Abstract:
:Nociceptive information is modulated by a large number of endogenous signaling agents that change over the course of recovery from injury. This plasticity makes understanding regulatory mechanisms involved in descending inhibition of pain scientifically and clinically important. Neurons that synthesize the neuropeptide TIP39 project to many areas that modulate nociceptive information. These areas are enriched in its receptor, the parathyroid hormone 2 receptor (PTH2R). We previously found that TIP39 affects several acute nociceptive responses, leading us to now investigate its potential role in chronic pain. Following nerve injury, both PTH2R and TIP39 knockout mice developed less tactile and thermal hypersensitivity than controls and returned to baseline sensory thresholds faster. Effects of hindpaw inflammatory injury were similarly decreased in knockout mice. Blockade of α-2 adrenergic receptors increased the tactile and thermal sensitivity of apparently recovered knockout mice, returning it to levels of neuropathic controls. Mice with locus coeruleus (LC) area injection of lentivirus encoding a secreted PTH2R antagonist had a rapid, α-2 reversible, apparent recovery from neuropathic injury similar to the knockout mice. Ablation of LC area glutamatergic neurons led to local PTH2R-ir loss, and barley lectin was transferred from local glutamatergic neurons to GABA interneurons that surround the LC. These results suggest that TIP39 signaling modulates sensory thresholds via effects on glutamatergic transmission to brainstem GABAergic interneurons that innervate noradrenergic neurons. TIP39's normal role may be to inhibit release of hypoalgesic amounts of norepinephrine during chronic pain. The neuropeptide may help maintain central sensitization, which could serve to enhance guarding behavior.
journal_name
Proc Natl Acad Sci U S Aauthors
Dimitrov EL,Kuo J,Kohno K,Usdin TBdoi
10.1073/pnas.1306342110subject
Has Abstractpub_date
2013-08-06 00:00:00pages
13156-61issue
32eissn
0027-8424issn
1091-6490pii
1306342110journal_volume
110pub_type
杂志文章abstract::Aire is a transcriptional regulator that induces expression of peripheral tissue antigens (PTA) in thymic medullary epithelial cells (MECs), driving immunological self-tolerance in differentiating T cells. To elucidate its mechanistic pathways, we examined its transcriptional impact in MECs in vivo by microarray analy...
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.1119351109
更新日期:2012-01-10 00:00:00
abstract::Human infants are predisposed to rapidly acquire their native language. The nature of these predispositions is poorly understood, but is crucial to our understanding of how infants unpack their speech input to recover the fundamental word-like units, assign them referential roles, and acquire the rules that govern 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.1017617108
更新日期:2011-04-12 00:00:00
abstract::Estrogen receptor alpha (ERalpha) plays a major role in the regulation of neuroendocrine functions and behaviors by estrogens. Although the generation of ERalpha knockout mice advanced our knowledge of ERalpha functions, gene deletion using this method is global and potentially confounded by developmental consequences...
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.0603045103
更新日期:2006-07-05 00:00:00
abstract::The regulation of cellular protein levels is a complex process involving many regulatory mechanisms, each introducing stochastic events, leading to variability of protein levels between isogenic cells. Previous studies have shown that perturbing genes involved in transcription regulation affects the amount of cell-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.1013148108
更新日期:2011-04-12 00:00:00
abstract::Neurons in the cochlear nuclei of duck embryos become responsive to tonal stimuli in an orderly spatial and temporal sequence. Cells responding to lower frequencies are recorded before those responding to higher frequencies. Auditory neurons are spatially arranged according to their characteristic frequencies, indicat...
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.70.6.1795
更新日期:1973-06-01 00:00:00
abstract::Miraculin (MCL) is a homodimeric protein isolated from the red berries of Richadella dulcifica. MCL, although flat in taste at neutral pH, has taste-modifying activity to convert sour stimuli to sweetness. Once MCL is held on the tongue, strong sweetness is sensed over 1 h each time we taste a sour solution. Neverthel...
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.1016644108
更新日期:2011-10-04 00:00:00
abstract::Most current gene transfer methods function satisfactorily in specialized systems involving established cell lines but are often not applicable with nonadherent, primary hematopoietic cells, which are notoriously difficult to transfect. To approach this problem, we have investigated an alternative method of gene trans...
