Angiotensin II Facilitates Breast Cancer Cell Migration and Metastasis

Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN) were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pre-treatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors

Cross-shell states in 15^{15}C: a test for p-sd interactions

The low-lying structure of $^{15}$C has been investigated via the neutron-removal $^{16}$C$(d,t)$ reaction. Along with bound neutron sd-shell hole states, unbound p-shell hole states have been firmly confirmed. The excitation energies and the deduced spectroscopic factors of the cross-shell states are an important measure of the $[(p)^{-1}(sd)^{2}]$ neutron configurations in $^{15}$C. Our results show a very good agreement with shell-model calculations using the SFO-tls interaction for $^{15}$C. However, a modification of the $p$-$sd$ and $sd$-$sd$ monopole terms was applied in order to reproduce the $N=9$ isotone $^{17}$O. In addition, the excitation energies and spectroscopic factors have been compared to the first calculations of $^{15}$C with the $ab~ initio$ self-consistent Green's function method employing the NNLO$_{sat}$ interaction. The results show the sensitivity to the size of the $N=8$ shell gap and highlight the need of going beyond the current truncation scheme in the theory

Excision of HIV-1 Proviral DNA by Recombinant Cell Permeable Tre-Recombinase

Over the previous years, comprehensive studies on antiretroviral drugs resulted in the successful introduction of highly active antiretroviral therapy (HAART) into clinical practice for treatment of HIV/AIDS. However, there is still need for new therapeutic approaches, since HAART cannot eradicate HIV-1 from the infected organism and, unfortunately, can be associated with long-term toxicity and the development of drug resistance. In contrast, novel gene therapy strategies may have the potential to reverse the infection by eradicating HIV-1. For example, expression of long terminal repeat (LTR)-specific recombinase (Tre-recombinase) has been shown to result in chromosomal excision of proviral DNA and, in consequence, in the eradication of HIV-1 from infected cell cultures. However, the delivery of Tre-recombinase currently depends on the genetic manipulation of target cells, a process that is complicating such therapeutic approaches and, thus, might be undesirable in a clinical setting. In this report we demonstrate that E.coli expressed Tre-recombinases, tagged either with the protein transduction domain (PTD) from the HIV-1 Tat trans-activator or the translocation motif (TLM) of the Hepatitis B virus PreS2 protein, were able to translocate efficiently into cells and showed significant recombination activity on HIV-1 LTR sequences. Tre activity was observed using episomal and stable integrated reporter constructs in transfected HeLa cells. Furthermore, the TLM-tagged enzyme was able to excise the full-length proviral DNA from chromosomal integration sites of HIV-1-infected HeLa and CEM-SS cells. The presented data confirm Tre-recombinase activity on integrated HIV-1 and provide the basis for the non-genetic transient application of engineered recombinases, which may be a valuable component of future HIV eradication strategies

Extending the Southern Shore of the Island of Inversion to F-28

Detailed spectroscopy of the neutron-unbound nucleus F-28 has been performed for the first time following proton/neutron removal from Ne-29/F-29 beams at energies around 230 MeV=nucleon. The invariant-mass spectra were reconstructed for both the F-27((*)) + n and F-26((*)) + 2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the F-28 ground state, with S-n(F-28) = -199(6) keV, while analysis of the 2n decay channel allowed a considerably improved S-n(F-27) = 1620(60) keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of F-28. Importantly, in the case of the ground state, the reconstructed F-27 + n momentum distribution following neutron removal from F-29 indicates that it arises mainly from the 1p(3/2) neutron intruder configuration. This demonstrates that the island of inversion around N = 20 includes F-28, and most probably F-29, and suggests that O-28 is not doubly magic

Border of the island of inversion:Unbound states in Ne 29

The nucleus Ne29 is situated at the border of the island of inversion. Despite significant efforts, no bound low-lying intruder f7/2 state, which would place Ne29 firmly inside the island of inversion, has yet been observed. Here, the first investigation of unbound states of Ne29 is reported. The states were populated in Ne30(p,pn) and Na30(p,2p) reactions at a beam energy of around 230 MeV/nucleon, and analyzed in terms of their resonance properties, partial cross sections, and momentum distributions. The momentum distributions are compared to calculations using the eikonal, direct reaction model, allowing ℓ assignments for the observed states. The lowest-lying resonance at an excitation energy of 1.48(4) MeV shows clear signs of a significant ℓ=3 component, giving first evidence for f7/2 single particle strength in Ne29. The excitation energies and strengths of the observed states are compared to shell-model calculations using the sdpf-u-mix interaction.</p

