Showing papers by "University of Kiel published in 2009"
TL;DR: In the new version, procedures to analyze the power of tests based on single-sample tetrachoric correlations, comparisons of dependent correlations, bivariate linear regression, multiple linear regression based on the random predictor model, logistic regression, and Poisson regression are added.
Abstract: G*Power is a free power analysis program for a variety of statistical tests. We present extensions and improvements of the version introduced by Faul, Erdfelder, Lang, and Buchner (2007) in the domain of correlation and regression analyses. In the new version, we have added procedures to analyze the power of tests based on (1) single-sample tetrachoric correlations, (2) comparisons of dependent correlations, (3) bivariate linear regression, (4) multiple linear regression based on the random predictor model, (5) logistic regression, and (6) Poisson regression. We describe these new features and provide a brief introduction to their scope and handling.
20,778 citations
Queen's University Belfast1, Collège de France2, English Heritage3, University of Arizona4, University of Sheffield5, University of Oxford6, University of Minnesota7, University of Hohenheim8, University of Kiel9, Lawrence Livermore National Laboratory10, University of Bergen11, ETH Zurich12, University of Waikato13, Woods Hole Oceanographic Institution14, Swiss Federal Institute for Forest, Snow and Landscape Research15, Cornell University16, University of Bristol17, University of Glasgow18, University of California, Irvine19, University of New South Wales20
TL;DR: In this paper, Heaton, AG Hogg, KA Hughen, KF Kaiser, B Kromer, SW Manning, RW Reimer, DA Richards, JR Southon, S Talamo, CSM Turney, J van der Plicht, CE Weyhenmeyer
Abstract: Additional co-authors: TJ Heaton, AG Hogg, KA Hughen, KF Kaiser, B Kromer, SW Manning, RW Reimer, DA Richards, JR Southon, S Talamo, CSM Turney, J van der Plicht, CE Weyhenmeyer
13,605 citations
TL;DR: It is demonstrated that IL-6 is a critical tumor promoter during early CAC tumorigenesis and the NF-kappaB-IL-6-Stat3 cascade is an important regulator of the proliferation and survival of tumor-initiating IECs.
1,913 citations
National Institutes of Health1, University of Tübingen2, University of Coimbra3, University College London4, University of Luxembourg5, University of Lübeck6, Washington University in St. Louis7, University of Bonn8, University of Florida9, University of Kiel10, Baylor College of Medicine11, Scripps Research Institute12, AARP13, Penn State Milton S. Hershey Medical Center14
TL;DR: It is demonstrated that an unequivocal role for common genetic variants in the etiology of typical PD and population-specific genetic heterogeneity in this disease is suggested, and supporting evidence that common variation around LRRK2 modulates risk for PD is provided.
Abstract: We performed a genome-wide association study (GWAS) in 1,713 individuals of European ancestry with Parkinson's disease (PD) and 3,978 controls. After replication in 3,361 cases and 4,573 controls, we observed two strong association signals, one in the gene encoding a-synuclein (SNCA; rs2736990, OR = 1.23, P = 2.24 x 10(-16)) and another at the MAPT locus (rs393152, OR = 0.77, P = 1.95 x 10(-16)). We exchanged data with colleagues performing a GWAS in Japanese PD cases. Association to PD at SNCA was replicated in the Japanese GWAS1, confirming this as a major risk locus across populations. We replicated the effect of a new locus detected in the Japanese cohort (PARK16, rs823128, OR = 0.66, P = 7.29 x 10(-8)) and provide supporting evidence that common variation around LRRK2 modulates risk for PD (rs1491923, OR = 1.14, P = 1.55 x 10(-5)). These data demonstrate an unequivocal role for common genetic variants in the etiology of typical PD and suggest population-specific genetic heterogeneity in this disease.
1,793 citations
TL;DR: The importance of lysosomal trafficking pathways is emphasized by recent findings that reveal new roles for lysOSomal membrane proteins in cellular physiology and in an increasing number of diseases that are characterized by defects inLysosome biogenesis.
Abstract: Lysosomes are the primary catabolic compartments of eukaryotic cells. They degrade extracellular material that has been internalized by endocytosis and intracellular components that have been sequestered by autophagy. In addition, specialized cells contain lysosome-related organelles that store and secrete proteins for cell-type-specific functions. The functioning of a healthy cell is dependent on the proper targeting of newly synthesized lysosomal proteins. Accumulating evidence suggests that there are multiple lysosomal delivery pathways that together allow the regulated and sequential deposition of lysosomal components. The importance of lysosomal trafficking pathways is emphasized by recent findings that reveal new roles for lysosomal membrane proteins in cellular physiology and in an increasing number of diseases that are characterized by defects in lysosome biogenesis.
