Transcription factor EB is a master regulator of genes involved in the maintenance of autophagic and lysosomal homeostasis, processes which have been implicated in the pathogenesis of GBA-related and sporadic Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). TFEB activation at the lysosomal level results in its translocation from the cytosol to the nucleus. Here, we aimed at…

Inherited retinal degeneration (IRD) refers to a group of untreatable blinding diseases characterized by a progressive loss of photoreceptors. IRD pathology is often linked to an excessive activation of cyclic nucleotide-gated channels (CNGC) leading to Na+- and Ca2+-influx, subsequent activation of voltage-gated Ca2+-channels (VGCC), and further Ca2+ influx. However, whether and how exactly…

The processing and perception of amplitude modulations (AMs) in the auditory system reflect a frequency-selective process, often described as a modulation filterbank. Previous studies on perceptual AM masking reported similar results for older listeners with hearing impairment (HI) and young listeners with normal hearing (NH), suggesting no effects of age nor hearing loss on AM frequency…

Neural activity in the primate brain correlates with both sensory evaluation and action selection aspects of decision-making. However, the neural mechanisms underlying the interplay between these processes remain unclear. Here, we examined the modulation of sensory evaluation by action selection in posterior parietal cortex (PPC) when monkeys used saccade choices to report their decisions about…

Human iPSCs provide powerful cellular models of Alzheimers disease (AD) and offer many advantages over non-human models, including the potential to reflect variation in individual-specific pathophysiology and clinical symptoms Previous studies have demonstrated that iPSC-neurons from individuals with AD reflect clinical markers, including β-amyloid (Aβ) levels and synaptic vulnerability. However,…

Aberrant angiogenesis could contribute to cognitive impairment, representing a therapeutic target for preventing dementia. However, most angiogenesis studies focus on model organisms. To test the relevance of angiogenesis to human cognitive aging, we evaluated associations of circulating blood markers of angiogenesis with brain aging trajectories in two deeply phenotyped human cohorts (n=435, age…

Recent studies have proposed that visual information can be maintained in an activity-silent state during working memory (WM) and that this activity-silent WM can be reactivated by task-irrelevant high-contrast visual impulses (i.e., “pinging the brain”). Although pinging the brain has become a popular tool for exploring activity-silent WM in recent years, its underlying mechanisms remain…

Intradermal (ID) Bacillus Calmette-Guérin (BCG) is the most widely administered vaccine in the world. However, ID BCG fails to achieve the level of protection needed in adults to alter the course of the tuberculosis epidemic. Recent studies in non-human primates have demonstrated high levels of protection against Mycobacterium tuberculosis (Mtb) following intravenous (IV) administration of BCG….

In solid tissues homeostasis and regeneration after injury involve a complex interplay between many different cell types. The mammalian liver harbors numerous epithelial and non-epithelial cells and little is known about the global signaling networks that govern their interactions. To better understand the hepatic cell network, we isolated and purified 10 different cell populations from normal…

Evolutionary increases in genome size, cell volume, and nuclear volume have been observed across the tree of life, with positive correlations documented between all three traits. Developmental tempo slows as genomes, nuclei, and cells increase in size, yet the driving mechanisms are poorly understood. To bridge this gap, we use a mathematical model of the somitogenesis clock to link slowed…