Quercetin preserves redox status and stimulates mitochondrial function in metabolically-stressed HepG2 cells

Hyperglycemia augments formation of intracellular reactive oxygen species (ROS) with associated mitochondrial damage and increased risk of insulin resistance in type 2 diabetes. We examined whether quercetin could reverse chronic high glucose-induced oxidative stress and mitochondrial dysfunction. Following long-term high glucose treatment, complex I activity was significantly decreased in isolated mitochondria from HepG2 cells. Quercetin dose-dependently recovered complex I activity and lowered cellular ROS generation under both high and normal glucose conditions. Respirometry studies showed that quercetin could counteract the detrimental increase in inner mitochondrial membrane proton leakage resulting from high glucose while it increased oxidative respiration, despite a decrease in electron transfer system (ETS) capacity, and lower non-ETS oxygen consumption. A quercetin-stimulated increase in cellular NAD+/NADH was evident within 2 h and a two-fold increase in PGC-1α mRNA within 6 h, in both normal and high glucose conditions. A similar pattern was also found for the mRNA expression of the repulsive guidance molecule b (RGMB) and its long non-coding RNA (lncRNA) RGMB-AS1 with quercetin, indicating a potential change of the glycolytic phenotype and suppression of aberrant cellular growth which is characteristic of the HepG2 cells. Direct effects of quercetin on PGC-1α activity were minimal, as quercetin only weakly enhanced PGC-1α binding to PPARα in vitro at higher concentrations. Our results suggest that quercetin may protect mitochondrial function from high glucose-induced stress by increasing cellular NAD+/NADH and activation of PGC-1α-mediated pathways. Lower ROS in combination with improved complex I activity and ETS coupling efficiency under conditions of amplified oxidative stress could reinforce mitochondrial integrity and improve redox status, beneficial in certain metabolic diseases

Open Science in Software Engineering

Open science describes the movement of making any research artefact available to the public and includes, but is not limited to, open access, open data, and open source. While open science is becoming generally accepted as a norm in other scientific disciplines, in software engineering, we are still struggling in adapting open science to the particularities of our discipline, rendering progress in our scientific community cumbersome. In this chapter, we reflect upon the essentials in open science for software engineering including what open science is, why we should engage in it, and how we should do it. We particularly draw from our experiences made as conference chairs implementing open science initiatives and as researchers actively engaging in open science to critically discuss challenges and pitfalls, and to address more advanced topics such as how and under which conditions to share preprints, what infrastructure and licence model to cover, or how do it within the limitations of different reviewing models, such as double-blind reviewing. Our hope is to help establishing a common ground and to contribute to make open science a norm also in software engineering.Comment: Camera-Ready Version of a Chapter published in the book on Contemporary Empirical Methods in Software Engineering; fixed layout issue with side-note

Prevalence and Predictors of Vitamin D Insufficiency in Children: A Great Britain Population Based Study

Objectives To evaluate the prevalence and predictors of vitamin D insufficiency (VDI) in children In Great Britain. Design A nationally representative cross-sectional study survey of children (1102) aged 4–18 years (999 white, 570 male) living in private households (January 1997–1998). Interventions provided information about dietary habits, physical activity, socio-demographics, and blood sample. Outcome measures were vitamin D insufficiency (<50 nmol/L). Results Vitamin D levels (mean = 62.1 nmol/L, 95%CI 60.4–63.7) were insufficient in 35%, and decreased with age in both sexes (p<0.001). Young People living between 53–59 degrees latitude had lower levels (compared with 50–53 degrees, p = 0.045). Dietary intake and gender had no effect on vitamin D status. A logistic regression model showed increased risk of VDI in the following: adolescents (14–18 years old), odds ratio (OR) = 3.6 (95%CI 1.8–7.2) compared with younger children (4–8 years); non white children (OR = 37 [95%CI 15–90]); blood levels taken December-May (OR = 6.5 [95%CI 4.3–10.1]); on income support (OR = 2.2 [95%CI 1.3–3.9]); not taking vitamin D supplementation (OR = 3.7 [95%CI 1.4–9.8]); being overweight (OR 1.6 [95%CI 1.0–2.5]); <1/2 hour outdoor exercise/day/week (OR = 1.5 [95%CI 1.0–2.3]); watched >2.5 hours of TV/day/week (OR = 1.6[95%CI 1.0–2.4]). Conclusion We confirm a previously under-recognised risk of VDI in adolescents. The marked higher risk for VDI in non-white children suggests they should be targeted in any preventative strategies. The association of higher risk of VDI among children who exercised less outdoors, watched more TV and were overweight highlights potentially modifiable risk factors. Clearer guidelines and an increased awareness especially in adolescents are needed, as there are no recommendations for vitamin D supplementation in older children

