Patent Foramen Ovale Closure in Obstructive Sleep Apnea Improves Blood Pressure and Cardiovascular Function.

UNLABELLED Obstructive sleep apnea (OSA) is a frequent syndrome characterized by intermittent hypoxemia and increased prevalence of arterial hypertension and cardiovascular morbidity. In OSA, the presence of patent foramen ovale (PFO) is associated with increased number of apneas and more severe oxygen desaturation. We hypothesized that PFO closure improves sleep-disordered breathing and, in turn, has favorable effects on vascular function and arterial blood pressure. In 40 consecutive patients with newly diagnosed OSA, we searched for PFO. After initial cardiovascular assessment, the 14 patients with PFO underwent initial device closure and the 26 without PFO served as control group. Conventional treatment for OSA was postponed for 3 months in both groups, and polysomnographic and cardiovascular examinations were repeated at the end of the follow-up period. PFO closure significantly improved the apnea-hypopnea index (ΔAHI -7.9±10.4 versus +4.7±13.1 events/h, P=0.0009, PFO closure versus control), the oxygen desaturation index (ΔODI -7.6±16.6 versus +7.6±17.0 events/h, P=0.01), and the number of patients with severe OSA decreased significantly after PFO closure (79% versus 21%, P=0.007). The following cardiovascular parameters improved significantly in the PFO closure group, although remained unchanged in controls: brachial artery flow-mediated vasodilation, carotid artery stiffness, nocturnal systolic and diastolic blood pressure (-7 mm Hg, P=0.009 and -3 mm Hg, P=0.04, respectively), blood pressure dipping, and left ventricular diastolic function. In conclusion, PFO closure in OSA patients improves sleep-disordered breathing and nocturnal oxygenation. This translates into an improvement of endothelial function and vascular stiffening, a decrease of nighttime blood pressure, restoration of the dipping pattern, and improvement of left ventricular diastolic function. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01780207.

Na+ channel function, regulation, structure, trafficking and sequestration.

This paper is the second of a series of three reviews published in this issue resulting from the University of California Davis Cardiovascular Symposium 2014: Systems approach to understanding cardiac excitation-contraction coupling and arrhythmias: Na(+) channel and Na(+) transport. The goal of the symposium was to bring together experts in the field to discuss points of consensus and controversy on the topic of sodium in the heart. The present review focuses on Na(+) channel function and regulation, Na(+) channel structure and function, and Na(+) channel trafficking, sequestration and complexing.

Impact of above- and below-ground invertebrates on temporal and spatial stability of grassland of different diversity

1. Recent theoretical studies suggest that the stability of ecosystem processes is not governed by diversity per se, but by multitrophic interactions in complex communities. However, experimental evidence supporting this assumption is scarce.2. We investigated the impact of plant diversity and the presence of above- and below-ground invertebrates on the stability of plant community productivity in space and time, as well as the interrelationship between both stability measures in experimental grassland communities.3. We sampled above-ground plant biomass on subplots with manipulated above- and below-ground invertebrate densities of a grassland biodiversity experiment (Jena Experiment) 1, 4 and 6 years after the establishment of the treatments to investigate temporal stability. Moreover, we harvested spatial replicates at the last sampling date to explore spatial stability.4. The coefficient of variation of spatial and temporal replicates served as a proxy for ecosystem stability. Both spatial and temporal stability increased to a similar extent with plant diversity. Moreover, there was a positive correlation between spatial and temporal stability, and elevated plant density might be a crucial factor governing the stability of diverse plant communities.5. Above-ground insects generally increased temporal stability, whereas impacts of both earthworms and above-ground insects depended on plant species richness and the presence of grasses. These results suggest that inconsistent results of previous studies on the diversity–stability relationship have in part been due to neglecting higher trophic-level interactions governing ecosystem stability.6. Changes in plant species diversity in one trophic level are thus unlikely to mirror changes in multitrophic interrelationships. Our results suggest that both above- and below-ground invertebrates decouple the relationship between spatial and temporal stability of plant community productivity by differently affecting the homogenizing mechanisms of plants in diverse plant communities.7.Synthesis. Species extinctions and accompanying changes in multitrophic interactions are likely to result not only in alterations in the magnitude of ecosystem functions but also in its variability complicating the assessment and prediction of consequences of current biodiversity loss.

