Author: Arif Nazim Nathoo
Publisher:
ISBN:
Category : Caenorhabditis elegans
Languages : en
Pages : 186

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Author: Elizabeth Ruiz Lancheros
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Book Description
"Nematode neuropeptides play critical roles in modulating neuronal networks acting independently or together with other neurotransmitters; consequently, they influence motor programs and all nematode behaviour outputs. The FMRF-amide like peptide (FLP) family of neuropeptides is particularly well-conserved across the phylum Nematoda and differs from its vertebrate counterpart. Peptides in this family are involved in neuromuscular functions, feeding/metabolism, and reproductive behaviors in free-living and parasitic nematodes. These unique characteristics of FLPs make their endogenous receptors, mainly G protein-coupled receptors (GPCRs), potential targets for the rational discovery of chemotherapeutic agents that target parasitic nematodes. Relatively few FLPs have been associated with a receptor and several important candidate neuropeptide-GPCRs remain orphans (unpaired with its endogenous ligand). In this work, we designed an in situ deorpanization strategy in the model free living nematode Caenorhabditis elegans. Based on the conservation of FLPs, it is expected that identification of receptors in C. elegans will enable the identification and characterization of homologous receptors in parasitic species. To validate the in situ strategy, we first developed an alternative bioassay to allow the characterization of neuroactive FLPs in C. elegans. A proof-of-concept study using the novel anthelmintic derquantel revealed that a cut-worm model can be used to remove the cuticle as a permeable barrier, allowing compounds like derquantel to reach their site of action and induce responses controlled by the neuromuscular system. Consistent with these observations, selected FLPs induced a range of locomotor effects (phenotypes) in cut-preparations. Based on this, FLP-phenotypes were used as a read-out method to screen candidate GPCRs in cut-preparations. Experiments with the ligand/receptor pair FLP18-6 (DVPGVLRFa)/NPR-5 revealed that an npr-5 knockout strain loses the phenotype induced by FLP-18 in wild type (wt) cut-preparations, and this was reversed by reintroducing NPR-5. These findings suggest that mutations in NPR-5 specifically disable the FLP-18 phenotype and validated the use of knockout strains with loss-of-function mutations in GPCR genes for in situ deorphanization using the cut-worm model. By performing a low-throughput screen of receptors for 7 FLPs in 28 knockout strains, 9 novel FLP-GPCR associations were identified; one of them was further characterized in a yeast expression system. Some FLPs were associated with more than one GPCR and one GPCR with more than one FLP in situ. This promiscuity becomes relevant in the rational search of drugs that target deorphanized FLP-GPCRs and impair parasite viability. To investigate the receptor interaction with endogenous ligand(s) and gain insight into how two receptors interact with the same ligand we used the cut-worm model and receptors expressed in yeast for structure-activity relationship studies. Results for the FLP-18 receptors NPR-4 and NPR-5 revealed that the FLP18-6 C-terminus is essential for receptor activation in vitro and peptide activity in the cut-worm model, more than N-terminus. The use of FLP18-6 alanine analogs confirmed these observations, identified the key role of specific peptide residues for receptor activation, and suggested a differential interaction of peptide side chains with each receptor. This information is valuable for further development of promiscuous non-peptide ligands that act on both receptors. Overall, the results presented here provide invaluable data on FLP-GPCR associations and interactions, as well as in situ and in vitro bioassays useful for ongoing efforts in anthelmintic discovery and neuropeptide GPCR characterization." --

Author: Timothy G. Geary
Publisher: Springer Science & Business Media
ISBN: 1441969020
Category : Medical
Languages : en
Pages : 246

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Book Description
The need to continually discover new agents for the control or treatment of invertebrate pests and pathogens is undeniable. Agriculture, both animal and plant, succeeds only to the extent that arthropod and helminth consumers, vectors and pathogens can be kept at bay. Humans and their companion animals are also plagued by invertebrate parasites. The deployment of chemical agents for these purposes inevitably elicits the selection of resistant populations of the targets of control, necessitating a regular introduction of new kinds of molecules. Experience in other areas of chemotherapy has shown that a thorough understanding of the biology of disease is an essential platform upon which to build a discovery program. Unfortunately, investment of research resources into understanding the basic physiology of invertebrates as a strategy to illuminate new molecular targets for pesticide and parasiticide discovery has been scarce, and the pace of introduction of new molecules for these indications has been slowed as a result. An exciting and so far unexploited area to explore in this regard is invertebrate neuropeptide physiology. This book was assembled to focus attention on this promising field by compiling a comprehensive review of recent research on neuropeptides in arthropods and helminths, with contributions from many of the leading laboratories working on these systems.

