Abstract:
:Synthesis of normal human hemoglobin A, alpha 2 beta 2, is based upon balanced expression of genes in the alpha-globin gene cluster on chromosome 16 and the beta-globin gene cluster on chromosome 11. Full levels of erythroid-specific activation of the beta-globin cluster depend on sequences located at a considerable distance 5' to the beta-globin gene, referred to as the locus-activating or dominant control region. The existence of an analogous element(s) upstream of the alpha-globin cluster has been suggested from observations on naturally occurring deletions and experimental studies. We have identified an individual with alpha-thalassemia in whom structurally normal alpha-globin genes have been inactivated in cis by a discrete de novo 35-kilobase deletion located approximately 30 kilobases 5' from the alpha-globin gene cluster. We conclude that this deletion inactivates expression of the alpha-globin genes by removing one or more of the previously identified upstream regulatory sequences that are critical to expression of the alpha-globin genes.
journal_name
Proc Natl Acad Sci U S Aauthors
Liebhaber SA,Griese EU,Weiss I,Cash FE,Ayyub H,Higgs DR,Horst Jdoi
10.1073/pnas.87.23.9431subject
Has Abstractpub_date
1990-12-01 00:00:00pages
9431-5issue
23eissn
0027-8424issn
1091-6490journal_volume
87pub_type
杂志文章abstract::Three of the four deoxynucleoside kinases required for growth of Lactobacillus acidophilus R-26 exist as heterodimeric pairs specific for deoxyadenosine (dAK) and deoxycytidine (dCK) or dAK and deoxyguanosine (dGK). However, only two tandem genes, dak/dgk, are found, and are expressed only as dAK/dGK in transformed Es...
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.93.25.14385
更新日期:1996-12-10 00:00:00
abstract::The yeast SIN1 protein is a nuclear protein that together with other proteins behaves as a transcriptional repressor of a family of genes. In addition, sin1 mutants are defective in proper mitotic chromosome segregation. In an effort to understand the basis for these phenotypes, we employed the yeast two-hybrid system...
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.93.16.8274
更新日期:1996-08-06 00:00:00
abstract::We have used the polymerase chain reaction to amplify the entire coding region of canine factor IX from a hemophilia B animal. When the sequence was compared to that which codes for normal canine factor IX, a single missense mutation was identified. This mutation (G----A at nucleotide 1477) results in the substitution...
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.86.24.10095
更新日期:1989-12-01 00:00:00
abstract::Sea urchins are a major component of recent marine communities where they exert a key role as grazers and benthic predators. However, their impact on past marine organisms, such as crinoids, is hard to infer in the fossil record. Analysis of bite mark frequencies on crinoid columnals and comprehensive genus-level dive...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
doi:10.1073/pnas.1201573109
更新日期:2012-05-01 00:00:00
abstract::Embryonic stem cells (derived from 129/Ola mice) containing a mutant hypoxanthine phosphoribosyltransferase gene that had been corrected in vitro in a planned manner by homologous recombination were injected into blastocysts obtained from C57BL/6J mice. The injected blastocysts were introduced into pseudopregnant fema...
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.86.22.8927
更新日期:1989-11-01 00:00:00
abstract::Mutations in BRCA1 are present in 45% of families that segregate with susceptibility for breast cancer and in 80-90% of families with both breast and ovarian cancer. Here we report that BRCA1 stimulates artificial and genomic promoter constructs containing p53-responsive elements. This activity of BRCA1 depends on 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.95.5.2302
更新日期:1998-03-03 00:00:00
abstract::Nearly 500 alkaloids have been detected in skin extracts from frogs of the family Dendrobatidae. All seem to have been sequestered unchanged into skin glands from alkaloid-containing arthropods. Ants, beetles, and millipedes seem to be the source of decahydroquinolines, certain izidines, coccinellines, and spiropyrrol...
