Early diagnosis remains the most reliable way to cure chidren with melanoma: Response

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48703/1/20398_ftp.pd

Yeast homotypic vacuole fusion requires the Ccz1–Mon1 complex during the tethering/docking stage

The function of the yeast lysosome/vacuole is critically linked with the morphology of the organelle. Accordingly, highly regulated processes control vacuolar fission and fusion events. Analysis of homotypic vacuole fusion demonstrated that vacuoles from strains defective in the CCZ1 and MON1 genes could not fuse. Morphological evidence suggested that these mutant vacuoles could not proceed to the tethering/docking stage. Ccz1 and Mon1 form a stable protein complex that binds the vacuole membrane. In the absence of the Ccz1–Mon1 complex, the integrity of vacuole SNARE pairing and the unpaired SNARE class C Vps/HOPS complex interaction were both impaired. The Ccz1–Mon1 complex colocalized with other fusion components on the vacuole as part of the cis-SNARE complex, and the association of the Ccz1–Mon1 complex with the vacuole appeared to be regulated by the class C Vps/HOPS complex proteins. Accordingly, we propose that the Ccz1–Mon1 complex is critical for the Ypt7-dependent tethering/docking stage leading to the formation of a trans-SNARE complex and subsequent vacuole fusion

A Significant Population of Very Luminous Dust-Obscured Galaxies at Redshift z ~ 2

Observations with Spitzer Space Telescope have recently revealed a significant population of high-redshift z~2 dust-obscured galaxies (DOGs) with large mid-IR to UV luminosity ratios. These galaxies have been missed in traditional optical studies of the distant universe. We present a simple method for selecting this high-z population based solely on the ratio of the observed mid-IR 24um to optical R-band flux density. In the 8.6 sq.deg Bootes NDWFS Field, we uncover ~2,600 DOG candidates (= 0.089/sq.arcmin) with 24um flux densities F24>0.3mJy and (R-[24])>14 (i.e., F[24]/F[R] > 1000). These galaxies have no counterparts in the local universe, and become a larger fraction of the population at fainter F24, representing 13% of the sources at 0.3~mJy. DOGs exhibit evidence of both star-formation and AGN activity, with the brighter 24um sources being more AGN- dominated. We have measured spectroscopic redshifts for 86 DOGs, and find a broad z distribution centered at ~2.0. Their space density is 2.82E-5 per cubic Mpc, similar to that of bright sub-mm-selected galaxies at z~2. These redshifts imply very large luminosities LIR>~1E12-14 Lsun. DOGs contribute ~45-100% of the IR luminosity density contributed by all z~2 ULIRGs, suggesting that our simple selection criterion identifies the bulk of z~2 ULIRGs. DOGs may be the progenitors of ~4L* present-day galaxies seen undergoing a luminous,short- lived phase of bulge and black hole growth. They may represent a brief evolution phase between SMGs and less obscured quasars or galaxies. [Abridged]Comment: Accepted for publication in the Astrophysical Journa

Latent ice recrystallization inhibition activity in nonantifreeze proteins : Ca2+-activated plant lectins and cation-activated antimicrobial peptides

Organisms living in polar regions have evolved a series of antifreeze (glyco) proteins (AFGPs) to enable them to survive by modulating the structure of ice. These proteins have huge potential for use in cellular cryopreservation, ice-resistant surfaces, frozen food, and cryosurgery, but they are limited by their relatively low availability and questions regarding their mode of action. This has triggered the search for biomimetic materials capable of reproducing this function. The identification of new structures and sequences capable of inhibiting ice growth is crucial to aid our understanding of these proteins. Here, we show that plant c-type lectins, which have similar biological function to human c-type lectins (glycan recognition) but no sequence homology to AFPs, display calcium-dependent ice recrystallization inhibition (IRI) activity. This IRI activity can be switched on/off by changing the Ca2+ concentration. To show that more (nonantifreeze) proteins may exist with the potential to display IRI, a second motif was considered, amphipathicity. All known AFPs have defined hydrophobic/hydrophilic domains, rationalizing this choice. The cheap, and widely used, antimicrobial Nisin was found to have cation-dependent IRI activity, controlled by either acid or addition of histidine-binding ions such as zinc or nickel, which promote its amphipathic structure. These results demonstrate a new approach in the identification of antifreeze protein mimetic macromolecules and may help in the development of synthetic mimics of AFPs

Mid-infrared Selection of Active Galactic Nuclei with the Wide-Field Infrared Survey Explorer. I. Characterizing WISE-selected Active Galactic Nuclei in COSMOS

