Computational methods for identifying a layered allosteric regulatory mechanism for ALS-causing mutations of Cu-Zn superoxide dismutase 1

The most prominent form of familial amyotrophic lateral sclerosis (fALS, Lou Gehrig's Disease) is caused by mutations of Cu-Zn superoxide dismutase 1 (SOD1). SOD1 maintains antioxidant activity under fALS causing mutations, suggesting that the mutations introduce a new, toxic, function. There are 100+ such known mutations that are chemically diverse and spatially distributed across the structure. The common phenotype leads us to propose an allosteric regulatory mechanism hypothesis: SOD1 mutants alter the correlated dynamics of the structure and differentially signal across an inherent allosteric network, thereby driving the disease mechanism at varying rates of efficiency. Two recently developed computational methods for identifying allosteric control sites are applied to the wild type crystal structure, 4 fALS mutant crystal structures, 20 computationally generated fALS mutants and 1 computationally generated non-fALS mutant. The ensemble of mutant structures is used to generate an ensemble of dynamics, from which two allosteric control networks are identified. One network is connected to the catalytic site and thus may be involved in the natural antioxidant function. The second allosteric control network has a locus bordering the dimer interface and thus may serve as a mechanism to modulate dimer stability. Though the toxic function of mutated SOD1 is unknown and likely due to several contributing factors, this study explains how diverse mutations give rise to a common function. This new paradigm for allostery controlled function has broad implications across allosteric systems and may lead to the identification of the key chemical activity of SOD1-linked ALS. Proteins 2011. © 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79415/1/22892_ftp.pd

On the Progenitor System of the Type Iax Supernova 2014dt in M61

We present pre-explosion and post-explosion Hubble Space Telescope images of the Type Iax supernova (SN Iax) 2014dt in M61. After astrometrically aligning these images, we do not detect any stellar sources at the position of the SN in the pre-explosion images to relatively deep limits (3 sigma limits of M_F438W > -5.0 mag and M_F814W > -5.9 mag). These limits are similar to the luminosity of SN 2012Z's progenitor system (M_F435W = -5.43 +/- 0.15 and M_F814W = -5.24 +/- 0.16 mag), the only probable detected progenitor system in pre-explosion images of a SN Iax, and indeed, of any white dwarf supernova. SN 2014dt is consistent with having a C/O white-dwarf primary/helium-star companion progenitor system, as was suggested for SN 2012Z, although perhaps with a slightly smaller or hotter donor. The data are also consistent with SN 2014dt having a low-mass red giant or main-sequence star companion. The data rule out main-sequence stars with M_init > 16 M_sun and most evolved stars with M_init > 8 M_sun as being the progenitor of SN 2014dt. Hot Wolf-Rayet stars are also allowed, but the lack of nearby bright sources makes this scenario unlikely. Because of its proximity (D = 12 Mpc), SN 2014dt is ideal for long-term monitoring, where images in ~2 years may detect the companion star or the luminous bound remnant of the progenitor white dwarf.Comment: 5 pages, 3 figures, submitted to ApJ

SciMiner: web-based literature mining tool for target identification and functional enrichment analysis

Summary:SciMiner is a web-based literature mining and functional analysis tool that identifies genes and proteins using a context specific analysis of MEDLINE abstracts and full texts. SciMiner accepts a free text query (PubMed Entrez search) or a list of PubMed identifiers as input. SciMiner uses both regular expression patterns and dictionaries of gene symbols and names compiled from multiple sources. Ambiguous acronyms are resolved by a scoring scheme based on the co-occurrence of acronyms and corresponding description terms, which incorporates optional user-defined filters. Functional enrichment analyses are used to identify highly relevant targets (genes and proteins), GO (Gene Ontology) terms, MeSH (Medical Subject Headings) terms, pathways and protein–protein interaction networks by comparing identified targets from one search result with those from other searches or to the full HGNC [HUGO (Human Genome Organization) Gene Nomenclature Committee] gene set. The performance of gene/protein name identification was evaluated using the BioCreAtIvE (Critical Assessment of Information Extraction systems in Biology) version 2 (Year 2006) Gene Normalization Task as a gold standard. SciMiner achieved 87.1% recall, 71.3% precision and 75.8% F-measure. SciMiner's literature mining performance coupled with functional enrichment analyses provides an efficient platform for retrieval and summary of rich biological information from corpora of users' interests

