Biology subjects

Park, H.

Publications and source records attributed to Park, H..

At least 127 records · Page 7Linked to original sources

bioRxiv2023

CRISPRi-TnSeq: A genome-wide high-throughput tool for bacterial essential-nonessential genetic interaction mapping

Genetic interaction networks can help identify functional connections between genes and pathways, which can be leveraged to establish (new) gene function, drug targets, and fill pathway gaps. Since there is no optimal tool that can map genetic interactions across many different bacterial strains and species, we develop CRISPRi-TnSeq, a genome-wide tool that maps genetic interactions between essential genes and nonessential genes through the knockdown of a targeted essential gene (CRISPRi) and the simultaneous knockout of individual nonessential genes (Tn-Seq). CRISPRi-TnSeq thereby identifies, on a genome-wide scale, synthetic and suppressor-type relationships between essential and nonessential genes, enabling the construction of essential-nonessential genetic interaction networks. To develop and optimize CRISPRi-TnSeq, CRISPRi strains were obtained for 13 essential genes in Streptococcus pneumoniae, involved in different biological processes including metabolism, DNA replication, transcription, cell division and cell envelope synthesis. Transposon-mutant libraries were constructed in each strain enabling screening of [~]24,000 gene-gene pairs, which led to the identification of 1,334 genetic interactions, including 754 negative and 580 positive genetic interactions. Through extensive network analyses and validation experiments we identify a set of 17 pleiotropic genes, of which a subset tentatively functions as genetic capacitors, dampening phenotypic outcomes and protecting against perturbations. Furthermore, we focus on the relationships between cell wall synthesis, integrity and cell division and highlight: 1) how essential gene knockdown can be compensated by rerouting flux through nonessential genes in a pathway; 2) the existence of a delicate balance between Z-ring formation and localization, and septal and peripheral peptidoglycan (PG) synthesis to successfully accomplish cell division; 3) the control of c-di-AMP over intracellular K+ and turgor, and thereby modulation of the cell wall synthesis machinery; 4) the dynamic nature of cell wall protein CozEb and its effect on PG synthesis, cell shape morphology and envelope integrity; 5) functional dependency between chromosome decatenation and segregation, and the critical link with cell division, and cell wall synthesis. Overall, we show that CRISPRi-TnSeq uncovers genetic interactions between closely functionally linked genes and pathways, as well as disparate genes and pathways, highlighting pathway dependencies and valuable leads for gene function. Importantly, since both CRISPRi and Tn-Seq are widely used tools, CRISPRi-TnSeq should be relatively easy to implement to construct genetic interaction networks across many different microbial strains and species.

genetics↗

bioRxiv2023

Lip movements and lexical features improve speech tracking differently for clear and multi-speaker speech

Visual speech plays a powerful role in facilitating auditory speech processing and has been a publicly noticed topic with the wide usage of face masks during the Covid-19 pandemic. In a previous magnetoencephalography (MEG) study we showed that occluding the mouth area significantly impairs neural speech tracking. To rule out the possibility that this deterioration is due to degraded sound quality, in the present follow-up study, we presented participants with audiovisual (AV) and audio-only (A) speech. We further independently manipulated the trials by adding a face mask and a distractor speaker. Our results clearly show that face masks only affect speech tracking in AV conditions, not in A conditions. This shows that face masks indeed primarily impact speech processing by blocking visual speech and not by acoustic degradation. Furthermore, we observe differences in the speech features that are used for visual speech processing. On the one hand, processing in clear speech, but not in noisy speech, is profiting more from lexical unit features (phonemes and word onsets) hinting at improved phoneme discrimination. On the other hand, we observe an improvement in speech tracking driven by the modulations of the lip area in clear speech and conditions with a distractor speaker, which might aid by providing temporal cues for subsequent auditory processing. With this work, we highlight the effects of face masks in AV speech tracking and show two separate ways how visual speech might support successful speech processing.

