An Efficient Algorithm for Clustering of Large-Scale Mass Spectrometry Data

High-throughput spectrometers are capable of producing data sets containing thousands of spectra for a single biological sample. These data sets contain a substantial amount of redundancy from peptides that may get selected multiple times in a LC-MS/MS experiment. In this paper, we present an efficient algorithm, CAMS (Clustering Algorithm for Mass Spectra) for clustering mass spectrometry data which increases both the sensitivity and confidence of spectral assignment. CAMS utilizes a novel metric, called F-set, that allows accurate identification of the spectra that are similar. A graph theoretic framework is defined that allows the use of F-set metric efficiently for accurate cluster identifications. The accuracy of the algorithm is tested on real HCD and CID data sets with varying amounts of peptides. Our experiments show that the proposed algorithm is able to cluster spectra with very high accuracy in a reasonable amount of time for large spectral data sets. Thus, the algorithm is able to decrease the computational time by compressing the data sets while increasing the throughput of the data by interpreting low S/N spectra.Comment: 4 pages, 4 figures, Bioinformatics and Biomedicine (BIBM), 2012 IEEE International Conference o

Pathways of urea transport in the mammalian kidney

Urea is the chief end product of nitrogen metabolism in mammals. Most of the urea produced is excreted by the kidneys. Excretion of a large fraction of the urea filtered by the glomerulus is required to keep pace with the rate of hepatic urea production. Consequently, the maintenance of nitrogen balance depends on a sustained high rate of renal urea excretion. One factor that might challenge the ability of the kidney to maintain a high rate of urea excretion is the need to limit water excretion. Theoretically, an increase in water absorption along the nephron would be expected to increase luminal urea concentration and consequently increase the driving force for passive urea reabsorption. Indeed, as demonstrated originally by Shannon [1] and confirmed in many subsequent studies, the rate of urea excretion decreases when water excretion decreases. However, the decline in urea excretion is relatively modest, even when the rate of water excretion is very low. In Shannon's studies in dogs [1], when water diuresis was established (water excretion 5–10 percent of filtered load), urea excretion was about 60 percent of the filtered load. During antidiuresis, when water excretion was reduced by 95% or more (to less than 0.5 percent of the glomerular filtration rate), urea excretion fell only by 25 to 30% (to 40 to 45 percent of the filtered load)

Rosiglitazone Activates Renal Sodium-and Water-Reabsorptive Pathways and Lowers Blood Pressure in Normal Rats

ABSTRACT Synthetic agonists of the peroxisomal proliferator-activated receptor subtype ␥ (PPAR-␥) are highly beneficial in the treatment of type II diabetes. However, they are also associated with fluid retention and edema, potentially serious side effects of unknown origin. These studies were designed to test the hypothesis that rosiglitazone (RGZ, PPAR-␥ agonist) may activate sodium-and water-reabsorptive processes in the kidney, possibly in response to a drop in mean arterial blood pressure (MAP), as well as directly through PPAR-␥. Targeted proteomics of the major renal sodium and water transporters and channel proteins was used to identify potentially regulated sites of renal sodium and water reabsorption. RGZ (47 or 94 mg/kg diet) was fed to male, Sprague-Dawley rats (ϳ270g) for 3 days. MAP, measured by radiotelemetry, was decreased significantly in rats fed either level of RGZ, relative to control rats. Delta MAP from baseline was Ϫ3.2 Ϯ 1.2 mm Hg in rats fed high-dose RGZ versus ϩ 3.4 Ϯ 0.8 for rats fed control diet. RGZ did not affect feed or water intake, but rats treated with high-dose RGZ had decreased urine volume (by 22%), sodium excretion (44%), kidney weight (9%), and creatinine clearance (35%). RGZ increased whole kidney protein abundance of the ␣-1 subunit of Na-K-ATPase, the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2), the sodium hydrogen exchanger (NHE3), the aquaporins 2 and 3, and endothelial nitric-oxide synthase. We conclude that both increases in renal tubule transporter abundance and a decrease in glomerular filtration rate likely contribute to the RGZ-induced sodium retention

