@article{GroopCooperPerkovicetal.2017, author = {Groop, Per-Henrik and Cooper, Mark E. and Perkovic, Vlado and Hocher, Berthold and Kanasaki, Keizo and Haneda, Masakazu and Schernthaner, Guntram and Sharma, Kumar and Stanton, Robert C. and Toto, Robert and Cescutti, Jessica and Gordat, Maud and Meinicke, Thomas and Koitka-Weber, Audrey and Thiemann, Sandra and von Eynatten, Maximilian}, title = {Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction}, series = {Diabetes obesity \& metabolism : a journal of pharmacology and therapeutics}, volume = {19}, journal = {Diabetes obesity \& metabolism : a journal of pharmacology and therapeutics}, number = {11}, publisher = {Wiley}, address = {Hoboken}, issn = {1462-8902}, doi = {10.1111/dom.13041}, pages = {1610 -- 1619}, year = {2017}, abstract = {Aims: The MARLINA-T2D study (ClinicalTrials. gov, NCT01792518) was designed to investigate the glycaemic and renal effects of linagliptin added to standard-of-care in individuals with type 2 diabetes and albuminuria. Methods: A total of 360 individuals with type 2 diabetes, HbA1c 6.5\% to 10.0\% (48-86 mmol/ mol), estimated glomerular filtration rate (eGFR) >= 30 mL/min/1.73 m(2) and urinary albumin-tocreatinine ratio (UACR) 30-3000 mg/g despite single agent renin-angiotensin-system blockade were randomized to double-blind linagliptin (n = 182) or placebo (n = 178) for 24 weeks. The primary and key secondary endpoints were change from baseline in HbA1c at week 24 and time-weighted average of percentage change from baseline in UACR over 24 weeks, respectively. Results: Baseline mean HbA1c and geometric mean (gMean) UACR were 7.8\% +/- 0.9\% (62.2 +/- 9.6 mmol/mol) and 126 mg/g, respectively; 73.7\% and 20.3\% of participants had microalbuminuria or macroalbuminuria, respectively. After 24 weeks, the placebo-adjusted mean change in HbA1c from baseline was -0.60\% (-6.6 mmol/mol) (95\% confidence interval [CI], -0.78 to -0.43 [-8.5 to -4.7 mmol/mol]; P <.0001). The placebo-adjusted gMean for time-weighted average of percentage change in UACR from baseline was -6.0\% (95\% CI, -15.0 to 3.0; P =.1954). The adverse-event profile, including renal safety and change in eGFR, was similar between the linagliptin and placebo groups. Conclusions: In individuals at early stages of diabetic kidney disease, linagliptin significantly improved glycaemic control but did not significantly lower albuminuria. There was no significant change in placebo-adjusted eGFR. Detection of clinically relevant renal effects of linagliptin may require longer treatment, as its main experimental effects in animal studies have been to reduce interstitial fibrosis rather than alter glomerular haemodynamics.}, language = {en} } @article{McLoughlinPalmerMakeigetal.2017, author = {McLoughlin, Grainne and Palmer, Jason and Makeig, Scott and Bigdely-Shamlo, Nima and Banaschewski, Tobias and Laucht, Manfred and Brandeis, D.}, title = {EEG Source Imaging Indices of Cognitive Control Show Associations with Dopamine System Genes}, series = {Brain Topography}, volume = {31}, journal = {Brain Topography}, number = {3}, publisher = {Springer}, address = {Dordrecht}, issn = {0896-0267}, doi = {10.1007/s10548-017-0601-z}, pages = {392 -- 406}, year = {2017}, abstract = {Cognitive or executive control is a critical mental ability, an important marker of mental illness, and among the most heritable of neurocognitive traits. Two candidate genes, catechol-O-methyltransferase (COMT) and DRD4, which both have a roles in the regulation of cortical dopamine, have been consistently associated with cognitive control. Here, we predicted that individuals with the COMT Met/Met allele would show improved response execution and inhibition as indexed by event-related potentials in a Go/NoGo task, while individuals with the DRD4 7-repeat allele would show impaired brain activity. We used independent component analysis (ICA) to separate brain source processes contributing to high-density EEG scalp signals recorded during the task. As expected, individuals with the DRD4 7-repeat polymorphism had reduced parietal P3 source and scalp responses to response (Go) compared to those