S-Adenosylmethionine metabolism and its relation to polyamine synthesis in rat liver. Effect of nutritional state, adrenal function, some drugs and partial hepatectomy

S-Adenosylmethionine metabolism and its relation to the synthesis and accumulation of polyamines was studied in rat liver under various nutritional conditions, in adrenalectomized or partially hepatectomized animals and after treatment with cortisol, thioacetamide or methylglyoxal bis(guanylhydrazone) {1,1'-[(methylethanediylidine)dinitrilo]diguanidine}. Starvation for 2 days only slightly affected S-adenosylmethionine metabolism. The ratio of spermidine/spermine decreased markedly, but the concentration of total polyamines did not change significantly. The activity of S-adenosylmethionine decarboxylase initially decreased and then increased during prolonged starvation. This increase was dependent on intact adrenals. Re-feeding of starved animals caused a rapid but transient stimulation of polyamine synthesis and also increased the concentrations of S-adenosylmethionine and S-adenosylhomocysteine. Similarly, cortisol treatment enhanced the synthesis of polyamines, S-adenosylmethionine and S-adenosylhomocysteine. Feeding with a methionine-deficient diet for 7-14 days profoundly increased the concentration of spermidine, whereas the concentrations of total polyamines and of S-adenosylmethionine showed no significant changes. The results show that nutritional state and adrenal function play a significant role in the regulation of hepatic metabolism of S-adenosylmethionine and polyamines. They further indicate that under a variety of physiological and experimental conditions the concentrations of S-adenosylmethionine and of total polyamines remain fairly constant and that changes in polyamine metabolism are not primarily connected with changes in the accumulation of S-adenosylmethionine or S-adenosylhomocysteine.     

Polygenic risk for schizophrenia,social dispositions,and pace of epigenetic aging: Results from the Young Finns Study

Schizophrenia is often regarded as a disorder of premature aging. We investigated (a) whether polygenic risk for schizophrenia (PRS_sch) relates to pace of epigenetic aging and (b) whether personal dispositions toward active and emotionally close relationships protect against accelerated epigenetic aging in individuals with high PRS_sch. The sample came from the population-based Young Finns Study (n = 1348). Epigenetic aging was measured with DNA methylation aging algorithms such as AgeAccel_Hannum, EEAA_Hannum, IEAA_Hannum, IEAA_Horvath, AgeAccel_Horvath, AgeAccel_Pheno, AgeAccel_Grim, and DunedinPACE. A PRS_sch was calculated using summary statistics from the most comprehensive genome-wide association study of schizophrenia to date. Social dispositions were assessed in terms of extraversion, sociability, reward dependence, cooperativeness, and attachment security. We found that PRS_sch did not have a statistically significant effect on any studied indicator of epigenetic aging. Instead, PRS_sch had a significant interaction with reward dependence (p = 0.001–0.004), cooperation (p = 0.009–0.020), extraversion (p = 0.019–0.041), sociability (p = 0.003–0.016), and attachment security (p = 0.007–0.014) in predicting AgeAccel_Hannum, EEAA_Hannum, or IEAA_Hannum. Specifically, participants with high PRS_sch appeared to display accelerated epigenetic aging at higher (vs. lower) levels of extraversion, sociability, attachment security, reward dependence, and cooperativeness. A rather opposite pattern was evident for those with low PRS_sch. No such interactions were evident when predicting the other indicators of epigenetic aging. In conclusion, against our hypothesis, frequent social interactions may relate to accelerated epigenetic aging in individuals at risk for psychosis. We speculate that this may be explained by social-cognitive impairments (perceiving social situations as overwhelming or excessively arousing) or ending up in less supportive or deviant social groups.     

Non-native and native shrubs have differing impacts on species diversity and composition of associated plant communities

The spread of non-native plants has been depicted as a serious threat to biodiversity. However, it remains unclear whether the indigenousness of the invading plant plays a marked role for the ecological consequences of an invasion as few studies have compared the ecological impacts of non-native shrubs with structurally or functionally comparable native shrubs. We studied patches of introduced and native shrubs to assess whether there are general differences in plant species composition or biomass between patches formed by non-native versus native shrubs. The indigenousness of the shrub (non-native vs. native) did not explain the variation in soil nutrients, neither the production of shoot biomass or allocation of growth to different parts of the shoot. The amount of light reaching ground level did not differ between patches of a non-native and a native shrub. However, species richness and biomass of herbaceous plants were lower in patches of non-native than native shrubs and the amount of litter was higher below non-native than native shrubs. Our results suggest that the indigenousness of the patch-forming plant may be an important factor for the diversity and composition of associated herbaceous vegetation. Based on our results, resource availability (light and nutrients) is not a sufficient explanation for the negative effects of non-native shrubs on plant communities. Further research is needed to investigate whether alternative explanations, such as the novelty of the toxic compounds produced by non-native plants, can explain the differences we observed.     

