Cenozoic inversion of the Weald-Boulonnais and the Dover Strait: new data

The Boulonnais is a former marine gulf superimposed on a zone of tectonic inversion, which was already excavated at least at the early Middle Eocene. New sedimentalogical and paleopedological data discover within the Boulonnais and fresh seismic sections able now to better understand the process of inversion step by step. The initial breaching probably took place in the late Eocene. The Dover Strait was probably open during the Lutetian, a part of the Oligocene and of the Late Neogene. Oligocene and Pliocene faunal assemblages are identical on both sides of the Strait. It was closed again for tectonic and eustatic reasons in the early Quaternary and reopen lately from Last Interglacial. This reopening is related with the evolution of the Western Channel and of its paleovalley system. This inversion of the Variscan front accommodates most of the shortening induced by the Pyrenean Orogen on the Western border of the European plate. The inversion of the Dover Strait region is almost synchronic with those of other basins of the Channel and North Sea areas. Tectonic, geomorphologic and climatic implications of this dynamic are discussed within the Western European context

Caffeine does not cause override of the G2/M block induced by UVc or gamma radiation in normal human skin fibroblasts

Caffeine has for many years been known to be involved in the sensitization of DNA to damage. One potential mechanism recently put forward is an override of the G2/M block induced by irradiation, which would leave the cells less time for DNA repair prior to mitosis. However, different cell types display a variety of responses and no clear pathway has yet emerged, especially as little is known about the capacity of this agent to enhance DNA damage in normal, untransformed cells. Continuous exposure to commonly used caffeine concentrations (1–5 mM) inhibited the proliferation of normal human fibroblasts (NHFs) in a dose-dependent manner to up to 80% at 5 mM. Exposure of exponentially growing NHFs to UVc radiation (20 J m–2) or γ radiation (2.5–8 Gy) led to a 45–60% inhibition of proliferation and protracted accumulation of cells in the G2/M phase. Addition of 2 mM caffeine after irradiation induced slowing of the S phase passage, with a resultant delay in G2/M accumulation mimicking a G2/M block override. These results were confirmed by stathmokinetic studies, which showed delayed entry of the cells into mitosis in the presence of caffeine. Our data demonstrate that caffeine primarily inhibits replicative DNA synthesis and suggest that, at least in normal cells, caffeine potentiates the cytotoxicity of radiation by intervening in DNA repair rather than by overriding the G2/M block. © 2000 Cancer Research Campaig

Thanatobiochemistry: post mortem study of the vitreous humor for the diagnosis of diabetic ketoacidosis death

Thanatobiochemistry refers to a post mortem study of biochemical parameters enabling to shed light on a cause of death. This discipline shines when suspected lethal pathology doesn\u27t have any noticeable macroscopic or microscopic features such as diabetic ketoacidosis. We relate the case of fourty-five years old patient followed-up for type I diabetes mellitus, discovered dead at home, for which only post mortem biochemical exploration of vitreous humor allowed to determine the cause of death by diabetic ketoacidosis

Crystal structure of Hop2-Mnd1 and mechanistic insights into its role in meiotic recombination

In meiotic DNA recombination, the Hop2-Mnd1 complex promotes Dmc1-mediated single-stranded DNA (ssDNA) invasion into homologous chromosomes to form a synaptic complex by a yet-unclear mechanism. Here, the crystal structure of Hop2-Mnd1 reveals that it forms a curved rod-like structure consisting of three leucine zippers and two kinked junctions. One end of the rod is linked to two juxtaposed winged-helix domains, and the other end is capped by extra ?-helices to form a helical bundle-like structure. Deletion analysis shows that the helical bundle-like structure is sufficient for interacting with the Dmc1-ssDNA nucleofilament, and molecular modeling suggests that the curved rod could be accommodated into the helical groove of the nucleofilament. Remarkably, the winged-helix domains are juxtaposed at fixed relative orientation, and their binding to DNA is likely to perturb the base pairing according to molecular simulations. These findings allow us to propose a model explaining how Hop2-Mnd1 juxtaposes Dmc1-bound ssDNA with distorted recipient double-stranded DNA and thus facilitates strand invasion

Focused methane migration formed pipe structures in permeable sandstones: Insights from uncrewed aerial vehicle-based digital outcrop analysis in Varna, Bulgaria

Focused fluid flow shapes the evolution of marine sedimentary basins by transferring fluids and pressure across geological formations. Vertical fluid conduits may form where localized overpressure breaches a cap rock (permeability barrier) and thereby transports overpressured fluids towards shallower reservoirs or the surface. Field outcrops of an Eocene fluid flow system at Pobiti Kamani and Beloslav Quarry (ca 15 km west of Varna, Bulgaria) reveal large carbonate‐cemented conduits, which formed in highly permeable, unconsolidated, marine sands of the northern Tethys Margin. An uncrewed aerial vehicle with an RGB sensor camera produces ortho‐rectified image mosaics, digital elevation models and point clouds of the two kilometre‐scale outcrop areas. Based on these data, geological field observations and petrological analysis of rock/core samples; fractures and vertical fluid conduits were mapped and analyzed with centimetre accuracy. The results show that both outcrops comprise several hundred carbonate‐cemented fluid conduits (pipes), oriented perpendicular to bedding, and at least seven bedding‐parallel calcite cemented interbeds which differ from the hosting sand formation only by their increased amount of cementation. The observations show that carbonate precipitation likely initiated around areas of focused fluid flow, where methane entered the formation from the underlying fractured subsurface. These first carbonates formed the outer walls of the pipes and continued to grow inward, leading to self‐sustaining and self‐reinforcing focused fluid flow. The results, supported by literature‐based carbon and oxygen isotope analyses of the carbonates, indicate that ambient seawater and advected fresh/brackish water were involved in the carbonate precipitation by microbial methane oxidation. Similar structures may also form in modern settings where focused fluid flow advects fluids into overlying sand‐dominated formations, which has wide implications for the understanding of how focusing of fluids works in sedimentary basins with broad consequences for the migration of water, oil and gas

Structural and functional analyses of the DMC1-M200V polymorphism found in the human population

The M200V polymorphism of the human DMC1 protein, which is an essential, meiosis-specific DNA recombinase, was found in an infertile patient, raising the question of whether this homozygous human DMC1-M200V polymorphism may cause infertility by affecting the function of the human DMC1 protein. In the present study, we determined the crystal structure of the human DMC1-M200V variant in the octameric-ring form. Biochemical analyses revealed that the human DMC1-M200V variant had reduced stability, and was moderately defective in catalyzing in vitro recombination reactions. The corresponding M194V mutation introduced in the Schizosaccharomyces pombe dmc1 gene caused a significant decrease in the meiotic homologous recombination frequency. Together, these structural, biochemical and genetic results provide extensive evidence that the human DMC1-M200V mutation impairs its function, supporting the previous interpretation that this single-nucleotide polymorphism is a source of human infertility

Prevalence of and Predictive Factors for Burnout Among French Urologists in Training

The burnout rate among young doctors currently seems to be increasing [1]. It is essential to be able to diagnose and prevent this condition to better take care of young caregivers. Burnout is defined as a “feeling of intense exhaustion, loss of control and inability to achieve concrete results at work” according to the World Health Organisation. The assessment questionnaire used most often is the Maslach Burnout Inventory (MBI), which covers (1) emotional exhaustion, (2) depersonalisation, and (3) personal accomplishment [2]