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.87.10.3655
更新日期:1990-05-01 00:00:00
abstract::Mouse teratocarcinoma cells induced to differentiate in vitro undergo a massive (30%) demethylation of DNA. A similar undermethylation is also observed in the mouse extraembryonic membranes, the yolk sac and placenta. In both cases, the decrease in methyl moieties occurs at a large number of CpG sites spread out over ...
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.81.8.2275
更新日期:1984-04-01 00:00:00
abstract::Massively parallel signature sequencing (MPSS) generates millions of short sequence tags corresponding to transcripts from a single RNA preparation. Most MPSS tags can be unambiguously assigned to genes, thereby generating a comprehensive expression profile of the tissue of origin. From the comparison of MPSS data fro...
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.0502583102
更新日期:2005-05-31 00:00:00
abstract::Rotifers of the asexual class Bdelloidea are unusual in possessing two or more divergent copies of every gene that has been examined. Phylogenetic analysis of the heat-shock gene hsp82 and the TATA-box-binding protein gene tbp in multiple bdelloid species suggested that for each gene, each copy belonged to one of two ...
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.2136686100
更新日期:2004-02-10 00:00:00
abstract::The utility of adenovirus (Ad) vectors for gene transduction can be limited by receptor specificity. We developed a gene-delivery vehicle in which the potent Ad5 vector was genetically reengineered to display the mucosal-targeting sigma1 protein of reovirus type 3 Dearing (T3D). A sigma1 construct containing all but a...
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.0400542101
更新日期:2004-04-20 00:00:00
abstract::The product of the Nijmegen breakage syndrome gene (NBS1) plays crucial roles in DNA damage response through its association with many proteins, including MRE11 and RAD50. However, it remains to be determined exactly how NBS1 accumulates at or near DNA double-strand breaks. Here we report that MDC1 directly binds to N...
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.0802885105
更新日期:2008-08-12 00:00:00
abstract::DNA topoisomerase I (top1) is the target of potent anticancer agents, including camptothecins and DNA intercalators, which reversibly stabilize (trap) top1 catalytic intermediates (cleavage complexes). The aim of the present study was to define the structural relationship between the site(s) of covalently bound interc...
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.190312697
更新日期:2000-09-26 00:00:00
abstract::We have used site-directed mutagenesis of cloned Moloney murine leukemia virus (MuLV) DNA to define a function encoded in the 3' region of the viral pol gene and required for efficient integration of viral DNA. One mutant, MuLV-SF1, contained a single base substitution (C to T at base 4950) that resulted in an arginin...
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.81.20.6461
更新日期:1984-10-01 00:00:00
abstract::The primary obstacle to producing renewable fuels from lignocellulosic biomass is a plant's recalcitrance to releasing sugars bound in the cell wall. From a sample set of wood cores representing 1,100 individual undomesticated Populus trichocarpa trees, 47 extreme phenotypes were selected across measured lignin 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.1009252108
更新日期:2011-04-12 00:00:00
abstract::Well-differentiated liposarcoma (WDLPS), one of the most common human sarcomas, is poorly responsive to radiation and chemotherapy, and the lack of animal models suitable for experimental analysis has seriously impeded functional investigation of its pathobiology and development of effective targeted therapies. Here, ...
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.1106127108
更新日期:2011-09-27 00:00:00
abstract::Recent laboratory studies have demonstrated that isoprene oxidation products can partition to atmospheric aerosols by reacting with condensed phase sulfuric acid, forming low-volatility organosulfate compounds. We have identified organosulfate compounds in free tropospheric aerosols by single particle mass spectrometr...
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.1012561107
更新日期:2010-12-14 00:00:00
abstract::Protected areas are crucial for biodiversity conservation because they provide safe havens for species threatened by land-use change and resulting habitat loss. However, protected areas are only effective when they stop habitat loss within their boundaries, and are connected via corridors to other wild areas. The effe...
