Contributors: Keith Pardee, Alexander A. Green, Melissa K. Takahashi, Dana Braff, Guillaume Lambert, Jeong Wook Lee, Tom Ferrante, Duo Ma, Nina Donghia, Melina Fan
... The recent Zika virus outbreak highlights the need for low-cost diagnostics that can be rapidly developed for distribution and use in pandemic regions. Here, we report a pipeline for the rapid design, assembly, and validation of cell-free, paper-based sensors for the detection of the Zika virus RNA genome. By linking isothermal RNA amplification to toehold switch RNA sensors, we detect clinically relevant concentrations of Zika virus sequences and demonstrate specificity against closely related Dengue virus sequences. When coupled with a novel CRISPR/Cas9-based module, our sensors can discriminate between viral strains with single-base resolution. We successfully demonstrate a simple, field-ready sample-processing workflow and detect Zika virus from the plasma of a viremic macaque. Our freeze-dried biomolecular platform resolves important practical limitations to the deployment of molecular diagnostics in the field and demonstrates how synthetic biology can be used to develop diagnostic tools for confronting global health crises.
Original investigation - Genetic and alarm call diversity across scattered populations of speckled ground squirrels (Spermophilus suslicus)
Contributors: Vera A. Matrosova, Mikhail Yu. Rusin, Elena V. Volodina, Svetlana V. Proyavka, Ludmila E. Savinetskaya, Olga N. Shekarova, Hanna V. Rashevska, Ilya A. Volodin
... Alarm calls of ground squirrels are innate signals, showing substantial geographical variation across populations without the masking effects of sex and age- related variation. This makes them a convenient model for studying population genetic effects on the evolution of alarm communication. We compared data on the alarm call structure and the mitochondrial DNA (mtDNA) complete control region (C-region) (998–1002bp) polymorphism in the same 90 individual speckled ground squirrels (Spermophilus suslicus) across 6 populations (15 individuals per population), separated by distances from 12 to 1274km. We calculated acoustic distances between each pair of populations based on acoustic variables of alarm calls, averaged for each individual using Euclidean distances of population centroids, in the space of canonical axes of discriminant function analysis. Genetic distances ranged of 0–1.1% within populations and of 0.5–4.9% between populations. Prominent differences were found between eastern and western populations separated by the Dnieper River. Both genetic and acoustic distances showed a significant positive correlation with geographical among populations. Positive correlation between acoustic and genetic distances did not reach significance. These results support effects of ecological selection on the alarm call variables rather than the genetic drift hypothesis. In addition, these results support the current taxonomic separation between subspecies of speckled ground squirrels differing in diploid chromosome sets 2n=34 (Spermophilus suslicus guttatus) and 2n=36 (Spermophilus suslicus odessanus).
Contributors: Linshu Zhou, Cunmei Jiang, Yingying Wu, Yufang Yang
... This study on event-related brain potential investigated whether music can convey the concept of movement. Using a semantic priming paradigm, natural musical excerpts were presented to non-musicians, followed by semantically congruent or incongruent pictures that depicted objects either in motion or at rest. The priming effects were tested in object decision and implicit recognition tasks to distinguish the effects of automatic conceptual activation from response competition. Results showed that in both tasks, pictures that were incongruent to preceding musical excerpts elicited larger N400 than congruent pictures, suggesting that music can prime the representations of movement concepts. Results of the multiple regression analysis showed that movement expression could be well predicted by specific acoustic and musical features, indicating the associations between music per se and the processing of iconic musical meaning.
Unsupervised and phonologically controlled interpolation of Austrian German language varieties for speech synthesis
Contributors: Markus Toman, Michael Pucher, Sylvia Moosmüller, Dietmar Schabus
... This paper presents an unsupervised method that allows for gradual interpolation between language varieties in statistical parametric speech synthesis using Hidden Semi-Markov Models (HSMMs). We apply dynamic time warping using Kullback–Leibler divergence on two sequences of HSMM states to find adequate interpolation partners. The method operates on state sequences with explicit durations and also on expanded state sequences where each state corresponds to one feature frame. In an intelligibility and dialect rating subjective evaluation of synthesized test sentences, we show that our method can generate intermediate varieties for three Austrian dialects (Viennese, Innervillgraten, Bad Goisern). We also provide an extensive phonetic analysis of the interpolated samples. The analysis includes input-switch rules, which cover historically different phonological developments of the dialects versus the standard language; and phonological processes, which are phonetically motivated, gradual, and common to all varieties. We present an extended method which linearly interpolates phonological processes but uses a step function for input-switch rules. Our evaluation shows that the integration of this kind of phonological knowledge improves dialect authenticity judgment of the synthesized speech, as performed by dialect speakers. Since gradual transitions between varieties are an existing phenomenon, we can use our methods to adapt speech output systems accordingly.
Coding interactions in Motivational Interviewing with computer-software: What are the advantages for process researchers?
Contributors: Florian E. Klonek, Vicenç Quera, Simone Kauffeld
... Motivational Interviewing (MI) is an evidence-based behavior change intervention. The interactional change processes that make MI effective have been increasingly studied using observational coding schemes. We introduce an implementation of a software-supported MI coding scheme—the Motivational Interviewing Treatment Integrity code (MITI)—and discuss advantages for process researchers. Furthermore, we compared reliability of the software version with prior results of the paper version. A sample of 14 double-coded dyadic interactions showed good to excellent interrater reliabilities. We selected a second sample of 22 sessions to obtain convergent validity results of the software version: substantial correlations were obtained between the software instrument and the Rating Scales for the Assessment of Empathic Communication. Finally, we demonstrate how the software version can be used to test whether single code frequencies obtained by using intervals shorter than 20min (i.e., 5 or 10min) are accurate estimates of the respective code frequencies for the entire session (i.e., behavior slicing). Our results revealed that coding only a 10-min interval provides accurate estimates of the entire session. Our study demonstrates that the software implementation of the MITI is a reliable and valid instrument. We discuss advantages of the software version for process research in MI.