Intruder configurations in 29^{29}Ne at the transition into the island of inversion: Detailed structure study of 28^{28}Ne

Detailed $\gamma$-ray spectroscopy of the exotic neon isotope $^{28}$Ne has been performed for the first time using the one-neutron removal reaction from $^{29}$Ne on a liquid hydrogen target at 240~MeV/nucleon. Based on an analysis of parallel momentum distributions, a level scheme with spin-parity assignments has been constructed for $^{28}$Ne and the negative-parity states are identified for the first time. The measured partial cross sections and momentum distributions reveal a significant intruder $p$-wave strength providing evidence of the breakdown of the $N=20$ and $N=28$ shell gaps. Only a weak, possible $f$-wave strength was observed to bound final states. Large-scale shell-model calculations with different effective interactions do not reproduce the large $p$-wave and small $f$-wave strength observed experimentally, indicating an ongoing challenge for a complete theoretical description of the transition into the island of inversion along the Ne isotopic chain

Low-lying single-particle structure of 17C and the N = 14 sub-shell closure

The first investigation of the single-particle structure of the bound states of 17C, via the C transfer reaction, has been undertaken. The measured angular distributions confirm the spin-parity assignments of and for the excited states located at 217 and 335 keV, respectively. The spectroscopic factors deduced for these states exhibit a marked single-particle character, in agreement with shell model and particle-core model calculations, and combined with their near degeneracy in energy provide clear evidence for the absence of the sub-shell closure. The very small spectroscopic factor found for the ground state is consistent with theoretical predictions and indicates that the strength is carried by unbound states. With a dominant valence neutron configuration and a very low separation energy, the excited state is a one-neutron halo candidate

Stopping power of fission fragments in thin Mylar and nickel foils

International audienceThe energy loss of heavy ions in thin Mylar and nickel foils was measured accurately using fission fragments from 239Pu(nth,f), mass and energy separated by the Lohengrin separator at ILL. The detection setup, placed at the focal plane of the Lohengrin separator enabled to measure precisely the kinetic energy difference of selected fragments after passing through the sample. From these data, the stopping powers in Mylar and nickel layers were extracted and compared to calculations. Whereas large deviations are observed with SRIM-2013 for Mylar, fairly good agreements are obtained with the semi-empirical approach of Knyazheva et al. (2006) and the calculations contained within the DPASS database. In nickel, SRIM-2013 and Knyazheva model are in agreement with our data within about 10%, while large deviations are observed with DPASS. We used our data to provide updated parameters for the Knyazheva model and rescale DPASS database for nickel and Mylar

Performance validation of the first arm of FALSTAFF: 252^{252}Cf and 235^{235}U fission fragment characterisation

International audienceThe renewed interest for the study of nuclear fission is mainly motivated by the development of GEN-IV reactor concepts, mostly foreseen to operate in the fast neutron energy domain. To support this development, new high-quality nuclear data are needed. In this context, a new experimental setup, the FALSTAFF spectrometer, dedicated to the study of nuclear fission is under development. Employing the double-velocity (2V) and energy-velocity (EV) methods, the fission fragment mass before and after neutron evaporation will be deduced and the correlation between prompt neutron multiplicity and fragment mass will be determined. The first arm of the spectrometer is achieved. It is composed of two SED-MWPC detectors (a combination of a foil to produce secondary electrons and a Multi-Wire Proportional Chamber to detect them) and an axial ionization chamber. The SED-MWPC give access to the velocity (V) via time-of-flight and position measurements. The ionization chamber measures the fragment kinetic energy (E) and the energy loss profile. Preliminary results for spontaneous fission of 252Cf and from the thermal-neutron induced fission experiment on 235U, performed at the Orphée reactor (CEA-Saclay, France), are presented