Biology subjects

Yan, Y.

Publications and source records attributed to Yan, Y..

At least 163 records · Page 9Linked to original sources

bioRxiv2023

Pseudorabies virus causes splenic injury via inducing the oxidative stress and apoptpsos related factors in mice

Pseudorabies virus (PRV) is an immunosuppressive disease that causes significant damage to the pig industry. This study aimed to detect the effects of PRV on oxidative stress related factors and cell apoptosis in the spleen, providing a basis for the research on the pathogenesis of PRV in mice model. Pathological observation was performed by hematoxylin and eosin Y staining. Biochemical and Flow cytometry method were performed to determine the reactive oxygen species profile of the spleen post-infection and apoptosis detection. In addition, q-PCR and Western blot were adopted to measure the apoptotic conditions of the spleen infected with PRV. The results indicated that the ROS level in the PRV infection group was remarkedly increased (p<0 01) at a time-dependent pattern. Furthermore, the Malondialdehyde levels in the spleen of mice in the infection group increased significantly (p<0.01) in a time-dependent mode. However, the Catalase, Superoxide dismutase, and Glutathione activity and expression levels in the infection group were significantly decreased with the control group (p<0 01) in a time-dependent manner. Furthermore, the ratio of splenocyte apoptosis in the infection group significantly increased (p<0 05, p<0 01) in a time-dependent manner. In conclusion, PRV infection causes apoptosis of the spleen via oxidative stress in mice.

microbiology↗

bioRxiv2023

Habitat fragmentation weakens the positive relationship between grassland plant richness and above-ground biomass

Habitat loss and fragmentation per se have been shown to be a major threat to global biodiversity and ecosystem function. However, little is known about how habitat loss and fragmentation per se alters the relationship between biodiversity and ecosystem function (BEF relationship) in the natural landscape context. Based on 130 landscapes identified by a stratified random sampling in the agro-pastoral ecotone of northern China, we investigated the effects of landscape context (habitat loss and fragmentation per se) on plant richness, above-ground biomass, and the relationship between them in grassland communities using a structural equation model. We found that habitat loss directly decreased plant richness and hence decreased above-ground biomass, while fragmentation per se directly increased plant richness and hence increased above-ground biomass. Fragmentation per se also directly decreased soil water content and hence decreased above-ground biomass. Meanwhile, habitat loss decreased the magnitude of the positive relationship between plant richness and above-ground biomass by reducing the percentage of grassland specialists in the community, while fragmentation per se had no significant modulating effect on this relationship. These results demonstrate that habitat loss and fragmentation per se have inconsistent effects on biodiversity and ecosystem function, with the BEF relationship being modulated by landscape context. Our findings emphasise that habitat loss rather than fragmentation per se can weaken the positive BEF relationship by decreasing the degree of habitat specialisation of the community. HighlightsO_LIBEF relationship is moderated by landscape context in fragmented landscapes. C_LIO_LIHabitat loss and fragmentation per se have inconsistent effects. C_LIO_LIHabitat loss can weaken the positive BEF relationship via reducing the percentage of grassland specialists in the community. C_LI

ecology↗

bioRxiv2023

Distinct Microstructural Heterogeneities Underpin Specific Micromechanical Properties in Human ACL Femoral and Tibial Entheses

The anterior cruciate ligament (ACL) is anchored to the femur and tibia by a specialized interface tissue called the enthesis, which transfers forces in multiple directions and magnitudes without accruing fatigue damage during loading cycles over a lifetime. However, the precise structural and mechanical characteristics of the ACL femoral enthesis (FE) and tibial enthesis (TE) and their intricate interplay are unknown. In this study, we identified two ultrathin-graded mineralization regions in the FE ([~]21 m) and TE ([~]14 m), both of which exhibited distinct biomolecular compositions and mineral assembly patterns. FE interface exhibited progressively maturing hydroxyapatites (HAps), whereas minerals at the TE interface region changed from an amorphous phase (ACP) to HAps with increasing crystallinity. The LC-MS/MS results revealed that MGP protein uniquely enriched at the TE interface may be favorable for stabilizing ACP, while CLEC11A enriched at the FE interface could facilitate osteogenesis of the interface. The finite element analysis results indicated that the FE model was more resistant to shearing, while the TE model facilitated tensile resistance. It suggested that the great discrepancy in biomolecular expression and the corresponding mineral assembling heterogeneities together contributed to the superior mechanical properties of both the FE and TE models. These findings provide new perspectives regarding the management of ACL injury and the development of high-performance interface materials.

