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Background Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. Methods We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. Results We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67–82]), than encephalopathy (54% [42–65]). Intensive care use was high (38% [35–41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27–32]. The hazard of death was comparatively lower for patients in the WHO European region. Interpretation Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission.

The impact of endurance training on spinal neural circuitries remains largely unknown. Some studies have reported higher H-reflexes in endurance trained athletes and therefore, adaptations within the Ia afferent pathways after long term endurance training have been suggested. In the present study we tested the hypothesis that cyclists (n = 12) demonstrate higher Hoffmann reflexes (H-reflexes) compared to recreationally active controls (n = 10). Notwithstanding, highly significant differences in endurance performance (VO2peak: 60.6 for cyclists vs. 46.3 ml/min/kg for controls (p < 0.001) there was no difference in the size of the SOL H-reflex between cyclists and controls (Hmax/Mmax ratio 61.3 vs. 60.0%, respectively (p = 0.840). Further analyses of the H and M recruitment curves for SOL revealed a significant steeper slope of the M recruitment curve in the group of cyclists (76.2 ± 3.8° vs. 72.0 ± 4.4°, p = 0.046) without a difference in the H-recruitment curve (84.6 ± 3.0° vs. 85.0 ± 2.8°, p = 0.784) compared to the control group. Cycling is classified as an endurance sport and thus the findings of the present study do not further support the assumption that long-term aerobic training leads to a general increase of the H-reflex. Amongst methodological differences in assessing the H-reflex, the training-specific sensorimotor control of the endurance sport itself might differently affect the responsiveness of spinal motoneurons on Ia-afferent inputs.

Abstract: The objective of this work was to distinguish the sexual dimorphism of horses of the Campolina breed, by morphometric measurements, and to classify them according to sex, using discriminating functions. Two-hundred and fifteen horses were measured, and 39 morphometric measurements were evaluated. The analysis of covariance and the discriminant analysis were performed. Males were taller and showed a wider chest, a greater scapular-humeral angle, and a larger neck, both in length and circumference. Females had a larger heart girth, wider hips, and a greater opening of the coxal-ground and femorotibial angles. Regarding classification, circumference measurements (85.58%) were more accurate in sexual differentiation than the linear (83.26%) and angular (73.02%) ones. As to classification error, of the total animals measured, 10 to 20% of the females were categorized as males. In addition, 11 to 38% of the males were categorized as females. It can be concluded that of the 39 morphometric measurements evaluated, 22 are responsible for sexual dimorphism in the Campolina horse breed. Circumference and linear measurements provide a more assertive classification to determine sexual dimorphism. Angular measurements show greater classification errors regarding the gender of the horses.

Arteriovenous malformations (AVMs) of the brain are abnormal connections between the arterial and venous cerebral vasculature that often lead to intracranial hemorrhage (ICH). The diagnosis of AVMs often takes place in the setting of ICH, however, there is no clear consensus on how to manage critically ill, comatose patients and whether it is best to treat the lesion initially. We present an initial treatment strategy that is focused on the management of intracranial hypertension by the means of decompressive craniectomy (DC) coupled with delayed AVM management. We retrospectively reviewed the medical records of three patients who arrived with ICH, obliterated cisterns, and midline shifts greater than 5mm from ruptured AVMs. Each of these patients received a DC, with later definite treatment for their AVMs and cranioplasties. We reported the preoperative and postoperative clinical status of patients using Glasgow Coma Scale (GCS) outcomes as well as physical exam findings. All three patients were transferred to the intensive care immediately after DC and had significant clinical improvement 15 days post-craniectomy. All patients underwent definitive AVM treatment within 6 weeks of the initial procedure. One patient was treated with endovascular-only embolization while the other two received surgical treatment. Patients showed a significant improvement in neurological status and clinical outcome. Decompressive hemicraniectomies may have a positive impact on mortality and neurological outcomes for select patients with cerebral hemorrhage originating from vascular malformations, especially in low-resource scenarios.

