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Randall, Joshua C. ; Winkler, Thomas W. ; Kutalik, Zoltán ; I. Berndt, Sonja ; Jackson, Anne U. ; Monda, Keri L. ; Kilpeläinen, Tuomas O. ; Esko, Tõnu ; Mägi, Reedik ; Li, Shengxu ; Workalemahu, Tsegaselassie ; Feitosa, Mary F. ; Croteau-Chonka, Damien C. ; Day, Felix R. ; Fall, Tove ; Ferreira, Teresa ; Gustafsson, Stefan ; Locke, Adam E. ; Mathieson, Iain ; Scherag, André ; Vedantam, Sailaja ; Wood, Andrew R. ; Liang, Liming ; Steinthorsdottir, Valgerdur ; Thorleifsson, Gudmar ; Dermitzakis, Emmanouil T. ; Dimas, Antigone S. ; Karpe, Fredrik ; Min, Josine L. ; Nicholson, George ; Clegg, Deborah J. ; Person, Thomas ; Krohn, Jon P. ; Bauer, Sabrina ; Buechler, Christa ; Eisinger, Kristina ; Bonnefond, Amélie ; Froguel, Philippe ; Hottenga, Jouke-Jan ; Prokopenko, Inga ; Waite, Lindsay L. ; Harris, Tamara B. ; Smith, Albert Vernon ; Shuldiner, Alan R. ; McArdle, Wendy L. ; Caulfield, Mark J. ; Munroe, Patricia B. ; Grönberg, Henrik ; Chen, Yii-Der Ida ; Li, Guo ; Beckmann, Jacques S. ; Johnson, Toby ; Thorsteinsdottir, Unnur ; Teder-Laving, Maris ; Khaw, Kay-Tee ; Wareham, Nicholas J. ; Zhao, Jing Hua ; Amin, Najaf ; Oostra, Ben A. ; Kraja, Aldi T. ; Province, Michael A. ; Cupples, L. Adrienne ; Heard-Costa, Nancy L. ; Kaprio, Jaakko ; Ripatti, Samuli ; Surakka, Ida ; Collins, Francis S. ; Saramies, Jouko ; Tuomilehto, Jaakko ; Jula, Antti ; Salomaa, Veikko ; Erdmann, Jeanette ; Hengstenberg, Christian ; Loley, Christina ; Schunkert, Heribert ; Lamina, Claudia ; Wichmann, Heinz Erich ; Albrecht, Eva ; Gieger, Christian ; Hicks, Andrew A. ; Johansson, Åsa ; Pramstaller, Peter P. ; Kathiresan, Sekar ; Speliotes, Elizabeth K. ; Penninx, Brenda W. J. H. ; Hartikainen, Anna-Liisa ; Jarvelin, Marjo-Riitta ; Gyllensten, Ulf ; Boomsma, Dorret I. ; Campbell, Harry ; Wilson, James F. ; Chanock, Stephen J. ; Farrall, Martin ; Goel, Anuj ; Medina-Gomez, Carolina ; Rivadeneira, Fernando ; Estrada, Karol ; Uitterlinden, André G. ; Hofman, Albert ; Zillikens, M. Carola ; Heijer, Martin den ; Kiemeney, Lambertus Adrianus ; Maschio, Andrea ; Hall, Per ; Tyrer, Jonathan ; Teumer, Alexander ; Völzke, Henry ; Kovacs, Peter ; Tönjes, Anke ; Mangino, Massimo ; Spector, Tim D. ; Hayward, Caroline ; Rudan, Igor ; Hall, Alistair S. ; Samani, Nilesh J. ; Attwood, Antony Paul ; Sambrook, Jennifer G. ; Hung, Joseph ; Palmer, Lyle J. ; Lokki, Marja-Liisa ; Sinisalo, Juha ; Boucher, Gabrielle ; Huikuri, Heikki ; Lorentzon, Mattias ; Ohlsson, Claes ; Eklund, Niina ; Eriksson, Johan G. ; Barlassina, Cristina ; Rivolta, Carlo ; Nolte, Ilja M. ; Snieder, Harold ; Klauw, Melanie M. van der ; Vliet-Ostaptchouk, Jana V. van ; Gejman, Pablo V. ; Shi, Jianxin ; Jacobs, Kevin B. ; Wang, Zhaoming ; Bakker, Stephan J. L. ; Mateo Leach, Irene ; Navis, Gerjan ; Harst, Pim van der ; Martin, Nicholas Gordon ; Medland, Sarah E. ; Montgomery, Grant W. ; Yang, Jian ; Chasman, Daniel I. ; Ridker, Paul M. ; Rose, Lynda M. ; Lehtimäki, Terho ; Raitakari, Olli ; Absher, Devin ; Iribarren, Carlos ; Basart, Hanneke ; Hovingh, Kees