Fan PC et al. (1985) Southeast Asian J Trop Med Public Health "Experimental infection of subperiodic Brugia malayi in laboratory rats with emphasis on evaluation by four techniques."

Hsu YP, Wu CC, Ho CM, Fan PC, Huang CM

[Southeast Asian J Trop Med Public Health, 1985]

Infective larvae of subperiodic B. malayi from South Kalimantan (Borneo), Indonesia collected from laboratory-raised Ae. togoi mosquitoes after feeding on infected mongolian gerbils (Meriones unguiculatus) were inoculated subcutaneously into the groin areas of 15 SD and 36 LE rats. Blood was examined weekly by membrane filtration and thick smears starting 10 weeks post-infection. Microfilariae were found in 3 SD and 4 LE rats, the mf infection rate of 20% and 11% respectively. The prepatent period was significantly shorter in the SD rats (99-112 days) than those in the LE rats (110-153 days). The patent period was longer in the LE rats (208-703 days) than in the SD rats (236-543 days), and the mf density was similar (17.5 mf/20 c.mm blood against 16 mf/20 c.mm blood). At necropsy, 6 (3 female and 3 male) adult worms were recovered from 3 of 6 SD rats and 12 (9 female and 3 male) adult worms from 4 of 20 LE rats; all worms were found in the testes. The results of xenodiagnostic, histochemical staining and measuring spicules and protuberances, demonstrated clearly the difference between both species of Brugia. All dissected Ar. subalbatus mosquitoes exposed to B. pahangi became infected (100%), but none of those to subperiodic B. malayi were infected (0%). The mf of both species of Brugia in thick films stained with naphthol-AS-TR-phosphate showed that the excretory and anal pores of subperiodic B. malayi mf exhibited acid phosphatase activity and only a little activity was seen in other parts; while B. pahangi mf showed heavy diffuse acid phosphatase activity along the entire length of the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Snodgrass CJ et al. (2015) Glycobiology "Conserved ion and amino acid transporters identified as phosphorylcholine-modified N-glycoproteins by metabolic labeling with propargylcholine in Caenorhabditis elegans cells."

Meteer JC, Snodgrass CJ, Burnham-Marusich AR, Berninsone PM

[Glycobiology, 2015]

Phosphorylcholine (PC) modification of proteins by pathogens has been implicated in mediating host-pathogen interactions. Parasitic nematodes synthesize PC-modified biomolecules that can modulate the host's antibody and cytokine production to favor nematode survival, contributing to long-term infections. Only two nematode PC-modified proteins (PC-proteins) have been unequivocally identified, yet discovering the protein targets of PC modification will be paramount to understanding the role(s) that this epitope plays in nematode biology. A major hurdle in the field has been the lack of techniques for selective purification of PC-proteins. The nonparasitic nematode Caenorhabditis elegans expresses PC-modified N-linked glycans, offering an attractive model to study the biology of PC-modification. We developed a robust method to identify PC-proteins by metabolic labeling of primary embryonic C. elegans cells with propargylcholine, an alkyne-modified choline analog. Cu(I)-catalyzed cycloaddition with biotin-azide enables streptavidin purification and subsequent high-throughput LC-MS identification of propargyl-labeled proteins. All proteins identified using stringent criteria are known or predicted to be membrane or secreted proteins, consistent with the model of a Golgi-resident, putative PC-transferase. Of the 55 PC-N-glycosylation sites reported, 33 have been previously observed as N-glycosylation sites in high-throughput screens of C. elegans. Several identified PC-proteins are nematode-specific proteins, but 10 of the PC-proteins are widely conserved ion transporters and amino acid transporters, while eight are conserved proteins involved in synaptic function. This finding suggests a functional role for PC-modification beyond immunomodulation. The approach presented in this study provides a method to identify PC-proteins in C. elegans and related nematodes.

Sonani RR et al. (2017) Bioresour Technol "Purification and antioxidant activity of phycocyanin from Synechococcus sp. R42DM isolated from industrially polluted site."

Bhastana B, Singh NK, Patel S, Chaubey MG, Madamwar D, Sonani RR, Jakharia K

[Bioresour Technol, 2017]

The cyanobacterium Synechococcus sp. R42DM, isolated from an industrially polluted site Vatva, Gujarat, India was recognized to produce phycocyanin (PC) as major phycobiliprotein. In present study, the combinatorial approach of chemical and physical methods i.e. Triton-X 100 treatment and ultra-sonication was designed for extraction of PC. From cell extract, the intact and functional-PC was purified up to purity 4.03 by ammonium sulphate fractionation and ion-exchange chromatography. The PC displayed considerable in vitro antioxidant and radical-scavenging activity. This PC was further noticed to scavenge intracellular-ROS and to increase tolerance against thermal and oxidative stress in Caenorhabditis elegans. Moreover, the PC was noticed to improve the physiological behaviour and longevity of C. elegans. In addition, the PC showed remarkable stability under physico-chemical stressors, which is desirable for their use in biomedical applications. In conclusion, present paper added up evidence in support of the prospective use of PC as an antioxidant nutraceutical.