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.222551599
更新日期:2002-10-29 00:00:00
abstract::Teratocarcinoma is a germ-line carcinoma giving rise to an embryoid tumor with structures derived from the three embryonic layers: mesoderm, endoderm, and ectoderm. Teratocarcinoma is widely used as an in vitro model system to study regulation of cell determination and differentiation during mammalian embryogenesis. M...
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.91.13.6088
更新日期:1994-06-21 00:00:00
abstract::Plants sense phosphate (Pi) deficiency and initiate signaling that controls adaptive responses necessary for Pi acquisition. Herein, evidence establishes that AtSIZ1 is a plant small ubiquitin-like modifier (SUMO) E3 ligase and is a focal controller of Pi starvation-dependent responses. T-DNA insertional mutated allel...
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.0500778102
更新日期:2005-05-24 00:00:00
abstract::Measurements of submicron particles by Fourier transform infrared spectroscopy in 14 campaigns in North America, Asia, South America, and Europe were used to identify characteristic organic functional group compositions of fuel combustion, terrestrial vegetation, and ocean bubble bursting sources, each of which often ...
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.1006461108
更新日期:2011-03-01 00:00:00
abstract::Toll-like receptors (TLRs) have been shown to participate in the recognition of pathogens by the innate immune system, but it is not clear how a restricted family of receptors has the capacity to recognize the wide spectrum of TLR stimuli known to exist. We report here that two members of the TLR family, TLR2 and TLR6...
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.250476497
更新日期:2000-12-05 00:00:00
abstract::Recent single-molecule experiments reveal that mechanical tension on DNA can control both the speed and direction of the DNA polymerase motor. We present a theoretical description of this tension-induced "tuning" and "switching." The internal conformational states of the enzyme motor are represented as nodes, and 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.1033134100
更新日期:2003-08-19 00:00:00
abstract::When we grasp and manipulate an object, populations of tactile nerve fibers become activated and convey information about the shape, size, and texture of the object and its motion across the skin. The response properties of tactile fibers have been extensively characterized in single-unit recordings, yielding importan...
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.1704856114
更新日期:2017-07-11 00:00:00
abstract::G protein-coupled receptors (GPCRs) have been found as monomers but also as dimers or higher-order oligomers in cells. The relevance of the monomeric or dimeric receptor state for G protein activation is currently under debate for class A rhodopsin-like GPCRs. Clarification of this issue requires the availability of 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.0705312104
更新日期:2007-07-17 00:00:00
abstract::Recently, we established that satellite III (TGGAA)n tandem repeats, which occur at the centromeres of human chromosomes, pair with themselves to form an unusual "self-complementary" antiparallel duplex containing (GGA)2 motifs in which two unpaired guanines from opposite strands intercalate between sheared G.A base 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.93.22.12159
更新日期:1996-10-29 00:00:00
abstract::Repeat proteins have recently been of great interest as potential alternatives to immunoglobulin antibodies due to their unique structural and biophysical features. We here present the development of a binding scaffold based on variable lymphocyte receptors, which are nonimmunoglobulin antibodies composed of Leucine-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.1113193109
更新日期:2012-02-28 00:00:00
abstract::Mutations of von Hippel-Lindau disease (VHL) tumor-suppressor gene product (pVHL) are found in patients with dominant inherited VHL syndrome and in the vast majority of sporadic clear cell renal carcinomas. The function of the pVHL protein has not been clarified. pVHL has been shown to form a complex with elongin B an...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 评论,杂志文章
doi:10.1073/pnas.96.22.12436
更新日期:1999-10-26 00:00:00
abstract::Although introduced hemosporidian (malaria) parasites (Apicomplexa: Haemosporida) have hastened the extinction of endemic bird species in the Hawaiian Islands and perhaps elsewhere, little is known about the temporal dynamics of endemic malaria parasite populations. Haemosporidian parasites do not leave informative fo...
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.1702512114
更新日期:2017-06-20 00:00:00
abstract::The long-term viability of a forest industry in the Amazon region of Brazil depends on the maintenance of adequate timber volume and growth in healthy forests. Using extensive high-resolution satellite analyses, we studied the forest damage caused by recent logging operations and the likelihood that logged forests wou...
