Nawa Y et al. (1982) J Parasitol "Stage-specific cross-resistance between Nippostrongylus brasiliensis and Strongyloides ratti (Nematoda) in rats."

Tada I, Mimori T, Nawa Y, Korenaga M

[J Parasitol, 1982]

Stage-specificity of cross-resistance between Nippostrongylus brasiliensis and Strongyloides ratti was investigated. Results showed that immunization with tissue-migrating larvae was sufficient to generate cross-resistance and that host defense mechanisms operating in the cross-resistance were directed against tissue-migrating larvae but not against intestinal adult worms. In addition, no significant potentiation of the cross-resistance was observed after multiple immunization. These observations suggest that host defense mechanisms against heterologous challenge infection were qualitatively and/or quantitatively different from those against homologous challenge infection.

Nawa Y et al. (1985) Parasite Immunol "Defective protective capacity of W/Wv mice against Strongyloides ratti infection and its reconstitution with bone marrow cells."

Kotani M, Nawa Y, Kiyota M, Korenaga M

[Parasite Immunol, 1985]

The susceptibility of congenitally anemic, and mast cell deficient W/Wv mice to infection with Strongyloides ratti was examined. After a primary infection, W/Wv mice showed greater and more persistent peak larval counts than did normal littermates. Worm expulsion was also slower in W/Wv mice than in +/+ mice. Furthermore, difference in susceptibility was expressed as early as 24 h after infection, suggesting not only that protective mechanisms of the gut but also of the connective tissue were defective in W/Wv mice. Reconstitution with bone marrow or spleen cells from +/+ mice was effective in restoring the protective response in W/Wv mice, whereas thymocytes or mesenteric lymph nodes had no effect. Both connective tissue and mucosal mast cells were repaired in W/Wv mice after marrow reconstitution and infection. Since relatively long incubation period was required for the expression of such reconstituting activities, bone marrow cells seem to contain precursor cells of the effector and/or regulator cells.

Nawa Y et al. (1988) Parasite Immunol "Impaired natural defence of beige (Chediak-Higashi syndrome) mice against tissue-migrating larvae of Strongyloides ratti and its reconstitution by bone marrow cells."

Nawa Y, Abe T, Imai J, Maruyama H

[Parasite Immunol, 1988]

The susceptibility of C57BL/6-bgJ/bgJ mice, which exhibit a murine counterpart of the Chediak-Higashi syndrome, to infection with Strongyloides ratti was examined. After a primary infection, the peak of the daily larval output in faeces (LPG) of bgJ/bgJ mice was approximately twice as high as that of their littermate bgJ/+mice. The total number of tissue migrating larvae recovered from bgJ/bgJ mice at 36 h after infection was also approximately twice as high as that from bgJ/+mice. However, after a primary infection, bgJ/bgJ mice could completely expel adult worms in the intestine by day 14. When an equal number of tissue migrating larvae obtained from the head of +/+ mice were implanted into bgJ/bgJ and bgJ/+mice, the magnitude and the kinetics of LPG were comparable between them, indicating that in both groups implanted larvae established in the intestine to become adult worms and then they were expelled by day 13. Thus, immune mechanisms involved in worm expulsion of bgJ/bgJ mice were comparable to those of bgJ/+mice. The higher susceptibility of bgJ/bgJ mice could be reduced to the level of bgJ/+mice by bone marrow grafting from bgJ/+mice 6 weeks prior to infection. Furthermore, when lethally irradiated bgJ/bgJ mice or bgJ/+mice were reconstituted with either type of bone marrow cells, the mice given bgJ/bgJ bone marrow cells showed higher susceptibility to infection with S. ratti regardless of the genotype of the recipients. These results indicate that the impaired natural defence of bgJ/bgJ mice is predetermined at the level of haemopoietic stem cells.

Perreault J et al. (2007) Mol Biol Evol "Ro-associated Y RNAs in metazoans: evolution and diversification."

Perreault J, Perreault JP, Boire G

[Mol Biol Evol, 2007]

The Y genes encode small non-coding RNAs whose functions remain elusive, whose numbers vary between species, and whose major property is to be bound by the Ro60 protein (or its ortholog in other species). To better understand the evolution of the Y gene family, we performed a homology search in 27 different genomes along with a structural search using Y RNA specific motifs. These searches confirmed that Y RNAs are well conserved in the animal kingdom and resulted in the detection of several new Y RNA genes, including the first Y RNAs in insects and a second Y RNA detected in Caenorhabditis elegans. Unexpectedly, Y5 genes were retrieved almost as frequently as Y1 and Y3 genes, and, consequently are not the result of a relatively recent apparition as is generally believed. Investigation of the organization of the Y genes demonstrated that the synteny was conserved among species. Interestingly, it revealed the presence of six putative "fossil" Y genes, all of which were Y4 and Y5 related. Sequence analysis led to inference of the ancestral sequences for all Y RNAs. In addition, the evolution of existing Y RNAs was deduced for many families, orders and classes. Moreover, a consensus sequence and secondary structure for each Y species was determined. Further evolutionary insight was obtained from the analysis of several thousand Y retropseudogenes among various species. Taken together, these results confirm the rich and diversified evolution history of Y RNAs.