Disappearance of the Progenitor of Supernova iPTF13bvn

Supernova (SN) iPTF13bvn in NGC 5806 was the first Type Ib SN to have been tentatively associated with a progenitor candidate in pre-explosion images. We performed deep ultraviolet (UV) and optical Hubble Space Telescope (HST) observations of the SN site 740 days after explosion. We detect an object in the optical bands that is fainter than the pre-explosion object. This dimming is likely not produced by dust absorption in the ejecta; thus, our finding confirms the connection of the progenitor candidate with the SN. The object in our data is likely dominated by the fading SN, which implies that the pre-SN flux is mostly due to the progenitor. We compare our revised pre-SN photometry with previously proposed progenitor models. Although binary progenitors are favored, models need to be refined. In particular, to comply with our deep UV detection limit, any companion star must be less luminous than a late-O star or substantially obscured by newly formed dust. A definitive progenitor characterization will require further observations to disentangle the contribution of a much fainter SN and its environment.Comment: 8 pages, 3 tables, 3 figures. Accepted for publication in ApJ

The Candidate Progenitor of the Type IIn SN 2010jl Is Not an Optically Luminous Star

A blue source in pre-explosion Hubble Space Telescope (HST)/Wide-Field Planetary Camera 2 (WFPC2) images falls within the 5σ astrometric error circle (~0farcs24) derived from post-explosion ground-based imaging of SN 2010jl. At the time the ground-based astrometry was published, however, the SN had not faded sufficiently for post-explosion HST follow-up observations to determine a more precise astrometric solution and/or confirm if the pre-explosion source had disappeared, both of which are necessary to ultimately disentangle the possible progenitor scenarios. Here we present HST/WFC3 imaging of the SN 2010jl field obtained in 2014, 2015, and 2016 when the SN had faded sufficiently to allow for new constraints on the progenitor. The SN, which is still detected in the new images, is offset by 0farcs061 ± 0farcs008 (15 ± 2 pc) from the underlying and extended source of emission that contributes at least partially, if not entirely, to the blue source previously suggested as the candidate progenitor in the WFPC2 data. This point alone rules out the possibility that the blue source in the pre-explosion images is the exploding star, but may instead suggest an association with a young (30 M_⊙) progenitor. We obtain new upper limits on the flux from a single star at the SN position in the pre-explosion WFPC2 and Spitzer/IRAC images that may ultimately be used to constrain the progenitor properties

The Massive Progenitor of the Type II-Linear Supernova 2009kr

We present early-time photometric and spectroscopic observations of supernova (SN) 2009kr in NGC 1832. We find that its properties to date support its classification as Type II-linear (SN II-L), a relatively rare subclass of core-collapse supernovae (SNe). We have also identified a candidate for the SN progenitor star through comparison of pre-explosion, archival images taken with WFPC2 on board the Hubble Space Telescope with SN images obtained using adaptive optics plus NIRC2 on the 10 m Keck-II telescope. Although the host galaxy's substantial distance (similar to 26 Mpc) results in large uncertainties in the relative astrometry, we find that if this candidate is indeed the progenitor, it is a highly luminous (M(V)(0) = -7.8 mag) yellow supergiant with initial mass similar to 18-24 M(circle dot). This would be the first time that an SN II-L progenitor has been directly identified. Its mass may be a bridge between the upper initial mass limit for the more common Type II-plateau SNe and the inferred initial mass estimate for one Type II-narrow SN.Hungarian OTKA K76816NSF AST-0707769, AST-0908886Sylvia & Jim Katzman FoundationTABASGO FoundationNASA through STScI AR-11248, GO-10877Harvard UniversityUC BerkeleyUniversity of VirginiaNASA/Swift NNX09AQ66GDOEAstronom

A Massive Progenitor of the Luminous Type IIn Supernova 2010jl

The bright, nearby, recently discovered supernova SN2010jl is a member of the rare class of relatively luminous Type~IIn events. Here we report archival HST observations of its host galaxy UGC5189A taken roughly 10yr prior to explosion, as well as early-time optical spectra of the SN. The HST images reveal a bright, blue point source at the position of the SN, with an absolute magnitude of -12.0 in the F300W filter. If it is not just a chance alignment, the source at the SN position could be (1) a massive young (less than 6 Myr) star cluster in which the SN resided, (2) a quiescent, luminous blue star with an apparent temperature around 14,000K, (3) a star caught during a bright outburst akin to those of LBVs, or (4) a combination of option 1 and options 2 or 3. Although we cannot confidently choose between these possibilities with the present data, any of them imply that the progenitor of SN2010jl had an initial mass above 30Msun. This reinforces mounting evidence that many SNe IIn result from very massive stars, that massive stars can produce visible SNe without collapsing quietly to black holes, and that massive stars can retain their H envelopes until shortly before explosion. Standard stellar evolution models fail to account for these observed properties.Comment: 6 pages, 4 figures, submitted to Ap

