Abstract:
:Developing autoreactive B cells edit their B cell antigen receptor (BCR) in the bone marrow and are clonally deleted when they fail to reexpress an innocent BCR. Here, inducible Cre-loxP-mediated gene inversion is used to change the specificity of the BCR on mature IgM+ IgD+ B cells in vivo to address the fate of lymphocytes encountering self-antigens at this developmental stage. Expression of an autoreactive BCR on mature B cells leads to their rapid elimination from the periphery, a process that is inhibited by constitutive bcl-2 transgene expression in an antigen dose-dependent manner. Thus, selection of mature B cells into the long-lived peripheral pool does not prevent their deletion upon encounter of self-antigens.
journal_name
Proc Natl Acad Sci U S Aauthors
Lam KP,Rajewsky Kdoi
10.1073/pnas.95.22.13171subject
Has Abstractpub_date
1998-10-27 00:00:00pages
13171-5issue
22eissn
0027-8424issn
1091-6490journal_volume
95pub_type
杂志文章abstract::Phenotypic capacitance refers to the ability of a genome to accumulate mutations that are conditionally hidden and only reveal phenotype-altering effects after certain environmental or genetic changes. Capacitance has important implications for the evolution of novel forms and functions, but experimentally studied mec...
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.1420902112
更新日期:2015-10-06 00:00:00
abstract::Reef-building corals are critically important species that are threatened by anthropogenic stresses including climate change. In attempts to understand corals' responses to stress and other aspects of their biology, numerous genomic and transcriptomic studies have been performed, generating a variety of hypotheses abo...
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.1722151115
更新日期:2018-05-15 00:00:00
abstract::Mitogen-stimulated scheduled DNA synthesis and DNA excision repair in human lymphocytes, as well as DNA polymerase a activity in a cell-free system, were inhibited by an electrophilic metabolite of benzo[a]pyrene. This metabolite, (+/-)-anti-(7r,8t)-dihydroxy-(9,10t)-epoxy-7,8,9,10-tetrahyd robenzo[a]pyrene (BPDE), co...
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.81.17.5300
更新日期:1984-09-01 00:00:00
abstract::The Per-Arnt-Sim (PAS) domain is a ubiquitous protein module with a common three-dimensional fold involved in a wide range of regulatory and sensory functions in all domains of life. The activation of these functions is thought to involve partial unfolding of N- or C-terminal helices attached to the PAS domain. Here w...
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.0601567103
更新日期:2006-08-01 00:00:00
abstract::Iron-sulfur (Fe-S) proteins are key players in vital processes involving energy homeostasis and metabolism from the simplest to most complex organisms. We report a 1.5 A x-ray crystal structure of the first identified outer mitochondrial membrane Fe-S protein, mitoNEET. Two protomers intertwine to form a unique dimeri...
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.0707189104
更新日期:2007-09-04 00:00:00
abstract::A PCR strategy is described for global amplification of DNA from a single eukaryotic cell that enables the comprehensive analysis of the whole genome. By comparative genomic hybridization, not only gross DNA copy number variations, such as monosomic X and trisomic 21 in single male cells and cells from Down's syndrome...
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.96.8.4494
更新日期:1999-04-13 00:00:00
abstract::Our research addresses the relationship between subnuclear localization and gene expression in fission yeast. We observed the relocalization of a heterochromatic region, the mating-type region, from its natural location at the spindle-pole body to the immediate vicinity of the nucleolus. Relocalization occurred in res...
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.1315581110
更新日期:2013-11-19 00:00:00
abstract::Variable regions of Ig chains provide the antigen recognition portion of B-cell receptors and derivative antibodies. Ig heavy-chain variable region exons are assembled developmentally from V, D, J gene segments. Each variable region contains three antigen-contacting complementarity-determining regions (CDRs), with CDR...
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.1709203114
更新日期:2017-08-08 00:00:00
abstract::In the northern hemisphere, there is compelling evidence for climate-related advances of spring events, but no such long-term biological time series exist for the southern hemisphere. We have studied a unique data set of dates of first arrival and laying of first eggs over a 55-year period for the entire community of ...
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.0510397103
更新日期:2006-04-18 00:00:00
abstract::Worldwide dissemination of antibiotic resistance in bacteria is facilitated by plasmids that encode postsegregational killing (PSK) systems. These produce a stable toxin (T) and a labile antitoxin (A) conditioning cell survival to plasmid maintenance, because only this ensures neutralization of toxicity. Shortage of a...
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.1308241111
更新日期:2014-02-18 00:00:00
abstract::CR1 is a short interspersed repetitive DNA element originally identified in the domestic chicken (Gallus gallus). However, unlike virtually all other such sequences described to date, CR1 is not confined to one or a few closely related species. It is probably a ubiquitous component of the avian genome, having been 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.88.13.5814
更新日期:1991-07-01 00:00:00
abstract::Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes parkinsonism in humans and subhuman primates, but not in rats and many other laboratory animals; mice are intermediate in their susceptibility. Since MPTP causes selective dopaminergic neurotoxicity when infused directly into rat sub...
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.84.10.3521
更新日期:1987-05-01 00:00:00
abstract::A special methionine tRNA (tRNAi) is universally required to initiate translation. Amongst species a tRNAi structural conservation is most apparent in the anticodon and T arms of the molecule but extends into the variable loop and the 3' strand of the D stem. This suggested that they could share a similar ancestral or...
