The evolution of metastasis represents a lethal stage of cancer progression. Yet, the evolutionary kinetics of metastatic disease remain unresolved. Here, using single cell CRISPR-Cas9 lineage tracing data, we show that in metastatic disease, gradual molecular evolution is punctuated by episodes of rapid evolutionary change associated with lineage divergence.
View Article and Find Full Text PDFThe evolution of antibiotic resistance is a fundamental problem in disease management but is rarely quantified on a single-cell level owing to challenges associated with capturing the spatial and temporal variation across a population. To evaluate cell biological phenotypic responses, we tracked the single-cell dynamics of filamentous bacteria through time in response to ciprofloxacin antibiotic stress. We measured the degree of phenotypic variation in nucleoid length and the accumulation of protein damage under ciprofloxacin antibiotic and quantified the impact on bacterial survival.
View Article and Find Full Text PDFPlatelets mediate arterial thrombosis, a leading cause of myocardial infarction and stroke. During injury, platelets adhere and spread over exposed subendothelial matrix substrates of the damaged blood vessel wall. The mechanisms which govern platelet activation and their interaction with a range of substrates are therefore regularly investigated using platelet spreading assays.
View Article and Find Full Text PDFAn important question in cancer evolution concerns which traits make a cell likely to successfully metastasize. Cell motility phenotypes, mediated by cell shape change, are strong candidates. We experimentally evolved breast cancer cells for metastatic capability, using selective regimes designed to simulate stages of metastasis, then quantified their motility behaviours using computer vision.
View Article and Find Full Text PDFTumour evolution depends on heritable differences between cells in traits affecting cell survival or replication. It is well established that cancer cells are genetically and phenotypically heterogeneous; however, the extent to which this phenotypic variation is heritable is far less well explored. Here, we estimate the broad-sense heritability ( ) of two cell traits related to cancer hallmarks--cell motility and generation time--within populations of four cancer cell lines and find that motility is strongly heritable.
View Article and Find Full Text PDFPurpose: Positive airway pressure (PAP) adherence is poor in comorbid OSA/PTSD. SensAwake™ (SA) is a wake-sensing PAP algorithm that lowers pressure when wake is detected. We compared auto-PAP (aPAP) with and without SA for comorbid OSA/PTSD.
View Article and Find Full Text PDFThe complexity of biological systems creates challenges for fully understanding their behaviour. This is particularly true for cell migration which requires the co-ordinated activity of hundreds of individual components within cells. Mathematical modelling can help understand these complex systems by breaking the system into discrete steps which can then be interrogated in silico.
View Article and Find Full Text PDFDuring symbiosis, organisms use a range of metabolic and protein-based signals to communicate. Of these protein signals, one class is defined as 'effectors', i.e.
View Article and Find Full Text PDFBackground And Objectives: The treatment of photodamaged skin with potassium-titanyl-phosphate (KTP) laser and intense pulsed light (IPL) has been reported in several studies. Each device has strengths and weaknesses; however, patient and device variability have made it difficult to ascertain the optimal device for photorejuvenation. The objective of this study was to obtain a head-to-head comparison of IPL and KTP laser for photorejuvenation.
View Article and Find Full Text PDFThe role of matrix metalloproteinases in the degradative events invoked in the cartilage and bone of arthritic joints has long been appreciated and attempts at the development of proteinase inhibitors as potential therapeutic agents have been made. However, the spectrum of these enzymes orchestrating connective tissue turnover and general biology is much larger than anticipated. Biochemical studies of the individual members of the matrix metalloproteinase family are now underway, ultimately leading to a more detailed understanding of the function of their domain structures and to defining their specific role in cellular systems and the way that they are regulated.
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