Gardiner TJ et al. (2009) RNA "A conserved motif of vertebrate Y RNAs essential for chromosomal DNA replication."

Langley AR, Gardiner TJ, Krude T, Christov CP

[RNA, 2009]

Noncoding Y RNAs are required for the reconstitution of chromosomal DNA replication in late G1 phase template nuclei in a human cell-free system. Y RNA genes are present in all vertebrates and in some isolated nonvertebrates, but the conservation of Y RNA function and key determinants for its function are unknown. Here, we identify a determinant of Y RNA function in DNA replication, which is conserved throughout vertebrate evolution. Vertebrate Y RNAs are able to reconstitute chromosomal DNA replication in the human cell-free DNA replication system, but nonvertebrate Y RNAs are not. A conserved nucleotide sequence motif in the double-stranded stem of vertebrate Y RNAs correlates with Y RNA function. A functional screen of human Y1 RNA mutants identified this conserved motif as an essential determinant for reconstituting DNA replication in vitro. Double-stranded RNA oligonucleotides comprising this RNA motif are sufficient to reconstitute DNA replication, but corresponding DNA or random sequence RNA oligonucleotides are not. In intact cells, wild-type hY1 or the conserved RNA duplex can rescue an inhibition of DNA replication after RNA interference against hY3 RNA. Therefore, we have identified a new RNA motif that is conserved in vertebrate Y RNA evolution, and essential and sufficient for Y RNA function in human chromosomal DNA replication.

Abe T et al. (1987) Parasite Immunol "Localization of mucosal mast cells in W/Wv mice after reconstitution with bone marrow cells or cultured mast cells, and its relation to the protective capacity to Strongyloides ratti infection."

Nawa Y, Abe T

[Parasite Immunol, 1987]

Localization of mast cells in the intestinal epithelium, villous lamina propria and basal lamina propria of mast cell-deficient WBB6F1 (W/Wv) mice reconstituted with either bone marrow cells or with cultured mast cells (BMMC) was compared to that of mast cell-sufficient C57BL/6 or C57BL/6-bgj/bgj (beige) mice after infection with Strongyloides ratti. In mast cell-sufficient C57BL/6 or beige mice, the maximum number of intestinal mucosal mast cells (MMC) was more than 160 MMC/10 villus crypt units (VCU) and more than 90% of MMC were located in the intestinal epithelium. When W/Wv mice were reconstituted with bone marrow cells of beige mice, worm expulsion was hastened and the MMC response became comparable to that of mast cell-sufficient mice in terms of cell numbers and their intra-epithelial localization. On the other hand, when W/Wv mice were reconstituted with BMMC of beige mice, only a few donor type MMC were detected in the intestine. The proportion of intra-epithelial MMC was lower than that of mast cell-sufficient mice or of marrow-reconstituted W/Wv mice. Even repeated injection of BMMC could not fully restore the number of intra-epithelial MMC to the level of that observed in mast cell-sufficient mice. Since mast cell-growth factor-producing activity of W/Wv mice was comparable to that of mast cell-sufficient mice, the ineffectiveness of BMMC-transfer in restoring protective activity or MMC responses in W/Wv mice seems to be attributed to the functional immaturity or inactivity of BMMC.

Abe T et al. (1988) Immunology "Worm expulsion and mucosal mast cell response induced by repetitive IL-3 administration in Strongyloides ratti-infected nude mice."

Abe T, Nawa Y

[Immunology, 1988]

After a primary infection of congenitally athymic nu/nu mice with Strongyloides ratti, worms were not expelled and the number of intestinal mucosal mast cells (MMC) remained at a low level. When S. ratti-infected nu/nu mice were treated by repetitive injections of semi-purified IL-3 from Day 5 to Day 10 post-infection (total 1.4 X 10(5) U), significant reduction of larval excretion in faeces (LPG) was observed on Day 13. The number of adult worms in the small intestine of IL-3-treated mice was significantly lower than that of untreated, infected nude mice. The higher dose of IL-3 treatment from Day 4 to Day 13 (total 5.8 X 10(5) U) caused more profound reduction of LPG as early as Day 9, although complete cessation of LPG was not observed until Day 13, the end of this series of experiments. By this higher dose of IL-3 treatment, adult worms were completely expelled from the small intestine, although a small number of residual worms, which could explain the persistent low level of LPG detected from Day 9 to Day 13, was found in the caecum. Histological examination revealed that the number of MMC, especially in the epithelium, of the small intestine of IL-3-treated mice was significantly higher than that of untreated mice.

