Biology subjects

Zhao, H.

Publications and source records attributed to Zhao, H..

At least 415 records · Page 23Linked to original sources

bioRxiv2022

Metabolic Engineering of Oleaginous Yeast Rhodotorula toruloides for Overproduction of Triacetic Acid Lactone

The plant-sourced polyketide triacetic acid lactone (TAL) has been recognized as a promising platform chemical for the biorefinery industry. However, its practical application was rather limited due to low natural abundance and inefficient cell factories for biosynthesis. Here we report the metabolic engineering of oleaginous yeast Rhodotorula toruloides for TAL overproduction. We first introduced a 2-pyrone synthase gene from Gerbera hybrida (GhPS) into R. toruloides and investigated the effects of different carbon sources on TAL production. We then systematically employed a variety of metabolic engineering strategies to increase the flux of acetyl-CoA by enhancing its biosynthetic pathways and disrupting its competing pathways. We found that overexpression of citrate lyase (ACL1) improved TAL production by 45% compared to the GhPS overexpressing strain, and additional overexpression of acetyl-CoA carboxylase (ACC1) further increased TAL production by 29%. Finally, we characterized the resulting strain I12-ACL1-ACC1 using fed-batch bioreactor fermentation in glucose or oilcane juice medium with acetate supplementation and achieved a titer of 28 g/L or 23 g/L TAL, respectively. This study demonstrates that R. toruloides is a promising host for production of TAL and other acetyl-CoA-derived polyketides from low-cost carbon sources. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=57 SRC="FIGDIR/small/481788v1_ufig1.gif" ALT="Figure 1"> View larger version (12K): org.highwire.dtl.DTLVardef@32eb52org.highwire.dtl.DTLVardef@f786dborg.highwire.dtl.DTLVardef@b6d3f5org.highwire.dtl.DTLVardef@115aa67_HPS_FORMAT_FIGEXP M_FIG C_FIG Triacetic acid lactone (TAL) is a promising platform chemical. Cao et al. overexpressed 2-pyrone synthase in oleaginous yeast Rhodotorula toruloides to produce TAL. They systematically evaluated various metabolic gene targets to increase acetyl-CoA and malonyl-CoA levels for TAL production and found that overexpression of both ACL1 and ACC1 led to 28 g/L or 23 g/L of TAL from glucose or oilcane juice with acetate supplementation, respectively, in fed-batch fermentation.

synthetic biology↗

bioRxiv2022

Single-cell transcriptomic and proteomic analysis of Parkinson's disease Brains

Parkinsons disease (PD) is a prevalent neurodegenerative disorder where recent evidence suggests pathogenesis may be mediated by inflammatory processes. The molecular architecture of the disease remains to be fully elucidated. We performed single-nucleus transcriptomics and unbiased proteomics using postmortem tissue obtained from the prefrontal cortex of 12 individuals with late-stage PD and age-matched controls. We analyzed [~]80,000 nuclei and identified eight major cell types, including brain-resident T cells, each with distinct transcriptional changes in line with the known genetics of PD. By analyzing Lewy body pathology in the same postmortem tissue, we found that -synuclein pathology is inversely correlated with chaperone expression in excitatory neurons. Examining cell-cell interactions, we found a selective abatement of neuron-astrocyte interactions and enhanced neuroinflammation. Proteomic analyses of the same brains identified synaptic proteins in prefrontal cortex that were preferentially downregulated in PD. Strikingly, comparing this dataset to a regionally similar published analysis for Alzheimers disease (AD), we found no common differentially expressed genes in neurons, but identified many shared differentially expressed genes in glial cells, suggesting that disease etiology in PD and AD are likely distinct. These data are presented as a resource for interrogating the molecular and cellular basis of PD and other neurodegenerative diseases. One Sentence SummaryWe provide an extensive single cell analysis profiling nearly 80,000 brain nuclei from prefrontal cortex of late-stage Parkinsons disease brains, demonstrate that -synuclein pathology is inversely correlated with chaperone expression in excitatory neurons, found a selective abatement of neuron-astrocyte interactions with enhanced neuroinflammation, and augmented the study with proteomic analysis and cross-comparisons with Alzheimers disease datasets, providing valuable insights into the pathways of neurodegeneration and a deep definition of the underlying molecular pathology for Parkinsons disease.

