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Aoki I et al. (2015) Curr Opin Neurobiol "Molecular biology of thermosensory transduction in C. elegans."

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Curr Opin Neurobiol,

2015]

As the environmental temperature prominently influences diverse biological aspects of the animals, thermosensation and the subsequent information processing in the nervous system has attracted much attention in biology. Thermotaxis in the nematode Caenorhabditis elegans is an ideal behavioral paradigm by which to address the molecular mechanism underlying thermosensory transduction. Molecular genetic analysis in combination with other physiological and behavioral studies revealed that sensation of ambient temperature is mediated mainly by cyclic guanosine monophosphate (cGMP) signaling in thermosensory neurons. The information of the previously perceived temperature is also stored within the thermosensory neurons, and the consequence of the comparison between the past and the present temperature is conveyed to the downstream interneurons to further regulate the motor-circuits that encode the locomotion.

Aoki, I. et al. (2017) International Worm Meeting "BK potassium channels regulate learning speed in C. elegans."

Aoki, I., Ihara, K., Kubo, Y., Mori, I., Tateyama, M., Shimomura, T.

[

International Worm Meeting,

2017]

Changing behavior at the right time is crucial for animals to survive in constantly fluctuating environments. In particular, the latency of behavior changes is critical; animals fail to discriminate a long-lasting change from a transient noise if the latency is too short, while they fail to feed and avoid dangers if it is too long. However, molecular and neural mechanisms underlying the regulation of the latency of behavior changes mostly remain elusive. In thermotaxis behavior of C. elegans, animals migrate toward the past cultivation temperature associated with food when put on a thermal gradient without food. A few hours after cultivation temperature is shifted, animals change their preferred temperature to a new cultivation temperature. Here we show that a mutation of slo-2 gene that encodes a BK-type Ca2+-dependent K+ channel, which was confirmed to be a gain-of-function (gf) mutation by electrophysiological analyses, decelerates the change in preferred temperature in thermotaxis behavior. We further found that the behavior change of the animals doubly mutant for slo-2 and slo-1 that encodes another BK-type K+ channel was faster, suggesting that SLO-1 and SLO-2 act redundantly to decelerate behavior change. While gf mutations of human slo-2 homolog cause epilepsies, we found that the expression of C. elegans slo-2 with analogous mutations decelerates the change of thermotaxis more than that of wild type slo-2, implicating similar molecular mechanisms underlying human epilepsies and C. elegans thermotaxis. A major thermosensory neuron AFD increases intracellular Ca2+ concentration in response to a temperature increase near the past cultivation temperature. While the onset temperature of AFD response also changed after cultivation temperature was shifted, the slo-2(gf) mutation decelerated the change in AFD responses. Furthermore, a mutation in cng-3 gene that encodes a cyclic nucleotide-gated cation channel suppressed the decelerated phenotypes of both thermotactic behavior and AFD responses caused by the slo-2(gf) mutation. We also showed by co-immunoprecipitation experiments that SLO-2 and CNG-3 physically interact, suggesting that Ca2+ influx through CNG-3 channel might locally activate SLO-2, which leads to decelerate updating of thermal memory stored in AFD thermosensory neurons and thereby the timing of behavior changes. Our study would serve as a starting point toward comprehensive understanding of neural bases of behavior changes.

Aoki I et al. (2018) Commun Biol "SLO potassium channels antagonize premature decision making in C. elegans."

Mori I, Nakano S, Shimomura T, Kubo Y, Tateyama M, Ihara K, Aoki I

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Commun Biol,

2018]

Animals must modify their behavior with appropriate timing to respond to environmental changes. Yet, the molecular and neural mechanisms regulating the timing of behavioral transition remain largely unknown. By performing forward genetics to reveal mechanisms that underlie the plasticity of thermotaxis behavior in C. elegans, we demonstrated that SLO potassium channels and a cyclic nucleotide-gated channel, CNG-3, determine the timing of transition of temperature preference after a shift in cultivation temperature. We further revealed that SLO and CNG-3 channels act in thermosensory neurons and decelerate alteration in the responsiveness of these neurons, which occurs prior to the preference transition after a temperature shift. Our results suggest that regulation of sensory adaptation is a major determinant of latency before animals make decisions to change their behavior.

