Biology subjects

Lee, U.

Publications and source records attributed to Lee, U..

At least 19 recordsLinked to original sources

bioRxiv2026

HP6/Umbrea, a rapidly evolving Drosophila HP1-family paralog, is a candidate HP1a-recruited plasticizer of heterochromatin

HP6/Umbrea, a rapidly evolving Drosophila (Heterochromatin Protein 1) HP1-family paralog, has well-documented sequence and regulatory evolution but an under-studied molecular function. In this manuscript, we hypothesize that HP6/Umbrea acts as an HP1-recruited plasticizer, providing support for this model using coarse-grained molecular-dynamics simulations of HP1a condensates. Retaining only the dimerizing chromoshadow domain (CSD), HP6/Umbrea notably lacks independent chromatin-binding capacity but binds HP1a directly, co-localizing with it in vivo. We report that when covalently tethered to an HP1a carrier, HP6/Umbrea partitions into HP1a condensates ~6-fold more strongly than when free, supporting HP1a-mediated recruitment as its entry route. Once incorporated, HP6/Umbrea leaves the phase-separation threshold, interfacial tension, and host partitioning statistically unchanged, but monotonically lowers dense-phase density. These observations are consistent with a spacer function rather than generic loss of cohesion. Importantly, unchanged short-time internal mobility suggests a packing effect, predicting increased permeability to large transcriptional machinery, potentially resulting in a position effect-variegation (PEV)-like modulation of heterochromatic silencing. Finally, comparative sequence analysis shows the C-terminal tail is a recently originated, purifying-selection-constrained innovation, which is consistent with an evolved function in this region. In sum, our simulations suggest a mechanistic basis for how HP6/Umbrea may have evolved as a condensate plasticizer and thus potentially act as a rheostat for leaky transcription.

evolutionary biology↗

bioRxiv2026

Naturally arising de novo open reading frames as potential zinc chelators in Drosophila melanogaster

A central open problem in the study of de novo gene origination is that the molecular mechanisms and functions driving the emergence of such evolutionarily young, de novo protein-coding genes remain poorly understood. Metal chelation, a simple, directly selectable activity that both requires no specific interaction partners and is also compatible with intrinsic disorder, is one possible function. This possibility was tested using sequence signatures in 7,849 transcriptionally supported, still-segregating Drosophila melanogaster de novo open reading frames. Interestingly, these new open reading frames (neORFs) are enriched for bis-histidine motifs at the metal-coordination-competent spacings H-x-H and H-x-x-x-H and show no enrichment at the incompatible even spacings relative to repeat-masked intergenic ORFs. Notably, these neORFs were also found to lack the C-x-x-C grammar of canonical metal-binding proteins. I report that this H-x-H bis-histidine signal is generated by translation of (CA) microsatellites into His-Thr-His in Drosophila melanogaster, as evidenced by a CAC-codon bias within H-x-H motifs and a fourfold threonine enrichment at the central position. I propose that recurrent microsatellite expansion supplies Drosophila with a distributed, independently originated class of candidate metal-binding de novo peptides. I then trace one neORF (ZMEG) from conserved ancestral non-coding sequence to a transcribed, melanogaster-lineage open reading frame whose (CA)9-derived His run presents a candidate His32-His36 bis-histidine site. I propose that such de novo proteins may constitute a class of molecules united not by common descent but by their shared origin in evolvable repeat sequence, highlighting the importance of emergence bias in molecular evolution.

evolutionary biology↗

bioRxiv2026

Robust PHP in Adult Hippocampus: Essential Assay Optimizations

Presynaptic homeostatic plasticity (PHP) is a potent form of homeostatic plasticity that has been documented at synapses as diverse as the glutamatergic Drosophila neuromuscular junction (NMJ), cholinergic mammalian NMJ (including human), and glutamatergic synapses in the mammalian brain. Published experimental evidence in favor of PHP in adult hippocampus and cerebellum includes patch-clamp electrophysiology, presynaptic capacitance measurement, calcium imaging, optical reporters of vesicle release and correlated three-dimensional electron microscopy. These studies are grounded in newly optimized experimental protocols that differ substantively from those typically used to study activity-dependent plasticity in neonatal and juvenile slice preparations. Here, we elaborate and extend our assays and methodologies for the study of PHP in the adult mammalian brain. Our assays are designed to optimize synapse, cell and tissue health and minimize the incorporation of unintended adverse experimental conditions that may interfere with the induction and/or expression of PHP. In addition, we provide benchmark criteria for assessment of cell health, necessary for analysis of PHP and, in so doing, advance our understanding of postsynaptic conditions necessary for PHP induction in the adult brain. Our data underscore why PHP may have been previously overlooked, inclusive of a recent manuscript challenging the robust expression of PHP in the mammalian brain (Dou et al., 2026 BioRxiv [preprint]).

