Publications by authors named "Ian Kaplan"

59 Publications

Supplemental forage ameliorates the negative impact of insecticides on bumblebees in a pollinator-dependent crop.

Proc Biol Sci 2021 Jun 30;288(1953):20210785. Epub 2021 Jun 30.

Department of Entomology, Purdue University, 901 West State Street, West Lafayette, IN, USA.

Insecticide use and insufficient forage are two of the leading stressors to pollinators in agroecosystems. While these factors have been well studied individually, the experimental designs do not reflect real-world conditions where insecticide exposure and lack of forage occur simultaneously and could interactively suppress pollinator health. Using outdoor enclosures, we tested the effects of insecticides (imidacloprid + lambda-cyhalothrin) and non-crop forage (clover) in a factorial design, measuring the survival, behaviour and performance of bumblebees (), as well as pollination of the focal crop, watermelon. Colony survival was synergistically reduced to 17% in watermelon alone + insecticides (survival was 100% in all other treatments). However, behavioural shifts in foraging were mainly owing to insecticides (e.g. 95% reduced visitation rate to watermelon flowers), while impacts on hive performance were primarily driven by clover presence (e.g. 374% increase in the number of live eggs). Insecticide-mediated reductions in foraging decreased crop pollination (fruit set) by 32%. Altogether, these data indicate that both insecticides and non-crop forage play integral roles in shaping pollinator health in agricultural landscapes, but the relative importance and interaction of these two factors depend on which aspect of 'health' is being considered.
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http://dx.doi.org/10.1098/rspb.2021.0785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242826PMC
June 2021

Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans.

Nature 2021 Jun 9. Epub 2021 Jun 9.

Janssen Vaccines & Prevention, Leiden, The Netherlands.

The Ad26.COV2.S vaccine has demonstrated clinical efficacy against symptomatic COVID-19, including against the B.1.351 variant that is partially resistant to neutralizing antibodies. However, the immunogenicity of this vaccine in humans against SARS-CoV-2 variants of concern remains unclear. Here we report humoral and cellular immune responses from 20 Ad26.COV2.S vaccinated individuals from the COV1001 phase I-IIa clinical trial against the original SARS-CoV-2 strain WA1/2020 as well as against the B.1.1.7, CAL.20C, P.1 and B.1.351 variants of concern. Ad26.COV2.S induced median pseudovirus neutralizing antibody titres that were 5.0-fold and 3.3-fold lower against the B.1.351 and P.1 variants, respectively, as compared with WA1/2020 on day 71 after vaccination. Median binding antibody titres were 2.9-fold and 2.7-fold lower against the B.1.351 and P.1 variants, respectively, as compared with WA1/2020. Antibody-dependent cellular phagocytosis, complement deposition and natural killer cell activation responses were largely preserved against the B.1.351 variant. CD8 and CD4 T cell responses, including central and effector memory responses, were comparable among the WA1/2020, B.1.1.7, B.1.351, P.1 and CAL.20C variants. These data show that neutralizing antibody responses induced by Ad26.COV2.S were reduced against the B.1.351 and P.1 variants, but functional non-neutralizing antibody responses and T cell responses were largely preserved against SARS-CoV-2 variants. These findings have implications for vaccine protection against SARS-CoV-2 variants of concern.
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http://dx.doi.org/10.1038/s41586-021-03681-2DOI Listing
June 2021

Distinct Biomarker Profiles and TCR Sequence Diversity Characterize the Response to PD-L1 Blockade in a Mouse Melanoma Model.

Mol Cancer Res 2021 Apr 22. Epub 2021 Apr 22.

Center for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland.

Only a subset of patients responds to immune checkpoint blockade (ICB) in melanoma. A preclinical model recapitulating the clinical activity of ICB would provide a valuable platform for mechanistic studies. We used melanoma tumors arising from an Hgf;Cdk4 genetically engineered mouse (GEM) model to evaluate the efficacy of an anti-mouse PD-L1 antibody similar to the anti-human PD-L1 antibodies durvalumab and atezolizumab. Consistent with clinical observations for ICB in melanoma, anti-PD-L1 treatment elicited complete and durable response in a subset of melanoma-bearing mice. We also observed tumor growth delay or regression followed by recurrence. For early treatment assessment, we analyzed gene expression profiles, T-cell infiltration, and T-cell receptor (TCR) signatures in regressing tumors compared with tumors exhibiting no response to anti-PD-L1 treatment. We found that CD8 T-cell tumor infiltration corresponded to response to treatment, and that anti-PD-L1 gene signature response indicated an increase in antigen processing and presentation, cytokine-cytokine receptor interaction, and natural killer cell-mediated cytotoxicity. TCR sequence data suggest that an anti-PD-L1-mediated melanoma regression response requires not only an expansion of the TCR repertoire that is unique to individual mice, but also tumor access to the appropriate TCRs. Thus, this melanoma model recapitulated the variable response to ICB observed in patients and exhibited biomarkers that differentiate between early response and resistance to treatment, providing a valuable platform for prediction of successful immunotherapy. IMPLICATIONS: Our melanoma model recapitulates the variable response to anti-PD-L1 observed in patients and exhibits biomarkers that characterize early antibody response, including expansion of the TCR repertoire.
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http://dx.doi.org/10.1158/1541-7786.MCR-20-0881DOI Listing
April 2021

T-cell receptor sequencing identifies prior SARS-CoV-2 infection and correlates with neutralizing antibody titers and disease severity.

medRxiv 2021 Mar 22. Epub 2021 Mar 22.

