Biology subjects

Li, S.

Publications and source records attributed to Li, S..

At least 1,171 records · Page 65Linked to original sources

bioRxiv2020

DMLDA-LocLIFT: Identification of multi-label protein subcellular localization using DMLDA dimensionality reduction and LIFT classifier

BackgroundMulti-label proteins occur in two or more subcellular locations, which play a vital part in cell development and metabolism. Prediction and analysis of multi-label subcellular localization (SCL) can present new angle with drug target identification and new drug design. However, the prediction of multi-label protein SCL using biological experiments is expensive and labor-intensive. Therefore, predicting large-scale SCL with machine learning methods has turned into a hot study topic in bioinformatics. MethodsIn this study, a novel multi-label learning means for protein SCL prediction, called DMLDA-LocLIFT, is proposed. Firstly, the dipeptide composition, encoding based on grouped weight, pseudo amino acid composition, gene ontology and pseudo position specific scoring matrix are employed to encode subcellular protein sequences. Then, direct multi-label linear discriminant analysis (DMLDA) is used to reduce the dimension of the fused feature vector. Lastly, the optimal feature vectors are input into the multi-label learning with Label-specIfic FeaTures (LIFT) classifier to predict the location of multi-label proteins. ResultsThe jackknife test showed that the overall actual accuracy on Gram-negative bacteria, Gram-positive bacteria, and plant datasets are 98.60%, 99.60%, and 97.90% respectively, which are obviously better than other state-of-the-art prediction methods. ConclusionThe proposed model can effectively predict SCL of multi-label proteins and provide references for experimental identification of SCL. The source codes and data are publicly available at https://github.com/QUST-AIBBDRC/DMLDA-LocLIFT/.

bioinformatics↗

bioRxiv2020

TGFβ Suppresses Type 2 Immunity to Cancer

The immune system employs two distinct defense strategies against infections: pathogen elimination typified by type 1 immunity, and pathogen containment exemplified by type 2 immunity in association with tissue repair. Akin to infectious diseases, cancer progresses with cancer cell acquisition of microorganism-like behavior propagating at the expense of the host. While immunological mechanisms of cancer cell elimination are well defined, whether immune-mediated cancer cell containment can be induced is poorly understood. Here we show that ablation of transforming growth factor-{beta} receptor II (TGF{beta}RII) in CD4+ T cells promotes tumor tissue healing and halts cancer progression. Notably, the restorative response is dependent on the T helper 2 cytokine IL-4 fortifying vasculature organization that spares only proximal layers of cancer cells from hypoxia, nutrient starvation and death. Thus, type 2 immunity represents an effective cancer defense mechanism, and TGF{beta} signaling in helper T cells may be targeted for novel cancer immunotherapy.

immunology↗

bioRxiv2020

Amorphous nickel titanium alloy film: a new choice for cryo electron microscopy sample preparation

Cryo-electron microscopy (cryoEM) has become one of the most important approach for structural biology. However, barriers are still there for an increase successful rate, a better resolution and improved efficiency from sample preparation, data collection to image processing. CryoEM sample preparation is one of the bottlenecks with many efforts made recently, including the optimization of supporting substrate (e.g. ultra-thin carbon, graphene, pure gold, 2d crystal of streptavidin, and affinity modification), which was aimed to solve air-water interface problem, or reduce beam induced motion (BIM), or change particle distribution in the grid hole. Here, we report another effort of developing a new supporting substrate, the amorphous nickel-titanium alloy (ANTA) film, for cryoEM sample preparation. Our investigations showed advantages of ANTA film in comparison with conventional carbon film, including superior electron conductivity and trace non-specific interaction with protein. These advantages yield less BIM and significantly improved particle distribution during cryoEM experiment of human apo-ferritn, thus resulting an improved reconstruction resolution from a reduced number of micrographs and particles. Unlike the pure gold film, the usage of the ANTA film is just same with the carbon film, compatible to conventional automatic cryoEM data collection procedure.

biophysics↗

bioRxiv2020

Polyploidization enhancing genetic recombination of the ancestral diploid genome in the evolution of hexaploid wheat

