Biology subjects

Xu, S.

Publications and source records attributed to Xu, S..

At least 397 records · Page 22Linked to original sources

bioRxiv2020

Revealing 29 sets of independently modulated genes in Staphylococcus aureus, their regulators and role in key physiological responses

The ability of Staphylococcus aureus to infect many different tissue sites is enabled, in part, by its Transcriptional Regulatory Network (TRN) that coordinates its gene expression to respond to different environments. We elucidated the organization and activity of this TRN by applying Independent Component Analysis (ICA) to a compendium of 108 RNAseq expression profiles from two S. aureus clinical strains (TCH1516 and LAC). ICA decomposed the S. aureus transcriptome into 29 independently modulated sets of genes (i-modulons) that revealed (1) high confidence associations between 21 i-modulons and known regulators; (2) an association between an i-modulon and {sigma}S, whose regulatory role was previously undefined; (3) the regulatory organization of 65 virulence factors in the form of three i-modulons associated with AgrR, SaeR and Vim-3, (4) the roles of three key transcription factors (codY, Fur and ccpA) in coordinating the metabolic and regulatory networks; and (5) a low dimensional representation, involving the function of few transcription factors, of changes in gene expression between two laboratory media (RPMI, CAMHB) and two physiological media (blood and serum). This representation of the TRN covers 842 genes representing 76% of the variance in gene expression that provides a quantitative reconstruction of transcriptional modules in S. aureus, and a platform enabling its full elucidation. Significance StatementStaphylococcus aureus infections impose an immense burden on the healthcare system. To establish a successful infection in a hostile host environment, S. aureus must coordinate its gene expression to respond to a wide array of challenges. This balancing act is largely orchestrated by the Transcriptional Regulatory Network (TRN). Here, we present a model of 29 independently modulated sets of genes that form the basis for a segment of the TRN in clinical USA300 strains of S. aureus. Using this model, we demonstrate the concerted role of various cellular systems (e.g. metabolism, virulence and stress response) underlying key physiological responses, including response during blood infection.

microbiology↗

bioRxiv2020

Viral Architecture of SARS-CoV-2 with Post-Fusion Spike Revealed by Cryo-EM

Since December 2019, the outbreak of Coronavirus Disease 2019 (COVID-19) spread from Wuhan, China to the world, it has caused more than 87,000 diagnosed cases and more than 3,000 deaths globally. To fight against COVID-19, we carried out research for the near native SARS-CoV-2 and report here our preliminary results obtained. The pathogen of the COVID-19, the native SARS-CoV-2, was isolated, amplified and purified in a BSL-3 laboratory. The whole viral architecture of SARS-CoV-2 was examined by transmission electron microscopy (both negative staining and cryo-EM). We observed that the virion particles are roughly spherical or moderately pleiomorphic. Spikes have nail-like shape towards outside with a long body embedded in the envelope. The morphology of virion observed in our result indicates that the S protein of SARS-CoV-2 is in post-fusion state, with S1 disassociated. This state revealed by cryo-EM first time could provide an important information for the identification and relevant clinical research of this new coronavirus.

microbiology↗

bioRxiv2020

Rapid Epistatic Mixed Model Association Studies by Controlling Multiple Polygenic Effects

SummaryWe have developed a rapid mixed model algorithm for exhaustive genome-wide epistatic association analysis by controlling multiple polygenic effects. Our model can simultaneously handle additive by additive epistasis, dominance by dominance epistasis and additive by dominance epistasis, and account for intrasubject fluctuations due to individuals with repeated records. Furthermore, we suggest a simple but efficient approximate algorithm, which allows examination of all pairwise interactions in a remarkably fast manner of linear with population size. Application to publicly available yeast and human data has showed that our mixed model-based method has similar performance with simple linear model-based Plink on computational efficiency. It took less than 40 hours for the pairwise analysis of 5,000 individuals genotyped with roughly 350,000 SNPs with five threads on Intel Xeon E5 2.6GHz CPU. Availability and implementationSource codes are freely available at https://github.com/chaoning/GMAT.

bioinformatics↗

bioRxiv2020

Saturation of influenza virus neutralization and antibody consumption can both lead to bistable growth kinetics

