Exploring modality switching effects in negated sentences: further evidence for grounded representations

Theories of embodied cognition (e.g., Perceptual Symbol Systems Theory; Barsalou, 1999, 2009) suggest that modality specific simulations underlie the representation of concepts. Supporting evidence comes from modality switch costs: participants are slower to verify a property in one modality (e.g., auditory, BLENDER-loud) after verifying a property in a different modality (e.g., gustatory, CRANBERRIES-tart) compared to the same modality (e.g., LEAVES-rustling, Pecher et al., 2003). Similarly, modality switching costs lead to a modulation of the N400 effect in event-related potentials (ERPs; Collins et al., 2011; Hald et al., 2011). This effect of modality switching has also been shown to interact with the veracity of the sentence (Hald et al., 2011). The current ERP study further explores the role of modality match/mismatch on the processing of veracity as well as negation (sentences containing “not”). Our results indicate a modulation in the ERP based on modality and veracity, plus an interaction. The evidence supports the idea that modality specific simulations occur during language processing, and furthermore suggest that these simulations alter the processing of negation

Modality switching and negation: ERP evidence for modality-specific simulations during negation processing

The Perceptual Symbol System Theory of cognition (Barsalou, 1999) suggests that modality-specific simulations underlie representation of concepts. This is evidenced by processing costs for switching modalities. That is, participants are slower to verify a property in the auditory modality (e.g., BLENDER-loud) after verifying a property in a different modality (e.g., CRANBERRIES-tart) and faster when verifying a property in the same modality (e.g., LEAVES-rustling). The modality switch cost has also been shown to lead to a modulation of the N400 event-related potential (ERP) (Collins, Pecher, Zeelenberg & Coulson, 2011 using a property verification task; Hald, Marshall, Janssen & Garnham, 2011 using a sentence verification task). In a separate line of research, ERP studies have indicated that without a discourse context, negated sentences are more difficult to process than affirmative sentences, leading to a different N400 pattern for negative sentences than for affirmative sentences (e.g., Fischler, Bloom, Childers, Roucos, & Perry, 1983.) Unlike affirmative sentences, sentences containing negation show a larger N400 for correct, semantically coherent single sentences (i.e., factually true sentences) than for semantically incorrect sentences (i.e., false sentences). However, Nieuwland and Kuperberg (2008,) found that the pragmatics of the sentence can change this N400 pattern to one closer to affirmative sentences. The goal of the current study was to explore whether the processing of negation could be aided by modality matching information. Other evidence suggests that comprehenders create a simulation of negative sentences (Kaup, Yaxley, Madden, Zwaan, & Lüdtke, 2007), but it is unclear whether modality matching information could modulate the processing cost of negation. Essentially, can modality matching information as reported by Collins et al., (2011) and Hald et al., (2011) lead to a modulation of the N400 for true negated sentences similar to that seen when discourse pragmatics supports negation? Furthermore, we were interested in whether the modality switch effect would lead to a similar pattern in the ERPs as that found with affirmative sentences (Collins et al., 2011 & Hald et al., 2011). Using a within-subjects design we used 160 pairs of experimental pairs which were either of the same or of a different modality. All experimental items were either visual or tactile modality and were drawn from existing sets of materials (Pecher, et al., 2003; Van Dantzig, et al., 2008). For example, a different modality pair was “A light bulb is very hot” followed by “Rice isn’t black” versus a same visual modality pair “A giraffe is spotted” followed by “Rice isn’t black”. We predicted that the underlined word is where a modulation in the N400 may be seen. Additionally, we explored veracity by making half of the experimental target sentences false (“Rice isn’t white”). Participants were asked to judge whether each sentence was typically true or false. Our initial results indicate a modulation in the ERP based on both modality and veracity. For true (“Rice isn’t black”) and false target statements (“Rice isn’t white”) different modality pairs elicit a larger frontal-central N400 like effect compared to same modality pairs (Figure 1), replicating Hald et al., (2011). When comparing true versus false, the different modality pairs elicit a large posterior N400 for true compared to false sentences (replicating the effect for negated sentences, i.e., Fischler et al., 1983). However for same modality pairs there is a reduction in the N400 to true statements; no difference is seen between true and false statements in the ERP (Figure 2). These results replicate and extend previous ERP findings using the modality switch paradigm. The evidence suggests that not only do modality-specific simulations occur but they can even aid the processing of negation