neuroscience↗

bioRxiv2022

dbDEMC 3.0: Functional Exploration of Differentially Expressed miRNAs in Cancers of Human and Model Organisms

microRNAs (miRNAs) are important regulators in gene expression. The deregulation of miRNA expression is widely reported in the transformation from physiological to pathological state of cells. A large amount of differentially expressed miRNAs (DEMs) have been identified in various human cancers by using high-throughput technologies, such as microarray and miRNA-seq. Through mining of published researches with high-throughput experiment information, the database of differentially expressed miRNAs in human cancers (dbDEMC) was constructed with the aim of providing a systematic resource for the storage and query of the DEMs. Here we report an update of the dbDEMC to version 3.0, containing two-fold more data entries than the previous version, now including also data from mouse and rat. The dbDEMC 3.0 contains 3,268 unique DEMs in 40 different cancer types. The current datasets for differential expression analysis have expanded to 9 generalized categories. Moreover, the current release integrates functional annotations of DEMs obtained from experimentally validated targets. The annotations can greatly benefit integrative analysis of DEMs. In summary, dbDEMC 3.0 provides a valuable resource for characterizing molecular functions and regulatory mechanisms of DEMs in human cancers. The dbDEMC 3.0 is freely accessible at https://www.biosino.org/dbDEMC.

bioinformatics↗

bioRxiv2022

Plasticity in structure and assembly of SARS-CoV-2 nucleocapsid protein

Worldwide SARS-CoV-2 sequencing efforts track emerging mutations in its spike protein, as well as characteristic mutations in other viral proteins. Besides their epidemiological importance, the observed SARS-CoV-2 sequences present an ensemble of viable protein variants, and thereby a source of information on viral protein structure and function. Charting the mutational landscape of the nucleocapsid (N) protein that facilitates viral assembly, we observe variability exceeding that of the spike protein, with more than 86% of residues that can be substituted, on average by 3-4 different amino acids. However, mutations exhibit an uneven distribution that tracks known structural features but also reveals highly protected stretches of unknown function. One of these conserved regions is in the central disordered linker proximal to the N-G215C mutation that has become dominant in the Delta variant, outcompeting G215 variants without further spike or N-protein substitutions. Structural models suggest that the G215C mutation stabilizes conserved transient helices in the disordered linker serving as protein-protein interaction interfaces. Comparing Delta variant N-protein to its ancestral version in biophysical experiments, we find a significantly more compact and less disordered structure. N-G215C exhibits substantially stronger self-association, shifting the unliganded protein from a dimeric to a tetrameric oligomeric state, which leads to enhanced co-assembly with nucleic acids. This suggests that the sequence variability of N-protein is mirrored by high plasticity of N-protein biophysical properties, which we hypothesize can be exploited by SARS-CoV-2 to achieve greater efficiency of viral assembly, and thereby enhanced infectivity.

biophysics↗

bioRxiv2022

Dopamine transporter and synaptic vesicle sorting defects initiate auxilin-linked Parkinson's disease

Auxilin participates in the uncoating of clathrin-coated vesicles (CCVs), thereby facilitating synaptic vesicle (SV) regeneration at presynaptic sites. Auxilin (DNAJC6/PARK19) loss-of- function mutations cause early-onset Parkinsons disease (PD). Here, we utilized auxilin-knockout (KO) mice to elucidate the mechanisms through which auxilin deficiency and clathrin-uncoating deficits lead to PD. We demonstrate that auxilin KO mice display the cardinal features of PD, including progressive motor deficits, -synuclein pathology, nigral dopaminergic loss, and neuroinflammation. Through unbiased proteomic and neurochemical analyses, we demonstrate that dopamine homeostasis is disrupted in auxilin KO brains, including via slower dopamine reuptake kinetics in vivo, an effect associated with dopamine transporter misrouting into axonal membrane deformities in the dorsal striatum. We also show that elevated macroautophagy and defective SV protein sorting contribute to ineffective dopamine sequestration and homeostasis, ultimately leading to neurodegeneration. This study advances our knowledge of how presynaptic endocytosis deficits lead to dopaminergic vulnerability and pathogenesis of PD.

neuroscience↗

bioRxiv2022

The endoplasmic reticulum membrane protein complex (EMC) negatively regulates intestinal homeostasis through the Hippo signaling pathway

