Abstract:
:Rodless retina (gene symbol, r) was discovered in mice by Keeler 70 years ago and was first described in this journal as an autosomal recessive mutation leading to "the absence of the visual cells (rods), the external nuclear layer, and the external molecular layer" [Keeler, C. E. (1924) Proc. Natl. Acad. Sci. USA 10, 329-333]. The mutation was studied by Keeler and others in the United States and Europe over the next decade, but Keeler's stock was destroyed in 1939, and mice definitively related to his by pedigree and progeny tests also appeared to have been lost by the end of World War II. In the early 1950s Brückner in Basel recognized mice with a similar retinal phenotype. Investigators in London and Strasbourg analyzed descendants of Brückner's mice and concluded, on the basis of different pathogenesis from r, that they carried a new mutation, which came later to be called retinal degeneration, rd. The relationship of r and rd has been unsettled ever since. Now that the rd phenotype is known to be due to a nonsense mutation in the rod photoreceptor cGMP phosphodiesterase beta-subunit gene, we hoped to settle the question by direct analysis of r DNA. DNA was liberated from 70-year-old histological sections of +/r and r/r eyes, the only extant r DNA, and the regions encompassing the nonsense mutation amplified by the polymerase chain reaction (PCR). Sequence analysis of the PCR products revealed the presence of the same nonsense mutation and two intron polymorphisms in r DNA. PCR and direct sequence analysis of 11 strains of mice known to carry rd (or a similar allele) also revealed the presence of the nonsense mutation and the same intron polymorphisms. The fact that all r and rd mice contain an identical defect and intron polymorphisms in the phosphodiesterase beta-subunit gene settles beyond reasonable doubt that a single mutation arising > 70 years ago is now widely distributed through inbred mouse strains. Because of the extensive use of the name in publications of the past 40 years, we propose that the gene continue to be designated retinal degeneration, rd.
journal_name
Proc Natl Acad Sci U S Aauthors
Pittler SJ,Keeler CE,Sidman RL,Baehr Wdoi
10.1073/pnas.90.20.9616subject
Has Abstractpub_date
1993-10-15 00:00:00pages
9616-9issue
20eissn
0027-8424issn
1091-6490journal_volume
90pub_type
杂志文章abstract::The heat-stable enterotoxin B (STB) of Escherichia coli is a 48-amino acid extracellular peptide that induces rapid fluid accumulation in animal intestinal models. Unlike other E. coli enterotoxins that elicit cAMP or cGMP responses in the gut [heat-labile toxin (LT) and heat-stable toxin A (STA), respectively], STB 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.90.8.3202
更新日期:1993-04-15 00:00:00
abstract::Cancer therapies using genes and other macromolecules might realize their full clinical potential if they could be delivered to tumor tissue in optimal quantities. Unfortunately, the compromised circulation within tumors poses a formidable resistance to adequate and uniform penetration of these agents. Previously, we ...
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.96.6.3137
更新日期:1999-03-16 00:00:00
abstract::Neurotrophins (NTs) have recently been found to regulate synaptic transmission in the hippocampus. Whole-cell and single-channel recordings from cultured hippocampal neurons revealed a mechanism responsible for enhanced synaptic strength. Specifically, brain-derived neurotrophic factor augmented glutamate-evoked, but ...
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.95.17.10235
更新日期:1998-08-18 00:00:00
abstract::The kinetics of hepatic uptake and degradation of sphingomyelin/cholesterol (2:1, M/M) small unilamellar liposomes were investigated in a BALB/c mouse. The tissue distribution of liposomes was determined by scintillation spectrometry. The percentage of intact liposomes in tissues was estimated by the technique of gamm...
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.77.7.4030
更新日期:1980-07-01 00:00:00
abstract::After decades of robust growth, the rise in US life expectancy stalled after 2010. Explanations for the stall have focused on rising drug-related deaths. Here we show that a stagnating decline in cardiovascular disease (CVD) mortality was the main culprit, outpacing and overshadowing the effects of all other causes 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.1920391117
更新日期:2020-03-31 00:00:00
abstract::A genetic defect in a CC-chemokine receptor (CCR)-5, the principal coreceptor for the macrophage-tropic HIV type 1 (HIV-1), recently was found to naturally protect CCR-5-defective, but healthy, individuals from HIV-1 infection. In this study, we mimic the natural resistance of the CCR-5-defective individuals by design...
