Abstract:
:We describe a functional profiling strategy to identify and characterize subtypes of neurons present in a peripheral ganglion, which should be extendable to neurons in the CNS. In this study, dissociated dorsal-root ganglion neurons from mice were exposed to various pharmacological agents (challenge compounds), while at the same time the individual responses of >100 neurons were simultaneously monitored by calcium imaging. Each challenge compound elicited responses in only a subset of dorsal-root ganglion neurons. Two general types of challenge compounds were used: agonists of receptors (ionotropic and metabotropic) that alter cytoplasmic calcium concentration (receptor-agonist challenges) and compounds that affect voltage-gated ion channels (membrane-potential challenges). Notably, among the latter are K-channel antagonists, which elicited unexpectedly diverse types of calcium responses in different cells (i.e., phenotypes). We used various challenge compounds to identify several putative neuronal subtypes on the basis of their shared and/or divergent functional, phenotypic profiles. Our results indicate that multiple receptor-agonist and membrane-potential challenges may be applied to a neuronal population to identify, characterize, and discriminate among neuronal subtypes. This experimental approach can uncover constellations of plasma membrane macromolecules that are functionally coupled to confer a specific phenotypic profile on each neuronal subtype. This experimental platform has the potential to bridge a gap between systems and molecular neuroscience with a cellular-focused neuropharmacology, ultimately leading to the identification and functional characterization of all neuronal subtypes at a given locus in the nervous system.
journal_name
Proc Natl Acad Sci U S Aauthors
Teichert RW,Smith NJ,Raghuraman S,Yoshikami D,Light AR,Olivera BMdoi
10.1073/pnas.1118833109subject
Has Abstractpub_date
2012-01-31 00:00:00pages
1388-95issue
5eissn
0027-8424issn
1091-6490pii
1118833109journal_volume
109pub_type
杂志文章abstract::DNA was extracted from the remains of 35 ground sloths from various parts of North and South America. Two specimens of Mylodon darwinii, a species that went extinct at the end of the last glaciation, yielded amplifiable DNA. However, of the total DNA extracted, only approximately 1/1000 originated from the sloth, wher...
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.93.1.181
更新日期:1996-01-09 00:00:00
abstract::The circadian clock is a global regulatory mechanism that controls the expression of 50 to 80% of transcripts in mammals. Some of the genes controlled by the circadian clock are oncogenes or tumor suppressors. Among these Myc has been the focus of several studies which have investigated the effect of clock genes and 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.2011225117
更新日期:2020-09-01 00:00:00
abstract::The major histocompatibility complex-encoded class I molecule, a noncovalent dimer of a polymorphic 45-kDa heavy chain and a nonpolymorphic 12-kDa beta 2-microglobulin (beta 2m) light chain, binds peptide antigen prior to its interaction with T-cell antigen receptors. We report here that the binding in aqueous solutio...
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.89.6.2242
更新日期:1992-03-15 00:00:00
abstract::The glycoprotein I complex, consisting of two polypeptides of Mr 210,000 and 150,000, was isolated from human platelet membranes by wheat germ lectin affinity chromatography. Glycocalicin, a soluble loosely bound membrane glycoprotein of Mr 150,000 related to the glycoprotein I system, was also purified. The isolated ...
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.76.6.2952
更新日期:1979-06-01 00:00:00
abstract::Somatic mutation and neoplastic transformation of diploid Syrian hamster embryo cells were examined concomitantly. Mutations induced by benzo[a]pyrene and N-methyl-N'-nitro-N-nitrosoguanidine were quantitated at the hypoxanthine phosphoribosyltransferase and Na(+)/K(+) ATPase loci and compared to phenotypic transforma...
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.75.7.3297
更新日期:1978-07-01 00:00:00
abstract::Diarthrodial joints are essential for load bearing and locomotion. Physiologically, articular cartilage sustains millions of cycles of mechanical loading. Chondrocytes, the cells in cartilage, regulate their metabolic activities in response to mechanical loading. Pathological mechanical stress can lead to maladaptive ...
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.1414298111
更新日期:2014-11-25 00:00:00
abstract::The x-ray structure of rubredoxin has been refined by energy minimization. The computed structure is constrained to have standard bond lengths, bond angles, and planar trans peptide groups. Also, since most of the steric overlaps have been relieved, it has a very low energy. As judged by the root mean square (RMS) dev...