G. ; Hyppönen, Elina ; Power, Chris ; Power, Chris ; Anderson, Denise ; Beilby, John P. ; Hui, Jennie ; Jolley, Jennifer ; Sager, Hendrik ; Bornstein, Stefan R. ; Schwarz, Peter E. H. ; Kristiansson, Kati ; Perola, Markus ; Lindström, Jaana ; Swift, Amy J. ; Uusitupa, Matti ; Atalay, Mustafa ; Lakka, Timo A. ; Rauramaa, Rainer ; Bolton, Jennifer L. ; Fowkes, Gerry ; Fraser, Ross M. ; Price, Jackie F. ; Fischer, Krista ; KrjutÅ¡kov, Kaarel ; Metspalu, Andres ; Mihailov, Evelin ; Langenberg, Claudia ; Luan, Jian'an ; Ong, Ken K. ; Chines, Peter S. ; Keinanen-Kiukaanniemi, Sirkka M. ; Saaristo, Timo E. ; Edkins, Sarah ; Franks, Paul W. ; Hallmans, Göran ; Shungin, Dmitry ; Morris, Andrew David ; Palmer, Colin N. A. ; Erbel, Raimund ; Moebus, Susanne ; Nöthen, Markus Maria ; Pechlivanis, Sonali ; Hveem, Kristian ; Narisu, Narisu ; Hamsten, Anders ; Humphries, Steve E. ; Strawbridge, Rona J. ; Tremoli, Elena ; Grallert, Harald ; Thorand, Barbara ; Illig, Thomas ; Koenig, Wolfgang ; Müller-Nurasyid, Martina ; Peters, Annette ; Böhm, Bernhard O. ; Kleber, Marcus E. ; März, Winfried ; Winkelmann, Bernhard R. ; Kuusisto, Johanna ; Laakso, Markku ; Arveiler, Dominique ; Cesana, Giancarlo ; Kuulasmaa, Kari ; Virtamo, Jarmo ; Yarnell, John W. G. ; Kuh, Diana ; Wong, Andrew ; Lind, Lars ; Faire, Ulf de ; Gigante, Bruna ; Magnusson, Patrik K. E. ; Pedersen, Nancy L. ; Dedoussis, George ; Dimitriou, Maria ; Kolovou, Genovefa ; Kanoni, Stavroula ; Stirrups, Kathleen ; Bonnycastle, Lori L. ; Njølstad, Inger ; Wilsgaard, Tom ; Ganna, Andrea ; Rehnberg, Emil ; Hingorani, Aroon ; Kivimaki, Mika ; Kumari, Meena ; Assimes, Themistocles L. ; Barroso, Inês ; Boehnke, Michael ; Borecki, Ingrid B. ; Deloukas, Panos ; Fox, Caroline S. ; Frayling, Timothy ; Groop, Leif C. ; Haritunians, Talin ; Hunter, David ; Ingelsson, Erik ; Kaplan, Robert ; Mohlke, Karen L. ; North, Kari E. ; Lindgren, Cecilia M. ; Qi, Lu ; Loos, Ruth J. F. ; Heid, Iris M. ; Hirschhorn, Joel N. ; McCarthy, Mark I. ; Abecasis, Gonçalo R. ; Stefansson, Kari ; Strachan, David P. ; Schlessinger, David ; O'Connell, Jeffrey R. ; Duijn, Cornelia M. van
Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
Casey, Jillian P. ; Magalhães, Tiago R. ; Conroy, Judith M. ; Regan, Regina ; Shah, Naisha ; Anney, Richard ; Shields, Denis C. ; Abrahams, Brett S. ; Almeida, Joana ; Bacchelli, Elena ; Bailey, Anthony J. ; Baird, Gillian ; Battaglia, Agatino ; Berney, Tom ; Bolshakova, Nadia ; Bolton, Patrick F. ; Bourgeron, Thomas ; Brennan, Sean ; Cali, Phil ; Correia, Catarina ; Corsello, Christina ; Coutanche, Marc ; Dawson, Geraldine ; Jonge, Maretha de ; Delorme, Richard ; Duketis, Eftichia ; Duque, Frederico ; Estes, Annette ; Farrar, Penny ; Fernandez, Bridget A. ; Folstein, Susan E. ; Foley, Suzanne ; Fombonne, Eric ; Freitag, Christine M. ; Gilbert, John ; Gillberg, Christopher ; Glessner, Joseph T. ; Green, Jonathan ; Guter, Stephen J. ; Hakonarson, Hakon ; Holt, Richard ; Hughes, Gillian ; Hus, Vanessa ; Igliozzi, Roberta ; Kim, Cecilia ; Klauck, Sabine M. ; Kolevzon, Alexander ; Lamb, Janine