Cyclin D 1‐induced proliferation is independent of beta‐catenin in H ead and N eck C ancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106775/1/odi12124.pd

Do sound waves transport the AGN energy in the Perseus cluster?

The level of random motions in the intracluster gas lying between 20 and 60 kpc radius in the core of the Perseus cluster has been measured by the Hitomi Soft X-ray Spectrometer (SXS) at 164 ± 10 km s$^{−1}$ . The maximum energy density in turbulent motions on that scale is therefore low. If dissipated as heat, the turbulent energy will be radiated away in less than 80 Myr and cannot spread across the core. A higher velocity is needed to prevent a cooling collapse. Gravity waves are shown to travel too slowly in a radial direction. Here we investigate propagation of energy by sound waves. The energy travels at ~1000 km s$^{−1}$ and can cross the core in a cooling time. We show that the displacement velocity amplitude of the gas required to carry the power is consistent with the Hitomi result and that the inferred density and temperature variations are consistent with $\textit{Chandra}$ observations.ACF, CP, CSR and HRR thank the Hitomi collaboration for the opportunity to participate in the analysis of the SXS data. ACF, CP, HRR and SAW acknowledge support from ERC Advanced Grant FEEDBACK, 340442

An in-depth study of a neutron star accreting at low Eddington rate: On the possibility of a truncated disc and an outflow

Due to observational challenges, our knowledge of low-level accretion flows around neutron stars is limited. We present $\textit{NuSTAR}$, $\textit{Swift}$ and $\textit{Chandra}$ observations of the low-mass X-ray binary IGR J17062-6143, which has been persistently accreting at ≃0.1 per cent of the Eddington limit since 2006. Our simultaneous $\textit{NuSTAR/Swift}$ observations show that the 0.5–79 keV spectrum can be described by a combination of a power law with a photon index of Γ ≃ 2, a blackbody with a temperature of kT$_{bb}$ ≃ 0.5 keV (presumably arising from the neutron star surface) and disc reflection. Modelling the reflection spectrum suggests that the inner accretion disc was located at R$_{in}$ ≳ 100 $\textit{GM/c}$$^{2}$ (≳225 km) from the neutron star. The apparent truncation may be due to evaporation of the inner disc into a radiatively-inefficient accretion flow, or due to the pressure of the neutron star magnetic field. Our $\textit{Chandra }$ gratings data reveal possible narrow emission lines near 1 keV that can be modelled as reflection or collisionally ionized gas, and possible low-energy absorption features that could point to the presence of an outflow. We consider a scenario in which this neutron star has been able to sustain its low accretion rate through magnetic inhibition of the accretion flow, which gives some constraints on its magnetic field strength and spin period. In this configuration, IGR J17062-6143 could exhibit a strong radio jet as well as a (propeller-driven) wind-like outflow.ND is supported by an Netherlands Organisation for Scientific Research (NWO) Vidi grant and an European Commission Marie Curie Intra-European fellowship (contract no.FP-PEOPLE-2013-IEF-627148). CP and ACF are supported by European Research Council (ERC) Advanced Grant Feedback340442. JMM acknowledges support from the Chandra guest observer program. DA acknowledges support from the Royal Society. RW is supported by an NWO Top grant, module 1. This work is based on data from the NuSTAR mission, a project led by California Institute of Technology, managed by the Jet Propulsion Laboratory, and funded by National Aeronautics and Space Administration (NASA).This is the final version of the article. It first appeared from Oxford University Press via https://doi.org/10.1093/mnras/stw235

THE RHYTHM OF FAIRALL 9. I. OBSERVING THE SPECTRAL VARIABILITY WITH XMM-NEWTON AND NuSTAR

© 2016. The American Astronomical Society. All rights reserved. We present a multi-epoch X-ray spectral analysis of the Seyfert 1 galaxy Fairall 9. Our analysis shows that Fairall 9 displays unique spectral variability in that its ratio residuals to a simple absorbed power law in the 0.5-10 keV band remain constant with time in spite of large variations in flux. This behavior implies an unchanging source geometry and the same emission processes continuously at work at the timescale probed. With the constraints from NuSTAR on the broad-band spectral shape, it is clear that the soft excess in this source is a superposition of two different processes, one being blurred ionized reflection in the innermost parts of the accretion disk, and the other a continuum component such as a spatially distinct Comptonizing region. Alternatively, a more complex primary Comptonization component together with blurred ionized reflection could be responsible

Antimicrobial Nodule-Specific Cysteine-Rich Peptides Induce Membrane Depolarization-Associated Changes in the Transcriptome of Sinorhizobium meliloti.

