Clathrin light chains negatively regulate plant immunity by hijacking the autophagy pathway.

The crosstalk between clathrin-mediated endocytosis (CME) and the autophagy pathway has been reported in mammals; however, the interconnection of CME with autophagy has not been established in plants. Here, we report that the Arabidopsis CLATHRIN LIGHT CHAIN (CLC) subunit 2 and 3 double mutant, clc2-1 clc3-1, phenocopies Arabidopsis AUTOPHAGY-RELATED GENE (ATG) mutants in both autoimmunity and nutrient sensitivity. Accordingly, the autophagy pathway is significantly compromised in the clc2-1 clc3-1 mutant. Interestingly, multiple assays demonstrate that CLC2 directly interacts with ATG8h/ATG8i in a domain-specific manner. As expected, both GFP-ATG8h/GFP-ATG8i and CLC2-GFP are subjected to autophagic degradation, and degradation of GFP-ATG8h is significantly reduced in the clc2-1 clc3-1 mutant. Notably, simultaneous knockout of ATG8h and ATG8i by CRISPR-Cas9 results in enhanced resistance against Golovinomyces cichoracearum, supporting the functional relevance of the CLC2-ATG8h/8i interactions. In conclusion, our results reveal a link between the function of CLCs and the autophagy pathway in Arabidopsis.

Conserved transcription factors NRZ1 and NRM1 regulate NLR receptor-mediated immunity.

Plant innate immunity mediated by the nucleotide-binding leucine-rich repeat (NLR) class of immune receptors plays an important role in defense against various pathogens. Although key biochemical events involving NLR activation and signaling have been recently uncovered, we know very little about the transcriptional regulation of NLRs and their downstream signaling components. Here, we show that the Toll-Interleukin 1 receptor homology domain containing NLR (TNL) gene N (Necrosis), which confers resistance to Tobacco mosaic virus, is transcriptionally induced upon immune activation. We identified two conserved transcription factors, N required C3H zinc finger 1 (NRZ1) and N required MYB-like transcription factor 1 (NRM1), that activate N in an immune responsive manner. Genetic analyses indicated that NRZ1 and NRM1 positively regulate coiled-coil domain-containing NLR- and TNL-mediated immunity and function independently of the signaling component Enhanced Disease Susceptibility 1. Furthermore, NRZ1 functions upstream of NRM1 in cell death signaling, and their gene overexpression induces ectopic cell death and expression of NLR signaling components. Our findings uncovered a conserved transcriptional regulatory network that is central to NLR-mediated cell death and immune signaling in plants.

High-quality assembled and annotated genomes of Nicotiana tabacum and Nicotiana benthamiana reveal chromosome evolution and changes in defense arsenals.

Nicotiana tabacum and Nicotiana benthamiana are widely used models in plant biology research. However, genomic studies of these species have lagged. Here we report the chromosome-level reference genome assemblies for N. benthamiana and N. tabacum with an estimated 99.5% and 99.8% completeness, respectively. Sensitive transcription start and termination site sequencing methods were developed and used for accurate gene annotation in N. tabacum. Comparative analyses revealed evidence for the parental origins and chromosome structural changes, leading to hybrid genome formation of each species. Interestingly, the antiviral silencing genes RDR1, RDR6, DCL2, DCL3, and AGO2 were lost from one or both subgenomes in N. benthamiana, while both homeologs were kept in N. tabacum. Furthermore, the N. benthamiana genome encodes fewer immune receptors and signaling components than that of N. tabacum. These findings uncover possible reasons underlying the hypersusceptible nature of N. benthamiana. We developed the user-friendly Nicomics (http://lifenglab.hzau.edu.cn/Nicomics/) web server to facilitate better use of Nicotiana genomic resources as well as gene structure and expression analyses.

Immunomodulatory drugs have divergent effects on humoral and cellular immune responses to SARS-CoV-2 vaccination in people living with rheumatoid arthritis.

