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Nobiletin Affects Circadian Rhythms and Oncogenic Characteristics in a Cell-Dependent Manner
The natural product nobiletin is a small molecule, widely studied with regard to its therapeutic effects, including in cancer cell lines and tumors. Recently, nobiletin has also been shown to affect circadian rhythms via their enhancement, resulting in protection against metabolic syndrome. We hypothesized that nobiletin’s anti-oncogenic effects, such as prevention of cell migration and formation of anchorage independent colonies, are correspondingly accompanied by modulation of circadian rhythms. Concurrently, we wished to determine whether the circadian and anti-oncogenic effects of nobiletin differed across cancer cell lines. In this study, we assessed nobiletin’s circadian and therapeutic characteristics to ascertain whether these effects depend on cell line, which here also varied in terms of baseline circadian rhythmicity. Three cell culture models where nobiletin’s effects on cell proliferation and migration have been studied previously were evaluated: U2OS (bone osteosarcoma), which possesses robust circadian rhythms; MCF7 (breast adenocarcinoma), which has weak circadian rhythms; and MDA-MB-231 (breast adenocarcinoma), which is arrhythmic. We found that circadian, migration, and proliferative effects following nobiletin treatment were subtle in the U2OS and MCF7 cells. On the other hand, changes were clear in MDA-MB-231s, where nobiletin rescued rhythmicity and substantially reduced oncogenic features, specifically two-dimensional cell motility and anchorage-independent growth. Based on these results and those previously described, we posit that the effects of nobiletin are indeed cell-type dependent, and that a positive correlation may exist between nobiletin’s circadian and therapeutic effects
The thermal emission of the exoplanets WASP-1b and WASP-2b
We present a comparative study of the thermal emission of the transiting
exoplanets WASP-1b and WASP-2b using the Spitzer Space Telescope. The two
planets have very similar masses but suffer different levels of irradiation and
are predicted to fall either side of a sharp transition between planets with
and without hot stratospheres. WASP-1b is one of the most highly irradiated
planets studied to date. We measure planet/star contrast ratios in all four of
the IRAC bands for both planets (3.6-8.0um), and our results indicate the
presence of a strong temperature inversion in the atmosphere of WASP-1b,
particularly apparent at 8um, and no inversion in WASP-2b. In both cases the
measured eclipse depths favor models in which incident energy is not
redistributed efficiently from the day side to the night side of the planet. We
fit the Spitzer light curves simultaneously with the best available radial
velocity curves and transit photometry in order to provide updated measurements
of system parameters. We do not find significant eccentricity in the orbit of
either planet, suggesting that the inflated radius of WASP-1b is unlikely to be
the result of tidal heating. Finally, by plotting ratios of secondary eclipse
depths at 8um and 4.5um against irradiation for all available planets, we find
evidence for a sharp transition in the emission spectra of hot Jupiters at an
irradiation level of 2 x 10^9 erg/s/cm^2. We suggest this transition may be due
to the presence of TiO in the upper atmospheres of the most strongly irradiated
hot Jupiters.Comment: 10 pages, submitted to Ap
High C/O Chemistry and Weak Thermal Inversion in the Extremely Irradiated Atmosphere of Exoplanet WASP-12b
The carbon-to-oxygen ratio (C/O) in a planet provides critical information about its primordial origins and subsequent evolution. A primordial C/O greater than 0.8 causes a carbide-dominated interior as opposed to the silicate-dominated composition as found on Earth; the solar C/O is 0.54. Theory, shows that high C/O leads to a diversity of carbon-rich planets that can have very different interiors and atmospheres from those in the solar system. Here we report the detection of C/O greater than or equal to 1 in a planetary atmosphere. The transiting hot Jupiter WASP-12b has a dayside atmosphere depleted in water vapour and enhanced in methane by over two orders of magnitude compared to a solar-abundance chemical equilibrium model at the expected temperatures. The observed concentrations of the prominent molecules CO, CH4, and H2O are consistent with theoretical expectations for an atmosphere with the observed C/O = 1. The C/O ratios are not known for giant planets in the solar system, although they are expected to equal the solar value. If high C/O ratios are common, then extrasolar planets are likely very different in interior composition, and formed very differently, from expectations based on solar composition, potentially explaining the large diversity in observed radii. We also find that the extremely irradiated atmosphere (greater than 2500 K) of WASP-12b lacks a prominent thermal inversion, or a stratosphere, and has very efficient day-night energy circulation. The absence of a strong thermal inversion is in stark contrast to theoretical predictions for the most highly irradiated hot-Jupiter atmospheres