bioengineering↗

bioRxiv2023

Artemisitene protected against murine schistosomiasis japonica through anti-parasite activity and immune regulation

Schistosoma japonicum (Sj) infection induced liver granulomatous inflammation and fibrosis. As an active artemisinin analog, the implication of artemisitene (ATT) in schistosomiasis were unclear. Herein, we found that ATT significantly reduced the count of total adult worms and eggs, and increased the count of single males, injured the tegument in the surface of Sj adult worms & gynecophoral canal of males. The transcription of 98 genes in females and 48 genes in males were significantly changed, and these genes were closely related to cellular anatomical entity through gene ontology analysis. So, ATT might possess anti-parasite activity. Meanwhile, ATT treatment significantly lowered the level of glutamic oxaloacetic transaminase (AST) and glutamic pyruvic transaminase (ALT) in sera, the size of mesenteric lymph node, and granuloma, the collagen area and -SMA expression level in the liver. Liver transcriptome and multi-cytokines analysis indicated its immune regulation effect. Flow cytometry verified that the count of eosinophils in the liver were significantly increased, while the frequency of neutrophils, M1/M2 and Th1/Th2 index were significantly decreased. Therefore, we provided strong evidence that ATT has therapeutic potential through Sj clearance and anti-liver disease. Tegument development injury and immune regulation including type 2 immunity enhancement might be the mechanisms. Author summaryCurrently, there were still 290 million people worldwide who were infected by Schistosoma, and the treatment for schistosomiasis relies majorly on the use of a single drug-praziquantel. In this study, we described for the first time that artemisinin-derived artemisitene (ATT), chemically remarkably different from praziquantel, possessed the therapeutic effects on murine schistosomiasis japonica. ATT displayed both anti-Schistsosoma japonicum and anti-liver inflammation & liver fibrosis effect. Through RNA-seq and scanning electronic microscope of adult female & male worms from hepatoportal veins with or without ATT treatment, we found that the mechanisms of ATTs anti-parasites could be through injuring tegument development and then interrupting adult worms especially adult female worms clearance by immune cells such as eosinophils. Moreover, through RNA-seq of liver total RNA, ELISA of multi-cytokines in liver lysates and flow cytometry analysis of liver single cells, we found that the anti-liver diseases efficacy of ATT was associated with immune regulation especially type 2 immunity enhancement. Therefore, ATT possessed the therapeutic potential against schistosomiasis japonica and further researches were necessary for its future clinical use.

immunology↗

bioRxiv2023

The circadian clock is a pacemaker of the axonal regenerative ability

Peripheral nervous system injuries lead to long-term neurological disability due to limited axonal regenerative ability. Injury-dependent and -independent physiological mechanisms have provided important molecular insight into neuronal regeneration. However, whether common molecular denominators underpin both injury-dependent and independent biological processes remain unclear. Here, we performed a comparative analysis of recently generated transcriptomic datasets associated with the regenerative ability of sciatic dorsal root ganglia (DRG). Surprisingly, circadian rhythms were identified as a the most significantly enriched biological process associated with regenerative capability. We demonstrate that DRG neurons possess an endogenous circadian clock with a 24h oscillations of circadian genes and that their regenerative ability displays a diurnal oscillation in a mouse model of sciatic nerve injury. Consistently, transcriptomic analysis of DRG neurons showed a significant time-of-day dependent enrichment for processes associated with axonal regeneration, development and growth, as well as circadian associated genes, including the core clock genes Bmal1 and Clock. Indeed, DRG-specific ablation of the non-redundant clock gene Bmal1 showed that it is required for regenerative gene expression, neuronal intrinsic circadian regeneration and target reinnervation. Lastly, lithium, a chrono-active compound, enhanced nerve regeneration, in wildtype but not in Bmal1 and Cry1/2-deficient mice. Together, these data demonstrate that daily rhythms and the molecular clock fine-tune the regenerative response of DRG neurons, and that chrono-active drugs, such as lithium, are a novel potential approach to nerve repair.

