The effects of ultraviolet irradiation on P680+ reduction in PS II core complexes measured for individual S-states and during repetitive cycling of the oxygen-evolving complex

Flash-induced absorbance measurements at 830 nm on both nanosecond and microsecond timescales have been used to characterise the effect of ultraviolet light on Photosystem II core particles. A combination of UV-A and UV-B, closely simulating the spectrum of sunlight below 350 nm, was found to have a primary effect on the donor side of P680. Repetitive measurements indicated reductions in the nanosecond components of the absorbance decay with a concomitant appearance and increase in the amplitude of a component with a 10 s time constant attributed to slow reduction of P680⁺ by Tyr_z when the function of the oxygen evolving complex is inhibited. Single-flash measurements show that the nanosecond components have amplitudes which vary with S-state. Increasing UV irradiation inhibited the amplitude of these components without changing their S-state dependence. In addition, UV irradiation resulted in a reduction in the total amplitude, with no change in the proportion of the 10 s contribution.Abbreviations BBY- PS II membrane fragments - P680- primary electron donor of PS II - PS II- Photosystem II - Q_A and Q_B– primary and secondary quinone electron acceptors of PS II - S-state- redox state of the oxygenevolving complex - Tyr_z– tyrosine residue in PS II - UV-A- ultraviolet radiation 320–400 nm - UV-B- ultraviolet radiation 280–320 nm     

P680+ reduction in oxygen-evolving Photosystem II core complexes

The kinetics of P680⁺ reduction in oxygen-evolving spinach Photosystem II (PS II) core particles were studied using both repetitive and single-flash 830 nm transient absorption. From measurements on samples in which PS II turnover is blocked, we estimate radical-pair lifetimes of 2 ns and 19 ns. Nanosecond single-flash measurements indicate decay times of 7 ns, 40 ns and 95 ns. Both the longer 40 ns and 95 ns components relate to the normal S-state controlled Y_z P680⁺ electron transfer dynamics. Our analysis indicates the existence of a 7 ns component which provides evidence for an additional process associated with modified interactions involving the water-splitting catalytic site. Corresponding microsecond measurements show decay times of 4 s and 90 s with the possibility of a small component with a decay time of 20–40 s. The precise origin of the 4 s component remains uncertain but appears to be associated with the water-splitting center or its binding site while the 90 s component is assigned to P680⁺-Q_A ^– recombination. An amplitude and kinetic analysis of the flash dependence data gives results that are consistent with the current model of the oxygen-evolving complex.Abbreviations PS II- Photosystem II- - P680- primary donor (Chl-a_II dimer) of PS II - Y_z- Tyr 161 donor to P680 - Q_A- quinone secondary acceptor to P680 - LHC- light-harvesting chlorophyll protein of PS II - BBY- Berthold, Babcock and Yocum PS II membrane fragment preparation - PPBQ- phenyl-p-benzoquinone     

Coupling of the thrombin receptor to G12 may account for selective effects of thrombin on gene expression and DNA synthesis in 1321N1 astrocytoma cells.

In 1321N1 astrocytoma cells, thrombin, but not carbachol, induces AP-1-mediated gene expression and DNA synthesis. To understand the divergent effects of these G protein-coupled receptor agonists on cellular responses, we examined Gq-dependent signaling events induced by thrombin receptor and muscarinic acetylcholine receptor stimulation. Thrombin and carbachol induce comparable changes in phosphoinositide and phosphatidylcholine hydrolysis, mobilization of intracellular Ca2+, diglyceride generation, and redistribution of protein kinase C; thus, activation of these Gq-signaling pathways appears to be insufficient for gene expression and mitogenesis. Thrombin increases Ras and mitogen-activated protein kinase activation to a greater extent than carbachol in 1321N1 cells. The effects of thrombin are not mediated through Gi, since ribosylation of Gi/Go proteins by pertussis toxin does not prevent thrombin-induced gene expression or thrombin-stimulated DNA synthesis. We recently reported that the pertussis toxin-insensitive G12 protein is required for thrombin-induced DNA synthesis. We demonstrate here, using transfection of receptors and G proteins in COS-7 cells, that G alpha 12 selectively couples the thrombin receptor to AP-1-mediated gene expression. This does not appear to result from increased mitogen-activated protein kinase activity but may reflect activation of a tyrosine kinase pathway. We suggest that preferential coupling of the thrombin receptor to G12 accounts for the selective ability of thrombin to stimulate Ras, mitogen-activated protein kinase, gene expression, and mitogenesis in 1321N1 cells.     