1,342 citations
University of Michigan1, University of Utah2, Washington University in St. Louis3, University of Kiel4, University of Toronto5, Memorial University of Newfoundland6, Celera Corporation7, Emory University8, Université Paris-Saclay9, University of California, San Francisco10, Baylor University Medical Center11, Veterans Health Administration12
TL;DR: The results provide strong support for the association of at least seven genetic loci and psoriasis (each with combined P < 5 × 10−8) and suggest priority targets for study in other auto-immune disorders.
Abstract: Psoriasis is a common immune-mediated disorder that affects the skin, nails and joints. To identify psoriasis susceptibility loci, we genotyped 438,670 SNPs in 1,409 psoriasis cases and 1,436 controls of European ancestry. We followed up 21 promising SNPs in 5,048 psoriasis cases and 5,041 controls. Our results provide strong support for the association of at least seven genetic loci and psoriasis (each with combined P < 5 x 10(-8)). Loci with confirmed association include HLA-C, three genes involved in IL-23 signaling (IL23A, IL23R, IL12B), two genes that act downstream of TNF-alpha and regulate NF-kappaB signaling (TNIP1, TNFAIP3) and two genes involved in the modulation of Th2 immune responses (IL4, IL13). Although the proteins encoded in these loci are known to interact biologically, we found no evidence for epistasis between associated SNPs. Our results expand the catalog of genetic loci implicated in psoriasis susceptibility and suggest priority targets for study in other auto-immune disorders.
1,207 citations
TL;DR: The Indian Ocean Dipole (IOD) events are often triggered by ENSO but can also occur independently, subject to eastern tropical preconditioning as mentioned in this paper, and the Indian Ocean has been discovered to have a much larger impact on climate variability than previously thought.
Abstract: In recent years, the Indian Ocean (IO) has been discovered to have a much larger impact on climate variability than previously thought This paper reviews climate phenomena and processes in which the IO is, or appears to be, actively involved We begin with an update of the IO mean circulation and monsoon system It is followed by reviews of ocean/atmosphere phenomenon at intraseasonal, interannual, and longer time scales Much of our review addresses the two important types of interannual variability in the IO, El Nino–Southern Oscillation (ENSO) and the recently identified Indian Ocean Dipole (IOD) IOD events are often triggered by ENSO but can also occur independently, subject to eastern tropical preconditioning Over the past decades, IO sea surface temperatures and heat content have been increasing, and model studies suggest significant roles of decadal trends in both the Walker circulation and the Southern Annular Mode Prediction of IO climate variability is still at the experimental stage, with varied success Essential requirements for better predictions are improved models and enhanced observations
1,144 citations
Harvard University1, Broad Institute2, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico3, McMaster University4, McGill University5, University of Leicester6, University of Lübeck7, University of Pennsylvania8, Vanderbilt University9, University of Missouri–Kansas City10, University of Münster11, University of Verona12, Queen's University Belfast13, University of Washington14, Boston University15, University of Helsinki16, National Institute for Health and Welfare17, Lund University18, University of Cambridge19, Vita-Salute San Raffaele University20, University of Ferrara21, University of Turin22, Hebrew University of Jerusalem23, University of Girona24, University of Milan25, University of Leeds26, University of Regensburg27, Ludwig Maximilian University of Munich28, University of Kiel29, Wellcome Trust Sanger Institute30, University of Paris31, MedStar Washington Hospital Center32, deCODE genetics33, University of Iceland34
TL;DR: SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with my Cardiovascular Infarction risk.
Abstract: We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls We carried out replication in an independent sample with an effective sample size of up to 19,492 SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations1, 2, 3, 4 (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9) We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10-3) We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk
1,092 citations
TL;DR: Voltage-oriented PI control of three-phase grid-connected pulsewidth-modulation rectifiers with LCL filters is addressed and an experimentally determined LCL filter transfer function is shown, which shows a lower resonance peak as expected from commonly used filter models.
