Genetic Evidence for a Link Between Glycolysis and DNA Replication

BACKGROUND: A challenging goal in biology is to understand how the principal cellular functions are integrated so that cells achieve viability and optimal fitness in a wide range of nutritional conditions. METHODOLOGY/PRINCIPAL FINDINGS: We report here a tight link between glycolysis and DNA synthesis. The link, discovered during an analysis of suppressors of thermosensitive replication mutants in bacterium Bacillus subtilis, is very strong as some metabolic alterations fully restore viability to replication mutants in which a lethal arrest of DNA synthesis otherwise occurs at a high, restrictive, temperature. Full restoration of viability by such alterations was limited to cells with mutations in three elongation factors (the lagging strand DnaE polymerase, the primase and the helicase) out of a large set of thermosensitive mutants affected in most of the replication proteins. Restoration of viability resulted, at least in part, from maintenance of replication protein activity at high temperature. Physiological studies suggested that this restoration depended on the activity of the three-carbon part of the glycolysis/gluconeogenesis pathway and occurred in both glycolytic and gluconeogenic regimens. Restoration took place abruptly over a narrow range of expression of genes in the three-carbon part of glycolysis. However, the absolute value of this range varied greatly with the allele in question. Finally, restoration of cell viability did not appear to be the result of a decrease in growth rate or an induction of major stress responses. CONCLUSIONS/SIGNIFICANCE: Our findings provide the first evidence for a genetic system that connects DNA chain elongation to glycolysis. Its role may be to modulate some aspect of DNA synthesis in response to the energy provided by the environment and the underlying mechanism is discussed. It is proposed that related systems are ubiquitous

Triggering, guiding and deviation of long air spark discharges with femtosecond laser filament

International audienceIn the perspective of the laser lightning rod, the ability of femtosecond filaments to trigger and to guide large scale discharges has been studied for several years. The present paper reports recent experimental results showing for the first time that filaments are able not only to trigger and guide but also to divert an electric discharge from its normal path. Laser filaments are also able to divert the spark without contact between laser and electrodes at large distance from the laser. A comparison between negative and positive discharge polarities also reveals important discrepancies in the guiding mechanism

Earthworm management in tropical agroecosystems

Ecological and demographic parameters of 26 species of native and exotic earthworms species common in tropical agroecosystems, with large environmental tolerance and/or extended distribution were investigated. Principal component analysis (PCA) isolated four groups : (i) large native endogeic and anecic species (16-32 g individual fresh wt) with long generation time (2-4 years), low fecundity (0.5-3.1 cocoons/year/adult) and one hatchling per cocoon ; (ii) medium size species (1.2-6 g) endogeic mesohumic, with intermediate fecundity (1.3-45 cocoons/year/adult) ; (iii) small species (0.17-1.25 g f.w.) mainly endogeic polyhumic, with short generation time (3-7 months), intermediate fecundity (10-68 cocoons/year/adult) and one hatchling per cocoon ; and (iv) generally small (80-150 mg f.w.) species mainly exotic and epigeic, with short generation time (1-3 months), very high fecundity (50-350 cocoons/year/adult) and up to three hatchlings per cocoon. Casts may be either large globular or small granular. The selective investigations of large organic particles and small mineral particles (clays) concentrates total organic matter in the casts. There is an intense mineralization rate of nitrogen in the casts (6-29% of organic N), exotic worms seeming to be less efficient than natives at mineralizing N. The mineral phosphorus content of casts is always at least 30% higher than in the non-ingested soil. All these worms ingest daily, on average, three times their own weight of soil at the adult stage (1-9) and much more when juvenile ; up to 1000 Mg dry soil/ha may transit yearly through earthworm guts. (Résumé d'auteur