Aoki I et al. (2022) PLoS One "cGMP dynamics that underlies thermosensation in temperature-sensing neuron regulates thermotaxis behavior in C. elegans."

Shiota M, Aoki I, Nakano S, Mori I, Tsukada Y

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PLoS One,

2022]

Living organisms including bacteria, plants and animals sense ambient temperature so that they can avoid noxious temperature or adapt to new environmental temperature. A nematode C. elegans can sense innocuous temperature, and navigate themselves towards memorize past cultivation temperature (Tc) of their preference. For this thermotaxis, AFD thermosensory neuron is pivotal, which stereotypically responds to warming by increasing intracellular Ca2+ level in a manner dependent on the remembered past Tc. We aimed to reveal how AFD encodes the information of temperature into neural activities. cGMP synthesis in AFD is crucial for thermosensation in AFD and thermotaxis behavior. Here we characterized the dynamic change of cGMP level in AFD by imaging animals expressing a fluorescence resonance energy transfer (FRET)-based cGMP probe specifically in AFD and found that cGMP dynamically responded to both warming and cooling in a manner dependent on past Tc. Moreover, we characterized mutant animals that lack guanylyl cyclases (GCYs) or phosphodiesterases (PDEs), which synthesize and hydrolyze cGMP, respectively, and uncovered how GCYs and PDEs contribute to cGMP and Ca2+ dynamics in AFD and to thermotaxis behavior.

Aoki I et al. (2022) PLoS Genet "OLA-1, an Obg-like ATPase, integrates hunger with temperature information in sensory neurons in C. elegans."

Kondo R, Ferrer I, Nakano S, Matsuyama HJ, Nawa K, Aoki I, Mori I, Yamashiro R, Jurado P

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PLoS Genet,

2022]

Animals detect changes in both their environment and their internal state and modify their behavior accordingly. Yet, it remains largely to be clarified how information of environment and internal state is integrated and how such integrated information modifies behavior. Well-fed C. elegans migrates to past cultivation temperature on a thermal gradient, which is disrupted when animals are starved. We recently reported that the neuronal activities synchronize between a thermosensory neuron AFD and an interneuron AIY, which is directly downstream of AFD, in well-fed animals, while this synchrony is disrupted in starved animals. However, it remained to be determined whether the disruption of the synchrony is derived from modulation of the transmitter release from AFD or from the modification of reception or signal transduction in AIY. By performing forward genetics on a transition of thermotaxis behavior along starvation, we revealed that OLA-1, an Obg-like ATPase, functions in AFD to promote disruption of AFD-AIY synchrony and behavioral transition. Our results suggest that the information of hunger is delivered to the AFD thermosensory neuron and gates transmitter release from AFD to disrupt thermotaxis, thereby shedding light onto a mechanism for the integration of environmental and internal state to modulate behavior.

Souza ACR et al. (2018) Genes (Basel) "Pathogenesis of the Candida parapsilosis Complex in the Model Host Caenorhabditis elegans."

Colombo AL, Fuchs BB, Jayamani E, Mylonakis E, Souza ACR, Alves VS

[

Genes (Basel),

2018]

Caenorhabditiselegans is a valuable tool as an infection model toward the study of Candida species. In this work, we endeavored to develop a C. elegans-Candidaparapsilosis infection model by using the fungi as a food source. Three species of the C. parapsilosis complex (C.parapsilosis (sensustricto), Candidaorthopsilosis and Candidametapsilosis) caused infection resulting in C. elegans killing. All three strains that comprised the complex significantly diminished the nematode lifespan, indicating the virulence of the pathogens against the host. The infection process included invasion of the intestine and vulva which resulted in organ protrusion and hyphae formation. Importantly, hyphae formation at the vulva opening was not previously reported in C. elegans-Candida infections. Fungal infected worms in the liquid assay were susceptible to fluconazole and caspofungin and could be found to mount an immune response mediated through increased expression of cnc-4, cnc-7, and fipr-22/23. Overall, the C. elegans-C. parapsilosis infection model can be used to model C. parapsilosis host-pathogen interactions.

