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1.
Adv Exp Med Biol ; 1155: 429-442, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468420

RESUMO

Taurine is traditionally used to treat Down Syndrome (DS); however, the actual foundation for this treatment is not well understood. DS patients suffer from disturbance of the proteostasis network (PN) due to aberrant calcium signaling, which eventually causes endoplasmic reticulum stress (ERS). Taurine has been suggested to play a role in modulating calcium homeostasis and ERS. This study examined whether taurine affects DS symptoms using C. elegans - a DS model in which calcineurins, Ca2+/calmodulin-dependent protein phosphatase is mutated to null. The DS nematode model has short body length, slow growth, fertility defects, serotonin-resistant egg-laying defects, and faulty thermal sensing. This study focused on whether taurine may ameliorate the severity of DS at the whole-body level, including reduction in ERS. When treated with taurine, DS nematodes appeared to have lower levels of ERS and phenotypes closer to the wild type. DS nematodes also showed improved egg laying efficiency and thermal sensing index comparable to the wild type. Our findings offer a new perspective on the effectiveness of taurine in treating DS and designing therapeutic strategies to lower ERS and restore disrupted PN.


Assuntos
Caenorhabditis elegans/fisiologia , Cálcio/fisiologia , Síndrome de Down , Estresse do Retículo Endoplasmático , Taurina/farmacologia , Animais , Modelos Animais de Doenças , Homeostase , Humanos
2.
Nat Commun ; 10(1): 3042, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31316054

RESUMO

Stress resistance and longevity are positively correlated but emerging evidence indicates that they are physiologically distinct. Identifying factors with distinctive roles in these processes is challenging because pro-longevity genes often enhance stress resistance. We demonstrate that TCER-1, the Caenorhabditis elegans homolog of human transcription elongation and splicing factor, TCERG1, has opposite effects on lifespan and stress resistance. We previously showed that tcer-1 promotes longevity in germline-less C. elegans and reproductive fitness in wild-type animals. Surprisingly, tcer-1 mutants exhibit exceptional resistance against multiple stressors, including infection by human opportunistic pathogens, whereas, TCER-1 overexpression confers immuno-susceptibility. TCER-1 inhibits immunity only during fertile stages of life. Elevating its levels ameliorates the fertility loss caused by infection, suggesting that TCER-1 represses immunity to augment fecundity. TCER-1 acts through repression of PMK-1 as well as PMK-1-independent factors critical for innate immunity. Our data establish key roles for TCER-1 in coordinating immunity, longevity and fertility, and reveal mechanisms that distinguish length of life from functional aspects of aging.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Regulação da Expressão Gênica/fisiologia , Imunidade Inata/genética , Longevidade/genética , Fatores de Alongamento de Peptídeos/metabolismo , Estresse Fisiológico/imunologia , Envelhecimento/genética , Envelhecimento/imunologia , Animais , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/imunologia , Suscetibilidade a Doenças/imunologia , Fertilidade/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Modelos Animais , Mutação , Fatores de Alongamento de Peptídeos/genética , Fatores de Alongamento de Peptídeos/imunologia , Estresse Fisiológico/genética
3.
BMC Biol ; 17(1): 56, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311534

RESUMO

BACKGROUND: Adaptive responses to stress are essential for cell and organismal survival. In metazoans, little is known about the impact of environmental stress on RNA homeostasis. RESULTS: By studying the regulation of a cadmium-induced gene named numr-1 in Caenorhabditis elegans, we discovered that disruption of RNA processing acts as a signal for environmental stress. We find that NUMR-1 contains motifs common to RNA splicing factors and influences RNA splicing in vivo. A genome-wide screen reveals that numr-1 is strongly and specifically induced by silencing of genes that function in basal RNA metabolism including subunits of the metazoan integrator complex. Human integrator processes snRNAs for functioning with splicing factors, and we find that silencing of C. elegans integrator subunits disrupts snRNA processing, causes aberrant pre-mRNA splicing, and induces the heat shock response. Cadmium, which also strongly induces numr-1, has similar effects on RNA and the heat shock response. Lastly, we find that heat shock factor-1 is required for full numr-1 induction by cadmium. CONCLUSION: Our results are consistent with a model in which disruption of integrator processing of RNA acts as a molecular damage signal initiating an adaptive stress response mediated by heat shock factor-1. When numr-1 is induced via this pathway in C. elegans, its function in RNA metabolism may allow it to mitigate further damage and thereby promote tolerance to cadmium.


