Non-intrusive assessment of photosystem II and photosystem I in whole coral tissues

Reef building corals (phylum Cnidaria) harbor endosymbiotic dinoflagellate algae (genus Symbiodinium) that generate photosynthetic products to fuel their host's metabolism. Non-invasive techniques such as chlorophyll (Chl) fluorescence analyses of Photosystem II (PSII) have been widely used to estimate the photosynthetic performance of Symbiodinium in hospite. However, since the spatial origin of PSII chlorophyll fluorescence in coral tissues is uncertain, such signals give limited information on depth-integrated photosynthetic performance of the whole tissue. In contrast, detection of absorbance changes in the near infrared (NIR) region integrates signals from deeper tissue layers due to weak absorption and multiple scattering of NIR light. While extensively utilized in higher plants, NIR bio-optical techniques are seldom applied to corals. We have developed a non-intrusive measurement method to examine photochemistry of intact corals, based on redox kinetics of the primary electron donor in Photosystem I (P700) and chlorophyll fluorescence kinetics (Fast-Repetition Rate fluorometry, FRRf). Since the redox state of P700 depends on the operation of both PSI and PSII, important information can be obtained on the PSII-PSI intersystem electron transfer kinetics. Under moderate, sub-lethal heat stress treatments (33°C for ~20 min), the coral Pavona decussata exhibited down-regulation of PSII electron transfer kinetics, indicated by slower rates of electron transport from QA to plastoquinone (PQ) pool, and smaller relative size of oxidized PQ with concomitant decrease of a specifically-defined P700 kinetics area, which represents the active pool of PSII. The maximum quantum efficiency of PSII (Fv/Fm) and functional absorption cross-section of PSII (σPSII) remained unchanged. Based on the coordinated response of P700 parameters and PSII-PSI electron transport properties, we propose that simple P700 kinetics parameters as employed here serve as indicators of the integrity of PSII-PSI electron transfer dynamics in corals.This work was supported by the award of Australian Research Council Discovery Project (ARC DP120101360) to WC and Future Fellowship (FT130100202) to DS. IV and LS were partly supported by a grant from the Hungarian National Research, Development and Innovation Office (NN110960

The application of adjuvant autologous antravesical macrophage cell therapy vs. BCG in non-muscle invasive bladder cancer: a multicenter, randomized trial

<p>Abstract</p> <p>Introduction</p> <p>While adjuvant immunotherapy with Bacille Calmette Guérin (BCG) is effective in non-muscle-invasive bladder cancer (BC), adverse events (AEs) are considerable. Monocyte-derived activated killer cells (MAK) are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM^®) to BCG in patients after transurethral resection (TURB) of BC.</p> <p>Materials and methods</p> <p>This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and ≥ 2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM). Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint) and prophylactic effects (secondary endpoint) were assessed.</p> <p>Results</p> <p>Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE), respectively (p < 0.001). Recurrence occurred significantly less frequent with BCG than with BEXIDEM (12% vs. 38%; p < 0.001).</p> <p>Discussion</p> <p>This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted.</p> <p>Trial registration</p> <p>The trial has been registered in the ISRCTN registry <url>http://isrctn.org</url> under the registration number ISRCTN35881130.</p

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Kereskedés az integrált Budapesti Értéktőzsdén

