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1.
Thorsten Thye Genevieve Scarisbrick Edmund N. L. Browne Margaret Amanua Chinbuah John Gyapong Ivy Osei Ellis Owusu-Dabo Stefan Niemann Sabine Rüsch-Gerdes Christian G. Meyer Rolf D. Horstmann 《PloS one》2009,4(7)
The gene of Cytotoxic T Lymphocyte-associated Antigen 4 (CTLA4), a negative regulator of T lymphocytes, contains a single-nucleotide polymorphism (SNP) at position +6230A->G (ct60A->G), which has been found associated with several autoimmune diseases and appears to reduce T-cell inhibitory activity. In Ghana, West Africa, we compared the frequencies of CTLA4 +6230 A/G and 6 haplotype-tagging SNPs in 2010 smear-positive, HIV-negative patients with pulmonary tuberculosis (TB) and 2346 controls matched for age, gender and ethnicity. We found no difference in allele frequencies between cases and controls. However, +6230A and a distinct CTLA4 haplotype and a diplotype comprising the +6230A allele were significantly less frequent among cases with large opacities in chest radiographs compared to those with small ones (Pcorrected [cor] = 0.002, Pcor = 0.00045, P = 0.0005, respectively). This finding suggests that an increased T-cell activity associated with the CTLA4 +6230G allele contributes to pathology rather than to protection in pulmonary TB. 相似文献
2.
The temperature dependence of the fluorescence of the Y-base of tRNAPhe (yeast) was investigated kinetically by the temperature jump method. In the range between -15 degrees C and +30 degrees C A NOVEL CONFORMATIONAL TRANSITION OF THE TRNA could be characterized. This conformational change was found in the absence of any artificial label; it is a characteristic property of tRNAPhe in its native structure. This transition accounts for 30% of the total fluorescence change. Its activation enthalpy is 16 kcal/mole (67 kJ/mole), and the transition enthalpy is between -2 kcal/mole and +2 kcal/mole (+/-8 kJ/mole). A model is represented in which this transition can be explained by a a change in the stacking pattern of the anticodon loop. The experimental findings are discussed with respect to several hypotheses about the molecular mechanism of protein biosynthesis which postulate conformational rearrangements of the anticodon loop. 相似文献
3.
Influence of melatonin treatment on human circadian rhythmicity before and after a simulated 9-hr time shift. 总被引:2,自引:0,他引:2
A Samel H M Wegmann M Vejvoda H Maass A Gundel M Schütz 《Journal of biological rhythms》1991,6(3):235-248
The hormone melatonin is currently proposed by some investigators to be an efficient means for decreasing the impairing effects of jet lag. Eight healthy male subjects, aged 20 to 32, underwent a 9-hr advance shift in the isolation facility of our institute during two periods each of 15 days' duration. In a double-blind, crossover design, subjects took either melatonin or placebo at 1800 hr local time for 3 days before the time shift and at 1400 hr for 4 days afterwards. The time shift was simulated on days 7 and 8 by shortening the sleep period by 6 hr and the following wake period by 3 hr. Body temperature was recorded every 90 min, and urine was collected at 3-hr intervals all day and night. Melatonin treatment enhanced the resynchronization speed of some, but not all, hormone and electrolyte excretion rates for several days after the time shift. The adaptation speed of the temperature rhythm significantly increased during one postshift day. In addition, the circadian temperature rhythm had a significantly higher amplitude under melatonin treatment than under placebo after the time displacement. For the placebo group, the rhythm of 6-hydroxymelatoninsulfate excretion exhibited an advance shift in five subjects, whereas the other three showed a delay shift, and adjustment did not achieve more than one-half of the expected value within 8 days. A significantly different adjustment could be observed in the melatonin-treated group: Seven subjects underwent an advance shift of the expected 9 hr within an average of 8 days. The results suggest that melatonin treatment can accelerate resynchronization of the melatonin excretion rhythm after eastward time zone transitions. The improvement is not, however, sufficiently great that we can recommend melatonin for the alleviation of jet lag. 相似文献
4.
Synopsis In serial cross-sections of human skeletal muscles stained for either NADH-tetrazolium reductase (NADH-TR) or -glycerophosphate dehydrogenase (-GPD), a linear relation was found between the total content of enzyme in a cell (expressed as the thickness of the section) and the absorbance of the formazan reaction product formed. Little variation (<4.8%) was found in the concentration of formazan (absorbance per unit thickness) when the same cell was measured in serial cross-sections of various thicknesses (2–10 m) along a longitudinal distance of at least 200 m along the cell. The reduction in enzyme activity was found to be negligible after aqueous preincubation. A maximum of 10–12% of the formazan produced in the NADH-TR reaction might be the result of nothing dehydrogenase activity, whereas this unspecific reaction might account for up to 20% of the formazan deposited in the -GPD reactions after 30 min incubation. The diffusion of Nitro BT into the tissue during the incubation period was found to be unhindered. The rates of formazan production decreased with increasing incubation time, especially in the -GPD reaction in both fibre types. The ratio of the mean absorbance of the formazan in type I fibres to that in type II fibres (in the same section) was 1.41 (coefficient of variation, 2.5%) in the NADH-TR reaction and 0.68 (coefficient of variation, 3.8%) in the -GPD reaction. These values were not affected either by variations in the incubation time (5–40 min) or by the thickness of the section (2–8 m). The concentrations of NADH-TR and -GPD seem to be constant along the length of the muscle fibre. The histochemical reactions reported, together with measurements of the thickness of the sections, seem suitable for the microphotometric quantification of the two enzymes in single fibres of human skeletal muscles. 相似文献
5.
6.
L1 is sequentially processed by two differently activated metalloproteases and presenilin/gamma-secretase and regulates neural cell adhesion, cell migration, and neurite outgrowth 下载免费PDF全文
Maretzky T Schulte M Ludwig A Rose-John S Blobel C Hartmann D Altevogt P Saftig P Reiss K 《Molecular and cellular biology》2005,25(20):9040-9053
The immunoglobulin superfamily recognition molecule L1 plays important functional roles in the developing and adult nervous system. Metalloprotease-mediated cleavage of this adhesion molecule has been shown to stimulate cellular migration and neurite outgrowth. We demonstrate here that L1 cleavage is mediated by two distinct members of the disintegrin and metalloprotease family, ADAM10 and ADAM17. This cleavage is differently regulated and leads to the generation of a membrane bound C-terminal fragment, which is further processed through gamma-secretase activity. Pharmacological approaches with two hydroxamate-based inhibitors with different preferences in blocking ADAM10 and ADAM17, as well as loss of function and gain of function studies in murine embryonic fibroblasts, showed that constitutive shedding of L1 is mediated by ADAM10 while phorbol ester stimulation or cholesterol depletion led to ADAM17-mediated L1 cleavage. In contrast, N-methyl-d-aspartate treatment of primary neurons stimulated ADAM10-mediated L1 shedding. Both proteases were able to affect L1-mediated adhesion and haptotactic migration of neuronal cells. In particular, both proteases were involved in L1-dependent neurite outgrowth of cerebellar neurons. Thus, our data identify ADAM10 and ADAM17 as differentially regulated L1 membrane sheddases, both critically affecting the physiological functions of this adhesion protein. 相似文献
7.