A. ; Leboyer, Marion ; Le Couteur, Ann ; Leventhal, Bennett L. ; Lord, Catherine ; Lund, Sabata C. ; Maestrini, Elena ; Mantoulan, Carine ; Marshall, Christian R. ; McConachie, Helen ; McDougle, Christopher J. ; McGrath, Jane ; McMahon, William M. ; Merikangas, Alison ; Miller, Judith ; Minopoli, Fiorella ; Mirza, Ghazala K. ; Munson, Jeff ; Nelson, Stanley F. ; Nygren, Gudrun ; Oliveira, Guiomar ; Pagnamenta, Alistair T. ; Papanikolaou, Katerina ; Parr, Jeremy R. ; Parrini, Barbara ; Pickles, Andrew ; Pinto, Dalila ; Piven, Joseph ; Posey, David J. ; Poustka, Annemarie ; Poustka, Fritz ; Ragoussis, Jiannis ; Roge, Bernadette ; Rutter, Michael L. ; Sequeira, Ana F. ; Soorya, Latha ; Sousa, Inês ; Sykes, Nuala ; Stoppioni, Vera ; Tancredi, Raffaella ; Tauber, Maïté ; Thompson, Ann P. ; Thomson, Susanne ; Tsiantis, John ; Engeland, Herman van ; Vincent, John B. ; Volkmar, Fred ; Vorstman, Jacob A. S. ; Wallace, Simon ; Wang, Kai ; Wassink, Thomas H. ; White, Kathy ; Wing, Kirsty ; Wittemeyer, Kerstin ; Yaspan, Brian L. ; Zwaigenbaum, Lonnie ; Betancur, Catalina ; Buxbaum, Joseph D. ; Cantor, Rita M. ; Cook, Edwin H. ; Coon, Hilary ; Cuccaro, Michael L. ; Geschwind, Daniel H. ; Haines, Jonathan L. ; Hallmayer, Joachim ; Monaco, Anthony P. ; Nurnberger, John I. ; Pericak-Vance, Margaret Ann ; Schellenberg, Gerard D. ; Scherer, Stephen W. ; Sutcliffe, James S. ; Szatmari, Peter ; Vieland, Veronica J. ; Wijsman, Ellen M. ; Green, Andrew ; Gill, Michael ; Gallagher, Louise ; Vicente, Astrid M. ; Ennis, Sean
Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
Anney, Richard ; Klei, Lambertus ; Pinto, Dalila ; Almeida, Joana ; Bacchelli, Elena ; Baird, Gillian ; Bolshakova, Nadia ; Bölte, Sven ; Bolton, Patrick F. ; Bourgeron, Thomas ; Brennan, Sean ; Brian, Jessica ; Casey, Jillian ; Conroy, Judith ; Correia, Catarina ; Corsello, Christina ; Crawford, Emily L. ; Jonge, Maretha de ; Delorme, Richard ; Duketis, Eftichia ; Duque, Frederico ; Estes, Annette ; Farrar, Penny ; Fernandez, Bridget A. ; Folstein, Susan E. ; Fombonne, Eric ; Gilbert, John ; Gillberg, Christopher ; Glessner, Joseph T. ; Green, Andrew ; Green, Jonathan ; Guter, Stephen J. ; Heron, Elizabeth A. ; Holt, Richard ; Howe, Jennifer L. ; Hughes, Gillian ; Hus, Vanessa ; Igliozzi, Roberta ; Jacob, Suma ; Kenny, Graham P. ; Kim, Cecilia ; Kolevzon, Alexander ; Kustanovich, Vlad ; Lajonchere, Clara M. ; Lamb, Janine A. ; Law-Smith, Miriam ; Leboyer, Marion ; Le Couteur, Ann ; Leventhal, Bennett L. ; Liu, Xiao-Qing ; Lombard, Frances ; Lord, Catherine ; Lotspeich, Linda ; Lotspeich, Linda ; Lund, Sabata C. ; Magalhães, Tiago R. ; Mantoulan, Carine ; McDougle, Christopher J. ; Melhem, Nadine M. ; Merikangas, Alison ; Minshew, Nancy J. ; Mirza, Ghazala K. ; Munson, Jeff ; Noakes, Carolyn ; Nygren, Gudrun ; Papanikolaou, Katerina ; Pagnamenta, Alistair T. ; Parrini, Barbara ; Paton, Tara ; Paton, Tara ; Pickles, Andrew ; Posey, David J. ; Poustka, Fritz ; Ragoussis, Jiannis ; Regan, Regina ; Roberts, Wendy ; Roeder, Kathryn ; Roge, Bernadette ; Rutter, Michael