Measuring the adaptive immune response to SARS-CoV-2 can enable the assessment of past infection as well as protective immunity and the risk of reinfection. While neutralizing antibody (nAb) titers are one measure of protection, such assays are challenging to perform at a large scale and the longevity of the SARS-CoV-2 nAb response is not fully understood. Here, we apply a T-cell receptor (TCR) sequencing assay that can be performed on a small volume standard blood sample to assess the adaptive T-cell response to SARS-CoV-2 infection. Samples were collected from a cohort of 302 individuals recovered from COVID-19 up to 6 months after infection. Previously published findings in this cohort showed that two commercially available SARS-CoV-2 serologic assays correlate well with nAb testing. We demonstrate that the magnitude of the SARS-CoV-2-specific T-cell response strongly correlates with nAb titer, as well as clinical indicators of disease severity including hospitalization, fever, or difficulty breathing. While the depth and breadth of the T-cell response declines during convalescence, the T-cell signal remains well above background with high sensitivity up to at least 6 months following initial infection. Compared to serology tests detecting binding antibodies to SARS-CoV-2 spike and nucleoprotein, the overall sensitivity of the TCR-based assay across the entire cohort and all timepoints was approximately 5% greater for identifying prior SARS-CoV-2 infection. Notably, the improved performance of T-cell testing compared to serology was most apparent in recovered individuals who were not hospitalized and were sampled beyond 150 days of their initial illness, suggesting that antibody testing may have reduced sensitivity in individuals who experienced less severe COVID-19 illness and at later timepoints. Finally, T-cell testing was able to identify SARS-CoV-2 infection in 68% (55/81) of convalescent samples having nAb titers below the lower limit of detection, as well as 37% (13/35) of samples testing negative by all three antibody assays. These results demonstrate the utility of a TCR-based assay as a scalable, reliable measure of past SARS-CoV-2 infection across a spectrum of disease severity. Additionally, the TCR repertoire may be useful as a surrogate for protective immunity with additive clinical value beyond serologic or nAb testing methods.
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http://dx.doi.org/10.1101/2021.03.19.21251426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010755PMC
March 2021

Emerging strategies for precision microbiome management in diverse agroecosystems.

Nat Plants 2021 03 8;7(3):256-267. Epub 2021 Mar 8.

Department of Entomology, Purdue University, West Lafayette, IN, USA.

Substantial efforts to characterize the structural and functional diversity of soil, plant and insect-associated microbial communities have illuminated the complex interacting domains of crop-associated microbiomes that contribute to agroecosystem health. As a result, plant-associated microorganisms have emerged as an untapped resource for combating challenges to agricultural sustainability. However, despite growing interest in maximizing microbial functions for crop production, resource efficiency and stress resistance, research has struggled to harness the beneficial properties of agricultural microbiomes to improve crop performance. Here, we introduce the historical arc of agricultural microbiome research, highlighting current progress and emerging strategies for intentional microbiome manipulation to enhance crop performance and sustainability. We synthesize current practices and limitations to managing agricultural microbiomes and identify key knowledge gaps in our understanding of microbe-assisted crop production. Finally, we propose research priorities that embrace a holistic view of crop microbiomes for achieving precision microbiome management that is tailored, predictive and integrative in diverse agricultural systems.
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http://dx.doi.org/10.1038/s41477-020-00830-9DOI Listing
March 2021

Phylogenetic farming: Can evolutionary history predict crop rotation via the soil microbiome?

Evol Appl 2020 Sep 22;13(8):1984-1999. Epub 2020 Apr 22.

Department of Entomology Purdue University West Lafayette IN USA.

Agriculture has long employed phylogenetic rules whereby farmers are encouraged to rotate taxonomically unrelated plants in shared soil. Although this forms a central tenet of sustainable agriculture, strangely, this on-farm "rule of thumb" has never been rigorously tested in a scientific framework. To experimentally evaluate the relationship between phylogenetic distance and crop performance, we used a plant-soil feedback approach whereby 35 crops and weeds varying in their relatedness to tomato () were tested in a two-year field experiment. We used community profiling of the bacteria and fungi to determine the extent to which soil microbes contribute to phenotypic differences in crop growth. Overall, tomato yield was ca. 15% lower in soil previously cultivated with tomato; yet, past the species level there was no effect of phylogenetic distance on crop performance. Soil microbial communities, on the other hand, were compositionally more similar between close plant relatives. Random forest regression predicted log phylogenetic distance to tomato with moderate accuracy (  = .52), primarily driven by bacteria in the genus . These data indicate that, beyond avoiding conspecifics, evolutionary history contributes little to understanding plant-soil feedbacks in agricultural fields; however, microbial legacies can be predicted by species identity and relatedness.
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http://dx.doi.org/10.1111/eva.12956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463318PMC
September 2020

Larval pesticide exposure impacts monarch butterfly performance.

Sci Rep 2020 09 2;10(1):14490. Epub 2020 Sep 2.

Department of Entomology, Purdue University, West Lafayette, IN, 47907, USA.

The long-term decline of monarch butterflies has been attributed to loss of their milkweed (Asclepias sp.) host-plants after the introduction of herbicide-tolerant crops. However, recent studies report pesticide residues on milkweed leaves that could act as a contributing factor when ingested as part of their larval diet. In this study, we exposed monarch larvae to six pesticides (insecticide: clothianidin; herbicides: atrazine, S-metolachlor; fungicides: azoxystrobin, pyraclostrobin, trifloxystrobin) on their primary host-plant, A. syriaca. Each was tested at mean and maximum levels reported from published analyses of milkweeds bordering cropland and thus represent field-relevant concentrations. Monarch lethal and sub-lethal responses were tracked over their complete development, from early instar larvae to adult death. Overall, we found no impact of any pesticide on immature development time and relatively weak effects on larval herbivory or survival to adulthood. Comparatively stronger effects were detected for adult performance; namely, a 12.5% reduction in wing length in response to the fungicides azoxystrobin and trifloxystrobin. These data collectively suggest that monarch responses to host-plant pesticides are largely sublethal and more pronounced in the adult stage, despite exposure only as larvae. This outcome has important implications for risk assessment and the migratory success of monarchs in North America.
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http://dx.doi.org/10.1038/s41598-020-71211-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468139PMC
September 2020

Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection at Both Individual and Population Levels.

medRxiv 2020 Aug 4. Epub 2020 Aug 4.

Immunotherapy, Cell Therapy and Biobank (ITCB), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.

T cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection. Here, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides (class II data in a forthcoming study). Then, at the population level, we performed T-cell repertoire sequencing on 1,015 samples (from 827 COVID-19 subjects) as well as 3,500 controls to identify shared "public" T-cell receptors (TCRs) associated with SARS-CoV-2 infection from both CD8 and CD4 T cells. Collectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection and is detectable for several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection based solely on TCR sequencing from blood samples, and observed, at 99.8% specificity, high early sensitivity soon after diagnosis (Day 3-7 = 83.8% [95% CI = 77.6-89.4]; Day 8-14 = 92.4% [87.6-96.6]) as well as lasting sensitivity after recovery (Day 29+/convalescent = 96.7% [93.0-99.2]). These results demonstrate an approach to reliably assess the adaptive immune response both soon after viral antigenic exposure (before antibodies are typically detectable) as well as at later time points. This blood-based molecular approach to characterizing the cellular immune response has applications in vaccine development as well as clinical diagnostics and monitoring.
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http://dx.doi.org/10.1101/2020.07.31.20165647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418734PMC
August 2020

A large-scale database of T-cell receptor beta (TCRβ) sequences and binding associations from natural and synthetic exposure to SARS-CoV-2.

Res Sq 2020 Aug 4. Epub 2020 Aug 4.

We describe the establishment and current content of the ImmuneCODE™ database, which includes hundreds of millions of T-cell Receptor (TCR) sequences from over 1,400 subjects exposed to or infected with the SARS-CoV-2 virus, as well as over 135,000 high-confidence SARS-CoV-2-specific TCRs. This database is made freely available, and the data contained in it can be downloaded and analyzed online or offline to assist with the global efforts to understand the immune response to the SARS-CoV-2 virus and develop new interventions.
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http://dx.doi.org/10.21203/rs.3.rs-51964/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418738PMC
August 2020

Prevalence of Malignancy Among Urban Black Rheumatoid Arthritis Patients.

Int J Clin Res Trials 2020 25;5(1). Epub 2020 Apr 25.

Department of Internal Medicine, Baptist Memorial Hospital-Tipton, 1995 Highway 51, South Covington, TN 38019, USA.

Background: Rheumatoid arthritis (RA) patients have an increased risk of malignancy with postulated risk factors that include chronic inflammation, smoking and the use of immunosuppressants have been postulated as drivers of higher malignancies rates. Our study aimed to describe the prevalence and type of malignancies encountered in an urban, predominantly Black RA patient population.

Methods: Cross sectional analysis of 1142 patients with RA diagnosis by ICD-codes of which 501 cases met the inclusion criteria for the study. Blacks accounted for 88.4% of the study population. Fifty-six patients had cancer recorded in their medical records and these cases were further reviewed for tumor type, timing of diagnosis and patient clinical characteristics.

Results: The cancer prevalence was 11.2% (56/501) in our Black RA population being studied. Mean age at cancer diagnosis was 59.9 ± 5.2 for the patients who developed cancer before RA diagnosis and 58.25 ± 16.02 for those who developed malignancy after RA diagnosis. There were 18 breast cancers, 4 colon and 4 cervical cancers; for lung, multiple myeloma, thyroid, squamous cell carcinoma and pancreas there were 3 cases each; for endometrial, Non-Hodgkin's lymphoma, meningioma and prostate, 2 cases each and 1 each for urinary bladder, esophageal adenocarcinoma, lymphoma, glioblastoma, liver, Hodgkin's lymphoma, sarcoma, ovary and renal cell carcinoma. No differences were found in years of RA duration, joint erosion, joint space narrowing or SENS score except for significantly higher ESR among the cancer group and RF seropositivity in the non-cancer group.Therapeutic modalities were not significantly different between the cancer and no cancer groups.

Conclusion: Breast cancer was the most prevalent malignancy among our Black RA population. Further studies are needed to identify the contributing factors to the malignancy risk of breast cancer in our Black RA population and whether it is gender-related since RA is more prevalence in women.
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http://dx.doi.org/10.15344/2456-8007/2020/145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357963PMC
April 2020

Obstructive Sleep Apnea Risk and Stroke among Blacks with Metabolic Syndrome: Results from Metabolic Syndrome Outcome (MetSO) Registry.

Int J Clin Res Trials 2020 26;5(1). Epub 2020 Feb 26.

Center for Healthful Behavior Change (CHBC), Department of Population Health, NYU Grossman School of Medicine, New York, NY, USA.

Introduction: The American Stroke Association estimates that stroke is the fifth leading cause of death in the United States. According to the Center for Disease Control and Prevention someone in the United States has a stoke every 40 seconds, affecting more than 795,000 people of which 140,000 result in death [1]. Emerging evidence suggests that obstructive sleep apnea (OSA) is a strong risk factor for stroke. This study using The Metabolic Syndrome Outcome (MetSO) registry explored whether blacks at risk for obstructive sleep apnea (OSA) are at greater risk for a stroke.

Method: The present study utilized data from the MetSO study, an NIH-funded cohort study of blacks with metabolic syndrome (MetS). Patients were diagnosed with MetS using standard criteria articulated in the joint interim statement for harmonizing the MetS. The study assessed OSA risk using the Apnea Risk Evaluation System (ARES); defining high risk as a total ARES score ≥6. Data was coded and analyzed by an experienced statistician using SPSS 20.0.

Results: A total of 1035 participants were screened for MetS in the MetSO registry. During the data collection period 875 participants were enrolled during the time of analysis. The average age of the sample was 62±14 years (range: 20-97); 71% were female, and all were of black race/ethnicity. Seventy-one percent reported finishing high school, and 43% reported annual income <10K. Descriptive analyses showed 93% of the participants were diagnosed with hypertension; 61%, diabetes; 72%, dyslipidemia; 90% were overweight/obese; 33% had a history of heart disease and 10% had a stroke history. Using the ARES screener, we estimated that 48% were at high risk for OSA. Logistic regression analysis, adjusting for age and gender, showed that patients at high risk for OSA had a nearly three-fold increase in the odds of having a stroke (OR = 2.79, 95% CI: 1.64-4.73).