Disruption of tissue homeostasis often results in many diseases. Balanced control of stem cell proliferation and differentiation underlines tissue homeostasis. However, how endogenous factors influence the proliferation and differentiation of intestinal stem cells (ISCs) under physiological conditions remains not fully understood. Here, we find that the endoplasmic reticulum membrane protein complex (EMC) negatively regulates ISC proliferation in adult Drosophila midgut. Compromising EMC function in progenitors leads to excessive ISC proliferation and intestinal homeostasis disruption. Mechanistically, the EMC complex associates with and stabilizes Hippo (Hpo), the key component of the Hpo signaling pathway. In the absence of the EMC complex, Yki (Yorkie) is activated to promote ISC proliferation. Furthermore, the role of the EMC complex in stem cell proliferation control is evolutionarily conserved. Thus, our study uncovers the molecular mechanism of the EMC complex in controlling stem cell proliferation. Our results provide new insight into the underlying mechanisms of how stem cell proliferation is properly controlled under physiological conditions.

cell biology↗

bioRxiv2022

Close relatives of MERS-CoV in bats use ACE2 as their functional receptors

Middle East Respiratory Syndrome coronavirus (MERS-CoV) and several bat coronaviruses employ Dipeptidyl peptidase-4 (DPP4) as their functional receptors1-4. However, the receptor for NeoCoV, the closest MERS-CoV relative yet discovered in bats, remains enigmatic5. In this study, we unexpectedly found that NeoCoV and its close relative, PDF-2180-CoV, can efficiently use some types of bat Angiotensin-converting enzyme 2 (ACE2) and, less favorably, human ACE2 for entry. The two viruses use their spikes S1 subunit carboxyl-terminal domains (S1-CTD) for high-affinity and species-specific ACE2 binding. Cryo-electron microscopy analysis revealed a novel coronavirus-ACE2 binding interface and a protein-glycan interaction, distinct from other known ACE2-using viruses. We identified a molecular determinant close to the viral binding interface that restricts human ACE2 from supporting NeoCoV infection, especially around residue Asp338. Conversely, NeoCoV efficiently infects human ACE2 expressing cells after a T510F mutation on the receptor-binding motif (RBM). Notably, the infection could not be cross-neutralized by antibodies targeting SARS-CoV-2 or MERS-CoV. Our study demonstrates the first case of ACE2 usage in MERS-related viruses, shedding light on a potential bio-safety threat of the human emergence of an ACE2 using "MERS-CoV-2" with both high fatality and transmission rate.

microbiology↗

bioRxiv2022

Impact of Nosema ceranae invasion on sucrose solution consumption, midgut epithelial cell structure, and lifespan of Apis cerana cerana workers

Nosema ceranae is an intracellular fungal parasite for honeybees, leading to chronic disease named bee nosemosis with worldwide distribution. Asian honeybee (Apis cerana) is the original host for N. ceranae, but the impact of N. ceranae infection on A. cerana physiology is largely unknown. In this current work, workers of Apis cerana cerana, a subspecies of Asian honeybee, were artificially inoculated with N. ceranae spores and reared under lab conditions, followed by detection of fungal spore load as well as host sucrose solution consumption, midgut epithelial cell structure, and lifespan. The result of spore counting suggested that the spore load in the host midgut decreased significantly during 1 dpi-2 dpi, whereas that displayed an elevated trend among 2 dpi-13 dpi. The sucrose solution consumption of workers in N. ceranae-inoculated groups among 1 dpi-20 dpi was always higher than that of workers in un-inoculated groups; additionally, the difference of sucrose solution consumption between these two groups at 4 dpi, 5 dpi, and 13 dpi was of significance. Based on microscopic observation of paraffin sections, darkly stained parasites were clearly detected in the midgut epithelial cells of N. ceranae-inoculated workers at 7 dpi-10 dpi, whereas no parasite was observed in those of un-inoculated workers. In addition, the boundaries of un-inoculated host epithelial cells were intact and the darkly stained nucleus were clear, while the boundaries of midgut epithelial cells of N. ceranae-inoculated workers were blurred, the nucleus were almost disappeared, and the nucleic acid substances were diffused. Moreover, the survival rates of workers in both N. ceranae-inoculated groups and un-inoculated groups at 1 dpi-5 dpi were pretty high and then started to decrease at 5 dpi; the survival rate of workers in N. ceranae-inoculated groups was always lower than that in un-inoculated groups, with significant difference between these two groups during 11 dpi-20 dpi. These results together indicate that the quantity of fungal spores continuously elevated with the microsporidian multiplication, causing energetic stress for workers and host cell structure damage, which further negatively affected the host lifespan. Our findings offer a solid basis not only for exploring the molecular mechanism underlying N. ceranae infection but also for investigating the interaction between N. ceranae and eastern honeybee.