The Type IIb Supernova 2013df and its Cool Supergiant Progenitor

We have obtained early-time photometry and spectroscopy of supernova (SN) 2013df in NGC 4414. The SN is clearly of Type IIb, with notable similarities to SN 1993J. From its luminosity at secondary maximum light, it appears that less 56Ni (≲0.06 M_☉) was synthesized in the SN 2013df explosion than was the case for the SNe IIb 1993J, 2008ax, and 2011dh. Based on a comparison of the light curves, the SN 2013df progenitor must have been more extended in radius prior to explosion than the progenitor of SN 1993J. The total extinction for SN 2013df is estimated to be AV = 0.30 mag. The metallicity at the SN location is likely to be solar. We have conducted Hubble Space Telescope (HST) Target of Opportunity observations of the SN with the Wide Field Camera 3, and from a precise comparison of these new observations to archival HST observations of the host galaxy obtained 14 yr prior to explosion, we have identified the progenitor of SN 2013df to be a yellow supergiant, somewhat hotter than a red supergiant progenitor for a normal Type II-Plateau SN. From its observed spectral energy distribution, assuming that the light is dominated by one star, the progenitor had effective temperature Teff = 4250 ± 100 K and a bolometric luminosity L_bol = 10^4.94 ± 0.06)L_☉. This leads to an effective radius R_eff = 545 ± 65 R_☉. The star likely had an initial mass in the range of 13–17 M_☉; however, if it was a member of an interacting binary system, detailed modeling of the system is required to estimate this mass more accurately. The progenitor star of SN 2013df appears to have been relatively similar to the progenitor of SN 1993J

Identification of the Red Supergiant Progenitor of Supernova 2005cs: Do the Progenitors of Type II-P Supernovae Have Low Mass?

The stars that end their lives as supernovae (SNe) have been directly observed in only a handful of cases, due mainly to the extreme difficulty in identifying them in images obtained prior to the SN explosions. Here we report the identification of the progenitor for the recent Type II-plateau (core-collapse) SN 2005cs in pre-explosion archival images of the Whirlpool Galaxy (M51) obtained with the Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS). From high-quality ground-based images of the SN from the Canada-France-Hawaii Telescope, we precisely determine the position of the SN and are able to isolate the SN progenitor to within 0".04 in the HST/ACS optical images. We further pinpoint the SN location to within 0".005 from HST/ACS ultraviolet images of the SN, confirming our progenitor identification. From photometry of the SN progenitor obtained with the pre-SN ACS images, and also limits to its brightness in pre-SN HST/NICMOS images, we infer that the progenitor is a red supergiant star of spectral type K0--M3, with initial mass 7--9 Msun. We also discuss the implications of the SN 2005cs progenitor identification and its mass estimate. There is an emerging trend that the most common Type II-plateau SNe originate from low-mass supergiants 8--15 Msun.Comment: Submitted to ApJ. A high resolution version can be found at http://astron.berkeley.edu/~weidong/sn05cs.p

What Powers the 3000-Day Light Curve of SN 2006gy?

SN 2006gy was the most luminous supernova (SN) ever observed at the time of its discovery and the first of the newly defined class of superluminous supernovae (SLSNe). The extraordinary energetics of SN 2006gy and all SLSNe (>10^(51) erg) require either atypically large explosion energies (e.g. pair-instability explosion) or the efficient conversion of kinetic into radiative energy (e.g. shock interaction). The mass-loss characteristics can therefore offer important clues regarding the progenitor system. For the case of SN 2006gy, both a scattered and thermal light echo from circumstellar material (CSM) have been reported at later epochs (day ∼800), ruling out the likelihood of a pair-instability event and leading to constraints on the characteristics of the CSM. Owing to the proximity of the SN to the bright host-galaxy nucleus, continued monitoring of the light echo has not been trivial, requiring the high resolution offered by the Hubble Space Telescope (HST) or ground-based adaptive optics (AO). Here, we report detections of SN 2006gy using HST and Keck AO at ∼3000 d post-explosion and consider the emission mechanism for the very late-time light curve. While the optical light curve and optical spectral energy distribution are consistent with a continued scattered-light echo, a thermal echo is insufficient to power the K′-band emission by day 3000. Instead, we present evidence for late-time infrared emission from dust that is radiatively heated by CSM interaction within an extremely dense dust shell, and we consider the implications on the CSM characteristics and progenitor system