Abstract:
:Recent work with prion diseases and synucleinopathies indicates that accurate diagnostic methods for protein-folding diseases can be based on the ultrasensitive, amplified measurement of pathological aggregates in biospecimens. A better understanding of the physicochemical factors that control the seeded polymerization of such aggregates, and their amplification in vitro, should allow improvements in existing assay platforms, as well as the development of new assays for other proteopathic aggregates. Here, we systematically investigated the effects of the ionic environment on the polymerization of tau, α-synuclein, and the prion protein (PrP) induced by aggregates in biospecimens. We screened salts of the Hofmeister series, a relative ordering of strongly and weakly hydrated salts that tend to precipitate or solubilize proteins. We found that sensitivities of tau-based assays for Alzheimer's seeds and PrP-based assays for prions were best in weakly hydrated anions. In contrast, we saw an inverse trend with different tau-based assays, improving detection sensitivity for progressive supranuclear palsy seeds by ≈106 Hofmeister analysis also improved detection of sporadic Creutzfeldt-Jakob disease prions in human nasal brushings and chronic wasting disease prions in deer-ear homogenates. Our results demonstrate strong and divergent influences of ionic environments on the amplification and detection of proteopathic seeds as biomarkers for protein-folding diseases.
journal_name
Proc Natl Acad Sci U S Aauthors
Metrick MA 2nd,do Carmo Ferreira N,Saijo E,Hughson AG,Kraus A,Orrú C,Miller MW,Zanusso G,Ghetti B,Vendruscolo M,Caughey Bdoi
10.1073/pnas.1909322116subject
Has Abstractpub_date
2019-11-12 00:00:00pages
23029-23039issue
46eissn
0027-8424issn
1091-6490pii
1909322116journal_volume
116pub_type
杂志文章abstract::Protein ubiquitination plays an important role in ATP-dependent protein turnover, and it also may regulate other cellular events. Covalent attachment of ubiquitin to other proteins is catalyzed by three different enzymes, E1, E2, and E3. We have previously shown that protein ubiquitination can be regulated by phosphor...
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.91.24.11601
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abstract::Experimental circular dichroic (CD) spectra of three proteins have been combined with estimates of the content of peptide-chain structural modes obtained from x-ray diffraction studies of the same proteins. Solution of the simultaneous equations at a series of wavelengths permits the construction of a CD spectrum for ...
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.68.5.969
更新日期:1971-05-01 00:00:00
abstract::Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by progressive ectopic mineralization of the skin, eyes, and arteries, for which no effective treatment exists. PXE is caused by inactivating mutations in the gene encoding ATP-binding cassette sub-family C member 6 (ABCC6), an ATP-dependen...
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.1319582110
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abstract::In all but the poorest countries of South Asia and Africa, the supply and quality of food will rise to meet the demand. Biotechnology, accelerated by genomics, will create wealth for both producers and consumers by reducing the cost and increasing the quality of food. Famine and malnutrition in the poorest countries m...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.95.5.1986
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abstract::Small solutes affect protein and nucleic acid processes because of favorable or unfavorable chemical interactions of the solute with the biopolymer surface exposed or buried in the process. Large solutes also exclude volume and affect processes where biopolymer molecularity and/or shape changes. Here, we develop an an...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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abstract::Indoor residual spraying (IRS) is used to control visceral leishmaniasis (VL) in India, but it is poorly quality assured. Quality assurance was performed in eight VL endemic districts in Bihar State, India, in 2014. Residual dichlorodiphenyltrichloroethane (DDT) was sampled from walls using Bostik tape discs, and DDT ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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abstract::Two differentiation antigens of spermatogenesis in the mouse are defined by monoclonal antibodies from hybridomas produced between the myeloma P3-X63Ag8 and spleen lymphocytes immunized with syngeneic testis cells. These antigens are on testis cells, and not liver, kidney, brain, spleen, or whole ovary. They are speci...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1979-01-01 00:00:00
abstract::Most variation in behavior has a genetic basis, but the processes determining the level of diversity at behavioral loci are largely unknown for natural populations. Expression of arginine vasopressin receptor 1a (Avpr1a) and oxytocin receptor (Oxtr) in specific regions of the brain regulates diverse social and reprodu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2017-04-04 00:00:00
abstract::Initiation of bovine papillomavirus (BPV) DNA synthesis in vivo and in vitro depends on the interaction of the viral initiator protein E1 with the replication origin (ori+ DNA). The viral E2 protein assists this interaction, resulting in a cooperative assembly of both proteins on the replication origin. Using gel mobi...
