Yang L et al. (2017) Biomed Microdevices "A microfluidic diode for sorting and immobilization of Caenorhabditis elegans."

Mu R, Li D, Arriola JGS, Zhang Y, Nelms BL, Hong T, Yang L

[Biomed Microdevices, 2017]

Caenorhabditis elegans (C. elegans) is a powerful model organism extensively used in studies of human aging and diseases. Despite the numerous advantages of C. elegans as a model system, two biological characteristics may introduce complexity and variability to most studies: 1. it exhibits different biological features, composition and behaviors at different developmental stages; 2. it has very high mobility. Therefore, synchronization and immobilization of worm populations are often required. Conventionally, these processes are implemented through manual and chemical methods, which can be laborious, time-consuming and of low-throughput. Here we demonstrate a microfluidic design capable of simultaneously sorting worms by size at a throughput of 97+/-4 worms per minute, and allowing for worm collection or immobilization for further investigations. The key component, a microfluidic diode structure, comprises a curved head and a straight tail, which facilitates worms to enter from the curved end but prevents them from translocating from the straight side. This design remarkably enhances the efficiency and accuracy of worm sorting at relatively low flow rates, and hence provides a practical approach to sort worms even with the presence of egg clusters and debris. In addition, we show that well-sorted worms could be immobilized, kept alive and identically orientated, which could facilitate many C. elegans-based studies.

Yang L et al. (2020) EMBO Rep "Neuronal lipolysis participates in PUFA-mediated neural function and neurodegeneration."

Liang J, Ding M, Shui G, Huang X, Yang L, Yavuz A, Lam SM

[EMBO Rep, 2020]

Lipid droplets (LDs) are dynamic cytoplasmic organelles present in most eukaryotic cells. The appearance of LDs in neurons is not usually observed under physiological conditions, but is associated with neural diseases. It remains unclear how LD dynamics is regulated in neurons and how the appearance of LDs affects neuronal functions. We discovered that mutations of two key lipolysis genes atgl-1 and lid-1 lead to LD appearance in neurons of Caenorhabditis elegans. This neuronal lipid accumulation protects neurons fromhyperactivation-triggered neurodegeneration, with a mild decrease in touch sensation. We also discovered that reduced biosynthesis of polyunsaturated fatty acids (PUFAs) causes similar effects and synergizes with decreased lipolysis. Furthermore, we demonstrated that these changes in lipolysis and PUFA biosynthesis increase PUFA partitioning toward triacylglycerol, and reduced incorporation of PUFAs into phospholipids increases neuronal protection. Together, these results suggest the crucial role of neuronal lipolysis in cell-autonomous regulation of neural functions and neurodegeneration.

Yang L et al. (2020) Biomed Res Int "Prediction of Protein-Protein Interactions with Local Weight-Sharing Mechanism in Deep Learning."

Han Y, Li W, Yang L, Zhang H, Dai Y

[Biomed Res Int, 2020]

Protein-protein interactions (PPIs) are important for almost all cellular processes, including metabolic cycles, DNA transcription and replication, and signaling cascades. The experimental methods for identifying PPIs are always time-consuming and expensive. Therefore, it is important to develop computational approaches for predicting PPIs. In this paper, an improved model is proposed to use a machine learning method in the study of protein-protein interactions. With the consideration of the factors affecting the prediction of the PPIs, a method of feature extraction and fusion is proposed to improve the variety of the features to be considered in the prediction. Besides, with the consideration of the effect affected by the different input order of the two proteins, we propose a "Y-type" Bi-RNN model and train the network by using a method which both needs backward and forward training. In order to insure the training time caused on the extra training either a backward one or a forward one, this paper proposes a weight-sharing policy to minimize the parameters in the training. The experimental results show that the proposed method can achieve an accuracy of 99.57%, recall of 99.36%, sensitivity of 99.76%, precision of 99.74%, MCC of 99.14%, and AUC of 99.56% under the benchmark dataset.

Yang L et al. (2005) Development "The roles of two C. elegans HOX co-factor orthologs in cell migration and vulva development."

