DNA damage induced via independent generation of the radical resulting from formal hydrogen atom abstraction from the C1′-position of a nucleotide

AbstractBackground: Deoxyribonucleotide radicals resulting from formal C1′-hydrogen atom abstraction are important reactive intermediates in a variety of DNA-damage processes. The reactivity of these radicals can be affected by the agents that generate them and the environment in which they are produced. As an initial step in determining the factors that control the reactivity of these important radical species, we developed a mild method for their generation at a defined site within a biopolymer.Results: Irradiation of oligonucleotides containing a photolabile nucleotide produced C1'-DNA radicals. In the absence of potential reactants other than O2, approximately 90% of the damage events involve formation of alkaline-labile lesions, with the remainder resulting in direct strand breaks. The ratio of alkaline-labile lesions to direct strand breaks (∼ 9:1) is independent of whether the radical is generated in single-stranded DNA or double-stranded DNA. Strand damage is almost completely quenched under anaerobic conditions in the presence of low thiol concentrations. Competition studies with 02 indicate that the trapping rate of C1′-DNA radicals by β-mercaptoethanol is ∼ 1.1 x 107 M−1s−1Conclusions: The mild generation of the C1'-DNA radical in the absence of exogenous oxidants makes it possible to examine their intrinsic reactivity. In the absence of other reactants, the formation of direct strand breaks from C1′-radicals is, at most, a minor pathway. Competition studies between β-mercaptoethanol and 02 indicate that significantly higher thiol concentrations than those in vivo or some means of increasing the effective thiol concentration near DNA are needed for these reagents to prevent the formation of DNA lesions arising from the C1'-radical under aerobic conditions

Congenital anomalies from a physics perspective. The key role of "manufacturing" volatility

Genetic and environmental factors are traditionally seen as the sole causes of congenital anomalies. In this paper we introduce a third possible cause, namely random "manufacturing" discrepancies with respect to ``design'' values. A clear way to demonstrate the existence of this component is to ``shut'' the two others and to see whether or not there is remaining variability. Perfect clones raised under well controlled laboratory conditions fulfill the conditions for such a test. Carried out for four different species, the test reveals a variability remainder of the order of 10%-20% in terms of coefficient of variation. As an example, the CV of the volume of E.coli bacteria immediately after binary fission is of the order of 10%. In short, ``manufacturing'' discrepancies occur randomly, even when no harmful mutation or environmental factors are involved. Not surprisingly, there is a strong connection between congenital defects and infant mortality. In the wake of birth there is a gradual elimination of defective units and this screening accounts for the post-natal fall of infant mortality. Apart from this trend, post-natal death rates also have humps and peaks associated with various inabilities and defects.\qL In short, infant mortality rates convert the case-by-case and mostly qualitative problem of congenital malformations into a global quantitative effect which, so to say, summarizes and registers what goes wrong in the embryonic phase. Based on the natural assumption that for simple organisms (e.g. rotifers) the manufacturing processes are shorter than for more complex organisms (e.g. mammals), fewer congenital anomalies are expected. Somehow, this feature should be visible on the infant mortality rate. How this conjecture can be tested is outlined in our conclusion.Comment: 43 pages, 9 figure

La Figuration narrative : deux regards

A l’occasion de quelques expositions, la question du statut de la Figuration narrative en regard de certaines tendances caractéristiques des années 1960, a été plusieurs fois et implicitement posée. L’objectif étant de savoir si on doit voir en sa manifestation la version française du Pop art ou bien la dynamique d’un “regard idéologique“, selon la terminologie de Bernard Rancillac, présentant des images de la vie quotidienne à la manière d’un commentaire ironique de l’état du monde. En résum..

Narrative Figuration: Two Ways of Seeing Things

At some exhibitions, people have on several occasions and implicitly raised the issue of the status of New Figuration with regard to certain trends of the 1960s. The aim being to know whether we should see in its manifestation the French version of Pop Art or, alternatively, the dynamics of an “ideological eye”, to borrow Bernard Rancillac’s terminology, presenting images of everyday life in the manner of an ironical commentary on the state of the world. In a nutshell, is New Figuration to be..

