Institution
Torrey Pines Institute for Molecular Studies
Nonprofit•San 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: Antigen & T cell. The organization has 2323 authors who have published 2217 publications receiving 112618 citations.
Topics: Antigen, T cell, Peptide, Solid-phase synthesis, Cytotoxic T cell
Papers published on a yearly basis
Papers
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TL;DR: This study demonstrates the power of mixture-based combinatorial libraries to identify distinctly different ligands for closely related receptors.
100 citations
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TL;DR: Evidence suggests that NKT-cell subsets can play opposing roles early in non-microbial liver inflammation in that type I NKT are proinflammatory whereas type II NKT cells inhibit type INKT-mediated liver injury.
99 citations
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TL;DR: Three‐dimensional cultures of dermal equivalent tissue express angiogenic activity to a greater extent than monolayer cultures, some of which can be assigned to VEGF.
Abstract: Human neonatal fibroblasts were cultured on a lactate-glycollate copolymer scaffold for 12–16 days to form a three-dimensional dermal equivalent tissue. The cellular content of vascular endothelial growth factor (VEGF) mRNA in these three-dimensional cultures was 22-fold greater than that observed in the same fibroblasts grown as monolayers. No induction was shown by hepatocyte growth factor (HGF) or angiopoietin 1 indicating that the effect was specific to VEGF. The predominant VEGF splice variant, detected by RT-PCR corresponded to the 121 amino acid form, with less of the 165 amino acid form. The cell-associated forms (189 and 206 amino acids) comprised less than 1% of the total VEGF mRNA. VEGF and HGF proteins, determined by ELISA, were secreted in physiologically significant amounts, 0.5–4 ng per 24 h/106 cells. Conditioned medium from the three-dimensional cultures stimulated proliferation of endothelial cells in a dose-dependent manner and induced cellular expression of integrin αvβ3. Conditioned medium from the same dermal fibroblasts cultured in monolayer showed little angiogenic activity in any of these assays. Using the chorioallantoic membrane (CAM) angiogenesis assay, the cultures stimulated blood vessel production 2.8-fold over scaffold alone. VEGF-neutralizing antibody reduced the vessel development in the CAM to the level in the scaffold control. Anti-HGF antibody had no significant effect. In conclusion, three-dimensional cultures of dermal equivalent tissue express angiogenic activity to a greater extent than monolayer cultures, some of which can be assigned to VEGF. J. Cell. Physiol. 183:74–82, 2000. © 2000 Wiley-Liss, Inc.
99 citations
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TL;DR: Different profiles of antibody specificities provide insight into the mechanisms behind the elicitation of better neutralizing antibodies with the DNA prime-protein boost approach, and the results support the use of this approach to further optimize Env formulations for HIV vaccine development.
Abstract: A major challenge in human immunodeficiency virus type 1 (HIV-1) vaccine development is to elicit potent and broadly neutralizing antibodies that are effective against primary viral isolates. Previously, we showed that DNA prime-protein boost vaccination using HIV-1 gp120 antigens was more effective in eliciting neutralizing antibodies against primary HIV-1 isolates than was a recombinant gp120 protein-only vaccination approach. In the current study, we analyzed the difference in antibody specificities in rabbit sera elicited by these two immunization regimens using peptide enzyme-linked immunosorbent assay and a competitive virus capture assay. Our results indicate that a DNA prime-protein boost regimen is more effective than a protein-alone vaccination approach in inducing antibodies that target two key neutralizing domains: the V3 loop and the CD4 binding site. In particular, positive antibodies targeting several peptides that overlap with the known CD4 binding area were detected only in DNA-primed sera. Different profiles of antibody specificities provide insight into the mechanisms behind the elicitation of better neutralizing antibodies with the DNA prime-protein boost approach, and our results support the use of this approach to further optimize Env formulations for HIV vaccine development.
99 citations
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TL;DR: The identity of the mammalian homolog to the yeast Sec12 guanine nucleotide exchange factor (18% identity) that promotes Sar1 activation is reported, and the dominant negative GDP‐restricted mutant Sar1[T39N] is shown to be a potent inhibitor of mSec12 activity.
Abstract: The Sar1 GTPase is an essential component of COPII vesicle coats involved in export of cargo from the endoplasmic reticulum of mammalian cells. To begin to elucidate its mechanism of action, we now report the identity of the mammalian homolog to the yeast Sec12 guanine nucleotide exchange factor (18% identity) that promotes Sar1 activation. Mammalian Sec12 (mSec12) is a type II transmembrane protein with a large cytosolic domain, a fragment of which has previously been reported as the transcription factor prolactin regulatory element binding protein (PREB). mSec12 promotes efficient guanine nucleotide exchange on Sar1, but not Arf1 or Rab GTPases. mSec12 is localized to the endoplasmic reticulum and an antibody to the cytosolic domain of mSec12 potently inhibits Sar1 recruitment and the formation of COPII vesicles in vitro. The dominant negative GDP-restricted mutant Sar1[T39N] is shown to be a potent inhibitor of mSec12 activity, consistent with its role in preventing COPII vesicle formation in vitro and during transient expression in vivo. We propose that mSec12 is an evolutionarily distant guanine nucleotide exchange factor directing Sar1 GTPase activation in mammalian cells. Its divergence from yeast Sec12p may reflect the specialized needs of the mammalian endoplasmic reticulum involving the formation of Sar1-dependent transitional elements (Aridor M, et al. J Cell Biol 2001;152:213–229) and selection of cargo into prebudding complexes.
99 citations
Authors
Showing all 2327 results
Name | H-index | Papers | Citations |
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Eric J. Topol | 193 | 1373 | 151025 |
John R. Yates | 177 | 1036 | 129029 |
George F. Koob | 171 | 935 | 112521 |
Ian A. Wilson | 158 | 971 | 98221 |
Peter G. Schultz | 156 | 893 | 89716 |
Gerald M. Edelman | 147 | 545 | 69091 |
Floyd E. Bloom | 139 | 616 | 72641 |
Stuart A. Lipton | 134 | 488 | 71297 |
Benjamin F. Cravatt | 131 | 666 | 61932 |
Chi-Huey Wong | 129 | 1220 | 66349 |
Klaus Ley | 129 | 495 | 57964 |
Nicholas J. Schork | 125 | 587 | 62131 |
Michael Andreeff | 117 | 959 | 54734 |
Susan L. McElroy | 117 | 570 | 44992 |
Peter E. Wright | 115 | 444 | 55388 |