Natural variation in infection specificity of Caenorhabditis briggsae isolates by two RNA viruses.

Antagonistic relationships such as host-virus interactions potentially lead to rapid evolution and specificity in interactions. The Orsay virus is so far the only horizontal virus naturally infecting the nematode C. elegans. In contrast, several related RNA viruses infect its congener C. briggsae, including Santeuil (SANTV) and Le Blanc (LEBV) viruses. Here we focus on the host's intraspecific variation in sensitivity to these two intestinal viruses. Many temperate-origin C. briggsae strains, including JU1264 and JU1498, are sensitive to both, while many tropical strains, such as AF16, are resistant to both. Interestingly, some C. briggsae strains exhibit a specific resistance, such as the HK104 strain, specifically resistant to LEBV. The viral sensitivity pattern matches the strains' geographic and genomic relationships. The heavily infected strains mount a seemingly normal small RNA response that is insufficient to suppress viral infection, while the resistant strains show no small RNA response, suggesting an early block in viral entry or replication. We use a genetic approach from the host side to map genomic regions participating in viral resistance polymorphisms. Using Advanced Intercrossed Recombinant Inbred Lines (RILs) between virus-resistant AF16 and SANTV-sensitive HK104, we detect Quantitative Trait Loci (QTLs) on chromosomes IV and III. Building RILs between virus-sensitive JU1498 and LEBV-resistant HK104 followed by bulk segregant analysis, we identify a chromosome II QTL. In both cases, further introgressions of the regions confirmed the QTLs. This diversity provides an avenue for studying virus entry, replication, and exit mechanisms, as well as host-virus specificity and the host response to a specific virus infection.

CaeNDR, the Caenorhabditis Natural Diversity Resource.

Studies of model organisms have provided important insights into how natural genetic differences shape trait variation. These discoveries are driven by the growing availability of genomes and the expansive experimental toolkits afforded to researchers using these species. For example, Caenorhabditis elegans is increasingly being used to identify and measure the effects of natural genetic variants on traits using quantitative genetics. Since 2016, the C. elegans Natural Diversity Resource (CeNDR) has facilitated many of these studies by providing an archive of wild strains, genome-wide sequence and variant data for each strain, and a genome-wide association (GWA) mapping portal for the C. elegans community. Here, we present an updated platform, the Caenorhabditis Natural Diversity Resource (CaeNDR), that enables quantitative genetics and genomics studies across the three Caenorhabditis species: C. elegans, C. briggsae and C. tropicalis. The CaeNDR platform hosts several databases that are continually updated by the addition of new strains, whole-genome sequence data and annotated variants. Additionally, CaeNDR provides new interactive tools to explore natural variation and enable GWA mappings. All CaeNDR data and tools are accessible through a freely available web portal located at caendr.org.

Genome-wide association and environmental suppression of the mortal germline phenotype of wild C. elegans.

The animal germline lineage needs to be maintained along generations. However, some Caenorhabditis elegans wild isolates display a mortal germline phenotype, leading to sterility after several generations at 25°C. Using a genome-wide association approach, we detect a significant peak on chromosome III around 5 Mb, confirmed by introgressions. Thus, a seemingly deleterious genotype is maintained at intermediate frequency in the species. Environmental rescue is a likely explanation, and indeed associated bacteria and microsporidia suppress the phenotype of wild isolates as well as mutants in small RNA inheritance (nrde-2) and histone modifications (set-2). Escherichia coli strains of the K-12 lineage suppress the phenotype compared to B strains. By shifting a wild strain from E. coli K-12 to E. coli B, we find that memory of the suppressing condition is maintained over several generations. Thus, the mortal germline phenotype of wild C. elegans is in part revealed by laboratory conditions and may represent variation in epigenetic inheritance and environmental interactions. This study also points to the importance of non-genetic memory in the face of environmental variation.

Praziquantel inhibits Caenorhabditis elegans development and species-wide differences might be cct-8-dependent.

