The mass profile of early-type galaxies in overdense environments: the case of the double source plane gravitational lens SL2SJ02176-0513

SL2SJ02176-0513 is a remarkable lens for the presence of two multiply-imaged systems at different redshifts lensed by a foreground massive galaxy at $z_{\rm lens}=0.656$: a bright cusp arc at $z_{\rm arc}=1.847$ and an additional double-image system at an estimated redshift of $z_{\rm dbl}\sim2.9$ based on photometry and lensing geometry. The system is located about 400 kpc away from the center of a massive group of galaxies. Mass estimates for the group are available from X-ray observations and satellite kinematics. Multicolor photometry provides an estimate of the stellar mass of the main lens galaxy. The lensing galaxy is modeled with two components (stars and dark matter), and we include the perturbing effect of the group environment, and all available constraints. We find that classic lensing degeneracies, e.g. between external convergence and mass density slope, are significantly reduced with respect to standard systems and infer tight constraints on the mass density profile: (i) the dark matter content of the main lens galaxy is in line with that of typical galaxies $f_{\rm dm}(<R_{\rm e})=0.41^{+0.09}_{-0.06}$; (ii) the required mass associated with the dark matter halo of the nearby group is consistent with X-ray and weak-lensing estimates ($\sigma_{\rm grp}=550^{+130}_{-240}$); (iii) accounting for the group contribution in the form of an external convergence, the slope of the mass density profile of the main lens galaxy alone is found to be $\alpha=-1.03^{+0.22}_{-0.16}$, consistent with the isothermal ($\alpha=-1$) slope. We demonstrate that multiple source plane systems together with good ancillary dataset can be used to disentangle local and environmental effects.Comment: 10 pages, 6 figures, submitted to A&

BRCA1 loss activates cathepsin L–mediated degradation of 53BP1 in breast cancer cells

Loss of 53BP1 rescues BRCA1 deficiency and is associated with BRCA1-deficient and triple-negative breast cancers (TNBC) and with resistance to genotoxic drugs. The mechanisms responsible for decreased 53BP1 transcript and protein levels in tumors remain unknown. Here, we demonstrate that BRCA1 loss activates cathepsin L (CTSL)–mediated degradation of 53BP1. Activation of this pathway rescued homologous recombination repair and allowed BRCA1-deficient cells to bypass growth arrest. Importantly, depletion or inhibition of CTSL with vitamin D or specific inhibitors stabilized 53BP1 and increased genomic instability in response to radiation and poly(adenosine diphosphate–ribose) polymerase inhibitors, compromising proliferation. Analysis of human breast tumors identified nuclear CTSL as a positive biomarker for TNBC, which correlated inversely with 53BP1. Importantly, nuclear levels of CTSL, vitamin D receptor, and 53BP1 emerged as a novel triple biomarker signature for stratification of patients with BRCA1-mutated tumors and TNBC, with potential predictive value for drug response. We identify here a novel pathway with prospective relevance for diagnosis and customization of breast cancer therapy

Targeting RNS/caveolin-1/MMP signaling cascades to protect against cerebral ischemia-reperfusion injuries: potential application for drug discovery

Reactive nitrogen species (RNS) play important roles in mediating cerebral ischemia-reperfusion injury. RNS activate multiple signaling pathways and participate in different cellular events in cerebral ischemia-reperfusion injury. Recent studies have indicated that caveolin-1 and matrix metalloproteinase (MMP) are important signaling molecules in the pathological process of ischemic brain injury. During cerebral ischemia-reperfusion, the production of nitric oxide (NO) and peroxynitrite (ONOO-), two representative RNS, down-regulates the expression of caveolin-1 (Cav-1) and, in turn, further activates nitric oxide synthase (NOS) to promote RNS generation. The increased RNS further induce MMP activation and mediate disruption of the blood-brain barrier (BBB), aggravating the brain damage in cerebral ischemia-reperfusion injury. Therefore, the feedback interaction among RNS/Cav-1/MMPs provides an amplified mechanism for aggravating ischemic brain damage during cerebral ischemia-reperfusion injury. Targeting the RNS/Cav-1/MMP pathway could be a promising therapeutic strategy for protecting against cerebral ischemia-reperfusion injury. In this mini-review article, we highlight the important role of the RNS/Cav-1/MMP signaling cascades in ischemic stroke injury and review the current progress of studies seeking therapeutic compounds targeting the RNS/Cav-1/MMP signaling cascades to attenuate cerebral ischemia-reperfusion injury. Several representative natural compounds, including calycosin-7-O-β-D-glucoside, baicalin, Momordica charantia polysaccharide (MCP), chlorogenic acid, lutein and lycopene, have shown potential for targeting the RNS/Cav-1/MMP signaling pathway to protect the brain in ischemic stroke. Therefore, the RNS/Cav-1/MMP pathway is an important therapeutic target in ischemic stroke treatment.published_or_final_versio

Cytochrome b sequence data suggest rapid speciation within the Paramecium aurelia species complex

Abstract: We investigated mitochondrial Cytochrome b sequences from all 15 members of the enigmatic Paramecium aurelia species complex (Ciliophora). The analysis revealed high genetic distances between the different A aurelia species (6.1-19.8%) and a largely unresolved, star-like phylogenetic tree. This result strongly supports a rapid radiation in the evolutionary history of this species complex and it correlates well with the hypothesis that the extant species diversity may have originated from the neutral consequences of a whole genome duplication in the common ancestor of P. aurelia. (c) 2008 Elsevier Inc. All rights reserved