Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

Epithelial–mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-β signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-β signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-β canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-β signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit

Understanding the local and remote source contributions to ambient O3 during a pollution episode using a combination of experimental approaches in the Guadalquivir valley, southern Spain

The Guadalquivir Valley is one of three major O3 hotspots in Spain. An airborne and surface measurement campaign was carried out from July 9th to 11th, 2019 to quantify the local/regional O3 contributions using experimental approaches. Air quality and meteorology data from surface measurements, a microlight aircraft, a helium balloon, and remote sensing data (TROPOMI-NO2-ESA) were used to obtain the 3D distribution of O3 and various tracer pollutants. O3 accumulation over 2.5 days started with inputs from oceanic air masses transported inland by sea breezes, which drew O3 and its precursors from a local/regional origin to the northeastern end of the basin. The orographic–meteorological setting of the valley caused vertical recirculation of the air masses inside the valley that caused the accumulation by increasing regional background O3 concentration by 25–30 ppb. Furthermore, possible Mediterranean O3 contributions and additional vertical recirculation through the entrainment zone of the convective boundary layer also contributed. Using particulate matter finer than 2.5 μm (PM2.5), ultrafine particles (UFP), and black carbon (BC) as tracers of local sources, we calculated that local contributions increased regional O3 levels by 20 ppb inside specific pollution plumes transported by the breeze into the valley, and by 10 ppb during midday when flying over an area with abundant agricultural burning during the morning. Air masses that crossed the southern boundaries of the Betic system at mid-altitude (400–1850 m a.s.l.) on July 10th and 11th may have provided additional O3. Meanwhile, a decreasing trend at high altitudes (3000–5000 m a.s.l.) was observed, signifying that the impact of stratospheric O3 intrusion decreased during the campaign

Growth differentiation factor 15 deficiency protects against atherosclerosis by attenuating CCR2-mediated macrophage chemotaxis

The TGF-β family member GDF-15 promotes lesion formation and plaque instability in atherosclerosis-prone LDLr-deficient mice

Targeting the TGF-β1 Pathway to Prevent Normal Tissue Injury After Cancer Therapy

Evidence supporting the critical role of transforming growth factor β1 in the development of normal tissue injury after cancer therapy is reviewed and the results of recent research aimed at preventing normal tissue injury by targeting the transforming growth factor β1 pathway are presented

Lessons from the COVID-19 air pollution decrease in Spain: Now what?

We offer an overview of the COVID-19 -driven air quality changes across 11 metropolises in Spain with the focuson lessons learned on how continuing abating pollution. Trafficflow decreased by up to 80% during the lockdownand remained relatively low during the full relaxation (June and July). After the lockdown a significant shift frompublic transport to private vehicles (+21% in Barcelona) persisted due to the pervasive fear that using publictransport might increase the risk of SARS-CoV-2 infection, which need to be reverted as soon as possible. NO2levels fell below 50% of the WHO annual air quality guidelines (WHOAQGs), but those of PM2.5were reducedless than expected due to the lower contributions from traffic, increased contributions from agricultural and do-mestic biomass burning, or meteorological conditions favoring high secondary aerosol formation yields. Evenduring the lockdown, the annual PM2.5WHOAQG was exceeded in cities within the NE and E regions withhigh NH3emissions from farming and agriculture. Decreases in PM10levels were greater than in PM2.5due to reduced emissions from road dust, vehicle wear, and construction/demolition. Averaged O3daily maximum 8-h(8hDM) experienced a generalized decrease in the rural receptor sites in the relaxation (June–July) with−20%reduced mobility. For urban areas O38hDM responses were heterogeneous, with increases or decreases depend-ing on the period and location. Thus, after canceling out the effect of meteorology, 5 out of 11 cities experiencedO3decreases during the lockdown, while the remaining 6 either did not experience relevant reductions or in-creased. During the relaxation period and coinciding with the growing O3season (June–July), most cities expe-rienced decreases. However, the O3WHOAQG was still exceeded during the lockdown and full relaxationperiods in several cities. For secondary pollutants, such as O3and PM2.5, further chemical and dispersion model-ing along with source apportionment techniques to identify major precursor reduction targets are required toevaluate their abatement potential

Transforming growth factor- directly induces p53-up-regulated modulator of apoptosis (PUMA) during the rapid induction of apoptosis in myc-driven B-cell lymphomas

Background: TGF-β induces apoptosis in Burkitt's lymphoma cells. Results: PUMA is a direct target gene of TGF-β signaling and is required for rapid apoptosis. Conclusion: TGF-β-mediated direct induction of PUMA contributes to apoptosis in human and murine c-Myc-driven lymphomas. Significance: These studies link TGF-β signaling and transcriptional activation of PUMA, two factors with critical roles in regulating B-cell survival