Specificity and Time of the Appearance of His+ Reversions Induced by Histidine Starvation in Salmonella typhimurium

It was previously established that reversion of the hisG46 allele of Salmonella typhimurium to prototrophy occurred upon histidine starvation. In this paper, it was shown that histidine starvation does not affect the appearance of mutants resistant to L-arabinose and rifampicin. Threonine starvation did not change the frequency of His+ revertants. Analysis of His+ revertant clones did not reveal additional L-arabinose resistance mutations. Thus, these experiments allowed the conclusion that amino acid starvation does not lead to a non-specific increase in the mutation rate. In addition, it was shown that spontaneous His+ revertants start to arise after two to three hours of histidine starvation, and this process lasts for four days. Nevertheless, original His- cells did not grow in a culture generating His+ revertants. Traces of histidine and novobiocin added to a minimal medium retarded reversion realization. However, the occurrence of revertants was not markedly inhibited by chloramphenicol. Based on the results, it is assumed that adaptive His+ reversions occurred due to a special mode of replication induced upon histidine starvation and requiring no de novo protein synthesis

The origin of His+ revertants of Salmonella typhimurium obtained on selective medium

The spontaneous reversion to His+ of the Salmonella typhimurium alleles hisD3052 and hisG46 was investigated. In fluctuation tests, the expected "jackpot" distribution of His+ revertants was not observed. The experimental distributions were close to Poisson distribution. The redistribution test showed no significant differences in the His+ colony counts between spread and unspread plates. An attempt at indirect selection of His+ revertants in fluid medium failed. It was also shown that the mean number of His+ reversion events and the mean number of revertants per plate were similar. At the same time, kanamycin-resistant mutants had jackpot distribution. Selection for His+ revertants (histidine starvation) did not increase mutation to Kanr. © 1992

Dependence of the appearance of his+ reversions on the density of salmonella typhimurium cell population

The dependence of the appearance of mutants on the number of viable cells plated on a selective medium was analyzed with the spontaneous His+ reversion system in the histidine auxotroph of Salmonella typhimurium strain BA13. The frequency of spontaneous His+ revertants was shown to be inversely proportional to the number of plated cells. Evaluation of residual culture growth on a histidine-deficient medium suggests that this factor cannot be the reason behind the inverse dependence. The results of experiments involving previously added His"1" revertants showed that the inverse relationship between mutant frequency and population density is not connected with the inhibition of preadaptive revertant growth by nonmutant cells. Moreover, an inhibitory effect of the culture medium on the frequency of spontaneous His+ revertants upon histidine starvation was detected. On the basis of these results, it was assumed that the His+ reversion generated by histidine starvation is suppressed by metabolites of starved cells

Specificity and time of the appearance of his+ reversions induced by histidine starvation in salmonella typhimurium

It was previously established that reversion of the hisG46 allele of Salmonella typhimurium to prototrophy occurred upon histidine starvation. In this paper, it was shown that histidine starvation does not affect the appearance of mutants resistant to L-arabinose and rifampicin. Threonine starvation did not change the frequency of His+ revenants. Analysis of His+ revertant clones did not reveal additional L-arabinose resistance mutations. Thus, these experiments allowed the conclusion that amino acid starvation does not lead to a nonspecific increase in the mutation rate. In addition, it was shown that spontaneous His+ revertants start to arise after two to three hours of histidine starvation, this process lasting for four days. Nevertheless, original His+ cells did not grow in a culture generating His+ revertants. Traces of histidine and novobiocin added to a minimal medium retarded reversion realization. However, the occurrence of revertants was not markedly inhibited by chloramphenicol. Based on the results, it is assumed that adaptive His+ reversions occurred due to a special mode of replication induced upon histidine starvation and requiring no de novo protein synthesis

