The CABB dataset: A multimodal corpus of communicative interactions for behavioural and neural analyses

We present a dataset of behavioural and fMRI observations acquired in the context of humans involved in multimodal referential communication. The dataset contains audio/video and motion-tracking recordings of face-to-face, task-based communicative interactions in Dutch, as well as behavioural and neural correlates of participants’ representations of dialogue referents. Seventy-one pairs of unacquainted participants performed two interleaved interactional tasks in which they described and located 16 novel geometrical objects (i.e., Fribbles) yielding spontaneous interactions of about one hour. We share high-quality video (from three cameras), audio (from head-mounted microphones), and motion-tracking (Kinect) data, as well as speech transcripts of the interactions. Before and after engaging in the face-to-face communicative interactions, participants’ individual representations of the 16 Fribbles were estimated. Behaviourally, participants provided a written description (one to three words) for each Fribble and positioned them along 29 independent conceptual dimensions (e.g., rounded, human, audible). Neurally, fMRI signal evoked by each Fribble was measured during a one-back working-memory task. To enable functional hyperalignment across participants, the dataset also includes fMRI measurements obtained during visual presentation of eight animated movies (35 minutes total). We present analyses for the various types of data demonstrating their quality and consistency with earlier research. Besides high-resolution multimodal interactional data, this dataset includes different correlates of communicative referents, obtained before and after face-to-face dialogue, allowing for novel investigations into the relation between communicative behaviours and the representational space shared by communicators. This unique combination of data can be used for research in neuroscience, psychology, linguistics, and beyond

Understanding clinical and biological heterogeneity to advance precision medicine in paediatric acute respiratory distress syndrome

Paediatric acute respiratory distress syndrome (PARDS) is a heterogeneous clinical syndrome that is associated with high rates of mortality and long-term morbidity. Factors that distinguish PARDS from adult acute respiratory distress syndrome (ARDS) include changes in developmental stage and lung maturation with age, precipitating factors, and comorbidities. No specific treatment is available for PARDS and management is largely supportive, but methods to identify patients who would benefit from specific ventilation strategies or ancillary treatments, such as prone positioning, are needed. Understanding of the clinical and biological heterogeneity of PARDS, and of differences in clinical features and clinical course, pathobiology, response to treatment, and outcomes between PARDS and adult ARDS, will be key to the development of novel preventive and therapeutic strategies and a precision medicine approach to care. Studies in which clinical, biomarker, and transcriptomic data, as well as informatics, are used to unpack the biological and phenotypic heterogeneity of PARDS, and implementation of methods to better identify patients with PARDS, including methods to rapidly identify subphenotypes and endotypes at the point of care, will drive progress on the path to precision medicine.</p

Mycobacterium tuberculosis ClpP Proteases Are Co-transcribed but Exhibit Different Substrate Specificities

PMCID: PMC3613350This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Transcutaneous electromyographic respiratory muscle recordings to quantify patient-ventilator interaction in mechanically ventilated children

BACKGROUND: To explore the feasibility of transcutaneous electromyographic respiratory muscle recordings to automatically quantify the synchronicity of patient-ventilator interaction in the pediatric intensive care unit. METHODS: Prospective observational study in a tertiary paediatric intensive care unit in an university hospital. Spontaneous breathing mechanically ventilated children < 18 years of age were eligible for inclusion. Patients underwent a 5-min continuous recording of ventilator pressure waveforms and transcutaneous electromyographic signal of the diaphragm. To evaluate patient-ventilator interaction, the obtained neural inspiration and ventilator pressurization timings were used to calculate trigger and cycle-off errors of each breath. Calculated errors were displayed in the dEMG-phase scale. RESULTS: Data of 23 patients were used for analysis. Based on the dEMG-phase scale, the median rates of synchronous, dyssynchronous and asynchronous breaths as classified by the automated analysis were 12.2% (1.9-33.8), 47.5% (36.3-63.1), and 28.9% (6.6-49.0). CONCLUSIONS: The dEMG-phase scale quantifying patient-ventilator breath synchronicity was demonstrated to be feasible and a reliable scale for mechanically ventilated children, reflected by high intra-class correlation coefficients. As this non-invasive tool is not restricted to a type of ventilator, it could easily be clinical implemented in the ventilated pediatric population. However; correlation studies between the EMG signal measured by surface EMG and esophageal catheters have to be performed

Can sacrificial feeding areas protect aquatic plants from herbivore grazing? Using behavioural ecology to inform wildlife management