Influenza virus is a major human health threat. Neutralizing antibodies elicited through prior infection or vaccination play an irreplaceable role in protection from subsequent infection. The efficacy of antibody-dependent vaccines relies on both virus replication and neutralization, but their quantitative relationship was unknown. Here we use mathematical models to quantitatively investigate viral survivability determined by antibody concentration and inocula size. We performed focus reduction assays for 49 seasonal influenza A/H3N2 viruses circulating during 2017-2019 against influenza antisera raised in ferrets, and find that the antibody consumption rates of individual reactions were either small or large, and this was strongly positively correlated with virus saturation. Regardless of antibody consumption rate, virus-antibody interactions always lead to antibody-induced bistable viral kinetics. As a result, at a specific interval of antibody concentration, small viral inocula are eliminated but not large virus inocula, which is triggered by saturated virus neutralization or antibody consumption. Our finding highlights virus-antibody interaction with different antigenic properties, thereby explaining commonly observed influenza re-infection and enhancing vaccine efficiency.

microbiology↗

bioRxiv2020

A Novel Non-hypermucoviscous ST11 Hypervirulent Carbapenem-resistant Klebsiella pneumoniae Lacking Classical Virulence Factors

BackgroundHypervirulent Klebsiella pneumoniae lacking classical virulence factors is uncommon, and the virulence mechanisms of this organism are not understood. MethodsFollowing a retrospective study of carbapenem-resistant K. pneumoniae based on core genome multilocus sequence typing (cgMLST), isolates that caused high mortality were investigated with a genome-wide association study (GWAS), proteome analysis and an animal model. ResultsThe sublineage of sequence type 11 (ST11) K. pneumoniae, which belongs to complex type 3176 (CT3176) and K-locus 47 (KL47), was highlighted due to the high mortality of infected patients. GWAS analysis showed that ampR was associated with the CT3176 isolates. In a mouse model, the mortality of ampR-carrying isolates was comparable to that of the typical hypervirulent isolate GM2. Even during the first 24 hours of infection, the bacterial load and pathological changes of the ampR-carrying isolates in the lungs were more severe than those of GM2. The ampR complement mutant was able to enhance the virulence of the KL47 isolate but not the virulence of KL1. Proteome analysis showed that the expression of WcaJ in the ampR+ isolates was significantly higher than that in the ampR- isolates, and this result was also confirmed by transcription tests and capsule staining. It is suggested that the enhancement of the initial stage of capsule synthesis may be the cause of the high virulence of these non-hypermucoviscous ST11 carbapenem-resistant K. pneumoniae isolates. ConclusionsNon-hypermucoviscous ST11 hypervirulent carbapenem-resistant K. pneumoniae warrants continued surveillance and investigation.

microbiology↗

bioRxiv2020

Seneca Valley virus intercellular transmission mediated by exosomes

Exosomes are cup-shaped vesicles that are secreted by cells and are involved in the intercellular transport of a variety of substances, including proteins, RNA, and liposomes. Studies have shown that pathogenic microorganisms are contained in exosomes extracted from pathogenic micro-infected cells. The Seneca Valley virus (SVV) is a non-encapsulated single-stranded positive-strand RNA virus that causes ulceration in the pigs nose, the appearance of blisters, and other clinical symptoms similar to foot-and-mouth disease (FMD). Whether exosomes from SVV-infected cells can mediate SVV intercellular transmission is of great significance. There have been no studies showing whether exosomes can carry SVV in susceptible and non-susceptible cells. Here, we first extracted and identified exosomes from SVV-infected IBRS-2 cells. It was confirmed that replication of SVV can be inhibited when IBRS-2 cells treated with exosomes inbihitor GW4869. Furthermore, laser confocal microscopy and qRT-PCR experiments were performed to investigate whether exosomes can carry SVV and enable the virus to proliferate in susceptible and non-susceptible cells. Finally, exosome-mediated intercellular transmission can not be completely blocked by SVV-specific neutralizing antibodies. Taken together, this study showed that exosomes extracted from the SVV-infected IBRS-2 cells can carry SVV and transmit productive SVV infection between SVV susceptible and non-susceptible cells, this transmit infection is resistant to SVV specific neutralization antibody. IMPORTANCEExosomes participate in intercellular communnication between cells. Exosomes derived from virus-infected cells can mediate virus transmission or/and regulate immune response. However, the function of exosomes that from SVV-infected host cells during SVV transmission is unclear. Here, we demonstrate SVV can utilize host exosomes to establish productive infection in intercellular transmission. Furthermore, exosome-mediated SVV transmission is resistant to SVVV-specific neutralizing antibodies. This discovery sheds light on neutralizing antibodies resistant to SVVV transmission by exosomes as a potential immune evasion mechanism.