Glyoxalase-1 overexpression partially prevents diabetes-induced impaired arteriogenesis in a rat hindlimb ligation model

We hypothesize that diabetes-induced impaired collateral formation after a hindlimb ligation in rats is in part caused by intracellular glycation and that overexpression of glyoxalase-I (GLO-I), i.e. the major detoxifying enzyme for advanced-glycation-endproduct (AGE) precursors, can prevent this. Wild-type and GLO-I transgenic rats with or without diabetes (induced by 55 mg/kg streptozotocin) were subjected to ligation of the right femoral artery. Laser Doppler perfusion imaging showed a significantly decreased blood perfusion recovery after 6 days in the diabetic animals compared with control animals, without any effect of Glo1 overexpression. In vivo time-of-flight magnetic resonance angiography at 7-Tesla showed a significant decrease in the number and volume of collaterals in the wild-type diabetic animals compared with the control animals. Glo1 overexpression partially prevented this decrease in the diabetic animals. Diabetes-induced impairment of arteriogenic adaptation can be partially rescued by overexpressing of GLO-I, indicating a role of AGEs in diabetes-induced impaired collateral formation.     

Greater Abundance of <Emphasis Type="Italic">Betula nana</Emphasis> and Early Onset of the Growing Season Increase Ecosystem CO<Subscript>2</Subscript> Uptake in West Greenland

Expansion of deciduous shrubs is a common observation throughout the Arctic, with implications for carbon (C) cycling. Shrubs may increase net ecosystem C uptake through greater leaf area and gross ecosystem photosynthesis (GEP), and/or through cooler summer soils and reduced ecosystem respiration (ER). We used a space-for-time substitution combined with experimental warming at a Low Arctic site in West Greenland to examine the biophysical effects of increased temperature and Betula nana abundance on ecosystem CO₂ exchange. Communities dominated by Betula were much stronger C sinks than graminoid communities due to greater GEP and lower ER. The warming treatment had little effect on GEP, ER, or net ecosystem CO₂ exchange (NEE). The start of the growing season has been advancing at our study site, as indicated by long-term observations of plant phenology. In a retrospective analysis, we estimate that earlier onset of the growing season has increased the strength of the ecosystem C sink at rates of 1.3 and 2.1 g C m^?2 y^?1 in Betula and graminoid tundra, respectively, since 2002. However, earlier, and presumably longer, growing seasons may be associated with greater potential for drought stress. Our data suggest that mid-summer drought-induced GEP declines may partially offset C gains associated with an earlier start to the growing season. Our results suggest greater deciduous shrub abundance and longer growing seasons will likely lead to greater net C uptake in our study area, while highlighting important complexities associated with drought and plant community composition.     

Diversity of Synechococcus at the Martha’s Vineyard Coastal Observatory: Insights from Culture Isolations,Clone Libraries,and Flow Cytometry

The cyanobacterium Synechococcus is a ubiquitous, important phytoplankter across the world’s oceans. A high degree of genetic diversity exists within the marine group, which likely contributes to its global success. Over 20 clades with different distribution patterns have been identified. However, we do not fully understand the environmental factors that control clade distributions. These factors are likely to change seasonally, especially in dynamic coastal systems. To investigate how coastal Synechococcus assemblages change temporally, we assessed the diversity of Synechococcus at the Martha’s Vineyard Coastal Observatory (MVCO) over three annual cycles with culture-dependent and independent approaches. We further investigated the abundance of both phycoerythrin (PE)-containing and phycocyanin (PC)-only Synechococcus with a flow cytometric setup that distinguishes PC-only Synechococcus from picoeukaryotes. We found that the Synechococcus assemblage at MVCO is diverse (13 different clades identified), but dominated by clade I representatives. Many clades were only isolated during late summer and fall, suggesting more favorable conditions for isolation at this time. PC-only strains from four different clades were isolated, but these cells were only detected by flow cytometry in a few samples over the time series, suggesting they are rare at this site. Within clade I, we identified four distinct subclades. The relative abundances of each subclade varied over the seasonal cycle, and the high Synechococcus cell concentration at MVCO may be maintained by the diversity found within this clade. This study highlights the need to understand how temporal aspects of the environment affect Synechococcus community structure and cell abundance.     