Allopolyploidy increases its evolutionary potential by fixing heterosis and the advantage of gene redundancy. Allelic combinations generated from genetic recombination potentially provide many variations to the selection pools for evolution. May there be any relationship between allopolyploidization and genetic recombination? To study the impact of polyploidy on genetic recombination, we selected wheat as a model and simulated its evolution pathway of allopolyploidy by developing synthetic hexaploid wheat. The change of homologous chromosome recombination were investigated on their diploid DD and tetraploid AABB genomes after their allohexaploidization, respectively. The genetic recombination of the ancestral diploid genome of Aegilops tauschii was enhanced significantly more than 2 folds after their hexaploidization. Hexaploidization enhancing genetic recombination of the ancestral diploid D genome was firstly reported to be a new way to increase evolutionary potential of wheat, which is beneficial for wheat to conquer their narrow origination of D genome, quickly spread and make it a major crop of the world. Finally, re-synthetizing hexaploid wheat using diverse Ae. tauschii species with tetraploid wheat can be considered as a pleiotropic strategy to speed adaptive evolution of bread wheat in breeding processes by increasing both gene allele types and genetic recombination variations.

evolutionary biology↗

bioRxiv2020

Tracing the origin of a new organ by inferring the genetic basis of rumen evolution

The rumen is the hallmark organ of ruminants and hosts a diverse ecosystem of microorganisms that facilitates efficient digestion of plant fibers. We used 897 transcriptomes from three Cetartiodactyla lineages: ruminants, camels and cetaceans, as well as data from ruminant comparative genomics and functional assays to explore the genetic basis of rumen origin and evolution. Comparative analyses reveal that the rumen and the first-chamber stomachs of camels and cetaceans shared a common tissue origin from the esophagus. The rumen recruited genes from other tissues/organs and up-regulated many esophagus genes to aquire functional innovations involving epithelium absorption, improvement of the ketone body metabolism and regulation of microbial community. These innovations involve such genetic changes as ruminant-specific conserved elements, newly evolved genes and positively selected genes. Our in vitro experiements validate the functions of one enhancer, one positively selected gene and two newly evolved antibacterial genes. Our study provides novel insights into the origin and evolution of a complex organ.

evolutionary biology↗

bioRxiv2020

Comprehensive Network Analysis and Experimental Verification of Dedu Safflower's Influence on Ascites Hepatocarcinoma

BackgroundDedu Safflower Powder is a kind of classical prescription of Mongolian Medicine, and its main ingredients are the safflower and the Scabiosa tschiliensis. In the former Mongolian Medicine clinical practice, Dedu Safflower Powder, etc. had obvious effect on curing hepatocarcinoma so as to ease ascites. But the principle of Dedu Safflower Powders curing ascites hepatocarcinoma has been not clear. AimH22 mouse hepatocarcinoma ascites models are used for researching the safflower and the Scabiosa tschiliensiss function of jointly being against hepatocarcinoma ascites, and for verifying their possible combination principle (miR-23a-DAPK1-PVT1 signal axis). MethodThrough simulating an interaction network of the safflower and the Scabiosa tschiliensis with target spots, the function target was predicted. H22 mouse hepatocarcinoma ascites models were randomly divided into a blank contrast group, a model contrast group, a safflower group, a Scabiosa tschiliensis group and a compatibility group of the safflower/the Scabiosa tschiliensis. On the 10th day, mice were killed to measure their weights and abdominal perimeters, also to collect ascites and blood for physical examinations. Kidney tissues were dissected at once and fixed in paraformaldehyde, for a real-time quantitative polymerase chain reaction (qRT-PCR) analysis. ResultIn the network, the DAPK1-PVT1 interaction showed the biggest edge betweenness, so it was predicted that DAPK1 and PVT1 were respectively presumed targets of the safflower and the Scabiosa tschiliensis. Compared with the model contrast group, the safflower group, the Scabiosa tschiliensis group and the safflower/Scabiosa tschiliensis group all had decreasing ascites volumes, body weights, abdominal perimeters. Compared with the model group, the safflower group and the safflower/Scabiosa tschiliensis group had rising DAPK1 expressions (p<0.05), while the safflower group had more obvious increasing DAPK1 (p<0.01); the Scabiosa tschiliensis group and the safflower/Scabiosa tschiliensis group had lowering PVT1 expressions (p<0.05), while the Scabiosa tschiliensis group had more obvious lowering PVT1 (p<0.01); the safflower group, the Scabiosa tschiliensis group and the safflower/Scabiosa tschiliensis group had lowering miR-23a expressions (p<0.05), while the safflower/Scabiosa tschiliensis group had more obvious lowering (p<0.01). ConclusionDAPK1 and PVT1 are respectively the presumed targets of the safflower and the Scabiosa tschiliensis. So Dedu Safflower Powder has good effects on ascites hepatocarcinoma, and that function may be partly related to regulation of miR-23a-DAPK1-PVT1 signal axis.