Assuntos
Cádmio/toxicidade , Caenorhabditis elegans/fisiologia , Regulação da Expressão Gênica , Resposta ao Choque Térmico/fisiologia , Processamento Pós-Transcricional do RNA/fisiologia , Processamento de RNA , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Resposta ao Choque Térmico/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , RNA Nuclear Pequeno/genética , RNA Nuclear Pequeno/metabolismo , Estresse Fisiológico
4.
Environ Pollut ; 246: 904-913, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31159140

RESUMO

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) has been frequently detected in environmental media and biological samples. However, knowledge of its adverse health consequences is limited. In the current study, Caenorhabditis elegans (C. elegans, L1 larvae) were exposed to TDCPP at environmentally relevant concentrations (control, 0.1, 1, 100 and 1000 µg L-1) for 72 h to explore any association between TDCPP and the aging process. Some of the degenerative age-related indicators were observed, including locomotion behaviors and lifespan. As crucial biomarkers of aging, the accumulation of lipofuscin, and lipid peroxidation (LPO) products exemplified by 4-hydroxynon-2-enal (4-HNE) were detected. This product forms as a result of oxidative stress, as confirmed by an N-acetyl-L-cysteine (NAC) pharmacological assay. Moreover, a significant increase in reactive oxide species (ROS) production in a dose-dependent manner using a fluorescent probe was observed. For the underlying molecular mechanism of the above aging phenotypes, significantly upregulated transcription of genes related to antioxidant systems, especially a subset of glutathione S-transferase (gst-5, gst-6, gst-9, gst-10, gst-19, gst-24, gst-26, gst-29, gst-33, and gst-38), was found by RNA-Seq and further confirmed by RT-qPCR. The elevated glutathione S-transferase (GST) was attributed to the significant increase in 4-HNE because mutations in gst-5 and gst-24 inhibited the conjugation of GSTs with 4-HNE. Therefore, GST play an indispensable role in the detoxification process of TDCPP exposure and further confirmed LPO accumulation at the molecular mechanism level. In conclusion, TDCPP accelerated the aging process induced by the LPO products, 4-HNE, response to reactive oxidative species in C. elegans.


Assuntos
Envelhecimento/efeitos dos fármacos , Aldeídos/metabolismo , Poluentes Ambientais/toxicidade , Compostos Organofosforados/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Caenorhabditis elegans/fisiologia , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos , Estresse Oxidativo
5.
Nat Commun ; 10(1): 2602, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31197136

RESUMO

Temperature is a key factor for determining the lifespan of both poikilotherms and homeotherms. It is believed that animals live longer at lower body temperatures. However, the precise mechanism remains largely unknown. Here, we report that autophagy serves as a boost mechanism for longevity at low temperature in the nematode Caenorhabditis elegans. The adiponectin receptor AdipoR2 homolog PAQR-2 signaling detects temperature drop and augments the biosynthesis of two ω-6 polyunsaturated fatty acids, γ-linolenic acid and arachidonic acid. These two polyunsaturated fatty acids in turn initiate autophagy in the epidermis, delaying an age-dependent decline in collagen contents, and extending the lifespan. Our findings reveal that the adiponectin receptor PAQR-2 signaling acts as a regulator linking low temperature with autophagy to extend lifespan, and suggest that such a mechanism may be evolutionally conserved among diverse organisms.


