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      Glyphosate inhibits melanization and increases susceptibility to infection in insects

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          Abstract

          Melanin, a black-brown pigment found throughout all kingdoms of life, has diverse biological functions including UV protection, thermoregulation, oxidant scavenging, arthropod immunity, and microbial virulence. Given melanin’s broad roles in the biosphere, particularly in insect immune defenses, it is important to understand how exposure to ubiquitous environmental contaminants affects melanization. Glyphosate—the most widely used herbicide globally—inhibits melanin production, which could have wide-ranging implications in the health of many organisms, including insects. Here, we demonstrate that glyphosate has deleterious effects on insect health in 2 evolutionary distant species, Galleria mellonella (Lepidoptera: Pyralidae) and Anopheles gambiae (Diptera: Culicidae), suggesting a broad effect in insects. Glyphosate reduced survival of G. mellonella caterpillars following infection with the fungus Cryptococcus neoformans and decreased the size of melanized nodules formed in hemolymph, which normally help eliminate infection. Glyphosate also increased the burden of the malaria-causing parasite Plasmodium falciparum in A. gambiae mosquitoes, altered uninfected mosquito survival, and perturbed the microbial composition of adult mosquito midguts. Our results show that glyphosate’s mechanism of melanin inhibition involves antioxidant synergy and disruption of the reaction oxidation–reduction balance. Overall, these findings suggest that glyphosate’s environmental accumulation could render insects more susceptible to microbial pathogens due to melanin inhibition, immune impairment, and perturbations in microbiota composition, potentially contributing to declines in insect populations.

          Abstract

          Glyphosate, the most commonly used herbicide in the world, inhibits the production of melanin. Melanin is an important pigment and a key component of the insect immune system; this study shows that glyphosate weakens insects’ melanin-based immune system and makes them more vulnerable to infections, including with the human malaria parasite Plasmodium falciparum.

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          Fiji: an open-source platform for biological-image analysis.

          Fiji is a distribution of the popular open-source software ImageJ focused on biological-image analysis. Fiji uses modern software engineering practices to combine powerful software libraries with a broad range of scripting languages to enable rapid prototyping of image-processing algorithms. Fiji facilitates the transformation of new algorithms into ImageJ plugins that can be shared with end users through an integrated update system. We propose Fiji as a platform for productive collaboration between computer science and biology research communities.
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            Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities.

            mothur aims to be a comprehensive software package that allows users to use a single piece of software to analyze community sequence data. It builds upon previous tools to provide a flexible and powerful software package for analyzing sequencing data. As a case study, we used mothur to trim, screen, and align sequences; calculate distances; assign sequences to operational taxonomic units; and describe the alpha and beta diversity of eight marine samples previously characterized by pyrosequencing of 16S rRNA gene fragments. This analysis of more than 222,000 sequences was completed in less than 2 h with a laptop computer.
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              More than 75 percent decline over 27 years in total flying insect biomass in protected areas

              Global declines in insects have sparked wide interest among scientists, politicians, and the general public. Loss of insect diversity and abundance is expected to provoke cascading effects on food webs and to jeopardize ecosystem services. Our understanding of the extent and underlying causes of this decline is based on the abundance of single species or taxonomic groups only, rather than changes in insect biomass which is more relevant for ecological functioning. Here, we used a standardized protocol to measure total insect biomass using Malaise traps, deployed over 27 years in 63 nature protection areas in Germany (96 unique location-year combinations) to infer on the status and trend of local entomofauna. Our analysis estimates a seasonal decline of 76%, and mid-summer decline of 82% in flying insect biomass over the 27 years of study. We show that this decline is apparent regardless of habitat type, while changes in weather, land use, and habitat characteristics cannot explain this overall decline. This yet unrecognized loss of insect biomass must be taken into account in evaluating declines in abundance of species depending on insects as a food source, and ecosystem functioning in the European landscape.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: VisualizationRole: Writing – review & editing
                Role: MethodologyRole: Writing – review & editing
                Role: Funding acquisitionRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Academic Editor
                Journal
                PLoS Biol
                PLoS Biol
                plos
                plosbiol
                PLoS Biology
                Public Library of Science (San Francisco, CA USA )
                1544-9173
                1545-7885
                12 May 2021
                May 2021
                12 May 2021
                : 19
                : 5
                : e3001182
                Affiliations
                [1 ] W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
                [2 ] Department of Otolaryngology, Head and Neck Surgery, Johns Hopkins Medicine, Baltimore, Maryland, United States of America
                [3 ] Department of Biology, Johns Hopkins University, Baltimore Maryland, United States of America
                University of California, San Francisco, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                [¤]

