Genetic stock identification (GSI) provides a method of characterizing stock‐specific abundance, run timing, and straying as they pertain to the population demographics and behavior of both hatchery ...and wild fish and thus assists with fisheries management. In this study, tissues were collected and genotyped at 13 microsatellite loci from adult Chinook Salmon Oncorhynchus tshawytscha that passed Bonneville Dam during four consecutive migration years (2004–2007). GSI methods were used to estimate the proportions of stocks in a broad genetic baseline, with high‐density coverage of Chinook Salmon across the eastern Pacific Rim. The estimates of abundance for interior Columbia River stocks showed widespread decline consistent with a shift to poor ocean conditions during the years when the fish in this study were at sea, but divergent stock‐ and age‐specific patterns were also observed. For example, the upper Columbia River spring‐run stock experienced a unique net gain in abundance during this period, and the interior Columbia River summer–fall‐run stock experienced a delayed decline of 4‐year‐olds. Stocks with early run timing shifted to later migrations. However, run timing distributions did not shift unidirectionally for all stocks across years, and stock membership in three major run timing categories was maintained. Of 9,215 total adults sampled, 27 (0.3%) were out‐of‐basin strays and a quarter of the strays were putatively of wild origin. The general concordance of GSI results with those based on more traditional methods supports the effectiveness of GSI as a tool for fisheries management.
Received May 5, 2013; accepted October 23, 2013
Published online February 10, 2014
Mass spectrometry-based proteomic experiments, in combination with liquid chromatography-based separation, can be used to compare complex biological samples across multiple conditions. These ...comparisons are usually performed on the level of protein lists generated from individual experiments. Unfortunately given the current technologies, these lists typically cover only a small fraction of the total protein content, making global comparisons extremely limited. Recently approaches have been suggested that are built on the comparison of computationally built feature lists instead of protein identifications. Although these approaches promise to capture a bigger spectrum of the proteins present in a complex mixture, their success is strongly dependent on the correctness of the identified features and the aligned retention times of these features across multiple experiments. In this experimental-computational study, we went one step further and performed the comparisons directly on the signal level. First signal maps were constructed that associate the experimental signals across multiple experiments. Then a feature detection algorithm used this integrated information to identify those features that are discriminating or common across multiple experiments. At the core of our approach is a score function that faithfully recognizes mass spectra from similar peptide mixtures and an algorithm that produces an optimal alignment (time warping) of the liquid chromatography experiments on the basis of raw MS signal, making minimal assumptions on the underlying data. We provide experimental evidence that suggests uniqueness and correctness of the resulting signal maps even on low accuracy mass spectrometers. These maps can be used for a variety of proteomic analyses. Here we illustrate the use of signal maps for the discovery of diagnostic biomarkers. An imple-mentation of our algorithm is available on our Web server.
The open-source Computational Proteomics Analysis System (CPAS) contains an entire data analysis and management pipeline for Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) proteomics, ...including experiment annotation, protein database searching and sequence management, and mining LC-MS/MS peptide and protein identifications. CPAS architecture and features, such as a general experiment annotation component, installation software, and data security management, make it useful for collaborative projects across geographical locations and for proteomics laboratories without substantial computational support.
Although ATP-sensitive K+ channels continue to be explored for their therapeutic potential, developments in high-affinity radioligands to investigate native and recombinant KATP channels have been ...less forthcoming. This study reports the identification and pharmacological characterization of a novel iodinated 1,4-dihydropyridine KATP channel opener, 125IA-312110 (9R)-9-(4-fluoro-3-125iodophenyl)-2,3,5,9-tetrahydro-4H-pyrano3,4-bthieno2,3-epyridin-8(7H)-one-1,1-dioxide. Binding of 125IA-312110 to guinea pig cardiac (KD = 5.8 nM) and urinary bladder (KD = 4.9 nM) membranes were of high affinity, saturable, and to a single set of binding sites. Displacement of 125IA-312110 by structurally diverse potassium channel openers (KCOs) indicated a similar rank order of potency in both guinea pig cardiac and bladder membranes (Ki, heart): A-312110 (4.3 nM) > N-cyano-N'-(1,1-dimethylpropyl)-N"-3-pyridylguanidine (P1075) > (-)-N-(2-ethoxyphenyl)-N'-(1,2,3-trimethylpropyl)-2-nitroethene-1,1-diamine (Bay X 9228) > pinacidil > (-)-cromakalim > N-(4-benzoyl phenyl)-3,3,3-trifluro-2-hydroxy-2-methylpropionamine (ZD6169) > 9-(3-cyanophenyl)-3,4,6,7,9,10-hexahydro-1,8-(2H,5H)-acridinedione (ZM244085) >> diazoxide (16.7 microM). Displacement by KATP channel blockers, the sulfonylurea glyburide, and the cyanoguanidine N-1-(3-chlorophenyl)cyclobutyl-N'-cyano-N"-3-pyridinyl-guanidine (PNU-99963) were biphasic in the heart but monophasic in bladder with about a 100- to 500-fold difference in Ki values between high- and low-affinity sites. Good correlations were observed between cardiac or bladder-binding affinities of KCOs with functional activation as assessed by their respective potencies to either suppress action potential duration (APD) in Purkinje fibers or to relax electrical field-stimulated bladder contractions. Collectively, these results demonstrate that 125IA-312110 binds with high affinity and has an improved activity profile compared with other radiolabeled KCOs. 125IA-312110 is a useful tool for investigation of the molecular and functional properties of the KATP channel complex and for the identification, in a high throughput manner, of both novel channel blockers and openers that interact with cardiac/smooth muscle-type KATP channels.
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![[125I]A-312110, a novel hig...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0026-895X/small "[125I]A-312110, a novel high-affinity 1,4-dihydropyridine ATP-sensitive K+ channel opener: characterization and pharmacology of binding")