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61.
Internal brain states form key determinants for sensory perception, sensorimotor coordination and learning. A prominent reflection of different brain states in the mammalian central nervous system is the presence of distinct patterns of cortical synchrony, as revealed by extracellular recordings of the electroencephalogram, local field potential and action potentials. Such temporal correlations of cortical activity are thought to be fundamental mechanisms of neuronal computation. However, it is unknown how cortical synchrony is reflected in the intracellular membrane potential (V(m)) dynamics of behaving animals. Here we show, using dual whole-cell recordings from layer 2/3 primary somatosensory barrel cortex in behaving mice, that the V(m) of nearby neurons is highly correlated during quiet wakefulness. However, when the mouse is whisking, an internally generated state change reduces the V(m) correlation, resulting in a desynchronized local field potential and electroencephalogram. Action potential activity was sparse during both quiet wakefulness and active whisking. Single action potentials were driven by a large, brief and specific excitatory input that was not present in the V(m) of neighbouring cells. Action potential initiation occurs with a higher signal-to-noise ratio during active whisking than during quiet periods. Therefore, we show that an internal brain state dynamically regulates cortical membrane potential synchrony during behaviour and defines different modes of cortical processing. 相似文献
62.
Srdja Drakulic Jay Rai Steen Vang Petersen Monika M. Golas Bjoern Sander 《Cellular and molecular life sciences : CMLS》2018,75(16):3009-3026
The pyruvate dehydrogenase complex (PDC) bridges glycolysis and the citric acid cycle. In human, PDC deficiency leads to severe neurodevelopmental delay and progressive neurodegeneration. The majority of cases are caused by variants in the gene encoding the PDC subunit E1α. The molecular effects of the variants, however, remain poorly understood. Using yeast as a eukaryotic model system, we have studied the substitutions A189V, M230V, and R322C in yeast E1α (corresponding to the pathogenic variants A169V, M210V, and R302C in human E1α) and evaluated how substitutions of single amino acid residues within different functional E1α regions affect PDC structure and activity. The E1α A189V substitution located in the heterodimer interface showed a more compact conformation with significant underrepresentation of E1 in PDC and impaired overall PDC activity. The E1α M230V substitution located in the tetramer and heterodimer interface showed a relatively more open conformation and was particularly affected by low thiamin pyrophosphate concentrations. The E1α R322C substitution located in the phosphorylation loop of E1α resulted in PDC lacking E3 subunits and abolished overall functional activity. Furthermore, we show for the E1α variant A189V that variant E1α accumulates in the Hsp60 chaperonin, but can be released upon ATP supplementation. Our studies suggest that pathogenic E1α variants may be associated with structural changes of PDC and impaired folding of E1α. 相似文献
63.
A C3Cl-type(bcc)-semi-infinite ferrimagnet with a single-ion uniaxial anisotropy and a magnetic impurity layer is considered through combining Green‘s function theory with the transfer-mairx method.The effect of the anisotropy term and the impurity layer on surface spin wave specirum is discussed.The influence of the impurity layer‘s distance from the surface or surface spin woves is also concerned. 相似文献
64.
Ioannidis JP Gwinn M Little J Higgins JP Bernstein JL Boffetta P Bondy M Bray MS Brenchley PE Buffler PA Casas JP Chokkalingam A Danesh J Smith GD Dolan S Duncan R Gruis NA Hartge P Hashibe M Hunter DJ Jarvelin MR Malmer B Maraganore DM Newton-Bishop JA O'Brien TR Petersen G Riboli E Salanti G Seminara D Smeeth L Taioli E Timpson N Uitterlinden AG Vineis P Wareham N Winn DM Zimmern R Khoury MJ;Human Genome Epidemiology Network the Network of Investigator Networks 《Nature genetics》2006,38(1):3-5
Networks of investigators have begun sharing best practices, tools and methods for analysis of associations between genetic variation and common diseases. A Network of Investigator Networks has been set up to drive the process, sponsored by the Human Genome Epidemiology Network. A workshop is planned to develop consensus guidelines for reporting results of genetic association studies. Published literature databases will be integrated, and unpublished data, including 'negative' studies, will be captured by online journals and through investigator networks. Systematic reviews will be expanded to include more meta-analyses of individual-level data and prospective meta-analyses. Field synopses will offer regularly updated overviews. 相似文献
65.