Conclusion: In the MetSO registry, a cohort of blacks with MetS, the prevalence of stroke is greater than in the general US population. Blacks at risk for OSA are particularly vulnerable to experiencing a stroke.
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http://dx.doi.org/10.15344/2456-8007/2020/143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316191PMC
February 2020

"The midwife helped me ... otherwise I could have died": women's experience of professional midwifery services in rural Afghanistan - a qualitative study in the provinces Kunar and Laghman.

BMC Pregnancy Childbirth 2020 Mar 6;20(1):140. Epub 2020 Mar 6.

Western Norway University of Applied Sciences, Bergen, Norway.

Background: Afghanistan has one of the world's highest maternal mortality ratios, with more than 60% of women having no access to a skilled birth attendant in some areas. The main challenges for childbearing Afghan women are access to skilled birth attendance, emergency obstetric care and reliable contraception. The NGO-based project Advancing Maternal and Newborn Health in Afghanistan has supported education of midwives since 2002, in accordance with the national plan for midwifery education. The aim of this study is to explore women's experiences of professional midwifery care in four villages in Afghanistan covered by the project, so as to reveal challenges and improve services in rural and conflict-affected areas of the country.

Methods: An exploratory case-study approach was adopted. Fourteen in-depth interviews and four focus-group discussions were conducted. A total of 39 women participated - 25 who had given birth during the last six months, 11 mothers-in-law and three community midwives in the provinces of Kunar and Laghman. Data generated by the interviews and observations was analysed using thematic content analysis.

Findings: Many of the women greatly valued the trained midwives' life-saving experience, skills and care, and the latter were important reasons for choosing to give birth in a clinic. Women further appreciated midwives' promotion of immediate skin-to-skin contact and breastfeeding. However, some women experienced rudeness, discrimination and negligence on the part of the midwives. Moreover, relatives' disapproval, shame and problems with transport and security were important obstacles to women giving birth in the clinics.

Conclusions: Local recruitment and professional education of midwives as promoted by Afghan authorities and applied in the project seem successful in promoting utilisation and satisfaction with maternal and neonatal health services in rural Afghanistan. Nevertheless, the quality of the services is still lacking, with some women complaining of disrespectful care. There seems to be a need to focus more on communication issues during the education of midwives. An increased focus on in-service training and factors promoting quality care and respectful communication is necessary and should be prioritised.
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http://dx.doi.org/10.1186/s12884-020-2818-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059669PMC
March 2020

Treatment of obstructive sleep apnea with CPAP improves chronic inflammation measured by neutrophil-to-lymphocyte ratio.

J Clin Sleep Med 2020 02 13;16(2):251-257. Epub 2020 Jan 13.

Division of Pulmonary and Critical Care Medicine, State University of New York Downstate Medical Center, Brooklyn, New York.

Study Objectives: Obstructive sleep apnea (OSA) is associated with chronic inflammation likely triggered by nocturnal, intermittent hypoxemia and increased adrenergic tone. The neutrophil-to-lymphocyte ratio (NLR) was recently described as a measure of subclinical systemic inflammation. Studies on the effect of continuous positive airway pressure (CPAP) therapy in OSA on subclinical inflammation measured by NLR are lacking. We hypothesize that NLR levels would improve as chronic inflammation diminishes in patients with OSA treated with CPAP.

Methods: We retrospectively reviewed patients in whom OSA was diagnosed and who were treated with CPAP therapy. Complete blood count (CBC) were obtained pretreatment and posttreatment for calculation of NLR, which was calculated by dividing the number of neutrophils by the number of lymphocytes. Patients with conditions known to affect NLR such as chronic infections, inflammatory diseases, active cardiovascular disease, and malignancies were excluded from the study. CPAP adherence downloads were obtained for all patients.

Results: Out of 184 patients in whom OSA was diagnosed and who were treated with CPAP, 109 met our study criteria, including baseline polysomnogram, baseline and posttreatment CBC, and available adherence download. We compared the NLR before and after treatment with CPAP. There was a significant difference in NLR before and after treatment with CPAP (P < .0001). There was also a significant difference in apnea-hypopnea index before and after treatment (P < .0001). We also assessed the relationship between CPAP adherence (percentage of days used for > 4 hours) and the change in NLR. NLR decreased significantly in both the adherent (CPAP use ≥ 70% of days; P = .014) and nonadherent groups (CPAP use < 70% of days; P = .0003). Finally, we noticed a significant direct correlation between CPAP adherence beyond 70% and the change in NLR (ΔNLR) (P = .046) in patients who had ≥ 70% adherence with CPAP, which was not observed in patients with < 70% adherence.

Conclusions: The NLR may be a useful marker for monitoring improvement, as CPAP had a desirable effect on the chronic inflammation induced by OSA when measured by NLR in this study. Our results specifically suggest that the NLR values decrease significantly in patients using CPAP regardless of adherence, but with a more direct relationship in those who use it beyond 70% of days, at least 4 hours a day.
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http://dx.doi.org/10.5664/jcsm.8176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053023PMC
February 2020

Conditioning the soil microbiome through plant-soil feedbacks suppresses an aboveground insect pest.

New Phytol 2020 04 3;226(2):595-608. Epub 2020 Feb 3.

Department of Terrestrial Ecology, Netherlands Institute of Ecology (NIOO-KNAW), Wageningen, 6700 AB, the Netherlands.

Soils and their microbiomes are now recognized as key components of plant health, but how to steer those microbiomes to obtain their beneficial functions is still unknown. Here, we assess whether plant-soil feedbacks can be applied in a crop system to shape soil microbiomes that suppress herbivorous insects in above-ground tissues. We used four grass and four forb species to condition living soil. Then we inoculated those soil microbiomes into sterilized soil and grew chrysanthemum as a focal plant. We evaluated the soil microbiome in the inocula and after chrysanthemum growth, as well as plant and herbivore parameters. We show that inocula and inoculated soil in which a focal plant had grown harbor remarkably different microbiomes, with the focal plant exerting a strong negative effect on fungi, especially arbuscular mycorrhizal fungi. Soil inoculation consistently induced resistance against the thrips Frankliniella occidentalis, but not against the mite Tetranychus urticae, when compared with sterilized soil. Additionally, plant species shaped distinct microbiomes that had different effects on thrips, chlorogenic acid concentrations in leaves and plant growth. This study provides a proof-of-concept that the plant-soil feedback concept can be applied to steer soil microbiomes with the goal of inducing resistance above ground against herbivorous insects.
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http://dx.doi.org/10.1111/nph.16385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155073PMC
April 2020

A Promiscuous CYP706A3 Reduces Terpene Volatile Emission from Arabidopsis Flowers, Affecting Florivores and the Floral Microbiome.