without the 7-repeat. Contrary to our expectation, the COMT homozygous Met allele was associated with a smaller frontal P3 source and scalp response to response-inhibition (NoGo) stimuli, suggesting that while more dopamine in frontal cortical areas has advantages in some tasks, it may also compromise response inhibition function. An interaction effect emerged for P3 source responses to Go stimuli. These were reduced in those with both the 7-repeat DRD4 allele and either the COMT Val/Val or the Met/Met homozygous polymorphisms but not in those with the heterozygous Val/Met polymorphism. This epistatic interaction between DRD4 and COMT replicates findings that too little or too much dopamine impairs cognitive control. The anatomic and functional separated maximally independent cortical EEG sources proved more informative than scalp channel measures for genetic studies of brain function and thus better elucidate the complex mechanisms in psychiatric illness.}, language = {en} } @article{SprengerErbanSeddigetal.2017, author = {Sprenger, Heike and Erban, Alexander and Seddig, Sylvia and Rudack, Katharina and Thalhammer, Anja and Le, Mai Q. and Walther, Dirk and Zuther, Ellen and Koehl, Karin I. and Kopka, Joachim and Hincha, Dirk K.}, title = {Metabolite and transcript markers for the prediction of potato drought tolerance}, series = {Plant Biotechnology Journal}, volume = {16}, journal = {Plant Biotechnology Journal}, number = {4}, publisher = {Wiley}, address = {Hoboken}, issn = {1467-7644}, doi = {10.1111/pbi.12840}, pages = {939 -- 950}, year = {2017}, abstract = {Potato (Solanum tuberosum L.) is one of the most important food crops worldwide. Current potato varieties are highly susceptible to drought stress. In view of global climate change, selection of cultivars with improved drought tolerance and high yield potential is of paramount importance. Drought tolerance breeding of potato is currently based on direct selection according to yield and phenotypic traits and requires multiple trials under drought conditions. Marker-assisted selection (MAS) is cheaper, faster and reduces classification errors caused by noncontrolled environmental effects. We analysed 31 potato cultivars grown under optimal and reduced water supply in six independent field trials. Drought tolerance was determined as tuber starch yield. Leaf samples from young plants were screened for preselected transcript and nontargeted metabolite abundance using qRT-PCR and GC-MS profiling, respectively. Transcript marker candidates were selected from a published RNA-Seq data set. A Random Forest machine learning approach extracted metabolite and transcript markers for drought tolerance prediction with low error rates of 6\% and 9\%, respectively. Moreover, by combining transcript and metabolite markers, the prediction error was reduced to 4.3\%. Feature selection from Random Forest models allowed model minimization, yielding a minimal combination of only 20 metabolite and transcript markers that were successfully tested for their reproducibility in 16 independent agronomic field trials. We demonstrate that a minimum combination of transcript and metabolite markers sampled at early cultivation stages predicts potato yield stability under drought largely independent of seasonal and regional agronomic conditions.}, language = {en} } @article{TorranceNottbuschAlvesetal.2017, author = {Torrance, Mark and Nottbusch, Guido and Alves, Rui A. and Arfe, Barbara and Chanquoy, Lucile and Chukharev-Hudilainen, Evgeny and Dimakos, Ioannis and Fidalgo, Raquel and Hyona, Jukka and Johannesson, Omar I. and Madjarov, George and Pauly, Dennis Nikolas and Uppstad, Per Henning and van Waes, Luuk and Vernon, Michael and Wengelin, Asa}, title = {Timed written picture naming in 14 European languages}, series = {Behavior research methods : a journal of the Psychonomic Society}, volume = {50}, journal = {Behavior research methods : a journal of the Psychonomic Society}, number = {2}, publisher = {Springer}, address = {New York}, issn = {1554-351X}, doi = {10.3758/s13428-017-0902-x}, pages = {744 -- 758}, year = {2017}, abstract = {We describe the Multilanguage Written