Naturally occurring polyphenols have the potential to prevent oxidative damage in various pathophysiological conditions. Various members of the flavonoid family were investigated to determine if they ...could protect mesencephalic dopamine (DA) neurones from injury and reduce apoptosis produced by oxidative stressors. Primary mesencephalic cultures were sensitive to oxidative insults (hydrogen peroxide, 4-hydroxynonenal, rotenone, 6-hydroxydopamine and
N-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium hydrochloride (MPP
+)) which produced concentration-dependent decreases in cellular viability across an apoptotic-necrotic continuum of injury. Flavonoids (catechin, quercetin, chrysin, puerarin, naringenin, genestein) protected mesencephalic cultures from injury by MPP
+, which was shown by DNA fragmentation studies and tyrosine hydroxylase (TH) immunocytochemistry of DA neurones to occur by apoptosis. Catechin also reduced injury produced by hydrogen peroxide, 4-hydroxynonenal, rotenone and 6-hydroxydopamine as shown by increases in cellular viability and
3HDA uptake. When the neuroprotection of catechin against MPP
+-induced injury was compared to that produced by the caspase-3 inhibitor, Z-DVED-FMK, both reduced DNA fragmentation and the injury patterns of TH-positive neurones. These data demonstrate the neuroprotective abilities of flavonoids which are able to attenuate the apoptotic injury of mesencephalic DA neurones. Since these DA neurones are under oxidative stress in Parkinsonism, our findings suggest that flavonoids could provide benefits along with other anti-oxidant therapies in Parkinson's disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Transiting extrasolar planets constitute only a small fraction of the range of stellar systems found to display periodic, shallow dimmings in wide-field surveys employing small-aperture camera ...arrays. Here we present an efficient selection strategy for follow-up observations, derived from analysis of the light curves of a sample of 67 SuperWASP targets that passed the selection tests we used in earlier papers, but which have subsequently been identified either as planet hosts or as astrophysical false positives. We determine the system parameters using Markov-chain Monte Carlo analysis of the SuperWASP light curves. We use a constrained optimization of χ2 combined with a Bayesian prior based on the main-sequence mass and radius expected from the Two Micron All Sky Survey J−H colour. The Bayesian nature of the analysis allows us to quantify both the departure of the host star from the main-sequence mass–radius relation and the probability that the companion radius is less than 1.5 Jupiter radii. When augmented by direct light-curve analyses that detect binaries with unequal primary and secondary eclipses, and objects with aperture blends that are resolved by SuperWASP, we find that only 13 of the original 67 stars, including the three known planets in the sample, would qualify for follow-up. This suggests that planet discovery ‘hit rates’ better than one-in-five should be achievable. In addition, the stellar binaries that qualify are likely to have astrophysically interesting stellar or substellar secondaries.
Mutations in Cu/Zn superoxide dismutase (SOD1) are linked to motor neuron death in familial amyotrophic lateral sclerosis (ALS) by an unclear mechanism, although misfolded SOD1 aggregates are ...commonly associated with disease. Proteomic analysis of the transgenic SOD1G93A ALS rat model revealed significant up-regulation of endoplasmic reticulum (ER)-resident protein-disulfide isomerase (PDI) family members in lumbar spinal cords. Expression of SOD1 mutants (mSOD1) led to an up-regulation of PDI in motor neuron-like NSC-34 cells but not other cell lines. Inhibition of PDI using bacitracin increased aggregate production, even in wild type SOD1 transfectants that do not readily form inclusions, suggesting PDI may protect SOD1 from aggregation. Moreover, PDI co-localized with intracellular aggregates of mSOD1 and bound to both wild type and mSOD1. SOD1 was also found in the microsomal fraction of cells despite being a predominantly cytosolic enzyme, confirming ER-Golgi-dependent secretion. In SOD1G93A mice, a significant up-regulation of unfolded protein response entities was also observed during disease, including caspase-12, -9, and -3 cleavage. Our findings therefore implicate unfolded protein response and ER stress-induced apoptosis in the patho-physiology of familial ALS. The possibility that PDI may be a therapeutic target to prevent SOD1 aggregation is also raised by this study.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ABSTRACT
We present fast (∼200 s sampling) $\it ugriz$ photometry of the low -mass AGN NGC 4395 with the Liverpool Telescope, followed by very fast (3 s sampling) us, gs, rs, is, and zs simultaneous ...monitoring with HiPERCAM on the 10.4m GTC. These observations provide the fastest ever AGN multiband photometry and very precise lag measurements. Unlike in all other AGN, gs lags us by a large amount, consistent with disc reprocessing but not with reprocessing in the broad-line region (BLR). There is very little increase in lag with wavelength at long wavelengths, indicating an outer edge (Rout) to the reprocessor. We have compared truncated disc reprocessing models to the combined HiPERCAM and previous X-ray/UV lags. For the normally accepted mass of 3.6 × 105M⊙, we obtain reasonable agreement with zero spin, Rout ∼ 1700Rg and the done physically motivated temperature-dependent disc colour-correction factor (f$\rm _{col}$). A smaller mass of 4 × 104M⊙ can only be accommodated if f$\rm _{col}=2.4$, which is probably unrealistically high. Disc self gravity is probably unimportant in this low-mass AGN but an obscuring wind may provide an edge. For the small mass, the dust sublimation radius is similar to Rout so the wind could be dusty. However, for the more likely large mass, the sublimation radius is further out so the optically thick base of a line-driven gaseous wind is more likely. The inner edge of the BLR is close to Rout in both cases. These observations provide the first good evidence for a truncated AGN disc and caution that truncation should be included in reverberation lag modelling.