Knowledge of Driving Vehicle Licensing Agency guidelines among NHS doctors:A multicentre observational study

Objectives: Over half of the UK population holds a driver's licence. The DVLA have produced guidelines to ensure drivers with medical conditions drive safely. Doctors should ensure that patients are given appropriate information and advice if they have a medical condition affecting their driving. We sought to evaluate doctors' knowledge of DVLA guidelines. Design: A 25-point questionnaire was designed from DVLA guidelines (‘The DVLA Questionnaire’). Five questions were included for each of neurology, cardiology, drug and alcohol abuse, visual, and respiratory disorders. Setting: Ealing Hospital, Northwick Park Hospital, Watford General Hospital, Norfolk and Norwich University Hospital and Leeds Teaching Hospitals Trust. Participants: 140 UK doctors. Main outcome measures: Questionnaire scores assessing knowledge of DVLA guidelines in five specialty areas. Results: The median overall questionnaire score was 28%, interquartile range 20–36% and range 0–100% [Watford 28%, Leeds 30%, Norfolk and Norwich 36%, Ealing 30%, Northwick Park 28%]. There were no significant differences between the scores for each centre (p = 0.1332), Mean scores for specialty areas were: neurology 33.1%, standard deviation 22.1; cardiology 35.6%, standard deviation 26.9; drug and alcohol abuse 30.6%, standard deviation 23.8; visual disorders 33.9%, standard deviation 23.5 and respiratory disorders 20.3%, standard deviation 24.8; overall score 30.7%. There was no significant difference between the scores of the specialty areas (p = 0.4060). Conclusions: Knowledge of DVLA guidelines in our cohort was low. There is a need for increased awareness among hospital doctors through focused education on driving restrictions for common medical conditions. Improving physician knowledge in this area may help optimise patient safety

Novel dimeric β-helical model of an ice nucleation protein with bridged active sites

<p>Abstract</p> <p>Background</p> <p>Ice nucleation proteins (INPs) allow water to freeze at high subzero temperatures. Due to their large size (>120 kDa), membrane association, and tendency to aggregate, an experimentally-determined tertiary structure of an INP has yet to be reported. How they function at the molecular level therefore remains unknown.</p> <p>Results</p> <p>Here we have predicted a novel β-helical fold for the INP produced by the bacterium <it>Pseudomonas borealis</it>. The protein uses internal serine and glutamine ladders for stabilization and is predicted to dimerize via the burying of a solvent-exposed tyrosine ladder to make an intimate hydrophobic contact along the dimerization interface. The manner in which <it>Pb</it>INP dimerizes also allows for its multimerization, which could explain the aggregation-dependence of INP activity. Both sides of the <it>Pb</it>INP structure have tandem arrays of amino acids that can organize waters into the ice-like clathrate structures seen on antifreeze proteins.</p> <p>Conclusions</p> <p>Dimerization dramatically increases the 'ice-active' surface area of the protein by doubling its width, increasing its length, and presenting identical ice-forming surfaces on both sides of the protein. We suggest that this allows sufficient anchored clathrate waters to align on the INP surface to nucleate freezing. As <it>Pb</it>INP is highly similar to all known bacterial INPs, we predict its fold and mechanism of action will apply to these other INPs.</p

Evidence of moderation effects in predicting active transport to school

Distance from home to school is an important influence on the decision to use active transport (AT); however, ecological perspectives would suggest this relationship may be moderated by individual, interpersonal and environmental factors. This study investigates whether (i) gender, (ii) biological maturation, (iii) perceived family support for physical activity (PA) and (iv) multiple deprivation moderate the relationship between distance to school and AT.A total of 611 children (11-12 years old, 334 females) were recruited from schools in Leicestershire, UK. Gender, family support for PA, and AT were self-reported. Home and school postcodes were used to determine multiple deprivation and distance to school (km). Predicted age at peak height velocity was used to indicate biological maturation.Logistic regressions revealed the main effects explained 40.2% of the variance in AT; however; distance to school was the only significant predictor. Further analyses revealed that distance to school had a greater negative impact on the use of AT in late-maturing (OR: 3.60, CI: 1.45-8.96), less deprived (OR: 3.54, CI: 1.17-10.72) and children with low family support of PA (OR: 0.26, CI: 0.11-0.61).This study provides evidence that, although distance to school might be the strongest predictor of AT, this relationship is complex

