Annalisa M. VanHook

Delaying premature aging

Premature Aging Cells from patients with Hutchinson-Gilford progeria syndrome (HGPS) have defects in nuclear architecture that lead to premature cellular senescence. Larrieu et al. investigated the mechanisms by which a small molecule called remodelin improves the phenotype of HGPS cells (see the Focus by Wilson). Remodelin restored a nuclear import pathway mediated by Transportin-1 that was defective in HGPS cells, thereby delaying premature senescence. These results could also be applied to delay cellular senescence in cells derived from aged healthy individuals. Sci. Signal. 11 , eaar5401; see also eaat9448 (2018).

A target for preventing kidney damage

Physiology Proteinuria, the appearance of protein in the urine, results when podocytes in the kidney are damaged. Rinschen et al. found that the activation of the transcriptional coactivator YAP and the expression of YAP target genes preceded proteinuria in rats with chemically induced nephrosis. YAP activity can be stimulated by mechanical stress, and activation of YAP in cultured podocytes depended on the stiffness of the substrate. A YAP inhibitor ameliorated proteinuria and damage-induced mechanosignaling in the nephrotic rat kidneys. Sci. Signal. 10 , eaaf8165 (2017).

Vitamin C prevents microglia activation

Neuroscience Changes in the levels of ascorbate, the reduced form of vitamin C, alter neuronal function and are associated with neurodegenerative disorders. Activation of microglia in response to tissue damage or pathogens also contributes to neurodegenerative disease. Portugal et al. showed that reducing vitamin C uptake through the sodium–vitamin C cotransporter 2 (SVCT2) triggered the activation of primary rodent and human microglia. Microglia activation was suppressed by ascorbate treatment or when SVCT2 internalization was blocked, suggesting that ascorbate could be used to keep microglia from becoming reactive. Sci. Signal. 10 , eaal2005 (2017).

A nuclear off-switch for fibrosis

Fibrosis CD44 is a receptor for the extracellular matrix component hyaluronan. The standard isoform of CD44 enhances the differentiation of myofibroblasts that drive fibrosis. In contrast, prevention or reversal of myofibroblast differentiation depends on an alternatively spliced isoform, CD44v7/8. Midgley et al. found that hyaluronidase 2 (HYAL2), a hyaluronan-degrading enzyme, had a nonenzymatic role in determining CD44 splicing. In human lung fibroblasts exposed to an antidifferentiation factor, HYAL2 displaced components of the splicing machinery on CD44 precursor mRNA to promote the production of CD44v7/8 mRNA. Sci. Signal. 10 , eaao1822 (2017).

Learning the smell of danger

Cell Biology If avoiding infection is not possible, being prepared is the next-best option for preventing pathogen-induced cellular damage. Ooi and Prahlad found that previous experience of the odor of a pathogenic bacterium in the nematode Caenorhabditis elegans enhanced heat shock factor 1 (HSF-1

The TRIC to building strong bones

Developmental Biology Osteoblasts are bone-building cells that secrete a collagen-rich matrix required for bone formation. Defects in collagen deposition cause the brittle bones that are characteristic of osteogenesis imperfecta. Zhao et al. found that mice lacking Tric-b , which encodes a cation