Abstract:
:Autoantibodies to glutamate decarboxylase 65 (GAD65Ab) are commonly believed to be a major characteristic for type 1 diabetes (T1D). We investigated the presence of GAD65Ab in healthy individuals (n = 238) and first-degree relatives (FDRs) of T1D patients (n = 27) who tested negative for GAD65Ab in conventional RIAs. Sera were applied to affinity columns coated with GAD65-specific mAbs to absorb anti-idiotypic antibodies (anti-Ids). The absorbed sera were analyzed for binding to GAD65 by RIAs. Both healthy individuals and FDRs present GAD65Ab that are inhibited by anti-Id, masking them in conventional detection methods. The presence of GAD65Ab-specific anti-Ids was confirmed by competitive ELISA. Remarkably, T1D patients (n = 54) and Stiff Person Syndrome patients (n = 8) show a specific lack of anti-Ids to disease-associated GAD65Ab epitopes. Purified anti-Ids from healthy individuals and FDRs inhibited the binding of GAD65Ab from T1D patients to GAD65. We conclude that masked GAD65Ab are present in the healthy population and that a lack of particular anti-Ids, rather than GAD65Ab per se, is a characteristic of T1D. The lack of these inhibitory antibodies may contribute to T cell activation by GAD65Ab.
journal_name
Proc Natl Acad Sci U S Aauthors
Oak S,Gilliam LK,Landin-Olsson M,Törn C,Kockum I,Pennington CR,Rowley MJ,Christie MR,Banga JP,Hampe CSdoi
10.1073/pnas.0800578105subject
Has Abstractpub_date
2008-04-08 00:00:00pages
5471-6issue
14eissn
0027-8424issn
1091-6490pii
0800578105journal_volume
105pub_type
杂志文章abstract::Alzheimer's disease is characterized by two primary pathological features: amyloid plaques and neurofibrillary tangles. The interconnection between amyloid and tau aggregates is of intense interest, but mouse models have yet to reveal a direct interrelationship. We now show that NO may be a key factor that connects am...
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.0601075103
更新日期:2006-08-22 00:00:00
abstract::Whether the mate sampling and choice performed by females in nature influences offspring performance is a controversial issue in theory and an open empirical question. Pronghorn (Antilocapra americana) females engage in an obvious and energetically expensive mate sampling process to identify vigorous males. Although 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.0608184103
更新日期:2006-10-31 00:00:00
abstract::Fish stocks experiencing high fishing mortality show a tendency to mature earlier and at a smaller size, which may have a genetic component and therefore long-lasting economic and biological effects. To date, the economic effects of such ecoevolutionary dynamics have not been empirically investigated. Using 70 y of da...
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.1212593110
更新日期:2013-07-23 00:00:00
abstract::The human fungal pathogen Candida albicans shows a significant lag in growth when diluted into fresh minimal medium. This lag is abolished by the addition of conditioned medium from a high-density culture. The active component of conditioned medium is tyrosol, which is released into the medium continuously during grow...
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.0401416101
更新日期:2004-04-06 00:00:00
abstract::Public responses where identical T cell receptors (TCRs) are clonally dominant and shared between different individuals are a common characteristic of CD8(+) T cell-mediated immunity. Focusing on TCR sharing, we analyzed approximately 3,400 TCR beta chains (TCRbetas) from mouse CD8(+) T cells responding to the influen...
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.0608907103
更新日期:2006-12-05 00:00:00
abstract::Myelinated fibers can be demonstrated in thin unstained brain sections of freshly killed uninjected animals. With this method myelinated fibers stand out as clearly as in stained Weigert sections from formalin-fixed brains. Unstained unfixed sections can be viewed under ordinary light within minutes after death of 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.71.3.598
更新日期:1974-03-01 00:00:00
abstract::Lufenuron is an insect growth regulator insecticide mainly used for the control of the cat flea. To understand mechanisms of resistance to lufenuron, we have characterized lufenuron resistance in a natural population of Drosophila melanogaster. In this study we have used precise genetic mapping to identify a mechanism...