immunology↗

bioRxiv2020

Response of Asplenium nidus to Drought Stress and Identification of Drought Tolerance Genes

To explore how Asplenium nidus responds to drought stress, and to mine drought-responsive genes for Asplenium nidus, we conducted a pot experiment in the IOT smart greenhouse. We measured a series of physiological and biochemical indexes for drought-treated plants, and analyzed the expression of drought-responsive genes in Asplenium nidus by RT-qPCR. The results show that the Asplenium nidus is a species with drought tolerance. Asplenium nidus inhibits plant photosynthesis and reduces life activities by limiting stomatal opening to adapt to drought. To resist drought stress, the Asplenium nidus changes the osmotic potential by increasing the proline content to maintain normal metabolic activities and prevents the damage of active oxygen by increasing the enzyme activities of SOD and POD. Based on the analysis of the relative expression levels of genes, AVP1-2 and AVP1-4 may be drought-resistant genes in Asplenium nidus. This study lays the foundation for in-depth research on drought tolerance mechanisms and drought-resistant gene mining of Asplenium nidus.

genetics↗

bioRxiv2020

A Hierarchical Approach Using Marginal Summary Statistics for Multiple Intermediates in a Mendelian Randomization or Transcriptome Analysis

BackgroundPrevious research has demonstrated the usefulness of hierarchical modeling for incorporating a flexible array of prior information in genetic association studies. When this prior information consists of effect estimates from association analyses of single nucleotide polymorphisms (SNP)-intermediate or SNP-gene expression, a hierarchical model is equivalent to a two-stage instrumental or transcriptome-wide association study (TWAS) analysis, respectively. MethodsWe propose to extend our previous approach for the joint analysis of marginal summary statistics (JAM) to incorporate prior information via a hierarchical model (hJAM). In this framework, the use of appropriate effect estimates as prior information yields an analysis similar to Mendelian Randomization (MR) and TWAS approaches such as FUSION and S-PrediXcan. However, hJAM is applicable to multiple correlated SNPs and multiple correlated intermediates to yield conditional estimates of effect for the intermediate on the outcome, thus providing advantages over alternative approaches. ResultsWe investigate the performance of hJAM in comparison to existing MR approaches (inverse-variance weighted MR and multivariate MR) and existing TWAS approaches (S-PrediXcan) for effect estimation, type-I error and empirical power. We apply hJAM to two examples: estimating the conditional effects of body mass index and type 2 diabetes on myocardial infarction and estimating the effects of the expressions of gene NUCKS1 and PM20D1 on the risk of prostate cancer. ConclusionsAcross numerous causal simulation scenarios, we demonstrate that hJAM is unbiased, maintains correct type-I error and has increased power. Key MessagesO_LIMendelian randomization and transcriptome-wide association studies (TWAS) can be viewed as similar approaches via a hierarchical model. C_LIO_LIThe hierarchal joint analysis of marginal summary statistics (hJAM) is a multivariate Mendelian randomization approach which offers a simple way to address the pleiotropy bias that is introduced by genetic variants associated with multiple risk factors or expressions of genes. C_LIO_LIhJAM incorporates the linkage disequilibrium structure of the single nucleotide polymorphism (SNPs) in a reference population to account for the correlation between SNPs. C_LIO_LIIn addition to Mendelian randomization and TWAS, hJAM offers flexibility to incorporate functional or genomic annotation or information from metabolomic studies. C_LI