Abstract: Voltage-oriented PI control of three-phase grid-connected pulsewidth-modulation rectifiers with LCL filters is addressed. LCL filters require resonance damping. Active resonance damping is state of the art to face the problem, but it is still under investigation because of the manifold solutions. It is often realized using many sensors and/or complex control algorithms. In contrast, pure PI control requires only one set of current sensors, and its implementation and design are rather simple and well known from the L filter control. PI control has already been shown to be a suitable solution also for LCL filters, but there are limitations. These are investigated in this paper. System stability is analyzed with respect to different ratios of LCL filter resonance and control frequencies. The latter are important parameters for system design and control. Both line and converter current control are analyzed. For a certain range of frequency ratios, the voltage-oriented PI control gives stable performance without additional feedback, but for ratios outside this range, stable operation is impossible. Experimental tests validate the theoretical results. In addition, an experimentally determined LCL filter transfer function is shown in this paper, which shows a lower resonance peak as expected from commonly used filter models.
697 citations
TL;DR: This paper attempts to summarize some ontogenetic and lifestyle traits that lead to an increased tolerance towards high environmental pCO2, and suggests that compensation of extracellular acid-base status in turn may be important in avoiding metabolic depression.
Abstract: . Future ocean acidification has the potential to adversely affect many marine organisms. A growing body of evidence suggests that many species could suffer from reduced fertilization success, decreases in larval- and adult growth rates, reduced calcification rates, and even mortality when being exposed to near-future levels (year 2100 scenarios) of ocean acidification. Little research focus is currently placed on those organisms/taxa that might be less vulnerable to the anticipated changes in ocean chemistry; this is unfortunate, as the comparison of more vulnerable to more tolerant physiotypes could provide us with those physiological traits that are crucial for ecological success in a future ocean. Here, we attempt to summarize some ontogenetic and lifestyle traits that lead to an increased tolerance towards high environmental pCO2. In general, marine ectothermic metazoans with an extensive extracellular fluid volume may be less vulnerable to future acidification as their cells are already exposed to much higher pCO2 values (0.1 to 0.4 kPa, ca. 1000 to 3900 μatm) than those of unicellular organisms and gametes, for which the ocean (0.04 kPa, ca. 400 μatm) is the extracellular space. A doubling in environmental pCO2 therefore only represents a 10% change in extracellular pCO2 in some marine teleosts. High extracellular pCO2 values are to some degree related to high metabolic rates, as diffusion gradients need to be high in order to excrete an amount of CO2 that is directly proportional to the amount of O2 consumed. In active metazoans, such as teleost fish, cephalopods and many brachyuran crustaceans, exercise induced increases in metabolic rate require an efficient ion-regulatory machinery for CO2 excretion and acid-base regulation, especially when anaerobic metabolism is involved and metabolic protons leak into the extracellular space. These ion-transport systems, which are located in highly developed gill epithelia, form the basis for efficient compensation of pH disturbances during exposure to elevated environmental pCO2. Compensation of extracellular acid-base status in turn may be important in avoiding metabolic depression. So far, maintained "performance" at higher seawater pCO2 (>0.3 to 0.6 kPa) has only been observed in adults/juveniles of active, high metabolic species with a powerful ion regulatory apparatus. However, while some of these taxa are adapted to cope with elevated pCO2 during their regular embryonic development, gametes, zygotes and early embryonic stages, which lack specialized ion-regulatory epithelia, may be the true bottleneck for ecological success – even of the more tolerant taxa. Our current understanding of which marine animal taxa will be affected adversely in their physiological and ecological fitness by projected scenarios of anthropogenic ocean acidification is quite incomplete. While a growing amount of empirical evidence from CO2 perturbation experiments suggests that several taxa might react quite sensitively to ocean acidification, others seem to be surprisingly tolerant. However, there is little mechanistic understanding on what physiological traits are responsible for the observed differential sensitivities (see reviews of Seibel and Walsh, 2003; Portner et al., 2004; Fabry et al., 2008; Portner, 2008). This leads us to the first very basic question of how to define general CO2 tolerance on the species level.
670 citations
TL;DR: The research concept and methodological framework presented here for discussion have initially been applied in different case studies and shall be developed further to provide a useful tool for the quantification and spatial modelling of multiple ecosystem services in different landscapes.
