Ewing sarcoma (EWS) is a paediatric bone cancer with high metastatic potential. Cellular plasticity resulting from dynamic cytoskeletal reorganization, typically regulated via the Rho pathway, is a ...prerequisite for metastasis initiation. Here, we interrogated the role of the Ewing sarcoma driver oncogene EWS-FLI1 in cytoskeletal reprogramming. We report that EWS-FLI1 strongly represses the activity of the Rho-F-actin signal pathway transcriptional effector MRTFB, affecting the expression of a large number of EWS-FLI1-anticorrelated genes including structural and regulatory cytoskeletal genes. Consistent with this finding, chromatin immunoprecipitation sequencing (ChIP-seq) revealed strong overlaps in myocardin-related transcription factor B (MRTFB) and EWS-FLI1 chromatin occupation, especially for EWS-FLI1-anticorrelated genes. Binding of the transcriptional co-activator Yes-associated protein (YAP)-1, enrichment of TEAD-binding motifs in these shared genomic binding regions and overlapping transcriptional footprints of MRTFB and TEAD factors led us to propose synergy between MRTFB and the YAP/TEAD complex in the regulation of EWS-FLI1-anticorrelated genes. We propose that EWS-FLI1 suppresses the Rho-actin pathway by perturbation of a MRTFB/YAP-1/TEAD transcriptional module, which directly affects the actin-autoregulatory feedback loop. As spontaneous fluctuations in EWS-FLI1 levels of Ewing sarcoma cells in vitro and in vivo, associated with a switch between a proliferative, non-migratory EWS-FLI1-high and a non-proliferative highly migratory EWS-FLI1-low state, were recently described, our data provide a mechanistic basis for the underlying EWS-FLI1-dependent reversible cytoskeletal reprogramming of Ewing sarcoma cells.
(1) To investigate whether there is an association between obesity and mental disorders in the general populations of diverse countries, and (2) to establish whether demographic variables (sex, age, ...education) moderate any associations observed.
Thirteen cross-sectional, general population surveys conducted as part of the World Mental Health Surveys initiative.
Household residing adults, 18 years and over (n=62 277).
DSM-IV mental disorders (anxiety disorders, depressive disorders, alcohol use disorders) were assessed with the Composite International Diagnostic Interview (CIDI 3.0), a fully structured diagnostic interview. Obesity was defined as a body mass index (BMI) of 30 kg/m(2) or greater; severe obesity as BMI 35+. Persons with BMI less than 18.5 were excluded from analysis. Height and weight were self-reported.
Statistically significant, albeit modest associations (odds ratios generally in the range of 1.2-1.5) were observed between obesity and depressive disorders, and between obesity and anxiety disorders, in pooled data across countries. These associations were concentrated among those with severe obesity, and among females. Age and education had variable effects across depressive and anxiety disorders.
The findings are suggestive of a modest relationship between obesity (particularly severe obesity) and emotional disorders among women in the general population. The study is limited by the self-report of BMI and cannot clarify the direction or nature of the relationship observed, but it may indicate a need for a research and clinical focus on the psychological heterogeneity of the obese population.
Purpose
We compared the effects of consumption of n-3 polyunsaturated fatty acids (PUFA)-enriched tomato juice versus plain tomato juice on the serum lipid profile and levels of biomarkers related to ...antioxidant status and cardiovascular disease (CVD) risk in women.
Methods
Eighteen healthy women participated in a 2-week intervention trial involving the daily intake of 500 mL of n-3 PUFA-enriched juice (
n
= 11) or plain tomato juice (
n
= 7). Each serving of enriched juice provided 250 mg of eicosapentaenoic acid (EPA) plus docosahexanoic acid (DHA). Both juices provided natural antioxidant compounds such as phenolics (181 mg) and lycopene (26.5 mg).
Results
Intervention with the enriched juice had no effect on the lipid profile, and serum levels of triglycerides and cholesterol (total, LDL, and HDL) remained unchanged. The serum antioxidant status improved following juice intake, as revealed by an increase in total antioxidant capacity and a slight decrease in lipid peroxidation. The serum levels of homocysteine, a cardiovascular risk factor, decreased following n-3 PUFA-enriched juice consumption. A decrease in vascular adhesion molecule 1 (VCAM-1) levels was also noted after intake of either plain or enriched tomato juice, whereas intercellular adhesion molecule 1 (ICAM-1) levels only decreased following intake of the enriched juice.
Conclusions
Overall, stronger positive amelioration of CVD risk factors was observed following the intake of n-3 PUFA-enriched juice than after plain tomato juice consumption, which suggested a possible synergistic action between n-3 PUFAs and tomato antioxidants.
Background: For decades, pig farmers have used gestation crates to confine pregnant sows. Gestation crates physically restrain sows for most of their life, preventing them from walking or turning ...around. Growing concern about animal welfare has been pressuring the industry for change, with recent legislation in several countries restricting the use of crates. Still, the notion that gestation crates negatively affect sow welfare has been challenged by producers in regions where crates are still used, who argue that, by facilitating health monitoring and preventing aggression, crates lead to lower sow mortality and higher piglet outputs per sow. We test whether these claims are valid by comparing these parameters across countries with different housing systems.
