RESUMO
The radiation-based sterile insect technique (SIT) has successfully suppressed field populations of several insect pest species, but its effect on mosquito vector control has been limited. The related incompatible insect technique (IIT)-which uses sterilization caused by the maternally inherited endosymbiotic bacteria Wolbachia-is a promising alternative, but can be undermined by accidental release of females infected with the same Wolbachia strain as the released males. Here we show that combining incompatible and sterile insect techniques (IIT-SIT) enables near elimination of field populations of the world's most invasive mosquito species, Aedes albopictus. Millions of factory-reared adult males with an artificial triple-Wolbachia infection were released, with prior pupal irradiation of the released mosquitoes to prevent unintentionally released triply infected females from successfully reproducing in the field. This successful field trial demonstrates the feasibility of area-wide application of combined IIT-SIT for mosquito vector control.
Assuntos
Aedes/microbiologia , Aedes/fisiologia , Controle de Mosquitos/métodos , Mosquitos Vetores/microbiologia , Mosquitos Vetores/fisiologia , Wolbachia/patogenicidade , Aedes/crescimento & desenvolvimento , Animais , China , Copulação , Estudos de Viabilidade , Feminino , Humanos , Mordeduras e Picadas de Insetos/prevenção & controle , Larva/crescimento & desenvolvimento , Larva/microbiologia , Larva/fisiologia , Masculino , Mosquitos Vetores/crescimento & desenvolvimento , Controle de Qualidade , ReproduçãoRESUMO
Liver kinase B1 (LKB1) has important roles in governing energy homeostasis by regulating the activity of the energy sensor kinase AMP-activated protein kinase (AMPK). The regulation of LKB1 function, however, is still poorly understood. Here we demonstrate that the orphan nuclear receptor Nur77 binds and sequesters LKB1 in the nucleus, thereby attenuating AMPK activation. This Nur77 function is antagonized by the chemical compound ethyl 2-[2,3,4-trimethoxy-6-(1-octanoyl)phenyl]acetate (TMPA), which interacts with Nur77 with high affinity and at specific sites. TMPA binding of Nur77 results in the release and shuttling of LKB1 to the cytoplasm to phosphorylate AMPKα. Moreover, TMPA effectively reduces blood glucose and alleviates insulin resistance in type II db/db and high-fat diet- and streptozotocin-induced diabetic mice but not in diabetic littermates with the Nur77 gene knocked out. This study attains a mechanistic understanding of the regulation of LKB1-AMPK axis and implicates Nur77 as a new and amenable target for the design and development of therapeutics to treat metabolic diseases.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Fenilacetatos/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Quinases Proteína-Quinases Ativadas por AMP , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Animais , Glicemia/efeitos dos fármacos , Células Cultivadas , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Ativação Enzimática/efeitos dos fármacos , Células HEK293 , Humanos , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Modelos Moleculares , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/antagonistas & inibidores , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Fenilacetatos/química , Fosforilação/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Transporte Proteico/efeitos dos fármacos , Estreptozocina , Relação Estrutura-AtividadeRESUMO
Six analogous dumbbell-shaped 3d-4f complexes MLn were obtained by the reaction of Ln(NO3)3 (Ln = Eu, Gd, Dy) and M(OAc)2 (M = Co, Ni) without any other organic ligands, and M5Gd4 exhibited a large magnetocaloric effect (-ΔSm = 31.0, 37.3 J kg-1 K-1 for Co5Gd4 and Ni5Gd4 respectively), while M5Dy4 and Co5Eu4 showed single molecule magnet behaviour. To the best of our knowledge, Co5Eu4 is the first Eu-based cluster to display single molecule magnet behaviour (Ueff = 16.4 K).