Subtle but significant effects of CO<inf>2</inf> acidified seawater on embryos of the intertidal snail, Littorina obtusata

Our understanding of the effects of ocean acidification on whole organism function is growing, but most current information is for adult stages of development. Here, we show the effects of reduced pH seawater (pH 7.6) on aspects of the development, physiology and behaviour of encapsulated embryos of the marine intertidal gastropod Littorina obtusata. We found reduced viability and increased development times under reduced pH conditions, and the embryos had significantly altered behaviours and physiologies. In acidified seawater, embryos spent more time stationary, had slower rotation rates, spent less time crawling, but increased their movement periodicity compared with those maintained under control conditions. Larval and adult heart rates were significantly lower in acidified seawater, and hatchling snails had an altered shell morphology (lateral length and spiral shell length) compared to control snails. Our findings show that ocean acidification may have multiple, subtle effects during the early development of marine animals that may have implications for their survival beyond those predicted using later life stages. © Inter-Research 2009

Predicting ecosystem shifts requires new approaches that integrate the effects of climate change across entire systems.

Most studies that forecast the ecological consequences of climate change target a single species and a single life stage. Depending on climatic impacts on other life stages and on interacting species, however, the results from simple experiments may not translate into accurate predictions of future ecological change. Research needs to move beyond simple experimental studies and environmental envelope projections for single species towards identifying where ecosystem change is likely to occur and the drivers for this change. For this to happen, we advocate research directions that (i) identify the critical species within the target ecosystem, and the life stage(s) most susceptible to changing conditions and (ii) the key interactions between these species and components of their broader ecosystem. A combined approach using macroecology, experimentally derived data and modelling that incorporates energy budgets in life cycle models may identify critical abiotic conditions that disproportionately alter important ecological processes under forecasted climates

Local delivery of novel MRTF/SRF inhibitors prevents scar tissue formation in a preclinical model of fibrosis

The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway represents a promising therapeutic target to prevent fibrosis. We have tested the effects of new pharmacological inhibitors of MRTF/SRF signalling in a preclinical model of fibrosis. CCG-222740, a novel MRTF/SRF inhibitor, markedly decreased SRF reporter gene activity and showed a greater inhibitory effect on MRTF/SRF target genes than the previously described MRTF-A inhibitor CCG-203971. CCG-222740 was also five times more potent, with an IC50 of 5 μM, in a fibroblast-mediated collagen contraction assay, was less cytotoxic, and a more potent inhibitor of alpha-smooth muscle actin protein expression than CCG-203971. Local delivery of CCG-222740 and CCG-203971 in a validated and clinically relevant rabbit model of scar tissue formation after glaucoma filtration surgery increased the long-term success of the surgery by 67% (P < 0.0005) and 33% (P < 0.01), respectively, and significantly decreased fibrosis and scarring histologically. Unlike mitomycin-C, neither CCG-222740 nor CCG-203971 caused any detectable epithelial toxicity or systemic side effects with very low drug levels measured in the aqueous, vitreous, and serum. We conclude that inhibitors of MRTF/SRF-regulated gene transcription such as CCG-222740, potentially represent a new therapeutic strategy to prevent scar tissue formation in the eye and other tissues

Speculation on the origin of sub-baseline excursions of CH4 at Cape Grim

The Advanced Global Atmospheric Gases Experiment (AGAGE) program has historically measured in situ methane (CH4 ) at Cape Grim via gas chromatography with flame ionization detection (GC-FID) in 40 minutely grab samples. By adding continuous, high precision in situ measurements of CH4 (Picarro cavity ring-down spectroscopy [CRDS]) at both Cape Grim, Tasmania, and Casey, Antarctica, a new feature has become apparent in the Cape Grim CH4 record. During the austral summer (December to February), the Cape Grim CH4 record periodically drops below baseline. For example, in Figure 1, a number of sustained episodes of depressed CH4 concentration can be seen below the baseline selected data shown in red. Notably, these episodes are also seen in the GC-FID record. In this presentation, we examine these sub-baseline excursions of CH4 . In conjunction with meteorology and a variety of other chemical species measured at Cape Grim, including radon, ozone, hydrogen and ethane, we speculate on a number of possible mechanisms that might be responsible for these dips in CH4 mixing ratio

Ocean acidification at a coastal CO2 vent induces expression of stress-related transcripts and transposable elements in the sea anemone Anemonia viridis

