Biology subjects

Nygaard, L.

Publications and source records attributed to Nygaard, L..

5 recordsLinked to original sources

bioRxiv2026

Associations Between Shape Iconicity Ratings and Speech Acoustics: Comparing Real Words and Pseudowords

Iconicity in spoken language refers to the mapping of speech sounds to meaning. For example, the pseudoword "bouba" is judged to sound rounded, whereas the pseudoword "kiki" is judged to sound pointed (Ramachandran & Hubbard, 2001). Recent work has found systematic relationships between speech acoustics and iconicity ratings in various meaning domains, including shape. To control for confounding by semantic knowledge, much research on iconicity relies on pseudowords. However, the role of iconicity in conveying the meanings of real words is still poorly understood. Here, we compared the relationship between speech acoustics and shape iconicity ratings for both pseudowords and real words. In this experiment, participants rated real words and pseudowords for how rounded or pointed they sounded. We compared the relationship between 12 acoustic parameters and the rounded/pointed ratings for both words and pseudowords. We found that the correlations between these acoustic parameters and the ratings were similar for real words and pseudowords, providing key evidence that iconicity of real words is linked to speech acoustics.

neuroscience↗

bioRxiv2026

Iconic Sound-Shape Correspondences in Aphasia

PurposeTo examine speech iconicity for shape in aphasia, we compared iconicity ratings from people with aphasia to those from neurologically intact individuals and evaluated how iconicity relates to phonological and semantic processing profiles in aphasia. MethodEleven people with aphasia and 11 age- and gender-matched neurologically intact participants rated how rounded or pointed 50 auditory pseudowords sounded using a 5-point scale. Ratings from participants with aphasia were compared to predicted iconicity ratings derived from reference ratings from prior work and to ratings from neurologically intact participants. For each participant with aphasia, correlations between individual ratings and predicted ratings were related to measures of phonological and semantic processing. ResultsRatings from people with aphasia were significantly correlated with both the predicted ratings and the ratings from neurologically intact participants. The strength of the correlation between individual ratings and predicted ratings did not differ significantly between groups, although there was a trend toward weaker correlations in the aphasia group. There were indications that greater language impairment was associated with greater disruption of iconicity ratings; in particular, deficits in phonological segmentation and semantic processing were associated with reduced sensitivity to shape iconicity. ConclusionThese findings suggest that sensitivity to shape iconicity is preserved in individuals with aphasia to varying degrees. The specific nature of language impairment appears to play an important role in determining iconicity processing in aphasia.

neuroscience↗

bioRxiv2026

DECODING HOW THE SOUNDS OF WORDS AND PSEUDOWORDS SIGNIFY SHAPE: AN fMRI STUDY

Iconicity refers to systematic links between word form and meaning. Although evidence for iconicity in natural language continues to grow, its neural basis remains unclear. Using functional magnetic resonance imaging (fMRI) and multivariate pattern analysis (MVPA), we examined iconic shape associations of auditory real words and pseudowords. The pseudowords were matched to the real words in phonemic and phonotactic properties, while differing primarily in the absence of learned semantic representations. Participants listened to each item and judged whether it sounded rounded or pointed. Searchlight MVPA revealed significant decoding for both stimulus types. For real words, iconic shape associations were decoded above chance in regions associated with visual and haptic shape processing (left lateral occipital complex and left anterior intraparietal sulcus), visual imagery (bilateral precuneus), phonological processing (bilateral supramarginal gyri), and semantic processing (left middle frontal and right superior frontal gyri). For pseudowords, significant decoding was found in regions associated with multisensory feature organization (right posterior intraparietal sulcus) and language processing (left angular and inferior frontal gyri). Together, these findings provide evidence for neural mechanisms mediating iconic associations, with language-related areas involved for both real words and pseudowords, and visual processing for real words.

neuroscience↗

bioRxiv2022

Accurate protein stability predictions from homology models

Calculating changes in protein stability ({Delta}{Delta}G) has been shown to be central for predicting the consequences of single amino acid substitutions in protein engineering as well as interpretation of genomic variants for disease risk. Structure-based calculations are considered most accurate, however the tools used to calculate {Delta}{Delta}Gs have been developed on experimentally resolved structures. Extending those calculations to homology models based on related proteins would greatly extend their applicability as large parts of e.g. the human proteome are not structurally resolved. In this study we aim to investigate the accuracy of {Delta}{Delta}G values predicted on homology models compared to crystal structures. Specifically, we identified four proteins with a large number of experimentally tested {Delta}{Delta}Gs and templates for homology modeling across a broad range of sequence identities, and selected three methods for {Delta}{Delta}G calculations to test. We find that {Delta}{Delta}G-values predicted from homology models compare equally well to experimental {Delta}{Delta}Gs as those predicted on experimentally established crystal structures, as long as the sequence identity of the model template to the target protein is at least 40%. In particular, the Rosetta cartesian_ddg protocol is robust against the small perturbations in the structure which homology modeling introduces. In an independent assessment, we observe a similar trend when using {Delta}{Delta}Gs to categorize variants as low or wild-type-like abundance. Overall, our results show that stability calculations performed on homology models can substitute for those on crystal structures with acceptable accuracy as long as the model is built on a template with sequence identity of at least 40% to the target protein.

biophysics↗

bioRxiv2020

Folliculin variants linked to Birt-Hogg-Dube syndrome are targeted for proteasomal degradation

Germline mutations in the folliculin (FLCN) tumor suppressor gene are linked to Birt-Hogg-Dube (BHD) syndrome, a dominantly inherited genetic disease characterized by predisposition to fibrofolliculomas, lung cysts, and renal cancer. Most BHD-linked FLCN variants include large deletions and splice site aberrations predicted to cause loss of function. The mechanisms by which missense variants and short in-frame deletions in FLCN trigger disease are unknown. Here, we present computational and experimental studies showing that the majority of such disease-causing FLCN variants cause loss of function due to proteasomal degradation of the encoded FLCN protein, rather than directly ablating FLCN function. Accordingly, several different single-site FLCN variants are present at strongly reduced levels in cells. In line with our finding that FLCN variants are protein quality control targets, several are also highly insoluble and fail to associate with the FLCN-binding partners FNIP1 and FNIP2. The lack of FLCN binding leads to rapid proteasomal degradation of FNIP1 and FNIP2. Half of the tested FLCN variants are mislocalized in cells, and one variant ({Delta}E510) forms perinuclear protein aggregates. A yeast-based screen revealed that the deubiquitylating enzyme Ubp15/USP7 and molecular chaperones regulate the turnover of the FLCN variants. Lowering the temperature to 29 {degrees}C led to a stabilization of two FLCN missense proteins, and for one variant (R362C), FLCN function was re-established at low temperature. In conclusion, we propose that most BHD-linked FLCN missense variants and small in-frame deletions operate by causing misfolding and degradation of the FLCN protein, and that stabilization of certain disease-linked variants may hold therapeutic potential.

molecular biology↗