The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, one of three core programs of the fourth-generation Sloan Digital Sky Survey (SDSS-IV), is producing a massive, ...high-dimensional integral field spectroscopic data set. However, leveraging the MaNGA data set to address key questions about galaxy formation presents serious data-related challenges due to the combination of its spatially interconnected measurements and sheer volume. For each galaxy, the MaNGA pipelines produce relatively large data files to preserve the spatial correlations of the spectra and measurements, but this comes at the expense of storing the data set in coarse units or "chunks." This coarse chunking and the total volume of the data make it time-consuming to download and curate locally stored data. Thus, accessing, querying, visually exploring, and performing statistical analyses across the whole data set at a fine-grained scale is extremely challenging using just FITS files. To overcome these challenges, we have developed Marvin, a toolkit consisting of a Python package, Application Programming Interface, and web application utilizing a remote database. Marvin allows users to seamlessly work with MaNGA data by abstracting both remote and local (on-disk) interactions to behind-the-scenes data-handling functions. Combining this capability with additional processing and querying tools, users can create powerful Python workflows that are easy to import and share. Marvin's web application uses these tools to enable "point-and-click" examination of data cubes and derived maps, as well as search queries for all publicly released MaNGA galaxies. Marvin's robust and sustainable design minimizes maintenance, while facilitating user-contributed extensions such as high-level analysis code.
ABSTRACT Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) is an optical fiber-bundle integral-field unit (IFU) spectroscopic survey that is one of three core programs in the ...fourth-generation Sloan Digital Sky Survey (SDSS-IV). With a spectral coverage of 3622-10354 and an average footprint of ∼500 arcsec2 per IFU the scientific data products derived from MaNGA will permit exploration of the internal structure of a statistically large sample of 10,000 low-redshift galaxies in unprecedented detail. Comprising 174 individually pluggable science and calibration IFUs with a near-constant data stream, MaNGA is expected to obtain ∼100 million raw-frame spectra and ∼10 million reduced galaxy spectra over the six-year lifetime of the survey. In this contribution, we describe the MaNGA Data Reduction Pipeline algorithms and centralized metadata framework that produce sky-subtracted spectrophotometrically calibrated spectra and rectified three-dimensional data cubes that combine individual dithered observations. For the 1390 galaxy data cubes released in Summer 2016 as part of SDSS-IV Data Release 13, we demonstrate that the MaNGA data have nearly Poisson-limited sky subtraction shortward of ∼8500 and reach a typical 10 limiting continuum surface brightness = 23.5 AB arcsec−2 in a five-arcsecond-diameter aperture in the g-band. The wavelength calibration of the MaNGA data is accurate to 5 km s−1 rms, with a median spatial resolution of 2.54 arcsec FWHM (1.8 kpc at the median redshift of 0.037) and a median spectral resolution of = 72 km s−1.
Telomere length has been associated with risk of many cancers, but results are inconsistent. Seven single nucleotide polymorphisms (SNPs) previously associated with mean leukocyte telomere length ...were either genotyped or well-imputed in 11108 case patients and 13933 control patients from Europe, Israel, the United States and Australia, four of the seven SNPs reached a P value under .05 (two-sided). A genetic score that predicts telomere length, derived from these seven SNPs, is strongly associated (P = 8.92x10(-9), two-sided) with melanoma risk. This demonstrates that the previously observed association between longer telomere length and increased melanoma risk is not attributable to confounding via shared environmental effects (such as ultraviolet exposure) or reverse causality. We provide the first proof that multiple germline genetic determinants of telomere length influence cancer risk.
The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is currently acquiring integral-field spectroscopy for the largest sample of galaxies to date. By 2020, the MaNGA Survey-which ...is one of three core programs in the fourth-generation Sloan Digital Sky Survey (SDSS-IV)-will have observed a statistically representative sample of 104 galaxies in the local universe (z 0.15). In addition to a robust data-reduction pipeline (DRP), MaNGA has developed a data-analysis pipeline (DAP) that provides higher-level data products. To accompany the first public release of its code base and data products, we provide an overview of the MaNGA DAP, including its software design, workflow, measurement procedures and algorithms, performance, and output data model. In conjunction with our companion paper (Belfiore et al.), we also assess the DAP output provided for 4718 observations of 4648 unique galaxies in the recent SDSS Data Release 15 (DR15). These analysis products focus on measurements that are close to the data and require minimal model-based assumptions. Namely, we provide stellar kinematics (velocity and velocity dispersion), emission-line properties (kinematics, fluxes, and equivalent widths), and spectral indices (e.g., D4000 and the Lick indices). We find that the DAP provides robust measurements and errors for the vast majority (>99%) of analyzed spectra. We summarize assessments of the precision and accuracy of our measurements as a function of signal-to-noise. We also provide specific guidance to users regarding the limitations of the data. The MaNGA DAP software is publicly available and we encourage community involvement in its development.