Sunagawa T et al. (2011) Planta Med "Procyanidins from apples (Malus pumila Mill.) extend the lifespan of Caenorhabditis elegans."

Shirasawa T, Tagashira M, Shimizu T, Sami M, Sunagawa T, Kanda T

[Planta Med, 2011]

Apple polyphenols (AP) mainly consist of procyanidins (PC), which are composed of (-)-epicatechins and (+)-catechins. In order to investigate the antiageing effects of PC, we measured the lifespan of CAENORHABDITIS ELEGANS worms treated with PC. Treatment with 65 g/mL PC extended the mean lifespan of wild-type N2 and FEM-1 worms by 12.1 % and 8.4 %, respectively, i.e., to a similar extent as resveratrol. In addition, treatment with 100 g/mL AP also significantly prolonged the mean lifespan of the same worms by 12.0 % and 5.3 %, respectively, i.e., to a similar extent as PC. In contrast, treatment with (-)-epicatechin did not extend the lifespan of the worms. PC did not modify the growth, food intake, or fecundity of C. elegans. Treatment with PC did not extend the lifespan of MEV-1 worms, which show excessive oxidative stress, indicating that PC had no antioxidant ability in the MEV-1 mutant. Moreover, treatment with PC had no effect on the longevity of SIR-2.1 worms, which lack the activity of SIR-2, a member of the sirtuin family of NAD (+)-dependent protein deacetylases. These results indicated that PC has SIR-2.1-dependent antiageing effects on C. elegans.

Li M et al. (2024) Nat Commun "Structural basis for C. elegans pairing center DNA binding specificity by the ZIM/HIM-8 family proteins."

Shi Y, Zhu C, Zhang Y, Han X, Wang S, Guang S, Hou X, Li F, Lv M, Xu M, Kuang Y, Liu Y, Xu Z, Huang X, Li M

[Nat Commun, 2024]

Pairing center (PC) on each chromosome of Caenorhabditis elegans is crucial for homolog pairing and initiating synapsis. Within each PC, clusters of 11/12 bp DNA motif recruit one of four paralogous meiosis-specific proteins: ZIM-1, ZIM-2, ZIM-3, or HIM-8. However, the mechanistic basis underlying the specificity of ZIM/HIM-8-PC DNA interaction remains elusive. Here, we describe crystal structures of HIM-8, ZIM-1 and ZIM-2 DNA binding domains (ZF1, ZF2 and CTD) in complex with their cognate PC DNA motifs, respectively. These structures demonstrated the ZF1-2-CTD folds as an integrated structural unit crucial for its DNA binding specificity. Base-specific DNA-contacting residues are exclusively distributed on ZF1-2 and highly conserved. Furthermore, the CTD potentially contributes to the conformational diversity of ZF1-2, imparting binding specificity to distinct PC DNA motifs. These findings shed light on the mechanism governing PC DNA motif recognition by ZIM/HIM-8 proteins, suggesting a co-evolution relationship between PC DNA motifs and ZF1-2-CTD in shaping the specific recognition.

Zhu J et al. (2023) J Genet Genomics "Phosphatidylcholine deficiency increases ferroptosis susceptibility in the C. elegans germline."

Man Lam S, Zhu J, Shui G, Huang X, Meng W

[J Genet Genomics, 2023]

Ferroptosis, a regulated and iron-dependent form of cell death characterized by peroxidation of membrane phospholipids, has tremendous potential for the therapy of human diseases. The causal link between phospholipid homeostasis and ferroptosis is incompletely understood. Here, we reveal that spin-4, a previously identified regulator of the "B12-one-carbon cycle-phosphatidylcholine (PC)" pathway, sustains germline development and fertility by ensuring PC sufficiency in the nematode Caenorhabditis elegans. Mechanistically, SPIN-4 regulates lysosomal activity which is required for B12-associated PC synthesis. PC deficiency-induced sterility can be rescued by reducing the levels of polyunsaturated fatty acids (PUFAs), reactive oxygen species (ROS) , and redox-active iron, which indicates that the sterility is mediated by germline ferroptosis. These results highlight the critical role of PC homeostasis in ferroptosis susceptibility and offer a new target for pharmacological approaches.

Nabeshima K (2012) Worm "Collaborative homologous pairing during C. elegans meiosis."