LIPH Expression in Skin and Hair Follicles of Normal Coat and Rex Rabbits

Natural mutations in the LIPH gene were shown to be responsible for hair growth defects in humans and for the rex short hair phenotype in rabbits. In this species, we identified a single nucleotide deletion in LIPH (1362delA) introducing a stop codon in the C-terminal region of the protein. We investigated the expression of LIPH between normal coat and rex rabbits during critical fetal stages of hair follicle genesis, in adults and during hair follicle cycles. Transcripts were three times less expressed in both fetal and adult stages of the rex rabbits than in normal rabbits. In addition, the hair growth cycle phases affected the regulation of the transcription level in the normal and mutant phenotypes differently. LIPH mRNA and protein levels were higher in the outer root sheath (ORS) than in the inner root sheath (IRS), with a very weak signal in the IRS of rex rabbits. In vitro transfection shows that the mutant protein has a reduced lipase activity compared to the wild type form. Our results contribute to the characterization of the LIPH mode of action and confirm the crucial role of LIPH in hair production

The Physical Relationship between Infectivity and Prion Protein Aggregates Is Strain-Dependent

Prions are unconventional infectious agents thought to be primarily composed of PrPSc, a multimeric misfolded conformer of the ubiquitously expressed host-encoded prion protein (PrPC). They cause fatal neurodegenerative diseases in both animals and humans. The disease phenotype is not uniform within species, and stable, self-propagating variations in PrPSc conformation could encode this ‘strain’ diversity. However, much remains to be learned about the physical relationship between the infectious agent and PrPSc aggregation state, and how this varies according to the strain. We applied a sedimentation velocity technique to a panel of natural, biologically cloned strains obtained by propagation of classical and atypical sheep scrapie and BSE infectious sources in transgenic mice expressing ovine PrP. Detergent-solubilized, infected brain homogenates were used as starting material. Solubilization conditions were optimized to separate PrPSc aggregates from PrPC. The distribution of PrPSc and infectivity in the gradient was determined by immunoblotting and mouse bioassay, respectively. As a general feature, a major proteinase K-resistant PrPSc peak was observed in the middle part of the gradient. This population approximately corresponds to multimers of 12–30 PrP molecules, if constituted of PrP only. For two strains, infectivity peaked in a markedly different region of the gradient. This most infectious component sedimented very slowly, suggesting small size oligomers and/or low density PrPSc aggregates. Extending this study to hamster prions passaged in hamster PrP transgenic mice revealed that the highly infectious, slowly sedimenting particles could be a feature of strains able to induce a rapidly lethal disease. Our findings suggest that prion infectious particles are subjected to marked strain-dependent variations, which in turn could influence the strain biological phenotype, in particular the replication dynamics

Les musiciennes de « musiques actuelles » en Suisse romande. Entre confinement et stratégies de maintien dans l’espace professionnel

International audienceLes difficultés spécifiques aux musiciennes pour intégrer l'espace professionnel musical et s'y stabiliser-qu'elles évoluent dans le monde plutôt légitime de la musique classique, ou dans des espaces dévolus à la création/diffusion des musiques dites « actuelles » (jazz-rock-pop-rap…) ont été bien documentées par de nombreux travaux récents menés en France. Ces recherches, essentiellement ethnographiques, ont permis d'appréhender très finement les obstacles auxquels font face les femmes qui tentent de s'installer durablement dans la profession musicale, dans la continuité de certains travaux anglophones qui ont très tôt pointé le poids de la domination masculine dans la structuration des carrières des musicien.ne.s inscrivant leur pratique dans le cadre des « popular musics ». Les recherches menées sut le cas français ont également contribué à mettre en lumière les stratégies, souvent ambivalentes, et les arrangements avec les normes de genre régissant ces milieux professionnels mis en place par certaines femmes pour malgré tout faire carrière de leur activité musicale. En proposant de s'intéresser au cas des musiciennes de musique « actuelles » en activité au début des années 2010 mais évoluant dans un espace géographique encore relativement peu traité sous cet angle (la Suisse romande), les analyses présentées ici s'inscrivent dans la continuité des travaux précités.Trois questions de recherche orienteront notre développement: dans quelle sous-partie de l’espace professionnel romand des musiques «actuelles» les femmes sont-elles le plus souvent situées ? Comment cette position informe-t-elle leur parcours et leurs chances de stabilisation? Quels arrangements leur permettent néanmoins de s’établir durablement dans la profession? Nous commencerons ainsi par montrer en quoi les femmes se distinguent des hommes au niveau de la structure de leurs carrières et ce que ces spécificités révèlent de la plus grande précarité des carrières féminines. A partir des analyses de notre matériel ethnographique, nous aborderons dans un deuxième temps dans le détail la typologie des «arrangements», des stratégies de musiciennes instrumentistes pour résister à la domination masculine dans le milieu professionnel