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.71.9.3736
更新日期:1974-09-01 00:00:00
abstract::Threats to species from commercial fishing are rarely identified until species have suffered large population declines, by which time remedial actions can have severe economic consequences, such as closure of fisheries. Many of the species most threatened by fishing are caught in multispecies fisheries, which can rema...
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.1314472110
更新日期:2013-10-01 00:00:00
abstract::The objective of this study has been to determine which Na,K-ATPase isoforms are expressed in red blood cells and whether kinetic differences in the uncoupled sodium efflux mode between the human red blood cell Na,K-ATPase and other preparations can be explained by differences in the underlying subunit composition. To...
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.94.11.5943
更新日期:1997-05-27 00:00:00
abstract::Activator 1 (A1; also called replication factor C), in conjunction with proliferating-cell nuclear antigen (PCNA), is essential for the elongation of primed DNA templates by DNA polymerases delta and epsilon. A1 contains five distinct subunits of 145, 40, 38, 37, and 36.5 kDa. Here we describe the isolation, 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.89.7.2516
更新日期:1992-04-01 00:00:00
abstract::Fluorescence imaging in the second near-infrared window (NIR-II, 1,000-1,700 nm) features deep tissue penetration, reduced tissue scattering, and diminishing tissue autofluorescence. Here, NIR-II fluorescent probes, including down-conversion nanoparticles, quantum dots, single-walled carbon nanotubes, and organic dyes...
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.1521175113
更新日期:2016-05-10 00:00:00
abstract::We have previously described a gene delivery system based upon the receptor-mediated endocytosis of DNA complexed with transferrin-polycation conjugates. This delivery system has been found to be very effective for both the internalization and the expression of genetic material in cells that have many transferrin rece...
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.88.10.4255
更新日期:1991-05-15 00:00:00
abstract::Transferrin, a nonheme iron-binding protein, is polymorphic in most vertebrate species that have been examined. In pigeons, it is controlled by an autosomal gene, with two known codominant alleles, Tf(A) and Tf(B). The two alleles are found in nearly equal frequencies and the three genotypes are at Hardy-Weinberg equi...
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.69.2.326
更新日期:1972-02-01 00:00:00
abstract::Beneficial mutations are the driving force of adaptive evolution. In asexual populations, the identification of beneficial alleles is confounded by the presence of genetically linked hitchhiker mutations. Parallel evolution experiments enable the recognition of common targets of selection; yet these targets are inhere...
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.1702314114
更新日期:2017-08-01 00:00:00
abstract::Immunoreactive and bioreactive corticotropin (ACTH-like) activities have been detected in the median eminence and remaining medial basal hypothalamus of both normal and hypophysectomized adult male rats: bioreactive ACTH (pg/100 mug of protein) 1028 in median eminence and 1289 in medial basal hypothalamus; immunoreact...
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.74.2.648
更新日期:1977-02-01 00:00:00
abstract::Signal transductions by the dual-function CXCR4 and CCR5 chemokine receptors/HIV type 1 (HIV-1) coreceptors were electrophysiologically monitored in Xenopus laevis oocytes that also coexpressed the viral receptor CD4 and a G protein-coupled inward-rectifying K+ channel (Kir 3.1). Large Kir 3.1-dependent currents gener...
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.95.14.8005
更新日期:1998-07-07 00:00:00
abstract::Deficiency of acyl CoA:cholesterol acyltransferase 2 (ACAT2) in mice results in a reduction in cholesterol ester synthesis in the small intestine and liver, which in turn limits intestinal cholesterol absorption, hepatic cholesterol gallstone formation, and the accumulation of cholesterol esters in the plasma lipoprot...
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.0336398100
更新日期:2003-02-04 00:00:00
abstract::Reptiles and fish have robust regenerative powers for tooth renewal. However, extant mammals can either renew their teeth one time (diphyodont dentition) or not at all (monophyodont dentition). Humans replace their milk teeth with permanent teeth and then lose their ability for tooth renewal. Here, we study tooth rene...
