Biology subjects

Liu, G.

Publications and source records attributed to Liu, G..

At least 163 records · Page 9Linked to original sources

bioRxiv2023

Nightmare or delight: taxonomic circumscription meets reticulate evolution in the phylogenomic era

Phylogenetic studies in the phylogenomics era have demonstrated that reticulate evolution greatly impedes the accuracy of phylogenetic inference, and consequently can obscure taxonomic treatments. However, the systematics community lacks a broadly applicable strategy for taxonomic delimitation in groups identified to have pervasive reticulate evolution. The red-fruit genus, Stranvaesia, provides an ideal model for testing the effect of reticulation on generic circumscription when hybridization and allopolyploidy define a groups evolutionary history. Here, we conducted phylogenomic analyses integrating data from hundreds of single-copy nuclear (SCN) genes and plastomes, and interrogated nuclear paralogs to clarify the inter/intra-generic relationship of Stranvaesia and its allies in the framework of Maleae. Analyses of phylogenomic discord and phylogenetic networks showed that allopolyploidization and introgression promoted the origin and diversification of the Stranvaesia clade, a conclusion further bolstered by cytonuclear and gene tree discordance. The well-inferred phylogenetic backbone revealed an updated generic delimitation of Stranvaesia and a new genus, Weniomeles, characterized by purple-black fruits, trunk and/or branches with thorns, and fruit core with multilocular separated by a layer of sclereids and a cluster of sclereids at the top of the locules. Here, we highlight a broadly-applicable workflow for inferring how analyses of reticulate evolution in phylogenomic data can directly shape taxonomic revisions.

evolutionary biology↗

bioRxiv2023

Asynchronous phylogeographic and demographic dynamics of rodent community in the low latitude Asia

It is increasing evident that demographic history and phylogeographic consequences of past climate changes were unfolded locally and varied from region to region. Despite the high Murinae rodent species richness and endemism in the low latitude Asia, how the past climatic fluctuations shaped the phylogeographic and demographic history in this area remains unknown. Here we trapped 253 field Murine individuals and successfully amplified COI gene sequence for DNA barcoding. The phylogenetic tree showed the Murinae diversification included ten species belong to Rattini and Murini tribes. The divergence dating suggested that the most common ancestor (TMRCA) of each rodent species was estimated in Early or Middle Pleistocene. Bayesian skyline plot (BSP) exhibited the onset of population growth of seven Murinae rodents occurred at penultimate or last glaciation, and while R. losea and R. norvegicus keep effective population size constant through their elapsed time. Additionally, the six rodent species range of refugia area in the LGM projected by ecological niche models (ENMs) exhibited expander than the suitable area on present, meanwhile the remaining four rodent species showed contracted refugia regions. Hence, our results suggested that the rodent community displayed the asynchronous demographic and phylogeographic dynamics in the low latitude Asia.

molecular biology↗

bioRxiv2023

A MSTNDel273C mutation with FGF5 knockout sheep by CRISPR/Cas9 promotes skeletal muscle myofiber hyperplasia via MEK-ERK-FOSL1 axis

Mutations in the well-known Myostatin (MSTN) produce a "double-muscle" phenotype, which makes it commercially invaluable for improving livestock meat production and providing high-quality protein for humans. However, mutations at different loci of the MSTN often produce a variety of different phenotypes. In the current study, we increased the delivery ratio of Cas9 mRNA to sgRNA from the traditional 1:2 to 1:10, which improves the efficiency of the homozygous mutation of biallelic gene. Here, a MSTNDel273C mutation with FGF5 knockout sheep, in which the MSTN and FGF5 dual-gene biallelic homozygous mutations were produced via the deletion of 3-base pairs of AGC in the third exon of MSTN, resulting in cysteine-depleted at amino acid position 273, and the FGF5 double allele mutation led to inactivation of FGF5 gene. The MSTNDel273C mutation with FGF5 knockout sheep highlights a dominant "double-muscle" phenotype, which can be stably inherited. Both F0 and F1 generation mutants highlight the excellent trait of high-yield meat with a smaller cross-sectional area and higher number of muscle fibers per unit area. Mechanistically, the MSTNDel273C mutation with FGF5 knockout mediated the activation of FOSL1 via the MEK-ERK-FOSL1 axis. The activated FOSL1 promotes skeletal muscle satellite cell proliferation and inhibits myogenic differentiation by inhibiting the expression of MyoD1, and resulting in smaller myotubes. In addition, activated ERK1/2 may inhibit the secondary fusion of myotubes by Ca2+-dependent CaMKII activation pathway, leading to myoblasts fusion to form smaller myotubes.

