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Pierisin is a DNA-targeting ADP-ribosyltransferase found in cabbage white butterfly (Pieris rapae). Pierisin transfers an ADP-ribosyl moiety to the 2-amino group of the guanine residue in DNA, yielding N2-(ADP-ribos-1-yl)-2'-deoxyguanosine (N2-ADPR-dG). Generally, such chemically modified DNA is recognized as DNA damage and elicits cellular responses, including DNA repair pathways. In Escherichia coli and human cells, it has been experimentally demonstrated that N2-ADPR-dG is a substrate of the nucleotide excision repair system. Although DNA repair machineries can remove most lesions, some unrepaired damages frequently lead to mutagenesis through DNA replication. Replication past the damaged DNA template is called translesion DNA synthesis (TLS). In vitro primer extension experiments have shown that eukaryotic DNA polymerase κ is involved in TLS across N2-ADPR-dG. In many cases, TLS is error-prone and thus a mutagenic process. Indeed, the induction of G:C to T:A and G:C to C:G mutations by N2-ADPR-dG in the hypoxanthine phosphoribosyltransferase gene mutation assay with Chinese hamster cells and supF shuttle vector plasmids assay using human fibroblasts has been reported. This review provides a detailed overview of DNA repair, TLS and mutagenesis of N2-ADPR-dG induced by cabbage butterfly pierisin-1.
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Reparo do DNA , DNA , Mutagênese , Animais , Humanos , DNA/genética , ADP Ribose Transferases/genética , ADP Ribose Transferases/metabolismo , Dano ao DNA , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Borboletas/genética , Borboletas/enzimologiaRESUMO
RATIONALE: Pyogenic spondylodiscitis is an infectious spinal disease that causes significant motor dysfunctions. Its diagnosis can be challenging owing to its rapid onset and nonspecific symptoms. PATIENT CONCERNS: A 79-year-old Japanese man with a history of type 2 diabetes mellitus and polymyalgia rheumatica presented to our department with tongue pain. Following partial glossectomy and wisdom tooth extraction under general anesthesia, on 10 postoperative day (POD) the patient developed right-sided abdominal pain and difficulty in walking. On 12 POD, the patient was admitted to a municipal hospital due to respiratory distress and paraplegia. DIAGNOSES: The patient was diagnosed with pyogenic spondylodiscitis and empyema. Blood tests revealed elevated C-reactive protein levels (36.5), white blood cell count (19,570), and neutrophil count (17,867). INTERVENTIONS: The patient received meropenem hydrate 3 g/2 days as empiric antibiotic treatment for acute infection. Upon admission to the emergency department on 16 POD, the lung abscess was drained, hemilaminectomy was performed. OUTCOMES: Blood cultures, sputum tests, and cultures from the thoracic and spinal abscesses drained during surgery revealed methicillin-sensitive Staphylococcus aureus. The infection was successfully managed, and the respiratory disturbance and inflammatory response improved. However, the lower half of the patient body remained paralyzed. Subsequently, the patient was transferred to a rehabilitation facility on 45 POD. The patient continued to undergo functional restoration training, gradually regained function, and eventually achieved the ability to walk with grasping gait. LESSONS: This is the first case report of S aureus causing pyogenic spondylodiscitis and empyema due to blood stream infection from a post-oral surgical wound. Pyogenic spondylodiscitis arising from a secondary hematogenous infection is difficult to diagnose and can lead to severe functional impairment. Prompt and appropriate diagnosis and treatment based on detailed patient interviews, additional blood tests, and computed tomography are essential.
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Discite , Neoplasias da Língua , Extração Dentária , Humanos , Masculino , Idoso , Extração Dentária/efeitos adversos , Discite/diagnóstico , Discite/microbiologia , Discite/etiologia , Neoplasias da Língua/cirurgia , Dente Serotino/cirurgia , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/etiologia , Empiema/etiologia , Empiema/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/microbiologia , Antibacterianos/uso terapêuticoRESUMO
Recent studies have shown a role of inflammation in muscle atrophy and sarcopenia. However, no anti-inflammatory pharmacotherapy has been established for the treatment of sarcopenia. Here, we investigate the potential role of PPARα and its ligands on inflammatory response and PGC-1α gene expression in LPS-treated C2C12 myotubes. Knockdown of PPARα, whose expression was upregulated upon differentiation, augmented IL-6 or TNFα gene expression. Conversely, PPARα overexpression or its activation by ligands suppressed 2-h LPS-induced cytokine expression, with pemafibrate attenuating NF-κB or STAT3 phosphorylation. Of note, reduction of PGC-1α gene expression by LPS treatment for 24 hours was partially reversed by fenofibrate. Our data demonstrate a critical inhibitory role of PPARα in inflammatory response of C2C12 myotubes and suggest a future possibility of PPARα ligands as a candidate for anti-inflammatory therapy against sarcopenia.