neuroscience↗

bioRxiv2023

GAN-MAT: Generative Adversarial Network-based Microstructural Profile Covariance Analysis Toolbox

AO_SCPLOWBSTRACTC_SCPLOWMultimodal magnetic resonance imaging (MRI) provides complementary information for investigating brain structure and function; for example, an in vivo microstructure-sensitive proxy can be estimated using the ratio between T1- and T2-weighted structural MRI. However, acquiring multiple imaging modalities is challenging in patients with inattentive disorders. In this study, we proposed a comprehensive framework to provide multiple imaging features related to the brain microstructure using only T1-weighted MRI. Our toolbox consists of (i) synthesizing T2-weighted MRI from T1-weighted MRI using a conditional generative adversarial network; (ii) estimating microstructural features, including intracortical covariance and moment features of cortical layer-wise microstructural profiles; and (iii) generating a microstructural gradient, which is a low-dimensional representation of the intracortical microstructure profile. We trained and tested our toolbox using T1- and T2-weighted MRI scans of 1,104 healthy young adults obtained from the Human Connectome Project database. We found that the synthesized T2-weighted MRI was very similar to the actual image and that the synthesized data successfully reproduced the microstructural features. The toolbox was validated using an independent dataset containing healthy controls and patients with episodic migraine as well as the atypical developmental condition of autism spectrum disorder. Our toolbox may provide a new paradigm for analyzing multimodal structural MRI in the neuroscience community, and is openly accessible at https://github.com/CAMIN-neuro/GAN-MAT.

neuroscience↗

bioRxiv2023

Analysis of spike protein variants evolved in a novel mouse model of persistent SARS-CoV-2 infection

SARS-CoV-2 mutation rates have increased over time, resulting in the emergence of several variants of concern. Persistent infection is assumed to be involved in the evolution of the variants; however, there is currently no animal model to recapitulate persistent infection. We established a novel model of persistent infection using xenografts of Calu-3 human lung cancer cells in immunocompromised mice. After infection with wild-type SARS-CoV-2, viruses were found in the tumor tissues for up to 30 days and acquired various mutations, predominantly in the spike (S) protein, some of which increased while others fluctuated for 30 days. Three isolated viral clones with defined mutations produced higher virus titers than the wild-type virus in Calu-3 cells without cytotoxic effects. In K18-hACE2 mice, the variants were less lethal than the wild-type virus. Infection with each variant induced production of cross-reactive antibodies to the receptor binding domain of wild-type S protein and provided protective immunity against subsequent challenge with wild-type virus. These results suggest that most of the SARS-CoV-2 variants acquired mutations promoting host adaptation in the Calu-3 xenograft mice. This model can be used in the future to further study persistent SARS-CoV-2 infection.

microbiology↗

bioRxiv2023

Isolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution

During the COVID-19 pandemic, human behavior change as a result of nonpharmaceutical interventions such as isolation may have induced directional selection for viral evolution. By combining previously published empirical clinical data analysis and multi-level mathematical modeling, we found that the SARS-CoV-2 variants selected for as the virus evolved from the pre-Alpha to the Delta variant had earlier and higher infectious periods but a shorter duration of infection. Selection for increased transmissibility shapes the viral load dynamics, and the isolation measure is likely to be a driver of these evolutionary transitions. In addition, we showed that a decreased incubation period and an increased proportion of asymptomatic infection were also positively selected for as SARS-CoV-2 mutated to the extent that people did not isolate. We demonstrated that the Omicron variants evolved in these ways to adapt to human behavior. The quantitative information and predictions we present here can guide future responses in the potential arms race between pandemic interventions and viral evolution.