Assuntos
Autofagia/fisiologia , Proteínas de Caenorhabditis elegans/fisiologia , Caenorhabditis elegans/fisiologia , Longevidade/fisiologia , Proteínas de Membrana/fisiologia , Animais , Animais Geneticamente Modificados , Ácido Araquidônico/biossíntese , Temperatura Baixa , Colágeno/metabolismo , Epiderme/metabolismo , Ácidos Graxos Ômega-6/biossíntese , Interferência de RNA , Transdução de Sinais/fisiologia
6.
Sci Total Environ ; 676: 767-781, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31055208

RESUMO

Emission of ionizing radiation (IR) in the environment is a natural phenomenon which can be enhanced by human activities. Ecosystems are then chronically exposed to IR. But environmental risk assessment of chronic exposure suffers from a lack of knowledge. Extrapolation of data from acute to chronic exposure is not always relevant, and can lead to uncertainties as effects could be different between the two irradiation modes, especially regarding reproduction endpoint, which is an ecologically relevant parameter. In the present study, we decided to refine the understanding of the molecular mechanisms involved in response to acute and chronic γ-irradiation by a global proteome label free LC-MS/MS analysis. C. elegans were exposed to 3 common cumulated radiation doses for acute or chronic exposure condition and global modification of the proteome was studied. This analysis of protein expression has demonstrated the modulation of proteins involved in regulatory biological processes such as lipid transport, DNA replication, germ cell development, apoptosis, ion transport, cuticle development, and aging at lower doses than those for which individual effects on reproduction have been previously observed. Thus, these proteins could constitute early and sensitive markers of radio-induced reprotoxicity; more specifically HAT-1, RPS-19 in acute and VIT-3 for chronic conditions that are expressed in a dose-dependent manner. Finally, to focus on reproduction process, this analysis showed either repression or overexpression of 12 common proteins in organisms exposed to acute or chronic irradiation, respectively. These proteins include the vitellogenin cluster notably involved in lipid transport and oocyte maturation and proteins involved in cuticle development and molting i.e. COL-14, GLF-1, NOAH-1, NOAH-2, ACN-1. These results show that protein expression modulation is a sensitive and predictive marker of radio-induced reproductive effects, but also highlight limitation of data extrapolation from acute to chronic exposure for environmental risk assessment.


Assuntos
Caenorhabditis elegans/efeitos da radiação , Raios gama , Proteoma/efeitos da radiação , Radiação Ionizante , Animais , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/metabolismo , Relação Dose-Resposta à Radiação , Reprodução
7.
Genetics ; 212(1): 25-51, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31053616

RESUMO

Caenorhabditis elegans lives in a complex habitat in which they routinely experience large fluctuations in temperature, and encounter physical obstacles that vary in size and composition. Their habitat is shared by other nematodes, by beneficial and harmful bacteria, and nematode-trapping fungi. Not surprisingly, these nematodes can detect and discriminate among diverse environmental cues, and exhibit sensory-evoked behaviors that are readily quantifiable in the laboratory at high resolution. Their ability to perform these behaviors depends on <100 sensory neurons, and this compact sensory nervous system together with powerful molecular genetic tools has allowed individual neuron types to be linked to specific sensory responses. Here, we describe the sensory neurons and molecules that enable C. elegans to sense and respond to physical stimuli. We focus primarily on the pathways that allow sensation of mechanical and thermal stimuli, and briefly consider this animal's ability to sense magnetic and electrical fields, light, and relative humidity. As the study of sensory transduction is critically dependent upon the techniques for stimulus delivery, we also include a section on appropriate laboratory methods for such studies. This chapter summarizes current knowledge about the sensitivity and response dynamics of individual classes of C. elegans mechano- and thermosensory neurons from in vivo calcium imaging and whole-cell patch-clamp electrophysiology studies. We also describe the roles of conserved molecules and signaling pathways in mediating the remarkably sensitive responses of these nematodes to mechanical and thermal cues. These studies have shown that the protein partners that form mechanotransduction channels are drawn from multiple superfamilies of ion channel proteins, and that signal transduction pathways responsible for temperature sensing in C. elegans share many features with those responsible for phototransduction in vertebrates.


