Understanding Radio-Selected Thermal Sources in M 33: Ultraviolet, Optical, Near-Infrared, Spitzer Mid-Infrared, and Radio Observations

We present ultraviolet, optical, near-infrared, Spitzer mid-infrared, and radio images of 14 radio-selected objects in M 33. These objects are thought to represent the youngest phase of star cluster formation. We have detected the majority of cluster candidates in M 33 at all wavelengths. From the near-IR images, we derived ages 2-10 Myr, K_S-band extinctions (A_K_S) of 0-1 mag, and stellar masses of 10^3-10^4 M_solar. We have generated spectral energy distributions (SEDs) of each cluster from 0.1 micron to 160 microns. From these SEDs, we have modeled the dust emission around these star clusters to determine the dust masses (1-10^3 M_solar) and temperatures (40-90 K) of the clusters' local interstellar medium. Extinctions derived from the JHK_S, Halpha, and UV images are similar to within a factor of 2 or 3. These results suggest that eleven of the fourteen radio-selected objects are optically-visible young star clusters with a surrounding H II region, that two are background objects, possibly AGN, and that one is a Wolf-Rayet star with a surrounding H II region.Comment: 57 pages total; 20 figures; 3 tables under review by ApJS; first review complet

Discovery of a New Low-Latitude Milky Way Globular Cluster using GLIMPSE

Spitzer Space Telescope imaging as part of the Galactic Legacy Mid-Plane Survey Extraordinaire (GLIMPSE) reveals a previously unidentified low-latitude rich star cluster near l=31.3 degrees, b=-0.1 degrees. Near-infrared JHK' photometry from the Wyoming Infrared Observatory indicates an extinction of A_V ~ 15+/-3 mag for cluster members. Analysis of 13CO features along the same sightline suggests a probable kinematic distance of 3.1 -- 5.2 kpc. The new cluster has an angular diameter of ~1-2 pc, a total magnitude m_{K_0}=2.1 corrected for extinction, and a luminosity of M_K ~ -10.3 at 3.1 kpc. In contrast to young massive Galactic clusters with ages <100 Myr, the new cluster has no significant radio emission. Comparison to theoretical K-band luminosity functions indicates an age of at least several Gyr and a mass of at least 10^5 solar masses. Unlike known old open clusters, this new cluster lies in the inner Galaxy at R_{GC} ~ 6.1 kpc. We designate this object ``GLIMPSE-C01'' and classify it as a Milky Way globular cluster passing through the Galactic disk. We also identify a region of star formation and fan-shaped outflows from young stellar objects in the same field as the cluster. The cluster's passage through the Galactic molecular layer may have triggered this star formation activity.Comment: Accepted for Publication in AJ Report with full resolution images available at http://physics.uwyo.edu/~chip/Glo

Identification of a novel truncating PALB2 mutation and analysis of its contribution to early-onset breast cancer in French-Canadian women

Abstract Background PALB2 has recently been identified as a breast cancer susceptibility gene. PALB2 mutations are rare causes of hereditary breast cancer but may be important in countries such as Finland where a founder mutation is present. We sought to estimate the contribution of PALB2 mutations to the burden of breast cancer in French Canadians from Quebec. Methods We screened all coding exons of PALB2 in a sample of 50 French-Canadian women diagnosed with either early-onset breast cancer or familial breast cancer at a single Montreal hospital. The genetic variants identified in this sample were then studied in 356 additional women with breast cancer diagnosed before age 50 and in 6,448 newborn controls. Results We identified a single protein-truncating mutation in PALB2 (c.2323 C>T, resulting in Q775X) in 1 of the 50 high-risk women. This variant was present in 2 of 356 breast cancer cases and in none of 6,440 newborn French-Canadian controls (P = 0.003). We also identified two novel new non-synonymous single nucleotide polymorphisms in exon 4 of PALB2 (c.5038 A>G [I76V] and c.5156 G>T [G115V]). G115V was found in 1 of 356 cases and in 15 of 6,442 controls (P = 0.6). The I76V variant was not identified in either the extended case series or the controls. Conclusion We have identified a novel truncating mutation in PALB2. The mutation was found in approximately 0.5% of unselected French-Canadian women with early-onset breast cancer and appears to have a single origin. Although mutations are infrequent, PALB2 can be added to the list of breast cancer susceptibility genes for which founder mutations have been identified in the French-Canadian population