A methodology for the evaluation of competition policy
The paper develops a methodology for the evaluation of competition policy. Based on the existing literature and experiences with policy evaluations in other areas of economic activity, the three-step / nine-building-blocks methodology provides guidance for evaluation projects and also assists in the identification of avenues for further academic research
PenQuest Volume 1, Number 2
Table of Contents for this Volume:
Untitled by Julie Ambrose
Night by Judith Gallo
Untitled by Judy Gozdur
the shamans by Charles Riddles
Untitled by Jerry Connell
Untitled by Laura Woods
Untitled by LEMA
Wicked Bird by Laura Jo Last
Untitled by Rick Dentos
Untitled by Jeni Moody
Untitled by Bettie W. Kwibs
Untitled by Joann Stagg
The Protector Stood by Laura Jo Last
Visions of Salome by Charles Riddles
Untitled by Thomas Tutten
Kennesaw Line by Don Ova-Dunaway
Stone Blood by Mary Ellen C. Wofford
Untitled by Roger Whitt Jr.
Untitled by C. Wingate
Untitled by Doug Dorey
Untitled by Karen Blumberg
Untitled by Beverly Oviatt
Untitled by Virginia Shrader
The Crapulous Credo of Charles C. by Charles Riddles
the brave and the true by David Reed
Untitled by Charles Gutierrez
Canoe Creek by Patricia Kraft
Untitled by Linda Bobinger
The Man in the Iron Lung by Patricia Kraft
Untitled by Roger Whitt, Jr.
Childish Things by Kathleen Gay
Untitled by Joseph Avanzini
The Lover by Mary S. Aken
Untitled by Ann Harrington
And He Taketh Away by David Reed
Untitled by Mary Graham
Untitled by Melody A. Cummons
Untitled by Karen Blumberg
To The Poets by Judith Gallo
Untitled by Ann Harringto
Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial
Background
Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
Evolution of Resistance to Aurora Kinase B Inhibitors in Leukaemia Cells
Aurora kinase inhibitors are new mitosis-targeting drugs currently in clinical trials for the treatment of haematological and solid malignancies. However, knowledge of the molecular factors that influence sensitivity and resistance remains limited. Herein, we developed and characterised an in vitro leukaemia model of resistance to the Aurora B inhibitor ZM447439. Human T-cell acute lymphoblastic leukaemia cells, CCRF-CEM, were selected for resistance in 4 µM ZM447439. CEM/AKB4 cells showed no cross-resistance to tubulin-targeted and DNA-damaging agents, but were hypersensitive to an Aurora kinase A inhibitor. Sequencing revealed a mutation in the Aurora B kinase domain corresponding to a G160E amino acid substitution. Molecular modelling of drug binding in Aurora B containing this mutation suggested that resistance is mediated by the glutamate substitution preventing formation of an active drug-binding motif. Progression of resistance in the more highly selected CEM/AKB8 and CEM/AKB16 cells, derived sequentially from CEM/AKB4 in 8 and 16 µM ZM447439 respectively, was mediated by additional defects. These defects were independent of Aurora B and multi-drug resistance pathways and are associated with reduced apoptosis mostly likely due to reduced inhibition of the catalytic activity of aurora kinase B in the presence of drug. Our findings are important in the context of the use of these new targeted agents in treatment regimes against leukaemia and suggest resistance to therapy may arise through multiple independent mechanisms
Social Ecology and Behavior of Coyotes
Behavioral patterns are subject to natural selection and behavior like any other attributes of an animal, which contributes to individual survival. The chapter summarizes a long-term study of coyotes that was conducted in the Grand Teton National Park, in the northwest comer of Wyoming. There is remarkable agreement in the results stemming from a limited number of field projects concerned with the social behavior and behavioral ecology of coyotes, and some general principles concerning social ecology, scent marking, predatory behavior, time budgeting, and reproductive and care-giving patterns can be developed that are applicable not only to coyotes but to many other carnivores
Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?
In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk
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