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PPAR alfa , Sarcopenia , Anti-Inflamatórios/metabolismo , Lipopolissacarídeos/metabolismo , Fibras Musculares Esqueléticas/metabolismo , NF-kappa B/metabolismo , PPAR alfa/metabolismo , Sarcopenia/metabolismo , Animais , CamundongosRESUMO
Hydropersulfide and hydropolysulfide metabolites are increasingly important reactive sulfur species (RSS) regulating numerous cellular redox dependent functions. Intracellular production of these species is known to occur through RSS interactions or through translational mechanisms involving cysteinyl t-RNA synthetases. However, regulation of these species under cell stress conditions, such as hypoxia, that are known to modulate RSS remain poorly understood. Here we define an important mechanism of increased persulfide and polysulfide production involving cystathionine gamma lyase (CSE) phosphorylation at serine 346 and threonine 355 in a substrate specific manner, under acute hypoxic conditions. Hypoxic phosphorylation of CSE occurs in an AMP kinase dependent manner increasing enzyme activity involving unique inter- and intramolecular interactions within the tetramer. Importantly, both cellular hypoxia and tissue ischemia result in AMP Kinase dependent CSE phosphorylation that regulates blood flow in ischemic tissues. Our findings reveal hypoxia molecular signaling pathways regulating CSE dependent persulfide and polysulfide production impacting tissue and cellular response to stress.
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Sulfeto de Hidrogênio , Humanos , Sulfeto de Hidrogênio/metabolismo , Fosforilação , Adenilato Quinase/metabolismo , Cistationina gama-Liase/genética , HipóxiaRESUMO
Transition metal dichalcogenide (TMDC) nanotubes exhibit unique physical properties due to their nanotube structures. The development of techniques for synthesizing TMDC nanotubes with controlled structures is very important for their science and applications. However, structural control efforts have been made only for the homostructures of TMDC nanotubes and not for their heterostructures that provide an important platform for their two-dimensional counterparts. In this study, we synthesized heterostructures of TMDC nanotubes, MoS2/WS2 heteronanotubes, and demonstrated a technique for controlling features of their structures, such as diameters, layer numbers, and crystallinity. The diameter of the heteronanotubes could be tuned with inner nanotube templates and was reduced by using small-diameter WS2 nanotubes. The layer number and crystallinity of the MoS2 outer wall could be controlled by controlling their precursors and synthesis temperatures, resulting in the formation of high-crystallinity TMDC heteronanotubes with specific chirality. This study can expand the research of van der Waals heterostructures.
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Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes are interacting comorbidities of obesity, and increased hepatic de novo lipogenesis (DNL), driven by hyperinsulinemia and carbohydrate overload, contributes to their pathogenesis. Fatty acid synthase (FASN), a key enzyme of hepatic DNL, is upregulated in association with insulin resistance. However, the therapeutic potential of targeting FASN in hepatocytes for obesity-associated metabolic diseases is unknown. Here, we show that hepatic FASN deficiency differentially affects NAFLD and diabetes depending on the etiology of obesity. Hepatocyte-specific ablation of FASN ameliorated NAFLD and diabetes in melanocortin 4 receptor-deficient mice but not in mice with diet-induced obesity. In leptin-deficient mice, FASN ablation alleviated hepatic steatosis and improved glucose tolerance but exacerbated fed hyperglycemia and liver dysfunction. The beneficial effects of hepatic FASN deficiency on NAFLD and glucose metabolism were associated with suppression of DNL and attenuation of gluconeogenesis and fatty acid oxidation, respectively. The exacerbation of fed hyperglycemia by FASN ablation in leptin-deficient mice appeared attributable to impairment of hepatic glucose uptake triggered by glycogen accumulation and citrate-mediated inhibition of glycolysis. Further investigation of the therapeutic potential of hepatic FASN inhibition for NAFLD and diabetes in humans should thus consider the etiology of obesity.