High-risk human papillomavirus infections in breast cancer in Syrian women and their association with Id-1 expression: a tissue microarray study

High-risk human papillomaviruses (HPVs) could be important risk factors for breast carcinogenesis and metastasis. Based on this hypothesis, we recently studied the effect of E6/E7 onco-proteins of high-risk HPV type 16 in two non-invasive human breast cancer cell lines, BT20 and MCF7; we reported that E6/E7 converts these cell lines to invasive cells. This is accompanied by an overexpression of Id-1, which is an important regulator of breast metastasis. In this investigation, we examined the presence of high-risk HPVs (16, 18, 31, 33 and 35) and the expression of their E6 onco-protein as well as their correlation with Id-1 gene expression, using polymerase chain reaction (PCR) and tissue microarray (TMA) analysis, respectively, in a cohort of 113 Syrian breast cancer patients. We found that high-risk HPV types 16, 18, 31, 33 and 35 are present in 8.84, 9.73, 7.07, 55.75 and 37.16% of our samples, respectively, which represent invasive breast cancers. Overall, 69 (61.06%) of the 113 samples are HPV positive; among these specimens 24 tissues (34.78%) are coinfected with more than one HPV type. Furthermore, we report that the expression of the E6 onco-protein of these high-risk HPVs is correlated with Id-1 overexpression in the majority of invasive breast cancer tissue samples. Our data suggest that high-risk HPV infections are associated with human breast cancer progression in Syrian women

Tunneling Nanotubes Provide a Unique Conduit for Intercellular Transfer of Cellular Contents in Human Malignant Pleural Mesothelioma

Tunneling nanotubes are long, non-adherent F-actin-based cytoplasmic extensions which connect proximal or distant cells and facilitate intercellular transfer. The identification of nanotubes has been limited to cell lines, and their role in cancer remains unclear. We detected tunneling nanotubes in mesothelioma cell lines and primary human mesothelioma cells. Using a low serum, hyperglycemic, acidic growth medium, we stimulated nanotube formation and bidirectional transfer of vesicles, proteins, and mitochondria between cells. Notably, nanotubes developed between malignant cells or between normal mesothelial cells, but not between malignant and normal cells. Immunofluorescent staining revealed their actin-based assembly and structure. Metformin and an mTor inhibitor, Everolimus, effectively suppressed nanotube formation. Confocal microscopy with 3-dimensional reconstructions of sectioned surgical specimens demonstrated for the first time the presence of nanotubes in human mesothelioma and lung adenocarcinoma tumor specimens. We provide the first evidence of tunneling nanotubes in human primary tumors and cancer cells and propose that these structures play an important role in cancer cell pathogenesis and invasion

TMPRSS2/ERG Promotes Epithelial to Mesenchymal Transition through the ZEB1/ZEB2 Axis in a Prostate Cancer Model

Prostate cancer is the most common non-dermatologic malignancy in men in the Western world. Recently, a frequent chromosomal aberration fusing androgen regulated TMPRSS2 promoter and the ERG gene (TMPRSS2/ERG) was discovered in prostate cancer. Several studies demonstrated cooperation between TMPRSS2/ERG and other defective pathways in cancer progression. However, the unveiling of more specific pathways in which TMPRSS2/ERG takes part, requires further investigation. Using immortalized prostate epithelial cells we were able to show that TMPRSS2/ERG over-expressing cells undergo an Epithelial to Mesenchymal Transition (EMT), manifested by acquisition of mesenchymal morphology and markers as well as migration and invasion capabilities. These findings were corroborated in vivo, where the control cells gave rise to discrete nodules while the TMPRSS2/ERG-expressing cells formed malignant tumors, which expressed EMT markers. To further investigate the general transcription scheme induced by TMPRSS2/ERG, cells were subjected to a microarray analysis that revealed a distinct EMT expression program, including up-regulation of the EMT facilitators, ZEB1 and ZEB2, and down-regulation of the epithelial marker CDH1(E-Cadherin). A chromatin immunoprecipitation assay revealed direct binding of TMPRSS2/ERG to the promoter of ZEB1 but not ZEB2. However, TMPRSS2/ERG was able to bind the promoters of the ZEB2 modulators, IL1R2 and SPINT1. This set of experiments further illuminates the mechanism by which the TMPRSS2/ERG fusion affects prostate cancer progression and might assist in targeting TMPRSS2/ERG and its downstream targets in future drug design efforts