Haag ES et al. (2019) Dev Cell "Still Searching for Specialized Ribosomes."

Haag ES, Dinman JD

[Dev Cell, 2019]

Reporting in Developmental Cell, Cenik etal. (2019) show that the maternal ribosome supply is sufficient for C.elegans embryonic development, arguing against tissue-specific specialized ribosomes in this context. Examination of ribosomal requirement with the genetic tool kit presented in Artiles etal. (2019) suggests a checkpoint that prevents uncoordinated growth.

Lima SL et al. (2020) Microb Pathog "Evaluation of the potential virulence of Candida haemulonii species complex and Candida auris isolates in Caenorhabditis elegans as an in vivo model and correlation to their biofilm production capacity."

Lima SL, Rossato L, Salles de Azevedo Melo A

[Microb Pathog, 2020]

Candida haemulonii species complex (Can. haemulonii sensu stricto, Can. duobushaemulonii and Can. haemulonii var. vulnera) and related species (Can. auris and Can. pseudohaemulonii) have attracted attention due to reduced susceptibility to azoles and amphotericin B. Furthermore, attributes of potential virulence have been recognized in Can. haemulonii species complex and Can. auris, like the capability to form biofilm, which represent the most important risk factors for persistent candidemia. However, the relationship between biofilm production and impact on host mortality is still unclear. To evaluate the potential virulence of Can. haemulonii species complex and Can. auris isolates by correlating biofilm production and capacity to kill Caenorhabditis elegans as an in vivo model. In this study, virulence factors were characterized among a total of sixty-six Can. haemulonii species complex and Can. auris isolates to gain insight about virulence traits of these pathogenic yeasts by evaluating the in vitro biofilm production and potential pathogenicity for Cae. elegans, as an in vivo infection model. All clinical isolates tested were biofilm producer, inter- and intra-specific differences on the biofilm forming capacity by the strains were observed. Can. auris and Can. haemuolonii var. vulnera showed similar biofilm production, both higher than Can. haemulonii sensu stricto and Can. duobushaemulonii. Regarding the virulence of the Cae. elegans model, Can. haemulonii species complex and Can. auris isolates were capable of causing infection in Cae. elegans, and our data suggest that the high biofilm production by Can. haemulonii var. vulnera and Can. duobushaemulonii isolates may impact in the pathogenicity caused on Cae. elegans.

Manalo RVM et al. (2020) Pharm Biol "Caffeine reduces deficits in mechanosensation and locomotion induced by L-DOPA and protects dopaminergic neurons in a transgenic Caenorhabditis elegans model of Parkinson's disease."

Medina PMB, Manalo RVM

[Pharm Biol, 2020]

CONTEXT: L-DOPA is the first-line drug for Parkinson's disease (PD). However, chronic use can lead to dyskinesia. Caffeine, which is a known neuroprotectant, can potentially act as an adjunct to minimise adverse effects of L-DOPA. OBJECTIVES: (Rhabditidae) strain UA57 overexpressing tyrosine hydroxylase (CAT-2) when treated with caffeine, L-DOPA or their combinations. MATERIALS AND METHODS: =20). Meanwhile, mechanosensation and locomotion under vehicle (0.1% DMSO), L-DOPA (60mM), caffeine (10mM) or 60mM L-DOPA + 10 or 20mM caffeine (60LC10 and 60LC20) treatments were scored for 3days. RESULTS: Taken together, we show that caffeine can protect DAergic neurons and can reduce aberrant locomotion and loss of sensation when co-administered with L-DOPA, which can potentially impact PD treatment and warrants further investigation.

Haroon S et al. (2019) Bio Protoc "Oxygen Consumption Measurements in Caenorhabditis elegans Using the Seahorse XF24."

Vermulst M, Haroon S

[Bio Protoc, 2019]

Mitochondria generate 90% of the energy required to sustain life. As a result, loss of mitochondrial function compromises almost every facet of human physiology. Accordingly, most mitochondrial diseases tend to present themselves as complex, multi-systemic disorders that can be difficult to diagnose. Depending on the severity of the mitochondrial dysfunction, the pathology can range from mild discomfort to severe epilepsy, blindness and paralysis. To develop therapies to these diseases, it will be important to optimize experimental techniques that can reliably quantify mitochondrial function, particularly in live cells or intact organisms. Here, we describe how a Seahorse XF24 Analyzer can be used to measure both basal and maximal respiration in the nematode <i>Caenorhabditis elegans</i>, and how this data can be interpreted to evaluate mitochondrial function.

Fornerod M et al. (1997) EMBO J "The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88."

van Deursen J, Murti KG, Fransen J, Davis D, Fornerod M, van Baal S, Reynolds A, Grosveld G

[EMBO J, 1997]

The oncogenic nucleoporin CAN/Nup214 is essential in vertebrate cells. Its depletion results in defective nuclear protein import, inhibition of messenger RNA export and cell cycle arrest. We recently found that CAN associates with proteins of 88 and 112 kDa, which we have now cloned and characterized. The 88 kDa protein is a novel nuclear pore complex (NPC) component, which we have named Nup88. Depletion of CAN from the NPC results in concomitant loss of Nup88, indicating that the localization of Nup88 to the NPC is dependent on CAN binding. The 112 kDa protein is the human homologue of yeast CRM1, a protein known to be required for maintenance of correct chromosome structure. This human CRM1 (hCRM1) localized to the NPC as well as to the nucleoplasm. Nuclear overexpression of the FG-repeat region of CAN, containing its hCRM1-interaction domain, resulted in depletion of hCRM1 from the NPC. In CAN-/- mouse embryos lacking CAN, hCRM1 remained in the nuclear envelope, suggesting that this protein can also bind to other repeat-containing nucleoporins. Lastly, hCRM1 shares a domain of significant homology with importin-beta, a cytoplasmic transport factor that interacts with nucleoporin repeat regions. We propose that hCRM1 is a soluble nuclear transport factor that interacts with the NPC.