Assuntos
Caenorhabditis elegans/fisiologia , Mecanotransdução Celular , Células Receptoras Sensoriais/fisiologia , Transdução de Sinais , Estresse Fisiológico , Sensação Térmica , Animais , Caenorhabditis elegans/metabolismo , Fenômenos Mecânicos , Sensação , Células Receptoras Sensoriais/metabolismo , Temperatura Ambiente
8.
Yakugaku Zasshi ; 139(5): 759-765, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31061346

RESUMO

Early detection and treatment are important for the successful eradication of various cancers; therefore, the development of economical, noninvasive novel cancer screening systems is critical. Previous reports using canine scent detection have demonstrated the existence of cancer-specific odors. However, it is difficult to introduce canine scent recognition into clinical practice because of the need to maintain accuracy. In this study, we developed a Nematode-Nose (N-NOSE) test using Caenorhabditis elegans to provide a novel, highly accurate cancer detection system that is economical, painless, rapid, and convenient. We demonstrated that wild-type C. elegans displayed attractive chemotaxis toward human cancer cell secretions, cancer tissues, and urine from cancer patients but avoided control urine. In parallel, C. elegans olfactory neurons showed a significantly stronger response to urine from cancer patients than to control urine. In contrast, G protein α mutants and animals with ablated olfactory neurons were not attracted to urine from cancer patients, suggesting that they sense odors in urine. We tested 242 samples to measure the performance of the N-NOSE test and found that the sensitivity was 95.8%, which is markedly higher than that of other existing tumor markers. Furthermore, the specificity was 95.0%. Importantly, this test could detect various cancer types tested at the early stage (stage 0 or 1). C. elegans scent-based analyses therefore might provide a new strategy for the detection and study of disease-associated scents.


Assuntos
Caenorhabditis elegans/fisiologia , Detecção Precoce de Câncer/métodos , Diagnóstico Precoce , Neoplasias/diagnóstico , Nervo Olfatório/fisiologia , Olfato/fisiologia , Animais , Humanos , Gradação de Tumores , Neoplasias/patologia , Urina
9.
Nat Commun ; 10(1): 1882, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015396

RESUMO

Glutamate is a major excitatory neurotransmitter, and impaired glutamate clearance following synaptic release promotes spillover, inducing extra-synaptic signaling. The effects of glutamate spillover on animal behavior and its neural correlates are poorly understood. We developed a glutamate spillover model in Caenorhabditis elegans by inactivating the conserved glial glutamate transporter GLT-1. GLT-1 loss drives aberrant repetitive locomotory reversal behavior through uncontrolled oscillatory release of glutamate onto AVA, a major interneuron governing reversals. Repetitive glutamate release and reversal behavior require the glutamate receptor MGL-2/mGluR5, expressed in RIM and other interneurons presynaptic to AVA. mgl-2 loss blocks oscillations and repetitive behavior; while RIM activation is sufficient to induce repetitive reversals in glt-1 mutants. Repetitive AVA firing and reversals require EGL-30/Gαq, an mGluR5 effector. Our studies reveal that cyclic autocrine presynaptic activation drives repetitive reversals following glutamate spillover. That mammalian GLT1 and mGluR5 are implicated in pathological motor repetition suggests a common mechanism controlling repetitive behaviors.


