Rare variant contribution to cholestatic liver disease in a South Asian population in the United Kingdom

This study assessed the contribution of five genes previously known to be involved in cholestatic liver disease in British Bangladeshi and Pakistani people. Five genes (ABCB4, ABCB11, ATP8B1, NR1H4, TJP2) were interrogated by exome sequencing data of 5236 volunteers. Included were non-synonymous or loss of function (LoF) variants with a minor allele frequency < 5%. Variants were filtered, and annotated to perform rare variant burden analysis, protein structure, and modelling analysis in-silico. Out of 314 non-synonymous variants, 180 fulfilled the inclusion criteria and were mostly heterozygous unless specified. 90 were novel and of those variants, 22 were considered likely pathogenic and 9 pathogenic. We identified variants in volunteers with gallstone disease (n = 31), intrahepatic cholestasis of pregnancy (ICP, n = 16), cholangiocarcinoma and cirrhosis (n = 2). Fourteen novel LoF variants were identified: 7 frameshift, 5 introduction of premature stop codon and 2 splice acceptor variants. The rare variant burden was significantly increased in ABCB11. Protein modelling demonstrated variants that appeared to likely cause significant structural alterations. This study highlights the significant genetic burden contributing to cholestatic liver disease. Novel likely pathogenic and pathogenic variants were identified addressing the underrepresentation of diverse ancestry groups in genomic research

Availability of phosphate for phytoplankton and bacteria and of labile organic carbon for bacteria at different pCO2 levels in a mesocosm study

Availability of phosphate for phytoplankton and bacteria and of glucose for bacteria at different pCO2 levels were studied in a mesocosm experiment (PeECE III). Using nutrient-depleted SW Norwegian fjord waters, three different levels of pCO2 (350 μatm: 1×CO2; 700 μatm: 2×CO2; 1050 μatm: 3×CO2) were set up, and nitrate and phosphate were added at the start of the experiment in order to induce a phytoplankton bloom. Despite similar responses of total particulate P concentration and phosphate turnover time at the three different pCO2 levels, the size distribution of particulate P and 33PO4 uptake suggested that phosphate transferred to the >10 μm fraction was greater in the 3×CO2 mesocosm during the first 6–10 days when phosphate concentration was high. During the period of phosphate depletion (after Day 12), specific phosphate affinity and specific alkaline phosphatase activity (APA) suggested a P-deficiency (i.e. suboptimal phosphate supply) rather than a P-limitation for the phytoplankton and bacterial community at the three different pCO2 levels. Specific phosphate affinity and specific APA tended to be higher in the 3×CO2 than in the 2×CO2 and 1×CO2 mesocosms during the phosphate depletion period, although no statistical differences were found. Glucose turnover time was correlated significantly and negatively with bacterial abundance and production but not with the bulk DOC concentration. This suggests that even though constituting a small fraction of the bulk DOC, glucose was an important component of labile DOC for bacteria. Specific glucose affinity of bacteria behaved similarly at the three different pCO2 levels with measured specific glucose affinities being consistently much lower than the theoretical maximum predicted from the diffusion-limited model. This suggests that bacterial growth was not severely limited by the glucose availability. Hence, it seems that the lower availability of inorganic nutrients after the phytoplankton bloom reduced the bacterial capacity to consume labile DOC in the upper mixed layer of the stratified mesocosms

Build-up and decline of organic matter during PeECE III

Increasing atmospheric carbon dioxide (CO2) concentrations due to anthropogenic fossil fuel combustion are currently changing the ocean's chemistry. Increasing oceanic [CO2] and consequently decreasing seawater pH have the potential to significantly impact marine life. Here we describe and analyze the build-up and decline of a natural phytoplankton bloom initiated during the 2005 mesocosm Pelagic Ecosystem CO2 Enrichment study (PeECE III). The draw-down of inorganic nutrients in the upper surface layer of the mesocosms was reflected by a concomitant increase of organic matter until day t11, the peak of the bloom. From then on, biomass standing stocks steadily decreased as more and more particulate organic matter was lost into the deeper layer of the mesocosms. We show that organic carbon export to the deeper layer was significantly enhanced at elevated CO2. This phenomenon might have impacted organic matter remineralization leading to decreased oxygen concentrations in the deeper layer of the high CO2 mesocosms as indicated by deep water ammonium concentrations. This would have important implications for our understanding of pelagic ecosystem functioning and future carbon cycling

