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[
Semin Nephrol,
2006]
The vacuolar H(+)-ATPase is a multisubunit protein consisting of a peripheral catalytic domain (V(1)) that binds and hydrolyzes adenosine triphosphate (ATP) and provides energy to pump H(+) through the transmembrane domain (V(0)) against a large gradient. This proton-translocating vacuolar H(+)-ATPase is present in both intracellular compartments and the plasma membrane of eukaryotic cells. Mutations in genes encoding kidney intercalated cell-specific V(0)
a4 and V(1) B1 subunits of the vacuolar H(+)-ATPase cause the syndrome of distal tubular renal acidosis. This review focuses on the function, regulation, and the role of vacuolar H(+)-ATPases in renal physiology. The localization of vacuolar H(+)-ATPases in the kidney, and their role in intracellular pH (pHi) regulation, transepithelial proton transport, and acid-base homeostasis are discussed.
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[
The Scientist,
1996]
Biologist H. Robert Horvitz discusses the genetics of cell death in the nematode C. elegans.
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[
WormBook,
2007]
Heterorhabditis bacteriophora is an entomopathogenic nematode (EPN) mutually associated with the enteric bacterium, Photorhabdus luminescens, used globally for the biological control of insects. Much of the previous research concerning H. bacteriophora has dealt with applied aspects related to biological control. However, H. bacteriophora is an excellent model to investigate fundamental processes such as parasitism and mutualism in addition to its comparative value to Caenorhabditis elegans. In June 2005, H. bacteriophora was targeted by NHGRI for a high quality genome sequence. This chapter summarizes the biology of H. bacteriophora in common and distinct from C. elegans, as well as the status of the genome project.
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Int J Parasitol,
2006]
Haemonchus contortus of small ruminants is a parasitic nematode of major socio-economic importance world-wide. While there is considerable knowledge of the morphological changes which take place during the life cycle of H. contortus, very little is understood about the molecular and biochemical processes which govern developmental changes in the parasite. Recent technological advances and the imminent genomic sequence for H. contortus provide unique opportunities to investigate the molecular basis of such processes in parasitic nematodes. This article reviews molecular and biochemical aspects of development in H. contortus, reports on some recent progress on signal transduction molecules in this parasite and emphasises the opportunities that new technologies and the free-living nematode, Caenorhabditis elegans, offer for investigating developmental aspects in H. contortus and related strongylid nematodes, also in relation to developing novel approaches for control.
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[
Can J Gastroenterol,
2000]
BACKGROUND: The rate of Helicobacter pylori resistance to antibiotics determines the cure rate of treatment regimens containing such antibiotics. AIMS: To review the literature to determine the rates of H pylori resistance to metronidazole and clarithromycin in Canada, and whether these rates vary in different regions of Canada. METHODS: The literature was reviewed extensively for the prevalence of antibiotic-resistant H pylori in Canada by searching MEDLINE from January 1980 to May 1999, as well as abstracts of the American Gastroenterology Association Digestive Disease Week, Canadian Digestive Disease Week and The European H pylori Study Group Meetings from January 1995 to May 1999. RESULTS: Eleven studies that estimated H pylori resistance to metronidazole resistance and nine that estimated resistance to clarithromycin in Canada were identified. Rates of resistance for metronidazole and clarithromycin varied from 11% to 48% and 0% to 12%, respectively. Studies that obtained their estimates using the E-test and those that did not clearly exclude patients who had undergone previous attempts at H pylori eradication had higher estimates of resistance, accounting for this variability in results. CONCLUSIONS: The prevalence of primary H pylori resistance in Canada appears to be 18% to 22% for metronidazole and less than 4% for clarithromycin. These rates appear to be consistent across the different regions studied in Canada, but many regions have not been studied.
