scholarly journals FMRFamide-like peptides expand the behavioral repertoire of a densely connected nervous system

2017 ◽  
Vol 114 (50) ◽  
pp. E10726-E10735 ◽  
Author(s):  
James Siho Lee ◽  
Pei-Yin Shih ◽  
Oren N. Schaedel ◽  
Porfirio Quintero-Cadena ◽  
Alicia K. Rogers ◽  
...  
Keyword(s):  
Nervous System ◽  
Single Cells ◽  
Meta Analysis ◽  
Reproductive Development ◽  
Parasitic Nematodes ◽  
Behavioral Repertoire ◽  
C Elegans ◽  
Free Living Nematode ◽  
Transcriptional Changes ◽  
Carrier Animal

Animals, including humans, can adapt to environmental stress through phenotypic plasticity. The free-living nematode Caenorhabditis elegans can adapt to harsh environments by undergoing a whole-animal change, involving exiting reproductive development and entering the stress-resistant dauer larval stage. The dauer is a dispersal stage with dauer-specific behaviors for finding and stowing onto carrier animals, but how dauers acquire these behaviors, despite having a physically limited nervous system of 302 neurons, is poorly understood. We compared dauer and reproductive development using whole-animal RNA sequencing at fine time points and at sufficient depth to measure transcriptional changes within single cells. We detected 8,042 genes differentially expressed during dauer and reproductive development and observed striking up-regulation of neuropeptide genes during dauer entry. We knocked down neuropeptide processing using sbt-1 mutants and demonstrate that neuropeptide signaling promotes the decision to enter dauer rather than reproductive development. We also demonstrate that during dauer neuropeptides modulate the dauer-specific nictation behavior (carrier animal-hitchhiking) and are necessary for switching from repulsion to CO2 (a carrier animal cue) in nondauers to CO2 attraction in dauers. We tested individual neuropeptides using CRISPR knockouts and existing strains and demonstrate that the combined effects of flp-10 and flp-17 mimic the effects of sbt-1 on nictation and CO2 attraction. Through meta-analysis, we discovered similar up-regulation of neuropeptides in the dauer-like infective juveniles of diverse parasitic nematodes, suggesting the antiparasitic target potential of SBT-1. Our findings reveal that, under stress, increased neuropeptide signaling in C. elegans enhances their decision-making accuracy and expands their behavioral repertoire.

scholarly journals The Ditylenchus destructor genome provides new insights into the evolution of plant parasitic nematodes

2016 ◽  
Vol 283 (1835) ◽  
pp. 20160942 ◽  
Author(s):  
Jinshui Zheng ◽  
Donghai Peng ◽  
Ling Chen ◽  
Hualin Liu ◽  
Feng Chen ◽  
...  
Keyword(s):  
Evolutionary History ◽  
Evolutionary Process ◽  
Parasitic Nematodes ◽  
Plant Parasitic Nematodes ◽  
Free Living ◽  
C Elegans ◽  
Free Living Nematode ◽  
Plant Nematode ◽  
Ditylenchus Destructor ◽  
Plant Parasitic

Plant-parasitic nematodes were found in 4 of the 12 clades of phylum Nematoda. These nematodes in different clades may have originated independently from their free-living fungivorous ancestors. However, the exact evolutionary process of these parasites is unclear. Here, we sequenced the genome sequence of a migratory plant nematode, Ditylenchus destructor . We performed comparative genomics among the free-living nematode, Caenorhabditis elegans and all the plant nematodes with genome sequences available. We found that, compared with C. elegans , the core developmental control processes underwent heavy reduction, though most signal transduction pathways were conserved. We also found D. destructor contained more homologies of the key genes in the above processes than the other plant nematodes. We suggest that Ditylenchus spp. may be an intermediate evolutionary history stage from free-living nematodes that feed on fungi to obligate plant-parasitic nematodes. Based on the facts that D. destructor can feed on fungi and has a relatively short life cycle, and that it has similar features to both C. elegans and sedentary plant-parasitic nematodes from clade 12, we propose it as a new model to study the biology, biocontrol of plant nematodes and the interaction between nematodes and plants.