In diesem Beitrag werden Daten von Primarschulkindern aus dem Kanton Zürich diskutiert. Individuelle Lernvoraussetzungen wurden via kognitive, sprachbezogene und affektive Variablen gemessen, ausserdem wurden die Sprachkompetenzen in Deutsch und Englisch über knapp zwei Schuljahre hinweg gemessen. Im Beitrag vergleiche ich verschiedene sonderpädagogisch geförderte Gruppen miteinander, sowohl im quer- als auch im Längsschnitt. Im Zentrum steht die Frage, ob gewisse Lernergruppen durch Fremdsprachen überfordert sind. Im Vergleich der Gruppen zeigt sich insbesondere im Längsschnitt, dass die sonderpädagogisch Geförderten im Vergleich zu den Nichtgeförderten nicht zurückfallen.

Endurance sports pose a plethora of mental demands that exercisers have to deal with. Unfortunately, investigations of exercise-specific demands and strategies to deal with them are insufficiently researched, leading to a gap in knowledge about athletic requirements and strategies used to deal with them. Here, we investigated which obstacles exercisers experience during an anaerobic (Wingate test) and an aerobic cycling test (incremental exercise test), as well as the strategies they considered helpful for dealing with these obstacles (qualitative analysis). In addition, we examined whether thinking of these obstacles and strategies in terms of if-then plans (or implementation intentions; i.e., “If I encounter obstacle O, then I will apply strategy S!”) improves performance over merely setting performance goals (i.e., goal intentions; quantitative analysis). N = 59 participants (age: M = 23.9 ± 6.5 years) performed both tests twice in a 2-within (Experimental session: 1 vs. 2) × 2-between (Condition: goal vs. implementation intention) design. Exercisers’ obstacles and strategies were assessed using structured interviews in Session 1 and subjected to thematic analysis. In both tests, feelings of exertion were the most frequently stated obstacle. Motivation to do well, self-encouragement, and focus on the body and on cycling were frequently stated strategies in both tests. There were also test-specific obstacles, such as boredom reported in the aerobic test. For session 2, the obstacles and strategies elicited in Session 1 were used to specify if-then plans. Bayesian mixed-factor ANOVA suggests, however, that if-then plans did not help exercisers to improve their performance. These findings shed novel light into the mental processes accompanying endurance exercise and the limits they pose on performance.

Previous research demonstrated that six sessions of cycling sprint-interval training (SIT) within a duration of only 2 weeks can increase endurance performance considerably. Primarily muscular mechanisms have been under investigation explaining such performance improvements. However, it has been shown in other exercise tasks that training-induced changes also occur at the level of the central nervous system. Therefore, we hypothesized to observe an enhanced neuromuscular performance in conjunction with an increase in endurance performance after 2 weeks of SIT. Therefore, we randomly assigned 19 healthy men (26 ± 5 years) to a control (n = 10) or a training group (n = 9), the latter performing a replication of the SIT protocol from Burgomaster et al. Before and after the training intervention, both groups performed a cycling endurance test until exhaustion. Neuromuscular function of the right vastus lateralis muscle was assessed before and after each endurance task by the means of maximal voluntary isometric contractions (MVCs). The variables of interest being MVC, voluntary activation was measured by peripheral nerve stimulations (VAPNS), by transcranial magnetic stimulation (VATMS), as well as potentiated resting twitches (Qtw,pot). We did not find any significant differences between the groups in the control variable time to exhaustion in the endurance task. In addition, we did not observe any time × group interaction effect in any of the neuromuscular parameters. However, we found a significant large-sized time effect in all neuromuscular variables (MVC, ηp2 = 0.181; VATMS, ηp2 = 0.250; VAPNS, ηp2 = 0.250; Qtw,pot, ηp2 = 0.304) as well as time to exhaustion ηp2 = 0.601). In contrast to other studies, we could not show that a short-term SIT is able to increase endurance performance. An unchanged endurance performance after training most likely explains the lack of differences in neuromuscular variables between groups. These findings demonstrate that replication studies are needed to verify results no matter how strong they seem to be. Differences over time for the variables of neuromuscular fatigue irrespective of group (MVC, + 9.3%; VATMS, + 0.2%; VAPNS, + 6.3%; Qtw,pot, + 6.3%) demonstrate test-retest effects that should be taken into consideration in future training studies and emphasize the inevitable necessity for controlled experiments.

