The suprasegmental signaling of attitude in German and Chinese : a phonetically oriented contribution to intercultural communication

In den letzten 15 Jahren ist ein wachsendes Interesse an den Erkenntnissen der interkulturellen Kommunikationsforschung zu verzeichnen. Während sich Anthropologie, Soziologie und Kulturpsychologie mit kulturell bedingten Unterschieden in der Mentalität, der Lebensweise und des Interaktionsethos beschäftigen, interessiert sich die Linguistik - vor allem die Sozio-linguistik - für die Probleme, die auf Unterschiede in den kommunikativen Gewohnheiten der Menschen zurückzuführen sind. Hierbei treten die suprasegmentellen Mittel immer mehr in den Vordergrund: Wie die Forschungen der Interaktionalen Soziolinguistik gezeigt haben, sind viele Missverständnisse in der interkulturellen Kommunikation auf Fehlinterpretationen von Intonation, Tonhöhe, Lautstärke, Geschwindigkeit und Stimmqualität zurückzuführen. In dieser Arbeit wird der interkulturelle Ansatz der Interaktionalen Soziolinguistik mit den Arbeitsmethoden der Experimentalphonetik kombiniert und auf das Deutsche und das Chinesische (Mandarin) angewandt. Nach einer einführenden Betrachtung des chinesischen Interaktionsethos, der mit den in den westlichen Welt vorherrschenden Interaktionsnormen verglichen wird, beschäftigt sich die Arbeit schwerpunktmäßig mit den Funktionen der supra-segmentellen Mittel in den zwei Sprachen, vor allem in Bezug auf die Kommunikation von Sprechereinstellung (attitude). Zu diesem Zweck werden Dialoge mit deutschen und chinesi-schen Sprechern organisiert, in denen unterschiedliche Sprechereinstellungen zum Ausdruck kommen. Diese werden in Hörtests mit deutschen und chinesischen Muttersprachlern analysiert und anhand von Sprechverhaltensmustern (interaction strategies) beschrieben. Die phonetische Exponenz dieser Sprechverhaltensmuster in den zwei Sprachen wird dann in einer mehrteiligen phonetischen Sprachanalyse bestimmt. Der Vergleich der phonetischen Exponenz dieser Sprechverhaltensmuster im Chinesischen und Deutschen gibt Aufschluss über die Faktoren, die in der suprasegmentellen Kommunikation zwischen Sprechern dieser Sprachen zu Problemen führen können. Ein besonderes Augenmerk liegt dabei auf der Rolle der Intonation in Chinesischen - ein Bereich, der fast gänzlich unerforscht ist.The last 15 years have seen a growing interest in the concerns and achievements of inter-cultural communication research, prompting a steady increase of scholarly writings on topics like intercultural management, cross-cultural business communication and intercultural com-munication at work. Thus, researchers in anthropology, sociology and psychology are taking a growing interest in the problems arising from culturally-patterned differences in mentality, way of life and norms of interaction. Linguists, on the other hand, especially those working in the sociologically and/or anthropologically-oriented disciplines, such as interactional socio-linguistics, are examining the linguistic problems of intercultural communication - those originating in differences in the use of language. In the latter field in particular, attention has come to focus strongly on the use of the suprasegmental features of intonation, pitch, loudness, tempo and voice quality, as differences in the use of these features have been found to cause frequent and serious misunderstandings of speaker meaning and intent. In this work the intercultural approach of interactional sociolinguistics is combined with the working methods of experimental phonetics and applied to German and Chinese (Mandarin). Following an introductory examination of the Chinese norms of interaction which are compared with those of the western world, this work focuses on the communicative functions of the suprasegmental features in the two languages, in particular in the signaling of attitude. To this aim, dialogs with German and Chinese speakers are organized, in the course of which different speaker attitudes are elicited. These attitudes are determined in listening tests with native speakers of German and Chinese and described in terms of patterns of speech behavior, referred to as interaction strategies. This is followed by the determination of the phonetic exponency of these interaction strategies in the two languages, achieved with the help of conscientious phonetic speech analyses. The phonetic exponency of the interactions strategies in German and Chinese is then compared to reveal the areas which can cause problems in suprasegmental communication between speakers of these two languages. Special emphasis is placed on the role of intonation in Chinese, a field of research which is virtually untouched

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

An Atlas of the Thioredoxin Fold Class Reveals the Complexity of Function-Enabling Adaptations

The group of proteins that contain a thioredoxin (Trx) fold is huge and diverse. Assessment of the variation in catalytic machinery of Trx fold proteins is essential in providing a foundation for understanding their functional diversity and predicting the function of the many uncharacterized members of the class. The proteins of the Trx fold class retain common features—including variations on a dithiol CxxC active site motif—that lead to delivery of function. We use protein similarity networks to guide an analysis of how structural and sequence motifs track with catalytic function and taxonomic categories for 4,082 representative sequences spanning the known superfamilies of the Trx fold. Domain structure in the fold class is varied and modular, with 2.8% of sequences containing more than one Trx fold domain. Most member proteins are bacterial. The fold class exhibits many modifications to the CxxC active site motif—only 56.8% of proteins have both cysteines, and no functional groupings have absolute conservation of the expected catalytic motif. Only a small fraction of Trx fold sequences have been functionally characterized. This work provides a global view of the complex distribution of domains and catalytic machinery throughout the fold class, showing that each superfamily contains remnants of the CxxC active site. The unifying context provided by this work can guide the comparison of members of different Trx fold superfamilies to gain insight about their structure-function relationships, illustrated here with the thioredoxins and peroxiredoxins

Discovery of novel heart rate-associated loci using the Exome Chip

Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses. Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods. We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants. Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies

Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6.

BACKGROUND: Genome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear. RESULTS: Here, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction. CONCLUSIONS: Our approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.BH