Broitman-Maduro G et al. (2022) Development "The ELT-3 GATA factor specifies endoderm in Caenorhabditis angaria in an ancestral gene network."

Sun S, Broitman-Maduro G, Maduro MF, Kikuchi T

[Development, 2022]

Endoderm specification in C. elegans occurs through a network in which maternally provided SKN-1/Nrf, with additional input from POP-1/TCF, activates the GATA factor cascade MED-1,2&#8594;END-1,3&#8594;ELT-2,7. Orthologues of the MED, END, and ELT-7 factors are found only among nematodes closely related to C. elegans, raising the question of how gut is specified in their absence in more distant species in the genus. We find that the C. angaria, C. portoensis and C. monodelphis orthologues of the elt-3 GATA factor gene are expressed in the early E lineage, just before their elt-2 orthologues. In C. angaria, Can-pop-1(RNAi), Can-elt-3(RNAi) and a Can-elt-3 null mutation result in a penetrant 'gutless' phenotype. Can-pop-1 is necessary for Can-elt-3 activation, showing that it acts upstream. Forced early E lineage expression of Can-elt-3 in C. elegans can direct the expression of a Can-elt-2 transgene and rescue an elt-7 end-1 end-3; elt-2 quadruple mutant strain to viability. Our results demonstrate an ancestral mechanism for gut specification and differentiation in Caenorhabditis involving a simpler POP-1&#8594;ELT-3&#8594;ELT-2 gene network.

Le HH et al. (2016) J Cell Biol "Tissue homogeneity requires inhibition of unequal gene silencing during development."

Strauss B, Bloodgood M, Jose AM, Le HH, Looney M

[J Cell Biol, 2016]

Multicellular organisms can generate and maintain homogenous populations of cells that make up individual tissues. However, cellular processes that can disrupt homogeneity and how organisms overcome such disruption are unknown. We found that 100-fold differences in expression from a repetitive DNA transgene can occur between intestinal cells in Caenorhabditis elegans These differences are caused by gene silencing in some cells and are actively suppressed by parental and zygotic factors such as the conserved exonuclease ERI-1. If unsuppressed, silencing can spread between some cells in embryos but can be repeat specific and independent of other homologous loci within each cell. Silencing can persist through DNA replication and nuclear divisions, disrupting uniform gene expression in developed animals. Analysis at single-cell resolution suggests that differences between cells arise during early cell divisions upon unequal segregation of an initiator of silencing. Our results suggest that organisms with high repetitive DNA content, which include humans, could use similar developmental mechanisms to achieve and maintain tissue homogeneity.

Mata-Cabana A et al. (2018) Bio Protoc "Nuclear/Cytoplasmic Fractionation of Proteins from Caenorhabditis elegans."

Nollen EAA, Sin O, Mata-Cabana A, Seinstra RI

[Bio Protoc, 2018]

<i>C. elegans</i> is widely used to investigate biological processes related to health and disease. To study protein localization, fluorescently-tagged proteins can be used <i>in vivo</i> or immunohistochemistry can be performed in whole worms. Here, we describe a technique to localize a protein of interest at a subcellular level in <i>C. elegans</i> lysates, which can give insight into the location, function and/or toxicity of proteins.

Lahaise M et al. (2023) Naunyn Schmiedebergs Arch Pharmacol "Cannflavins isolated from Cannabis sativa impede Caenorhabditis elegans response to noxious heat."

Lahaise M, Beaudry F, Boujenoui F

[Naunyn Schmiedebergs Arch Pharmacol, 2023]

Cannflavins, flavonoids abundantly present in Cannabis sativa, possess a distinct chemical structure comprising a vanillyl group. Notably, the capsaicin structure also contains a vanillyl group, which is considered essential for interacting with the vanilloid receptor. The vanilloid receptor plays a crucial role in the perception of pain, heat, and inflammation and mediates the analgesic effects of capsaicin. Therefore, we postulated that prolonged exposure to cannflavin A (Can A) and cannflavin B (Can B) would provoke vanilloid receptor desensitization and hinder nocifensive responses to noxious thermal stimuli. C. elegans wild-type (N2) and mutants were exposed to Can A and Can B solutions for 60&#xa0;min and then aliquoted on Petri dishes divided into quadrants for thermal stimulation. We then determined the thermal avoidance index for each C. elegans experimental group. Proteomics was performed to identify proteins and pathways associated with Can A or B treatment. Prolonged exposure to Can A and Can B hindered heat avoidance (32-35&#xa0;&#xb0;C) in C. elegans. No antinociceptive effect was observed 6&#xa0;h post Can A or B exposure. Proteomics and Reactome pathway enrichment analyses identified hierarchical differences between Can A- and B-treated nematodes. However, both treatments were related to eukaryotic translation initiation (R-CEL-72613) and metabolic processes strongly associated with pain development. Our study aids in characterizing the pharmacological activity of cannflavins isolated from Cannabis sativa and outlines a possible application as pain therapy.

Dowen RH et al. (2019) Curr Biol "Maternal Inheritance: Longevity Programs Nourish Progeny via Yolk."

Ahmed S, Dowen RH

[Curr Biol, 2019]

Epigenetic effects can be mediated by changes in chromatin state that are transmitted from parent to child via gametes, but support is gathering for maternal yolk, which is deposited into ooctyes, as an extranuclear epigenetic factor that can contribute to phenotypic plasticity across generations in Caenorhabditis elegans.