- BioRxiv Biochemistry
- BioRxiv Bioinformatics
- BioRxiv Biophysics
- BioRxiv Cancer Biology
- BioRxiv Pharmacology and Toxicology
- BioRxiv Systems Biology
- BioRxiv Zoology
- by Freitas, B., Gil, D., Thebaud, C., Mila, B.Acoustic signaling is key to individual and species recognition, playing a major role in sexual and social communication. Since reproductive isolation is often maintained through pre-mating mechanisms, song can be an early isolating trait leading to assortative mating, promoting reproductive divergence, and potentially contributing to speciation. However, whether song differences alone are sufficient to prevent interbreeding or if other traits also contribute, remains a matter of debate. Playback experiments provide a more direct way to test the role of song […]
- by Hannah, J., Di Liberto, G. M.Trust is a critical component of human communication, providing a foundation for understanding, information exchange, and social coordination. Much of the research on trust in speech communication has focused on how vocal characteristics impact perceived trustworthiness. However, little is known about how trust in a speaker affects the neural processing of speech. Here, we demonstrate a two-stage experimental framework to study that question using non-invasive EEG. First, participants engage in a trust-building stage, where they play an investment game with […]
- by Mullen, P., Shaweis, H., Zwart, M. F.Adaptive behavior requires evaluating whether sensory feedback matches expectations derived from motor commands. In cerebellar theories, climbing fibers arising from the inferior olive (IO) convey prediction error signals that instruct learning, yet how these signals are constructed remains unresolved. Using larval zebrafish performing visuomotor behaviors in virtual reality, we combined two-photon calcium imaging with glutamate sensors to measure excitatory input to the IO and climbing fiber output under identical conditions. IO activity scaled with discrepancies between expected and experienced optic […]
- by Medina Tretmanis, J., Avila-Arcos, M. C., Jay, F., Huerta-Sanchez, E.Motivation: Local Ancestry Inference (LAI) allows us to study evolutionary processes in admixed populations, uncover ancestry-specific disease risk factors, and to better understand the demographic history of these populations. Many methods for LAI exist, however, these methods usually focus on cases of intercontinental admixture. In this work, we evaluate both existing and novel methods in challenging scenarios, such as downsampled reference panels, intracontinental admixture, and distant admixture events. Results: We present four novel LAI implementations based on neural network architectures, […]
- by Paylakhi, S., Geurgas, R., Yasko, A., Wedow, R., Tegtmeyer, M.Height and most disease risk are known polygenic traits: characteristics governed by multiple genes at different loci instead of a select few. Though we are beginning to understand how genetic variation impacts cell morphology, whether such an analogous polygenic architecture operates at the cellular level, where morphology integrates cytoskeletal organization, organelle positioning, and metabolic state, has yet to be systematically tested. Here, we demonstrate that cellular morphology behaves as a polygenic trait by integrating multimodal modeling, perturbation profiling, and population […]
- by Sierra, R. A., Ramirez-Lugo, L., Illescas-Huerta, E., Bolanos, A. R., Sotres-Bayon, F.To obtain rewards, animals must select actions while facing threats, often under competing appetitive and defensive drives and with uncertainty about harm. While neural circuits controlling isolated threats or rewards are well characterized, it remains unclear which specific cortical and subcortical nodes are causally necessary to organize behavior during motivational conflict. Here, we used the step-down avoidance-mediated conflict (SDAmC) task in adult male rats, which quantifies avoidance, risk assessment, and reward approach within the same session. We performed pharmacological inactivation […]
- by Kobayashi, T., Nozaki, D.In real-world motor tasks, body movements unfold in a high-dimensional space, whereas task errors are defined in a lower-dimensional space. How such low-dimensional errors propagate across redundant motor degrees of freedom to generate rapid corrective responses remains poorly understood. To address this question, we developed a redundant bimanual task in which participants manipulated a virtual stick with both hands to move its tip to a visual target. Visual perturbations either displaced the stick tip (end-effector relevant errors) or altered the […]