Assuntos
Comportamento Animal/fisiologia , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiologia , Ácido Glutâmico/metabolismo , Terminações Pré-Sinápticas/fisiologia , Receptores de Glutamato Metabotrópico/metabolismo , Animais , Animais Geneticamente Modificados , Conjuntos de Dados como Assunto , Transportador 2 de Aminoácido Excitatório/metabolismo , Perfilação da Expressão Gênica , Interneurônios/metabolismo , Locomoção/fisiologia , Modelos Animais , Receptor de Glutamato Metabotrópico 5 , Receptores de Glutamato Metabotrópico/genética
10.
Biosci Biotechnol Biochem ; 83(8): 1484-1489, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30999822

RESUMO

Rice kefiran is superior in functionality, has high concentration of mucilaginous polysaccharide, and low lipid content, compared to conventional kefiran. However, reports on its physiological functionality, especially studies on life expectancy and aging, in model organisms are rare. In this study, nematodes were used as model organisms that were fed rice kefiran, along with Escherichia coli OP50, as a result of which, the lifespan of nematodes was extended and age-related retardation of mobility was suppressed. It also increased the heat stress resistance in nematodes. Experiments using daf-16 deletion mutant revealed that rice kefiran functions via DAF-16. Thus, this study revealed the longevity, anti-aging and heat stress tolerance effects of rice kefiran in nematodes.


Assuntos
Envelhecimento/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Grão Comestível/metabolismo , Fermentação , Fatores de Transcrição Forkhead/metabolismo , Lactobacillus/metabolismo , Oryza/metabolismo , Polissacarídeos/metabolismo , Adaptação Fisiológica , Animais , Caenorhabditis elegans/fisiologia , Temperatura Alta
11.
Nat Protoc ; 14(5): 1455-1488, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953041

RESUMO

Sleep is nearly universal among animals, yet remains poorly understood. Recent work has leveraged simple model organisms, such as Caenorhabditis elegans and Drosophila melanogaster larvae, to investigate the genetic and neural bases of sleep. However, manual methods of recording sleep behavior in these systems are labor intensive and low in throughput. To address these limitations, we developed methods for quantitative imaging of individual animals cultivated in custom microfabricated multiwell substrates, and used them to elucidate molecular mechanisms underlying sleep. Here, we describe the steps necessary to design, produce, and image these plates, as well as analyze the resulting behavioral data. We also describe approaches for experimentally manipulating sleep. Following these procedures, after ~2 h of experimental preparation, we are able to simultaneously image 24 C. elegans from the second larval stage to adult stages or 20 Drosophila larvae during the second instar life stage at a spatial resolution of 10 or 27 µm, respectively. Although this system has been optimized to measure activity and quiescence in Caenorhabditis larvae and adults and in Drosophila larvae, it can also be used to assess other behaviors over short or long periods. Moreover, with minor modifications, it can be adapted for the behavioral monitoring of a wide range of small animals.


Assuntos
Caenorhabditis elegans/fisiologia , Drosophila melanogaster/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Larva/fisiologia , Sono/fisiologia , Animais , Comportamento Animal/fisiologia , Microscopia , Fotografação
12.
Nat Commun ; 10(1): 1791, 2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30996251

RESUMO

Apoptotic death of cells damaged by genotoxic stress requires regulatory input from surrounding tissues. The C. elegans scaffold protein KRI-1, ortholog of mammalian KRIT1/CCM1, permits DNA damage-induced apoptosis of cells in the germline by an unknown cell non-autonomous mechanism. We reveal that KRI-1 exists in a complex with CCM-2 in the intestine to negatively regulate the ERK-5/MAPK pathway. This allows the KLF-3 transcription factor to facilitate expression of the SLC39 zinc transporter gene zipt-2.3, which functions to sequester zinc in the intestine. Ablation of KRI-1 results in reduced zinc sequestration in the intestine, inhibition of IR-induced MPK-1/ERK1 activation, and apoptosis in the germline. Zinc localization is also perturbed in the vasculature of krit1-/- zebrafish, and SLC39 zinc transporters are mis-expressed in Cerebral Cavernous Malformations (CCM) patient tissues. This study provides new insights into the regulation of apoptosis by cross-tissue communication, and suggests a link between zinc localization and CCM disease.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Apoptose/fisiologia , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Zinco/metabolismo , Animais , Animais Geneticamente Modificados , Apoptose/efeitos da radiação , Proteínas Reguladoras de Apoptose/genética , Encéfalo/patologia , Encéfalo/cirurgia , Caenorhabditis elegans/fisiologia , Caenorhabditis elegans/efeitos da radiação , Proteínas de Caenorhabditis elegans/genética , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteína KRIT1/genética , Proteína KRIT1/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Mutagênese , Mutação , Fosforilação/fisiologia , Alinhamento de Sequência , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
13.
PLoS Genet ; 15(3): e1007706, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30849079

