From micro to mesoscale: Understanding the influence of macroalgal communities on Ostreopsis Schmidt blooms.

Harmful Algal Blooms (HABs) are increasing in temperate areas, and the growth rates of benthic harmful dinoflagellates may be favoured in the context of global climate change. Benthic dinoflagellates, including species belonging to the Ostreopsis Schmidt genus, are known to develop on the surface of macroalgae and different macroalgal morphotypes and communities could host higher or lower cell abundances. The physical structure of the macroalgal substrate at the small scale (cm, microhabitat scale) and the structural complexity of the macroalgal community at the medium scale (few m, mesohabitat scale) could play a relevant role in bloom facilitation: the hypothesis that Ostreopsis species could be associated with macroalgal turfs and shrubs, structurally less complex communities than canopy-forming macroalgae, is especially under discussion and, if confirmed, could link bloom occurrence to regime shifts in temperate ecosystems. The present study, performed in two locations of the Ligurian Sea (Rochambeau, France and Vernazzola, Italy) aimed at understanding marine vegetation's role at the micro and mesohabitat scales in controlling the distribution and abundance of Ostreopsis. The abundance of the microalgal cells was quantified at different spatial scales, from cm to a few m, on different macroalgal species and communities, including artificial substrates, to tease apart the micro and mesohabitat effects. The results obtained show a high spatio-temporal variability, potentially hiding habitat-related patterns. The substrate's preferences diminish when cell abundances are very high, as in the case of Rochambeau, while in presence of moderate cell abundances as in Vernazzola or the first phases of blooms, it is possible to appreciate differences in abundances among substrates (in our study, Dictyota fasciola (Roth) Lamouroux supporting higher abundances). Our results open new research topics such as the study of blooms at a larger scale (macrohabitat) and testing different sampling methods to standardise the cells' abundances independently on the substrate.

Decreased pH impairs sea urchin resistance to predatory fish: A combined laboratory-field study to understand the fate of top-down processes in future oceans.

Changing oceans represent a serious threat for a wide range of marine organisms, with severe cascading effects on ecosystems and their services. Sea urchins are particularly sensitive to decreased pH expected for the end of the century and their key ecological role in regulating community structure and functioning could be seriously compromised. An integrated approach of laboratory and field experiments has been implemented to investigate the effects of decreased pH on predator-prey interaction involving sea urchins and their predators. Our results suggest that under future Ocean Acidification scenarios adult sea urchins defence strategies, such as spine length, test robustness and oral plate thickness, could be compromised together with their survival chance to natural predators. Sea urchins represent the critical linkage between top-down and bottom-up processes along Mediterranean rocky reefs, and the cumulative impacts of global and local stressors could lead to a decline producing cascading effects on benthic ecosystems.

Habitat effects on Ostreopsis cf. ovata bloom dynamics.

In the last few decades, Ostreopsis spp., toxic benthic dinolagellates of tropical origin, generated large interest in the Mediterranean Sea, where several bloom events have been observed. Ecology and proliferation dynamics of O. cf. ovata are driven by complex interactions among biotic and abiotic drivers, and understanding mechanisms triggering bloom events is still far from being complete. The aim of the present study is to highlight the role of different habitat conditions, elucidating the effects of i) exposure to hydrodynamic conditions, ii) macroalgal community and iii) urbanisation level, in driving O. cf. ovata bloom dynamics. A significant effect of hydrodynamics was observed only for cells in seawater, with higher abundances in sheltered zones, irrespective of the urbanisation level. Similarly, a significant effect of the dominant macroalgal community, with higher abundances in Corallinales and turf dominated communities, and lower ones in Cystoseira amentacea canopies, has been recorded, consistently in the differently urbanised sites. Additionally, stretches of the coast suffering from a more intense anthropic exploitation are in general more prone to the proliferation of potentially toxic benthic microalgae. All these results imply a larger risk exposure to toxic effects for humans in urban beaches and sheltered areas, usually more attended by swimmers and bathers. These findings underline the need to preserve, and eventually restore, canopy dominated assemblages, which presently are under regression because of human threats, providing a straightforward example that restoration of relevant habitats implies a cascading improvement of human welfare.

The human POMC gene promoter: where do we stand?

Proopiomelanocortin (POMC) is crucial for several life-essential functions and its regulation has been studied extensively in the past decades. The first studies provided the framework for POMC promoter activity, namely the identification for the major response elements contained in the promoter, e.g., the glucocorticoid response element, the Nur response element, while subsequent studies showed the importance of cooperation and interplay between transcription factors to achieve optimal promoter activity. The involvement of constitutive repressors of POMC transcription, such as Bmp4, provided the latest clues to our understanding of POMC promoter activity. This increased knowledge benefits the clinician as it allows genetic testing and early recognition of patients with congenital ACTH deficiency due to mutations in TPIT and paves the way to new medical treatments in Cushing's disease. The present review will illustrate the current standing on regulation of the human POMC promoter, focusing on its activity in corticotropes.

