Pearlman E et al. (2000) Parasite Immunol "Immune mechanisms in Onchocerca volvulus-mediated corneal disease (river blindness)."

Hall LR, Pearlman E

[Parasite Immunol, 2000]

Infection with the parasitic nematode Onchocerca volvulus can lead to severe visual impairment and blindness. In an effort to characterize the molecular basis for the inflammatory response in the cornea, we have developed a murine model for O. volvulus-mediated keratitis in which parasite antigens are injected into the corneal stroma of sensitized mice. This model reproduces the two main clinical features of human disease, corneal opacification and neovascularization. Histological analysis of corneas from these mice reveals a biphasic recruitment of neutrophils and eosinophils to the central cornea, along with a small, but persistent number of CD3+ cells. In this review, we present evidence that production of antigen-specific T cell and antibody responses are essential for development of O. volvulus keratitis, and we propose a sequence of molecular and cellular events that lead to migration of inflammatory cells to the cornea and to loss of corneal clarity.

Hall LR et al. (1999) Clin Microbiol Rev "Pathogenesis of onchocercal keratitis (River blindness)."

Pearlman E, Hall LR

[Clin Microbiol Rev, 1999]

Onchocerciasis is a major cause of blindness. Although the World Health Organization has been successful in reducing onchocerciasis as a public health problem in parts of West Africa, there remain an estimated 17 million people infected with Onchocerca volvulus, the parasite that causes this disease. Ocular pathology can be manifested in any part of the eye, although disease manifestations are frequently characterized as either posterior or anterior eye disease. This review focuses on onchocerca-mediated keratitis that results from an inflammatory response in the anterior portion of the eye and summarizes what is currently known about human disease. This review also describes studies with experimental models that have been established to determine the immunological mechanisms underlying interstitial keratitis. The pathogenesis of keratitis is thought to be due to the host inflammatory response to degenerating parasites in the eye; therefore, the primary clinical symptoms of onchocercal keratitis (corneal opacification and neovascularization) are induced after injection of soluble O. volvulus antigens into the corneal stroma. Experimental approaches have demonstrated an essential role for sensitized T helper cells and shown that cytokines can regulate the severity of keratitis by controlling recruitment of inflammatory cells into the cornea. Chemokines are also important in inflammatory cell recruitment to the cornea, and their role in onchocerciasis is being examined. Further understanding of the molecular basis of the development of onchocercal keratitis may lead to novel approaches to immunologically based intervention.

Ernst IM et al. (2013) Ageing Res Rev "Vitamin E supplementation and lifespan in model organisms."

Nikolai S, Rimbach G, Pallauf K, Ernst IM, Roeder T, Bendall JK, Paulsen L, Huebbe P

[Ageing Res Rev, 2013]

We have conducted a comprehensive literature review regarding the effect of vitamin E on lifespan in model organisms including single-cell organisms, rotifers, Caenorhabditis elegans, Drosophila melanogaster and laboratory rodents. We searched Pubmed and ISI Web of knowledge for studies up to 2011 using the terms "tocopherols", "tocotrienols", "lifespan" and "longevity" in the above mentioned model organisms. Twenty-four studies were included in the final analysis. While some studies suggest an increase in lifespan due to vitamin E, other studies did not observe any vitamin E-mediated changes in lifespan in model organisms. Furthermore there are several studies reporting a decrease in lifespan in response to vitamin E supplementation. Different outcomes between studies may be partly related to species-specific differences, differences in vitamin E concentrations and the vitamin E congeners administered. The findings of our literature review suggest that there is no consistent beneficial effect of vitamin E on lifespan in model organisms which is consistent with reports in human intervention studies.

Tamarozzi F et al. (2011) Clin Microbiol Rev "Onchocerciasis: the role of Wolbachia bacterial endosymbionts in parasite biology, disease pathogenesis, and treatment."

Gentil K, Halliday A, Taylor MJ, Hoerauf A, Pearlman E, Tamarozzi F

[Clin Microbiol Rev, 2011]

The discovery of Wolbachia intracellular bacteria within filarial nematodes, including Onchocerca volvulus, the causative agent of onchocerciasis or "river blindness," has delivered a paradigm shift in our understanding of the parasite's biology, to where we now know that the bacterial endosymbionts are essential for normal development of larvae and embryos and may support the long-term survival of adult worms. The apparent mutualistic dependency has also offered a novel approach to the treatment of onchocerciasis through the use of antibiotics to eliminate Wolbachia, delivering for the first time a treatment which has significant macrofilaricidal efficacy. Studies with other filarial nematode species have also highlighted a role for Wolbachia in transmission and infection of the mammalian host through a fascinating manipulation of mast cell-mediated vasodilation to enhance infectivity of vector-borne larvae. Wolbachia has also been identified as the principal driver of innate and adaptive Th1 inflammatory immunity, which can either contribute to disease pathogenesis or, with the Wolbachia-mediated recruitment of mast cells, enhance infectivity. The Wolbachia activation of innate inflammation also drives inflammatory adverse events in response to chemotherapy with either diethylcarbamazine (DEC) or ivermectin. In this review we summarize the experimental and field trial data which have uncovered the importance of Wolbachia symbiosis in onchocerciasis.

Felix MA et al. (2002) Hermann, Editeurs des Sciences et des Arts. Paris, France. "Caenorhabditis elegans. Un organisme modele en biologie."

Labouesse M, Segalat L, Felix MA

[Hermann, Editeurs des Sciences et des Arts. Paris, France., 2002]

L'espce Caenorhabditis elegans fut dcrite en 1900 Alger par E. Maupas, qui s'intressait son mode de reproduction hermaphrodite. Plus tard, vers le milieu du vingtime sicle, V. Nigon et ses collaboratuers Lyon tudirent les reorganizations cellulaires accompagnant la fecundation et les premiers clivages. J. Brun isola les preiers mutants morpholgiques.

