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      The novel pyridazine pyrazolecarboxamide insecticide dimpropyridaz inhibits chordotonal organ function upstream of TRPV channels

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          Abstract

          BACKGROUND

          Pyridazine pyrazolecarboxamides (PPCs) are a novel insecticide class discovered and optimized at BASF. Dimpropyridaz is the first PPC to be submitted for registration and controls many aphid species as well as whiteflies and other piercing–sucking insects.

          RESULTS

          Dimpropyridaz and other tertiary amide PPCs are proinsecticides that are converted in vivo into secondary amide active forms by N‐dealkylation. Active secondary amide metabolites of PPCs potently inhibit the function of insect chordotonal neurons. Unlike Group 9 and 29 insecticides, which hyperactivate chordotonal neurons and increase Ca 2+ levels, active metabolites of PPCs silence chordotonal neurons and decrease intracellular Ca 2+ levels. Whereas the effects of Group 9 and 29 insecticides require TRPV (Transient Receptor Potential Vanilloid) channels, PPCs act in a TRPV‐independent fashion, without compromising cellular responses to Group 9 and 29 insecticides, placing the molecular PPC target upstream of TRPVs.

          CONCLUSIONS

          PPCs are a new class of chordotonal organ modulator insecticide for control of piercing–sucking pests. Dimpropyridaz is a PPC proinsecticide that is activated in target insects to secondary amide forms that inhibit the firing of chordotonal organs. The inhibition occurs at a site upstream of TRPVs and is TRPV‐independent, providing a novel mode of action for resistance management. © 2023 BASF Corporation. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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          Most cited references44

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          Ultra-sensitive fluorescent proteins for imaging neuronal activity

          Summary Fluorescent calcium sensors are widely used to image neural activity. Using structure-based mutagenesis and neuron-based screening, we developed a family of ultra-sensitive protein calcium sensors (GCaMP6) that outperformed other sensors in cultured neurons and in zebrafish, flies, and mice in vivo. In layer 2/3 pyramidal neurons of the mouse visual cortex, GCaMP6 reliably detected single action potentials in neuronal somata and orientation-tuned synaptic calcium transients in individual dendritic spines. The orientation tuning of structurally persistent spines was largely stable over timescales of weeks. Orientation tuning averaged across spine populations predicted the tuning of their parent cell. Although the somata of GABAergic neurons showed little orientation tuning, their dendrites included highly tuned dendritic segments (5 - 40 micrometers long). GCaMP6 sensors thus provide new windows into the organization and dynamics of neural circuits over multiple spatial and temporal scales.
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            Fast and Easy Multiresidue Method Employing Acetonitrile Extraction/Partitioning and “Dispersive Solid-Phase Extraction” for the Determination of Pesticide Residues in Produce

            A simple, fast, and inexpensive method for the determination of pesticide residues in fruits and vegetables is introduced. The procedure involves initial single-phase extraction of 10 g sample with 10 mL acetonitrile, followed by liquid–liquid partitioning formed by addition of 4 g anhydrous MgSO4 plus 1 g NaCl. Removal of residual water and cleanup are performed simultaneously by using a rapid procedure called dispersive solid-phase extraction (dispersive-SPE), in which 150 mg anhydrous MgSO4 and 25 mg primary secondary amine (PSA) sorbent are simply mixed with 1 mL acetonitrile extract. The dispersive-SPE with PSA effectively removes many polar matrix components, such as organic acids, certain polar pigments, and sugars, to some extent from the food extracts. Gas chromatography/mass spectrometry (GC/MS) is then used for quantitative and confirmatory analysis of GC-amenable pesticides. Recoveries between 85 and 101% (mostly >95%) and repeatabilities typically <5% have been achieved for a wide range of fortified pesticides, including very polar and basic compounds such as methamidophos, acephate, omethoate, imazalil, and thiabendazole. Using this method, a single chemist can prepare a batch of 6 previously chopped samples in <30 min with approximately $1 (U.S.) of materials per sample.
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              A Drosophila mechanosensory transduction channel.

              Mechanosensory transduction underlies a wide range of senses, including proprioception, touch, balance, and hearing. The pivotal element of these senses is a mechanically gated ion channel that transduces sound, pressure, or movement into changes in excitability of specialized sensory cells. Despite the prevalence of mechanosensory systems, little is known about the molecular nature of the transduction channels. To identify such a channel, we analyzed Drosophila melanogaster mechanoreceptive mutants for defects in mechanosensory physiology. Loss-of-function mutations in the no mechanoreceptor potential C (nompC) gene virtually abolished mechanosensory signaling. nompC encodes a new ion channel that is essential for mechanosensory transduction. As expected for a transduction channel, D. melanogaster NOMPC and a Caenorhabditis elegans homolog were selectively expressed in mechanosensory organs.
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                Author and article information

                Contributors
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                Journal
                Pest Management Science
                Pest Management Science
                Wiley
                1526-498X
                1526-4998
                May 2023
                March 2023
                May 2023
                : 79
                : 5
                : 1635-1649
                Affiliations
                [1 ] Department of Cellular Neurobiology University of Göttingen Göttingen Germany
                [2 ] BASF Corp Research Triangle Park NC USA
                Article
                10.1002/ps.7352
                36622360
                0d2e3a02-3b5b-452d-844a-d83854149eb9
                © 2023

                http://creativecommons.org/licenses/by-nc-nd/4.0/

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