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result(s) for
"Thompson, Todd A."
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A noninteracting low-mass black hole–giant star binary system
by
Bieryla, Allyson
,
Covey, Kevin
,
Lindegren, Lennart
in
Astronomi, astrofysik och kosmologi
,
Astronomy, Astrophysics and Cosmology
,
Binary stars
2019
Black hole binary systems with companion stars are typically found via their x-ray emission, generated by interaction and accretion. Noninteracting binaries are expected to be plentiful in the Galaxy but must be observed using other methods. We combine radial velocity and photometric variability data to show that the bright, rapidly rotating giant star 2MASS J05215658+4359220 is in a binary system with a massive unseen companion. The system has an orbital period of ~83 days and near-zero eccentricity. The photometric variability period of the giant is consistent with the orbital period, indicating star spots and tidal synchronization. Constraints on the giant’s mass and radius imply that the unseen companion is
3.3
−
0.7
+
2.8
solar masses, indicating that it is a noninteracting low-mass black hole or an unexpectedly massive neutron star.
Journal Article
The Tripartite Nexus: Autophagy, Cancer, and Tripartite Motif-Containing Protein Family Members
by
Mandell, Michael A.
,
Thompson, Todd A.
,
Saha, Bhaskar
in
Autophagy
,
autophagy regulation
,
Cancer therapies
2020
Autophagy is a cellular degradative process that has multiple important actions in cancer. Autophagy modulation is under consideration as a promising new approach to cancer therapy. However, complete autophagy dysregulation is likely to have substantial undesirable side effects. Thus, more targeted approaches to autophagy modulation may prove clinically beneficial. One potential avenue to achieving this goal is to focus on the actions of tripartite motif-containing protein family members (TRIMs). TRIMs have key roles in an array of cellular processes, and their dysregulation has been extensively linked to cancer risk and prognosis. As detailed here, emerging data shows that TRIMs can play important yet context-dependent roles in controlling autophagy and in the selective targeting of autophagic substrates. This review covers how the autophagy-related actions of TRIM proteins contribute to cancer and the possibility of targeting TRIM-directed autophagy in cancer therapy.
Journal Article
Antioxidants Abrogate Alpha-Tocopherylquinone-Mediated Down-Regulation of the Androgen Receptor in Androgen-Responsive Prostate Cancer Cells
by
Scariano, John K.
,
MacKenzie, Debra A.
,
Thompson, Todd A.
in
Activation
,
alpha-Tocopherol - pharmacology
,
Androgen receptors
2016
Tocopherylquinone (TQ), the oxidation product of alpha-tocopherol (AT), is a bioactive molecule with distinct properties from AT. In this study, AT and TQ are investigated for their comparative effects on growth and androgenic activity in prostate cancer cells. TQ potently inhibited the growth of androgen-responsive prostate cancer cell lines (e.g., LAPC4 and LNCaP cells), whereas the growth of androgen-independent prostate cancer cells (e.g., DU145 cells) was not affected by TQ. Due to the growth inhibitory effects induced by TQ on androgen-responsive cells, the anti-androgenic properties of TQ were examined. TQ inhibited the androgen-induced activation of an androgen-responsive reporter and inhibited the release of prostate specific antigen from LNCaP cells. TQ pretreatment was also found to inhibit AR activation as measured using the Multifunctional Androgen Receptor Screening assay. Furthermore, TQ decreased androgen-responsive gene expression, including TM4SF1, KLK2, and PSA over 5-fold, whereas AT did not affect the expression of androgen-responsive genes. Of importance, the antiandrogenic effects of TQ on prostate cancer cells were found to result from androgen receptor protein down-regulation produced by TQ that was not observed with AT treatment. Moreover, none of the androgenic endpoints assessed were affected by AT. The down-regulation of androgen receptor protein by TQ was abrogated by co-treatment with antioxidants. Overall, the biological actions of TQ were found to be distinct from AT, where TQ was found to be a potent inhibitor of cell growth and androgenic activity in androgen-responsive prostate cancer cells.
Journal Article
The All-Sky Automated Survey for Supernovae (ASAS-SN) Light Curve Server v1.0
by
Shappee, B. J.
,
Holoien, T. W.-S.
,
Will, D.
in
ASTRONOMY AND ASTROPHYSICS
,
binaries: eclipsing
,
quasars: general
2017
The All-Sky Automated Survey for Supernovae (ASAS-SN) is working toward imaging the entire visible sky every night to a depth of V ∼ 17 mag. The present data covers the sky and spans ∼2-5 years with ∼100-400 epochs of observation. The data should contain some ∼1 million variable sources, and the ultimate goal is to have a database of these observations publicly accessible. We describe here a first step, a simple but unprecedented web interface https://asas-sn.osu.edu/ that provides an up to date aperture photometry light curve for any user-selected sky coordinate. The V band photometry is obtained using a two-pixel (16 0) radius aperture and is calibrated against the APASS catalog. Because the light curves are produced in real time, this web tool is relatively slow and can only be used for small samples of objects. However, it also imposes no selection bias on the part of the ASAS-SN team, allowing the user to obtain a light curve for any point on the celestial sphere. We present the tool, describe its capabilities, limitations, and known issues, and provide a few illustrative examples.
