10 research outputs found

    Protein Sialylation Regulates a Gene Expression Signature that Promotes Breast Cancer Cell Pathogenicity

    No full text
    Many mechanisms have been proposed for how heightened aerobic glycolytic metabolism fuels cancer pathogenicity, but there are still many unexplored pathways. Here, we have performed metabolomic profiling to map glucose incorporation into metabolic pathways upon transformation of mammary epithelial cells by 11 commonly mutated human oncogenes. We show that transformation of mammary epithelial cells by oncogenic stimuli commonly shunts glucose-derived carbons into synthesis of sialic acid, a hexosamine pathway metabolite that is converted to CMP-sialic acid by cytidine monophosphate <i>N</i>-acetylneuraminic acid synthase (CMAS) as a precursor to glycoprotein and glycolipid sialylation. We show that CMAS knockdown leads to elevations in intracellular sialic acid levels, a depletion of cellular sialylation, and alterations in the expression of many cancer-relevant genes to impair breast cancer pathogenicity. Our study reveals the heretofore unrecognized role of sialic acid metabolism and protein sialylation in regulating the expression of genes that maintain breast cancer pathogenicity

    Solar Wind Electrons Alphas and Protons (SWEAP) Investigation: Design of the Solar Wind and Coronal Plasma Instrument Suite for Solar Probe Plus

    Get PDF
    International audienceThe Solar Wind Electrons Alphas and Protons (SWEAP) Investigation on Solar Probe Plus is a four sensor instrument suite that provides complete measurements of the electrons and ionized helium and hydrogen that constitute the bulk of solar wind and coronal plasma. SWEAP consists of the Solar Probe Cup (SPC) and the Solar Probe Analyzers (SPAN). SPC is a Faraday Cup that looks directly at the Sun and measures ion and electron fluxes and flow angles as a function of energy. SPAN consists of an ion and electron electrostatic analyzer (ESA) on the ram side of SPP (SPAN-A) and an electron ESA on the anti-ram side (SPAN-B). The SPAN-A ion ESA has a time of flight section that enables it to sort particles by their mass/charge ratio, permitting differentiation of ion species. SPAN-A and -B are rotated relative to one another so their broad fields of view combine like the seams on a baseball to view the entire sky except for the region obscured by the heat shield and covered by SPC. Observations by SPC and SPAN produce the combined field of view and measurement capabilities required to fulfill the science objectives of SWEAP and Solar Probe Plus. SWEAP measurements, in concert with magnetic and electric fields, energetic particles, and white light contextual imaging will enable discovery and understanding of solar wind acceleration and formation, coronal and solar wind heating, and particle acceleration in the inner heliosphere of the solar system. SPC and SPAN are managed by the SWEAP Electronics Module (SWEM), which distributes power, formats onboard data products, and serves as a single electrical interface to the spacecraft. SWEAP data products include ion and electron velocity distribution functions with high energy and angular resolution. Full resolution data are stored within the SWEM, enabling high resolution observations of structures such as shocks, reconnection events, and other transient structures to be selected for download after the fact. This paper describes the implementation of the SWEAP Investigation, the driving requirements for the suite, expected performance of the instruments, and planned data products, as of mission preliminary design review
    corecore