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Myostatin is a protein synthesized and secreted by skeletal muscle that negatively regulates muscle mass. The extent to which circulating myostatin levels change in the context of aging is controversial, largely due to methodological barriers. We developed a specific and sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay to(More)
Statistical tools enable unified analysis of data from multiple global proteomic experiments, producing unbiased estimates of normalization terms despite the missing data problem inherent in these studies. The modeling approach, implementation, and useful visualization tools are demonstrated via a case study of complex biological samples assessed using the(More)
BACKGROUND Congenital disorders of glycosylation (CDG) are autosomal recessive disorders that produce increased serum carbohydrate-deficient transferrin (CDT) isoforms. Methods to resolve CDT from fully glycosylated transferrin (Trf) have been based on a neutral shift in the isoelectric focusing (IEF) pattern or on a reduction in the negative charge,(More)
MOTIVATION Using stable isotopes in global proteome scans, labeled molecules from one sample are pooled with unlabeled molecules from another sample and subsequently subjected to mass-spectral analysis. Stable-isotope methodologies make use of the fact that identical molecules of different stable-isotope compositions are differentiated in a mass(More)
Treatment of cancer patients is greatly facilitated by detection of the cancer prior to metastasis. One of the obstacles to early cancer detection is the lack of availability of biomarkers with sufficient specificity. With modem differential proteomic techniques, the potential exists to identify high specificity cancer biomarkers. We have delineated a set(More)
BACKGROUND Improved tests are needed for detection and management of prostate cancer. We hypothesized that differential gene expression in prostate tissue could help identify candidate blood biomarkers for prostate cancer and that blood from men with advanced prostate disease could be used to verify the biomarkers presence in circulation. METHODS We(More)
Urinary exosome-like vesicles (ELVs) are a heterogenous mixture (diameter 40-200 nm) containing vesicles shed from all segments of the nephron including glomerular podocytes. Contamination with Tamm-Horsfall protein (THP) oligomers has hampered their isolation and proteomic analysis. Here we improved ELV isolation protocols employing density centrifugation(More)
Osteogenesis Imperfecta (OI) is a human syndrome characterized by exquisitely fragile bones due to osteoporosis. The majority of autosomal dominant OI cases result from point or splice site mutations in the type I collagen genes, which are thought to lead to aberrant osteoid within developing bones. OI also occurs in humans with homozygous mutations in(More)
BACKGROUND Transthyretin-associated hereditary amyloidosis (ATTR) is an inherited disease in which variants in the primary structure of transthyretin (TTR; prealbumin) lead to the extracellular polymerization of insoluble protein fibrils, causing organ failure and ultimately death when major organs are involved. We have developed an integrated approach to(More)
OBJECTIVE To determine the specific type of amyloid from nerve biopsies using laser microdissection (LMD) and mass spectrometric (MS)-based proteomic analysis. DESIGN, SETTING, AND PATIENTS Twenty-one nerve biopsy specimens (17 sural, 3 sciatic, and 1 root amyloidoma) infiltrated by amyloid were studied. Immunohistochemical subtyping was unable to(More)