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.0503709102
更新日期:2005-09-06 00:00:00
abstract::DEAD-box RNA helicase proteins use the energy of ATP hydrolysis to drive the unwinding of duplex RNA. However, the mechanism that couples ATP utilization to duplex RNA unwinding is unknown. We measured ATP utilization and duplex RNA unwinding by DbpA, a non-processive bacterial DEAD-box RNA helicase specifically 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.0913081107
更新日期:2010-03-02 00:00:00
abstract::A light beam hitting the retina produces an excitatory process; however, around the edge of the light beam, sensory cells are inhibited and lose their sensitivity. This combination of stimulation and inhibition produces a discrepancy between the luminance pattern presented to the eye and the brightness pattern that is...
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.69.4.885
更新日期:1972-04-01 00:00:00
abstract::The Kell blood group is a major antigenic system in human erythrocytes. Kell antigens reside on a 93-kDa membrane glycoprotein that is surface-exposed and associated with the underlying cytoskeleton. We isolated tryptic peptides and, based on the amino acid sequence of one of the peptides and by using the PCR, prepare...
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.88.14.6353
更新日期:1991-07-15 00:00:00
abstract::Poly([14C]adenosine diphosphate ribose) was synthesized from [14C]NAD+ with calf thymus nuclei. The fraction containing poly(adenosine diphosphate ribose) eluted with 0.22--0.40 M phosphate buffer (pH 6.8) from a hydroxylapatite column, was completely hydrolyzed with venom phosphodiesterase, and was separated by DEAE-...
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.76.2.595
更新日期:1979-02-01 00:00:00
abstract::A modification of the polymerase chain reaction has been used to establish the fact that a collection of Staphylococcus aureus toxins are "superantigens," each of which interacts with the T-cell alpha beta receptor of human T cells by means of a specific set of V beta elements. ...
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.86.22.8941
更新日期:1989-11-01 00:00:00
abstract::We developed a "continual engagement" model to better integrate knowledge from policy makers, communities, and researchers with the goal of promoting more effective action to balance poverty alleviation and wildlife conservation in 4 pastoral ecosystems of East Africa. The model involved the creation of a core boundar...
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.0900313106
更新日期:2016-04-26 00:00:00
abstract::The clinical efficacy of local anesthetic and antiarrhythmic drugs is due to their voltage- and frequency-dependent block of Na+ channels. Quaternary local anesthetic analogs such as QX-314, which are permanently charged and membrane-impermeant, effectively block cardiac Na+ channels when applied from either side 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.92.25.11839
更新日期:1995-12-05 00:00:00
abstract::Insig-1 and -2 are closely related proteins of the endoplasmic reticulum (ER) that block proteolytic activation of sterol regulatory element-binding proteins (SREBPs), transcription factors that activate the synthesis of cholesterol and fatty acids in liver and other organs. When cellular cholesterol levels are high, ...
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.0130116100
更新日期:2003-03-18 00:00:00
abstract::It is widely accepted that modern humans originated in sub-Saharan Africa approximately 150-200 thousand years ago (ka), but their route of dispersal across the currently hyperarid Sahara remains controversial. Given that the first modern humans north of the Sahara are found in the Levant approximately 120-90 ka, nort...
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.0804472105
更新日期:2008-10-28 00:00:00
abstract::Through rapid genetic adaptation and natural selection, the Plasmodium falciparum parasite--the deadliest of those that cause malaria--is able to develop resistance to antimalarial drugs, thwarting present efforts to control it. Genome-wide association studies (GWAS) provide a critical hypothesis-generating tool for 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.1210585109
更新日期:2012-08-07 00:00:00
abstract::The phase transition for turbulent diffusion, reported by Avellaneda and Majda [Avellaneda, M. & Majda, A. J. (1994) Philos. Trans. R. Soc. London A 346, 205-233, and several earlier papers], is traced to a modeling assumption in which the energy spectrum of the turbulent fluid is singularly dependent on the viscosity...
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.92.24.11005
更新日期:1995-11-21 00:00:00
abstract::Spermatogonia are the male germ stem cells that continuously produce sperm for the next generation. Spermatogenesis is a complicated process that proceeds through mitotic phase of stem cell renewal and differentiation, meiotic phase, and postmeiotic phase of spermiogenesis. Full recapitulation of spermatogenesis in vi...
