Luz SL et al. (2014) Mem Inst Oswaldo Cruz "Outstanding insecurities concerning the use of an Ov16-based ELISA in the Amazonia onchocerciasis focus."

Rubio M, Luz SL, Shelley AJ, Crainey JL

[Mem Inst Oswaldo Cruz, 2014]

In a recent issue of Memorias do Instituto Oswaldo Cruz, published in Rio de Janeiro in February 2014 (109: 87-92), Adami et al. have published a survey reporting Mansonella parasite prevalence in the Amazon Region. This report makes a useful contribution to the existing knowledge of filarial parasite distribution within the Amazon area, parasite prevalence rates in relation to age and occupation and provides observations on the possible clinical impact of Mansonella ozzardi. Their publication also provides an account of what appears to be a novel ELISA that has recently been used in the Simuliidae and Onchocerciasis Laboratory of the Oswaldo Cruz Institute, Rio de Janeiro, Brazil. We are concerned that the publication of this ELISA may have created an excessively positive impression of the effectiveness of the onchocerciasis recrudescence serological surveillance tools that are presently available for use in the Amazonia onchocerciasis focus. In this letter we have, thus, sought to highlight some of the limitations of this ELISA and suggest how continuing insecurities concerning the detection of antibodies to Onchocerca volvulus within the Amazonia onchocerciasis focus might be minimised.

Penna B et al. (2021) Sci Rep "Comparative genomics of MRSA strains from human and canine origins reveals similar virulence gene repertoire."

Silva-Carvalho MC, Ferreira FA, Bandeira PT, Figueiredo AMS, Vieira-da-Motta O, Silva MB, Vasconcelos ATR, de Souza VS, Botelho AMN, Planet PJ, de Sousa VS, Soares AER, Rabello RF, Ramundo MS, Penna B

[Sci Rep, 2021]

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen associated with a wide variety of infections in humans. The ability of MRSA to infect companion animals has gained increasing attention in the scientific literature. In this study, 334 dogs were screened for MRSA in two cities located in Rio de Janeiro State. The prevalence of MRSA in dogs was 2.7%. Genotyping revealed isolates from sequence types (ST) 1, 5, 30, and 239 either colonizing or infecting dogs. The genome of the canine ST5 MRSA (strain SA112) was compared with ST5 MRSA from humans-the main lineage found in Rio de Janeiro hospitals-to gain insights in the origin of this dog isolate. Phylogenetic analysis situated the canine genome and human strain CR14-035 in the same clade. Comparative genomics revealed similar virulence profiles for SA112 and CR14-035. Both genomes carry S. aureus genomic islands SA, SA, and SA. The virulence potential of the canine and human strains was similar in a Caenorhabditis elegans model. Together, these results suggest a potential of canine MRSA to infect humans and vice versa. The circulation in community settings of a MRSA lineage commonly found in hospitals is an additional challenge for public health surveillance authorities.

Burnett J et al. (2023) MicroPubl Biol "Quantifying the Over-retraction (Ore) phenotype in C. elegans male tail tip morphogenesis."

Hubbard EJA, Burnett J

[MicroPubl Biol, 2023]

Morphometrics, the quantitative analysis of biological structures, reduces subjectivity and increases reproducibility in characterizing morphological phenotypes. In <i>C. elegans</i> males, the rounded adult tail tip emerges from a stage-specific retraction of epidermal cells regulated by the heterochronic pathway via LIN-41/TRIM71. Precocious tail tip morphogenesis in <i>lin-41</i> reduction-of-function conditions results in a blunted tail (Ore) phenotype, previously described qualitatively (Del Rio-Albrechtsen et al., 2006). We present a quantitative method to assess the Ore phenotype by measuring the tail tip position relative to the cloacal opening. This method can be used to study variation in Ore phenotypes and to validate <i>lin-41</i> loss-of-function reagents.

Weinberg F et al. (2014) Gene Expr Patterns "Expression pattern and first functional characterization of riok-1 in Caenorhabditis elegans."

Brummer T, Schmidt E, Fatouros C, Baumeister R, Schulze E, Weinberg F

[Gene Expr Patterns, 2014]

Rio kinases are atypical serine/threonine kinases that emerge as potential cooperation partners in Ras-driven tumors. In the current study, we performed an RNAi screen in Caenorhabditis elegans to identify suppressors of oncogenic Ras signaling. Aberrant Ras/Raf signaling in C. elegans leads to the formation of a multi-vulva (Muv) phenotype. We found that depletion of riok-1, the C. elegans orthologue of the mammalian RioK1, suppressed the Muv phenotype. By using a promoter GFP construct, we could show that riok-1 is expressed in neuronal cells, the somatic gonad, the vulva, the uterus and the spermatheca. Furthermore, we observed developmental defects in the gonad upon riok-1 knockdown in a wildtype background. Our data suggest that riok-1 is a modulator of the Ras signaling pathway, suggesting implications for novel interventions in the context of Ras-driven tumors.