Understanding the efficacy of SARS-CoV-2 vaccination in people on immunosuppressive drugs, including those with rheumatoid arthritis (RA), is critical for their protection. Vaccine induced protection requires antibodies, CD4+ T cells, and CD8+ T cells, but it is unclear if these are equally affected by immunomodulatory drugs. Here, we determined how humoral and cellular SARS-CoV-2 vaccination responses differed between people with RA and controls, and which drug classes impacted these responses. Blood was collected from participants with RA on immunomodulatory drugs and controls after their second, third, and fourth SARS-CoV-2 vaccinations. Receptor binding domain (RBD)-specific antibodies were quantified by ELISA. Spike-specific memory T cells were quantitated using flow cytometry. Linear mixed models assessed the impact of age, sex, and immunomodulatory drug classes on SARS-CoV-2 vaccination responses. Compared to non-RA controls (n = 35), participants with RA on immunomodulatory drugs (n = 62) had lower anti-RBD IgG and spike-specific CD4+ T cell levels, but no deficits in spike-specific CD8+ T cells, following SARS-CoV-2 vaccination. Use of costimulation inhibitors was associated with lower humoral responses. JAK inhibitors were associated with fewer spike-specific CD4+ T cells. Participants with RA on immunomodulatory drugs mounted weaker responses to SARS-CoV-2 vaccination, with different drug classes impacting the cellular and humoral compartments.

Effects of Mindful Self-Compassion Program on Psychological Well-being and Levels of Compassion in People Affected by Breast Cancer.

Context: Preliminary studies have suggested that Mindful Self-Compassion (MSC) programs can reduce psychological problems, such as anxiety and depression, but they have rarely been investigated in people with cancer. Objective: The study intended to investigate the effects of a standard MSC program on psychological well-being and levels of compassion in people with breast cancer. Design: The study was an internal service evaluation that used a pre-post, quasi-experimental design. Setting: The study took place at Breast Cancer Haven, a national cancer-support charity, in London, UK. Participants: Of the 63 people who attended the courses, 38 completed the questionnaires both at baseline and postintervention (60%). Of the 49 participants who provided demographic details, 43 were living with breast cancer; one had bowel cancer; and five didn't have cancer. Of those 49 participants, 44 were females and 5 were males; 43% were aged 29-50 years and 57% were aged 51-69 years; and 73% were of European American/White ethnicity. Intervention: Participants took part in a standard MSC program exploring mindfulness and self-compassion for eight weeks, three hours each week, plus a four-hour retreat. Outcome Measures: At baseline and postintervention, participants completed four questionnaires measuring: (1) self-compassion-the Self-Compassion Scale - Short Form (SCS-SF), (2) satisfaction with life-the Satisfaction with Life Scale (SWLS), (3) stress and depression-Depression, Anxiety, and Stress Scale (DASS), and (4) mindfulness-Cognitive and Affective Mindfulness Scale-Revised (CAMS-R). They also completed a short feedback form about their course experiences. Results: The study found statistically significant increases in self-compassion (n = 37), with P < .001; satisfaction with life (n = 36), with P < .001; and mindfulness (n = 35), with P < .001, between baseline and postintervention as well as significant decreases in stress (n = 38), with P < .001, and depression (n = 36), with P < .001 (Wilcoxon signed rank test). Participants stated that while they had found the course to be challenging, they also had found new ways to be aware of and respond to their needs for kindness and self-compassion. They felt the course had changed their lives for the future. Conclusions: The findings support the beneficial effects of a standard MSC course on the psychological well-being of people with breast cancer. Further larger, more rigorous mixed-method studies are required to corroborate these preliminary findings.

Antiretroviral Regimen and Pregnancy Outcomes of Women Living with HIV in a US Cohort.

Women who are pregnant and living with HIV have traditionally been excluded from clinical trials regarding new pharmacotherapy. Immediate initiation of antiretroviral therapy (ART) is recommended for women who are pregnant and living with HIV. Integrase inhibitors (INSTIs) are first-line recommended agents as they lead to more rapid HIV viral load reduction. We conducted a retrospective study of women who are pregnant and living with HIV who received prenatal care at the University of Washington. Mothers were categorized by ART class: INSTI, protease inhibitors (PI), and non-nucleoside reverse transcriptase inhibitors (NNRTI). Chi-square and t-tests were used for the analysis of baseline characteristics, and generalized estimating equations were used to adjust for HIV viral suppression between groups. There were a total of 234 mother-infant pairs whose pregnancies progressed beyond 20 weeks. The study demonstrated that women on INSTI regimens were more likely to have a shorter time to viral load suppression than women on NNRTI regimens. Additionally, seven congenital anomalies were identified in this cohort, none of which were neural tube defects. There was no perinatal transmission of HIV to any of the infants. This small cohort of women provides high-quality data regarding the safety and efficacy of INSTI use for both mothers and infants in resource-rich settings.

LncRNA gets into the balancing act.

