The metastasis inducer CCN1 (CYR61) activates the fatty acid synthase (FASN)-driven lipogenic phenotype in breast cancer cells

The angiogenic inducer CCN1 (Cysteine-rich 61, CYR61) is differentially activated in metastatic breast carcinomas. However, little is known about the precise mechanisms that underlie the pro-metastatic actions of CCN1. Here, we investigated the impact of CCN1 expression on fatty acid synthase (FASN), a metabolic oncogene thought to provide cancer cells with proliferative and survival advantages. Forced expression of CCN1 in MCF-7 cells robustly up-regulated FASN protein expression and also significantly increased FASN gene promoter activity 2- to 3-fold, whereas deletion of the sterol response element-binding protein (SREBP) binding site in the FASN promoter completely abrogated CCN1-driven transcriptional activation. Pharmacological blockade of MAPK or PI-3´K activation similarly prevented the ability of CCN1 to induce FASN gene activation. Pharmacological inhibition of FASN activity with the mycotoxin cerulenin or the small compound C75 reversed CCN1-induced acquisition of estrogen independence and resistance to hormone therapies such as tamoxifen and fulvestrant in anchorage-independent growth assays. This study uncovers FASNdependent endogenous lipogenesis as a new mechanism controlling the metastatic phenotype promoted by CCN1. Because estrogen independence and progression to a metastatic phenotype are hallmarks of therapeutic resistance and mortality in breast cancer, this previously unrecognized CCN1-driven lipogenic phenotype represents a novel metabolic target to clinically manage metastatic disease progression.Fil: Menendez, Javier A.. Instituto Catalán de Oncología; España. Institut d; EspañaFil: Vellón, Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Espinoza, Ingrid. University Of Mississippi; Estados UnidosFil: Lupu, Ruth. Mayo Clinic Cancer Center; Estados Unido

Nuclear forces and their impact on neutron-rich nuclei and neutron-rich matter

We review the impact of nuclear forces on matter at neutron-rich extremes. Recent results have shown that neutron-rich nuclei become increasingly sensitive to three-nucleon forces, which are at the forefront of theoretical developments based on effective field theories of quantum chromodynamics. This includes the formation of shell structure, the spectroscopy of exotic nuclei, and the location of the neutron dripline. Nuclear forces also constrain the properties of neutron-rich matter, including the neutron skin, the symmetry energy, and the structure of neutron stars. We first review our understanding of three-nucleon forces and show how chiral effective field theory makes unique predictions for many-body forces. Then, we survey results with three-nucleon forces in neutron-rich oxygen and calcium isotopes and neutron-rich matter, which have been explored with a range of many-body methods. Three-nucleon forces therefore provide an exciting link between theoretical, experimental and observational nuclear physics frontiers.Comment: 28 pages, 13 figures, 1 tabl

Three-nucleon forces and spectroscopy of neutron-rich calcium isotopes

We study excited-state properties of neutron-rich calcium isotopes based on chiral two- and three-nucleon interactions. We first discuss the details of our many-body framework, investigate convergence properties, and for two-nucleon interactions benchmark against coupled-cluster calculations. We then focus on the spectroscopy of 47-56Ca, finding that with both 3N forces and an extended pfg9/2 valence space, we obtain a good level of agreement with experiment. We also study electromagnetic transitions and find that experimental data are well described by our calculations. In addition, we provide predictions for unexplored properties of neutron-rich calcium isotopes.Comment: 15 pages, 22 figures, published versio

Exploring sd-shell nuclei from two- and three-nucleon interactions with realistic saturation properties

We study ground- and excited-state properties of all sd-shell nuclei with neutron and proton numbers 8 <= N,Z <= 20, based on a set of low-resolution two- and three-nucleon interactions that predict realistic saturation properties of nuclear matter. We focus on estimating the theoretical uncertainties due to variation of the resolution scale, the low-energy couplings, as well as from the many-body method. The experimental two-neutron and two-proton separation energies are reasonably well reproduced, with an uncertainty range of about 5 MeV. The first excited 2+ energies also show overall agreement, with a more narrow uncertainty range of about 500 keV. In most cases, this range is dominated by the uncertainties in the Hamiltonian.Comment: 6 pages, 4 figure