cell biology↗

bioRxiv2023

A subset of CD4+ effector memory T cells limit immunity to pulmonary viral infection and prevent tissue pathology via activation of latent TGFβ

A rapid immune response to pathogen re-exposure underpins immunological memory, with protection against divergent pathogens such as heterologous or novel viral strains requiring cross-reactive memory T cells. Understanding the pathways that control memory T cell function is therefore important for the rational design of viral vaccines and will aid the discovery of therapies to boost anti-viral immunity. Here, we identify a sub-population of memory T cells that limit secondary immune responses to viral re-infection, which is crucial in preventing host tissue damage. We show that a population of CD4+ effector memory T (TEM) cells activate the important immunoregulatory cytokine TGF{beta}, via expression of an integrin, v{beta}8. Integrin v{beta}8 expression marks a transcriptionally distinct sub-population of CD4+ TEM, enriched for anti-inflammatory pathways. Loss of integrin v{beta}8 on murine CD4+ TEM, but not Foxp3+ regulatory T cells (TREG), led to exacerbated virus-specific CD8+ T cell responses following secondary influenza A virus (IAV) infection, which was associated with enhanced viral clearance. However, although accelerating clearance, loss of integrin v{beta}8 expression on CD4+ TEM resulted in enhanced lung pathology following secondary IAV infection, which was completely reversed by adoptive transfer of v{beta}8+ CD4+ TEM cells. These data highlight a new pathway by which a distinct CD4+ memory T cell subset restrains anti-viral immunity to prevent host tissue damage during secondary viral infection. Such pathways could be targeted therapeutically to either boost memory T-cell-mediated immunity or restrain host tissue damage during viral infection.

immunology↗

bioRxiv2023

GenBank genomics highlight the genomic features, genetic diversity and regulation of morphological, metabolic and disease-resistance traits in Nicotiana tabacum

Nicotiana tabacum is a model organism in plant molecular and pathogenic research and has significant potential in the production of biofuels and active pharmaceutical compounds in synthetic biology. Because of the large allotetraploid genome of tobacco, its genomic features, genetic diversity and genetic regulation of many complex traits remain unknown. In this study, we present a nearly complete chromosome-scale assembly of N. tabacum and provide evidence that homoeologous exchange between subgenomes and epigenetic remodelling are likely mechanisms of genome stabilization and subgenome coordination following polyploidization. By leveraging GenBank-scale sequencing and phenotyping data from 5196 lines, geography at the continent scale, rather than types assigned on the basis of curing crop practices, was found to be the most important correlate of genetic structure. Using 178 marker{square}trait associations detected in genome-wide association analysis, a reference genotype-to-phenotype map was built for 39 morphological, developmental, and disease-resistance traits. A novel gene, auxin response factor 9 (Arf9), associated with wider leaves after being knocked out, was fine-mapped to a single nucleotide polymorphism (SNP). This point mutation alters the translated amino acid from Ala203 to Pro203, likely preventing homodimer formation during DNA binding. Our analysis also revealed signatures of positive and polygenic selection for multiple traits during the process of selective breeding. Overall, this study demonstrated the power of leveraging GenBank genomics to gain insights into the genomic features, genetic diversity, and regulation of complex traits in N. tabacum, laying a foundation for future research on plant functional genomics, crop breeding, and the production of biopharmaceuticals and biofuels.