A Single Dose of Prednisolone as a Modulator of Undercarboxylated Osteocalcin and Insulin Sensitivity Post-Exercise in Healthy Young Men: A Study Protocol

Background: Undercarboxylated osteocalcin (ucOC) increases insulin sensitivity in mice. In humans, data are supportive, but the studies are mostly cross-sectional. Exercise increases whole-body insulin sensitivity, in part via ucOC, while acute glucocorticoid treatment suppresses ucOC in humans and mice.Objectives: A single dose of prednisolone reduces the rise in ucOC produced by exercise, which partly accounts for the failed increase in insulin sensitivity following exercise.Methods: Healthy young men (n=12) aged 18 to 40 years will be recruited. Initial assessments will include analysis of fasting blood, body composition, aerobic power (VO2peak), and peak heart rate. Participants will then be randomly allocated, double-blind, to a single dose of 20 mg of prednisolone or placebo. The two experimental trials will involve 30 minutes of interval exercise (90%-95% peak heart rate), followed by 3 hours of recovery and 2 hours of euglycaemic- hyperinsulinaemic clamp (insulin clamp). Seven muscle biopsies and blood samples will be obtained at rest, following exercise and post-insulin clamps.Results: The study is funded by the National Heart Foundation of Australia and Victoria University. Enrollment has already commenced and data collection will be completed in 2016.Conclusion: If the hypothesis is confirmed, the study will provide novel insights into the potential role of ucOC in insulin sensitivity in human subjects and will elucidate pathways involved in exercise-induced insulin sensitivity

Fitness costs of disrupting circadian rhythms in malaria parasites

Circadian biology assumes that biological rhythms maximize fitness by enabling organisms to coordinate with their environment. Despite circadian clocks being such a widespread phenomenon, demonstrating the fitness benefits of temporal coordination is challenging and such studies are rare. Here, we tested the consequences—for parasites—of being temporally mismatched to host circadian rhythms using the rodent malaria parasite, Plasmodium chabaudi. The cyclical nature of malaria infections is well known, as the cell cycles across parasite species last a multiple of approximately 24 h, but the evolutionary explanations for periodicity are poorly understood. We demonstrate that perturbation of parasite rhythms results in a twofold cost to the production of replicating and transmission stages. Thus, synchronization with host rhythms influences in-host survival and between-host transmission potential, revealing a role for circadian rhythms in the evolution of host–parasite interactions. More generally, our results provide a demonstration of the adaptive value of circadian rhythms and the utility of using an evolutionary framework to understand parasite traits

The effects of acute high-intensity interval exercise and hyperinsulinemic-euglycemic clamp on osteoglycin levels in young and middle-aged men

Osteoglycin (OGN) is a leucine-rich proteoglycan that has been implicated in the regulation of glucose in animal models. However, its relationship with glucose control in humans is unclear. We examined the effect of high-intensity interval exercise (HIIE) and hyperinsulinemic-euglycemic clamp on circulating levels of OGN as well as whether circulating OGN levels are associated with markers of glycemic control and cardio-metabolic health. Serum was analyzed for OGN (ELISA) levels from 9 middle-aged obese men (58.1 ± 2.2 years, body mass index [BMI] = 33.1 ± 1.4 kg∙m − 2, mean ± SEM) and 9 young men (27.8 ± 1.6 years, BMI = 24.4 ± 0.08 kg∙m − 2) who previously completed a study involving a euglycemic-hyperinsulinemic clamp at rest and after HIIE (4 x 4 minutes cycling at approximately 95% peak heart rate (HRpeak), interspersed with 2 minutes of active recovery). Blood pressure, body composition (dual-energy X-ray absorptiometry), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) were assessed. Serum OGN was higher in the young cohort compared with the middle-aged cohort (65.2 ± 10.1 ng/mL versus 36.5 ± 4. 5 ng/mL, p ≤ 0.05). Serum OGN was unaffected by acute HIIE but decreased after the insulin clamp compared with baseline (~ − 27 %, p = 0.01), post-exercise (~ − 35 %, p = 0.01), and pre-clamp (~ − 32 %, p = 0.02) time points, irrespective of age. At baseline, lower circulating OGN levels were associated with increased age, BMI, and fat mass, whereas higher OGN levels were related to lower fasting glucose. Higher OGN levels were associated with a higher glucose infusion rate. Exercise had a limited effect on circulating OGN. The mechanisms by which OGN affects glucose regulation should be explored in the future