Insect chemical ecology: chemically mediated interactions and novel applications in agriculture

Forum PaperInsect chemical ecology (ICE) evolved as a discipline concerned with plant–insect interactions, and also with a strong focus on intraspecific pheromone-mediated communication. Progress in this field has rendered a more complete picture of how insects exploit chemical information in their surroundings in order to survive and navigate their world successfully. Simultaneously, this progress has prompted new research questions about the evolution of insect chemosensation and related ecological adaptations, molecular mechanisms that mediate commonly observed behaviors, and the consequences of chemically mediated interactions in different ecosystems. Themed meetings, workshops, and summer schools are ideal platforms for discussing scientific advancements as well as identifying gaps and challenges within the discipline. From the 11th to the 22nd of June 2018, the 11th annual PhD course in ICE was held at the Swedish University of Agricultural Sciences (SLU) Alnarp, Sweden. The course was made up of 35 student participants from 22 nationalities (Fig. 1a) as well as 32 lecturers. Lectures and laboratory demonstrations were supported by literature seminars, and four broad research areas were covered: (1) multitrophic interactions and plant defenses, (2) chemical communication focusing on odor sensing, processing, and behavior, (3) disease vectors, and (4) applied aspects of basic ICE research in agriculture. This particular article contains a summary and brief synthesis of these main emergent themes and discussions from the ICE 2018 course. In addition, we also provide suggestions on teaching the next generation of ICE scientists, especially during unprecedented global situationsinfo:eu-repo/semantics/publishedVersio

Non-canonical odor coding in the mosquito

Aedes aegypti mosquitoes are a persistent human foe, transmitting arboviruses including dengue when they feed on human blood. Mosquitoes are intensely attracted to body odor and carbon dioxide, which they detect using ionotropic chemosensory receptors encoded by three large multi-gene families. Genetic mutations that disrupt the olfactory system have modest effects on human attraction, suggesting redundancy in odor cod-ing. The canonical view is that olfactory sensory neurons each express a single chemosensory receptor that defines its ligand selectivity. We discovered that Ae. aegypti uses a different organizational principle, with many neurons co-expressing multiple chemosensory receptor genes. In vivo electrophysiology demon-strates that the broad ligand-sensitivity of mosquito olfactory neurons depends on this non-canonical co-expression. The redundancy afforded by an olfactory system in which neurons co-express multiple chemosensory receptors may increase the robustness of the mosquito olfactory system and explain our long-standing inability to disrupt the detection of humans by mosquitoes

Post-mortem neuropathologic examination of a 5-case series of CAR T-cell treated patients

Introduction: Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy for the treatment of refractory hematopoietic malignancies. Adverse events are common, and neurotoxicity is one of the most important. However, the physiopathology is unknown and neuropathologic information is scarce.Materials and methods: Post-mortem examination of 6 brains from patients that underwent CAR T-cell therapy from 2017 to 2022. In all cases, polymerase chain reaction (PCR) in paraffin blocks for the detection of CAR T cells was performed.Results: Two patients died of hematologic progression, while the others died of cytokine release syndrome, lung infection, encephalomyelitis, and acute liver failure. Two out of 6 presented neurological symptoms, one with extracranial malignancy progression and the other with encephalomyelitis. The neuropathology of the latter showed severe perivascular and interstitial lymphocytic infiltration, predominantly CD8+, together with a diffuse interstitial histiocytic infiltration, affecting mainly the spinal cord, midbrain, and hippocampus, and a diffuse gliosis of basal ganglia, hippocampus, and brainstem. Microbiological studies were negative for neurotropic viruses, and PCR failed to detect CAR T -cells. Another case without detectable neurological signs showed cortical and subcortical gliosis due to acute hypoxic-ischemic damage. The remaining 4 cases only showed a mild patchy gliosis and microglial activation, and CAR T cells were detected by PCR only in one of them.Conclusions: In this series of patients that died after CAR T-cell therapy, we predominantly found non-specific or minimal neuropathological changes. CAR T-cell related toxicity may not be the only cause of neurological symptoms, and the autopsy could detect additional pathological findings

