RESUMO
MPYS (also known as STING, MITA, and TMEM173) is a type I IFN stimulator that is essential for host defense against DNA virus infection and appears important in defense against certain bacteria. The in vivo significance and mechanisms by which MPYS mediates host defense against nonviral pathogens are unknown. Using an MPYS-deficient mouse (Tmem173(
Assuntos
Antígenos Ly/biossíntese , Movimento Celular/imunologia , Listeriose/imunologia , Listeriose/patologia , Proteínas de Membrana/fisiologia , Monócitos/imunologia , Animais , Movimento Celular/genética , Células Cultivadas , Modelos Animais de Doenças , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Listeriose/genética , Fígado/imunologia , Fígado/microbiologia , Fígado/patologia , Proteínas de Membrana/deficiência , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Monócitos/microbiologia , Monócitos/patologia , Baço/imunologia , Baço/microbiologiaRESUMO
Research using Hong's Psychological Reactance Scale has been fraught with methodological concerns. Researchers have been unable to find a stable, a nd replicable factor structure. Here, results suggested t hat Hong's Psychological Reactance Scale is a unidimensional one with an average alpha of .74 (SD=.46). This value was attained by first analyzing correlation matrices reproduced from three reports on Hong's Psychological Reactance Scale and then verifying this new factor structure with original data. Tests for internal consistency supported a 1-factor solution. Tests for external consistency supported prior findings in relation to Psychological Reactance and offer evidence that the 1-factor solution is externally valid. While the authors contend that a 1-factor solution is appropriate, further testing is needed for external consistency and refinement of the measure.
Assuntos
Psicologia/métodos , Comportamento Social , Inquéritos e Questionários , Análise Fatorial , HumanosRESUMO
TRPM2 is a member of the transient receptor potential melastatin-related (TRPM) family of cation channels, which possesses both ion channel and ADP-ribose hydrolase functions. TRPM2 has been shown to gate in response to oxidative and nitrosative stresses, but the mechanism through which TRPM2 gating is induced by these types of stimuli is not clear. Here we show through structure-guided mutagenesis that TRPM2 gating by ADP-ribose and both oxidative and nitrosative stresses requires an intact ADP-ribose binding cleft in the C-terminal nudix domain. We also show that oxidative/nitrosative stress-induced gating can be inhibited by pharmacological reagents predicted to inhibit NAD hydrolysis to ADP-ribose and by suppression of ADP-ribose accumulation by cytosolic or mitochondrial overexpression of an enzyme that specifically hydrolyzes ADP-ribose. Overall, our data are most consistent with a model of oxidative and nitrosative stress-induced TRPM2 activation in which mitochondria are induced to produce free ADP-ribose and release it to the cytosol, where its subsequent accumulation induces TRPM2 gating via interaction within a binding cleft in the C-terminal NUDT9-H domain of TRPM2.