genetics↗

bioRxiv2020

A Prokaryotic Membrane Sculpting BAR Domain Protein

Bin/Amphiphysin/RVS (BAR) domain proteins belong to a superfamily of coiled-coil proteins influencing membrane curvature in eukaryotes and are associated with vesicle biogenesis, vesicle-mediated protein trafficking, and intracellular signaling. Here we report the first prokaryotic BAR domain protein, BdpA, from Shewanella oneidensis MR-1, known to produce redox-active membrane vesicles and micrometer-scale outer membrane extensions (OMEs). BdpA is required for uniform size distribution of membrane vesicles and scaffolding OMEs into a consistent diameter and curvature. Cryogenic transmission electron microscopy reveals a strain lacking BdpA produces lobed, disordered OMEs rather than membrane tubes produced by the wild type strain. Overexpression of BdpA promotes OME formation during conditions where they are less common. Heterologous expression results in OME production in Marinobacter atlanticus and Escherichia coli. Based on the ability of BdpA to alter membrane curvature in vivo, we propose that BdpA and its homologs comprise a newly identified class of prokaryotic BAR (P-BAR) domains.

microbiology↗

bioRxiv2020

Fine Sieving of Collected Atmospheric Particles using Oil Electrophoresis (iSCAPE)

It is rather challenging to separate atmospheric particles from nano-to micro-metre mixed in a sample. Here, a system named iSCAPE was invented to efficiently sieve particles out from a mixture by employing an electrostatic field and a non-conductive mineral oil. Tests with atmospheric particles of different cities as well as soil and road dust samples demonstrated that the iSCAPEd particles under different operating conditions moved rapidly with different velocities and both directions. Particles of different sources such as ambient air, soil or road were shown to have different polarity-charged particle fractions, and exhibited clearly different particle electrical mobility graphs after the iSCAPE sieving from seconds to minutes. Data also revealed that after the sieving some particles were enriched at specific mobility ranges. Bacterial ATP measurements implied that the iSCAPE can be also used to efficiently separate bacteria of different sizes and charge polarity. Experimental data here suggest that the iSCAPE sieving strongly replies on the electrostatic field strength, mineral oil viscosity and the run time. In theory, the iSCAPE system can be used to extract any desired targets from a complex sample, thus opening up many outstanding opportunities for environmental, biomedical and life science fields. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=69 SRC="FIGDIR/small/894998v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@8d50f9org.highwire.dtl.DTLVardef@1bf1b1aorg.highwire.dtl.DTLVardef@18c70ddorg.highwire.dtl.DTLVardef@145c317_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2020

Anti-tumor effects of an Id antagonist with no acquired resistance

Id proteins are helix-loop-helix (HLH) transcriptional regulators frequently overexpressed in cancer. Id proteins inhibit basic HLH transcription factors through protein-protein interactions, often inhibiting differentiation and sustaining proliferation. We recently identified a small-molecule, AGX51, which targets Id proteins for degradation and impairs ocular neovascularization in mouse models. Here we show that AGX51 treatment of cancer cell lines impaired cell growth and viability that results from a dramatic increase in ROS production upon Id degradation. In mouse models, AGX51 treatment suppressed breast cancer colonization in the lung, regressed the growth of paclitaxel-resistant breast tumors when combined with paclitaxel and reduced tumor burden in a model of sporadic colorectal neoplasia. Furthermore, in cells and mice, we failed to observe acquired resistance to AGX51 likely the result of the immutability of the binding pocket and efficient degradation of the Id proteins. Thus, AGX51 is a first-in-class compound that antagonizes Id proteins, shows strong anti-tumor effects and may be further developed for the management of multiple cancers.

cancer biology↗

bioRxiv2019

NADPH diaphorase neuronal dystrophy in gracile nucleus, cuneatus nucleus and spinal trigeminal nucleus in aged rat