Abstract: Landscapes differ in their capacities to provide ecosystem goods and services, which are the benefits humans obtain from nature. Structures and functions of ecosystems needed to sustain the provision of ecosystem services are altered by various human activities. In this paper, a concept for the assessment of multiple ecosystem services is proposed as a basis for discussion and further development of a respective evaluation instrument. Using quantitative and qualitative assessment data in combination with land cover and land use information originated from remote sensing and GIS, impacts of human activities can be evaluated. The results reveal typical patterns of different ecosystems‘ capacities to provide ecosystem services. The proposed approach thus delivers useful integrative information for environmental management and landscape planning, aiming at a sustainable use of services provided by nature. The research concept and methodological framework presented here for discussion have initially been applied in different case studies and shall be developed further to provide a useful tool for the quantification and spatial modelling of multiple ecosystem services in different landscapes. An exemplary application of the approach dealing with food provision in the Halle-Leipzig region in Germany is presented. It shows typical patterns of ecosystem service distribution around urban areas. As the approach is new and still rather general, there is great potential for improvement, especially with regard to a data-based quantification of the numerous hypotheses, which were formulated as base for the assessment. Moreover, the integration of more detailed landscape information on different scales will be needed in future in order to take the heterogeneous distribution of landscape properties and values into account. Therefore, the purpose of this paper is to foster critical discussions on the methodological development presented here.
TL;DR: Impaired autophagic degradation contributes to the pathogenesis of several human diseases including lysosomal storage disorders and muscle diseases, and has been shown to possess important housekeeping and quality control functions that contribute to health and longevity.
Aberdeen Royal Infirmary1, Guy's and St Thomas' NHS Foundation Trust2, University of Amsterdam3, King's College London4, Charité5, University of Rome Tor Vergata6, University of Paris7, Technische Universität München8, University of Verona9, University of Manchester10, University of Cambridge11, University of Szeged12, University of Marburg13, University of Kiel14, Erasmus University Rotterdam15, University College Cork16
TL;DR: Phototherapy represents a safe and very effective treatment option for moderate to severe forms of psoriasis vulgaris and has a good cost-benefit ratio, but the potentially significant costs for, and time required of, the patient must be considered.
Abstract: Of the 131 studies on monotherapy or combination therapy assessed, 56 studies on the different forms of phototherapy fulfilled the criteria for inclusion in the guidelines. Approximately three-quarters of all patients treated with phototherapy attained at least a PASI 75 response after 4 to 6 weeks, and clearance was frequently achieved (levels of evidence 2 and 3). Phototherapy represents a safe and very effective treatment option for moderate to severe forms of psoriasis vulgaris. The onset of clinical effects occurs within 2 weeks. Of the unwanted side effects, UV erythema from overexposure is by far the most common and is observed frequently. With repeated or long-term use, the consequences of high, cumulative UV doses (such as premature aging of the skin) must be taken into consideration. In addition, carcinogenic risk is associated with oral PUVA and is probable for local PUVA and UVB. The practicability of the therapy is limited by spatial, financial, human, and time constraints on the part of the physician, as well as by the amount of time required by the patient. From the perspective of the cost-bearing institution, phototherapy has a good cost-benefit ratio. However, the potentially significant costs for, and time required of, the patient must be considered.
TL;DR: Sialylation leads to increased anti-inflammatory activity of IgG antibodies, facilitates the escape of microorganisms from the host's immune system, and in polymeric form is involved in the regulation of embryogenesis and neuronal growth and function.
TL;DR: In this paper, the authors provide nonspecialists working in the general area of digital communications with a comprehensive overview of this exciting research field, with focus on spatial multiplexing and spatial diversity techniques.
Abstract: The use of multiple antennas for wireless communication systems has gained overwhelming interest during the last decade - both in academia and industry. Multiple antennas can be utilized in order to accomplish a multiplexing gain, a diversity gain, or an antenna gain, thus enhancing the bit rate, the error performance, or the signal-to-noise-plus-interference ratio of wireless systems, respectively. With an enormous amount of yearly publications, the field of multiple-antenna systems, often called multiple-input multiple-output (MIMO) systems, has evolved rapidly. To date, there are numerous papers on the performance limits of MIMO systems, and an abundance of transmitter and receiver concepts has been proposed. The objective of this literature survey is to provide non-specialists working in the general area of digital communications with a comprehensive overview of this exciting research field. To this end, the last ten years of research efforts are recapitulated, with focus on spatial multiplexing and spatial diversity techniques. In particular, topics such as transmitter and receiver structures, channel coding, MIMO techniques for frequency-selective fading channels, diversity reception and space-time coding techniques, differential and non-coherent schemes, beamforming techniques and closed-loop MIMO techniques, cooperative diversity schemes, as well as practical aspects influencing the performance of multiple-antenna systems are addressed. Although the list of references is certainly not intended to be exhaustive, the publications cited will serve as a good starting point for further reading.
TL;DR: This study investigated 16 known FOXO3A SNPs in an extensive collection of 1,762 German centenarians/nonagenarians and younger controls and provided evidence that polymorphisms in this gene were indeed associated with the ability to attain exceptional old age, and confirmed the initial discovery in the Japanese sample.
Abstract: The human forkhead box O3A gene (FOXO3A) encodes an evolutionarily conserved key regulator of the insulin–IGF1 signaling pathway that is known to influence metabolism and lifespan in model organisms A recent study described 3 SNPs in the FOXO3A gene that were statistically significantly associated with longevity in a discovery sample of long-lived men of Japanese ancestry [Willcox et al (2008) Proc Natl Acad Sci USA 105:13987–13992] However, this finding required replication in an independent population Here, we have investigated 16 known FOXO3A SNPs in an extensive collection of 1,762 German centenarians/nonagenarians and younger controls and provide evidence that polymorphisms in this gene were indeed associated with the ability to attain exceptional old age The FOXO3A association was considerably stronger in centenarians than in nonagenarians, highlighting the importance of centenarians for genetic longevity research Our study extended the initial finding observed in Japanese men to women and indicates that both genders were likely to be equally affected by variation in FOXO3A Replication in a French centenarian sample generated a trend that supported the previous results Our findings confirmed the initial discovery in the Japanese sample and indicate FOXO3A as a susceptibility gene for prolonged survival in humans
TL;DR: The addition of sorafenib to CP did not improve any of the end points over placebo plus CP and cannot be recommended in the second-line setting for patients with advanced melanoma.
Abstract: Purpose This phase III, randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy and safety of sorafenib with carboplatin and paclitaxel (CP) in patients with advanced melanoma who had progressed on a dacarbazine- or temozolomide-containing regimen. Patients and Methods A total of 270 patients were randomly assigned to receive intravenous paclitaxel 225 mg/m2 plus intravenous carboplatin at area under curve 6 (AUC 6) on day 1 of a 21-day cycle followed by either placebo (n = 135) or oral sorafenib 400 mg (n = 135) twice daily on days 2 to 19. The primary efficacy end point was progression-free survival (PFS); secondary and tertiary end points included overall survival and incidence of best response, respectively. Results The median PFS was 17.9 weeks for the placebo plus CP arm and 17.4 weeks for the sorafenib plus CP arm (hazard ratio, 0.91; 99% CI, 0.63 to 1.31; two-sided log-rank test P = .49). Response rate was 11% with placebo versus 12% with sorafenib. Dermatologic e...
TL;DR: A comprehensive cytogenetic analysis of BCL2 and MYC status on all aggressive lymphomas may identify a group of high-risk patients who may benefit from chemotherapeutic regimens that include rituximab and/or BCL 2-targeted therapy.
TL;DR: The results indicate that 15q13.3 microdeletions constitute the most prevalent risk factor for common epilepsies identified to date.
Abstract: We identified 15q13.3 microdeletions encompassing the CHRNA7 gene in 12 of 1,223 individuals with idiopathic generalized epilepsy (IGE), which were not detected in 3,699 controls (joint P = 5.32 x 10(-8)). Most deletion carriers showed common IGE syndromes without other features previously associated with 15q13.3 microdeletions, such as intellectual disability, autism or schizophrenia. Our results indicate that 15q13.3 microdeletions constitute the most prevalent risk factor for common epilepsies identified to date.
King's College London1, Wellcome Trust Sanger Institute2, University of Cambridge3, University of Greifswald4, University of Lübeck5, University of Leicester6, University of Ottawa7, University of Pennsylvania8, University of Helsinki9, National Institutes of Health10, Broad Institute11, Harvard University12, European Bioinformatics Institute13, MedStar Washington Hospital Center14, Cambridge University Hospitals NHS Foundation Trust15, Imperial College London16, Children's Hospital of Philadelphia17, Leeds General Infirmary18, University of Regensburg19, GlaxoSmithKline20, Lund University21, Helsinki University Central Hospital22, Technische Universität München23, University of Kiel24, University of Washington25, Ludwig Maximilian University of Munich26, Queen Mary University of London27
TL;DR: A long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction is identified and it is shown that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.
