New insights on final Epigravettian funerary behavior at Arene Candide cave (Western Liguria, Italy)

We gained new insights on Epigravettian funerary behavior at the Arene Candide cave through the osteological and spatial analysis of the burials and human bone accumulations found in the cave during past excavations. Archaeothanathological information on the human skeletal remains was recovered from diaries, field pictures and notes, and data from recent excavations was integrated. The secondary deposits have traditionally been interpreted as older burials that were disturbed to make space for new inhumations. Our results suggest that those disturbances were not casual: older burials were intentionally displaced to bury younger inhumations. Subsequently, some skeletal elements, especially crania, were arranged around the new burial; these were often placed within stone niches. Based on the composition of some clusters, which contain the bones of two individuals displaced together, it is possible that a double burial composed of two adults was originally present at the site. This would be a burial type that had not been recognized at Arene Candide until now. Strikingly, this potential double burial contained an individual showing pathological bowing of the limbs, a finding which is not infrequent in skeletons from Gravettian and Epigravettian multiple burials. In addition, the crania and other skeletal elements derived from this burial were intentionally placed around a new inhumation, whose skeleton possibly shows a milder form of the same disease (possibly hereditary rickets). This and other observations suggest that the five individuals belonging to the second phase of this “cemetery” (AMS dates spanning 12,030 – 11,180 cal BP) might have been buried over a relatively brief time span. Our study demonstrated similar behaviors in the first phase of mortuary use of the cave (12,820 – 12,420 cal BP), indicating a remarkable persistence in Final Epigravettian funerary models despite their archaeologically apparent rarity and intermittent nature

An in vivo magnetic resonance spectroscopy study of the effects of caloric and non-caloric sweeteners on liver lipid metabolism in rats

We aimed to elucidate the effects of caloric and non-caloric sweeteners on liver lipid metabolism in rats using in vivo magnetic resonance spectroscopy (MRS) and to determine their roles in the development of liver steatosis. Wistar rats received normal chow and either normal drinking water, or solutions containing 13% (w/v) glucose, 13% fructose, or 0.4% aspartame. After 7 weeks, in vivo hepatic dietary lipid uptake and de novo lipogenesis were assessed with proton-observed, carbon-13-edited MRS combined with13C-labeled lipids and13C-labeled glucose, respectively. The molecular basis of alterations in hepatic liver metabolism was analyzed in detail ex vivo using immunoblotting and targeted quantitative proteomics. Both glucose and fructose feeding increased adiposity, but only fructose induced hepatic lipid accumulation. In vivo MRS showed that this was not caused by increased hepatic uptake of dietary lipids, but could be attributed to an increase in de novo lipogenesis. Stimulation of lipogenesis by fructose was confirmed by a strong upregulation of lipogenic enzymes, which was more potent than with glucose. The non-caloric sweetener aspartame did not significantly affect liver lipid content or metabolism. In conclusion, liquid fructose more severely affected liver lipid metabolism in rats than glucose, while aspartame had no effect.</p

Development of type 1 diabetes in a patient treated with anti-TNF-α therapy for active rheumatoid arthritis

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Human remains from Arma di Nasino (Liguria) provide novel insights into the paleoecology of early Holocene foragers in northwestern Italy

We report the discovery and analysis of new Mesolithic human remains-dated to ca. 10,200-9000&nbsp;cal. BP-from Arma di Nasino in Liguria, northwestern Italy, an area rich in Upper Paleolithic and Neolithic attestations, but for which little information on Early Holocene occupation was available. The multi-proxy isotopic profile of the two individuals reveals that-despite the proximity of the site to the Mediterranean seashore and the use of shellfish as decorative elements in burials-the ecology of these foragers was based on the exploitation of high-altitude resources, presumably in the nearby western Alps. This constitutes the first direct evidence in northwestern Italy of a significant ecological shift towards higher altitudes following deglaciation, especially when compared to isotopic data of the Late Pleistocene hunter-gatherers from the nearby site of Arene Candide Cave, who exploited terrestrial resources nearer to the coast and at lower altitudes. While the biochemistry of Nasino's skeletal assemblage revealed new details on Early Holocene lifeways in the area, the osteobiography of one individual offers glimpses into the life experience of a specific female forager, depicting a scenario of early skeletal trauma, developmental disturbances, long-term impairments, and resilience amongst the last European hunter-gatherers

Methodologies for quantitative systems pharmacology (QSP) models:Design and Estimation

With the increased interest in the application of quantitative systems pharmacology (QSP) models within medicine research and development, there is an increasing need to formalize model development and verification aspects. In February 2016, a workshop was held at Roche Pharma Research and Early Development to focus discussions on two critical methodological aspects of QSP model development: optimal structural granularity and parameter estimation. We here report in a perspective article a summary of presentations and discussions.</p

