Li YH et al. (2010) Mech Ageing Dev "Systematic analysis and prediction of longevity genes in Caenorhabditis elegans."

Guo Z, Li YH, Dong MQ

[Mech Ageing Dev, 2010]

An important task of aging research is to find genes that regulate lifespan. However, identification of genes related to longevity (referred to as longevity genes hereafter) through web-lab experiments such as genetic screens is a tedious and labor-intensive activity. Developing an algorithm to predict longevity genes should facilitate aging research. In this paper, we systematically analyzed properties of longevity genes in Caenorhabditis elegans and found that, when compared to genes not yet known to be involved in longevity, known longevity genes display the following features: (i) longer genomic sequences and protein sequences, (ii) a stronger tendency to co-express with other genes during a transition from dauer state (an extremely long lifespan) to non-dauer state (a normal lifespan), (iii) significant enrichment in certain functions and RNAi phenotypes, (iv) higher sequence conservation, and (v) higher in several network topological features such as degrees in a functional interaction network. Based on these features, we developed an algorithm to predict longevity genes in C. elegans and obtained 243 novel longevity genes with a precision rate of 0.85. Some of the predicted genes have been validated by published articles or wet lab experiments. The contribution of each feature to the predicted results was also evaluated.

Li YH et al. (2016) Oncotarget "Towards understanding the lifespan extension by reduced insulin signaling: bioinformatics analysis of DAF-16/FOXO direct targets in Caenorhabditis elegans."

Li YH, Zhang GG

[Oncotarget, 2016]

DAF-16, the C. elegans FOXO transcription factor, is an important determinant in aging and longevity. In this work, we manually curated FOXODB (http://lyh.pkmu.cn/foxodb/), a database of FOXO direct targets. It now covers 208 genes. Bioinformatics analysis on 109 DAF-16 direct targets in C. elegans found interesting results. (i) DAF-16 and transcription factor PQM-1 co-regulate some targets. (ii) Seventeen targets directly regulate lifespan. (iii) Four targets are involved in lifespan extension induced by dietary restriction. And (iv) DAF-16 direct targets might play global roles in lifespan regulation.

Gopal E et al. (2015) J Pharmacol Exp Ther "Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates."

Ganapathy V, Ramachandran S, Gopal E, Babu E, Prasad PD, Bhutia YD

[J Pharmacol Exp Ther, 2015]

NaCT (SLC13A5) is a Na(+)-coupled transporter for Krebs cycle intermediates and is expressed predominantly in the liver. Human NaCT is relatively specific for citrate compared with other Krebs cycle intermediates. The transport activity of human NaCT is stimulated by Li(+), whereas that of rat NaCT is inhibited by Li(+). We studied the influence of Li(+) on NaCTs cloned from eight different species. Li(+) stimulated the activity of only NaCTs from primates (human, chimpanzee, and monkey); by contrast, NaCTs from nonprimate species (mouse, rat, dog, and zebrafish) were inhibited by Li(+). Caenorhabditis elegans NaCT was not affected by Li(+). With human NaCT, the Li(+)-induced increase in transport activity was associated with the conversion of the transporter from a low-affinity/high-capacity type to a high-affinity/low-capacity type. H(+) was able to substitute for Li(+) in eliciting the stimulatory effect. The amino acid Phe500 in human NaCT was critical for Li(+)/H(+)-induced stimulation. Mutation of this amino acid to tryptophan (F500W) markedly increased the basal transport activity of human NaCT in the absence of Li(+), but the ability of Li(+) to stimulate the transporter was almost completely lost with this mutant. Substitution of Phe500 with tryptophan in human NaCT converted the transporter from a low-affinity/high-capacity type to a high-affinity/low-capacity type, an effect similar to that of Li(+) on the wild-type NaCT. These studies show that Li(+)-induced activation of NaCT is specific for the transporter in primates and that the region surrounding Phe500 in primate NaCTs is important for the Li(+) effect.

