Feasibility of Bilinear Mechanical Characterization of the Abdominal Aorta in a Hypertensive Mouse Model.

A change in elastin and collagen content is indicative of damage caused by hypertension, which changes the non-linear behavior of the vessel wall. This study was aimed at investigating the feasibility of monitoring the non-linear material behavior in an angiotensin II hypertensive mice model. Aortas from 13 hypertensive mice were imaged with pulse wave imaging (PWI) over 4 wk using a 40-MHz linear array.

An Engineered IL15 Cytokine Mutein Fused to an Anti-PD1 Improves Intratumoral T-cell Function and Antitumor Immunity.

The use of cytokines for immunotherapy shows clinical efficacy but is frequently accompanied by severe adverse events caused by excessive and systemic immune activation. Here, we set out to address these challenges by engineering a fusion protein of a single, potency-reduced, IL15 mutein and a PD1-specific antibody (anti-PD1-IL15m). This immunocytokine was designed to deliver PD1-mediated, avidity-driven IL2/15 receptor stimulation to PD1 tumor-infiltrating lymphocytes (TIL) while minimally affecting circulating peripheral natural killer (NK) cells and T cells.

Heterogeneity in old fibroblasts is linked to variability in reprogramming and wound healing.

Age-associated chronic inflammation (inflammageing) is a central hallmark of ageing, but its influence on specific cells remains largely unknown. Fibroblasts are present in most tissues and contribute to wound healing. They are also the most widely used cell type for reprogramming to induced pluripotent stem (iPS) cells, a process that has implications for regenerative medicine and rejuvenation strategies.

Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses.

Aging is accompanied by the functional decline of tissues. However, a systematic study of epigenomic and transcriptomic changes across tissues during aging is missing. Here, we generated chromatin maps and transcriptomes from four tissues and one cell type from young, middle-aged, and old mice-yielding 143 high-quality data sets.

Turning back time with emerging rejuvenation strategies.

Ageing is associated with the functional decline of all tissues and a striking increase in many diseases. Although ageing has long been considered a one-way street, strategies to delay and potentially even reverse the ageing process have recently been developed. Here, we review four emerging rejuvenation strategies-systemic factors, metabolic manipulations, senescent cell ablation and cellular reprogramming-and discuss their mechanisms of action, cellular targets, potential trade-offs and application to human ageing.

Cross-Platform Comparison of Untargeted and Targeted Lipidomics Approaches on Aging Mouse Plasma.

Lipidomics - the global assessment of lipids - can be performed using a variety of mass spectrometry (MS)-based approaches. However, choosing the optimal approach in terms of lipid coverage, robustness and throughput can be a challenging task. Here, we compare a novel targeted quantitative lipidomics platform known as the Lipidyzer to a conventional untargeted liquid chromatography (LC)-MS approach.

Correction: WRAP53 Is Essential for Cajal Body Formation and for Targeting the Survival of Motor Neuron Complex to Cajal Bodies.

[This corrects the article DOI: 10.1371/journal.pbio.

Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging.

In the adult brain, the neural stem cell (NSC) pool comprises quiescent and activated populations with distinct roles. Transcriptomic analysis revealed that quiescent and activated NSCs exhibited differences in their protein homeostasis network. Whereas activated NSCs had active proteasomes, quiescent NSCs contained large lysosomes.

Bursts of Reprogramming: A Path to Extend Lifespan?

In a thought-provoking study, Ocampo et al. show that the cyclic expression of stem cell reprogramming factors in vivo increases the lifespan of a mouse model of premature aging and provides health benefits to chronologically old, normal mice.

H3K4me3 breadth is linked to cell identity and transcriptional consistency.

Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to mark the transcription start sites of active genes. Here, we show that H3K4me3 domains that spread more broadly over genes in a given cell type preferentially mark genes that are essential for the identity and function of that cell type. Using the broadest H3K4me3 domains as a discovery tool in neural progenitor cells, we identify novel regulators of these cells.

CDK-mediated activation of the SCF(FBXO) (28) ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer.

SCF (Skp1/Cul1/F-box) ubiquitin ligases act as master regulators of cellular homeostasis by targeting key proteins for ubiquitylation. Here, we identified a hitherto uncharacterized F-box protein, FBXO28 that controls MYC-dependent transcription by non-proteolytic ubiquitylation. SCF(FBXO28) activity and stability are regulated during the cell cycle by CDK1/2-mediated phosphorylation of FBXO28, which is required for its efficient ubiquitylation of MYC and downsteam enhancement of the MYC pathway.

Aging and reprogramming: a two-way street.

Aging is accompanied by the functional decline of cells, tissues, and organs, as well as a striking increase in a wide range of diseases. The reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) opens new avenues for the aging field and has important applications for therapeutic treatments of age-related diseases. Here we review emerging studies on how aging and age-related pathways influence iPSC generation and property.

WRAP53 is essential for Cajal body formation and for targeting the survival of motor neuron complex to Cajal bodies.

The WRAP53 gene gives rise to a p53 antisense transcript that regulates p53. This gene also encodes a protein that directs small Cajal body-specific RNAs to Cajal bodies. Cajal bodies are nuclear organelles involved in diverse functions such as processing ribonucleoproteins important for splicing.

Sorafenib induces apoptosis and autophagy in prostate cancer cells in vitro.

The multiple tyrosine kinase inhibitor sorafenib has recently demonstrated clinical effects in patients with androgen-independent prostate cancer. These observations provided the rational for investigating the anti-tumoral properties of this compound on prostate cancer cell lines at the molecular level. Two hormone refractory (PC3 and DU145) and one hormone responsive cell line (22Rv1) were used.

Extract from Asteraceae Brachylaena ramiflora induces apoptosis preferentially in mutant p53-expressing human tumor cells.

The p53 tumor suppressor gene is inactivated by point mutation in a large fraction of human tumors, allowing evasion of apoptosis and tumor progression. p53 mutation is often associated with increased resistance to therapy. Pharmacological reactivation of mutant p53 is an attractive therapeutic strategy.

The p53 target Wig-1 regulates p53 mRNA stability through an AU-rich element.

The p53 target gene Wig-1 encodes a double-stranded-RNA-binding zinc finger protein. We show here that Wig-1 binds to p53 mRNA and stabilizes it through an AU-rich element (ARE) in the 3' UTR of the p53 mRNA. This effect is mirrored by enhanced p53 protein levels in both unstressed cells and cells exposed to p53-activating stress agents.

Wrap53, a natural p53 antisense transcript required for p53 induction upon DNA damage.

Antisense transcription is a widespread phenomenon in the mammalian genome. It is thought to play a role in regulation of gene expression, but its exact functional significance is largely unknown. We have identified a natural antisense transcript of p53, designated Wrap53, that regulates endogenous p53 mRNA levels and further induction of p53 protein by targeting the 5' untranslated region of p53 mRNA.