Biology subjects

Graves, J.

Publications and source records attributed to Graves, J..

4 recordsLinked to original sources

bioRxiv2022

A unitary model of auditory frequency change perception

Changes in the frequency content of sounds over time are arguably the most basic form of information about the behavior of sound-emitting objects. In perceptual studies, such changes have mostly been investigated separately, as aspects of either pitch or timbre. Here, we propose a unitary account of "up" and "down" subjective judgments of frequency change, based on a model combining auditory correlates of acoustic cues in a sound-specific and listener-specific manner. To do so, we introduce a generalized version of so-called Shepard tones, allowing symmetric manipulations of spectral information on a fine scale, usually associated to pitch (spectral fine structure, SFS), and on a coarse scale, usually associated timbre (spectral envelope, SE). In a series of behavioral experiments, listeners reported "up" or "down" shifts across pairs of generalized Shepard tones that differed in SFS, in SE, or in both. We observed the classic properties of Shepard tones for either SFS or SE shifts: subjective judgements followed the smallest log-frequency change direction, with cases of ambiguity and circularity. Interestingly, when both SFS and SE changes were applied concurrently (synergistically or antagonistically), we observed a trade-off between cues. Listeners were encouraged to report when they perceived "both" directions of change concurrently, but this rarely happened, suggesting a unitary percept. A computational model could accurately fit the behavioral data by combining different cues reflecting frequency changes after auditory filtering. The model revealed that cue weighting depended on the nature of the sound. When presented with harmonic sounds, listeners put more weight on SFS-related cues, whereas inharmonic sounds led to more weight on SE-related cues. Moreover, these stimulus-based factors were modulated by inter-individual differences, revealing variability across listeners in the detailed recipe for "up" and "down" judgments. We argue that frequency changes are tracked perceptually via the adaptive combination of a diverse set of cues, in a manner that is in fact similar to the derivation of other basic auditory dimensions such as spatial location.

neuroscience↗

bioRxiv2020

Pre-attentive processing of neutral and emotional sounds in congenital amusia

Congenital amusia is a life-long deficit of musical processing. This deficit can extend to the processing of language and in particular, emotional prosody. In a previous behavioral study, we revealed that while amusic individuals had difficulties in explicitly recognizing emotions for short vowels, they rated the emotional intensity of these same vowels as did their matched control participants. This finding led to the hypothesis that congenital amusics might be impaired for explicit emotional prosody recognition, but not for its implicit processing. With the aim to investigate amusics automatic processing of prosody, the present study measured electroencephalography (EEG) when participants listened passively to vowels presented within an oddball paradigm. Emotionally neutral vowel served as the standard and either emotional (anger and sadness) or neutral vowels as deviants. Evoked potentials were compared between participants with congenital amusia and control participants matched in age, education, and musical training. The MMN was rather preserved for all deviants in amusia, whereas an earlier negative component was found decreased in amplitude in amusics compared to controls for the neutral and sadness deviants. For the most salient deviant (anger), the P3a was decreased in amplitude for amusics compared to controls. These results showed some preserved automatic detection of emotional deviance in amusia despite an early deficit to process subtle acoustic changes. In addition, the automatic attentional shift in response to salient deviants at later processing stages was reduced in amusics in comparison to the controls. In the three ERPs related to the deviance, between-group differences were larger over bilateral prefrontal areas, previously shown to display functional impairments in congenital amusia. Our present study thus provides further understanding of the dichotomy between implicit and explicit processing in congenital amusia, in particular for vocal stimuli with emotional content.

neuroscience↗

bioRxiv2018

Platypus Induced Pluripotent Stem Cells: the Unique Pluripotency Signature of a Monotreme

Summary StatementThe generation and transcriptome analysis of the first induced pluripotent stem cells from the platypus reveals SOX2 has been a key driver of the expanded pluripotency regulatory network in placental mammals.\n\nABSTRACTThe mechanisms by which pluripotency has evolved remain unclear. To gain insight into the evolution of mammalian pluripotency we have generated induced pluripotent stem cells (piPSCs) from the platypus. Deep sequencing of the piPSC transcriptome revealed that piPSCs robustly express the core eutherian pluripotency factors OCT4, SOX2 and NANOG. Given the more extensive role of SOX3 over SOX2 in avian pluripotency, our data indicate that between 315 million years and 166 million years ago primitive mammals replaced the role of SOX3 in the vertebrate pluripotency network with SOX2. DAX1/NR0B1 is not expressed in piPSCs and an analysis of the platypus DAX1 promoter revealed the absence of a proximal SOX2-binding DNA motif known to be critical for DAX1 expression in eutherian pluripotent stem cells, suggesting that the acquisition of SOX2 responsiveness by DAX1 has facilitated its recruitment into the pluripotency network of eutherians. We further show that the expression ratio of X chromosomes to autosomes (X1-5 X1-5:AA) is approximately equal to 1 indicating that there is no upregulation of X-linked genes and that there is no preference for silencing of maternal or paternal alleles (ie imprinting).

cell biology↗

bioRxiv2018

Multiple sclerosis-associated changes in the composition and immune functions of spore-forming bacteria

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by adaptive and innate immune system dysregulation. Recent work has revealed moderate alteration of gut microbial communities in subjects with MS and in experimental, induced models. However, a mechanistic understanding linking the observed changes in the microbiota and the presence of the disease is still missing. Chloroform-resistant, spore-forming bacteria have been shown to exhibit immunomodulatory properties in vitro and in vivo, but they have not yet been characterized in the context of human disease. This study addresses the community composition and immune function of this bacterial fraction in MS. We identify MS-associated spore-forming taxa and show that their presence correlates with impaired differentiation of IL-10 secreting, regulatory T lymphocytes in-vitro. Colonization of antibiotic-treated mice with spore-forming bacteria allowed us to identify some bacterial taxa favoring IL-10+ lymphocyte differentiation and others inducing differentiation of pro-inflammatory, IFN{gamma}+ T lymphocytes. However, when fed into antibiotic-treated mice, both MS and control derived spore-forming bacteria were able to induce immunoregulatory responses.\n\nOur analysis also identified Akkermansia muciniphila as a key organism that may interact either directly or indirectly with spore-forming bacteria to exacerbate the inflammatory effects of MS-associated gut microbiota. Thus, changes in the spore-forming fraction may influence T lymphocyte-mediated inflammation in MS. This experimental approach of isolating a subset of microbiota based on its functional characteristics may be useful to investigate other microbial fractions at greater depth.\n\nImportanceDespite the rapid emergence of microbiome related studies in human diseases, few go beyond a simple description of relative taxa levels in a select group of patients. Our study integrates computational analysis with in vitro and in vivo exploration of inflammatory properties of both complete microbial communities and individual taxa, revealing novel functional associations. We specifically show that while small differences exist between the microbiomes of MS patients and healthy subjects, these differences are exacerbated in the chloroform resistant fraction. We further demonstrate that, when purified from MS patients, this fraction is associated with impaired immunomodulatory responses in vitro.

immunology↗