Anthelmintic drugs are used to treat parasitic roundworm and flatworm infections in humans and other animals. Caenorhabditis elegans is an established model to investigate anthelmintics used to treat roundworms. In this study, we use C. elegans to examine the mode of action and the mechanisms of resistance against the flatworm anthelmintic drug praziquantel (PZQ), used to treat trematode and cestode infections. We found that PZQ inhibited development and that this developmental delay varies by genetic background. Interestingly, both enantiomers of PZQ are equally effective against C. elegans, but the right-handed PZQ (R-PZQ) is most effective against schistosome infections. We conducted a genome-wide association mapping with 74 wild C. elegans strains to identify a region on chromosome IV that is correlated with differential PZQ susceptibility. Five candidate genes in this region: cct-8, znf-782, Y104H12D.4, Y104H12D.2, and cox-18, might underlie this variation. The gene cct-8, a subunit of the protein folding complex TRiC, has variation that causes a putative protein coding change (G226V), which is correlated with reduced developmental delay. Gene expression analysis suggests that this variant correlates with slightly increased expression of both cct-8 and hsp-70. Acute exposure to PZQ caused increased expression of hsp-70, indicating that altered TRiC function might be involved in PZQ responses. To test if this variant affects development upon exposure to PZQ, we used CRISPR-Cas9 genome editing to introduce the V226 allele into the N2 genetic background (G226) and the G226 allele into the JU775 genetic background (V226). These experiments revealed that this variant was not sufficient to explain the effects of PZQ on development. Nevertheless, this study shows that C. elegans can be used to study PZQ mode of action and resistance mechanisms. Additionally, we show that the TRiC complex requires further evaluation for PZQ responses in C. elegans.

Interplay Between Polymorphic Short Tandem Repeats and Gene Expression Variation in Caenorhabditis elegans.

Short tandem repeats (STRs) have orders of magnitude higher mutation rates than single nucleotide variants (SNVs) and have been proposed to accelerate evolution in many organisms. However, only few studies have addressed the impact of STR variation on phenotypic variation at both the organismal and molecular levels. Potential driving forces underlying the high mutation rates of STRs also remain largely unknown. Here, we leverage the recently generated expression and STR variation data among wild Caenorhabditis elegans strains to conduct a genome-wide analysis of how STRs affect gene expression variation. We identify thousands of expression STRs (eSTRs) showing regulatory effects and demonstrate that they explain missing heritability beyond SNV-based expression quantitative trait loci. We illustrate specific regulatory mechanisms such as how eSTRs affect splicing sites and alternative splicing efficiency. We also show that differential expression of antioxidant genes and oxidative stresses might affect STR mutations systematically using both wild strains and mutation accumulation lines. Overall, we reveal the interplay between STRs and gene expression variation by providing novel insights into regulatory mechanisms of STRs and highlighting that oxidative stress could lead to higher STR mutation rates.

Confused or not: decoding brain activity and recognizing confusion in reasoning learning using EEG.

Objective.Confusion is the primary epistemic emotion in the learning process, influencing students' engagement and whether they become frustrated or bored. However, research on confusion in learning is still in its early stages, and there is a need to better understand how to recognize it and what electroencephalography (EEG) signals indicate its occurrence. The present work investigates confusion during reasoning learning using EEG, and aims to fill this gap with a multidisciplinary approach combining educational psychology, neuroscience and computer science.Approach.First, we design an experiment to actively and accurately induce confusion in reasoning. Second, we propose a subjective and objective joint labeling technique to address the label noise issue. Third, to confirm that the confused state can be distinguished from the non-confused state, we compare and analyze the mean band power of confused and unconfused states across five typical bands. Finally, we present an EEG database for confusion analysis, together with benchmark results from conventional (Naive Bayes, Support Vector Machine, Random Forest, and Artificial Neural Network) and end-to-end (Long Short Term Memory, Residual Network, and EEGNet) machine learning methods.Main results.Findings revealed: 1. Significant differences in the power of delta, theta, alpha, beta and lower gamma between confused and non-confused conditions; 2. A higher attentional and cognitive load when participants were confused; and 3. The Random Forest algorithm with time-domain features achieved a high accuracy/F1 score (88.06%/0.88 for the subject-dependent approach and 84.43%/0.84 for the subject-independent approach) in the binary classification of the confused and non-confused states.Significance.The study advances our understanding of confusion and provides practical insights for recognizing and analyzing it in the learning process. It extends existing theories on the differences between confused and non-confused states during learning and contributes to the cognitive-affective model. The research enables researchers, educators, and practitioners to monitor confusion, develop adaptive systems, and test recognition approaches.

