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排序方式: 共有420条查询结果,搜索用时 602 毫秒
1.
Increased neuronal firing in computer simulations of sodium channel mutations that cause generalized epilepsy with febrile seizures plus 总被引:4,自引:0,他引:4
Generalized epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant familial syndrome with a complex seizure phenotype. It is caused by mutations in one of 3 voltage-gated sodium channel subunit genes (SCN1B, SCN1A, and SCN2A) and the GABA(A) receptor gamma2 subunit gene (GBRG2). The biophysical characterization of 3 mutations (T875M, W1204R, and R1648H) in SCN1A, the gene encoding the CNS voltage-gated sodium channel alpha subunit Na(v)1.1, demonstrated a variety of functional effects. The T875M mutation enhanced slow inactivation, the W1204R mutation shifted the voltage dependency of activation and inactivation in the negative direction, and the R1648H mutation accelerated recovery from inactivation. To determine how these changes affect neuronal firing, we used the NEURON simulation software to design a computational model based on the experimentally determined properties of each GEFS+ mutant sodium channel and a delayed rectifier potassium channel. The model predicted that W1204R decreased the threshold, T875M increased the threshold, and R1648H did not affect the threshold for firing a single action potential. Despite the different effects on the threshold for firing a single action potential, all of the mutations resulted in an increased propensity to fire repetitive action potentials. In addition, each mutation was capable of driving repetitive firing in a mixed population of mutant and wild-type channels, consistent with the dominant nature of these mutations. These results suggest a common physiological mechanism for epileptogenesis resulting from sodium channel mutations that cause GEFS+. 相似文献
2.
Judit Gervai Zsofia Nemoda Krisztina Lakatos Zsolt Ronai Ildiko Toth Krisztina Ney Maria Sasvari-Szekely 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2005,(1):126-130
Following up the results of a previous population association study (Lakatos et al. [2000: Mol Psychiatry 5:633-637; Lakatos et al. [2002: Mol Psychiatry 7:27-31]) by analyses based on parental genetic data confirmed the link between infant attachment and the dopamine D4 receptor (DRD4) gene. Extended transmission disequilibrium tests (ETDT) were performed to determine whether biased transmission of exon III 48 basepair repeat alleles occurred to infants displaying disorganized and secure attachment behavior with their mothers. The overall allele-wise TDTs were significant for both groups (P = 0.038 and 0.020, respectively): a trend for preferential transmission of the seven-repeat allele to disorganized infants was observed (TDT(chi)(2) = 3.27, df = 1, P = 0.071), and there was a significant non-transmission of the same allele to securely attached infants (TDT(chi)(2) = 6.00, df = 1, P = 0.014). Analysis of haplotypes of the exon III repeat and the -521 C/T promoter polymorphisms in family trios showed that the transmission bias in the larger secure group was due to the low-rate transmission of the T.7 haplotype containing both the seven-repeat and the -521 T alleles (TDT(chi)(2) = 4.46, df = 1, P = 0.035). This suggests that not carrying the T.7 haplotype of the DRD4 gene may act as a resilience factor in the optimal development of early attachment. 相似文献
3.
Targeted recruitment of a histone H4-specific methyltransferase by the transcription factor YY1 总被引:3,自引:0,他引:3
Rezai-Zadeh N Zhang X Namour F Fejer G Wen YD Yao YL Gyory I Wright K Seto E 《Genes & development》2003,17(8):1019-1029
4.
Emma Beard John Marsden Jamie Brown Ildiko Tombor John Stapleton Susan Michie Robert West 《Addiction (Abingdon, England)》2019,114(10):1866-1884
Time series analyses are statistical methods used to assess trends in repeated measurements taken at regular intervals and their associations with other trends or events, taking account of the temporal structure of such data. Addiction research often involves assessing associations between trends in target variables (e.g. population cigarette smoking prevalence) and predictor variables (e.g. average price of a cigarette), known as a multiple time series design, or interventions or events (e.g. introduction of an indoor smoking ban), known as an interrupted time series design. There are many analytical tools available, each with its own strengths and limitations. This paper provides addiction researchers with an overview of many of the methods available (GLM, GLMM, GLS, GAMM, ARIMA, ARIMAX, VAR, SVAR, VECM) and guidance on when and how they should be used, sample size det ermination, reporting and interpretation. The aim is to provide increased clarity for researchers proposing to undertake these analyses concerning what is likely to be acceptable for publication in journals such as Addiction. Given the large number of choices that need to be made when setting up time series models, the guidance emphasizes the importance of pre‐registering hypotheses and analysis plans before the analyses are undertaken. 相似文献
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7.
