-
[
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.
-
[
Nature Neuroscience,
2004]
At first glance, the nervous systems of vertebrates and invertebrates seem bilaterally symmetrical, but on closer inspection left-right asymmetries become apparent. Humans, for example, show gross anatomical differences between right and left temporal lobes, and visual and language faculties are asymmetrically distributed between the two hemispheres. How these asymmetries arise during development remains something of a mystery (for review, see ref.1). In the nematode Caenorhabditis elegans, the AWC and ASE chemosensory neuron pairs are bilaterally symmetrical based on anatomical considerations, but nevertheless display asymmetrical gene expression patterns. A recent study in nature by Johnston and Hobert identifies a microRNA (miRNA) as a crucial mediator of this asymmetry in the ASE neurons.
-
[
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 Neurosci,
1995]
A range of neuroanatomical results supports the idea that 'save wire' is an organizing principle of brain structure: that the theory of combinatorial optimization of networks applies to the anatomy of the nervous system. In particular, optimization of the placement of components operates at several hierarchical levels in the nervous system, from gross to microscopic anatomy, and from invertebrates to primates. That is, when anatomical positioning of interconnected neural components is treated like a problem of wire minimization in microchip layout, a hypothesis of 'best of all possible brains' is consistent with the observed siting of brains, ganglia, and even somata of individual neurons that minimizes the length of interconnections. In the case of the positioning of ganglia of Caenorhabditis elegans, optimization predictions of one-in-a-million precision can be verified.AD - Committee on History and Philosophy of Science, University of Maryland, College Park 20742, USA.FAU - Cherniak, CAU - Cherniak CLA - engPT - Journal ArticlePT - ReviewPT - Review, TutorialCY - ENGLANDTA - Trends NeurosciJID - 7808616SB - IM
-
[
Chromosoma,
2011]
Faithful repair of DNA double-strand breaks (DSBs) is vital for animal development, as inappropriate repair can cause gross chromosomal alterations that result in cellular dysfunction, ultimately leading to cancer, or cell death. Correct processing of DSBs is not only essential for maintaining genomic integrity, but is also required in developmental programs, such as gametogenesis, in which DSBs are deliberately generated. Accordingly, DSB repair deficiencies are associated with various developmental disorders including cancer predisposition and infertility. To avoid this threat, cells are equipped with an elaborate and evolutionarily well-conserved network of DSB repair pathways. In recent years, Caenorhabditis elegans has become a successful model system in which to study DSB repair, leading to important insights in this process during animal development. This review will discuss the major contributions and recent progress in the C. elegans field to elucidate the complex networks involved in DSB repair, the impact of which extends well beyond the nematode phylum.
-
[
Genesis,
2014]
Despite their gross morphological symmetry, animal nervous systems can perceive and process information in a left/right asymmetric manner. How left/right asymmetric functional features develop in the context of a bilaterally symmetric structure is a very poorly understood problem, in part because very few morphological or molecular correlates of functional asymmetries have been identified so far in vertebrate or invertebrate nervous systems. One of the very few systems in which a molecular correlate for functional lateralization has been uncovered is the taste sensory system of the nematode Caenorhabditis elegans, which is composed of a pair of bilaterally symmetric neurons, ASE left (ASEL) and ASE right (ASER). ASEL and ASER are similar in morphology, connectivity, and molecular composition, but they express distinct members of a putative chemoreceptor gene family and respond in a fundamentally distinct manner to taste cues. Extensive forward and reverse genetic analysis has uncovered a complex gene regulatory network, composed of transcription factors, miRNAs, chromatin regulators, and intercellular signals, that instruct the asymmetric features of these two neurons. In this review, this system is described in detail, drawing a relatively complete picture of asymmetry control in a nervous system.
-
[
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.
-
[
Brief Funct Genomic Proteomic,
2008]
Since the completion of the Caenorhabditis elegans genome sequence 10 years ago, efforts of the large community of C. elegans geneticists have resulted in a high-quality annotation of the structures and sequence relatedness of nearly all the protein encoding and RNA genes. Based on increasingly accurate gene counts in other species, it now appears that C. elegans has more functional genes than most insects and approximately the same number as most mammals. In the last few years, draft genome sequences for several other nematodes have been published (C. briggsae and Brugia malayi) or publicly released (C. remanei, C. brenneri, C. japonica, Pristionchus pacificus, Trichinella spiralis and Haemonchus contortus). Comparisons of gene content within the phylum and to other phyla reveal complex patterns of genome evolution. These patterns include substantial numbers of genes conserved across all the major metazoan phyla (core metazoan genes) and many nematode-specific genes and gene families. Nematode-specific genes are located predominantly on autosomal arms, which also have higher recombination rates. It appears that evolutionary innovations occur mostly in these regions, probably facilitated by higher recombination. Few of these genes have gross phenotypes when knocked down by RNAi, suggesting that many of them function in specific aspects of nematode biology that were not tested, including chemosensation, pathogen response and xenobiotic detoxification.
-
[
PLoS Negl Trop Dis,
2018]
We briefly review cysteine proteases (orthologs of mammalian cathepsins B, L, F, and C) that are expressed in flatworm and nematode parasites. Emphasis is placed on enzyme activities that have been functionally characterized, are associated with the parasite gut, and putatively contribute to degrading host proteins to absorbable nutrients [1-4]. Often, gut proteases are expressed as multigene families, as is the case with Fasciola [5] and Haemonchus [6], presumably expanding the range of substrates that can be degraded, not least during parasite migration through host tissues [5]. The application of the free-living planarian and Caenorhabditis elegans as investigative models for parasite cysteine proteases is discussed. Finally, because of their central nutritive contribution, targeting the component gut proteases with small-molecule chemical inhibitors and understanding their utility as vaccine candidates are active areas of research [7].