Fourie R et al. (2021) Front Cell Infect Microbiol "Candida albicans SET3 Plays a Role in Early Biofilm Formation, Interaction With Pseudomonas aeruginosa and Virulence in Caenorhabditis elegans."

Sebolai O, Fourie R, Albertyn J, Pohl CH, Gcilitshana O

[

Front Cell Infect Microbiol,

2021]

The yeast Candida albicans exhibits multiple morphologies dependent on environmental cues. Candida albicans biofilms are frequently polymicrobial, enabling interspecies interaction through proximity and contact. The interaction between C. albicans and the bacterium, Pseudomonas aeruginosa, is antagonistic in vitro, with P. aeruginosa repressing the yeast-to-hyphal switch in C. albicans. Previous transcriptional analysis of C. albicans in polymicrobial biofilms with P. aeruginosa revealed upregulation of genes involved in regulation of morphology and biofilm formation, including SET3, a component of the Set3/Hos2 histone deacetylase complex (Set3C). This prompted the question regarding the involvement of SET3 in the interaction between C. albicans and P. aeruginosa, both in vitro and in vivo. We found that SET3 may influence early biofilm formation by C. albicans and the interaction between C. albicans and P. aeruginosa. In addition, although deletion of SET3 did not alter the morphology of C. albicans in the presence of P. aeruginosa, it did cause a reduction in virulence in a Caenorhabditis elegans infection model, even in the presence of P. aeruginosa.

Zhu Q et al. (2020) Oxid Med Cell Longev "A Dihydroflavonoid Naringin Extends the Lifespan of C. elegans and Delays the Progression of Aging-Related Diseases in PD/AD Models via DAF-16."

Zhou XG, Qu Y, Luo HR, Zhu Q, Wu GS, Chen JN

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Oxid Med Cell Longev,

2020]

Naringin is a dihydroflavonoid, which is rich in several plant species used for herbal medicine. It has a wide range of biological activities, including antineoplastic, anti-inflammatory, antiphotoaging, and antioxidative activities. So it would be interesting to know if naringin has an effect on aging and aging-related diseases. We examined the effect of naringin on the aging of Caenorhabditis elegans (C. elegans). Our results showed that naringin could extend the lifespan of C. elegans. Moreover, naringin could also increase the thermal and oxidative stress tolerance, reduce the accumulation of lipofuscin, and delay the progress of aging-related diseases in C. elegans models of AD and PD. Naringin could not significantly extend the lifespan of long-lived mutants from genes in insulin/IGF-1 signaling (IIS) and nutrient-sensing pathways, such as daf-2, akt-2, akt-1, eat-2, sir-2.1, and rsks-1. Naringin treatment prolonged the lifespan of long-lived glp-1 mutants, which have decreased reproductive stem cells. Naringin could not extend the lifespan of a null mutant of the fox-head transcription factor DAF-16. Moreover, naringin could increase the mRNA expression of genes regulated by daf-16 and itself. In conclusion, we show that a natural product naringin could extend the lifespan of C. elegans and delay the progression of aging-related diseases in C. elegans models via DAF-16.

Coomansingh-Springer C et al. (2019) Heliyon "Internal parasitic burdens in brown rats (Rattus norvegicus) from Grenada, West Indies."