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.94.21.11567
更新日期:1997-10-14 00:00:00
abstract::A human peripheral T-cell cDNA library was screened with two labeled synthetic oligonucleotides encoding regions of a human placenta protein-tyrosine-phosphatase (protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48). One positive clone was isolated and the nucleotide sequence was determined. It contained 1305 bas...
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.86.14.5257
更新日期:1989-07-01 00:00:00
abstract::Damage to the protooncogene MYC has been implicated in the genesis of diverse human tumors, but the tumorigenic potential of the isolated gene has been disputed. Here we report the use of a retroviral vector to test the potency of human MYC for neoplastic transformation in avian cells. We found that sustained and abun...
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.87.6.2102
更新日期:1990-03-01 00:00:00
abstract::GB virus B (GBV-B), which infects tamarins, is the virus most closely related to hepatitis C virus (HCV). HCV has a protein (p7) that is believed to form an ion channel. It is critical for viability. In vitro studies suggest that GBV-B has an analogous but larger protein (p13). We found that substitutions of the -1 an...
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.0511297103
更新日期:2006-02-28 00:00:00
abstract::The LSD1-CoREST histone demethylase complex is required to repress neuronal genes in nonneuronal tissues. Here we show that sumoylation of Braf35, one of the subunits of the complex, is required to maintain full repression of neuron-specific genes and for occupancy of the LSD1-CoREST complex at its gene targets. Inter...
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.1121522109
更新日期:2012-05-22 00:00:00
abstract::In eukaryotes, microtubules are essential for cellular plasticity and dynamics. Here we show that P300/CBP-associated factor (PCAF), a kinetochore-associated acetyltransferase, acts as a negative modulator of microtubule stability through acetylation of EB1, a protein that controls the plus ends of microtubules. PCAF ...
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.1202639109
更新日期:2012-10-09 00:00:00
abstract::Trace greenhouse gases are a fundamentally important component of Earth's global climate system sensitive to global change. However, their concentration in the pre-Pleistocene atmosphere during past warm greenhouse climates is highly uncertain because we lack suitable geochemical or biological proxies. This long-stand...
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.1102409108
更新日期:2011-06-14 00:00:00
abstract::Combining genotypes across datasets is central in facilitating advances in genetics. Data aggregation efforts often face the challenge of record matching-the identification of dataset entries that represent the same individual. We show that records can be matched across genotype datasets that have no shared markers ba...
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.1619944114
更新日期:2017-05-30 00:00:00
abstract::cDNA clones specific for the light subunit of porcine calpain I have been isolated from a porcine kidney cDNA library. The complete primary structure of the light subunit has been revealed by nucleotide sequence analysis of the cDNA clones isolated and amino acid sequence analysis of peptides isolated from the purifie...
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.82.18.6075
更新日期:1985-09-01 00:00:00
abstract::A water-soluble component of membranes of cells from a Burkitt's lymphoma cultured cell line was used to develop an antiserum that detects an antigen(s) on acute leukemia cells. This antiserum did not react with nonlymphoid cultured cell lines except for human embryonic kidney cells infected with the Rauscher murine l...
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.70.2.495
更新日期:1973-02-01 00:00:00
abstract::The phenomenon of selective translation of T4 template RNA by ribosomes from T4-infected cells, or factors derived therefrom, has been extended to studies on the initiation of protein synthesis. A high-salt extract derived from T4-infected ribosomes inhibits the formation of initiation complexes of MS2 and Escherichia...
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.67.2.696
更新日期:1970-10-01 00:00:00
abstract::B-1a cells reside in both the peritoneal cavity and the spleen. LPS stimulates splenic B-1a to differentiate to plasma cells producing natural IgM specific for microbial and self antigens. However, there are conflicting views as to whether the B-1a cells divide before this differentiation occurs, and hence how the 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.0700001104
更新日期:2007-03-13 00:00:00
abstract::The bacteriophage P1 Cre/loxP system has become a powerful tool for in vivo manipulation of the genomes of transgenic mice. Although in vitro studies have shown that Cre can catalyze recombination between cryptic "pseudo-loxP" sites in mammalian genomes, to date there have been no reports of loxP-site infidelity in tr...