Leguminous plants establish symbiosis with nitrogen-fixing alpha- and betaproteobacteria, collectively called rhizobia, which provide combined nitrogen to support plant growth. Members of the inverted repeat-lacking clade of legumes impose terminal differentiation on their endosymbiotic bacterium partners with the help of the nodule-specific cysteine-rich (NCR) peptide family composed of close to 600 members. Among the few tested NCR peptides, cationic ones had antirhizobial activity measured by reduction or elimination of the CFU and uptake of the membrane-impermeable dye propidium iodide. Here, the antimicrobial spectrum of two of these peptides, NCR247 and NCR335, was investigated, and their effect on the transcriptome of the natural target Sinorhizobium meliloti was characterized. Both peptides were able to kill quickly a wide range of Gram-negative and Gram-positive bacteria; however, their spectra were only partially overlapping, and differences were found also in their efficacy on given strains, indicating that the actions of NCR247 and NCR335 might be similar though not identical. Treatment of S. meliloti cultures with either peptide resulted in a quick downregulation of genes involved in basic cellular functions, such as transcription-translation and energy production, as well as upregulation of genes involved in stress and oxidative stress responses and membrane transport. Similar changes provoked mainly in Gram-positive bacteria by antimicrobial agents were coupled with the destruction of membrane potential, indicating that it might also be a common step in the bactericidal actions of NCR247 and NCR335

Exogenous WNT5A and WNT11 proteins rescue CITED2 dysfunction in mouse embryonic stem cells and zebrafish morphants

Mutations and inadequate methylation profiles of CITED2 are associated with human congenital heart disease (CHD). In mouse, Cited2 is necessary for embryogenesis, particularly for heart development, and its depletion in embryonic stem cells (ESC) impairs cardiac differentiation. We have now determined that Cited2 depletion in ESC affects the expression of transcription factors and cardiopoietic genes involved in early mesoderm and cardiac specification. Interestingly, the supplementation of the secretome prepared from ESC overexpressing CITED2, during the onset of differentiation, rescued the cardiogenic defects of Cited2-depleted ESC. In addition, we demonstrate that the proteins WNT5A and WNT11 held the potential for rescue. We also validated the zebrafish as a model to investigate cited2 function during development. Indeed, the microinjection of morpholinos targeting cited2 transcripts caused developmental defects recapitulating those of mice knockout models, including the increased propensity for cardiac defects and severe death rate. Importantly, the co-injection of anti-cited2 morpholinos with either CITED2 or WNT5A and WNT11 recombinant proteins corrected the developmental defects of Cited2-morphants. This study argues that defects caused by the dysfunction of Cited2 at early stages of development, including heart anomalies, may be remediable by supplementation of exogenous molecules, offering the opportunity to develop novel therapeutic strategies aiming to prevent CHD.Agência financiadora: Fundação para a Ciência e a Tecnologia (FCT) Comissão de Coordenação e Desenvolvimento Regional do Algarve (CCDR Algarve) ALG-01-0145-FEDER-28044; DFG 568/17-2 Algarve Biomedical Center (ABC) Municipio de Louléinfo:eu-repo/semantics/publishedVersio

Using stated preference methods to assess environmental impacts of forest biomass power plants in Portugal

As a renewable energy source, the use of forest biomass for electricity generation is advantageous in comparison with fossil fuels, however the activity of forest biomass power plants causes adverse impacts, affecting particularly neighbouring communities. The main objective of this study is to estimate the effects of the activity of forest biomass power plants on the welfare of two groups of stakeholders, namely local residents and the general population and we apply two stated preference methods: contingent valuation and discrete choice experiments, respectively. The former method was applied to estimate the minimum compensation residents of neighbouring communities of two forest biomass power plants in Portugal would be willing to accept. The latter method was applied among the general population to estimate their willingness to pay to avoid specific environmental impacts. The results show that the presence of the selected facilities affects individuals’ well-being. On the other hand, in the discrete choice experiments conducted among the general population all impacts considered were significant determinants of respondents’ welfare levels. The results of this study stress the importance of performing an equity analysis of the welfare effects on different groups of stakeholders from the installation of forest biomass power plants, as their effects on welfare are location and impact specific. Policy makers should take into account the views of all stakeholders either directly or indirectly involved when deciding crucial issues regarding the sitting of new forest biomass power plants, in order to achieve an efficient and equitable outcome

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives