Background
Tnt1 was the first active plant retrotransposon identified in tobacco after nitrate reductase gene disruption. The Tnt1 superfamily comprises elements from Nicotiana (Tnt1 and Tto1) and Lycopersicon (Retrolyc1 and Tlc1) species. The study presented here was conducted to characterise Tnt1-related sequences in 20 wild species of Solanum and five cultivars of Solanum tuberosum. 相似文献Background
In several autoimmune diseases, including multiple sclerosis (MS), a compromised regulatory T cell (Treg) function is believed to be critically involved in the disease process. In vitro, the biologically active metabolite of vitamin D has been shown to promote Treg development. A poor vitamin D status has been linked with MS incidence and MS disease activity. In the present study, we assess a potential in vivo correlation between vitamin D status and Treg function in relapsing remitting MS (RRMS) patients.Methodology/Principal Findings
Serum levels of 25-hydroxyvitamin D (25(OH)D) were measured in 29 RRMS patients. The number of circulating Tregs was assessed by flow-cytometry, and their functionality was tested in vitro in a CFSE-based proliferation suppression assay. Additionally, the intracellular cytokine profile of T helper cells was determined directly ex-vivo by flow-cytometry. Serum levels of 25(OH)D correlated positively with the ability of Tregs to suppress T cell proliferation (R = 0.590, P = 0.002). No correlation between 25(OH)D levels and the number of Tregs was found. The IFN-γ/IL-4 ratio (Th1/Th2-balance) was more directed towards IL-4 in patients with favourable 25(OH)D levels (R = −0.435, P = 0.023).Conclusions/Significance
These results show an association of high 25(OH)D levels with an improved Treg function, and with skewing of the Th1/Th2 balance towards Th2. These findings suggest that vitamin D is an important promoter of T cell regulation in vivo in MS patients. It is tempting to speculate that our results may not only hold for MS, but also for other autoimmune diseases. Future intervention studies will show whether modulation of vitamin D status results in modulation of the T cell response and subsequent amelioration of disease activity. 相似文献Background
S100B is a potential marker of neurological and psychiatric illness. In schizophrenia, increased S100B levels, as well as associations with acute positive and persisting negative symptoms, have been reported. It remains unclear whether S100B elevation, which possibly reflects glial dysfunction, is the consequence of disease or compensatory processes, or whether it is an indicator of familial risk.Methods
Serum samples were acquired from two large independent family samples (n = 348 and n = 254) in the Netherlands comprising patients with psychotic disorder (n = 140 and n = 82), non-psychotic siblings of patients with psychotic disorder (n = 125 and n = 94) and controls (n = 83 and n = 78). S100B was analyzed with a Liaison automated chemiluminescence system. Associations between familial risk of psychotic disorder and S100B were examined.Results
Results showed that S100B levels in patients (P) and siblings (S) were not significantly different from controls (C) (dataset 1: P vs. C: B = 0.004, 95% CI −0.005 to 0.013, p = 0.351; S vs. C: B = 0.000, 95% CI −0.009 to 0.008, p = 0.926; and dataset 2: P vs. C: B = 0.008, 95% CI −0.011 to 0.028, p = 0.410; S vs. C: B = 0.002, 95% CI −0.016 to 0.021, p = 0.797). In patients, negative symptoms were positively associated with S100B (B = 0.001, 95% CI 0.000 to 0.002, p = 0.005) in one of the datasets, however with failure of replication in the other. There was no significant association between S100B and positive symptoms or present use or type of antipsychotic medication.Conclusions
S100B is neither an intermediate phenotype, nor a trait marker for psychotic illness. 相似文献The reference compounds, progesterone, Org 2058, and DHT all induced prolactin production. Oestradiol also slightly induced prolactin production and enhanced the response to Org 2058. Tibolone and Δ4-tibolone were similar with regard to potency to induce prolactin levels in the culture supernatant. Their potency was lower than that of Org 2058, similar to that of progesterone and higher than that of DHT. The efficacies of tibolone, Δ4-tibolone and Org 2058 were similar (200-fold induction). The estrogenic tibolone metabolites 3- and 3β-OH tibolone also significantly stimulated prolactin production. Their potency, however, was low since significance was reached only at the highest concentrations tested.
The PR antagonist Org 31710 inhibited both tibolone- and Δ4-tibolone-induced prolactin production. The responses of tibolone and Δ4-tibolone were not affected by co-incubation with the androgen receptor antagonist OH-flutamide. The effect of tibolone, but not Δ4-tibolone, was antagonized approximately 50% in combination with the highest dose (1 μM) estrogen receptor antagonist, ICI 164384. The induction of prolactin by 3- and 3β-OH tibolone was antagonized most potently by Org 31710, but also by ICI 164384 and OH-flutamide.
Tibolone is metabolized differently in epithelial and stromal cells of the human endometrium. The epithelial cells mostly produce the progestagenic/androgenic Δ4-tibolone. The stromal cells produce predominantly the 3β-OH tibolone, and some Δ4-tibolone, but the net effect observed with regard to prolactin production is progestagenic. When the metabolites 3-OH, 3β-OH, and Δ4-tibolone were added to the cultures no conversions were observed. The HPLC analyses showed no evidence for the production of sulfated metabolites.
In conclusion, the net effects on endometrial stromal cells are predominantly progestagenic. Tibolone is converted by epithelial cells into Δ4-tibolone which displays progestagenic and androgenic activities, whereas in stromal cells also the estrogenic metabolites 3- and 3β-OH tibolone are formed. 相似文献