A versenyképesség megőrzése és erősítése mind az ország, mind a tőkepiac alapvető érdeke. Ezen kihívás egyik eredménye a 2005-ben létrejött tőzsdei integráció. A modern távkereskedési rendszeréhez (MMTS I-II.) a világ bármely pontjáról nyitott interface-en keresztül kapcsolódhatnak a piaci szereplők, így akár az egyéni vagy intézményi befektetők, mezőgazdasági termelők, spekulánsok is. Ahhoz, hogy a mezőgazdasági termelők, feldolgozók ki tudják használni a tőzsde adta lehetőségeket, és az árbiztosításuk reményében hedge (fedezeti), illetve opciós ügyleteket tudjanak kötni eredményesen, először meg kell ismerniük a jelentős átalakuláson átesett – és folyamatosan változó – tőzsde alapvető működését. A Budapesti Értéktőzsde jelenlegi stratégiájának célja, hogy hosszú távon a hazai pénz- és tőkepiaci kultúra alakításának meghatározó szereplője maradjon. Ennek érdekében kiszolgálja a forrást bevonni kívánó gazdasági társaságokat és a befektetők minél szélesebb rétegét. - The maintenance and strengthening of competitiveness is the fundamental interest of both country and capital market. An outcome of this challenge is the integration of stock exchange in 2005. Market participants may connect to this up-to-date distance trading system (MMTS I-II) from any point on the world via an open interface, including individuals, institutional investors, agricultural producers or even speculators. To exploit the opportunities afforded by the exchange in making successful hedging or options deals (in the hope of price insurance) farmers and food processors have to be aware of the significant changes that have occurred (and still occurring) in the operations of the exchange. It is at present a strategic goal of Budapest Stock Exchange to remain on long term the determining institution in the development of domestic money and capital markets. Consequently it serves commercial enterprises requiring resources and the widest possible circle of investors

Kereskedés az integrált Budapesti ÉrtéktÅ‘zsdén

A versenyképesség megÅ‘rzése és erÅ‘sítése mind az ország, mind a tÅ‘kepiac alapvetÅ‘ érdeke. Ezen kihívás egyik eredménye a 2005-ben létrejött tÅ‘zsdei integráció. A modern távkereskedési rendszeréhez (MMTS I-II.) a világ bármely pontjáról nyitott interface-en keresztül kapcsolódhatnak a piaci szereplÅ‘k, így akár az egyéni vagy intézményi befektetÅ‘k, mezÅ‘gazdasági termelÅ‘k, spekulánsok is. Ahhoz, hogy a mezÅ‘gazdasági termelÅ‘k, feldolgozók ki tudják használni a tÅ‘zsde adta lehetÅ‘ségeket, és az árbiztosításuk reményében hedge (fedezeti), illetve opciós ügyleteket tudjanak kötni eredményesen, elÅ‘ször meg kell ismerniük a jelentÅ‘s átalakuláson átesett – és folyamatosan változó – tÅ‘zsde alapvetÅ‘ működését. A Budapesti ÉrtéktÅ‘zsde jelenlegi stratégiájának célja, hogy hosszú távon a hazai pénz- és tÅ‘kepiaci kultúra alakításának meghatározó szereplÅ‘je maradjon. Ennek érdekében kiszolgálja a forrást bevonni kívánó gazdasági társaságokat és a befektetÅ‘k minél szélesebb rétegét. - The maintenance and strengthening of competitiveness is the fundamental interest of both country and capital market. An outcome of this challenge is the integration of stock exchange in 2005. Market participants may connect to this up-to-date distance trading system (MMTS I-II) from any point on the world via an open interface, including individuals, institutional investors, agricultural producers or even speculators. To exploit the opportunities afforded by the exchange in making successful hedging or options deals (in the hope of price insurance) farmers and food processors have to be aware of the significant changes that have occurred (and still occurring) in the operations of the exchange. It is at present a strategic goal of Budapest Stock Exchange to remain on long term the determining institution in the development of domestic money and capital markets. Consequently it serves commercial enterprises requiring resources and the widest possible circle of investors.tÅ‘zsdei integráció, garanciarendszer, származékos szekció, határidÅ‘s arany kontraktus, exchange integration, system of guaranties, derivatives market, gold contract with time limits, Agribusiness, International Relations/Trade,