cancer biology↗

bioRxiv2020

Basal forebrain-derived acetylcholine encodes valence-free reinforcement prediction error.

Acetylcholine (Ach) is released by the cholinergic basal forebrain (CBF) throughout the cortical mantle and is implicated in behavioral functions ranging from arousal to attention to learning. Yet what signal ACh provides to cortex remains unresolved, hindering our understanding of its functional roles. Here we demonstrate that the CBF signals unsigned reinforcement prediction error, in contrast to dopamine (DA) neurons that encode reward prediction error. We show that both CBF neuronal activity and acetylcholine (ACh) release at cortical targets signal reinforcement delivery, acquire responses to predictive stimuli and show diminished responses to expected outcomes, hallmarks of a prediction error. To compare ACh with DA, we simultaneously monitored the activity of both neuromodulators during a serial reversal learning task. ACh tracked learning as swiftly as DA during acquisition but lagged slightly during extinction, suggesting that these neuromodulators play complementary roles in reinforcement as their patterns of innervation, cellular targets, and signaling mechanisms are themselves complementary. Through retrograde viral tracing we show that the cholinergic and dopaminergic systems engage overlapping upstream circuits, accounting for their coordination during learning. This predictive and valence-free signal explains how ACh can proactively and retroactively improve the processing of behaviorally important stimuli, be they good or bad.

neuroscience↗

bioRxiv2020

Emerging viruses in British Columbia salmon discovered via a viral immune response biomarker panel and metatranscriptomic sequencing

The emergence of infectious agents poses a continual economic and environmental challenge to aquaculture production, yet the diversity, abundance and epidemiology of aquatic viruses are poorly characterised. In this study, we applied salmon host transcriptional biomarkers to identify and select fish in a viral disease state but only those that we also showed to be negative for established viruses. This was followed by metatranscriptomic sequencing to determine the viromes of dead and dying farmed Atlantic (Salmo salar) and Chinook (Oncorhynchus tshawytscha) salmon in British Columbia. We found that the application of the biomarker panel increased the probability of discovering viruses in aquaculture populations. We discovered viruses that have not previously been characterized in British Columbian Atlantic salmon farms. To determine the epidemiology of the newly discovered or emerging viruses we conducted high-throughput RT-PCR to reveal their prevalence in British Columbia (BC), and detected some of the viruses we first discovered in farmed Atlantic salmon in Chinook and sockeye salmon, suggesting a broad host range. Finally, we applied in-situ hybridisation to confirm infection and explore the tissue tropism of each virus.

genomics↗

bioRxiv2020

Longitudinal analysis of naturally acquired antibodies to PfEMP1 CIDR domain variants and their association with malaria protection