Sym M, Yang L, Kenyon C

[Development, 2005]

Anteroposterior cell migration and patterning in C. elegans are governed by multiple, interacting signaling pathways and transcription factors. In this study, we have investigated the role of ceh-20, the C. elegans ortholog of the HOX co-factor Extradenticle (Exd/Pbx), and unc-62, the C. elegans ortholog of Homothorax (Hth/Meis/Prep), in two processes that are regulated by Hox gene lin-39: cell migration and vulva formation. As in lin-39 mutants, the anterior migrations of neuroblasts in the Q lineage are truncated in Hox co-factor mutants. Surprisingly, though, our findings suggested that the roles of ceh-20 and unc-62 are different from that of lin-39; specifically, ceh-20 and unc-62 but not lin-39 are required for the transmembrane protein MIG-13 to promote anterior migration. To our knowledge, ceh-20 and unc-62 are the only genes that have been implicated in the mig-13 pathway. We find that ceh-20 and unc-62 are also required for several steps in vulva development. Surprisingly, ceh-20 and unc-62 mutants have phenotypes that are starkly different from those of lin-39 mutants. Thus, in this process, too, ceh-20 and unc-62 are likely to have functions that are independent of lin-39.

Yang L et al. (1998) West Coast Worm Meeting "Two new genes required for positioning QR descendants along the anterior-posterior body axis"

Kenyon CJ, Yang L

[West Coast Worm Meeting, 1998]

The QL and QR neuroblasts, which are born as bilaterally symmetric left/right homologs in the posterior of the worm, generate identical cell lineages. During the first larval stage, the descendants of QR migrate anteriorly whereas those of QL migrate posteriorly. One gene required for the anterior migration of the QR lineage which gives rise to SDQR and AVM, but not for the posterior migration of the QL lineage which gives rise to SDQL and PVM, is mig-13. This gene was cloned and characterized in our lab by Mary Sym (unpublished). mig-13 encodes a transmembrane protein that acts outside of the Q cells to promote anterior cell migrations. To further understand the regulation of anterior cell migration, we are studying two mutants with altered QR descendant migrations, mu232 and mu290. These mutants were isolated in two recent screens for Q cell migration mutants conducted in our lab by Queelim Ch'ng and Mary Sym. In these two mutants, as in mig-13 mutants, SDQR and AVM (which are normally found in the anterior body region) are found just anterior to the birthplace of QR whereas the final positions of SDQL and PVM are unaffected. In addition, like mig-13 mutants, the QR descendant AQR (which is normally found in the head) can be found anywhere along the anterior-posterior axis, suggesting that these genes are not required for motility but are required for positioning these cells. Thus, these new genes are candidates for components of a signalling pathway involving mig-13. We have mapped mu232 and mu290 to chromosomes V and III, respectively. Further mapping and additional phenotypic analysis are in progress.

Yang L et al. (2021) Food Funct "Pyrroloquinoline quinone extends Caenorhabditis elegans' longevity through the insulin/IGF1 signaling pathway-mediated activation of autophagy."

Wang M, Li K, Zhang Q, Ye Q, Luo S, Shi L, Liang X, Zhang X, Yang L

[Food Funct, 2021]

Aging is the leading cause of human morbidity and death worldwide. Pyrroloquinoline quinone (PQQ) is a water-soluble vitamin-like compound that has strong anti-oxidant capacity. Beneficial effects of PQQ on lifespan have been discovered in the model organism <i>Caenorhabditis elegans</i> (<i>C. elegans</i>), yet the underlying mechanisms remain unclear. In the current study, we hypothesized that the longevity-extending effect of PQQ may be linked to autophagy and insulin/IGF1 signaling (IIS) in <i>C. elegans.</i> Our data demonstrate that PQQ at a concentration of 1 mM maximally extended the mean life of <i>C. elegans</i> by 33.1%. PQQ increased locomotion and anti-stress ability, and reduced fat accumulation and reactive oxygen species (ROS) levels. There was no significant lifespan extension in PQQ-treated <i>daf-16</i>, <i>daf-2</i>, and <i>bec-1</i> mutants, suggesting that these IIS- and autophagy-related genes may mediate the anti-aging effects of the PQQ. Furthermore, PQQ raised mRNA expression and the nuclear localization of the pivotal transcription factor <i>daf-16</i>, and then activated its downstream targets <i>sod-3</i>, <i>clt-1</i>, and <i>hsp16.2</i>. Enhanced activity of the autophagy pathway was also observed in PQQ-fed <i>C. elegans</i>, as evidenced by increased expression of the key autophagy genes including <i>lgg-1</i>, and <i>bec-1</i>, and also by an increase in the GFP::LGG-1 puncta. Inactivation of the IIS pathway-related genes <i>daf-2</i> or <i>daf-16</i> by RNAi partially blocked the increase in autophagy activity caused by PQQ treatment, suggesting that autophagy may be regulated by IIS. This study demonstrates that anti-aging properties of PQQ, in the <i>C. elegans</i> model, may be mediated <i>via</i> the IIS pathway and autophagy.

