Adjusting Phenotypes by Noise Control

Genetically identical cells can show phenotypic variability. This is often caused by stochastic events that originate from randomness in biochemical processes involving in gene expression and other extrinsic cellular processes. From an engineering perspective, there have been efforts focused on theory and experiments to control noise levels by perturbing and replacing gene network components. However, systematic methods for noise control are lacking mainly due to the intractable mathematical structure of noise propagation through reaction networks. Here, we provide a numerical analysis method by quantifying the parametric sensitivity of noise characteristics at the level of the linear noise approximation. Our analysis is readily applicable to various types of noise control and to different types of system; for example, we can orthogonally control the mean and noise levels and can control system dynamics such as noisy oscillations. As an illustration we applied our method to HIV and yeast gene expression systems and metabolic networks. The oscillatory signal control was applied to p53 oscillations from DNA damage. Furthermore, we showed that the efficiency of orthogonal control can be enhanced by applying extrinsic noise and feedback. Our noise control analysis can be applied to any stochastic model belonging to continuous time Markovian systems such as biological and chemical reaction systems, and even computer and social networks. We anticipate the proposed analysis to be a useful tool for designing and controlling synthetic gene networks

Divergence in transcriptional and regulatory responses to mating in male and female fruitflies

Mating induces extensive physiological, biochemical and behavioural changes in female animals of many taxa. In contrast, the overall phenotypic and transcriptomic consequences of mating for males, hence how they might differ from those of females, are poorly described. Post mating responses in each sex are rapidly initiated, predicting the existence of regulatory mechanisms in addition to transcriptional responses involving de novo gene expression. That post mating responses appear different for each sex also predicts that the genome-wide signatures of mating should show evidence of sex-specific specialisation. In this study, we used high resolution RNA sequencing to provide the first direct comparisons of the transcriptomic responses of male and female Drosophila to mating, and the first comparison of mating-responsive miRNAs in both sexes in any species. As predicted, the results revealed the existence of sex- and body part-specific mRNA and miRNA expression profiles. More genes were differentially expressed in the female head-thorax than the abdomen following mating, whereas the opposite was true in males. Indeed, the transcriptional profile of male head-thorax tissue was largely unaffected by mating, and no differentially expressed genes were detected at the most stringent significance threshold. A subset of ribosomal genes in females were differentially expressed in both body parts, but in opposite directions, consistent with the existence of body part-specific resource allocation switching. Novel, mating-responsive miRNAs in each sex were also identified, and a miRNA-mRNA interactions analysis revealed putative targets among mating-responsive genes. We show that the structure of genome-wide responses by each sex to mating is strongly divergent, and provide new insights into how shared genomes can achieve characteristic distinctiveness

School-level variation in health outcomes in adolescence: analysis of three longitudinal studies in England

School factors are associated with many health outcomes in adolescence. However, previous studies report inconsistent findings regarding the degree of school-level variation for health outcomes, particularly for risk behaviours. This study uses data from three large longitudinal studies in England to investigate school-level variation in a range of health indicators. Participants were drawn from the Longitudinal Study of Young People in England, the Me and My School Study and the Research with East London Adolescent Community Health Survey. Outcome variables included risk behaviours (smoking, alcohol/cannabis use, sexual behaviour), behavioural difficulties and victimisation, obesity and physical activity, mental and emotional health, and educational attainment. Multi-level models were used to calculate the proportion of variance in outcomes explained at school level, expressed as intraclass correlations (ICCs) adjusted for gender, ethnicity and socio-economic status of the participants. ICCs for health outcomes ranged from nearly nil to .28 and were almost uniformly lower than for attainment (.17-.23). Most adjusted ICCs were smaller than unadjusted values, suggesting that school-level variation partly reflects differences in pupil demographics. School-level variation was highest for risk behaviours. ICCs were largely comparable across datasets, as well as across years within datasets, suggesting that school-level variation in health remains fairly constant across adolescence. School-level variation in health outcomes remains significant after adjustment for individual demographic differences between schools, confirming likely effects for school environment. Variance is highest for risk behaviours, supporting the utility of school environment interventions for these outcomes

Mechanism of induction of complement susceptibility of erythrocytes by spider and bacterial sphingomyelinases

We have recently shown that the sphingomyelinase toxins P1 and P2 from the venom of the spider Loxosceles intermedia induce complement (C)-dependent lysis of autologous erythrocytes by induction of the cleavage of cell surface glycophorins through activation of an endogenous metalloproteinase facilitating the activation of the alternative pathway of C. Phospholipase D (PLD) from Corynebacterium pseudotuberculosis shows some degree of homology with the spider sphingomyelinases and can induce similar clinical symptoms to those observed after spider envenomation. The aim of this study was to investigate if the bacterial PLD-induced haemolysis of human erythrocytes was C dependent and if cleavage of glycophorins occurred. We show here that haemolysis of both PLD- and P1-treated human erythrocytes was C dependent, but while PLD-mediated haemolysis was dependent on activation of the classical pathway of C, P1 induced lysis via both the classical and alternative pathways. P1, but not PLD, induced cleavage of glycophorins and no change in expression of complement regulators was induced by either of the toxins. In both cases, annexin V binding sites were exposed, suggesting that the membrane asymmetry had been disturbed causing exposure of phosphatidylserine to the cell surface. Our results suggest that C susceptibility induced by L. intermedia and C. pseudotuberculosis PLD is a result of exposure of phosphatidylserine, and the higher potency of P1 toxin can be explained by its additional effect of cleavage of glycophorins

Natural Glasses

International audienceNatural glasses have been used since prehistoric times and are strongly linked to human evolution. On Earth, glasses are typically produced by rapid cooling of melts, and as in the case of minerals and rocks, natural glasses can provide key information on the evolution of the Earth. However, we are aware that natural glasses are products that are not solely terrestrial and that the formation mechanisms give rise to a variety of natural amorphous materials. On the Earth's surface, glasses are scarce compared to other terrestrial bodies (i. e., the Moon), since the conditions on the surface give rise to devitrification or weathering. In order to provide an exhaustive overview, we shall classify natural glasses based on the mechanisms by which they were formed: temperature related, temperaturepressure related, temperature-pressure-volatile related, and others. In this chapter, we will review the most common natural glasses and their technological applications and also the scientific and technological advancements achieved from the study of these natural amorphous materials. Finally, we will provide some insights into the structure and properties of natural glasses and melts