Temporal and small-scale spatial variation in grassland productivity, biomass quality, and nutrient limitation

Characterization of spatial and temporal variation in grassland productivity and nutrition is crucial for a comprehensive understanding of ecosystem function. Although within-site heterogeneity in soil and plant properties has been shown to be relevant for plant community stability, spatiotemporal variability in these factors is still understudied in temperate grasslands. Our study aimed to detect if soil characteristics and plant diversity could explain observed small-scale spatial and temporal variability in grassland productivity, biomass nutrient concentrations, and nutrient limitation. Therefore, we sampled 360 plots of 20 cm × 20 cm each at six consecutive dates in an unfertilized grassland in Southern Germany. Nutrient limitation was estimated using nutrient ratios in plant biomass. Absolute values of, and spatial variability in, productivity, biomass nutrient concentrations, and nutrient limitation were strongly associated with sampling date. In April, spatial heterogeneity was high and most plots showed phosphorous deficiency, while later in the season nitrogen was the major limiting nutrient. Additionally, a small significant positive association between plant diversity and biomass phosphorus concentrations was observed, but should be tested in more detail. We discuss how low biological activity e.g., of soil microbial organisms might have influenced observed heterogeneity of plant nutrition in early spring in combination with reduced active acquisition of soil resources by plants. These early-season conditions are particularly relevant for future studies as they differ substantially from more thoroughly studied later season conditions. Our study underlines the importance of considering small spatial scales and temporal variability to better elucidate mechanisms of ecosystem functioning and plant community assembly.

Plant diversity effects on grassland productivity are robust to both nutrient enrichment and drought

Global change drivers are rapidly altering resource availability and biodiversity. While there is consensus that greater biodiversity increases the functioning of ecosystems, the extent to which biodiversity buffers ecosystem productivity in response to changes in resource availability remains unclear. We use data from 16 grassland experiments across North America and Europe that manipulated plant species richness and one of two essential resources—soil nutrients or water—to assess the direction and strength of the interaction between plant diversity and resource alteration on above-ground productivity and net biodiversity, complementarity, and selection effects. Despite strong increases in productivity with nutrient addition and decreases in productivity with drought, we found that resource alterations did not alter biodiversity–ecosystem functioning relationships. Our results suggest that these relationships are largely determined by increases in complementarity effects along plant species richness gradients. Although nutrient addition reduced complementarity effects at high diversity, this appears to be due to high biomass in monocultures under nutrient enrichment. Our results indicate that diversity and the complementarity of species are important regulators of grassland ecosystem productivity, regardless of changes in other drivers of ecosystem function.

Governance and the Capacity to Manage Resilience in Regional Social-Ecological Systems

The sustainability of regional development can be usefully explored through several different lenses. In situations in which uncertainties and change are key features of the ecological landscape and social organization, critical factors for sustainability are resilience, the capacity to cope and adapt, and the conservation of sources of innovation and renewal. However, interventions in social-ecological systems with the aim of altering resilience immediately confront issues of governance. Who decides what should be made resilient to what? For whom is resilience to be managed, and for what purpose? In this paper we draw on the insights from a diverse set of case studies from around the world in which members of the Resilience Alliance have observed or engaged with sustainability problems at regional scales. Our central question is: How do certain attributes of governance function in society to enhance the capacity to manage resilience? Three specific propositions were explored: ( 1) participation builds trust, and deliberation leads to the shared understanding needed to mobilize and self-organize; ( 2) polycentric and multilayered institutions improve the fit between knowledge, action, and social-ecological contexts in ways that allow societies to respond more adaptively at appropriate levels; and ( 3) accountable authorities that also pursue just distributions of benefits and involuntary risks enhance the adaptive capacity of vulnerable groups and society as a whole. Some support was found for parts of all three propositions. In exploring the sustainability of regional social-ecological systems, we are usually faced with a set of ecosystem goods and services that interact with a collection of users with different technologies, interests, and levels of power. In this situation in our roles as analysts, facilitators, change agents, or stakeholders, we not only need to ask: The resilience of what, to what? We must also ask: For whom?

