Degradation of IF1 controls energy metabolism during osteogenic differentiation of stem cells

Differentiation of human mesenchymal stem cells (hMSCs) requires the rewiring of energy metabolism. Herein, we demonstrate that the ATPase inhibitory factor 1 (IF1) is expressed in hMSCs and in prostate and colon stem cells but is not expressed in the differentiated cells. IF1 inhibits oxidative phosphorylation and regulates the activity of aerobic glycolysis in hMSCs. Silencing of IF1 in hMSCs mimics the metabolic changes observed in osteocytes and accelerates cellular differentiation. Activation of IF1 degradation acts as the switch that regulates energy metabolism during differentiation. We conclude that IF1 is a stemness marker important for maintaining the quiescence stateThis work was supported by grants from the Ministerio de Educación y Ciencia (BFU2010-18903), the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, and Comunidad de Madrid (S2011/BMD-2402), Spai

Association of single nucleotide polymorphisms in Pre-miR-27a, Pre-miR-196a2, Pre-miR-423, miR-608 and Pre-miR-618 with breast cancer susceptibility in a South American population

Indexación: Web of ScienceBackground MicroRNAs (miRNAs) are a novel class of endogenous, non-coding, single-stranded RNAs capable of regulating gene expression by suppressing translation or degrading mRNAs. Single nucleotide polymorphisms (SNP) can alter miRNA expression, resulting in diverse functional consequences. Previous studies have examined the association of miRNA SNPs with breast cancer (BC) susceptibility. The contribution of miRNA gene variants to BC susceptibility in South American women had been unexplored. Our study evaluated the association of the SNPs rs895819 in pre-miR27a, rs11614913 in pre-miR-196a2, rs6505162 in pre-miR-423, rs4919510 in miR-608, and rs2682818 in pre-mir-618 with familial BC and early-onset non-familial BC in non-carriers of BRCA1/2 mutations from a South American population. Results We evaluated the association of five SNPs with BC risk in 440 cases and 807 controls. Our data do not support an association of rs11614913:C > T and rs4919510:C > G with BC risk. The rs6505162:C > A was significantly associated with increased risk of familial BC in persons with a strong family history of BC (OR = 1.7 [95 % CI 1.0–2.0] p = 0.05). The rs2682818:C > A genotype C/A is associated with an increased BC risk in non-familial early-onset BC. For the rs895819:A > G polymorphism, the genotype G/G is significantly associated with reduced BC risk in families with a moderate history of BC (OR = 0.3 [95 % CI 0.1–0.8] p = 0.01). Conclusions The contribution of variant miRNA genes to BC in South American women had been unexplored. Our findings support the following conclusions: a) rs6505162:C > A in pre-miR-423 increases risk of familial BC in families with a strong history of BC; b) the C/A genotype at rs2682818:C > A (pre-miR-618) increases BC risk in non-familial early-onset BC; and c) the G/G genotype at rs895819:A > G (miR-27a) reduces BC risk in families with a moderate history of BC.http://bmcgenet.biomedcentral.com/articles/10.1186/s12863-016-0415-

Towards a new methodology for the characterisation of crack tip fields based on a hybrid computational approach

This work presents a hybrid optimisation technique for the simultaneous calculation of crack tip characterising parameters and its spatial location, which can significantly affect the characterising parameters if the position used is inaccurate. The hybrid technique combines initial use of a genetic algorithm to obtain a well-conditioned set of initial parameter values that is then passed to an interior point optimisation algorithm for subsequent fast optimisation. Use of the hybrid technique is also amenable to easy automation. The capability of the technique is demonstrated using the CJP crack tip field model, with digital image correlation (DIC) being used to measure the 2D crack tip displacement field. This model was chosen, not only for its demonstrated sensitivity to accuracy in crack tip location, but also for its proven utility in providing effective crack growth correlation in the presence of plasticity-induced shielding across a wide range of growth rates. The results obtained from the hybrid technique are shown to be reliable through comparison with results obtained using other established techniques

Characterization of non-planar crack tip displacement fields using a differential geometry approach in combination with 3D digital image correlation

This paper describes a novel differential geometry method that is used in combination with 3D digital image correlation (3D-DIC) for crack tip field characterization on non-planar (curved) surfaces. The proposed approach allows any of the two-dimensional crack tip field models currently available in the literature to be extended to the analysis of a 3D developable surface with zero Gaussian curvature. The method was validated by analyzing the crack tip displacement fields on hollow thin-walled cylindrical specimens, manufactured from either 304L or 2024-T3 alloy that contained a central circumferential crack. The proposed approach was checked via a comparison between experimentally measured displacement fields (3D-DIC) and those reconstructed from a modified 2D crack tip model (utilizing either 2, 3, or 4 terms of the William's expansion series) and implementing a 3D geometrical correction. Further validation was provided by comparing model-derived stress intensity factors with values provided by empirical correlations