- by Koelbl, J. M., Haugh, J. M.Haptotaxis is an understudied form of directed cell migration in which movements are biased by gradients of immobilized ligands. For example, fibroblasts and other mesenchymal cells sense and respond to gradients of extracellular matrix (ECM) composition, which is relevant during tissue morphogenesis and repair. As a step towards understanding how haptotactic gradients spatially bias cell adhesion, intracellular signal transduction, and cytoskeletal dynamics, we formulated a phase field model of whole-cell migration, in which the occupancy of potential adhesion sites changes […]
- by Kukkoaho, P., Annala, M., Tanner, K., Siddique, F., Kaunisto, H., Kandikanti, N., Kaksonen, S., Leskinen, K., Saavalainen, P., Kesseli, J., Nykter, M., Aalto-Setälä, K., Kaukinen, K., Lindfors, K., Juuti-Uusitalo, K.Celiac disease is a wheat induced immune-mediated enteropathy. Intestinal organoid models for adult stem cell based celiac disease exist, but planar intestinal models derived from celiac disease patients that would allow direct assessment from both sides of the epithelium have been lacking. We aimed to bridge this gap by setting up a two dimensional in vitro model based on small intestinal epithelial cells derived from induced pluripotent stem cells from celiac disease patients. Induced pluripotent stem cells from celiac disease […]
- by Goswami, V., Faiz, A., Dutt, G., Kumar, A., Bashir, S., Gupta, A., Das, S., Joshi, A., Das, S. K.Cytoplasmic vacuolization is a fundamental process associated with phagocytosis, lysosomal acidification, and autophagy, yet robust in-vitro models for its quantification and pharmacological screening remainlimitedor insufficiently established. In this study, we demonstrate that thermally activated calcium sulfate (ACS) induces extensive vacuolation across mammalian cell lines including HeLa, RAW 264.7, 3T3-L1, and SH-SY5Y, thereby establishing a versatile platform to study vacuole biogenesis. To ensure reproducibility, particle heterogeneity was addressed using sedimentation-based fractionation, with homogeneous suspensions obtained at the 5th minute producing stable […]
- by Kawahara, R., Hane, M., Wu, D., Zhang, B., Sakamoto, F., Nakagawa, T., Omoto, T., Bienes, K. M., Bansal, N., Sumer-Bayraktar, Z., Chatterjee, S., Himori, K., Nagai-Okatani, C., Kuno, A., Kashima, M., Kolarich, D., Matsui, Y., Kitajima, K., Kadomatsu, K., Sato, C., Thaysen-Andersen, M.Sex-specific differences in the glycoproteome remain poorly defined despite growing evidence that protein glycosylation is a key determinant of sex biology. Here we present a tissue-resolved glycoproteome atlas of adult male and female C57BL/6J mice, integrating transcriptomics, proteomics and glycoproteomics with sialic acid speciation and lectin microarray profiling across 19 tissues. Quantitative analysis of >26,800 protein- and site-specific N-glycoforms from 1,512 glycoproteins revealed highly distinct tissue glycoproteomes shaped by coordinated regulation of protein abundance and glyco-enzyme expression. Multi-omics integration identified […]
- by Sharma, A., Emery, R., Pitsillides, A. A., Clarkin, C. E.Background: Bone formation during development and repair is divergently modulated by osteoblast (OB)-derived vascular endothelial growth factor (VEGF) which drives the skeletal sexual dimorphism of the bone vasculature. While the extracellular matrix (ECM) provides both structural and instructive cues to developing vasculature, the contributions of the bone matrix to this skeletal vascular dimorphism in bone remains undefined at the cellular level. Methods: Primary OBs were isolated from neonatal female and male C57BL/6 long bones and cultured under basal or osteogenic […]
- by Mallick, A., Du, Y., Haynes, C. M.Mitochondrial dysfunction and extracellular protein aggregation occur in neurodegenerative diseases such as Alzheimers disease. However, it remains unclear if these processes are functionally linked. Here, we identify a signaling pathway that is activated upon accumulation of aggregation-prone proteins in the extracellular space. We find that the transcription factor ATFS-1, which regulates the mitochondrial unfolded protein response, also regulates transcripts required for endosomal recycling, multiple plasma membrane-localized signaling receptors, and secreted proteins that bind aggregation-prone proteins in the extracellular space, including […]
- by Kushida, Y., Abe, K., Oguma, Y.Mesenchymal stem cells (MSCs) cultured in hypoxic conditions have been suggested to have more therapeutic efficacy than those cultured under normoxic conditions, and there is growing interest in using hypoxic MSCs for clinical treatment, particularly human umbilical cord (hUC)-MSCs. We investigated how hUC-MSCs and human bone marrow (hBM)-MSCs change from normoxia to hypoxia (1% O2) for 2 weeks of culture. In the growth speed and population doubling time, hUC-MSCs cultured under hypoxia exhibited a significantly higher proliferation rate beyond cancerous […]