Picture Naming Dataset. This gives trial-level data and time and agreement norms for written naming of the 260 pictures of everyday objects that compose the colorized Snodgrass and Vanderwart picture set (Rossion \& Pourtois in Perception, 33, 217-236, 2004). Adult participants gave keyboarded responses in their first language under controlled experimental conditions (N = 1,274, with subsamples responding in Bulgarian, Dutch, English, Finnish, French, German, Greek, Icelandic, Italian, Norwegian, Portuguese, Russian, Spanish, and Swedish). We measured the time to initiate a response (RT) and interkeypress intervals, and calculated measures of name and spelling agreement. There was a tendency across all languages for quicker RTs to pictures with higher familiarity, image agreement, and name frequency, and with higher name agreement. Effects of spelling agreement and effects on output rates after writing onset were present in some, but not all, languages. Written naming therefore shows name retrieval effects that are similar to those found in speech, but our findings suggest the need for cross-language comparisons as we seek to understand the orthographic retrieval and/or assembly processes that are specific to written output.}, language = {en} } @article{BrandEkkekakis2017, author = {Brand, Ralf and Ekkekakis, Panteleimon}, title = {Affective-Reflective Theory of physical inactivity and exercise}, series = {German Journal of Exercise and Sport Research}, volume = {48}, journal = {German Journal of Exercise and Sport Research}, number = {1}, publisher = {Springer}, address = {New York}, issn = {2509-3142}, doi = {10.1007/s12662-017-0477-9}, pages = {48 -- 58}, year = {2017}, abstract = {This article introduces a new theory, the Affective-Reflective Theory (ART) of physical inactivity and exercise. ART aims to explain and predict behavior in situations in which people either remain in a state of physical inactivity or initiate action (exercise). It is a dual-process model and assumes that exercise-related stimuli trigger automatic associations and a resulting automatic affective valuation of exercise (type-1 process). The automatic affective valuation forms the basis for the reflective evaluation (type-2 process), which can follow if self-control resources are available. The automatic affective valuation is connected with an action impulse, whereas the reflective evaluation can result in action plans. The two processes, in constant interaction, direct the individual towards or away from changing behavior. The ART of physical inactivity and exercise predicts that, when there is an affective-reflective discrepancy and self-control resources are low, behavior is more likely to be governed by the affective type-1 process. This introductory article explains the underlying concepts and main theoretical roots from which the ART of physical inactivity and exercise was developed (field theory, affective responses to exercise, automatic evaluation, evaluation-behavior link, dual-process theorizing). We also summarize the empirical tests that have been conducted to refine the theory in its present form.}, language = {en} } @article{IetswaartRosaWuetal.2017, author = {Ietswaart, Robert and Rosa, Stefanie and Wu, Zhe and Dean, Caroline and Howard, Martin}, title = {Cell-Size-Dependent Transcription of FLC and Its Antisense Long Non-coding RNA COOLAIR Explain Cell-to-Cell Expression Variation}, series = {Cell systems}, volume = {4}, journal = {Cell systems}, publisher = {Cell Press}, address = {Cambridge}, issn = {2405-4712}, doi = {10.1016/j.cels.2017.05.010}, pages = {622 -- 635}, year = {2017}, abstract = {Single-cell quantification of transcription kinetics and variability promotes a mechanistic understanding of gene regulation. Here, using single-molecule RNA fluorescence in situ hybridization and mathematical modeling, we dissect cellular RNA dynamics for Arabidopsis FLOWERING LOCUS C (FLC). FLC expression quantitatively determines flowering time and is regulated by antisense (COOLAIR) transcription. In cells without observable COOLAIR expression, we quantify FLC transcription initiation, elongation, intron