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.82.14.4587
更新日期:1985-07-01 00:00:00
abstract::Oxidative stress plays a central role in many human diseases and in aging. In Caenorhabditis elegans the SKN-1 protein induces phase II detoxification gene transcription, a conserved oxidative stress response, and is required for oxidative stress resistance and longevity. Oxidative stress induces SKN-1 to accumulate 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.0508105102
更新日期:2005-11-08 00:00:00
abstract::Murine mucopolysaccharidosis type VII is a heritable disease caused by a spontaneous mutation, gus(mps), closely linked to the beta-glucuronidase structural gene on chromosome 5. Mice homozygous for the mutation have a > 200-fold decrease in beta-glucuronidase mRNA levels and virtually no enzyme activity detectable by...
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.90.14.6567
更新日期:1993-07-15 00:00:00
abstract::Utrophin levels have recently been shown to be more abundant in slow vs. fast muscles, but the nature of the molecular events underlying this difference remains to be fully elucidated. Here, we determined whether this difference is due to the expression of utrophin A or B, and examined whether transcriptional regulato...
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.0932671100
更新日期:2003-06-24 00:00:00
abstract::Two molecular forms of pyrophosphate-dependent phosphofructokinase (PP(i)-PFK; pyrophosphate:D-fructose-6-phosphate 1-phosphotransferase; EC 2.7.1.90) have been found whose activity depends upon association and dissociation characteristics regulated by fructose 2,6-bisphosphate (Fru-2,6-P(2)). PP(i)-PFK was purified 2...
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.81.16.5051
更新日期:1984-08-01 00:00:00
abstract::The yeast fatty acid synthase (M(r) = 2.5 x 10(6)) is organized in an alpha 6 beta 6 complex. In these studies, the synthase structure has been examined by negative-stain and cryo-electron microscopy. Side and end views of the structure indicate that the molecule, shaped similar to a prolate ellipsoid, has a high-dens...
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.89.14.6585
更新日期:1992-07-15 00:00:00
abstract::Accumulation of misfolded proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), an intracellular signaling pathway that adjusts the protein folding capacity of the ER according to need. If homeostasis in the ER protein folding environment cannot be reestablished, cells commit to apop...
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.1010580107
更新日期:2010-09-14 00:00:00
abstract::The extent to which stratospheric intrusions on synoptic scales influence the tropospheric ozone (O3) levels remains poorly understood, because quantitative detection of stratospheric air has been challenging. Cosmogenic 35S mainly produced in the stratosphere has the potential to identify stratospheric air masses at ...
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.1609919113
更新日期:2016-10-04 00:00:00
abstract::Using short-term cultures of hamster embryo cells, we have examined the effects of the free-radical scavenger superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) and the enzyme catalase (hydrogen-peroxide:hydrogenperoxide oxidoreductase, EC 1.11.1.6) on x-ray- and bleomycin-induced transformation ...
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.80.5.1304
更新日期:1983-03-01 00:00:00
abstract::We review a program of research that uses neuroimaging techniques to determine the functional and neural architecture of human working memory. A first set of studies indicates that verbal working memory includes a storage component, which is implemented neurally by areas in the left-hemisphere posterior parietal corte...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.95.20.12061
更新日期:1998-09-29 00:00:00
abstract::An effective plant alkaloid chemical defense requires a variety of transport processes, but few alkaloid transporters have been characterized at the molecular level. Previously, a gene fragment encoding a putative plasma membrane proton symporter was isolated, because it was coordinately regulated with several nicotin...
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.1108620108
更新日期:2011-11-01 00:00:00
abstract::Improper function of voltage-gated sodium channels (NaVs), obligatory membrane proteins for bioelectrical signaling, has been linked to a number of human pathologies. Small-molecule agents that target NaVs hold considerable promise for treatment of chronic disease. Absent a comprehensive understanding of channel struc...
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.1603486113
更新日期:2016-05-24 00:00:00
abstract::How cells achieve their final sizes is a pervasive biological question. One strategy to increase cell size is for the cell to amplify its chromosomal DNA content through endoreduplication cycles. Although endoreduplication is widespread in eukaryotes, we know very little about its molecular mechanisms. Successful prog...
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.0505883102
更新日期:2005-12-20 00:00:00
abstract::Long-term synaptic plasticity requires both gene expression in the nucleus and local protein synthesis at synapses. The effector proteins that link molecular events in the cell body with local maintenance of synaptic strength are not known. We now show that treatment with serotonin (5-HT) that produces long-term facil...
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.1835674100
更新日期:2003-11-11 00:00:00
abstract::The pivotal step on the mitochondrial pathway to apoptosis is permeabilization of the mitochondrial outer membrane (MOM) by oligomers of the B-cell lymphoma-2 (Bcl-2) family members Bak or Bax. However, how they disrupt MOM integrity is unknown. A longstanding model is that activated Bak and Bax insert two α-helices, ...
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.1415142111
更新日期:2014-09-30 00:00:00
abstract::Analysis of variations in the concentrations or structures of biomolecules (e.g., mRNAs, proteins, peptides, natural products) that occur either naturally or in response to environmental or genetic perturbations can provide important insight into complex biological processes. Many biological samples are mixtures that ...
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.96.10.5372
更新日期:1999-05-11 00:00:00
abstract::Antiviral and macrophage-priming activities in the supernatant medium of a subclone of a concanavalin A-stimulated mouse T-cell hybridoma were investigated. The two activities were associated with a molecular weight of approximately 50,000 and could not be separated by various approaches. Both activities were eliminat...
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.80.12.3782
更新日期:1983-06-01 00:00:00
abstract::The hepatic pigment accumulated in 3,5-diethoxycarbonyl-1,4-dihydrocollidine-treated rats, which has been reported to inhibit ferrochelatase, has been isolated and purified. The pigment has been resolved into one major, one minor, and two trace components, all of which appear to be isomeric porphyrins. The major fract...
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.78.3.1490
更新日期:1981-03-01 00:00:00