Effects of Selection and Drift on G Matrix Evolution in a Heterogeneous Environment: A Multivariate Qst–Fst Test With the Freshwater Snail Galba truncatula

Unraveling the effect of selection vs. drift on the evolution of quantitative traits is commonly achieved by one of two methods. Either one contrasts population differentiation estimates for genetic markers and quantitative traits (the Qst–Fst contrast) or multivariate methods are used to study the covariance between sets of traits. In particular, many studies have focused on the genetic variance–covariance matrix (the G matrix). However, both drift and selection can cause changes in G. To understand their joint effects, we recently combined the two methods into a single test (accompanying article by Martin et al.), which we apply here to a network of 16 natural populations of the freshwater snail Galba truncatula. Using this new neutrality test, extended to hierarchical population structures, we studied the multivariate equivalent of the Qst–Fst contrast for several life-history traits of G. truncatula. We found strong evidence of selection acting on multivariate phenotypes. Selection was homogeneous among populations within each habitat and heterogeneous between habitats. We found that the G matrices were relatively stable within each habitat, with proportionality between the among-populations (D) and the within-populations (G) covariance matrices. The effect of habitat heterogeneity is to break this proportionality because of selection for habitat-dependent optima. Individual-based simulations mimicking our empirical system confirmed that these patterns are expected under the selective regime inferred. We show that homogenizing selection can mimic some effect of drift on the G matrix (G and D almost proportional), but that incorporating information from molecular markers (multivariate Qst–Fst) allows disentangling the two effects

Multivariate Qst–Fst Comparisons: A Neutrality Test for the Evolution of the G Matrix in Structured Populations

Neutrality tests in quantitative genetics provide a statistical framework for the detection of selection on polygenic traits in wild populations. However, the existing method based on comparisons of divergence at neutral markers and quantitative traits (Qst–Fst) suffers from several limitations that hinder a clear interpretation of the results with typical empirical designs. In this article, we propose a multivariate extension of this neutrality test based on empirical estimates of the among-populations (D) and within-populations (G) covariance matrices by MANOVA. A simple pattern is expected under neutrality: D = 2Fst/(1 − Fst)G, so that neutrality implies both proportionality of the two matrices and a specific value of the proportionality coefficient. This pattern is tested using Flury's framework for matrix comparison [common principal-component (CPC) analysis], a well-known tool in G matrix evolution studies. We show the importance of using a Bartlett adjustment of the test for the small sample sizes typically found in empirical studies. We propose a dual test: (i) that the proportionality coefficient is not different from its neutral expectation [2Fst/(1 − Fst)] and (ii) that the MANOVA estimates of mean square matrices between and among populations are proportional. These two tests combined provide a more stringent test for neutrality than the classic Qst–Fst comparison and avoid several statistical problems. Extensive simulations of realistic empirical designs suggest that these tests correctly detect the expected pattern under neutrality and have enough power to efficiently detect mild to strong selection (homogeneous, heterogeneous, or mixed) when it is occurring on a set of traits. This method also provides a rigorous and quantitative framework for disentangling the effects of different selection regimes and of drift on the evolution of the G matrix. We discuss practical requirements for the proper application of our test in empirical studies and potential extensions

Near-field thermal radiation exchanged by a plasmonic metal particle and a surrounding bubble

International audienc