Familial adenomatous polyposis (FAP) is a genetic disease causing hundreds of premalignant polyps in affected persons and is an ideal model to study transitions of early precancer states to colorectal cancer (CRC). We performed deep multiomic profiling of 93 samples, including normal mucosa, benign polyps and dysplastic polyps, from six persons with FAP. Transcriptomic, proteomic, metabolomic and lipidomic analyses revealed a dynamic choreography of thousands of molecular and cellular events that occur during precancerous transitions toward cancer formation.
View Article and Find Full Text PDFThe intensive nutrient requirements needed to sustain T cell activation and proliferation, combined with competition for nutrients within the tumor microenvironment, raise the prospect that glucose availability may limit CAR-T cell function. Here, we seek to test the hypothesis that stable overexpression (OE) of the glucose transporter GLUT1 in primary human CAR-T cells would improve their function and antitumor potency. We observe that GLUT1OE in CAR-T cells increases glucose consumption, glycolysis, glycolytic reserve, and oxidative phosphorylation, and these effects are associated with decreased T cell exhaustion and increased Th differentiation.
View Article and Find Full Text PDFIn a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling. We observed substantial early immune responses in peripheral blood mononuclear cells and xenograft tissue obtained from decedent 1 (male), associated with downstream T cell and natural killer cell activity.
View Article and Find Full Text PDFMore than 65 million individuals worldwide are estimated to have Long COVID (LC), a complex multisystemic condition, wherein patients of all ages report fatigue, post-exertional malaise, and other symptoms resembling myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). With no current treatments or reliable diagnostic markers, there is an urgent need to define the molecular underpinnings of these conditions. By studying bioenergetic characteristics of peripheral blood lymphocytes in over 16 healthy controls, 15 ME/CFS, and 15 LC, we find both ME/CFS and LC donors exhibit signs of elevated oxidative stress, relative to healthy controls, especially in the memory subset.
View Article and Find Full Text PDFPreterm birth (PTB) is the leading cause of death in children under five, yet comprehensive studies are hindered by its multiple complex etiologies. Epidemiological associations between PTB and maternal characteristics have been previously described. This work used multiomic profiling and multivariate modeling to investigate the biological signatures of these characteristics.
View Article and Find Full Text PDFCurrent healthcare practices are reactive and use limited physiological and clinical information, often collected months or years apart. Moreover, the discovery and profiling of blood biomarkers in clinical and research settings are constrained by geographical barriers, the cost and inconvenience of in-clinic venepuncture, low sampling frequency and the low depth of molecular measurements. Here we describe a strategy for the frequent capture and analysis of thousands of metabolites, lipids, cytokines and proteins in 10 μl of blood alongside physiological information from wearable sensors.
View Article and Find Full Text PDFThe experience of a downward change in one's financial situation is so common that most consumers will experience it during their lifetime, and this prevalence has been compounded by the recent COVID-19 pandemic. Limited research, however, has examined the impact of economic hardship on consumers' food-related behavior. Using a sample of Canadians and Americans (n = 519; M = 38.
View Article and Find Full Text PDFExercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear. Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity.
View Article and Find Full Text PDFTobacco prevention messages generally take one of three tactics: They can be educational, attack the tobacco industry, or attack particular brands. Being a smoker and smoking a particular brand may form an essential part of a person's self-identity. As such, reactance theory suggests that attack messages can unintentionally attack smokers' self-image.
View Article and Find Full Text PDFThe extended parallel process model (EPPM) proposes fear appeals are most effective when they combine threat and efficacy. Three studies conducted in the workplace safety context examine the use of various EPPM factors and their effects, especially multiplicative effects. Study 1 was a content analysis examining the use of EPPM factors in actual workplace safety messages.
View Article and Find Full Text PDFPoor eating habits are an important public health issue that has large health and economic implications. Many food preferences are established early, but because people make more and more independent eating decisions as they move through adolescence, the transition to independent living during the university days is an important event. To study the phenomenon of food selection, the heath belief model was applied to predict the likelihood of healthy eating among university students.
View Article and Find Full Text PDFFetal Alcohol Syndrome Disorder (FASD) is one of the most preventable sources of developmental abnormalities, and has a singular cause-alcohol consumption during pregnancy. Estimates for the costs of treatment of a single case of FASD range often above one million dollars. The primary strategy for prevention currently centers on no alcohol consumption during pregnancy.
View Article and Find Full Text PDFWhen Mark McGwire broke Roger Maris's home run record in September of 1998, he was instantly declared an American hero and held up as a positive role model for teenagers and young adults. The extensive media attention focused on McGwire made the general public aware of his use of a muscle-building dietary supplement, Androstenedione. It also increased the public's awareness of McGwire's public service to prevent child abuse.
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