Abstract:
:Mutations in the gene encoding the endothelin receptor type B (EDNRB) produce congenital aganglionic megacolon and pigment abnormalities in mice and humans. Here we report a naturally occurring null mutation of the EDNRB gene in spotting lethal (sl) rats, which exhibit aganglionic megacolon associated with white coat color. We found a 301-bp deletion spanning the exon 1-intron 1 junction of the EDNRB gene in sl rats. A restriction fragment length polymorphism caused by this deletion perfectly cosegregates with the sl phenotype. The deletion leads to production of an aberrantly spliced EDNRB mRNA that lacks the coding sequence for the first and second putative transmembrane domains of the G-protein-coupled receptor. Radioligand binding assays revealed undetectable levels of functional EDNRB in tissues from homozygous sl/sl rats. We conclude that EDNRB plays an essential role in the normal development of two neural crest-derived cell lineages, epidermal melanocytes and enteric neurons, in three mammalian species--humans, mice, and rats. The EDNRB-deficient rat may also prove valuable in defining the postnatal physiologic role of this receptor.
journal_name
Proc Natl Acad Sci U S Aauthors
Gariepy CE,Cass DT,Yanagisawa Mdoi
10.1073/pnas.93.2.867subject
Has Abstractpub_date
1996-01-23 00:00:00pages
867-72issue
2eissn
0027-8424issn
1091-6490journal_volume
93pub_type
杂志文章abstract::In vitro translation of Rous sarcoma virus (RSV) virion RNA in the messenger-dependent reticulocyte lysate system yielded polypeptides that were not synthesized by translation of RNA from a transformation-defective deletion mutant of RSV. These RSV-specific products migrated on sodium dodecyl sulfate/polyacrylamide ge...
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.74.8.3302
更新日期:1977-08-01 00:00:00
abstract::Cellular metabolism alters patterns of gene expression through a variety of mechanisms, including alterations in histone modifications and transcription factor activity. Nicotinamide adenine dinucleotide (NAD)-dependent proteins such as poly(ADP ribose) polymerases (PARPs) and sirtuin deacetylases play important roles...
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.1002130107
更新日期:2010-12-14 00:00:00
abstract::Reproducible quantification of large biological cohorts is critical for clinical/pharmaceutical proteomics yet remains challenging because most prevalent methods suffer from drastically declined commonly quantified proteins and substantially deteriorated quantitative quality as cohort size expands. MS2-based data-inde...
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.1800541115
更新日期:2018-05-22 00:00:00
abstract::We have investigated the role of cAMP in NO- and prostanoid-independent relaxations that are widely attributed to an endothelium-derived hyperpolarizing factor (EDHF). Under control conditions EDHF-type relaxations evoked by acetylcholine (ACh) in rabbit iliac arteries were transient, but in the presence of the cAMP p...
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.092089799
更新日期:2002-04-30 00:00:00
abstract::We examined the effect of the inhibition of initiation of DNA replication on the membrane association of the chromosomal origin of replication of Bacillus subtilis and the Staphylococcus aureus-Bacillus pumilus chimeric plasmid pSL103, using temperature-sensitive mutants of B. subtilis that have specifically affected ...
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.77.5.2834
更新日期:1980-05-01 00:00:00
abstract::The rate of change of climate codetermines the global warming impacts on natural and socioeconomic systems and their capabilities to adapt. Establishing past rates of climate change from temperature proxy data remains difficult given their limited spatiotemporal resolution. In contrast, past greenhouse gas radiative f...
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.0707386105
更新日期:2008-02-05 00:00:00
abstract::We have previously identified a generally occurring short-range mobility of nucleosome cores on DNA in relatively low ionic strength conditions. Here we report that this mobility of histone octamers positioned on constructs of 5S rDNA is suppressed by the binding of histone H1 or H5 to the nucleosome. Histone H5 is 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.91.22.10275
更新日期:1994-10-25 00:00:00
abstract::A cyclophilin (CyP) purified to homogeneity from the polycentric anaerobic rumen fungus Orpinomyces sp. strain PC-2 had a molecular mass of 20.5 kDa and a pI of 8.1. The protein catalyzed the isomerization of the prolyl peptide bond of N-succinyl-Ala-Ala-(cis,trans)-Pro-Phe p-nitroanilide with a kcat/Km value of 9.3 x...