molecular biology↗

bioRxiv2022

Characterizing RNA-binding Ligands on Structures, Chemical Information, Binding Affinity and Drug-likeness

Recent studies suggest RNAs playing essential roles in many cell activities and act as promising drug targets. However, limited development has been achieved in detecting RNA-ligand interactions. To guide the discovery of RNA-binding ligands, it is necessary to characterize them comprehensively. We established a database, RNALID that collects RNA-ligand interactions validated by low-throughput experiment. RNALID contains 358 RNA-ligand interactions. Comparing to other databases, 94.5% of ligands in RNALID are completely or partially novel collections, and 51.78% have novel two-dimensional (2D) structures. The ligand structure analysis indicated that multivalent ligands (MV), ligands binding with cellular mRNA (mRNA), ligands binding with RNA from virus (vRNA) and ligands binding with RNA containing repetitive sequence (rep RNA) are more structurally conserved in both 2D and 3D structures than other ligand types. Binding affinity analysis revealed that interactions between ligands and rep RNA were significantly stronger (two-tailed MW-U test P-value = 0.012) than the interactions between ligands and non-rep RNAs; the interactions between ligands and vRNA were significantly stronger (two-tailed MW-U test P-value = 0.012) than those between ligands and mRNA. Drug-likeness analysis indicated that small molecule (SM) ligands binding with non-rep RNA or vRNA may have higher probability to be drugs than other types of ligands. Comparing ligands in RNALID to FDA-approved drugs and ligands without bioactivity indicated that RNA-binding ligands are different from them in chemical properties, structural properties and drug-likeness. Thus, characterizing the RNA-ligand interactions in RNALID in multiple respects provides new insights into discovering and designing druggable ligands binding with RNA. KEY POINTSO_LIWe established a database, RNALID, by collecting RNA-ligand interactions validated by low-throughput experiments, which contains 358 RNA-ligand interactions, and 94.5% of them are completely or partially novel collections. C_LIO_LILigands in RNALID were divided into fourteen types, and were analyzed on chemical properties, spatial properties, binding affinity and drug-likeness. Small molecule (SM) ligands binding with non-repeat RNA or virus RNA were indicated having higher probability to be drugs than other types of ligands. C_LIO_LILigands in RNALID were different from protein-binding ligands and ligands without bioactivity in chemical properties, structural properties and drug-likeness. C_LI

bioinformatics↗

bioRxiv2022

PlasmidMaker: a Versatile, Automated, and High Throughput End-to-End Platform for Plasmid Construction

Plasmids are used extensively in basic and applied biology. However, design and construction of plasmids, specifically the ones carrying complex genetic information, remains one of the most time-consuming, labor-intensive, and rate-limiting steps in performing sophisticated biological experiments. Here, we report the development of a versatile, robust, automated end-to-end platform named PlasmidMaker that allows error-free construction of plasmids with virtually any sequences in a high-throughput manner. This platform consists of a most versatile DNA assembly method using Pyrococcus furiosus Argonaute (PfAgo)-based artificial restriction enzymes, a user-friendly frontend for plasmid design, and a backend that streamlines the workflow and integration with a robotic system. As a proof of concept, we used this platform to generate 101 plasmids from six different species ranging from 5 to 18 kb in size from up to 11 DNA fragments within 3 days. PlasmidMaker should greatly expand the potential of synthetic biology.

synthetic biology↗

bioRxiv2021

CSNet: Estimating cell-type-specific gene co-expression networks from bulk gene expression data

Inferring and characterizing gene co-expression networks has led to important insights on the molecular mechanisms of complex diseases. Most co-expression analyses to date have been performed on gene expression data collected from bulk tissues with different cell type compositions across samples. As a result, the co-expression estimates only offer an aggregate view of the underlying gene regulations and can be confounded by heterogeneity in cell type compositions, failing to reveal gene coordination that may be distinct across different cell types. In this paper, we describe a flexible framework for estimating cell-type-specific gene co-expression networks from bulk sample data, without making specific assumptions on the distributions of gene expression profiles in different cell types. We develop a novel sparse least squares estimator, referred to as CSNet, that is efficient to implement and has good theoretical properties. Using CSNet, we analyzed the bulk gene expression data from a cohort study on Alzheimers disease and identified previously unknown cell-type-specific co-expressions among Alzheimers disease risk genes, suggesting cell-type-specific disease pathology for Alzheimers disease.

