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1.
Artigo em Inglês | MEDLINE | ID: mdl-31311717

RESUMO

BACKGROUND: Conduct disorder (CD), which is characterized by severe aggressive and antisocial behavior, is linked to emotion processing and regulation deficits. However, the neural correlates of emotion regulation are yet to be investigated in adolescents with CD. Furthermore, it remains unclear whether CD is associated with deficits in emotional reactivity, emotion regulation, or both. METHODS: We used functional magnetic resonance imaging to study effortful emotion regulation by cognitive reappraisal in 59 female adolescents 15 to 18 years of age (30 with a CD diagnosis and 29 typically developing (TD) control adolescents). RESULTS: Behaviorally, in-scanner self-report ratings confirmed successful emotion regulation within each group individually but significant group differences in emotional reactivity and reappraisal success when comparing the groups (CD < TD). Functional magnetic resonance imaging results revealed significantly lower activation in left dorsolateral prefrontal cortex and angular gyrus in CD compared with TD adolescents during emotion regulation, but no group differences for emotional reactivity. Furthermore, connectivity between left dorsolateral prefrontal cortex and the bilateral putamen, right prefrontal cortex, and amygdala was reduced in CD compared with TD adolescents during reappraisal. Callous-unemotional traits were unrelated to neural activation, but these traits correlated negatively with behavioral reports of emotional reactivity. CONCLUSIONS: Our results demonstrate reduced prefrontal brain activity and functional connectivity during effortful emotion regulation in female adolescents with CD. This sheds light on the neural basis of the behavioral deficits that have been reported previously. Future studies should investigate whether cognitive interventions are effective in enhancing emotion-regulation abilities and/or normalizing prefrontal and temporoparietal activity in female adolescents with CD.


Assuntos
Transtorno da Conduta/fisiopatologia , Conectoma , Regulação Emocional/fisiologia , Córtex Pré-Frontal/fisiopatologia , Adolescente , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiopatologia , Transtorno da Conduta/diagnóstico por imagem , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Lobo Occipital/diagnóstico por imagem , Lobo Occipital/fisiopatologia , Córtex Pré-Frontal/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Tálamo/fisiopatologia
2.
Peptides ; 38(1): 22-32, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22922160

RESUMO

Ureases (EC 3.5.1.5) are metalloenzymes that hydrolyze urea into ammonia and CO(2). These proteins have insecticidal and fungicidal effects not related to their enzymatic activity. The insecticidal activity of urease is mostly dependent on the release of internal peptides after hydrolysis by insect digestive cathepsins. Jaburetox is a recombinant version of one of these peptides, expressed in Escherichia coli. The antifungal activity of ureases in filamentous fungi occurs at submicromolar doses, with damage to the cell membranes. Here we evaluated the toxic effect of Canavalia ensiformis urease (JBU) on different yeast species and carried out studies aiming to identify antifungal domain(s) of JBU. Data showed that toxicity of JBU varied according to the genus and species of yeasts, causing inhibition of proliferation, induction of morphological alterations with formation of pseudohyphae, changes in the transport of H(+) and carbohydrate metabolism, and permeabilization of membranes, which eventually lead to cell death. Hydrolysis of JBU with papain resulted in fungitoxic peptides (~10 kDa), which analyzed by mass spectrometry, revealed the presence of a fragment containing the N-terminal sequence of the entomotoxic peptide Jaburetox. Tests with Jaburetox on yeasts and filamentous fungi indicated a fungitoxic activity similar to ureases. Plant ureases, such as JBU, and its derived peptides, may represent a new alternative to control medically important mycoses as well as phytopathogenic fungi, especially considering their potent activity in the range of 10(-6)-10(-7)M.


Assuntos
Antifúngicos/farmacologia , Canavalia/química , Proteínas de Plantas/farmacologia , Urease/farmacologia , Sequência de Aminoácidos , Metabolismo dos Carboidratos/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Fungos/efeitos dos fármacos , Glucose/metabolismo , Hidrólise , Dados de Sequência Molecular , Papaína/química , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacologia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Estrutura Terciária de Proteína , Urease/química , Leveduras/efeitos dos fármacos
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