Effective wildlife management is needed for conservation, economic and human well-being objectives. However, traditional population control methods are frequently ineffective, unpopular with stakeholders, may affect non-target species, and can be both expensive and impractical to implement. New methods which address these issues and offer effective wildlife management are required. We used an individual-based model to predict the efficacy of a sacrificial feeding area in preventing grazing damage by mute swans (Cygnus olor) to adjacent river vegetation of high conservation and economic value. The accuracy of model predictions was assessed by a comparison with observed field data, whilst prediction robustness was evaluated using a sensitivity analysis. We used repeated simulations to evaluate how the efficacy of the sacrificial feeding area was regulated by (i) food quantity, (ii) food quality, and (iii) the functional response of the forager. Our model gave accurate predictions of aquatic plant biomass, carrying capacity, swan mortality, swan foraging effort, and river use. Our model predicted that increased sacrificial feeding area food quantity and quality would prevent the depletion of aquatic plant biomass by swans. When the functional response for vegetation in the sacrificial feeding area was increased, the food quantity and quality in the sacrificial feeding area required to protect adjacent aquatic plants were reduced. Our study demonstrates how the insights of behavioural ecology can be used to inform wildlife management. The principles that underpin our model predictions are likely to be valid across a range of different resource-consumer interactions, emphasising the generality of our approach to the evaluation of strategies for resolving wildlife management problems

Characterization of the Interaction and Cross-Regulation of Three Mycobacterium tuberculosis RelBE Modules

RelBE represents a typical bacterial toxin-antitoxin (TA) system. Mycobacterium tuberculosis H37Rv, the pathogen responsible for human tuberculosis, contains three RelBE-like modules, RelBE, RelFG, and RelJK, which are at least partly expressed in human macrophages during infection. RelBE modules appear to be autoregulated in an atypical manner compared to other TA systems; however, the molecular mechanisms and potential interactions between different RelBE modules remain to be elucidated. In the present study, we characterized the interaction and cross-regulation of these Rel toxin-antitoxin modules from this unique pathogen. The physical interactions between the three pairs of RelBE proteins were confirmed and the DNA-binding domain recognized by three RelBE-like pairs and domain structure characteristics were described. The three RelE-like proteins physically interacted with the same RelB-like protein, and could conditionally regulate its binding with promoter DNA. The RelBE-like modules exerted complex cross-regulation effects on mycobacterial growth. The relB antitoxin gene could replace relF in cross-neutralizing the relG toxin gene. Conversely, relF enhanced the toxicity of the relE toxin gene, while relB increased the toxicity of relK. This is the first report of interactions between different pairs of RelBE modules of M. tuberculosis

Positive feedback and noise activate the stringent response regulator Rel in mycobacteria

Phenotypic heterogeneity in an isogenic, microbial population enables a subset of the population to persist under stress. In mycobacteria, stresses like nutrient and oxygen deprivation activate the stress response pathway involving the two-component system MprAB and the sigma factor, SigE. SigE in turn activates the expression of the stringent response regulator, rel. The enzyme polyphosphate kinase 1 (PPK1) regulates this pathway by synthesizing polyphosphate required for the activation of MprB. The precise manner in which only a subpopulation of bacterial cells develops persistence, remains unknown. Rel is required for mycobacterial persistence. Here we show that the distribution of rel expression levels in a growing population of mycobacteria is bimodal with two distinct peaks corresponding to low (L) and high (H) expression states, and further establish that a positive feedback loop involving the mprAB operon along with stochastic gene expression are responsible for the phenotypic heterogeneity. Combining single cell analysis by flow cytometry with theoretical modeling, we observe that during growth, noise-driven transitions take a subpopulation of cells from the L to the H state within a "window of opportunity" in time preceding the stationary phase. We find evidence of hysteresis in the expression of rel in response to changing concentrations of PPK1. Our results provide, for the first time, evidence that bistability and stochastic gene expression could be important for the development of "heterogeneity with an advantage" in mycobacteria.Comment: Accepted for publication in PLoS On

Conditional Gene Expression in Mycobacterium abscessus

Mycobacterium abscessus is an emerging human pathogen responsible for lung infections, skin and soft-tissue infections and disseminated infections in immunocompromised patients. It may exist either as a smooth (S) or rough (R) morphotype, the latter being associated with increased pathogenicity in various models. Genetic tools for homologous recombination and conditional gene expression are desperately needed to allow the study of M. abscessus virulence. However, descriptions of knock-out (KO) mutants in M. abscessus are rare, with only one KO mutant from an S strain described so far. Moreover, of the three major tools developed for homologous recombination in mycobacteria, only the one based on expression of phage recombinases is working. Several conditional gene expression tools have recently been engineered for Mycobacterium tuberculosis and Mycobacterium smegmatis, but none have been tested yet in M. abscessus. Based on previous experience with genetic tools allowing homologous recombination and their failure in M. abscessus, we evaluated the potential interest of a conditional gene expression approach using a system derived from the two repressors system, TetR/PipOFF. After several steps necessary to adapt TetR/PipOFF for M. abscessus, we have shown the efficiency of this system for conditional expression of an essential mycobacterial gene, fadD32. Inhibition of fadD32 was demonstrated for both the S and R isotypes, with marginally better efficiency for the R isotype. Conditional gene expression using the dedicated TetR/PipOFF system vectors developed here is effective in S and R M. abscessus, and may constitute an interesting approach for future genetic studies in this pathogen