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Diabetes Mellitus Tipo 2 , Hiperglicemia , Hepatopatia Gordurosa não Alcoólica , Animais , Humanos , Camundongos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Ácido Graxo Sintase Tipo I/genética , Ácido Graxo Sintases , Hiperglicemia/complicações , Leptina , Óxido Nítrico Sintase , Obesidade/complicações , Obesidade/genéticaRESUMO
OBJECTIVE: This study aimed to analyze the clinical characteristics, treatment strategies, and surgical outcomes of subependymoma patients from the 2022 Neurospinal Society of Japan multicenter intramedullary spinal cord tumor study. METHODS: Twenty-six patients with spinal cord subependymoma who were included in the index study of 1,033 patients were retrospectively analyzed. RESULTS: Mean patient age was 49.4 years. Seventeen patients were men and 9 were women. Sensory disturbance was reported in 22 patients and motor weakness in 18. Median duration of symptoms was 24 months. The tumor was eccentrically located in 19 patients (73.1%) and unilateral in 17 (65.4%). Gross total resection was achieved in 6 patients (23.1%). The same rate for ependymoma patients in the index study was significantly higher (74.8%). Median follow-up was 40.5 months (interquartile range, 18-68 months). In 2 patients who underwent only partial resection, reoperation was required owing to progression 68 and 90 months after surgery, respectively. No recurrence occurred in patients who underwent gross total resection. Five patients experienced neurological worsening after surgery. CONCLUSION: Although spinal cord subependymoma can be difficult to distinguish from other intramedullary spinal cord lesions before surgery, it is characterized by an indolent clinical course and eccentric location. Surgical treatment should prioritize functional preservation because the prognosis is good even after subtotal resection.
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BACKGROUND: Intraspinal juxta-facet cysts of the spine are known to predominate at the lumbar level and is relatively rare at the cervical level. Most cervical spinal lesions are found incidentally, but they sometimes cause myelopathy or radiculopathy in a chronic course. OBSERVATIONS: The authors present a rare case of hemorrhagic cervical juxta-facet cyst presenting with Brown-Séquard syndrome. An 86-year-old woman presented with acute-onset right hemiparesis following neck pain and was admitted to the local hospital. She was started on antithrombotic therapy with a suspected diagnosis of cerebral infarction, but quadriplegia progressed 2 days later. Cervical magnetic resonance imaging revealed an intraspinal mass at the C4-5 level and she was referred to the authors' hospital. Her neurological findings on admission revealed right Brown-Séquard syndrome. In emergency surgery, the mass was resected with a posterior approach. Pathological findings showed hemosiderin deposition and fibroblast proliferation, consistent with a juxta-facet cyst with intracystic hemorrhage. The patient recovered well and returned to an independent daily life. LESSONS: Rarely, juxta-facet cyst of the cervical spine can cause acute Brown-Séquard syndrome due to intraspinal hemorrhage. In a case of hemiparesis that develops following neck pain, hemorrhagic cervical juxta-facet cyst should be taken into consideration as a differentiation.
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Endocrine-disrupting chemicals (EDCs) often affect homeostatic regulation in living organisms by directly acting on nuclear receptors (NRs). Retinoid X receptors (RXRs), the most highly conserved members of the NR superfamily during evolution, function as partners to form heterodimers with other NRs, such as retinoic acid, thyroid hormone, and vitamin D3 receptors. RXRs also homodimerize and induce the expression of target genes upon binding with their natural ligand, 9-cis-retinoic acid (9cRA), and typical EDCs organotin compounds, such as tributyltin and triphenyltin. In the present study, we established a new yeast reporter gene assay (RGA) to detect the ligands of freshwater cladoceran Daphnia magna ultraspiracle (Dapma-USP), a homolog of vertebrate RXRs. D. magna has been used as a representative crustacean species for aquatic EDC assessments in the Organization for Economic Corporation and Development test guidelines. Dapma-USP was expressed along with the Drosophila melanogaster steroid receptor coactivator Taiman in yeast cells carrying the lacZ reporter plasmid. The RGA for detecting agonist activity of organotins and o-butylphenol was improved by use of mutant yeast strains lacking genes encoding cell wall mannoproteins and/or plasma membrane drug efflux pumps as hosts. We also showed that a number of other human RXR ligands, phenol and bisphenol A derivatives, and terpenoid compounds such as 9c-RA exhibited antagonist activity on Dapma-USP. Our newly established yeast-based RGA system is valuable as the first screening tool to detect ligand substances for Dapma-USP and for evaluating the evolutionary divergence of the ligand responses of RXR homologs between humans and D. magna.