Boolean network model predicts cell cycle sequence of fission yeast

A Boolean network model of the cell-cycle regulatory network of fission yeast (Schizosaccharomyces Pombe) is constructed solely on the basis of the known biochemical interaction topology. Simulating the model in the computer, faithfully reproduces the known sequence of regulatory activity patterns along the cell cycle of the living cell. Contrary to existing differential equation models, no parameters enter the model except the structure of the regulatory circuitry. The dynamical properties of the model indicate that the biological dynamical sequence is robustly implemented in the regulatory network, with the biological stationary state G1 corresponding to the dominant attractor in state space, and with the biological regulatory sequence being a strongly attractive trajectory. Comparing the fission yeast cell-cycle model to a similar model of the corresponding network in S. cerevisiae, a remarkable difference in circuitry, as well as dynamics is observed. While the latter operates in a strongly damped mode, driven by external excitation, the S. pombe network represents an auto-excited system with external damping.Comment: 10 pages, 3 figure

The 2013 M_w 7.7 Balochistan Earthquake: Seismic Potential of an Accretionary Wedge

Great earthquakes rarely occur within active accretionary prisms, despite the intense long‐term deformation associated with the formation of these geologic structures. This paucity of earthquakes is often attributed to partitioning of deformation across multiple structures as well as aseismic deformation within and at the base of the prism (Davis et al., 1983). We use teleseismic data and satellite optical and radar imaging of the 2013 M_w 7.7 earthquake that occurred on the southeastern edge of the Makran plate boundary zone to study this unexpected earthquake. We first compute a multiple point‐source solution from W‐phase waveforms to estimate fault geometry and rupture duration and timing. We then derive the distribution of subsurface fault slip from geodetic coseismic offsets. We sample for the slip posterior probability density function using a Bayesian approach, including a full description of the data covariance and accounting for errors in the elastic structure of the crust. The rupture nucleated on a subvertical segment, branching out of the Chaman fault system, and grew into a major earthquake along a 50° north‐dipping thrust fault with significant along‐strike curvature. Fault slip propagated at an average speed of 3.0  km/s for about 180 km and is concentrated in the top 10 km with no displacement on the underlying décollement. This earthquake does not exhibit significant slip deficit near the surface, nor is there significant segmentation of the rupture. We propose that complex interaction between the subduction accommodating the Arabia–Eurasia convergence to the south and the Ornach Nal fault plate boundary between India and Eurasia resulted in the significant strain gradient observed prior to this earthquake. Convergence in this region is accommodated both along the subduction megathrust and as internal deformation of the accretionary wedge

Gevolgen van groei voor financiële resultaten op melkveebedrijven in Nederland en EU : deelrapport 1 van het project "Groeien in rendement" = Implications of expansion on financial results of dairy farms in the Netherlands and the EU : report Part 1 of the project "Expansion with financial return"

Dairy farm expansions in the Netherlands and the EU and their impact on economic results are the focus of this report. After expansion successful expanders realize better results for nearly all types of revenues and costs. The high investments by expansion of Dutch dairy farms during the period 2000-2007 do not seem detrimental to their competitiveness compared to neighboring EU countries. However, they increase the risk of liquidity problems during periods of low milk prices

The Ornaments of the Arma Veirana Early Mesolithic Infant Burial

Personal ornaments are widely viewed as indicators of social identity and personhood. Ornaments are ubiquitous from the Late Pleistocene to the Holocene, but they are most often found as isolated objects within archaeological assemblages without direct evidence on how they were displayed. This article presents a detailed record of the ornaments found in direct association with an Early Mesolithic buried female infant discovered in 2017 at the site of Arma Veirana (Liguria, Italy). It uses microscopic, 3D, and positional analyses of the ornaments as well as a preliminary perforation experiment to document how they were perforated, used, and what led to their deposit as part of the infant’s grave goods. This study provides important information on the use of beads in the Early Mesolithic, in general, as well as the relationship between beads and young subadults, in particular. The results of the study suggest that the beads were worn by members of the infant’s community for a considerable period before they were sewn onto a sling, possibly used to keep the infant close to the parents while allowing their mobility, as seen in some modern forager groups. The baby was then likely buried in this sling to avoid reusing the beads that had failed to protect her or simply to create a lasting connection between the deceased infant and her community.Funding was provided by the Wenner-Gren Foundation (#9412), L.S.B. Leakey Foundation, National Geographic Society Waitt Program (#W391-15), Hyde Family Foundation [via the Human Origins Migrations and Evolutionary Research (HOMER) consortium], Social Sciences and Humanities Research Council (SSHRC) Insight Development Grant (#430–2018-00846), University of Colorado Denver, Washington University in St. Louis, Université de Montréal, and ERC n. 724046 – SUCCESS (to S.B.; http://www.erc-success.eu/). Part of the ornament analysis was supported by the European Research Council under the European Union’s Horizon 2020 Research and Innovation Program (grant agreement no. 639286 HIDDEN FOODS to E.C; http://www.hidden-foods.eu) to E.C. CHEI (University of California San Diego) supported 3D imaging. S. Talamo has received funding from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 803147 RESOLUTION, https://site.unibo.it/resolution-erc/en). The micro-CT scans have been co-funded by EuroBioimaging, Italian Multi-sited Multi-modal Molecular Imaging (MMMI) Node, application n.EuBI_FANE130