-
[
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
-
[
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.
-
[
Int J Biochem Cell Biol,
2013]
Dicarbonyl/L-xylulose reductase (DCXR) is a highly conserved and phylogenetically widespread enzyme converting L-xylulose into xylitol. It also reduces highly reactive -dicarbonyl compounds, thus performing a dual role in carbohydrate metabolism and detoxification. Enzymatic properties of DCXR from yeast, fungi and mammalian tissue extracts are extensively studied. Deficiency of the DCXR gene causes a human clinical condition called pentosuria and low DCXR activity is implicated in age-related diseases including cancers, diabetes, and human male infertility. While mice provide a model to study clinical condition of these diseases, it is necessary to adopt a physiologically tractable model in which genetic manipulations can be readily achieved to allow the fast genetic analysis of an enzyme with multiple biological roles. Caenorhabditis elegans has been successfully utilized as a model to study DCXR. Here, we discuss the biochemical properties and significance of DCXR activity in various human diseases, and the utility of C. elegans as a research platform to investigate the molecular and cellular mechanism of the DCXR biology.
-
[
Trends in Genetics,
1994]
Recently, Krishnan et al. Reported the cloning and sequencing of the Drosophila shaking-B (shakB; alias Passover, or Pas) gene, required for the jump response to an optical stimulus. The predicted gene product was similar to those of both the Drosophila gene lethal (1) optic ganglion reduced [l(1)ogre] and the Caenorhabditis elegans gene
unc-7, which together define a new family of evolutionarily conserved proteins that may be membrane-associated. Below I describe three additional members of this family, as identified by sequence homologies. An alignment of all these sequences permits a more informed prediction of the general structure of members of this family. The structure is that of a new type of multipass transmembrane protein. On the basis of the phenotypes of mutant organisms, I suggest that the encoded proteins may be members of a family of invertebrate
-
[
Parasitol Res,
2015]
Parasites including helminthes, protozoa, and medical arthropod vectors are a major cause of global infectious diseases, affecting one-sixth of the world's population, which are responsible for enormous levels of morbidity and mortality important and remain impediments to economic development especially in tropical countries. Prevalent drug resistance, lack of highly effective and practical vaccines, as well as specific and sensitive diagnostic markers are proving to be challenging problems in parasitic disease control in most parts of the world. The impressive progress recently made in genome-wide analysis of parasites of medical importance, including trematodes of Clonorchis sinensis, Opisthorchis viverrini, Schistosoma haematobium, S. japonicum, and S. mansoni; nematodes of Brugia malayi, Loa loa, Necator americanus, Trichinella spiralis, and Trichuris suis; cestodes of Echinococcus granulosus, E. multilocularis, and Taenia solium; protozoa of Babesia bovis, B. microti, Cryptosporidium hominis, Eimeria falciformis, E. histolytica, Giardia intestinalis, Leishmania braziliensis, L. donovani, L. major, Plasmodium falciparum, P. vivax, Trichomonas vaginalis, Trypanosoma brucei and T. cruzi; and medical arthropod vectors of Aedes aegypti, Anopheles darlingi, A. sinensis, and Culex quinquefasciatus, have been systematically covered in this review for a comprehensive understanding of the genetic information contained in nuclear, mitochondrial, kinetoplast, plastid, or endosymbiotic bacterial genomes of parasites, further valuable insight into parasite-host interactions and development of promising novel drug and vaccine candidates and preferable diagnostic tools, thereby underpinning the prevention and control of parasitic diseases.
-
[
Wiad Parazytol,
2007]
Toll-like receptors (TLRs) are amongst the most highly conserved in the evolution of receptor family, being found in both immune and other cells. TLRs were observed in vascular endothelial cells, epithelial cells, microglia cells, adipocytes, and intestinal and renal cells. TLRs plays a key role in the innate immune response to a variety of pathogens. At present, very little is known about the role of TLRs in host defense against parasitic pathogen infections. The first study shows that TLRs contribute to both innate and adaptive immune responses following infection with protozoan parasite Leishmania major. The TLRs recognizing PAMPs associated with the parasite L. major are essential for the activation of the innate and adaptive immune responses to infection. A study concerning recognition of the role of TLRs in the host-parasite relationship would be an interesting challenge for future study.
-
[
Trends Neurosci,
2000]
A steadily increasing number of cDNAs for proteins that are structurally related to the TRP ion channels have been cloned in recent years. All these proteins display a topology of six transmembrane segments that is shared with some voltage-gated channels and the cyclic-nucleotide-gated channels. The TRP channels can be divided, on the basis of their homology, into three TRP channel (TRPC) subfamilies: short (S), long (L) and osm (O). From the evidence available to date, this subdivision can also be made according to channel function. Thus, the STRPC family, which includes Drosophila TRP and TRPL and the mammalian homologues, TRPC1-7, is a family of Ca2+-permeable cation channels that are activated subsequent to receptor-mediated stimulation of different isoforms of phospholipase C. Members of the OTRPC family are Ca2+-permeable channels involved in pain transduction (vanilloid and vanilloid-like receptors), epithelial Ca2+ transport and, at least in Caenorhabditis elegans, in chemo-, mechano- and osmoregulation. The LTRPC family is less well characterized.
-
[
International Journal of Developmental Biology,
1998]
Pleiotropy , a situation in which a single gene influences multiple phenotypic tra its, can arise in a variety of ways. This paper discusses possible underlying mechanisms and proposes a classification of the various phenomena involved.
-
[
Mol Genet Metab,
2007]
3-Hydroxy-3-methylglutaryl-CoA lyase (HL) deficiency is a rare autosomal recessive genetic disorder that affects ketogenesis and l-leucine catabolism, which generally appears during the first year of life. Patients with HL deficiency have a reduced capacity to synthesize ketone bodies. The disease is caused by lethal mutations in the HL gene (HMGCL). To date, up to 30 variant alleles (28 mutations and 2 SNPs) in 93 patients have been reported, with a recognizable population-specific mutational spectrum. This disorder is frequent in Saudi Arabia and the Iberian Peninsula (Portugal and Spain), where two mutations (122G>A and 109G>A) have been identified in 87% and 94% of the cases, respectively. In most countries a few patients have a high level of allelic heterogeneity. The mutations are distributed along the gene sequences, although some clustering was observed in exon 2, conforming a possible hot spot. Recently, the crystal structures of the human and two bacterial HL have been published. These experimentally obtained structures confirmed the overall architecture, previously predicted by our group and others using bioinformatic approaches, which shows the (betaalpha)8-barrel structure of the enzyme. In addition, the crystals confirmed the presence of an additional COOH domain containing important structures and residues for enzyme functionality and oligomerization processes. Here, we review all HMGCL mis-sense mutations identified to date, and their implication in enzyme structure and function is discussed. We found that genotype-phenotype correlations are difficult to establish because the evolution of the disease seems more related to the causes of hypoglycaemia (fasting or acute illness) than to a particular genotype.
-
[
Curr Biol,
2003]
A novel protein in Caenorhabditis elegans, SAS-4, is a component of centrioles and is required for centriole duplication. Depletion of SAS-4 results in stunted centrioles and a smaller centrosome, suggesting a link to organelle size control.