L. ; Schlitt, Sabine ; Shah, Naisha ; Sheffield, Val C. ; Soorya, Latha ; Sousa, Inês ; Stoppioni, Vera ; Sykes, Nuala ; Tancredi, Raffaella ; Thompson, Ann P. ; Thomson, Susanne ; Tryfon, Ana ; Tsiantis, John ; Engeland, Herman van ; Vincent, John B. ; Volkmar, Fred ; Vorstman, JAS ; Wallace, Simon ; Wing, Kirsty ; Wittemeyer, Kerstin ; Wood, Shawn ; Zurawiecki, Danielle ; Zwaigenbaum, Lonnie ; Bailey, Anthony J. ; Battaglia, Agatino ; Cantor, Rita M. ; Coon, Hilary ; Cuccaro, Michael L. ; Dawson, Geraldine ; Ennis, Sean ; Freitag, Christine M. ; Geschwind, Daniel H. ; Haines, Jonathan L. ; Klauck, Sabine M. ; McMahon, William M. ; Maestrini, Elena ; Miller, Judith ; Monaco, Anthony P. ; Nelson, Stanley F. ; Nurnberger, John I. ; Oliveira, Guiomar ; Parr, Jeremy R. ; Pericak-Vance, Margaret Ann ; Piven, Joseph ; Schellenberg, Gerard D. ; Scherer, Stephen W. ; Vicente, Astrid M. ; Wassink, Thomas H. ; Wijsman, Ellen M. ; Betancur, Catalina ; Buxbaum, Joseph D. ; Cook, Edwin H. ; Gallagher, Louise ; Gill, Michael ; Hallmayer, Joachim ; Paterson, Andrew D. ; Sutcliffe, James S. ; Szatmari, Peter ; Vieland, Veronica J. ; Hakonarson, Hakon ; Devlin, Bernie
While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
Zeuschner, Philip Alexander ; Hölters, Sebastian ; Stöckle, Michael ; Seliger, Barbara ; Müller, Anja ; Bachmann, Hagen Sjard ; Grünwald, Viktor ; Christoph, Daniel C. ; Stenzl, Arnulf ; Grimm, Marc-Oliver ; Brüning, Fabian ; Goebell, Peter Jürgen ; Augustin, Marinela ; Roos, Frederik ; Harde, Johanna ; Benz-Rüd, Iris ; Staehler, Michael ; Junker, Kerstin
Simple Summary: Treatment of metastatic renal cell carcinoma (mRCC) remains a challenge due to the lack of biomarkers indicating the optimal drug for each patient. This study analyzed blood samples of patients with predominant clear cell mRCC who were treated with the mTOR inhibitor everolimus after failure of one prior tumor therapy. In an exploratory approach, predictive blood biomarkers were searched. We found lower levels of the protein thrombospondin-2 (TSP-2) at the start of the therapy and higher lactate dehydrogenase (LDH) levels in serum two weeks after therapy initiation to be associated with therapy response. Of note, these blood biomarkers had a higher predictive value than baseline patient parameters or risk classifications. Polymorphisms in the mTOR gene appeared to be associated with therapy response, but were not significant. To conclude, it seems feasible to identify patients showing longtime responses to everolimus and possible to increase tumor therapy response rates based on biomarkers for individual therapy selection.