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.92.7.2587
更新日期:1995-03-28 00:00:00
abstract::Point mutations in vascular smooth muscle α-actin (SM α-actin), encoded by the gene ACTA2, are the most prevalent cause of familial thoracic aortic aneurysms and dissections (TAAD). Here, we provide the first molecular characterization, to our knowledge, of the effect of the R258C mutation in SM α-actin, expressed wit...
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.1507587112
更新日期:2015-08-04 00:00:00
abstract::Superficial cells from early amphibian embryos display regional specializations of their cell surfaces. That portion of the plasma membrane facing the perivitelline space (apical surface) is nonadhesive, whereas, in the same cell, the lateral and basal portions of the plasma membrane will adhere to other cells. These ...
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.77.6.3460
更新日期:1980-06-01 00:00:00
abstract::The repeatability of evolutionary change is difficult to quantify because only a single outcome can usually be observed for any precise set of circumstances. In this study, however, we have quantified the frequency of parallel and divergent genetic changes in 12 initially identical populations of Escherichia coli 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.0602917103
更新日期:2006-06-13 00:00:00
abstract::Animal foraging and competition are defined by the partitioning of three primary niche axes: space, time, and resources. Human disturbance is rapidly altering the spatial and temporal niches of animals, but the impact of humans on resource consumption and partitioning-arguably the most important niche axis-is poorly u...
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.2012774117
更新日期:2020-10-27 00:00:00
abstract::A simple protocol for the rescue of a synthetic genome into a paramyxovirus has been developed. First, a synthetic Sendai virus-like RNA, containing the antisense coding region of the chloramphenicol acetyltransferase gene replacing the coding region of the Sendai virus genome, was transcribed from a cDNA. When introd...
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.88.13.5537
更新日期:1991-07-01 00:00:00
abstract::Myoglobin-mediated oxygen delivery to intracellular mitochondria is demonstrated in cardiac myocytes isolated from the hearts of mature rats. Myocytes are held at high ambient oxygen pressure, 40-340 torr (5-45 kPa); sarcoplasmic myoglobin is fully oxygenated. In this condition oxygen availability does not limit respi...
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.84.21.7503
更新日期:1987-11-01 00:00:00
abstract::HIV-1 reverse transcriptase (RT) catalyzes the synthesis of DNA from DNA or RNA templates. During this process, it must transfer its primer from one template to another RNA or DNA template. Binary complexes made of RT and a primer/template bind an additional single-stranded RNA molecule of the same nucleotide sequence...
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.94.21.11279
更新日期:1997-10-14 00:00:00
abstract::ErbB2 interacting protein (Erbin) is a widely expressed protein and participates in inhibition of several intracellular signaling pathways. Its mRNA has been found to be present in relatively high levels in the heart. However, its physiological role in the heart has not been explored. In the present work, we elucidate...
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.1320350111
更新日期:2014-04-22 00:00:00
abstract::Activation energies for the individual steps of secretory and viral fusion are reported to be large [Oberhauser, A. F., Monck, J. R. & Fernandez, J. M. (1992) Biophys. J. 61, 800-809; Clague, M. J., Schoch, C., Zech, L. & Blumenthal, R. (1990) Biochemistry 29, 1303-1308]. Understanding the cause for these large activa...
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.95.16.9274
更新日期:1998-08-04 00:00:00
abstract::A transformation-defective mutant of Abelson murine leukemia virus (A-MuLV), called A-MuLV-P92td, has been isolated. The mutant encodes a serologically identifiable A-MuLV protein of molecular weight 92,000 (P92) but it lacks the ability to transform either fibroblasts or bone marrow lymphoid cells. In contrast to the...
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.77.8.4993
更新日期:1980-08-01 00:00:00
abstract::Evolutionary game dynamics describe not only frequency-dependent genetic evolution, but also cultural evolution in humans. In this context, successful strategies spread by imitation. It has been shown that the details of strategy update rules can have a crucial impact on evolutionary dynamics in theoretical models and...