Supplementary report to the final report of the coral reef expert group: S5. Statistical power of existing AIMS Long-Term Reef Monitoring Programs

[Extract] This report presents estimates of power to detect changes in the rate of coral cover recovery and species richness of herbivorous fishes. Estimates are based on the variability in existing time-series derived from the Australian Institute of Marine Science (AIMS) long-term reef monitoring programs. The objective is to provide a basis for monitoring program design considerations under the Reef 2050 Integrated Monitoring and Reporting Program (RIMReP). Collectively, the AIMS programs provide the only time series of sufficient spatial and temporal coverage to allow estimation of variability at the scales necessary for considering design options at the scale of the Great Barrier Reef (the Reef).An accessible copy of this report is not yet available from this repository, please contact [email protected] for more information

Signatures of Dark Matter Scattering Inelastically Off Nuclei

Direct dark matter detection focuses on elastic scattering of dark matter particles off nuclei. In this study, we explore inelastic scattering where the nucleus is excited to a low-lying state of 10-100 keV, with subsequent prompt de-excitation. We calculate the inelastic structure factors for the odd-mass xenon isotopes based on state-of-the-art large-scale shell-model calculations with chiral effective field theory WIMP-nucleon currents. For these cases, we find that the inelastic channel is comparable to or can dominate the elastic channel for momentum transfers around 150 MeV. We calculate the inelastic recoil spectra in the standard halo model, compare these to the elastic case, and discuss the expected signatures in a xenon detector, along with implications for existing and future experiments. The combined information from elastic and inelastic scattering will allow to determine the dominant interaction channel within one experiment. In addition, the two channels probe different regions of the dark matter velocity distribution and can provide insight into the dark halo structure. The allowed recoil energy domain and the recoil energy at which the integrated inelastic rates start to dominate the elastic channel depend on the mass of the dark matter particle, thus providing a potential handle to constrain its mass.Comment: 9 pages, 7 figures. Matches resubmitted version to Phys. Rev. D. One figure added; supplemental material (fits to the structure functions) added as an Appendi

Inelastic light scattering and the excited states of many-electron quantum dots

A consistent calculation of resonant inelastic (Raman) scattering amplitudes for relatively large quantum dots, which takes account of valence-band mixing, discrete character of the spectrum in intermediate and final states, and interference effects, is presented. Raman peaks in charge and spin channels are compared with multipole strengths and with the density of energy levels in final states. A qualitative comparison with the available experimental results is given.Comment: 5 pages, accepted in J. Phys.: Condens. Matte

Genetic and environmental factors affecting some reproductive traits of Holstein cows in Cuba

International audienc

Nonlinear Breathing-like Localized Modes in C60 Nanocrystals

We study the dynamics of nanocrystals composed of C60 fullerene molecules. We demonstrate that such structures can support long-lived strongly localized nonlinear oscillatory modes, which resemble discrete breathers in simple lattices. We reveal that at room temperatures the lifetime of such nonlinear localized modes may exceed tens of picoseconds; this suggests that C60 nanoclusters should demonstrate anomalously slow thermal relaxation when the temperature gradient decays in accord to a power law, thus violating the Cattaneo-Vernotte law of thermal conductivity.Comment: 6 pages, 6 figure

Spin-dependent WIMP scattering off nuclei

Chiral effective field theory (EFT) provides a systematic expansion for the coupling of WIMPs to nucleons at the momentum transfers relevant to direct cold dark matter detection. We derive the currents for spin-dependent WIMP scattering off nuclei at the one-body level and include the leading long-range two-body currents, which are predicted in chiral EFT. As an application, we calculate the structure factor for spin-dependent WIMP scattering off 129,131Xe nuclei, using nuclear interactions that have been developed to study nuclear structure and double-beta decays in this region. We provide theoretical error bands due to the nuclear uncertainties of WIMP currents in nuclei.Comment: 6 pages, 3 figures, published versio