Lewis E et al. (1994) Parasite "Cuticulin genes of nematodes."

Bazzicalupo P, Zei F, Lassandro F, Lewis E, Ristoratore F, Nola M, Sebastiano M, Favre R, Cermola M

[Parasite, 1994]

Two genes coding for cuticlin components of Coenorhabditis elegans have been cloned and their structure is described. Recombinant proteins have been produced in E. coli and antibodies raised against them. Nucleic acid and specific antibodies are being used to isolate the homologues from the parasitic species Ascaris lumbricoides and Brugia pahangi.

Bucher EA et al. (1994) Seminars in Developmental Biology "Gastrulation in the nematode Caenorhabditis elegans."

Bucher EA, Seydoux GC

[Seminars in Developmental Biology, 1994]

Gastrulation in Caenorhabditis elegans has been described by following the movements of individual nuclei in living embryos by Nomarski microscopy. Gastrulation starts in the 26-cell stage when the two gut precursors, Ea and Ep, move into the blastocoele. The migration of Ea and Ep does not depend on interactions with specific neighboring cells and appears to rely on the earlier fate specification of the E lineage. In particular, the long cell cycle length of Ea and Ep appears important for gastrulation. Later in embryogenesis, the precursors to the germline, muscle and pharynx join the E descendants in the interior. As in other organisms, the movement of gastrulation permit novel cell contacts that are important for the specification of certain cell fates.

McGhee JD (2013) Wiley Interdiscip Rev Dev Biol "The Caenorhabditis elegans intestine."

McGhee JD

[Wiley Interdiscip Rev Dev Biol, 2013]

The transcriptional regulatory hierarchy that controls development of the Caenorhabditis elegans endoderm begins with the maternally provided SKN-1 transcription factor, which determines the fate of the EMS blastomere of the four-cell embryo. EMS divides to produce the posterior E blastomere (the clonal progenitor of the intestine) and the anterior MS blastomere, a major contributor to mesoderm. This segregation of lineage fates is controlled by an intercellular signal from the neighboring P2 blastomere and centers on the HMG protein POP-1. POP-1 would normally repress the endoderm program in both E and MS but two consequences of the P2-to-EMS signal are that POP-1 is exported from the E-cell nucleus and the remaining POP-1 is converted to an endoderm activator by complexing with SYS-1, a highly diverged -catenin. In the single E cell, a pair of genes encoding small redundant GATA-type transcription factors, END-1 and END-3, are transcribed under the combined control of SKN-1, the POP-1/SYS-1 complex, as well as the redundant pair of MED-1/2 GATA factors, themselves direct zygotic targets of SKN-1 in the EMS cell. With the expression of END-1/END-3, the endoderm is specified. END-1 and END-3 then activate transcription of a further set of GATA-type transcription factors that drive intestine differentiation and function. One of these factors, ELT-2, appears predominant; a second factor, ELT-7, is partially redundant with ELT-2. The mature intestine expresses several thousand genes, apparently all controlled, at least in part, by cis-acting GATA-type motifs.

Elliott TS et al. (2014) Curr Opin Chem Biol "Genetic code expansion and bioorthogonal labelling enables cell specific proteomics in an animal."

Chin JW, Elliott TS, Bianco A

[Curr Opin Chem Biol, 2014]

The site specific, co-translational introduction of unnatural amino acids into proteins produced in cells has been facilitated by the development of the pyrrolysyl-tRNA synthetase/tRNACUA pair. This pair can now be used to direct the site-specific incorporation of designer amino acids in E. coli, yeast, mammalian cells, and animals (the worm, C. elegans and the fly, D. melanogaster). Developments in encoding components of rapid bioorthogonal reactions are providing new opportunities for labelling and visualising proteins. A new method called stochastic orthogonal recoding of translation with chemoselective modification (SORT-M) leverages advances in genetic code expansion and bioorthogonal chemistry to label proteomes with diverse chemistry at diverse codons in E. coli, mammalian cells, and in spatially and temporally defined sets of cells in the fly. Proteomes in targeted sets of cells have been visualised by SORT-M and proteins in targeted cells have been identified by SORT-M.

Maduro MF (2015) Mol Reprod Dev "Developmental robustness in the Caenorhabditis elegans embryo."

Maduro MF

[Mol Reprod Dev, 2015]

Developmental robustness is the ability of an embryo to develop normally despite many sources of variation, from differences in the environment to stochastic cell-to-cell differences in gene expression. The nematode Caenorhabditis elegans exhibits an additional level of robustness: Unlike most other animals, the embryonic pattern of cell divisions is nearly identical from animal to animal. The endoderm (gut) lineage is an ideal model for studying such robustness as the juvenile gut has a simple anatomy, consisting of 20 cells that are derived from a single cell, E, and the gene regulatory network that controls E specification shares features with developmental regulatory networks in many other systems, including genetic redundancy, parallel pathways, and feed-forward loops. Early studies were initially concerned with identifying the genes in the network, whereas recent work has focused on understanding how the endoderm produces a robust developmental output in the face of many sources of variation. Genetic control exists at three levels of endoderm development: Progenitor specification, cell divisions within the developing gut, and maintenance of gut differentiation. Recent findings show that specification genes regulate all three of these aspects of gut development, and that mutant embryos can experience a "partial" specification state in which some, but not all, E descendants adopt a gut fate. Ongoing studies using newer quantitative and genome-wide methods promise further insights into how developmental gene-regulatory networks buffer variation. Mol. Reprod. Dev. 2015. 2015 Wiley Periodicals, Inc.