genetics↗

bioRxiv2023

Impacts of Age on the Gut Microbiota in Captive Giant Pandas

The gut microbiota is the most complex and most abundant symbiotic microbial ecosystem in animals. Aging is one of the main factors that cause gut microbiota structure changes, and the relationship between age and the gut microbiota in the giant panda has been a key focus of attention. The giant panda has a specialized diet of bamboo, and it relies on the microbiota that colonizes its gut to complete digestion. However, there is no in-depth understanding of the changes in the gut microbiota across the lifespan of giant pandas. Here, we identified the differences in the gut microbiota between four age groups (cubs, juveniles, adults, and geriatrics) using 16S rRNA gene high-throughput sequencing on an Illumina MiSeq platform. The results revealed that Firmicutes (mean{+/-}SD: 65.45{+/-}30.21%; range: 0.91-99.62%) and Proteobacteria (mean{+/-}SD: 31.49{+/-}27.99%; range: 0.26-85.35%) were the dominant phyla. The relative abundance of Escherichia-Shigella was high in both the cubs and juveniles. It is interesting to note that the adults had the highest richness and lowest diversity, while the cubs had the opposite. In summary, our study indicates that the gut microbial community composition, abundance, and functional pathways differ across four age groups of giant pandas. Exploring the influence of age, an endogenous influencing factor, on gut microbes provides basic scientific data for monitoring gut microbial dynamics and formulating gut microbial health management approaches, thereby improving the protection of giant pandas.

microbiology↗

bioRxiv2023

FarmGTEx TWAS-server: an interactive web server for customized TWAS analysis in both human and farm animals

Transcriptome-wide association study (TWAS) is a powerful strategy for elucidating the molecular mechanisms behind the genetic loci of complex phenotypes. However, TWAS analysis is still daunting in many species due to the complication of the TWAS analysis pipeline, including the construction of the gene expression reference panel, gene expression prediction, and the subsequent association analysis in the large cohorts of genome-wide association study (GWAS). Farm animals are major protein sources and biomedical models for humans. To facilitate the translation of genetic findings across species, here we provide an interactive and easy-to-use multi-species TWAS web server for the entire community, called the FarmGTEx TWAS-server (http://twas.farmgtex.org), which is based on the GTEx and FarmGTEx projects. It includes gene expression data from 49, 34, and 23 tissues in 838 humans, 5,457 pigs, and 4,889 cattle, representing 38,180, 21,037, and 17,942 distinct eGenes in prediction models for humans, pigs, and cattle, respectively. It allows users to conduct gene expression prediction for any individuals with genotypes, GWAS summary statistics imputation, customized TWAS, and popular downstream functional annotation. It also provides 479,203, 1,208, and 657 tissue-gene-trait association trios for the research community, representing 1,129 human traits, 41 cattle traits, and 11 pig traits. In summary, the FarmGTEx TWAS-server is a one-stop solution for performing TWAS analysis for researchers without programming skills in both human and farm animal research communities. It will be maintained and updated timely within the FarmGTEx project to facilitate gene mapping and phenotype prediction within and across species.

bioinformatics↗

bioRxiv2023

The scheduling of adolescence with Netrin-1 and UNC5C

Dopamine axons are the only axons known to grow during adolescence. Here, using rodent models, we examined how two proteins, Netrin-1 and its receptor, UNC5C, guide dopamine axons towards the prefrontal cortex and shape behaviour. We demonstrate in mice (Mus musculus) that dopamine axons reach the cortex through a transient gradient of Netrin-1 expressing cells - disrupting this gradient reroutes axons away from their target. Using a seasonal model (Siberian hamsters; Phodopus sungorus) we find that mesocortical dopamine development can be regulated by a natural environmental cue (daylength) in a sexually dimorphic manner - delayed in males, but advanced in females. The timings of dopamine axon growth and UNC5C expression are always phase-locked. Adolescence is an ill-defined, transitional period; we pinpoint neurodevelopmental markers underlying this period.

neuroscience↗

bioRxiv2023

Evolutionary transcriptomics reveals longevity mostly driven by polygenic and indirect selection in mammals

The maximum lifespan varies more than 100-fold in mammals. This experiment of nature may uncover of the evolutionary forces and molecular features that define longevity. To understand the relationship between gene expression variation and maximum lifespan, we carried out a comparative transcriptomics analysis of liver, kidney, and brain tissues of 106 mammalian species. We found that expression is largely conserved and very limited genes exhibit common expression patterns with longevity in all the three organs analyzed. However, many pathways, e.g., "Insulin signaling pathway", and "FoxO signaling pathway", show accumulated correlations with maximum lifespan across mammals. Analyses of selection features further reveal that methionine restriction related genes whose expressions associated with longevity, are under strong selection in long-lived mammals, suggesting that a common approach could be utilized by natural selection and artificial intervention to control lifespan. These results suggest that natural lifespan regulation via gene expression is likely to be driven through polygenic model and indirect selection.

