The Yeast Pif1 Helicase Prevents Genomic Instability Caused by G-Quadruplex-Forming CEB1 Sequences In Vivo

In budding yeast, the Pif1 DNA helicase is involved in the maintenance of both nuclear and mitochondrial genomes, but its role in these processes is still poorly understood. Here, we provide evidence for a new Pif1 function by demonstrating that its absence promotes genetic instability of alleles of the G-rich human minisatellite CEB1 inserted in the Saccharomyces cerevisiae genome, but not of other tandem repeats. Inactivation of other DNA helicases, including Sgs1, had no effect on CEB1 stability. In vitro, we show that CEB1 repeats formed stable G-quadruplex (G4) secondary structures and the Pif1 protein unwinds these structures more efficiently than regular B-DNA. Finally, synthetic CEB1 arrays in which we mutated the potential G4-forming sequences were no longer destabilized in pif1Δ cells. Hence, we conclude that CEB1 instability in pif1Δ cells depends on the potential to form G-quadruplex structures, suggesting that Pif1 could play a role in the metabolism of G4-forming sequences.     

Analysis of center-of-pressure data during unipedal and bipedal standing using fractional Brownian motion modeling

To question the relation between uni-and bipedal postural skills, 21 subjects were required to stand on a force platform through uni- and bipedal conditions. These two protocols are commonly used paradigms to assess the balance capacities of healthy and disabled patients. The recorded displacements of the center of pressure (CP) were decomposed along mediolateral and anteroposterior axes and assessed through variance positions and parameters obtained from fractional Brownian motion (fBm) modeling to determine the nature and the spatiotemporal organization of the successive controlling mechanisms. The variances underline the relative independence of the two tasks. Nevertheless, as highlighted by the fBm framework, postural correction is initiated for the unipedal stance after shorter time delays and longer covered distances. When compared to bipedal standing, one of the main characteristics of unipedal standing is to induce better-controlled CP trajectories, as deduced from the scaling regimes computed from the fBm modeling. Lastly, the control of the CP trajectories during the shortest time intervals along the anteroposterior axis appears identical for both uni- and bipedal conditions. Unipedal and bipedal standing controls should thus be viewed as two complementary tasks, each providing specific and complementary insights into the postural control organization.     

Lack of Association of the N-acetyltransferase NAT1*10 Allele with Prostate Cancer Incidence, Grade, or Stage Among Smokers in Finland

Genetic variations in xenobiotic metabolizing genes can influence susceptibility to many environmentally induced cancers. Inheritance of the N-acetyltransferase 1 allele (NAT1*10), linked with increased metabolic activation of pro-carcinogens, is associated with an increased susceptibility to many cancers in which cigarette- or meat-derived carcinogens have been implicated in their etiology. The role of NAT1*10 in prostate cancer is under studied. Although cigarette smoking is not considered a risk factor for prostate cancer, a recent review suggests it may play a role in disease progression. Consequently, we examined the association of NAT1*10 with prostate cancer risk, grade, and stage among 400 Finnish male smokers using a case-control study design. Following genotyping of 206 patients and 196 healthy controls, our results do not support the role of NAT1*10 in relation to prostate cancer risk (OR?=?1.28; 95% CI, 0.66-2.47), aggressive disease (OR?=?0.58; 95% CI, 0.13-2.67), or advanced disease (OR?=?1.19; 95% CI, 0.49-2.91).     

Effects of the bark beetle nematode, Contortylenchus reversus, on gallery construction,fecundity, and egg viability of the Douglas Fir beetle, Dendroctonus pseudotsugae (Coleoptera: Scolytidae)

Healthy and Contortylenchus reversus infected Douglas Fir beetles were colonized in logs in the laboratory. At 7, 14, and 23 days after introduction of the beetles into the logs, the bark was removed from some of the logs and the length and shape of the primary gallery, the number of eggs laid, and the egg viability were determined for each pair of parent beetles. Parasitism caused a 25, 28, and 27% reduction in the length of the primary egg gallery built by the infected female at 7, 14, and 23 days, respectively, after the start of colonization. In addition, the number of eggs laid by the infected females by 7, 14, and 23 days after the start of colonization were 50, 33, and 45%, respectively, lower than that of healthy female beetles. Despite the differences in gallery length between control and infected females, linear regression analysis showed that the rates of gallery construction were not significantly different. However, infected female beetles showed significantly lower rates of egg-laying than did healthy female beetles. Nematode parasitism did not affect gallery shape and egg viability of female Douglas Fir beetles. Mating of healthy female beetles with infected males affected neither the gallery length nor the fecundity of the uninfected females.     

