GM-CSF Protects Macrophages from DNA Damage by Inducing Differentiation.

At inflammatory loci, pro-inflammatory activation of macrophages produces large amounts of reactive oxygen species (ROS) that induce DNA breaks and apoptosis. Given that M-CSF and GM-CSF induce two different pathways in macrophages, one for proliferation and the other for survival, in this study we wanted to determine if these growth factors are able to protect against the DNA damage produced during macrophage activation. In macrophages treated with DNA-damaging agents we found that GM-CSF protects better against DNA damage than M-CSF.

Identity Noise and Adipogenic Traits Characterize Dermal Fibroblast Aging.

During aging, stromal functions are thought to be impaired, but little is known whether this stems from changes of fibroblasts. Using population- and single-cell transcriptomics, as well as long-term lineage tracing, we studied whether murine dermal fibroblasts are altered during physiological aging under different dietary regimes that affect longevity. We show that the identity of old fibroblasts becomes undefined, with the fibroblast states present in young skin no longer clearly demarcated.

Myeloid p38α signaling promotes intestinal IGF-1 production and inflammation-associated tumorigenesis.

The protein kinase p38α plays a key role in cell homeostasis, and p38α signaling in intestinal epithelial cells protects against colitis-induced tumorigenesis. However, little is known on the contribution of p38α signaling in intestinal stromal cells. Here, we show that myeloid cell-specific downregulation of p38α protects mice against inflammation-associated colon tumorigenesis.

Measuring NLR Oligomerization IV: Using Förster Resonance Energy Transfer (FRET)-Fluorescence Lifetime Imaging Microscopy (FLIM) to Determine the Close Proximity of Inflammasome Components.

Intracellular signaling and cellular activation have been demonstrated to reside on multi-protein complexes rather than in isolated proteins. Consequently, techniques to resolve these complexes have gained much attention over the last few years. Förster Resonance Energy Transfer (FRET) coupled with Fluorescence Lifetime Imaging Microscopy (FLIM) is a powerful tool to discriminate direct interactions between two proteins within a multi-protein complex.

Genomic profiling of pediatric ALK-positive anaplastic large cell lymphoma: a Children's Cancer and Leukaemia Group Study.

Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is a T-cell malignancy in which ALK expression is a consequence of the t(2;5) or a variant translocation involving Chromosome 2. For the most part, this disease presents in the pediatric population and most, but not all, patients are successfully treated. Although the t(2;5) product nucleophosmin-ALK has been extensively studied for its transforming properties, very little is known regarding cooperative genetic mutations that may contribute to lymphomagenesis and may predict survival outcome, specifically in a purely pediatric population.