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Lynn F. James

Bio: Lynn F. James is an academic researcher from Agricultural Research Service. The author has contributed to research in topics: Locoweed & Oxytropis sericea. The author has an hindex of 41, co-authored 182 publications receiving 5564 citations. Previous affiliations of Lynn F. James include United States Department of Agriculture.


Papers
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Journal ArticleDOI
09 Apr 1982-Science
TL;DR: In this article, the indolizidine alkaloids swainsonine and noxide have been identified as constituents of spotted locoweed and the inhibition of lysosomal α-mannosidase by these alkaloid compounds has been investigated.
Abstract: The indolizidine alkaloids swainsonine and swainsonine N-oxide have been isolated and identified as constituents of spotted locoweed. The inhibition of lysosomal α-mannosidase by these alkaloids su...

389 citations

Journal ArticleDOI
TL;DR: The effects of poisonous plants on livestock and their effects on livestock are studied in detail in a number of studies.
Abstract: Effects of poisonous plants on livestock , Effects of poisonous plants on livestock , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی

185 citations

Journal ArticleDOI
TL;DR: Lentiginosine was found to be a reasonably good inhibitor of the fungal alpha-glucosidase, amyloglucosinase (Ki = 1 x 10(-5) M), but it did not inhibit other alpha-GLUCosidases (i.e., sucrase, maltase, yeast alpha- glucosidease, glucosid enzyme I) nor any other glycosidases.
Abstract: Lentiginosine, a dihydroxyindolizidine alkaloid, was extracted from the leaves of Astragalus lentiginosus with hot methanol and was purified to homogeneity by ion-exchange, thin-layer, and radial chromatography. A second dihydroxyindolizidine, the 2-epimer of lentiginosine, was also purified to apparent homogeneity from these extracts. Gas chromatography of the two isomers (as the TMS derivatives) showed that they were better than 95% pure; lentiginosine eluted at 8.65 min and the 2-epimer at 9.00 min. Both compounds had a molecular ion in their mass spectra of 157, and the NMR spectra demonstrated that both were dihydroxyindolizidines differing in the configuration of the hydroxyl group at carbon 2. Lentiginosine was found to be a reasonably good inhibitor of the fungal alpha-glucosidase, amyloglucosidase (Ki = 1 x 10(-5) M), but it did not inhibit other alpha-glucosidases (i.e., sucrase, maltase, yeast alpha-glucosidase, glucosidase I) nor any other glycosidases. The 2-epimer had no activity against any of the glycosidases tested.

152 citations

Journal ArticleDOI
TL;DR: Careful observation of cause and effect, followed by a coordinated approach to identify the responsible entities, has proved extremely fruitful in discovering roles for phytochemical constituents.

136 citations


Cited by
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Journal ArticleDOI
TL;DR: It is shown that cyclopamine can reverse the retention of partially misfolded Smo in the endoplasmic reticulum through binding-mediated effects on protein conformation, which suggests a role for small molecules in the physiological regulation of Smo.
Abstract: The steroidal alkaloid cyclopamine has both teratogenic and antitumor activities arising from its ability to specifically block cellular responses to vertebrate Hedgehog signaling. We show here, using photoaffinity and fluorescent derivatives, that this inhibitory effect is mediated by direct binding of cyclopamine to the heptahelical bundle of Smoothened (Smo). Cyclopamine also can reverse the retention of partially misfolded Smo in the endoplasmic reticulum, presumably through binding-mediated effects on protein conformation. These observations reveal the mechanism of cyclopamine's teratogenic and antitumor activities and further suggest a role for small molecules in the physiological regulation of Smo.

1,440 citations

Journal ArticleDOI
28 Nov 2003
TL;DR: Recent advances in the understanding of the plant's ability to metabolize Se into volatile Se forms (phytovolatilization) are discussed, along with the application of phytoremediation for the cleanup of Se contaminated environments.
Abstract: Plants vary considerably in their physiological response to selenium (Se). Some plant species growing on seleniferous soils are Se tolerant and accumulate very high concentrations of Se (Se accumulators), but most plants are Se nonaccumulators and are Se-sensitive. This review summarizes knowledge of the physiology and biochemistry of both types of plants, particularly with regard to Se uptake and transport, biochemical pathways of assimilation, volatilization and incorporation into proteins, and mechanisms of toxicity and tolerance. Molecular approaches are providing new insights into the role of sulfate transporters and sulfur assimilation enzymes in selenate uptake and metabolism, as well as the question of Se essentiality in plants. Recent advances in our understanding of the plant's ability to metabolize Se into volatile Se forms (phytovolatilization) are discussed, along with the application of phytoremediation for the cleanup of Se contaminated environments.