NADPH-diaphorase (N-d) activity is commonly used to identify NOS-ergic neurons. In our previous study, N-d positive neuritic dystrophy and spheroid termed aging-related N-d Body is discovered in the lumbosacral spinal cord in the normal aging rats. Histological studies also reveal that N-d positive neurodegenerative changes occur in the gracile nucleus. We re-examined N-d activity in gracile nucleus in aged rat. We found N-d positive neuritic dystrophy and spheroid also occurred in the cuneatus nucleus and spinal trigeminal nucleus. Besides regular coronal section, longitudinal oriented dystrophic neurites were detected in the sagittal and horizontal section in gracile nucleus and dorsal column. We fziurther examined the medullary oblongata with regular classical histology including Golgi staining, immunocytochemistry of NOS and phosphorylated tau protein, neuronal tracing method with wheat germ agglutinin conjugated alexa-fluor-488 through sciatic nerve, and spinal cord transection at thoracic level. Most of N-d positive neuritic dystrophy and spheroid did not showed colocalization with NOS or phosphorylated tau protein. Neuronal tracing and spinal cord transection revealed that N-d dystrophic neurites in gracile nucleus originated from terminal of sensory projection from spinal cord and peripheral somatic input. The results suggested that aging-related N-d dystrophy in the gracile nucleus was unique morphological feature. In conclusion, it was postulated that the N-d dystrophy as a morphological marker of aging degenerative damage in normal aged organisms.

neuroscience↗

bioRxiv2019

ACPT gene is inactivated in mammalian lineages that lack enamel and teeth

Loss of tooth or enamel is widespread in multiple mammal lineages. Although several studies have been reported, the evolutionary mechanisms of tooth / enamel loss are still unclear. Most previous studies have found that some tooth-related genes have been inactivated in toothless and / or enamel-less mammals, such as ENAM, ODAM, C4orf26, AMBN, AMTN, DSPP, etc. Here, we conducted evolutionary analyses on ACPT plays a key role in amelogenesis, to interrogate the mechanisms. We obtained the ACPT sequences from 116 species, including edentulous and enamel-less mammals, then evolutionary analyses were implemented. The results showed that variant ORF-disrupting mutations have been detected in ACPT coding region among nine edentulous baleen whales and three enamel-less taxa (pygmy sperm whale, aardvark, nine-banded armadillo). Furtherly, selective pressure uncovered that the selective constraints have been relaxed among all toothless and enamel-less lineages. Moreover, our results support the hypothesis that mineralized teeth were lost or degenerated in the common ancestor of crown Mysticeti through two shared single-base sites deletion in exon 4 and 5 of ACPT among all living baleen whales. DN / dS values on transitional branches were used to estimate ACPT inactivation times. In the case of aardvark, inactivation of ACPT was estimated at ~23.60-28.32 Ma, which is earlier than the oldest pangolin fossil time (Orycteropus minutus, ~19Ma), suggesting that ACPT inactivation may result in degeneration or loss of enamel. Conversely, the inactivation time of ACPT estimated in armadillo (~10.18-11.30 Ma) is later than the oldest fossil time, suggesting that inactivation of ACPT may result from degeneration or loss of enamel in these mammals. Our findings suggested that different mechanisms of degeneration of tooth / enamel might exist among toothless and enamel-less lineages during evolution. Our study further considered that ACPT is a novel gene for studying tooth evolution.

evolutionary biology↗

bioRxiv2019

Protective functions of ZO-2/Tjp2 expressed in hepatocytes and cholangiocytes against liver injury and cholestasis

