EUVE Observations of the Magnetic Cataclysmic Variable QQ Vulpeculae

We present simultaneous X-ray (lambda_peak ~ 44A) and EUV (lambda_peak = 89A) light curves for the magnetic cataclysmic variable QQ Vulpeculae, obtained with the EUVE satellite. We find that the unique shape of the X-ray light curve is different from previously obtained X-ray light curves of QQ Vul and provides evidence for two-pole accretion. Detailed examination of the photometric data indicates that QQ Vul undergoes a stellar eclipse of the X-ray emitting region, indicative of a high binary inclination. We discuss possible implications for the nature of this system given the observed shape of its EUV and X-ray light curves.Comment: 12 pages including 4 figures, accepted to PAS

Cranberry Polyphenols in Esophageal Cancer Inhibition: New Insights

Esophageal adenocarcinoma (EAC) is a cancer characterized by rapidly rising incidence and poor survival, resulting in the need for new prevention and treatment options. We utilized two cranberry polyphenol extracts, one proanthocyanidin enriched (C-PAC) and a combination of anthocyanins, flavonoids, and glycosides (AFG) to assess inhibitory mechanisms utilizing premalignant Barrett’s esophagus (BE) and EAC derived cell lines. We employed reverse phase protein arrays (RPPA) and Western blots to examine cancer-associated pathways and specific signaling cascades modulated by C-PAC or AFG. Viability results show that C-PAC is more potent than AFG at inducing cell death in BE and EAC cell lines. Based on the RPPA results, C-PAC significantly modulated 37 and 69 proteins in JH-EsoAd1 (JHAD1) and OE19 EAC cells, respectively. AFG treatment significantly altered 49 proteins in both JHAD1 and OE19 cells. Bioinformatic analysis of RPPA results revealed many previously unidentified pathways as modulated by cranberry polyphenols including NOTCH signaling, immune response, and epithelial to mesenchymal transition. Collectively, these results provide new insight regarding mechanisms by which cranberry polyphenols exert cancer inhibitory effects targeting EAC, with implications for potential use of cranberry constituents as cancer preventive agents

Dosage effect on uropathogenic Escherichia coli anti-adhesion activity in urine following consumption of cranberry powder standardized for proanthocyanidin content: a multicentric randomized double blind study

International audienc

Calorie restriction activates new adult born olfactory‐bulb neurones in a ghrelin‐dependent manner but acyl‐ghrelin does not enhance subventricular zone neurogenesis

The ageing and degenerating brain show deficits in neural stem/progenitor cell (NSPC) plasticity that are accompanied by impairments in olfactory discrimination. Emerging evidence suggests that the gut hormone ghrelin plays an important role in protecting neurones, promoting synaptic plasticity and increasing hippocampal neurogenesis in the adult brain. In the present study, we investigated the role of ghrelin with respect to modulating adult subventricular zone (SVZ) NSPCs that give rise to new olfactory bulb (OB) neurones. We characterised the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHSR), using an immunohistochemical approach in GHSR‐eGFP reporter mice to show that GHSR is expressed in several regions, including the OB but not in the SVZ of the lateral ventricle. These data suggest that acyl‐ghrelin does not mediate a direct effect on NSPC in the SVZ. Consistent with these findings, treatment with acyl‐ghrelin or genetic silencing of GHSR did not alter NSPC proliferation within the SVZ. Similarly, using a bromodeoxyuridine pulse‐chase approach, we show that peripheral treatment of adult rats with acyl‐ghrelin did not increase the number of new adult‐born neurones in the granule cell layer of the OB. These data demonstrate that acyl‐ghrelin does not increase adult OB neurogenesis. Finally, we investigated whether elevating ghrelin indirectly, via calorie restriction (CR), regulated the activity of new adult‐born cells in the OB. Overnight CR induced c‐Fos expression in new adult‐born OB cells but not in developmentally born cells, whereas neuronal activity was absent following re‐feeding. These effects were not present in ghrelin−/− mice, suggesting that adult‐born cells are uniquely sensitive to changes in ghrelin mediated by fasting and re‐feeding. In summary, ghrelin does not promote neurogenesis in the SVZ and OB; however, new adult‐born OB cells are activated by CR in a ghrelin‐dependent manner

ART influences HIV persistence in the female reproductive tract and cervicovaginal secretions

The recently completed HIV prevention trials network study 052 is a landmark collaboration demonstrating that HIV transmission in discordant couples can be dramatically reduced by treating the infected individual with antiretroviral therapy (ART). However, the cellular and virological events that occur in the female reproductive tract (FRT) during ART that result in such a drastic decrease in transmission were not studied and remain unknown. Here, we implemented an in vivo model of ART in BM/liver/thymus (BLT) humanized mice in order to better understand the ability of ART to prevent secondary HIV transmission. We demonstrated that the entire FRT of BLT mice is reconstituted with human CD4+ cells that are shed into cervicovaginal secretions (CVS). A high percentage of the CD4+ T cells in the FRT and CVS expressed CCR5 and therefore are potential HIV target cells. Infection with HIV increased the numbers of CD4+ and CD8+ T cells in CVS of BLT mice. Furthermore, HIV was present in CVS during infection. Finally, we evaluated the effect of ART on HIV levels in the FRT and CVS and demonstrated that ART can efficiently suppress cell-free HIV-RNA in CVS, despite residual levels of HIV-RNA+ cells in both the FRT and CVS