Abe T et al. (1987) Parasite Immunol "Reconstitution of mucosal mast cells in W/WV mice by adoptive transfer of bone marrow-derived cultured mast cells and its effects on the protective capacity to Strongyloides ratti-infection."

Abe T, Nawa Y

[Parasite Immunol, 1987]

Bone marrow-derived cultured mast cells (BMMC) were transferred intravenously into W/WV mice to examine if they could reconstitute defective mucosal mast cell response or defective protective capacity against infection with Strongyloides ratti. When mast cell growth factor-producing activity of W/WV mice were examined, mesenteric lymph node cells obtained at 7 to 14 days after infection could produce this factor in vitro by stimulation with S. ratti-adult worm antigen. A single injection of BMMC (1 X 10(7] on day 7 post-infection (p.i.) neither caused an increase in number of intestinal mucosal mast cells not altered the kinetics of faecal larval output (LPG). On the other hand, serial injections of BMMC (5 X 10(6] from day 5 to 10 p.i. (total 3 X 10(7) cells) resulted in the significant increase in number of intestinal mucosal mast cells. However, this treatment too could not alter the kinetics of LPG. Therefore, adoptive transfer of BMMC could cause the increase in number of histologically detectable-mucosal mast cells, but these cells are, by themselves, not sufficient to cause the expulsion of S. ratti adult worms from the intestine.

Abe T et al. (1988) Parasitol Res "Kinetic study of mast-cell growth factor production by lymphocytes during the course of Strongyloides ratti infection in mice."

Nawa Y, Abe T

[Parasitol Res, 1988]

Mast-cell growth factor (MCGF) activity in the media conditioned by mesenteric lymph node or spleen cells from Strongyloides ratti-infected C57BL/6 mice was examined by using factor-dependent cell line FDC-P2 or bone marrow-derived, cultured mast cells (BMMC) as indicators. Mesenteric lymph node cells from infected mice spontaneously released MCGF activity by culturing for 24 h, showing peak production on days 5-7. MCGF production by mesenteric lymph node cells was augmented after stimulation with adult worm antigen or with concanavalin A (con A). The peak of MCGF production by antigen-stimulated lymph node cells was observed on days 5-7 and declined thereafter. MCGF production by antigen-stimulated spleen cells was lower than that by lymph node cells and reached a peak on day 7 or later. Normal lymph node or spleen cells did not produce MCGF activity even after stimulation with adult worm antigen. The peak of MCGF production by mesenteric lymph node cells preceded the peak of intestinal mastocytosis at the infected site by 4-6 days. The cells producing MCGF had a phenotype of Thy-1+, L3T4+, and Lyt-2-. The possible importance of mucosal mast cells in worm expulsion is discussed.

Erickson DL et al. (2006) J Bacteriol "Serotype differences and lack of biofilm formation characterize Yersinia pseudotuberculosis infection of the Xenopsylla cheopis flea vector of Yersinia pestis."

Hinnebusch BJ, Erickson DL, Wren BW, Jarrett CO

[J Bacteriol, 2006]

Yersinia pestis, the agent of plague, is usually transmitted by fleas. To produce a transmissible infection, Y. pestis colonizes the flea midgut and forms a biofilm in the proventricular valve, which blocks normal blood feeding. The enteropathogen Yersinia pseudotuberculosis, from which Y. pestis recently evolved, is not transmitted by fleas. However, both Y. pestis and Y. pseudotuberculosis form biofilms that adhere to the external mouthparts and block feeding of Caenorhabditis elegans nematodes, which has been proposed as a model of Y. pestis-flea interactions. We compared the ability of Y. pestis and Y. pseudotuberculosis to infect the rat flea Xenopsylla cheopis and to produce biofilms in the flea and in vitro. Five of 18 Y. pseudotuberculosis strains, encompassing seven serotypes, including all three serotype O3 strains tested, were unable to stably colonize the flea midgut. The other strains persisted in the flea midgut for 4 weeks but did not increase in numbers, and none of the 18 strains colonized the proventriculus or produced a biofilm in the flea. Y. pseudotuberculosis strains also varied greatly in their ability to produce biofilms in vitro, but there was no correlation between biofilm phenotype in vitro or on the surface of C. elegans and the ability to colonize or block fleas. Our results support a model in which a genetic change in the Y. pseudotuberculosis progenitor of Y. pestis extended its pre-existing ex vivo biofilm-forming ability to the flea gut environment, thus enabling proventricular blockage and efficient flea-borne transmission.