This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Normal human cells have a limited capacity to proliferate, a process termed replicative aging. Increasing evidence has implicated telomeres, the structures that cap the ends of the chromosomes, as the molecular clock that counts the number of times the cell has divided. The mechanism of lagging-strand DNA synthesis prevents DNA polymerase from replicating the DNA all the way to the 5''''end of a linear chromosome, leaving a 3''''overhang and causing the chromosomes to shorten every time a cell divides. Human telomeres are composed of many kilobases of the repetitive sequence TTAGGG that, together with telomere-binding proteins, prevent the cell from recognizing the end of the chromosome as a DNA break needing repair. Cellular senescence may occur when some of the telomeres have shortened sufficiently to induce a DNA damage signal. Cancer cells escape the proliferative limits of replicative aging by up-regulating the expression of telomerase, an enzyme capable of adding telomere repeats to the ends of the chreomsomes and maintaining their length. Using methods for identifying the presence of modified nucleotides in subtelomeric DNA, for purifying telomeres (based on the presence of the 3''''G-rich overhang) that yields a greater than 1000-fold enrichment in a single step, for determining the size of the overhangs, and for measuring telomere sizes in interphase nuclei. Chromatographic separation for the telomeric nucleobases has been developed. It is a HILIC based separation appropriate for these very hydrophilic compounds and it also affords high mass spectrometric sensitivity. The method has been adapted to be used on nano-LC columns and nano electro spray ionization to increase the sensitivity

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000954-34
Application #
8361332
Study Section
Special Emphasis Panel (ZRG1-BCMB-K (40))
Project Start
2011-01-01
Project End
2011-12-31
Budget Start
2011-01-01
Budget End
2011-12-31
Support Year
34
Fiscal Year
2011
Total Cost
$5,405
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Lucey, Brendan P; Mawuenyega, Kwasi G; Patterson, Bruce W et al. (2017) Associations Between ?-Amyloid Kinetics and the ?-Amyloid Diurnal Pattern in the Central Nervous System. JAMA Neurol 74:207-215
Lin, Xiaobo; Racette, Susan B; Ma, Lina et al. (2017) Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans. Arterioscler Thromb Vasc Biol 37:2364-2369
Cade, W Todd; Levy, Philip T; Tinius, Rachel A et al. (2017) Markers of maternal and infant metabolism are associated with ventricular dysfunction in infants of obese women with type 2 diabetes. Pediatr Res 82:768-775
Ovod, Vitaliy; Ramsey, Kara N; Mawuenyega, Kwasi G et al. (2017) Amyloid ? concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement 13:841-849
Wei, Xiaochao; Song, Haowei; Yin, Li et al. (2016) Fatty acid synthesis configures the plasma membrane for inflammation in diabetes. Nature 539:294-298
Shields-Cutler, Robin R; Crowley, Jan R; Miller, Connelly D et al. (2016) Human Metabolome-derived Cofactors Are Required for the Antibacterial Activity of Siderocalin in Urine. J Biol Chem 291:25901-25910
Mertins, Philipp; Mani, D R; Ruggles, Kelly V et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534:55-62
Murata, Takahiro; Dietrich, Hans H; Horiuchi, Tetsuyoshi et al. (2016) Mechanisms of magnesium-induced vasodilation in cerebral penetrating arterioles. Neurosci Res 107:57-62
Hölttä, Mikko; Dean, Robert A; Siemers, Eric et al. (2016) A single dose of the ?-secretase inhibitor semagacestat alters the cerebrospinal fluid peptidome in humans. Alzheimers Res Ther 8:11
Sterl, Karin; Wang, Songyan; Oestricker, Lauren et al. (2016) Metabolic responses to xenin-25 are altered in humans with Roux-en-Y gastric bypass surgery. Peptides 82:76-84

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