Systems Analysis of miRNA Biomarkers to Inform Drug Safety

microRNAs (miRNAs or miRs) are short non-coding RNA molecules which have been shown to be dysregulated and released into the extracellular milieu as a result of many drug and non-drug-induced pathologies in different organ systems. Consequently, circulating miRs have been proposed as useful biomarkers of many disease states, including drug-induced tissue injury. miRs have shown potential to support or even replace the existing traditional biomarkers of drug-induced toxicity in terms of sensitivity and specificity, and there is some evidence for their improved diagnostic and prognostic value. However, several pre-analytical and analytical challenges, mainly associated with assay standardization, require solutions before circulating miRs can be successfully translated into the clinic. This review will consider the value and potential for the use of circulating miRs in drug-safety assessment and describe a systems approach to the analysis of the miRNAome in the discovery setting, as well as highlighting standardization issues that at this stage prevent their clinical use as biomarkers. Highlighting these challenges will hopefully drive future research into finding appropriate solutions, and eventually circulating miRs may be translated to the clinic where their undoubted biomarker potential can be used to benefit patients in rapid, easy to use, point-of-care test systems

Ancestry reported by white adults with cutaneous melanoma and control subjects in central Alabama

BACKGROUND: We sought to evaluate the hypothesis that the high incidence of cutaneous melanoma in white persons in central Alabama is associated with a predominance of Irish and Scots descent. METHODS: Frequencies of country of ancestry reports were tabulated. The reports were also converted to scores that reflect proportional countries of ancestry in individuals. Using the scores, we computed aggregate country of ancestry indices as estimates of group ancestry composition. HLA-DRB1*04 allele frequencies and relationships to countries of ancestry were compared in probands and controls. Results were compared to those of European populations with HLA-DRB1*04 frequencies. RESULTS: Ninety evaluable adult white cutaneous melanoma probands and 324 adult white controls reported countries of ancestry of their grandparents. The respective frequencies of Ireland, and Scotland and "British Isles" reported countries of ancestry were significantly greater in probands than in controls. The respective frequencies of Wales, France, Italy and Poland were significantly greater in controls. 16.7% of melanoma probands and 23.8% of controls reported "Native American" ancestry; the corresponding "Native American" country of ancestry index was not significantly different in probands and controls. The frequency of HLA-DRB1*04 was significantly greater in probands, but was not significantly associated with individual or aggregate countries of ancestry. The frequency of DRB1*04 observed in Alabama was compared to DRB1*04 frequencies reported from England, Wales, Ireland, Orkney Island, France, Germany, and Australia. CONCLUSION: White adults with cutaneous melanoma in central Alabama have a predominance of Irish, Scots, and "British Isles" ancestry and HLA-DRB1*04 that likely contributes to their high incidence of cutaneous melanoma

Behavioral Coping Phenotypes and Associated Psychosocial Outcomes of Pregnant and Postpartum Women During the COVID-19 Pandemic

The impact of COVID-19-related stress on perinatal women is of heightened public health concern given the established intergenerational impact of maternal stress-exposure on infants and fetuses. There is urgent need to characterize the coping styles associated with adverse psychosocial outcomes in perinatal women during the COVID-19 pandemic to help mitigate the potential for lasting sequelae on both mothers and infants. This study uses a data-driven approach to identify the patterns of behavioral coping strategies that associate with maternal psychosocial distress during the COVID-19 pandemic in a large multicenter sample of pregnant women (N = 2876) and postpartum women (N = 1536). Data was collected from 9 states across the United States from March to October 2020. Women reported behaviors they were engaging in to manage pandemic-related stress, symptoms of depression, anxiety and global psychological distress, as well as changes in energy levels, sleep quality and stress levels. Using latent profile analysis, we identified four behavioral phenotypes of coping strategies. Critically, phenotypes with high levels of passive coping strategies (increased screen time, social media, and intake of comfort foods) were associated with elevated symptoms of depression, anxiety, and global psychological distress, as well as worsening stress and energy levels, relative to other coping phenotypes. In contrast, phenotypes with high levels of active coping strategies (social support, and self-care) were associated with greater resiliency relative to other phenotypes. The identification of these widespread coping phenotypes reveals novel behavioral patterns associated with risk and resiliency to pandemic-related stress in perinatal women. These findings may contribute to early identification of women at risk for poor long-term outcomes and indicate malleable targets for interventions aimed at mitigating lasting sequelae on women and children during the COVID-19 pandemic

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo