Mündliches Argumentieren im Spannungsfeld zwischen Kollaboration und Abgrenzung – Zu lokalen Gruppenidentitäten in schulischen Einigungsdiskussionen

There is a need for more precise descriptions of disfluency markers in the actual oral dialogic productions of learners of French as a foreign language to inform language pedagogy. This research aims at documenting communicative strategies used by learners of French when confronted with gaps in communication, namely phenomena of hesitation and repairs (repetition, self-correction and false start) occurring during SLA learners' spontaneous speech at different stages of proficiency. It is based on a longitudinal oral learner corpus of actual spontaneous speech by Jamaican learners of French. We will also compare the observed results with the descriptors available in the Common European Framework describing a conscious communicative strategy of self-correction and suggest pedagogical ways to improve oral communication

Focal structural variants revealed by whole genome sequencing disrupt the histone demethylase KDM4C in B cell lymphomas

Histone methylation-modifiers, like EZH2 and KMT2D, are recurrently altered in B-cell lymphomas. To comprehensively describe the landscape of alterations affecting genes encoding histone methylation-modifiers in lymphomagenesis we investigated whole genome and transcriptome data of 186 mature B-cell lymphomas sequenced in the ICGC MMML-Seq project. Besides confirming common alterations of KMT2D (47% of cases), EZH2 (17%), SETD1B (5%), PRDM9 (4%), KMT2C (4%), and SETD2 (4%) also identified by prior exome or RNAseq studies, we here unravel KDM4C in chromosome 9p24, encoding a histone demethylase, to be recurrently altered. Focal structural variation was the main mechanism of KDM4C alterations, which was independent from 9p24 amplification. We identified KDM4C alterations also in lymphoma cell lines including a focal homozygous deletion in a classical Hodgkin lymphoma cell line. By integrating RNAseq and genome sequencing data we predict KDM4C structural variants to result in loss-of-function. By functional reconstitution studies in cell lines, we provide evidence that KDM4C can act as tumor suppressor. Thus, we show that identification of structural variants in whole genome sequencing data adds to the comprehensive description of the mutational landscape of lymphomas and, moreover, establish KDM4C as putative tumor suppressive gene recurrently altered in subsets of B-cell derived lymphomas

DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control

Although Burkitt lymphomas and follicular lymphomas both have features of germinal center B cells, they are biologically and clinically quite distinct. Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples. Comparison of Burkitt and follicular lymphoma samples showed differential methylation of intragenic regions that strongly correlated with expression of associated genes, for example, genes active in germinal center dark-zone and light-zone B cells. Integrative pathway analyses of regions differentially methylated in Burkitt and follicular lymphomas implicated DNA methylation as cooperating with somatic mutation of sphingosine phosphate signaling, as well as the TCF3-ID3 and SWI/SNF complexes, in a large fraction of Burkitt lymphomas. Taken together, our results demonstrate a tight connection between somatic mutation, DNA methylation and transcriptional control in key B cell pathways deregulated differentially in Burkitt lymphoma and other germinal center B cell lymphomas

Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Sjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.Research reported in this publication was supported by the National Institutes of Health (NIH): R01AR073855 (C.J.L.), R01AR065953 (C.J.L.), R01AR074310 (A.D.F.), P50AR060804 (K.L.S.), R01AR050782 (K.L.S), R01DE018209 (K.L.S.), R33AR076803 (I.A.), R21AR079089 (I.A.); NIDCR Sjögren’s Syndrome Clinic and Salivary Disorders Unit were supported by NIDCR Division of Intramural Research at the National Institutes of Health funds - Z01-DE000704 (B.W.); Birmingham NIHR Biomedical Research Centre (S.J.B.); Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2155 – Projektnummer 390874280 (T.W.); Research Council of Norway (Oslo, Norway) – Grant 240421 (TR.R.), 316120 (M.W-H.); Western Norway Regional Health Authority (Helse Vest) – 911807, 912043 (R.O.); Swedish Research Council for Medicine and Health (L.R., G.N., M.W-H.); Swedish Rheumatism Association (L.R., G.N., M.W-H.); King Gustav V’s 80-year Foundation (G.N.); Swedish Society of Medicine (L.R., G.N., M.W-H.); Swedish Cancer Society (E.B.); Sjögren’s Syndrome Foundation (K.L.S.); Phileona Foundation (K.L.S.). The Stockholm County Council (M.W-H.); The Swedish Twin Registry is managed through the Swedish Research Council - Grant 2017-000641. The French ASSESS (Atteinte Systémique et Evolution des patients atteints de Syndrome de Sjögren primitive) was sponsored by Assistance Publique-Hôpitaux de Paris (Ministry of Health, PHRC 2006 P060228) and the French society of Rheumatology (X.M.).publishedVersio

Genome-wide association study identifies Sjögren's risk loci with functional implications in immune and glandular cells.

Sjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.We thank all the research and clinical staff, consortium investigators, and study participants (detailed in Supplementary Information), and funding agencies who made this study possible. The content of this publication is solely the responsibility of the authors and does not represent the official views of the funding agencies listed below. Research reported in this publication was supported by the National Institutes of Health (NIH): R01AR073855 (C.J.L.), R01AR065953 (C.J.L.), R01AR074310 (A.D.F.), P50AR060804 (K.L.S.), R01AR050782 (K.L.S), R01DE018209 (K.L.S.), R33AR076803 (I.A.), R21AR079089 (I.A.); NIDCR Sjögren’s Syndrome Clinic and Salivary Disorders Unit were supported by NIDCR Division of Intramural Research at the National Institutes of Health funds - Z01-DE000704 (B.W.); Birmingham NIHR Biomedical Research Centre (S.J.B.); Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2155 – Projektnummer 390874280 (T.W.); Research Council of Norway (Oslo, Norway) – Grant 240421 (TR.R.), 316120 (M.W-H.); Western Norway Regional Health Authority (Helse Vest) – 911807, 912043 (R.O.); Swedish Research Council for Medicine and Health (L.R., G.N., M.W-H.); Swedish Rheumatism Association (L.R., G.N., M.W-H.); King Gustav V’s 80-year Foundation (G.N.); Swedish Society of Medicine (L.R., G.N., M.W-H.); Swedish Cancer Society (E.B.); Sjögren’s Syndrome Foundation (K.L.S.); Phileona Foundation (K.L.S.). The Stockholm County Council (M.W-H.); FOREUM Foundation for Research in Rheumatology (R.J., M.W-H). The Swedish Twin Registry