(2017) Toxicol Sci "4-Bromodiphenyl Ether Induces Germ Cell Apoptosis by Induction of ROS and DNA Damage in Caenorhabditis elegans."

[Toxicol Sci, 2017]

The corresponding authorship has been updated to reflect Yang Luan and Jinfu Zhango as co-corresponding authors in the final version.

Fechner S et al. (2018) MicroPubl Biol "The bodies of dpy-10(e128) are twice as stiff as wild type"

Loizeau F, Pruitt B, Nekimken AL, Goodman MB, Fechner S

[MicroPubl Biol, 2018]

DPY-10 is a collagen protein in the nematodes cuticle. Mutations in the dpy-10 gene induce various morphological changes that lead to animals with a dumpy (Dpy) or roller (Rol) phenotype (Levy, Yang and Kramer, 1993).

Hunter CP et al. (1991) International C. elegans Meeting "NON-AUTONOMY OF HER-1 FUNCTION IMPLICATES CELL INTERACTIONS IN C. ELEGANS SEX DETERMINATION."

Hunter CP, Wood WB

[International C. elegans Meeting, 1991]

Activity of the her-l gene is required for normal male development in C. elegans. Loss-of-function her-l mutations cause feminization of XO animals (normally male) to produce fertile hermaphrodites, while gain-of-function her-l mutations cause masculinization of XX animals ( normally hermaphrodite) to produce pseudo-males. Genetic analysis indicated that her-l functions early in the hierarchy of regulatory interactions among the major sex determination genes (1). We have analyzed her-l genetic mosaics to determine which cells must express her-l for wild-type male development. If her-l functions cell- autonomously, then in XO animals her-l (+) cells will follow male fates, and her-1(-) cells will follow hermaphrodite fates. If her-l or a her-l regulated activity functions non-autonomously, then the her-l genotype of a cell may not determine its sexual phenotype. The phenotypes of XO her-l genetic mosaics are variable, but clearly show that both her-1(-) and her-l (+) cells can follow either hermaphrodite or male fates. We conclude that her-l is neither necessary nor sufficient to cell-autonomously determine male sexual phenotypes and, therefore, that her-l or a her-l regulated activity must be able to function non-autonomously. The observed patterns of non-autonomous effects suggest that many or all cells express and respond to her-l activity. These findings implicate cell interactions in C. elegans sex determination. Earlier genetic analysis indicated that her-l might directly control tra-2 activity (1). Molecular characterization of the gene products of her-l and tra-2 (see abstracts by M. Perry et al. and P. Kuwabara et al) is consistent with a model in which a secreted ligand encoded by her-l interacts with a cell-surface receptor encoded by tra-2. We will discuss the possible role of such an interaction in coordinating the sex determination decision.

Forrester S et al. (2007) Foodborne Pathog Dis "Evaluation of the pathogenicity of Listeria spp. in Caenorhabditis elegans."

Schwab U, Wiedmann M, Hoose WA, Milillo SR, Forrester S

[Foodborne Pathog Dis, 2007]

Caenorhabditis has proven to be a useful model for studying host-pathogen interactions as well as the ability of nematodes to serve as vectors for the dispersal of foodborne pathogens. In this study, we evaluated whether C. elegans can serve as a host for Listeria spp. While there was an effect of growth media on C. elegans killing, C. elegans exposed to L. monocytogenes and L. innocua pregrown in Luria-Bertani medium showed reduced survival when compared to nonpathogenic E. coli OP50, while L. seeligeri showed survival similar to E. coli OP50. In a preference assay, C. elegans preferred E. coli over L. monocytogenes and L. innocua, but showed no preference between L. monocytogenes and L. innocua. A gentamicin assay indicated that L. monocytogenes did not persist within the C. elegans intestinal tract. Our findings that L. monocytogenes and L. innocua strains tested have equally deleterious effects on C. elegans and that L. monocytogenes did not establish intestinal infection conflict with other recently published results, which found intestinal infection and killing of C. elegans by L. monocytogenes. Further studies are thus needed to clarify the interactions between L. monocytogenes and C. elegans, including effects of environmental conditions and strain differences on killing and intestinal infection.