Children’s and adolescents’ rising animal-source food intakes in 1990–2018 were impacted by age, region, parental education and urbanicity

Animal-source foods (ASF) provide nutrition for children and adolescents’ physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the world’s child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 15–19 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes.publishedVersio

Incident type 2 diabetes attributable to suboptimal diet in 184 countries

The global burden of diet-attributable type 2 diabetes (T2D) is not well established. This risk assessment model estimated T2D incidence among adults attributable to direct and body weight-mediated effects of 11 dietary factors in 184 countries in 1990 and 2018. In 2018, suboptimal intake of these dietary factors was estimated to be attributable to 14.1 million (95% uncertainty interval (UI), 13.8–14.4 million) incident T2D cases, representing 70.3% (68.8–71.8%) of new cases globally. Largest T2D burdens were attributable to insufficient whole-grain intake (26.1% (25.0–27.1%)), excess refined rice and wheat intake (24.6% (22.3–27.2%)) and excess processed meat intake (20.3% (18.3–23.5%)). Across regions, highest proportional burdens were in central and eastern Europe and central Asia (85.6% (83.4–87.7%)) and Latin America and the Caribbean (81.8% (80.1–83.4%)); and lowest proportional burdens were in South Asia (55.4% (52.1–60.7%)). Proportions of diet-attributable T2D were generally larger in men than in women and were inversely correlated with age. Diet-attributable T2D was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, central and eastern Europe and central Asia, where burdens were larger in rural residents and in lower educated individuals. Compared with 1990, global diet-attributable T2D increased by 2.6 absolute percentage points (8.6 million more cases) in 2018, with variation in these trends by world region and dietary factor. These findings inform nutritional priorities and clinical and public health planning to improve dietary quality and reduce T2D globally.publishedVersio

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Reverse chemical ecology applied to odorant receptors in the crop pest insect Spodoptera littoralis : towards innovative strategies in crop protection

Les insectes détectent, grâce à leurs récepteurs olfactifs (OR), une diversité de composées volatils présents dans l’environnement, qu’ils utilisent pour des activités vitales comme l’identification des sources de nourritures et des partenaires sexuels. Identifier des sémiochimiques qui ont un effet attractif ou répulsif est un enjeu pour manipuler le comportement des insectes nuisibles à des fins de biocontrôle. Appliquées aux Lépidoptères, de telles stratégies visent essentiellement les adultes, alors que le stade ravageur est principalement la chenille.Ainsi mon travail de thèse a consisté à rechercher des sémiochimiques actifs sur le comportement des chenilles chez un ravageur modèle, la noctuelle Spodoptera littoralis, en mettant en œuvre une approche d’écologie chimique inverse à partir des OR. Tout d’abord, une étude transcriptomique a permis d’identifier le répertoire des gènes chimiosensoriels exprimés chez la chenille. Nous avons ensuite étudié la fonction de certains récepteurs en utilisant un système d’expression hétérologue in vivo chez la drosophile, afin d’identifier quels sont les volatils détectés par l’insecte. Enfin, nous avons combiné des approches de modélisation in silico ligand-ciblée, des analyses fonctionnelles in vivo chez la drosophile et des tests comportementaux, afin d’identifier de nouveaux ligands des OR ciblés actifs sur le comportement.Ce travail a permis de valider l’utilisation des OR pour accélérer de découverte de nouveaux sémiochimiques actifs sur les comportements qui, à terme, pourraient servir au bioncontrôle des chenilles herbivores. Les données obtenues apportent également des connaissances fondamentales dans le domaine de la neurobiologie et de l’éthologie des larves.Insects detect, via their odorant receptors (OR), a variety of volatile compounds found in the environment and use them to carry out vital activities such as identifying food sources and sexual partners. The identification of attractive or repellent semiochemicals that interfere with crop pest behaviors is a major issue for their biocontrol. Yet, their application for the control of pest Lepidoptera mainly targets adults, whereas the caterpillars represent the feeding stage.In this context, my work consisted in searching semiochemicals active on the behavior of caterpillars in a model crop pest, the moth Spodoptera littoralis, using a reverse chemical ecology targeting the larval ORs. First, a transcriptomic study allowed us to identify the repertoire of chemosensory genes expressed in the larva. Then, the function of some ORs was determined via their heterologous expression in Drosophila, in order to identify which olfactory cues are detected by larvae. Last, we combined in silico ligand-targeted modeling, functional analyzes of ORs expressed in Drosophila and behavioral assays to identify new ligands for the targeted ORs that are active on the larval behavior.This work validates the use of ORs as targets to accelerate the discovery of new semiochemicals active on behaviors, which, in the long term could be used for the bioncontrol of herbivorous caterpillars. The data obtained also provide fundamental knowledge in the field of neurobiology and the ethology of larvae