neuroscience↗

bioRxiv2023

Eyes on nature: Embedded vision cameras for multidisciplinary biodiversity monitoring

Global environmental challenges require comprehensive data to manage and protect biodiversity. Currently, vision-based biodiversity monitoring efforts are mixed, incomplete, human-dependent, and passive. To tackle these issues, we present a portable, modular, low-power device with embedded vision for biodiversity monitoring. Our camera uses interchangeable lenses to resolve barely visible and remote subjects, as well as customisable algorithms for blob detection, region-of-interest classification, and object detection to identify targets. We showcase our system in six case studies from the ethology, landscape ecology, agronomy, pollination ecology, conservation biology, and phenology disciplines. Using the same devices, we discovered bats feeding on durian tree flowers, monitored flying bats and their insect prey, identified nocturnal insect pests in paddy fields, detected bees visiting rapeseed crop flowers, triggered real-time alerts for waterbirds, and tracked flower phenology over months. We measured classification accuracies between 55% and 96% in our field surveys and used them to standardise observations over highly-resolved time scales. The cameras are amenable to situations where automated vision-based monitoring is required off the grid, in natural and agricultural ecosystems, and in particular for quantifying species interactions. Embedded vision devices such as this will help addressing global biodiversity challenges and facilitate a technology-aided global food systems transformation.

ecology↗

bioRxiv2023

Interchromosomal Colocalization with Parental Genes Is Linked to the Function and Evolution of Mammalian Retrocopies

Retrocopies are gene duplicates arising from reverse transcription of mature mRNA transcripts and their insertion back into the genome. While long being regarded as processed pseudogenes, more and more functional retrocopies have been discovered. How the stripped- down retrocopies recover expression capability and become functional paralogs continually intrigues evolutionary biologists. Here, we investigated the function and evolution of retrocopies in the context of three-dimensional (3D) genome organization. By mapping retrocopy-parent pairs onto sequencing-based and imaging-based chromatin contact maps in human and mouse cell lines and onto Hi-C interaction maps in five other mammals, we found that retrocopies and their parental genes show a higher-than-expected interchromosomal colocalization frequency. The spatial interactions between retrocopies and parental genes occur frequently at loci in active subcompartments and near nuclear speckles. Accordingly, colocalized retrocopies are more actively transcribed and translated, and are more evolutionarily conserved than noncolocalized ones. The active transcription of colocalized retrocopies may result from their permissive epigenetic environment and shared regulatory elements with parental genes. Population genetic analysis of retroposed gene copy number variants (retroCNVs) in human populations revealed that retrocopy insertions are not entirely random in regard to interchromosomal interactions and that colocalized retroCNVs are more likely to reach high frequencies, suggesting that both insertion bias and natural selection contribute to the colocalization of retrocopy-parent pairs. Further dissection implies that reduced selection efficacy, rather than positive selection, contributes to the elevated allele frequency of colocalized retroCNVs. Overall, our results hint a role of interchromosomal colocalization in the "resurrection" of initially neutral retrocopies.

evolutionary biology↗

bioRxiv2023

Reward positivity biases interval production in a continuous timing task

The neural circuits of reward processing and interval timing (including perception and production) are functionally intertwined, suggesting that it might be possible for momentary reward processing to influence subsequent timing behavior. Previous animal and human studies have mainly focused on the effect of reward on interval perception, whereas its impact on interval production is less clear. In this study, we examined whether feedback, as an example of performance-contingent reward, biases interval production. We recorded EEG from 20 participants while they engaged in a continuous drumming task with different realistic tempos (1728 trials per participant). Participants received color-coded feedback after each beat about whether they were correct (on time) or incorrect (early or late). Regression-based EEG analysis was used to unmix the rapid occurrence of a feedback response called the reward positivity (RewP), which is traditionally observed in more slow-paced tasks. Using linear mixed modelling, we found that RewP amplitude predicted timing behavior for the upcoming beat. This performance-biasing effect of the RewP was interpreted as reflecting the impact of fluctuations in dopaminergic activities on timing, and the necessity of continuous paradigms to make such observations was highlighted.

neuroscience↗

bioRxiv2023

Prestimulus neural variability affects behavioral performances mediated by poststimulus-evoked responses at the intraindividual and interindividual levels