Plant Cell 2019 12 18;31(12):2947-2972. Epub 2019 Oct 18.

Institut de Biologie Moléculaire des Plantes du Centre National de la Recherche Scientifique (CNRS), Unité Propre de Recherche 2357, Université de Strasbourg, 67084 Strasbourg, France

Flowers are essential but vulnerable plant organs, exposed to pollinators and florivores; however, flower chemical defenses are rarely investigated. We show here that two clustered terpene synthase and cytochrome P450 encoding genes ( and ) on chromosome 5 of Arabidopsis () are tightly coexpressed in floral tissues, upon anthesis and during floral bud development. TPS11 was previously reported to generate a blend of sesquiterpenes. By heterologous coexpression of and in yeast () and , we demonstrate that CYP706A3 is active on TPS11 products and also further oxidizes its own primary oxidation products. Analysis of headspace and soluble metabolites in and mutants indicate that CYP706A3-mediated metabolism largely suppresses sesquiterpene and most monoterpene emissions from opening flowers, and generates terpene oxides that are retained in floral tissues. In flower buds, the combined expression of and also suppresses volatile emissions and generates soluble sesquiterpene oxides. Florivory assays with the specialist demonstrate that insect larvae avoid feeding on buds expressing and accumulating terpene oxides. Composition of the floral microbiome appears also to be modulated by expression. and simultaneously evolved within and form the most versatile functional gene cluster described in higher plants so far.plantcell;31/12/2947/FX1F1fx1.
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http://dx.doi.org/10.1105/tpc.19.00320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925022PMC
December 2019

Assessment of interstitial lung disease among black rheumatoid arthritis patients.

Clin Rheumatol 2019 Dec 30;38(12):3413-3424. Epub 2019 Aug 30.

Department of Internal Medicine, Division of Rheumatology, Division of Pulmonary and Critical Care and Division of Radiology, State University of New York Downstate Medical Center and New York City Health & Hospitals Kings County, Brooklyn, NY, 11203, USA.

Background: Conflicting reports exist regarding the racial and the gender distribution of rheumatoid arthritis-related interstitial lung disease (RA-ILD). In a major population study of predominately Whites, RA-ILD was reported mainly among smoker middle-aged men. However, recent data suggest that the disease is that of elderly women. Our study aimed to assess the prevalence and identify the gender differences and clinical characteristics of RA-ILD in a predominantly Black population.

Methods: Cross-sectional analysis of data obtained from the records of 1142 patients with RA diagnosis by ICD codes of which 503 cases met the inclusion criteria for the study. Eighty-six patients had chronic respiratory symptoms of cough and dyspnea and were further assessed by our multidisciplinary group of investigators. Thirty-two subjects with an established diagnosis of rheumatoid arthritis met the diagnostic criteria for interstitial lung disease.

Results: Of the 32 patients with RA-ILD, mean age was 62.6 ± 2.2 (± SEM), 93.7% were females, and 89% Blacks with a BMI = 29.2 (Kg/m). Usual interstitial pneumonia (UIP) was found in 24/32 (75%) of the cases. Seventy-two percent of the RA-ILD patient had seropositive RA. Smoking history was reported in 31.3% of the cohort, gastroesophageal reflux disease (GERD) in 32.3%, and cardiovascular disease (CVD) risk factors in 65.6%.

Conclusion: Our study indicates RA-ILD among Blacks is predominantly a disease of elderly females with higher rates of GERD and CVD risk factors. Further studies are needed to identify the pathogenetic differences accounting for the gender distribution of RA-ILD among Black and White populations.Key Points• First study to assess ILD among predominantly Black RA patients.• The prevalence of RA-associated ILD was 6.36%, affecting mostly women in their sixth decade with seropositive disease.• COPD was the most common airway disease among non-RA-ILD Black population.• GERD was found in approximately one-third of patients with RA-associated ILD versus one-fifth of those RA patients without any lung disease.
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http://dx.doi.org/10.1007/s10067-019-04760-6DOI Listing
December 2019

Using host-associated differentiation to track source population and dispersal distance among insect vectors of plant pathogens.

Evol Appl 2019 Apr 12;12(4):692-704. Epub 2019 Feb 12.

Department of Entomology Purdue University Lafayette Indiana.

Small, mobile insects are notoriously challenging to track across landscapes and manage in agricultural fields. However, genetic differentiation among insect populations and host plants acquired through host-associated differentiation could be exploited to infer movement within crop systems and damage potential. Although many insects exhibit host-associated differentiation, management strategies for insect vectors of plant pathogens assume a homogenous population. Nevertheless, phenotypic changes derived from host-associated differentiation could manifest in altered behavior or physiology affecting the likelihood of vector-pathogen-plant interactions, or the subsequent efficiency of pathogen transmission. We used SNPs to assess genotypic structure and host-associated differentiation in the cowpea aphid, Koch (Hemiptera: Aphididae). To do so, we sampled across the Midwestern United States. from two host plants, alfalfa () and black locust ()-putative source populations for winged migrants. Simultaneously, we sampled winged landing in pumpkin fields where they transmit viruses. Structure analyses supported host-associated differentiation by identifying two major genotypic groups: an alfalfa group containing a single multilocus genotype and a locust group containing all others. Winged locust-group aphids landed at a much greater magnitude within focal fields during year 2 than year 1, while those in the alfalfa group remained fairly consistent. Spatial autocorrelation analyses indicated locust-group aphid movement was characterized by small-scale dispersal during year 2, likely originating from populations within 10 km. We also detected strong temporal differences in colonization from the two host plants. Early in the summer, most winged aphids (79.4%) derived from the locust group, whereas late in the summer more (58.3%) were from the alfalfa group. Because early crop growth stages are more susceptible to damage from aphid-vectored viruses, these data implicate locust as the more important source and illustrate how host-associated differentiation can be used to track dispersal and inform management of heterogeneous pest populations.
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http://dx.doi.org/10.1111/eva.12733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439873PMC
April 2019

Insect Exclusion Screens Reduce Cucumber Beetle Infestations in High Tunnels, Increasing Cucurbit Yield.