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.0912515107
更新日期:2010-02-16 00:00:00
abstract::The development of osteoclastic cell lines would greatly facilitate analysis of the cellular and molecular biology of bone resorption. Several cell lines have previously been reported to be capable of osteoclastic differentiation. However, such cell lines form at best only occasional excavations, suggesting that osteo...
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.90.12.5578
更新日期:1993-06-15 00:00:00
abstract::Mesothelin is a differentiation antigen present on the surface of ovarian cancers, mesotheliomas, and several other types of human cancers. Because among normal tissues, mesothelin is present only on mesothelial cells, it represents a good target for antibody-mediated delivery of cytotoxic agents. In the present study...
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.95.2.669
更新日期:1998-01-20 00:00:00
abstract::Single-stranded DNA oligonucleotides can achieve targeted base-pair substitution with modest efficiency but high precision. We show that "oligo targeting" can be used effectively to study missense mutations in DNA mismatch repair (MMR) genes. Inherited inactivating mutations in DNA MMR genes are causative for the canc...
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.1520813113
更新日期:2016-04-12 00:00:00
abstract::The decrease with age of the adrenal-secreted dehydroepiandrosterone sulfate (DHEAS) in serum has suggested that it may be causally related to longevity. For the PAQUID [People (Personnes) Aged (Agées) About What (Quid, in Latin)] cohort of elderly subjects, we have previously reported higher DHEAS in men than in wome...
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.121177998
更新日期:2001-07-03 00:00:00
abstract::Carbon monoxide (CO) synthesized by heme oxygenase 2 (HO2) and nitric oxide (NO) produced by neuronal NO synthase (nNOS) mediate nonadrenergic/noncholinergic (NANC) intestinal relaxation. In many areas of the gastrointestinal tract, NO and CO function as coneurotransmitters. In the internal anal sphincter (IAS), NANC ...
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.0308695100
更新日期:2004-02-24 00:00:00
abstract::Efforts to understand the dramatic declines in mortality over the past century have focused on life expectancy. However, understanding changes in disparity in age of death is important to understanding mechanisms of mortality improvement and devising policy to promote health equity. We derive a novel decomposition 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.1601112113
更新日期:2016-07-26 00:00:00
abstract::Intron removal from tRNA precursors involves cleavage by a tRNA splicing endonuclease to yield tRNA 3'-halves beginning with a 5'-hydroxyl, and 5'-halves ending in a 2',3'-cyclic phosphate. A tRNA ligase then incorporates this phosphate into the internucleotide bond that joins the two halves. Although this 3'-P RNA sp...
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.1018307108
更新日期:2011-01-25 00:00:00
abstract::We document male-biased sex ratios among U.S.-born children of Chinese, Korean, and Asian Indian parents in the 2000 U.S. Census. This male bias is particularly evident for third children: If there was no previous son, sons outnumbered daughters by 50%. By contrast, the sex ratios of eldest and younger children with 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.0800703105
更新日期:2008-04-15 00:00:00
abstract::Animal models of human cytomegalovirus (CMV) infections have not been available to study pathogenesis or to evaluate antiviral drugs. Severe combined immunodeficient mice implanted with human fetal tissues (SCID-hu) were found to support CMV replication and may provide a model for this species-specific virus. When con...
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.90.1.104
更新日期:1993-01-01 00:00:00
abstract::Mature immunologically competent dendritic cells are the most efficient antigen-presenting cells that powerfully activate T cells and initiate and sustain immune responses. Indeed, dendritic cells are able to efficiently capture antigens, express high levels of costimulatory molecules, and produce the combination of c...
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.190204697
更新日期:2000-09-26 00:00:00
abstract::Liddle syndrome is a mendelian form of hypertension characterized by constitutively elevated renal Na reabsorption that can result from activating mutations in the beta or gamma subunit of the epithelial Na channel. All reported mutations have deleted the last 45-76 normal amino acids from the cytoplasmic C terminus o...
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.92.25.11495
更新日期:1995-12-05 00:00:00