Lipid-dependent topogenesis and function of membrane proteins

Membranes are essential for the integrity and function of the cell. The collective property of the lipid bilayer is critical in providing an optimal functioning environment for membrane proteins. The simple yet well-characterized bacterium Escherichia coli serves an ideal model system to study the function of specific lipids since its lipid content can be easily manipulated. The most abundant lipid in E. coli membrane is phosphatidylethanolamine (PE, 70-80%). A PE-lacking E. coli mutant displays a complex mixture of deficient phenotypes, suggesting a profound role for PE in different aspects of cell function. A novel role of PE as a topological and functional determinant for membrane proteins has been established using lactose permease (LacY) as a model protein. PE is found to be required for energy-dependent uphill transport process of LacY. In PE-lacking membranes, LacY undergoes a dramatic conformational change, and the first half of the protein adopts an inverted topology with respect to the bilayer plane. ^ The work reported here was initiated to understand the molecular properties of lipids that enable their function as topological and functional determinants for membrane proteins. A glycolipid, monoglucosyldiacylglycerol (MGlcDAG) which shares physicochemical similarities with PE, was introduced to PE-lacking E. coli membranes. The introduction of MGlcDAG suppresses many of the PE-deficient phenotypes, and in particular supports the function and native topology of LacY. ^ The lipid-sensitive topogenic signals encoded in the amino acid sequence of LacY were also identified. Native LacY adopts an inverted topology when synthesized without PE, but mutation of specific acidic residues in the cytoplasmic extra-membrane domains can prevent this inversion and supports a native topological organization of LacY in PE-lacking membranes. These results suggest that it is the interplay between the collective charge properties of the lipid bilayer and extra-membrane loops of protein that determines the final orientation of transmembrane domains. By comparing the similarities as well as differences between these two lipids, we established how specific physical and chemical properties of lipids influence various cell functions and elucidated the molecular basis for the novel role of lipids in determining membrane protein topology. ^

Determine whether markers of lipid metabolism, inflammation and/or liver function are altered in tuberculosis patients with diabetes

The mechanism for higher susceptibility of diabetes patients to TB is unknown. Chronic hyperglycemia has been shown to be associated with altered immunity to Mycobacterium tuberculosis, and may explain the higher risk of TB among diabetes patients. However, it is possible that other conditions that frequently occur in these patients are also contributing to TB susceptibility. Our goal was to determine whether lipid metabolism, liver function and/or chronic inflammation are altered in tuberculosis (TB) patients with diabetes (DM), compared to non-DM.^ Confirmed TB patients who were 20 years or older (n=159) were selected from a database in the south Texas and northeast Mexico area. Differences between serum values for liver function, lipid metabolism and/or chronic inflammation were compared between TB patients with DM to non-DM.^ We found that CRP was the most frequent alteration, with about 80% having high values suggestive of chronic inflammation. The other frequent abnormalities were high triglycerides in about 40% of the patients and low HDL cholesterol in about 60% of the patients. Otherwise, less than 10% of the TB patients had an abnormal finding for any of the other laboratory tests. The abnormalities were not more frequent among the patients with either DM (versus non-DM) or high HbA1c (versus normal).^ A possible explanation for the high levels or CRP may be that everyone in the study had TB, which in itself causes inflammation and may have masked the increased CRP levels that characterize diabetes patients. There was a mild alteration in lipid metabolism in patients with DM, which is unlikely to explain altered immunity to TB. Otherwise, liver function tests were normal in patients with DM. Therefore the processing of anti-TB medications should be no different between the TB patients with and without diabetes. Our findings, however, do not rule out that other study populations have more remarkable metabolic alterations associated with diabetes. Therefore, it would be interesting to conduct a similar study in patients from different ethnic groups (White, African American, or Native American) in order to see if the same pattern is observed.^

Evaluating alternative therapies. Support/imagery and immune function in breast cancer: A pilot study

Cancer patients increasingly request alternative therapies such as imagery techniques and support groups. Although research suggests evidence of enhanced psychosocial functioning with supportive group therapy and enhanced immune function with imagery techniques, studies are anecdotal or limited to case studies or descriptive reports. The efficacy of these alternative therapies should be validated by randomized, controlled trials and the mechanisms of action mediating immune function and outcome examined.^ In a 12-month pilot study, we evaluate the feasibility of conducting a controlled study with clinical trial methodology to test the effects of imagery/relaxation and support on quality of life, emotional well-being, and immune function for women after breast cancer. Using a randomized pre-post test design with three intervention waves, we assigned women (n = 47) to either standard care (n = 15), standard care plus 6-weekly support sessions (n = 16) or imagery/relaxation sessions (n = 16).^ The primary aim of this pilot study is to determine the feasibility of conducting a clinical trial of alternative therapies in a clinical care setting. Secondary aims are to determine parameter estimates for the effects of the two treatment groups on quality of life, coping, social support, and immune function and describe methodology issues related to trials of alternative therapies.^ The research provides direction for future studies of alternative therapies by describing the recruitment, clinical trial experience, and related methodology issues. The study extends previous work by differentiating the effects of support group from mental imagery among outpatient groups who are homogeneous regarding cancer type and treatment stage. The study provides data for future longitudinal studies of disease progression by differentiating the effectiveness of interventions designed to enhance quality of life, coping, social support, and immune function and subsequently, alter the clinical course of disease. ^

