Functional consequences of sphingomyelinase-induced changes in erythrocyte membrane structure.

Inflammation enhances the secretion of sphingomyelinases (SMases). SMases catalyze the hydrolysis of sphingomyelin into phosphocholine and ceramide. In erythrocytes, ceramide formation leads to exposure of the removal signal phosphatidylserine (PS), creating a potential link between SMase activity and anemia of inflammation. Therefore, we studied the effects of SMase on various pathophysiologically relevant parameters of erythrocyte homeostasis. Time-lapse confocal microscopy revealed a SMase-induced transition from the discoid to a spherical shape, followed by PS exposure, and finally loss of cytoplasmic content. Also, SMase treatment resulted in ceramide-associated alterations in membrane-cytoskeleton interactions and membrane organization, including microdomain formation. Furthermore, we observed increases in membrane fragility, vesiculation and invagination, and large protein clusters. These changes were associated with enhanced erythrocyte retention in a spleen-mimicking model. Erythrocyte storage under blood bank conditions and during physiological aging increased the sensitivity to SMase. A low SMase activity already induced morphological and structural changes, demonstrating the potential of SMase to disturb erythrocyte homeostasis. Our analyses provide a comprehensive picture in which ceramide-induced changes in membrane microdomain organization disrupt the membrane-cytoskeleton interaction and membrane integrity, leading to vesiculation, reduced deformability, and finally loss of erythrocyte content. Understanding these processes is highly relevant for understanding anemia during chronic inflammation, especially in critically ill patients receiving blood transfusions

Does a reduced glucose intake prevent hyperglycemia in children early after cardiac surgery? a randomized controlled crossover study

Introduction: Hyperglycemia in children after cardiac surgery can be treated with intensive insulin therapy, but hypoglycemia is a potential serious side effect. The aim of this study was to investigate the effects of reducing glucose intake below standard intakes to prevent hyperglycemia, on blood glucose concentrations, glucose kinetics and protein catabolism in children after cardiac surgery with cardiopulmonary bypass (CPB).Methods: Subjects received a 4-hour low glucose (LG; 2.5 mg/kg per minute) and a 4-hour standard glucose (SG; 5.0 mg/kg per minute) infusion in a randomized blinded crossover setting. Simultaneously, an 8-hour stable isotope tracer protocol was conducted to determine glucose and leucine kinetics. Data are presented as mean ± SD or median (IQR); comparison was made by paired samples t test.Results: Eleven subjects (age 5.1 (20.2) months) were studied 9.5 ± 1.9 hours post-cardiac surgery. Blood glucose concentrations were lower during LG than SG (LG 7.3 ± 0.7 vs. SG 9.3 ± 1.8 mmol/L; P < 0.01), although the glycemic target (4.0-6.0 mmol/L) was not achieved. No hypoglycemic events occurred. Endogenous glucose production was higher during LG than SG (LG 2.9 ± 0.8 vs. SG 1.5 ± 1.1 mg/kg per minute; P = 0.02), due to increased glycogenolysis (LG 1.0 ± 0.6 vs. SG 0.0 ± 1.0 mg/kg per minute; P < 0.05). Leucine balance, indicating protein balance, was negative but not affected by glucose intake (LG -54.8 ± 14.6 vs. SG -58.8 ± 16.7 μmol/kg per hour; P = 0.57).Conclusions: Currently recommended glucose intakes aggravated hyperglycemia in children early after cardiac surgery with CPB. Reduced glucose intake decreased blood glucose concentrations without causing hypoglycemia or affecting protein catabolism, but increased glycogenolysis.Trial registration: Dutch trial register NTR2079

Towards net zero CO2 in 2050: an emission reduction pathway for organic soils in Germany