Safety and tolerability of high doses of taspoglutide, a once-weekly human GLP-1 analogue, in diabetic patients treated with metformin: a randomized double-blind placebo-controlled study.

AIMS: The study objective was to investigate the safety and tolerability of up-titration to high doses of taspoglutide, a once-weekly human glucagon-like peptide-1 analogue, in subjects with Type 2 diabetes inadequately controlled on metformin alone. METHODS: In this double-blind phase II trial, subjects were randomized to placebo or taspoglutide (20 mg; three separate groups) administered once weekly by subcutaneous injection for 4 weeks. This was followed by dose maintenance at 20 mg, or titration to 30 mg (20/30) or 40 mg (20/40) once weekly with matched placebo for an additional 4 weeks. Subjects were monitored for adverse events (AEs) throughout the study and 4-week follow-up. RESULTS: One hundred and twenty-nine subjects were randomized and treated [mean age 57 years, mean baseline glycated haemoglobin (HbA(1c)), 7.9%]. The most frequently reported AEs were nausea and vomiting. The number of patients reporting gastrointestinal AEs did not increase following titration to higher doses of taspoglutide or when continuing the initial 20 mg regimen. Three subjects were withdrawn from the study as a result of gastrointestinal AEs (one before and two after titration to higher doses). Although not designed to investigate efficacy, improvement in glycaemic control was observed in all active arms of the study. The proportion of subjects achieving HbA(1c) < 7.0% after 8 weeks of treatment was 72, 53 and 70% in the 20/20-, 20/30- and 20/40-mg arms, respectively, vs. 19% for placebo. CONCLUSIONS: Taspoglutide was safe, well tolerated at high doses and efficacious for lowering HbA(1c). Up-titration of dose was not associated with a worsening AE profile.

Low Ca(2+) pump activity in diabetic nephropathy.

Elevated cell Na(+)-H(+) exchange (NHE) activity characterizes diabetic nephropathy (DN), but the mechanisms of this abnormality are unclear. Recent evidence suggests that NHE and the Ca(2+) pump share similar regulatory pathways, but whether abnormalities in Ca(2+) metabolism characterize DN is not known. We investigated Ca(2+) efflux rates, NHE activity, cytosolic Ca(2+) ([Ca(2+)](i)) concentrations, and intracellular pH (pH(i)) in human skin fibroblasts from 20 patients with type 1 (insulin-dependent) diabetes and nephropathy; 20 patients with diabetes with normoalbuminuria matched for age, sex, and duration of diabetes; and 10 individuals without diabetes. Ca(2+) pump-mediated Ca(2+) efflux was significantly lower in patients with nephropathy than in patients with normoalbuminuria and individuals without diabetes (0.074 +/- 0.01 versus 0.115 +/- 0.01 versus 0.131 +/- 0.02 nmol.mg(protein)(-1).min(-1); analysis of variance [ANOVA], P = 0.015). Elevated maximal velocity of the Na(+)-H(+) exchanger was confirmed in fibroblasts from patients with nephropathy (14.4 +/- 1.2 versus 7.1 +/- 0.7 versus 8.0 +/- 1.2 mmol H(+).l cell(-1).min(-1); ANOVA, P < 0.0001). A reverse correlation between Ca(2+) pump activity and NHE rates could be shown. Adjustment for glycated hemoglobin and plasma lipid levels did not affect these findings. Finally, [Ca(2+)](i) concentrations and pH(i) were normal in all patients. Low Ca(2+) pump activity is a concomitant event of elevated NHE rates in DN; the molecular dysfunction(s) underlying these abnormalities remains to be established.

Role of prolactin in the in vitro development of interleukin-2-driven anti-tumoural lymphokine-activated killer cells.

Exogenous prolactin (PRL) has been shown to synergize with low-dose interleukin-2 (IL-2) and induce the proliferation and lymphokine-activated killer (LAK) maturation of natural killer (NK) cells. PRL itself can also generate LAK activity. Here we show that its local production occurs during, and is necessary for, LAK development. IL-2-stimulated peripheral blood mononuclear cells (PBMC) and purified NK cells were exposed to anti-human (h)PRL antiserum, and residual LAK activity was measured on day 7 against the promyelocytic leukaemia cell line HL-60. Inhibition of LAK activity was much more evident in PBMC compared with NK cell cultures (47% decrease. P - 0.013 and 18.5% decrease. P = 0.048, respectively). Up-modulation of a 32S-methionine-labelled 27,000 MW protein was detected in the lysates and supernatants of IL-2-stimulated PBMC immunoprecipitated with an anti-PRL antiserum. By contrast, the cytoplasmic PRL immunoreactivity observed in freshly isolated NK cells and in IL-2-stimulated, but not unstimulated, NK cell cultures was not associated with PRL gene activation, and can thus be referred to internalized PRL. Preferential re-uptake of externally derived PRL by IL-2-stimulated NK cells was also indicated by up-modulation of the PRL receptor. These data, as a whole, indicate that the PRL promotion of LAK differentiation is mainly mediated by paracrine secretion, with a minor contribution from internalized PRL.