                Current address: Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, United States of America

                ‡ NAB and AC are joint senior authors on this work.

                Author information
                https://orcid.org/0000-0003-0411-0509
                https://orcid.org/0000-0002-6830-9456
                https://orcid.org/0000-0002-9402-9167
                Article
                PBIOLOGY-D-20-01680
                10.1371/journal.pbio.3001182
                8115815
                33979323
                b141d67f-863e-4eba-963a-a37094a05c3c
                © 2021 Smith et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 8 June 2020
                : 11 March 2021
                Page count
                Figures: 7, Tables: 0, Pages: 35
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100011780, Johns Hopkins Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health;
                Award ID: Casadevall_123
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Award ID: R01 AI052733
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: 5T32GM008752-18
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: 1T32AI138953-01A1
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R35GM128871
                Award Recipient :
                D.F.Q.S., E.C., A.C. are funded by National Institute of Allergy and Infection Disease R01 AI052733 and Johns Hopkins Malaria Research Institute ( https://malaria.jhsph.edu/) Pilot Grant # Casadevall_123. D.F.Q.S. is funded by National Institutes of Health 5T32GM008752-18 and 1T32AI138953-01A1. A.J.B. and N.A.B. are funded by National Institutes of Health R35GM128871. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The salaries of D.F.Q.S., A.C., and E.C. are in part funded by the National Institute of Allergy and Infection Disease. The salaries of D.F.Q.S., A.J.B., and N.A.B., are in part funded by the National Institutes of Health. The salary of E.C. is in part funded by Johns Hopkins Malaria Research Institute.
                Categories
                Research Article
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Levodopa
                Biology and Life Sciences
                Biochemistry
                Neurochemistry
                Neurochemicals
                Levodopa
                Biology and Life Sciences
                Neuroscience
                Neurochemistry
                Neurochemicals
                Levodopa
                Physical Sciences
                Materials Science
                Materials
                Pigments
                Organic Pigments
                Melanin
                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Disease Vectors
                Insect Vectors
                Mosquitoes
                Biology and Life Sciences
                Species Interactions
                Disease Vectors
                Insect Vectors
                Mosquitoes
                Biology and Life Sciences
                Zoology
                Entomology
                Insects
                Mosquitoes
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Invertebrates
                Arthropoda
                Insects
                Mosquitoes
                Biology and Life Sciences
                Zoology
                Animals
                Invertebrates
                Arthropoda
                Insects
                Mosquitoes
                Biology and Life Sciences
                Biochemistry
                Antioxidants
                Biology and Life Sciences
                Zoology
                Entomology
                Insects
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Invertebrates
                Arthropoda
                Insects
                Biology and Life Sciences
                Zoology
                Animals
                Invertebrates
                Arthropoda
                Insects
                Medicine and Health Sciences
                Medical Conditions
                Parasitic Diseases
                Physical Sciences
                Chemistry
                Chemical Reactions
                Oxidation
                Biology and Life Sciences
                Developmental Biology
                Life Cycles
                Larvae
                Custom metadata
                The datasets presented in this manuscript are publicly available Figshare data repository at: https://figshare.com/projects/Glyphosate_Inhibits_Melanization_and_Increases_Susceptibility_to_Infection_in_Insects/99341. Additionally, the Figshare Digital Object Identifiers (DOIs) for the individual figure datasets are listed in S1 Table.

                Life sciences
                Life sciences

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