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1.
Front Immunol ; 14: 1118003, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37122724

RESUMO

Salmonella enterica serovar Paratyphi A (S. Paratyphi A) is a pathogen that can cause enteric fever. According to the recent epidemic trends of typhoid fever, S. Paratyphi A has been the major important causative factor in paratyphoid fever. An effective vaccine for S. Paratyphi A has not been developed, which made it a tricky public health concern. Until now, how S. Paratyphi A interacts with organisms remain unknown. Here using lifespan assay, we found that S. Paratyphi A could infect Caenorhabditis elegans (C. elegans) at 25°C, and attenuate thermotolerance. The immune response of C. elegans was mediated by tir-1, nsy-1, sek-1, pmk-1, mpk-1, skn-1, daf-2 and daf-16, suggesting that S. Paratyphi A could regulate the MAPK and insulin pathways. Furthermore, we observed several phenotypical changes when C. elegans were fed S. Paratyphi A, including an accelerated decline in body movement, reduced the reproductive capacity, shortened spawning cycle, strong preference for OP50, arrested pharyngeal pumping and colonization of the intestinal lumen. The virulence of S. Paratyphi A requires living bacteria and is not mediated by secreting toxin. Using hydrogen peroxide analysis and quantitative RT-PCR, we discovered that S. Paratyphi A could increase oxidative stress and regulate the immune response in C. elegans. Our results sheds light on the infection mechanisms of S. Paratyphi A and lays a foundation for drugs and vaccine development.


Assuntos
Proteínas de Caenorhabditis elegans , Febre Tifoide , Vacinas Tíficas-Paratíficas , Animais , Salmonella paratyphi A , Caenorhabditis elegans , Imunidade , Proteínas de Caenorhabditis elegans/genética , Fatores de Transcrição Forkhead
2.
Methods Mol Biol ; 2668: 277-299, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37140803

RESUMO

Caenorhabditis elegans is a microscopic model nematode characterized by body transparency and ease of genetic manipulation. Release of extracellular vesicles (EVs) is observed from different tissues; of particular interest are the EVs released by the cilia of sensory neurons. C. elegans ciliated sensory neurons produce EVs that are environmentally released and/or captured by neighboring glial cells. In this chapter, we describe a methodological approach to image the biogenesis, release, and capture of EVs by glial cells in anesthetized animals. This method will allow the experimenter to visualize and quantify the release of ciliary-derived EVs.


Assuntos
Proteínas de Caenorhabditis elegans , Vesículas Extracelulares , Animais , Caenorhabditis elegans/genética , Cílios/fisiologia , Vesículas Extracelulares/fisiologia , Proteínas de Caenorhabditis elegans/genética , Células Receptoras Sensoriais
3.
PLoS One ; 18(5): e0285328, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37155688

RESUMO

In epidermal tissues, extracellular matrices (ECMs) function as barriers between the organism and environment. Despite being at the interface with the environment, little is known about the role of animal barrier ECMs in sensing stress and communicating with cytoprotective gene pathways in neighboring cells. We and others have identified a putative damage sensor in the C. elegans cuticle that regulates osmotic, detoxification, and innate immune response genes. This pathway is associated with circumferential collagen bands called annular furrows; mutation or loss of furrow collagens causes constitutive activation of osmotic, detoxification, and innate immune response genes. Here, we performed a genome-wide RNAi screen for modulators of osmotic stress response gene gpdh-1 in a furrow collagen mutant strain. RNAi of six genes identified in this screen were tested under other conditions and for effects on other stress responses. The functions of these genes suggest negative feedback within osmolyte accumulation pathways and interactions with ATP homeostasis and protein synthesis. Loss of these gpdh-1 modulators had distinct effects on canonical detoxification and innate immune response genes.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Interferência de RNA , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Retroalimentação , Matriz Extracelular/metabolismo , Colágeno/metabolismo
4.
Physiol Res ; 72(2): 149-166, 2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-37159850