neuroscience↗

bioRxiv2025

Korean Natural Farming practices are dominated by a limited number of microbes and decrease fungal diversity

Korean Natural Farming (KNF) practices claim to cultivate and transfer "indigenous micro-organisms" (IMOs) to donor soils as a method of probiotic soil enhancement. We investigated whether IMO cultivation can propagate unique microbiomes and maintain microbial diversity through successive IMO stages for restoration of flood contaminated soils. Employing a balanced study design using soil samples from salt marsh, deciduous forest, and urban greenspace (plus sterilized controls), samples underwent the first two IMO cultivation steps followed by 16S rRNA and ITS metagenomic sequencing. Notably, IMO cultivation was dominated by limited bacterial taxa (Enterobacterales, Pseudomonadales, Bacillales) and fungal taxa (Rhizopodaceae, particularly R. oryzae). While bacterial diversity was maintained or increased during two IMO stages, fungal diversity consistently decreased. Principal Coordinates Analysis also revealed distinct clustering by inoculum source (i.e. human-altered, human- transported (HAHT) vs. natural vs. sterile) that persisted throughout cultivation. Our evidence suggests that the IMO process enriches for specific taxa likely adapted to cultivated conditions and fails to maintain fungal diversity, contrasting greatly with KNFs proposed benefit of propagating locale-specific, fungal-dominated indigenous microbiomes. However, our results demonstrate that early IMO cultures may capture and sustain bacterial diversity in soil, opening the door for future studies of KNF efficacy and sustainability. Sustainability StatementThis work is primarily associated with UN Sustainable Development Goal SDG 15 (Life on Land). By scientifically evaluating Korean Natural Farming "indigenous Microorganism" (IMO) practices through metagenomic sequencing, this study provides evidence-based insights into microbial community dynamics relevant to soil restoration and terrestrial ecosystem health. The findings inform low-cost bioremediation strategies for flood- contaminated urban soils, which is of growing importance as climate-driven extreme precipitation events intensify. Additional relevant SDGs include: SDG 13 (Climate Action), SDG 11 (Sustainable Cities and Communities), SDG 2 (Zero Hunger), and SDG 3 (Good Health and Well-being).

microbiology↗

bioRxiv2025

Sub-second Fluctuation between Top-Down and Bottom-Up Modes Distinguishes Diverse Human Brain States

Information continuously flows between regions of the human brain, exhibiting distinct patterns that dynamically shift across states of consciousness, cognitive modes, and neuropsychiatric conditions. In this study, we introduce Relative Phase Analysis (RPA), a method that leverages phase-lead/lag relationships to reveal the real-time dynamics of dominant directional patterns and their rapid transitions. We demonstrate that the human brain switches on a sub-second timescale between a top-down mode-where anterior regions drive posterior activity-and a bottom-up mode, characterized by reverse directionality. These dynamics are most pronounced during full consciousness and gradually become less distinct as awareness diminishes. Furthermore, we find from simultaneous EEG-fMRI recordings that the top-down mode is expressed when higher-order cognitive networks are more active while the bottom-up mode is expressed when sensory systems are more active. Moreover, comparisons of an attention deficit hyperactivity disorder (ADHD) inattentive cohort with typically developing individuals reveal distinct imbalances in these transition dynamics, highlighting the potential of RPA as a diagnostic biomarker. Complementing our empirical findings, a coupled-oscillator model of the structural brain network recapitulates these emergent patterns, suggesting that such directional modes and transitions may arise naturally from inter-regional neural interactions. Altogether, this study provides a framework for understanding whole-brain dynamics in real-time and identifies sub-second fluctuations in top-down versus bottom-up directionality as a fundamental mechanism underlying human information processing.