Algebraic entropy and the space of initial values for discrete dynamical systems

A method to calculate the algebraic entropy of a mapping which can be lifted to an isomorphism of a suitable rational surfaces (the space of initial values) are presented. It is shown that the degree of the $n$th iterate of such a mapping is given by its action on the Picard group of the space of initial values. It is also shown that the degree of the $n$th iterate of every Painlev\'e equation in sakai's list is at most $O(n^2)$ and therefore its algebraic entropy is zero.Comment: 10 pages, pLatex fil

Complexity and integrability in 4D bi-rational maps with two invariants

In this letter we give fourth-order autonomous recurrence relations with two invariants, whose degree growth is cubic or exponential. These examples contradict the common belief that maps with sufficiently many invariants can have at most quadratic growth. Cubic growth may reflect the existence of non-elliptic fibrations of invariants, whereas we conjecture that the exponentially growing cases lack the necessary conditions for the applicability of the discrete Liouville theorem.Comment: 16 pages, 2 figure

Aurora kinases are expressed in medullary thyroid carcinoma (MTC) and their inhibition suppresses in vitro growth and tumorigenicity of the MTC derived cell line TT

International audienceBACKGROUND: The Aurora kinase family members, Aurora-A, -B and -C, are involved in the regulation of mitosis, and alterations in their expression are associated with cell malignant transformation. To date no information on the expression of these proteins in medullary thyroid carcinoma (MTC) are available. We here investigated the expression of the Aurora kinases in human MTC tissues and their potential use as therapeutic targets. METHODS: The expression of the Aurora kinases in 26 MTC tissues at different TNM stages was analyzed at the mRNA level by quantitative RT-PCR. We then evaluated the effects of the Aurora kinase inhibitor MK-0457 on the MTC derived TT cell line proliferation, apoptosis, soft agar colony formation, cell cycle and ploidy. RESULTS: The results showed the absence of correlation between tumor tissue levels of any Aurora kinase and tumor stage indicating the lack of prognostic value for these proteins. Treatment with MK-0457 inhibited TT cell proliferation in a time- and dose-dependent manner with IC50 = 49.8 ± 6.6 nM, as well as Aurora kinases phosphorylation of substrates relevant to the mitotic progression. Time-lapse experiments demonstrated that MK-0457-treated cells entered mitosis but were unable to complete it. Cytofluorimetric analysis confirmed that MK-0457 induced accumulation of cells with ≥ 4N DNA content without inducing apoptosis. Finally, MK-0457 prevented the capability of the TT cells to form colonies in soft agar. CONCLUSIONS: We demonstrate that Aurora kinases inhibition hampered growth and tumorigenicity of TT cells, suggesting its potential therapeutic value for MTC treatment

TPH2 Gene Polymorphisms and Major Depression – A Meta-Analysis

BACKGROUND: Tryptophan hydroxylase-2 (TPH2) is the rate-limiting enzyme in the synthetic pathway for brain serotonin and is considered key factor for maintaining normal serotonin transmission in the central neuron system (CNS). Gene-disease association studies have reported a relationship between TPH2 and major depressive disorder (MDD) in different populations, however subsequent studies have produced contradictory results. OBJECTIVES: We performed a systematic overview and a meta-analysis with all available data up-to-date. METHODS: We scrutinized PubMed, Embase, HuGNet and China National Knowledge Infrastructure (CNKI ) and last update was held on October 2011. We also searched the manuscripts and the supplementary documents of the published genome-wide association studies in the field. Effect sizes of independent loci that have been studied in more than 3 articles were synthesized using fixed and random effects models. RESULTS: We found 27 eligible articles that studied a total of 74 single nucleotide polymorphisms (SNPs). Finally, 12 independent loci were included in the meta-analysis. The synthesis of the data shown that two SNPs (rs4570625 and rs17110747) were associated with MDD using fixed effects models. SNP rs4570625 had low heterogeneity and remained significant using the more conservative random effects calculations with a summary OR = 0.83 (95% CI: 0.73-0.96). CONCLUSION: The current study identified a SNP (rs4570625) with strong epidemiological credibility; however more studies are required to provide robust evidence for other weak associations