Abstract: There is an unmet need for predictive biomarkers in metastatic renal cell carcinoma (mRCC) therapy. The phase IV MARC-2 trial searched for predictive blood biomarkers in patients with predominant clear cell mRCC who benefit from second-line treatment with everolimus. In an exploratory approach, potential biomarkers were assessed employing proteomics, ELISA, and polymorphism analyses. Lower levels of angiogenesis-related protein thrombospondin-2 (TSP-2) at baseline (≤665 parts per billion, ppb) identified therapy responders with longer median progression-free survival (PFS; ≤665 ppb at baseline: 6.9 months vs. 1.8, p = 0.005). Responders had higher lactate dehydrogenase (LDH) levels in serum two weeks after therapy initiation (>27.14 nmol/L), associated with a longer median PFS (3.8 months vs. 2.2, p = 0.013) and improved overall survival (OS; 31.0 months vs. 14.0 months, p < 0.001). Baseline TSP-2 levels had a stronger relation to PFS (HR 0.36, p = 0.008) than baseline patient parameters, including IMDC score. Increased serum LDH levels two weeks after therapy initiation were the best predictor for OS (HR 0.21, p < 0.001). mTOR polymorphisms appeared to be associated with therapy response but were not significant. Hence, we identified TSP-2 and LDH as promising predictive biomarkers for therapy response on everolimus after failure of one VEGF-targeted therapy in patients with clear cell mRCC.
Bracht, Eva ; Monzani, Lucas ; Boer, Diana ; Haslam, S. Alexander ; Kerschreiter, Rudolf ; Lemoine, Jérémy E. ; Steffens, Niklas K. ; Akfirat, Serap Arslan ; Avanzi, Lorenzo ; Barghi, Bita ; Dumont, Kitty ; Edelmann, Charlotte M. ; Epitropaki, Olga ; Fransen, Katrien ; Gießner, Steffen R. ; Gleibs, Ilka Helene ; González, Roberto ; Laguía González, Ana ; Lipponen, Jukka ; Markovits, Yannis ; Molero, Fernando ; Moriano, Juan A. ; Neves, Pedro D. ; Orosz, Gábor ; Roland-Lévy, Christine ; Schuh, Sebastian C. ; Sekiguchi, Tomoki ; Song, Lynda Jiwen ; Story, Joana S. P. ; Stouten, Jeroen ; Tatachari, Srinivasan ; Valdenegro, Daniel ; Bunderen, Lisanne van ; Vörös, Viktor ; Humborstad, Sut I. Wong ; Youssef, Farida ; Zhang, Xin-an ; Dick, Rolf van
Innovation is considered essential for today's organizations to survive and thrive. Researchers have also stressed the importance of leadership as a driver of followers' innovative work behavior (FIB). Yet, despite a large amount of research, three areas remain understudied: (a) The relative importance of different forms of leadership for FIB; (b) the mechanisms through which leadership impacts FIB; and (c) the degree to which relationships between leadership and FIB are generalizable across cultures. To address these lacunae, we propose an integrated model connecting four types of positive leadership behaviors, two types of identification (as mediating variables), and FIB. We tested our model in a global data set comprising responses of N = 7,225 participants from 23 countries, grouped into nine cultural clusters. Our results indicate that perceived LMX quality was the strongest relative predictor of FIB. Furthermore, the relationships between both perceived LMX quality and identity leadership with FIB were mediated by social identification. The indirect effect of LMX on FIB via social identification was stable across clusters, whereas the indirect effects of the other forms of leadership on FIB via social identification were stronger in countries high versus low on collectivism. Power distance did not influence the relations.