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.1213202110
更新日期:2013-05-28 00:00:00
abstract::Phalloidin, a toxic bicyclic peptide of rapid action from the toadstool, Amanita phalloides, gives rise to polymerization of G-actin to filamentous structures (Ph-actin) in a medium of low ionic strength. Ph-actin closely resembles the microfilaments found in liver membrane fractions (Ph-filaments) after in vivo or in...
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.71.7.2803
更新日期:1974-07-01 00:00:00
abstract::The spleen from a patient with adult Gaucher's disease was shown to be deficient in a beta-glucosidase (EC 3.2.1.21) isoenzyme that has optimal activity at pH 4.0-4.3, and is stimulated by 0.02% Triton X-100. A mixture of spleen homogenates from a control and from the patient contained beta-glucosidase activity equiva...
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.68.11.2810
更新日期:1971-11-01 00:00:00
abstract::Behavioral sensitization of the gill-withdrawal reflex of Aplysia is caused by presynaptic facilitation at the synapses of the mechanoreceptor sensory neurons of the reflex onto the motor neurons and interneurons. The presynaptic facilitation has been shown to be simulated by serotonin (the putative presynaptic facili...
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.77.11.6912
更新日期:1980-11-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease of motor neurons. The inherited form of the disease, familial ALS, represents 5-10% of the total cases, and the best documented of these are due to lesions in SOD1, the gene encoding copper-zinc superoxide dismutase (CuZnSOD). The mechanism by w...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.0730423100
更新日期:2003-04-01 00:00:00
abstract::TGF-β activated kinase 1 (TAK1) is a critical signaling hub responsible for translating antigen binding signals to immune receptors for the activation of the AP-1 and NF-κB master transcriptional programs. Despite its importance, known substrates of TAK1 are limited to kinases of the MAPK and IKK families and include ...
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.1608355113
更新日期:2016-08-16 00:00:00
abstract::We present a simple molecular indexing method for quantitative targeted RNA sequencing, in which mRNAs of interest are selectively captured from complex cDNA libraries and sequenced to determine their absolute concentrations. cDNA fragments are individually labeled so that each molecule can be tracked from the origina...
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.1323732111
更新日期:2014-02-04 00:00:00
abstract::Antisense RNA to the 27/32-kDa rat liver gap junction (GJ) protein was used to explore the role of GJs in preimplantation embryos. When all blastomeres of two- and four-cell embryos were injected with GJ antisense RNA, the percentage of embryos compacted at 60 hr of development was reduced to less than 20%, while 90% ...
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.86.14.5444
更新日期:1989-07-01 00:00:00
abstract::Population intelligence quotients increased throughout the 20th century-a phenomenon known as the Flynn effect-although recent years have seen a slowdown or reversal of this trend in several countries. To distinguish between the large set of proposed explanations, we categorize hypothesized causal factors by whether 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.1718793115
更新日期:2018-06-26 00:00:00
abstract::p70 S6 kinase (p70(S6k)) is a mitogen-activated protein kinase that plays a central role in the control of mRNA translation. It physiologically phosphorylates the S6 protein of the 40s ribosomal subunit in response to mitogenic stimuli and is a downstream component of the rapamycin-sensitive pathway, which includes 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.95.14.8351
更新日期:1998-07-07 00:00:00
abstract::During neurogenesis of the mammalian neocortex, neural progenitor cells divide to generate daughter cells that either become neurons or remain as progenitor cells. The mouse numb (m-numb) gene encodes a membrane-associated protein that is asymmetrically localized to the apical cell membrane of dividing cortical progen...
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.97.12.6844
更新日期:2000-06-06 00:00:00
abstract::hK7 or human stratum corneum chymotryptic enzyme belongs to the human tissue kallikrein (hKs) serine proteinase family and is strongly expressed in the upper layers of the epidermis. It participates in skin desquamation but is also implicated in diverse skin diseases and is a potential biomarker of ovarian cancer. 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.0707811104
更新日期:2007-10-09 00:00:00
abstract::Most paleo-episodes of ocean acidification (OA) were either too slow or too small to be instructive in predicting near-future impacts. The end-Cretaceous event (66 Mya) is intriguing in this regard, both because of its rapid onset and also because many pelagic calcifying species (including 100% of ammonites and more 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.1418604112
更新日期:2015-05-26 00:00:00