Sasado T Morinaga C Niwa K Shinomiya A Yasuoka A Suwa H Hirose Y Yoda H Henrich T Deguchi T Iwanami N Watanabe T Kunimatsu S Osakada M Okamoto Y Kota Y Yamanaka T Tanaka M Kondoh H Furutani-Seiki M 《Mechanisms of development》2004,121(7-8):817-828
The development of germ cells has been intensively studied in Medaka (Oryzias latipes). We have undertaken a large-scale screen to identify mutations affecting the development of primordial germ cells (PGCs) in Medaka. Embryos derived from mutagenized founder fish were screened for an abnormal distribution or number of PGCs at embryonic stage 27 by RNA in situ hybridization for the Medaka vasa homologue (olvas). At this stage, PGCs coalesce into two bilateral vasa-expressing foci in the ventrolateral regions of the trunk after their migration and group organization. Nineteen mutations were identified from a screen corresponding to 450 mutagenized haploid genomes. Eleven of the mutations caused altered PGC distribution. Most of these alterations were associated with morphological abnormalities and could be grouped into four phenotypic classes: Class 1, PGCs dispersed into bilateral lines; Class 2, PGCs dispersed in a region more medial than that in Class 1; Class 3, PGCs scattered laterally and over the yolk sac area; and Class 4, PGCs clustered in a single median focus. Eight mutations caused a decrease in the number of PGCs. This decrease was observed in the offspring of heterozygous mothers, indicating the contribution of a maternal factor in determining PGC abundance. Taken together, these mutations should prove useful in identifying molecular mechanisms underlying the early PGC development and migration. 相似文献
8.
Andr Neumann Taras Bodnar Dietmar Pfeifer Thorsten Dickhaus 《Biometrical journal. Biometrische Zeitschrift》2019,61(1):40-61
Multivariate multiple test procedures have received growing attention recently. This is due to the fact that data generated by modern applications typically are high‐dimensional, but possess pronounced dependencies due to the technical mechanisms involved in the experiments. Hence, it is possible and often necessary to exploit these dependencies in order to achieve reasonable power. In the present paper, we express dependency structures in the most general manner, namely, by means of copula functions. One class of nonparametric copula estimators is constituted by Bernstein copulae. We extend previous statistical results regarding bivariate Bernstein copulae to the multivariate case and study their impact on multiple tests. In particular, we utilize them to derive asymptotic confidence regions for the family‐wise error rate (FWER) of multiple test procedures that are empirically calibrated by making use of Bernstein copulae approximations of the dependency structure among the test statistics. This extends a similar approach by Stange et al. (2015) in the parametric case. A simulation study quantifies the gain in FWER level exhaustion and, consequently, power that can be achieved by exploiting the dependencies, in comparison with common threshold calibrations like the Bonferroni or ?idák corrections. Finally, we demonstrate an application of the proposed methodology to real‐life data from insurance. 相似文献
9.
Biosynthesis of the NiFe hydrogenase active site is a complex process involving the action of the Hyp proteins: HypA-HypF. Here we investigate the mechanism of NiFe site biosynthesis in Ralstonia eutropha by examining the interactions between HypC, HypD, HypE, and HypF1. Using an affinity purification procedure based on the Strep-tag II, we purified HypC and HypE from different genetic backgrounds as complexes with other hydrogenase-related proteins and characterized them using immunological analysis. Copurification of HypC and HoxH, the active site-containing subunit of the soluble hydrogenase in R. eutropha, from several different genetic backgrounds suggests that this complex forms early in the maturation process. With respect to the Hyp proteins, it is shown that HypE and HypF1 formed a stable complex both in vivo and in vitro. Furthermore, HypC and HypD functioned as a unit. Together, they were able to interact with HypE to form a range of complexes probably varying in stoichiometry. The HypC/HypD/HypE complexes did not involve HypF1 but appeared to be more stable when HypF1 was also present in the cells. We hypothesize that HypF1 is able to modify some component of the HypC/HypD/HypE complex. Since we have also seen that HypF1 and HypE form a complex, it is likely that HypF1 modifies HypE. On the basis of these results, we propose a complete catalytic cycle for HypE. First, it is modified by HypF1, and then it can form a complex with HypC/HypD. This activated HypE/HypC/HypD complex could then decompose by donating active site components to the immature hydrogenase and regenerate unmodified HypE. 相似文献
10.