Changing climate—changing pathogens: Toxoplasma gondii in North-Western Europe

In this review, we describe the effects of global climate change for one specific pathogen: the parasite Toxoplasma gondii. It is postulated that an increase of T. gondii prevalence in humans can occur in some regions of North-Western Europe as a result of changing environmental conditions. Such a change can be predicted by using Global Climate Change models. We have elaborated such a prediction for one scenario (SRES A1) by using one specific model (CCSR/NRIES) as an example. Next to environmental factors, also anthropogenic factors may contribute to increased prevalence of T. gondii in this region. In order to counter the potential severe consequences of a potential increase resulting from the combination of climatic and anthropogenic factors, there is an urgent need for the development of a human vaccine. Until a vaccine that offers complete protection is developed, the emphasis should be on treatment optimization and prevention

Effects of ocean acidification on invertebrate settlement at volcanic CO<inf>2</inf> vents

We present the first study of the effects of ocean acidification on settlement of benthic invertebrates and microfauna. Artificial collectors were placed for 1 month along pH gradients at CO2 vents off Ischia (Tyrrhenian Sea, Italy). Seventy-nine taxa were identified from six main taxonomic groups (foraminiferans, nematodes, polychaetes, molluscs, crustaceans and chaetognaths). Calcareous foraminiferans, serpulid polychaetes, gastropods and bivalves showed highly significant reductions in recruitment to the collectors as pCO2 rose from normal (336-341 ppm, pH 8.09-8.15) to high levels (886-5,148 ppm) causing acidified conditions near the vents (pH 7.08-7.79). Only the syllid polychaete Syllis prolifera had higher abundances at the most acidified station, although a wide range of polychaetes and small crustaceans was able to settle and survive under these conditions. A few taxa (Amphiglena mediterranea, Leptochelia dubia, Caprella acanthifera) were particularly abundant at stations acidified by intermediate amounts of CO2 (pH 7. 41-7.99). These results show that increased levels of CO2 can profoundly affect the settlement of a wide range of benthic organisms. © 2010 Springer-Verlag

Real-Time PCR Improves Helicobacter pylori Detection in Patients with Peptic Ulcer Bleeding

Background and aims: Histological and rapid urease tests to detect H. pylori in biopsy specimens obtained during peptic ulcer bleeding episodes (PUB) often produce false-negative results. We aimed to examine whether immunohistochemistry and real-time PCR can improve the sensitivity of these biopsies. Patients and Methods: We selected 52 histology-negative formalin-fixed paraffin-embedded biopsy specimens obtained during PUB episodes. Additional tests showed 10 were true negatives and 42 were false negatives. We also selected 17 histology-positive biopsy specimens obtained during PUB to use as controls. We performed immunohistochemistry staining and real-time PCR for 16S rRNA, ureA, and 23S rRNA for H. pylori genes on all specimens. Results: All controls were positive for H. pylori on all PCR assays and immunohistochemical staining. Regarding the 52 initially negative biopsies, all PCR tests were significantly more sensitive than immunohistochemical staining (p<0.01). Sensitivity and specificity were 55% and 80% for 16S rRNA PCR, 43% and 90% for ureA PCR, 41% and 80% for 23S rRNA PCR, and 7% and 100% for immunohistochemical staining, respectively. Combined analysis of PCR assays for two genes were significantly more sensitive than ureA or 23S rRNA PCR tests alone (p<0.05) and marginally better than 16S rRNA PCR alone. The best combination was 16S rRNA+ureA, with a sensitivity of 64% and a specificity of 80%. Conclusions: Real-time PCR improves the detection of H. pylori infection in histology-negative formalin-fixed paraffin-embedded biopsy samples obtained during PUB episodes. The low reported prevalence of H. pylori in PUB may be due to the failure of conventional tests to detect infection