Journal Article
Longitudinal Assessment of Lung Cancer Progression in Mice Using the Sodium Iodide Symporter Reporter Gene and SPECT/CT Imaging
by
McBride, Amber A.
,
Price, Dominique N.
,
Anton, Martina
in
60 APPLIED LIFE SCIENCES
,
A549 Cells
,
Adenocarcinoma
2016
Lung cancer has the highest mortality rate of any tissue-specific cancer in both men and women. Research continues to investigate novel drugs and therapies to mitigate poor treatment efficacy, but the lack of a good descriptive lung cancer animal model for preclinical drug evaluation remains an obstacle. Here we describe the development of an orthotopic lung cancer animal model which utilizes the human sodium iodide symporter gene (hNIS; SLC5A5) as an imaging reporter gene for the purpose of non-invasive, longitudinal tumor quantification. hNIS is a glycoprotein that naturally transports iodide (I-) into thyroid cells and has the ability to symport the radiotracer 99mTc-pertechnetate (99mTcO4-). A549 lung adenocarcinoma cells were genetically modified with plasmid or lentiviral vectors to express hNIS. Modified cells were implanted into athymic nude mice to develop two tumor models: a subcutaneous and an orthotopic xenograft tumor model. Tumor progression was longitudinally imaged using SPECT/CT and quantified by SPECT voxel analysis. hNIS expression in lung tumors was analyzed by quantitative real-time PCR. Additionally, hematoxylin and eosin staining and visual inspection of pulmonary tumors was performed. We observed that lentiviral transduction provided enhanced and stable hNIS expression in A549 cells. Furthermore, 99mTcO4- uptake and accumulation was observed within lung tumors allowing for imaging and quantification of tumor mass at two-time points. This study illustrates the development of an orthotopic lung cancer model that can be longitudinally imaged throughout the experimental timeline thus avoiding inter-animal variability and leading to a reduction in total animal numbers. Furthermore, our orthotopic lung cancer animal model is clinically relevant and the genetic modification of cells for SPECT/CT imaging can be translated to other tissue-specific tumor animal models.
Journal Article
The origin of the elements: a century of progress
2020
This review assesses the current state of knowledge of how the elements were produced in the Big Bang, in stellar lives and deaths, and by interactions in interstellar gas. We begin with statements of fact and discuss the evidence that convinced astronomers that the Sun is fusing hydrogen, that low-mass stars produce heavy elements through neutron capture, that massive stars can explode as supernovae and that supernovae of all types produce new elements. Nucleosynthesis in the Big Bang, through cosmic ray spallation, and in exploding white dwarfs is only ranked below the above facts in certainty because the evidence, while overwhelming, is so far circumstantial. Next, we highlight the flaws in our current understanding of the predictions for lithium production in the Big Bang and/or its destruction in stars and for the production of the elements with atomic number Z ∼ 45 . While the theory that neutron star mergers produce elements through neutron-capture has powerful circumstantial evidence, we are unconvinced that they produce all of the elements past nickel. Also in dispute is the exact mechanism or mechanisms that cause the white dwarfs to explode. It is difficult to determine the origin of rare isotopes because signatures of their production are weak. We are uncertain about the production sites of some lithium and nitrogen isotopes and proton-rich heavy nuclei. Finally, Betelgeuse is probably not the next star to become a supernovae in the Milky Way, in part because Betelgeuse may collapse directly to a black hole instead. The accumulated evidence in this review shows that we understand the major production sites for the elements, but islands of uncertainty in the periodic table exist. Resolving these uncertainties requires in particular understanding explosive events with compact objects and understanding the nature of the first stars and is therefore primed for new discoveries in the next decades. This article is part of the theme issue ‘Mendeleev and the periodic table’.
Journal Article
Variants in autophagy‐related genes and clinical characteristics in melanoma: a population‐based study
2016
Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy‐related (ATG) genes have been investigated in relation to melanoma progression. We examined five single‐nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population‐based case–control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0.47; 95% Confidence Intervals (CI) = 0.27–0.81, P = 0.02) and a decrease in Breslow thickness (P = 0.03). The ATG16L heterozygous genotype (AG) (rs2241880) was associated with younger age at diagnosis (P = 0.02). Two SNPs in ATG5 were found to be associated with increased stage (rs2245214 CG, OR 1.47; 95% CI = 1.11–1.94, P = 0.03; rs510432 CC, OR 1.84; 95% CI = 1.12–3.02, P = 0.05). Finally, we identified inverse associations between ATG5 (GG rs2245214) and melanomas on the scalp or neck (OR 0.20, 95% CI = 0.05–0.86, P = 0.03); ATG10 (CC) (rs1864182) and brisk tumor infiltrating lymphocytes (TILs) (OR 0.42; 95% CI = 0.21–0.88, P = 0.02), and ATG5 (CC) (rs510432) with nonbrisk TILs (OR 0.55; 95% CI = 0.34–0.87, P = 0.01). Our data suggest that ATG SNPs might be differentially associated with specific host and tumor characteristics including age at diagnosis, TILs, and stage. These associations may be critical to understanding the role of autophagy in cancer, and further investigation will help characterize the contribution of these variants to melanoma progression. Autophagy is critical in cancer risk and progression, and inherited variants in autophagy genes have not been investigated in relation to melanoma. In a large population‐based study of melanoma, two SNPs were associated with stage at diagnosis and tumor infiltrating lymphocytes; one SNP was associated with thinner Breslow thickness, earlier stage at diagnosis and younger age of diagnosis. Autophagy SNPs may influence melanoma progression and should be investigated further.