Recent measurements of rotation periods ( ) in the benchmark open clusters Praesepe (670 Myr), NGC 6811 (1 Gyr), and NGC 752 (1.4 Gyr) demonstrate that, after converging onto a tight sequence of ...slowly rotating stars in mass-period space, stars temporarily stop spinning down. These data also show that the duration of this epoch of stalled spin-down increases toward lower masses. To determine when stalled stars resume spinning down, we use data from the K2 mission and the Palomar Transient Factory to measure for 58 dwarf members of the 2.7 Gyr old cluster Ruprecht 147, 39 of which satisfy our criteria designed to remove short-period or near-equal-mass binaries. Combined with the Kepler data for the approximately coeval cluster NGC 6819 (30 stars with M > 0.85 ), our new measurements more than double the number of 2.5 Gyr benchmark rotators and extend this sample down to 0.55 . The slowly rotating sequence for this joint sample appears relatively flat (22 2 days) compared to sequences for younger clusters. This sequence also intersects the Kepler intermediate-period gap, demonstrating that this gap was not created by a lull in star formation. We calculate the time at which stars resume spinning down and find that 0.55 stars remain stalled for at least 1.3 Gyr. To accurately age-date low-mass stars in the field, gyrochronology formulae must be modified to account for this stalling timescale. Empirically tuning a core-envelope coupling model with open cluster data can account for most of the apparent stalling effect. However, alternative explanations, e.g., a temporary reduction in the magnetic braking torque, cannot yet be ruled out.
Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide ...association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5 × 10(-8)), as did 2 previously reported but unreplicated loci and all 13 established loci. Newly associated SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes in the associated regions, including one involved in telomere biology.
Purinergic receptors and nucleotide-binding domain leucine-rich repeat containing (NLR) proteins have been shown to control viral infection. Here, we show that the NLR family member NLRP3 and the ...purinergic receptor P2Y2 constitutively interact and regulate susceptibility to HIV-1 infection. We found that NLRP3 acts as an inhibitory factor of viral entry that represses F-actin remodeling. The binding of the HIV-1 envelope to its host cell receptors (CD4, CXCR4, and/or CCR5) overcomes this restriction by stimulating P2Y2. Once activated, P2Y2 enhances its interaction with NLRP3 and stimulates the recruitment of the E3 ubiquitin ligase CBL to NLRP3, ultimately leading to NLRP3 degradation. NLRP3 degradation is permissive for PYK2 phosphorylation (PYK2Y402∗) and subsequent F-actin polymerization, which is required for the entry of HIV-1 into host cells. Taken together, our results uncover a mechanism by which HIV-1 overcomes NLRP3 restriction that appears essential for the accomplishment of the early steps of HIV-1 entry.
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•NLRP3 and P2Y2 interact and regulate susceptibility to HIV-1 infection•NLRP3 is an intrinsic inhibitory factor for HIV-1 that represses F-actin remodeling•HIV-1 Env binding to host receptors overcomes NLRP3 restriction by activating P2Y2•P2Y2 activation leads to CBL-mediated NLRP3 degradation and favors viral entry
Paoletti et al. identified a constitutive interaction between NLRP3 and P2Y2 that regulates HIV-1 entry into target cells. They revealed that NLRP3 represses viral entry by impairing F-actin reorganization. HIV-1 overcomes this host cellular resistance by inducing NLRP3 degradation through the activation of P2Y2-dependent signaling pathway.
Cathepsin K (CatK) is the predominant mammalian bone-degrading protease and thus an ideal target for antiosteoporotic drug development. Rodent models of osteoporosis are preferred due to their close ...reflection of the human disease and their ease of handling, genetic manipulation and economic affordability. However, large differences in the potency of CatK inhibitors for the mouse/rat vs. the human protease orthologs have made it impossible to use rodent models. This is even more of a problem considering that the most advanced CatK inhibitors, including odanacatib (ODN) and balicatib, failed in human clinical trials due to side effects and rodent models are not available to investigate the mechanism of these failures. Here, we elucidated the structural elements of the potency differences between mouse and human CatK (hCatK) using ODN. We determined and compared the structures of inhibitor-free mouse CatK (mCatK), hCatK and ODN bound to hCatK. Two structural differences were identified and investigated by mutational analysis. Humanizing subsite 2 in mCatK led to a 5-fold improvement of ODN binding, whereas the replacement of Tyr61 in mCatK with Asp resulted in an hCatK with comparable ODN potency. Combining both sites further improved the inhibition of the mCatK variant. Similar results were obtained for balicatib. These findings will allow the generation of transgenic CatK mice that will facilitate the evaluation of CatK inhibitor adverse effects and to explore routes to avoid them.
The role of sex in biomedical studies has often been overlooked, despite evidence of sexually dimorphic effects in some biological studies. Here, we used high-throughput phenotype data from 14,250 ...wildtype and 40,192 mutant mice (representing 2,186 knockout lines), analysed for up to 234 traits, and found a large proportion of mammalian traits both in wildtype and mutants are influenced by sex. This result has implications for interpreting disease phenotypes in animal models and humans.
Previous genome-wide association studies have identified a melanoma-associated locus at 1q42.1 that encompasses a ∼100-kb region spanning the PARP1 gene. Expression quantitative trait locus (eQTL) ...analysis in multiple cell types of the melanocytic lineage consistently demonstrated that the 1q42.1 melanoma risk allele (rs3219090G) is correlated with higher PARP1 levels. In silico fine-mapping and functional validation identified a common intronic indel, rs144361550 (-/GGGCCC; r
= 0.947 with rs3219090), as displaying allele-specific transcriptional activity. A proteomic screen identified RECQL as binding to rs144361550 in an allele-preferential manner. In human primary melanocytes, PARP1 promoted cell proliferation and rescued BRAF
-induced senescence phenotypes in a PARylation-independent manner. PARP1 also transformed TERT-immortalized melanocytes expressing BRAF
. PARP1-mediated senescence rescue was accompanied by transcriptional activation of the melanocyte-lineage survival oncogene MITF, highlighting a new role for PARP1 in melanomagenesis.
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