- by Xie, K., Chen, J., Sahlas, E., Fadaie, F., Arafat, T., Rodriguez-Cruces, R., Naish, M., Ngo, A., Dascal, A., Barnett, A., Audrain, S., Pana, R., Lariviere, S., Hadjinicolaou, A., Weil, A. G., Obaid, S., Dudley, R., Schrader, D. V., Zhang, Z., Concha, L., Bernasconi, A., Bernasconi, N., Bernhardt, B. C.Resting-state functional magnetic resonance imaging (MRI) studies have reported abnormal intrinsic functional connectivity (FC) across distributed circuits in patients with temporal lobe epilepsy (TLE), indicating a system-level impact of the disorder. However, findings remain inconsistent due to limited sample sizes and methodological heterogeneity, leaving the structural determinants and clinical relevance of FC alterations unresolved. To identify a robust and reproducible FC signature, we conducted a data-driven, connectome-wide mega-analysis in a large multicentre cohort of 652 participants (297 TLE, 73 disease […]
- by Yang, G., Inoko, M., Ogura, K., Ishida-Ishihara, S., Tsukada, Y., Funahashi, A., Sato, M., Uehara, R.Though whole-genome duplication (WGD) contributes to cancer progression, the mechanism of post-WGD cell proliferation remains unclear. Here, using 6-day live-imaging, we analyzed the proliferation dynamics of more than 150 post-WGD HCT116 cell lineages. A quantitative comparison of mitotic patterns and cell fates between proliferative and non-proliferative lineages revealed that multipolar chromosome segregation in early mitosis is a key factor limiting the proliferative capacity of post-WGD progenies. Multipolar chromosome segregation suppressed post-WGD cell viability, particularly when accompanied by drastic chromosome loss […]
- by Cramb, K. M. L., Noor, H., Thomas-Wright, I., Caiazza, M. C., Szunyogh, S., Milosevic, I., Beccano-Kelly, D., Cragg, S. J., Wade-Martins, R.Striatal dopamine release defects are an early pathological feature observed in diverse models of Parkinson's disease. However, the underlying molecular mechanisms responsible, and potential links to disease aetiology in humans, have been elusive. Here, we tested the hypothesis that dopamine release deficits are a characteristic feature of disease-relevant human neurons, using human Parkinson's patient iPSC-derived dopamine neurons carrying the SNCA-triplication mutation. We reveal deficits in dopamine release from SNCA-triplication patient-derived neurons, and identify that this is due to reduced dopamine […]
- by MacLean, J., Zhou, M., Bidelman, G.Entrainment and predictive coding aid speech perception in both quiet and noisy environments. Isochronous, periodic auditory rhythmic cues facilitate entrainment and temporal expectations which can benefit encoding and perception of target speech. However, most studies using isochronous cues confound periodicity with predictability. To this end, we characterized how systematic changes in the acoustic dimensions of stimulus rate, target phase, periodicity, and predictably of an entraining sound precursor impact the subsequent identification of concurrent speech targets. Target concurrent vowel pairs were […]
- by Murgia, N., Molnar, B., Reinert, J., Chanthongdee, K., Lacorte, A., Xu, L., Mihaly, L., Ercsey-Ravasz, M., Korber, C., Barbier, E.Individuals vary widely in their responses to stress and threat, with some developing persistent fear after adverse experiences while others remain resilient. Such variability also extends to social contexts, where individuals can acquire information about danger by observing others in distress through observational fear learning. The neural mechanisms underlying individual differences in responses to socially conveyed threat remain poorly understood. Here, we examined how variability in OFL relates to large-scale brain network organization. Rats observed conspecifics receiving tone-shock pairings and […]
- by Murgia, N., Chanthongdee, K., Kardash, T., Xu, L., Toivainen Eloff, S., Coppola, A., Prasad, S., Barbier, E.Stress is a major trigger of relapse in alcohol use disorder (AUD), and dysfunction of prefrontal cortex (PFC) circuits has been implicated in this process. Epigenetic regulators may contribute to relapse by shaping transcriptional programs within these circuits. Here, we investigated the role of the histone methyltransferase PRDM2 in stress-induced alcohol seeking. Analysis of postmortem human tissue showed that PRDM2 expression in the PFC was reduced in both men and women with AUD compared with control individuals. To examine the […]