Aggregator

Protein post-translational modifications (PTM) play a crucial role in the modulation of synaptic function and their alterations are involved in the onset and progression of neurodegenerative disorders. S-palmitoylation is a PTM catalyzed by zinc finger DHHC domain containing (zDHHC) S-acyltransferases that affects both localization and activity of proteins regulating synaptic plasticity and amyloid-β (Aβ) metabolism. Here, we found significant increases of both zDHHC7 expression and protein...

Synaptic loss and dendritic degeneration are common pathologies in several neurodegenerative diseases characterized by progressive cognitive and/or motor decline, such as Alzheimer's disease (AD) and frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS). An essential regulator of neuronal health, the cAMP-dependent transcription factor CREB positively regulates synaptic growth, learning, and memory. Phosphorylation of CREB by protein kinase A (PKA) and other cellular kinases promotes...

Large international study finds “trust gap” in 43 out of 68 countries

Protein post-translational modifications (PTM) play a crucial role in the modulation of synaptic function and their alterations are involved in the onset and progression of neurodegenerative disorders. S-palmitoylation is a PTM catalyzed by zinc finger DHHC domain containing (zDHHC) S-acyltransferases that affects both localization and activity of proteins regulating synaptic plasticity and amyloid-β (Aβ) metabolism. Here, we found significant increases of both zDHHC7 expression and protein...

The identification of causal relationships between specific genes and social, behavioral, and health outcomes is challenging due to environmental confounding from population stratification and dynastic genetic effects. Existing methods to eliminate environmental confounding leverage random genetic variation resulting from recombination and require within-family dyadic genetic data (i.e., parent-child and/or sibling pairs), meaning they can only be applied in relatively small and selected...

Cancers invoke various pathways to mitigate external and internal stresses to continue their growth and progression. We previously reported that the eIF2 kinase GCN2 and the integrated stress response are constitutively active in prostate cancer (PCa) and are required to maintain amino acid homeostasis needed to fuel tumor growth. However, although loss of GCN2 function reduces intracellular amino acid availability and PCa growth, there is no appreciable cell death. Here, we discovered that the...

OBJECTIVE: Determine how preventable causes of death contribute to the life expectancy gap between Mexico and Spain.

Disorder and flexibility in protein structures are essential for biological function but can also contribute to diseases, such as neurodegenerative disorders. However, characterizing protein folding on a proteome-wide scale within biological matrices remains challenging. Here we present a method using a bifunctional chemical probe, named TME, to capture in situ, enrich and quantify endogenous protein disorder in cells. TME exhibits a fluorescence turn-on effect upon selective conjugation with...

No abstract

Genome instability is a hallmark of aging, with the highly repetitive ribosomal DNA (rDNA) within the nucleolus being particularly prone to genome instability. Nucleolar enlargement accompanies aging in organisms ranging from yeast to mammals, and treatment with many antiaging interventions results in small nucleoli. Here, we report that an engineered system to reduce nucleolar size robustly extends budding yeast replicative lifespan in a manner independent of protein synthesis rate or rDNA...

Aging is the greatest risk factor for breast cancer; however, how age-related cellular and molecular events impact cancer initiation is unknown. In this study, we investigated how aging rewires transcriptomic and epigenomic programs of mouse mammary glands at single-cell resolution, yielding a comprehensive resource for aging and cancer biology. Aged epithelial cells exhibit epigenetic and transcriptional changes in metabolic, pro-inflammatory and cancer-associated genes. Aged stromal cells...

The age-associated decline in intestinal stem cell (ISC) function is a key factor in intestinal aging in organisms, resulting in impaired intestinal function and increased susceptibility to age-related diseases. Consequently, it is imperative to develop effective therapeutic strategies to prevent ISC aging and functional decline. In this study, we utilized an aging Drosophila model screening of amino acids and found that asparagine (Asn), a nonessential amino acid in vivo, exhibits its profound...

Sex differences, driven in part by steroid hormones, shape the structure and function of the brain throughout the lifespan and manifest across brain health and disease. The influence of steroid hormones on neuroplasticity, particularly in the adult hippocampus, differs between the sexes, which has important implications for disorders and diseases that compromise hippocampus integrity, such as depression and Alzheimer disease. This Review outlines the intricate relationship between steroid...

Sex differences, driven in part by steroid hormones, shape the structure and function of the brain throughout the lifespan and manifest across brain health and disease. The influence of steroid hormones on neuroplasticity, particularly in the adult hippocampus, differs between the sexes, which has important implications for disorders and diseases that compromise hippocampus integrity, such as depression and Alzheimer disease. This Review outlines the intricate relationship between steroid...

Stunning photos document the vast, fragile enterprise that feeds us