is managed through the Swedish Research Council - Grant 2017-000641. The French ASSESS (Atteinte Systémique et Evolution des patients atteints de Syndrome de Sjögren primitive) was sponsored by Assistance Publique-Hôpitaux de Paris (Ministry of Health, PHRC 2006 P060228) and the French society of Rheumatology (X.M.). We want to acknowledge the following invesigators who recruited patients: Jacques-Eric Gottenberg, Valerie Devauchelle-Pensec, Jean Jacques Dubost, Anne-Laure Fauchais, Vincent Goeb, Eric Hachulla, Claire Larroche, Véronique Le Guern, Jacques Morel, Aleth Perdriger, Emmanuelle Dernis, Stéphanie Rist, Damien Sene, Olivier Vittecoq. We also thank Sarah Tubiana and all staff members of the Bichat Hospital Biological Resource Center (Paris) for centralizing and managing biological collection. We also thank Rezvan Kiani Dehkordi, Karolina Tandre, Käth Nilsson, Marianne Eidsheim, Kjerstin Jacobsen, Ingeborg Kvivik and Kjetil Bårdsen for collecting patient blood samples. We acknowledge the SNP&SEQ Technology Platform, Uppsala, part of National Genomics Infrastructure (NGI) Sweden, for genotyping of Scandinavian samples, and the Swedish Twin Registry for access to data. The SNP&SEQ Technology Platform was supported by Science for Life Laboratory, Uppsala University, the Knut and Alice Wallenberg Foundation and the Swedish Research Council. Last, we thank the investigators for the following dbGaP studies: Phs000428.v2.p2: This study used control data from the Health and Retirement Study in dbGaP (phs000428.v2.p2) submitted by David Weir, PhD at the University of Michigan and funded by the National Institute of Aging RC2 AG036495 and RC4 AG039029. Phs000672.v1.p1: Genotype data from the Sjögren’s International Collaborative Clinical Alliance (SICCA) Registry was obtained through dbGAP accession number phs000672.v1.p1. This study was supported by the National Institute of Dental and Craniofacial Research (NIDCR), the National Eye Institute, and the Office of Research on Women’s Health through contract number N01-DE-32636. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health (NIH) to the Johns Hopkins University (contract numbers HHSN268200782096C, HHSN268201100011I, HHSN268201200008I). Funds for genotyping were provided by the NIDCR through CIDR’s NIH contract. Assistance with data cleaning and imputation was provided by the University of Washington. We thank investigators from the following studies that provided DNA samples for genotyping: the Genetic Architecture of Smoking and Smoking Cessation, Collaborative Genetic Study of Nicotine Dependence (phs000404.v1.p1); Age-Related Eye Disease Study (AREDS) - Genetic Variation in Refractive Error Substudy (phs000429.v1.p1); and National Institute of Mental Health’s Human Genetics Initiative (phs000021.v3.p2, phs000167.v1.p1). We thank the many clinical collaborators and research participants who contributed to this research. Phs000196.v3.p1: Investigators and Parkinson Disease patients that contributed to this Genome-wide Association Study of Parkinson Disease. phs000187.v1.p1: Research support to collect data and develop an application to support the High Density SNP Association Analysis of Melanoma project was provided by 3P50CA093459, 5P50CA097007, 5R01ES011740, and 5R01CA133996

Zum ko-konstruierten Argumentieren Jugendlicher in schulischen Gruppendiskussionen

The article presents data from group interactions in school among peers (aged 11-12 years) discussing a given (fictive) problem. The setting provokes argumentative practices and allows the students to act within their own peer-culture. This article shows that these practices are not only controversial and self-justifying, but that they are often created as a joint project through argumentative co-constructions. The participants add arguments although they have already reached a consensus. This observed practice reveals the functions of reasoning in a new light: arguments are not only used in order to persuade the other but also for expanding a topic and for demonstrating group-membership (display of identity), which plays an important role for constructing argumentative tasks in school

Ko-konstruiertes Begründen unter Kindern. Eine gesprächsanalytische Studie von Kleingruppeninteraktionen in der Primarschule

In der Arbeit werden Kleingruppeninteraktionen von Grundschulkindern untersucht, die eine kontroverse Fragestellung argumentativ bearbeiten. Bei der gesprächsanalytischen Auswertung der Videodaten zeigt sich, dass die Kinder ihre Argumente auf verschiedenen Ebenen ko-konstruieren, wie z.B. auf der Ebene der argumentativen Strukturelemente und der Morphosyntax. Hieran wird deutlich, wie das Argumentieren eingesetzt werden kann, um Problemlöseprozesse explorativ zu gestalten und Gruppenidentitäten auszuhandeln. «Dialogisches Sprechen» ist ein Teilkompetenzbereich in schulischen Lehrplänen. Vor allem das gemeinsame Argumentieren wird als bedeutende Komponente in der kindlichen Sprach- und Kognitionsentwicklung angesehen. Die Arbeit befasst sich mit dem mündlichen Argumentieren von Primarschulkindern (7-12 Jahre) Deutschschweizer Schulen, die ohne die Leitung von Erwachsenen eine Gruppendiskussion führen. Bei der gesprächsanalytischen Auswertung der Videodaten fällt auf, dass die Kinder ihre Argumente auf verschiedenen Ebenen ko-konstruieren, wie z.B. auf der Ebene der argumentativen Strukturelemente «Behauptung», «Begründung» und «Stütze». In den Daten werden verschiedene konditionelle Relevanzen ko-konstruierter Begründungen herausgearbeitet. Daneben werden auf der sprachlichen Ebene Kohäsionsformen, die die Interagierenden während des Ko-Konstruktionsprozesses einsetzen, untersucht. Da die Gesprächsdaten bei verschiedenen Altersstufen erhoben wurden (Klasse 2, 4 und 6) und ein großes Datensample vorliegt (60 Gruppengespräche), können Aussagen zum ko-konstruierten Begründen im Entwicklungsverlauf bzw. zum Erwerb argumentativer Kompetenzen getroffen werden. Zum Beispiel wird die persuasive Funktion des Begründens zunehmend durch explorative Funktionen abgelöst, die nicht nur auf intensivierten Konsens deuten, sondern auch identitätsstiftende Funktionen einnehmen können

„verbAndskasten !MÜS!sen wir haben“. Zum argumentativen Potenzial von Prosodie am Beispiel von Einigungsdiskussionen bei Grundschulkindern

 “we !MUST! have a first aid kit” – On the argumentative potential of prosody in consensual discussions among primary school childrenProsody has proved to be an important means of contextualising and marking statements as argumentatively meaningful – and therefore persuasively functional – for the process of reaching an agreement in group discussions. This paper shows how primary school children use prosodic devices to mark implicit arguments through accentuation, to compensate for missing reasoning, to enhance the persuasive strength of an argument or to mark collaborative reasoning. In contrast to explicit lexical markers, prosody is understood as an implicit resource, which allows younger children to engage in discussions and to successfully persuade others. “we !MUST! have a first aid kit” – On the argumentative potential of prosody in consensual discussions among primary school childrenProsody has proved to be an important means of contextualising and marking statements as argumentatively meaningful – and therefore persuasively functional – for the process of reaching an agreement in group discussions. This paper shows how primary school children use prosodic devices to mark implicit arguments through accentuation, to compensate for missing reasoning, to enhance the persuasive strength of an argument or to mark collaborative reasoning. In contrast to explicit lexical markers, prosody is understood as an implicit resource, which allows younger children to engage in discussions and to successfully persuade others

From flat propositions to deep co-constructed and modalized argumentations: Oral argumentative skills among elementary school children from grades 2 to 6

Drawing on a corpus of 180 peer discussions of second, fourth and sixth graders in German-speaking Swiss elementary schools (ages 7–12), we comment on three aspects of oral argumentative competence: (1) giving reasons, (2) argumentative complexity and co-constructions, and (3) modalization of arguments. We combine qualitative and quantitative analyses, both based in the approach of conversation analysis, and show that, as children get older, they not only give more reasons for their arguments, but also match them to their partner’s perspective, modalize their different standpoints to a greater extent, and produce arguments that are more complex and co-constructed. We observe a bigger change in these argumentative practices between the second and fourth grades than between the fourth and sixth

Collaborative decision-making in argumentative group discussions among primary school children

Whenpeoplehavetoreachagreementonagivenproblem,theycanrely on various practices and resources. The present study focuses on collaborative processes of group decision-making and investigates the use of argumentative and alternative strategies. This allows to reconstruct the development across different age groups. The analyses are based on video-recorded group discussions among primary school children (grade 2, 4, 6). The results show how the pupils increas- ingly manage to combine various strategies and cooperatively elaborate the breadth and depth of their argumentation. We also find that younger pupils mainly use argumentation to handle disagreement, while older pupils also start engaging in argumentative elaborations in contexts in which everyone agrees