The position and number of hair whorls have been associated with the behavior, temperament, and laterality of horses. The easy observation of whorls assists in the prediction of reactivity, and thus permits the development of better measures of handling, training, mounting, and riding horses. However, little is known about the genetics involved in the formation of hair whorls. Therefore, the aim of this study was to perform a genome-wide association analysis to identify chromosome regions and candidate genes associated with hair whorl traits. Data from 342 Quarter Horses genotyped for approximately 53,000 SNPs were used in an association study using a single-step procedure. The following traits were analyzed: vertical position of hair whorl on the head, number of whorls on the head, and number of whorls on the left and right sides of the neck. The traits had between one and three genomic windows associated. Each of them explained at least 4% of the additive variance. The windows accounted for 20–80% of additive variance for each trait analyzed. Many of the prospected genes are related to hair follicle growth. Some of these genes exert a pleiotropic effect on neurological and behavioral traits. This is the first indication of biological and physiological activity that might explain the association of hair whorls and temperament.

In this contribution, I describe the evolution of the role that Alemannic dialects and Standard High German play in the Swiss German educational context. Drawing on a content analysis of a collection of school-related documents from 1950 to 2014, I describe the change in the roles attributed to dialects and the standard language, respectively. The task of German-language education shifts from the two-fold goal of teaching standard-language literacy and cultivating the “pure” dialect in the 1950s to a clear prioritization of standard language skills both in orality and in literacy towards the end of the twentieth century. I discuss these changes in relation to the backdrop of the media discourse on identity, language, multilingual education, language norms, and other social issues such as migration.

Some language-acquisition researchers not only pursue their scholarly agenda but also act outside academia as experts in language policy-making. However, the relationship between scholarly quality and political impact is complicated, and oftentimes policy is not based on robust scholarly evidence. In this contribution, I focus on research findings in language learning that have been taken up in language planning and policy (e.g., the notion of linguistic interdependence). Drawing on concrete cases, I discuss problems of individual expertise and quality of research. Where there are methodological inadequacies and/or lack of expertise, problematic or even utterly false conclusions can be drawn from research. A critical review of influential claims in the field of applied linguistics with respect to robustness of the evidence and its fit to the actual policy problem should allow us to determine which theories and research strands may be useful for language-policy recommendations and which are probably not. A critical review of linguists’ involvement in policy-making suggests that often a more appropriate appellation for so-called evidence-based policy would be policy-based evidence. In my discussion, I address two delimitation problems: defining the boundary between pseudoscience and real science (in the wide sense of the term, including social sciences and humanities) and defining the boundary between scholarly rigor and political advocacy by academics.

Starting in the mid 1970s, Chile implemented comprehensive structural market reforms. Using manufacturing plant-level data on Chilean firms for years 1980 to 2001, we estimate the role of reforms on efficiency. We analyze aggregate productivity constructed from micro data to find that in the aftermath of the reforms, efficiency gains were explained by within-plant improvements and by the net entry of new units. We also find that plants producing traded goods and plants facing liquidity constraints experienced the largest efficiency gains. Trade openness and a superior access to external finance seem to have partially accounted for the improvement in manufacturing performance.

PURPOSE:Active recovery is often used by athletes after strenuous exercise or competition but its underlying mechanisms are not well understood. We hypothesized that active recovery speeds-up recovery processes within the muscle and the central nervous system (CNS). METHODS:We assessed muscular and CNS recovery by measuring the voluntary activation (VA) in the vastus lateralis muscle with transcranial magnetic stimulation (VATMS) and peripheral nerve stimulation (VAPNS) during maximal voluntary contractions (MVC) of the knee extensors in 11 subjects. Measurements were performed before and after a fatiguing cycling time-trial, after an active and a passive recovery treatment and after another fatiguing task (1 min MVC). The measurements were performed a second time 24 h after the time-trial. RESULTS:We observed a time × group interaction effect for VATMS (p = 0.013). Post-hoc corrected T-tests demonstrated an increased VATMS after active recovery when measured after the 1 min MVC performed 24 h after the time-trial (mean ± SD; 95.2 ± 4.1% vs. 89.2 ± 6.6%, p = 0.026). No significant effects were observed for all other variables. CONCLUSIONS:Active recovery increased aspects of central, rather than muscle recovery. However, no effect on MVC was seen, implying that even if active recovery speeds up CNS recovery, without affecting the recovery of muscle contractile properties, this doesn´t translate into increases in overall performance.

