36 research outputs found

    A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila

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    Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol

    Transmembrane solute transport in the apicomplexan parasite Plasmodium

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    Apicomplexa are a large group of eukaryotic, single-celled parasites, with complex life cycles that occur within a wide range of different microenvironments. They include important human pathogens such as Plasmodium, the causal agent of malaria, and Toxoplasma, which causes toxoplasmosis most often in immunocompromised individuals. Despite environmental differences in their life cycles, these parasites retain the ability to obtain nutrients, remove waste products, and control ion balances. They achieve this flexibility by relying on proteins that can deliver and remove solutes. This reliance on transport proteins for essential functions makes these pathways excellent potential targets for drug development programmes. Transport proteins are frequently key mediators of drug resistance by their ability to remove drugs from their sites of action. The study of transport processes mediated by integral membrane proteins and, in particular, identification of their physiological functions and localisation, and differentiation from host orthologues has already established new validated drug targets. Our understanding of how apicomplexan parasites have adapted to changing environmental challenges has also increased through the study of their transporters. This brief introduction to membrane transporters of apicomplexans highlights recent discoveries focusing on Plasmodium and emphasises future directions

    Non-nociceptive roles of opioids in the CNS: opioids' effects on neurogenesis, learning, memory and affect.

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    Mortality due to opioid use has grown to the point where, for the first time in history, opioid-related deaths exceed those caused by car accidents in many states in the United States. Changes in the prescribing of opioids for pain and the illicit use of fentanyl (and derivatives) have contributed to the current epidemic. Less known is the impact of opioids on hippocampal neurogenesis, the functional manipulation of which may improve the deleterious effects of opioid use. We provide new insights into how the dysregulation of neurogenesis by opioids can modify learning and affect, mood and emotions, processes that have been well accepted to motivate addictive behaviours

    Non-Stabilized Vinyl Anion Equivalents from Styrenes by N-Heterocyclic Carbene Catalysis and Its Use in Catalytic Nucleophilic Aromatic Substitution

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    A protocol for the catalytic nucleophilic activation of unactivated styrenes is reported, which enables the generation of a non-stabilized alkenyl anion equivalent as a transient intermediate. In the reaction, N-heterocyclic carbenes add across styrenes to generate ylide intermediates, which can then be used in intramolecular nucleophilic aromatic substitution reactions of aryl fluorides, chlorides, and methyl ethers. The method allows for straightforward access to complex polyaromatic compounds.Ito S., Fujimoto H., Tobisu M.. Non-Stabilized Vinyl Anion Equivalents from Styrenes by N-Heterocyclic Carbene Catalysis and Its Use in Catalytic Nucleophilic Aromatic Substitution. Journal of the American Chemical Society, 144, 15, 6714-6718, April 11, 2022. © 2022 American Chemical Society. https://doi.org/10.1021/jacs.2c02579

    A Much Faster Algorithm for Finding a Maximum Clique with Computational Experiments

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    Chewing Lice Found on Captive Tufted Puffin, Fratercula cirrhata

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    During the postmortem of tufted puffin chicks (Fratercula cirrhata), who died a few days after hatching in the aquarium, a large number of chewing lice were collected. These lice were identified as Quadraceps helgovauki (Philopteridae) based on morphological caracteristics. This is the first record of Q. helgovauki from F. cirrhata and in Japan.国内水族館で飼育され、孵化後3日で死亡したエトピリカ(Fratercula cirrhata)のヒナの剖検において、多数のハジラミ類が採集された。ハジラミは形態学的にニシツノメドリから報告のある Quadraceps helgovaukiと同定された。本種はエトピリカから初めて記録され、また国内初記録であった

    Association of CYP2D6 polymorphisms and extrapyramidal symptoms in schizophrenia patients receiving risperidone: a retrospective study

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    Abstract Background Risperidone is mainly metabolized by cytochrome P450 (CYP) 2D6 in the liver. The gene encoding CYP2D6 is highly polymorphic. The average steady-state plasma concentration of risperidone active moiety is higher in the CYP2D6 intermediate metabolizers (IMs) compared with that in the extensive metabolizers (EMs). An association between drug-induced extrapyramidal symptoms scale (DIEPSS) score and CYP2D6 polymorphisms has not been reported to date. This study investigates the association of CYP2D6 polymorphisms with the severity of extrapyramidal symptoms in schizophrenia patients receiving risperidone therapy. Methods Schizophrenia patients undergoing risperidone treatment were recruited for the study in the Kobe University Hospital. We evaluated extrapyramidal symptoms of schizophrenia using the DIEPSS. CYP2D6*10 and CYP2D6*14 were analyzed using TaqMan® assays, and CYP2D6*5 was analyzed using the long-PCR method. Patients with CYP2D6*1/*5, *1/*14, *5/*10, *10/*10, and *10/*14 were classified as IMs, and patients with CYP2D6*1/*1 and *1/*10 were classified as EMs. Patients with CYP2D6*5/*5, *5/*14, and *14/*14 were classified as poor metabolizers (PMs). Results A total of 22 patients were included in the study. No patients were classified as PMs. The dose of risperidone (mg/day) was not significantly different between EMs (n = 15) and IMs (n = 7) (median with the interquartile range: 4.0 (2.0–6.0) vs. 4.0 (2.0–7.0) mg, p = 0.31). The age and disease duration of schizophrenia were not significantly different between the EMs and IMs. The DIEPSS score in the IMs was significantly higher than that in the EMs (median with the interquartile range: 5.0 (3.5–6.5) vs. 0.0 (0.0–3.0), p < 0.001). The multiple regression analysis showed that CYP2D6 IMs is a significant risk factor for the DIEPSS (p < 0.05). Conclusion Special attentions should be paid to the onset of extrapyramidal symptoms in schizophrenia patients identified as CYP2D6 IM undergoing risperidone therapy