Écologie chimique inverse appliquée aux récepteurs olfactifs de l'insecte ravageur des cultures Spodoptera littoralis : vers des stratégies innovantes en protection des cultures

Insects detect, via their odorant receptors (OR), a variety of volatile compounds found in the environment and use them to carry out vital activities such as identifying food sources and sexual partners. The identification of attractive or repellent semiochemicals that interfere with crop pest behaviors is a major issue for their biocontrol. Yet, their application for the control of pest Lepidoptera mainly targets adults, whereas the caterpillars represent the feeding stage.In this context, my work consisted in searching semiochemicals active on the behavior of caterpillars in a model crop pest, the moth Spodoptera littoralis, using a reverse chemical ecology targeting the larval ORs. First, a transcriptomic study allowed us to identify the repertoire of chemosensory genes expressed in the larva. Then, the function of some ORs was determined via their heterologous expression in Drosophila, in order to identify which olfactory cues are detected by larvae. Last, we combined in silico ligand-targeted modeling, functional analyzes of ORs expressed in Drosophila and behavioral assays to identify new ligands for the targeted ORs that are active on the larval behavior.This work validates the use of ORs as targets to accelerate the discovery of new semiochemicals active on behaviors, which, in the long term could be used for the bioncontrol of herbivorous caterpillars. The data obtained also provide fundamental knowledge in the field of neurobiology and the ethology of larvae.Les insectes détectent, grâce à leurs récepteurs olfactifs (OR), une diversité de composées volatils présents dans l’environnement, qu’ils utilisent pour des activités vitales comme l’identification des sources de nourritures et des partenaires sexuels. Identifier des sémiochimiques qui ont un effet attractif ou répulsif est un enjeu pour manipuler le comportement des insectes nuisibles à des fins de biocontrôle. Appliquées aux Lépidoptères, de telles stratégies visent essentiellement les adultes, alors que le stade ravageur est principalement la chenille.Ainsi mon travail de thèse a consisté à rechercher des sémiochimiques actifs sur le comportement des chenilles chez un ravageur modèle, la noctuelle Spodoptera littoralis, en mettant en œuvre une approche d’écologie chimique inverse à partir des OR. Tout d’abord, une étude transcriptomique a permis d’identifier le répertoire des gènes chimiosensoriels exprimés chez la chenille. Nous avons ensuite étudié la fonction de certains récepteurs en utilisant un système d’expression hétérologue in vivo chez la drosophile, afin d’identifier quels sont les volatils détectés par l’insecte. Enfin, nous avons combiné des approches de modélisation in silico ligand-ciblée, des analyses fonctionnelles in vivo chez la drosophile et des tests comportementaux, afin d’identifier de nouveaux ligands des OR ciblés actifs sur le comportement.Ce travail a permis de valider l’utilisation des OR pour accélérer de découverte de nouveaux sémiochimiques actifs sur les comportements qui, à terme, pourraient servir au bioncontrôle des chenilles herbivores. Les données obtenues apportent également des connaissances fondamentales dans le domaine de la neurobiologie et de l’éthologie des larves