We present the results of a survey using the WASP archive to search for high-frequency pulsations in F-, A- and B-type stars. Over 1.5 million targets have been searched for pulsations with ...amplitudes greater than 0.5 millimagnitude. We identify over 350 stars which pulsate with periods less than 30 min. Spectroscopic follow-up of selected targets has enabled us to confirm 10 new rapidly oscillating Ap stars, 13 pulsating Am stars and the fastest known δ Scuti star. We also observe stars which show pulsations in both the high-frequency domain and the low-frequency δ Scuti range. This work shows the power of the WASP photometric survey to find variable stars with amplitudes well below the nominal photometric precision per observation.
Context. Small planets transiting bright nearby stars are essential to our understanding of the formation and evolution of exoplanetary systems. However, few constitute prime targets for atmospheric ...characterization, and even fewer are part of multiple star systems. Aims. This work aims to validate TOI-4336 A b, a sub-Neptune-sized exoplanet candidate identified by the TESS space-based transit survey around a nearby M dwarf. Methods. We validated the planetary nature of TOI-4336 A b through the global analysis of TESS and follow-up multi-band high-precision photometric data from ground-based telescopes, medium- and high-resolution spectroscopy of the host star, high-resolution speckle imaging, and archival images. Results. The newly discovered exoplanet TOI-4336 A b has a radius of 2.1 ± 0.1 R ⊕ . Its host star is an M3.5-dwarf star with a mass of 0.33 ± 0.01 M ⊙ and a radius of 0.33 ± 0.02 R ⊙ , and is a member of a hierarchical triple M-dwarf system 22 pc away from the Sun. The planet’s orbital period of 16.3 days places it at the inner edge of the habitable zone of its host star, which is the brightest of the inner binary pair. The parameters of the system make TOI-4336 A b an extremely promising target for the detailed atmospheric characterization of a temperate sub-Neptune by transit transmission spectroscopy with JWST.
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FMFMET, NUK, UL, UM, UPUK
ABSTRACT We report the discovery of EPIC 201702477b, a transiting brown dwarf in a long period (40.73691 0.00037 day) and eccentric (e = 0.2281 0.0026) orbit. This system was initially reported as a ...planetary candidate based on two transit events seen in K2 Campaign 1 photometry and later validated as an exoplanet candidate. We confirm the transit and refine the ephemeris with two subsequent ground-based detections of the transit using the Las Cumbres Observatory Global Telescope 1 m telescope network. We rule out any transit timing variations above the level of ∼30 s. Using high precision radial velocity measurements from HARPS and SOPHIE we identify the transiting companion as a brown dwarf with a mass, radius, and bulk density of 66.9 1.7 MJ, 0.757 0.065 RJ, and 191 51 g cm−3 respectively. EPIC 201702477b is the smallest radius brown dwarf yet discovered, with a mass just below the H-burning limit. It has the highest density of any planet, substellar mass object, or main-sequence star discovered so far. We find evidence in the set of known transiting brown dwarfs for two populations of objects-high mass brown dwarfs and low mass brown dwarfs. The higher-mass population have radii in very close agreement to theoretical models, and show a lower-mass limit around 60 MJ. This may be the signature of mass-dependent ejection of systems during the formation process.
ABSTRACT
Near IR spectroscopic reverberation of Active Galactic Nuclei (AGN) potentially allows the infrared (IR) broad line region (BLR) to be reverberated alongside the disc and dust continua, ...while the spectra can also reveal details of dust astro-chemistry. Here, we describe results of a short pilot study (17 near-IR spectra over a 183 d period) for Mrk 509. The spectra give a luminosity-weighted dust radius of 〈Rd,lum〉 = 186 ± 4 light-days for blackbody (large grain dust), consistent with previous (photometric) reverberation campaigns, whereas carbon and silicate dust give much larger radii. We develop a method of calibrating spectral data in objects where the narrow lines are extended beyond the slit width. We demonstrate this by showing our resultant photometric band light curves are consistent with previous results, with a hot dust lag at >40 d in the K band, clearly different from the accretion disc response at <20 d in the z band. We place this limit of 40 d by demonstrating clearly that the modest variability that we do detect in the H and K band does not reverberate on time-scales of less than 40 d. We also extract the Pa β line light curve, and find a lag which is consistent with the optical BLR H β line of ∼70–90 d. This is important as direct imaging of the near-IR BLR is now possible in a few objects, so we need to understand its relation to the better studied optical BLR.
We present the results of concurrent X-ray and optical monitoring of the Seyfert 1 galaxy Mrk 79 over a period of more than 5 yr. We find that on short to medium time-scales (days to a few tens of ...days) the 2–10 keV X-ray and optical u- and V-band fluxes are significantly correlated, with a delay between the bands consistent with 0 d. We show that most of these variations may be well reproduced by a model where the short-term optical variations originate from reprocessing of X-rays by an optically thick accretion disc. The optical light curves, however, also display long time-scale variations over thousands of days, which are not present in the X-ray light curve. These optical variations must originate from an independent variability mechanism and we show that they can be produced by variations in the (geometrically) thin disc accretion rate as well as by varying reprocessed fractions through changes in the location of the X-ray corona.
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