Caloric restriction reveals a metabolomic and lipidomic signature in liver of male mice

Lipid composition, particularly membrane unsaturation, has been proposed as being a lifespan determinant, but it is currently unknown whether caloric restriction (CR), an accepted life-extending intervention, affects cellular lipid profiles. In this study, we employ a liquid chromatography quadrupole time-of-flight-based methodology to demonstrate that CR in the liver of male C57BL/6 mice: (i) induces marked changes in the cellular lipidome, (ii) specifically reduces levels of a phospholipid peroxidation product, 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphatidylcholine, (iii) alters cellular phosphoethanolamine and triglyceride distributional profiles, (iv) affects mitochondrial electron transport chain complexes, increasing complex II and decreasing complex III and (v) is associated with specific changes in liver metabolic pathways. These data demonstrate that CR induces a specific lipidome and metabolome reprogramming event in mouse liver which is associated with lower protein oxidative damage, as assessed by mass spectrometry-based measurements. Such changes may be critical to the increased lifespan and healthspan observed in C57BL/6 mice following CR

Geometric multigrid methods for Darcy-Forchheimer flow in fractured porous media

In this paper, we present a monolithic multigrid method for the efficient solution of flow problems in fractured porous media. Specifically, we consider a mixed-dimensional model which couples Darcy flow in the porous matrix with Forchheimer flow within the fractures. A suitable finite volume discretization permits to reduce the coupled problem to a system of nonlinear equations with a saddle point structure. In order to solve this system, we propose a full approximation scheme (FAS) multigrid solver that appropriately deals with the mixed-dimensional nature of the problem by using mixed-dimensional smoothing and inter-grid transfer operators. Remarkably, the nonlinearity is localized in the fractures, and no coupling between the porous matrix and the fracture unknowns is needed in the smoothing procedure. Numerical experiments show that the proposed multigrid method is robust with respect to the fracture permeability, the Forchheimer coefficient and the mesh size.Comment: arXiv admin note: text overlap with arXiv:1811.0126

Surf and turf: animal resources in the human diet in Cantabrian Spain during the Mesolithic (11.5 – 7.5 Ky cal. BP)

The beginning of the Holocene involved a series of climatic and environmental changes that affected the ways of life of the last hunter-gatherers. In the case of the Spanish Cantabrian region, these changes transformed the material culture and the way human groups interacted with the environment and, therefore, the subsistence strategies of the end of the Upper Pleistocene. In terms of the use of faunal resources, this period was characterised by an increase in the exploitation of coastal resources, mainly molluscs, but also crustaceans and echinoderms, which make up the so-called “shell middens”, while at the same time the percentage of macromammals was reduced and animals considered to have a “low energy range” were introduced into the diet. In this paper we assess the role played by each of these animal resources in the subsistence of Mesolithic human groups, determining their nutritional contribution and establishing a prey ranking based on the caloric intake of each resource. For this purpose, we collected archaeofaunal data from 14 sites from recent archaeological excavations with levels dated between ca. 11.5 and 7.5 ky cal BP in which the consumption of vertebrates and invertebrates is documented. At each of these sites we analysed diversity, homogeneity and species richness using Simpson's and Shannon's indexes, as well as the effective numbers of species for terrestrial and coastal resources, assessing the relationship between the two. With the palaeoecological and palaeoeconomic data from these archaeological sites (most of them located in caves), we estimate the weight that the different animal resources consumed by the last hunter-gatherer communities of the Cantabrian region had in their diet.Programa Estatal de Fomento de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico of the Spanish Ministry of Science and Innovatio

Mixed-dimensional geometric multigrid methods for single-phase flow in fractured porous media

This paper deals with the efficient numerical solution of single-phase flow problems in fractured porous media. A monolithic multigrid method is proposed for solving two-dimensional arbitrary fracture networks with vertical and/or horizontal possibly intersecting fractures. The key point is to combine two-dimensional multigrid components (smoother and intergrid transfer operators) in the porous matrix with their one-dimensional counterparts within the fractures, giving rise to a mixed-dimensional geometric multigrid method. This combination seems to be optimal since it provides an algorithm whose convergence matches the multigrid convergence factor for solving the Darcy problem. Several numerical experiments are presented to demonstrate the robustness of the monolithic mixed-dimensional multigrid method with respect to the permeability of the fractures, the grid size, and the number of fractures in the network.The work of the first and fourth authors was supported by Spanish project PGC2018-099536-A-I00 (MCIU/AEI/FEDER, UE). The work of the second author was supported by the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement 705402, POROSOS. The work of the third author was partially supported by the Spanish project FEDER/MCYT MTM2016-75139-R. The work of the fourth author was supported by the DGA (Grupo de referencia APEDIF, ref. E24 17R)