processing, and lariat degradation, as well as mRNA release from the locus and degradation. In these heterogeneously sized cells, FLC mRNA number increases linearly with cell size, resulting in a large cell-to-cell variability in transcript level. This variation is accounted for by cell-sizedependent, Poissonian FLC mRNA production, but not by large transcriptional bursts. In COOLAIRexpressing cells, however, antisense transcription increases with cell size and contributes to FLC transcription decreasing with cell size. Our analysis therefore reveals an unexpected role for antisense transcription in modulating the scaling of transcription with cell size.}, language = {en} } @article{JonesArpWhitmanetal.2017, author = {Jones, Benjamin M. and Arp, Christopher D. and Whitman, Matthew S. and Nigro, Debora and Nitze, Ingmar and Beaver, John and Gadeke, Anne and Zuck, Callie and Liljedahl, Anna and Daanen, Ronald and Torvinen, Eric and Fritz, Stacey and Grosse, Guido}, title = {A lake-centric geospatial database to guide research and inform management decisions in an Arctic watershed in northern Alaska experiencing climate and land-use changes}, series = {AMBIO}, volume = {46}, journal = {AMBIO}, publisher = {Springer}, address = {Dordrecht}, issn = {0044-7447}, doi = {10.1007/s13280-017-0915-9}, pages = {769 -- 786}, year = {2017}, abstract = {Lakes are dominant and diverse landscape features in the Arctic, but conventional land cover classification schemes typically map them as a single uniform class. Here, we present a detailed lake-centric geospatial database for an Arctic watershed in northern Alaska. We developed a GIS dataset consisting of 4362 lakes that provides information on lake morphometry, hydrologic connectivity, surface area dynamics, surrounding terrestrial ecotypes, and other important conditions describing Arctic lakes. Analyzing the geospatial database relative to fish and bird survey data shows relations to lake depth and hydrologic connectivity, which are being used to guide research and aid in the management of aquatic resources in the National Petroleum Reserve in Alaska. Further development of similar geospatial databases is needed to better understand and plan for the impacts of ongoing climate and land-use changes occurring across lake-rich landscapes in the Arctic.}, language = {en} } @article{KroepflMarschallFrancesconietal.2017, author = {Kr{\"o}pfl, Nina and Marschall, Talke A. and Francesconi, Kevin A. and Schwerdtle, Tanja and Kuehnelt, Doris}, title = {Quantitative determination of the sulfur-containing antioxidant ergothioneine by HPLC/ICP- QQQ-MS}, series = {Journal of Analytical Atomic Spectrometry}, volume = {32}, journal = {Journal of Analytical Atomic Spectrometry}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {0267-9477}, doi = {10.1039/c7ja00030h}, pages = {1571 -- 1581}, year = {2017}, abstract = {Interest in the sulfur-containing antioxidant ergothioneine calls for reliable analytical methods for its quantification. In this work, a method based on reversed-phase high performance liquid chromatography (RP-HPLC) coupled with elemental mass spectrometry detection in mass shift mode (inductively coupled plasma triple quadrupole mass spectrometry, ICP-QQQ-MS) using oxygen as the reaction gas was developed for the element-selective determination of ergothioneine in complex biological matrices. Application of an instrumental setup using a 6-port-valve and the introduction of a methanol gradient allowed the time-efficient analysis of samples containing strongly retained sulfur species besides ergothioneine without compromising ICPMS detection. In aqueous solution, limits of detection and quantification (LOD and LOQ) of the optimized method for m/z 32 -> 48 (SO+) were 0.23 mu g S per L and 0.80 mu g S per L, respectively; measurements in a complex matrix (human hepatocyte carcinoma cells, HepG2) resulted in an LOD of 0.6 mu g S per L and an LOQ of 2.3 mu g S per L. Recoveries of ergothioneine from cell pellets spiked with the analyte before cell lysis (97 +/- 3\%) matched those obtained for cell culture medium spiked before syringe filtration (96 +/- 9\%) demonstrating