There are significant intra-individual and inter-individual variabilities in audiovisual temporal perception. Previous studies have shown that prestimulus neural variability could reflect behavioral variabilities. We aimed to investigate whether prestimulus neural variability can predict behavioral variability in audiovisual temporal perception. Furthermore, We also explored whether prestimulus neural variability directly influences behavioral responses or indirectly impacts perceptual decisions through post-stimulus-evoked responses. We analyzed the electroencephalography (EEG) data from a paradigm where the twenty-eight human subjects performed a simultaneity judgment (SJ) task in the beep-flash stimulus. The prestimulus weighted permutation entropy (WPE) was the indicator of neural variability in this study. We found that prestimulus frontal WPE could predict the individuals TBW in auditory- and visual-leading conditions. In addition, increased prestimulus parietal WPE was associated with more asynchronous responses. Prestimulus frontal WPE may be associated with top-down cognitive control, while parietal WPE may be related to bottom-up cortical excitability. Furthermore, poststimulus evoked responses could mediate the relation between prestimulus WPE and the individuals TBW or perceptual responses. These results suggested that prestimulus WPE was a marker in reflecting intra-individual and inter-individual variabilities in audiovisual temporal perception. Significantly, prestimulus WPE might influence perceptual responses by affecting poststimulus sensory representations.

neuroscience↗

bioRxiv2023

Unravelling Biosynthesis and Biodegradation Potentials of Microbial Dark Matters in Hypersaline Lakes

Biosynthesis and biodegradation of microorganisms critically underpin the development of biotechnology, new drugs and therapies, and environmental remediation. However, the vast majority of uncultured microbial species along with their metabolic capacities in extreme environments remain obscured. To unravel the metabolic potentials of these microbial dark matters (MDMs), we investigated four deep-inland hypersaline lakes with largely diversified environmental parameters in Xinjiang Uygur Zizhiqu, China. Metagenomic binning obtained 3,030 metagenome-assembled genomes (MAGs) spanning 82 phyla, of which 2,363 MAGs could not be assigned to a known genus. These unknown MAGs were abundantly observed with distinct taxa among lakes, possibly linked to the diversification of physiochemical conditions. Analysis of biosynthetic potentials identified 9,635 biosynthesis gene clusters (BGCs), of which 9,403 BGCs were considered novel. We found that some MAGs from putatively novel phyla consistently comprised enriched BGCs, which may have substantial potentials in biotechnological applications. In addition, biodegradation potentials such as dehalogenation, anaerobic ammonium oxidation (Anammox), polycyclic aromatic hydrocarbon (PAH), and plastic degradation were found in new microbial clades from hypersaline lakes. These findings substantially expanded the genetic repository of biosynthesis and biodegradation potentials, which can further assist the development of new and innovative applications in biotechnology.

microbiology↗

bioRxiv2023

Not alpha power: prestimulus beta power predicts the magnitude of individual temporal order bias for audiovisual stimuli

Individuals exhibit significant variations in audiovisual temporal order perception. Previous studies have investigated the neural mechanisms underlying these individual differences by analyzing ongoing neural oscillations using stimuli specific to each participant. This study explored whether these effects could extend to different paradigms with the same stimuli across subjects in each paradigm. The two human participants groups performed a temporal order judgment (TOJ) task in two experimental paradigms while recording EEG. One is the beep-flash paradigm, while the other is the stream-bounce paradigm. We focused on the correlation between individual temporal order bias (i.e., point of subjective simultaneity (PSS)) and spontaneous neural oscillations. In addition, we also explored whether the frontal cortex could modulate the correlation through a simple mediation model. We found that the beta band power in the auditory cortex could negatively predict the individuals PSS in the beep-flash paradigm. Similarly, the same effects were observed in the visual cortex during the stream-bounce paradigm. Furthermore, the frontal cortex could influence the power in the sensory cortex and further shape the individuals PSS. These results suggested that the individuals PSS was modulated by auditory or visual cortical excitability depending on the experimental stimuli. The frontal cortex could shape the relation between sensory cortical excitability and the individuals PSS in a top-down manner. In conclusion, our findings indicated that the prefrontal cortex could effectively regulate an individuals temporal order bias, providing insights into audiovisual temporal order perception mechanisms and potential interventions for modulating temporal perception.

