Zhao H et al. (2001) Mol Biol Cell "A conserved mechanism of synaptogyrin localization."

Nonet ML, Zhao H

[Mol Biol Cell, 2001]

We have studied the localization of synaptogyrin family members in vivo. Both native and green fluorescent protein (GFP)-tagged Caenorhabditis elegans synaptogyrin (SNG-1) are expressed in neurons and synaptically localized. Deletion and mutational analysis with the use of GFP-tagged SNG-1 has defined a 38 amino acid sequence within the C terminus of SNG-1 and a single arginine in the cytoplasmic loop between transmembrane domain 2 and 3 that are required for SNG-1 localization. These domains may represent components of signals that target synaptogyrin for endocytosis from the plasma membrane and direct synaptogyrin to synaptic vesicles, respectively. In chimeric studies, these regions were sufficient to relocalize cellugyrin, a nonneuronal form of synaptogyrin, from nonsynaptic regions such as the sensory dendrites and the cell body to synaptic vesicles. Furthermore, GFP-tagged rat synaptogyrin is synaptically localized in neurons of C. elegans and in cultured hippocampal neurons. Similarly, the C-terminal domain of rat synaptogyrin is necessary for localization in hippocampal neurons. Our study suggests that the mechanisms for synaptogyrin localization are likely to be conserved from C. elegans to vertebrates.

Zhao H et al. (2023) IEEE/ACM Trans Comput Biol Bioinform "The Intrinsic Similarity of Topological Structure in Biological Neural Networks."

Zhao H, Shi Z, Gong Z, He S, Shao C

[IEEE/ACM Trans Comput Biol Bioinform, 2023]

Most previous studies mainly have focused on the analysis of structural properties of individual neuronal networks from C. elegans. In recent years, an increasing number of synapse-level neural maps, also known as biological neural networks, have been reconstructed. However, it is not clear whether there are intrinsic similarities of structural properties of biological neural networks from different brain compartments or species. To explore this issue, we collected nine connectomes at synaptic resolution including C. elegans, and analyzed their structural properties. We found that these biological neural networks possess small-world properties and modules. Excluding the Drosophila larval visual system, these networks have rich clubs. The distributions of synaptic connection strength for these networks can be fitted by the truncated pow-law distributions. Additionally, compared with the power-law model, a log-normal distribution is a better model to fit the complementary cumulative distribution function (CCDF) of degree for these neuronal networks. Moreover, we also observed that these neural networks belong to the same superfamily based on the significance profile (SP) of small subgraphs in the network. Taken together, these findings suggest that biological neural networks share intrinsic similarities in their topological structure, revealing some principles underlying the formation of biological neural networks within and across species.

Zhao H et al. (2022) Entropy (Basel) "Modeling the Evolution of Biological Neural Networks Based on Caenorhabditis elegans Connectomes across Development."

Shi Z, He S, Gong Z, Zhao H

[Entropy (Basel), 2022]

Knowledge of the structural properties of biological neural networks can help in understanding how particular responses and actions are generated. Recently, Witvliet et al. published the connectomes of eight isogenic Caenorhabditis elegans hermaphrodites at different postembryonic ages, from birth to adulthood. We analyzed the basic structural properties of these biological neural networks. From birth to adulthood, the asymmetry between in-degrees and out-degrees over the C. elegans neuronal network increased with age, in addition to an increase in the number of nodes and edges. The degree distributions were neither Poisson distributions nor pure power-law distributions. We have proposed a model of network evolution with different initial attractiveness for in-degrees and out-degrees of nodes and preferential attachment, which reproduces the asymmetry between in-degrees and out-degrees and similar degree distributions via the tuning of the initial attractiveness values. In this study, we present the well-preserved structural properties of C. elegans neuronal networks across development, and provide some insight into understanding the evolutionary processes of biological neural networks through a simple network model.

Zhao H et al. (2015) Antonie Van Leeuwenhoek "Expression of serine proteinase P186 of Arthrobotrys oligospora and analysis of its nematode-degrading activity."

