Abstract:
:We have generated RANK (receptor activator of NF-kappaB) nullizygous mice to determine the molecular genetic interactions between osteoprotegerin, osteoprotegerin ligand, and RANK during bone resorption and remodeling processes. RANK(-/-) mice lack osteoclasts and have a profound defect in bone resorption and remodeling and in the development of the cartilaginous growth plates of endochondral bone. The osteopetrosis observed in these mice can be reversed by transplantation of bone marrow from rag1(-/-) (recombinase activating gene 1) mice, indicating that RANK(-/-) mice have an intrinsic defect in osteoclast function. Calciotropic hormones and proresorptive cytokines that are known to induce bone resorption in mice and human were administered to RANK(-/-) mice without inducing hypercalcemia, although tumor necrosis factor alpha treatment leads to the rare appearance of osteoclast-like cells near the site of injection. Osteoclastogenesis can be initiated in RANK(-/-) mice by transfer of the RANK cDNA back into hematopoietic precursors, suggesting a means to critically evaluate RANK structural features required for bone resorption. Together these data indicate that RANK is the intrinsic cell surface determinant that mediates osteoprotegerin ligand effects on bone resorption and remodeling as well as the physiological and pathological effects of calciotropic hormones and proresorptive cytokines.
journal_name
Proc Natl Acad Sci U S Aauthors
Li J,Sarosi I,Yan XQ,Morony S,Capparelli C,Tan HL,McCabe S,Elliott R,Scully S,Van G,Kaufman S,Juan SC,Sun Y,Tarpley J,Martin L,Christensen K,McCabe J,Kostenuik P,Hsu H,Fletcher F,Dunstan CR,Lacey DL,Boyle WJdoi
10.1073/pnas.97.4.1566keywords:
subject
Has Abstractpub_date
2000-02-15 00:00:00pages
1566-71issue
4eissn
0027-8424issn
1091-6490pii
97/4/1566journal_volume
97pub_type
杂志文章abstract::Nitric oxide (NO) biology has focused on the tightly regulated enzymatic mechanism that transforms L-arginine into a family of molecules, which serve both signaling and defense functions. However, very little is known of the pathways that metabolize these molecules or turn off the signals. The paradigm is well exempli...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.24.14100
更新日期:1998-11-24 00:00:00
abstract::Message passing is a fundamental technique for performing calculations on networks and graphs with applications in physics, computer science, statistics, and machine learning, including Bayesian inference, spin models, satisfiability, graph partitioning, network epidemiology, and the calculation of matrix eigenvalues....
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1914893116
更新日期:2019-11-19 00:00:00
abstract::A synthetic polymer has been prepared which contains dodecyl groups (to bind small substrate molecules) and methyleneimidazole side chains (as nucleophilic catalytic sites) linked to a polyethyleneimine framework. This macromolecule, with a high local concentration of binding and catalytic groups, catalyzes the hydrol...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.68.2.263
更新日期:1971-02-01 00:00:00
abstract::Eosinophils have been associated with fibrosis. To investigate their direct role in fibrosis, human peripheral blood eosinophil sonicate was added to human lung or dermal fibroblasts, and proliferation ([(3)H]thymidine) and collagen synthesis ([(3)H]proline) were evaluated. Proliferation was enhanced significantly in ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.17.9660
更新日期:1999-08-17 00:00:00
abstract::GT-2 is a plant transcriptional activator that contains two separate, but similar, trihelix DNA-binding domains. GT-1 is similar to GT-2, although it contains only one of such domains. cDNAs that encode GT-2 were isolated from rice (OS-GT2) and Arabidopsis (AT-GT2). Evidence is presented for the existence of an Arabid...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.6.3318
更新日期:1998-03-17 00:00:00
abstract::The role of the intradiscal polypeptide loops in bovine rhodopsin has been investigated by deletions in the N-terminal tail and in loops B-C, D-E, and E-F as well as by single amino acid substitutions in the D-E loop. Mutants with three types of phenotypes were observed. Type I mutants showed a rhodopsin-like chromoph...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.13.4991
更新日期:1990-07-01 00:00:00
abstract::Spatial working memory or short-term place memory is impaired in schizophrenia. The efficiency of antipsychotic drugs, particularly of typical antipsychotics, on cognitive deficit in schizophrenia remains disputable. Inhibition of serotonin (5-HT) 2A/2C receptors is important for cognitive improvement in schizophrenic...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0711273105
更新日期:2008-01-22 00:00:00