evolutionary biology↗

bioRxiv2023

Defective phagocytosis leads to neurodegeneration through systemic increased innate immune signaling

In nervous system development, disease and injury, neurons undergo programmed cell death, leaving behind cell corpses that are removed by phagocytic glia. Altered glial phagocytosis has been implicated in several neurological diseases including Alzheimers disease, Parkinsons disease, and traumatic brain injury. To untangle the links between glial phagocytosis and neurodegeneration, we investigated Drosophila mutants lacking the phagocytic receptor Draper. Loss of Draper leads to persistent neuronal cell corpses and age-dependent neurodegeneration. Here we investigate whether the phagocytic defects observed in draper mutants lead to chronic increased immune activation that promotes neurodegeneration. A major immune response in Drosophila is the activation of two NF{kappa}B signaling pathways that produce antimicrobial peptides, primarily in the fat body. We found that the antimicrobial peptide Attacin-A is highly upregulated in the fat body of aged draper mutants and that inhibition of the Immune deficiency (Imd) pathway in the glia and fat body of draper mutants led to reduced neurodegeneration, indicating that immune activation promotes neurodegeneration in draper mutants. Taken together, these findings indicate that phagocytic defects lead to neurodegeneration via increased immune signaling, both systemically and locally in the brain.

neuroscience↗

bioRxiv2023

HSV-1 Oncolytic Virus Targeting CEACAM6-Expressing Tumors Using a Bispecific T-Cell Engager

VG21306 is a novel oncolytic virus (OV) that encodes a secretable bispecific T-cell engager targeting Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6)-expressing tumors. Delivering a T-cell engager locally to a tumor mass will circumvent physical barriers that prevent antibodies from penetrating the tumor, and will mitigate the off-tumor, on-target toxicity risk. Both in vitro and in vivo testing demonstrated the expression of a functional T-cell engager capable of binding both targets. The efficacy of the engager was demonstrated in vitro, where addition of the engager payload to the OV enhanced anti-tumor efficacy against tumor cells overexpressing CEACAM6. Moreover, we have demonstrated the engagers ability to induce bystander killing in cells lacking CEACAM6 expression, as well as engaging exhausted T cells and inducing tumor cell death. The safety of the engager was demonstrated by the lack of binding to normal human tissue or normal tissue adjacent to tumors, as well as the absence of any measurable leakage of the expressed engager into the blood of mice treated by intratumoral OV injection.

cancer biology↗

bioRxiv2022

Origin of wiring specificity in an olfactory map: dendrite targeting of projection neurons

How does wiring specificity of neural maps emerge during development? Formation of the adult Drosophila olfactory glomerular map begins with patterning of projection neuron (PN) dendrites at the early pupal stage. To better understand the origin of wiring specificity of this map, we created genetic tools to systematically characterize dendrite patterning across development at PN type-specific resolution. We find that PNs use lineage and birth order combinatorially to build the initial dendritic map. Specifically, birth order directs dendrite targeting in rotating and binary manners for PNs of the anterodorsal and lateral lineages, respectively. Two-photon- and adaptive optical lattice light-sheet microscope-based time-lapse imaging reveals that PN dendrites initiate active targeting with direction-dependent branch stabilization on the timescale of seconds. Moreover, PNs that are used in both the larval and adult olfactory circuits prune their larval-specific dendrites and re-extend new dendrites simultaneously to facilitate timely olfactory map organization. Our work highlights the power and necessity of type-specific neuronal access and time-lapse imaging in identifying wiring mechanisms that underlie complex patterns of functional neural maps.

neuroscience↗

bioRxiv2022

An Optimized Circular Polymerase Extension Reaction-based Method for Functional Analysis of SARS-CoV-2

SUMMARYReverse genetics systems have been crucial for studying specific viral genes and their relevance in the virus lifecycle, and become important tools for the rational attenuation of viruses and thereby for vaccine design. Recent rapid progress has been made in the establishment of reverse genetics systems for functional analysis of SARS-CoV-2, a coronavirus that causes the ongoing COVID-19 pandemic that has resulted in detrimental public health and economic burden. Among the different reverse genetics approaches, CPER (circular polymerase extension reaction) has become one of the leading methodologies to generate recombinant SARS-CoV-2 infectious clones due to its accuracy, efficiency, and flexibility. Here, we report an optimized CPER methodology which, through the use of a modified linker plasmid and by performing DNA nick ligation and direct transfection of permissive cells, overcomes certain intrinsic limitations of the traditional CPER approaches for SARS-CoV-2, allowing for efficient virus rescue. This optimized CPER system may facilitate research studies to assess the contribution of SARS-CoV-2 genes and individual motifs or residues to virus replication, pathogenesis and immune escape, and may also be adapted to other viruses.

