The appearance of the substantia nigra (SN) can aid diagnosis of Parkinson's disease (PD). The effect of age and sex on the appearance of nigrosome-1 (SN subregion) on magnetic resonance imaging (MRI), and the relationship between nigrosome-1 (viewed with MRI) and SN echogenicity (viewed with transcranial ultrasound) is unknown. The study aimed to address these knowledge gaps.
View Article and Find Full Text PDFSubject-specific finite element models of knee joint contact mechanics are used in assessment of interventions and disease states. Cartilage thickness distribution is one factor influencing the distribution of pressure. Precision of cartilage geometry capture varies between imaging protocols.
View Article and Find Full Text PDFPoor physical function and possession of the e4 allele of the apolipoprotein E (APOE) gene are each associated with increased dementia risk, but it is unclear how these exposures interact to influence brain health. Purpose: To investigate whether self-reported walking pace (a marker of physical function) and the presence of APOE-ε4 allele interact to modify brain health outcomes. Methods: We used data from a prospective cohort study of middle-aged to older adults from the UK Biobank who self-reported walking pace (slow or steady-to-brisk), and who were initially free of dementia (n = 415,110).
View Article and Find Full Text PDFThe transcription factor GATA-3 and the transcriptional program it regulates have emerged as oncogenic drivers across diverse T-cell lymphomas (TCL), many of which are resistant to conventional chemotherapeutic agents and characterized by recurrent losses of key tumor suppressor genes, including TP53 and PTEN, both of which are clients of the nuclear export protein XPO1. Here we demonstrated that XPO1 is highly expressed by malignant T cells expressing GATA-3 and by lymphoma-associated macrophages (LAM) within their tumor microenvironment (TME). Using complementary genetically engineered mouse (GEM) models, we demonstrated that TP53 and/or PTEN deficient TCL, and LAM within their TME, are sensitive to the selective XPO1 antagonist selinexor.
View Article and Find Full Text PDFDysfunction of motile cilia can impair mucociliary clearance in the airway and result in primary ciliary dyskinesia (PCD). We previously showed that mutations in central pair apparatus (CPA) genes perturb ciliary motility and result in PCD in mouse models. However, little is known about how epithelial cell types in the ciliary microenvironment of the upper airway respond to defects in ciliary motility and mucociliary clearance.
View Article and Find Full Text PDF