neuroscience↗

bioRxiv2023

Targeted Protein O-GlcNAcylation Using Bifunctional Small Molecules

Protein O-linked {beta}-N-acetylglucosamine modification (O-GlcNAcylation) plays a crucial role in regulating essential cellular processes. The disruption of O-GlcNAcylation homeostasis has been linked to various human diseases, including cancer, diabetes, and neurodegeneration. However, there are limited chemical tools for protein- and site-specific O-GlcNAc modification, rendering the precise study of O-GlcNAcylation challenging. To address this, we have developed first-in-class heterobifunctional small molecules, named O-GlcNAcylation targeting chimeras (OGTACs), which enable protein-specific O-GlcNAcylation in cells. OGTACs promote O-GlcNAcylation of proteins such as BRD4, CK2, and EZH2 in cellulo by recruiting O-GlcNAc transferase (OGT), with temporal and magnitude control. Mass spectrometry data revealed that OGTACs induced site-selective O-GlcNAcylation of BRD4. Overall, OGTACs represent a promising approach for inducing protein-specific O-GlcNAcylation, thus enabling functional dissection and offering new directions for O-GlcNAc-targeting therapeutic development.

cell biology↗

bioRxiv2023

Brain cell-specific origin of circulating microRNA biomarkers in experimental temporal lobe epilepsy

The diagnosis of epilepsy is complex and challenging and would benefit from the availability of molecular biomarkers, ideally measurable in a biofluid such as blood. Experimental and human epilepsy are associated with altered brain and blood levels of various microRNAs (miRNAs). Evidence is lacking, however, as to whether any of the circulating pool of miRNAs originates from the brain. To explore the link between circulating miRNAs and the pathophysiology of epilepsy, we first sequenced argonaute 2 (Ago2)-bound miRNAs in plasma samples collected from mice subject to status epilepticus induced by intraamygdala microinjection of kainic acid. This identified time-dependent changes in plasma levels of miRNAs with known neuronal and microglial-cell origins. To explore whether the circulating miRNAs had originated from the brain, we generated mice expressing FLAG-Ago2 in neurons or microglia using tamoxifen-inducible Thy1 or Cx3cr1 promoters, respectively. FLAG immunoprecipitates from the plasma of these mice after seizures contained miRNAs, including let-7i-5p and miR-19b-3p. Taken together, these studies confirm that a portion of the circulating pool of miRNAs in experimental epilepsy originates from the brain, increasing support for miRNAs as mechanistic biomarkers of epilepsy.

neuroscience↗

bioRxiv2023

Cryo-EM structures of Kv1.2 potassium channels, conducting and non-conducting

We present near-atomic-resolution cryo-EM structures of the mammalian voltage-gated potassium channel Kv1.2 in open, C-type inactivated, toxin-blocked and sodium-bound states at 3.2 [A], 2.5 [A], 3.2 [A], and 2.9[A]. These structures, all obtained at nominally zero membrane potential in detergent micelles, reveal distinct ion-occupancy patterns in the selectivity filter. The first two structures are very similar to those reported in the related Shaker channel and the much-studied Kv1.2-2.1 chimeric channel. On the other hand, two new structures show unexpected patterns of ion occupancy. First, the toxin -Dendrotoxin, like Charybdotoxin, is seen to attach to the negatively-charged channel outer mouth, and a lysine residue penetrates into the selectivity filter, with the terminal amine coordinated by carbonyls, partially disrupting the outermost ion-binding site. In the remainder of the filter two densities of bound ions are observed, rather than three as observed with other toxin-blocked Kv channels. Second, a structure of Kv1.2 in Na+ solution does not show collapse or destabilization of the selectivity filter, but instead shows an intact selectivity filter with ion density in each binding site. We also attempted to image the C-type inactivated Kv1.2 W366F channel in Na+ solution, but the protein conformation was seen to be highly variable and only a low-resolution structure could be obtained. These findings present new insights into the stability of the selectivity filter and the mechanism of toxin block of this intensively studied, voltage-gated potassium channel.