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Daphnia , Saccharomyces cerevisiae , Animais , Humanos , Receptores X de Retinoides/genética , Receptores X de Retinoides/metabolismo , Ligantes , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Genes Reporter , Daphnia/genética , Daphnia/metabolismo , Drosophila melanogaster/genética , Vertebrados/genética , Vertebrados/metabolismoRESUMO
Transverse thermoelectric generation using magnetic materials is essential to develop active thermal engineering technologies, for which the improvements of not only the thermoelectric output but also applicability and versatility are required. In this study, using combinatorial material science and lock-in thermography technique, we have systematically investigated the transverse thermoelectric performance of Sm-Co-based alloy films. The high-throughput material investigation revealed the best Sm-Co-based alloys with the large anomalous Nernst effect (ANE) as well as the anomalous Ettingshausen effect (AEE). In addition to ANE/AEE, we discovered unique and superior material properties in these alloys: the amorphous structure, low thermal conductivity, and large in-plane coercivity and remanent magnetization. These properties make it advantageous over conventional materials to realize heat flux sensing applications based on ANE, as our Sm-Co-based films can generate thermoelectric output without an external magnetic field. Importantly, the amorphous nature enables the fabrication of these films on various substrates including flexible sheets, making the large-scale and low-cost manufacturing easier. Our demonstration will provide a pathway to develop flexible transverse thermoelectric devices for smart thermal management.
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Ecdysone agonists are a class of insecticides that activate the ecdysone receptor (EcR) heterodimerized with the ultraspiracle (USP). Here, we report a new luciferase reporter assay for ecdysone agonists. The assay employs mammalian HEK293T cells transiently transfected with the EcR and USP genes of Chilo suppressalis, along with the taiman (Tai) gene of Drosophila melanogaster that encodes a steroid receptor coactivator. This assay system gave results consistent with those of radioligand binding assays and showed sensitivity superior to that of the existing in vitro methods. In addition, use of the heterologous host cells precludes perturbation from intrinsic players of the ecdysone signaling, which is a potential drawback of insect cell-based methods. This reporter system is suitable for detailed structure-activity analysis of ecdysone agonists and will serve as a valuable tool for the rational design of novel insect growth regulators.
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Proteínas de Drosophila , Inseticidas , Receptores de Esteroides , Animais , Humanos , Ecdisona/farmacologia , Ecdisona/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Células HEK293 , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Luciferases/genética , Hormônios Juvenis , Mamíferos/metabolismoAssuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Inibidores do Transportador 2 de Sódio-Glicose , Canagliflozina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Hipoglicemiantes , Transportador 2 de Glucose-Sódio , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Remodelação VascularRESUMO
BACKGROUND: Spinal glomus arteriovenous malformations (AVMs) are rare and can cause neurological morbidity due to spinal hemorrhage, venous hypertension, or mass effect. OBSERVATIONS: The authors presented a rare case of spinal glomus AVM presenting with groin pain due to nerve root compression by a feeder aneurysm. A 41-year-old woman was referred to the hospital with initial right groin pain that had worsened over 2 months. Magnetic resonance imaging showed intra- and extramedullary abnormal flow voids at the T11-12 level, and spinal angiography revealed an intramedullary AVM, with extramedullary protrusion of an aneurysm on the feeder vessel, which arose from the sulcal artery of the anterior spinal artery. Because compression of the right L1 nerve root by the aneurysm was the likely cause of the patient's pain, endovascular embolization was performed. The feeder aneurysm disappeared after partial n-butyl 2-cyanoacrylate embolization, and the groin pain disappeared immediately after treatment. Her clinical status has been stable with no recurrence during 1 year of follow-up. LESSONS: This is the first report of glomus-type AVM presenting with radiculopathy alone. One should not overlook the possibility of spinal AVM among patients with groin pain.