Stayability, which can be defined as the probability of a cow calving at a certain age when given the opportunity, is an important reproductive trait in beef cattle because it is directly related to herd profitability. The objective of this study was to estimate genetic parameters and to identify possible genomic regions associated with the phenotypic expression of stayability in Nellore cows. The variance components were estimated by Bayesian inference using a threshold animal model that included the systematic effects of contemporary group and sexual precocity and the random effects of animal and residual. The SNP effects were estimated by the single-step genomic BLUP method using information of 2,838 animals (2,020 females and 930 sires) genotyped with the Illumina High-Density BeadChip Array (San Diego, CA, USA). The variance explained by windows formed by 200 consecutive SNPs was used to identify genomic regions of largest effect on the expression of stayability. The heritability was 0.11 ± 0.01 when A matrix (pedigree) was used and 0.14 ± 0.01 when H matrix (relationship matrix that combines pedigree information and SNP data) was used. A total of 147 candidate genes for stayability were identified on chromosomes 1, 2, 5, 6, 9 and 20 and on the X chromosome. New candidate regions for stayability were detected, most of them related to reproductive, immunological and central nervous system functions.

Bcl-2 is commonly overexpressed in tumors, where it is often associated with unfavorable outcome. However, it has also been linked to a favorable sensitivity to microtubule-targeting agents (MTAs). We show that Bcl-2– overexpressing lung and breast cancer cells were more sensitive to both paclitaxel and vinorelbine. Bcl-2 overexpression also significantly potentiated in vivo efficacy of paclitaxel, in terms of tumor volume decrease and survival benefits, in models of nude mice bearing lung cancer xenografts. To further investigate this favorable effect of Bcl-2, a genomic approach was taken. It revealed that Bcl-2 overexpression induced up-regulation of the proapoptotic protein Bim in lung cancer cells and that, conversely, Bcl-2 silencing decreased Bim expression level. A gene regulation study implicated the transcription factor Forkhead box-containing protein, class O3a in Bim up-regulation. Lastly, we show that Bim was responsible for MTA-triggered lung cancer cell death through a dynamin-related protein 1–mediated mitochondrial fragmentation. The Bcl-2–governed Bim induction evidence offers for the first time an explanation for the favorable higher sensitivity to treatment shown by Bcl-2–overexpressing cells. We suggest that Bim could be a powerful predictive factor for tumor response to MTA chemotherapy. Our data also give new insight into some failures in the efficacy of therapies targeted against Bcl-2.

Despite the potential of repetitive transcranial magnetic stimulation (rTMS) to improve performances in patients suffering from motor neuronal afflictions, its effect on motor performance enhancement in healthy subjects during a specific sport task is still unknown. We hypothesised that after an intermittent theta burst (iTBS) treatment, performance during the Wingate Anaerobic Test (WAnT), will increase and supraspinal fatigue following the exercise will be lower in comparison to a control treatment.Ten subjects participated in two randomised experiments consisting of a WAnT 5 minutes after either an iTBS or a control treatment. We determined voluntary activation (VA) of the right knee extensors with TMS (VATMS) and with peripheral nerve stimulation (VAPNS) of the femoral nerve, before and after the WAnT. T-tests were applied to the WAnT results and a 2 way within subject ANOVA was applied to VA results. The iTBS treatment increased the peak power and the maximum pedalling cadence and suppressed the reduction of VATMS following the WAnT compared to the control treatment. No behavioural changes related to fatigue (mean power and fatigue index) were observed.These results indicate for the first time that iTBS could be used as a potential intervention to improve anaerobic performance in a sport specific task.