Dick, Rolf van ; Cordes, Berrit L. ; Lemoine, Jérémy E. ; Steffens, Niklas K. ; Haslam, S. Alexander ; Akfirat, Serap Arslan ; Ballada, Christine Joy A. ; Bazarov, Tahir ; Aruta, John Jamir Benzon ; Avanzi, Lorenzo ; Bodla, Ali Ahmad ; Bunjak, Aldijana ; Černe, Matej ; Dumont, Kitty ; Edelmann, Charlotte M. ; Epitropaki, Olga ; Fransen, Katrien ; García-Ael, Cristina ; Gießner, Steffen R. ; Gleibs, Ilka Helene ; Godlewska-Werner, Dorota ; González, Roberto ; Kark, Ronit ; Laguia Gonzalez, Ana ; Lam, Hodar ; Lipponen, Jukka ; Lupina-Wegener, Anna ; Markovits, Yannis ; Maskor, Mazlan ; Molero, Fernando ; Monzani, Lucas ; Moriano Leon, Juan A. ; Neves, Pedro ; Orosz, Gábor ; Pandey, Diwakar ; Retowski, Sylwiusz ; Roland-Lévy, Christine ; Samekin, Adil ; Schuh, Sebastian C. ; Sekiguchi, Tomoki ; Song, Lynda Jiwen ; Story, Joana ; Stouten, Jeroen ; Sultanova, Lilia ; Tatachari, Srinivasan ; Valdenegro, Daniel ; Bunderen, Lisanne van ; Van Dijk, Dina ; Humborstad, Sut I. Wong ; Youssef, Farida ; Zhang, Xin-an ; Kerschreiter, Rudolf
Do leaders who build a sense of shared social identity in their teams thereby protect them from the adverse effects of workplace stress? This is a question that the present paper explores by testing the hypothesis that identity leadership contributes to stronger team identification among employees and, through this, is associated with reduced burnout. We tested this model with unique datasets from the Global Identity Leadership Development (GILD) project with participants from all inhabited continents. We compared two datasets from 2016/2017 (n = 5290; 20 countries) and 2020/2021 (n = 7294; 28 countries) and found very similar levels of identity leadership, team identification and burnout across the five years. An inspection of the 2020/2021 data at the onset of and later in the COVID-19 pandemic showed stable identity leadership levels and slightly higher levels of both burnout and team identification. Supporting our hypotheses, we found almost identical indirect effects (2016/2017, b = −0.132; 2020/2021, b = −0.133) across the five-year span in both datasets. Using a subset of n = 111 German participants surveyed over two waves, we found the indirect effect confirmed over time with identity leadership (at T1) predicting team identification and, in turn, burnout, three months later. Finally, we explored whether there could be a “too-much-of-a-good-thing” effect for identity leadership. Speaking against this, we found a u-shaped quadratic effect whereby ratings of identity leadership at the upper end of the distribution were related to even stronger team identification and a stronger indirect effect on reduced burnout.
