15 research outputs found

    ERP evidence for Slavic and German word stress cue sensitivity in English

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    Word stress is demanding for non-native learners of English, partly because speakers from different backgrounds weight perceptual cues to stress like pitch, intensity, and duration differently. Slavic learners of English and particularly those with a fixed stress language background like Czech and Polish have been shown to be less sensitive to stress in their native and non-native languages. In contrast, German English learners are rarely discussed in a word stress context. A comparison of these varieties can reveal differences in the foreign language processing of speakers from two language families. We use electroencephalography (EEG) to explore group differences in word stress cue perception between Slavic and German learners of English. Slavic and German advanced English speakers were examined in passive multi-feature oddball experiments, where they were exposed to the word impact as an unstressed standard and as deviants stressed on the first or second syllable through higher pitch, intensity, or duration. The results revealed a robust Mismatch Negativity (MMN) component of the event-related potential (ERP) in both language groups in response to all conditions, demonstrating sensitivity to stress changes in a non-native language. While both groups showed higher MMN responses to stress changes to the second than the first syllable, this effect was more pronounced for German than for Slavic participants. Such group differences in non-native English word stress perception from the current and previous studies are argued to speak in favor of customizable language technologies and diversified English curricula compensating for non-native perceptual variation

    Genome-wide significant association with seven novel multiple sclerosis risk loci

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    Objective: A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors. Methods: The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis. Results: Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5×10−8) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03×10−12), CD28 (rs6435203, p=1.35×10−9), LPP (rs4686953, p=3.35×10−8), ETS1 (rs3809006, p=7.74×10−9), DLEU1 (rs806349, p=8.14×10−12), LPIN3 (rs6072343, p=7.16×10−12) and IFNGR2 (rs9808753, p=4.40×10−10). Cis expression quantitative locus effects were observed in silico for rs6435203 on CD28 and for rs9808753 on several immunologically relevant genes in the IFNGR2 locus. Conclusions: This study adds seven loci to the list of genuine MS genetic risk factors and further extends the list of established loci shared across autoimmune diseases

    Genome-wide significant association with seven novel multiple sclerosis risk loci

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    Objective: A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors. Methods: The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis. Results: Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5×10−8) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03×10−12), CD28 (rs6435203, p=1.35×10−9), LPP (rs4686953, p=3.35×10−8), ETS1 (rs3809006, p=7.74×10−9), DLEU1 (rs806349, p=8.14×10−12), LPIN3 (rs6072343, p=7.16×10−12) and IFNGR2 (rs9808753, p=4.40×10−10). Cis expression quantitative locus effects were observed in silico for rs6435203 on CD28 and for rs9808753 on several immunologically relevant genes in the IFNGR2 locus. Conclusions: This study adds seven loci to the list of genuine MS genetic risk factors and further extends the list of established loci shared across autoimmune diseases

    Anticipatory changes in human motoneuron discharge patterns during motor preparation. (London),

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    The influence of motor preparation on human motoneuron activity was studied by combining single motor unit recording techniques with reaction-time (RT) methods. The tonic activity of wrist extensor motor units associated with voluntary isometric contractions was analysed during preparation for a ballistic wrist extensor muscle contraction, using a time preparation procedure. Two durations of the preparatory period elapsing between the warning signal and the response signal were used in separate blocks of trials: a short preparatory period (1 s) allowing optimum time preparation, and a longer, non-optimum one (3 s). Changes in motoneuron tonic discharge patterns not associated with any changes in the force output were observed during the preparatory period, which suggests that these changes were subtle enough to prevent any changes in muscle contraction from occurring before the forthcoming movement. The changes observed were a lengthening of the mean interspike interval (ISI) and a decrease in the ISI variability. These data confirm that inhibitory mechanisms are activated during motor preparation and suggest that spinal inhibitory mechanisms are involved in the preparatory processes. The mechanisms possibly involved, such as presynaptic inhibition, dysfacilitation processes or AHP conductance changes, are discussed. The fact that the preparation-induced effects on motoneuron activity were particularly prominent during the last part of the 3 s preparatory period suggests that they were probably related to the neural processes underlying temporal estimation. The anticipatory changes in motoneuron activity observed here during preparation for action provide evidence that central influences act on spinal motoneurons well before it is time to act

    The value of ECG parameters as markers of treatment response in Fabry cardiomyopathy

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    OBJECTIVE: Best treatment outcomes in Fabry disease (FD) associated cardiomyopathy can be obtained when treatment is started as early as possible. The rationale of this study was to assess the role of ECG changes for identification of cardiac involvement and patients at an earlier stage of the disease more likely deriving a benefit from enzyme replacement therapy (ERT). METHODS: A retrospective analysis of patient data was performed from an observational, longitudinal, prospective cohort. Treatment response was defined as absence or presence of disease progression, defined as new onset or increase in left ventricular (LV) mass &gt;10%. Demographic, clinical, ECG and echocardiographic parameters at baseline were tested for their value in determining absence or presence of disease progression under ERT at 5-year follow-up. RESULTS: The study population consisted of a total of 38 patients (25 men, mean age 36±13 years, overall median follow-up duration 6.4±1.2 years). Patients in the progression group (14 men, 4 women) had a longer QRS duration (99±11 ms vs 84±13 ms, p&lt;0.05 for men, 93±9 years vs 81±5 years, p&lt;0.05 for women) and QTc interval (401±15 ms vs 372±10 ms, p&lt;0.005 for men) and a higher amount of ECG abnormalities (86% vs 18%, p&lt;0.005 for men and 100% vs 0%, p&lt;0.005 for women) at the time of ERT initiation. An abnormal baseline ECG was significantly associated with disease progression (sensitivity 94.1%, specificity 88.9%, positive likelihood ratio of 8.47, p&lt;0.005). CONCLUSIONS: An abnormal ECG at the time of treatment initiation is significantly associated with cardiac disease progression in FD. This effect seems to be independent of age, gender or LV mass at baseline and suggests maximal treatment benefit when ERT is initiated before ECG abnormalities develop

    TPP2 mutation associated with sterile brain inflammation mimicking MS

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    Objective To ascertain the genetic cause of a consanguineous family from Syria suffering from a sterile brain inflammation mimicking a mild nonprogressive form of MS. Methods We used homozygosity mapping and next-generation sequencing to detect the disease-causing gene in the affected siblings. In addition, we performed RNA and protein expression studies, enzymatic activity assays, immunohistochemistry, and targeted sequencing of further MS cases from Austria, Germany, Canada and Jordan. Results In this study, we describe the identification of a homozygous missense mutation (c.82T&gt;G, p.Cys28Gly) in the tripeptidyl peptidase II (TPP2) gene in all 3 affected siblings of the family. Sequencing of all TPP2-coding exons in 826 MS cases identified one further homozygous missense variant (c.2027C&gt;T, p.Thr676Ile) in a Jordanian MS patient. TPP2 protein expression in whole blood was reduced in the affected siblings. In contrast, TPP2 protein expression in postmortem brain tissue from MS patients without TPP2 mutations was highly upregulated. Conclusions The homozygous TPP2 mutation (p.Cys28Gly) is likely responsible for the inflammation phenotype in this family. TPP2 is an ubiquitously expressed serine peptidase that removes tripeptides from the N-terminal end of longer peptides. TPP2 is involved in various biological processes including the destruction of major histocompatibility complex Class I epitopes. Recessive loss-of-function mutations in TPP2 were described in patients with Evans syndrome, a rare autoimmune disease affecting the hematopoietic system. Based on the gene expression results in our MS autopsy brain samples, we further suggest that TPP2 may play a broader role in the inflammatory process in MS

    Maternofetal consequences of <it>Coxiella burnetii</it> infection in pregnancy: a case series of two outbreaks

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    <p>Abstract</p> <p>Background</p> <p>A high complication rate of Q fever in pregnancy is described on the basis of a limited number of cases. All pregnant women with proven Q fever regardless of clinical symptoms should therefore receive long-term cotrimoxazole therapy. But cotrimoxazole as a folic acid antagonist may cause harm to the fetus. We therefore investigated the Q fever outbreaks, Soest in 2003 and Jena in 2005, to determine the maternofetal consequences of <it>Coxiella burnetii</it> infection contracted during pregnancy.</p> <p>Methods</p> <p>Different outbreak investigation strategies were employed at the two sides. Antibody screening was performed with an indirect immunofluorescence test. Medical history and clinical data were obtained and serological follow up performed at delivery. Available placental tissue, amniotic fluid and colostrum/milk were further investigated by polymerase chain reaction and by culture.</p> <p>Results</p> <p>11 pregnant women from Soest (screening rate: 49%) and 82 pregnant women from Jena (screening rate: 27%) participated in the outbreak investigation. 11 pregnant women with an acute <it>C. burnetii</it> infection were diagnosed. Three women had symptomatic disease.</p> <p>Three women, who were infected in the first trimester, were put on long-term therapy. The remaining women received cotrimoxazole to a lesser extent (n=3), were treated with macrolides for three weeks (n=1) or after delivery (n=1), were given no treatment at all (n=2) or received antibiotics ineffective for Q fever (n=1). One woman and her foetus died of an underlying disease not related to Q fever. One woman delivered prematurely (35<sup>th</sup> week) and one child was born with syndactyly. We found no obvious association between <it>C. burnetii</it> infection and negative pregnancy outcome.</p> <p>Conclusions</p> <p>Our data do not support the general recommendation of long-term cotrimoxazole treatment for Q fever infection in pregnancy. Pregnant women with symptomatic <it>C. burnetii</it> infections and with chronic Q fever should be treated. The risk-benefit ratio of treatment in these patients, however, remains uncertain. If cotrimoxazole is administered, folinic acid has to be added.</p
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