The use of Caenorhabditis elegans in parasitic nematode research

Parasitology ◽  
2004 ◽  
Vol 128 (S1) ◽  
pp. S49-S70 ◽  
Author(s):  
J. S. GILLEARD
Keyword(s):  
Caenorhabditis Elegans ◽  
Parasitic Nematode ◽  
Expression System ◽  
Nematode Species ◽  
Current Status ◽  
Evolutionary Development ◽  
Parasitic Nematodes ◽  
Free Living ◽  
C Elegans ◽  
Free Living Nematode

There is increasing interest in the use of the free-living nematode Caenorhabditis elegans as a tool for parasitic nematode research and there are now a number of compelling examples of its successful application. C. elegans has the potential to become a standard tool for molecular helminthology researchers, just as yeast is routinely used by molecular biologists to study vertebrate biology. However, in order to exploit C. elegans in a meaningful manner, we need a detailed understanding of the extent to which different aspects of C. elegans biology have been conserved with particular groups of parasitic nematodes. This review first considers the current state of knowledge regarding the conservation of genome organisation across the nematode phylum and then discusses some recent evolutionary development studies in free-living nematodes. The aim is to provide some important concepts that are relevant to the extrapolation of information from C. elegans to parasitic nematodes and also to the interpretation of experiments that use C. elegans as a surrogate expression system. In general, examples have been specifically chosen because they highlight the importance of careful experimentation and interpretation of data. Consequently, the focus is on the differences that have been found between nematode species rather than the similarities. Finally, there is a detailed discussion of the current status of C. elegans as a heterologous expression system to study parasite gene function and regulation using successful examples from the literature.

Metabolism and inactivation of neurotransmitters in nematodes

Parasitology ◽  
1996 ◽  
Vol 113 (S1) ◽  
pp. S157-S173 ◽  
Author(s):  
R. E. Isaac ◽  
D. Macgregor ◽  
D. Coates
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Free Living ◽  
Nervous Systems ◽  
Target Proteins ◽  
C Elegans ◽  
Free Living Nematode ◽  
Increasing Knowledge ◽  
Insight Into

SUMMARYThe nematode nervous system employs many of the same neurotransmitters as are found in higher animals. The inactivation of neurotransmitters is absolutely essential for the correct functioning of the nervous system, In this article we discuss the various mechanisms used generally in animal nervous systems for synaptic inactivation of neurotransmitters and review the evidence for similar mechanisms operating in parasitic and free-living nematodes. The sequencing of the entireCaenorhabditis elegansgenome means that the sequence of nematode genes can be accessed from theC. elegansdatabase (ACeDB) and this wealth of information together with the increasing knowledge of the genetics of this free-living nematode will have great impact on all aspects of nematode neurobiology. The review will provide an insight into how this information may be exploited to identify and characterize target proteins for the development of novel anti-nematode drugs.

scholarly journals Caenorhabditis elegans: nature and nurture gift to nematode parasitologists

Parasitology ◽  
2017 ◽  
Vol 145 (8) ◽  
pp. 979-987 ◽  
Author(s):  
Gustavo Salinas ◽  
Gastón Risi
Keyword(s):  
Animal Model ◽  
Caenorhabditis Elegans ◽  
Parasitic Nematode ◽  
Model Organism ◽  
Parasitic Nematodes ◽  
Free Living ◽  
C Elegans ◽  
Free Living Nematode ◽  
Basic Biology ◽  
Nature And Nurture

AbstractThe free-living nematode Caenorhabditis elegans is the simplest animal model organism to work with. Substantial knowledge and tools have accumulated over 50 years of C. elegans research. The use of C. elegans relating to parasitic nematodes from a basic biology standpoint or an applied perspective has increased in recent years. The wealth of information gained on the model organism, the use of the powerful approaches and technologies that have advanced C. elegans research to parasitic nematodes and the enormous success of the omics fields have contributed to bridge the divide between C. elegans and parasite nematode researchers. We review key fields, such as genomics, drug discovery and genetics, where C. elegans and nematode parasite research have convened. We advocate the use of C. elegans as a model to study helminth metabolism, a neglected area ready to advance. How emerging technologies being used in C. elegans can pave the way for parasitic nematode research is discussed.

scholarly journals Plant-Based Natural Products for the Discovery and Development of Novel Anthelmintics against Nematodes

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 426 ◽  
Author(s):  
Maoxuan Liu ◽  
Sujogya Kumar Panda ◽  
Walter Luyten
Keyword(s):  
Medicinal Plants ◽  
Mechanisms Of Action ◽  
Model System ◽  
Parasitic Nematodes ◽  
Great Promise ◽  
Botanical Origin ◽  
Free Living ◽  
C Elegans ◽  
Structure Activity ◽  
Free Living Nematode

Intestinal parasitic nematodes infect approximately two billion people worldwide. In the absence of vaccines for human intestinal nematodes, control of infections currently relies mainly on chemotherapy, but resistance is an increasing problem. Thus, there is an urgent need for the discovery and development of new anthelmintic drugs, especially ones with novel mechanisms of action. Medicinal plants hold great promise as a source of effective treatments, including anthelmintic therapy. They have been used traditionally for centuries and are mostly safe (if not, their toxicity is well-known). However, in most medicinal plants the compounds active against nematodes have not been identified thus far. The free-living nematode C. elegans was demonstrated to be an excellent model system for the discovery of new anthelmintics and for characterizing their mechanism of action or resistance. The compounds discussed in this review are of botanical origin and were published since 2002. Most of them need further studies of their toxicity, mechanisms and structure-activity relationship to assess more fully their potential as drugs.

scholarly journals The astacin metalloprotease moulting enzyme NAS-36 is required for normal cuticle ecdysis in free-living and parasitic nematodes

Parasitology ◽  
2010 ◽  
Vol 138 (2) ◽  
pp. 237-248 ◽  
Author(s):  
GILLIAN STEPEK ◽  
GILLIAN McCORMACK ◽  
ANDREW J. BIRNIE ◽  
ANTONY P. PAGE
Keyword(s):  
Direct Consequence ◽  
Gastrointestinal Nematode ◽  
Nematode Species ◽  
Parasitic Nematodes ◽  
Recombinant Enzymes ◽  
Free Living ◽  
C Elegans ◽  
Collagenous Matrix ◽  
Free Living Nematode ◽  
Similar Range

SUMMARYNematodes represent one of the most abundant and species-rich groups of animals on the planet, with parasitic species causing chronic, debilitating infections in both livestock and humans worldwide. The prevalence and success of the nematodes is a direct consequence of the exceptionally protective properties of their cuticle. The synthesis of this cuticle is a complex multi-step process, which is repeated 4 times from hatchling to adult and has been investigated in detail in the free-living nematode, Caenorhabditis elegans. This process is known as moulting and involves numerous enzymes in the synthesis and degradation of the collagenous matrix. The nas-36 and nas-37 genes in C. elegans encode functionally conserved enzymes of the astacin metalloprotease family which, when mutated, result in a phenotype associated with the late-stage moulting defects, namely the inability to remove the preceding cuticle. Extensive genome searches in the gastrointestinal nematode of sheep, Haemonchus contortus, and in the filarial nematode of humans, Brugia malayi, identified NAS-36 but not NAS-37 homologues†. Significantly, the nas-36 gene from B. malayi could successfully complement the moult defects associated with C. elegans nas-36, nas-37 and nas-36/nas-37 double mutants, suggesting a conserved function for NAS-36 between these diverse nematode species. This conservation between species was further indicated when the recombinant enzymes demonstrated a similar range of inhibitable metalloprotease activities.

