Lexical and postlexical prominence in Tashlhiyt Berber and Moroccan Arabic

Tashlhiyt Berber (Afro-Asiatic, Berber) and Moroccan Arabic (Afro-Asiatic, Semitic), two languages spoken in Morocco, have been in contact for over 1200 years. The influence of Berber languages on the lexicon and the segmental-phonological structure of Moroccan Arabic is well-documented, whereas possible similarities in the prosodic-phonological domain have not yet been addressed in detail. This thesis brings together evidence from production and perception to bear on the question whether Tashlhiyt Berber and Moroccan Arabic also exhibit convergence in the domain of phonological prominence. Experimental results are interpreted as showing that neither language has lexical prominence asymmetries in the form of lexical stress. This lack of stress in Moroccan Arabic is unlike the undisputed presence of lexical stress in most other varieties of Arabic, which in turn suggests that this aspect of the phonology of Moroccan Arabic has resulted from contact with (Tashlhiyt) Berber. A further, theoretical contribution is made with respect to the possible correspondence between lexical and postlexical prominence structure from a typological point of view. One of the tenets of the Autosegmental Metrical approach to intonation analysis holds that prominence-marking intonational events (pitch accents) associate with lexically stressed syllables. Exactly how prominence marking is achieved in languages that lack lexical stress is little-understood, and this thesis' discussion of postlexical prominence in Tashlhiyt Berber and Moroccan Arabic provides new insights that bear on this topic. A first set of production experiments investigates, for both languages, if there are acoustic correlates to what some researchers have considered to be lexically stressed syllables. It is shown that neither language exhibits consistent acoustic enhancement of presumed stressed syllables relative to unstressed syllables. The second set of production experiments reports on the prosodic characteristics of question word interrogatives in both languages. It is shown that question words are the locus of postlexical prominence-marking events that however do not exhibit association to a sub-lexical phonological unit. A final perception experiment serves the goal of showing how native speakers of Tashlhiyt Berber and Moroccan Arabic deal with the encoding of a postlexical prominence contrast that is parasitic on a lexical prominence contrast. This is achieved by means of a 'stress deafness' experiment, the results of which show that speakers of neither language can reliably encode a lexically-specified prominence difference. Results from all three types of experiment thus converge in suggesting that lexical prominence asymmetries are not specified in the phonology of either language

Acoustic correlates of lexical stress in Moroccan Arabic

Presently there is no consensus regarding the interpretation and analysis of the stress system of Moroccan Arabic. This paper tests whether the acoustic realisation of syllables support one widely adopted interpretation of lexical stress, according to which stress is either penultimate or final depending on syllable weight. The experiment reports on word-initial syllables that differ in presumed stress status. Target words were embedded in a carrier sentence within a scripted mock dialogue to ensure that the measurements reflect lexical stress rather than phrase-level prominence. Results from all four acoustic parameters tested (f0, duration, Centre of Gravity and vowel quality) showed that there were no differences as a function of presumed stress status, thus failing to support an interpretation according to which stressed syllables are acoustically differentiated. We consider the results in relation to previous claims and observations, and conclude that the absence of acoustic correlates of presumed stress is compatible with the view that Moroccan Arabic lacks lexical stress

Word-level prominence and “stress deafness” in Maltese English bilinguals

This study investigates “stress deafness” in bilingual speakers of Maltese and Maltese English. Although both reportedly have lexical stress, the acoustic cues to prominence appear to be relatively weak. Further, word-initial pitch peaks make pitch an unreliable cue to lexical stress, which can be elsewhere in the word. In a sequence recall task, we show that speakers dominant in Maltese exhibit a classic “stress deafness” effect, similar to speakers of French. Speakers who identify as balanced or Maltese English dominant have more diverse results and do not show such a strong tendency towards “stress deafness”. These speakers may rely on their exposure to other varieties of English to identify (and recall) word prominences. This study suggests that the nature of stress in Maltese might need to be revisited.peer-reviewe

Results of the IROCA international clinical audit in prostate cancer radiotherapy at six comprehensive cancer centres

To assess adherence to standard clinical practice for the diagnosis and treatment of patients undergoing prostate cancer (PCa) radiotherapy in four European countries using clinical audits as part of the international IROCA project. Multi-institutional, retrospective cohort study of 240 randomly-selected patients treated for PCa (n = 40/centre) in the year 2015 at six European hospitals. Clinical indicators applicable to general and PCa-specific radiotherapy processes were evaluated. All data were obtained directly from medical records. The audits were performed in the year 2017. Adherence to clinical protocols and practices was satisfactory, but with substantial inter-centre variability in numerous variables, as follows: staging MRI (range 27.5-87.5% of cases); presentation to multidisciplinary tumour board (2.5-100%); time elapsed between initial visit to the radiation oncology department and treatment initiation (42-102.5 days); number of treatment interruptions ≥ 1 day (7.5-97.5%). The most common deviation from standard clinical practice was inconsistent data registration, mainly failure to report data related to diagnosis, treatment, and/or adverse events. This clinical audit detected substantial inter-centre variability in adherence to standard clinical practice, most notably inconsistent record keeping. These findings confirm the value of performing clinical audits to detect deviations from standard clinical practices and procedures

Yeast Two-Hybrid, a Powerful Tool for Systems Biology

A key property of complex biological systems is the presence of interaction networks formed by its different components, primarily proteins. These are crucial for all levels of cellular function, including architecture, metabolism and signalling, as well as the availability of cellular energy. Very stable, but also rather transient and dynamic protein-protein interactions generate new system properties at the level of multiprotein complexes, cellular compartments or the entire cell. Thus, interactomics is expected to largely contribute to emerging fields like systems biology or systems bioenergetics. The more recent technological development of high-throughput methods for interactomics research will dramatically increase our knowledge of protein interaction networks. The two most frequently used methods are yeast two-hybrid (Y2H) screening, a well established genetic in vivo approach, and affinity purification of complexes followed by mass spectrometry analysis, an emerging biochemical in vitro technique. So far, a majority of published interactions have been detected using an Y2H screen. However, with the massive application of this method, also some limitations have become apparent. This review provides an overview on available yeast two-hybrid methods, in particular focusing on more recent approaches. These allow detection of protein interactions in their native environment, as e.g. in the cytosol or bound to a membrane, by using cytosolic signalling cascades or split protein constructs. Strengths and weaknesses of these genetic methods are discussed and some guidelines for verification of detected protein-protein interactions are provided

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (OR=1.11, P=5.7×10−15), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7 ×10−6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 ×10−11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3 ×10−5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by non-allelic homologous recombination

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest