SWI/SNF regulates a transcriptional programme that induces senescence to prevent liver cancer

Oncogene-induced senescence (OIS) is a potent tumour suppressor mechanism. To identify senescence regulators relevant to cancer, we screened an shRNA library targeting genes deleted in hepatocellular carcinoma (HCC). Here, we describe how knockdown of the SWI/SNF component ARID1B prevents OIS and cooperates with RAS to induce liver tumours. ARID1B controls p16INK4a and p21CIP1a transcription but also regulates DNA damage, oxidative stress and p53 induction, suggesting that SWI/SNF uses additional mechanisms to regulate senescence. To systematically identify SWI/SNF targets regulating senescence, we carried out a focused shRNA screen. We discovered several new senescence regulators including ENTPD7, an enzyme that hydrolyses nucleotides. ENTPD7 affects oxidative stress, DNA damage and senescence. Importantly, expression of ENTPD7 or inhibition of nucleotide synthesis in ARID1B-depleted cells results in re-establishment of senescence. Our results identify novel mechanisms by which epigenetic regulators can affect tumor progression and suggest that pro-senescence therapies could be employed against SWI/SNF-mutated cancers

New VR magnification ratios of QSO 0957+561

We present VR magnification ratios of QSO 0957+561, which are inferred from the GLITP light curves of Q0957+561A and new frames taken with the 2.56m Nordic Optical Telescope about 14 months after the GLITP monitoring. From two photometric approaches and a reasonable range for the time delay in the system (415-430 days), we do not obtain achromatic optical continuum ratios, but ratios depending on the wavelength. These new measurements are consistent with differential extinction in the lens galaxy, the Lyman limit system, the damped Ly-alpha system, or the host galaxy of the QSO. The possible values for the differential extinction and the ratio of total to selective extinction in the V band are reasonable. Moreover, crude probability arguments suggest that the ray paths of the two components cross a similar dusty environment, including a network of compact dust clouds and compact dust voids. As an alternative (in fact, the usual interpretation of the old ratios), we also try to explain the new ratios as caused by gravitational microlensing in the deflector. From magnification maps for each of the gravitationally lensed images, using different fractions of the surface mass density represented by the microlenses, as well as different sizes and profiles of the V-band and R-band sources, several synthetic distributions of V-band and R-band ratios are derived. In some gravitational scenarios, there is an apparent disagreement between the observed pair of ratios and the simulated distributions. However, several microlensing pictures work well. To decide between either extinction, or microlensing, or a mixed scenario (extinction + microlensing), new observational and interpretation efforts are required.Comment: PS and PDF versions are created from the LaTeX file and 5 EPS figures, two additional figues (Figs. 6 and 7) in JPEG format, scheduled for the ApJ 20 January 2005 issu

Brentwood Community Health Care Assessment

BACKGROUND: The Community Alliance for Research Empowering Social Change (CARES) is an academic–community research partnership designed to train community members on research methods and develop the infrastructure for community-based participatory research (CBPR) to examine and address racial/ethnic health disparities. The Brentwood Community Health Assessment (BCHA) was developed through a CBPR pilot project grant from CARES. OBJECTIVES: The purpose of the BCHA is to assess health care utilization and identify existing barriers to health care access among a multi-ethnic community in the Hamlet of Brentwood, New York. METHODS: Using CBPR approaches, the community–academic research partnership develop the study design and survey instrument. Trained Bilingual (English/Spanish) data collectors verbally administered surveys door-to-door to residents of Brentwood from October 2010 to May 2011. Inclusion criteria required participants to be at least 18 years of age and speak either English or Spanish. RESULTS: Overall, 232 residents completed the BCHA; 49% were male, 66% Hispanic, 13% non-Hispanic White, 13% non-Hispanic Black, 29% had less than a high school education, and 33% were born in United States. The assessment results revealed that most residents are able to access health care when needed and the most significant barriers to health care access are insurance and cost. CONCLUSIONS: We describe the community–academic partnered process used to develop and implement the BCHA and report assessment findings; the community-partnered approach improved data collection and allowed access into one of Suffolk County’s most vulnerable communities

