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Understanding progression mechanisms and developing new targeted therapies is imperative in pancreatic ductal adenocarcinoma (PDAC). In this study, 80 metastatic PDAC patients were prospectively recruited and divided into discovery (n=37) and validation (n=43) cohorts. Tumor and plasma samples taken at diagnosis were pair analyzed using whole exome sequencing (WES) in patients belonging to the discovery cohort alone. The variant allele frequency (VAF) of KRAS mutations was measured by ddPCR in plasma at baseline and response assessment in all patients. Plasma WES identified at least one pathogenic variant across the cohort, uncovering oncogenic mechanisms, DNA repair, microsatellite instability, and alterations in the TGFb pathway. Interestingly, actionable mutations were mostly found in plasma rather than tissue. Patients with shorter survival showed enrichment in cellular organization regulatory pathways. Through WES we could identify a specific molecular profile of patients with liver metastasis, which exhibited exclusive mutations in genes related to the adaptive immune response pathway, highlighting the importance of the immune system in liver metastasis development. Moreover, KRAS mutations in plasma (both at diagnosis and persistent at follow-up) correlated with shorter progression free survival (PFS). Patients presenting a reduction of over 84.75 % in KRAS VAF at response assessment had similar PFS to KRAS-negative patients. Overall, plasma WES reveals molecular profiles indicative of rapid progression, potentially actionable targets, and associations between adaptive immune response pathway alterations and liver tropism. [ABSTRACT FROM AUTHOR]

Fluvial tufa located in the Queiles and Val river valleys (Moncayo Natural Park, Iberian Range, NE Iberia), are investigated following morphostratigraphic descriptions, radiocarbon dating and palynological and anthracological analyses. The studied tufa deposits have been chronologically framed within the Early-Mid Holocene (ca. 9500 to 4000 cal yr BP) in agreement with regional tufa build-up. Similarly, both climatic and palaeoenvironmental conditions reconstructed for this period fit with regional data from lacustrine records. The obtained pollen profiles and charcoal results show the existence of a local riparian woodland, where diverse mesophytes like deciduous Quercus , Corylus , Salix , Populus , Ulmus , Juglans and Hedera define the main vegetation features in the river valleys. Unexpectedly, both pollen and anthracological data also place Taxus baccata and Castanea sativa populations growing near the study area, and denoting, in the case of chestnut, its native and long-term presence in the Iberian Range. Deciduous ( Quercus faginea/pyrenaica type) and evergreen oaks ( Quercus ilex/coccifera type) were the main spread regional forest which conformed the meso-Mediterranean vegetation belt of the Moncayo Range and borderlands, accompanied by many warm-loving shrubs like Olea , Phillyrea , Rhamnus and Pistacia , pointing out the optimal thermic period of the Holocene. Pine ( Pinus nigra/sylvestris type) and montane broadleaved communities ( Betula , Fagus ) were usually confined to high-altitude elevations, but anthracological record also address local presence. The combination of pollen and charcoal analyses together with the dating tufa of build-ups, represent an essential tool to complete the regional palaeoclimatic and palaeohydrological reconstructions as well as to address precisely the past distribution of unusual taxa. [ABSTRACT FROM AUTHOR]

Abstract: Volatile sulphur compounds (VSCs) are of prime importance in the overall aroma of cheese and make a significant contribution to their typical flavours. Thus, the control of VSCs formation offers considerable potential for industrial applications. Here, lactic acid bacteria (LAB) from different ecological origins were screened for their abilities to produce VSCs from L-methionine. From the data presented, VSC-forming abilities were shown to be strain-specific and were correlated with the C-S lyase enzymatic activities determined using different approaches. High VSCs formation were detected for those strains that were also shown to possess high thiol-producing abilities (determined either by agar plate or spectrophotometry assays). Moreover, differences in C-S lyase activities were shown to correspond with the enzymatic potential of the strains as determined by in situ gel visualization. Therefore, the assessment of the C-S lyase enzymatic potential, by means of either of these techniques, could be used as a valuable approach for the selection of LAB strains with high VSC-producing abilities thus, representing an effective way to enhance cheese sulphur aroma compounds synthesis. In this regard, this study highlights the flavour forming potential of the Streptococcus thermophilus STY-31, that therefore could be used as a starter culture in cheese manufacture. Furthermore, although C-S lyases are involved in both biosynthetic and catabolic pathways, an association between methionine and cysteine auxotrophy of the selected strains and their VSCs-producing abilities could not be found. [Copyright &y& Elsevier]

