It Cuts Both Ways: An Annelid Model System for the Study of Regeneration in the Laboratory and in the Classroom

The mechanisms supporting regeneration and successful recovery of function have fascinated scientists and the general public for quite some time, with the earliest description of regeneration occurring in the 8th century BC through the Greek mythological story of Prometheus. While most animals demonstrate the capacity for wound-healing, the ability to initiate a developmental process that leads to a partial or complete replacement of a lost structure varies widely among animal taxa. Variation also occurs within single species based on the nature and location of the wound and the developmental stage or age of the individual. Comparative studies of cellular and molecular changes that occur both during, and following, wound healing may point to conserved genomic pathways among animals of different regenerative capacity. Such insights could revolutionize studies within the field of regenerative medicine. In this review, we focus on several closely related species of Lumbriculus (Clitellata: Lumbriculidae), as we present a case for revisiting the use of an annelid model system for the study of regeneration. We hope that this review will provide a primer to Lumbriculus biology not only for regeneration researchers but also for STEM teachers and their students.Fil: Martinez Acosta, Veronica G.. University Of The Incarnate Word; Estados UnidosFil: Arellano Carbajal, Fausto. Universidad Autonoma de Queretaro.; MéxicoFil: Gillen, Kathy. Kenyon College; Estados UnidosFil: Tweeten, Kay A.. St. Catherine University; Estados UnidosFil: Zattara, Eduardo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Indiana University; Estados Unidos. National Museum Of Natural History. Departamento de Zoología. Area de Invertebrados; Estados Unido

The nematode Caenorhabditis elegans as a model to assess the anthelmintic potential from plant extracts

"Los nematodos parásitos afectan la productividad pecuaria, dando lugar a pérdidas económicas considerables. Sin embargo, son pocos los antihelmínticos disponibles en el mercado y la resistencia de los parásitos a los existentes va en incremento, por lo que su control es actualmente ineficiente. En este sentido, la búsqueda de nuevas estrategias para controlar la parasitosis es una necesidad actual. Una posibilidad para el control estriba en la investigación de metabolitos derivados de plantas, ya que el conocimiento sobre su uso tradicional es un referente de inicio. Sin embargo, la eficacia antihelmíntica, así como los mecanismos de acción de plantas con uso tradicional como anti-parasitarios, poco se han investigado científicamente, y en la mayoría de los casos se desconocen los compuestos activos responsables del efecto anti-parasitario. Una de las limitantes del estudio experimental del potencial antihelmíntico es la dificultad de trabajar con modelos parásitos. En este sentido, el nematodo de vida libre C. elegans es un modelo útil para entender el mecanismo de acción de drogas antihelmínticas. Por un lado, este nematodo se puede mantener y manipular en laboratorio con facilidad; por otro, comparte características fisiológicas y homología genética con nematodos parásitos, lo que permite comparaciones válidas. En esta revisión se pretende mostrar el potencial de la búsqueda de compuestos activos derivados de plantas tradicionalmente utilizadas como anti-parasitarios como punto de partida en el desarrollo de nuevos fármacos antihelmínticos, así como resaltar las ventajas que C. elegans proporciona para entender los mecanismos de acción de nuevos compuestos.""Parasitic nematodes affect livestock productivity, leading to economic losses. Despite their importance, few anthelmintics have been developed and several parasites have developed resistance to them, rendering control of parasitic infections very inefficient. In this sense, the search for new strategies to control parasitic nematodes is timely and relevant. One possibility is to conduct research on metabolites derived from plants with anthelmintic potential, since knowledge about its traditional use is a good starting point. However, the anthelmintic efficacy and mechanisms of action of plants traditionally used, have been scarcely investigated, and the bioactive compounds responsible for the effects remain mostly unknown. One of the limitations that experimental studies on potential anthelmintic face is the difficulty of working with parasite models. In this respect, the free-living nematode C. elegans is a useful tool for understanding the mechanism of action of anthelmintic drugs as well as mechanisms of resistance. First, C. elegans can be maintained and easily manipulated in the laboratory; in addition, C. elegans shares physiological characteristics and has genetic homology with nematode parasites, allowing valid comparisons. This review aims to underscore the potential of finding active compounds derived from plants traditionally used as anthelmintic as a starting point in the development of new drugs, as well as highlight the benefits that C. elegans provides for understanding mechanisms of action of novel anthelmintic.