Malaria pathogenicity is determined, in part, by the adherence of Plasmodium falciparum infected erythrocytes to the microvasculature mediated via specific interactions between PfEMP1 variant domains to host endothelial receptors. Naturally acquired antibodies against specific PfEMP1 variants can play an important role in clinical protection against malaria. We evaluated IgG responses against a repertoire of PfEMP1 CIDR domain variants to determine the rate and order of variant-specific antibody acquisition and their association with protection against febrile malaria in a prospective cohort study conducted in an area of intense, seasonal malaria transmission. Using longitudinal data, we found that IgG to the pathogenic domain variants CIDR1.7 and CIDR1.8 were acquired the earliest. Furthermore, IgG to CIDR{gamma}3 was associated with reduced prospective risk of febrile malaria and recurrent malaria episodes. Future studies will need to validate these findings in other transmission settings and determine the functional activity of these naturally acquired CIDR variant-specific antibodies.

immunology↗

bioRxiv2020

Exosome-mediated apoptosis pathway during WSSV infection in crustacean mud crab

MicroRNAs are regulatory molecules that can be packaged into exosomes to modulate recipients cellular response, while their role during viral infection is beginning to be appreciated. However, the involvement of exosomal miRNAs during immunoregulation in invertebrates has not been addressed. Here, we found that exosomes released from WSSV-injected mud crabs could suppress viral invasion by inducing apoptosis of hemocytes. Besides, miR-137 and miR-7847 were found to be less packaged in mud crab exosomes during viral infection, with both miR-137 and miR-7847 shown to be negative apoptosis regulators by targeting the apoptosis-inducing factor (AIF). Moreover, our data revealed that AIF did not only translocate to the nucleus to induce DNA fragmentation, but could also competitively bind to HSP70 to disintegrate the HSP70-Bax (Bcl-2-associated X protein) complex, which eventually activated the mitochondria apoptosis pathway via free Bax. Therefore, our findings provides a novel mechanism underlying the crosstalk between exosomal miRNAs and apoptosis pathway in innate immunity in invertebrates.

immunology↗

bioRxiv2020

IL4-driven microglia modulate stress resilience through BDNF-dependent neurogenesis

Adult neurogenesis in the dentate gyrus of the hippocampus is regulated by specific groups of microglia and is functionally implicated in behavioral responses to stress. However, the role of microglia in modulating hippocampal neurogenesis in stress responses remains poorly understood. Here we investigated the effects of IL4-driven Arg1+ microglia in the restoration of hippocampal neurogenesis and conferment of stress resilience. We found that low IL4 levels in the hippocampus of mice was associated with greater stress vulnerability and, conversely, overexpression of IL4 in the hippocampus induced a large number of Arg1+ microglia and ameliorated stress-induced depressive-like behaviors. Knockdown of microglial IL4 receptors in the hippocampus of mice exacerbated the stress-induced inflammatory response and abolished the antidepressant effects of IL4 overexpression. Enhancement or inhibition of IL4 signaling in hippocampal microglia modulated neurogenesis, and blockade of neurogenesis abolished the resilience to stress-induced depression. We further show that IL4-activated microglia is associated with upregulation of BDNF levels and neurogenesis. Taken together, our findings suggest that IL4-driven microglia in the hippocampus trigger BDNF-dependent neurogenesis in response to chronic stress, helping protect against depressive-like symptoms. These findings identify the modulation of a specific microglial phenotype as a treatment strategy for mood disorders. In BriefZhang et al. show that IL4-induced Arg1+ microglia restore hippocampal neurogenesis and promote resilience against stress in mice by increasing BDNF levels. Targeting microglia with immunomodulatory factors may be a strategy for treating mood disorders. HighlightsO_LIVulnerability to stress in mice is associated with reduced IL4 signaling in the hippocampus C_LIO_LIBrain-derived IL4 promotes adult hippocampal neurogenesis and stress resistance by driving Arg1+ microglia C_LIO_LIIL4-driven Arg1+ microglia enhance hippocampal neurogenesis via a BDNF-dependent pathway C_LI

neuroscience↗

bioRxiv2020

Analysis of metagenome-assembled genomes from the mouse gut microbiota reveals distinctive strain-level characteristics

