Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy

Background: Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN), urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration >= 5 years, cases of DN were defined as albuminuria >300 mg/d and diabetic retinopathy (n = 66). Controls were matched for gender and diabetes duration (n = 82). Methodology/Principal Findings: Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS). Data were evaluated employing the previously developed model for DN. Upon unblinding, the model for DN showed 93.8% sensitivity and 91.4% specificity, with an AUC of 0.948 (95% CI 0.898-0.978). Of 65 previously identified peptides, 60 were significantly different between cases and controls of this study. In <10% of cases and controls classification by proteome analysis not entirely resulted in the expected clinical outcome. Analysis of patient's subsequent clinical course revealed later progression to DN in some of the false positive classified DN control patients. Conclusions: These data provide the first independent confirmation that profiling of the urinary proteome by CE-MS can adequately identify subjects with DN, supporting the generalizability of this approach. The data further establish urinary collagen fragments as biomarkers for diabetes-induced renal damage that may serve as earlier and more specific biomarkers than the currently used urinary albumin

Electrochemical Impedance Analysis of Biofunctionalized Conducting Polymer-Modified Graphene-CNTs Nanocomposite for Protein Detection

We report an electrodeposited poly(pyrrole-co-pyrrolepropylic acid) copolymer modified electroactive graphene-carbon nanotubes composite deposited on a glassy carbon electrode to detect the protein antigen (cTnI). The copolymer provides pendant carboxyl groups for the site-specific covalent immobilization of protein antibody, anti-troponin I. The hybrid nanocomposite was used as a transducer for biointerfacial impedance sensing for cTnI detection. The results show that the hybrid exhibits a pseudo capacitive behaviour with a maximum phase angle of 49 degrees near 1 Hz, which is due to the inhomogeneous and porous structure of the hybrid composition. The constant phase element of copolymer is 0.61 (n = 0.61), whereas, it is 0.88 (n = 0.88) for the hybrid composites, indicating a comparatively homogeneous microstructure after biomolecular functionalization. The transducer shows a linear change in charge transfer characteristic (R-et) on cTnI immunoreaction for spiked human serum in the concentration range of 1.0 pg mL(-1) - 10.0 ng mL(-1). The sensitivity of the transducer is 167.8 +/- 14.2 Omega cm(2) per decade, and it also exhibits high specificity and good reproducibility

Elemental compositions of comet 81P/Wild 2 samples collected by Stardust

We measured the elemental compositions of material from 23 particles in aerogel and from residue in seven craters in aluminum foil that was collected during passage of the Stardust spacecraft through the coma of comet 81P/Wild 2. These particles are chemically heterogeneous at the largest size scale analyzed (similar to 180 ng). The mean elemental composition of this Wild 2 material is consistent with the CI meteorite composition, which is thought to represent the bulk composition of the solar system, for the elements Mg, Si, Mn, Fe, and Ni to 35%, and for Ca and Ti to 60%. The elements Cu, Zn, and Ga appear enriched in this Wild 2 material, which suggests that the CI meteorites may not represent the solar system composition for these moderately volatile minor elements