Stoev, Pavel ; Komerički, Ana ; Akkari, Nesrine ; Liu, Shanlin ; Zhou, Xin ; Weigand, Alexander ; Hostens, Jeroen ; Hunter, Christopher I. ; Edmunds, Scott C. ; Porco, David ; Zapparoli, Marzio ; Georgiev, Teodor ; Mietchen, Daniel ; Roberts, David ; Faulwetter, Sarah ; Smith, Vincent ; Penev, Lyubomir
We demonstrate how a classical taxonomic description of a new species can be enhanced by applying new generation molecular methods, and novel computing and imaging technologies. A cave-dwelling centipede, Eupolybothrus cavernicolus Komerički & Stoev sp. n. (Chilopoda: Lithobiomorpha: Lithobiidae), found in a remote karst region in Knin, Croatia, is the first eukaryotic species for which, in addition to the traditional morphological description, we provide a fully sequenced transcriptome, a DNA barcode, detailed anatomical X-ray microtomography (micro-CT) scans, and a movie of the living specimen to document important traits of its ex-situ behaviour. By employing micro-CT scanning in a new species for the first time, we create a high-resolution morphological and anatomical dataset that allows virtual reconstructions of the specimen and subsequent interactive manipulation to test the recently introduced ‘cybertype’ notion. In addition, the transcriptome was recorded with a total of 67,785 scaffolds, having an average length of 812 bp and N50 of 1,448 bp (see GigaDB). Subsequent annotation of 22,866 scaffolds was conducted by tracing homologs against current available databases, including Nr, SwissProt and COG. This pilot project illustrates a workflow of producing, storing, publishing and disseminating large data sets associated with a description of a new taxon. All data have been deposited in publicly accessible repositories, such as GigaScience GigaDB, NCBI, BOLD, Morphbank and Morphosource, and the respective open licenses used ensure their accessibility and re-usability.
The MR signal is sensitive to diffusion. This effect can be increased by the use of large, balanced bipolar gradients. The gradient systems of MR scanners are calibrated at installation and during regular servicing visits. Because the measured apparent diffusion constant (ADC) depends on the square of the amplitude of the diffusion sensitizing gradients, errors in the gradient calibration are exaggerated. If the error is varying among the different gradient axes, it will affect the estimated degree of anisotropy. To assess the gradient calibration accuracy in a whole-body MRI scanner, ADC values were calculated for a uniform water phantom along each gradient direction while monitoring the temperature. Knowledge of the temperature allows the expected diffusion constant of water to be calculated independent of the MRI measurement. It was found that the gradient axes (±x, ±y, ±z) were calibrated differently, resulting in offset ADC values. A method is presented to rescale the amplitude of each of the six principal gradient axes within the MR pulse sequence. The scaling factor is the square root of the ratio of the expected and observed diffusion constants. In addition, fiber tracking results in the human brain were noticeably affected by improving the gradient system calibration. Magn Reson Med 58:763–768, 2007. © 2007 Wiley-Liss, Inc. Keywords: diffusion tensor imaging, apparent diffusion constant, magnetic field gradient, fibre tracking, anisotropy
Hoogakker, Babette A. A. ; Smith, Robin S. ; Singarayer, Joy ; Marchant, Robert ; Prentice, I. Colin ; Allen, Judy R. M. ; Anderson, R. Scott ; Bhagwat, Shonil A. ; Behling, Hermann ; Borisova, Olga ; Bush, Mark B. ; Correa-Metrio, Alexander ; De Vernal, Anne ; Finch, Jemma M. ; Fréchette, Bianca ; Lozano-García, Socorro ; Gosling, William D. ; Granoszewski, Wojciech ; Grimm, Eric C. ; Grüger, Eberhard ; Hanselman, Jennifer ; Harrison, Sandy P. ; Hill, Trevor R. ; Huntley, Brian ; Jimenez-Moreno, Gonzalo ; Kershaw, Arnold Peter ; Ledru, Marie-Pierre ; Magri, Donatella ; McKenzie, Merna ; Müller, Ulrich ; Nakagawa, Takeshi ; Novenko, Elena ; Penny, Daniel ; Sadori, Laura ; Scott, Louis ; Stevenson, Janelle ; Valdes, Paul J. ; Vandergoes, Marcus ; Velichko, Andrey ; Whitlock, Cathy ; Tzedakis, Chronis
