Peng H et al. (2008) Bioinformatics "Straightening Caenorhabditis elegans images."

Long F, Liu X, Myers EW, Kim SK, Peng H

[Bioinformatics, 2008]

MOTIVATION: C. elegans, a roundworm found in soil, is a widely studied model organism with about 1000 cells in the adult. Producing high-resolution fluorescence images of C. elegans to reveal biological insights is becoming routine, motivating the development of advanced computational tools for analyzing the resulting image stacks. For example worm bodies usually curve significantly in images. Thus one must "straighten" the worms if they are to be compared under a canonical coordinate system. RESULTS: We develop a worm straightening algorithm (WSA) that restacks cutting planes orthogonal to a "backbone" that models the anterior-posterior axis of the worm. We formulate the backbone as a parametric cubic spline defined by a series of control points. We develop two methods for automatically determining the locations of the control points. Our experimental methods show that our approaches effectively straighten both 2D and 3D worm images. SUPPLEMENTARY INFORMATION: The example data sets and programs are available upon request. CONTACT: pengh@janelia.hhmi.org.

Peng H et al. (2009) Bioinformatics "VANO: a volume-object image annotation system."

Myers EW, Long F, Peng H

[Bioinformatics, 2009]

VANO is a cross-platform image annotation system that enables one to conveniently visualize and annotate 3D volume objects including nuclei and cells. An application of VANO typically starts with an initial collection of objects produced by a segmentation computation. The objects can then be labeled, categorized, deleted, added, split, merged, and redefined. VANO has been used to build high-resolution digital atlases of the nuclei of C. elegans at the L1 stage and the nuclei of D. melanogaster''s ventral nerve cord at the late embryonic stage. AVAILABILITY: Platform independent executables of VANO, a sample dataset, and a detailed description of both its design and usage are available at: research.janelia.org/peng/proj/vano. VANO is open-source for co-development.

Peng CY et al. (2011) Commun Integr Biol "C. elegans model of neuronal aging."

Hsu JM, Peng CY, Pan CL, Chen CH

[Commun Integr Biol, 2011]

Aging of the nervous system underlies the behavioral and cognitive decline associated with senescence. Understanding the molecular and cellular basis of neuronal aging will therefore contribute to the development of effective treatments for aging and age-associated neurodegenerative disorders. Despite this pressing need, there are surprisingly few animal models that aim at recapitulating neuronal aging in a physiological context. We recently developed a C. elegans model of neuronal aging, and showed that age-dependent neuronal defects are regulated by insulin signaling. We identified electrical activity and epithelial attachment as two critical factors in the maintenance of structural integrity of C. elegans touch receptor neurons. These findings open a new avenue for elucidating the molecular mechanisms that maintain neuronal structures during the course of aging.

Peng Y et al. (2017) Nature "Cysteine protease cathepsin B mediates radiation-induced bystander effects."

Mitani S, Chen YZ, Zheng L, Liu B, Liang Q, Zhang M, Li H, Yoshina S, Zhao X, Yu JS, Guo H, Peng Y, Chen JT, Xue D, Wu X

[Nature, 2017]

The radiation-induced bystander effect (RIBE) refers to a unique process in which factors released by irradiated cells or tissues exert effects on other parts of the animal not exposed to radiation, causing genomic instability, stress responses and altered apoptosis or cell proliferation. Although RIBEs have important implications for radioprotection, radiation safety and radiotherapy, the molecular identities of RIBE factors and their mechanisms of action remain poorly understood. Here we use Caenorhabditis elegans as a model in which to study RIBEs, and identify the cysteine protease CPR-4, a homologue of human cathepsin B, as the first RIBE factor in nematodes, to our knowledge. CPR-4 is secreted from animals irradiated with ultraviolet or ionizing gamma rays, and is the major factor in the conditioned medium that leads to the inhibition of cell death and increased embryonic lethality in unirradiated animals. Moreover, CPR-4 causes these effects and stress responses at unexposed sites distal to the irradiated tissue. The activity of CPR-4 is regulated by the p53 homologue CEP-1 in response to radiation, and CPR-4 seems to exert RIBEs by acting through the insulin-like growth factor receptor DAF-2. Our study provides crucial insights into RIBEs, and will facilitate the identification of additional RIBE factors and their mechanisms of action.

Peng H et al. (2010) Bioinformatics "Automatic reconstruction of 3D neuron structures using a graph-augmented deformable model."