Nucleosome destabilization by polyamines

The roles and molecular interactions of polyamines (PAs) in the nucleus are not fully understood. Here their effect on nucleosome stability, a key regulatory factor in eukaryotic gene control, is reported, as measured in agarose embedded nuclei of H2B-GFP expressor HeLa cells. Nucleosome stability was assessed by quantitative microscopy [[1], [2]] in situ, in close to native state of chromatin, preserving the nucleosome constrained topology of the genomic DNA. A robust destabilizing effect was observed in the millimolar concentration range in the case of spermine, spermidine as well as putrescine, which was strongly pH and salt concentration-dependent, and remained significant also at neutral pH. The integrity of genomic DNA was not affected by PA treatment, excluding DNA break-elicited topological relaxation as a factor in destabilization. The binding of PAs to DNA was demonstrated by the displacement of ethidium bromide, both from deproteinized nuclear halos and from plasmid DNA. The possibility that DNA methylation patterns may be influenced by PA levels is contemplated in the context of gene expression and DNA methylation correlations identified in the NCI-60 panel-based CellMiner database: methylated loci in subsets of high-ODC1 cell lines and the dependence of PER3 DNA methylation on PA metabolism.This work was supported by OTKA K 128770, K 138524, COST CA 15214, Stipendium Hungaricum scholarship by the Tempus Public Foundation (to RB) and the Richter Talentum Fund (EFN and NH). We are thankful to the NIH Developmental Therapeutics Program for providing the drugs investigated

Viable protoplast formation of the coral endosymbiont alga Symbiodinium spp. in a microfluidics platform

Symbiodiniaceae is an important dinoflagellate family which lives in endosymbiosis with reef invertebrates, including coral polyps, making them central to the holobiont. With coral reefs currently under extreme threat from climate change, there is a pressing need to improve our understanding on the stress tolerance and stress avoidance mechanisms of Symbiodinium spp. Reactive oxygen species (ROS) such as singlet oxygen are central players in mediating various stress responses; however, the detection of ROS using specific dyes is still far from definitive in intact Symbiodinium cells due to the hindrance of uptake of certain fluorescent dyes because of the presence of the cell wall. Protoplast technology provides a promising platform for studying oxidative stress with the main advantage of removed cell wall, however the preparation of viable protoplasts remains a significant challenge. Previous studies have successfully applied cellulose-based protoplast preparation in Symbiodiniaceae; however, the protoplast formation and regeneration process was found to be suboptimal. Here, we present a microfluidics-based platform which allowed protoplast isolation from individually trapped Symbiodinium cells, by using a precisely adjusted flow of cell wall digestion enzymes (cellulase and macerozyme). Trapped single cells exhibited characteristic changes in their morphology, cessation of cell division and a slight decrease in photosynthetic activity during protoplast formation. Following digestion and transfer to regeneration medium, protoplasts remained photosynthetically active, regrew cell walls, regained motility, and entered exponential growth. Elevated flow rates in the microfluidic chambers resulted in somewhat faster protoplast formation; however, cell wall digestion at higher flow rates partially compromised photosynthetic activity. Physiologically competent protoplasts prepared from trapped cells in microfluidic chambers allowed for the first time the visualization of the intracellular localization of singlet oxygen (using Singlet Oxygen Sensor Green dye) in Symbiodiniaceae, potentially opening new avenues for studying oxidative stress

Olive Oil Improves While Trans Fatty Acids Further Aggravate the Hypomethylation of LINE-1 Retrotransposon DNA in an Environmental Carcinogen Model

DNA methylation is an epigenetic mechanism that is crucial for mammalian development and genomic stability. Aberrant DNA methylation changes have been detected not only in malignant tumor tissues; the decrease of global DNA methylation levels is also characteristic for aging. The consumption of extra virgin olive oil (EVOO) as part of a balanced diet shows preventive effects against age-related diseases and cancer. On the other hand, consuming trans fatty acids (TFA) increases the risk of cardiovascular diseases as well as cancer. The aim of the study was to investigate the LINE-1 retrotransposon (L1-RTP) DNA methylation pattern in liver, kidney, and spleen of mice as a marker of genetic instability. For that, mice were fed with EVOO or TFA and were pretreated with environmental carcinogen 7,12-dimethylbenz[a]anthracene (DMBA)&mdash;a harmful substance known to cause L1-RTP DNA hypomethylation. Our results show that DMBA and its combination with TFA caused significant L1-RTP DNA hypomethylation compared to the control group via inhibition of DNA methyltransferase (DNMT) enzymes. EVOO had the opposite effect by significantly decreasing DMBA and DMBA + TFA-induced hypomethylation, thereby counteracting their effects