Polyamines may regulate S-phase progression but not the dynamic changes of chromatin during the cell cycle

Several studies suggest that polyamines may stabilize chromatin and play a role in its structural alterations. In line with this idea, we found here by chromatin precipitation and micrococcal nuclease (MNase) digestion analyses, that spermidine and spermine stabilize or condense the nucleosomal organization of chromatin in vitro. We then investigated the possible physiological role of polyamines in the nucleosomal organization of chromatin during the cell cycle in Chinese hamster ovary (CHO) cells deficient in ornithine decarboxylase (ODC) activity. An extended polyamine deprivation (for 4 days) was found to arrest 70% of the odc⁻ cells in S phase. MNase digestion analyses revealed that these cells have a highly loosened and destabilized nucleosomal organization. However, no marked difference in the chromatin structure was detected between the control and polyamine-depleted cells following the synchronization of the cells at the S-phase. We also show in synchronized cells that polyamine deprivation retards the traverse of the cells through the S phase already in the first cell cycle. Depletion of polyamines had no significant effect on the nucleosomal organization of chromatin in G₁–early S. The polyamine-deprived cells were also capable of condensing the nucleosomal organization of chromatin in the S/G₂ phase of the cell cycle. These data indicate that polyamines do not regulate the chromatin condensation state during the cell cycle, although they might have some stabilizing effect on the chromatin structure. Polyamines may, however, play an important role in the control of S-phase progression. J. Cell Biochem. 68:200–212, 1998. © 1998 Wiley-Liss, Inc.     

WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk

We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ～2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2 × 10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3 × 10(-12), and -0.16 SD per G allele, P = 1.2 × 10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3 × 10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9 × 10(-6) and rs2707466: OR = 1.22, P = 7.2 × 10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5 × 10(-13)相似文献   

Tryptophan hydroxylase 1 gene haplotypes modify the effect of a hostile childhood environment on adulthood harm avoidance

We conducted a series of tests to determine whether there is any association between tryptophan hydroxylase 1 (TPH1) and temperament in adulthood. In addition to testing for main effects, we investigated whether TPH1 gene variation modifies the influence of childhood environment on temperament in adulthood. The subjects were 341 healthy adults whose childhood environment was assessed by their mothers in 1980 and who self-rated their temperaments twice, in 1997 and 2001. We found no association between the TPH1 gene and temperament; however, among women, the TPH1 gene modified a relationship between adverse childhood environment and harm avoidance in adulthood. This finding was confirmed in the same sample in another test setting 4 years later. The presence of the A/A haplotype of the TPH1 intron 7 A218A and A779C polymorphism predicted a high level of adulthood harm avoidance in the presence of a hostile childhood environment as defined in terms of emotional rejection, maternal neglect and harsh and inconsistent discipline. In addition, the findings suggest a gene-environment correlation for novelty seeking in men.     

Circulating IgG antibodies against fungal and actinomycete antigens in the sera of farmer's lung patients from different countries

Sixty-nine farmer's lung patients and 28 normal controls from four countries (Finland, Switzerland, Canada and the United States) were investigated for antibody levels against 13 antigens commonly used for the screening panel for hypersensitivity pneumonitis. Of these antigens, eight were from the Medical College of Wisconsin (United States) and five were from the University of Kuopio (Finland). IgG antibodies against these antigens were studied in 97 sera using a sensitive biotin-avidin-linked enzyme immunoassay. The results indicate that the mean antibody titer against Micropolyspora faeni was highest in the United States (U.S.) followed by Finland. Both Finnish and U.S. antigens reacted almost identically against various groups of patients, although the degree of reactivity varied considerably. Higher antibody levels against Thermoactinomyces vulgaris were detected in Finnish patients than patients from other countries while patients from all four countries showed elevated levels of antibodies against T. candidus. This study demonstrates that antigens from identical species, irrespective of geographic origin, reacted similarly. However, variability between antigens of the same species was still considerably significant. Since the microbiological flora of moldy hay varies widely in different regions, the microbial species associated with the disease at a given geographical area has to be determined before selecting antigens for serological studies. The antigens currently used in various laboratories are crude preparations and need to be purified and standardized for dependable results. Until such antigens are available, all antigenic preparations used in the immunological evaluation of patients should be immunochemically characterized for their reproducibility and reliability although the ultimate goal should be to obtain standardized pure antigens for dependable immunodiagnosis of farmer's lung.