Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Visually induced auditory expectancy in music reading: a behavioral and electrophysiological study

*no abstrac

The effect of speech degradation on the ability to track and predict turn structure in conversation

Conversation represents a considerable amount of the daily language usage and plays an important role in language acquisition. In conversation, listeners simultaneously process their interlocutor’s turn and prepare their own next turn. As such the turn-taking dynamics heavily relies on prediction. In other words, listeners avail prior knowledge to constrain both speech perception and production. Here we explored the relation between prediction and comprehension while watching two interlocutors having a conversation. We capitalize on gaze switch as a proxy of predictive behaviour to class dialogue turns as more or less well predicted and explore how this affects dialogue comprehension. Moreover, we study the extent to which speech degradation, by increasing the global uncertainty of the context, affects the relation between predictions, brain correlates of prediction errors (N400) and global comprehension. Results show that 1) listeners direct gaze to the current speaker, in particular in challenging conditions, 2) gaze behaviour possibly affects the semantic processing of the upcoming turn (N400), 3) participants with a more efficient gaze predictive behaviour better solve semantic uncertainties at the turn onset, in particular in the most challenging listening condition. Our findings contribute to a better understanding of the relation between predictions, neural predictions errors and speech comprehension under challenging conditions

Musical Training for Auditory Rehabilitation in Hearing Loss

Despite the overall success of cochlear implantation, language outcomes remain suboptimal and subject to a large inter-individual variability. Early auditory rehabilitation techniques have mostly focused on low-level sensory abilities. However, a new body of literature suggests that cognitive operations are critical for auditory perception remediation. We argue in this paper that musical training is a particularly appealing candidate for such therapies, as it involves highly relevant cognitive abilities, such as temporal predictions, hierarchical processing and auditory-motor interactions. We review recent studies demonstrating that music can enhance both language perception and production at multiple levels, from syllable processing to turn taking in natural conversation

Cognitive and methodological considerations on the effects of musical expertise on speech segmentation

Both speech and music are constituted by sequences of sound elements that unfold in time and require listeners to engage cognitive functions such as sequencing, attention, and memory. We recently ran a set of experiments with the aim of testing the effect of musical expertise on a rather high cognitive function: speech segmentation. Here, we will present the main concepts underlying the investigation of speech segmentation as well as its link to music and musical expertise. Interestingly, our results seem to show that musical training and expertise have effects on brain plasticity that may go beyond primary regions. Moreover, to facilitate and improve future research in this domain, we will here describe several delicate methodological precautions that need to be taken into account (e.g., the choice of stimuli, participants, data analyses). Finally, we will give some possible future directions to better understand the impact that music may have on speech processing

Temporal aspects of the feeling of familiarity for music and the emergence of conceptual processing

We tested whether the emergence of familiarity to a melody may trigger or co-occur with the processing of the concept(s) conveyed by emotions to, or semantic association with, the melody. With this objective, we recorded ERPs while participants were presented with highly familiar and less familiar melodies in a gating paradigm. The ERPs time locked to a tone of the melody called the "familiarity emergence point" showed a larger fronto-central negativity for highly familiar compared with less familiar melodies between 200 and 500 msec, with a peak latency around 400 msec. This latency and the sensitivity to the degree of familiarity/conceptual information suggest that this component was an N400, a marker of conceptual processing. Our data suggest that the feeling of familiarity evoked by a musical excerpt could be accompanied by other processing mechanisms at the conceptual level. Coupling the gating paradigm with ERP analyses might become a new avenue for investigating the neurocognitive basis of implicit musical knowledge

Influence of expressive versus mechanical musical performance on short-term memory for musical excerpts

International audienceAlthough adequate emotion regulation is considered to be essential in every day life, it is especially important in social interactions. However, the question as to what extent two different regulation strategies are effective in changing decision-making in a consequential socially interactive context remains unanswered. We investigated the effect of expressive suppression and emotional reappraisal on strategic decision-making in a social interactive task, that is, the Ultimatum Game. As hypothesized, participants in the emotional reappraisal condition accepted unfair offers more often than participants in the suppression and no-regulation condition. Additionally, the effect of emotional reappraisal influenced the amount of money participants proposed during a second interaction with partners that had treated them unfairly in a previous interaction. These results support and extend previous findings that emotional reappraisal as compared to expressive suppression, is a powerful regulation strategy that influences and changes how we interact with others even in the face of inequity