Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam 1066CX, the Netherlands; Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern 3012, Switzerland. Electronic address:
Published: June 2018
AI Article Synopsis
Article Abstract
Inhibitors of poly(ADP-ribose) (PAR) polymerase (PARPi) have recently entered the clinic for the treatment of homologous recombination (HR)-deficient cancers. Despite the success of this approach, drug resistance is a clinical hurdle, and we poorly understand how cancer cells escape the deadly effects of PARPi without restoring the HR pathway. By combining genetic screens with multi-omics analysis of matched PARPi-sensitive and -resistant Brca2-mutated mouse mammary tumors, we identified loss of PAR glycohydrolase (PARG) as a major resistance mechanism. We also found the presence of PARG-negative clones in a subset of human serous ovarian and triple-negative breast cancers. PARG depletion restores PAR formation and partially rescues PARP1 signaling. Importantly, PARG inactivation exposes vulnerabilities that can be exploited therapeutically.
Autophagy is an essential cellular recycling process that maintains protein and organelle homeostasis. ATG9A vesicle recruitment is a critical early step in autophagy to initiate autophagosome biogenesis. The mechanisms of ATG9A vesicle recruitment are best understood in the context of starvation-induced non-selective autophagy, whereas less is known about the signals driving ATG9A vesicle recruitment to autophagy initiation sites in the absence of nutrient stress.
Periodontitis is one of the most common diseases and primary causes of tooth loss. The main factor that causes periodontitis is an overactive host immunological response. An in-depth investigation into the molecular pathways that cause periodontitis can aid in creating novel therapeutic approaches for periodontitis and its related systemic disorders.
Although mammals resist both acute weight loss and weight gain, the neural circuitry mediating bi-directional defense against weight change is incompletely understood. Global constitutive deletion of the melanocortin-3-receptor (MC3R) impairs the behavioural response to both anorexic and orexigenic stimuli, with MC3R knockout mice demonstrating increased weight gain following anabolic challenges and increased weight loss following anorexic challenges (i.e.
State Key Laboratory of Silicate Materials for Architectures, School of Materials Science and Engineering, Wuhan University of Technology, Wuhan 430070, China.
Polyvinylidene fluoride (PVDF) film, with high energy density and excellent mechanical properties, has drawn attention as an energy storage device. However, conduction loss in PVDF under high electric fields hinders improvement in efficiency due to electrode-limited and bulk-limited conduction. Well-aligned multilayer interfaces of two-dimensional (2D) nanocoatings can block charge injection, reducing electrode-limited conduction loss in dielectric polymers.
Deer are the most abundant large herbivores in temperate and boreal forests across the Northern Hemisphere. They are ecosystem engineers known to alter understory vegetation and future tree species composition by selective browsing. Also, deer have strong impacts on faunistic groups, often mediated by vegetation.