The laboratorial mouse harbors a unique gut microbiota with potential value for human microbiota-associated studies. Mouse gut microbiota has been explored at the genus and species levels, but features rarely been showed at the strain level. The identification of 833,051 and 658,438 nonredundant genes of faeces and gut content samples from the laboratorial C57/BL mice showed over half of these genes were newly found compared to the previous mouse gut microbial gene catalogue. Metagenome-assembled genomes (MAGs) was used to reconstruct 46 nonredundant MAGs belonging to uncultured specieses. These MAGs included members across all phyla in mouse gut (i.e. Firmicutes, Bacteroidetes, Proteobacteria, Deferribacteres, Verrucomicrobia, and Tenericutes) and allowed a strain-level delineating of the mouse gut microbiota. Comparison of MAGs with human gut colonies revealed distinctive genomic and functional characteristics of mouses Bacteroidetes and Firmicutes strains. Genomic characteristics of rare phyla in mouse gut microbiota were demonstrated by MAG approach, including strains of Mucispirillum schaedleri, Parasutterella excrementihominis, Helicobacter typhlonius, and Akkermansia muciniphila. ImportanceThe identification of nonredundant genes suggested the existence of unknown microbes in the mouse gut samples. The metagenome-assembled genomes (MAGs) instantiated the specificity of mouse gut species and revealed an intestinal microbial correlation between mouse and human. The cultivation of faeces and gut contents sample validated the existence of MAGs and estimate their accuracy. Full-length 16S ribosomal RNA gene sequencing enabled taxonomic characterization. This study highlighted a unique ecosystem in the gut of laboratorial mice that obviously differed with the human gut flora at the strain level. The outcomes may be beneficial to researches based on laboratorial mouse models.

microbiology↗

bioRxiv2020

DeepTE: a computational method for de novo classification of transposons with convolu-tional neural network

MotivationTransposable elements (TEs) classification is an essential step to decode their roles in genome evolution. With a large number of genomes from non-model species becoming available, accurate and efficient TE classification has emerged as a new challenge in genomic sequence analysis. ResultsWe developed a novel tool, DeepTE, which classifies unknown TEs using convolutional neural networks. DeepTE transferred sequences into input vectors based on k-mer counts. A tree structured classification process was used where eight models were trained to classify TEs into super families and orders. DeepTE also detected domains inside TEs to correct false classification. An additional model was trained to distinguish between non-TEs and TEs in plants. Given unclassified TEs of different species, DeepTE can classify TEs into seven orders, which include 15, 24, and 16 super families in plants, metazoans, and fungi, respectively. In several benchmarking tests, DeepTE outperformed other existing tools for TE classification. In conclusion, DeepTE successfully leverages convolutional neural network for TE classification, and can be used to precisely identify and annotate TEs in newly sequenced eukaryotic genomes. AvailabilityDeepTE is accessible at https://github.com/LiLabAtVT/DeepTE Contactsongli@vt.edu

bioinformatics↗

bioRxiv2020

Systematically gap-filling the genome-scale model of CHO cells

ObjectiveChinese hamster ovary (CHO) cells are the leading cell factories for producing recombinant proteins in the biopharmaceutical industry. In this regard, constraint-based metabolic models are useful platforms to perform computational analysis of cell metabolism. These models need to be regularly updated in order to include the latest biochemical data of the cells, and to increase their predictive power. Here, we provide an update to iCHO1766, the metabolic model of CHO cells. ResultsWe expanded the existing model of Chinese hamster metabolism with the help of four gap-filling approaches, leading to the addition of 773 new reactions and 335 new genes. We incorporated these into an updated genome-scale metabolic network model of CHO cells, named iCHO2101. In this updated model, the number of reactions and pathways capable of carrying flux is substantially increased. ConclusionsThe present CHO model is an important step towards more complete metabolic models of CHO cells.

systems biology↗

bioRxiv2020

Construction of Nanobody Library in Mammalian Cells by Linear-double-stranded DNA Based AND Gate Genetic Circuit