RESUMO

In the natural environment, animals often encounter multiple sensory cues that are simultaneously present. The nervous system integrates the relevant sensory information to generate behavioral responses that have adaptive values. However, the neuronal basis and the modulators that regulate integrated behavioral response to multiple sensory cues are not well defined. Here, we address this question using a behavioral decision in C. elegans when the animal is presented with an attractive food source together with a repulsive odorant. We identify specific sensory neurons, interneurons and neuromodulators that orchestrate the decision-making process, suggesting that various states and contexts may modulate the multisensory integration. Among these modulators, we characterize a new function of a conserved TGF-ß pathway that regulates the integrated decision by inhibiting the signaling from a set of central neurons. Interestingly, we find that a common set of modulators, including the TGF-ß pathway, regulate the integrated response to the pairing of different foods and repellents. Together, our results provide mechanistic insights into the modulatory signals regulating multisensory integration.


Assuntos
Caenorhabditis elegans/fisiologia , Animais , Animais Geneticamente Modificados , Comportamento Animal/fisiologia , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/fisiologia , Alimentos , Genes de Helmintos , Interneurônios/fisiologia , Cetonas , Mutação , Neuropeptídeos/genética , Neuropeptídeos/fisiologia , Neurotransmissores/fisiologia , Odorantes , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/fisiologia , Células Receptoras Sensoriais/fisiologia , Transdução de Sinais , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/fisiologia
14.
Proc Natl Acad Sci U S A ; 116(15): 7226-7231, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30902894

RESUMO

The roundworm Caenorhabditis elegans exhibits robust escape behavior in response to rapidly rising temperature. The behavior lasts for a few seconds, shows history dependence, involves both sensory and motor systems, and is too complicated to model mechanistically using currently available knowledge. Instead we model the process phenomenologically, and we use the Sir Isaac dynamical inference platform to infer the model in a fully automated fashion directly from experimental data. The inferred model requires incorporation of an unobserved dynamical variable and is biologically interpretable. The model makes accurate predictions about the dynamics of the worm behavior, and it can be used to characterize the functional logic of the dynamical system underlying the escape response. This work illustrates the power of modern artificial intelligence to aid in discovery of accurate and interpretable models of complex natural systems.


Assuntos
Caenorhabditis elegans/fisiologia , Reação de Fuga/fisiologia , Temperatura Alta , Modelos Biológicos , Animais
15.
Sensors (Basel) ; 19(6)2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30917520

RESUMO

The nematode Caenorhabditis elegans (C. elegans) is often used as an alternative animal model due to several advantages such as morphological changes that can be seen directly under a microscope. Limitations of the model include the usage of expensive and cumbersome microscopes, and restrictions of the comprehensive use of C. elegans for toxicological trials. With the general applicability of the detection of C. elegans from microscope images via machine learning, as well as of smartphone-based microscopes, this article investigates the suitability of smartphone-based microscopy to detect C. elegans in a complete Petri dish. Thereby, the article introduces a smartphone-based microscope (including optics, lighting, and housing) for monitoring C. elegans and the corresponding classification via a trained Histogram of Oriented Gradients (HOG) feature-based Support Vector Machine for the automatic detection of C. elegans. Evaluation showed classification sensitivity of 0.90 and specificity of 0.85, and thereby confirms the general practicability of the chosen approach.