The plant hormone salicylic acid plays an important role in balancing plant immunity and growth. In this issue of Cell Host & Microbe, Liu et al. (2022) discovered that a long non-coding RNA, lncSABC1, promotes growth in uninfected plants and unleashes defenses when pathogens attack by transcriptionally regulating salicylic acid biosynthesis.

Polycistronic Artificial microRNA-Mediated Resistance to Cucumber Green Mottle Mosaic Virus in Cucumber.

Cucumber green mottle mosaic virus (CGMMV), as a typical seed-borne virus, causes costly and devastating diseases in the vegetable trade worldwide. Genetic sources for resistance to CGMMV in cucurbits are limited, and environmentally safe approaches for curbing the accumulation and spread of seed-transmitted viruses and cultivating completely resistant plants are needed. Here, we describe the design and application of RNA interference-based technologies, containing artificial microRNA (amiRNA) and synthetic trans-acting small interfering RNA (syn-tasiRNA), against conserved regions of different strains of the CGMMV genome. We used a rapid transient sensor system to identify effective anti-CGMMV amiRNAs. A virus seed transmission assay was developed, showing that the externally added polycistronic amiRNA and syn-tasiRNA can successfully block the accumulation of CGMMV in cucumber, but different virulent strains exhibited distinct influences on the expression of amiRNA due to the activity of the RNA-silencing suppressor. We also established stable transgenic cucumber plants expressing polycistronic amiRNA, which conferred disease resistance against CGMMV, and no sequence mutation was observed in CGMMV. This study demonstrates that RNA interference-based technologies can effectively prevent the occurrence and accumulation of CGMMV. The results provide a basis to establish and fine-tune approaches to prevent and treat seed-based transmission viral infections.

Fecal microbiome differs between patients with systemic sclerosis with and without small intestinal bacterial overgrowth.

Introduction: Gastrointestinal manifestations of systemic sclerosis affect up to 90% of patients, with symptoms including diarrhea and constipation. Small intestinal bacterial overgrowth is a condition associated with increased numbers of pathogenic bacteria in the small bowel. While currently unknown, it has been suggested that dysregulation of the fecal microbiota may play a role in the development of systemic sclerosis and small intestinal bacterial overgrowth. Objectives: Our study aimed to describe the fecal microbiota of patients with systemic sclerosis and compare it between those with and without a diagnosis of small intestinal bacterial overgrowth. We also compared the fecal microbiota of systemic sclerosis patients with that of healthy controls to understand the association between particular bacterial taxa and clinical gastrointestinal manifestations of systemic sclerosis. Methods: A total of 29 patients with systemic sclerosis underwent breath testing to assess for small intestinal bacterial overgrowth, provided stool samples to determine taxonomic assignments, and completed the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0, which details symptoms and quality-of-life factors. Stool samples were compared between systemic sclerosis patients with and without small intestinal bacterial overgrowth, and between patients with systemic sclerosis and a healthy control cohort (n = 20), aged 18-80 years. Results: Fecal microbiome analyses demonstrated differences between systemic sclerosis patients with and without small intestinal bacterial overgrowth and differences in the diversity of species between healthy controls and patients with systemic sclerosis. Trends were also observed in anticentromere antibody systemic sclerosis patients, including higher Alistipies indistincus spp. levels associated with increased methane levels of breath gas testing and higher Slakia spp. levels associated with increased rates of fecal soiling. Conclusions: Our results suggest that changes to the fecal microbiome occur in patients with small intestinal bacterial overgrowth and systemic sclerosis when compared to healthy controls. As a cross-sectional study, the potential pathophysiologic role of an altered microbiome in the development of systemic sclerosis was not considered and hence needs to be further investigated.

Mode and Intensity of Physical Activity During the Postacute Phase of Sport-Related Concussion: A Systematic Review.