RESUMO

The expansion of industry and the use of pesticides in agriculture represent one of the major causes of environmental contamination. Unfortunately, individuals and animals are exposed to these foreign and often toxic substances on a daily basis. Therefore, it is crucial to monitor the impact of such chemicals on human health. Several in vitro studies have addressed this issue, but it is difficult to explore the impact of these compounds on living organisms. A nematode Caenorhabditis elegans has become a useful alternative to animal models mainly because of its transparent body, fast growth, short life cycle, and easy cultivation. Furthermore, at the molecular level, there are significant similarities between humans and C. elegans. These unique features make it an excellent model to complement mammalian models in toxicology research. Heavy metals and pesticides, which are considered environmental contaminants, are known to have affected the locomotion, feeding behavior, brood size, growth, life span, and cell death of C. elegans. Today, there are increasing numbers of research articles dedicated to this topic, of which we summarized the most recent findings dedicated to the effect of heavy metals, heavy metal mixtures, and pesticides on the well-characterized nervous system of this nematode.


Assuntos
Síndromes Neurotóxicas , Praguicidas , Animais , Humanos , Caenorhabditis elegans , Praguicidas/toxicidade , Internacionalidade , Locomoção , Mamíferos
5.
Curr Biol ; 33(9): R361-R363, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-37160094

RESUMO

Cannabinoids can enhance the preference for calorific foods through hedonic feeding behaviors. A new study identifies and characterizes these indulgent behaviors in the nematode Caenorhabditis elegans, providing insights into the mechanisms of their regulation.


Assuntos
Meio Ambiente , Neurociências , Animais , Caenorhabditis elegans , Comportamento Alimentar , Alimentos
6.
Cells ; 12(9)2023 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-37174736

RESUMO

Chlordecone (CLD) is an organochlorine pesticide (OCP) that is currently banned but still contaminates ecosystems in the French Caribbean. Because OCPs are known to increase the risk of Parkinson's disease (PD), we tested whether chronic low-level intoxication with CLD could reproduce certain key characteristics of Parkinsonism-like neurodegeneration. For that, we used culture systems of mouse midbrain dopamine (DA) neurons and glial cells, together with the nematode C. elegans as an in vivo model organism. We established that CLD kills cultured DA neurons in a concentration- and time-dependent manner while exerting no direct proinflammatory effects on glial cells. DA cell loss was not impacted by the degree of maturation of the culture. The use of fluorogenic probes revealed that CLD neurotoxicity was the consequence of oxidative stress-mediated insults and mitochondrial disturbances. In C. elegans worms, CLD exposure caused a progressive loss of DA neurons associated with locomotor deficits secondary to alterations in food perception. L-DOPA, a molecule used for PD treatment, corrected these deficits. Cholinergic and serotoninergic neuronal cells were also affected by CLD in C. elegans, although to a lesser extent than DA neurons. Noticeably, CLD also promoted the phosphorylation of the aggregation-prone protein tau (but not of α-synuclein) both in midbrain cell cultures and in a transgenic C. elegans strain expressing a human form of tau in neurons. In summary, our data suggest that CLD is more likely to promote atypical forms of Parkinsonism characterized by tau pathology than classical synucleinopathy-associated PD.


Assuntos
Clordecona , Doença de Parkinson , Transtornos Parkinsonianos , Praguicidas , Animais , Humanos , Camundongos , Caenorhabditis elegans/metabolismo , Clordecona/metabolismo , Praguicidas/toxicidade , Ecossistema , Transtornos Parkinsonianos/patologia , Doença de Parkinson/metabolismo , Neurônios Dopaminérgicos/metabolismo , Mesencéfalo/patologia
7.
Int J Mol Sci ; 24(9)2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37175557