microbiology↗

bioRxiv2022

Different tissues in the maternal-fetal interface harbor distinct microbiomes showing associations related to their anatomical position or function

The human placenta was thought to be sterile in healthy pregnancies which has been challenged by the development of DNA sequence-based techniques, although it is still open to controversy. Nonetheless, little is known whether different parts of fetal appurtenances contain district microbiome profiles. Here, DNA 16S rRNA sequencing was performed of the amniotic fluid cells (AC), amnion membrane (AM), the placenta of fetal surface (remove the amniotic membrane, PL), maternal blood (MB), and umbilical cord blood (UCB) at V3-V4 hypervariable region from participants with cesarean delivery. Then sequence raw data were followed by taxonomic classification at 97% similarity and diversity analysis at the genus level. The differences and associations among the five tissues were analyzed. At the phylum composition level, the most abundant microorganisms were Proteobacteria in all five tissues, and followed by Firmicutes in AC, AM, and MB groups, Actinobacteria in UCB and Bacteroidetes in PL, respectively. As the maternal-fetal barrier, PL and AM had the lower OUT number and weaker co-occurrence network compared with the other three tissues. At the beta diversity clustering level, the microbiota constituents in the MB and UCB were highly similar; the microbiota profiles of PL and AM were also remarkably alike; AC was immensely different from those two clusters. Therefore, the five tissues were distinctly separated into three clusters. Our study reveals that different pregnancy-related anatomical sites harbor unique microbial compositions and show different degrees of correlation with other tissues.

microbiology↗

bioRxiv2022

β-Lapachone Regulates Mammalian Inositol Pyrophosphate Levels in an NQO1- and Oxygen-dependent Manner

1Inositol pyrophosphates (PP-InsPs) are energetic signalling molecules with important functions in mammals. As their biosynthesis depends on ATP concentration, PP-InsPs are tightly connected to cellular energy homeostasis. Consequently, an increasing number of studies involves PP-InsPs in metabolic disorders, such as type 2 diabetes, aspects of tumorigenesis, and hyperphosphatemia. Research conducted in yeast suggests that the PP-InsP pathway is activated in response to reactive oxygen species (ROS). However, the precise modulation of PP-InsPs during cellular ROS signalling is unknown. Here, we report how mammalian PP-InsP levels are changing during exposure to exogenous (H2O2) and endogenous ROS. Using capillary electrophoresis electrospray ionization mass spectrometry (CE-ESI-MS), we found that PP-InsP levels decrease upon exposure to oxidative stressors in HCT116 cells. Application of quinone drugs, particularly {beta}-lapachone ({beta}-lap), under normoxic and hypoxic conditions enabled us to produce ROS in cellulo and to show that {beta}-lap treatment caused PP-InsP changes that are oxygen dependent. Experiments in MDA-MB-231 breast cancer cells deficient of NAD(P)H:quinone oxidoreductase-1 (NQO1) demonstrated that {beta}-lap requires NQO1-bioactivation to regulate the cellular metabolism of PP-InsPs. Critically, significant reductions in cellular ATP concentrations were not directly mirrored in reduced PP-InsP levels as shown in NQO1-deficient MDA-MB-231 cells treated with {beta}-lap. The data presented here unveil new aspects of {beta}-lap pharmacology and its impact on PP-InsP levels. Our identification of different quinone drugs as modulators of PP-InsP synthesis will allow to better appreciate their overall impact on cellular function. 2 Significance StatementInositol pyrophosphates (PP-InsPs) are messenger molecules regulating various functions in mammals. They are associated with the oxidative stress response, but the underlying mechanism is unclear. We investigate PP-InsP signalling in mammalian cells subjected to reactive oxygen species (ROS). Applying the quinone {beta}-lapachone ({beta}-lap) generated intracellular ROS resulting in decreased PP-InsP levels. This indicates a key role of PP-InsPs in cellular signalling under oxidative stress. Moreover, {beta}-lap mediated PP-InsP signalling required oxygen and the enzyme NAD(P)H:quinone oxidoreductase-1 (NQO1). Since quinone drugs are cytotoxic, our data provide a basis for further investigations into the role of PP-InsPs during quinone-dependent chemotherapies. This is of special relevance since a phase II clinical trial demonstrated {beta}-lap efficacy in a combination chemotherapy against pancreatic cancer.

