Institution
Rockefeller University
Education•New York, New York, United States•
About: Rockefeller University is a education organization based out in New York, New York, United States. It is known for research contribution in the topics: Population & Gene. The organization has 15867 authors who have published 32938 publications receiving 2940261 citations. The organization is also known as: Rockefeller University & Rockefeller Institute.
Topics: Population, Gene, Virus, RNA, Antigen
Papers published on a yearly basis
Papers
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TL;DR: A new automated modeling technique that significantly improves the accuracy of loop predictions in protein structures by predicting loops of known structure in only approximately correct environments with errors typical of comparative modeling without misalignment is described.
Abstract: Comparative protein structure prediction is limited mostly by the errors in alignment and loop modeling. We describe here a new automated modeling technique that significantly improves the accuracy of loop predictions in protein structures. The positions of all nonhydrogen atoms of the loop are optimized in a fixed environment with respect to a pseudo energy function. The energy is a sum of many spatial restraints that include the bond length, bond angle, and improper dihedral angle terms from the CHARMM-22 force field, statistical preferences for the main-chain and side-chain dihedral angles, and statistical preferences for nonbonded atomic contacts that depend on the two atom types, their distance through space, and separation in sequence. The energy function is optimized with the method of conjugate gradients combined with molecular dynamics and simulated annealing. Typically, the predicted loop conformation corresponds to the lowest energy conformation among 500 independent optimizations. Predictions were made for 40 loops of known structure at each length from 1 to 14 residues. The accuracy of loop predictions is evaluated as a function of thoroughness of conformational sampling, loop length, and structural properties of native loops. When accuracy is measured by local superposition of the model on the native loop, 100, 90, and 30% of 4-, 8-, and 12-residue loop predictions, respectively, had <2 A RMSD error for the mainchain N, C(alpha), C, and O atoms; the average accuracies were 0.59 +/- 0.05, 1.16 +/- 0.10, and 2.61 +/- 0.16 A, respectively. To simulate real comparative modeling problems, the method was also evaluated by predicting loops of known structure in only approximately correct environments with errors typical of comparative modeling without misalignment. When the RMSD distortion of the main-chain stem atoms is 2.5 A, the average loop prediction error increased by 180, 25, and 3% for 4-, 8-, and 12-residue loops, respectively. The accuracy of the lowest energy prediction for a given loop can be estimated from the structural variability among a number of low energy predictions. The relative value of the present method is gauged by (1) comparing it with one of the most successful previously described methods, and (2) describing its accuracy in recent blind predictions of protein structure. Finally, it is shown that the average accuracy of prediction is limited primarily by the accuracy of the energy function rather than by the extent of conformational sampling.
1,999 citations
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Cornell University1, University of Pennsylvania2, NewYork–Presbyterian Hospital3, Hannover Medical School4, Rockefeller University5, National Taiwan University6, Oslo University Hospital7, University of Oslo8, Memorial Sloan Kettering Cancer Center9, Eppley Institute for Research in Cancer and Allied Diseases10, University of Nebraska Medical Center11
TL;DR: It is shown that PDAC-derived exosomes induce liver pre-metastatic niche formation in naive mice and consequently increase liver metastatic burden and suggests that exosomal MIF primes the liver for metastasis and may be a prognostic marker for the development of PDAC liver metastasis.
Abstract: Lyden and colleagues report that pancreatic cancer-derived exosomes induce a pre-metastatic niche in the liver by promoting TGFβ secretion from Kupffer cells, leading to fibronectin production in hepatic stellate cells and macrophage recruitment.
1,973 citations
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TL;DR: A new family member, Stat3, becomes activated through phosphorylation on tyrosine as a DNA binding protein in response to epidermal growth factor and interleukin-6 but not interferon gamma (IFN-gamma).
Abstract: The STAT family of proteins carries out a dual function: signal transduction and activation of transcription. A new family member, Stat3, becomes activated through phosphorylation on tyrosine as a DNA binding protein in response to epidermal growth factor (EGF) and interleukin-6 (IL-6) but not interferon gamma (IFN-gamma). It is likely that this phosphoprotein forms homodimers as well as heterodimers with the first described member of the STAT family, Stat91 (renamed Stat1 alpha), which is activated by the IFNs and EGF. Differential activation of different STAT proteins in response to different ligands should help to explain specificity in nuclear signaling from the cell surface.
1,968 citations
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TL;DR: This article reviews theoretical and empirical work using the allostatic load model vis-à-vis the effects of chronic stress on physical and mental health and proposes policies for promoting successful aging.
1,944 citations
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TL;DR: It is shown that different viruses are targeted by unique sets of ISGs, and that each viral species is susceptible to multiple antiviral genes, which together encompass a range of inhibitory activities.
Abstract: The type I interferon response protects cells against invading viral pathogens. The cellular factors that mediate this defence are the products of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified since their discovery more than 25 years ago, only a few have been characterized with respect to antiviral activity. For most ISG products, little is known about their antiviral potential, their target specificity and their mechanisms of action. Using an overexpression screening approach, here we show that different viruses are targeted by unique sets of ISGs. We find that each viral species is susceptible to multiple antiviral genes, which together encompass a range of inhibitory activities. To conduct the screen, more than 380 human ISGs were tested for their ability to inhibit the replication of several important human and animal viruses, including hepatitis C virus, yellow fever virus, West Nile virus, chikungunya virus, Venezuelan equine encephalitis virus and human immunodeficiency virus type-1. Broadly acting effectors included IRF1, C6orf150 (also known as MB21D1), HPSE, RIG-I (also known as DDX58), MDA5 (also known as IFIH1) and IFITM3, whereas more targeted antiviral specificity was observed with DDX60, IFI44L, IFI6, IFITM2, MAP3K14, MOV10, NAMPT (also known as PBEF1), OASL, RTP4, TREX1 and UNC84B (also known as SUN2). Combined expression of pairs of ISGs showed additive antiviral effects similar to those of moderate type I interferon doses. Mechanistic studies uncovered a common theme of translational inhibition for numerous effectors. Several ISGs, including ADAR, FAM46C, LY6E and MCOLN2, enhanced the replication of certain viruses, highlighting another layer of complexity in the highly pleiotropic type I interferon system.
1,926 citations
Authors
Showing all 15925 results
Name | H-index | Papers | Citations |
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Bruce S. McEwen | 215 | 1163 | 200638 |
David Baltimore | 203 | 876 | 162955 |
Ronald M. Evans | 199 | 708 | 166722 |
Lewis C. Cantley | 196 | 748 | 169037 |
Ronald Klein | 194 | 1305 | 149140 |
Scott M. Grundy | 187 | 841 | 231821 |
Jie Zhang | 178 | 4857 | 221720 |
Andrea Bocci | 172 | 2402 | 176461 |
Ralph M. Steinman | 171 | 453 | 121518 |
Masayuki Yamamoto | 171 | 1576 | 123028 |
Zena Werb | 168 | 473 | 122629 |
Nahum Sonenberg | 167 | 647 | 104053 |
Michel C. Nussenzweig | 165 | 516 | 87665 |
Harvey F. Lodish | 165 | 782 | 101124 |
Dennis R. Burton | 164 | 683 | 90959 |