J Econ Entomol 2019 08;112(4):1765-1773

Department of Entomology, Purdue University, West Lafayette, IN.

As high tunnel vegetable production acreage increases in the United States, so does the need for management strategies tailored to their unique growing environment. Cucumbers are an ideal crop in these systems; they can be vertically trellised to maximize the production area and provide high yields to balance the increased costs associated with high tunnel construction. One of the most limiting factors in cucurbit production in general is the cucumber beetle complex and the bacterial pathogen they transmit. In this study, we investigated the optimal size of netting installed on high tunnels to prevent cucumber beetle colonization while maintaining ventilation to reduce heat stress. Of the three mesh sizes investigated across 4 yr, the intermediate mesh with a pore size of 0.72 × 0.97 mm was optimal to exclude cucumber beetles, maintain ventilation, and produce the highest yields for both cucumber and melon plants. The smallest (0.16 mm2) and intermediate mesh sizes resulted in secondary pest outbreaks (e.g., aphids), which did not occur in open tunnels and to a lesser extent in tunnels covered with the largest (1.00 × 4.00 mm) mesh. Despite these secondary pests, yield was higher in small- and intermediate-sized mesh treatments due to relief from cucumber beetle infestations, including striped (Acalymma vittatum Fabr. (Coleoptera: Chrysomelidae)) and spotted (Diabrotica undecimpunctata howardi Barber (Coleoptera: Chrysomelidae)) beetles. Overall, we conclude that insect exclusion netting is an effective method to exclude cucumber beetles from high tunnels, but mesh size should be carefully considered when weighing the collective effects on yield and primary/secondary pest abundance.
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http://dx.doi.org/10.1093/jee/toz060DOI Listing
August 2019

Assessment of Cardiovascular Disease Risk and Therapeutic Patterns among Urban Black Rheumatoid Arthritis Patients.

Med Sci (Basel) 2019 Feb 20;7(2). Epub 2019 Feb 20.

Department of Medicine, Division of Rheumatology SUNY Downstate Medical Center/Health + Hospitals Kings County, Brooklyn, NY 11201, USA.

Rheumatoid arthritis (RA) patients have nearly twice the risk of cardiovascular disease (CVD) compared to the general population. We aimed to assess, in a predominantly Black population, the prevalence of traditional and RA-specific CVD risk factors and therapeutic patterns. Utilizing ICD codes, we identified 503 RA patients ≥18 years old who were seen from 2010 to 2017. Of them, 88.5% were Black, 87.9% were women and 29.4% were smokers. CVD risk factors (obesity, diabetes, hypertension, dyslipidemia) were higher than in previously reported White RA cohorts. Eighty-seven percent of the patients had at least one traditional CVD risk factor, 37% had three or more traditional CVD risk factors and 58% had RA-specific risk factors (seropositive RA, >10 years of disease, joint erosions, elevated inflammatory markers, extra-articular disease, body mass index (BMI) < 20). CV outcomes (coronary artery disease/myocardial infarction, heart failure, atrial fibrillation and stroke) were comparable to published reports. Higher steroid use, which increases CVD risk, and lesser utilization of biologics (decrease CV risk) were also observed. Our Black RA cohort had higher rates of traditional CVD risk factors, in addition to chronic inflammation from aggressive RA, which places our patients at a higher risk for CVD outcomes, calling for revised risk stratification strategies and effective interventions to address comorbidities in this vulnerable population.
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http://dx.doi.org/10.3390/medsci7020031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410013PMC
February 2019

Tomato PEPR1 ORTHOLOG RECEPTOR-LIKE KINASE1 Regulates Responses to Systemin, Necrotrophic Fungi, and Insect Herbivory.

Plant Cell 2018 09 21;30(9):2214-2229. Epub 2018 Aug 21.

Department of Botany and Plant Pathology, Purdue University, West Lafayette, Indiana 47907

Endogenous peptides regulate plant immunity and growth. Systemin, a peptide specific to the Solanaceae, is known for its functions in plant responses to insect herbivory and pathogen infections. Here, we describe the identification of the tomato () PEPR1/2 ORTHOLOG RECEPTOR-LIKE KINASE1 (PORK1) as the TOMATO PROTEIN KINASE1b (TPK1b) interacting protein and demonstrate its biological functions in systemin signaling and tomato immune responses. Tomato RNA interference (RNAi) plants with significantly reduced expression showed increased susceptibility to tobacco hornworm (), reduced seedling growth sensitivity to the systemin peptide, and compromised systemin-mediated resistance to Systemin-induced expression of (), a classical marker for systemin signaling, was abrogated in RNAi plants. Similarly, in response to systemin and wounding, the expression of jasmonate pathway genes was attenuated in RNAi plants. TPK1b, a key regulator of tomato defense against and , was phosphorylated by PORK1. Interestingly, wounding- and systemin-induced phosphorylation of TPK1b was attenuated when expression was suppressed. Our data suggest that resistance to and is dependent on PORK1-mediated responses to systemin and subsequent phosphorylation of TPK1b. Altogether, PORK1 regulates tomato systemin, wounding, and immune responses.
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http://dx.doi.org/10.1105/tpc.17.00908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181013PMC
September 2018

Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study.

Lancet Oncol 2018 03 26;19(3):347-355. Epub 2018 Jan 26.

Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.