CHIP28 water channels are localized in constitutively water-permeable segments of the nephron

The sites of water transport along the nephron are well characterized, but the molecular basis of renal water transport remains poorly understood. CHIP28 is a 28-kD integral protein which was proposed to mediate transmembrane water movement in red cells and kidney (Preston, G. M., T. P. Carroll, W. B. Guggino, and P. Agre. 1992. Science [Wash. DC]. 256:385-387). To determine whether CHIP28 could account for renal epithelial water transport, we used specific polyclonal antibodies to quantitate and localize CHIP28 at cellular and subcellular levels in rat kidney using light and electron microscopy. CHIP28 comprised 3.8% of isolated proximal tubule brush border protein. Except for the first few cells of the S1 segment, CHIP28 was immunolocalized throughout the convoluted and straight proximal tubules where it was observed in the microvilli of the apical brush border and in basolateral membranes. Very little CHIP28 was detected in endocytic vesicles or other intracellular structures in proximal tubules. Uninterrupted, heavy immunostaining of CHIP28 was also observed over both apical and basolateral membranes of descending thin limbs, including both short and long loops of Henle. These nephron sites have constitutively high osmotic water permeabilities. CHIP28 was not detected in ascending thin limbs, thick ascending limbs, or distal tubules, which are highly impermeable to water. Moreover, CHIP28 was not detected in collecting duct epithelia, where water permeability is regulated by antidiuretic hormone. These determinations of abundance and structural organization provide evidence that the CHIP28 water channel is the predominant pathway for constitutive transepithelial water transport in the proximal tubule and descending limb of Henle's loop

Altered renal sodium transporter expression in an animal model of type 2 diabetes mellitus

Hemodynamic factors play an important role in the development and/or progression of diabetic nephropathy. We hypothesized that renal sodium transporter dysregulation might contribute to the hemodynamic alterations in diabetic nephropathy. Otsuka Long Evans Tokushima Fatty (OLETF) rats were used as an animal model for type 2 diabetes. Long Evans Tokushima (LETO) rats were used as controls. Renal sodium transporter regulation was investigated by semiquantitative immunoblotting and immunohistochemistry of the kidneys of 40-week-old animals. The mean serum glucose level in OLETF rats was increased to 235+/-25 mg/dL at 25 weeks, and the hyperglycemia continued up to the end of 40 weeks. Urine protein/ creatinine ratios were 10 times higher in OLETF rats than in LETO rats. At 40th week, the abundance of the epithelial sodium channel (ENaC) beta-subunit was increased in OLETF rats, but the abundance of the ENaC gamma-subunit was decreased. No significant differences were observed in the ENaC alpha-subunit or other major sodium transporters. Immunohistochemistry for the ENaC beta-subunit showed increased immunoreactivity in OLETF rats, whereas the ENaC gamma-subunit showed reduced immunoreactivity in these rats. In OLETF rats, ENaC beta-subunit upregulation and ENaC gamma-subunit downregulation after the development of diabetic nephropathy may reflect an abnormal sodium balance

First Results from a Broadband Search for Dark Photon Dark Matter in the 4444 to 52 μ52\,\mueV range with a coaxial dish antenna

We present first results from a dark photon dark matter search in the mass range from 44 to 52 $\mu{\rm eV}$ ($10.7 - 12.5\,{\rm GHz}$) using a room-temperature dish antenna setup called GigaBREAD. Dark photon dark matter converts to ordinary photons on a cylindrical metallic emission surface with area $0.5\,{\rm m}^2$ and is focused by a novel parabolic reflector onto a horn antenna. Signals are read out with a low-noise receiver system. A first data taking run with 24 days of data does not show evidence for dark photon dark matter in this mass range, excluding dark photon - photon mixing parameters $\chi \gtrsim 10^{-12}$ in this range at 90% confidence level. This surpasses existing constraints by about two orders of magnitude and is the most stringent bound on dark photons in this range below 49 $\mu$eV.Comment: 7 pages, 4 figure