Validation of DE50-MD dogs as a model for the brain phenotype of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD), a fatal musculoskeletal disorder, is associated with neurodevelopmental disorders and cognitive impairment caused by brain dystrophin deficiency. Dog models of DMD represent key translational tools to study dystrophin biology and to develop novel therapeutics. However, characterization of dystrophin expression and function in the canine brain is lacking. We studied the DE50-MD canine model of DMD that has a missense mutation in the donor splice site of exon 50. Using a battery of cognitive tests, we detected a neurocognitive phenotype in DE50-MD dogs including reduced attention, problem-solving and exploration of novel objects. Through a combination of capillary immunoelectrophoresis, immunolabelling, qPCR and RNAScope in situ hybridization we show that regional dystrophin expression in the adult canine brain reflects that of humans, and that the DE50-MD dog lacks full length dystrophin (Dp427) protein expression but retains expression of the two shorter brain-expressed isoforms, Dp140 and Dp71. Thus, the DE50-MD dog is a translationally-relevant pre-clinical model to study the consequences of Dp427 deficiency in the brain and to develop therapeutic strategies for the neurological sequelae of DMD.

A Disruption of the National Identity in the Brazilian-American Novel Samba Dreamers / Ruptura com a identidade nacional no romance brasileiro- estadunidense Samba Dreamers

The intensification of anti-immigration policies and discourses in the United States during Donald Trump’s administration reveals a reaction against the foreigner characterized, as Jacques Derrida proposes, by the widening of ethnocentric and xenophobic circles in face of the fluxes of capital, people, and information in contemporaneity. In this context, it is part of the critic’s responsibilities to address the link between literature and national identity, while attesting to the way literature transgresses the borders imposed upon it. This is the stance this article intends to take as it analyses Kathleen de Azevedo’s 2006 Brazilian-American novel Samba Dreamers. For this purpose, I depart from a discussion about the intrinsic relationship between hospitality and hostility to the foreigner, as well as from the possibility of literature of saying everything (tout dire), to argue that this novel objects to stable notions of nation, gestures towards a displacement of identity beyond the constraints of the state, and invites a post-national mode of thinking.Keywords: immigrant writing; post-nationalist literature; Brazilian-American literature; national identity.Resumo: A intensificação de políticas e discursos anti-imigração nos Estados Unidos durante a presidência de Donald Trump revela uma reação ao estrangeiro caracterizada, como coloca Jacques Derrida, pelo espessamento dos círculos etnocêntricos e xenofóbicos diante dos fluxos contemporâneos de capital, pessoas e informações. Nesse contexto, é papel do crítico abordar a relação entre literatura e identidade nacional, atentando para as formas pelas quais a literatura transpõe as fronteiras que lhe são impostas. Este é o posicionamento que se pretende ter aqui, enquanto se analisa o romance brasileiro-estadunidense Samba Dreamers, de Kathleen de Azevedo (2006). Para isso, parte-se de uma discussão sobre a relação intrínseca entre hospitalidade e hostilidade ao estrangeiro, assim como da possibilidade da literatura de dizer tudo (tout dire), para propor que o romance se opõe a noções estáveis de nação, articula o deslocamento da ideia de identidade para além dos limites geopolíticos do estado e convida a um pensamento pós-nacional.Palavras-chave: escrita de imigrantes; literatura pós-nacional; literatura brasileiro-estadunidense; identidade nacional.

Natural Infant-Directed Speech Facilitates Neural Tracking of Prosody

Infants prefer to be addressed with infant-directed speech (IDS). IDS benefits language acquisition through amplified low-frequency amplitude modulations. It has been reported that this amplification increases electrophysiological tracking of IDS compared to adult-directed speech (ADS). It is still unknown which particular frequency band triggers this effect. Here, we compare tracking at the rates of syllables and prosodic stress, which are both critical to word segmentation and recognition. In mother-infant dyads (n=30), mothers described novel objects to their 9-month-olds while infants' EEG was recorded. For IDS, mothers were instructed to speak to their children as they typically do, while for ADS, mothers described the objects as if speaking with an adult. Phonetic analyses confirmed that pitch features were more prototypically infant-directed in the IDS-condition compared to the ADS-condition. Neural tracking of speech was assessed by speech-brain coherence, which measures the synchronization between speech envelope and EEG. Results revealed significant speech-brain coherence at both syllabic and prosodic stress rates, indicating that infants track speech in IDS and ADS at both rates. We found significantly higher speech-brain coherence for IDS compared to ADS in the prosodic stress rate but not the syllabic rate. This indicates that the IDS benefit arises primarily from enhanced prosodic stress. Thus, neural tracking is sensitive to parents’ speech adaptations during natural interactions, possibly facilitating higher-level inferential processes such as word segmentation from continuous speech.

