122 research outputs found
MAJOR MERGERS BETWEEN GALAXIES: Their role in the high-redshift universe & two nearby case studies
MAJOR MERGERS BETWEEN GALAXIES: Their role in the high-redshift universe & two nearby case studies
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HST/WFC3 Observations of an Off-Nuclear Superbubble in Arp 220
We present a high spatial resolution optical and infrared study of the
circumnuclear region in Arp 220, a late-stage galaxy merger. Narrowband imaging
using HST/WFC3 has resolved the previously observed peak in H+[NII]
emission into a bubble-shaped feature. This feature measures 1.6" in diameter,
or 600 pc, and is only 1" northwest of the western nucleus. The bubble is
aligned with the western nucleus and the large-scale outflow axis seen in
X-rays. We explore several possibilities for the bubble origin, including a jet
or outflow from a hidden active galactic nucleus (AGN), outflows from high
levels of star formation within the few hundred pc nuclear gas disk, or an
ultraluminous X-ray source. An obscured AGN or high levels of star formation
within the inner 100 pc of the nuclei are favored based on the alignment
of the bubble and energetics arguments.Comment: Accepted for publication in ApJ. 12 pages, 10 figure
Tumor-specific T cells signal tumor destruction via the lymphotoxin β receptor
BACKGROUND: Previously, we reported that adoptively transferred perforin k/o (PKO), and IFN-γ k/o (GKO), or perforin/IFN-γ double k/o (PKO/GKO) effector T cells mediated regression of B16BL6-D5 (D5) pulmonary metastases and showed that TNF receptor signaling played a critical role in mediating tumor regression. In this report we investigated the role of lymphotoxin-α (LT-α) as a potential effector molecules of tumor-specific effector T cells. METHODS: Effector T cells were generated from tumor vaccine-draining lymph node (TVDLN) of wt, GKO, LT-α deficient (LKO), or PKO/GKO mice and tested for their ability to mediate regression of D5 pulmonary metastases in the presence or absence of LT-βR-Fc fusion protein or anti-IFN-γ antibody. Chemokine production by D5 tumor cells was determined by ELISA, RT-PCR and Chemotaxis assays. RESULTS: Stimulated effector T cells from wt, GKO, or PKO/GKO mice expressed ligands for LT-β receptor (LT-βR). D5 tumor cells were found to constitutively express the LT-βR. Administration of LT-βR-Fc fusion protein completely abrogated the therapeutic efficacy of GKO or PKO/GKO but not wt effector T cells (p < 0.05). Consistent with this observation, therapeutic efficacy of effector T cells deficient in LT-α, was greatly reduced when IFN-γ production was neutralized. While recombinant LT-α1β2 did not induce apoptosis of D5 tumor cells in vitro, it induced secretion of chemokines by D5 that promoted migration of macrophages. CONCLUSION: The contribution of LT-α expression by effector T cells to anti-tumor activity in vivo was not discernable when wt effector T cells were studied. However, the contribution of LT-β R signaling was identified for GKO or PKO/GKO effector T cells. Since LT-α does not directly induce killing of D5 tumor cells in vitro, but does stimulate D5 tumor cells to secrete chemokines, these data suggest a model where LT-α expression by tumor-specific effector T cells interacts via cross-linking of the LT-βR on tumor cells to induce secretion of chemokines that are chemotactic for macrophages. While the contribution of macrophages to tumor elimination in our system requires additional study, this model provides a possible explanation for the infiltration of inate effector cells that is seen coincident with tumor regression
Mass of the Southern Black Hole in NGC 6240 from Laser Guide Star Adaptive Optics
NGC 6240 is a pair of colliding disk galaxies, each with a black hole in its
core. We have used laser guide star adaptive optics on the Keck II telescope to
obtain high-resolution (") near-infrared integral-field spectra of
the region surrounding the supermassive black hole in the south nucleus of this
galaxy merger. We use the K-band CO absorption bandheads to trace stellar
kinematics. We obtain a spatial resolution of about 20 pc and thus directly
resolve the sphere of gravitational influence of the massive black hole. We
explore two different methods to measure the black hole mass. Using a Jeans
Axisymmetric Multi-Gaussian mass model, we investigate the limit that a relaxed
mass distribution produces all of the measured velocity dispersion, and find an
upper limit on the black hole mass at 2.0 \pm 0.2 \times 10^9 M_{\sun}. When
assuming the young stars whose spectra we observe remain in a thin disk, we
compare Keplerian velocity fields to the measured two-dimensional velocity
field measured and fit for a mass profile containing a black hole point mass
plus a radially-varying spherical component, which suggests a lower limit for
the black hole mass of 8.7 \pm 0.3 \times 10^8 M_{\sun}. Our measurements of
the stellar velocity dispersion place this AGN within the scatter of the
- relation. As NGC 6240 is a merging system, this may
indicate that the relation is preserved during a merger at least until the
final coalescence of the two nuclei.Comment: 10 pages, 12 figures; accepted to Ap
Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history
Background: There is no international consensus up to which age women with a diagnosis of triple-negative breast cancer (TNBC) and no family history of breast or ovarian cancer should be offered genetic testing for germline BRCA1 and BRCA2 (gBRCA) mutations. Here, we explored the association of age at TNBC diagnosis with the prevalence of pathogenic gBRCA mutations in this patient group.
Methods: The study comprised 802 women (median age 40 years, range 19–76) with oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 negative breast cancers, who had no relatives with breast or ovarian cancer. All women were tested for pathogenic gBRCA mutations. Logistic regression analysis was used to explore the association between age at TNBC diagnosis and the presence of a pathogenic gBRCA mutation.
Results: A total of 127 women with TNBC (15.8%) were gBRCA mutation carriers (BRCA1: n = 118, 14.7%; BRCA2: n = 9, 1.1%). The mutation prevalence was 32.9% in the age group 20–29 years compared to 6.9% in the age group 60–69 years. Logistic regression analysis revealed a significant increase of mutation frequency with decreasing age at diagnosis (odds ratio 1.87 per 10 year decrease, 95%CI 1.50–2.32, p < 0.001). gBRCA mutation risk was predicted to be > 10% for women diagnosed below approximately 50 years.
Conclusions: Based on the general understanding that a heterozygous mutation probability of 10% or greater justifies gBRCA mutation screening, women with TNBC diagnosed before the age of 50 years and no familial history of breast and ovarian cancer should be tested for gBRCA mutations. In Germany, this would concern approximately 880 women with newly diagnosed TNBC per year, of whom approximately 150 are expected to be identified as carriers of a pathogenic gBRCA mutation
Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers
Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates.
Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS.
Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS.
Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management
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