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.0604093103
更新日期:2006-08-22 00:00:00
abstract::The determination of macromolecular structures requires weighting of experimental evidence relative to prior physical information. Although it can critically affect the quality of the calculated structures, experimental data are routinely weighted on an empirical basis. At present, cross-validation is the most rigorou...
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.0506412103
更新日期:2006-02-07 00:00:00
abstract::The amino acid sequence of blastokinin, also called uteroglobin, has been determined by a combined study of both the intact native molecule and the peptide fragments resulting from tryptic and chymotryptic digestions. Sequence analyses performed by automated methods and by sequential digestion with leucine aminopeptid...
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.75.11.5516
更新日期:1978-11-01 00:00:00
abstract::Microorganisms must sense their environment and rapidly tune their metabolism to ambient conditions to efficiently use available resources. We have identified a gene encoding a response regulator, NblR, that complements a cyanobacterial mutant unable to degrade its light-harvesting complex (phycobilisome), in response...
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.95.18.11008
更新日期:1998-09-01 00:00:00
abstract::DNA was prepared from 15 different mouse and rat cell lines transformed by chemical carcinogens in vitro and in vivo. These DNAs were applied to NIH3T3 mouse fibroblast cultures by using the calcium phosphate transfection technique. DNAs of five donor lines were able to induce foci on the recipient monolayers. Ten oth...
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.76.11.5714
更新日期:1979-11-01 00:00:00
abstract::We report a machine-learning strategy for design of organic structure directing agents (OSDAs) for zeolite beta. We use machine learning to replace a computationally expensive molecular dynamics evaluation of the stabilization energy of the OSDA inside zeolite beta with a neural network prediction. We train the neural...
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.1818763116
更新日期:2019-02-26 00:00:00
abstract::Molecular imaging probes have potential for in vivo identification of apoptosis and other intracellular processes. TcapQ, a cell-penetrating, near-infrared fluorescent peptide probe designed to be optically silent through intramolecular fluorescence quenching and activated by effector caspases, has been previously des...
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.0812884106
更新日期:2009-06-09 00:00:00
abstract::Glutaredoxins (GRXs), also known as thioltransferases, use glutathione as a cofactor for reduction of disulfides in prokaryotes and eukaryotes. We demonstrate that the vaccinia virus O2L open reading frame encodes a functional GRX, as predicted by Johnson et al. [Johnson, G. P., Goebel, S. J., Perkus, M. E., Davis, S....
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.89.15.7060
更新日期:1992-08-01 00:00:00
abstract::The 2012-2015 drought has left California with severely reduced snowpack, soil moisture, ground water, and reservoir stocks, but the impact of this estimated millennial-scale event on forest health is unknown. We used airborne laser-guided spectroscopy and satellite-based models to assess losses in canopy water conten...
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.1523397113
更新日期:2016-01-12 00:00:00
abstract::We have detected a proteolytic mechanism in chloroplasts that selectively and rapidly degrades the imported small subunit of ribulose 1,5-bisphosphate carboxylase when pools of the chloroplast-synthesized large subunit are depleted. This degradation system is constitutively present and appears to be responsible for pr...
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.80.9.2632
更新日期:1983-05-01 00:00:00
abstract::Most teenage fears subside with age, a change that may reflect brain maturation in the service of refined fear learning. Whereas adults clearly demarcate safe situations from real dangers, attenuating fear to the former but not the latter, adolescents' immaturity in prefrontal cortex function may limit their ability 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.1005494108
更新日期:2011-03-15 00:00:00
abstract::Insulin activation of phosphoinositide 3-kinase (PI3K) signaling regulates glucose homeostasis through the production of phosphatidylinositol 3,4,5-trisphosphate (PIP3). The dual-specificity phosphatase and tensin homolog deleted on chromosome 10 (PTEN) blocks PI3K signaling by dephosphorylating PIP3, and is inhibited...
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.1213773111
更新日期:2014-01-07 00:00:00