PDE11A gene polymorphism in testicular cancer: sperm parameters and hormonal profile.

PURPOSE: Testicular germ cell tumours (TGCTs) is the most common malignancy among young adult males. The etiology is multifactorial and both environmental and genetic factors play an important role in the origin and development of TGCT. Genetic susceptibility may result from the interaction of multiple common and low-penetrance genetic variants and one of the main candidate genes is PDE11A. Many PDE11A polymorphisms were found responsible for a reduced PDE activity in TGCT patients, who often also display impaired hormone and sperm profile. The aim of this study was to investigate testicular function and PDE11A sequence in testicular cancer cases. METHODS: Semen analysis was performed in 116 patients with unilateral and bilateral sporadic TGCTs and in 120 cancer-free controls. We also investigated hormone profile and PDE11A polymorphisms using peripheral blood samples. RESULTS: Our data revealed that TGCT patients showed lower testosterone levels, higher gonadotropins levels and worse semen quality than controls, although the mean and the medians of sperm parameters are within the reference limits. PDE11A sequencing detected ten polymorphisms not yet associated with TGCTs before. Among these, G223A in homozygosity and A288G in heterozygosity were significantly associated with a lower risk of testicular tumour and they displayed a positive correlation with total sperm number. CONCLUSIONS: Our findings highlight the key role of PDE11A in testis and suggest the presence of an underlying complex and fine molecular mechanism which controls testis-specific gene expression and susceptibility to testicular cancer.

How methane hydrate recovers at very high pressure the hexagonal ice structure.

Methane hydrate was recently shown, both experimentally and through simulations, to be stable up to the remarkably high pressure of 150 GPa. A new methane hydrate high-pressure (MH-IV) phase, reminiscent of ice at ambient pressure, was described for pressures above approximately 40 GPa. We disentangle here the main contributions to the relative stability of the lower pressure, denoted MH-III, and the high-pressure MH-IV structures. Through several simulation techniques, including metadynamics and path integral molecular dynamics for nuclear quantum effects, we analyze the phase transition mechanism, which implies hydrogen bond breaking and reforming, as well as methane reordering. The transition pathway is far from trivial, and the quantum delocalization of the hydrogen nuclei plays a significant role.

Topologically frustrated ionisation in a water-ammonia ice mixture.

Water and ammonia are considered major components of the interiors of the giant icy planets and their satellites, which has motivated their exploration under high P-T conditions. Exotic forms of these pure ices have been revealed at extreme (~megabar) pressures, notably symmetric, ionic, and superionic phases. Here we report on an extensive experimental and computational study of the high-pressure properties of the ammonia monohydrate compound forming from an equimolar mixture of water and ammonia. Our experiments demonstrate that relatively mild pressure conditions (7.4 GPa at 300 K) are sufficient to transform ammonia monohydrate from a prototypical hydrogen-bonded crystal into a form where the standard molecular forms of water and ammonia coexist with their ionic counterparts, hydroxide (OH-) and ammonium [Formula: see text] ions. Using ab initio atomistic simulations, we explain this surprising coexistence of neutral/charged species as resulting from a topological frustration between local homonuclear and long-ranged heteronuclear ionisation mechanisms.

A systematic study of ideal and double layer reconstructions of ABO3(001) surfaces (A = Sr, Ba; B = Ti, Zr) from first principles.

We conducted a comparative study of various reconstructions for the (001) surfaces of SrTiO(3), BaTiO(3), SrZrO(3) and BaZrO(3) perovskites through calculations within the density functional theory. The atomic structure, the thermodynamic stability and the charge distribution of ideal AO or BO(2) terminations, as well as the so-called AO or BO(2) double layer reconstructions were analysed, and it was found that of all the BO(2) double layer reconstructions the most stable are the (2 × 2) and the (√2 × âˆš2) ones. This is mainly due to stress release through the formation of long B-chains. On Ti-based perovskites, these double layer reconstructions were found to be thermodynamically stable, which was not the case for Zr-based perovskites, for which AO terminations dominated most of the stability domain. We also found that the BO(2) double layer reconstructions are accompanied by a substantial charge redistribution, with an almost neutral surface plane. This charge redistribution has important consequences for the reactivity and the behaviour of the electric field close to the surface.

Combination of (100), (110) and (111) facets in MgO crystals shapes from dry to wet environment.

At the onset of dissolution in water, cubic MgO smoke crystals present (110) cuts of the edges of the cubes. Next, (111) facets progressively dominate the shape of the crystallites, which finally transform into truncated octahedra. The morphology of the crystallites that are derived from surface energies computed within the density functional theory (DFT), only involve (100) and (111) facets. We explain the unexpected (110) cuts via a "constrained" Wulff equilibrium shape that arises from a slower kinetics of formation of (111) facets than (110) ones. Experiment and theory fully agree on the hierarchy of hydroxylated surface energies: Gamma(111) < Gamma(100) < Gamma(110), both supporting the partial dissociation of water on MgO(100). Finally, from low to high P(H2O) (high to low T), DFT-based calculations predict a switch from Wulff shapes involving dry (100) facets, in which the (100)/(111) area ratio decreases upon increasing P(H2O), to shapes involving hydroxylated (100) surfaces, in which the above ratio increases with P(H2O).

Water on extended and point defects at MgO surfaces.

The interaction of water with extended defects such as mono- and diatomic steps at the MgO(100) surface is investigated through first-principles simulations, as a function of water coverage. At variance with flat MgO(100) terraces, water adsorption is always dissociative on mono- and diatomic steps, as well as on MgO(110) surfaces. In most of the equilibrium configurations, the oxygen of the hydroxyl groups is two- or fourfold coordinated, but single-coordinated OH groups can be stabilized at diatomic step edges. The structural properties of the hydroxyl groups are discussed as a function of their coordination numbers and mutual interactions, as well as the surface defect morphology. It is shown that characteristics of water adsorption are primarily driven by the coordination number of the surface acid-base pair where the dissociation occurs. However, the OH groups resulting from water dissociation are also considerably stabilized by the electrostatic interaction with coadsorbed protons. At low coverage such an interaction, considerably stronger than hydrogen bonding, practically hinders any proton diffusion away from its neighboring hydroxyl. The computed adsorption energies allow us to discuss the onset of water desorption from flat MgO(100) terraces, diatomic and monoatomic steps, and from Mg-O divacancy.