Candida albicans Infection of Caenorhabditis elegans Induces Antifungal Immune Defenses

Candida albicans yeast cells are found in the intestine of most humans, yet this opportunist can invade host tissues and cause life-threatening infections in susceptible individuals. To better understand the host factors that underlie susceptibility to candidiasis, we developed a new model to study antifungal innate immunity. We demonstrate that the yeast form of C. albicans establishes an intestinal infection in Caenorhabditis elegans, whereas heat-killed yeast are avirulent. Genome-wide, transcription-profiling analysis of C. elegans infected with C. albicans yeast showed that exposure to C. albicans stimulated a rapid host response involving 313 genes (124 upregulated and 189 downregulated, ∼1.6% of the genome) many of which encode antimicrobial, secreted or detoxification proteins. Interestingly, the host genes affected by C. albicans exposure overlapped only to a small extent with the distinct transcriptional responses to the pathogenic bacteria Pseudomonas aeruginosa or Staphylococcus aureus, indicating that there is a high degree of immune specificity toward different bacterial species and C. albicans. Furthermore, genes induced by P. aeruginosa and S. aureus were strongly over-represented among the genes downregulated during C. albicans infection, suggesting that in response to fungal pathogens, nematodes selectively repress the transcription of antibacterial immune effectors. A similar phenomenon is well known in the plant immune response, but has not been described previously in metazoans. Finally, 56% of the genes induced by live C. albicans were also upregulated by heat-killed yeast. These data suggest that a large part of the transcriptional response to C. albicans is mediated through “pattern recognition,” an ancient immune surveillance mechanism able to detect conserved microbial molecules (so-called pathogen-associated molecular patterns or PAMPs). This study provides new information on the evolution and regulation of the innate immune response to divergent pathogens and demonstrates that nematodes selectively mount specific antifungal defenses at the expense of antibacterial responses

Caenorhabditis elegans Genomic Response to Soil Bacteria Predicts Environment-Specific Genetic Effects on Life History Traits

With the post-genomic era came a dramatic increase in high-throughput technologies, of which transcriptional profiling by microarrays was one of the most popular. One application of this technology is to identify genes that are differentially expressed in response to different environmental conditions. These experiments are constructed under the assumption that the differentially expressed genes are functionally important in the environment where they are induced. However, whether differential expression is predictive of functional importance has yet to be tested. Here we have addressed this expectation by employing Caenorhabditis elegans as a model for the interaction of native soil nematode taxa and soil bacteria. Using transcriptional profiling, we identified candidate genes regulated in response to different bacteria isolated in association with grassland nematodes or from grassland soils. Many of the regulated candidate genes are predicted to affect metabolism and innate immunity suggesting similar genes could influence nematode community dynamics in natural systems. Using mutations that inactivate 21 of the identified genes, we showed that most contribute to lifespan and/or fitness in a given bacterial environment. Although these bacteria may not be natural food sources for C. elegans, we show that changes in food source, as can occur in environmental disturbance, can have a large effect on gene expression, with important consequences for fitness. Moreover, we used regression analysis to demonstrate that for many genes the degree of differential gene expression between two bacterial environments predicted the magnitude of the effect of the loss of gene function on life history traits in those environments

Variants in CXCR4 associate with juvenile idiopathic arthritis susceptibility

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease among children, the etiology of which involves a strong genetic component, but much of the underlying genetic determinants still remain unknown. Our aim was to identify novel genetic variants that predispose to JIA. METHODS: We performed a genome-wide association study (GWAS) and replication in a total of 1166 JIA cases and 9500 unrelated controls of European ancestry. Correlation of SNP genotype and gene expression was investigated. Then we conducted targeted resequencing of a candidate locus, among a subset of 480 cases and 480 controls. SUM test was performed to evaluate the association of the identified rare functional variants. RESULTS: The CXCR4 locus on 2q22.1 was found to be significantly associated with JIA, peaking at SNP rs953387. However, this result is subjected to subpopulation stratification within the subjects of European ancestry. After adjusting for principal components, nominal significant association remained (p < 10(-4)). Because of its interesting known function in immune regulation, we carried out further analyses to assess its relationship with JIA. Expression of CXCR4 was correlated with CXCR4 rs953387 genotypes in lymphoblastoid cell lines (p = 0.014) and T-cells (p = 0.0054). In addition, rare non-synonymous and stop-gain sequence variants in CXCR4, putatively damaging for CXCR4 function, were significantly enriched in JIA cases (p = 0.015). CONCLUSION: Our results suggest the association of CXCR4 variants with JIA, implicating that this gene may be involved in the pathogenesis of autoimmune disease. However, because this locus is subjected to population stratification within the subjects of European ancestry, additional replication is still necessary for this locus to be considered a true risk locus for JIA. This cell-surface chemokine receptor has already been targeted in other diseases and may serve as a tractable therapeutic target for a specific subset of pediatric arthritis patients with additional replication and functional validation of the locus

Effects of Role-Play for Problem-Solving Skills and Engagement in Online Forums

The body of research found that it is difficult to improve the quality of an online discussion experience because of the affordances and the limitations of asynchronous online communication technologies (An et al., Comput Educ 53: 749–760, 2009; Bachner, Cases on critical and qualitative perspectives in online higher education. Hershey, PA: IGI Global, 2014; Dennen and Wieland, Dis Educ 28(3): 281–297, 2007; Rourke and Kanuka, J Dis Educ 23(1): 19–48, 2009; Thomas, J Comput Assist Learn 18: 351–366, 2002). To address this issue, this study investigated an instructional strategy to increase engagement using a collaborative role-play online discussion where students assumed different roles. This study aimed to assess the quality of interaction by means of the Interaction Analysis Model (IAM) for examining social construction of knowledge and of learning experiences of teachers during computer conferencing designed to learn problem-solving skills. Two major models guided the study: Problem Solving Approach Model (Branford and Stein, The IDEAL problem solver: A guide for improving thinking, learning, and creativity. New York, NY: Freeman, 1993) and Interaction Analysis Model (IAM) for Computer-Mediated Communication rooted in social constructivist theory (Gunawardena et al., J Educ Comput Res 17(4): 397–431, 1997). After analyzing the progress of the discussion transcripts, this study found that the role-play discussion constructed better knowledge socially and improved higher mental operation. The threaded discussion postings from four structured online debates showed that the algorithmic format of problem-solving steps promoted and were closely interrelated to five phases of IAM. The study also found that this problem-solving exercise through computer-mediated communication helped teachers be equipped with a frame of reference to the problems, which resulted in helping teachers to establish boundaries, name problems, form opinions, and uncover solutions (Entman, J Commun 43(4): 51–58, 1993; Goffman, Frame analysis: An essay on the organization of experience. London: Harper and Row, 1974). This study will benefit online instructors as well as instructional designers who strive to find ways to make online discussion engaging