evolutionary biology↗

bioRxiv2023

Whole-brain structural connectome asymmetry in autism

AO_SCPLOWBSTRACTC_SCPLOWAutism spectrum disorder is a common neurodevelopmental condition that manifests as a disruption in sensory and social skills. Although it has been shown that the brain morphology of individuals with autism is asymmetric, how this differentially affects the structural connectome organization of each hemisphere remains under-investigated. We studied whole-brain structural connectivity-based brain asymmetry in 47 individuals with autism and 37 healthy controls using diffusion magnetic resonance imaging obtained from the Autism Brain Imaging Data Exchange initiative. By leveraging dimensionality reduction techniques, we constructed low-dimensional representations of structural connectivity and calculated their asymmetry index. We compared the asymmetry index between individuals with autism and neurotypical controls and found atypical structural connectome asymmetry in the sensory, default-mode, and limbic networks and the caudate in autism. Network communication provided topological underpinnings by demonstrating that the temporal and dorsolateral prefrontal regions showed reduced global network communication efficiency and decreased send-receive network navigation in the caudate region in individuals with autism. Finally, supervised machine learning revealed that structural connectome asymmetry is associated with communication-related autistic symptoms and nonverbal intelligence. Our findings provide insights into macroscale structural connectome alterations in autism and their topological underpinnings.

neuroscience↗

bioRxiv2023

LINKIN-associated proteins necessary for tissue integrity during collective cell migration

Cell adhesion plays essential roles in almost every aspect of metazoan biology. LINKIN (Human: ITFG1, Caenorhabditis elegans: lnkn-1) is a conserved transmembrane protein that has been identified to be necessary for tissue integrity during migration. In C. elegans, loss of lnkn-1 results in the detachment of the lead migratory cell from the rest of the developing male gonad. Previously, three interactors of ITFG1/lnkn-1 - RUVBL1/ruvb-1, RUVBL2/ruvb-2, and alpha-tubulin - were identified by immunoprecipitation-mass spectrometry (IP-MS) analysis using human HEK293T cells and then validated in the nematode male gonad. The ITFG1-RUVBL1 interaction has since been independently validated in a breast cancer cell line model that also implicates the involvement of the pair in metastasis. Here, we showed that epitope-tagged ITFG1 localized to the cell surface of MDA-MB-231 breast cancer cells. Using IP-MS analysis, we identified a new list of potential interactors of ITFG1. Loss-of-function analysis of their C. elegans orthologs found that three of the interactors - ATP9A/tat-5, NME1/ndk-1, and ANAPC2/apc-2 - displayed migratory detachment phenotypes similar to that of lnkn-1. Taken together with the other genes whose reduction-of-function phenotype is similar to that of lnkn-1 (notably cohesion and condensin), suggests the involvement of membrane remodeling and chromosome biology in LINKIN-dependent cell adhesion and supports the hypothesis for a structural role of chromosomes in post-mitotic cells.

developmental biology↗

bioRxiv2023

Advancing Glycan Analysis: A New Platform Integrating SERS, Boronic Acids, and Machine Learning Algorithms

Glycans are the most abundant and diverse fundamental biomolecules. Profiling glycans is essential to elucidate biomolecular mechanisms and to predict biological consequences; however, the analysis of glycans remains challenging due to their structural complexity. A novel glycan detection platform is established through the integration of surface-enhanced Raman spectroscopy (SERS), boronic acid receptors, and machine learning tools. SERS is able to distinguish isomeric structures and provide fingerprint information of molecules. Boronic acid receptors can selectively bind with glycans, and the reaction influences molecular vibrations, leading to unique Raman spectral patterns. For proof-of-concept, two boronic acids, 4-mercaptophenylboronic acid (4MBA) and 1-thianthrenylboronic acid (1TBA) were used for glycan detection. The spectra were analyzed by the machine learning algorithm. The sensing platform successfully recognized the stereoisomers (glucose, mannose, and galactose), the structural isomers with -1,4 and -1,6 glycosidic linkages, and the {beta}-1,4 glycosidic linkage within lactose molecules. The collective spectra that combine the spectra from both boronic acid receptors could improve the performance of the support vector machine model due to the enrichment of the structural information of glycans. In addition to qualitative analysis, this new sensor could quantify the mole fraction of sialic acid in lactose background using the machine learning regression technique. The quantification accuracy reached a coefficient of determination (R2) value of 0.998 and a normalized mean square error (NMSE) of 0.00195. This low-cost, rapid, and highly accessible sensor will provide the scientific community with another option for frequent glycan screening in standard biological laboratories.