Enhancing photoelectrochemical CO2 reduction with silicon photonic crystals.

The effectiveness of silicon (Si) and silicon-based materials in catalyzing photoelectrochemistry (PEC) CO2 reduction is limited by poor visible light absorption. In this study, we prepared two-dimensional (2D) silicon-based photonic crystals (SiPCs) with circular dielectric pillars arranged in a square array to amplify the absorption of light within the wavelength of approximately 450 nm. By investigating five sets of n + p SiPCs with varying dielectric pillar sizes and periodicity while maintaining consistent filling ratios, our findings showed improved photocurrent densities and a notable shift in product selectivity towards CH4 (around 25% Faradaic Efficiency). Additionally, we integrated platinum nanoparticles, which further enhanced the photocurrent without impacting the enhanced light absorption effect of SiPCs. These results not only validate the crucial role of SiPCs in enhancing light absorption and improving PEC performance but also suggest a promising approach towards efficient and selective PEC CO2 reduction.

Natural variation in C. elegans short tandem repeats.

Short tandem repeats (STRs) represent an important class of genetic variation that can contribute to phenotypic differences. Although millions of single nucleotide variants (SNVs) and short indels have been identified among wild Caenorhabditis elegans strains, the natural diversity in STRs remains unknown. Here, we characterized the distribution of 31,991 STRs with motif lengths of 1-6 bp in the reference genome of C. elegans Of these STRs, 27,667 harbored polymorphisms across 540 wild strains and only 9691 polymorphic STRs (pSTRs) had complete genotype data for more than 90% of the strains. Compared with the reference genome, the pSTRs showed more contraction than expansion. We found that STRs with different motif lengths were enriched in different genomic features, among which coding regions showed the lowest STR diversity and constrained STR mutations. STR diversity also showed similar genetic divergence and selection signatures among wild strains as in previous studies using SNVs. We further identified STR variation in two mutation accumulation line panels that were derived from two wild strains and found background-dependent and fitness-dependent STR mutations. We also performed the first genome-wide association analyses between natural variation in STRs and organismal phenotypic variation among wild C. elegans strains. Overall, our results delineate the first large-scale characterization of STR variation in wild C. elegans strains and highlight the effects of selection on STR mutations.

Interfacial Engineering of Semicoherent Interface at Purified CsPbBr3 Quantum Dots/2D-PbSe for Optimal CO2 Photoreduction Performance.

Heterogeneous photocatalysts are extensively used to achieve interfacial electric fields for acceleration of oriented charge carrier transport and further promotion of photocatalytic redox reactions. Unfortunately, the incoherent interfaces are almost present in the heterostructures owing to large lattice mismatch accompanied by the interfacial defects and high density of gap states, acting as high energy barriers for charge migration. In this work, we report the atomic engineering of CsPbBr3/PbSe heterogeneous interfaces and conversion from incoherent features to semicoherent characters via methyl acetate (MeOAc) purification of CsPbBr3 quantum dots (QDs) before composited with two-dimensional (2D)-PbSe, which is confirmed by high-resolution transmission electron microscopy. The photocatalytic performances and theoretical calculations indicate that semicoherent interfaces are favorable for improving the activity and reactivity of the heterostructure, triggering 3 times enhanced photocatalytic CO2 reduction rate with 91% selectivity and satisfactory stability. This study proposes a facile method for photocatalytic heterojunctions to transform incoherent interfaces to photocatalytically beneficial semicoherent boundaries, accompanying with a systematic analysis of the consequent chemical dynamics to demonstrate the mechanism of the semicoherent interface for supporting photocatalysis. The understandings gained from this work are valuable for rational interfacial lattice engineering of heterogeneous photocatalysts for efficient solar fuel production.