biochemistry↗

bioRxiv2022

Kinetic model derivation for design, building and operation of solid waste treatment unit based on system dynamics and computer simulation

Solid waste disposal is significantly important to maintain normal operation of both natural and artificial ecosystems. In this study, a kinetic model of solid waste treatment unit (SWTU) was upfront developed based on microbial ecology, system dynamics, cybernetics and digital simulation, which accurately described the relationships and interactions between solid waste decomposition (SWD) processes and biotic/abiotic factors. Then a specific SWTU prototype was designed and built from this kinetic model. A 370-day experiment demonstrated that SWTU maintained normal operation with robust stability and desired dynamic behaviors, and effectively disposed the solid waste. Therefore, this kinetic model was highly valid due to its high structural and behavioral similarity with the prototype. This research could lay a strong theoretical foundation for further closed-loop control and optimization of SWTU, and provide scientific guidance to environmental management and sustainable development.

ecology↗

bioRxiv2022

A novel method revealing animal evolutionary relationships based on milk Mid-infrared

Mid-infrared spectra (MIRS) can effectively reflect the chemical bonds in milk, which has been widely used in dairy herd improvement. However, the relationship between MIRS and animal evolution remains largely unclear. This study firstly found great differences in MIRS and the components of milk by analyzing MIRS information of 12 different mammal species. A five-level discriminant model of evolutionary level based on MIRS was established with a test set kappa coefficient >0.97. In addition, a regression model of genetic distance was also established to estimate the genetic distance of different animal species with a correlation coefficient of R >0.94. These results showed that this method could be used for accurate mammalian evolutionary relationship assessment. We further clarified the potential relationship between MIRS and genes, such as PPP3CA and SCD that could change MIRS by regulating specific milk components. In conclusion, we expand the application of MIRS in animal species identification and evolution research and provide new perspectives for the research on the formation mechanism of different animal milk special components.

evolutionary biology↗

bioRxiv2022

The rVSV-EBOV vaccine provides limited cross-protection against Sudan virus in guinea pigs

Recombinant vesicular stomatitis viruses (rVSVs) engineered to express heterologous viral glycoproteins have proven to be remarkably effective vaccines. Indeed, rVSV-EBOV, which expresses the Ebola virus (EBOV) glycoprotein, recently received clinical approval in the United States and Europe for its ability to prevent EBOV disease. Analogous rVSV vaccines expressing the glycoproteins of different human-pathogenic filoviruses have also been developed and shown to be effective in pre-clinical evaluations, yet these vaccine candidates have not progressed far beyond research laboratories. As the current outbreak of Sudan virus (SUDV) intensifies in Uganda, the need for proven countermeasures is rendered even more acute. Here we demonstrate that an rVSV-based vaccine expressing the SUDV glycoprotein (rVSV-SUDV) generates a potent humoral immune response that completely protects guinea pigs from SUDV disease and death. Although the cross-protection generated by rVSV vaccines for different filoviruses is thought to be limited, we wondered whether rVSV-EBOV might also provide protection against SUDV, which is closely related to EBOV. Surprisingly, nearly 60% of guinea pigs that were vaccinated with rVSV-EBOV and challenged with SUDV survived, suggesting that rVSV-EBOV offers limited protection against SUDV, at least in the guinea pig model. These results were confirmed by a back-challenge experiment in which animals that had been vaccinated with rVSV-EBOV and survived EBOV challenge were inoculated with SUDV and survived. Whether these data are applicable to the efficacy of rVSV-EBOV in humans is unknown, and they should therefore be interpreted cautiously. Nevertheless, this study confirms the potency of the rVSV-SUDV vaccine, and it highlights the potential for rVSV-EBOV to elicit a cross-protective immune response.

microbiology↗