Sternson S, Atasoy D, Peng H, Ruan Z

[Bioinformatics, 2010]

MOTIVATION: Digital reconstruction of 3D neuron structures is an important step toward reverse engineering the wiring and functions of a brain. However, despite a number of existing studies, this task is still challenging, especially when a 3D microscopic image has low single-to-noise ratio and discontinued segments of neurite patterns. RESULTS: We developed a graph-augmented deformable model (GD) to reconstruct (trace) the 3D structure of a neuron when it has a broken structure and/or fuzzy boundary. We formulated a variational problem using the geodesic shortest path, which is defined as a combination of Euclidean distance, exponent of inverse intensity of pixels along the path and closeness to local centers of image intensity distribution. We solved it in two steps. We first used a shortest path graph algorithm to guarantee that we find the global optimal solution of this step. Then we optimized a discrete deformable curve model to achieve visually more satisfactory reconstructions. Within our framework, it is also easy to define an optional prior curve that reflects the domain knowledge of a user. We investigated the performance of our method using a number of challenging 3D neuronal image datasets of different model organisms including fruit fly, Caenorhabditis elegans, and mouse. In our experiments, the GD method outperformed several comparison methods in reconstruction accuracy, consistency, robustness and speed. We further used GD in two real applications, namely cataloging neurite morphology of fruit fly to build a 3D 'standard' digital neurite atlas, and estimating the synaptic bouton density along the axons for a mouse brain. AVAILABILITY: The software is provided as part of the V3D-Neuron 1.0 package freely available at http://penglab.janelia.org/proj/v3d.

Peng H et al. (2022) BMC Microbiol "Immunological pathogenesis of Bovine E. coli infection in a model of C. elegans."

Zhong S, Li X, Pei Z, Tao L, Pan Y, Bai H, Gong Y, Li F, Wang L, Li J, Liao Y, Chen Z, Ma C, Wu C, Peng H, Li C

[BMC Microbiol, 2022]

BACKGROUND: Cattle industry is critical for China's livestock industry, whereas E. coli infection and relevant diseases could lead huge economic loss. Traditional mammalian models would be costly, time consuming and complicated to study pathological changes of bovine E. coli. There is an urgent need for a simple but efficient animal model to quantitatively evaluate the pathological changes of bovine-derived E. coli in vivo. Caenorhabditis elegans (C. elegans) has a broad host range of diverse E. coli strains with advantages, including a short life cycle, a simple structure, a transparent body which is easily visualized, a well-studied genetic map, an intrinsic immune system which is conservable with more complicated mammalians. RESULTS: Here, we considered that O126 was the dominant serotype, and a total of 19 virulence factors were identified from 41 common E. coli virulence factors. Different E. coli strains with diverse pathogenicity strengths were tested in C. elegans in E. coli with higher pathogenicity (EC3/10), Nsy-1, Sek-1 and Pmk-1 of the p38 MAPK signaling pathway cascade and the expression of the antimicrobial peptides Abf-3 and Clec-60 were significantly up-regulated comparing with other groups. E. coli with lower pathogenicity (EC5/13) only activated the expression of Nsy-1 and Sek-1 genes in the p38 MAPK signaling pathway, Additionally, both groups of E. coli strains caused significant upregulation of the antimicrobial peptide Spp-1. CONCLUSION: Thirteen E. coli strains showed diverse pathogenicity in nematodes and the detection rate of virulence factors did not corresponding to the virulence in nematodes, indicating complex pathogenicity mechanisms. We approved that C. elegans is a fast and convenient detection model for pathogenic bacteria virulence examinations.

Peng H et al. (2016) J Agric Food Chem "Inhibition of Fat Accumulation by Hesperidin in Caenorhabditis elegans."

Gan L, Wei Z, Yang Y, Yang X, Peng H, Luo H, Wu Z

[J Agric Food Chem, 2016]