Is enhancing cGMP-PKG signalling a promising therapeutic target for heart failure with preserved ejection fraction?

Heart failure with preserved ejection fraction, i.e. HFpEF, is highly prevalent in ageing populations, accounting for more than 50 % of all cases of heart failure in Western societies, and is closely associated with comorbidities such as obesity, diabetes and arterial hypertension. However, all large multicentre trials of potential HFpEF treatments conducted to date have failed to produce positive outcomes. These disappointing results suggest that a ‘one size fits all’ strategy may be ill-suited to HFpEF and support the use of tailored, personalised therapeutic approaches with specific treatments designed for specific comorbidity-related HFpEF phenotypes. The accumulation of a multitude of cardiovascular comorbidities over time leads to increased systemic inflammation, oxidative stress and coronary microvascular endothelial inflammation, eventually resulting in degradation of cyclic guanosine monophosphate (cGMP) via multiple pathways, thereby reducing protein kinase G (PKG) activity. The importance of cGMP-PKG pathway modulation is supported by growing evidence that suggests that this pathway may be a promising therapeutic target, evidence that is mainly based on its role in the phosphorylation of the giant cytoskeletal protein titin. This review will focus on the preclinical and early clinical evidence in the field of cGMP-enhancing therapies and PKG activation.     

Echocardiographic findings associated with mortality or transplant in patients with pulmonary arterial hypertension: A systematic review and meta-analysis

Background

Identification of patients at risk of deterioration is essential to guide clinical management in pulmonary arterial hypertension (PAH). This study aims to provide a comprehensive overview of well-investigated echocardiographic findings that are associated with clinical deterioration in PAH.

Methods

MEDLINE and EMBASE databases were systematically searched for longitudinal studies published by April 2015 that reported associations between echocardiographic findings and mortality, transplant or clinical worsening. Meta-analysis using random effect models was performed for echocardiographic findings investigated by four or more studies. In case of statistical heterogeneity a sensitivity analysis was conducted.

Results

Thirty-seven papers investigating 51 echocardiographic findings were included. Meta-analysis of univariable hazard ratios (HRs) and sensitivity analysis showed that presence of pericardial effusion (pooled HR 1.70; 95?% CI 1.44–1.99), right atrial area (pooled HR 1.71; 95?% CI 1.38–2.13) and tricuspid annular plane systolic excursion (TAPSE; pooled HR 1.72; 95?% CI 1.34–2.20) were the most well-investigated and robust predictors of mortality or transplant.

Conclusions

This meta-analysis substantiates the clinical yield of specific echocardiographic findings in the prognostication of PAH patients in day-to-day practice. In particular, pericardial effusion, right atrial area and TAPSE are of prognostic value.

     

It Is Tough and Tiring but It Works—Children’s Experiences of Undergoing Radiotherapy

Approximately 300 children ages 0 to 18 are diagnosed with cancer in Sweden every year, and 80 to 90 of them undergo radiotherapy treatment. The aim was to describe children’s experiences of preparing for and undergoing radiotherapy, and furthermore to describe children’s suggestions for improvement. Thirteen children between the ages of 5 and 15 with various cancer diagnoses were interviewed. Data was analyzed using qualitative content analysis. The findings revealed five categories: positive and negative experiences with hospital stays and practical arrangements; age-appropriate information, communication, and guidance to various degrees; struggle with emotions; use of distraction and other suitable coping strategies; and children’s suggestions for improvement during radiotherapy. An overarching theme emerged: “It is tough and tiring but it works”. Some key areas were: explanatory visits, the need for information and communication, being afraid, discomfort and suffering, the need for media distraction, dealing with emotions, and the need for support. A systematic, family-centered preparation program could possible help families prepare and individualized distraction during radiotherapy could contribute to reducing distress. Further studies with interventions could clarify successful programs.