RESUMO

The mechanistic target of rapamycin (mTOR) kinase is one of the top drug targets for promoting health and lifespan extension. Besides rapamycin, only a few other mTOR inhibitors have been developed and shown to be capable of slowing aging. We used machine learning to predict novel small molecules targeting mTOR. We selected one small molecule, TKA001, based on in silico predictions of a high on-target probability, low toxicity, favorable physicochemical properties, and preferable ADMET profile. We modeled TKA001 binding in silico by molecular docking and molecular dynamics. TKA001 potently inhibits both TOR complex 1 and 2 signaling in vitro. Furthermore, TKA001 inhibits human cancer cell proliferation in vitro and extends the lifespan of Caenorhabditis elegans, suggesting that TKA001 is able to slow aging in vivo.


Assuntos
Proteínas de Caenorhabditis elegans , Neoplasias , Animais , Humanos , Caenorhabditis elegans/metabolismo , Longevidade , Inibidores de MTOR , Simulação de Acoplamento Molecular , Serina-Treonina Quinases TOR/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Sirolimo/farmacologia , Proliferação de Células , Inteligência Artificial , Neoplasias/tratamento farmacológico
8.
Proc Natl Acad Sci U S A ; 120(19): e2218023120, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37126715

RESUMO

Many chemosensory cues evoke responses of the same valence under widely varying physiological conditions. It remains unclear whether similar or distinct neural mechanisms are involved in the detection and processing of such chemosensory cues across contexts. We show that in Caenorhabditis elegans, a chemosensory cue is processed by distinct neural mechanisms at two different life stages that share the same valence state. Both starved adults and dauer larvae are attracted to carbon dioxide (CO2), but CO2 evokes different patterns of neural activity and different motor outputs at the two life stages. Moreover, the same interneuron within the CO2 microcircuit plays a different role in driving CO2-evoked motor output at the two life stages. The dauer-specific patterns of CO2-evoked activity in this interneuron require a dauer-specific gap junction complex and insulin signaling. Our results demonstrate that functionally distinct microcircuits are engaged in response to a chemosensory cue that triggers the same valence state at different life stages, revealing an unexpected complexity to chemosensory processing.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/fisiologia , Sinais (Psicologia) , Dióxido de Carbono , Interneurônios/fisiologia , Transdução de Sinais/fisiologia , Larva
9.
J Cell Biol ; 222(8)2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37158801

RESUMO

The maintenance of plasma membrane integrity and a capacity for efficiently repairing damaged membranes are essential for cell survival. Large-scale wounding depletes various membrane components at the wound sites, including phosphatidylinositols, yet little is known about how phosphatidylinositols are generated after depletion. Here, working with our in vivo C. elegans epidermal cell wounding model, we discovered phosphatidylinositol 4-phosphate (PtdIns4P) accumulation and local phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] generation at the wound site. We found that PtdIns(4,5)P2 generation depends on the delivery of PtdIns4P, PI4K, and PI4P 5-kinase PPK-1. In addition, we show that wounding triggers enrichment of the Golgi membrane to the wound site, and that is required for membrane repair. Moreover, genetic and pharmacological inhibitor experiments support that the Golgi membrane provides the PtdIns4P for PtdIns(4,5)P2 generation at the wounds. Our findings demonstrate how the Golgi apparatus facilitates membrane repair in response to wounding and offers a valuable perspective on cellular survival mechanisms upon mechanical stress in a physiological context.