Hesperidin, abundant in citrus fruits, has a wide range of pharmacological effects including anticarcinogenic, anti-inflammatory, antioxidative, radioprotective and antiviral activities. However, relatively few studies on the effects of hesperidin on lipid metabolism have been reported. Here, using Caenorhaditis elegans as a model animal, we found that 100 M hesperidin significantly decreased fat accumulation both in high fat worms cultured in nematode growth medium containing 10 mM glucose (83.5%+/-1.2 vs control by Sudan black B staining and 87.6%+/-2.0 vs control by Oil Red O staining, P<0.001) and daf-2 mutant worms (87.8%+/-1.4 vs control by Oil Red O staining, P<0.001). Furthermore, 50 M hesperidin decreased the ratio of oleic acid to stearic acid (C18:19/C18:0) (P<0.05), and supplementation of oleic acid could restore the inhibitory effect of hesperidin on fat accumulation. Hesperidin significantly downregulated the expression of stearoyl-CoA desaturase, fat-6 and fat-7 (P<0.05), and mutation of fat-6 and fat-7 reversed fat accumulation inhibited by hesperidin. In addition, hesperidin decreased the expression of other genes involved in lipid metabolism, including pod-2, mdt-15, acs-2 and kat-1 (P<0.05). These results suggested that hesperidin reduced fat accumulation by affecting several lipid metabolism pathways, such as fat-6 and fat-7. This study provided new insights into elucidating the mechanism underlying the regulation of lipid metabolism by hesperidin.

Peng D et al. (2016) Environ Microbiol "A novel metalloproteinase virulence factor is involved in Bacillus thuringiensis pathogenesis in nematodes and insects."

Sun M, Liu G, Lin J, Zhu L, Zheng W, Peng D, Zheng J, Huang Q

[Environ Microbiol, 2016]

The Gram-positive soil bacterium Bacillus thuringiensis has been developed as the leading microbial insecticide for years. The pathogenesis of B. thuringiensis requires common extracellular factors that depend on the PlcR regulon, which regulates a large number of virulence factors; however, the precise role of many of these proteins is not known. In this study, we describe the complete lifecycle of a nematicidal B. thuringiensis strain in the free living nematode Caenorhabditis elegans using in vitro and in vivo molecular techniques to follow host and bacterial effectors during the infection process. We then focus on the metalloproteinase ColB, a collagenase, which was found highly important for destruction of the intestine thereby facilitates the adaptation and colonization of B. thuringiensis in C. elegans. In vivo green fluorescent protein (GFP) reporter-gene studies showed that ColB expression is highly induced and regulated by the global activator PlcR. Finally, we demonstrated that ColB also takes part in B. thuringiensis virulence in an insect model following injection and oral infection. Indeed, addition of purified ColB accelerates the action of Cry toxin proteins in insects, too. These results give novel insights into host adaptation for B. thuringiensis and other B. cereus group bacteria and highlight the role of collagenase metalloproteases to synergize infection process.

Peng Y et al. (2021) Foods "Theanine Improves High-Dose Epigallocatechin-3-Gallate-Induced Lifespan Reduction in Caenorhabditis elegans."

Liu Z, Huang J, Lu Y, Gong Y, Peng Y, Dai S, Xiong L

[Foods, 2021]

Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea. Our previous report showed that induced hormesis was a critical determinant for the promotion of a healthy lifespan in <i>Caenorhabditis elegans</i>. In the present study, we investigated the anti-aging effects of the main active ingredients in green tea. We found that galloylated catechins (EGCG and epicatechin gallate) could extend the lifespan of <i>C. elegans</i>, while their metabolites (gallic acid, epicatechin, and epigallocatechin) could not. Interestingly, the combination with theanine, not caffeine, could alleviate the adverse effects induced by high-dose EGCG, including the promotion of lifespan and locomotor ability. This was due to the attenuation of the excess production of reactive oxygen species and the activation of DAF-16. These findings will facilitate further studies on the health benefits of tea active components and their interactions.

Peng D et al. (2018) Appl Microbiol Biotechnol "Nematode-specific cadherin CDH-8 acts as a receptor for Cry5B toxin in Caenorhabditis elegans."

Ye X, Wan D, Cheng C, Peng D, Sun M

[Appl Microbiol Biotechnol, 2018]

Parasitic nematodes of animals and plants cause worldwide devastating impacts on people's lives and agricultural crops. The crystal protein Cry5B produced by Bacillus thuringiensis has efficient and specific activity against a wide range of nematodes. However, the action mode of this toxin has not yet been thoroughly determined. Here, a nematode-specific cadherin CDH-8 was demonstrated to be a receptor for Cry5B toxin by using Caenorhabditis elegans as a model, providing evidence that the cadherin mutant worm cdh-8(RB815) possesses significant resistance to Cry5B, and the CDH-8 fragments bind specifically to Cry5B. Furthermore, CDH-8 was identified to be required for the oligomerization of Cry5B toxin in vivo and contribute to the internalization and pore formation of Cry5B in nematode cells. This study will facilitate a better understanding of the action mode of nematicidal Cry toxins and help the design of Cry toxin-based products for the control of plant or animal parasitic nematodes.