scholarly journals A Transcription Factor DAF5 Functions in Haemonchus Contortus Development

2021 ◽  
Author(s):  
Wenda Di ◽  
Fangfang Li ◽  
Li He ◽  
Chunqun Wang ◽  
Caixian Zhou ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Developmental Stages ◽  
Reproductive Organs ◽  
Bimolecular Fluorescence Complementation ◽  
Parasitic Nematodes ◽  
C Elegans ◽  
Free Living Nematode ◽  
And Function ◽  
Reproductive Processes

Abstract Background: Daf5 (Dauer abnormal formation gene), located in the downstream of DAF-7 signalling pathway, mainly functions in dauer formation and reproductive processes in the free-living nematode Caenorhabditis elegans. Although its structure and function have been studied clearly in C. elegans, it was totally unknown in Haemonchus contortus, a socio-economically important parasitic nematode of gastric ruminants.Methods: Here, we identified and characterized a homologue of Daf5, Hcdaf5 and its inferred product (HcDAF5) in H. contortus. Using an integrated molecular approach, we studied the transcriptional profiles of Hcdaf5 and the anatomical expression of HcDAF5 in H. contortus. RNA interference (RNAi) was performed to explore its function in transition from the exsheathed third-stage larvae (xL3) to the fourth-stage larvae (L4) in vitro. Interaction of HcDAF5 and HcDAF3 (a co-SMAD) was also detected by bimolecular fluorescence complementation system (BiFc) in vitro.Results: Here, we showed that HcDAF5 is a member of the Sno/Ski superfamily. Hcdaf5 was transcribed in all developmental stages of H. contortus, with a significant up-regulation in L3. Immunohistochemistry localized native HcDAF5 to the reproductive organs, cuticle and intestine. RNAi revealed specific siRNAs (small interfering RNA) could retard the xL3 development. In addition, the interaction between HcDAF5 and HcDAF3 indicated the SDS box region of HcDAF5 is dispensable for the binding of HcDAF5 to HcDAF3 and the region in HcDAF3 that binds to HcDAF5 is MH2 domain.Conclusion: In summary, these findings show that Hcdaf5 functions in developmental processes of H. contortus, and this is the first characterization of daf-5 gene in parasitic nematodes.

Molecular cloning andin vitroexpression ofC. elegansand parasitic nematode ionotropic receptors

Parasitology ◽  
1996 ◽  
Vol 113 (S1) ◽  
pp. S175-S190 ◽  
Author(s):  
J. T. Fleming ◽  
H. A. Baylis ◽  
D. B. Sattelle ◽  
J. A. Lewis
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Cell Biology ◽  
Acetylcholine Receptors ◽  
Resistance Mechanisms ◽  
Parasitic Nematodes ◽  
Sequence Information ◽  
Ionotropic Receptors ◽  
Anthelmintic Drug ◽  
C Elegans ◽  
Free Living Nematode

SUMMARYThe free living nematode,C. elegansis understood at a level of detail equalled by few other organisms, and much of the cell biology and sequence information is proving of considerable utility in the study of parasitic nematodes. Already,C. elegansprovides a convenient vehicle for investigating anthelmintic drug action and resistance mechanisms. Among the ionotropic receptors, with their important roles in the behaviour and development of the organism, are targets for anthelmintics. The subunits of nicotinic acetylcholine receptors ofC. elegansform a large and diverse multigene family. Members of this family are among the 11 genes associated with resistance to the anthelmintic drug levamisole.

scholarly journals On the role of dauer in the adaptation of nematodes to a parasitic lifestyle