The carbon balance of South America: A review of the status, decadal trends and main determinants

Copyright © 2012 European Geosciences Union. This is the published version available at http://www.biogeosciences-discuss.net/9/627/2012/bgd-9-627-2012.htmlWe attempt to summarize the carbon budget of South America and relate it to its dominant controls: population and economic growth, changes in land use practices and a changing atmospheric environment and climate. Flux estimation methods which we consider sufficiently reliable are fossil fuel emission inventories, biometric analysis of old-growth rainforests, estimation of carbon release associated with deforestation based on remote sensing and inventories, and finally inventories of agricultural exports. Other routes to estimating land-atmosphere CO2 fluxes include atmospheric transport inverse modelling and vegetation model predictions but are hampered by the data paucity and the need for improved parameterisation. The available data we analyze suggest that South America was a net source to the atmosphere during the 1980s (∼0.3–0.4 Pg C yr−1) and close to neutral (∼0.1 Pg C yr−1) in the 1990s with carbon uptake in old-growth forests nearly compensating carbon losses due to fossil fuel burning and deforestation. Annual mean precipitation over tropical South America measured by Amazon River discharge has a long-term upward trend, although over the last decade, dry seasons have tended to be drier and longer (and thus wet seasons wetter), with the years 2005 and 2010 experiencing strong droughts. It is currently unclear what the effect of these climate changes on the old-growth forest carbon sink will be but first measurements suggest it may be weakened. Based on scaling of forest census data the net carbon balance of South America seems to have been an increased source roughly over the 2005–2010 period (a total of ∼1 Pg C of dead tree biomass released over several years) due to forest drought response. Finally, economic development of the tropical forest regions of the continent is advancing steadily with exports of agricultural products being an important driver and witnessing a strong upturn over the last decade

An adolescent with both Wegener's Granulomatosis and chronic blastomycosis

We report a case of Wegener's Granulomatosis (WG) associated with blastomycosis. This appears to be the first case report of WG co-existing with a tissue proven blastomycosis infection. The temporal correlation of the two conditions suggests that blastomycosis infection (and therefore possibly other fungal infections), may trigger the systemic granulomatous vasculitis in a predisposed individual; a provocative supposition warranting further study

GS-nitroxide (JP4-039)-mediated radioprotection of human fanconi anemia cell lines

Fanconi anemia (FA) is an inherited disorder characterizedby defective DNA repair and cellular sensitivity to DNAcrosslinking agents. Clinically, FA is associated with highrisk for marrow failure, leukemia and head and necksquamous cell carcinoma (HNSCC). Radiosensitivity in FApatients compromises the use of total-body irradiation forhematopoietic stem cell transplantation and radiationtherapy for HNSCC. A radioprotector for the surroundingtissue would therefore be very valuable during radiotherapyfor HNSCC. Clonogenic radiation survival curves weredetermined for pre- or postirradiation treatment with theparent nitroxide Tempol or JP4-039 in cells of four FApatient-derived cell lines and two transgene-correctedsubclonal lines. FancG-/- (PD326) and FancD2-/- (PD20F)patient lines were more sensitive to the DNA crosslinkingagent mitomycin C (MMC) than their transgene-restoredsubclonal cell lines (both P , 0.0001). FancD2-/- cells weremore radiosensitive than the transgene restored subclonalcell line (n2.0 6 0.7 and 4.7 6 2.2, respectively, P 0.03).In contrast, FancG-/- cells were radioresistant relative to thetransgene-restored subclonal cell line (n 9.4 6 1.5 and 2.26 05, respectively, P0.001). DNA strand breaks measuredby the comet assay correlated with radiosensitivity. Celllines from a Fanc-C and Fanc-A patients showed radiosensitivitysimilar to that of Fanc-D2-/- cells. A fluorophoretaggedJP4-039 (BODIPY-FL) analog targeted the mitochondriaof the cell lines. Preirradiation or postirradiationtreatment with JP4-039 at a lower concentration thanTempol significantly increased the radioresistance andstabilized the antioxidant stores of all cell lines. Tempolincreased the toxicity of MMC in FancD2-/- cells. These dataprovide support for the potential clinical use of JP4-039 fornormal tissue radioprotection during chemoradiotherapy inFA patients. © 2011 by Radiation Research Society