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101.
Zeilhofer HU 《Cellular and molecular life sciences : CMLS》2005,62(18):2027-2035
Alterations in synaptic transmission within the spinal cord dorsal horn play a key role in the development of pathological pain. While N-methyl-D-aspartate (NMDA) receptors and activity-dependent synaptic plasticity have been the focus of research for many years, recent evidence attributes very specific functions to inhibitory glycinergic and γ-aminobutyric acid (GABA)-ergic neurotransmission in the generation of inflammatory and neuropathic pain. The central component of inflammatory pain originates from a disinhibition of dorsal horn neurons, which are relieved from glycinergic neurotransmission by the inflammatory mediator prostaglandin E2 (PGE2). PGE2 activates prostaglandin E receptors of the EP2 subtype and leads to a protein kinase A-dependent phosphorylation and inhibition of glycine receptors containing the α3 subunit (GlyRα3). This GlyRα3 is distinctly expressed in the superficial dorsal horn, where nociceptive afferents terminate. Other but probably very similar disinhibitory mechanisms may well contribute to abnormal pain occurring after peripheral nerve injury.Received 11 March 2005; received after revision 1 April 2005; accepted 19 April 2005 相似文献
102.
Monoclonal antibodies show that neurofibrillary tangles and neurofilaments share antigenic determinants 总被引:49,自引:0,他引:49
B H Anderton D Breinburg M J Downes P J Green B E Tomlinson J Ulrich J N Wood J Kahn 《Nature》1982,298(5869):84-86
103.
Conclusions The total proton load found in these ecosystems exceeds by far the known rates of buffering in soils by silicate weathering and release of basic cations (see above).Under the present proton load most forest soils will therefore acidify and besides losses of nutrients the occurrence of possible toxic ions in the soil unavoidable (Al-buffer range)20, 21.The proportion of the total proton load of the soil that is represented by the internal production emphasizes the importance of acid deposition as main cause of soil acidification and destabilization of forest ecosystems under Central European conditions. 相似文献
104.
105.
Generation of pluripotent stem cells from adult human testis 总被引:2,自引:0,他引:2
Conrad S Renninger M Hennenlotter J Wiesner T Just L Bonin M Aicher W Bühring HJ Mattheus U Mack A Wagner HJ Minger S Matzkies M Reppel M Hescheler J Sievert KD Stenzl A Skutella T 《Nature》2008,456(7220):344-349
Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of these cells revealed many similarities to human embryonic stem cells, and the germline stem cells produced teratomas after transplantation into immunodeficient mice. The human adult germline stem cells differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of human embryonic stem cells. We conclude that the generation of human adult germline stem cells from testicular biopsies may provide simple and non-controversial access to individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells. 相似文献
106.
Roell W Lewalter T Sasse P Tallini YN Choi BR Breitbach M Doran R Becher UM Hwang SM Bostani T von Maltzahn J Hofmann A Reining S Eiberger B Gabris B Pfeifer A Welz A Willecke K Salama G Schrickel JW Kotlikoff MI Fleischmann BK 《Nature》2007,450(7171):819-824
Ventricular tachyarrhythmias are the main cause of sudden death in patients after myocardial infarction. Here we show that transplantation of embryonic cardiomyocytes (eCMs) in myocardial infarcts protects against the induction of ventricular tachycardia (VT) in mice. Engraftment of eCMs, but not skeletal myoblasts (SMs), bone marrow cells or cardiac myofibroblasts, markedly decreased the incidence of VT induced by in vivo pacing. eCM engraftment results in improved electrical coupling between the surrounding myocardium and the infarct region, and Ca2+ signals from engrafted eCMs expressing a genetically encoded Ca2+ indicator could be entrained during sinoatrial cardiac activation in vivo. eCM grafts also increased conduction velocity and decreased the incidence of conduction block within the infarct. VT protection is critically dependent on expression of the gap-junction protein connexin 43 (Cx43; also known as Gja1): SMs genetically engineered to express Cx43 conferred a similar protection to that of eCMs against induced VT. Thus, engraftment of Cx43-expressing myocytes has the potential to reduce life-threatening post-infarct arrhythmias through the augmentation of intercellular coupling, suggesting autologous strategies for cardiac cell-based therapy. 相似文献
107.
Michel M. Dacorogna Cindy L. Gauvreau Ulrich A. Müller Richard B. Olsen Olivier V. Pictet 《Journal of forecasting》1996,15(3):203-227
A forecasting model based on high-frequency market makers quotes of financial instruments is presented. The statistical behaviour of these time series leads to discussion of the appropriate time scale for forecasting. We introduce variable time scales in a general way and define the new concept of intrinsic time. The latter reflects better the actual trading activity. Changing time scale means forecasting in two steps, first an intrinsic time forecast against physical time, then a price forecast against intrinsic time. The forecasting model consists, for both steps, of a linear combination of non-linear price-based indicators. The indicator weights are continuously re-optimized through a modified linear regression on a moving sample of past prices. The out-of-sample performance of this algorithm is reported on a set of important FX rates and interest rates over many years. It is remarkably consistent. Results for short horizons as well as techniques to measure this performance are discussed. 相似文献
108.
A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1 总被引:16,自引:0,他引:16
Hampe J Franke A Rosenstiel P Till A Teuber M Huse K Albrecht M Mayr G De La Vega FM Briggs J Günther S Prescott NJ Onnie CM Häsler R Sipos B Fölsch UR Lengauer T Platzer M Mathew CG Krawczak M Schreiber S 《Nature genetics》2007,39(2):207-211
We performed a genome-wide association study of 19,779 nonsynonymous SNPs in 735 individuals with Crohn disease and 368 controls. A total of 7,159 of these SNPs were informative. We followed up on all 72 SNPs with P 0.4), these data suggest that the underlying biological process may be specific to Crohn disease. 相似文献
109.
A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease 总被引:6,自引:0,他引:6
Buch S Schafmayer C Völzke H Becker C Franke A von Eller-Eberstein H Kluck C Bässmann I Brosch M Lammert F Miquel JF Nervi F Wittig M Rosskopf D Timm B Höll C Seeger M ElSharawy A Lu T Egberts J Fändrich F Fölsch UR Krawczak M Schreiber S Nürnberg P Tepel J Hampe J 《Nature genetics》2007,39(8):995-999
With an overall prevalence of 10-20%, gallstone disease (cholelithiasis) represents one of the most frequent and economically relevant health problems of industrialized countries. We performed an association scan of >500,000 SNPs in 280 individuals with gallstones and 360 controls. A follow-up study of the 235 most significant SNPs in 1,105 affected individuals and 873 controls replicated the disease association of SNP A-1791411 in ABCG8 (allelic P value P(CCA) = 4.1 x 10(-9)), which was subsequently attributed to coding variant rs11887534 (D19H). Additional replication was achieved in 728 German (P = 2.8 x 10(-7)) and 167 Chilean subjects (P = 0.02). The overall odds ratio for D19H carriership was 2.2 (95% confidence interval: 1.8-2.6, P = 1.4 x 10(-14)) in the full German sample. Association was stronger in subjects with cholesterol gallstones (odds ratio = 3.3), suggesting that His19 might be associated with a more efficient transport of cholesterol into the bile. 相似文献
110.
Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes 总被引:6,自引:0,他引:6
Waters MF Minassian NA Stevanin G Figueroa KP Bannister JP Nolte D Mock AF Evidente VG Fee DB Müller U Dürr A Brice A Papazian DM Pulst SM 《Nature genetics》2006,38(4):447-451
Potassium channel mutations have been described in episodic neurological diseases. We report that K+ channel mutations cause disease phenotypes with neurodevelopmental and neurodegenerative features. In a Filipino adult-onset ataxia pedigree, the causative gene maps to 19q13, overlapping the SCA13 disease locus described in a French pedigree with childhood-onset ataxia and cognitive delay. This region contains KCNC3 (also known as Kv3.3), encoding a voltage-gated Shaw channel with enriched cerebellar expression. Sequencing revealed two missense mutations, both of which alter KCNC3 function in Xenopus laevis expression systems. KCNC3(R420H), located in the voltage-sensing domain, had no channel activity when expressed alone and had a dominant-negative effect when co-expressed with the wild-type channel. KCNC3(F448L) shifted the activation curve in the negative direction and slowed channel closing. Thus, KCNC3(R420H) and KCNC3(F448L) are expected to change the output characteristics of fast-spiking cerebellar neurons, in which KCNC channels confer capacity for high-frequency firing. Our results establish a role for KCNC3 in phenotypes ranging from developmental disorders to adult-onset neurodegeneration and suggest voltage-gated K+ channels as candidates for additional neurodegenerative diseases. 相似文献