neuroscience↗

bioRxiv2025

Post-mitotic transcriptional activation and 3D regulatory interactions show locus- and differentiation-specific sensitivity to cohesin depletion

Prior studies showed that structural loops collapse upon acute cohesin depletion, while regulatory enhancer-promoter (E-P) loops largely persist, consistent with minimal transcriptional changes. However, these studies, conducted in asynchronous cells, could not resolve whether cohesin is required for the establishment of regulatory interactions and transcriptional activation during cell division or cell state transitions. To address this gap, we degraded RAD21, a core cohesin subunit, in naive mouse embryonic stem cells (ESCs) transitioning from mitosis to G1 either in self-renewal condition or during differentiation toward formative pluripotency. Although most structural loops failed to be re-established without cohesin, about 35% of regulatory loops reformed at normal or higher frequencies. Cohesin-independent loops showed characteristics of strong active enhancers and promoters and a significant association with H3K27ac mitotic bookmarks. However, inhibition of CBP/p300 during mitotic exit did not impact these cohesin-independent interactions, suggesting the presence of complex compensatory mechanisms. At the transcriptional level, cohesin depletion induced only minor changes, supporting that post-mitotic transcriptional reactivation is largely independent of cohesin. The few genes with impaired reactivation were directly bound by RAD21 at their promoters, engaged in many structural loops, and located within strongly insulated TADs with low gene density. Importantly, degrading cohesin during the M-to-G1 transition in the presence of EpiLC differentiation signals revealed a larger group of susceptible genes, including key signature genes and transcription factors. Impaired activation of these genes was partly due to the failure to establish de novo EpiLC-specific interactions in the absence of cohesin. These experiments revealed locus-specific and context-specific dependencies between cohesin, E-P interactions, and transcription.

molecular biology↗

bioRxiv2024

Proximity to Explosive Synchronization Determines Network Collapse and Recovery Trajectories in Neural and Economic Crises

When complex systems move away from criticality--a balance between order and chaos--they are no longer optimized. Furthermore, when criticality is lost too quickly, or recovery is delayed, system damage can result. However, the mechanism for these abnormally fast or slow critical transitions remains unknown. Here, we show that the proximity of a complex network to explosive synchronization (ES), a first-order phase transition, determines the trajectories of criticality loss and recovery after perturbations. Our computational models revealed characteristic dynamics based on network proximity to ES, enabling us to infer network phase transition types from empirical data and predict criticality transition patterns. We validated our predictions using empirical data from the human brain under anesthesia and the stock market during an economic crisis, demonstrating that early and prolonged recoveries can be systematically predicted. This study has implications for designing resilient networks that withstand perturbations and recover quickly.

systems biology↗

bioRxiv2024

TAD hierarchy restricts poised LTR activation and loss of TAD hierarchy promotes LTR co-option in cancer

Transposable elements (TEs) are abundant in the human genome, and they provide the sources for genetic and functional diversity. The regulation of TEs expression and their functional consequences in physiological conditions and cancer development remain to be fully elucidated. Previous studies suggested TEs are repressed by DNA methylation and chromatin modifications. The effect of 3D chromatin topology on TE regulation remains elusive. Here, by integrating transcriptome and 3D genome architecture studies, we showed that haploinsufficient loss of NIPBL selectively activates alternative promoters at the long terminal repeats (LTRs) of the TE subclasses. This activation occurs through the reorganization of topologically associating domain (TAD) hierarchical structures and recruitment of proximal enhancers. These observations indicate that TAD hierarchy restricts transcriptional activation of LTRs that already possess open chromatin features. In cancer, perturbation of the hierarchical chromatin topology can lead to co-option of LTRs as functional alternative promoters in a context-dependent manner and drive aberrant transcriptional activation of novel oncogenes and other divergent transcripts. These data uncovered a new layer of regulatory mechanism of TE expression beyond DNA and chromatin modification in human genome. They also posit the TAD hierarchy dysregulation as a novel mechanism for alternative promoter-mediated oncogene activation and transcriptional diversity in cancer, which may be exploited therapeutically.

cancer biology↗

bioRxiv2024

Comparative Single Cell Analysis of Transcriptional Bursting Reveals the Role of Genome Organization on de novo Transcript Origination