1,243 citations

Journal ArticleDOI
TL;DR: GDC-0449, an orally active small molecule that targets the hedgehog pathway, appears to have antitumor activity in locally advanced or metastatic basal-cell carcinoma.
Abstract: Background Mutations in hedgehog pathway genes, primarily genes encoding patched homologue 1 (PTCH1) and smoothened homologue (SMO), occur in basal-cell carcinoma. In a phase 1 clinical trial, we assessed the safety and pharmacokinetics of GDC-0449, a small-molecule inhibitor of SMO, and responses of metastatic or locally advanced basal-cell carcinoma to the drug. Methods We selected 33 patients with metastatic or locally advanced basal-cell carcinoma to receive oral GDC-0449 at one of three doses; 17 patients received 150 mg per day, 15 patients received 270 mg per day, and 1 patient received 540 mg per day. We assessed tumor responses with the use of Response Evaluation Criteria in Solid Tumors (RECIST), physical examination, or both. Molecular aspects of the tumors were examined. Results The median duration of the study treatment was 9.8 months. Of the 33 patients, 18 had an objective response to GDC-0449, according to assessment on imaging (7 patients), physical examination (10 patients), or both (1 p...

1,074 citations

Journal ArticleDOI
TL;DR: A number of inhibitors have been identified that interfere with glycoprotein biosynthesis, processing, or transport, such as tunicamycin, tridecaptin, and flavomycin this paper.
Abstract: A number of glycoproteins have oligosaccharides linked to protein in a GlcNAc----asparagine bond. These oligosaccharides may be either of the complex, the high-mannose or the hybrid structure. Each type of oligosaccharides is initially biosynthesized via lipid-linked oligosaccharides to form a Glc3Man9GlcNAc2-pyrophosphoryl-dolichol and transfer of this oligosaccharide to protein. The oligosaccharide portion is then processed, first of all by removal of all three glucose residues to give a Man9GlcNAc2-protein. This structure may be the immediate precursor to the high-mannose structure or it may be further processed by the removal of a number of mannose residues. Initially four alpha 1,2-linked mannoses are removed to give a Man5 - GlcNAc2 -protein which is then lengthened by the addition of a GlcNAc residue. This new structure, the GlcNAc- Man5 - GlcNAc2 -protein, is the substrate for mannosidase II which removes the alpha 1,3- and alpha 1,6-linked mannoses . Then the other sugars, GlcNAc, galactose, and sialic acid, are added sequentially to give the complex types of glycoproteins. A number of inhibitors have been identified that interfere with glycoprotein biosynthesis, processing, or transport. Some of these inhibitors have been valuable tools to study the reaction pathways while others have been extremely useful for examining the role of carbohydrate in glycoprotein function. For example, tunicamycin and its analogs prevent protein glycosylation by inhibiting the first step in the lipid-linked pathway, i.e., the formation of Glc NAc-pyrophosphoryl-dolichol. These antibiotics have been widely used in a number of functional studies. Another antibiotic that inhibits the lipid-linked saccharide pathway is amphomycin, which blocks the formation of dolichyl-phosphoryl-mannose. In vitro, this antibiotic gives rise to a Man5GlcNAc2 -pyrophosphoryl-dolichol from GDP-[14C]mannose, indicating that the first five mannose residues come directly from GDP-mannose rather than from dolichyl-phosphoryl-mannose. Other antibodies that have been shown to act at the lipid-level are diumycin , tsushimycin , tridecaptin, and flavomycin. In addition to these types of compounds, a number of sugar analogs such as 2-deoxyglucose, fluoroglucose , glucosamine, etc. have been utilized in some interesting experiments. Several compounds have been shown to inhibit glycoprotein processing. One of these, the alkaloid swainsonine , inhibits mannosidase II that removes alpha-1,3 and alpha-1,6 mannose residues from the GlcNAc- Man5GlcNAc2 -peptide. Thus, in cultured cells or in enveloped viruses, swainsonine causes the formation of a hybrid structure.(ABSTRACT TRUNCATED AT 400 WORDS)

1,067 citations

01 Jan 1987
TL;DR: A number of glycoproteins have oligosaccharides linked to protein in a GlcNAc----asparagine bond that are either of the complex, the high-mannose or the hybrid structure and a number of inhibitors have been identified that interfere with glycoprotein biosynthesis, processing, or transport.

900 citations