Increasing nutrient inputs driven by global environmental pressures may lead to changes in prokaryotic plankton biomass and community composition in coastal environments. Nutrient addition ...experiments (inorganic, organic, and mixed) were performed at the continental shelf outside the Ría de Vigo, in spring, summer and autumn 2014, and the results contrasted with those from similar previous experiments carried out inside the ría in 2013. The mixed nutrient additions caused the greatest changes in community composition, mostly consisting of blooms of Vibrionales. Inorganic nutrients yielded increased proportions of Oceanospirillales and Alteromonadales. Euclidean distances among samples were used to estimate compositional resistance to disturbances derived from nutrient additions. Changes in prokaryotic biomass were used as an indicator of biomass resistance. Generally, prokaryotic communities were more resistant to inorganic than organic nutrient additions. Communities sampled inside the ría, presumably exposed to greater perturbations, showed milder variability in the non-amended control than those from outside the ría. By contrast, shelf communities, with higher ambient organic matter concentrations, were more resistant to organic and mixed nutrient additions than those from the ría. Our data suggest that the perturbation history is related to the resistance of microbial communities to changes in nutrient inputs into the coastal ocean.
Aims. We probe the high-energy (>60 MeV) emission from the black hole X-ray binary system, Cygnus X-1, and investigate its origin. Methods. We analyzed 7.5 yr of data by Fermi-LAT with the latest ...Pass 8 software version. Results. We report the detection of a signal at ~8σ statistical significance that is spatially coincident with Cygnus X-1 and has a luminosity of 5.5 × 1033 erg s-1, above 60 MeV. The signal is correlated with the hard X-ray flux: the source is observed at high energies only during the hard X-ray spectral state, when the source is known to display persistent, relativistic radio-emitting jets. The energy spectrum, extending up to ~20 GeV without any sign of spectral break, is well fit by a power-law function with a photon index of 2.3 ± 0.2. There is a hint of orbital flux variability, with high-energy emission mostly coming around the superior conjunction. Conclusions. We detected GeV emission from Cygnus X-1 and probed that the emission is most likely associated with the relativistic jets. The evidence of flux orbital variability indicates the anisotropic inverse-Compton on stellar photons as the mechanism at work, thus constraining the emission region to a distance 1011–1013 cm from the black hole.
SPROUTY-2 (SPRY2) is a modulator of tyrosine kinase receptor signaling with receptor- and cell type-dependent inhibitory or enhancing effects. Studies on the action of SPRY2 in major cancers are ...conflicting and its role remains unclear. Here we have dissected SPRY2 action in human colon cancer. Global transcriptomic analyses show that SPRY2 downregulates genes encoding tight junction proteins such as claudin-7 and occludin and other cell-to-cell and cell-to-matrix adhesion molecules in human SW480-ADH colon carcinoma cells. Moreover, SPRY2 represses LLGL2/HUGL2, PATJ1/INADL and ST14, main regulators of the polarized epithelial phenotype, and ESRP1, an epithelial-to-mesenchymal transition (EMT) inhibitor. A key action of SPRY2 is the upregulation of the major EMT inducer ZEB1, as these effects are reversed by ZEB1 knock-down by means of RNA interference. Consistently, we found an inverse correlation between the expression level of claudin-7 and those of SPRY2 and ZEB1 in human colon tumors. Mechanistically, ZEB1 upregulation by SPRY2 results from the combined induction of ETS1 transcription factor and the repression of microRNAs (miR-200 family, miR-150) that target ZEB1 RNA. Moreover, SPRY2 increased AKT activation by epidermal growth factor, whereas AKT and also Src inhibition reduced the induction of ZEB1. Altogether, these data suggest that AKT and Src are implicated in SPRY2 action. Collectively, these results show a tumorigenic role of SPRY2 in colon cancer that is based on the dysregulation of tight junction and epithelial polarity master genes via upregulation of ZEB1. The dissection of the mechanism of action of SPRY2 in colon cancer cells is important to understand the upregulation of this gene in a subset of patients with this neoplasia that have poor prognosis.
The responses of coastal microbial communities to nutrient inputs depend on the magnitude and nature of those inputs. To understand the response of prokaryote communities to contrasting levels of ...nutrient inputs from different sources, three nutrient addition experiments were performed in the Ría de Vigo in spring, summer, and autumn. The experiments consisted of controlled inorganic (nitrate, ammonium and phosphate), organic (glucose and a mix of 18 amino acids), and mixed (inorganic and organic); as well as natural (atmospheric and riverine) nutrient additions to surface water samples taken from the middle of the embayment and incubated for 48h, under in situ temperature and irradiance conditions. Prokaryote community DNA was collected and analyzed using high-throughput amplicon sequencing of the 16S rRNA gene. The joint addition of inorganic and organic nutrients provoked the most pronounced changes in community composition, systematically leading to great increases in the proportion of sequence reads belonging to Vibrionales, while natural amendments only caused subtle alterations. The proportion of reads assigned to the Planktomarina genus, bacteria belonging to the order Rhodobacterales, tended to increase when natural atmospheric nutrients were added. Overall, the fraction of reads belonging to the order Flavobacteriales did not show relevant changes, although the contribution of sequences affiliated to Polaribacter and Aurantivirga genera increased after atmospheric and riverine inputs in summer, and autumn. The proportion of Vibrionales reads also increased after controlled organic amendments in autumn, and to a lesser extent after riverine additions in spring and summer. In general, our findings suggest that an increasing input of nitrogenous organic matter from allochthonous sources into this coastal environment might promote the growth of potentially pathogenic bacteria belonging to the order Vibrionales.