Spermatogenesis is a key developmental process underlying the origination of newly evolved genes. However, rapid cell type-specific transcriptomic divergence of the Drosophila germline has posed a significant technical barrier for comparative single-cell RNA-sequencing (scRNA-Seq) studies. By quantifying a surprisingly strong correlation between species- and cell type-specific divergence in three closely related Drosophila species, we apply a new statistical procedure to identify a core set of 198 genes that are highly predictive of cell type identity while remaining robust to species-specific differences that span over 25-30 million years of evolution. We then utilize cell type classifications based on the 198-gene set to show how transcriptional divergence in cell type increases throughout spermatogenic developmental time. After validating these cross-species cell type classifications using RNA fluorescence in situ hybridization (FISH) and imaging, we then investigate the influence of genome organization on the molecular evolution of spermatogenesis vis-a-vis transcriptional bursting. We first show altering transcriptional burst size contributes to pre-meiotic transcription and altering bursting frequency contributes to post-meiotic expression. We then report global differences in autosomal vs. X chromosomal transcription may arise in a developmental stage preceding full testis organogenesis by showing evolutionarily conserved decreases in X-linked transcription bursting kinetics in all examined somatic and germline cell types. Finally, we provide evidence supporting the cultivator model of de novo gene origination by demonstrating how the appearance of newly evolved testis-specific transcripts potentially provides short-range regulation of neighboring genes transcriptional bursting properties during key stages of spermatogenesis. Significance StatementUnderstanding the divergence and evolution of novel genes and expression is an essential question in evolutionary biology. However, rapid transcriptomic divergence in tissues such as testis has significantly hindered comparative single-cell RNA-Seq studies and understanding of the rapidly evolving components of the cell types. Here, we provide a novel strategy that does not rely on preexisting marker genes for cell type identity to overcome the challenge. We found that genome organization affects expressional evolution through transcriptional bursting dynamics. Our results also support the cultivator model of de novo gene origination--a model emphasizing the genomic environment in shaping novel gene origination--by illustrating how newly evolved transcripts alter the transcriptional bursting kinetics of neighboring genes.

evolutionary biology↗

bioRxiv2024

Psilocybin induces dose-dependent changes in functional network organization in rat cortex

Psilocybin produces an altered state of consciousness in humans and is associated with complex spatiotemporal changes in brain networks. Given the emphasis on rodent models for mechanistic studies, there is a need for characterization of the effect of psilocybin on brain-wide network dynamics. Previous rodent studies of psychedelics, using electroencephalogram, have primarily been done with sparse electrode arrays that offered limited spatial resolution precluding network level analysis, and have been restricted to lower gamma frequencies. Therefore, in the study, we used electroencephalographic recordings from 27 sites (electrodes) across rat cortex (n=6 male, 6 female) to characterize the effect of psilocybin (0.1 mg/kg, 1 mg/kg, and 10 mg/kg delivered over an hour) on network organization as inferred through changes in node degree (index of network density) and connection strength (weighted phase-lag index). The removal of aperiodic component from the electroencephalogram localized the primary oscillatory changes to theta (4-10 Hz), medium gamma (70-110 Hz), and high gamma (110-150 Hz) bands, which were used for the network analysis. Additionally, we determined the concurrent changes in theta-gamma phase-amplitude coupling. We report that psilocybin, in a dose-dependent manner, 1) disrupted theta-gamma coupling [p<0.05], 2) increased frontal high gamma connectivity [p<0.05] and posterior theta connectivity [p[≤]0.049], and 3) increased frontal high gamma [p<0.05] and posterior theta [p[≤]0.046] network density. The medium gamma frontoparietal connectivity showed a nonlinear relationship with psilocybin dose. Our results suggest that high-frequency network organization, decoupled from local theta-phase, may be an important signature of psilocybin-induced non-ordinary state of consciousness.

neuroscience↗

bioRxiv2023

Xbra modulates the activity of linker region phosporlated Smad1 during Xenopus somitogenesis

