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Parkin, an E3 ubiquitin ligase, has been found to be responsible for autosomal recessive juvenile parkinsonism characterized primarily by selective loss of dopaminergic neurons with subsequent defects in movements. However, the molecular mechanisms underlying this neuron loss remain elusive. Here, we characterized Drosophila parkin loss-of-function mutants,(More)
Analysis of parallel genotyping and expression profiling data has shown that mRNA expression levels are highly heritable. Currently, only a tiny fraction of this genetic variance can be mechanistically accounted for. The influence of trans-acting polymorphisms on gene expression traits is often mediated by transcription factors (TFs). We present a method(More)
The various organs of the body harbor blood vessel networks that display unique structural and functional features; however, the mechanisms that control organ-specific vascular development and physiology remain mostly unknown. In the developing mouse brain, αvβ8 integrin-mediated TGF-β activation and signaling is essential for normal blood vessel growth and(More)
p53 is a representative tumor suppressor whose dysfunction is a major cause of human cancer syndrome. Here we isolated flies lacking Dmp53, which encodes the single Drosophila orthologue of mammalian p53 family. Dmp53 null mutants well developed into adults, only displaying mild defects in longevity and fertility. However, genomic stability and viability of(More)
To identify therapeutic targets for glioblastoma (GBM), we performed genome-wide CRISPR-Cas9 knockout (KO) screens in patient-derived GBM stem-like cells (GSCs) and human neural stem/progenitors (NSCs), non-neoplastic stem cell controls, for genes required for their in vitro growth. Surprisingly, the vast majority GSC-lethal hits were found outside of(More)
With the world's focus on reducing our dependency on fossil-fuel energy, the scientific community can investigate new plastic materials that are much less dependent on petroleum than are conventional plastics. Given increasing environmental issues, the idea of replacing plastics with water-based gels, so-called hydrogels, seems reasonable. Here we report(More)
BACKGROUND Pulmonary arterial hypertension (PAH) is a rare but fatal lung disease of diverse origins. PAH is now further subclassified as idiopathic PAH, familial PAH, and associated PAH varieties. Heterozygous mutations in BMPR2 can be detected in 50% to 70% of patients with familial PAH and 10% to 40% of patients with idiopathic PAH. Although endothelial(More)
Polymeric microparticles have been widely investigated as platforms for delivery of drugs, vaccines, and imaging contrast agents and are increasingly used in a variety of clinical applications. Microparticles activate the inflammasome complex and induce the processing and secretion of IL-1β, a key innate immune cytokine. Recent work suggests that although(More)
Gene expression data and genotype variation data are now capable of providing genome-wide patterns across many different clinical conditions. However, the separate analysis of these data has limitations in elucidating the complex network of gene interactions underlying complex traits, such as common human diseases. More information about the identity of key(More)