C. elegans as a model for inter-individual variation in metabolism.

Individuals can exhibit differences in metabolism that are caused by the interplay of genetic background, nutritional input, microbiota and other environmental factors1-4. It is difficult to connect differences in metabolism to genomic variation and derive underlying molecular mechanisms in humans, owing to differences in diet and lifestyle, among others. Here we use the nematode Caenorhabditis elegans as a model to study inter-individual variation in metabolism. By comparing three wild strains and the commonly used N2 laboratory strain, we find differences in the abundances of both known metabolites and those that have not to our knowledge been previously described. The latter metabolites include conjugates between 3-hydroxypropionate (3HP) and several amino acids (3HP-AAs), which are much higher in abundance in one of the wild strains. 3HP is an intermediate in the propionate shunt pathway, which is activated when flux through the canonical, vitamin-B12-dependent propionate breakdown pathway is perturbed5. We show that increased accumulation of 3HP-AAs is caused by genetic variation in HPHD-1, for which 3HP is a substrate. Our results suggest that the production of 3HP-AAs represents a 'shunt-within-a-shunt' pathway to accommodate a reduction-of-function allele in hphd-1. This study provides a step towards the development of metabolic network models that capture individual-specific differences of metabolism and more closely represent the diversity that is found in entire species.

The impact of species-wide gene expression variation on Caenorhabditis elegans complex traits.

Phenotypic variation in organism-level traits has been studied in Caenorhabditis elegans wild strains, but the impacts of differences in gene expression and the underlying regulatory mechanisms are largely unknown. Here, we use natural variation in gene expression to connect genetic variants to differences in organismal-level traits, including drug and toxicant responses. We perform transcriptomic analyses on 207 genetically distinct C. elegans wild strains to study natural regulatory variation of gene expression. Using this massive dataset, we perform genome-wide association mappings to investigate the genetic basis underlying gene expression variation and reveal complex genetic architectures. We find a large collection of hotspots enriched for expression quantitative trait loci across the genome. We further use mediation analysis to understand how gene expression variation could underlie organism-level phenotypic variation for a variety of complex traits. These results reveal the natural diversity in gene expression and possible regulatory mechanisms in this keystone model organism, highlighting the promise of using gene expression variation to understand how phenotypic diversity is generated.

A high-responsivity CsPbBr3 nanowire photodetector induced by CdS@CdxZn1-xS gradient-alloyed quantum dots.

Benefitting from excellent thermal and moisture stability, inorganic halide perovskite materials have established themselves quickly as promising candidates for fabricating photoelectric devices. However, due to their high trap state density and rapid carrier recombination rate, the photoelectric conversion efficiencies of current inorganic halide perovskite materials are still lower than expected. Here, after systematic research on the optoelectronic properties of CsPbBr3 nanowires (NWs) decorated with binary CdS quantum dots (QDs), CdS@ZnS core/shell QDs, and gradient-alloyed CdS@CdxZn1-xS QDs, respectively, we proposed a facile method to improve the quantum efficiency of perovskite-based photodetectors with low cost, in which the aforementioned QDs are firstly integrated with CsPbBr3 NWs, which act as a photosensitive layer. Notably, the responsivity of the CsPbBr3 NW photodetector decorated with CdS@CdxZn1-xS QDs was enhanced about 10-fold compared to that of pristine CsPbBr3 NW devices. This value is far superior to those for hybrids composed of binary CdS QDs and CdS@ZnS core/shell QDs. The high responsivity enhancement phenomena are interpreted based on the unique funnel-shaped energy level of CdS@CdxZn1-xS QDs, which is favorable for light-harvesting and photocarrier separation. This work indicates that our unique QD/NW hybrid nanostructure is a desirable building block for fabricating high-performance photodetectors.

Changes in body shape implicate cuticle stretch in C. elegans growth control.

Growth control establishes organism size, requiring mechanisms to sense and adjust growth during development. Studies of single cells revealed that size homeostasis uses distinct control methods. In multicellular organisms, mechanisms that regulate single cell growth must integrate control across organs and tissues during development to generate adult size and shape. We leveraged the roundworm Caenorhabditis elegans as a scalable and tractable model to collect precise growth measurements of thousands of individuals, measure feeding behavior, and quantify changes in animal size and shape during a densely sampled developmental time course. As animals transitioned from one developmental stage to the next, we observed changes in body aspect ratio while body volume remained constant. Then, we modeled a physical mechanism by which constraints on cuticle stretch could cause changes in C. elegans body shape. The model-predicted shape changes are consistent with those observed in the data. Theoretically, cuticle stretch could be sensed by the animal to initiate larval-stage transitions, providing a means for physical constraints to influence developmental timing and growth rate in C. elegans.

Local adaptation and spatiotemporal patterns of genetic diversity revealed by repeated sampling of Caenorhabditis elegans across the Hawaiian Islands.