Journal Article
A Complicated Groundwater Flow System Supporting Ridge-and-Swale Wetlands in a Lake Michigan Strandplain
2020
Beach ridges and wetland swales formed in embayments along Great Lakes shorelines during Holocene lake-level changes. Vegetation differences among swales suggested influence from differing groundwater flow systems. We characterized the hydrology across 79 ridge/swale wetlands in the Manistique/Thompson embayments of Lake Michigan using chemical and physical methods. Cross-sections were built from geologic data, and nested piezometers were installed across three ridges/swales where upwelling was noted. Stainless steel piezometers driven in 30 swales were sampled and water analyzed for specific conductance, alkalinity, and major ions. Surface water from 11 swales was analyzed. Water dominated by Ca-Mg-HCO
3
was prevalent across the strandplain, with specific conductance generally less than 100 μS/cm. Conductivity, Ca, Mg, and HCO
3
in groundwater were greater at identified groundwater discharges; where an amalgamated beach ridge forms a surficial groundwater divide; and swales nearer Lake Michigan that likely receive greatly mineralized water from a deeper aquifer. Repositioning of the shoreline as the embayments filled over the past 4700 years, coupled with isostatic rebound and changes in lake water levels, altered head differentials and changed the sources of discharge from local, intermediate, and deep flow systems over time. Extant plant communities are consistent with the groundwater dependence of these wetlands.
Journal Article
Groundwater Controls on Wetland Vegetation of a Ridge-and-Swale Chronosequence in a Lake Michigan Embayment
by
Thompson, Todd A.
,
Wilcox, Douglas A.
,
Carlson Mazur, Martha L.
in
Aquifers
,
Bays
,
Beach ridges
2020
A chronosequence of wetland swales between beach ridges in the Manistique/Thompson embayments of Lake Michigan contains plant communities that differ across the strandplain. We characterized vegetation in 33 swales and compared distribution with previously reported groundwater flow systems. Older swales near a groundwater divide created by the peak Nipissing ridge receive local flows and hold sedge/leatherleaf floating mats that transition to swamp. Farther lakeward, another groundwater divide is created by discharge of calcareous waters released by termination of an underlying clay confining layer, resulting in swales dominated by northern white cedar. Cedar swamp continues lakeward in swales having flow-through calcareous groundwater, but several swales are perched above those flows. Farther lakeward, a large amalgamated beach ridge creates another groundwater divide with discharges that again support cedar swamp. Calcareous discharge from the confined aquifer, with downslope flow-through waters, then supports more cedar swamp. Flow-through waters meet yet another calcareous discharge, resulting in ponding and development of floating mats. Finally, a deep regional aquifer discharges at the Lake Michigan shore and supports marsh/shoreline species. Our results have implications for assessing potential responses to climate change, interpretation of past climate changes in paleoecological studies, and management of wetlands facing future climate changes.
Journal Article
A nova outburst powered by shocks
2017
Classical novae are runaway thermonuclear burning events on the surfaces of accreting white dwarfs in close binary star systems, sometimes appearing as new naked-eye sources in the night sky
1
. The standard model of novae predicts that their optical luminosity derives from energy released near the hot white dwarf, which is reprocessed through the ejected material
2
–
5
. Recent studies using the Fermi Large Area Telescope have shown that many classical novae are accompanied by gigaelectronvolt γ-ray emission
6
,
7
. This emission likely originates from strong shocks, providing new insights into the properties of nova outflows and allowing them to be used as laboratories for the study of the unknown efficiency of particle acceleration in shocks. Here, we report γ-ray and optical observations of the Milky Way nova ASASSN-16ma, which is among the brightest novae ever detected in γ-rays. The γ-ray and optical light curves show a remarkable correlation, implying that the majority of the optical light comes from reprocessed emission from shocks rather than the white dwarf
8
. The ratio of γ-ray to optical flux in ASASSN-16ma directly constrains the acceleration efficiency of non-thermal particles to be around 0.005, favouring hadronic models for the γ-ray emission
9
. The need to accelerate particles up to energies exceeding 100 gigaelectronvolts provides compelling evidence for magnetic field amplification in the shocks.
A tight correlation between gamma rays and optical emission in nova ASASSN-16ma indicates that the optical light comes from reprocessed emission from shocks in the ejecta, rather than an energy release near the hot white dwarf, as in the standard model.
Journal Article