bioengineering↗

bioRxiv2023

Mouse mammary tumor virus is implicated in severity of colitis and dysbiosis in the IL-10-/- mouse model of inflammatory bowel disease

BackgroundFollowing viral infection, genetically manipulated mice lacking immunoregulatory function may develop colitis and dysbiosis in a strain specific fashion that serves as a model for inflammatory bowel disease (IBD). We found that one such model of spontaneous colitis, the interleukin (IL)-10 knockout (IL-I0-/-) model derived from the SvEv mouse, had evidence of increased mouse mammary tumor virus (MMTV) viral RNA expression compared to the SvEv wildtype. MMTV is endemic in several mouse strains as an endogenously encoded betaretrovirus that is passaged as an exogenous agent in breast milk. As MMTV requires a viral superantigen to replicate in the gut associated lymphoid tissue prior to the development of systemic infection, we evaluated whether MMTV may contribute to the development of colitis in the IL-10-/- model. ResultsViral preparations extracted from IL-10-/- weanling stomachs revealed augmented MMTV load compared to the SvEv wildtype. Illumina sequencing of the viral genome revealed that the two largest contigs shared 96.4% - 97.3% identity with the mtv-1 endogenous loci and the MMTV(HeJ) exogenous virus from the C3H mouse. The MMTV sag gene cloned from IL-10-/- spleen encoded the MTV-9 superantigen that preferentially activates T cell receptor V{beta}-12 subsets, which were expanded in the IL-10-/- versus the SvEv colon. Evidence of MMTV cellular immune responses to MMTV Gag peptides was observed in the IL-10-/- splenocytes with amplified interferon-{gamma} production versus the SvEv wildtype. To address the hypothesis that MMTV may contribute to colitis, we used HIV reverse transcriptase inhibitors, tenofovir and emtricitabine, and the HIV protease inhibitor, lopinavir boosted with ritonavir, for 12 weeks treatment versus placebo. The combination anti-retroviral therapy with known activity against MMTV was associated with reduced colonic MMTV RNA and improved histological score in IL10-/- mice, as well as diminished secretion of pro-inflammatory cytokines and modulation of the microbiome associated with colitis. ConclusionsThis study suggests that immunogenetically manipulated mice with deletion of IL-10 may have reduced capacity to contain MMTV infection in a mouse-strain specific manner, and the antiviral inflammatory responses may contribute to the complexity of IBD with the development of colitis and dysbiosis.

microbiology↗

bioRxiv2023

Astrocytic connection to engram neurons increased after learning

Astrocytes directly participate in learning and memory. However, the structural association between astrocytes and memory-encoding engram neurons after learning remains to be elucidated. We developed astrocyte-enhanced green fluorescent protein reconstitution across synaptic partners (eGRASP) to examine tripartite synapses between astrocytes and engram neurons. Using astrocyte-eGRASP, we found that astrocytes had increased connections to engram neurons after learning. Dendritic spines with astrocytic contacts showed enhanced morphology. Live-cell imaging of astrocyte-eGRASP revealed that astrocytic connections are stabilized by neuronal activity. These results indicate that astrocytes distinguish contact between engram neurons and generate engram-specific contact patterns during learning.

neuroscience↗

bioRxiv2023

Keratinocytes coordinate inflammatory responses and regulate development of secondary lymphedema

Epidermal changes are histological hallmarks of secondary lymphedema, but it is unknown if keratinocytes contribute to its pathophysiology. Using clinical lymphedema specimens and mouse models, we show that keratinocytes play a primary role in lymphedema development by producing T-helper 2 (Th2) -inducing cytokines. Specifically, we find that keratinocyte proliferation and expression of protease-activated receptor 2 (PAR2) are early responses following lymphatic injury and regulate the expression of Th2-inducing cytokines, migration of Langerhans cells, and skin infiltration of Th2-differentiated T cells. Furthermore, inhibition of PAR2 activation with a small molecule inhibitor or the proliferation inhibitor teriflunomide (TF) prevents activation of keratinocytes stimulated with lymphedema fluid. Finally, topical TF is highly effective for decreasing swelling, fibrosis, and inflammation in a preclinical mouse model. Our findings suggest that lymphedema is a chronic inflammatory skin disease, and topically targeting keratinocyte activation may be a clinically effective therapy for this condition.

immunology↗

bioRxiv2023

Netrin-1 binding to Unc5B regulates Blood-Retina Barrier integrity

BackgroundThe blood brain barrier (BBB) preserves neuronal function in the central nervous system (CNS) by tightly controlling metabolite exchanges with the blood. In the eye, the retina is likewise protected by the blood-retina barrier (BRB) to maintain phototransduction. We showed that the secreted guidance cue Netrin-1 regulated BBB integrity, by binding to endothelial Unc5B and regulating canonical {beta}-catenin dependent expression of BBB gene expression ObjectiveHere, we investigated if Netrin-1-binding to endothelial Unc5B also controlled BRB integrity, and if this process involved Norrin/{beta}-catenin signaling, which is the major known driver of BRB development and maintenance. MethodsWe analyzed Tamoxifen-inducible loss- and gain-of-function alleles of Unc5B, Ntn1 and Ctnnb1 in conjunction with tracer injections and biochemical signaling studies. ResultsInducible endothelial Unc5B deletion, and inducible global Ntn1 deletion in postnatal mice reduced phosphorylation of the Norrin receptor LRP5, leading to reduced {beta}-catenin and LEF1 expression, conversion of retina endothelial cells from a barrier-competent Claudin-5+/PLVAP-state to a Claudin-5-/PLVAP+ leaky phenotype, and extravasation of injected low molecular weight tracers. Inducible Ctnnb1 gain of function rescued vascular leak in Unc5B mutants, and Ntn1 overexpression induced BRB tightening. Unc5B expression in pericytes contributed to BRB permeability, via regulation of endothelial Unc5B. Mechanistically, Netrin-1-Unc5B signaling promoted {beta}-catenin dependent BRB signaling by enhancing phosphorylation of the Norrin receptor LRP5 via the Discs large homologue 1 (Dlg1) intracellular scaffolding protein. ConclusionsThe data identify Netrin1-Unc5B as novel regulators of BRB integrity, with implications for diseases associated with BRB disruption.

cell biology↗

bioRxiv2023

Predicting the efficacy of BH3 mimetics through the profiling of multiple protein complexes

BH3 mimetics are protein-protein interaction (PPI) inhibitors that saturate anti-apoptotic proteins in the BCL2 family to induce apoptosis in cancer cells, a prominent example of protein complex-targeting therapies. Despite the remarkable success of the BH3 mimetic ABT-199 in treating hematological malignancies, only a fraction of patients respond to ABT-199 and eventually develop resistance, necessitating the predictive biomarkers for both initial responses and resistance development. We here used the single-molecule pull-down and co-immunoprecipitation platform to quantify more than 20 different types of PPI complexes using [~]1.2x106 cells in total, revealing the rewired status of the BCL2 family PPI network. By comparing the obtained multi-dimensional data with BH3 mimetic efficacies determined ex vivo, we constructed an analysis model for ABT-199 efficacy that designates the BCL2-BAX and BCLxL-BAK complexes as the primary mediators of drug effectiveness and resistance. We then applied this model to assist in therapeutic decision-making for acute myeloid leukemia patients in a prospective manner. Our work demonstrates a capability for the extensive characterization of PPI complexes in clinical specimens, potentially opening a new avenue of precision medicine for protein complex-targeting therapies.

molecular biology↗

bioRxiv2022

Systems Level Identification Of A Matrisome-Associated Macrophage Polarization State In Multi-Organ Fibrosis

Tissue fibrosis affects multiple organs and involves a master-regulatory role of macrophages which respond to an initial inflammatory insult common in all forms of fibrosis. The recently unraveled multi-organ heterogeneity of macrophages in healthy and fibrotic human disease suggest that tissue resident macrophages, expressing osteopontin (SPP1), associate with lung and liver fibrosis. However, the conservation of this SPP1+ macrophage population across different tissues, and its specificity to fibrotic diseases with different etiologies remain unclear. Integrating 13 single cell RNA-sequencing datasets to profile 225,985 tissue macrophages from healthy and fibrotic heart, lung, liver, kidney, skin and endometrium, we extended the association of SPP1+ macrophages with fibrosis to all these tissues. We also identified a subpopulation expressing matrisome-associated genes (e.g., matrix metalloproteinases and their tissue inhibitors), functionally enriched for ECM remodeling and cell metabolism, representative of a matrisome-associated macrophage (MAM) polarization state within SPP1+ macrophages. Importantly, the MAM polarization state follows a differentiation trajectory from SPP1+ macrophages, which was conserved across all fibrotic tissues and driven by NFATC1 and HIVEP3 regulons. Unlike SPP1+ macrophages, the MAM polarization state shows a positive association with ageing in mice and humans, and across multiple tissues during homeostasis. These results suggest an advanced, age-dependent polarization state of SPP1+ macrophages in fibrotic tissues as a result of prolonged inflammatory cues within each tissue microenvironment.

systems biology↗

bioRxiv2022

Esr1+ hypothalamic-habenula neurons shape aversive states.

Excitatory projections from the lateral hypothalamic area (LHA) to the lateral habenula (LHb) drive aversive responses. We used Patch-seq guided multimodal classification to define the structural and functional heterogeneity of the LHA-LHb pathway. Our classification identified six glutamatergic neuron types with unique electrophysiological properties, molecular profiles, and projection patterns. We found that genetically-defined LHA-LHb neurons signal distinct aspects of emotional or naturalistic behaviors: Esr1+ LHA-LHb neurons induce aversion, whereas Npy+ LHA-LHb neurons control rearing behavior. Repeated optogenetic drive of Esr1+ LHA-LHb neurons induces a behaviorally persistent aversive state, and large-scale recordings showed a region-specific neural representation of the aversive state in the prelimbic region of the prefrontal cortex. We further found that exposure to unpredictable mild shocks induced a sex-specific sensitivity to develop a stress state in female mice, which was associated with a specific shift in the intrinsic properties of bursting-type Esr1+ LHA-LHb neurons. In summary, we describe the diversity of LHA-LHb neuron types, and provide evidence for the role of Esr1+ neurons in aversion and sexually dimorphic stress sensitivity.

neuroscience↗

bioRxiv2022

Effects of parental verbal abuse experience on the Glutamate response to swear words in the ventromedial prefrontal cortex: A functional H1-magnetic resonance spectroscopy study

