Daniel Copeland

Natural genetic variation in Arabidopsis thaliana defense metabolism genes modulates field fitness.

Natural populations persist in complex environments, where biotic stressors, such as pathogen and insect communities, fluctuate temporally and spatially. These shifting biotic pressures generate heterogeneous selective forces that can maintain standing natural variation within a species. To directly test if genes containing causal variation for the Arabidopsis thaliana defensive compounds, glucosinolates (GSL) control field fitness and are therefore subject to natural selection, we conducted a multi-year field trial using lines that vary in only specific causal genes. Interestingly, we found that variation in these naturally polymorphic GSL genes affected fitness in each of our environments but the pattern fluctuated such that highly fit genotypes in one trial displayed lower fitness in another and that no GSL genotype or genotypes consistently out-performed the others. This was true both across locations and within the same location across years. These results indicate that environmental heterogeneity may contribute to the maintenance of GSL variation observed within Arabidopsis thaliana. DOI: http://dx.doi.org/10.7554/eLife.05604.001

The Quantitative Basis of the Arabidopsis Innate Immune System to Endemic Pathogens Depends on Pathogen Genetics.

The most established model of the eukaryotic innate immune system is derived from examples of large effect monogenic quantitative resistance to pathogens. However, many host-pathogen interactions involve many genes of small to medium effect and exhibit quantitative resistance. We used the Arabidopsis-Botrytis pathosystem to explore the quantitative genetic architecture underlying host innate immune system in a population of Arabidopsis thaliana. By infecting a diverse panel of Arabidopsis accessions with four phenotypically and genotypically distinct isolates of the fungal necrotroph B. cinerea, we identified a total of 2,982 genes associated with quantitative resistance using lesion area and 3,354 genes associated with camalexin production as measures of the interaction. Most genes were associated with resistance to a specific Botrytis isolate, which demonstrates the influence of pathogen genetic variation in analyzing host quantitative resistance. While known resistance genes, such as receptor-like kinases (RLKs) and nucleotide-binding site leucine-rich repeat proteins (NLRs), were found to be enriched among associated genes, they only account for a small fraction of the total genes associated with quantitative resistance. Using publically available co-expression data, we condensed the quantitative resistance associated genes into co-expressed gene networks. GO analysis of these networks implicated several biological processes commonly connected to disease resistance, including defense hormone signaling and ROS production, as well as novel processes, such as leaf development. Validation of single gene T-DNA knockouts in a Col-0 background demonstrate a high success rate (60%) when accounting for differences in environmental and Botrytis genetic variation. This study shows that the genetic architecture underlying host innate immune system is extremely complex and is likely able to sense and respond to differential virulence among pathogen genotypes.

Bowel Endometriosis: Diagnosis and Management

&NA; The most common location of extragenital endometriosis is the bowel. Medical treatment may not provide long‐term improvement in patients who are symptomatic, and consequently most of these patients may require surgical intervention. Over the past century, surgeons have continued to debate the optimal surgical approach to treating bowel endometriosis, weighing the risks against the benefits. In this expert review we will describe how the recommended surgical approach depends largely on the location of disease, in addition to size and depth of the lesion. For lesions approximately 5‐8 cm from the anal verge, we encourage conservative surgical management over resection to decrease the risk of short‐ and long‐term complications.

Plastic Transcriptomes Stabilize Immunity to Pathogen Diversity: The Jasmonic Acid and Salicylic Acid Networks Within the Arabidopsis/Botrytis Pathosystem

When confronted with genetic diversity in a pathogen, plant immunity networks coordinate to determine the resistance via dramatic reshaping of the transcriptomic response. To respond to pathogen attack, selection and associated evolution has led to the creation of plant immune system that are a highly effective and inducible defense system. Central to this system are the plant defense hormones jasmonic acid (JA) and salicylic acid (SA) and crosstalk between the two, which may play an important role in defense responses to specific pathogens or even genotypes. Here, we used the Arabidopsis thaliana-Botrytis cinerea pathosystem to test how the host’s defense system functions against genetic variation in a pathogen. We measured defense-related phenotypes and transcriptomic responses in Arabidopsis wild-type Col-0 and JA- and SA-signaling mutants, coi1-1 and npr1-1, individually challenged with 96 diverse B. cinerea isolates. Those data showed genetic variation in the pathogen influences on all components within the plant defense system at the transcriptional level. We identified four gene coexpression networks and two vectors of defense variation triggered by genetic variation in B. cinerea. This showed that the JA and SA signaling pathways functioned to constrain/canalize the range of virulence in the pathogen population, but the underlying transcriptomic response was highly plastic. These data showed that plants utilize major defense hormone pathways to buffer disease resistance, but not the metabolic or transcriptional responses to genetic variation within a pathogen.