The objective of this study was to perform a genome-wide association study (GWAS) to detect chromosome regions associated with indicator traits of sexual precocity in Nellore cattle. Data from Nellore animals belonging to farms which participate in the DeltaGen® and Paint® animal breeding programs, were used. The traits used in this study were the occurrence of early pregnancy (EP) and scrotal circumference (SC). Data from 72,675 females and 83,911 males with phenotypes were used; of these, 1,770 females and 1,680 males were genotyped. The SNP effects were estimated with a single-step procedure (WssGBLUP) and the observed phenotypes were used as dependent variables. All animals with available genotypes and phenotypes, in addition to those with only phenotypic information, were used. A single-trait animal model was applied to predict breeding values and the solutions of SNP effects were obtained from these breeding values. The results of GWAS are reported as the proportion of variance explained by windows with 150 adjacent SNPs. The 10 windows that explained the highest proportion of variance were identified. The results of this study indicate the polygenic nature of EP and SC, demonstrating that the indicator traits of sexual precocity studied here are probably controlled by many genes, including some of moderate effect. The 10 windows with large effects obtained for EP are located on chromosomes 5, 6, 7, 14, 18, 21 and 27, and together explained 7.91% of the total genetic variance. For SC, these windows are located on chromosomes 4, 8, 11, 13, 14, 19, 22 and 23, explaining 6.78% of total variance. GWAS permitted to identify chromosome regions associated with EP and SC. The identification of these regions contributes to a better understanding and evaluation of these traits, and permits to indicate candidate genes for future investigation of causal mutations.

Questo documento sulla valutazione è uno studio complementare alla Guida per lo sviluppo e l’attuazione di curricoli per una educazione plurilingue e interculturale del Consiglio d’Europa. Dà inizialmente una breve descrizione dei vari obiettivi della valutazione nell‘educazione plurilingue ed interculturale, cui segue una breve spiegazione di ciò che gli autori intendono con “valutazione“. Infine, descrive ed analizza la valutazione di alcune competenze correlate ad aspetti essenziali dell‘educazione plurilingue ed interculturale.ASSESSMENT IN PLURILINGUAL AND INTERCULTURAL EDUCATIONThis satellite to the Guide for the Development and Implementation of Curricula for Plurilingual and Intercultural Education focuses on assessment aspects. First, a brief overview is given of the various aims of assessment in plurilingual and intercultural education. The authors’ understanding of assessment is then briefly outlined. Finally, the assessment of selected competences having to do with core aspects of plurilingual and intercultural education is presented and discussed.

A partir de mediados de la década de los 70, Chile implementó un número relevante de reformas estructurales a sus mercados. En este trabajo estimamos el efecto de estas reformas sobre la eficiencia agregada, utilizando datos de plantas manufactureras chilenas para el período entre 1980 y 2001. Descomponemos la productividad agregada construida a partir de datos microeconómicos, encontrando que, luego de las reformas, las ganancias de eficiencia se explican tanto por mejoras al interior de las empresas como por la entrada neta de nuevos establecimientos. También encontramos que las mayores ganancias fueron obtenidas por las plantas que producen bienes transables y por aquellasrestringidas en su liquidez. Así, nuestros resultados sugieren que la apertura comercial y el mejor acceso al financiamiento externo explican en parte el mejor desempeño manufacturero en Chile.

Insulin growth factor I (IGF-I) and prolactin (PRL) are peptide hormones that exert complementary effects on reproductive traits by acting on folliculogenesis. In view of the lack of information about the IGF-I and PRL genes in Bos indicus, the objective of this study was to partially characterize the promoter regions of these genes and to screen animals of different ages at first pregnancy for the presence of polymorphisms in these regions. In addition, we determined whether polymorphisms influence the regulation of the two hormone genes, evaluating their association with sexual precocity. The animals were divided into three groups according to age at first pregnancy: 1) 100 heifers considered to be sexually precocious that became pregnant at 15-16 months of age, 2) 100 heifers that became pregnant during the normal breeding season at 24 months of age, and 3) 100 heifers that did not become pregnant until 24 months of age. For the IGF-I gene, PCR-RFLP-SnaBI analysis showed the presence of genotypes AB and BB at frequencies of 0.02 and 0.98, respectively. Sequencing of the IGF-I gene fragment revealed a single nitrogen base change from cytosine to thymine, corresponding to the restriction site of SnaBI. The polymorphisms identified in the 5’-flanking region of the IGF-I gene may serve as a basis for future studies of molecular markers in cattle. For the PRL gene, PCR-RFLP-HaeIII analysis showed the presence of only one migration pattern, a finding characterizing the region studied as monomorphic. The study of other regions in the IGF-I and PRL genes might provide molecular data that can be used in the future for the selection of sexually precocious animals.