Author: Victoria Groß
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

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Author: Jie Dong
Publisher:
ISBN:
Category : Cadmium
Languages : en
Pages : 394

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Author: Mikhail Soloviev
Publisher: John Wiley & Sons
ISBN: 0470196491
Category : Science
Languages : en
Pages : 432

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Book Description
The definitive guide to peptidomics- a hands-on lab reference The first truly comprehensive book about peptidomics for protein and peptide analysis, this reference provides a detailed description of the hows and whys of peptidomics and how the techniques have evolved. With chapters contributed by leading experts, it covers naturally occurring peptides, peptidomics methods and new developments, and the peptidomics approach to biomarker discovery. Explaining both the principles and the applications, Peptidomics: Methods and Applications: * Features examples of applications in diverse fields, including pharmaceutical science, toxicity biomarkers, and neuroscience * Details the successful peptidomic analyses of biological material ranging from plants to mammals * Describes a cross section of analytical techniques, including traditional methodologies, emerging trends, and new techniques for high throughput approaches An enlightening reference for experienced professionals, this book is sufficiently detailed to serve as a step-by-step guide for beginning researchers and an excellent resource for students taking biotechnology and proteomics courses. It is an invaluable reference for protein chemists and biochemists, professionals and researchers in drug and biopharmaceutical development, analytical and bioanalytical chemists, toxicologists, and others.

Author: Josh Dubnau
Publisher: Cambridge University Press
ISBN: 1107009030
Category : Medical
Languages : en
Pages : 309

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Book Description
A comprehensive portrayal of the behaviour genetics of the fruit fly (Drosophila melanogaster) and the methods used in these studies.

Author: Anna Menini
Publisher: CRC Press
ISBN: 1420071998
Category : Science
Languages : en
Pages : 438

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Book Description
Comprehensive Overview of Advances in OlfactionThe common belief is that human smell perception is much reduced compared with other mammals, so that whatever abilities are uncovered and investigated in animal research would have little significance for humans. However, new evidence from a variety of sources indicates this traditional view is likely

Author: Donald L. Riddle
Publisher: Firefly Books
ISBN: 9780879695323
Category : Medical
Languages : en
Pages : 1252

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Book Description
Defines the current status of research in the genetics, anatomy, and development of the nematode C. elegans, providing a detailed molecular explanation of how development is regulated and how the nervous system specifies varied aspects of behavior. Contains sections on the genome, development, neural networks and behavior, and life history and evolution. Appendices offer genetic nomenclature, a list of laboratory strain and allele designations, skeleton genetic maps, a list of characterized genes, a table of neurotransmitter assignments for specific neurons, and information on codon usage. Includes bandw photos. For researchers in worm studies, as well as the wider community of researchers in cell and molecular biology. Annotation copyrighted by Book News, Inc., Portland, OR

Author: John H. Byrne
Publisher: Oxford University Press
ISBN: 0190456787
Category : Science
Languages : en
Pages : 608

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Book Description
Invertebrates have proven to be extremely useful model systems for gaining insights into the neural and molecular mechanisms of sensory processing, motor control and higher functions such as feeding behavior, learning and memory, navigation, and social behavior. A major factor in their enormous contributions to neuroscience is the relative simplicity of invertebrate nervous systems. In addition, some invertebrates, primarily the molluscs, have large cells, which allow analyses to take place at the level of individually identified neurons. Individual neurons can be surgically removed and assayed for expression of membrane channels, levels of second messengers, protein phosphorylation, and RNA and protein synthesis. Moreover, peptides and nucleotides can be injected into individual neurons. Other invertebrate model systems such as Drosophila and Caenorhabditis elegans offer tremendous advantages for obtaining insights into the neuronal bases of behavior through the application of genetic approaches. The Oxford Handbook of Invertebrate Neurobiology reviews the many neurobiological principles that have emerged from invertebrate analyses, such as motor pattern generation, mechanisms of synaptic transmission, and learning and memory. It also covers general features of the neurobiology of invertebrate circadian rhythms, development, and regeneration and reproduction. Some neurobiological phenomena are species-specific and diverse, especially in the domain of the neuronal control of locomotion and camouflage. Thus, separate chapters are provided on the control of swimming in annelids, crustaea and molluscs, locomotion in hexapods, and camouflage in cephalopods. Unique features of the handbook include chapters that review social behavior and intentionality in invertebrates. A chapter is devoted to summarizing past contributions of invertebrates to the understanding of nervous systems and identifying areas for future studies that will continue to advance that understanding.