Beryllium abundances in stars hosting giant planets

We have derived beryllium abundances in a wide sample of stars hosting planets, with spectral types in the range F7V-K0V, aimed at studying in detail the effects of the presence of planets on the structure and evolution of the associated stars. Predictions from current models are compared with the derived abundances and suggestions are provided to explain the observed inconsistencies. We show that while still not clear, the results suggest that theoretical models may have to be revised for stars with Teff<5500K. On the other hand, a comparison between planet host and non-planet host stars shows no clear difference between both populations. Although preliminary, this result favors a ``primordial'' origin for the metallicity ``excess'' observed for the planetary host stars. Under this assumption, i.e. that there would be no differences between stars with and without giant planets, the light element depletion pattern of our sample of stars may also be used to further investigate and constraint Li and Be depletion mechanisms.Comment: A&A in press -- accepted on the 22/02/2002 (11 pages, 6 figures included

Analisi scientifiche sulle tempere murali di Villa Pace

International audienceThe morphology, mineralogy, and solid-liquid phase separation of the Cu and Zn precipitates formed with sulfide produced in a sulfate-reducing bioreactor were studied at pH 3, 5, and 7. The precipitates formed at pH 7 display faster settling rates, better dewaterability, and higher concentrations of settleable solids as compared to the precipitates formed at pH 3 and 5. These differences were linked to the agglomeration of the sulfidic precipitates and coprecipitation of the phosphate added to the bioreactor influent. The Cu and Zn quenched the intensity of the dissolved organic matter peaks identified by fluorescence-excitation emission matrix spectroscopy, suggesting a binding mechanism that decreases supersaturation, especially at pH 5. X-ray absorption fine structure spectroscopy analyses confirmed the precipitation of Zn-S as sphalerite and Cu-S as covellite in all samples, but also revealed the presence of Zn sorbed on hydroxyapatite. These analyses further showed that CuS structures remained amorphous regardless of the pH, whereas the ZnS structure was more organized at pH 5 as compared to the ZnS formed at pH 3 and 7, in agreement with the cubic sphalerite-type structures observed through scanning electron microscopy at pH 5

Anaerobic digestion of whole-crop winter wheat silage for renewable energy production

With biogas production expanding across Europe in response to renewable energy incentives, a wider variety of crops need to be considered as feedstock. Maize, the most commonly used crop at present, is not ideal in cooler, wetter regions, where higher energy yields per hectare might be achieved with other cereals. Winter wheat is a possible candidate because, under these conditions, it has a good biomass yield, can be ensiled, and can be used as a whole crop material. The results showed that, when harvested at the medium milk stage, the specific methane yield was 0.32 m3 CH4 kg–1 volatile solids added, equal to 73% of the measured calorific value. Using crop yield values for the north of England, a net energy yield of 146–155 GJ ha–1 year–1 could be achieved after taking into account both direct and indirect energy consumption in cultivation, processing through anaerobic digestion, and spreading digestate back to the land. The process showed some limitations, however: the relatively low density of the substrate made it difficult to mix the digester, and there was a buildup of soluble chemical oxygen demand, which represented a loss in methane potential and may also have led to biofoaming. The high nitrogen content of the wheat initially caused problems, but these could be overcome by acclimatization. A combination of these factors is likely to limit the loading that can be applied to the digester when using winter wheat as a substrat

ANEURISMA DA AORTA TORÁCICA 29 ANOS APÓS LACERAÇÃO E REPARAÇÃO PRIMÁRIA

A laceração traumática da aorta é uma lesão de elevada mortalidade pré-hospitalar e intra-hospitalar. A sobrevivência a este tipo de lesões é rara e escasseiam dados sobre o prognóstico a longo-prazo destes doentes. Descrevemos um caso clínico de reparação primária de laceração da aorta torácica que se apresentou 29 anos após a repa- ração inicial com aneurisma da aorta torácica na mesma topografia. Foi submetido a reparação endovascular do aneurisma. Discutem-se as técnicas de reparação da laceração da aorta e a evidência existente sobre o prognóstico destes doentes, nomea- damente a incidência de lesões secundárias após a cirurgia inicial, e a necessidade de equacionar um plano de seguimento