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A 34-year-old man visited our Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, because of dry mouth and weight loss. His plasma glucose level was 32.8 mmol/L and serum levels of ketone bodies were increased, but with metabolic alkalemia. He was also suffering from renal tubular hypomagnesemia and hypokalemia. Abdominal computed tomography showed bilateral renal cysts. These findings were suggestive of maturity-onset diabetes of the young type 5. Genetic testing showed heterozygous hepatocyte nuclear factor 1 beta gene deletion. In the present case, it seemed reasonable to view hepatocyte nuclear factor 1 beta gene deletion as the common cause of maturity-onset diabetes of the young type 5-associated diabetic ketoacidosis and tubular malfunction-induced hypokalemic alkalosis. This case exemplifies the importance of hepatocyte nuclear factor 1 beta gene abnormality as a potential cause of diabetic ketoacidosis with alkalemia.
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Alcalose , Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Adulto , Diabetes Mellitus Tipo 2/genética , Cetoacidose Diabética/complicações , Cetoacidose Diabética/diagnóstico , Fator 1-beta Nuclear de Hepatócito/genética , Humanos , MasculinoRESUMO
Smoking cessation increases body weight. The underlying mechanisms, however, have not been fully understood. We here report an establishment of a mouse model that exhibits an augmented body weight gain after nicotine withdrawal. High fat diet-fed mice were infused with nicotine for two weeks, and then with vehicle for another two weeks using osmotic minipumps. Body weight increased immediately after nicotine cessation and was significantly higher than that of mice continued on nicotine. Mice switched to vehicle consumed more food than nicotine-continued mice during the first week of cessation, while oxygen consumption was comparable. Elevated expression of orexigenic agouti-related peptide was observed in the hypothalamic appetite center. Pair-feeding experiment revealed that the accelerated weight gain after nicotine withdrawal is explained by enhanced energy intake. As a showcase of an efficacy of pharmacologic intervention, exendin-4 was administered and showed a potent suppression of energy intake and weight gain in mice withdrawn from nicotine. Our current model provides a unique platform for the investigation of the changes of energy regulation after smoking cessation.
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Nicotina/efeitos adversos , Síndrome de Abstinência a Substâncias/patologia , Aumento de Peso , Proteína Relacionada com Agouti/metabolismo , Animais , Calorimetria , Respiração Celular/efeitos dos fármacos , Modelos Animais de Doenças , Ingestão de Energia/efeitos dos fármacos , Exenatida/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Síndrome de Abstinência a Substâncias/genética , Aumento de Peso/efeitos dos fármacos , Aumento de Peso/genéticaRESUMO
A comprehensive understanding of the roles of various nanointerfaces in thermal transport is of critical significance but remains challenging. A two-dimensional van der Waals (vdW) heterostructure with tunable interface lattice mismatch provides an ideal platform to explore the correlation between thermal properties and nanointerfaces and achieve controllable tuning of heat flow. Here, we demonstrate that interfacial engineering is an efficient strategy to tune thermal transport via systematic investigation of the thermal conductance (G) across a series of large-area four-layer stacked vdW materials using an improved polyethylene glycol-assisted time-domain thermoreflectance method. Owing to its rich interfacial mismatch and weak interfacial coupling, the vertically stacked MoSe2-MoS2-MoSe2-MoS2 heterostructure demonstrates the lowest G of 1.5 MW m-2 K-1 among all vdW structures. A roadmap to tune G via homointerfacial mismatch, interfacial coupling, and heterointerfacial mismatch is further demonstrated for thermal tuning. Our work reveals the roles of various interfacial effects on heat flow and highlights the importance of the interfacial mismatch and coupling effects in thermal transport. The design principle is also promising for application in other areas, such as the electrical tuning of energy storage and conversion and the thermoelectricity tuning of thermoelectronics.