Meng Q, Qiao J, Chen C, Zhao H, Gong S, Tian L, Cai X, Luo J, Liu T

[Antonie Van Leeuwenhoek, 2015]

The nematode-trapping fungi possess a unique capability of predating and invading nematodes. As a representative nematode-trapping fungus, Arthrobotrys oligospora has been widely used to study the interactions between nematode-trapping fungi and their hosts. Serine proteinase is one of the important virulence factors during process of invasion of the nematode-trapping fungi into nematodes. In this study, using reverse transcription polymerase chain reaction, we amplified the gene sequence of serine proteinase 186 from A. oligospora, cloned it into pPIC9K vector and expressed it in the yeast Pichia pastoris. The expressed recombinant serine proteinase186 (reP186) was purified via Ni-affinity chromatography. The in vitro nematode-degrading activity of reP186 was analyzed. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot analysis revealed that reP186 with molecular weight of 33kDa was successfully obtained. ReP186 was capable of degrading a series of protein substrates including casein, gelatin, bovine serum albumin, denatured collagen and nematode cortical layer. The reP186 exhibited the maximal activity at pH 8.0 and 55C and was highly sensitive to the inhibitor, phenylmethanesulfonylfluoride. Treatment of Caenorhabditis elegans and Haemonchus contortus with reP186 for 12, 24 and 36h, respectively, resulted in 62, 88 and 100% of killing rates for C. elegans, and 52, 65 and 84% of killing rates for H. contortus, respectively, indicating a relatively strong nematode-degrading bioactivity of reP186.

Zhao H et al. (2016) PLoS One "Identifying Multi-Dimensional Co-Clusters in Tensors Based on Hyperplane Detection in Singular Vector Spaces."

Liu X, Zhao H, Chen L, Wang DD, Yan H

[PLoS One, 2016]

Co-clustering, often called biclustering for two-dimensional data, has found many applications, such as gene expression data analysis and text mining. Nowadays, a variety of multi-dimensional arrays (tensors) frequently occur in data analysis tasks, and co-clustering techniques play a key role in dealing with such datasets. Co-clusters represent coherent patterns and exhibit important properties along all the modes. Development of robust co-clustering techniques is important for the detection and analysis of these patterns. In this paper, a co-clustering method based on hyperplane detection in singular vector spaces (HDSVS) is proposed. Specifically in this method, higher-order singular value decomposition (HOSVD) transforms a tensor into a core part and a singular vector matrix along each mode, whose row vectors can be clustered by a linear grouping algorithm (LGA). Meanwhile, hyperplanar patterns are extracted and successfully supported the identification of multi-dimensional co-clusters. To validate HDSVS, a number of synthetic and biological tensors were adopted. The synthetic tensors attested a favorable performance of this algorithm on noisy or overlapped data. Experiments with gene expression data and lineage data of embryonic cells further verified the reliability of HDSVS to practical problems. Moreover, the detected co-clusters are well consistent with important genetic pathways and gene ontology annotations. Finally, a series of comparisons between HDSVS and state-of-the-art methods on synthetic tensors and a yeast gene expression tensor were implemented, verifying the robust and stable performance of our method.

H Zhao et al. (1999) International C. elegans Meeting "The mechanisms of synaptic localization of sng-1, the C. elegans homologue of vertebrate synaptogyrin"

L Wei, ML Nonet, H Zhao

[International C. elegans Meeting, 1999]