Abstract: The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.
University of Lübeck1, University of Leicester2, University of Regensburg3, University of Leeds4, Harvard University5, French Institute of Health and Medical Research6, University of Washington7, Lund University8, National Institutes of Health9, Wellcome Trust Sanger Institute10, University of Milan11, University of Pavia12, Medical Research Council13, University of Mainz14, University of Kiel15, Synlab Group16, Medical University of Graz17, Heidelberg University18, Technische Universität München19, University of Cambridge20
TL;DR: A three-stage analysis of genome-wide SNP data in 1,222 German individuals with myocardial infarction and 1,298 controls is presented and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43 is identified.
Abstract: We present a three-stage analysis of genome-wide SNP data in 1,222 German individuals with myocardial infarction and 1,298 controls, in silico replication in three additional genome-wide datasets of coronary artery disease (CAD) and subsequent replication in similar to 25,000 subjects. We identified one new CAD risk locus on 3q22.3 in MRAS (P = 7.44 x 10(-13); OR = 1.15, 95% CI = 1.11-1.19), and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43 (P = 4.81 x 10(-7); OR = 1.08, 95% CI = 1.05-1.11).
TL;DR: Pheophytinase (PPH), a chloroplast-located and senescence-induced hydrolase widely distributed in algae and land plants, is identified and proposed that the sequence of early chlorophyll catabolic reactions be revised.
Abstract: During leaf senescence, chlorophyll is removed from thylakoid membranes and converted in a multistep pathway to colorless breakdown products that are stored in vacuoles. Dephytylation, an early step of this pathway, increases water solubility of the breakdown products. It is widely accepted that chlorophyll is converted into pheophorbide via chlorophyllide. However, chlorophyllase, which converts chlorophyll to chlorophyllide, was found not to be essential for dephytylation in Arabidopsis thaliana. Here, we identify pheophytinase (PPH), a chloroplast-located and senescence-induced hydrolase widely distributed in algae and land plants. In vitro, Arabidopsis PPH specifically dephytylates the Mg-free chlorophyll pigment, pheophytin (phein), yielding pheophorbide. An Arabidopsis mutant deficient in PPH (pph-1) is unable to degrade chlorophyll during senescence and therefore exhibits a stay-green phenotype. Furthermore, pph-1 accumulates phein during senescence. Therefore, PPH is an important component of the chlorophyll breakdown machinery of senescent leaves, and we propose that the sequence of early chlorophyll catabolic reactions be revised. Removal of Mg most likely precedes dephytylation, resulting in the following order of early breakdown intermediates: chlorophyll → pheophytin → pheophorbide. Chlorophyllide, the last precursor of chlorophyll biosynthesis, is most likely not an intermediate of breakdown. Thus, chlorophyll anabolic and catabolic reactions are metabolically separated.
University of Bremen1, University of Tübingen2, Autonomous University of Barcelona3, University of Kiel4, Oregon State University5, Alfred Wegener Institute for Polar and Marine Research6, Commonwealth Scientific and Industrial Research Organisation7, Aix-Marseille University8, Cardiff University9, Australian National University10, University of Barcelona11, National Taiwan Ocean University12, University of Bordeaux13, Université du Québec à Montréal14, University of Bergen15, University of Cambridge16, University of Limerick17, Newcastle University18, University of Sfax19, Dalhousie University20, University of Liverpool21, Université du Québec22, National Oceanography Centre23, Geoscience Australia24, University of California, Davis25
TL;DR: This article presented an updated synthesis of sea surface temperatures during the Last Glacial Maximum, rigorously defined as the period between 23 and 19 thousand years before present, from the Multiproxy Approach for the Reconstruction of the Glacial Ocean Surface (MARGO) project.
Abstract: Observation-based reconstructions of sea surface temperature from relatively stable periods in the past, such as the Last Glacial Maximum, represent an important means of constraining climate sensitivity and evaluating model simulations1. The first quantitative global reconstruction of sea surface temperatures during the Last Glacial Maximum was developed by the Climate Long-Range Investigation, Mapping and Prediction (CLIMAP) project in the 1970s and 1980s (refs 2, 3). Since that time, several shortcomings of that earlier effort have become apparent4. Here we present an updated synthesis of sea surface temperatures during the Last Glacial Maximum, rigorously defined as the period between 23 and 19 thousand years before present, from the Multiproxy Approach for the Reconstruction of the Glacial Ocean Surface (MARGO) project5. We integrate microfossil and geochemical reconstructions of surface temperatures and include assessments of the reliability of individual records. Our reconstruction reveals the presence of large longitudinal gradients in sea surface temperature in all of the ocean basins, in contrast to the simulations of the Last Glacial Maximum climate available at present6, 7.