Background: Treatment options are limited for patients with thymic carcinoma. These aggressive tumours are not typically associated with paraneoplastic autoimmune disorders, and strong PD-L1 expression has been reported in thymic epithelial tumours. We aimed to assess the activity of pembrolizumab, a monoclonal antibody that targets PD-1, in patients with advanced thymic carcinoma.

Methods: We completed a single-arm phase 2 study of pembrolizumab in patients with recurrent thymic carcinoma who had progressed after at least one line of chemotherapy. This was a single-centre study performed at Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. Key inclusion criteria were an Eastern Cooperative Oncology Group performance status of 0-2, no history of autoimmune disease or other malignancy requiring treatment or laboratory abnormality, and adequate organ function. Patients received 200 mg of pembrolizumab every 3 weeks for up to 2 years. The primary objective of the study was the proportion of patients who had achieved a response assessed with Response Evaluation Criteria in Solid Tumors version 1.1. Analysis was per protocol, in all eligible patients. The study is registered with ClinicalTrials.gov, number NCT02364076, and is closed to accrual; we report the final analysis.

Findings: 41 patients were enrolled from March 12, 2015, to Dec 16, 2016, of whom 40 were eligible and evaluable and one was excluded because of elevated liver enzymes at screening. The median follow-up was 20 months (IQR 14-26). The proportion of patients who achieved a response was 22·5% (95% CI 10·8-38·5); one (3%) patient achieved a complete response, eight (20%) patients achieved partial responses, and 21 (53%) patients achieved stable disease. The most common grade 3 or 4 adverse events were increased aspartate aminotransferase and alanine aminotransferase (five [13%] patients each). Six (15%) patients developed severe autoimmune toxicity, including two (5%) patients with myocarditis. There were 17 deaths at the time of analysis, but no deaths due to toxicity.

Interpretation: Pembrolizumab is a promising treatment option in patients with thymic carcinoma. Because severe autoimmune disorders are more frequent in thymic carcinoma than in other tumour types, careful monitoring is essential.

Funding: Merck & Co.
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http://dx.doi.org/10.1016/S1470-2045(18)30062-7DOI Listing
March 2018

Steering Soil Microbiomes to Suppress Aboveground Insect Pests.

Trends Plant Sci 2017 09 27;22(9):770-778. Epub 2017 Jul 27.

Department of Terrestrial Ecology, NIOO-KNAW, Postbus 50, 6700 AB Wageningen, The Netherlands; Institute of Biology, Section Plant Ecology and Phytochemistry, Leiden University, PO Box 9505, 2300 RA Leiden, The Netherlands.

Soil-borne microbes affect aboveground herbivorous insects through a cascade of molecular and chemical changes in the plant, but knowledge of these microbe-plant-insect interactions is mostly limited to one or a few microbial strains. Yet, the soil microbial community comprises thousands of unique taxa interacting in complex networks, the so-called 'microbiome', which provides plants with multiple beneficial functions. There has been little exploration of the role and management of whole microbiomes in plant-insect interactions, calling for the integration of this complexity in aboveground-belowground research. Here, we propose holistic approaches to select soil microbiomes that can be used to protect plants from aboveground attackers.
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http://dx.doi.org/10.1016/j.tplants.2017.07.002DOI Listing
September 2017

Does fear beget fear? Risk-mediated habitat selection triggers predator avoidance at lower trophic levels.

Oecologia 2017 Sep 20;185(1):1-11. Epub 2017 Jul 20.

Department of Entomology, Purdue University, 901W. State St, West Lafayette, IN, 47907, USA.

Non-consumptive effects (NCEs) of predators are ubiquitous in food webs with well-detailed impacts on trophic cascades over multiple levels. However, integrating NCEs with other predator-mediated interactions, like intraguild predation, as well as context-specific habitat factors that shape top-down pressure, remains a challenge. Focusing on two common seed predators, mice (Peromyscus spp.) and carabid beetles (Coleoptera: Carabidae), we quantify trophic and behavioral consequences of predation risk and availability of refuge vegetation on both intraguild predators (mice) and intraguild prey (beetles). In a 2-year field experiment, we manipulated refuge habitat (red clover), small mammal access, and moonlight, which small mammals use as an indirect cue of predation risk. We found that avoidance of predation risk by mice in simulated moonlight reduced carabid activity density in vegetation by up to 50% compared to exposed habitat, but had no cascading effects on seed predation. We linked patterns observed in the field with behavioral mechanisms by observing beetle foraging activity, and found that exposure to both indirect and direct vertebrate predator cues reduced movement by 50%, consistent with predator-mediated activity reductions observed in the field. However, predation risk increased carabid seed consumption by 43%. Thus, weak effects of predation risk on seed removal in the field may be explained by overcompensatory seed feeding by beetles. This work demonstrates that predators elicit responses that cascade over multiple trophic levels, triggering behavioral changes in species lower on the food chain. These behavior-mediated cascades are controlled by their spatiotemporal context and have important downstream impacts on predator-prey dynamics.
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http://dx.doi.org/10.1007/s00442-017-3909-1DOI Listing
September 2017

Carnivore Attractant or Plant Elicitor? Multifunctional Roles of Methyl Salicylate Lures in Tomato Defense.

J Chem Ecol 2017 Jun 9;43(6):573-585. Epub 2017 Jun 9.

Department of Entomology, Smith Hall, Purdue University, West Lafayette, IN, 47907, USA.