Assuntos
Caenorhabditis elegans/fisiologia , Aprendizado de Máquina , Microscopia , Animais , Caenorhabditis elegans/isolamento & purificação , Processamento de Imagem Assistida por Computador , Smartphone
16.
Genetics ; 212(1): 213-229, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30867196

RESUMO

During meiosis, a series of evolutionarily conserved events allow for reductional chromosome division, which is required for sexual reproduction. Although individual meiotic processes have been extensively studied, we currently know far less about how meiosis is regulated and coordinated. In the Caenorhabditis elegans gonad, mitogen-activated protein kinase (MAPK) signaling drives oogenesis while undergoing spatial activation and deactivation waves. However, it is currently unclear how MAPK activation is governed and how it facilitates the progression of oogenesis. Here, we show that the oocyte and germline-related 2 (ogr-2) gene affects proper progression of oogenesis. Complete deletion of ogr-2 results in delayed meiotic entry and late spatial onset of double-strand break repair. Elevated levels of apoptosis are observed in this mutant, independent of the meiotic canonical checkpoints; however, they are dependent on the MAPK terminal member MPK-1/ERK. MPK-1 activation is elevated in diplotene in ogr-2 mutants and its aberrant spatial activation correlates with stages where meiotic progression defects are evident. Deletion of ogr-2 significantly reduces the expression of lip-1, a phosphatase reported to repress MPK-1, which is consistent with OGR-2 localization at chromatin in germ cells. We suggest that OGR-2 modulates the expression of lip-1 to promote the timely progression of meiosis through MPK-1 spatial deactivation.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Proteínas de Ciclo Celular/metabolismo , Sistema de Sinalização das MAP Quinases , Meiose , Oogênese , Proteínas Tirosina Fosfatases/metabolismo , Animais , Caenorhabditis elegans/fisiologia , Feminino
17.
Genetics ; 212(1): 231-243, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30898771

RESUMO

Precise signaling at the neuromuscular junction (NMJ) is essential for proper muscle contraction. In the Caenorhabditis elegans pharynx, acetylcholine (ACh) released from the MC and M4 motor neurons stimulates two different types of contractions in adjacent muscle cells, termed pumping and isthmus peristalsis. MC stimulates rapid pumping through the nicotinic ACh receptor EAT-2, which is tightly localized at the MC NMJ, and eat-2 mutants exhibit a slow pump rate. Surprisingly, we found that eat-2 mutants also hyperstimulated peristaltic contractions, and that they were characterized by increased and prolonged Ca2+ transients in the isthmus muscles. This hyperstimulation depends on cross talk with the GAR-3 muscarinic ACh receptor as gar-3 mutation specifically suppressed the prolonged contraction and increased Ca2+ observed in eat-2 mutant peristalses. Similar GAR-3-dependent hyperstimulation was also observed in mutants lacking the ace-3 acetylcholinesterase, and we suggest that NMJ defects in eat-2 and ace-3 mutants result in ACh stimulation of extrasynaptic GAR-3 receptors in isthmus muscles. gar-3 mutation also suppressed slow larval growth and prolonged life span phenotypes that result from dietary restriction in eat-2 mutants, indicating that cross talk with the GAR-3 receptor has a long-term impact on feeding behavior and eat-2 mutant phenotypes.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Contração Muscular , Músculos/metabolismo , Junção Neuromuscular/metabolismo , Receptores Muscarínicos/metabolismo , Receptores Nicotínicos/metabolismo , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/fisiologia , Neurônios Motores , Músculos/fisiologia , Faringe/metabolismo , Faringe/fisiologia , Receptores Muscarínicos/fisiologia , Receptores Nicotínicos/fisiologia , Transdução de Sinais
18.
Proc Natl Acad Sci U S A ; 116(14): 7107-7112, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30872487