Este artigo avalia o mercado reprimido de eletricidade, gás natural e álcool na Região Administrativa de Araçatuba (RAA), comparando o consumo com o consumo médio do estado de São Paulo e do estado da Flórida, EUA, onde se acredita que a demanda é plenamente satisfeita. O artigo apresenta uma projeção para o atendimento da demanda no contexto do desenvolvimento limpo em um cenário hipotético.This article assesses the restrained market of electricity, natural gas and alcohol in the Araçatuba Administrative Region (RAA), comparing the its consumption with the average consumption of the states of São Paulo and Florida (USA), where the demand is believed to be fully satisfied. Projections are made for answering the demand in a clean development context for a hypothetical scenario.

Cell-based assays (CBA) have increased the sensitivity of the neuromyelitis optica (NMO)-IgG/aquaporin-4-antibody detection compared to classical tissue-based indirect assays. We describe the sensitivity of an optimized immunohistochemistry (IHC-o) to detect NMO-IgG/aquaporin-4-antibody in comparison with that of two CBA: an in-house (CBA-ih) and a commercial (CBA-c) assay (Euroimmun, Germany). Coded serum from 103 patients with definite NMO and 122 inflammatory controls were studied by IHC-o, CBA-ih, and CBA-c. IHC-o used the same protocol described to detect antibodies against cell surface antigens. CBA-ih used live cells transfected with the aquaporin-4-M23-isoform. The sensitivity of the IHC-o was 74.8% (95% confidence interval [CI] 65-83) and was similar to that of the CBA-ih 75.7% (95% CI 66-84) and the CBA-c 73.8% (95% CI 64-82). The specificity of the three assays was 100% (95% CI 97-100). Interassay concordance was high, 100 of 103 samples were coincident in all techniques. The optimized immunohistochemistry proves to be as sensitive and specific as the cell-based assays. This assay extends the available tools for NMO-IgG/aquaporin-4-antibody detection.

We previously showed that vinflunine, a microtubule-targeting drug of the Vinca-alkaloid family exerted its anti-angiogenic/anti-migratory activities through an increase in microtubule dynamics and an inhibition of microtubule targeting to adhesion sites. Such effect was associated with a reduction of EB1 comet length at microtubule (+) ends. In this work we first showed that the pro-angiogenic vascular endothelial growth factor VEGF suppressed microtubule dynamics in living Human Umbilical Vein Endothelial Cells (HUVECs), increased EB1 comet length by 40%, and induced EB1 to bind all along the microtubules, without modifying its expression level. Such microtubule (+) end stabilization occurred close to the plasma membrane in the vicinity of focal adhesion as shown by TIRF microscopy experiments. Vinflunine completely abolished the effect of VEGF on EB1 comets. Interestingly, we found a correlation between the reduction of EB1 comet length by vinflunine and the inhibition of cell migration. By using 2D gel electrophoresis we demonstrated for the first time that EB1 underwent several post-translational modifications in endothelial and tumor cells. Particularly, the C-terminal EEY sequence was poorly detectable in control and VEGF-treated HUVECs suggesting the existence of a non-tyrosinated form of EB1. By using specific antibodies that specifically recognized and discriminated the native tyrosinated form of EB1 and a putative C-terminal detyrosinated form, we showed that a detyrosinated form of EB1 exists in HUVECs and tumor cells. Interestingly, vinflunine decreased the level of the detyrosinated form and increased the native tyrosinated form of EB1. Using 3-L-Nitrotyrosine incorporation experiments, we concluded that the EB1 C-terminal modifications result from a detyrosination/retyrosination cycle as described for tubulin. Altogether, our results show that vinflunine inhibits endothelial cell migration through an alteration of EB1 comet length and EB1 detyrosination/retyrosination cycle.

We previously reported that a 24 amino acid peptide (NFL-TBS.40-63) corresponding to the tubulin-binding site located on the light neurofilament subunit, selectively enters in glioblastoma cells where it disrupts their microtubule network and inhibits their proliferation. Here, we analyzed the structure-function relationships using an alanine-scanning strategy, in order to identify residues essential for these biological activities. We showed that the majority of modified peptides present a decreased or total loss to penetrate in these cells, or to alter microtubules. Correspondingly, circular dichroism measurements showed that this peptide forms either β-sheet or α-helix structures according to the solvent and that alanine substitution modified or destabilized the structure, in relation with changes in the biological activities. Moreover, substitution of serine residues by phosphoserine or aspartic acid concomitantly decreased the cell penetrating activity and the structure stability. These results indicate the importance of structure for the activities, including selectivity to glioblastoma cells of this peptide, and its regulation by phosphorylation.