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lieke E. Vlaar ◽  
Andre Bertran ◽  
Mehran Rahimi ◽  
Lemeng Dong ◽  
Jan E. Kammenga ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Meta Analysis ◽  
Nematode Species ◽  
Life Cycles ◽  
Signalling Pathway ◽  
Parasitic Nematodes ◽  
Wide Range ◽  
Free Living Nematode ◽  
Parasitic Lifestyle ◽  
Dauer Signalling Pathway

AbstractNematodes are presumably the most abundant Metazoa on Earth, and can even be found in some of the most hostile environments of our planet. Various types of hypobiosis evolved to adapt their life cycles to such harsh environmental conditions. The five most distal major clades of the phylum Nematoda (Clades 8–12), formerly referred to as the Secernentea, contain many economically relevant parasitic nematodes. In this group, a special type of hypobiosis, dauer, has evolved. The dauer signalling pathway, which culminates in the biosynthesis of dafachronic acid (DA), is intensively studied in the free-living nematode Caenorhabditis elegans, and it has been hypothesized that the dauer stage may have been a prerequisite for the evolution of a wide range of parasitic lifestyles among other nematode species. Biosynthesis of DA is not specific for hypobiosis, but if it results in exit of the hypobiotic state, it is one of the main criteria to define certain behaviour as dauer. Within Clades 9 and 10, the involvement of DA has been validated experimentally, and dauer is therefore generally accepted to occur in those clades. However, for other clades, such as Clade 12, this has hardly been explored. In this review, we provide clarity on the nomenclature associated with hypobiosis and dauer across different nematological subfields. We discuss evidence for dauer-like stages in Clades 8 to 12 and support this with a meta-analysis of available genomic data. Furthermore, we discuss indications for a simplified dauer signalling pathway in parasitic nematodes. Finally, we zoom in on the host cues that induce exit from the hypobiotic stage and introduce two hypotheses on how these signals might feed into the dauer signalling pathway for plant-parasitic nematodes. With this work, we contribute to the deeper understanding of the molecular mechanisms underlying hypobiosis in parasitic nematodes. Based on this, novel strategies for the control of parasitic nematodes can be developed.

scholarly journals Transcriptional landscape of PTEN loss in primary prostate cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Eddie Luidy Imada ◽  
Diego Fernando Sanchez ◽  
Wikum Dinalankara ◽  
Thiago Vidotto ◽  
Ericka M. Ebot ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Meta Analysis ◽  
Pten Loss ◽  
Primary Prostate Cancer ◽  
Expression Atlas ◽  
Transcriptomic Signature ◽  
Transcriptional Changes ◽  
New Biomarkers ◽  
Adaptive Immune Systems ◽  
Transcriptional Landscape

Abstract Background PTEN is the most frequently lost tumor suppressor in primary prostate cancer (PCa) and its loss is associated with aggressive disease. However, the transcriptional changes associated with PTEN loss in PCa have not been described in detail. In this study, we highlight the transcriptional changes associated with PTEN loss in PCa. Methods Using a meta-analysis approach, we leveraged two large PCa cohorts with experimentally validated PTEN and ERG status by Immunohistochemistry (IHC), to derive a transcriptomic signature of PTEN loss, while also accounting for potential confounders due to ERG rearrangements. This signature was expanded to lncRNAs using the TCGA quantifications from the FC-R2 expression atlas. Results The signatures indicate a strong activation of both innate and adaptive immune systems upon PTEN loss, as well as an expected activation of cell-cycle genes. Moreover, we made use of our recently developed FC-R2 expression atlas to expand this signature to include many non-coding RNAs recently annotated by the FANTOM consortium. Highlighting potential novel lncRNAs associated with PTEN loss and PCa progression. Conclusion We created a PCa specific signature of the transcriptional landscape of PTEN loss that comprises both the coding and an extensive non-coding counterpart, highlighting potential new players in PCa progression. We also show that contrary to what is observed in other cancers, PTEN loss in PCa leads to increased activation of the immune system. These findings can help the development of new biomarkers and help guide therapy choices.

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