The Bmp/Smad1 pathway plays a crucial role in developmental processes and tissue homeostasis. Mitogen-activated protein kinase (Mapk)/Erk mediated phosphorylation of Smad1 in the linker region leads to Smad1 degradation, cytoplasmic retention and inhibition of Bmp/Smad1 signaling. While Fgf/Erk pathway has been documented to inhibit Bmp/Smad1 signaling, several studies also suggests the cooperative interaction between these two pathways in different context. However, the precise role and molecular pathway of this collaborative interaction remain obscure. Here, we identified Xbra induced by Fgf/Erk signaling as a factor in a protective mechanism for Smad1. Xbra physically interacted with the linker region phosphorylated Smad1 to make Xbra/Smad1/Smad4 trimeric complex, leading to Smad1 nuclear localization and protecting it from ubiquitin-mediated proteasomal degradation. This interaction of Xbra/Smad1/Smad4 led to sustained nuclear localization of Smad1 and the upregulation of lateral mesoderm genes, while concurrently suppression of neural and blood forming genes. Taken together, the results suggests Xbra-dependent cooperative interplays between Fgf/Erk and Bmp/Smad1 signaling during lateral mesoderm specification in Xenopus embryos.

developmental biology↗

bioRxiv2023

Systematic mapping and modeling of 3D enhancer-promoter interactions in early mouse embryonic lineages reveal regulatory principles that determine the levels and cell-type specificity of gene expression

Mammalian embryogenesis commences with two pivotal and binary cell fate decisions that give rise to three essential lineages, the trophectoderm (TE), the epiblast (EPI) and the primitive endoderm (PrE). Although key signaling pathways and transcription factors that control these early embryonic decisions have been identified, the non-coding regulatory elements via which transcriptional regulators enact these fates remain understudied. To address this gap, we have characterized, at a genome-wide scale, enhancer activity and 3D connectivity in embryo-derived stem cell lines that represent each of the early developmental fates. We observed extensive enhancer remodeling and fine-scale 3D chromatin rewiring among the three lineages, which strongly associate with transcriptional changes, although there are distinct groups of genes that are irresponsive to topological changes. In each lineage, a high degree of connectivity or "hubness" positively correlates with levels of gene expression and enriches for cell-type specific and essential genes. Genes within 3D hubs also show a significantly stronger probability of coregulation across lineages, compared to genes in linear proximity or within the same contact domains. By incorporating 3D chromatin features, we build a novel predictive model for transcriptional regulation (3D-HiChAT), which outperformed models that use only 1D promoter or proximal variables in predicting levels and cell-type specificity of gene expression. Using 3D-HiChAT, we performed genome-wide in silico perturbations to nominate candidate functional enhancers and hubs in each cell lineage, and with CRISPRi experiments we validated several novel enhancers that control expression of one or more genes in their respective lineages. Our study comprehensively identifies 3D regulatory hubs associated with the earliest mammalian lineages and describes their relationship to gene expression and cell identity, providing a framework to understand lineage-specific transcriptional behaviors. HIGHLIGHTS- Cell lines representing early embryonic lineages undergo drastic enhancer remodeling and fine-scale 3D chromatin reorganization - Highly interacting 3D hubs strongly enrich for highly expressed, cell-type specific and essential genes - 3D chromatin features greatly improve prediction of cell-type specific gene expression compared to 1D promoter features - In silico and experimental perturbations identify novel enhancers regulating the expression of two or more genes in early embryonic lineages

molecular biology↗

bioRxiv2023

L-type Ca2+ channels mediate regulation of glutamate release by subthreshold potential changes