Assuntos
Membrana Celular , Complexo de Golgi , Fosfatidilinositol 4,5-Difosfato , Fosfatidilinositóis , Animais , Caenorhabditis elegans/genética , Estresse Mecânico
10.
Elife ; 122023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37166173

RESUMO

Nociceptive habituation is a conserved process through which pain sensitivity threshold is adjusted based on past sensory experience and which may be dysregulated in human chronic pain conditions. Noxious heat habituation in Caenorhabditis elegans involves the nuclear translocation of CaM kinase-1 (CMK-1) in the FLP thermo-nociceptors neurons, causing reduced animal heat sensitivity and avoidance responses. The phosphorylation of CMK-1 on T179 by CaM kinase kinase-1 (CKK-1) is required for nuclear entry. Recently, we identified a specific nuclear export sequence (NES) required to maintain CMK-1 in the cytoplasm at rest (20°C) and showed that Ca2+/CaM binding is sufficient to enhance CMK-1 affinity for IMA-3 via a specific nuclear localization signal (NLS) in order to promote nuclear entry after persistent heat stimulation (90 min at 28°C) (Ippolito et al., 2021). Here, we identified additional functional NES and NLS on CMK-1, whose activity can counteract previously identified elements. Furthermore, we clarify the relationship between the CaM-binding-dependent and T179-dependent effects. T179 phosphorylation can promote nuclear entry both downstream of CaM binding and as part of an independent/parallel pathway. Moreover, T179 phosphorylation can also produce the opposite effect by promoting nuclear export. Taken together, our studies suggest that multiple calcium-dependent regulatory mechanisms converge to bias the activity pattern across a network of NES/NLS elements, in order to control CMK-1 nucleo-cytoplasmic shuttling, and actuate stimulation-dependent nociceptive plasticity.


Assuntos
Caenorhabditis elegans , Cálcio , Animais , Humanos , Caenorhabditis elegans/metabolismo , Cálcio/metabolismo , Nociceptores/metabolismo , Transporte Ativo do Núcleo Celular , Sinais de Localização Nuclear/metabolismo , Núcleo Celular/metabolismo
11.
Proc Natl Acad Sci U S A ; 120(20): e2219341120, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37155851

RESUMO

An animal adapts its motor behavior to navigate the external environment. This adaptation depends on proprioception, which provides feedback on an animal's body postures. How proprioception mechanisms interact with motor circuits and contribute to locomotor adaptation remains unclear. Here, we describe and characterize proprioception-mediated homeostatic control of undulatory movement in the roundworm Caenorhabditis elegans. We found that the worm responds to optogenetically or mechanically induced decreases in midbody bending amplitude by increasing its anterior amplitude. Conversely, it responds to increased midbody amplitude by decreasing the anterior amplitude. Using genetics, microfluidic and optogenetic perturbation response analyses, and optical neurophysiology, we elucidated the neural circuit underlying this compensatory postural response. The dopaminergic PDE neurons proprioceptively sense midbody bending and signal to AVK interneurons via the D2-like dopamine receptor DOP-3. The FMRFamide-like neuropeptide FLP-1, released by AVK, regulates SMB head motor neurons to modulate anterior bending. We propose that this homeostatic behavioral control optimizes locomotor efficiency. Our findings demonstrate a mechanism in which proprioception works with dopamine and neuropeptide signaling to mediate motor control, a motif that may be conserved in other animals.


Assuntos
Proteínas de Caenorhabditis elegans , Neuropeptídeos , Animais , Caenorhabditis elegans/fisiologia , Dopamina/farmacologia , Retroalimentação Sensorial , Locomoção/fisiologia , Proteínas de Caenorhabditis elegans/genética , Neuropeptídeos/genética
12.
Nat Commun ; 14(1): 2824, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37198172

RESUMO

To study how natural allelic variation explains quantitative developmental system variation, we characterized natural differences in germ stem cell niche activity, measured as progenitor zone (PZ) size, between two Caenorhabditis elegans isolates. Linkage mapping yielded candidate loci on chromosomes II and V, and we found that the isolate with a smaller PZ size harbours a 148 bp promoter deletion in the Notch ligand, lag-2/Delta, a central signal promoting germ stem cell fate. As predicted, introducing this deletion into the isolate with a large PZ resulted in a smaller PZ size. Unexpectedly, restoring the deleted ancestral sequence in the isolate with a smaller PZ did not increase-but instead further reduced-PZ size. These seemingly contradictory phenotypic effects are explained by epistatic interactions between the lag-2/Delta promoter, the chromosome II locus, and additional background loci. These results provide first insights into the quantitative genetic architecture regulating an animal stem cell system.