Sharma RN, Armstrong E, Vishakha V, Acuna AM, Coomansingh-Springer C

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Heliyon,

2019]

This study identified the endoparasites in Brown rat (Rattus norvegicus) during May to July 2017 in Grenada, West Indies. A total of 162 rats, 76 females and 86 males were trapped from St. George and St. David parishes in Grenada. The collected fecal samples were examined for parasitic eggs and/or oocysts using simple fecal flotation technique. Adult parasites found in the intestinal tract were examined for identification. The overall prevalence of intestinal parasites among rats was 79 %. Ten helminth species were recovered, several of which were reported for the first time in rodents in Grenada. The internal parasites consist of seven nematodes (Angiostrongylus spp., Nippostrongylus braziliensis, Heterakis spumosa, Strongyloides ratti, Aspiculuris tetraptera, Syphacia spp. and Protospirura spp.), one cestode (Hymenolepsis diminuta), one acanthocephalan (Moniliformis moniliformis) and one protozoa species (Eimeria spp.). The most prevalent zoonotic species were Angiostrongylus spp. (35.2%), Hymenolepsis diminuta (7.4%) and Moniliformis moniliformis (3.1%). Several nonzoonotic endoparasites; which included Nippostrongylus braziliensis (50.6%), Heterakis spumosa (15.4%), Strongyloides ratti (43.2%), Aspiculuris tetraptera (2.5%), Syphacia spp. (1.9%), Protospirura spp. (1.2%) and Eimeria spp. (4.7%) were also identified. The most prevalent parasites were Nippostrongylus brasiliensis (50.6%), Strongyloides ratti (43.2%) and Angiostrongylus spp. (35.2%). Co-infections occurred with up to six species per rat showing different combinations of parasitic infections.

Wu CJ et al. (2019) Appl Environ Microbiol "Genotypic and Phenotypic Characteristics of Aeromonas Isolates from Fish and Patients in Tainan City."

Shu CY, Li CW, Ko WC, Su YC, Chen YW, Lee NY, Su SL, Wu CJ, Chen PL, Li MC, Lin YT

[

Appl Environ Microbiol,

2019]

The present study aimed to isolate Aeromonas from fish sold in the markets as well as in sushi and seafood shops and compare their virulence factors and antimicrobial characteristics with those of clinical isolates. Among the 128 fish isolates and 47 clinical isolates, A. caviae, A. dhakensis, and A. veronii were the principal species. A. dhakensis isolates carried at least 5 virulence genes, more than other Aeromonas species. The predominant genotype of virulence genes was hlyA/lip/alt/col/el in both A. dhakensis and A. hydrophila isolates, alt/col/ela in A. caviae isolates, and act in A. veronii isolates. A. dhakensis, A. hydrophila, and A. veronii isolates more often exhibited hemolytic and proteolytic activity and showed greater virulence than A. caviae in Caenorhabditis elegans and the C2C12 cell line. However, the link between the genotypes and phenotypes of the studied virulence genes in Aeromonas species is not evident. Among the four major clinical Aeromonas species, nearly all (99.0%) A. dhakensis, A. hydrophila, and A. veronii isolates harbored blaCphA, which encodes a carbapenemase, but only a minority (6.7%, 7/104) were nonsusceptible to carbapenem. Regarding AmpC -lactamase genes, blaAQU-1 was exclusively found in A. dhakensis isolates and blaMOX3 only in A. caviae isolates, but only 7.6% (6) of the 79 Aeromonas isolates carrying blaAQU-1 or blaMOX3 exhibited a cefotaxime resistance phenotype. In conclusion, fish Aeromonas isolates carry a variety of combinations of virulence and B-lactamase resistance genes and exhibit virulence phenotypes and antimicrobial resistance profiles similar to those of clinical isolates.IMPORTANCEAeromonas species can cause severe infections in immunocompromised individuals upon exposure to virulent pathogens in the environment, but the characteristics of environmental Aeromonas species remain unclear. Our study showed several pathogenic Aeromonas species possessing virulence traits and antimicrobial resistance similar to those of Aeromonas isolates causing clinical diseases were present in fish intended for human consumption in Tainan City.

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