bioRxiv Science⌕ Search

Biology subjects

Hsieh, T.-H.

Publications and source records attributed to Hsieh, T.-H..

4 recordsLinked to original sources

Musicians and non-musicians consonant/dissonant perception investigated by EEG and fMRI

The perception of two (or more) simultaneous musical notes, depending on their pitch interval(s), could be broadly categorized as consonant or dissonant. Previous studies have suggested that musicians and non-musicians adopt different strategies when discerning music intervals: the frequency ratio (perfect fifth or tritone) for the former, and frequency differences (e.g., roughness vs. non-roughness) for the latter. To extend and replicate this previous finding, in this follow-up study we reran the ElectroEncephaloGraphy (EEG) experiment, and separately collected functional magnetic resonance imaging (fMRI) data of the same protocol. The behavioral results replicated our previous findings that musicians used pitch intervals and nonmusicians roughness for consonant judgments. And the ERP amplitude differences between groups in both frequency ratio and frequency differences were primarily around N1 and P2 periods along the midline channels. The fMRI results, with the joint analyses by univariate, multivariate, and connectivity approaches, further reinforce the involvement of midline and related-brain regions in consonant/dissonance judgments. Additional representational similarity analysis (or RSA), and the final spatio-temporal searchlight RSA (or ss-RSA), jointly combined the fMRI-EEG into the same representational space, providing final support on the neural substrates of neurophysiological signatures. Together, these analyses not just exemplify the importance of replication, that musicians rely more on top-down knowledge for consonance/dissonance perception; but also demonstrate the advantages of multiple analyses in constraining the findings from both EEG and fMRI. Significance StatementIn this study, the neural correlates of consonant and dissonant perception has been revisited with both EEG and fMRI. Behavioral results of the current study well replicated the pattern of our earlier work (Kung et al., 2014), and the ERP results, though showing that both musicians and nonmusicians processed rough vs. non-rough notes similarly, still supported the top-down modulation in musicians likely through long-term practice. The fMRI results, combining univariate (GLM contrast and functional connectivity) and multivariate (MVPA searchlight and RSA on voxel-, connectivity-, and spatio-temporal RSA searchlight-level) analyses, commonly speak to lateralized and midline regions, at different time windows, as the core brain networks that underpin both musicians and nonmusicians consonant/dissonant perceptions.

neuroscience↗

Ultrastructural details of mammalian chromosome architecture

Over the past decade, 3C-related methods, complemented by increasingly detailed microscopic views of the nucleus, have provided unprecedented insights into chromosome folding in vivo. Here, to overcome the resolution limits inherent to the majority of genome-wide chromosome architecture mapping studies, we extend a recently-developed Hi-C variant, Micro-C, to map chromosome architecture at nucleosome resolution in human embryonic stem cells and fibroblasts. Micro-C maps robustly capture well-described features of mammalian chromosome folding including A/B compartment organization, topologically associating domains (TADs), and cis interaction peaks anchored at CTCF binding sites, while also providing a detailed 1-dimensional map of nucleosome positioning and phasing genome-wide. Compared to high-resolution in situ Hi-C, Micro-C exhibits substantially improved signal-to-noise with an order of magnitude greater dynamic range, enabling not only localization of domain boundaries with single-nucleosome accuracy, but also resolving more than 20,000 additional looping interaction peaks in each cell type. Intriguingly, many of these newly-identified peaks are localized along stripe patterns and form transitive grids, consistent with their anchors being pause sites impeding the process of cohesin-dependent loop extrusion. Together, our analyses provide the highest resolution maps of chromosome folding in human cells to date, and provide a valuable resource for studies of chromosome folding mechanisms.

genomics↗

Condensin-dependent chromatin condensation represses transcription globally during quiescence

Quiescence is a stress-resistant state in which cells reversibly exit the mitotic cell cycle and suspend most cellular processes. Quiescence is essential for stem cell maintenance and its misregulation is implicated in tumor formation. One of the conserved hallmarks of quiescent cells, from Saccharomyces cerevisiae to humans, is highly condensed chromatin. Here, we use Micro-C XL to map chromatin contacts at single-nucleosome resolution genome-wide to elucidate mechanisms and functions of condensed chromatin in quiescent S. cerevisiae cells. We describe previously uncharacterized chromatin domains on the order of 10-60 kilobases that in quiescent cells are formed by condensin-mediated chromatin loops. Conditional depletion of condensin prevents chromatin condensation during quiescence entry and leads to widespread transcriptional de-repression. We further demonstrate that condensin-dependent chromatin compaction is conserved in quiescent human fibroblasts. We propose that condensin-dependent condensation of chromatin represses transcription throughout the quiescent cell genome.

molecular biology↗

Biologics-associated Risks for Incident Skin and Soft Tissue Infections in Psoriasis Patients: Results from Propensity Score-Stratified Survival Analysis

BackgroundHow biologics affect psoriasis patients risks for SSTIs in a pragmatic clinical setting remains unclear.\n\nMethodsIn a cohort of adult psoriasis outpatients (aged 20 years or older) who visited the Dermatology Clinic in 2010-2015, we compared incident SSTI risks between patients using biologics (users) versus nonbiologics (nonusers). We also estimated SSTI risks in biologics-associated time-periods relative to nonbiologics only in users. We applied random effects Cox proportional hazard models with propensity score-stratification to account for differential baseline hazards.\n\nResultsOver a median follow-up of 2.8 years (interquartile range: 1.5, 4.3), 172 of 922 patients ever received biologics (18.7%); 233 SSTI incidents occurred during 2518.3 person-years, with an overall incidence of 9.3/100 person-years (95% confidence interval [CI]: 8.1, 10.6). In univariate analysis, users showed an 89% lower risk for SSTIs than nonusers (hazard ratio [HR]: 0.11, 95%CI: 0.05, 0.26); the association persisted in a multivariable model (adjusted HR: 0.26, 95%CI: 0.12, 0.58). Among biologics users, biologics-exposed time-periods were associated with a nonsignificant 21% increased risk (adjusted HR: 1.21, 95%CI: 0.41, 3.59).\n\nConclusionsDespite of adjusting for the underlying risk profiles, risk comparisons between biologics users and nonusers remained confounded by treatment selection. By comparing time-periods being exposed versus unexposed to biologics among users, the current analysis did not find evidence for an increased SSTI risk that was associated with biologics use in psoriasis patients.

epidemiology↗