Several lines of evidence indicate verbal abuse (VA) critically impacts the developing brain; however, whether VA results in changes in brain neurochemistry has not been established in humans. Here, we hypothesized that exposure to recurrent parental VA elicits heightened glutamate (Glu) responses during the presentation of swear words, which can be measured with functional magnetic resonance spectroscopy (fMRS). During an emotional Stroop task consisting of blocks of color and swear words, metabolite concentration changes were measured in the ventromedial prefrontal cortex (vmPFC) and the left amygdalohippocampal region (AMHC) of healthy adults (14 F/27 M, 23{+/-}4 years old) using fMRS. The dynamic changes in Glu and their associations with the emotional state of the participants were finally evaluated based on 36 datasets from the vmPFC and 30 from the AMHC. A repeated-measures analysis of covariance revealed a modest effect of parental VA severity on Glu changes in the vmPFC. Furthermore, the total score on the Verbal Abuse Questionnaire by parents (pVAQ) was associated with the Glu response to swear words ({Delta}GluSw e). The interaction term of {Delta}GluSw e and baseline N-acetyl aspartate (NAA) level in the vmPFC could be used to predict state-trait anxiety level and depressive mood. We could not find any significant associations between {Delta}GluSw e in the AMHC and either pVAQ or emotional states. We conclude that parental VA exposure in individuals is associated with a greater Glu response towards VA-related stimuli in the vmPFC and that the accompanying low NAA level may be associated with anxiety level or depressive mood.

neuroscience↗

bioRxiv2022

Investigating the roles for essential genes in the regulation of the circadian clock in Synechococcus elongatus using CRISPR interference

Circadian rhythms are approximately 24-hour cycles that allow organisms to anticipate predictable environmental changes such as light intensity, temperature, and humidity. Circadian rhythms are found widely throughout nature where cyanobacteria are the simplest organisms known to carry out circadian rhythmicity. Circadian rhythmicity in cyanobacteria is carried out via the KaiA, KaiB and KaiC core oscillator proteins that keep ~24h time. A series of input and output proteins; CikA, SasA and RpaA, regulate the clock by sensing environmental changes, and time rhythmic activities, including global rhythms of gene expression. Our previous work identified a novel set of KaiC-interacting proteins, some of which are encoded by genes that are essential for viability. To understand the relationship of these essential genes to the clock we applied CRISPR interference (CRISPRi) which utilizes a deactivated Cas9 protein and single guide RNA (sgRNA) to reduce the expression of target genes but not fully abolish their expression to allow for survival. Eight candidate genes were targeted, and strains were analyzed by quantitative Reverse Transcriptase (RT)-PCR for reduction of gene expression and rhythms of gene expression were monitored to analyze circadian phenotypes. We present data that reduced expression of SynPCC942_0001, which encodes for the {beta}-clamp of the replicative DNA polymerase, or SynPCC7942_1081, which likely encodes for KtrA involved in K+ transport, displayed a long circadian period compared to the wild type. As neither of these proteins have been previously implicated in the circadian clock, these data suggest that diverse cellular processes, DNA replication and K+ transport, can influence the circadian clock and represent new avenues to understand clock function.

microbiology↗

bioRxiv2022

The history of multisensory discrepancies affects the ventriloquism effect and the immediate aftereffect differentially.

Multisensory integration and recalibration are two processes by which perception deals with discrepant signals. Both are often studied in the spatial ventriloquism paradigm. There, integration is probed by the presentation of discrepant audio-visual stimuli, while recalibration manifests as an aftereffect in subsequent unisensory judgements. Both biases are typically quantified against the degree of audio-visual discrepancy, reflecting the possibility that both may arise from common underlying multisensory principles. We tested a specific prediction of this: that both processes should also scale similarly with the history of multisensory discrepancies experienced in previous trials. Analysing data from ten experiments we confirmed the expected dependency of each bias on the immediately presented discrepancy. And in line with the aftereffect being a cumulative process, this scaled with the discrepancies presented in multiple preceding audio-visual trials. However, the ventriloquism bias did not depend on the history of multisensory discrepancies and also did not depend on the aftereffect biases in previous trials - making these two multisensory processes experimentally dissociable. These findings support the notion that the ventriloquism bias and the aftereffect reflect distinct functions, with integration maintaining a stable percept by reducing immediate sensory discrepancies and recalibration maintaining an accurate percept by accounting for consistent discrepancies.

neuroscience↗