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Interpretable deep learning framework for understanding molecular changes in human brains with Alzheimer's disease: implications for microglia activation and sex differences

1 month ago
The utilization of artificial intelligence in studying the dysregulation of gene expression in Alzheimer's disease (AD) affected brain tissues remains underexplored, particularly in delineating common and specific transcriptomic signatures across different brain regions implicated in AD-related cellular and molecular processes, which could help illuminate novel disease biology for biomarker and target discovery. Herein we developed a deep learning framework, which consisted of multi-layer...
Maitry Ronakbhai Trivedi

Tau PET positivity in individuals with and without cognitive impairment varies with age, amyloid-β status, APOE genotype and sex

1 month ago
Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (N = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive...
Rik Ossenkoppele

Inactivation of Histone Chaperone HIRA Unmasks a Link Between Normal Embryonic Development of Melanoblasts and Maintenance of Adult Melanocyte Stem Cells

1 month ago
Evidence indicates that the integrity of in utero development influences late life healthy or unhealthy aging; however, specific links between them are unclear. Histone chaperone HIRA is thought to play a role in both life stages, and here, we explore this role using the murine pigmentary system by investigating and comparing the effects of its lineage-specific knockout, either conditionally during embryogenesis or postnatally. Embryonic knockout of Hira in tyrosinase+ neural crest-derived...
Farah Jaber-Hijazi

LIN-39 is a neuron-specific developmental determinant of longevity in Caenorhabditis elegans with reduced insulin signaling

1 month ago
The nuclear chromatin landscape changes with age. Here, we investigate whether chromatin alterations distinguish also animals with unusual aging rates, focusing on Caenorhabditis elegans with reduced insulin/IGF-like signaling (IIS), i.e., daf-2 mutants. In these animals, enhancer regions that close with age tend to open and become transcriptionally active. We identify LIN-39 as a transcription factor (TF) binding these regions and being required for the longevity of daf-2 mutants. LIN-39 acts...
Alan Kavšek

Interpretable deep learning framework for understanding molecular changes in human brains with Alzheimer's disease: implications for microglia activation and sex differences

1 month ago
The utilization of artificial intelligence in studying the dysregulation of gene expression in Alzheimer's disease (AD) affected brain tissues remains underexplored, particularly in delineating common and specific transcriptomic signatures across different brain regions implicated in AD-related cellular and molecular processes, which could help illuminate novel disease biology for biomarker and target discovery. Herein we developed a deep learning framework, which consisted of multi-layer...
Maitry Ronakbhai Trivedi

Mitochondrial origins of the pressure to sleep

1 month ago
To gain a comprehensive, unbiased perspective on molecular changes in the brain that may underlie the need for sleep, we have characterized the transcriptomes of single cells isolated from rested and sleep-deprived flies. Here we report that transcripts upregulated after sleep deprivation, in sleep-control neurons projecting to the dorsal fan-shaped body^(1,2) (dFBNs) but not ubiquitously in the brain, encode almost exclusively proteins with roles in mitochondrial respiration and ATP synthesis....
Raffaele Sarnataro

Therapeutic effects of PDGF-AB/BB against cellular senescence in human intervertebral disc

1 month ago
Accumulation of senescent cells is closely linked with intervertebral disc (IVD) degeneration, a prevalent age-dependent chronic disorder causing low back pain. While previous studies have highlighted that platelet-derived growth factor (PDGF) mitigated IVD degeneration through anti-apoptotic and pro-anabolic effects, its impact on IVD cell senescence remains elusive. In this study, human NP and AF cells derived from aged, degenerated IVDs were treated with recombinant human (rh) PDGF-AB/BB for...
Changli Zhang

Physiological and injury-induced microglial dynamics across the lifespan

1 month ago
Microglia are the brain's resident immune cells known for their dynamic responses to tissue and vascular injury. However, few studies have explored how microglial activity differs across the life stages of early development, adulthood, and aging. Using two-photon live imaging, we confirm that microglia in the adult cerebral cortex exhibit highly ramified processes and relatively immobile somata under basal conditions. Their responses to focal laser-induced injury occur over minutes and are...
Taryn Tieu

Arabidopsis phospholipase Dζ2 facilitates vacuolar acidification and autophagy under phosphorus starvation by interacting with VATD

1 month ago
Vacuolar acidification is crucial for the homeostasis of intracellular pH and the recycling of proteins and nutrients in cells, thereby playing important roles in various physiological processes related to vacuolar function. The key factors regulating vacuolar acidification and underlying mechanisms remain unclear. Here, we report that Arabidopsis phospholipase Dζ2 (PLDζ2) promotes the acidification of the vacuolar lumen to stimulate autophagic degradation under phosphorus deficiency. The pldζ2...
Bin Guan

Training and retraining liquid crystal elastomer metamaterials for pluripotent functionality

1 month ago
Training has emerged as a promising materials design technique in which function can be achieved through repeated physical modification of an existing material rather than by direct chemical functionalization, cutting, or reprocessing. This work investigates both the ability to train for function and then to erase that function on-demand in macroscopic metamaterials made from liquid crystal elastomers. We first show that the Poisson's ratio of these disordered arrays can be tuned via directed...
Savannah D Gowen

Heterochronic parabiosis uncovers AdipoR1 as a critical player in retinal rejuvenation

1 month ago
Aging induces substantial structural and functional decline in the retina, yet the molecular drivers of this process remain elusive. In this study, we used heterochronic parabiosis (HP) combined with single-cell RNA sequencing to generate comprehensive transcriptomic profiles of murine retinas from young, aged, and HP pairs, aiming to identify antiaging targets. Our analysis revealed extensive transcriptional alterations across retinal cell types with aging. HP experiments demonstrated that...
Yidan Liu