The nematode Caenorhabditis elegans is among the most widely studied organisms, but relatively little is known about its natural ecology. Genetic diversity is low across much of the globe but high in the Hawaiian Islands and across the Pacific Rim. To characterize the niche and genetic diversity of C. elegans on the Hawaiian Islands and to explore how genetic diversity might be influenced by local adaptation, we repeatedly sampled nematodes over a three-year period, measured various environmental parameters at each sampling site, and whole-genome sequenced the C. elegans isolates that we identified. We found that the typical Hawaiian C. elegans niche comprises moderately moist native forests at high elevations (500-1,500 m) where ambient air temperatures are cool (15-20°C). Compared to other Caenorhabditis species found on the Hawaiian Islands (e.g., Caenorhabditis briggsae and Caenorhabditis tropicalis), we found that C. elegans were enriched in native habitats. We measured levels of genetic diversity and differentiation among Hawaiian C. elegans and found evidence of seven genetically distinct groups distributed across the islands. Then, we scanned these genomes for signatures of local adaptation and identified 18 distinct regions that overlap with hyper-divergent regions, which may be maintained by balancing selection and are enriched for genes related to environmental sensing, xenobiotic detoxification, and pathogen resistance. These results provide strong evidence of local adaptation among Hawaiian C. elegans and contribute to our understanding of the forces that shape genetic diversity on the most remote volcanic archipelago in the world.

Natural variation in fecundity is correlated with species-wide levels of divergence in Caenorhabditis elegans.

Life history traits underlie the fitness of organisms and are under strong natural selection. A new mutation that positively impacts a life history trait will likely increase in frequency and become fixed in a population (e.g., a selective sweep). The identification of the beneficial alleles that underlie selective sweeps provides insights into the mechanisms that occurred during the evolution of a species. In the global population of Caenorhabditis elegans, we previously identified selective sweeps that have drastically reduced chromosomal-scale genetic diversity in the species. Here, we measured the fecundity of 121 wild C. elegans strains, including many recently isolated divergent strains from the Hawaiian islands and found that strains with larger swept genomic regions have significantly higher fecundity than strains without evidence of the recent selective sweeps. We used genome-wide association (GWA) mapping to identify three quantitative trait loci (QTL) underlying the fecundity variation. In addition, we mapped previous fecundity data from wild C. elegans strains and C. elegans recombinant inbred advanced intercross lines that were grown in various conditions and detected eight QTL using GWA and linkage mappings. These QTL show the genetic complexity of fecundity across this species. Moreover, the haplotype structure in each GWA QTL region revealed correlations with recent selective sweeps in the C. elegans population. North American and European strains had significantly higher fecundity than most strains from Hawaii, a hypothesized origin of the C. elegans species, suggesting that beneficial alleles that caused increased fecundity could underlie the selective sweeps during the worldwide expansion of C. elegans.

Selfing is the safest sex for Caenorhabditis tropicalis.

Mating systems have profound effects on genetic diversity and compatibility. The convergent evolution of self-fertilization in three Caenorhabditis species provides a powerful lens to examine causes and consequences of mating system transitions. Among the selfers, Caenorhabditis tropicalis is the least genetically diverse and most afflicted by outbreeding depression. We generated a chromosomal-scale genome for C. tropicalis and surveyed global diversity. Population structure is very strong, and islands of extreme divergence punctuate a genomic background that is highly homogeneous around the globe. Outbreeding depression in the laboratory is caused largely by multiple Medea-like elements, genetically consistent with maternal toxin/zygotic antidote systems. Loci with Medea activity harbor novel and duplicated genes, and their activity is modified by mito-nuclear background. Segregating Medea elements dramatically reduce fitness, and simulations show that selfing limits their spread. Frequent selfing in C. tropicalis may therefore be a strategy to avoid Medea-mediated outbreeding depression.

Natural Variation in a Dendritic Scaffold Protein Remodels Experience-Dependent Plasticity by Altering Neuropeptide Expression.