Ocean acidification threatens to disrupt interactions between organisms throughout marine ecosystems. The diversity of reef-building organisms decreases as seawater CO2 increases along natural gradients, yet soft-bodied animals, such as sea anemones, are often resilient. We sequenced the polyA-enriched transcriptome of adult sea anemone Anemonia viridis and its dinoflagellate symbiont sampled along a natural CO2 gradient in Italy to assess stress levels in these organisms. We found that about 1.4% of the anemone transcripts, but only ~0.5% of the Symbiodinium sp. transcripts were differentially expressed. Processes enriched at high seawater CO2 were mainly linked to cellular stress, including significant up-regulation of protective cellular functions and deregulation of metabolic pathways. Transposable elements were differentially expressed at high seawater CO2, with an extreme up-regulation (> 100-fold) of the BEL-family of long terminal repeat retrotransposons. Seawater acidified by CO2 generated a significant stress reaction in A. viridis, but no bleaching was observed and Symbiodinium sp. appeared to be less affected. These observed changes indicate the mechanisms by which A. viridis acclimate to survive chronic exposure to ocean acidification conditions. We conclude that many organisms that are common in acidified conditions may nevertheless incur costs due to hypercapnia and/or lowered carbonate saturation states

Cigarette smoke exposure inhibits extracellular MMP-2 (gelatinase A) activity in human lung fibroblasts

BACKGROUND: Exposure to cigarette smoke is considered a major risk factor for the development of lung diseases, since its causative role has been assessed in the induction and maintenance of an inflamed state in the airways. Lung fibroblasts can contribute to these processes, due to their ability to produce proinflammatory chemotactic molecules and extracellular matrix remodelling proteinases. Among proteolytic enzymes, gelatinases A and B have been studied for their role in tissue breakdown and mobilisation of matrix-derived signalling molecules. Multiple reports linked gelatinase deregulation and overexpression to the development of inflammatory chronic lung diseases such as COPD. METHODS: In this study we aimed to determine variations in the gelatinolytic pattern of human lung fibroblasts (HFL-1 cell line) exposed to cigarette smoke extract (CSE). Gelatinolytic activity levels were determined by using gelatin zymography for the in-gel detection of the enzymes (proenzyme and activated forms), and the subsequent semi-quantitative densitometric evaluation of lytic bands. Expression of gelatinases was evaluated also by RT-PCR, zymography of the cell lysates and by western blotting. RESULTS: CSE exposure at the doses used (1–10%) did not exert any significant cytotoxic effects on fibroblasts. Zymographic analysis showed that CSE exposure resulted in a linear decrease of the activity of gelatinase A. Control experiments allowed excluding a direct inhibitory effect of CSE on gelatinases. Zymography of cell lysates confirmed the expression of MMP-2 in all conditions. Semi-quantitative evaluation of mRNA expression allowed assessing a reduced transcription of the enzyme, as well as an increase in the expression of TIMP-2. Statistical analyses showed that the decrease of MMP-2 activity in conditioned media reached the statistical significance (p = 0.0031 for 24 h and p = 0.0012 for 48 h), while correlation analysis showed that this result was independent from CSE cytotoxicity (p = 0.7833 for both exposures). CONCLUSION: Present work describes for the first time that, apart well characterized proinflammatory responses, human lung fibroblasts may react to CSE with a significant reduction of extracellular MMP-2 lytic activity. Therefore, fibroblasts may actively participate to the alteration of the proteolysis/antiproteolysis balance, which reflects the defective repair of the extracellular matrix. Such event should provide a further contribution to the maintenance of the inflamed state in the lungs

Endothelial repair in stented arteries is accelerated by inhibition of Rho-associated protein kinase.

AIMS: Stent deployment causes endothelial cell (EC) denudation, which promotes in-stent restenosis and thrombosis. Thus endothelial regrowth in stented arteries is an important therapeutic goal. Stent struts modify local hemodynamics, however the effects of flow pertubation on EC injury and repair are incompletely understood. By studying the effects of stent struts on flow and EC migration we identified an intervention that promotes endothelial repair in stented arteries. METHODS AND RESULTS: In vitro and in vivo models were developed to monitor endothelialization under flow and the influence of stent struts. A 2D parallel-plate flow chamber with 100 μm ridges arranged perpendicular to the flow was used. Live cell imaging coupled to computational fluid dynamic simulations revealed that EC migrate in the direction of flow upstream from the ridges but subsequently accumulate downstream from ridges at sites of bidirectional flow. The mechanism of EC trapping by bidirectional flow involved reduced migratory polarity associated with altered actin dynamics. Inhibition of Rho-associated protein kinase (ROCK) enhanced endothelialization of ridged surfaces by promoting migratory polarity under bidirectional flow (p<0.01). To more closely mimic the in vivo situation we cultured EC on the inner surface of polydimethylsiloxane tubing containing Coroflex Blue stents (65 μm struts) and monitored migration. ROCK inhibition significantly enhanced EC accumulation downstream from struts under flow (p<0.05). We investigated the effects of ROCK inhibition on re-endothelialization in vivo using a porcine model of EC denudation and stent placement. En face staining and confocal microscopy revealed that inhibition of ROCK using fasudil (30 mg/day via osmotic minipump) significantly increased re-endothelialization of stented carotid arteries (p<0.05). CONCLUSIONS: Stent struts delay endothelial repair by generating localised bidirectional flow which traps migrating EC. ROCK inhibitors accelerate endothelial repair of stented arteries by enhancing EC polarity and migration through regions of bidirectional flow