•Nutrient additions into coastal systems change communities of prokaryotic plankton.•The magnitude and nature of those inputs determine the extent and direction of the changes in prokaryotic composition.•Addition of organic nitrogen into coastal systems or estuaries can promote blooms of potentially pathogenic Vibrio bacteria.
Pigment epithelium-derived factor (PEDF) is a multifunctional secreted glycoprotein that displays broad anti-tumor activity based on dual targeting of the tumor microenvironment (anti-angiogenic ...action) and the tumor cells (direct anti-tumor action). Here, we show that PEDF expression is high in melanocytes, but it is lost during malignant progression of human melanoma. Using a high-throughput analysis of the data from microarray studies of molecular profiling of human melanoma, we found that PEDF expression is lost in highly invasive melanomas. In paired cell lines established from the same lesion but representing the high and low extremes of malignant potential, abundant PEDF expression was restricted to the poorly aggressive counterparts. We used RNA interference to directly address the functional consequences of PEDF silencing. PEDF knockdown in poorly aggressive melanoma cell lines augmented migration, invasion and vasculogenic mimicry, which translated into an increased in vivo metastatic potential. PEDF interference also significantly enhanced the migratory and invasive capability of normal melanocytes and moderately increased their proliferative potential. Our results show that loss of PEDF enables melanoma cells to acquire an invasive phenotype and, therefore, modulation of this multifunctional factor could be critical for the malignant progression of human melanoma.
The presence of hypoxic regions in solid tumors is an adverse prognostic factor for patient outcome. Here, we show that hypoxia induces the expression of Ephrin-A3 through a novel hypoxia-inducible ...factor (HIF)-mediated mechanism. In response to hypoxia, the coding EFNA3 mRNA levels remained relatively stable, but HIFs drove the expression of previously unknown long noncoding (lnc) RNAs from EFNA3 locus and these lncRNA caused Ephrin-A3 protein accumulation. Ephrins are cell surface proteins that regulate diverse biological processes by modulating cellular adhesion and repulsion. Mounting evidence implicates deregulated ephrin function in multiple aspects of tumor biology. We demonstrate that sustained expression of both Ephrin-A3 and novel EFNA3 lncRNAs increased the metastatic potential of human breast cancer cells, possibly by increasing the ability of tumor cells to extravasate from the blood vessels into surrounding tissue. In agreement, we found a strong correlation between high EFNA3 expression and shorter metastasis-free survival in breast cancer patients. Taken together, our results suggest that hypoxia could contribute to metastatic spread of breast cancer via HIF-mediated induction of EFNA3 lncRNAs and subsequent Ephrin-A3 protein accumulation.
Ten zoanthamine-type alkaloids from two marine zoanthids belonging to the
Zoanthus genus (
Zoanthus nymphaeus and
Zoanthus sp.) along with one semisynthetic derivative were evaluated for their ...antiplatelet activities on human platelet aggregation induced by several stimulating agents. 11-Hydroxyzoanthamine (
11) and a synthetic derivative of norzoanthamine (
16) showed strong inhibition against thrombin-, collagen- and arachidonic acid-induced aggregation, zoanthenol (
15) displayed a selective inhibitory activity induced by collagen, while zoanthaminone (
10) behaved as a potent aggregant agent. These evaluations allowed us to deduce several structure–activity relationships and suggest some mechanisms of action for this type of compounds.
Ten zoanthamine-type alkaloids from two marine zoanthids belonging to the
Zoanthus genus (
Z. nymphaeus and
Zoanthus sp.) along with one semisynthetic derivative were evaluated for their antiplatelet activities on human platelet aggregation induced by several stimulating agents.
Long-duration γ-ray bursts (GRBs) are the most luminous sources of electromagnetic radiation known in the Universe. They arise from outflows of plasma with velocities near the speed of light that are ...ejected by newly formed neutron stars or black holes (of stellar mass) at cosmological distances
. Prompt flashes of megaelectronvolt-energy γ-rays are followed by a longer-lasting afterglow emission in a wide range of energies (from radio waves to gigaelectronvolt γ-rays), which originates from synchrotron radiation generated by energetic electrons in the accompanying shock waves
. Although emission of γ-rays at even higher (teraelectronvolt) energies by other radiation mechanisms has been theoretically predicted
, it has not been previously detected
. Here we report observations of teraelectronvolt emission from the γ-ray burst GRB 190114C. γ-rays were observed in the energy range 0.2-1 teraelectronvolt from about one minute after the burst (at more than 50 standard deviations in the first 20 minutes), revealing a distinct emission component of the afterglow with power comparable to that of the synchrotron component. The observed similarity in the radiated power and temporal behaviour of the teraelectronvolt and X-ray bands points to processes such as inverse Compton upscattering as the mechanism of the teraelectronvolt emission
. By contrast, processes such as synchrotron emission by ultrahigh-energy protons
are not favoured because of their low radiative efficiency. These results are anticipated to be a step towards a deeper understanding of the physics of GRBs and relativistic shock waves.
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