Global Regulation of Nucleotide Biosynthetic Genes by c-Myc

The c-Myc transcription factor is a master regulator and integrates cell proliferation, cell growth and metabolism through activating thousands of target genes. Our identification of direct c-Myc target genes by chromatin immunoprecipitation (ChIP) coupled with pair-end ditag sequencing analysis (ChIP-PET) revealed that nucleotide metabolic genes are enriched among c-Myc targets, but the role of Myc in regulating nucleotide metabolic genes has not been comprehensively delineated.Here, we report that the majority of genes in human purine and pyrimidine biosynthesis pathway were induced and directly bound by c-Myc in the P493-6 human Burkitt's lymphoma model cell line. The majority of these genes were also responsive to the ligand-activated Myc-estrogen receptor fusion protein, Myc-ER, in a Myc null rat fibroblast cell line, HO.15 MYC-ER. Furthermore, these targets are also responsive to Myc activation in transgenic mouse livers in vivo. To determine the functional significance of c-Myc regulation of nucleotide metabolism, we sought to determine the effect of loss of function of direct Myc targets inosine monophosphate dehydrogenases (IMPDH1 and IMPDH2) on c-Myc-induced cell growth and proliferation. In this regard, we used a specific IMPDH inhibitor mycophenolic acid (MPA) and found that MPA dramatically inhibits c-Myc-induced P493-6 cell proliferation through S-phase arrest and apoptosis.Taken together, these results demonstrate the direct induction of nucleotide metabolic genes by c-Myc in multiple systems. Our finding of an S-phase arrest in cells with diminished IMPDH activity suggests that nucleotide pool balance is essential for c-Myc's orchestration of DNA replication, such that uncoupling of these two processes create DNA replication stress and apoptosis

Probing the relationship between Universal Stress Protein C (UspC) and flagellar biosynthesis in Escherichia coli

UspC, like other members of the UspA superfamily, is induced in response to a variety of starvation conditions and environmental insults. The biochemistry and physiological role of UspC have remained largely uncharacterized. It has been established that strains of Escherichia coli deficient in uspC lack flagella. It was hypothesized that UspC is a positive regulator of the flagellar biosynthesis pathway. To test this hypothesis, several techniques were used. The motility of a uspC deficient strain of E. coli was rescued by introduction of flhDC, the master regulator of flagellar biosynthesis, on a plasmid under a constitutive promoter. Gene expression was compared in wild type and ∆uspC E. coli using microarrays. Finally, plasmids were constructed containing promoter regions from flagellar biosynthesis genes fliA and fliC transcriptionally fused to the lux operon. The results of these experiments suggest that UspC is indeed a positive regulator of the flagellar biosynthesis pathway and offer the opportunity for future experiments to better characterize the biochemistry of this enigmatic protein

Psychosocial risk, prenatal counseling and maternal behavior: findings from PRAMS, 2004-2008

ObjectiveTo determine the impact of prenatal counseling regarding psychosocial risk factors on maternal behavior.Study designWe analyzed data from 198,323 women participating in the Pregnancy Risk Assessment Monitoring System (PRAMS). The χ(2) and logistic regression analyses assessed the relationship between psychosocial risk, prenatal counseling and maternal behavior.ResultsThe odds of receiving risk-appropriate prenatal counseling were significantly greater for participants who used alcohol (odds ratio, 1.13; 95% confidence interval, 1.08-1.17) and tobacco (odds ratio, 2.02; 95% confidence interval, 1.91-2.13). After receiving counseling, women quit using alcohol (72.9% vs 27.1%; P < .01) and tobacco (79.9% vs 20.1%; P < .01) at a significantly greater rate and women with unintended pregnancies were more likely to use postpartum contraception (83.6% vs 16.4%; P < .01) than women who were not counseled. However, no significant differences were found in the rates of intimate partner violence during pregnancy (56.1% vs 43.9%; P = .09) between women who did and did not receive counseling.ConclusionCounseling regarding psychosocial risk factors during pregnancy may positively impact maternal behavior