Effects of rising temperature on pelagic biogeochemistry in mesocosm systems: a comparative analysis of the AQUASHIFT Kiel experiments

A comparative analysis of data, obtained during four indoor-mesocosm experiments with natural spring plankton communities from the Baltic Sea, was conducted to investigate whether biogeochemical cycling is affected by an increase in water temperature of up to 6 °C above present-day conditions. In all experiments, warming stimulated in particular heterotrophic bacterial processes and had an accelerating effect on the temporal development of phytoplankton blooms. This was also mirrored in the build-up and partitioning of organic matter between particulate and dissolved phases. Thus, warming increased both the magnitude and rate of dissolved organic carbon (DOC) build-up, whereas the accumulation of particulate organic carbon (POC) and phosphorus (POP) decreased with rising temperature. In concert, the observed temperature-mediated changes in biogeochemical components suggest strong shifts in the functioning of marine pelagic food webs and the ocean’s biological carbon pump, hence providing potential feedback mechanisms to Earth’s climate system

Prengel, Annedore: Pädagogische Beziehungen zwischen Anerkennung, Verletzung und Ambivalenz. Opladen: Budrich 2013. [Rezension]

Rezension von: Annedore Prengel: Pädagogische Beziehungen zwischen Anerkennung, Verletzung und Ambivalenz. Opladen: Budrich 2013, 136 S. ISBN 978-3-8474-0098-

Sepsis in pregnancy: a rodent model exploring the cardiovascular adaptation and susceptibility to infection

Sepsis is a major cause of maternal mortality worldwide and is therefore an area of particular importance. Septic shock is characterised by cardiovascular collapse and multi organ dysfunction resulting from an overwhelming immune response to a bacterial infection. Nitric oxide (NO) release during pregnancy may exacerbate sepsis-induced hypotension. The endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), is an important regulator of vascular NO production in sepsis. DDAH1 (Dimethylargnine Dimethylamino Hydrolase) regulates ADMA concentrations in the vasculature. The objective of this thesis was to understand the impact of sepsis on cardiovascular function during pregnancy using a polymicrobial sepsis model in rodents. In addition, the impact of treatment with L-257, a DDAH1-selective inhibitor on maternal outcomes during septic shock in pregnancy was investigated. Mortality was significantly increased during pregnancy as compared to non-pregnant controls (10% vs 50%). Cardiovascular collapse ensued in the 24 hours preceding the humane endpoint in both groups and was comparable. The cytokine and chemokine response during pregnancy did not demonstrate an immunocompromised phenotype or Th1/Th2 bias. Leukocyte trafficking to lung was increased during pregnancy and appeared to be exaggerated as compared to non-pregnant controls. Bacterial load in blood and peritoneal fluid was not increased during pregnancy and nor were NO levels elevated. DDAH1 inhibition appeared to be valuable during sepsis in pregnancy. Findings indicated that treatment with L-257 and Imipenem treatment improved haemodynamic function, decreased the bacterial load and consequently improved survival in experimental septic shock to 50%. DDAH1 inhibition provided cardiovascular support without impairing the pathogen-specific immune response. Aortic cell lysate showed increased ADMA concentration following L-257 treatment. Therefore, DDAH1 inhibition may offer a new therapeutic pathway for pregnant women with septic shock and may result in better outcomes for both mothers and babies.Open Acces

Eckermann, Torsten: Kinder und ihre Peers beim kooperativen Lernen. Differenz bearbeiten - Unterschiede herstellen Wiesbaden: VS Verlag für Sozialwissenschaften 2017 (371 S.) [Rezension]

Rezension von: Eckermann, Torsten: Kinder und ihre Peers beim kooperativen Lernen. Differenz bearbeiten - Unterschiede herstellen Wiesbaden: VS Verlag für Sozialwissenschaften 2017 (371 S.; ISBN 978-3-658-15751-7; 49,99 EUR)

Individualität und Kooperation: Chancen und Herausforderungen gegenseitiger Ansätze

 Education in school is the social institute for pupils which not only involves to impart knowledge, but it includes also the development of social skills. Unfortunately, it is that parents in Russia prefer for their children „family learning“ at home instead of sending them to school. The article discusses arguments in favour of cooperation between parents, teachers and science education in questions of education development. The theory of cooperation is a vital model of understanding social development instead of rivalry. It has both possibilities: development of individuality and development of mutuality by diversity. It is a way to support the reformation of education and of school. The reflexive student evaluations also nurture a positive mindset towards forms of cooperation