TL;DR: Looking at the effects of quercetin supplementation on blood pressure, lipid metabolism, markers of oxidative stress, inflammation, and body composition in an at-risk population of overweight or obese subjects aged 25–65 years with metabolic syndrome traits provides further evidence that quercETin may provide protection against CVD.
Abstract: Regular consumption of flavonoids may reduce the risk for CVD. However, the effects of individual flavonoids, for example, quercetin, remain unclear. The present study was undertaken to examine the effects of quercetin supplementation on blood pressure, lipid metabolism, markers of oxidative stress, inflammation, and body composition in an at-risk population of ninety-three overweight or obese subjects aged 25-65 years with metabolic syndrome traits. Subjects were randomised to receive 150 mg quercetin/d in a double-blinded, placebo-controlled cross-over trial with 6-week treatment periods separated by a 5-week washout period. Mean fasting plasma quercetin concentrations increased from 71 to 269 nmol/l (P<0-001) during quercetin treatment. In contrast to placebo, quercetin decreased systolic blood pressure (SBP) by 2.6 mmHg (P<0.01) in the entire study group, by 2-9 mmHg (P<0.01) in the subgroup of hypertensive subjects and by 3-7 mmHg (P<0.001) in the subgroup of younger adults aged 25-50 years. Quercetin decreased serum HDL-cholesterol concentrations (P<0.001), while total cholesterol, TAG and the LDL:HDL-cholesterol and TAG:HDL-cholesterol ratios were unaltered. Quercetin significantly decreased plasma concentrations of atherogenic oxidised LDL, but did not affect TNF-alpha and C-reactive protein when compared with placebo. Quercetin supplementation had no effects on nutritional status. Blood parameters of liver and kidney function, haematology and serum electrolytes did not reveal any adverse effects of quercetin. In conclusion, quercetin reduced SBP and plasma oxidised LDL concentrations in overweight subjects with a high-CVD risk phenotype. Our findings provide further evidence that quercetin may provide protection against CVD.
French Institute of Health and Medical Research1, University of Lübeck2, University of Leicester3, University of Leeds4, Centre national de la recherche scientifique5, Queen's University Belfast6, Pasteur Institute of Lille7, Glasgow Royal Infirmary8, University of Kiel9, University of Regensburg10, Heidelberg University11, University of Cambridge12
TL;DR: The SLC22A3-LPAL2-LPA gene cluster is identified as a strong susceptibility locus for coronary artery disease through a genome-wide haplotype association (GWHA) study and may have wide utility for analyzing GWA data for other complex traits.
Abstract: We identify the SLC22A3-LPAL2-LPA gene cluster as a strong susceptibility locus for coronary artery disease (CAD) through a genome-wide haplotype association (GWHA) study. This locus was not identified from previous genome-wide association (GWA) studies focused on univariate analyses of SNPs. The proposed approach may have wide utility for analyzing GWA data for other complex traits.
TL;DR: Overexpression of CRLF2 was associated with activation of the JAK-STAT pathway in cell lines and transduced primary B-cell progenitors, sustaining their proliferation and indicating a causal role of C RLF2 overexpression in lymphoid transformation.
deCODE genetics1, Emory University2, University of Iceland3, University of Tromsø4, University Hospital of North Norway5, Norwegian University of Science and Technology6, Norwegian Institute of Public Health7, Vanderbilt University Medical Center8, The Chinese University of Hong Kong9, Ludwig Maximilian University of Munich10, University of Kiel11, University of Münster12, St George's, University of London13, Karolinska University Hospital14
TL;DR: A variant in the ZFHX3 gene on chromosome 16q22, rs7193343-T, associated significantly with AF is identified, and this variant also associated with ischemic stroke and cardioembolic stroke in a combined analysis of five stroke samples.