bioinformatics↗

bioRxiv2021

Using antibody synergy to engineer a high potency biologic cocktail against C. difficile

Here we show that transgenic spirulina may solve key challenges of developing effective monoclonal protein therapeutics for diseases afflicting gastrointestinal (GI) tissues. We describe, as a paradigm for this novel approach, LMN-201: an investigational four-component treatment for Clostridioides difficile (C. difficile) infection comprising four monoclonal protein therapeutics produced and delivered within spirulina biomass. Three antibody-like moieties within LMN-201 were rationally designed using a multiplicative potency framework, termed synthetic avidity, that increased in vitro toxin neutralization potency by >200-fold relative to the individual components. The fourth moiety, a lysin enzyme protein, adds direct, toxinotype-agnostic antibacterial activity. In rodent challenge models, species-relevant LMN-201-like cocktails reduced disease burden and mortality. In a human GI pharmacokinetic study, LMN-201 was present at concentrations 100- to 1,000-fold above the estimated minimally effective therapeutic threshold at the distal intestine. In a Phase 2 study in participants suffering from C. difficile infection (CDI), seven days of treatment with LMN-201 plus standard-of-care antibiotics achieved initial clinical cure in 21/21 (100%) participants, sustained clinical cure through four weeks in 19/21 (90.5%) participants, and had a favorable safety profile. These findings support LMN-201 with standard-of-care antibiotics as a viable treatment option for CDI, validate spirulina as a scalable platform for oral biologics, and establish a generalizable strategy for engineering high-potency combination protein therapeutics for diseases with a GI tissue nexus.

bioengineering↗

bioRxiv2021

Metabolitin-based molecular drug delivery by targeting GPR158 in glioblastoma

Glioblastoma multiforme (GBM) is a lethal form of intracranial tumor. One of the obstacles to treat GBM is the blood-brain barrier which limit the transportation of drugs into the tumor site. Here, based on our previous study on metabolitin (MTL) and osteocalcin, we generated a molecular drug delivery system that consisted of metabolitin and small molecules such as fluorescent dye or peptide drugs for diagnosis and treatment. And we designed a GBM diagnostic probe (MTL-ICG) and therapeutic peptide drug (MTL-NBD) that can cross the blood-brain barrier (BBB). In a NIR animal live imaging system, we found MTL-ICG can penetrate cross BBB and label the GBM site. The in vitro experiment showed that MTL-NBD had inhibitory effect on GBM cell line (U87-MG). Besides, after orthotopic transplantation of GBM into mouse cortex, treatment of MTL-NBD intravenously showed inhibition trend, which were similar with the effect of NBD, a known anti-tumor polypeptide drug. In addition, we found the GPR158, the receptor of osteocalcin, was also high expressed in grafting site. Taken together, these findings suggest that MTL is a promising cell penetrating peptide targeting GPR158 in GBM, which provide a novel delivery tool for GBM.

cancer biology↗

bioRxiv2021

Mapping of individual sensory nerve axons from digits to spinal cord with the Transparent Embedding Solvent System

Understanding the connections and projections of neurons has been a fundamental issue for neuroscience. Although strategies have been developed to map the projection of individual axons within the mouse brain, high resolution mapping of individual peripheral nerve axons in peripheral organs or spinal cord has never been achieved. Here, we designed the Transparent Embedding Solvent System (TESOS) method and developed a technical pipeline for imaging, reconstructing and analyzing large samples containing various tissue types at sub-micron resolution. The mouse whole body was reconstructed at micron-scale resolution. We were able to image, reconstruct and analyze the complete axonal projection of individual sensory neurons within an intact mouse paw or spinal cord at sub-micron resolution. Furtherly, we imaged and reconstructed the entire projection course of individual sensory neurons from adult mouse digits to the spinal cord. The TESOS method provides an efficient tool for micron-scale connectome mapping of the peripheral nervous system.

neuroscience↗

bioRxiv2021

A live attenuated influenza virus-vectored intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2 infection

Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 day and 7 days after single-dose vaccination or 6 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight, caused by either the prototype-like strain or beta variant of SARS-CoV-2. Lasted data showed that the animals could be well protected against beta variant challenge 9 months after vaccination. Notably, the weight loss and lung pathological changes of hamsters could still be significantly reduced when the hamster was vaccinated 24 h after challenge. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to fight against the ongoing COVID-19 pandemic, compensating limitations of current intramuscular vaccines, particularly at the start of an outbreak.

pathology↗

bioRxiv2021

pGlycoQuant with a deep residual network for precise and minuscule-missing-value quantitative glycoproteomics enabling the functional exploration of site-specific glycosylation

Interpreting large-scale glycoproteomic data for intact glycopeptide identification has been tremendously advanced by software tools. However, software tools for quantitative analysis of intact glycopeptides remain lagging behind, which greatly hinders exploring the differential expression and functions of site-specific glycosylation in organisms. Here, we report pGlycoQuant, a generic software tool for accurate and convenient quantitative intact glycopeptide analysis, supporting both primary and tandem mass spectrometry quantitation for multiple quantitative strategies. pGlycoQuant enables intact glycopeptide quantitation with very low missing values via a deep residual network, thus greatly expanding the quantitative function of several powerful search engines, currently including pGlyco 2.0, pGlyco3, Byonic and MSFragger-Glyco. The pGlycoQuant-based site-specific N-glycoproteomic study conducted here quantifies 6435 intact N-glycopeptides in three hepatocellular carcinoma cell lines with different metastatic potentials and, together with in vitro molecular biology experiments, illustrates core fucosylation at site 979 of the L1 cell adhesion molecule (L1CAM) as a potential regulator of HCC metastasis. pGlycoQuant is freely available at https://github.com/expellir-arma/pGlycoQuant/releases/. We have demonstrated pGlycoQuant to be a powerful tool for the quantitative analysis of site-specific glycosylation and the exploration of potential glycosylation-related biomarker candidates, and we expect further applications in glycoproteomic studies.

systems biology↗

bioRxiv2021

Senataxin and RNase H2 act redundantly to suppress genome instability during class switch recombination

Class switch recombination generates antibody distinct isotypes critical to a robust adaptive immune system and defects are associated with auto-immune disorders and lymphomagenesis. Transcription is required during class switch to recruit the cytidine deaminase AID--an essential step for the formation of DNA double-strand breaks--and strongly induces the formation of R loops within the immunoglobulin heavy chain locus. However, the impact of R loops on double-strand break formation and repair during class switch recombination remains unclear. Here we report that cells lacking two enzymes involved in R loop removal-- Senataxin and RNase H2--exhibit increased R loop formation and genome instability at the immunoglobulin heavy chain locus without impacting class switch recombination efficiency, transcriptional activity, or AID recruitment. Senataxin and RNase H2-deficient cells also exhibit increased insertion mutations at switch junctions, a hallmark of alternative end joining. Importantly, these phenotypes were not observed in cells lacking Senataxin or RNase H2B alone. We propose that Senataxin acts redundantly with RNase H2 to mediate timely R loop removal, promoting efficient repair while suppressing AID-dependent genome instability and insertional mutagenesis.

immunology↗

bioRxiv2021

Investigating Emotion Dynamics and Its Association with Multimedia Content During Video Watching Through EEG Microstate Analysis

EEG microstates have been widely adopted to understand the complex and dynamic-changing process in dynamic brain systems, but how microstates are temporally modulated by emotion dynamics is still unclear. An investigation of EEG microstates under video-evoking emotion dynamics modulation would provide a novel insight into the understanding of temporal dynamics of functional brain networks. In the present study, we postulate that emotional states dynamically modulate the microstate patterns, and perform an in-depth investigation between EEG microstates and emotion dynamics under a video-watching task. By mapping from subjective-experienced emotion states and objective-presented stimulation content to EEG microstates, we gauge the comprehensive associations among microstates, emotions, and multimedia stimulation. The results show that emotion dynamics could be well revealed by four EEG microstates (MS1, MS2, MS3, and MS4), where MS3 and MS4 are found to be highly correlated to different emotion states (emotion task effect and level effect) and the affective information involved in the multimedia content (visual and audio). In this work, we reveal the microstate patterns related to emotion dynamics from sensory and stimulation dimensions, which deepens the understanding of the neural representation under emotion dynamics modulation and will be beneficial for the future study of brain dynamic systems.

neuroscience↗