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.0911131107
更新日期:2010-01-12 00:00:00
abstract::Transcripts from mitochondrial (maxicircle) genes of kinetoplastid organisms undergo RNA editing characterized by a series of reactions that insert and delete uridine nucleotides within the sequence of the pre-mRNAs. Guide RNAs, which complement fully edited mRNAs, provide the information for the edited sequence by 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.91.5.1776
更新日期:1994-03-01 00:00:00
abstract::Understanding the gene-expression patterns during liver regeneration may help to reveal how regenerative processes are initiated and controlled as well as shed new light onto processes that lead to liver disease. Using high-density oligonucleotide arrays, we have examined the gene-expression program in the livers of 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.122359899
更新日期:2002-08-20 00:00:00
abstract::Targeting neuroendocrine tumors expressing somatostatin receptor subtypes (sst) with radiolabeled somatostatin agonists is an established diagnostic and therapeutic approach in oncology. While agonists readily internalize into tumor cells, permitting accumulation of radioactivity, radiolabeled antagonists do not, and ...
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.0607761103
更新日期:2006-10-31 00:00:00
abstract::Morphological studies have provided ample evidence for synaptic connections between cerebellar Purkinje cells (PCs), but the functional properties of these synapses remain elusive. We report on direct recordings of synaptically connected PCs in mice cerebellar slices. In PCs filled with a fluorescent dye to aid axon v...
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.0707489104
更新日期:2007-11-06 00:00:00
abstract::Two decades after the discovery of the first animal microRNA (miRNA), the number of miRNAs in animal genomes remains a vexing question. Here, we report findings from analyzing 1,323 short RNA sequencing samples (RNA-seq) from 13 different human tissue types. Using stringent thresholding criteria, we identified 3,707 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.1420955112
更新日期:2015-03-10 00:00:00
abstract::Maximum likelihood estimators and other direct optimization-based estimators dominated statistical estimation and prediction for decades. Yet, the principled foundations supporting their dominance do not apply to the discrete high-dimensional inference problems of the 21st century. As it is well known, statistical dec...
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.0712329105
更新日期:2008-03-04 00:00:00
abstract::The structure of the proline-specific aminopeptidase (EC 3.4.11.9) from Escherichia coli has been solved and refined for crystals of the native enzyme at a 2.0-A resolution, for a dipeptide-inhibited complex at 2.3-A resolution, and for a low-pH inactive form at 2.7-A resolution. The protein crystallizes as a tetramer...
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.95.7.3472
更新日期:1998-03-31 00:00:00
abstract::Signaling lymphocytic activation molecule family 3 (SLAMF3/Ly9) is a coregulatory molecule implicated in T-cell activation and differentiation. Systemic lupus erythematosus (SLE) is characterized by aberrant T-cell activation and compromised IL-2 production, leading to abnormal regulatory T-cell (Treg) development/fun...
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.1605081113
更新日期:2016-08-16 00:00:00
abstract::By optically probing with a focused, low-power laser beam, we measured the spontaneous deflection fluctuations of the sensory hair bundles on frog saccular hair cells with a sensitivity of about 1 pm/square root of Hz. The preparation was illuminated by two orthogonally polarized laser beams separated by only about 0....
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.86.14.5371
更新日期:1989-07-01 00:00:00
abstract::Using tunicamycin, we have investigated the role of glycoproteins in membrane transport. Tunicamycin is a glucosamine-containing antibiotic that specifically inhibits dolichol pyrophosphate-mediated glycosylation of asparaginyl residues of glycoproteins. Inhibition of protein glycosylation in chick embryo fibroblasts ...
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.76.2.791
更新日期:1979-02-01 00:00:00
abstract::Previous studies have identified nuclear matrix attachment regions (MARs) that are closely associated with transcriptional enhancers in the IgH, Igkappa, and T cell receptor (TCR) beta loci, but have yielded conflicting information regarding their functional significance. In this report, a combination of in vitro and ...
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.96.21.11970
更新日期:1999-10-12 00:00:00
abstract::Recently, hepatic peroxisome proliferator-activated receptor (PPAR)γ has been implicated in hepatic lipid accumulation. We found that the C3H mouse strain does not express PPARγ in the liver and, when subject to a high-fat diet, is resistant to hepatic steatosis, compared with C57BL/6 (B6) mice. Adenoviral PPARγ2 inje...
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.1203218109
更新日期:2012-08-21 00:00:00