Assuntos
Proteínas de Caenorhabditis elegans , Epistasia Genética , Animais , Nicho de Células-Tronco , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Mapeamento Cromossômico , Células Germinativas/metabolismo
13.
Sci Rep ; 13(1): 8026, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37198238

RESUMO

Sleep is a universal state of behavioral quiescence in both vertebrates and invertebrates that is controlled by conserved genes. We previously found that AP2 transcription factors control sleep in C. elegans, Drosophila, and mice. Heterozygous deletion of Tfap2b, one of the mammalian AP2 paralogs, reduces sleep in mice. The cell types and mechanisms through which Tfap2b controls sleep in mammals are, however, not known. In mice, Tfap2b acts during early embryonic stages. In this study, we used RNA-seq to measure the gene expression changes in brains of Tfap2b-/- embryos. Our results indicated that genes related to brain development and patterning were differentially regulated. As many sleep-promoting neurons are known to be GABAergic, we measured the expression of GAD1, GAD2 and Vgat genes in different brain areas of adult Tfap2b+/- mice using qPCR. These experiments suggested that GABAergic genes are downregulated in the cortex, brainstem and cerebellum areas, but upregulated in the striatum. To investigate whether Tfap2b controls sleep through GABAergic neurons, we specifically deleted Tfap2b in GABAergic neurons. We recorded the EEG and EMG before and after a 6-h period of sleep deprivation and extracted the time spent in NREM and in REM sleep as well as delta and theta power to assess NREM and REM sleep, respectively. During baseline conditions, Vgat-tfap2b-/- mice exhibited both shortened NREM and REM sleep time and reduced delta and theta power. Consistently, weaker delta and theta power were observed during rebound sleep in the Vgat-tfap2b-/- mice after sleep deprivation. Taken together, the results indicate that Tfap2b in GABAergic neurons is required for normal sleep.


Assuntos
Caenorhabditis elegans , Privação do Sono , Camundongos , Animais , Privação do Sono/genética , Eletroencefalografia , Sono/fisiologia , Neurônios GABAérgicos , Fases do Sono/fisiologia , Mamíferos
14.
Environ Monit Assess ; 195(6): 675, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37188927

RESUMO

Biological effect-based monitoring is essential for predicting or alerting to a possible deterioration in drinking water quality. In the present study, a reporter gene assay based on oxidative stress-mediated Pgst-4::GFP induction in the Caenorhabditis elegans strain VP596 (VP596 assay) was assessed for its applicability in evaluating drinking water safety and quality. This assay was used to measure the oxidative stress response in VP596 worms exposed to six ubiquitous components (As3+, Al3+, F-, NO3--N, CHCl3, and residual chlorine) in drinking water, eight mixtures of these six components designed through orthogonal design, ninety-six unconcentrated water samples from source to tap water in two supply systems, and organic extracts (OEs) of twenty-five selected water samples. Pgst-4::GFP fluorescence was not induced by Al3+, F-, NO3--N, and CHCl3, and was significantly enhanced by As3+ and residual chlorine only at concentrations higher than their respective drinking water guideline levels. Pgst-4::GFP induction was not detected in any of the six-component mixtures. Induction of Pgst-4::GFP was observed in 9.4% (3/32) of the source water samples but not in the drinking water samples. However, a notable induction effect was revealed in the three OEs of drinking water, with a relative enrichment factor of 200. These results suggest that the VP596 assay has limited utility for screening drinking water safety by testing unconcentrated water samples; however, it offers a supplemental in vivo tool for prioritizing water samples for an enhanced quality assessment, monitoring pollutant removal performance by drinking water treatment plants, and evaluating water quality in water supplies.


