individuals, with some showing considerable or complete skew of the X chromosome that remains active^(5-7). Parent-of-X origin can modify epigenetics through DNA methylation^(8,9) and...

In Alzheimer's disease (AD), amyloid-β (Aβ) triggers the aggregation and spreading of tau pathology, which drives neurodegeneration and cognitive decline. However, the pathophysiological link between Aβ and tau remains unclear, which hinders therapeutic efforts to attenuate Aβ-related tau accumulation. Aβ has been found to trigger neuronal hyperactivity and hyperconnectivity, and preclinical research has shown that tau spreads across connected neurons in an activity-dependent manner. Here, we...

Distinct tau amyloid assemblies underlie diverse tauopathies but defy rapid classification. Cell and animal experiments indicate tau functions as a prion, as different strains propagated in cells cause unique, transmissible neuropathology after inoculation. Strain amplification requires compatibility of the monomer and amyloid template. We used cryo-electron microscopy to study one cell-based yellow fluorescent protein (YFP)-tagged strain, resolving its amyloid nature. We then used sequential...

Oxygen is essential for human life, yet a growing body of preclinical research is demonstrating that chronic continuous hypoxia can be beneficial in models of mitochondrial disease, autoimmunity, ischemia, and aging. This research is revealing exciting new and unexpected facets of oxygen biology, but translating these findings to patients poses major challenges, because hypoxia can be dangerous. Overcoming these barriers will require integrating insights from basic science, high-altitude...

In a super-aging society, the increase in the elderly population is closely tied to a rise in infectious diseases due to factors such as weakened immune systems and decreased vaccine efficacy in older adults. Various opportunistic pathogens commonly encountered in everyday life can cause infections and diseases when an individual's immune defence is weakened due to aging. These factors underscore the importance of preventive measures against pathogenic infections and the aging of immune systems...

Blink-related oscillations (BROs) are newly discovered neurophysiological brainwave responses associated with spontaneous blinking, and represent environmental monitoring and awareness processes as the brain evaluates new visual information appearing after eye re-opening. BRO responses have been demonstrated in healthy young adults across multiple task states and are modulated by both task and environmental factors, but little is known about this phenomenon in aging. To address this, we...