A suppressive oligodeoxynucleotide enhances the efficacy of myelin cocktail/IL-4-tolerizing DNA vaccination and treats autoimmune disease

Targeting pathogenic T cells with Ag-specific tolerizing DNA vaccines encoding autoantigens is a powerful and feasible therapeutic strategy for Th1-mediated autoimmune diseases. However, plasmid DNA contains abundant unmethylated CpG motifs, which induce a strong Th1 immune response. We describe here a novel approach to counteract this undesired side effect of plasmid DNA used for vaccination in Th1-mediated autoimmune diseases. In chronic relapsing experimental autoimmune encephalomyelitis (EAE), combining a myelin cocktail plus IL-4-tolerizing DNA vaccine with a suppressive GpG oligodeoxynucleotide (GpG-ODN) induced a shift of the autoreactive T cell response toward a protective Th2 cytokine pattern. Myelin microarrays demonstrate that tolerizing DNA vaccination plus GpG-ODN further decreased anti-myelin autoantibody epitope spreading and shifted the autoreactive B cell response to a protective IgG1 isotype. Moreover, the addition of GpG-ODN to tolerizing DNA vaccination therapy effectively reduced overall mean disease severity in both the chronic relapsing EAE and chronic progressive EAE mouse models. In conclusion, suppressive GpG-ODN effectively counteracted the undesired CpG-induced inflammatory effect of a tolerizing DNA vaccine in a Th1-mediated autoimmune disease by skewing both the autoaggressive T cell and B cell responses toward a protective Th2 phenotype. These results demonstrate that suppressive GpG-ODN is a simple and highly effective novel therapeutic adjuvant that will boost the efficacy of Ag-specific tolerizing DNA vaccines used for treating Th1-mediated autoimmune diseases.     

Longitudinal axons are guided by Slit/Robo signals from the floor plate

Longitudinal axons grow long distances along precise pathways to connect major CNS regions. However, during embryonic development, it remains largely undefined how the first longitudinal axons choose specific positions and grow along them. Here, we review recent evidence identifying a critical role for Slit/Robo signals to guide pioneer longitudinal axons in the embryonic brain stem. These studies indicate that Slit/Robo signals from the floor plate have dual functions: to repel longitudinal axons away from the ventral midline, and also to maintain straight longitudinal growth. These dual functions likely cooperate with other guidance cues to establish the major longitudinal tracts in the brain.Key words: Slit, Robo, longitudinal axon, hindbrain, axon guidance     

Influence of Plant Root Exudates on the Mobility of Fuel Volatile Compounds in Contaminated Soils

Vegetation and its associated microorganisms play an important role in the behaviour of soil contaminants. One of the most important elements is root exudation, since it can affect the mobility, and therefore, the bioavailability of soil contaminants. In this study, we evaluated the influence of root exudates on the mobility of fuel derived compounds in contaminated soils. Samples of humic acid, montmorillonite, and an A horizon from an alumi-umbric Cambisol were contaminated with volatile contaminants present in fuel: oxygenates (MTBE and ETBE) and monoaromatic compounds (benzene, toluene, ethylbenzene and xylene). Natural root exudates obtained from Holcus lanatus and Cytisus striatus and ten artificial exudates (components frequently found in natural exudates) were added to the samples, individually and as a mixture, to evaluate their effects on contaminant mobility. Fuel compounds were analyzed by headspace-gas chromatography-mass spectrometry. In general, the addition of natural and artificial exudates increased the mobility of all contaminants in humic acid. In A horizon and montmorillonite, natural or artificial exudates (as a mixture) decreased the contaminant mobility. However, artificial exudates individually had different effects: carboxylic components increased and phenolic components decreased the contaminant mobility. These results established a base for developing and improving phytoremediation processes of fuel-contaminated soils.