The extent to which behavior is shaped by experience varies between individuals. Genetic differences contribute to this variation, but the neural mechanisms are not understood. Here, we dissect natural variation in the behavioral flexibility of two Caenorhabditis elegans wild strains. In one strain, a memory of exposure to 21% O2 suppresses CO2-evoked locomotory arousal; in the other, CO2 evokes arousal regardless of previous O2 experience. We map that variation to a polymorphic dendritic scaffold protein, ARCP-1, expressed in sensory neurons. ARCP-1 binds the Ca2+-dependent phosphodiesterase PDE-1 and co-localizes PDE-1 with molecular sensors for CO2 at dendritic ends. Reducing ARCP-1 or PDE-1 activity promotes CO2 escape by altering neuropeptide expression in the BAG CO2 sensors. Variation in ARCP-1 alters behavioral plasticity in multiple paradigms. Our findings are reminiscent of genetic accommodation, an evolutionary process by which phenotypic flexibility in response to environmental variation is reset by genetic change.

Deep sampling of Hawaiian Caenorhabditis elegans reveals high genetic diversity and admixture with global populations.

Hawaiian isolates of the nematode species Caenorhabditis elegans have long been known to harbor genetic diversity greater than the rest of the worldwide population, but this observation was supported by only a small number of wild strains. To better characterize the niche and genetic diversity of Hawaiian C. elegans and other Caenorhabditis species, we sampled different substrates and niches across the Hawaiian islands. We identified hundreds of new Caenorhabditis strains from known species and a new species, Caenorhabditis oiwi. Hawaiian C. elegans are found in cooler climates at high elevations but are not associated with any specific substrate, as compared to other Caenorhabditis species. Surprisingly, admixture analysis revealed evidence of shared ancestry between some Hawaiian and non-Hawaiian C. elegans strains. We suggest that the deep diversity we observed in Hawaii might represent patterns of ancestral genetic diversity in the C. elegans species before human influence.

Natural Infection of C. elegans by an Oomycete Reveals a New Pathogen-Specific Immune Response.

In its natural habitat, the nematode Caenorhabditis elegans encounters a plethora of other organisms, including many that are pathogenic [1, 2]. The study of interactions between C. elegans and various pathogens has contributed to characterizing key mechanisms of innate immunity [2-4]. However, how C. elegans recognizes different pathogens to mount pathogen-specific immune responses remains still largely unknown [3, 5-8]. Expanding the range of known C. elegans-infecting pathogens and characterizing novel pathogen-specific immune responses are key steps toward answering this question. We report here that the oomycete Myzocytiopsis humicola is a natural pathogen of C. elegans, and we describe its infection strategy. We identify a new host immune response to pathogen exposure that involves induction of members of a previously uncharacterized gene family encoding chitinase-like (CHIL) proteins. We demonstrate that this response is highly specific against M. humicola and antagonizes the infection. We propose that CHIL proteins may diminish the ability of the oomycete to infect by hindering pathogen attachment to the host cuticle. This work expands our knowledge of natural eukaryotic pathogens of C. elegans and introduces a new pathosystem to address how animal hosts recognize and respond to oomycete infections.

The Local Coexistence Pattern of Selfing Genotypes in Caenorhabditis elegans Natural Metapopulations.

To study the interplay of rare outcrossing and metapopulation structure, we focus on the nematode Caenorhabditis elegans Its remarkably low outcrossing rate is at the extreme end of the spectrum for facultative selfing organisms. At the demographic level, C. elegans natural populations undergo boom and bust dynamics on ephemeral resources, with the dauer diapause larva acting as the dispersal form. Here we investigate the small-scale genetic structure of C. elegans populations in two localities over several years, using 2b restriction-associated DNA sequencing of nearly 1000 individuals. We find a remarkably small number of genome-wide haplotypes, almost exclusively in the homozygous state, confirming the low effective outcrossing rate. Most strikingly, the major haplotypes in a locality remain intact and do not effectively recombine over several years. From the spatial pattern of diversity, we estimate that each subpopulation or deme is seeded by a mean of 3-10 immigrating individuals. Populations are thus formed by clones that compete at two levels, within a subpopulation and at the metapopulation level. We test for the presence of local phenotypic variation in pathogen resistance and dauer larva nictation, which could possibly explain the maintenance of different genotypes by heterogeneous selection in different local environments or lifecycles. This study is the first to address the local spatiotemporal genetic structure of C. elegans on feeding substrates. We conclude that these animals coexist as competing homozygous clones at the smallest population scale as well as in the metapopulation.