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Mammalian prions are neurotropic pathogens formed from PrPSc assemblies, a misfolded variant of the host‐encoded prion protein PrPC. Multiple PrPSc conformations or strains self‐propagate in host populations or mouse models of prion diseases, exhibiting distinct biological and biochemical phenotypes. Constrained interactions between PrPSc and PrPC conformations confer species specificity and regulate cross‐species transmission. The pathogenicity of fibrillar assemblies derived from bacterially expressed recombinant PrP (rPrP) has been instrumental in demonstrating the protein‐only nature of prions. Yet, their ability to encode different strains and transmit between species remains poorly studied, hampering their use in exploring structure‐to‐strain relationships. Fibrillar assemblies from rPrP with hamster, mouse, human, and bovine primary structures were generated and tested for transmission and adaptation in tg7 transgenic mice expressing hamster PrPC. All assemblies, except the bovine ones, were fully pathogenic on the primary passage, causing clinical disease, PrPSc brain deposition, and spongiform degeneration. They exhibited divergent adaptation processes and strain properties upon subsequent passage. Assemblies of hamster origin propagated without apparent need for adaptation, those of mouse origin adapted abruptly, and those of human origin required serial passages for optimal fitness. Molecular analyses revealed the presence of endogenously truncated PrPSc species in the resulting synthetic strains that lack the 90–140 amino acid region considered crucial for infectivity. In conclusion, rPrP assemblies provide a facile means of generating novel prion strains with adaptative/evolutive properties mimicking genuine prions. The PrP amino acid backbone is sufficient to encode different strains with specific adaptative properties, offering insights into prion transmission and strain diversity. [ABSTRACT FROM AUTHOR]

Evaporites are typically described as impermeable seals that create some of the world's highest reservoir pressures beneath the salt seal. However, several laboratory studies demonstrate that evaporites can retain open pore spaces that hydraulically connect the sediments above and below them in sedimentary basins. During the Messinian Salinity Crisis (5.97–5.33 Ma), up to 2,400 m thickness of evaporites were rapidly deposited in the Western Mediterranean, which may have generated high pore fluid overpressure in the basin sediments. Here we use one‐dimensional numerical modelling to quantify the temporal evolution of overpressure at two distinct locations of the Western Mediterranean, the Liguro‐Provençal and Algero‐Balearic basins, from the Miocene to Present. We reconstruct the sedimentation history of the basin, considering disequilibrium compaction as an overpressure mechanism and constraining model parameters (such as permeability and porosity) using laboratory experiments and the literature. In the Liguro‐Provençal basin the highest overpressure of 11.2 MPa occurs within the halite during deposition of Pliocene to Quaternary sediment, while in the Algero‐Balearic basin at the base of the Emile Baudot Escarpment, the highest overpressure of 3.1 MPa also occurs within the halite but during stage 3 of the Messinian Salinity Crisis (5.55–5.33 Ma). In the Algero‐Balearic basin an overpressure of 3.1 MPa could have been sufficient to hydro fracture the sediments, which agrees with the development of fluid escape features observed on seismic reflection profiles. In general, our models with evaporite deposition rates above 20 m kyr−1 and permeabilities below 10–18 m2, suggest that high overpressure, approaching lithostatic, can be generated in salt basins. [ABSTRACT FROM AUTHOR]

Aims: The amino acid sequence of prion protein (PrP) is a key determinant in the transmissibility of prion diseases. While PrP sequence is highly conserved among mammalian species, minor changes in the PrP amino acid sequence may confer alterations in the transmissibility of prion diseases. Classical bovine spongiform encephalopathy (C‐BSE) is the only zoonotic prion strain reported to date causing variant Creutzfeldt‐Jacob disease (vCJD) in humans, although experimental transmission points to atypical L‐BSE and some classical scrapie isolates as also zoonotic. The precise molecular elements in the human PrP sequence that limit the transmissibility of prion strains such as sheep/goat scrapie or cervid chronic wasting disease (CWD) are not well known. Methods: The transmissibility of a panel of diverse prions from different species was compared in transgenic mice expressing either wild‐type human PrPC (MDE‐HuTg340) or a mutated human PrPC harbouring Val166‐Gln168 amino acid changes (VDQ‐HuTg372) in the β2‐α2 loop instead of Met166‐Glu168 wild‐type variants. Results: VDQ‐HuTg372 mice were more susceptible to prions than MDE‐HuTg340 mice in a strain‐dependent manner. Conclusions: Met166‐Glu168 amino acid residues present in wild‐type human PrPC are molecular determinants that limit the propagation of most prion strains assayed in the human PrP context. [ABSTRACT FROM AUTHOR]

SUMMARY Recent pore‐scale observations and geomechanical investigations suggest the lack of true cohesion in methane hydrate‐bearing sediments (MHBSs) and propose that their mechanical behavior is governed by kinematic constrictions at pore‐scale. This paper presents a constitutive model for MHBS, which does not rely on physical bonding between hydrate crystals and sediment grains but on the densification effect that pore invasion with hydrate has on the sediment mechanical properties. The Hydrate‐CASM extends the critical state model Clay and Sand Model (CASM) by implementing the subloading surface model and introducing the densification mechanism. The model suggests that the decrease of the sediment available void volume during hydrate formation stiffens its structure and has a similar mechanical effect as the increase of sediment density. In particular, the model attributes stress‐strain changes observed in MHBS to the variations in sediment available void volume with hydrate saturation and its consequent effect on isotropic yield stress and swelling line slope. The model performance is examined against published experimental data from drained triaxial tests performed at different confining stress and with distinct hydrate saturation and morphology. Overall, the simulations capture the influence of hydrate saturation in both the magnitude and trend of the stiffness, shear strength, and volumetric response of synthetic MHBS. The results are validated against those obtained from previous mechanical models for MHBS that examine the same experimental data. The Hydrate‐CASM performs similarly to previous models, but its formulation only requires one hydrate‐related empirical parameter to express changes in the sediment elastic stiffness with hydrate saturation. [ABSTRACT FROM AUTHOR]

A better understanding of the effect of methane hydrate morphology and saturation on elastic wave velocity of hydrate‐bearing sediments is needed for improved seafloor hydrate resource and geohazard assessment. We conducted X‐ray synchrotron time‐lapse 4‐D imaging of methane hydrate evolution in Leighton Buzzard sand and compared the results to analogous hydrate formation and dissociation experiments in Berea sandstone, on which we measured ultrasonic P and S wave velocities and electrical resistivity. The imaging experiment showed that initially hydrate envelops gas bubbles and methane escapes from these bubbles via rupture of hydrate shells, leading to smaller bubbles. This process leads to a transition from pore‐floating to pore‐bridging hydrate morphology. Finally, pore‐bridging hydrate coalesces with that from adjacent pores creating an interpore hydrate framework that interlocks the sand grains. We also observed isolated pockets of gas within hydrate. We observed distinct changes in gradient of P and S wave velocities increase with hydrate saturation. Informed by a theoretical model of idealized hydrate morphology and its influence on elastic wave velocity, we were able to link velocity changes to hydrate morphology progression from initial pore‐floating, then pore‐bridging, to an interpore hydrate framework. The latter observation is the first evidence of this type of hydrate morphology and its measurable effect on velocity. We found anomalously low S wave velocity compared to the effective medium model, probably caused by the presence of a water film between hydrate and mineral grains. Key Points: We observe the evolution of methane hydrate morphology in porous media by 4‐D X‐ray CT imaging and laboratory geophysical experimentsX‐ray CT shows that hydrate morphology evolves from an initial pore‐floating, to pore‐bridging, to a final interpore hydrate frameworkWe found anomalously low S wave velocity probably caused by the presence of water films between hydrate and host grains [ABSTRACT FROM AUTHOR]

Abstract: During recent years, 3‐D techniques such as LiDAR and Structure‐from‐Motion (SfM) photogrammetry have been increasingly used for gully erosion assessment. However, innovative image‐based approaches based on these advances may also be used to provide accurate cross‐sectional measurements which are less expensive and time‐demanding. In this work, we present the FreeXSapp methodology, a new piece of freely‐available software based on existing SfM tools (MicMac and PMVS2) and augmented‐reality targets (ArUco markers) which performs the automated 3‐D reconstruction, scaling, orientation and analysis of gully cross‐sections (XSs) from images taken from the gully margin using a smartphone camera. As a field application, the volume of a 60‐m‐long medium‐size gully was evaluated, where a total of 10 XSs were measured and analyzed in approximately 30 min. The relative accuracy in estimating width and depth dimensions was in the order of 0.5%, with a precision ratio (relative to the camera–XS distance) of ~1500. Overall, using this methodology showed excellent performance in terms of time and cost requirements when compared with typical 3‐D and conventional 2‐D techniques. The FreeXSapp interface is downloadable for free for Windows operating systems at http://www.uco.es/users/ccastillo/freexsapp. Copyright © 2018 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Methane hydrate saturation estimates from remote geophysical data and borehole logs are needed to assess the role of hydrates in climate change, continental slope stability, and energy resource potential. Here we present laboratory hydrate formation/dissociation experiments in which we determined the methane hydrate content independently from pore pressure and temperature and from electrical resistivity. Using these laboratory experiments, we demonstrate that hydrate formation does not take up all the methane gas or water even if the system is under two phase water‐hydrate stability conditions and gas is well distributed in the sample. The experiment started with methane gas and water saturations of 16.5% and 83.5%, respectively; during the experiment, hydrate saturation proceeded up to 26% along with 12% gas and 62% water remaining in the system. The coexistence of hydrate and gas is one possible explanation for discrepancies between estimates of hydrate saturation from electrical and acoustic methods. We suggest that an important mechanism for this coexistence is the formation of a hydrate film enveloping methane gas bubbles, trapping the remaining gas inside. [ABSTRACT FROM AUTHOR]

Locating and quantifying overpressures are essential to understand basin evolution and hydrocarbon migration in deep basins and thickly sedimented continental margins. Overpressures influence sediment cohesion and hence fault slip in seismically active areas or failure on steep slopes, and may drive catastrophic fluid expulsion. They also represent a significant drilling hazard. Here, we present a method to calculate the pore pressure due to disequilibrium compaction. Our method provides an estimate of the compaction factor, surface porosity and sedimentation rate of each layer in a sediment column using a decompaction model and the constraints imposed by seismic data and geological observations. For a range of surface porosities, an ad hoc iterative equation determines the compaction factor that gives a calculated layer thickness that matches the observed thickness within a tolerance. The surface porosity and compaction factor are then used to obtain a density profile and a corresponding estimate of P-wave velocity ( V p). The selected parameters are those that give a good match with both the observed and calculated layer thicknesses and V p profiles. We apply our method to the centre of the Eastern Black Sea Basin ( EBSB), where overpressures have been linked to a low-velocity zone ( LVZ) at ca. 5500-8500 m depth. These overpressures were generated by the relatively high sedimentation rate of ca. 0.28 m ka−1 of the low permeability organic-rich Maikop formation at 33.9-20.5 Ma and an even higher sedimentation rate of ca. 0.85 m ka−1 at 13-11 Ma. We estimate a maximum pore pressure of ca. 138 MPa at ca. 8285 m depth, associated with a ratio of overpressure to vertical effective stress in hydrostatic conditions ( [ABSTRACT FROM AUTHOR]

The study aimed to assess the diagnostic yield of a colonoscopy screening programme in first-degree relatives of colorectal cancer (CRC) patients and to identify factors associated with advanced neoplasia. We conducted a cross-sectional study. Individual characteristics, family trees and colonoscopy findings of asymptomatic first-degree relatives of CRC patients were collected. The findings were classified into cancer (invasive carcinoma and/or non-invasive high-grade neoplasia), high-risk adenomas (≥ 10 mm and/or a villous component) and low-risk adenomas (tubular < 10 mm). The dependent variable was the presence of advanced neoplasia, defined as cancer and/or high-risk adenoma. Two hundred and sixty-three relatives (147 females), 50.0 ± 11.5 (range, 25-75) years of age, agreed to participate out of a total of 618 who were invited (acceptance rate 42.5%). Index cases were diagnosed at 63.8 ± 12.4 (range, 37-88) years of age. The closest familial relationship was parent/offspring in 168 (63.9%) participants and sibling in 95 (36.1%) participants; 14.8% had three or more relatives with CRC/cancer associated with Lynch syndrome, and two or more affected generations were identified in 24.0%. Advanced neoplasia was found in 56 (21.3%) participants. Of these, invasive cancer, non-invasive high-grade neoplasia and high-risk adenomas were detected in five (1.9%), six (2.3%) and 45 (17.1%) participants, respectively. Low-risk adenomas were detected in 20 (7.6%) participants. Male sex (odds ratio, 2.59; P = 0.003) and sibling relationship (odds ratio, 2.74; P = 0.001) were independently associated with advanced neoplasia. We detected advanced neoplasia in a considerable number of participants. Our data support colonoscopy screening in first-degree relatives of patients with CRC at an earlier age than in the medium-risk population. Male sex and sibling relationship were predictors of advanced neoplasia. [ABSTRACT FROM AUTHOR]