A new global synthesis and biomization of long (> 40 kyr) pollen-data records is presented, and used with simulations from the HadCM3 and FAMOUS climate models to analyse the dynamics of the global terrestrial biosphere and carbon storage over the last glacial–interglacial cycle. Global modelled (BIOME4) biome distributions over time generally agree well with those inferred from pollen data. The two climate models show good agreement in global net primary productivity (NPP). NPP is strongly influenced by atmospheric carbon dioxide (CO2) concentrations through CO2 fertilization. The combined effects of modelled changes in vegetation and (via a simple model) soil carbon result in a global terrestrial carbon storage at the Last Glacial Maximum that is 210–470 Pg C less than in pre-industrial time. Without the contribution from exposed glacial continental shelves the reduction would be larger, 330–960 Pg C. Other intervals of low terrestrial carbon storage include stadial intervals at 108 and 85 kaBP, and between 60 and 65 kaBP during Marine Isotope Stage 4. Terrestrial carbon storage, determined by the balance of global NPP and decomposition, influences the stable carbon isotope composition (δ 13C) of seawater because terrestrial organic carbon is depleted in 13C. Using a simple carbon-isotope mass balance equation we find agreement in trends between modelled ocean δ 13C based on modelled land carbon storage, and palaeo-archives of ocean δ 13C, confirming that terrestrial carbon storage variations may be important drivers of ocean δ 13 C changes.
Hoogakker, Babette A. A. ; Smith, Robin S. ; Singarayer, Joy ; Marchant, Robert ; Prentice, I. Colin ; Allen, Judy R. M. ; Anderson, R. Scott ; Bhagwat, Shonil A. ; Behling, Hermann ; Borisova, Olga ; Bush, Mark B. ; Correa-Metrio, Alexander ; De Vernal, Anne ; Finch, Jemma M. ; Fréchette, Bianca ; Lozano-García, Socorro ; Gosling, William D. ; Granoszewski, Wojciech ; Grimm, Eric C. ; Grüger, Eberhard ; Hanselman, Jennifer ; Harrison, Sandy P. ; Hill, Trevor R. ; Huntley, Brian ; Jimenez-Moreno, Gonzalo ; Kershaw, Arnold Peter ; Ledru, Marie-Pierre ; Magri, Donatella ; McKenzie, Merna ; Müller, Ulrich ; Nakagawa, Takeshi ; Novenko, Elena ; Penny, Daniel ; Sadori, Laura ; Scott, Louis ; Stevenson, Janelle ; Valdes, Paul J. ; Vandergoes, Marcus ; Velichko, Andrey ; Whitlock, Cathy ; Tzedakis, Chronis
A new global synthesis and biomization of long (> 40 kyr) pollen-data records is presented and used with simulations from the HadCM3 and FAMOUS climate models and the BIOME4 vegetation model to analyse the dynamics of the global terrestrial biosphere and carbon storage over the last glacial–interglacial cycle. Simulated biome distributions using BIOME4 driven by HadCM3 and FAMOUS at the global scale over time generally agree well with those inferred from pollen data. Global average areas of grassland and dry shrubland, desert, and tundra biomes show large-scale increases during the Last Glacial Maximum, between ca. 64 and 74 ka BP and cool substages of Marine Isotope Stage 5, at the expense of the tropical forest, warm-temperate forest, and temperate forest biomes. These changes are reflected in BIOME4 simulations of global net primary productivity, showing good agreement between the two models. Such changes are likely to affect terrestrial carbon storage, which in turn influences the stable carbon isotopic composition of seawater as terrestrial carbon is depleted in 13C.