scispace - formally typeset
Search or ask a question
Institution

Torrey Pines Institute for Molecular Studies

NonprofitSan Diego, California, United States
About: Torrey Pines Institute for Molecular Studies is a nonprofit organization based out in San Diego, California, United States. It is known for research contribution in the topics: T cell & Antigen. The organization has 2323 authors who have published 2217 publications receiving 112618 citations.


Papers
More filters
Journal ArticleDOI
TL;DR: The entropy-based information metric takes into account the frequency distribution of the different scaffolds and is a complementary measure of scaffold diversity enabling a more comprehensive analysis.
Abstract: Scaffold diversity analysis of compound databases has multiple applications in medicinal chemistry and drug discovery including library design, compounds acquisition, virtual screening and assessment of structure-activity-relationships. The scaffold diversity is commonly measured based on frequency counts. Further information can be obtained by considering the specific distribution of the molecules in those scaffolds. To this end, we introduce in this work the use of an entropy-based information metric to assess the scaffold diversity of compound data sets. As a test case we analyzed the scaffold diversity of 16 data sets of active compounds comparable in size targeting five protein classes of interest in drug design. The diversity was also assessed in terms of frequency counts and scaffold retrieval curves. The entropy-based information metric takes into account the frequency distribution of the different scaffolds and is a complementary measure of scaffold diversity enabling a more comprehensive analysis.

75 citations

Journal ArticleDOI
15 Jul 1999-Genomics
TL;DR: Northern hybridization and RT-PCR demonstrated that the expression level of MAGED1 in different normal adult tissues is comparable to that in testis and fetal liver, suggesting that the biology of the MAGE-family genes is more complex than previously thought.

75 citations

Journal ArticleDOI
01 Sep 2000-Traffic
TL;DR: The results suggest that the low level of wild‐type CFTR in the Golgi region reflects a limiting step in selective recruitment by the ER export machinery, an event that is largely deficient in ΔF508.
Abstract: The pathway of transport of the cystic fibrosis transmembrane regulator (CFTR) through the early exocytic pathway has not been examined. In contrast to most membrane proteins that are concentrated during export from the ER and therefore readily detectable at elevated levels in pre-Golgi intermediates and Golgi compartments, wild-type CFTR could not be detected in these compartments using deconvolution immunofluorescence microscopy. To determine the basis for this unusual feature, we analyzed CFTR localization using quantitative immunoelectron microscopy (IEM). We found that wild-type CFTR is present in pre-Golgi compartments and peripheral tubular elements associated with the cis and trans faces of the Golgi stack, albeit at a concentration 2-fold lower than that found in the endoplasmic reticulum (ER). delta F508 CFTR, a mutant form that is not efficiently delivered to the cell surface and the most common mutation in cystic fibrosis, could also be detected at a reduced concentration in pre-Golgi intermediates and peripheral cis Golgi elements, but not in post-Golgi compartments. Our results suggest that the low level of wild-type CFTR in the Golgi region reflects a limiting step in selective recruitment by the ER export machinery, an event that is largely deficient in delta F508. We raise the possibility that novel modes of selective anterograde and retrograde traffic between the ER and the Golgi may serve to regulate CFTR function in the early secretory compartments.

75 citations

Journal ArticleDOI
01 Oct 1998-Genomics
TL;DR: A rapid screening method for cross-species amplification of homologous microsatellite loci indicated that there was no correlation between numbers of alleles in humans and in baboons, but a high correlation between median allele sizes.

75 citations

Journal ArticleDOI
TL;DR: The data suggest that the SK1-S1P axis could be an attractive target for the development of treatments to ameliorate adipose inflammation and insulin resistance associated with obesity and type 2 diabetes.
Abstract: Adipose dysfunction resulting from chronic inflammation and impaired adipogenesis has increasingly been recognized as a major contributor to obesity-mediated insulin resistance, but the molecular mechanisms that maintain healthy adipocytes and limit adipose inflammation remain unclear. Here, we used genetic and pharmacological approaches to delineate a novel role for sphingosine kinase 1 (SK1) in metabolic disorders associated with obesity. SK1 phosphorylates sphingosine to form sphingosine 1 phosphate (S1P), a bioactive sphingolipid with numerous roles in inflammation. SK1 mRNA expression was increased in adipose tissue of diet-induced obese (DIO) mice and obese type 2 diabetic humans. In DIO mice, SK1 deficiency increased markers of adipogenesis and adipose gene expression of the anti-inflammatory molecules IL-10 and adiponectin and reduced adipose tissue macrophage (ATM) recruitment and proinflammatory molecules TNFα and IL-6. These changes were associated with enhanced insulin signaling in adipose and muscle and improved systemic insulin sensitivity and glucose tolerance in SK1−/− mice. Specific pharmacological inhibition of SK1 in WT DIO mice also reduced adipocyte and ATM inflammation and improved overall glucose homeostasis. These data suggest that the SK1-S1P axis could be an attractive target for the development of treatments to ameliorate adipose inflammation and insulin resistance associated with obesity and type 2 diabetes.

75 citations


Authors

Showing all 2327 results

NameH-indexPapersCitations
Eric J. Topol1931373151025
John R. Yates1771036129029
George F. Koob171935112521
Ian A. Wilson15897198221
Peter G. Schultz15689389716
Gerald M. Edelman14754569091
Floyd E. Bloom13961672641
Stuart A. Lipton13448871297
Benjamin F. Cravatt13166661932
Chi-Huey Wong129122066349
Klaus Ley12949557964
Nicholas J. Schork12558762131
Michael Andreeff11795954734
Susan L. McElroy11757044992
Peter E. Wright11544455388
Network Information
Related Institutions (5)
Scripps Research Institute
32.8K papers, 2.9M citations

94% related

Merck & Co.
48K papers, 1.9M citations

93% related

GlaxoSmithKline
21.1K papers, 1.1M citations

92% related

Novartis
50.5K papers, 1.9M citations

92% related

Genentech
17.1K papers, 1.4M citations

91% related

Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20235
202210
202153
202060
201950
201842