abstract::The intracellular pathogen Salmonella enterica serovar Typhimurium requires the mgtC gene to cause disease. The mgtC transcript includes a long leader region that harbors a short proline codon-rich ORF--termed mgtP--the translation of which is predicted to favor formation of one of two alternative stem-loop structures...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1316209111
更新日期:2014-02-25 00:00:00
abstract::The wetting of microstructured surfaces is studied both experimentally and theoretically. Even relatively simple surface topographies such as grooves with rectangular cross section exhibit a large variety of different wetting morphologies as observed by atomic force microscopy. This polymorphism arises from liquid wed...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0407721102
更新日期:2005-02-08 00:00:00
abstract::Human T-cell leukemia virus type I (HTLV-I) is a causative agent of adult T-cell leukemia (ATL). To elucidate the role of HTLV-I in leukemogenesis, we examined the biological activity of a defective HTLV-I provirus with the env-pX 3' long terminal repeat region cloned from leukemic cells of an ATL patient. Transfectio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.3.1071
更新日期:1990-02-01 00:00:00
abstract::We examined iron nitrosylation of non-heme protein and enzymatic activity of the Fe-S cluster protein, aconitase, in acute cardiac allograft rejection. Heterotopic transplantation of donor hearts was performed in histocompatibility matched (isografts: Lewis --> Lewis) and mismatched (allografts: Wistar-Furth --> Lewis...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0636938100
更新日期:2003-03-18 00:00:00
abstract::The eukaryotic proteasome mediates degradation of polyubiquitinated proteins. Here we report the single-particle cryoelectron microscopy (cryo-EM) structures of the endogenous 26S proteasome from Saccharomyces cerevisiae at 4.6- to 6.3-Å resolution. The fine features of the cryo-EM maps allow modeling of 18 subunits i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1601561113
更新日期:2016-03-08 00:00:00
abstract::Carcinogenic 9-anthryloxirane binds covalently to calf thymus DNA and poly(dA-dT). Application of the technique for DNA sequence determination shows that acid cleavage of the modified DNA frees approximately half of the anthryl groups from the DNA. HPLC analysis indicates that an adenine adduct and the glycol derived ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.16.5250
更新日期:1985-08-01 00:00:00
abstract::The tumorigenic properties of Rous sarcoma virus are attributable to a 60,000-dalton protein, pp60v--src, encoded by a single viral gene, v-src. A homologous gene, c-src, that contains the information for a 60,000-dalton protein, pp60c--src, has been identified in all tested vertebrate cells. By screening a recombinan...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.9.5842
更新日期:1981-09-01 00:00:00
abstract::A nuclear protein, termed leucine-rich acidic nuclear protein (LANP), has been isolated from among rat cerebellar proteins whose expression was transiently increased during an early stage of postnatal development. The amino acid sequence, deduced from its cDNA, showed that LANP contains 247 amino acids consisting of t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.21.9670
更新日期:1994-10-11 00:00:00
abstract::A major virulence factor of Plasmodium falciparum is the adherence of parasitized erythrocytes to the wall of postcapillary venules via a specific interaction between parasite-derived erythrocyte surface ligands and receptors on endothelial cells. To study this phenomenon in vitro, we selected a parasite population th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.23.10805
更新日期:1994-11-08 00:00:00
abstract::One signature of adaptive radiation is a high level of trait change early during the diversification process and a plateau toward the end of the radiation. Although the study of the tempo of evolution has historically been the domain of paleontologists, recently developed phylogenetic tools allow for the rigorous exam...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0904862106
更新日期:2009-10-27 00:00:00
abstract::Dendritic cell (DC) lectins mediate the recognition, uptake, and processing of antigens, but they can also be coopted by pathogens for infection. These distinct activities depend upon the routing of antigens within the cell. Antigens directed to endosomal compartments are degraded, and the peptides are presented on ma...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1820165116
更新日期:2019-07-23 00:00:00
abstract::Orchids employing sexual deceit attract males of their pollinator species through specific volatile signals that mimic female-released sex pheromones. One of these signals proved to be 2-ethyl-5-propylcyclohexan-1,3-dione (chiloglottone1), a new natural product that was shown to be most important in the relations betw...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0900646106