Multigrid solvers for multipoint flux approximations of the Darcy problem on rough quadrilateral grids

In this work, an efficient blackbox-type multigrid method is proposed for solving multipoint flux approximations of the Darcy problem on logically rectangular grids. The approach is based on a cell-centered multigrid algorithm, which combines a piecewise constant interpolation and the restriction operator by Wesseling/Khalil with a line-wise relaxation procedure. A local Fourier analysis is performed for the case of a Cartesian uniform grid. The method shows a robust convergence for different full tensor coefficient problems and several rough quadrilateral grids.Francisco J. Gaspar has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska–Curie grant agreement no. 705402, POROSOS. The work of Laura Portero is supported by the Spanish project MTM2016-75139-R (AEI/FEDER, UE) and the Young Researchers Programme 2018 from the Public University of Navarre. Andrés Arrarás acknowledges support from the Spanish project PGC2018-099536-A-I00 (MCIU/AEI/FEDER, UE) and the Young Researchers Programme 2018 from the Public University of Navarre. The work of Carmen Rodrigo is supported by the Spanish project PGC2018-099536-A-I00 (MCIU/AEI/FEDER, UE) and the DGA (Grupo de referencia APEDIF, ref. E24_17R)

Precisión de diámetro abdominal sagital como predictor de la grasa abdominal en brasileños adultos: una comparación con la circunferencia de la cintura

Aim: We aim was to compare the sagittal abdominal diameter (SAD) with waist circumference (WC) as a predictor of central obesity among adults and to identify the sensitivity and specificity of the best cut-off point for SAD.Methods: A cross-sectional study of 266 Brazilians adults (euthrophic and overweight), aged 31-84 years old, of which 89 men and 177 women, was carried out. Anthropometric measurements such as SAD, weight, height, waist and hip circumferences, waist and hip ratio, body mass index, body fat percentage were performed. Receiver Operating Characteristics (ROC) curve was used to identify the sensitivity and specificity of the best cut off point for SAD as a predictor of central obesity. Statistical analysis were considered significant with a value of p < 0.05.Results: the SAD measurement was positively correlated with WC for both genders, although stronger among overweight and obesity women (r = 0.71; p < 0.001 and r = 0.79; p < 0.001, respectively) than men. ROC curves identified the best cut-off points for SAD of 23.1 cm and 20.1 cm for men and women (96% and 85% sensitivity, 86% and 84% specificity, respectively).Conclusion: SAD measurement may be used as an anthropometric tool to identify central obesity among women for presenting adequate sensitivity and specificity.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Physiol, BR-04023062 São Paulo, BrazilSão Paulo State Univ UNESP, Dept Publ Hlth, Ctr Metab Exercise & Nutr CeMENutri, Botucatu, SP, BrazilPUC, Sch Nutr, Campinas, SP, BrazilSão Paulo State Univ UNESP, Dept Stat, Botucatu, SP, BrazilUniversidade Federal de São Paulo, Dept Physiol, BR-04023062 São Paulo, BrazilWeb of Scienc

Relationship between heat shock proteins and cellular resistance to drugs and ageing

Background and aims Ageing is a multifactorial degenerative process which causes a decrease in the cellular capacity for repair and adaptation to external stressors. In this way, it is important to maintain the proper balance of the proteome. Heat shock proteins (HSP) will intervene in this balance, which are responsible for the correct assembly, folding and translocation of other proteins when cells are subjected to stressors. This type of protein is overexpressed in human tumor cells, while its deficit, both in function and quantity, contributes to ageing processes. The present work aims to analyze the response of cells from studies carried out in normal and tumor cells that are subjected to stressors. Methods and results A PubMed search was performed using the keywords “cell ageing, cell longevity, resistance, HSP, heat shock proteins, thermal shock proteins”. This search generated 212 articles. Subsequently, a series of inclusion and exclusion criteria were applied to select the articles of interest to be evaluated. Normal cells subjected to external stressors at low doses increase the number of HSP, causing them to become more resistant. In addition, tumor cells expressing high levels of HSP show greater resistance to treatment and increased cell replication. HSP intervene in the cellular resistance of both normal and tumor cells. Conclusions In the case of normal cells, the increase in HSP levels makes them respond effectively to an external stressor, increasing their resistance and not causing cell death. In the case of tumor cells, there is an increase in resistance to treatment.Funding for open access charge: Universidad de Málaga/CBUA