Contributors: Nicolas Renier, Zhuhao Wu, David J. Simon, Jing Yang, Pablo Ariel, Marc Tessier-Lavigne
... The visualization of molecularly labeled structures within large intact tissues in three dimensions is an area of intense focus. We describe a simple, rapid, and inexpensive method, iDISCO, that permits whole-mount immunolabeling with volume imaging of large cleared samples ranging from perinatal mouse embryos to adult organs, such as brains or kidneys. iDISCO is modeled on classical histology techniques, facilitating translation of section staining assays to intact tissues, as evidenced by compatibility with 28 antibodies to both endogenous antigens and transgenic reporters like GFP. When applied to degenerating neurons, iDISCO revealed unexpected variability in number of apoptotic neurons within individual sensory ganglia despite tight control of total number in all ganglia. It also permitted imaging of single degenerating axons in adult brain and the first visualization of cleaved Caspase-3 in degenerating embryonic sensory axons in vivo, even single axons. iDISCO enables facile volume imaging of immunolabeled structures in complex tissues.
Cortical pitch response components index stimulus onset/offset and dynamic features of pitch contours
Contributors: Ananthanarayan Krishnan, Jackson T. Gandour, Saradha Ananthakrishnan, Venkatakrishnan Vijayaraghavan
... Voice pitch is an important information-bearing component of language that is subject to experience dependent plasticity at both early cortical and subcortical stages of processing. We have already demonstrated that pitch onset component (Na) of the cortical pitch response (CPR) is sensitive to flat pitch and its salience. In regards to dynamic pitch, we do not yet know whether the multiple pitch-related transient components of the CPR reflect specific temporal attributes of such stimuli. Here we examine the sensitivity of the multiple transient components of CPR to changes in pitch acceleration associated with the Mandarin high rising lexical tone. CPR responses from Chinese listeners were elicited by three citation forms varying in pitch acceleration and duration. Results showed that the pitch onset component (Na) was invariant to changes in acceleration. In contrast, Na–Pb and Pb–Nb showed a systematic increase in the interpeak latency and decrease in amplitude with increase in pitch acceleration that followed the time course of pitch change across the three stimuli. A strong correlation with pitch acceleration was observed for these two components only – a putative index of pitch-relevant neural activity associated with the more rapidly-changing portions of the pitch contour. Pc–Nc marks unambiguously the stimulus offset. We therefore propose that in the early stages of cortical sensory processing, a series of neural markers flag different temporal attributes of a dynamic pitch contour: onset of temporal regularity (Na); changes in temporal regularity between onset and offset (Na–Pb, Pb–Nb); and offset of temporal regularity (Pc–Nc). At the temporal electrode sites, the stimulus with the most gradual change in pitch acceleration evoked a rightward asymmetry. Yet within the left hemisphere, stimuli with more gradual change were indistinguishable. These findings highlight the emergence of early hemispheric preferences and their functional roles as related to sensory and cognitive properties of the stimulus.
Contributors: Sebastian Jentschke, Angela D. Friederici, Stefan Koelsch
... Music is a basic and ubiquitous socio-cognitive domain. However, our understanding of the time course of the development of music perception, particularly regarding implicit knowledge of music-syntactic regularities, remains contradictory and incomplete. Some authors assume that the acquisition of knowledge about these regularities lasts until late childhood, but there is also evidence for the presence of such knowledge in four- and five-year-olds. To explore whether such knowledge is already present in younger children, we tested whether 30-month-olds (N = 62) show neurophysiological responses to music-syntactically irregular harmonies. We observed an early right anterior negativity in response to both irregular in-key and out-of-key chords. The N5, a brain response usually present in older children and adults, was not observed, indicating that processes of harmonic integration (as reflected in the N5) are still in development in this age group. In conclusion, our results indicate that 30-month-olds already have acquired implicit knowledge of complex harmonic music-syntactic regularities and process musical information according to this knowledge.
Article - Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders
Contributors: Elaine Y. Hsiao, Sara W. McBride, Sophia Hsien, Gil Sharon, Embriette R. Hyde, Tyler McCue, Julian A. Codelli, Janet Chow, Sarah E. Reisman, Joseph F. Petrosino
... Neurodevelopmental disorders, including autism spectrum disorder (ASD), are defined by core behavioral impairments; however, subsets of individuals display a spectrum of gastrointestinal (GI) abnormalities. We demonstrate GI barrier defects and microbiota alterations in the maternal immune activation (MIA) mouse model that is known to display features of ASD. Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naive mice with a metabolite that is increased by MIA and restored by B. fragilis causes certain behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in a mouse model of ASD and identify a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders.
Contributors: Frank Rudzicz
... This paper presents a system that transforms the speech signals of speakers with physical speech disabilities into a more intelligible form that can be more easily understood by listeners. These transformations are based on the correction of pronunciation errors by the removal of repeated sounds, the insertion of deleted sounds, the devoicing of unvoiced phonemes, the adjustment of the tempo of speech by phase vocoding, and the adjustment of the frequency characteristics of speech by anchor-based morphing of the spectrum. These transformations are based on observations of disabled articulation including improper glottal voicing, lessened tongue movement, and lessened energy produced by the lungs. This system is a substantial step towards full automation in speech transformation without the need for expert or clinical intervention.