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Juvenile hormones (JHs) are sesquiterpenoids that play important roles in the regulation of growth, metamorphosis, and reproduction in insects. Synthetic JH agonists (JHAs) have been used as insecticides and are categorized as a class of insect growth regulators (IGRs). Natural JHs and synthetic JHAs bind to the JH receptor methoprene-tolerant (Met), which forms a functional JH-receptor complex with steroid receptor coactivators, such as Drosophila melanogaster Taiman (Tai). The ligand-bound Met-Tai complex induces the transcription of JH response genes by binding to specific DNA elements referred to as JH response elements (JHREs). In the present study, we established a reporter gene assay (RGA) for detecting natural JHs and synthetic JHAs in a yeast strain expressing D. melanogaster Met and Tai. The yeast RGA system detected various juvenoid ligands in a dose-dependent manner. The rank order of the ligand potencies of the juvenoids examined in the yeast RGA linearly correlated with those of RGAs for Met-Tai established in mammalian and insect cells. Our new yeast RGA is rapid, easy to handle, cost-effective, and valuable for screening novel JHAs.
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Hormônios Juvenis , Metoprene , Animais , Drosophila/genética , Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Genes Reporter , Hormônios Juvenis/agonistas , Hormônios Juvenis/genética , Mamíferos/genética , Metoprene/metabolismo , Metoprene/farmacologia , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismoRESUMO
A reporter gene assay (RGA) is used to investigate the activity of synthetic chemicals mimicking the molting hormones (MHs) and juvenile hormones (JHs) of insects, so-called insect growth regulators (IGRs). The MH receptor, a heterodimer of the ecdysone receptor (EcR) and ultraspiracle (USP), and the JH receptor Methoprene-tolerant (Met) are ligand-dependent transcription factors. Ligand-bound EcR-USP and Met bind to specific cis-acting DNA elements, referred to as the ecdysone-responsive element (EcRE) and the JH-responsive element (JHRE), respectively, in order to transactivate target genes. Insect hormone-induced transactivation systems have been reconstituted by the introduction of reporter genes under the control of EcRE and JHRE, or two-hybrid reporter genes, into insect, mammalian, and yeast cells expressing receptor proteins. RGA is easy to use and convenient for examining the MH- and JH-like activities of synthetic chemicals and is suitable for the high-throughput screening of novel structural classes of chemicals targeting EcR-USP and Met.
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Juvenile hormone (JH) agonists constitute a subclass of insect growth regulators and play important roles in insect pest management. In this work, a multi-step virtual screening program was executed to find novel JH agonists. A database of 5 million purchasable compounds was sequentially processed with three computational filters: (i) shape and chemical similarity as compared to known JH-active compounds; (ii) molecular docking simulations against a Drosophila JH receptor, methoprene-tolerant; and (iii) free energy calculation of ligand-receptor binding using a modified MM/PBSA (molecular mechanics/Poisson-Boltzmann surface area) protocol. The 11 candidates that passed the three filters were evaluated in a luciferase reporter assay, leading to the identification of a hit compound that contains a piperazine ring system (EC50=870 nM). This compound is structurally dissimilar to known JH agonists and synthetically easy to access; therefore, it is a promising starting point for further structure optimization.
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Biologists have reported on the chemical defences and the phenetic similarity of net-winged beetles (Coleoptera: Lycidae) and their co-mimics. Nevertheless, our knowledge has remained fragmental, and the evolution of mimetic patterns has not been studied in the phylogenetic context. We illustrate the general appearance of ~ 600 lycid species and ~ 200 co-mimics and their distribution. Further, we assemble the phylogeny using the transcriptomic backbone and ~ 570 species. Using phylogenetic information, we closely scrutinise the relationships among aposematically coloured species, the worldwide diversity, and the distribution of aposematic patterns. The emitted visual signals differ in conspicuousness. The uniform coloured dorsum is ancestral and was followed by the evolution of bicoloured forms. The mottled patterns, i.e. fasciate, striate, punctate, and reticulate, originated later in the course of evolution. The highest number of sympatrically occurring patterns was recovered in New Guinea and the Andean mountain ecosystems (the areas of the highest abundance), and in continental South East Asia (an area of moderate abundance but high in phylogenetic diversity). Consequently, a large number of co-existing aposematic patterns in a single region and/or locality is the rule, in contrast with the theoretical prediction, and predators do not face a simple model-like choice but cope with complex mimetic communities. Lycids display an ancestral aposematic signal even though they sympatrically occur with differently coloured unprofitable relatives. We show that the highly conspicuous patterns evolve within communities predominantly formed by less conspicuous Müllerian mimics and, and often only a single species displays a novel pattern. Our work is a forerunner to the detailed research into the aposematic signalling of net-winged beetles.