Nabeshima K

[Worm, 2012]

In preparation for meiotic chromosome segregation, homologous chromosomes need to pair, synapse (i.e., assemble the synaptonemal complex, SC), and then recombine to generate a physical linkage (i.e., chiasma) between them. In many organisms meiotic pairing capacity distributed along the entire chromosome length supports presynaptic alignment. In contrast, the prevailing model for C. elegans proposes that presynaptic homologous pairing is performed solely by a master pairing-site, the pairing center (PC). In this model, the remaining chromosomal regions (the non-PC regions) are not actively involved in presynaptic pairing, and the SC assembling from the PC aligns the homologous chromosomes along non-PC regions and holds them together. Our recent work, however, demonstrates that C. elegans chromosomes establish presynaptic alignment along the entire chromosome length, suggesting that the non-PC regions are also actively involved in the presynaptic pairing process. Furthermore, we have also discovered that the chromodomain protein MRG-1 facilitates this presynaptic non-PC pairing. The phenotype of the mrg-1 mutant indicates that the PC and the non-PC collaborate in successful pairing and synapsis. Therefore, homologous pairing mechanisms in C. elegans possibly share more similarity with those in other organisms than previously thought. Here, we elaborate on these observations and discuss a hypothetical model for presynaptic pairing in C. elegans based on our novel findings.

Dombecki CR et al. (2011) Dev Cell "The chromodomain protein MRG-1 facilitates SC-independent homologous pairing during meiosis in Caenorhabditis elegans."

Klerkx EP, Dombecki CR, Chiang AC, Kang HJ, Nabeshima K, Neva BJ, Bilgir C, Stefanski NA

[Dev Cell, 2011]

Homologous chromosome pairing is a prerequisite to establish physical linkage between homologs, which is critical for faithful chromosome segregation during meiosis I. The establishment of pairing is genetically separable from subsequent synapsis, defined as stabilization of pairing by the synaptonemal complex (SC). The underlying mechanism of presynaptic pairing is poorly understood. In the nematode Caenorhabditis elegans, a unique cis-acting element, the pairing center (PC), is essential for presynaptic pairing; however, it is not known whether and how the remainder of the chromosome contributes to presynaptic pairing. Here we report direct evidence for presynaptic pairing activity intrinsic to non-PC regions, which is facilitated by a conserved chromodomain protein, MRG-1. In mrg-1 loss-of-function mutants, pairing is compromised specifically in non-PC regions, leading to nonhomologous SC assembly. Our data support a model in which presynaptic alignment in non-PC regions collaborates with initial PC pairing to ensure correct homologous synapsis.

Pedersen M et al. (2020) Netw Neurosci "Reducing the influence of intramodular connectivity in participation coefficient."

Zalesky A, Omidvarnia A, Shine JM, Jackson GD, Pedersen M

[Netw Neurosci, 2020]

Both natural and engineered networks are often modular. Whether a network node interacts with only nodes from its own module or nodes from multiple modules provides insight into its functional role. The participation coefficient (<i>PC</i>) is typically used to measure this attribute, although its value also depends on the size and connectedness of the module it belongs to and may lead to nonintuitive identification of highly connected nodes. Here, we develop a normalized <i>PC</i> that reduces the influence of intramodular connectivity compared with the conventional <i>PC</i>. Using brain, <i>C. elegans</i>, airport, and simulated networks, we show that our measure of participation is not influenced by the size or connectedness of modules, while preserving conceptual and mathematical properties, of the classic formulation of <i>PC</i>. Unlike the conventional <i>PC</i>, we identify London and New York as high participators in the air traffic network and demonstrate stronger associations with working memory in human brain networks, yielding new insights into nodal participation across network modules.

Zhu J et al. (2022) Life Metab "Reduced phosphatidylcholine synthesis suppresses the embryonic lethality of seipin deficiency."

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

[Life Metab, 2022]

Seipin plays a vital role in lipid droplet homeostasis, and its deficiency causes congenital generalized lipodystrophy type II in humans. It is not known whether the physiological defects are all caused by cellular lipid droplet defects. Loss-of-function mutation of <i>seip-1</i>, the <i>Caenorhabditis elegans</i> seipin ortholog, causes embryonic lethality and lipid droplet abnormality. We uncover <i>nhr-114</i> and <i>spin-4</i> as two suppressors of <i>seip-1</i> embryonic lethality. Mechanistically, <i>nhr-114</i> and <i>spin-4</i> act in the "B12-one-carbon cycle-phosphatidylcholine (PC)" axis, and reducing PC synthesis suppresses the embryonic lethality of <i>seip-1</i> mutants. Conversely, PC deficiency enhances the lipid droplet abnormality of <i>seip-1</i> mutants. The suppression of <i>seip-1</i> embryonic lethality by PC reduction requires polyunsaturated fatty acid. In addition, the suppression is enhanced by the knockdown of phospholipid scramblase <i>epg-3</i>. Therefore, seipin and PC exhibit opposite actions in embryogenesis, while they function similarly in lipid droplet homeostasis. Our results demonstrate that seipin-mediated embryogenesis is independent of lipid droplet homeostasis.