INTRODUCTION: Sports-related concussions (SRCs) have received attention due to their prevalence in youth. An SRC results from a strong force causing neurological impairment. Recent research has recommended rehabilitation within the first week post-SRC after 24 to 48 hours of rest. The postacute phase is defined as 48 hours to 7 days post-SRC. It is imperative to evaluate the most effective mode and intensity of physical activity to reduce symptoms and improve outcomes. METHODS: CINAHL, PubMed, SPORTDiscus, and Web of Science databases were used to search the terms "brain concussion" AND "exercise" and variations of these terms. The evidence level for each study was evaluated using the 2011 Oxford Center for Evidence-Based Medicine Guide. The methodological rigor of each study was evaluated using a scale adapted from Medlicott and Harris. RESULTS: Two thousand sixty-eight records were identified. Six studies were included in this systematic review. Three studies were classified as moderately strong. The remaining 3 studies were considered weak. Five of the studies used either a cycle ergometer or a treadmill. The sixth study used walking, cycling, and swimming, as well as sports drills. All of these modes of exercise were determined to be safe. All studies utilized low- and moderate-intensity interventions, which were found to be nondetrimental and showed improved recovery time and symptom resolution. Five of the studies also incorporated components of high-intensity exercise that was also found to be nondetrimental, and they showed a positive influence on recovery time and symptom resolution. However, all activity in each of the reviewed studies started at a low level and progressed up to a higher level only as each individual client's symptoms permitted. DISCUSSION: Overall, this review found that various modes of activity at light-, moderate-, and high-intensity levels are efficacious and can be safely used during the postacute phase of SRC. CONCLUSION: Though the volume of literature at this time is limited, therapists should consider prescribing closely monitored individualized exercise programs utilizing progressive intensities when treating patients during the postacute phase of SRC.

Artificial microRNA-mediated resistance to cucumber green mottle mosaic virus in Nicotiana benthamiana.

MAIN CONCLUSION: We describe a Nicotiana benthamiana system for rapid identification of artificial microRNA (amiRNA) to control cucumber green mottle mosaic virus (CGMMV) disease. Although artificial miRNA technology has been used to control other viral diseases, it has not been applied to reduce severe cucumber green mottle mosaic virus (CGMMV) disease and crop loss in the economically important cucurbits. We used our system to identify three amiRNAs targeting CGMMV RNA (amiR1-CP, amiR4-MP and amiR6-Rep) and show that their expression reduces CGMMV replication and disease in virus-infected plants. This work streamlines the process of generating amiRNA virus-resistant crops and can be broadly applied to identify active antiviral amiRNAs against a broad spectrum of viruses to control disease in diverse crops.

Development of the iCook 4-H Curriculum for Youth and Adults: Cooking, Eating, and Playing Together for Childhood Obesity Prevention.

The objective was to describe the development process of a curriculum (iCook 4-H) targeted to low-income, rural, and/or diverse youths and their adult primary meal preparer to promote cooking, eating, and playing together. Lessons learned highlighted the importance of grounding the curriculum in Social Cognitive Theory and applying the experiential 4-H learning model using a multiphased, community-based participatory approach with cyclical development and evaluation, and key modifications made for dissemination and distribution. Findings across 4 testing phases over 6 years and 5 states demonstrated the time-intensive, cyclical process that required flexibility with fidelity to form a hands-on, interactive curriculum.

Evaluation of a charity-led secondary breast cancer support day: a model of survivorship care.

It has been estimated that there are 36,000 women living with secondary breast cancer in the UK. Many feel isolated and unsupported, their information needs unmet and unaware of available support services such as palliative care or support groups that could help to improve their quality of life. To try to address these needs, a monthly support day was established in 2014 by the national UK breast cancer charity Breast Cancer Haven (BCH) at their Yorkshire centre. The support day provides an opportunity for personal introductions and discussion with other people with secondary breast cancer, to obtain information about breast cancer-related topics of their choice, to eat a healthy lunch and to experience a visualisation/relaxation session. To evaluate how helpful this support day was to its participants, they were asked to complete a feedback form at the end of the day. A total of 171 forms were completed from 26 support days during the period February 2014-July 2018. Participants stated that they found the support day helpful, relaxing, informative, supportive and enjoyable. All except two felt it met their needs and expectations and the majority found the length of the day just right. The personal introduction and discussion session were most frequently cited as the most useful part of the day, with the majority of participants (N = 144, 96.7%) rating it as very or moderately helpful. These findings show that the BCH support day, developed to address the needs of people with secondary breast cancer, is a model of survivorship care that can have a positive impact on their lives.

Ripple Effect Mapping Outcomes of a Childhood Obesity Prevention Program From Youth and Adult Dyads Using a Qualitative Approach: iCook 4-H.