RESUMO

Feeding is vital for animal survival and is tightly regulated by the endocrine and nervous systems. To study the mechanisms of humoral regulation of feeding behavior, we investigated serotonin (5-HT) and octopamine (OA) signaling in Caenorhabditis elegans, which uses pharyngeal pumping to ingest bacteria into the gut. We reveal that a cross-modulation mechanism between 5-HT and OA, which convey feeding and fasting signals, respectively, mainly functions in regulating the pumping and secretion of both neuromodulators via ADF/RIC/SIA feedforward neurocircuit (consisting of ADF, RIC, and SIA neurons) and ADF/RIC/AWB/ADF feedback neurocircuit (consisting of ADF, RIC, AWB, and ADF neurons) under conditions of food supply and food deprivation, respectively. Food supply stimulates food-sensing ADFs to release more 5-HT, which augments pumping via inhibiting OA secretion by RIC interneurons and, thus, alleviates pumping suppression by OA-activated SIA interneurons/motoneurons. In contrast, nutrient deprivation stimulates RICs to secrete OA, which suppresses pumping via activating SIAs and maintains basal pumping and 5-HT production activity through excitation of ADFs relayed by AWB sensory neurons. Notably, the feedforward and feedback circuits employ distinct modalities of neurosignal integration, namely, disinhibition and disexcitation, respectively.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Octopamina/farmacologia , Serotonina/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Proteínas de Caenorhabditis elegans/fisiologia , Ingestão de Alimentos/fisiologia , Jejum/fisiologia , Privação de Alimentos/fisiologia , Interneurônios/patologia , Neurônios Motores/fisiologia , Células Receptoras Sensoriais/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
19.
Adv Exp Med Biol ; 1134: 163-175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30919337

RESUMO

Changes in energy metabolism occur not only in diseases such as cancer but also in the normal development and aging processes of various organisms. These metabolic changes result to lead to imbalances in energy metabolism related to cellular and tissue homeostasis. In the model organism C. elegans, which is used to study aging, an imbalance in age-related energy metabolism exists between mitochondrial oxidative phosphorylation and aerobic glycolysis. Cellular lactate and pyruvate are key intermediates in intracellular energy metabolic pathways and can indicate age-related imbalances in energy metabolism. Thus, the cellular lactate/pyruvate ratio can be monitored as a biomarker during aging. Moreover, recent studies have proposed a candidate novel biomarker for aging and age-related declines in the nematode C. elegans.


Assuntos
Envelhecimento , Caenorhabditis elegans/metabolismo , Metabolismo Energético , Mitocôndrias/metabolismo , Animais , Caenorhabditis elegans/fisiologia , Ácido Láctico , Fosforilação Oxidativa , Ácido Pirúvico
20.
BMC Ecol ; 19(1): 15, 2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30925873

RESUMO

BACKGROUND: By altering their habitats, engineering species can improve their own fitness. However, the effect of this strategy on the fitness of coexisting species or on the structure of the respective food web is poorly understood. In this study, bacteria and bacterivorous nematodes with short (Caenorhabditis elegans) and long (Plectus acuminatus) life cycles were exposed to the mucus secreted by the freshwater flatworm Polycelis tenuis. The growth, reproduction, and feeding preferences of the nematodes in the presence/absence of the mucus were then determined. In addition, confocal laser scanning microscopy (CLSM) was used to examine the structural footprint of the mucus and the mucus colonization dynamics of bacteria and protozoans. RESULTS: Mucus exposure resulted in a greater reproductive output in P. acuminatus than in C. elegans. In a cafeteria experiment, both nematode species were attracted by bacteria-rich patches and were not deterred by mucus. CLSM showed that the flatworms spread a layer of polysaccharide-rich mucus ca. 15 µm thick from their tails. Subsequent colonization of the mucus by bacteria and protozoans resulted in an architecture that progressively resembled a complex biofilm. The presence of protozoans reduced nematode reproduction, presumably due to competition for their bacterial food supply. CONCLUSION: Animal secretions such as mucus may have broader, community-level consequences and contribute to fueling microbial food webs.


Assuntos
Cromadoria/fisiologia , Cadeia Alimentar , Muco/fisiologia , Turbelários/fisiologia , Animais , Fenômenos Fisiológicos Bacterianos , Caenorhabditis elegans/fisiologia
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