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.91.19.8895
更新日期:1994-09-13 00:00:00
abstract::The Mediator complex forms the bridge between transcriptional activators and RNA polymerase II. Mediator subunit Med1/TRAP220 is a key component of Mediator originally found to associate with nuclear hormone receptors. Med1 deficiency causes lethality at embryonic day 11.5 because of defects in heart and placenta deve...
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.0604494103
更新日期:2006-12-05 00:00:00
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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.94.6.2478
更新日期:1997-03-18 00:00:00
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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.2017138117
更新日期:2020-11-03 00:00:00
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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.1412059112
更新日期:2015-03-10 00:00:00
abstract::PIF3 is a phytochrome-interacting basic helix-loop-helix transcription factor that negatively regulates light responses, including hypocotyl elongation, cotyledon opening, and hypocotyl negative gravitropism. However, the role of PIF3 in chlorophyll biosynthesis has not been clearly defined. Here, we show that PIF3 al...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.0812219106
更新日期:2009-05-05 00:00:00
abstract::Palmitoylation is a common lipid modification known to regulate the functional properties of various proteins and is a vital step in the biosynthesis of voltage-activated sodium (Nav) channels. We discovered a mutation in an intracellular loop of rNav1.2a (G1079C), which results in a higher apparent affinity for exter...
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.1108497108
更新日期:2011-12-13 00:00:00
abstract::Antibody against carcinoembryonic antigen (CEA) was conjugated with p-[1,2-dicarba-closo-[1-3H]do-decaboran(12)-2-yl] benzenediazonium ion by an azo-coupling reaction, resulting in 30 boron atoms per IgG molecule with no loss of antibody protein. Antibody immunoreactivity was not appreciably affected by this conjugati...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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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.85.6.1917
更新日期:1988-03-01 00:00:00
abstract::Obligate intracellular pathogens such as Leishmania specifically target host phagocytes for survival and replication. Phosphoinositide 3-kinase γ (PI3Kγ), a member of the class I PI3Ks that is highly expressed by leukocytes, controls cell migration by initiating actin polymerization and cytoskeletal reorganization, wh...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2012-01-24 00:00:00
abstract::Dihydropteridine reductase (EC 1.6.99.7) is a member of the recently identified family of proteins known as short-chain dehydrogenases. When the x-ray structure of dihydropteridine reductase is correlated with conserved amino acid sequences characteristic of this enzyme class, two important common structural regions c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.91.12.5582
更新日期:1994-06-07 00:00:00
abstract::In virtually all multicellular eukaryotes, mitochondria are transmitted exclusively through one parent, usually the mother. In this short review, we discuss some of the major consequences of uniparental transmission of mitochondria, including deleterious effects in males and selection for increased transmission throug...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
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更新日期:2015-08-18 00:00:00
abstract::A microfluidic mixer is applied to study the kinetics of calmodulin conformational changes upon Ca2+ binding. The device facilitates rapid, uniform mixing by decoupling hydrodynamic focusing from diffusive mixing and accesses time scales of tens of microseconds. The mixer is used in conjunction with multiphoton micros...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.0710810105
更新日期:2008-01-15 00:00:00
abstract::Genomic clones of the human non-N-methyl-D-aspartate (non-NMDA) glutamate receptor subunit GluR5 were isolated by high-stringency screening of a cosmid library using the rat cDNA as a probe. The chromosomal localization of the human GluR5 gene has been established. Southern hybridization of DNA isolated from mapping 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.90.1.178
更新日期:1993-01-01 00:00:00
abstract::We have determined the nucleotide sequences of cDNAs encoding the precursor of the beta subunit of rat lutropin, a polypeptide hormone that regulates gonadal function, including the development of gametes and the production of steroid sex hormones. The cDNAs were prepared from poly(A)+ RNA derived from the pituitary g...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.80.15.4649
更新日期:1983-08-01 00:00:00
abstract::We have cloned a full-length cDNA coding for human alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) from a human liver cDNA library constructed in phage lambda gt11. The library was screened by using a rabbit antibody against human ADH as a first probe, by the modified method of Young and Davis [Yo...
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.82.9.2703
更新日期:1985-05-01 00:00:00
abstract::At the synapse, presynaptic membranes specialized for vesicular traffic are linked to postsynaptic membranes specialized for signal transduction. The mechanisms that connect pre- and postsynaptic membranes into synaptic junctions are unknown. Neuroligins and beta-neurexins are neuronal cell-surface proteins that bind ...
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.96.3.1100
更新日期:1999-02-02 00:00:00
abstract::The c-fos protooncogene is transcriptionally activated by a wide variety of agents including serum, growth factors, and phorbol esters. This induction is rapid and transient and is mediated through a number of identified promoter elements. Growth hormone (GH) is also known to induce transcription of c-fos in a variety...
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.90.14.6721
更新日期:1993-07-15 00:00:00