While numerous studies have implicated copy number variants (CNVs) in a range of neurological phenotypes, the impact relative to disease severity has been difficult to ascertain due to small sample sizes, lack of phenotypic details, and heterogeneity in platforms used for discovery. Using a customized microarray enriched for genomic hotspots, we assayed for large CNVs among 1,227 individuals with various neurological deficits including dyslexia (376), sporadic autism (350), and intellectual disability (ID) (501), as well as 337 controls. We show that the frequency of large CNVs (>1 Mbp) is significantly greater for ID-associated phenotypes compared to autism (p = 9.58 × 10(-11), odds ratio = 4.59), dyslexia (p = 3.81 × 10(-18), odds ratio = 14.45), or controls (p = 2.75 × 10(-17), odds ratio = 13.71). There is a striking difference in the frequency of rare CNVs (>50 kbp) in autism (10%, p = 2.4 × 10(-6), odds ratio = 6) or ID (16%, p = 3.55 × 10(-12), odds ratio = 10) compared to dyslexia (2%) with essentially no difference in large CNV burden among dyslexia patients compared to controls. Rare CNVs were more likely to arise de novo (64%) in ID when compared to autism (40%) or dyslexia (0%). We observed a significantly increased large CNV burden in individuals with ID and multiple congenital anomalies (MCA) compared to ID alone (p = 0.001, odds ratio = 2.54). Our data suggest that large CNV burden positively correlates with the severity of childhood disability: ID with MCA being most severely affected and dyslexics being indistinguishable from controls. When autism without ID was considered separately, the increase in CNV burden was modest compared to controls (p = 0.07, odds ratio = 2.33).

In this reply to Wolfgang Teubert's contribution, some of the central tenets of his position are questioned. The primacy of literacy for linguistic investigations as advocated by Teubert is challenged, since the most important function of language is oral communication, and most of the world's languages exist exclusively in oral use. Counter-evidence to Teubert's claim according to which oral languages do not develop metalinguistic awareness (as e.g. the concept of "word") is given. The author scrutinizes the value added by Teubert's programmatic suggestion of "hermeneutic corpus linguistics" to the linguistic disciplines, since the sole focus on "discourse objects" unnecessarily narrows down the scope of linguistic investigation. Moreover, it seems to lead to backgrounding and neglect of what linguistics is all about: the comprehensive study of the structures, meaning potentials and usage patterns of the languages and varieties of the world, and the study of their usage-based emergence and evolution.

In this contribution, different varieties of German (Swiss German dialects, Standard High German) are compared with regard to their conceptual and syntactic elaboration of spatial descriptions. The case study examines a particular scene from the informant's picture-book based narratives, a scene wich refers to a dog climbing onto a window sill and then falling out of the window. The analysis shows considerable variability with respect to the linguistic means used to describe the scene, and the author argues that there are corresponding differences in the cognitive construal of the spatial event. The data show consistently that the Swiss German dialects tend to be more detailed in their elaboration of the path of the moving figure (e.g., the dog can be construed as falling "into" the window "out"), whereas speakers of Standard High German tend to use a generic, semantically and syntactically simpler construction. The analysis of this particular scene is demonstrated to coincide with a generally observable tendency of Swiss German dialects: Within motion verb predicates, the constituents encoding spatial arguments tend to be both syntactically and semantically enriched.

Chlorophenols (CPs) are the precursors of the main source for the so-called musty taint, especially in wine. Currently, different fast methods for the determination of the chloroanisoles (CAs), mainly 2,4,6-trichloroanisole (TCA), the principal causative agent, are used for the quality control of cork stoppers. The methods available for CPs present either a long sample preparation step or are less representative for a batch, because of the very small sample size. We present a new fast method for the determination of chlorophenols and chloroanisoles at the ppt level by GC-MSMS using in situ derivatization and solid-phase microextraction (SPME) preconcentration. We present first results of the development of a new tool for efficient quality control in the cork stopper production.