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.0308668101
更新日期:2004-05-25 00:00:00
abstract::Since cdc48 mutants were isolated by the first genetic screens for cell division cycle (cdc) mutants in yeast, the requirement of the chaperone-like ATPase Cdc48/p97 during cell division has remained unclear. Here, we discover an unanticipated function for Caenorhabditis elegans CDC-48 in DNA replication linked to cel...
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.0805944105
更新日期:2008-09-02 00:00:00
abstract::Microtubule-associated protein 2 kinase (MAP kinase), which exists in several forms, is a protein serine/threonine kinase that participates in a growth factor-activated protein kinase cascade in which it activates a ribosomal protein S6 kinase (pp90rsk) while being regulated itself by a cytoplasmic factor (MAP kinase ...
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.88.14.6142
更新日期:1991-07-15 00:00:00
abstract::Complement-stimulated granulocytes adhere to and induce significant 51Cr release from endothelial cells in vitro. Platelets were stimulated to undergo release, and these release products significantly enhanced granulocyte-endothelial cell adherence and granulocyte-induced 51Cr release from endothelial cells. Platelet ...
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.79.22.7019
更新日期:1982-11-01 00:00:00
abstract::In the mammalian retina, extensive processing of spatiotemporal and chromatic information occurs. One key principle in signal transfer through the retina is parallel processing. Two of these parallel pathways are the ON- and OFF-channels transmitting light and dark signals. This dual system is created in the outer ple...
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.96.24.14130
更新日期:1999-11-23 00:00:00
abstract::Understanding the origin, nature, and functional significance of complex patterns of neural activity, as recorded by diverse electrophysiological and neuroimaging techniques, is a central challenge in neuroscience. Such patterns include collective oscillations emerging out of neural synchronization as well as highly h...
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.1712989115
更新日期:2018-02-13 00:00:00
abstract::The microsomal triglyceride (TG) transfer protein (MTP) is a heterodimeric lipid transfer protein that catalyzes the transport of triglyceride, cholesteryl ester, and phosphatidylcholine between membranes. Previous studies showing that the proximal cause of abetalipoproteinemia is an absence of MTP indicate that MTP 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.93.21.11991
更新日期:1996-10-15 00:00:00
abstract::Epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and amphiregulin are structurally and functionally related growth regulatory proteins. These secreted polypeptides all bind to the 170-kDa cell-surface EGF receptor, activating its intrinsic kinase activity. However, amphiregulin exhibits dif...
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.87.13.4905
更新日期:1990-07-01 00:00:00
abstract::In the presence of a single-stranded-DNA-binding protein (SSB), the elongation of primed DNA templates by DNA polymerase delta (pol delta) is dependent on ATP and two protein factors, activator 1 (A1) and proliferating cell nuclear antigen (PCNA). We have examined the interaction of these proteins with (dA)4500.(dT)12...
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.87.15.5672
更新日期:1990-08-01 00:00:00
abstract::Regulation of translation is critical for maintaining cellular protein levels, and thus protein homeostasis. The conserved RNA-binding protein CsrA (also called RsmA; for carbon storage regulator and regulator of secondary metabolism, respectively; hereafter called CsrA) represents a well-characterized example of regu...
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.1602425113
更新日期:2016-09-06 00:00:00
abstract::The hippocampus has a well-documented role for spatial navigation across species, but its role for spatial memory in nonnavigational tasks is uncertain. In particular, when monkeys are tested in tasks that do not require navigation, spatial memory seems unaffected by lesions of the hippocampus. However, the interpreta...
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.1320562111
更新日期:2014-03-18 00:00:00
abstract::Adriamycin (doxorubicin) was encapsulated in human erythrocytes by means of a dialysis technique involving transient hypotonic hemolysis followed by isotonic resealing. Up to 1.6 mg of the drug was entrapped per ml of packed erythrocytes, with the efficiency of encapsulation being 60-80%. In vitro incubation of the Ad...
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.83.18.7029
更新日期:1986-09-01 00:00:00