Effect of exacerbations on health status in subjects with chronic obstructive pulmonary disease

<p>Abstract</p> <p>Background</p> <p>Acute exacerbations may cause deteriorations in the health status of subjects with chronic obstructive pulmonary disease (COPD). The present study prospectively evaluated the effects of such exacerbations on the health status and pulmonary function of subjects with COPD over a 6-month period, and examined whether those subjects showed a steeper decline in their health status versus those subjects without exacerbations.</p> <p>Methods</p> <p>A total of 156 subjects with COPD (mean age 71.4 ± 6.3 years) were included in the analysis. At baseline and after 6 months, their pulmonary function and health status were evaluated using the Chronic Respiratory Disease Questionnaire (CRQ) and the St. George's Respiratory Questionnaire (SGRQ). An acute exacerbation was defined as a worsening of respiratory symptoms requiring the administration of systemic corticosteroids or antibiotics, or both.</p> <p>Results</p> <p>Forty-eight subjects experienced one or more exacerbations during the 6-month study period, and showed a statistically and clinically significant decline in Symptom scores on the SGRQ, whereas subjects without exacerbations did not show a clinically significant decline. Logistic multiple regression analyses confirmed that the exacerbations significantly influenced the Fatigue and Mastery domains of the CRQ, and the Symptoms in the SGRQ. Twelve subjects with frequent exacerbations demonstrated a more apparent decline in health status.</p> <p>Conclusion</p> <p>Although pulmonary function did not significantly decline during the 6-month period, acute exacerbations were responsible for a decline in health status. To minimize deteriorations in health status, one must prevent recurrent acute exacerbations and reduce the exacerbation frequencies in COPD subjects.</p

Ocean acidification through the lens of ecological theory

Ocean acidification, chemical changes to the carbonate system of seawater, is emerging as a key environmental challenge accompanying global warming and other human-induced perturbations. Considerable research seeks to define the scope and character of potential outcomes from this phenomenon, but a crucial impediment persists. Ecological theory, despite its power and utility, has been only peripherally applied to the problem. Here we sketch in broad strokes several areas where fundamental principles of ecology have the capacity to generate insight into ocean acidification's consequences. We focus on conceptual models that, when considered in the context of acidification, yield explicit predictions regarding a spectrum of population- and community-level effects, from narrowing of species ranges and shifts in patterns of demographic connectivity, to modified consumer–resource relationships, to ascendance of weedy taxa and loss of species diversity. Although our coverage represents only a small fraction of the breadth of possible insights achievable from the application of theory, our hope is that this initial foray will spur expanded efforts to blend experiments with theoretical approaches. The result promises to be a deeper and more nuanced understanding of ocean acidification and the ecological changes it portends

Stability of Strong Species Interactions Resist the Synergistic Effects of Local and Global Pollution in Kelp Forests

Foundation species, such as kelp, exert disproportionately strong community effects and persist, in part, by dominating taxa that inhibit their regeneration. Human activities which benefit their competitors, however, may reduce stability of communities, increasing the probability of phase-shifts. We tested whether a foundation species (kelp) would continue to inhibit a key competitor (turf-forming algae) under moderately increased local (nutrient) and near-future forecasted global pollution (CO2). Our results reveal that in the absence of kelp, local and global pollutants combined to cause the greatest cover and mass of turfs, a synergistic response whereby turfs increased more than would be predicted by adding the independent effects of treatments (kelp absence, elevated nutrients, forecasted CO2). The positive effects of nutrient and CO2 enrichment on turfs were, however, inhibited by the presence of kelp, indicating the competitive effect of kelp was stronger than synergistic effects of moderate enrichment of local and global pollutants. Quantification of physicochemical parameters within experimental mesocosms suggests turf inhibition was likely due to an effect of kelp on physical (i.e. shading) rather than chemical conditions. Such results indicate that while forecasted climates may increase the probability of phase-shifts, maintenance of intact populations of foundation species could enable the continued strength of interactions and persistence of communities