BACKGROUND & AIMSTight junctions (TJs) establish tissue barriers that maintain osmotic homeostasis and, in the liver, isolate bile flow from the blood circulation. ZO-2/Tjp2 is a scaffold protein that tethers TJ transmembrane proteins to the actin cytoskeleton. Missense mutations in Tjp2 have recently been shown to cause progressive cholestatic liver disease in humans. However, the underlying mechanisms still remain elusive. To study the role of Tjp2 in cholestatic liver disease, we generated and characterized mice lacking Tjp2 in hepatocytes, cholangiocytes, or both. METHODSTjp2 was inactivated in the mouse liver (both in hepatocytes and cholangiocytes) or hepatocytes or cholangiocytes only. Liver function tests were carried out by biochemical analysis of plasma and liver samples and liver tissue was evaluated by immunohistochemistry and histology. The mice were also subjected to cholic acid (CA) diet to assess their susceptibility to liver insults. RESULTSDeletion of Tjp2 in the mouse liver did not result in apparent changes in TJ structure and composition, but lead to progressive cholestasis with lower expression levels of the bile acid (BA) transporter ABCB11/Bsep and the detoxification enzyme Cyp2b10. Feeding a CA diet that is well tolerated by control mice caused severe cholestasis and necrotic liver injury in mice lacking hepatic Tjp2. Administration of a CAR agonist, TCPOBOP, protected these mice from CA induced injury by enhancing the expression of the detoxifying enzyme Cyp2b10 in hepatocytes. Mice lacking Tjp2 in only hepatocytes or in only cholangiocytes showed less severe CA diet induced liver injury. CONCLUSIONLoss of Tjp2 from hepatocytes and cholangiocytes both contribute to progressive cholestatic liver disease and higher susceptibility to liver injury. In hepatocytes, Tjp2 exerts a protective role by regulating expression levels of BA transporters and detoxification enzymes. The mice may provide a new animal model for cholestatic liver disease linked to Tjp2 mutations in humans.

physiology↗

bioRxiv2019

Synergism of gut microbiota to double-stranded RNAs in RNA interference of a leaf beetle

RNA interference (RNAi) has emerged as an efficient tool to control insect pests. When lethal double-stranded RNAs (dsRNAs) were ingested by the insects, strong gene silencing and mortality can be induced. To exert their function, dsRNA molecules must pass through insects gut and enter epithelial cells and/or the hemolymph. Gut bacteria are known to inhabit on the epithelial surface to confer host new capabilities to counter both biotic and abiotic stress. Whether there is a crosstalk between gut bacteria and dsRNAs and the effects of the microbiome on RNAi efficiency remains unknown. Here, using a leaf beetle-gut microbiota system, we investigated whether and how gut bacteria interact with dsRNA molecules and its effects on host insects. We firstly showed that the leaf beetle Plagiodera versicolora (Coleoptera) is highly susceptible to RNAi. Then, we found that ingestion of dsRNAs by non-axenic P. versicolora larvae results in (i) significantly accelerated mortality compared to axenic larvae, and (ii) over-growth and dysbiosis of the gut microbiota. The latter is mainly caused by the bacterial utilization of the dsRNA degraded products initiated by the host insect. Furthermore, we found that Pseudomonas putida, a gut bacterium of P. versicolora, was a main commensal-to-pathogen strain that accelerated the death of P. versicolora larvae. Taken together, our findings reveal a synergistic role of gut microbiota to dsRNA-induced mortality of pest insects, which provides new insights in the ecological functions of insect gut bacteria, and also contributes to a better understanding of the RNAi mechanisms in insects.

ecology↗

bioRxiv2019

The Role of Carbon Nanoparticle in Lymph Node Detection and Parathyroid Gland Protection during Thyroidectomy - a Meta Analysis

ObjectiveTo assess the efficiency of the carbon nanoparticles (CNs) in lymph node identification and parathyroid gland protection during thyroidectomy.\n\nMethodsA systematic literature search for relevant literatures published up to December 2018 in PubMed, Embase, Web of Science and Cochrane Library was performed. Both English and Chinese literatures were retrieved and analyzed. Randomized controlled trials or nonrandomized controlled trials on the use of CNs during thyroidectomy were enrolled in this study. The primary outcomes included the number of lymph nodes harvesed, rate of lymph nodes involvement, and the rates of accidental parathyroidectomy, hypoparathyroidism, and hypocalcemia. Weighted mean differences (WMDs), odds ratios (ORs) and risk differences (RDs) were calculated for the dichotomous outcome variables. Between-study heterogeneity was tested using the Q tests and the I2 statistics. All analyses were performed using Review Manager (version 5.3.5).\n\nResults25 studies comprising 3266 patients were included in this analysis. The total number of lymph nodes harvested in the groups of carbon nanoparticles was significant higher than that in the control groups (WMD, 2.36; 95% CI, 1.40 to 3.32; P <0.01). Administrating carbon nanoparticles was associated with a lower incidence of accidental parathyroid gland removal (OR = 0.30, 95% CI = 0.23 to 0.40, P <0.01) and lower rates of both postoperative transient hypoparathyroidism (OR =0.46, 95% CI = 0.33 to 0.64, P <0.01) and transient hypocalcemia (OR =0.55, 95% CI = 0.09 to 3.43, P =0.52). There was no significant difference of identified lymph node metastatic rates between the patients with and without use of carbon nanoparticles. Subgroup analyses indicated that the application of CNs in thyroid cancer reoperation also decreased the rate of transient hypoparathyroidism (OR =0.20, 95% CI = 0.36 to 0.04, P =0.01) and the possibility of accidental parathyroid glands removal (OR = 0.19, 95% CI = 0.05 to 0.73, P<0.05).\n\nConclusionsThe application of CNs for thyroidectomy results in higher number of lymph node harvested and better parathyroid gland protection during initial surgery and reoperation for thyroid cancer.