Macoilin, a Conserved Nervous System–Specific ER Membrane Protein That Regulates Neuronal Excitability

Genome sequence comparisons have highlighted many novel gene families that are conserved across animal phyla but whose biological function is unknown. Here, we functionally characterize a member of one such family, the macoilins. Macoilins are characterized by several highly conserved predicted transmembrane domains towards the N-terminus and by coiled-coil regions C-terminally. They are found throughout Eumetazoa but not in other organisms. Mutants for the single Caenorhabditis elegans macoilin, maco-1, exhibit a constellation of behavioral phenotypes, including defects in aggregation, O2 responses, and swimming. MACO-1 protein is expressed broadly and specifically in the nervous system and localizes to the rough endoplasmic reticulum; it is excluded from dendrites and axons. Apart from subtle synapse defects, nervous system development appears wild-type in maco-1 mutants. However, maco-1 animals are resistant to the cholinesterase inhibitor aldicarb and sensitive to levamisole, suggesting pre-synaptic defects. Using in vivo imaging, we show that macoilin is required to evoke Ca2+ transients, at least in some neurons: in maco-1 mutants the O2-sensing neuron PQR is unable to generate a Ca2+ response to a rise in O2. By genetically disrupting neurotransmission, we show that pre-synaptic input is not necessary for PQR to respond to O2, indicating that the response is mediated by cell-intrinsic sensory transduction and amplification. Disrupting the sodium leak channels NCA-1/NCA-2, or the N-,P/Q,R-type voltage-gated Ca2+ channels, also fails to disrupt Ca2+ responses in the PQR cell body to O2 stimuli. By contrast, mutations in egl-19, which encodes the only Caenorhabditis elegans L-type voltage-gated Ca2+ channel α1 subunit, recapitulate the Ca2+ response defect we see in maco-1 mutants, although we do not see defects in localization of EGL-19. Together, our data suggest that macoilin acts in the ER to regulate assembly or traffic of ion channels or ion channel regulators

Anthelmintic effect of Psidium guajava and Tagetes erecta on wild-type and Levamisole-resistant Caenorhabditis elegans strains

"Ethnopharmacological relevance Psidium guajava and Tagetes erecta have been used traditionally to treat gastrointestinal parasites, but their active metabolites and mechanisms of action remain largely unknown. Aim of the study To evaluate the anthelmintic potential of Psidium guajava and Tagetes erecta extracts on Levamisole-sensitive and Levamisole-resistant strains of the model nematode Caenorhabditis elegans. Materials and methods Aqueous extracts of Psidium guajava (PGE) and Tagetes erecta (TEE) were assayed on locomotion and egg-laying behaviors of the wild-type (N2) and Levamisole-resistant (CB193) strains of Caenorhabditis elegans. Results Both extracts paralyzed wild-type and Levamisole-resistant nematodes in a dose-dependent manner. In wild-type worms, TEE 25 mg/mL induced a 75% paralysis after 8 h of treatment and PGE 25 mg/mL induced a 100% paralysis after 4 h of treatment. PGE exerted a similar paralyzing effect on N2 wild-type and CB193 Levamisole-resistant worms, while TEE only partially paralyzed CB193 worms. TEE 25 mg/mL decreased N2 egg-laying by 65% with respect to the untreated control, while PGE did it by 40%. Conclusions Psidium guajava leaves and Tagetes erecta flower-heads possess hydrosoluble compounds that block the motility of Caenorhabditis elegans by a mechanism different to that of the anthelmintic drug Levamisole. Effects are also observable on oviposition, which was diminished in the wild-type worms. The strong anthelmintic effects in crude extracts of these plants warrants future work to identify their active compounds and to elucidate their molecular mechanisms of action.