Methods: We use publicly available data from InterPig, a network of pig production economists in 17 countries that provides harmonized methods for meaningful comparisons of production and cost indicators. We focus on the last five years (2015-2019) of data available. Annual sow mortality and the number of pigs sold per sow were compared among (1) countries where gestation crates are the norm (CRATE), (2) countries where gestation crates are restricted to four weeks after insemination (RESTRICTED), and (3) countries where gestation crates are banned (BANNED).
Results: Sow mortality was significantly higher (F
2,85=5.03;
P=0.009), and annual pig production per sow significantly lower (F
2,85=5.99;
P=0.004), in the CRATE than in the RESTRICTED group.
Conclusions: Claims of higher mortality and reduced productivity per sow in crate-free systems are not substantiated by this industry-validated dataset. While many factors differ among the country groups (e.g., genetics, nutrition, climate), the observation that factors other than crating have a greater influence on performance challenges claims of an overall negative effect of loose housing on the parameters investigated. This evidence should be considered in policies affecting the welfare of breeding pigs.
In the present study, the residual toxicity and impact of aged nZVI after a leaching experiment on heavy metal (Pb, Zn) polluted soils was evaluated. No negative effects on physico-chemical soil ...properties were observed after aged nZVI exposure. The application of nZVI to soil produced a significant increase in Fe availability. The impact on soil biodiversity was assessed by fluorescence in situ hybridization (FISH). A significant effect of nZVI application on microbial structure has been recorded in the Pb-polluted soil nZVI-treated. Soil bacteria molecular response, evaluated by RT-qPCR using exposure biomarkers (pykA, katB) showed a decrease in the cellular activity (pykA) due to enhanced intracellular oxidative stress (katB). Moreover, ecotoxicological standardised test on Caenorhabditis elegans (C. elegans) showed a decrease in the growth endpoint in the Pb-polluted soil, and particularly in the nZVI-treated. A different pattern has been observed in Zn-polluted soils: no changes in soil biodiversity, an increase in biological activity and a significant decrease of Zn toxicity on C. elegans growth were observed after aged nZVI exposure. The results reported indicated that the pollutant and its nZVI interaction should be considered to design soil nanoremediation strategies to immobilise heavy metals.
•No negative effects on soil properties were observed after exposure with aged nZVI•The nZVI treatment produced an increase in soil Fe availability•Pb-nZVI soil showed changes in biodiversity, enhanced oxidative stress and Pb toxicity•Increased biological activity and decreased Zn toxicity were observed in Zn-nZVI soil•Impact of aged nZVI exposure mainly depends on the heavy metal contaminant
Abstract In a severe COVID-19 patient case (78-year old male) that was under active immunotherapy for high-grade non-muscle invasive bladder cancer was followed. He received a shorter hospitalization ...period, as hypothesis it was suggested that active immunotherapy played a crucial role together to anti-inflammatory and antiviral treatment in precluding the evolution of pulmonary symptoms to a poor prognosis.
Aims. ω Centauri (NGC 5139) contains many variable stars of different types and, in particular, more than one hundred RR Lyrae stars. This enabled gathering a homogeneous sample (in terms of ...instrument, image quality, and time coverage) of high-quality near-infrared (NIR) RR Lyrae light curves by performing an extensive time-series campaign aimed at this object. We have conducted a variability survey of ω Cen in the NIR, using ESO’s 4.1 m Visible and Infrared Survey Telescope for Astronomy (VISTA). This is the first paper of a series describing our results. Methods. ω Cen was observed using VIRCAM mounted on VISTA. A total of 42 epochs in J and 100 epochs in KS were obtained, distributed over a total timespan of 352 days. Point-spread function photometry was performed using DAOPHOT in the inner and DoPhot in the outer regions of the cluster. Periods of the known variable stars were improved when necessary using an ANOVA analysis. Results. We collected an unprecedented homogeneous and complete NIR catalog of RR Lyrae stars in the field of ω Cen, allowing us to study for the first time all the RR Lyrae stars associated with the cluster, except for four stars that are located far away from the cluster center. We derived membership status, subclassifications between RRab and RRc subtypes, periods, amplitudes, and mean magnitudes for all the stars in our sample. Additionally, four new RR Lyrae stars were discovered, two of which are very likely cluster members. We also discuss here the distribution of ω Cen stars in the Bailey (period-amplitude) diagram. We provide reference lines in this plane for both Oosterhoff Type I (OoI) and Oosterhoff Type II (OoII) components in J and KS. Conclusions. We clarify the status of many (candidate) RR Lyrae stars that have been reported as unclear in previous studies. This includes stars with anomalous positions in the color−magnitude diagram, uncertain periods or/and variability types, and possible field interlopers. We conclude that ω Cen hosts a total of 88 RRab and 101 RRc stars, which makes for a grand total of 189 probable members. We confirm that most RRab stars in the cluster appear to belong to an OoII component, as previously found using visual data.
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