Subthreshold depolarization enhances neurotransmitter release evoked by action potentials and plays a key role in modulating synaptic transmission by combining analog and digital signals. This process is known to be Ca2+-dependent. However, the underlying mechanism of how small changes in basal Ca2+ caused by subthreshold depolarization can regulate transmitter release triggered by a large increase in local Ca2+ is not well understood. This study aimed to investigate the source and signaling mechanisms of Ca2+ that couple subthreshold depolarization with the enhancement of glutamate release in hippocampal cultures and CA3 pyramidal neurons. Subthreshold depolarization increased presynaptic Ca2+ levels, the frequency of spontaneous release, and the amplitude of evoked release, all of which were abolished by blocking L-type Ca2+ channels. A high concentration of intracellular Ca2+ buffer or blockade of calmodulin and phospholipase C abolished depolarization induced increases in transmitter release. Estimation of the readily releasable pool size using hypertonic sucrose showed depolarization induced increases in readily releasable pool size, and this increase was abolished by blockade of calmodulin or phospholipase C. Our results provide mechanistic insights into the modulation of transmitter release by subthreshold potential change and highlight the role of L-type Ca2+ channels in coupling subthreshold depolarization to the activation of Ca2+-dependent signaling molecules that regulate transmitter release. SIGNIFICANCENeuronal activities are encoded by action potentials, but subthreshold changes in resting membrane potentials also play important roles in regulating neuronal functions including synaptic transmission. It is, however, poorly understood how small changes in basal Ca2+ induced by subthreshold depolarization regulate transmitter release triggered by a large increase in local Ca2+ in presynaptic terminals. We demonstrate that L-type Ca2+ channels are the major source of presynaptic Ca2+ influx at basal state and during subthreshold depolarization, resulting in the activation of signaling molecules such as calmodulin and phospholipase C, which facilitate transmitter release by increasing both release probability and the readily releasable pool size. Our results provide mechanistic insight into how subthreshold potential changes contribute to regulating transmitter release.

neuroscience↗

bioRxiv2022

The Role of the 3-Dimensional Genome in New Gene Evolution

Previous evolutionary models of duplicate gene evolution have overlooked the pivotal role of genome architecture. Here, we show that proximity-based regulatory recruitment of distally duplicated genes (enhancer capture) is an efficient mechanism for modulating tissue-specific production of pre-existing proteins. By leveraging genomic asymmetries in synteny and function that distinguish new genes evolving under enhancer capture-divergence (ECD) from those evolving under previous models, we performed a co-expression analysis on Drosophila melanogaster tissue data to show the generality of ECD as a significant evolutionary driver of asymmetric, distally duplicated genes. We use the recently evolved gene HP6/Umbrea, which duplicated <15 million years ago (mya), as an example of the ECD process. By assaying genome-wide chromosomal conformations in multiple Drosophila species, we show that HP6/Umbrea was inserted into a pre-existing, evolutionarily stable 3D genomic structure spanning over 125kb. We then utilize this data to identify a newly discovered enhancer (FLEE1), buried within the coding region of the highly conserved, essential gene MFS18, that likely neo-functionalized HP6/Umbrea, thereby driving the new duplicate gene copy to fixation. Finally, we demonstrate ancestral transcriptional co-regulation of HP6/Umbreas future insertion site using single-cell transcriptomics, illustrating how enhancer capture provides a highly evolvable, one-step solution to Ohnos Dilemma. The intuitive molecular mechanism underpinning the ECD model unveils a novel and robust framework to understand the fixation and neofunctionalization of distally duplicated genes.

evolutionary biology↗

bioRxiv2021

Explosive Synchronization-Based Brain Modulation Reduces Hypersensitivity in The Brain Network: A Computational Model Study

Fibromyalgia (FM) is a chronic pain condition that is characterized by hypersensitivity to multi-modal sensory stimuli, widespread pain, and fatigue. We have previously proposed explosive synchronization (ES), a phenomenon wherein a small perturbation to a network can lead to an abrupt state transition, as a potential mechanism of the hypersensitive FM brain. Therefore, we hypothesized that converting a brain network from ES to general synchronization (GS) may reduce the hypersensitivity of FM brain. To find an effective brain network modulation to convert ES into GS, we constructed a large-scale brain network model near criticality (i.e., an optimally balanced state between order and disorders), which reflects brain dynamics in conscious wakefulness, and adjusted two parameters: local structural connectivity and signal randomness of target brain regions. The network sensitivity to global stimuli was compared between the brain networks before and after the modulation. We found that only increasing the local connectivity of hubs (nodes with intense connections) changes ES to GS, reducing the sensitivity, whereas other types of modulation such as decreasing local connectivity, increasing and decreasing signal randomness are not effective. This study would help to develop a network mechanism-based brain modulation method to reduce the hypersensitivity in FM. Author summaryPhase transitions, the physical processes of transition between system states in nature, are divided into two broad categories: first and second-order phase transitions. For example, boiling water presents abrupt transition (a first-order) along with high sensitivity to temperature change, distinct from gradual magnetization near Curie temperature (a second-order). Recently, we found that chronic pain shows specific brain network configurations that can induce the first-order transition, so-called explosive synchronization. In this modeling study, we tried to identify a modulation method that can convert a first-order transition into a second-order transition in the brain network, expecting that it may inhibit the hypersensitivity in chronic pain. We found that increasing structural connectivity of hubs changes the type of phase transition in the brain network, significantly reducing network sensitivity.