Nanobody is one special type of single-domain antibody fragment with multiple advantages over traditional antibody. Our previous work established linear-double-stranded DNA (ldsDNA, or PCR amplicon) as novel biological parts for building AND gate genetic circuits in mammalian cells. During this AND-gate circuit formation process, the co-transfected up- and down-stream ldsDNAs could be linked together to form intact gene expression cassette. Here, we employed this ldsDNA-based AND-gate (LBAG) strategy to construct nanobody library in mammalian cells. The sequence complexity of complementary determining regions (CDRs) was introduced into ldsDNA by PCR amplification. After being co-transfected into mammalian cells, the up- and down-stream ldsDNAs undergo AND gate linkage and form full nanobody coding regions, containing CDR1-3. High throughput sequencing identified 22,173 unique oligonucleotide sequences in total generated by this strategy. Thus, we developed a novel method to construct nanobody library, which is a start point for building high content nanobody library in mammalian cells.

immunology↗

bioRxiv2020

Dissecting endothelial to haematopoietic stem cell transition by single-cell transcriptomic and functional analyses

Haematopoietic stem cells (HSCs) in adults are believed to be born from hemogenic endothelial cells (HECs) in mid-gestational mouse embryos. Due to rare and transient nature, the HSC-competent ECs have never been stringently identified and accurately captured, let alone their genuine vasculature precursors. Here, we firstly used high-precision single-cell transcriptomics to unbiasedly examine relevant EC populations at continuous developmental stages and transcriptomically identified putative HSC-primed HECs. Combining computational prediction and in vivo functional validation, we precisely captured HSC-competent HECs by newly constructed Neurl3-EGFP reporter mouse model, and realized enrichment further by surface marker combination. Surprisingly, endothelial-haematopoietic bi-potential was rarely but reliably witnessed in culture of single HECs. Noteworthy, primitive vascular ECs experienced two-step fate choices to become HSC-primed HECs, resolving several previously observed contradictions. Taken together, comprehensive understanding of endothelial evolutions and molecular programs underlying HSC-primed HEC specification in vivo will facilitate future investigations directing HSC production in vitro.

developmental biology↗

bioRxiv2020

A hybrid spectral library combining DIA-MS data and a targeted virtual library substantially deepens the proteome coverage

Data-independent acquisition mass spectrometry (DIA-MS) is a rapidly evolving technique that enables relatively deep proteomic profiling with superior quantification reproducibility. DIA data mining predominantly relies on a spectral library of sufficient proteome coverage that, in most cases, is built on data-dependent acquisition-based analysis of the same sample. To expand the proteome coverage for a pre-determined protein family, we report herein on the construction of a hybrid spectral library that supplements a DIA experiment-derived library with a protein family-targeted virtual library predicted by deep learning. Leveraging this DIA hybrid library substantially deepens the coverage of three transmembrane protein families (G protein coupled receptors; ion channels; and transporters) in mouse brain tissues with increases in protein identification of 37-87%, and peptide identification of 58-161%. Moreover, of the 412 novel GPCR peptides exclusively identified with the DIA hybrid library strategy, 53.6% were validated as present in mouse brain tissues based on orthogonal experimental measurement.

bioinformatics↗

bioRxiv2020

Distinct neural signals in speech preparation differentially modulate auditory responses

Actions influence sensory processing in a complex way to shape behavior. For example, during actions, a copy of motor signals--termed corollary discharge (CD) or efference copy (EC)--can be transmitted to sensory regions and modulate perception. However, the sole inhibitory function of the motor copies is challenged by mixed empirical observations as well as multifaceted computational demands for behaviors. We hypothesized that the content in the motor signals available at distinct stages of actions determined the nature of signals (CD vs. EC) and constrained their modulatory functions on perceptual processing. We tested this hypothesis using speech in which we could precisely control and quantify the course of action. In three electroencephalography (EEG) experiments using a novel delayed articulation paradigm, we found that preparation without linguistic contents suppressed auditory responses to all speech sounds, whereas preparing to speak a syllable selectively enhanced the auditory responses to the prepared syllable. A computational model demonstrated that a bifurcation of motor signals could be a potential algorithm and neural implementation to achieve the distinct functions in the motor-to-sensory transformation. These results suggest that distinct motor signals are generated in the motor-to-sensory transformation and integrated with sensory input to modulate perception.

neuroscience↗