Abstract: Daniel Gudbjartsson and colleagues report a genome-wide association study for atrial fibrillation, a condition associated with increased risk of stroke. They report a variant in ZFHX3 associated with atrial fibrillation as well as ischemic stroke. We expanded our genome-wide association study on atrial fibrillation (AF) in Iceland, which previously identified risk variants on 4q25, and tested the most significant associations in samples from Iceland, Norway and the United States. A variant in the ZFHX3 gene on chromosome 16q22, rs7193343-T, associated significantly with AF (odds ratio OR = 1.21, P = 1.4 × 10−10). This variant also associated with ischemic stroke (OR = 1.11, P = 0.00054) and cardioembolic stroke (OR = 1.22, P = 0.00021) in a combined analysis of five stroke samples.
TL;DR: The major floral regulatory pathways are reviewed and current and novel strategies for altering bolting and flowering behavior in crop plants are discussed.
TL;DR: TNFAIP3 (A20), a key regulator of NF-κB activity, is identified as a novel tumor suppressor gene in cHL and PMBL and the significantly higher frequency of TNFAIP 3 mutations in EBV− than EBV+ cHL suggests complementing functions of TN FAIP3 inactivation and EBV infection in c HL pathogenesis.
Abstract: Proliferation and survival of Hodgkin and Reed/Sternberg (HRS) cells, the malignant cells of classical Hodgkin lymphoma (cHL), are dependent on constitutive activation of nuclear factor kappaB (NF-kappaB). NF-kappaB activation through various stimuli is negatively regulated by the zinc finger protein A20. To determine whether A20 contributes to the pathogenesis of cHL, we sequenced TNFAIP3, encoding A20, in HL cell lines and laser-microdissected HRS cells from cHL biopsies. We detected somatic mutations in 16 out of 36 cHLs (44%), including missense mutations in 2 out of 16 Epstein-Barr virus-positive (EBV(+)) cHLs and a missense mutation, nonsense mutations, and frameshift-causing insertions or deletions in 14 out of 20 EBV(-) cHLs. In most mutated cases, both TNFAIP3 alleles were inactivated, including frequent chromosomal deletions of TNFAIP3. Reconstitution of wild-type TNFAIP3 in A20-deficient cHL cell lines revealed a significant decrease in transcripts of selected NF-kappaB target genes and caused cytotoxicity. Extending the mutation analysis to primary mediastinal B cell lymphoma (PMBL), another lymphoma with constitutive NF-kappaB activity, revealed destructive mutations in 5 out of 14 PMBLs (36%). This report identifies TNFAIP3 (A20), a key regulator of NF-kappaB activity, as a novel tumor suppressor gene in cHL and PMBL. The significantly higher frequency of TNFAIP3 mutations in EBV(-) than EBV(+) cHL suggests complementing functions of TNFAIP3 inactivation and EBV infection in cHL pathogenesis.
TL;DR: In this paper, the authors compare methods to determine the degree of compactness (DC) and limits of field bulk density for plant growth under no-tillage in subtropical soils.
Abstract: The concept of degree of compactness (DC), referred to as field bulk density (BD) as a percentage of a reference bulk density (BD ref ), was developed to characterize compactness of soil frequently disturbed, but for undisturbed soil such as under no-tillage critical degree of compactness values have not been tested. The objective of this study was to compare methods to determine BD ref and limits of DC and BD for plant growth under no-tillage in subtropical soils. Data from the literature and other databases were used to establish relationships between BD and clay or clay plus silt content, and between DC and macroporosity and yield of crops under no-tillage in subtropical Brazil. Data of BD ref reached by the soil Proctor test on disturbed soil samples, by uniaxial compression with loads of 200 kPa on disturbed and undisturbed soil samples, and 400, 800 and 1600 kPa on undisturbed soil samples, were used. Also, comparisons were made with critical bulk density based on the least limiting water range (BDc LLWR) and on observed root and/or yield restriction in the field (BDc Rest). Using vertical uniaxial compression with a load of 200 kPa on disturbed or undisturbed samples generates low BD ref and high DC-values. The standard Proctor test generates higher BD ref -values, which are similar to those in a uniaxial test with a load of 1600 kPa for soils with low clay content but lower for soils with high clay content. The BDc LLWR does not necessarily restrict root growth or crop yield under no-tillage, since field investigations led to higher BDc Rest-values. A uniaxial load greater than 800 kPa is promising to determine BD ref for no-tillage soils. The BD ref is highly correlated to the clay content and thus pedotransfer functions may be established to estimate the former based on the latter. Soil ecological properties are affected before compaction restricts plant growth and yield. The DC is an efficient parameter to identify soil compaction affecting crops. The effect of compaction on ecological properties must also be further considered.