neuroscience↗

bioRxiv2020

Criticality Creates a Functional Platform for Network Transitions between Internal and External Processing Modes in the Human Brain

Continuous switching between internal and external modes in the brain is a key process of constructing inner models of the outside world. However, how the brain continuously switches between two modes remains elusive. Here, we propose that a large synchronization fluctuation of the brain network emerging only near criticality (i.e., a balanced state between order and disorder) spontaneously creates temporal windows with distinct preferences for integrating internal information of the network and external stimuli. Using a computational model and empirical data analysis during alterations of consciousness in human, we present that synchronized and incoherent networks respectively bias toward internal and external information with specific network configurations. The network preferences are the most prominent in conscious states; however, they disrupt in altered states of consciousness. We suggest that criticality produces a functional platform of the brains capability for continuous switching between two modes, which is crucial for the emergence of consciousness.

neuroscience↗

bioRxiv2020

New Genes in Drosophila Quickly Evolved Essential Functions in Viability During Development

It is a conventionally held dogma that the genetic basis underlying development is conserved in a long evolutionary time scale. Ample experiments based on mutational, biochemical, functional, and complementary knockdown/knockout approaches have revealed the unexpectedly important role of recently evolved new genes in the development of Drosophila. The recent progress in the analyses of gene effects and improvements in the computational identification of new genes, which has led to large sample sizes of new genes, open the door to investigate the evolution of gene essentiality with a phylogenetically high resolution. These advancements also raised interesting issues related to phenotypic effect analyses of genes, particularly of those that recently originated. Here we reported our analyses of these issues, including the dating of gene ages, the interpretation of RNAi data that may confuse false positive/false negative rates, and the potential confounding impact of compensation and developmental effects that were not considered during previous CRISPR knockout experiments. We further analyzed new data from knockdowns of 702 new genes (~66% of total 1,070 Drosophila melanogaster new genes), revealing a similarly high proportion of essential genes from recent evolution, compared to those found in distant ancestors of D. melanogaster. Knockout of a few young genes detected analogous essentiality. Furthermore, our experimentally determined distribution and comparison of knockdown efficiency in different RNAi libraries provided valuable data for general functional analyses of genes. Taken together, these data, along with an improved understanding of the phenotypic effect analyses of new genes, provide further evidence to the conclusion that new genes in Drosophila quickly evolved essential functions in viability during development.

developmental biology↗

bioRxiv2020

Neural correlates of the shamanic state of consciousness

Despite the use of shamanism as a healing practice for several millennia, few empirical studies of the shamanic state of consciousness exist. We investigated the neural correlates of shamanic trance using high-density electroencephalography (EEG) in 24 shamanic practitioners and 24 healthy controls during rest, shamanic drumming, and classical music listening, followed by a validated assessment of altered states of consciousness. EEG data were used to assess changes in absolute power, connectivity, signal diversity, and criticality, which were correlated with assessment measures. We also compared assessment scores to those of individuals in a previous study under the influence of psychedelics. Shamanic practitioners were significantly different from controls in several domains of altered states of consciousness, with scores comparable to or exceeding that of healthy volunteers under the influence of psychedelics. Practitioners also displayed increased gamma power during drumming that positively correlated with elementary visual alterations. Furthermore, shamanic practitioners had decreased low alpha and increased low beta connectivity during drumming and classical music, and decreased neural signal diversity in the gamma band during drumming that inversely correlated with insightfulness. Finally, criticality in practitioners was increased during drumming in the low and high beta and gamma bands, with increases in the low beta band correlating with complex imagery and elementary visual alterations. These findings suggest that psychedelic drug-induced and non-pharmacologic alterations in consciousness have overlapping phenomenal traits but are distinct states of consciousness, as reflected by the unique brain-related changes during shamanic trance compared to previous literature investigating the psychedelic state.

neuroscience↗