Inokuchi A et al. (2015) J Appl Toxicol "Effects of lithium on growth, maturation, reproduction and gene expression in the nematode Caenorhabditis elegans."

Matsusaki H, Yamamoto R, Takumi S, Morita F, Inokuchi A, Arizono K, Tominaga N, Ishibashi H

[J Appl Toxicol, 2015]

Lithium (Li) has been widely used to treat bipolar disorder, and industrial use of Li has been increasing; thus, environmental pollution and ecological impacts of Li have become a concern. This study was conducted to clarify the potential biological effects of LiCl and Li(2)CO(3) on a nematode, Caenorhabditis elegans as a model system for evaluating soil contaminated with Li. Exposure of C. elegans to LiCl and Li(2)CO(3) decreased growth/maturation and reproduction. The lowest observed effect concentrations for growth, maturation and reproduction were 1250, 313 and 10 000m, respectively, for LiCl and 750, 750 and 3000m, respectively, for Li(2)CO(3). We also investigated the physiological function of LiCl and LiCO(3) in C. elegans using DNA microarray analysis as an eco-toxicogenomic approach. Among approximately 300 unique genes, including metabolic genes, the exposure to 78m LiCl downregulated the expression of 36 cytochrome P450, 16 ABC transporter, 10 glutathione S-transferase, 16 lipid metabolism and two vitellogenin genes. On the other hand, exposure to 375m Li(2)CO(3) downregulated the expression of 11 cytochrome P450, 13 ABC transporter, 13 lipid metabolism and one vitellogenin genes. No gene was upregulated by LiCl or Li(2)CO(3). These results suggest that LiCl and Li(2)CO(3) potentially affect the biological and physiological function in C. elegans associated with alteration of the gene expression such as metabolic genes. Our data also provide experimental support for the utility of toxicogenomics by integrating gene expression profiling into a toxicological study of an environmentally important organism such as C. elegans.

McColl G et al. (2008) J Biol Chem "Pharmacogenetic analysis of lithium-induced delayed aging in Caenorhabditis elegans."

Melov S, McColl G, Lithgow GJ, Vantipalli MC, Killilea DW, Hubbard AE

[J Biol Chem, 2008]

Lithium (Li+) has been used to treat mood affect disorders, including bipolar, for decades (1;2). This drug is neuroprotective and has several identified molecular targets. However, it has a narrow therapeutic range and the underlying mechanism(s) of its therapeutic action is not understood. Here we describe a pharmacogenetic study of Li+ in the nematode Caenorhabditis elegans. Exposure to Li+ at clinically relevant concentrations throughout adulthood increases survival during normal aging (up to 46% median increase). Longevity is extended via a novel mechanism with altered expression of genes encoding nucleosome-associated functions. Li+ treatment results in reduced expression of the worm ortholog of LSD-1 (T08D10.2), a histone demethylase; knockdown by RNA interference (RNAi) of T08D10.2 is sufficient to extend longevity (~25% median increase), suggesting Li+ regulates survival by modulating histone methylation and chromatin structure.

Wu H et al. (1991) Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi "[Studies on dynamic of antibodies detected in sera from jirds infected with Brugia malayi before and after treatment]."

Wu H, Li YH

[Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi, 1991]

Indirect immunofluorescent antibody test (IFAT) and immunoenzymatic staining technique (IEST), using frozen section of Brugia malayi and Setaria cervi adult worms, were applied to detect levels of IgG and IgM antibodies in jirds infected with Brugia malayi before and after treatment. Both methods could show the dynamic of antibodies during the course of infection. The peak of IgG and IgM antibodies were at the 12-14th week and 2-6th week after infection respectively. A high correlation was observed between the levels of IgG antibody and the period of infection, whereas the antibody titer had no relation with the density of infection. During 6 months after treatment, the levels of antibodies detected by IFAT and IEST using two antigens decreased to low titre. It is considered that IFAT and IEST using heterologous and homologous antigens could be equally used for the serodiagnosis and the evaluation of cure in filariasis.