The Paris Agreement reflects the global endeavour to limit the increase of global average temperature to 2 °C, better 1.5 °C above pre-industrial levels to prevent dangerous climate change. This requires that global anthropogenic net carbon dioxide (CO2) emissions are reduced to zero around 2050. The German Climate Protection Plan substantiates this goal and explicitly mentions peatlands, which make up 5 % of the total area under land use and emit 5.7 % of total annual greenhouse gas emissions in Germany. Based on inventory reporting and assumptions of land use change probability, we have developed emission reduction pathways for organic soils in Germany that on a national level comply with the IPCC 1.5 °C pathways. The more gradual pathway 1 requires the following interim (2030, 2040) and ultimate (2050) milestones: Cropland use stopped and all Cropland converted to Grassland by 2030; Water tables raised to the soil surface on 15 % / 60 % / 100 % of all Grassland, on 50 % / 75 % / 100 % of all Forest land, and ultimately on 2/3 of all Settlements and on 100 % of all Wetlands. Also a more direct pathway 2 without interim ‘moist’ water tables and the climate effect (radiative forcing) of different scenarios is presente

A molecular marker closely lined to the male sterile Ms2 gene in common wheat (Triticum aestivum)

Women with a history of preeclampsia are at increased risk for future cardiovascular disease. Determination of cardiovascular biomarkers may be useful to understand the pathophysiological mechanism of cardiovascular disease development in these women.We performed an analysis in the Preeclampsia Risk EValuation in FEMales study, a retrospective cohort consisting of 339 women with a history of early preeclampsia and 332 women after normotensive pregnancy. Women attended a follow-up visit ten years after the index pregnancy. A subset of 8 different cardiovascular biomarkers was investigated, reflecting inflammatory, metabolic, thrombotic and endothelial function markers. Associations between PE and these novel biomarkers were analyzed by linear regression analysis and adjusted for traditional cardiovascular risk factors.Mean age of 671 women of the PREVFEM cohort was 39 years and women were on average 10 years post index pregnancy. Women post preeclampsia had significantly higher levels of SE-selectin (adjusted difference 4.55, 99\%CI 0.37; 8.74) and PAPPA (adjusted difference 19.08; 99\%CI 13.18; 24.99), whereas ApoB (adjusted difference -0.23 99\%CI -0.32; -0.14) was inversely associated with preeclampsia, compared to women with a previous normotensive pregnancy. Adiponectin, leptin, sICAM-1, sVCAM-1 and PAI-1 were not different between both groups.We demonstrated an independent association of preeclampsia with SE-selectin and PAPPA (markers of vascular dysfunction), which may contribute to future cardiovascular events in women post preeclampsia. However, ApoB (an apolipoprotein) was significantly lower and could point at a protective mechanism in our PE study women

PYTHIA hadronization process tuning in the GENIE neutrino interaction generator

9 pages, 7 figures, proceedings of the CETUP*-Workshop on Neutrino Interactions, July 22-31, 2014 at Lead/Dead Wood, South Dakota, USA9 pages, 7 figures, proceedings of the CETUP*-Workshop on Neutrino Interactions, July 22-31, 2014 at Lead/Dead Wood, South Dakota, USAv1: 9 pages, 7 figures, proceedings of the CETUP*-Workshop on Neutrino Interactions, July 22-31, 2014 at Lead/Dead Wood, South Dakota, USA. v2: 15 pages, 8 figures, 1 table, will be published by Journal of Physics G: Nuclear and Particle Physics (IoP

Working Papers, Open Access and Cyber-Infrastructure in Classical Studies

Princeton–Stanford Working Papers in Classics is a web-based series of work-in-progress scripts by members of two leading departments of classics. It introduces the humanities to a new form of scholarly communication and represents a major advance in the free availability of classical-studies scholarship in cyberspace. This article both reviews the initial performance of this open-access experiment and the benefits and challenges of working papers more generally for classical studies. After two years of operation Princeton–Stanford Working Papers in Classics has proven to be a clear success. This series has built up a large international readership and a sizeable body of preprints and performs important scholarly and community-outreach functions. As this performance is largely due to its congruency with the working arrangements of ancient historians and classicists and the global demand for open-access scholarship, the series confirms the viability of this means of scholarly communication and the likelihood of its expansion in our discipline. But modifications are required to increase the benefits this series brings and the amount of scholarship it makes freely available online. Finally departments wishing to replicate its success will have to consider other important developments, such as the increasing availability of postprints, the linking of research funding to open access, and the emergence of new cyber-infrastructure