Face Specific vs. Expertise Hypotheses: Insights into the Underlying Mechanisms of Face Processing in Prosopagnosia

<p>A prominent debate in visual perception centers on the nature of mechanisms underlying face processing. One side of this debate argues that faces are processed by specialised mechanisms that are not involved in any form of object processing. By contrast, the other side argues that faces are processed by generic mechanisms common to all objects for which we are experts. To distinguish between these two hypotheses, I investigated whether participants with impaired face processing (developmental prosopagnosia) can acquire expertise with novel objects called greebles. To do so, I recruited 10 developmental prosopagnosics and 10 neurotypical control participants. All participants completed a standard training program for developing expertise with greebles, as well as two similar training programs with upright faces and inverted faces. Prosopagnosics were able to acquire expertise with greebles to the same extent as controls but were impaired when learning upright faces. These results demonstrate that deficits for face processing in individuals with prosopagnosia are dissociated from their ability to gain expertise with objects. Overall, the results support the hypothesis that face processing relies on specialised mechanisms, rather than generic expertise mechanisms. Despite their deficits, though, prosopagnosics still showed some evidence of learning with upright faces and showed better learning with upright faces than inverted faces. These findings suggest that prosopagnosics have face-specific mechanisms that are somewhat functional, and that training could be a useful rehabilitation tool in developmental prosopagnosia. Finally, I found substantial heterogeneity among the patterns of performance of the prosopagnosics, suggesting that further investigations into the subtypes of prosopagnosia are warranted.</p>

Face Specific vs. Expertise Hypotheses: Insights into the Underlying Mechanisms of Face Processing in Prosopagnosia

<p>A prominent debate in visual perception centers on the nature of mechanisms underlying face processing. One side of this debate argues that faces are processed by specialised mechanisms that are not involved in any form of object processing. By contrast, the other side argues that faces are processed by generic mechanisms common to all objects for which we are experts. To distinguish between these two hypotheses, I investigated whether participants with impaired face processing (developmental prosopagnosia) can acquire expertise with novel objects called greebles. To do so, I recruited 10 developmental prosopagnosics and 10 neurotypical control participants. All participants completed a standard training program for developing expertise with greebles, as well as two similar training programs with upright faces and inverted faces. Prosopagnosics were able to acquire expertise with greebles to the same extent as controls but were impaired when learning upright faces. These results demonstrate that deficits for face processing in individuals with prosopagnosia are dissociated from their ability to gain expertise with objects. Overall, the results support the hypothesis that face processing relies on specialised mechanisms, rather than generic expertise mechanisms. Despite their deficits, though, prosopagnosics still showed some evidence of learning with upright faces and showed better learning with upright faces than inverted faces. These findings suggest that prosopagnosics have face-specific mechanisms that are somewhat functional, and that training could be a useful rehabilitation tool in developmental prosopagnosia. Finally, I found substantial heterogeneity among the patterns of performance of the prosopagnosics, suggesting that further investigations into the subtypes of prosopagnosia are warranted.</p>

Age-Related Decline in Pragmatic Reasoning of Older Adults

As speech is often ambiguous, pragmatic reasoning—the process of integrating multiple sources of information including semantics, ostensive cues and contextual information (Bohn & Frank, 2019)—is essential to understanding a speaker’s intentions. Despite current literature suggesting that certain social cognitive processes such as gaze-processing (Slessor et al., 2014) appear to be impaired in late adulthood, it is not well understood if pragmatic reasoning decline with age. Here, we examined young adults’ (aged 19-25; n=41) and older adults’ (aged 60-79; n=41) ability to engage in pragmatic reasoning in a cue integration task. In Experiment 1, participants had to integrate contextual (participants and speaker knew there were two novel objects but the latter could only see one), semantic (“There’s the [novel-label]” or “Where’s the [novel-label]”), and gaze (speaker looked at the mutually-visible object) cues to identify the referent (Nurmsoo & Bloom, 2008). In Experiment 2, participants received contextual and semantic cues less gaze cue. In both experiments, the target referent object for “There” and “Where” trials was the mutually-visible object and the object the speaker could not see respectively. Overall, young adults outperformed older adults, even in the simpler two-cue Experiment 2 (ps&lt;.006). While older adults were significantly above chance in “There” trials for both experiments as well as “Where” trials in Experiment 2 (ps&lt;.05), they had specific difficulty in integrating three cues in “Where” trials, where a more sophisticated interpretation of the multiple cues was required (p=.42). Our findings provide important insights into an age-related decline of pragmatic reasoning in older adults.