Assuntos
Água Potável , Purificação da Água , Animais , Qualidade da Água , Caenorhabditis elegans , Cloro , Monitoramento Ambiental/métodos , Abastecimento de Água
15.
Cells ; 12(8)2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-37190079

RESUMO

Oxidative stress is a contributing factor to Parkinson's disease (PD). Considering the prevalence of sporadic PD, environmental exposures are postulated to increase reactive oxygen species and either incite or exacerbate neurodegeneration. We previously determined that exposure to the common soil bacterium, Streptomyces venezuelae (S. ven), enhanced oxidative stress and mitochondrial dysfunction in Caenorhabditis elegans, leading to dopaminergic (DA) neurodegeneration. Here, S. ven metabolite exposure in C. elegans was followed by RNA-Seq analysis. Half of the differentially identified genes (DEGs) were associated with the transcription factor DAF-16 (FOXO), which is a key node in regulating stress response. Our DEGs were enriched for Phase I (CYP) and Phase II (UGT) detoxification genes and non-CYP Phase I enzymes associated with oxidative metabolism, including the downregulated xanthine dehydrogenase gene, xdh-1. The XDH-1 enzyme exhibits reversible interconversion to xanthine oxidase (XO) in response to calcium. S. ven metabolite exposure enhanced XO activity in C. elegans. The chelation of calcium diminishes the conversion of XDH-1 to XO and results in neuroprotection from S. ven exposure, whereas CaCl2 supplementation enhanced neurodegeneration. These results suggest a defense mechanism that delimits the pool of XDH-1 available for interconversion to XO, and associated ROS production, in response to metabolite exposure.


Assuntos
Caenorhabditis elegans , Xantina Desidrogenase , Animais , Xantina Desidrogenase/metabolismo , Caenorhabditis elegans/metabolismo , Cálcio/metabolismo , Xantina Oxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo
16.
Biotechniques ; 74(4): 186-198, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37191015

RESUMO

Targeted protein degradation, with its rapid protein depletion kinetics, allows the measurement of acute changes in the cell. The auxin-inducible degron (AID) system, rapidly degrades AID-tagged proteins only in the presence of auxin. The AID system being inducible makes the study of essential genes and dynamic processes like cell differentiation, cell cycle and genome organization feasible. The AID degradation system has been adapted to yeast, protozoans, C. elegans, Drosophila, zebrafish, mouse and mammalian cell lines. Using the AID system, researchers have unveiled novel functions for essential proteins at developmental stages that were previously difficult to investigate due to early lethality. This comprehensive review discusses the development, advancements, applications and drawbacks of the AID system and compares it with other available protein degradation systems.


Assuntos
Caenorhabditis elegans , Ácidos Indolacéticos , Animais , Camundongos , Proteólise , Ácidos Indolacéticos/farmacologia , Ácidos Indolacéticos/metabolismo , Caenorhabditis elegans/metabolismo , Peixe-Zebra/genética , Proteínas/metabolismo , Saccharomyces cerevisiae , Mamíferos/metabolismo
17.
Elife ; 122023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37140564

RESUMO

Various aspects of olfactory memory are represented as modulated responses across different classes of neurons in C. elegans.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/fisiologia , Neurônios , Olfato/fisiologia
18.
Elife ; 122023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37140557

RESUMO

A major goal in neuroscience is to elucidate the principles by which memories are stored in a neural network. Here, we have systematically studied how four types of associative memories (short- and long-term memories, each as positive and negative associations) are encoded within the compact neural network of Caenorhabditis elegans worms. Interestingly, sensory neurons were primarily involved in coding short-term, but not long-term, memories, and individual sensory neurons could be assigned to coding either the conditioned stimulus or the experience valence (or both). Moreover, when considering the collective activity of the sensory neurons, the specific training experiences could be decoded. Interneurons integrated the modulated sensory inputs and a simple linear combination model identified the experience-specific modulated communication routes. The widely distributed memory suggests that integrated network plasticity, rather than changes to individual neurons, underlies the fine behavioral plasticity. This comprehensive study reveals basic memory-coding principles and highlights the central roles of sensory neurons in memory formation.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/fisiologia , Interneurônios , Proteínas de Caenorhabditis elegans/fisiologia , Células Receptoras Sensoriais/fisiologia , Redes Neurais de Computação
19.
PLoS One ; 18(5): e0285262, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37141255