更新日期:2009-06-02 00:00:00
abstract::Fuchs endothelial corneal dystrophy (FECD) is a leading cause of corneal endothelial (CE) degeneration resulting in impaired visual acuity. It is a genetically complex and age-related disorder, with higher incidence in females. In this study, we established a nongenetic FECD animal model based on the physiologic outco...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1912546116
更新日期:2020-01-07 00:00:00
abstract::After fertilization of the sea urchin, Strongyl-ocentrotus purpuratus, a crosslinked fertilization membrane is formed; the crosslinks (dityrosine residues) are synthesized in a reaction catalyzed by an ovoperoxidase that is released from the cortical granules during fertilization. The substrate for ovoperoxidase activ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.7.3183
更新日期:1978-07-01 00:00:00
abstract::The mechanisms involved in the uptake of uni- and multi-lamellar lipid vesicles by BALB/c mouse 3T3 cells have been investigated. Vesicles are incorporated into cells both by endocytosis and by a nonendocytotic mechanism which we propose involves fusion of vesicles with the plasma membrane. The nonendocytotic pathway ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.5.1603
更新日期:1976-05-01 00:00:00
abstract::Dehydroepiandrosterone (DHEA) is a neurosteroid with potential effects on neurogenesis and neuronal survival in humans. However, most studies on DHEA have been performed in rodents, and there is little direct evidence for biological effects on the human nervous system. Furthermore, the mechanism of its action is unkno...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0307325101
更新日期:2004-03-02 00:00:00
abstract::A detailed conformational analysis of the known crystal structures of vitamin A, carotenoid, and xanthenoid derivatives has been made. These studies suggest that the visual chromophore 11-cis retinal and its isomers may each occur in several different conformational states, which would be expected to have different li...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.69.6.1569
更新日期:1972-06-01 00:00:00
abstract::Diarthrodial joints are essential for load bearing and locomotion. Physiologically, articular cartilage sustains millions of cycles of mechanical loading. Chondrocytes, the cells in cartilage, regulate their metabolic activities in response to mechanical loading. Pathological mechanical stress can lead to maladaptive ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1414298111
更新日期:2014-11-25 00:00:00
abstract::The 1,25-dihydroxyvitamin D3 [1,25-(OH)2vitamin D3] analog KH1060 exerts very potent effects on cell proliferation and cell differentiation via the vitamin D receptor (VDR). However, the activities of KH1060 are not associated with an increased affinity for the VDR. We now show that increased stabilization of the VDR-...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.20.10685
更新日期:1996-10-01 00:00:00
abstract::Protein framework alterations in heritable Cu, Zn superoxide dismutase (SOD) mutants cause misassembly and aggregation in cells affected by the motor neuron disease ALS. However, the mechanistic relationship between superoxide dismutase 1 (SOD1) mutations and human disease is controversial, with many hypotheses postul...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1308531111
更新日期:2014-10-28 00:00:00
abstract::Developmentally regulated genes in Drosophila, which are conserved through evolution, are potential candidates for key functions in biological processes such as cell cycle, programmed cell death, and cancer. We report cloning and characterization of the human homologue of the Drosophila seven in absentia gene (HUMSIAH...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.17.9039
更新日期:1996-08-20 00:00:00
abstract::We have developed an in situ hybridization assay capable of detecting enteroviral RNA in myocardial cells, using molecularly cloned coxsackievirus B3 cDNA as a diagnostic probe. Because of the high degree of nucleic acid sequence homology among the numerous enteroviral serotypes, including the group A and B coxsackiev...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.17.6272
更新日期:1987-09-01 00:00:00
abstract::The Golgi apparatus is a membrane-bounded organelle with the characteristic shape of a series of stacked flat cisternae. During mitosis in mammalian cells, the Golgi apparatus is once fragmented into small vesicles and then reassembled to form the characteristic shape again in each daughter cell. The mechanism and det...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1619264114
更新日期:2017-05-16 00:00:00