that sample preparation did not impair the quantitative determination of ergothioneine. When HepG2 cells were exposed to ergothioneine via the culture medium, they showed low absorption; approximately 3\% of the added ergothioneine was found in cell lysates, while most of it (>= 85\%) remained in the cell culture medium. The method is capable of separating ergothioneine from other biologically relevant sulfur-containing species and is expected to be of broad future use. Furthermore, the potential use for the simultaneous separation of selenium species, thereby extending the scope of possible applications, was demonstrated by applying it to water extracts of oyster mushrooms.}, language = {en} } @article{GanghofEppner2017, author = {Ganghof, Steffen and Eppner, Sebastian}, title = {Patterns of accountability and representation}, series = {Politics}, volume = {39}, journal = {Politics}, number = {1}, publisher = {Sage Publ.}, address = {London}, issn = {0263-3957}, doi = {10.1177/0263395717710566}, pages = {113 -- 130}, year = {2017}, abstract = {Arend Lijphart uses an average of five standardized variables - the executive-parties dimension (EPD) - to describe patterns of democracy and explain differences in democracies' performance. The article suggests ways to improve the descriptive part of the project. It argues that the EPD maps different approaches to achieving accountability and representation, rather than differences in consensus. This re-conceptualization leads to a more coherent and valid measurement. It is also argued that more systematic adjustments are needed for differences in constitutional structures (presidentialism and bicameralism). The article presents data on a revised EPD and its components for 36 democracies in the period from 1981 to 2010. As to the explanatory part of the project, we contend that the EPD often hinders adequate causal analysis rather than facilitating it. We show this by re-analysing democracies' performance with respect to turnout and capital punishment.}, language = {en} } @article{DolotovskayaBordalloHausetal.2017, author = {Dolotovskaya, Sofya and Bordallo, Juan Torroba and Haus, Tanja and Noll, Angela and Hofreiter, Michael and Zinner, Dietmar and Roos, Christian}, title = {Comparing mitogenomic timetrees for two African savannah primate genera (Chlorocebus and Papio)}, series = {Zoological Journal of the Linnean Society}, volume = {181}, journal = {Zoological Journal of the Linnean Society}, number = {2}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0024-4082}, doi = {10.1093/zoolinnean/zlx001}, pages = {471 -- 483}, year = {2017}, abstract = {Complete mitochondrial (mtDNA) genomes have proved to be useful in reconstructing primate phylogenies with higher resolution and confidence compared to reconstructions based on partial mtDNA sequences. Here, we analyse complete mtDNA genomes of African green monkeys (genus Chlorocebus), a widely distributed primate genus in Africa representing an interesting phylogeographical model for the evolution of savannah species. Previous studies on partial mtDNA sequences revealed nine major clades, suggesting several cases of para- and polyphyly among Chlorocebus species. However, in these studies, phylogenetic relationships among several clades were not resolved, and divergence times were not estimated. We analysed complete mtDNA genomes for ten Chlorocebus samples representing major mtDNA clades to find stronger statistical support in the phylogenetic reconstruction than in the previous studies and to estimate divergence times. Our results confirmed para- and polyphyletic relationships of most Chlorocebus species, while the support for the phylogenetic relationships between the mtDNA clades increased compared to the previous studies. Our results indicate an initial west-east division in the northern part of the Chlorocebus range with subsequent divergence into north-eastern and southern clades. This phylogeographic scenario contrasts with that for another widespread African savannah primate genus, the baboons (Papio), for which a dispersal from southern Africa into East and West Africa was suggested.}, language = {en} }