J. Hauschild-Quintern B. Petersen G. J. Cost H. Niemann 《Cellular and molecular life sciences : CMLS》2013,70(16):2969-2983
Zinc-finger nucleases (ZFNs) are engineered site-specific DNA cleavage enzymes that may be designed to recognize long target sites and thus cut DNA with high specificity. ZFNs mediate permanent and targeted genetic alteration via induction of a double-strand break at a specific genomic site. Compared to conventional homology-based gene targeting, ZFNs can increase the targeting rate by up to 100,000-fold; gene disruption via mutagenic DNA repair is similarly efficient. The utility of ZFNs has been shown in many organisms, including insects, amphibians, plants, nematodes, and several mammals, including humans. This broad range of tractable species renders ZFNs a useful tool for improving the understanding of complex physiological systems, to produce transgenic animals, cell lines, and plants, and to treat human disease. 相似文献
66.
Yuan J Dong Z Guo JP McGeehan J Xiao X Wang J Cali I McGeer PL Cashman NR Bessen R Surewicz WK Kneale G Petersen RB Gambetti P Zou WQ 《Cellular and molecular life sciences : CMLS》2008,65(4):631-643
Human prion diseases are characterized by the accumulation in the brain of proteinase K (PK)-resistant prion protein designated
PrP27 – 30 detectable by the 3F4 antibody against human PrP109 – 112. We recently identified a new PK-resistant PrP species,
designated PrP*20, in uninfected human and animal brains. It was preferentially detected with the 1E4 antibody against human PrP 97 – 108 but
not with the anti-PrP 3F4 antibody, although the 3F4 epitope is adjacent to the 1E4 epitope in the PrP*20 molecule. The present study reveals that removal of the N-terminal amino acids up to residue 91 significantly increases accessibility
of the 1E4 antibody to PrP of brains and cultured cells. In contrast to cells expressing wild-type PrP, cells expressing pathogenic
mutant PrP accumulate not only PrP*20 but also a small amount of 3F4-detected PK-resistant PrP27 – 30. Remarkably, during the course of human prion disease, a
transition from an increase in 1E4-detected PrP*20 to the occurrence of the 3F4-detected PrP27 – 30 was observed. Our study suggests that an increase in the level of PrP*20 characterizes the early stages of prion diseases.
Received 17 October 2007; received after revision 5 December 2007; accepted 14 December 2007 相似文献
67.
Zusammenfassung Es wird gezeigt, dass während der Perfusion der Submandibularis-Drüse der Katze mit chloridfreier Sulfatlösung die sekretorischen Potentialdifferenzen der Azinuszellmembran unverändert bleiben und dass inzwischen die Sekretion und der Kaliumtransport von der Drüse zur Perfusionsflüssigkeit völlig aufhört. 相似文献
68.
69.
Parental origin of mutations of the retinoblastoma gene 总被引:20,自引:0,他引:20
Retinoblastoma and osteosarcoma arise from cells that have lost both functional copies of the retinoblastoma gene. Using the cloned retinoblastoma gene and other linked polymorphic loci, it is possible to reconstruct the sequential loss of the two homologous gene copies that precedes the development of these tumours. In non-hereditary tumours, the loss of each of the two homologues occurs somatically; in hereditary cases, the initial mutation is in the germline. Recently, Toguchida et al. reported that the paternally derived copy is preferentially the first one to become mutant during the genesis of non-hereditary osteosarcomas. We report here a similar analysis of patients with retinoblastoma in which we find no such predilection for initial somatic mutations. In contrast, when an initial mutation was a new germline mutation, it was derived from the father, a result which is consistent with new germline mutations arising primarily during spermatogenesis. 相似文献
70.
O. H. Petersen 《Cellular and molecular life sciences : CMLS》1976,32(4):471-472
Summary It is shown that excitation of the - or -adrenoceptors in mouse parotid acinar cells causes a marked reduction of surface cell membrane resistance. The -adrenoceptor induced membrane effect is an increase in K conductance. The -adrenoceptor induced membrane effect does not seem to be mediated by cyclic AMP. 相似文献