Exploration-Avoidance and an Anthropogenic Toxin (Lead Pb) in a Wild Parrot (Kea: Nestor notabilis)

<p><b>The ecological study of personality in animals is a relatively new field of behavioural investigation and of increasing importance to wildlife conservation. Kea (Nestor notabilis), hill country parrots endemic to South Island, New Zealand, are a good model for studying personality in an ecological context because they have a neophilic and explorative nature and are accessible for experimentation in the field. The study of personality is relevant to kea conservation if particular personality types (e.g., explorative) cause increased mortality, especially where kea come into contact with anthropogenic dangers. Its relevance may be even greater if, due to kea's social nature, social facilitation spreads that risk to other personality types. In this study I use experimental presentations of novel objects to investigate individual variation in exploration-avoidance behaviour in kea and apply my findings to the risk of lead exposure and poisoning because lead is present as novel objects in kea habitat. Analyses of blood lead levels and reactions to novel objects indicate that sex and age class, but more specifically personality, underlie a kea's reactions to novel objects and lead objects. Kea with explorative personalities have higher blood lead levels than aversive individuals. My results also indicate that social context, i.e., the presence of conspecifics and group size, are influential. Kea are more inclined to investigate novel objects in the presence of conspecifics, indicating that social facilitation plays a role in the exploration of novelty. Significant relationships between dominance category and behavioural response to novel objects indicates that social rank is related to personality, with dominant individuals being more explorative and subordinate individuals less explorative. These results highlight the potentially heavy cost of explorativity where kea and human habitats overlap. Explorative kea may be subject to an increased risk of injury or death and, if they facilitate exploration in aversive kea, increases the risk to those kea as well. Lead is a known cause of death in kea and as such affects kea survival. Lead has also been shown to have deleterious effects on other species at low levels.</b></p> <p>Kea live in a highly seasonal and periodically severe environment, the dangers of which arecompounded by various anthropogenic hazards including lead exposure. Kea are a longlivedand slowreproducing species at a high risk of decline from even a small reduction in itssurvival rate an imposed reduction in numbers could result in nonrecovery.</p>

Exploration-Avoidance and an Anthropogenic Toxin (Lead Pb) in a Wild Parrot (Kea: Nestor notabilis)

<p><b>The ecological study of personality in animals is a relatively new field of behavioural investigation and of increasing importance to wildlife conservation. Kea (Nestor notabilis), hill country parrots endemic to South Island, New Zealand, are a good model for studying personality in an ecological context because they have a neophilic and explorative nature and are accessible for experimentation in the field. The study of personality is relevant to kea conservation if particular personality types (e.g., explorative) cause increased mortality, especially where kea come into contact with anthropogenic dangers. Its relevance may be even greater if, due to kea's social nature, social facilitation spreads that risk to other personality types. In this study I use experimental presentations of novel objects to investigate individual variation in exploration-avoidance behaviour in kea and apply my findings to the risk of lead exposure and poisoning because lead is present as novel objects in kea habitat. Analyses of blood lead levels and reactions to novel objects indicate that sex and age class, but more specifically personality, underlie a kea's reactions to novel objects and lead objects. Kea with explorative personalities have higher blood lead levels than aversive individuals. My results also indicate that social context, i.e., the presence of conspecifics and group size, are influential. Kea are more inclined to investigate novel objects in the presence of conspecifics, indicating that social facilitation plays a role in the exploration of novelty. Significant relationships between dominance category and behavioural response to novel objects indicates that social rank is related to personality, with dominant individuals being more explorative and subordinate individuals less explorative. These results highlight the potentially heavy cost of explorativity where kea and human habitats overlap. Explorative kea may be subject to an increased risk of injury or death and, if they facilitate exploration in aversive kea, increases the risk to those kea as well. Lead is a known cause of death in kea and as such affects kea survival. Lead has also been shown to have deleterious effects on other species at low levels.</b></p> <p>Kea live in a highly seasonal and periodically severe environment, the dangers of which arecompounded by various anthropogenic hazards including lead exposure. Kea are a longlivedand slowreproducing species at a high risk of decline from even a small reduction in itssurvival rate an imposed reduction in numbers could result in nonrecovery.</p>

Oscillatory visual mechanisms revealed by random temporal sampling

It is increasingly apparent that functionally significant neural activity is oscillatory in nature. Demonstrating the implications of this mode of operation for perceptual/cognitive function remains somewhat elusive. This report describes the technique of random temporal sampling for the investigation of visual oscillatory mechanisms. The technique is applied in visual recognition experiments using different stimulus classes (words, familiar objects, novel objects, and faces). Classification images reveal variations of perceptual effectiveness according to the temporal features of stimulus visibility. These classification images are also decomposed into their power and phase spectra. Stimulus classes lead to distinct outcomes and the power spectra of classification images are highly generalizable across individuals. Moreover, stimulus class can be reliably decoded from the power spectrum of individual classification images. These findings and other aspects of the results validate random temporal sampling as a promising new method to study oscillatory visual mechanisms.