OBJECTIVE: To describe the impact of the iCook 4-H intervention study based on data gathered through ripple effect mapping focus groups through an explorative approach. DESIGN: Youth-adult dyads responded about ways in which iCook had affected the individual, family, and community. Three questions were asked: (1) What were people doing differently as a result of iCook? (2) Who benefited from iCook and how? (3) Were there changes in the way community groups and institutions did things as a result of iCook? SETTING: Ripple effect mapping sessions took place across 5 states (Maine, Nebraska, South Dakota, Tennessee, and West Virginia). PARTICIPANTS: Seventy dyad participants (n = 35 youth, n = 35 adults) from the iCook 4-H intervention. MAIN OUTCOME MEASURE: Three core themes of iCook 4-H were assessed: cooking, eating, and playing together. ANALYSIS: Direct content analysis and word frequencies were used. RESULTS: Seven categories emerged: improved health, increased community involvement, increased knowledge, increased communication, changed motivation, financial mindfulness, and increased appreciation for family. An overarching theme that was determined was that learning new skills together through trying new things (cooking, eating, and playing) leads to positive individual family and community change. CONCLUSIONS AND IMPLICATIONS: Ripple effect mapping was effective in determining the perceived impact of iCook 4-H on oneself, family, and community.

A Two-Headed Monster to Avert Disaster: HBS1/SKI7 Is Alternatively Spliced to Build Eukaryotic RNA Surveillance Complexes.

The cytosolic RNA exosome, a 3'→5' exoribonuclease complex, contributes to mRNA degradation in eukaryotes, limiting the accumulation of poorly-translated, improperly translated, or aberrant mRNA species. Disruption of cytosolic RNA exosome activity allows aberrant RNA species to accumulate, which can then be detected by host antiviral immune systems as a signature of pathogen infection, activating antiviral defenses. SKI7 is a critical component of the cytosolic RNA exosome in yeast, bridging the catalytic exoribonuclease core with the SKI2/SKI3/SKI8 adaptor complex that guides aberrant RNA substrates into the exosome. The ortholog of SKI7 was only recently identified in humans as an alternative splice form of the HBS1 gene, which encodes a decoding factor translational GTPase that rescues stalled ribosomes. Here, we identify the plant orthologs of HBS1/SKI7. We found that HBS1 and SKI7 are typically encoded by alternative splice forms of a single locus, although some plant lineages have evolved subfunctionalized genes that apparently encode only HBS1 or only SKI7. In all plant lineages examined, the SKI7 gene is subject to regulation by alternative splicing that can yield unproductive transcripts, either by removing deeply conserved SKI7 coding sequences, or by introducing premature stop codons that render SKI7 susceptible to nonsense-mediated decay. Taking a comparative, evolutionary approach, we define crucial features of the SKI7 protein shared by all eukaryotes, and use these deeply conserved features to identify SKI7 proteins in invertebrate lineages. We conclude that SKI7 is a conserved cytosolic RNA exosome subunit across eukaryotic lineages, and that SKI7 is consistently regulated by alternative splicing, suggesting broad coordination of nuclear and cytosolic RNA metabolism.

A role for small RNA in regulating innate immunity during plant growth.

Plant genomes encode large numbers of nucleotide-binding (NB) leucine-rich repeat (LRR) immune receptors (NLR) that mediate effector triggered immunity (ETI) and play key roles in protecting crops from diseases caused by devastating pathogens. Fitness costs are associated with plant NLR genes and regulation of NLR genes by micro(mi)RNAs and phased small interfering RNAs (phasiRNA) is proposed as a mechanism for reducing these fitness costs. However, whether NLR expression and NLR-mediated immunity are regulated during plant growth is unclear. We conducted genome-wide transcriptome analysis and showed that NLR expression gradually increased while expression of their regulatory small RNAs (sRNA) gradually decreased as plants matured, indicating that sRNAs could play a role in regulating NLR expression during plant growth. We further tested the role of miRNA in the growth regulation of NLRs using the tobacco mosaic virus (TMV) resistance gene N, which was targeted by miR6019 and miR6020. We showed that N-mediated resistance to TMV effectively restricted this virus to the infected leaves of 6-week old plants, whereas TMV infection was lethal in 1- and 3-week old seedlings due to virus-induced systemic necrosis. We further found that N transcript levels gradually increased while miR6019 levels gradually decreased during seedling maturation that occurs in the weeks after germination. Analyses of reporter genes in transgenic plants showed that growth regulation of N expression was post-transcriptionally mediated by MIR6019/6020 whereas MIR6019/6020 was regulated at the transcriptional level during plant growth. TMV infection of MIR6019/6020 transgenic plants indicated a key role for miR6019-triggered phasiRNA production for regulation of N-mediated immunity. Together our results demonstrate a mechanistic role for miRNAs in regulating innate immunity during plant growth.