Epistasis × environment interactions among Arabidopsis thaliana glucosinolate genes impact complex traits and fitness in the field

Despite the growing number of studies showing that genotype × environment and epistatic interactions control fitness, the influences of epistasis × environment interactions on adaptive trait evolution remain largely uncharacterized. Across three field trials, we quantified aliphatic glucosinolate (GSL) defense chemistry, leaf damage, and relative fitness using mutant lines of Arabidopsis thaliana varying at pairs of causal aliphatic GSL defense genes to test the impact of epistatic and epistasis × environment interactions on adaptive trait variation. We found that aliphatic GSL accumulation was primarily influenced by additive and epistatic genetic variation, leaf damage was primarily influenced by environmental variation and relative fitness was primarily influenced by epistasis and epistasis × environment interactions. Epistasis × environment interactions accounted for up to 48% of the relative fitness variation in the field. At a single field site, the impact of epistasis on relative fitness varied significantly over 2xa0yr, showing that epistasis × environment interactions within a location can be temporally dynamic. These results suggest that the environmental dependency of epistasis can profoundly influence the response to selection, shaping the adaptive trajectories of natural populations in complex ways, and deserves further consideration in future evolutionary studies.

Combining Digital Imaging and Genome Wide Association Mapping to Dissect Uncharacterized Traits in Plant/Pathogen Interactions

Plant resistance to generalist pathogens with broad host ranges, such as Botrytis cinerea, is typically quantitative and highly polygenic. Recent studies have begun to elucidate the molecular genetic basis underpinning plant-pathogen interactions using commonly measured traits including lesion size and/or pathogen biomass. Yet with the advent of digital imaging and phenomics, there are a large number of additional resistance traits available to study quantitative resistance. In this study, we used high-throughput digital imaging analysis to investigate previously uncharacterized visual traits of plant-pathogen interactions related disease resistance using the Arabidopsis thaliana/Botrytis cinerea pathosystem. Using a large collection of 75 visual traits collected from every lesion, we focused on lesion color, lesion shape, and lesion size, to test how these aspects of the interaction are genetically related. Using genome wide association (GWA) mapping in A. thaliana, we show that lesion color and shape are genetically separable traits associated with plant-disease resistance. Using defined mutants in 23 candidate genes from the GWA mapping, we could identify and show that novel loci associated with each different plant-pathogen interaction trait, which expands our understanding of the functional mechanisms driving plant disease resistance. Summary Digital imaging allows the identification of genes controlling novel lesion traits.

Digital Imaging Combined with Genome-Wide Association Mapping Links Loci to Plant-Pathogen Interaction Traits

Computer vision allows the identification of genes controlling uncharacterized lesion traits in Arabidopsis. Plant resistance to generalist pathogens with broad host ranges, such as Botrytis cinerea (Botrytis), is typically quantitative and highly polygenic. Recent studies have begun to elucidate the molecular genetic basis of plant-pathogen interactions using commonly measured traits, including lesion size and/or pathogen biomass. However, with the advent of digital imaging and high-throughput phenomics, there are a large number of additional traits available to study quantitative resistance. In this study, we used high-throughput digital imaging analysis to investigate previously poorly characterized visual traits of plant-pathogen interactions related to disease resistance using the Arabidopsis (Arabidopsis thaliana)/Botrytis pathosystem. From a large collection of visual lesion trait measurements, we focused on color, shape, and size to test how these aspects of the Arabidopsis/Botrytis interaction are genetically related. Through genome-wide association mapping in Arabidopsis, we show that lesion color and shape are genetically separable traits associated with plant disease resistance. Moreover, by employing defined mutants in 23 candidate genes identified from the genome-wide association mapping, we demonstrate links between loci and each of the different plant-pathogen interaction traits. These results expand our understanding of the functional mechanisms driving plant disease resistance.

Surgical Endoscopic Diagnosis of Infertility

Conception requires a series of coordinated, well-timed steps: ovulation, coitus, fertilization, implantation, and gestation. These steps require the cooperation of multiple systems and organs in the body as well as a healthy male sperm and female egg. Disruption at any of these points can contribute to infertility. Advances in surgical technique have enabled surgeons to treat more challenging cases of infertility with less risk than in the past. An infertility workup begins with a good history and physical exam. Blood and semen samples, as well as imaging studies, often provide additional information. When no obvious diagnosis is elucidated from this initial work-up, videolaparoscopy may be considered for direct view of the abdomen and pelvis using a small telescope-like camera through small abdominal incisions. Treatment of any structural causes of infertility may be performed using specialized instruments that require small incisions and minimal recovery time. As a result of videolaparoscopy, there are more opportunities and less invasive approaches for physicians to intervene on behalf of patients facing infertility (Nezhat et al., 2013).