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.240471297
更新日期:2000-12-05 00:00:00
abstract::Previous work has shown that serotonin induces an increase in membrane K+ conductance in Aplysia neuron R15 and that this response is mediated by cAMP. The present study examines the role of protein phosphorylation in the response to serotonin. A specific inhibitor of cAMP-dependent protein kinase was injected intrace...
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.79.12.3877
更新日期:1982-06-01 00:00:00
abstract::Fas, a member of the tumor necrosis factor receptor family, can induce apoptosis when activated by Fas ligand binding or anti-Fas antibody crosslinking. Genetic studies have shown that a defect in Fas-mediated apoptosis resulted in abnormal development and function of the immune system in mice. A point mutation in 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.92.25.11894
更新日期:1995-12-05 00:00:00
abstract::Harvey and Kirsten murine sarcoma viruses each encode a structurally and functionally related 21-kilodalton protein (p21), which is the transforming protein of each virus. Using probes from the 0.9-kilobase (kb) p21-coding region of each virus (called v-Ha-ras and v-Ki-ras, respectively), we have molecularly cloned fr...
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.79.16.4848
更新日期:1982-08-01 00:00:00
abstract::HD domain phosphohydrolase enzymes are characterized by a conserved set of histidine and aspartate residues that coordinate an active site metallocenter. Despite the important roles these enzymes play in nucleotide metabolism and signal transduction, few have been both biochemically and structurally characterized. Her...
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.1613610113
更新日期:2016-11-29 00:00:00
abstract::The DNA templates containing immediate early (IE) genes of human cytomegalovirus (CMV) were transcribed in vitro by using a HeLa cell extract. When IE region 1, 2, and 3 were used, transcription was detected qualitatively only from IE region 1. Transcription was detected with DNA representing IE region 2 when the IE r...
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.81.3.659
更新日期:1984-02-01 00:00:00
abstract::Molecular adaptation is typically assumed to proceed by sequential fixation of beneficial mutations. In diploids, this picture presupposes that for most adaptive mutations, the homozygotes have a higher fitness than the heterozygotes. Here, we show that contrary to this expectation, a substantial proportion of adaptiv...
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.1114573108
更新日期:2011-12-20 00:00:00
abstract::By considering temperature effects on the mechanical unfolding rates of proteins and RNA, whose energy landscape is rugged, the question posed in the title is answered in the affirmative. Adopting a theory by Zwanzig [Zwanzig, R. (1988) Proc. Natl. Acad. Sci. USA 85, 2029-2030], we show that, because of roughness char...
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.1833310100
更新日期:2003-09-02 00:00:00
abstract::Immunoglobulin sequences were compared by using a technique that takes into account the dissimilarity in physicochemical properties of amino acids. Exterior residues showed greater structural variability than interior residues. High structural variability was found at positions known from crystallographic studies to b...
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.74.6.2551
更新日期:1977-06-01 00:00:00
abstract::Humans respond to foreign antigen by generating plasma Abs and memory B cells (MBCs). The Ab response then declines, sometimes to below the limit of detection. In contrast, MBCs are generally thought to be long-lived. We tested and compared Plasmodium falciparum (Pf)-specific Ab and MBC responses in two populations 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.1200472109
更新日期:2012-05-22 00:00:00
abstract::The Sleeping Beauty (SB) transposon mutagenesis screen is a powerful tool to facilitate the discovery of cancer genes that drive tumorigenesis in mouse models. In this study, we sought to identify genes that functionally cooperate with sonic hedgehog signaling to initiate medulloblastoma (MB), a tumor of the cerebellu...
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.1318639110
更新日期:2013-11-12 00:00:00
abstract::Cotransfection assays were used to show that the members of the GTP-binding protein Gq class of alpha subunits could activate phospholipase C (PLC) beta 2. Similar experiments also demonstrated that G beta 1 gamma 1, G beta 1 gamma 5, and G beta 2 gamma 5 could activate the beta 2 isoform of PLC but not the beta 1 iso...
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.90.11.5297
更新日期:1993-06-01 00:00:00
abstract::Intestinal trefoil factor (ITF) is an essential regulator of colonic epithelial restitution, the rapid migration of colonocytes over mucosal wounds. High levels of ITF are frequently present in colorectal cancers and derived cell lines. Mucosal restitution requires the detachment of epithelium from substrate, which wo...
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.97.2.799
更新日期:2000-01-18 00:00:00