An Impact Mapping Method to Generate Robust Qualitative Evaluation of Community-Based Research Programs for Youth and Adults.

Ripple Effect Mapping (REM) is an evaluation approach that has traditionally been used in community settings to visually map the impact of programming and community interventions. This manuscript utilizes the Community Capitals Framework (CCF) to inform REM and to better highlight the changes and impact between various levels of a community, following a childhood obesity prevention intervention. The addition of in-depth qualitative analyses makes this approach particularly useful for the evaluation of interventions with a research-community partnership focus. The objective of this study was to describe a CCF-informed REM approach with detailed protocol, training, and application to the community-based, childhood obesity prevention intervention, iCook 4-H, which targeted youth and adult pairs. This protocol includes the steps required to prepare for REM sessions of, ideally, six youth and adult pairs, one facilitator, and one or two evaluators/note takers. REM sessions typically begin with an icebreaker and appreciative inquiry activities that inform the REM mapping process that follows. In-depth qualitative analysis of the notes and map images captured during REM sessions ensure the rigor required for research-related interventions. Researchers, community members, and participants can use CCF-informed REM collectively as a robust evaluation tool to demonstrate, through visual mapping, the positive effects of community-partnered research programs.

A home-based body weight supported treadmill training program for children with cerebral palsy: A case series.

BACKGROUND AND PURPOSE: Contemporary approaches to the treatment of cerebral palsy (CP) advocate a task-specific approach that emphasizes repetition and practice of specific tasks. Recent studies suggest that body-weight-supported treadmill training (BWSTT) programs may be beneficial in clinical settings. The purposes of this case series were to explore the outcomes and feasibility of a home-based BWSTT program for three children with CP. CASE DESCRIPTION: Three children with CP at Gross Motor Function Classification System (GMFCS) Levels III or IV participated in this case series. Examination included the Functional Assessment Questionnaire (FAQ), the 10-meter walk test, the Gross Motor Function Measure (GMFM-66), and the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT). A harness system was used to conduct the BWSTT program over an 8-12 week period. OUTCOMES: All of the families reported enjoying the BWSTT program and found the harness easy to use. Participant 2 increased from a 2 to a 4 on the FAQ, while Participant 3 increased from a 6 to a 7. DISCUSSION: Two of the participants demonstrated post-intervention improvements in functional mobility. In addition to mobility outcomes, future research should explore the potential health benefits of a home-based BWSTT program.

Identification of I-7 expands the repertoire of genes for resistance to Fusarium wilt in tomato to three resistance gene classes.

The tomato I-3 and I-7 genes confer resistance to Fusarium oxysporum f. sp. lycopersici (Fol) race 3 and were introgressed into the cultivated tomato, Solanum lycopersicum, from the wild relative Solanum pennellii. I-3 has been identified previously on chromosome 7 and encodes an S-receptor-like kinase, but little is known about I-7. Molecular markers have been developed for the marker-assisted breeding of I-3, but none are available for I-7. We used an RNA-seq and single nucleotide polymorphism (SNP) analysis approach to map I-7 to a small introgression of S. pennellii DNA (c. 210 kb) on chromosome 8, and identified I-7 as a gene encoding a leucine-rich repeat receptor-like protein (LRR-RLP), thereby expanding the repertoire of resistance protein classes conferring resistance to Fol. Using an eds1 mutant of tomato, we showed that I-7, like many other LRR-RLPs conferring pathogen resistance in tomato, is EDS1 (Enhanced Disease Susceptibility 1) dependent. Using transgenic tomato plants carrying only the I-7 gene for Fol resistance, we found that I-7 also confers resistance to Fol races 1 and 2. Given that Fol race 1 carries Avr1, resistance to Fol race 1 indicates that I-7-mediated resistance, unlike I-2- or I-3-mediated resistance, is not suppressed by Avr1. This suggests that Avr1 is not a general suppressor of Fol resistance in tomato, leading us to hypothesize that Avr1 may be acting against an EDS1-independent pathway for resistance activation. The identification of I-7 has allowed us to develop molecular markers for marker-assisted breeding of both genes currently known to confer Fol race 3 resistance (I-3 and I-7). Given that I-7-mediated resistance is not suppressed by Avr1, I-7 may be a useful addition to I-3 in the tomato breeder's toolbox.