scientific communication and education↗

bioRxiv2019

On the delay in propagation of action potentials

The signal delay during the propagation of action potentials is one of the key issues in understanding the mechanisms of generation and propagation of neural signals. Here we reanalyzed related experimental data to demonstrate that action potentials in the propagation process along a myelinated axon are highly overlapped in the time scale. The shift in time of two successive signals from neighboring nodes, defined as delay time{tau} in this work, is only tens of microseconds (16.3-87.0 s), thus is only ~ 0.8-4.4 % of the measured average duration of an action potential, ~ 2 ms. This fact may reveal a huge gap to the commonly accepted picture for propagation of neural signal. We could apply the electromagnetic soliton-like model to well explain this phenomenon, and attribute{tau} to the waiting time that one signal source (i.e., ion channel cluster at one node) needs to take when it generates an electromagnetic neural pulse with increasing intensity until the intensity is higher than a certain point so as to activate neighboring signal source. This viewpoint may shed some light on a better understanding of the exact physical mechanism of neural signal communication in a variety of biosystems.\n\nStatement of SignificanceThe delay time during the propagation of action potentials is an important term in understanding the mechanisms of generation and propagation of neural signals. In this article we analyzed published experimental data and showed that action potentials from two neighboring Ranvier nodes are highly overlapped in time, with an average shift of tens of microseconds, which occupied only ~ 0.8-4.4 % of the average duration of an action potential (2 ms). The electromagnetic soliton-model seemed the best model to explain this phenomenon.\n\nThe viewpoint of this article may shed some light on a better understanding of the exact physical mechanism of neural signal communication, and be tractive to researchers in a variety of fields, such as neuroscience, brain-computer interface, etc..

biophysics↗

bioRxiv2019

De novo assembly of a Tibetan genome and identification of novel structural variants associated with high altitude adaptation

Structural variants (SVs) may play important roles in human adaption to extreme environments such as high altitude but have been under-investigated. Here, combining long-read sequencing with multiple scaffolding techniques, we assembled a high-quality Tibetan genome (ZF1), with a contig N50 length of 24.57 mega-base pairs (Mb) and a scaffold N50 length of 58.80 Mb. The ZF1 assembly filled 80 remaining N-gaps (0.25 Mb in total length) in the reference human genome (GRCh38). Markedly, we detected 17,900 SVs, among which the ZF1-specific SVs are enriched in GTPase activity that is required for activation of the hypoxic pathway. Further population analysis uncovered a 163-bp intronic deletion in the MKL1 gene showing large divergence between highland Tibetans and lowland Han Chinese. This deletion is significantly associated with lower systolic pulmonary arterial pressure, one of the key adaptive physiological traits in Tibetans. Moreover, with the use of the high quality de novo assembly, we observed a much higher rate of genome-wide archaic hominid (Altai Neanderthal and Denisovan) shared non-reference sequences in ZF1 (1.32%-1.53%) compared to other East Asian genomes (0.70%-0.98%), reflecting a unique genomic composition of Tibetans. One such archaic-hominid shared sequence, a 662-bp intronic insertion in the SCUBE2 gene, is enriched and associated with better lung function (the FEV1/FVC ratio) in Tibetans. Collectively, we generated the first high-resolution Tibetan reference genome, and the identified SVs may serve as valuable resources for future evolutionary and medical studies.

genomics↗