The thermal equation of state of FeTiO_3 ilmenite based on in situ X-ray diffraction at high pressures and temperatures

We present in situ measurements of the unit-cell volume of a natural terrestrial ilmenite (Jagersfontein mine, South Africa) and a synthetic reduced ilmenite (FeTiO_3) at simultaneous high pressure and high temperature up to 16 GPa and 1273 K. Unit-cell volumes were determined using energy-dispersive synchrotron X-ray diffraction in a multi-anvil press. Mössbauer analyses show that the synthetic sample contained insignificant amounts of Fe^(3+) both before and after the experiment. Results were fit to Birch-Murnaghan thermal equations of state, which reproduce the experimental data to within 0.5 and 0.7 GPa for the synthetic and natural samples, respectively. At ambient conditions, the unit-cell volume of the natural sample [V_0 = 314.75 ± 0.23 (1 ) Å^3] is significantly smaller than that of the synthetic sample [V_0 = 319.12 ± 0.26 Å^3]. The difference can be attributed to the presence of impurities and Fe^(3+) in the natural sample. The 1 bar isothermal bulk moduli K_(T0) for the reduced ilmenite is slightly larger than for the natural ilmenite (181 ± 7 and 165 ± 6 GPa, respectively), with pressure derivatives K_0' = 3 ± 1. Our results, combined with literature data, suggest that the unit-cell volume of reduced ilmenite is significantly larger than that of oxidized ilmenite, whereas their thermoelastic parameters are similar. Our data provide more appropriate input parameters for thermo-chemical models of lunar interior evolution, in which reduced ilmenite plays a critical role

Towards Nonlinear Photonic Wires in Z-cut LiNbO3

International audienceUsing a modified Proton Exchange process we have realized Photonic Wires in X-cut LiNbO3. They exhibit highly confined mode, low propagation losses, low strain induced polarization coupling and no reduction of the nonlinear properties. We are now transferring this technique to Z-cut LiNbO3 in order to realize very efficient nonlinear devices in PPLN

Glucocorticoids and neurodegeneration

Series: Endocrinology research and clinical developmentsGlucocorticoids (GCs) exert wide-spread actions in central nervous system ranging from gene transcription, cellular signaling, modulation of synaptic structure and transmission, glial responses to altered neuronal circuitry and behavior through the activation of two steroid hormone receptors, glucocorticoid receptor (NR3C1, GR) and mineralocorticoid receptor (NR3C2, MR). These highly-related receptors exert both genomic and non-genomic actions in the brain, which are context-dependent and essential for adaptive responses to stress resulting in modulations of behavior, learning and memory processes. Thus, GCs through their receptors are implicated in neural plasticity as they modulate the dendritic and synaptic structure of neurons as well as the survival and fate of newly-generated cells (neuro- and glio-genesis) in adult brain. GCs are also important in fetal brain programming as inappropriate variations in their levels during critical developmental periods are suggested to be casually related to the development of brain pathologies and maladaptive responses of hypothalamic-pituitary adrenal (HPA) axis to stress during adulthood. They regulate immune responses in brain, which have important consequences for neuronal survival. In situations of chronic stress and HPA axis dysfunction resulting in chronically high or low GCs levels, a multitude of molecular, structural and functional changes occur in the brain, eventually leading to maladaptive behavior. In fact, clinical studies suggest a causal relation of deregulated GC responses with development of neurodegenerative disorders such as Alzheimer´s (AD) and Parkinson‘s (PD) diseases. AD and PD patients have high levels of circulating cortisol while animal studies suggest that this chronic GC elevation participates in neurodegenerative processes in both AD and PD pathologies. This chapter will focus on the role of HPA axis and GCs on neurodegenerative processes involved in AD and PD pathogenesis.(undefined

Analysis of High-Index Contrast Lithium Niobate Waveguides Fabricated by High Vacuum Proton Exchange

International audience—High-index contrast waveguides fabricated with precise control and reproducibility are of high interest for nonlinear and/or electro-optical highly efficient and compact devices for quantum and classical optical data processing. Here we present a new process to fabricate planar and channel optical waveguides on lithium niobate substrates that we called High Vacuum Proton Exchange (HiVacPE). The main purpose was to improve the reproducibility and the quality of the produced waveguides by limiting and controlling the water traces in the melt, which is used for the ionic exchange. Moreover, we discovered that, when the acidity of the bath is increased, depending on substrate orientation (Z-cut or X-cut) the waveguides are completely different in term of crystallographic properties, index profiles and nonlinearity. The best-obtained channel waveguides exhibit a refractive index contrast as high as 0.04 without any degradation of the crystal nonlinearity and state of the art propagation losses (0.16dB/cm). We have also demonstrated that the HiVacPE process allows fabricating waveguides on Z-cut substrate with high-index contrast up to 0.11 without degrading the crystal nonlinearity but high strain induced propagation losses. On top of that, we proposed an original and very useful method of analyzing waveguides with complex index profiles. This method can be used for the analysis of any waveguides whose core contains several layers