The Wide-field Infrared Survey Explorer (WISE) is an extremely capable and efficient black hole finder. We present a simple mid-infrared color criterion, W1 – W2 ≥ 0.8 (i.e., [3.4]–[4.6] ≥0.8, Vega), which identifies 61.9 ± 5.4 active galactic nucleus (AGN) candidates per deg^2 to a depth of W2 ~ 15.0. This implies a much larger census of luminous AGNs than found by typical wide-area surveys, attributable to the fact that mid-infrared selection identifies both unobscured (type 1) and obscured (type 2) AGNs. Optical and soft X-ray surveys alone are highly biased toward only unobscured AGNs, while this simple WISE selection likely identifies even heavily obscured, Compton-thick AGNs. Using deep, public data in the COSMOS field, we explore the properties of WISE-selected AGN candidates. At the mid-infrared depth considered, 160 μJy at 4.6 μm, this simple criterion identifies 78% of Spitzer mid-infrared AGN candidates according to the criteria of Stern et al. and the reliability is 95%. We explore the demographics, multiwavelength properties and redshift distribution of WISE-selected AGN candidates in the COSMOS field

Measurement of the branching fractions of the radiative leptonic τ decays τ→eγνν[bar] and τ→μγνν[bar] at BABAR

We perform a measurement of the τ→lγνν [bar] (l=e,μ) branching fractions for a minimum photon energy of 10 MeV in the τ rest frame, using 431  fb^(−1) of e^+ e^− collisions collected at the center-of-mass energy of the Υ(4S) resonance with the BABAR detector at the PEP-II storage rings. We find B(τ→μγνν [bar])=(3.69±0.03±0.10)×10^(−3) and B(τ→eγνν[bar]¯ )=(1.847±0.015±0.052)×10^(−2), where the first quoted error is statistical and the second is systematic. These results are substantially more precise than previous measurements

Multi-Institutional Datasets Validate the Recursive Partitioning Analysis for Overall Survival in Patients Undergoing Spine Radiosurgery for Spine Metastasis

Purpose/Objective(s): The recently published spine radiosurgery (sSRS) recursive partitioning analysis (RPA) for overall survival (OS) separated patients into 3 distinct prognostic groups. We sought to externally validate this RPA using a multi-institutional dataset. Materials/Methods: A total of 444 patients were utilized to develop the recently published sSRS RPA predictive of OS in patients with spine metastases. The RPA identified three distinct prognostic classes. RPA Class 1 was defined as KPS \u3e70 and controlled systemic disease (n=142); RPA Class 2 was defined as KPS\u3e70 with uncontrolled systemic disease or KPS ≤70, age ≥54 and absence of visceral metastases (n=207); RPA Class 3 was defined as KPS ≤70 and age \u3c54 years or KPS≤70, age ≥54 years and presence of visceral metastases (n=95). We utilized data from large tertiary care centers to validate this RPA. A total of 749 patients were in the validation cohort and were divided based on their RPA Class. Kaplan-Meier method was used to estimate OS and log-rank test was used to compare OS between RPA classes. Results: In the validation cohort (749 patients), the median OS was 11.0 months. One-hundred-thirteen (15.1%) patients were in RPA Class 1, 432 (57.7%) patients in RPA Class 2 and 204 (27.2%) patients in RPA Class 3. The median OS in the validation cohort based on RPA Class was 27.1 months for Class 1, 13.0 months for Class 2 and 3.5 months for Class 3. Patients in RPA Class 1 had a significantly better OS compared to those in Class 2 of the validation cohort (p\u3c0.01). Similarly, patients in RPA Class 2 had a significantly better OS compared to those in Class 3 (p\u3c0.01). Conclusion: The external datasets from two large centers validated the spine SRS RPA successfully for RPA for OS for patients undergoing sSRS for spinal metastases. This is the first RPA for OS to have been externally validated using a large dataset. Based on this validation, upfront spine SRS is strongly supported for patients in RPA Class 1. Upfront SRS is also supported for RPA Class 2 patients. Patients in RPA Class 3 would benefit most from upfront conventional radiotherapy given their poor expected survival. Given successful external validation, this RPA helps guide physicians to identify those patients with spinal metastases who most benefit from sSRS

The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression.

Molecular classification of cancers into subtypes has resulted in an advance in our understanding of tumour biology and treatment response across multiple tumour types. However, to date, cancer profiling has largely focused on protein-coding genes, which comprise <1% of the genome. Here we leverage a compendium of 58,648 long noncoding RNAs (lncRNAs) to subtype 947 breast cancer samples. We show that lncRNA-based profiling categorizes breast tumours by their known molecular subtypes in breast cancer. We identify a cohort of breast cancer-associated and oestrogen-regulated lncRNAs, and investigate the role of the top prioritized oestrogen receptor (ER)-regulated lncRNA, DSCAM-AS1. We demonstrate that DSCAM-AS1 mediates tumour progression and tamoxifen resistance and identify hnRNPL as an interacting protein involved in the mechanism of DSCAM-AS1 action. By highlighting the role of DSCAM-AS1 in breast cancer biology and treatment resistance, this study provides insight into the potential clinical implications of lncRNAs in breast cancer