Fraser Aird Ildiko Halasz Eva Redei 《Alcoholism, clinical and experimental research》1997,21(9):1560-1566
This study was designed to determine whether the previously described sexually dimorphic changes in rat hypothalamic corticotrop-in-releasing factor (CRF) and anterior pituitary pro-opiomelanocortin (POMC) mRNA expression in response to fetal alcohol exposure (FAE) are present prepubertally and whether they are altered by maternal adrenalectomy. Hypothalamic CRF and anterior pituitary POMC mRNA levels were determined in male and female offspring of adrenalectomized (ADX) and sham-adrenalectomized (Sham) dams exposed to alcohol (FAE) or a pair-fed (PF) control diet during the last 2 weeks of gestation. CRF and POMC mRNA levels were measured by Northern blotting at 1, 7, 14, and 21 days of age. In offspring of control PF dams, CRF mRNA levels increased faster in females, increasing by day 7, followed by a decrease at days 14 and 21, whereas in males there was a gradual increase from days 1 to 21. FAE altered the ontogenic profile of CRF mRNA in female offspring by delaying and exaggerating the rise of CRF expression to day 14, but produced no effect in males. Maternal adrenalectomy, combined with FAE, resulted in an early rise of CRF mRNA on day 14 in male offspring. In females, the combined ADX/FAE treatment resulted in significantly increased CRF mRNA levels, compared with those of ADX/PF offspring, on days 7 and 14. By day 21, these differences in CRF mRNA levels between the ADX/FAE and ADX/PF offspring had disappeared. POMC mRNA levels generally increased by day 7, followed by a dramatic decrease by day 14 and another increase by day 21. FAE male offspring showed decreased levels of POMC mRNA, whereas females were not affected. Maternal adrenalectomy reversed this inhibition in male offspring, resulting in POMC mRNA levels similar to those measured in male offspring of PF control animals. In contrast, POMC mRNA levels of female offspring of ADX dams decreased in response to FAE. These data suggest that the previously observed switch from suppressed to enhanced POMC expression in FAE males is the result of developmental events beyond weaning. Because this sexually dimorphic regulation of CRF and POMC expression by prenatal alcohol exposure and maternal adrenalectomy occurs before the presence of adult levels of sex steroids, this suggests an organizational effect on the developing hypothalamic-pituitary-adrenal function. 相似文献
8.
Julia Sarkadi Mate Jankovics Zoltan Kis Jozsef Skare Kinga Fodor Eva Gonczol Ildiko Visontai Zoltan Vajo Istvan Jankovics 《Archives of virology》2013,158(12):2577-2581
Chinese painted quails immunized with a single dose (6 μg HA) of inactivated H5N1 (clade 1) influenza vaccine NIBRG-14 and challenged with 100 LD50 of the heterologous A/Swan/Nagybaracska/01/06(H5N1) (clade 2.2) strain were protected, whereas unvaccinated quails died after challenge. No viral antigens or RNA were detected in cloacal swabs from immunized animals. Sera obtained post-immunization gave low titres in serological assays against the vaccine and the challenge viruses. Our results demonstrate the protective efficacy of the NIBRG-14 strain against the challenge virus and the usefulness of these small birds in protection studies of influenza vaccines. 相似文献
9.
Origins of netropsin binding affinity and specificity: correlations of thermodynamic and structural data. 总被引:9,自引:4,他引:9
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L A Marky K J Breslauer 《Proceedings of the National Academy of Sciences of the United States of America》1987,84(13):4359-4363
We report complete thermodynamic profiles for netropsin binding to an oligomeric and to several polymeric DNA host duplexes. These data allow us to reach the following conclusions: netropsin binding by deep penetration into the minor groove is overwhelmingly enthalpy driven and exhibits a very high binding affinity (K approximately 10(9) at 25 degrees C); deep penetration into the minor groove is required to form those drug-DNA interactions responsible for the enthalpy-driven high binding affinity of netropsin; I-C base pairs form binding sites for netropsin that thermodynamically are equivalent to those formed by A-T base pairs; the positive binding entropies reflect entropic contributions from molecular events other than just water spine disruption; the thermodynamic binding data primarily reflect local netropsin-DNA interactions rather than long-range binding-induced conformational changes at regions distant from the binding site; the enhanced binding affinity associated with deep penetration of netropsin into the minor groove does not result from more favorable electrostatic interactions; the binding of netropsin to the central AATT core of the decamer duplex [d(GCGAATTCGC)]2 is thermodynamically modeled best by netropsin binding to the poly[d(AT)].poly[d(AT)] duplex rather than the poly(dA).poly(dT) duplex. We propose correlations between our thermodynamic data and specific molecular interactions defined by NMR and x-ray structural studies on similar and identical drug-DNA complexes. 相似文献
10.
Gillitzer A Peluso M Laugwitz KL Münch G Massberg S Konrad I Gawaz M Ungerer M 《Arteriosclerosis, thrombosis, and vascular biology》2005,25(8):1750-1755
Background- We recently reported the development of culture-derived (CD) platelets with the aim to express any protein of interest in these platelets. We now report a specific protocol of retroviral infection into the progenitor cells and subsequent selection, which allows to generate large amounts of highly homogenous transgene-expressing CD platelets and to study transgene function rapidly and reliably at large-scale ex vivo and in vivo settings. METHODS AND RESULTS: After retroviral infection and selection, the activation-dependent expression profile of surface markers, aggregation, and granule release were investigated. The function of transgene-expressing CD platelets, the precursor cells of which had been retrovirally infected, compared well to noninfected CD platelets or freshly isolated platelets. Hence, the retroviral infection protocol did not alter platelet physiology. In contrast, adenoviral infection of precursors to CD platelets resulted in marked functional alterations that obviated their use in analytic experiments. Additionally, sufficient amounts of selected CD platelets were generated to warrant intravenous injections into living mice. This approach permitted study of their adhesive profile at endothelial lesions and their effect on thrombus formation in vivo by intravital videofluorescence microscopy. CONCLUSIONS: The novel selection method allowed us to produce recombinant transgene-expressing platelets in sufficient amounts to study genetically modified platelets in vitro and in vivo. 相似文献