As cancers progress, they become increasingly aggressive-metastatic tumours are less responsive to first-line therapies than primary tumours, they acquire resistance to successive therapies and eventually cause death. Mutations are largely conserved between primary and metastatic tumours from the same patients, suggesting that non-genetic phenotypic plasticity has a major role in cancer progression and therapy resistance. However, we lack an understanding of metastatic cell states and the mechanisms by which they transition.
View Article and Find Full Text PDFThe formation of the mammalian brain requires regionalization and morphogenesis of the cranial neural plate, which transforms from an epithelial sheet into a closed tube that provides the structural foundation for neural patterning and circuit formation. Sonic hedgehog (SHH) signaling is important for cranial neural plate patterning and closure, but the transcriptional changes that give rise to the spatially regulated cell fates and behaviors that build the cranial neural tube have not been systematically analyzed. Here we used single-cell RNA sequencing to generate an atlas of gene expression at six consecutive stages of cranial neural tube closure in the mouse embryo.
View Article and Find Full Text PDFBackground: Spinal muscular atrophy is a group of autosomal recessive inherited neurological disorders secondary to a genetic mutation that leads to progressive muscle weakness and atrophy. Recently approved by the Food and Drug Administration, Nusinersen is the first treatment specifically for spinal muscular atrophy. This drug must be administered intrathecally, as it does not cross the blood-brain barrier.
View Article and Find Full Text PDFIntroduction: Obtaining satisfactory coronal plane alignment is important for success in revision total knee arthroplasty (TKA). The study objective was to determine tibial coronal plane alignment after TKA when a tibial stem was used and assess if there was an anatomic conflict in tibial stemmed component alignment.
Materials And Methods: A radiographic review of 88 revision TKA cases was performed.