Mendes TK et al. (2015) PLoS One "Investigating the role of RIO protein kinases in Caenorhabditis elegans."

Bertram SE, Colaiacovo MP, Hofmann A, Breugelmans B, Novakovic S, Boag PR, Esmaillie R, Gasser RB, Raymant G, Nadarajan S, Mendes TK

[PLoS One, 2015]

RIO protein kinases (RIOKs) are a relatively conserved family of enzymes implicated in cell cycle control and ribosomal RNA processing. Despite their functional importance, they remain a poorly understood group of kinases in multicellular organisms. Here, we show that the C. elegans genome contains one member of each of the three RIOK sub-families and that each of the genes coding for them has a unique tissue expression pattern. Our analysis showed that the gene encoding RIOK-1 (riok-1) was broadly and strongly expressed. Interestingly, the intestinal expression of riok-1 was dependent upon two putative binding sites for the oxidative and xenobiotic stress response transcription factor SKN-1. RNA interference (RNAi)-mediated knock down of riok-1 resulted in germline defects, including defects in germ line stem cell proliferation, oocyte maturation and the production of endomitotic oocytes. Taken together, our findings indicate new functions for RIOK-1 in post mitotic tissues and in reproduction.

Hao H et al. (2019) Nucleus "SUN/KASH interactions facilitate force transmission across the nuclear envelope."

Starr DA, Hao H

[Nucleus, 2019]

LINC complexes (Linker of Nucleoskeleton and Cytoskeleton), consisting of inner nuclear membrane SUN proteins and outer nuclear membrane KASH proteins, are essential for nuclear positioning, cell migration and chromosome dynamics. Crystal structures of the central SUN-KASH interaction domains revealed close interfaces predicted to mediate LINC complex formation and function. However, the in vivo significance of these conserved interactions were unclear. Cain et al (2018) used a combination of Caenorhabditis elegans genetics, imaging in cultured NIH 3T3 fibroblasts, and Molecular Dynamic simulations, to study SUN-KASH interactions in cells. The study found that a conserved aromatic residue at the -7 position of the C-terminal KASH domain and conserved cysteines in both the KASH and SUN domains play important roles in force transmission across the nuclear envelope. Other properties of LINC complexes may also play significant roles in transmitting mechanical forces generated by the cytoskeleton across the nuclear envelope. For example, the helicies preceding the SUN domain activate SUN proteins and may be important for activating KASH-SUN interactions or for association of SUN and/or KASH proteins with the membrane. The longer coiled-coils spanning the perinuclear space may also play a role in mediating force transmission. Finally, LINC complexes may be arranged in higher-order structures to facilitate high force-bearing processes.

Yen PL et al. (2023) Environ Toxicol Pharmacol "Chronic exposure to di(2-ethylhexyl) phthalate (DEHP) weakens innate immunity and leads to immunosenescence in C. elegans."

Huang ML, Lin TA, Yang CR, Liao VH, Yen PL

[Environ Toxicol Pharmacol, 2023]

Di(2-ethylhexyl) phthalate (DEHP), a widespread contaminant, has numerous adverse impacts on human health and ecosystems. Chronic DEHP exposure has been found to accelerate aging; however, its potential threat to age-dependent innate immune decline remains unknown. This study aims to evaluate the effects of chronic DEHP exposure on innate immunosenescence in Caenorhabditis elegans. We show that the length of the exposure period significantly impacts DEHP-induced age-related declines, which is linked to immunosenescence and oxidative stress. We found that the DEHP-caused immunosenescence is accompanied with downregulation of an antimicrobial gene lys-7 as well as an enhancement of the nuclear translocation of HLH-30, an orthologue of mammalian transcription factor EB (TFEB). Moreover, DEHP exposure increases the expression of riok-1, a human RIO kinase homolog, which is associated with DEHP-induced HLH-30/TFEB translocation. Our findings suggest that early-life and chronic exposure to DEHP, mostly due to parent compound rather than its metabolite mono(2-ethylhexyl) phthalate (MEHP), may weaken the innate immunity in C. elegans and may enhance susceptibility to infections or promote immunosenescence in aged populations.

Shelley AJ et al. (2001) Med Vet Entomol "Biting behaviour and potential vector status of anthropophilic blackflies in a new focus of human onchocerciasis at Minacu, central Brazil."

