Biology subjects

Tian, D.

Publications and source records attributed to Tian, D..

41 records · Page 3Linked to original sources

bioRxiv2020

IgY antibodies against Ebola virus possess post-exposure protection and excellent thermostability

Ebola virus (EBOV) is the most virulent pathogens that cause hemorrhagic fever with high mortality rates in humans and nonhuman primates. The postexposure antibody therapies to prevent EBOV infection are considered efficient. However, due to the poor thermal stability of mammalian antibody, their application in the tropics has been limited. Here, we developed a thermostable therapeutic antibody against EBOV based on chicken immunoglobulin Y (IgY). The IgY antibodies demonstrated excellent thermal stability, which retained their neutralizing activity at 25{degrees}C for one year, in contrast to conventional polyclonal or monoclonal antibodies (MAbs). We immunized laying hens with a variety of EBOV vaccine candidates and confirmed that VSV {Delta} G/EBOVGP encoding the EBOV glycoprotein could induce high titer neutralizing antibodies against EBOV. The therapeutic efficacy of immune IgY antibodies in vivo was evaluated in the newborn Balb/c mice model. Lethal dose of virus challenged mice were treated 2 or 24 h post-infection with different doses of anti-EBOV IgY. The group receiving a high dose of 106 NAU/kg (neutralizing antibody units/kilogram) achieved complete protection with no signs of disease, while the low-dose group was only partially protected. In contrast, all mice receiving naive IgY died within 10 days. In conclusion, the anti-EBOV IgY exhibits excellent thermostability and protective efficacy, and it is very promising to be developed as alternative therapeutic entities. Author SummaryAlthough several Ebola virus therapeutic antibodies have been reported in recent years, however, due to the poor thermal stability of mammalian antibody, their application in tropical endemic areas has been limited. We developed a highly thermostable therapeutic antibody against EBOV based on chicken immunoglobulin Y (IgY). The IgY antibodies demonstrated excellent thermal stability, which retained their neutralizing activity at 25{degrees}C for one year. The newborn mice receiving passive transfer of IgY achieved complete protection against a lethal dose of virus challenge indicating that the anti-EBOV IgY provides a promising countermeasure to solve the current clinical application problems of Ebola antibody-based treatments in Africa.

immunology↗

bioRxiv2019

Population genetics of the highly polymorphic RPP8 gene family

Plant NLR resistance genes provide some of the most extreme examples of polymorphism in eukaryotic genomes, rivalling even the vertebrate major histocompatibility complex. Surprisingly, this is also true in Arabidopsis thaliana, a predominantly selfing species with low heterozygosity. Here, we investigate how gene duplication and intergenic exchange contribute to this extraordinary variation. RPP8 is a three-locus system that is configured chromosomally as either a direct-repeat tandem duplication or as a single copy locus, plus a locus 2 Mb distant. We sequenced 48 RPP8 alleles from 37 accessions of A. thaliana and 12 RPP8 alleles from A. lyrata to investigate the patterns of interlocus shared variation. The tandem duplicates display fixed differences and share less variation with each other than either shares with the distant paralog. A high level of shared polymorphism among alleles at one of the tandem duplicates, the single-copy locus and the distal locus, must involve both classical crossing over and intergenic gene conversion. Despite these polymorphism-enhancing mechanisms, the observed nucleotide diversity could not be replicated under neutral forward-in-time simulations. Only by adding balancing selection to the simulations do they approach level of polymorphism observed at RPP8. In this NLR gene triad, genetic architecture, gene function and selection all combine to generate diversity.

evolutionary biology↗

bioRxiv2019

MOCHI enables discovery of heterogeneous interactome modules in 3D nucleome

The composition of the cell nucleus is highly heterogeneous, with different constituents forming complex interactomes. However, the global patterns of these interwoven heterogeneous interactomes remain poorly understood. Here we focus on two different interactomes, chromatin interaction network and gene regulatory network, as a proof-of-principle, to identify heterogeneous interactome modules (HIMs) in the nucleus. Each HIM represents a cluster of gene loci that are in spatial contact more frequently than expected and that are regulated by the same group of transcription factor proteins. We develop a new algorithm MOCHI to facilitate the discovery of HIMs based on network motif clustering in heterogeneous interactomes. By applying MOCHI to five different cell types, we found that HIMs have strong spatial preference within the nucleus and exhibit distinct functional properties. Through integrative analysis, this work demonstrates the utility of MOCHI to identify HIMs, which may provide new perspectives on 3D genome organization and function.

bioinformatics↗

bioRxiv2018

Plant leaf tooth feature extraction

Leaf tooth can indicate several systematically informative features and is extremely useful for circumscribing fossil leaf taxa. Moreover, it can help discriminate species or even higher taxa accurately. Previous studies extract features that are not strictly defined in botany; therefore, a uniform standard to compare the accuracies of various feature extraction methods cannot be used. For efficient and automatic retrieval of plant leaves from a leaf database, in this study, we propose an image-based description and measurement of leaf teeth by referring to the leaf structure classification system in botany. First, image preprocessing is carried out to obtain a binary map of plant leaves. Then, corner detection based on the curvature scale-space (CSS) algorithm is used to extract the inflection point from the edges; next, the leaf tooth apex is extracted by screening the convex points; then, according to the definition of the leaf structure, the characteristics of the leaf teeth are described and measured in terms of number of orders of teeth, tooth spacing, number of teeth, sinus shape, and tooth shape. In this manner, data extracted from the algorithm can not only be used to classify plants, but also provide scientific and standardized data to understand the history of plant evolution. Finally, to verify the effectiveness of the extraction method, we use leaf tooth features and simple linear discriminant analysis to classify leaves; the results show that the proposed method achieves high accuracy as compared to other methods.

bioinformatics↗

bioRxiv2018

Verified the effectiveness of AsCpf1 system in a variety of vertebrate species

CRISPR/Cpf1 system is a novel genomic editing tool. Because of its more sophisticated components, and lower off-target rate, it has the potential to become a better gene-editing tool. Previous reports showed that CRISPR/Cpf1 could work effectively in multiple species. But our data show that AsCpf1 activity has a big difference in different vertebrates. Using in vitro experiments, we finally learned that the difference between species is due to temperature.

developmental biology↗