biophysics↗

bioRxiv2023

Dual-color GRAB sensors for monitoring spatiotemporal serotonin release in vivo

The serotonergic system plays important roles in both physiological and pathological processes, and is a widely used therapeutic target for many psychiatric disorders. Although several genetically encoded GFP-based serotonin (5-HT) sensors were recently developed, their sensitivities and spectral profiles are relatively limited. To overcome these limitations, we optimized green fluorescent G-protein-coupled receptor (GPCR)-activation-based 5-HT (GRAB5-HT) sensors and developed a new red fluorescent GRAB5-HT sensor. These sensors have excellent cell surface trafficking, high specificity, sensitivity, and spatiotemporal resolution, making them suitable for monitoring 5-HT dynamics in vivo. Besides recording subcortical 5-HT release in freely moving mice, we observed both uniform and gradient 5-HT release in the mouse dorsal cortex with mesoscopic imaging. Finally, we performed dual-color imaging and observed seizure-induced waves of 5-HT release throughout the cortex following calcium and endocannabinoid waves. In summary, these 5-HT sensors can offer valuable insights regarding the serotonergic system in both physiological and pathological states.

neuroscience↗

bioRxiv2023

Neural representation strength of predicted category features biases decision behavior

Theories of prediction-for-perception propose that the brain predicts the information contents of upcoming stimuli to facilitate their perceptual categorization. A mechanistic understanding should therefore address where, when, and how the brain predicts the stimulus features that change behavior. However, typical approaches do not address these predicted stimulus features. Instead, multivariate classifiers are trained to contrast the bottom-up patterns of neural activity between two stimulus categories. These classifiers then quantify top-down predictions as reactivations of the category contrast. However, a category-contrast cannot quantify the features reactivated for each category-which might be from either category, or both. To study the predicted category-features, we randomly sampled features of stimuli that afford two categorical perceptions and trained multivariate classifiers to discriminate the features specific to each. In a cueing design, we show where, when and how trial-by-trial category-feature reactivation strength directly biases decision behavior, transforming our conceptual and mechanistic understanding of prediction-for-perception.

neuroscience↗

bioRxiv2023

Prokaryotic Gabija complex senses and executes nucleotide depletion and DNA cleavage for antiviral defense

The Gabija antiviral system consists of the GajA and GajB proteins. We previously revealed that GajA is a DNA nicking endonuclease. In this work, we found that the DNA binding of GajA is strictly inhibited by NTP. Furthermore, the antiviral defense of GajA requires the assistance from GajB, which senses DNA termini produced from the DNA nicking by GajA to hydrolyze (d)A/(d)GTP. The synergy between the DNA cleavage by GajA and the nucleotide hydrolysis by GajB results in an efficient abortive infection defense against virulent bacteriophages. GajA binds to GajB to form stable complexes in vivo and in vitro. However, a functional Gabija complex requires the molecular ratio between GajB and GajA below 1:1. Through (i) sequential sensing and executing the nucleotide depletion and DNA cleavage to cause a cascade suicide effect and (ii) stoichiometry regulation of the DNA/nucleotide processing complex, the Gabija system exhibits a unique mechanism distinct from other known prokaryotic antiviral systems.

microbiology↗

bioRxiv2023

Decoding State-Dependent Cortical-Cerebellar Cellular Functional Connectivity in the Mouse Brain

ABSTRACTThe cerebellum participates in motor tasks, but also a broad spectrum of cognitive functions. However, cerebellar connections with higher areas such as cortex are not direct and the mechanisms by which the cerebellum integrates and processes diverse information streams are not clear. We investigated the functional connectivity between single cerebellar neurons and population activity of the dorsal cortex using mesoscale imaging. Our findings revealed dynamic coupling between individual cerebellar neurons and diverse cortical networks, and such functional association can be influenced by local excitatory and inhibitory connections. While the cortical representations of individual cerebellar neurons displayed marked changes across different brain states, the overall assignments to specific cortical topographic areas at the population level remained stable. Simple spikes and complex spikes of the same Purkinje cells displayed either similar or distinct cortical functional connectivity patterns. Moreover, the spontaneous functional connectivity patterns aligned with cerebellar neurons functional responses to external stimuli in a modality-specific manner. Importantly, the tuning properties of subsets of cerebellar neurons differed between anesthesia and awake states, mirrored by state-dependent changes in their long-range functional connectivity patterns. Collectively, our results provide a comprehensive view of the state-dependent cortical-cerebellar functional connectivity landscape and demonstrate that remapping of long-range functional network association could underlie state-dependent change in sensory processing.

neuroscience↗