The spectrum of endogenous human chromogranin A-derived peptides identified using a modified proteomic strategy.

The hypothesis that chromogranin A (CgA), a protein of neuroendocrine cell secretory granules, may be a precursor of biologically active peptides, rests on observed activities of peptide fragments largely produced by exogenous protease digestion of the bovine protein. Here we have adopted a modified proteomic strategy to isolate and characterise human CgA-derived peptides produced by endogenous prohormone convertases. Initial focus was on an insulinoma as previous studies have shown that CgA is rapidly processed in pancreatic beta cells and that tumours arising from these express appropriate prohormone convertases. Eleven novel peptides were identified arising from processing at both monobasic and dibasic sites and processing was most evident in the C-terminal domain of the protein. Some of these peptides were identified in endocrine tumours, such as mid-gut carcinoid and phaeochromocytoma, which arise from endocrine cells of different phenotype and in different anatomical sites. Two of the most interesting peptides, GR-44 and ER-37, representing the C-terminal region of CgA, were found to be amidated. These data would imply that the intact protein is C-terminally amidated and that these peptides are probably biologically active. The spectrum of novel CgA-derived peptides, described in the present study, should provide a basis for biological evaluation of authentic entities.

Selection Power and Selection Labor for Information Retrieval

This study examines the relation between selection power and selection labor for information retrieval (IR). It is the first part of the development of a labor theoretic approach to IR. Existing models for evaluation of IR systems are reviewed and the distinction of operational from experimental systems partly dissolved. The often covert, but powerful, influence from technology on practice and theory is rendered explicit. Selection power is understood as the human ability to make informed choices between objects or representations of objects and is adopted as the primary value for IR. Selection power is conceived as a property of human consciousness, which can be assisted or frustrated by system design. The concept of selection power is further elucidated, and its value supported, by an example of the discrimination enabled by index descriptions, the discovery of analogous concepts in partly independent scholarly and wider public discourses, and its embodiment in the design and use of systems. Selection power is regarded as produced by selection labor, with the nature of that labor changing with different historical conditions and concurrent information technologies. Selection labor can itself be decomposed into description and search labor. Selection labor and its decomposition into description and search labor will be treated in a subsequent article, in a further development of a labor theoretic approach to information retrieval.

Endogenous expression and localization of myostatin and its relation to MHC distribution in C2C12 skeletal muscle cells

Myostatin is a negative regulator of skeletal muscle growth. We have previously reported that recombinant myostatin protein inhibits DNA and protein synthesis in C2C12 cells. Our objective was to assess if C2C12 cells express myostatin, determine its sub-cellular localization and the developmental stage of C2C12 cells in which myostatin mRNA and protein are expressed. To study the endogenous expression of myostatin, C2C12 myoblasts were allowed to progress to myotubes, and changes in the levels of endogenous myostatin mRNA expression were determined by RT-PCR. The myostatin protein and the two major myosin heavy chain (MHC) isoforms (MHC-I and -II) were determined by Western blot. Confirmation of the relative MHC expression patterns was obtained by a modified polyacrylamide gel electropheretic (PAGE) procedure. Imunofluorescence staining was employed to localize the site of myostatin expression and the relative distribution of the MHC isoforms. Co-expression of these proteins was studied using a dual staining approach. Expression of myostatin mRNA was found in myotubes but not in myoblasts. Myostatin protein was seen in most but not all, of the nuclei of polynucleated fibers expressing MHC-II, and myostatin was detected in the cytoplasm of myotube. The localization of myostatin protein in myotube nuclei was confirmed by Western blot of isolated nuclear and cytoplasmic fractions. Incubation of C2C12 myotubes with graded doses of dexamethasone dose-dependently increased the intensity of nuclear myostatin immunostaining and also resulted in the appearance of cytoplasmic expression. In conclusion, myostatin was expressed mostly in C2C12 myotubes nuclei expressing MHC-II. Its predominant

The smooth muscle pharmacology of maximakinin, a receptor-selective, bradykinin-related nonadecapeptide from the venom of the Chinese toad, Bombina maxima.

Structural homologues of vertebrate regulatory peptides found in defensive skin secretions of anuran amphibians often display enhanced bioactivity and receptor binding when compared with endogenous mammalian peptide ligands. Maximakinin, a novel N-terminally extended bradykinin (DLPKINRKGPRPPGFSPFR) from the skin venom of a Chinese toad (Bombina maxima), displays such activity enhancement when compared with bradykinin but is additionally highly selective for mammalian arterial smooth muscle bradykinin receptors displaying a 50-fold increase in molar potency in this smooth muscle type. In contrast, a 100-fold decrease in molar potency was observed at bradykinin receptors in intestinal and uterine smooth muscle preparations. Maximakinin has thus evolved as a “smart” defensive weapon in the toad with receptor/tissue selective targeting. Natural selection of amphibian skin venom peptides for antipredator defence, through inter-species delivery by an exogenous secretory mode, produces subtle structural stabilisation modifications that can potentially provide new insights for the design of selectively targeted peptide therapeutics.

Simultaneous feature selection and feature weighting using Hybrid Tabu Search/K-nearest neighbor classifier

Feature selection and feature weighting are useful techniques for improving the classification accuracy of K-nearest-neighbor (K-NN) rule. The term feature selection refers to algorithms that select the best subset of the input feature set. In feature weighting, each feature is multiplied by a weight value proportional to the ability of the feature to distinguish pattern classes. In this paper, a novel hybrid approach is proposed for simultaneous feature selection and feature weighting of K-NN rule based on Tabu Search (TS) heuristic. The proposed TS heuristic in combination with K-NN classifier is compared with several classifiers on various available data sets. The results have indicated a significant improvement in the performance in classification accuracy. The proposed TS heuristic is also compared with various feature selection algorithms. Experiments performed revealed that the proposed hybrid TS heuristic is superior to both simple TS and sequential search algorithms. We also present results for the classification of prostate cancer using multispectral images, an important problem in biomedicine.

The endogenous granulocyte colony-stimulating factor response following autologous peripheral blood stem cell transplantation is inpaired in patients with myeloma

Granulocyte colony-stimulating factor (G-CSF) levels were studied in 23 patients (10 myeloma, 13 relapsed Hodgkin's disease, non-Hodgkin's lymphoma or germ cell tumours), post autologous peripheral blood stem cell transplantation (PBSCT). The two groups had similar previous chemotherapy and numbers of CD34+ cells transplanted. All patients received G-CSF by injection starting 8 d post transplantation. Twenty out of 23 patients showed raised endogenous levels of G-CSF before cytokine administration. Myeloma patients showed significantly lower levels of endogenous G-CSF than the other patients (0.767 versus 3.262 ng/ml, P <0.05). Further rises in G-CSF levels were seen following the administration of exogenous G-CSF which then fell, despite ongoing administration of G-CSF, as neutrophil recovery occurred.