High-throughput phenotyping of infection by diverse microsporidia species reveals a wild C. elegans strain with opposing resistance and susceptibility traits.

Animals are under constant selective pressure from a myriad of diverse pathogens. Microsporidia are ubiquitous animal parasites, but the influence they exert on shaping animal genomes is mostly unknown. Using multiplexed competition assays, we measured the impact of four different species of microsporidia on 22 wild isolates of Caenorhabditis elegans. This resulted in the identification and confirmation of 13 strains with significantly altered population fitness profiles under infection conditions. One of these identified strains, JU1400, is sensitive to an epidermal-infecting species by lacking tolerance to infection. JU1400 is also resistant to an intestinal-infecting species and can specifically recognize and destroy this pathogen. Genetic mapping of JU1400 demonstrates that these two opposing phenotypes are caused by separate loci. Transcriptional analysis reveals the JU1400 sensitivity to epidermal microsporidia infection results in a response pattern that shares similarity to toxin-induced responses. In contrast, we do not observe JU1400 intestinal resistance being regulated at the transcriptional level. The transcriptional response to these four microsporidia species is conserved, with C. elegans strain-specific differences in potential immune genes. Together, our results show that phenotypic differences to microsporidia infection amongst C. elegans are common and that animals can evolve species-specific genetic interactions.

A comprehensive survey of C. elegans argonaute proteins reveals organism-wide gene regulatory networks and functions.

Argonaute (AGO) proteins associate with small RNAs to direct their effector function on complementary transcripts. The nematode Caenorhabditis elegans contains an expanded family of 19 functional AGO proteins, many of which have not been fully characterized. In this work, we systematically analyzed every C. elegans AGO using CRISPR-Cas9 genome editing to introduce GFP::3xFLAG tags. We have characterized the expression patterns of each AGO throughout development, identified small RNA binding complements, and determined the effects of ago loss on small RNA populations and developmental phenotypes. Our analysis indicates stratification of subsets of AGOs into distinct regulatory modules, and integration of our data led us to uncover novel stress-induced fertility and pathogen response phenotypes due to ago loss.

High-throughput small molecule screen identifies inhibitors of microsporidia invasion and proliferation in C. elegans.

Microsporidia are a diverse group of fungal-related obligate intracellular parasites that infect most animal phyla. Despite the emerging threat that microsporidia represent to humans and agricultural animals, few reliable treatment options exist. Here, we develop a high-throughput screening method for the identification of chemical inhibitors of microsporidia infection, using liquid cultures of Caenorhabditis elegans infected with the microsporidia species Nematocida parisii. We screen a collection of 2560 FDA-approved compounds and natural products, and identify 11 candidate microsporidia inhibitors. Five compounds prevent microsporidia infection by inhibiting spore firing, whereas one compound, dexrazoxane, slows infection progression. The compounds have in vitro activity against several other microsporidia species, including those known to infect humans. Together, our results highlight the effectiveness of C. elegans as a model host for drug discovery against intracellular pathogens, and provide a scalable high-throughput system for the identification and characterization of microsporidia inhibitors.

A parental transcriptional response to microsporidia infection induces inherited immunity in offspring.

Parental infection can result in the production of offspring with enhanced immunity phenotypes. Critically, the mechanisms underlying inherited immunity are poorly understood. Here, we show that Caenorhabditis elegans infected with the intracellular microsporidian parasite N. parisii produce progeny that are resistant to microsporidia infection. We determine the kinetics of the response and show that intergenerational immunity prevents host-cell invasion by Nematocida parisii and enhances survival to the bacterial pathogen Pseudomonas aeruginosa We demonstrate that immunity is induced by the parental transcriptional response to infection, which can be mimicked through maternal somatic depletion of PALS-22 and the retinoblastoma protein ortholog, LIN-35. We find that other biotic and abiotic stresses (viral infection and cadmium exposure) that induce a similar transcriptional response as microsporidia also induce immunity in progeny. Together, our results reveal how a parental transcriptional signal can be induced by distinct stimuli and protect offspring against multiple classes of pathogens.

Nodding behavior observed in Japanese stiltgrass, Microstegium vimineum , seedlings from time-lapse observations.

Invasive species are the second main cause of biodiversity loss because of their exceptional ability to supplant native species by creating major upheavals in ecosystems. Inexpensive and prevalent time-lapse photography provides an exciting opportunity to better understand the aggressive behavior of invasive species including how they invade and conquer new territory. One of the most pervasive invasive species in the Eastern United States is Japanese stiltgrass, Microstegium vimineum (Trin.) A. Campus, which originated from Southeast Asia. Previous research has examined the conditions that enable Japanese stiltgrass to become invasive, but nothing is known regarding root and shoot behavior. Here time-lapse was used to examine Japanese stiltgrass seedlings, early in their development, as a first step to observe its behavior. Our results demonstrate that Japanese stiltgrass shoots appear to drop or collapse and then resurrect back to an upright stature - sometimes the same plant exhibits this behavior multiple times. We have shown, in addition, that emergent stilt root growth rate increases with increased root length. This and similar kinds of analyses may provide insight into how Japanese stiltgrass thrives aggressively in a non-native environment with the goal of developing better methods of controlling this noxious weed.

Belonging through sport participation for young adults with intellectual and developmental disabilities: A scoping review.

BACKGROUND: Research suggests that sport facilitates belonging for diverse athletes. This scoping review characterizes literature on sport participation and belonging for young adults with intellectual and developmental disabilities. MATERIALS AND METHODS: A search of five databases identified 17,497 articles. Selected articles (N = 39) underwent data extraction and analysis guided by a theoretical framework of belonging, outlining four processes through which belonging is experienced by individuals with intellectual and developmental disabilities. RESULTS: Articles originated from developed countries and in the context of Special Olympics (N = 17). Studies commonly used qualitative interviews with proxy respondents. While all studies described at least one belonging process, only 11 studies applied the term "belonging," and no study defined the construct. CONCLUSION: Belonging is not well-conceptualized in sports literature for athletes with intellectual and developmental disabilities. Understanding belonging through sport participation for this population may inform sport-based policies and programming.