The mechanisms by which synaptic vesicle (SV) proteins are localized to SVs are poorly understood, with respect to the targeting signals within SV proteins and the molecules involved in their sorting pathways. To address these issues, we chose to study sng-1 , the C. elegans homologue of vertebrate synaptogyrin, a four transmembrane domain protein of SVs with both the N- and C-terminus facing the cytoplasm. sng-1 encodes a 248 amino acid protein with 30% identity to rat synaptogyrin. Immunohistochemistry using an antibody raised against the C-terminal domain of SNG-1 was performed on wild type animals and transgenic animals expressing a C-terminal SNG-1-GFP fusion. This revealed a punctate staining pattern along the nerve cords and the SAB motor axons in the head, suggesting that both native SNG-1 and SNG-1::GFP are localized to nerve terminals. In addition, SNG-1::GFP colocalizes with another SV protein, synaptotagmin. Moreover, in unc-104 mutants, which are deficient in axonal transport of SVs, SNG-1::GFP accumulates in neuronal cell bodies. These results strongly suggest that SNG-1::GFP is targeted to SVs in C. elegans . Deletion analysis using SNG-1::GFP shows that the C-terminal, but not the N-terminal domain of SNG-1, is necessary for its synaptic localization. The required region has been mapped within 40 amino acids and we are currently attempting to further refine the localization signal. However, the C-terminal domain of SNG-1 is not sufficient to target other membrane proteins to SVs. To identify proteins that interact with SNG-1 and may mediate its synaptic localization, a yeast two-hybrid screen was performed using the C-terminal domain of SNG-1 as bait. Positive clones were obtained from two different C. elegans cDNA libraries and are currently being analyzed. In parallel work, we are assessing whether the localization signal is conserved between C. elegans and vertebrates by similar deletion analysis. Preliminary results suggest that synaptogyrin-GFP is targeted to SVs of ganglion cells in retina preparations of multiple species.

Zhao C et al. (1993) Worm Breeder's Gazette "Cloning of the lin-32 Gene"

Emmons SW, Zhao C

[Worm Breeder's Gazette, 1993]

Cloning of the lin-32 gene Connie Zhao and Scott W. Emmons, Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461

Thomas JH et al. (1994) Worm Breeder's Gazette "lin-36, a Class B Synthetic Multivulva Gene, Encodes a Novel Protein"

Thomas JH, Horvitz HR

[Worm Breeder's Gazette, 1994]

lin-36, a Class B Synthetic Multivulva Gene, Encodes a Novel Protein Jeffrey H. Thomas and H. Robert Horvitz, HHMI, Dept. Biology, MIT, Cambridge, MA 02139, USA

Bowerman B et al. (2019) Dev Cell "Breaking Symmetry: Worm Cue Finally Found."

Bowerman B, Sugioka K

[Dev Cell, 2019]

In this issue of Developmental Cell, Zhao etal. (2019) show that the Aurora A kinase AIR-1 is the long-sought cue that downregulates cortical actomyosin to establish anterior-posterior polarity in the C.elegans zygote, diffusing from centrosomes to the overlying cortex to phosphorylate yet to be identified target(s).

Sun J et al. (2013) Exp Parasitol "Parasitism of secondary-stage juvenile of Heterodera glycines and four larva stages of Caenorhabditis elegans by Hirsutella spp."

Sun J, Xie H, Xiang M, Liu X, Qiu J

[Exp Parasitol, 2013]

The fungi Hirsutella rhossiliensis and Hirsutella minnesotensis generally parasitize only plant-parasitic nematodes in nature but parasitize the bacterivorous nematode Caenorhabditis elegans on agar plates. To establish a model system for studying the interaction between fungi and nematodes, we compared the parasitism of the first- to fourth-stage larvae (L1-L4) of C. elegans and second-stage juvenile (J2) of Heterodera glycines by twenty isolates of Hirsutella spp. Although parasitism differed substantially among isolates, both H. minnesotensis and H. rhossiliensis parasitized a higher percentage of H. glycines J2s than of C. elegans larvae. Parasitism of C. elegans L1s was correlated with parasitism of H. glycines J2s. Parasitism of C. elegans by H. rhossiliensis and H. minnesotensis was negatively correlated with larva size and motility, i.e., parasitism was higher for the younger stages. The C. elegans L1 is recommended for studying parasitism of nematodes by H. rhossiliensis and H. minnesotensis.