Synthetic plant volatile lures attract natural enemies, but may have non-target effects due to the multifunctional nature of volatile signals. For example, methyl salicylate (MeSA) is used to attract predators, yet also serves as a signaling hormone involved in plant pathogen defense. We investigated the consequences of deploying MeSA lures to attract predators for tomato (Solanum lycopersicum) defense against herbivores. To understand the spatial distribution of the lure's effect, we exposed tomatoes in the field to MeSA along a linear distance gradient and induced defenses by simulating feeding by hornworm caterpillars in a fully crossed factorial design (+/- MeSA, +/- herbivory). Subsequently, we analyzed activity of several defensive proteins (protease inhibitors, polyphenol oxidase, peroxidase), development of hornworm larvae (Manduca sexta), growth of fungal pathogens (Cladosporium and Alternaria), and attractiveness to herbivores and predators. Overall, MeSA-exposed plants were more resistant to both insects and pathogens. Secondary pathogen infection was reduced by 25% in MeSA exposed plants, possibly due to elevated polyphenol oxidase activity. Interestingly, we found that lures affected plant pathogen defenses equivalently across all distances (up to 4 m away) indicating that horizontal diffusion of a synthetic volatile may be greater than previously assumed. While thrips avoided colonizing hornworm- damaged tomato plants, this induced resistance was not observed upon pre-exposure to MeSA, suggesting that MeSA suppresses the repellant effect induced by herbivory. Thus, using MeSA lures in biological control may inadvertently protect crops from pathogens, but has mixed effects on plant resistance to insect herbivores.
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http://dx.doi.org/10.1007/s10886-017-0856-6DOI Listing
June 2017

High tunnels: protection for rather than from insect pests?

Pest Manag Sci 2017 Dec 23;73(12):2439-2446. Epub 2017 Aug 23.

Department of Entomology, Purdue University, West Lafayette, IN, USA.

Background: High tunnels are a season extension tool creating a hybrid of field and greenhouse growing conditions. High tunnels have recently increased in the USA and thus research on their management is lacking. One purported advantage of these structures is protection from common field pests, but evidence to support this claim is lacking. We compared insect pest populations in high tunnels with field production over two years for three crops: tomato, broccoli and cucumber.

Results: Greenhouse pests (e.g. aphids, whiteflies) were more prevalent in high tunnels, compared to field plots. Hornworms (tobacco (Manduca sexta L.) and tomato (M. quinquemaculata Haworth)), a common field pest on tomato, were also more abundant in high tunnels, requiring chemical control while field populations were low. The crucifer caterpillar complex (imported cabbageworm (Pieris rapae L.), diamondback moth (Plutella xylostella L.) and cabbage looper (Trichoplusia ni Hübner)) was also more abundant in high tunnels in 2010. Cucumber beetle (striped (Acalymma vittatum F.) and spotted (Diabrotica undecimpunctata Mannerheim)) densities were higher in high tunnels in 2010 and field plots in 2011.

Conclusion: The common assumption that high tunnels offer protection from field pests was not supported. Instead, high tunnel growing conditions may facilitate higher pest populations. © 2017 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.4634DOI Listing
December 2017

A cry for help or sexual perfumes? An alternative hypothesis for wasp attraction to the scent of caterpillar-wounded plants.

Authors:
Ian Kaplan

Plant Cell Environ 2017 03 29;40(3):327-329. Epub 2016 Dec 29.

Department of Entomology, Purdue University, West Lafayette, IN, USA.

This article comments on: Combined use of herbivore-induced plant volatiles and sex pheromones for mate location in braconid parasitoids.
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http://dx.doi.org/10.1111/pce.12864DOI Listing
March 2017

Indirect plant-parasitoid interactions mediated by changes in herbivore physiology.

Curr Opin Insect Sci 2016 04 7;14:112-119. Epub 2016 Mar 7.

Department of Bioagricultural Sciences & Pest Management, Colorado State University, United States.

In occupying an intermediate trophic position, herbivorous insects serve a vital link between plants at the base of the food chain and parasitoids at the top. Although these herbivore-mediated indirect plant-parasitoid interactions are well-documented, new studies have uncovered previously undescribed mechanisms that are fundamentally changing how we view tri-trophic relationships. In this review we highlight recent advances in this field focusing on both plant-driven and parasitoid-driven outcomes that flow up and down the trophic web, respectively. From the bottom-up, plant metabolites can impact parasitoid success by altering host immune function; however, few have considered the potential effects of other plant defense strategies such as tolerance on parasitoid ecology and behavior. From the top-down, parasitoids have long been considered plant bodyguards, but in reality the consequences of parasitism for herbivory rates and induction of plant defensive chemistry are far more complicated with cascading effects on community-level interactions.
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http://dx.doi.org/10.1016/j.cois.2016.03.004DOI Listing
April 2016

Eco-evolutionary factors drive induced plant volatiles: a meta-analysis.

New Phytol 2016 Apr 4;210(1):284-94. Epub 2016 Jan 4.

Department of Entomology, Purdue University, 901 W. State Street, West Lafayette, IN, 47907, USA.

Herbivore-induced plant volatiles (HIPVs) mediate critical ecological functions, but no studies have quantitatively synthesized data published on HIPVs to evaluate broad patterns. We tested three hypotheses that use eco-evolutionary theory to predict volatile induction: feeding guild (chewing arthropods > sap feeders), diet breadth (specialist herbivores > generalists), and selection history (domesticated plants < wild species). To test these hypotheses, we extracted data from 236 experiments that report volatiles produced by herbivore-damaged and undamaged plants. These data were subjected to meta-analysis, including effects on total volatiles and major biochemical classes. Overall, we found that chewers induced more volatiles than sap feeders, for both total volatiles and most volatile classes (e.g. green leaf volatiles, monoterpenes). Although specialist herbivores induced more total volatiles than generalists, this was inconsistent across chemical classes. Contrary to our expectation, domesticated species induced stronger volatile responses than wild species, even when controlling for plant taxonomy. Surprisingly, this is the first quantitative synthesis of published studies on HIPVs. Our analysis provides support for perceptions in the published literature (chewers > sap feeders), while challenging other commonly held notions (wild > crop). Despite the large number of experiments, we identified several gaps in the existing literature that should guide future investigations.
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http://dx.doi.org/10.1111/nph.13804DOI Listing
April 2016

Editorial overview: Ecology: Beyond a taxonomically driven approach for describing pattern and process in complex insect communities.

Curr Opin Insect Sci 2014 Aug 28;2:v-vii. Epub 2014 Jul 28.

Department of Entomology, Purdue University, West Lafayette, IN 47907, USA. Electronic address:

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http://dx.doi.org/10.1016/j.cois.2014.07.006DOI Listing
August 2014
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