Dias AP, Shelley AJ, Garritano P, Lowry CA, Maia-Herzog M, Camargo M, Costa EG

[Med Vet Entomol, 2001]

Monthly collections were made of man-biting female blackflies: Simulium auripellitum Enderlein, S. guianense Wise, S. minusculum Lutz and S. nigrimanum Macquart (Diptera: Simuliidae) from four catching stations in the newly discovered focus of human onchocerciasis at Minacu (13 degrees 35 minutes S 48 degrees 18 minutes W), 300 km north of Brasilia in Goias State. These provided baseline data on biting habits, population density and seasonal prevalence during the year before completion of the Serra da Mesa hydroelectric dam on the Rio Tocantins near Minacu, in a project investigating the effect of dam construction on onchocerciasis transmission in the area. All four simuliid species were most abundant during the dry season, and only bit in low numbers (S. auripellitum S. minusculum, S. nigrimanum) or were absent (S. guianense) in the wet season. Simulium minusculum was the predominant species at all catching stations, being particularly abundant by the large River Tocantins. The other three species were mainly associated with smaller rivers. In the dry season, biting rhythms of S. minusculum varied with catching site, while S. nigrimanum showed peaks of activity in early morning and during the afternoon. Experimental infection with Onchocerca volvulus (Leuckart) (Nematoda: Onchocercidae), from a human volunteer, showed that this parasite could develop fully in the four simuliid species, which are all considered to be potential vectors in the area.

Kuhn EC et al. (2021) Environ Sci Pollut Res Int "Ecotoxicological assessment of Uruguay River and affluents pre- and post-pesticides' application using Caenorhabditis elegans for biomonitoring."

Kuhn EC, Gralha T, Jacques MT, Camargo S, Meyer S, Teixeira D, Schwerdtle T, Bornhorst J, Roehrs R, Avila DS

[Environ Sci Pollut Res Int, 2021]

Uruguay River is the mostimportant river in western Rio Grande do Sul, separating Brazil from Argentina and Uruguay. However, its pollution is of great concern due to agricultural activities in the region and the extensive use of pesticides. In a long term, this practice leads to environmental pollution, especially to the aquatic system. The objective of this study was to analyze the physicochemical characteristics, metals and pesticides levels in water samples obtained before and after the planting and pesticides' application season from three sites: Uruguay River and two minor affluents, Mezomo Dam and Salso Stream. For biomonitoring, the free-living nematode Caenorhabditis elegans was used, which were exposed for 24 h. We did not find any significant alteration in physicochemical parameters. In the pre- and post-pesticides' samples we observed a residual presence of three pesticides (tebuconazole, imazethapyr, and clomazone) and metals which levels were above the recommended (As, Hg, Fe, and Mn). Exposure to both pre- and post-pesticides' samples impaired C. elegans reproduction and post-pesticides samples reduced worms' survival rate and lifespan. PCA analysis indicated that the presence of metals and pesticides are important variables that impacted C. elegans biological endpoints. Our data demonstrates that Uruguay River and two affluents are contaminated independent whether before or after pesticides' application season. In addition, it reinforces the usefulness of biological indicators, since simple physicochemical analyses are not sufficient to attest water quality and ecological safety.

Chen YW et al. (2018) Front Immunol "RIOK-1 Is a Suppressor of the p38 MAPK Innate Immune Pathway in Caenorhabditis elegans."

Chen PL, Chen CS, Ko WC, Chen YW

[Front Immunol, 2018]

Innate immunity is the primary defense mechanism against infection in metazoans. However, aberrant upregulation of innate immune-signaling pathways can also be detrimental to the host. The p38 MAPK/PMK-1 innate immune-signaling pathway has been demonstrated to play essential roles in cellular defenses against numerous infections in metazoans, including <i>Caenorhabditis elegans</i>. However, the negative regulators that maintain the homeostasis of this important innate immune pathway remain largely understudied. By screening a focused RNAi library against the kinome of <i>C. elegans</i>, we identified RIOK-1, a human RIO kinase homolog, as a novel suppressor of the p38 MAPK/PMK-1 signal pathway. We demonstrated that the suppression of <i>riok-1</i> confers resistance to <i>Aeromonas dhakensis</i> infection in <i>C. elegans</i>. Using quantitative real time-PCR and <i>riok-1</i> reporter worms, we found the expression levels of <i>riok-1</i> to be significantly upregulated in worms infected with <i>A. dhakensis</i>. Our genetic epistasis analysis suggested that <i>riok-1</i> acts on the upstream of the p38 MAPK/<i>pmk-1</i> genetic pathway. Moreover, the suppression of <i>riok-1</i> enhanced the p38 MAPK signal, suggesting that <i>riok-1</i> is a negative regulator of this innate pathway in <i>C. elegans</i>. Our epistatic results put <i>riok-1</i> downstream of <i>skn-1</i>, which encodes a p38 MAPK downstream transcription factor and serves as a feedback loop to the p38 MAPK pathway during an <i>A. dhakensis</i> infection. In conclusion, <i>riok-1</i> is proposed as a novel innate immune suppressor and as a negative feedback loop model involving p38 MAPK, SKN-1, and RIOK-1 in <i>C. elegans</i>.