Biochar and Managed Perennial Ecosystems

Biochar is a carbon-rich material that is similar to charcoal. It is produced when biomass is burned in the absence of oxygen, a process otherwise known as pyrolysis. Pyrolysis and the production of biochar are currently being promoted as a means to both produce domestic fuel (bio-oil) while concurrently producing a co-product that increases crop yield and sequesters carbon in the soil (biochar). While there may be many potential benefits in the application of biochar to agricultural soils, such as enhanced soil fertility and improved soil water status, there are no studies of higher-order ecological and ecosystem effects of biochar and its potential synergistic interactions (either positive or negative) on complex perennial systems. The goal of this field experiment is to determine how biochar and manure addition directly affect ecosystem structure and function in perennial systems, specifically soil nutrients, water, plants, and soil organisms.

(Table 1) Species richness and diversity of tundra plants in herbivore exclosure and control plots near Barrow, Alaska

To determine the role lemmings play in structuring plant communities and their contribution to the 'greening of the Arctic', we measured plant cover and biomass in 50 + year old lemming exclosures and control plots in the coastal tundra near Barrow, Alaska. The response of plant functional types to herbivore exclusion varied among land cover types. In general, the abundance of lichens and bryophytes increased with the exclusion of lemmings, whereas graminoids decreased, although the magnitude of these responses varied among land cover types. These results suggest that sustained lemming activity promotes a higher biomass of vascular plant functional types than would be expected without their presence and highlights the importance of considering herbivory when interpreting patterns of greening in the Arctic. In light of the rapid environmental change ongoing in the Arctic and the potential regional to global implications of this change, further exploration regarding the long-term influence of arvicoline rodents on ecosystem function (e.g. carbon and energy balance) should be considered a research priority.

Antagonistic interactions between the african weaver ant Oecophylla longinoda and the parasitoid Anagyrus pseudococci potentially limits suppression of the invasive mealybug Rastrococcus iceryoides

The ant Oecophylla longinoda Latreille forms a trophobiotic relationship with the invasive mealybug Rastrococus iceryoides Green and promotes the latter's infestations to unacceptable levels in the presence of their natural enemies. In this regard, the antagonistic interactions between the ant and the parasitoid Anagyrus pseudococci Girault were assessed under laboratory conditions. The percentage of parasitism of R. iceryoides by A. pseudococci was significantly higher on "ant-excluded" treatments (86.6% ± 1.27%) compared to "ant-tended" treatments (51.4% ± 4.13%). The low female-biased sex-ratio observed in the "ant-tended" treatment can be attributed to ants' interference during the oviposition phase, which disrupted parasitoids' ability to fertilize eggs. The mean foraging time, host handling time and number of successful oviposition in "ant-excluded" treatment were significantly higher compared to "ant-tended" treatments. When ant workers were allowed access to sterilized sand grains, mummified and unmummified R. iceryoides, they selectively removed the mummified mealybugs, indicating that they recognized the mummies as potential foods (1.2 ± 0.46 to 7.8 ± 1.17 mummies at 10 min intervals for 2 h). Percentage emergence from mummified R. iceryoides removed by the ants was significantly lower compared to emergence from mummies not exposed to ants. Although, host seeking parasitoids frequently evaded attacks, some were killed by the foraging ant workers (2.0 ± 0.38 to 6.0 ± 0.88 at 10 min intervals for 2 h). These results suggest for the first time that the presence of O. longinoda has a detrimental effect on the abundance, reproductive success and possibly oviposition strategy of female parasitoids, which might be a delimiting factor in field conditions if both natural enemies are to be recommended for use within the same agro-ecosystem.