Palty R et al. (2004) J Biol Chem "Lithium-calcium exchange is mediated by a distinct potassium-independent sodium-calcium exchanger."

Ohana E, Argaman M, Palty R, Beharier O, Silverman WF, Hershfinkel M, Elgazar V, Volokita M, Sekler I

[J Biol Chem, 2004]

Sodium-calcium exchangers have long been considered inert with respect to monovalent cations such as lithium, choline, and N-methyl-d-glucamine. A key question that has remained unsolved is how despite this, Li(+) catalyzes calcium exchange in mammalian tissues. Here we report that a Na(+)/Ca(2+) exchanger, NCLX cloned from human cells (known as FLJ22233), is distinct from both known forms of the exchanger, NCX and NCKX in structure and kinetics. Surprisingly, NCLX catalyzes active Li(+)/Ca(2+) exchange, thereby explaining the exchange of these ions in mammalian tissues. The NCLX protein, detected as both 70- and 55-KDa polypeptides, is highly expressed in rat pancreas, skeletal muscle, and stomach. We demonstrate, moreover, that NCLX is a K(+)-independent exchanger that catalyzes Ca(2+) flux at a rate comparable with NCX1 but without promoting Na(+)/Ba(2+) exchange. The activity of NCLX is strongly inhibited by zinc, although it does not transport this cation. NCLX activity is only partially inhibited by the NCX inhibitor, KB-R7943. Our results provide a cogent explanation for a fundamental question. How can Li(+) promote Ca(2+) exchange whereas the known exchangers are inert to Li(+) ions? Identification of this novel member of the Na(+)/Ca(2+) superfamily, with distinct characteristics, including the ability to transport Li(+), may provide an explanation for this phenomenon.

Wu H et al. (1990) Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi "[Studies on dynamics of antibodies in sera from rabbits immunized with homologous and heterologous adult filarial antigens]."

Wu H, Li YH

[Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi, 1990]

The indirect immunofluorescent antibody test (IFAT) and immunoenzymatic staining technique (IEST) with frozen sections of Brugia malayi and Setaria cervi adult worms as antigens were used to detect IgG levels in rabbits immunized with three different filarial antigens. The results showed the dynamics of the specific IgG antibody in the course of immunization. The peaks (GMRT 76.11-861.08) of IgG levels in immunized rabbits appeared at the 4th week after primary immunization, which returned to (4.00-32.0 up to the 8th week after primary immunization and rose to (20.11-181.02) at the 1st week after second immunization. It is suggested that IFAT and IEST, especially the latter, can be applied for serodiagnosis of filarial infection and both antigens are considered to be of similar diagnostic effect.

Sun Y et al. (2024) J Cell Biol "A RAB transition orchestrates membrane trafficking in unconventional protein secretion."

Sun Y, Ge L, Zhang M

[J Cell Biol, 2024]

Rab GTPases function as intracellular molecular switches that regulate vesicular transport. In the current issue, Li et al. (https://doi.org/10.1083/jcb.202306107) revealed RAB-8 to RAB-11 transition governing the unconventional secretion of membrane proteins in the intestinal epithelium of C. elegans.

Li T et al. (2022) STAR Protoc "Live imaging of postembryonic developmental processes in C.elegans."

Wang X, Zou Y, Li T, Feng Z

[STAR Protoc, 2022]

Live imaging is an important tool to track dynamic processes such as neuronal patterning events. Here, we describe a protocol for time-lapse microscopy analysis using neuronal migration and dendritic growth as examples. This protocol can provide detailed information for understanding cellular dynamics during postembryonic development in Caenorhabditis elegans (C. elegans). For complete details on the use and execution of this protocol, please refer to Feng etal. (2020), Li etal. (2021), and Wang etal. (2021).