The pulsation modes of the pre-white dwarf PG 1159-035

Context. PG 1159-035, a pre-white dwarf with Teff ~_140 000 K, is the prototype of both two classes: the PG 1159 spectroscopic class and the DOV pulsating class. Previous studies of PG 1159-035 photometric data obtained with the Whole Earth Telescope (WET) showed a rich frequency spectrum allowing the identification of 122 pulsation modes. Analyzing the periods of pulsation, it is possible to measure the stellar mass, the rotational period and the inclination of the rotation axis, to estimate an upper limit for the magnetic field, and even to obtain information about the inner stratification of the star. Aims. We have three principal aims: to increase the number of detected and identified pulsation modes in PG 1159-035, study trapping of the star’s pulsation modes, and to improve or constrain the determination of stellar parameters. Methods. We used all available WET photometric data from 1983, 1985, 1989, 1993 and 2002 to identify the pulsation periods. Results. We identified 76 additional pulsation modes, increasing to 198 the number of known pulsation modes in PG 1159-035, the largest number of modes detected in any star besides the Sun. From the period spacing we estimated a mass M/Mʘ = 0.59 ± 0.02 for PG 1159-035, with the uncertainty dominated by the models, not the observation. Deviations in the regular period spacing suggest that some of the pulsation modes are trapped, even though the star is a pre-white dwarf and the gravitational settling is ongoing. The position of the transition zone that causes the mode trapping was calculated at rc/R. = 0.83 ± 0.05. From the multiplet splitting, we calculated the rotational period Prot = 1.3920 ± 0.0008 days and an upper limit for the magnetic field, B < 2000 G. The total power of the pulsation modes at the stellar surface changed less than 30% for l = 1 modes and less than 50% for l = 2 modes. We find no evidence of linear combinations between the 198 pulsation mode frequencies. PG 1159-035 models have not significative convection zones, supporting the hypothesis that nonlinearity arises in the convection zones in cooler pulsating white dwarf stars

The pulsation modes of the pre-white dwarf PG 1159-035

Context. PG 1159-035, a pre-white dwarf with Teff ~_140 000 K, is the prototype of both two classes: the PG 1159 spectroscopic class and the DOV pulsating class. Previous studies of PG 1159-035 photometric data obtained with the Whole Earth Telescope (WET) showed a rich frequency spectrum allowing the identification of 122 pulsation modes. Analyzing the periods of pulsation, it is possible to measure the stellar mass, the rotational period and the inclination of the rotation axis, to estimate an upper limit for the magnetic field, and even to obtain information about the inner stratification of the star. Aims. We have three principal aims: to increase the number of detected and identified pulsation modes in PG 1159-035, study trapping of the star’s pulsation modes, and to improve or constrain the determination of stellar parameters. Methods. We used all available WET photometric data from 1983, 1985, 1989, 1993 and 2002 to identify the pulsation periods. Results. We identified 76 additional pulsation modes, increasing to 198 the number of known pulsation modes in PG 1159-035, the largest number of modes detected in any star besides the Sun. From the period spacing we estimated a mass M/Mʘ = 0.59 ± 0.02 for PG 1159-035, with the uncertainty dominated by the models, not the observation. Deviations in the regular period spacing suggest that some of the pulsation modes are trapped, even though the star is a pre-white dwarf and the gravitational settling is ongoing. The position of the transition zone that causes the mode trapping was calculated at rc/R. = 0.83 ± 0.05. From the multiplet splitting, we calculated the rotational period Prot = 1.3920 ± 0.0008 days and an upper limit for the magnetic field, B < 2000 G. The total power of the pulsation modes at the stellar surface changed less than 30% for l = 1 modes and less than 50% for l = 2 modes. We find no evidence of linear combinations between the 198 pulsation mode frequencies. PG 1159-035 models have not significative convection zones, supporting the hypothesis that nonlinearity arises in the convection zones in cooler pulsating white dwarf stars