Anemone abundance and productivity at North Vulcano Island in May 2011

Increased seawater pCO2, and in turn 'ocean acidification' (OA), is predicted to profoundly impact marine ecosystem diversity and function this century. Much research has already focussed on calcifying reef-forming corals (Class: Anthozoa) that appear particularly susceptible to OA via reduced net calcification. However, here we show that OA-like conditions can simultaneously enhance the ecological success of non-calcifying anthozoans, which not only play key ecological and biogeochemical roles in present day benthic ecosystems but also represent a model organism should calcifying anthozoans exist as less calcified (soft-bodied) forms in future oceans. Increased growth (abundance and size) of the sea anemone (Anemonia viridis) population was observed along a natural CO2 gradient at Vulcano, Italy. Both gross photosynthesis (PG) and respiration (R) increased with pCO2 indicating that the increased growth was, at least in part, fuelled by bottom up (CO2 stimulation) of metabolism. The increase of PG outweighed that of R and the genetic identity of the symbiotic microalgae (Symbiodinium spp.) remained unchanged (type A19) suggesting proximity to the vent site relieved CO2 limitation of the anemones' symbiotic microalgal population. Our observations of enhanced productivity with pCO2, which are consistent with previous reports for some calcifying corals, convey an increase in fitness that may enable non-calcifying anthozoans to thrive in future environments, i.e. higher seawater pCO2. Understanding how CO2-enhanced productivity of non- (and less-) calcifying anthozoans applies more widely to tropical ecosystems is a priority where such organisms can dominate benthic ecosystems, in particular following localized anthropogenic stress.

Carbon/Nitrogen ratio of plant tissues and biomass of belowground consumers after 11 years of experimental treatment, Toolik lake

Theory and observation indicate that changes in the rate of primary production can alter the balance between the bottom-up influences of plants and resources and the top-down regulation of herbivores and predators on ecosystem structure and function. The Exploitation Ecosystem Hypothesis (EEH) posited that as aboveground net primary productivity (ANPP) increases, the additional biomass should support higher trophic levels. We developed an extension of EEH to include the impacts of increases in ANPP on belowground consumers in a similar manner as aboveground, but indirectly through changes in the allocation of photosynthate to roots. We tested our predictions for plants aboveground and for phytophagous nematodes and their predators belowground in two common arctic tundra plant communities subjected to 11 years of increased soil nutrient availability and/or exclusion of mammalian herbivores. The less productive dry heath (DH) community met the predictions of EEH aboveground, with the greatest ANPP and plant biomass in the fertilized plots protected from herbivory. A palatable grass increased in fertilized plots while dwarf evergreen shrubs and lichens declined. Belowground, phytophagous nematodes also responded as predicted, achieving greater biomass in the higher ANPP plots, whereas predator biomass tended to be lower in those same plots (although not significantly). In the higher productivity moist acidic tussock (MAT) community, aboveground responses were quite different. Herbivores stimulated ANPP and biomass in both ambient and enriched soil nutrient plots; maximum ANPP occurred in fertilized plots exposed to herbivory. Fertilized plots became dominated by dwarf birch (a deciduous shrub) and cloudberry (a perennial forb); under ambient conditions these two species coexist with sedges, evergreen dwarf shrubs, and Sphagnum mosses. Phytophagous nematodes did not respond significantly to changes in ANPP, although predator biomass was greatest in control plots. The contrasting results of these two arctic tundra plant communities suggest that the predictions of EEH may hold for very low ANPP communities, but that other factors, including competition and shifts in vegetation composition toward less palatable species, may confound predicted responses to changes in productivity in higher ANPP communities such as the MAT studied here.

(Table 1) Carbon pools in different vegetation components in grazed and ungrazed plots near Ny-Ålesund, Spitzbergen

The carbon (C) sink strength of arctic tundra is under pressure from increasing populations of arctic breeding geese. In this study we examined how CO2 and CH4 fluxes, plant biomass and soil C responded to the removal of vertebrate herbivores in a high arctic wet moss meadow that has been intensively used by barnacle geese (Branta leucopsis) for ca. 20 years. We used 4 and 9 years old grazing exclosures to investigate the potential for recovery of ecosystem function during the growing season (July 2007). The results show greater above- and below-ground vascular plant biomass within the grazing exclosures with graminoid biomass being most responsive to the removal of herbivory whilst moss biomass remained unchanged. The changes in biomass switched the system from net emission to net uptake of CO2 (0.47 and -0.77 µmol/m**2/s in grazed and exclosure plots, respectively) during the growing season and doubled the C storage in live biomass. In contrast, the treatment had no impact on the CH4 fluxes, the total litter C pool or the soil C concentration. The rapid recovery of the above ground biomass and CO2 fluxes demonstrates the plasticity of this high arctic ecosystem in terms of response to changing herbivore pressure.