X-Ray and Optical Observations of A 0535+26

We present recent contemporaneous X-ray and optical observations of the Be/X-ray binary system A\,0535+26 with the \textit{Fermi}/Gamma-ray Burst Monitor (GBM) and several ground-based observatories. These new observations are put into the context of the rich historical data (since $\sim$1978) and discussed in terms of the neutron star Be-disk interaction. The Be circumstellar disk was exceptionally large just before the 2009 December giant outburst, which may explain the origin of the unusual recent X-ray activity of this source. We found a peculiar evolution of the pulse profile during this giant outburst, with the two main components evolving in opposite ways with energy. A hard 30-70 mHz X-ray QPO was detected with GBM during this 2009 December giant outburst. It becomes stronger with increasing energy and disappears at energies below 25\,keV. In the long-term a strong optical/X-ray correlation was found for this system, however in the medium-term the H$_\alpha$ EW and the V-band brightness showed an anti-correlation after $\sim$2002 Agust. Each giant X-ray outburst occurred during a decline phase of the optical brightness, while the H$_\alpha$ showed a strong emission. In late 2010 and before the 2011 February outburst, rapid V/R variations are observed in the strength of the two peaks of the H$_\alpha$ line. These had a period of $\sim$\,25 days and we suggest the presence of a global one-armed oscillation to explain this scenario. A general pattern might be inferred, where the disk becomes weaker and shows V/R variability beginning $\sim$\,6 months following a giant outburst.Comment: 18, 11 figures, 1 tabl

Enhancement of Naringenin Bioavailability by Complexation with Hydroxypropoyl-β-Cyclodextrin

The abundant flavonoid aglycone, naringenin, which is responsible for the bitter taste in grapefruits, has been shown to possess hypolipidemic and anti-inflammatory effects both in vitro and in vivo. Recently, our group demonstrated that naringenin inhibits hepatitis C virus (HCV) production, while others demonstrated its potential in the treatment of hyperlipidemia and diabetes. However, naringenin suffers from low oral bioavailability critically limiting its clinical potential. In this study, we demonstrate that the solubility of naringenin is enhanced by complexation with β-cyclodextrin, an FDA approved excipient. Hydroxypropoyl-β-cyclodextrin (HPβCD), specifically, increased the solubility of naringenin by over 400-fold, and its transport across a Caco-2 model of the gut epithelium by 11-fold. Complexation of naringenin with HPβCD increased its plasma concentrations when fed to rats, with AUC values increasing by 7.4-fold and Cmax increasing 14.6-fold. Moreover, when the complex was administered just prior to a meal it decreased VLDL levels by 42% and increased the rate of glucose clearance by 64% compared to naringenin alone. These effects correlated with increased expression of the PPAR co-activator, PGC1α in both liver and skeletal muscle. Histology and blood chemistry analysis indicated this route of administration was not associated with damage to the intestine, kidney, or liver. These results suggest that the complexation of naringenin with HPβCD is a viable option for the oral delivery of naringenin as a therapeutic entity with applications in the treatment of dyslipidemia, diabetes, and HCV infection.National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (K01DK080241)Harvard Clinical Nutrition Research Center (P30-DK040561)European Research Council (Starting Grant (TMIHCV 242699))Massachusetts General Hospital (BioMEMS Resource Center (P41 EB-002503))Alexander Silberman Institute of Life Science

Developmental and Lactational Exposure to Dieldrin Alters Mammary Tumorigenesis in Her2/neu Transgenic Mice

Breast cancer is the most common cancer in Western women and while its precise etiology is unknown, environmental factors are thought to play a role. The organochlorine pesticide dieldrin is a persistent environmental toxicant thought to increase the risk of breast cancer and reduce survival in the human population. The objective of this study was to define the effect of developmental exposure to environmentally relevant concentrations of dieldrin, on mammary tumor development in the offspring. Sexually mature FVB-MMTV/neu female mice were treated with vehicle (corn oil), or dieldrin (0.45, 2.25, and 4.5 µg/g body weight) daily by gavage for 5 days prior to mating and then once weekly throughout gestation and lactation until weaning. Dieldrin concentrations were selected to produce serum levels representative of human background body burdens, occupational exposure, and overt toxicity. Treatment had no effect on litter size, birth weight or the number of pups surviving to weaning. The highest dose of dieldrin significantly increased the total tumor burden and the volume and number of tumors found in the thoracic mammary glands. Increased mRNA and protein expression of the neurotrophin BDNF and its receptor TrkB was increased in tumors from the offspring of dieldrin treated dams. This study indicates that developmental exposure to the environmental contaminant dieldrin causes increased tumor burden in genetically predisposed mice. Dieldrin exposure also altered the expression of BNDF and TrkB, novel modulators of cancer pathogenesis

The challenge of habitat modelling for threatened low density species using heterogeneous data : the case of Cuvier’s beaked whales in the Mediterranean

We are grateful to the ACCOBAMS Secretariat for their support in this work, including a small grant for the analysis.The Mediterranean population of Cuvieŕs beaked whale (Ziphius cavirostris), a deep-diving cetacean, is genetically distinct from the Atlantic, and subject to a number of conservation threats, in particular underwater noise. It is also cryptic at the surface and relatively rare, so obtain robust knowledge on distribution and abundance presents unique challenges. Here we use multiplatform and multiyear survey data to analyse the distribution and abundance of this species across the Mediterranean Sea. We use a novel approach combining heterogeneous data gathered with different methods to obtain a single density index for the region. A total of 594,996 km of survey effort and 507 sightings of Cuvier’s beaked whales, from 1990 to 2016, were pooled together from 24 different sources. Data were divided into twelve major groups according to platform height, speed and sea state. Both availability bias and effective strip width were calculated from the sightings with available perpendicular distance data. This was extrapolated to the rest of the sightings for each of the twelve groups. Habitat preference models were fitted into a GAM framework using counts of groups as a response variable with the effective searched area as an offset. Depth, coefficient of variation of depth, longitude and marine regions (as defined by the International Hydrographic Organization) were identified as important predictors. Predicted abundance of groups per grid cell were multiplied by mean group size to obtain a prediction of the abundance of animals. A total abundance of 5799 (CV = 24.0%) animals was estimated for the whole Mediterranean basin. The Alborán Sea, Ligurian Sea, Hellenic Trench, southern Adriatic Sea and eastern Ionian Sea were identified as being the main hot spots in the region. It is important to urge that the relevant stakeholders incorporate this information in the planning and execution of high risk activities in these high-risk areas.PostprintPeer reviewe