Making Climate Change Mitigation and Adaptability Real in Africa with Conservation Agriculture

In this report, the authors have gathered essential information on how the agricultural sector can respond to climate change through Conservation Agriculture (CA). This document aims to serve as a basis for decision-making based on science and agricultural experimentation in Africa

Effectiveness of steroids versus placebo in preventing upper airway obstruction after extubation in critically ill children: rationale and design of a multicentric, double-blind, randomized study

BACKGROUND: Post-extubation upper airway obstruction (UAO) is a frequent complication causing stridor and respiratory distress, which occasionally require reintubation, thereby increasing morbidity and mortality rates. Contradictory results have been obtained in studies assessing the effectiveness of steroids in preventing post-extubation UAO, and the available evidence is limited. We designed a multicentric randomized, placebo-controlled study to explore the effectiveness of dexamethasone in preventing post-extubation UAO in children. METHODS: A multicentric, prospective, double-blind, randomized, placebo-controlled, phase IV clinical trial has been designed. The sample will include pediatric patients who are between 1 month and 16 years of age and who have been intubated for more than 48 h. Patients who have airway disorders or who have received steroids within the previous seven days will be excluded. Patients will be randomly assigned to receive either placebo or a therapy with dexamethasone 0.25 mg/kg every 6 h to be started 6 to 12 h prior to extubation (to a total of four doses). Randomization will be performed at a 1:1 ratio. Follow-up of patients will be carried out for 48 h after extubation. The main objective of this study is to access the reduction in the incidence of moderate to severe UAO symptoms following extubation. Secondary objectives include assessing the decrease in the incidence of reintubation, evaluating the use of additional therapies for UAO, and monitoring potential side effects of dexamethasone. DISCUSSION: The results of this study will contribute to the existing evidence on prophylaxis for post-extubation airway obstruction. TRIAL REGISTRATION: EudraCT identifier: 2009-016596-30. Registered on May 11, 2010

Larval Development in Tropical Gar (Atractosteus tropicus) Is Dependent on the Embryonic Thermal Regime: Ecological Implications under a Climate Change Context

In ectotherm species, environmental temperature plays a key role in development, growth, and survival. Thus, determining how temperature affects fish populations is of utmost importance to accurately predict the risk of climate change over fisheries and aquaculture, critical to warrant nutrition and food security in the coming years. Here, the potential effects of abnormal thermal regimes (24, 28 and 32 C; TR24, TR28, and TR32, respectively) exclusively applied during embryogenesis in tropical gar (Atractosteus tropicus) has been explored to decipher the potential consequences on hatching and growth from fertilization to 16 days post-fertilization (dpf), while effects on skeletal development and body morphology were explored at fertilization and 16 dpf. Egg incubation at higher temperatures induced an early hatching and mouth opening. A higher hatching rate was obtained in eggs incubated at 28 C when compared to those at 24 C. No differences were found in fish survival at 16 dpf, with values ranging from 84.89 to 88.86%, but increased wet body weight and standard length were found in larvae from TR24 and TR32 groups. Thermal regime during embryogenesis also altered the rate at which the skeletal development occurs. Larvae from the TR32 group showed an advanced skeletal development, with a higher development of cartilaginous structures at hatching but reduced at 16 dpf when compared with the TR24 and TR28 groups. Furthermore, this advanced skeletal development seemed to determine the fish body morphology. Based on biometric measures, a principal component analysis showed how along development, larvae from each thermal regime were clustered together, but with each population remaining clearly separated from each other. The current study shows how changes in temperature may induce craniofacial and morphological alterations in fish during early stages and contribute to understanding the possible effects of global warming in early development of fish and its ecological implications.Versión del edito