• Unique 60-m thick clastic laminated cave record covering 71–26 ky. • New dating and palaeoenviromental inferences from Pyrenean glaciers. • Identification of two main glacier stabilization phases at ~30–36 ky and ~15 ky. • Backflooding due to the blockage of the cave entrance by the Ara glacier. In Alpine regions, speleothem development on karst systems largely occurs during warm interglacial or interstadial phases due to their limited growth during cold stages. Still, recent attention has been given to the role of clastic sediments in caves, less dependent on temperature conditions. Yet, only a small number of caves worldwide preserve both speleothems and detrital deposits. Here we present an outstanding record of fine-grain laminated sediments and carbonate speleothems from the Granito cave (South Central Pyrenees, Spain) associated with seasonal to annual hydroclimatic pulses through the Last Glacial Cycle (LGC). Analysis of cave clastic facies together with new absolute dates on glacial deposits along the valley has provided new insights into the karst-glacial interactions in relation with long-term landscape evolution, with support of geomorphological, sedimentological, mineralogical, palynological, geochemical and geochronological data (U/Th series, OSL and IRSL). The Granito cave was formed before 153.6±1.2 ky (Marine Isotopic Stage, MIS 6), as indicated by the oldest stalagmites dated in the cave, although speleothem formation occurred preferentially during MIS 5 and the Holocene interglacial stages. A 60 m thick clastic deposit was IRSL dated from 71.8±5.6 ky to after 26.5±2.5 ky corresponding with the maximum ice extent (MIE) during the LGC and subsequent glacial stabilization at 30.3±1.7 – 36.2±2.2 ky. The sediment infill was produced by water ponded in the cave coeval with the presence of glacial ice blocking the cave entrance. The cave clastic sequence includes channel, slackwater and backswamp facies, interpreted to result from pulses of sediment-laden water flow under vadose and phreatic flow regimes. The cave sediment's mineralogical composition points to an exogenous source associated with glacial till sediments overlying the hillslope above the cave and along the Ara River valley. The palynological results obtained from the cave sediments show the dominance of an open landscape composed of steppe vegetation indicating cold glacial climatic conditions. The opening of the cave occurred before 14.9±1.5 ky, the stabilization age of the innermost Ara glacier moraine, giving rise to scouring and cut-and-fill sequences within the detrital infill. Speleothem growth during the Holocene indicates the return to warm climatic conditions with the development of a soil and vegetation cover above the cave. This study shows how a combined interpretation of clastic and speleothem lithofacies is critical for elucidating landscape evolution and surface-groundwater palaeohydrological changes in northern Iberia during the LGC. [ABSTRACT FROM AUTHOR]

Fish carpaccio is a ready-to-eat product with a very limited shelf life. In the present work, the use of high pressure treatment (HP) and/or antimicrobial edible film was studied in order to improve quality and stability of salmon carpaccio. In a preliminary part of the work, a film composed of gelatin plus chitosan incorporating clove essential oil was selected, based on its physicochemical and antimicrobial properties. Eugenol and β-caryophyllene, the main volatile components of the film, migrated to salmon muscle, the release being favored by HP and storage time. Concurrently, reducing power of the muscle increased, resulting in prevention of lipid oxidation derived from either HP or refrigerated storage. HP treatment reduced total microbial counts by 1.5 log cycles from the onset of storage, whereas the film reduced it by 2 log cycles after 3 days. The combination of HP and edible film exerted the most intense antimicrobial effect, total bacterial counts, luminescent bacteria, H 2 S-producing organisms, pseudomonads, enterobacteria, and lactic acid bacteria remaining constant or under detection limit over the whole storage period (11 days). The combined use of HP treatment and gelatin–chitosan–clove essential oil film is an effective way of improving quality and stability of salmon carpaccio. [ABSTRACT FROM AUTHOR]

Perennial ice deposits in caves represent unique, but underexplored, terrestrial sequences that potentially contain outstanding palaeoclimatic records. Here, we present a pioneer palaeoenvironmental study of an ice deposit preserved in a small sag-type cave (A294) in the Central Pyrenees (northern Iberian Peninsula). The 9.25-m-thick sequence, which is dated from 6100 ± 107 to 1888 ± 64 cal BP, represents the oldest known firn ice record worldwide. The stratigraphy (detrital layers, unconformities, and cross stratification), plant macrofossils, and isotopic signature (similarity between the ice linear distribution, δ 2 H = 7.83 δ 18 O + 8.4 , and the Global Meteoric Water Line) of the ice point to the diagenesis of snow introduced to the cave by winter snowstorms. Four phases of rapid ice accumulation (6100–5515, 4945–4250, 3810–3155, and 2450–1890 cal BP) are related to wetter and colder winters. Comparison of the isotopic composition ( δ 18 O and deuterium excess) of the ice with other paleoclimate records show that both source effects and the North Atlantic Oscillation (NAO) mechanism exert a dominant influence on the ice cave record. The NAO signal may be a combination of source effects and rainfall amount. Three intervals with low ice accumulation occurred between the phases of rapid accumulation and were related to drier, and possibly warmer, winters. These centennial-scale episodes appear to be in-phase with regional arid events, as established from high altitude lacustrine records and can be correlated to global Rapid Climate Change events. The current warming trend has dramatically decreased the volume of the ice deposit in cave A294. [ABSTRACT FROM AUTHOR]

