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Comprehensive Map (comprehensive + map)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Driving in the melanoma landscape

EXPERIMENTAL DERMATOLOGY, Issue 6 2009
Meenhard Herlyn
Abstract:, The melanoma landscape is rapidly evolving. The melanoma oncologists have now the first successful targets for therapy that have a genetic base , albeit in rare forms of the malignancy. Once melanoma becomes part of the Cancer Genome Atlas consortium, a comprehensive map of genetic changes will be established to point the field to true drivers of the disease that will become new targets for therapy. The same abnormalities will also serve as biomarkers for diagnosis, prognosis and therapy follow-up. Melanomas as a group are heterogenous as are tumor cells within one lesion. New strategies will move towards individualized therapies and combination therapies to target all cells within a tumor. [source]

Intrahepatic amino acid and glucose metabolism in a D -galactosamine,induced rat liver failure model

HEPATOLOGY, Issue 2 2001
Kosuke Arai
A better understanding of the hepatic metabolic pathways affected by fulminant hepatic failure (FHF) would help develop nutritional support and other nonsurgical medical therapies for FHF. We used an isolated perfused liver system in combination with a mass-balance model of hepatic intermediary metabolism to generate a comprehensive map of metabolic alterations in the liver in FHF. To induce FHF, rats were fasted for 36 hours, during which they received 2 D -galactosamine injections. The livers were then perfused for 60 minutes via the portal vein with amino acid,supplemented Eagle minimal essential medium containing 3% wt/vol bovine serum albumin and oxygenated with 95% O2/5% CO2. Control rats were fasted for 36 hours with no other treatment before perfusion. FHF rat livers exhibited reduced amino acid uptake, a switch from gluconeogenesis to glycolysis, and a decrease in urea synthesis, but no change in ammonia consumption compared with normal fasted rat livers. Mass-balance analysis showed that hepatic glucose synthesis was inhibited as a result of a reduction in amino acid entry into the tricarboxylic acid cycle by anaplerosis. Furthermore, FHF inhibited intrahepatic aspartate synthesis, which resulted in a 50% reduction in urea cycle flux. Urea synthesis by conversion of exogenous arginine to ornithine was unchanged. Ammonia removal was quantitatively maintained by glutamine synthesis from glutamate and a decrease in the conversion of glutamate to ,-ketoglutarate. Mass-balance analysis of hepatic metabolism will be useful in characterizing changes during FHF, and in elucidating the effects of nutritional supplements and other treatments on hepatic function. [source]

A combination of neutral loss and targeted product ion scanning with two enzymatic digestions facilitates the comprehensive mapping of phosphorylation sites

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 15 2007
Juan Casado-Vela
Abstract We propose here a new strategy for the exhaustive mapping of phosphorylation sites in the Xenopus laevis Cdc25 phosphatase, which regulates cell cycle progression in eukaryotic cells. Two different MS analyses in a linear IT were used to identify the phosphorylated residues. First, a data-dependent neutral loss (DDNL) analysis triggered the fragmentation of peptides that show enhanced neutral loss of phosphoric acid. Second, a targeted product ion scanning (TPIS) mass analysis was carried out in which MS2 events are triggered for specific m/z values. Full coverage of the protein sequence was obtained by combining the two analyses with two enzymatic digestions, trypsin and chymotrypsin, yielding a comprehensive map of the phosphorylation sites. Previous reports have shown Cdc25C to be phosphorylated by Cdc2,cyclin B at four residues (Thr48, Thr67, Thr138 and Ser205). By using this combination of scan modes, we have identified four additional phosphorylation sites (Thr86, Ser99, Thr112 and Ser163) in a recombinant Cdc25C protein containing 198 residues of the NH2 -terminal noncatalytic domain. The sensitivity of this combined approach makes it extremely useful for the comprehensive characterization of phosphorylation sites, virtually permitting complete coverage of the protein sequence with peptides within the mass detection range of the linear IT. [source]

A high-resolution radiation hybrid map of porcine chromosome 6

ANIMAL GENETICS, Issue 5 2004
H. Cao
Summary A high-resolution comprehensive map was constructed for porcine chromosome (SSC) 6, where quantitative trait loci (QTL) for reproduction and meat quality traits have been reported to exist. A radiation hybrid (RH) map containing 105 gene-based markers and 15 microsatellite markers was constructed for this chromosome using a 3000-rad porcine/hamster RH panel. In total, 40 genes from human chromosome (HSA) 1p36.3-p22, 29 from HSA16q12-q24, 17 from HSA18p11.3-q12 and 19 from HSA19q13.1-q13.4 were assigned to SSC6. All primers for these gene markers were designed based on porcine gene or EST sequences, and the orthologous status of the gene markers was confirmed by direct sequencing of PCR products amplified from separate Meishan and Large White genomic DNA pools. The RH map spans SSC6 and consists of six linkage groups created by using a LOD score threshold of 4. The boundaries of the conserved segments between SSC6 and HSA1, 16, 18 and 19 were defined more precisely than previously reported. This represents the most comprehensive RH map of SSC6 reported to date. Polymorphisms were detected for 38 of 105 gene-based markers placed on the RH map and these are being exploited in ongoing chromosome wide scans for QTL and eventual fine mapping of genes associated with prolificacy in a Meishan × Large White multigenerational commercial population. [source]

An integrated comparative map of the porcine X chromosome

ANIMAL GENETICS, Issue 3 2002
S. A. McCoard
The objectives of this study were to assign both microsatellite and gene-based markers on porcine chromosome X to two radiation hybrid (RH) panels and to develop a more extensive integrated map of SSC-X. Thirty-five microsatellite and 20 gene-based markers were assigned to T43RH, and 16 previously unreported microsatellite and 15 gene-based markers were added to IMpRH map. Of these, 30 microsatellite and 12 gene-based markers were common to both RH maps. Twenty-two gene-based markers were submitted to BLASTN analysis for identification of orthologues of genes on HSA-X. Single nucleotide polymorphisms (SNPs) were detected for 12 gene-based markers, and nine of these were placed on the genetic map. A total of 92 known loci are present on at least one porcine chromosome X map. Thirty-seven loci are present on all three maps; 31 loci are found on only one map. Location of 33 gene-based markers on the comprehensive map translates into an integrated comparative map that supports conservation of gene order between SSC-X and HSA-X. This integrated map will be valuable for selection of candidate genes for porcine quantitative trait loci (QTLs) that map to SSC-X. [source]

GSK3,: role in therapeutic landscape and development of modulators

BRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2010
S Phukan
Glycogen synthase kinase-3 beta (GSK3,) is a multifunctional serine/threonine kinase which was originally identified as a regulator of glycogen metabolism. It plays a key role in the regulation of numerous signalling pathways including cellular process such as cell cycle, inflammation and cell proliferation. Over the last few years there is a considerable rise in the number of journals and patents publication by different workers worldwide. Many pharmaceutical companies are focusing on GSK3, as a therapeutic target for the treatment of disease conditions. The present review is focused on signalling pathways of different disease conditions where GSK3, is implicated. In this review, we present a comprehensive map of GSK3, signalling pathways in disease physiologies. Structural analysis of GSK3, along with molecular modelling reports from numerous workers are reviewed in context of design and development of GSK3, inhibitors. Patent landscape of the small molecule modulators is profiled. The chemo space for small molecule modulators extracted from public and proprietary Kinase Chembiobase for GSK3, are discussed. Compounds in different clinical phases of discovery are analysed. The review ends with the overall status of this important therapeutic target and challenges in development of its modulators. [source]