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[
Seminars in Developmental Biology,
1992]
At the 4-cell stage of the C. elegans embryo, three axes can be defined: anterior-posterior (A-P), dorsal-ventral (D-V), and left-right (L-R). The A-P axis first becomes obvious in the newly fertilized 1-cell embryo. Pronouned cytoplasmic assymmetries arise along the A-P axis during the first cell cycle, after which the zygote undergoes a series of stem cell-like cleavages with an A-P orientation of the mitotic spindle; these cleavages generate several somatic founder cells and a primordial germ cell. The D-V and L-R axes are defined by the direction of spindle rotation as the 2-cell embryo divides into four cells. In contrast to the A-P axis, there do not appear to be cellular asymmetries associated with the D-V and L-R axes, and both axes can easily be reversed by micromanipulation. Thus, with respect to the roles that the embryonic axes serve in cell-fate determination in the early C. elegans embryo, it appears that internally transmitted developmental information is differentially segregated along the A-P axis, but not along the D-V or L-R axes. Instead, D-V and L-R differences in the fates of cells within lineages appear to be dictated by differential
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[
Cell Microbiol,
2018]
Legionella pneumophila is a ubiquitous environmental bacterium that has evolved to infect and proliferate within amoebae and other protists. It is thought that accidental inhalation of contaminated water particles by humans is what has enabled this pathogen to proliferate within alveolar macrophages and cause pneumonia. However, the highly evolved macrophages are equipped more sophisticated innate defense mechanisms than protists, such as the evolution of phagotrophic feeding into phagocytosis with more evolved innate defense processes. Not surprisingly, the majority of proteins involved in phagosome biogenesis (~80%) have origins in the phagotrophy stage of evolution. There are a plethora of highly evolved cellular and innate metazoan processes, not represented in Protist biology, that are modulated by L. pneumophila; including TLR2 signaling, NF-B, apoptotic and inflammatory processes, histone modification, caspases, and the NLRC-Naip5 inflammasomes. Importantly, L. pneumophila infects hemocytes of the invertebrate Galleria mellonella, kill G. mellonella larvae, and proliferate in and kill Drosophila adult flies and Caenorhabditis elegans. Although co-evolution with protist hosts has provided a substantial blueprint for L. pneumophila to infect macrophages, we discuss the further evolutionary aspects of co-evolution of L. pneumophila and its adaptation to modulate various highly evolved innate metazoan processes prior to becoming a human pathogen.
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Curr Opin Neurobiol,
1998]
Ion channels in the amiloride-sensitive Na+ channel/degenerin (NaC/DEG) family of cation channels have very diverse functions. They can be constitutively active (e.g. the epithelial Na+ channel), gated by a ligand (e.g. the peptide-gated channel FaNaC or H+-gated cation channels [ASICs]) or possibly activated by stretch (degenerins of Caenorhabditis elegans). Despite this functional diversity, the heterologous expressed channels share the following properties: permeability to Na+, inhibition by the diuretic amiloride and no voltage gating. This review will focus on recent advances in this ion channel family, with special emphasis on H+-gated cation channels.
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Nature Cell Biology,
1999]
Studies on the role of cholesterol- and caveolin-rich membrane microdomains in localizing Ras to the plasma membrane and enabling its signalling activity reveal intriguing differences both between mammalian H-Ras and K-Ras and between requirements for Ras signalling in mammalian and nematode cells.
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[
Annu Rev Microbiol,
1992]
Oxygenases that incorporate one or two atoms of dioxygen into substrates are found in many metabolic pathways. In this article, representative oxygenases, principally those found in bacterial pathways for the degradation of hydrocarbons, are reviewed. Monooxygenases, discussed in this chapter, incorporate one hydroxyl group into substrates. In this reaction, two atoms of dioxygen are reduced to one hydroxyl group and one H2O molecule by the concomitant oxidation of NAD(P)H. Dioxygenases catalyze the incorporation of two atoms of dioxygen into substrates. Two types of dioxygenases, aromatic-ring dioxygenases and aromatic-ring-cleavage dioxygenases, are discussed. The aromatic-ring dioxygenases incorporate two hydroxyl groups into aromatic substrates, and cis-diols are formed. This reaction also requires NAD(P)H as an electron donor. Aromatic-ring-cleavage dioxygenases incorporate two atoms of dioxygen into aromatic substrates, and the aromatic ring is cleaved. This reaction does not require an external reductant. All the oxygenases possess a cofactor, a transition metal, flavin or pteridine, that interacts with dioxygen. The concerted reactions between dioxygen and carbon in organic compounds are spin forbidden. The cofactor is used to overcome this restriction. For the oxygenases that require the NAD(P)H cofactor, the enzyme reaction is separated into two steps, the oxidation of NAD(P)H to generate two reducing equivalents, and the hydroxylation of substrates. Flavoprotein hydroxylases that catalyze the monohydroxylation of the aromatic ring carry out these two reactions on a single polypeptide chain. In other oxygenases, the NAD(P)H oxidation and a hydroxylation reaction are catalyzed by two separate polypeptides that are linked by a short electron-transport chain. Two reducing equivalents generated by the oxidation of NAD(P)H are transferred through the electron-transport chain to the cofactor on a hydroxylase component that they reduce. Dioxygen couples with the reduced cofactor and subsequently hydroxylates substrates. The electron-transport chains associated with oxygenases contain at least two redox centers. The first redox center is usually a flavin, while the second is an iron-sulfur cluster. The electron transport is initiated by a single two-electron transfer from NAD(P)H to a flavin, followed by two single-electron transfers from the flavin to an iron-sulfur cluster. The primary sequences of many oxygenases have been determined, and according to their sequence similarities, the oxygenases can be grouped into several protein families. Among proteins of the same family, the sequences in regions involved in cofactor binding are strongly conserved. Local sequence similarities are also observed among oxygenases from different families, primarily in regions involved in cofactor binding.