Abstract This study was conducted in Ejulve cave (Spain, southwestern Europe) over a period of four years (2013–2016) to identify the factors affecting the isotopic composition of rainfall, dripwaters, and farmed calcite. The results indicate that δ18O of rainfall in the study area was mainly controlled by the temperature effect (r 2 = 0.82, p -value < 0.001) with source effect and amount effect being secondary controls. Additionally, it exhibited a seasonal pattern with lower values indicated during winter and higher in summer. The use of effective infiltration to evaluate the recharge of the epikarst is extremely important in semi-arid karst climate conditions. This analysis revealed that while the amount effect exerted a moderate control on the annual δ18O in rainfall, it had a lower influence on the isotopic variability of the rainfall potentially infiltrating the karst aquifer. The sampling of 12 drip locations in Ejulve cave indicated that seepage and seasonal drips featured similar δ18O values in dripwaters. The homogenisation process during the infiltration in the epikarst was not complete, therefore, the δ18O seasonality seen in rainfall was also observed in dripwater δ18O, albeit attenuated and lagged. With the seasonal increase in rainfall in autumn, drip rates of seasonal and seepage groups increased within a few weeks. However, the lower δ18O of autumn–winter rain was observed in dripwaters with a lag as long as 21 weeks. The δ18O in farmed calcite showed a small variation of 0.11‰ while the δ13C varied seasonally with a variation of about 0.22‰ and indicated higher values during summer and autumn and lower values in winter and spring. Seasonal and seepage sites exhibited similar δ18O variability. However, δ13C was more positive in seepage sites and was enhanced by degassing kinetics to produce a variability of up to 0.42‰ in contrast to the 0.29‰ observed in the seasonal sites. The δ18O of calcite showed dependence on the δ18O of dripwater with a weak influence of the drip rate. However, δ13C exhibited a higher correlation with the drip rate and high δ13C was explained by enhanced degassing and low water availability while low δ13C values were in concordance with higher microbial activity, vegetation productivity, and greater water availability. The ventilation of the cave during late autumn through spring favoured the higher calcite deposition rates found during that time. [ABSTRACT FROM AUTHOR]

Abstract: Information on the effectiveness of wildlife management actions is scarce, despite the great relevance of this type of information for maximizing conservation goals while minimizing resource expenditure. Here we assess the management effectiveness of a four-year hunting moratorium, addressed to protecting a declining waterbird game species: common coot Fulica atra. We also studied the indirect benefits that this management action could have had on a non-target endangered species (crested coot Fulica cristata), currently being reintroduced in the study region (Comunidad Valenciana, eastern Spain). We found that wintering common coots interrupted their marked negative trend coinciding with the hunting moratorium, and Before-After-Control-Impact modelling confirmed this fact. However breeding common coots continued their negative trend in numbers. We also found that crested coots increased their wintering numbers during the hunting moratorium years but not during breeding. We detected a strong and time variant cost of release on survival probability of crested coots, but annual survival probability was found to be constant and low for experienced birds, with no clear effects of the hunting moratorium on survival probability. We conclude that the moratorium had some positive effect on both species, but we suggest that lack of enforcement during a traditional hunting practice at the end of each hunting season, most likely precluded the moratorium having a long-lasting effect on the breeding numbers and probably on survival, of both species. Hence, when fully-enforced hunting moratoria are difficult to implement, we recommend the creation of hunting preserves of high habitat quality to attract coots during the winter, allowing its subsequent reproduction during the breeding season. [Copyright &y& Elsevier]

Abstract: Translocations have become one of the most commonly used tools for biodiversity restoration worldwide, however one out of three re-introduction plans fails to create a viable population or to successfully reinforce the existing one. We used results from the analysis of individual-based information on the re-introduction of a threatened waterfowl species, the crested coots Fulica cristata, to provide guidelines to maximise re-introduction success. We found that about a third of the post-release mortality took place within the first month after release. This immediate ‘cost of release’ in terms of local survival or ‘release risk factor’ seems to be a common feature of re-introduction projects, and it is likely due to the inexperience of captive-born individuals to face the new environment. This hypothesis was supported by the positive association between survival and time spent in the wild Results suggested that coots released between February and May have a slightly higher survival. A joint measure of survival and breeding probabilities indicated that birds released in late winter (February-March) had a higher chance to survive and reproduce compared to birds released later in the year. From an applied perspective our results can be used within an adaptive management framework to determine the optimum period of release, providing substantial support for future decision-making in the management of waterfowl, and other long-term projects of re-introduction of threatened vertebrate species. [Copyright &y& Elsevier]