RESUMO

Parasitic nematodes pose a significant threat to human and animal health, as well as cause economic losses in the agricultural sector. The use of anthelmintic drugs, such as Ivermectin (IVM), to control these parasites has led to widespread drug resistance. Identifying genetic markers of resistance in parasitic nematodes can be challenging, but the free-living nematode Caenorhabditis elegans provides a suitable model. In this study, we aimed to analyze the transcriptomes of adult C. elegans worms of the N2 strain exposed to the anthelmintic drug Ivermectin (IVM), and compare them to those of the resistant strain DA1316 and the recently identified Abamectin Quantitative Trait Loci (QTL) on chromosome V. We exposed pools of 300 adult N2 worms to IVM (10-7 and 10-8 M) for 4 hours at 20°C, extracted total RNA and sequenced it on the Illumina NovaSeq6000 platform. Differentially expressed genes (DEGs) were determined using an in-house pipeline. The DEGs were compared to genes from a previous microarray study on IVM-resistant C. elegans and Abamectin-QTL. Our results revealed 615 DEGs (183 up-regulated and 432 down-regulated genes) from diverse gene families in the N2 C. elegans strain. Of these DEGs, 31 overlapped with genes from IVM-exposed adult worms of the DA1316 strain. We identified 19 genes, including the folate transporter (folt-2) and the transmembrane transporter (T22F3.11), which exhibited an opposite expression in N2 and the DA1316 strain and were deemed potential candidates. Additionally, we compiled a list of potential candidates for further research including T-type calcium channel (cca-1), potassium chloride cotransporter (kcc-2), as well as other genes such as glutamate-gated channel (glc-1) that mapped to the Abamectin-QTL.


Assuntos
Anti-Helmínticos , Ivermectina , Animais , Humanos , Ivermectina/farmacologia , Ivermectina/metabolismo , Caenorhabditis elegans/metabolismo , Transcriptoma , Locos de Características Quantitativas , Anti-Helmínticos/farmacologia , Resistência a Medicamentos/genética
20.
Adv Virus Res ; 115: 135-158, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37173064

RESUMO

Viruses continue to pose a public health threat raising the need for effective management strategies. Currently existing antiviral therapeutics are often specific to only a single viral species, and resistance to the therapeutic can often arise, and therefore new therapeutics are needed. The C. elegans-Orsay virus system offers a powerful platform for studying RNA virus-host interactions that could ultimately lead to novel targets for antiviral therapy. The relative simplicity of C. elegans, the well-established experimental tools, and its extensive evolutionary conservation of genes and pathways with mammals are key features of this model. Orsay virus, a bisegmented positive sense RNA virus, is a natural pathogen of C. elegans. Orsay virus infection can be studied in a multicellular organismal context, overcoming some of the limitations inherent to tissue culture-based systems. Moreover, compared to mice, the rapid generation time of C. elegans enables robust and facile forward genetics. This review aims to summarize studies that have laid the foundation for the C. elegans-Orsay virus experimental system, experimental tools, and key examples of C. elegans host factors that impact Orsay virus infection that have evolutionarily conserved function in mammalian virus infection.


Assuntos
Nodaviridae , Vírus de RNA , Viroses , Animais , Camundongos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Interações entre Hospedeiro e Microrganismos , Interferência de RNA , Nodaviridae/genética , Interações Hospedeiro-Patógeno/genética , Mamíferos
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