Charge Induced Vortex Lattice Instability

It has been predicted that superconducting vortices should be electrically charged and that this effect is particularly enhanced for, high temperature superconductors.\cite{kho95,bla96} Hall effect\cite{hag91} and nuclear magnetic resonance (NMR) experiments\cite{kum01} suggest the existence of vortex charging, but the effects are small and the interpretation controversial. Here we show that the Abrikosov vortex lattice, characteristic of the mixed state of superconductors, will become unstable at sufficiently high magnetic field if there is charge trapped on the vortex core. Our NMR measurements of the magnetic fields generated by vortices in Bi$_{2}$Sr$_{2}$CaCu$_{2}$O$_{8+y}$ single crystals\cite{che07} provide evidence for an electrostatically driven vortex lattice reconstruction with the magnitude of charge on each vortex pancake of $\mathbf{\sim 2}$x$\mathbf{10^{-3} e}$, depending on doping, in line with theoretical estimates.\cite{kho95,kna05}Comment: to appear in Nature Physics; 6 pages, 7 figure

Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection

Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169+ sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4+CD25+ T cells and an increased number of B220+CD19+ B cells. The reduction in CD4+CD25+ T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome

Impact of N on the atomic-scale Sb distribution in quaternary GaAsSbN-capped InAs quantum dots

The use of GaAsSbN capping layers on InAs/GaAs quantum dots (QDs) has recently been proposed for micro- and optoelectronic applications for their ability to independently tailor electron and hole confinement potentials. However, there is a lack of knowledge about the structural and compositional changes associated with the process of simultaneous Sb and N incorporation. In the present work, we have characterized using transmission electron microscopy techniques the effects of adding N in the GaAsSb/InAs/GaAs QD system. Firstly, strain maps of the regions away from the InAs QDs had revealed a huge reduction of the strain fields with the N incorporation but a higher inhomogeneity, which points to a composition modulation enhancement with the presence of Sb-rich and Sb-poor regions in the range of a few nanometers. On the other hand, the average strain in the QDs and surroundings is also similar in both cases. It could be explained by the accumulation of Sb above the QDs, compensating the tensile strain induced by the N incorporation together with an In-Ga intermixing inhibition. Indeed, compositional maps of column resolution from aberration-corrected Z-contrast images confirmed that the addition of N enhances the preferential deposition of Sb above the InAs QD, giving rise to an undulation of the growth front. As an outcome, the strong redshift in the photoluminescence spectrum of the GaAsSbN sample cannot be attributed only to the N-related reduction of the conduction band offset but also to an enhancement of the effect of Sb on the QD band structure

The International-Trade Network: Gravity Equations and Topological Properties

This paper begins to explore the determinants of the topological properties of the international - trade network (ITN). We fit bilateral-trade flows using a standard gravity equation to build a "residual" ITN where trade-link weights are depurated from geographical distance, size, border effects, trade agreements, and so on. We then compare the topological properties of the original and residual ITNs. We find that the residual ITN displays, unlike the original one, marked signatures of a complex system, and is characterized by a very different topological architecture. Whereas the original ITN is geographically clustered and organized around a few large-sized hubs, the residual ITN displays many small-sized but trade-oriented countries that, independently of their geographical position, either play the role of local hubs or attract large and rich countries in relatively complex trade-interaction patterns

Human-carnivore relations: conflicts, tolerance and coexistence in the American West

Carnivore and humans live in proximity due to carnivore recovery efforts and ongoing human encroachment into carnivore habitats globally. The American West is a region that uniquely exemplifies these human-carnivore dynamics, however, it is unclear how the research community here integrates social and ecological factors to examine human-carnivore relations. Therefore, strategies promoting human-carnivore coexistence are urgently needed. We conducted a systematic review on human-carnivore relations in the American West covering studies between 2000 and 2018. We first characterized human-carnivore relations across states of the American West. Second, we analyzed similarities and dissimilarities across states in terms of coexistence, tolerance, number of ecosystem services and conflicts mentioned in literature. Third, we used Bayesian modeling to quantify the effect of social and ecological factors influencing the scientific interest on coexistence, tolerance, ecosystem services and conflicts. Results revealed some underlying biases in human-carnivore relations research. Colorado and Montana were the states where the highest proportion of studies were conducted with bears and wolves the most studied species. Non-lethal management was the most common strategy to mitigate conflicts. Overall, conflicts with carnivores were much more frequently mentioned than benefits. We found similarities among Arizona, California, Utah, and New Mexico according to how coexistence, tolerance, services and conflicts are addressed in literature. We identified percentage of federal/private land, carnivore family, social actors, and management actions, as factors explaining how coexistence, tolerance, conflicts and services are addressed in literature. We provide a roadmap to foster tolerance towards carnivores and successful coexistence strategies in the American West based on four main domains, (1) the dual role of carnivores as providers of both beneficial and detrimental contributions to people, (2) social-ecological factors underpinning the provision of beneficial and detrimental contributions, (3) the inclusion of diverse actors, and (4) cross-state collaborative management