Aspergillus fumigatus is an important opportunistic fungal pathogen. The cAMP-dependent protein kinase (PKA) signaling pathway plays an important role in regulating morphology, growth, and virulence in a number of fungal pathogens of plants and animals. We have constructed a mutant of A. fumigatus that lacks the regulatory subunit of PKA, pkaR, and analyzed the growth and development, sensitivity to oxidative damage, and virulence of the mutant, along with those of the wild type and a complemented mutant. Both growth and germination rates of the mutant are reduced, and there are morphological abnormalities in conidiophores, leading to reduced conidiation. Conidia from the ⌬pkaR mutant are more sensitive to killing by hydrogen peroxide, menadione, paraquat, and diamide. However, the hyphae of the mutant are killed to a greater extent only by paraquat and diamide, whereas they are less susceptible to the effects of hydrogen peroxide. In an immunosuppressed mouse model, intranasally administered conidia of the mutant are significantly less virulent than those of the wild type or a complemented mutant. Unregulated PKA signaling is detrimental to the virulence of A. fumigatus, perhaps through the reduced susceptibility of the mutant to damage by oxidizing agents and reduced growth kinetics.Aspergillus fumigatus is an important fungal pathogen of immunocompromised hosts (23,34). Despite the recent introduction of newer antifungals with anti-Aspergillus activity, the morbidity and mortality of invasive aspergillosis (IA) remains high, especially once the infection has disseminated (7). In nature, the fungus plays a key role in the compost cycle by recycling carbon and nitrogen from plant material (24, 42). In this environment, A. fumigatus is likely to be exposed to broad fluctuations in pH, temperatures up to 50°C, and reactive oxygen species (24,33,45). These stressors are not unlike the kinds of factors an organism might encounter in vivo (13). Therefore, adaptive mechanisms that confer resistance to environmental stress may contribute to the efficient colonization and persistence of the organism in the human host.The cyclic AMP-dependent protein kinase (PKA) is a wellknown regulator of the stress response in eukaryotes. PKA is a heterotetramer, made up of a dimer of regulatory subunits and two catalytic subunits. Fungal regulatory subunits are homologues of mammalian type II subunits, based on the autoinhibition site (29). When cAMP binds to the regulatory subunits, a conformational change occurs, which releases the catalytic subunits to autophosphorylate and to phosphorylate downstream targets. PKA signaling in Saccharomyces cerevisiae regulates the general stress control pathway (11,26). Mutants lacking BCY1, the gene encoding the regulatory subunit of PKA in S. cerevisiae, have unregulated PKA activity; these mutants are pseudohyphal in morphology and hypersensitive to killing with hydrogen peroxide (15, 44).The PKA pathway also regulates morphology and virulence in a number of fungal pathogens of humans and pla...

The purpose of our study was to explore Asian American women's body image experiences from an intersectional framework. Utilizing grounded theory methodology, we sought to understand how gender and race intersect with unique experiences of oppression to contribute to body dissatisfaction among Asian American women. Twenty Asian American undergraduate women born in the United States participated in semi-structured interviews. The core category "body image" was composed of attitudes and perceptions about body weight, shape, and size; facial features (e.g., eye size); and skin complexion or tone. Five categories emerged that informed the body image experiences of Asian American women: (1) navigating cultural beauty norms, (2) experiences of sexism and racism, (3) parental influences, (4) peer influences, and (5) identity management processes. Each of these categories appeared to have both positive and negative consequences for appearance evaluation, ranging from self-consciousness to confidence. Participants also described coping strategies for managing these experiences. We encourage psychologists and clinicians to consider culture-specific beauty standards for Asian American women as well as salient racial and cultural factors (e.g., perceived discrimination and biculturative stress) that may influence body image beliefs. Our results offer a new model for understanding Asian American women's body dissatisfaction as rooted in experiences of racism and sexism.

BackgroundIntrauterine growth restriction (IUGR) is a common complication of pregnancy and is associated with significant neurological deficits in infants, including white matter damage. Previous work using an animal model of IUGR has demonstrated that IUGR rats exhibit neurobehavioral deficits and developmental delays in oligodendrocyte maturation and myelination, but the mechanisms which cause this delay are unknown. Inflammation may be an important etiological factor in IUGR and has been recognized as playing a fundamental role in the pathogenesis of myelin disorders, including cerebral palsy.MethodsTo create the model, the uterine arteries of pregnant rats were ligated at embryonic day 15. Rats delivered spontaneously. Cytokine and chemokine expression was evaluated at one prenatal and three postnatal time points, and myelin protein expression and oligodendrocyte cell numbers were evaluated by several methods at postnatal day 14. IL-4 was identified as a potential inhibitor of myelination, and rat pups were injected with IL-4 function blocking antibody from postnatal days 1–5 and myelination was assessed.ResultsHere, we show a novel mechanism of white matter injury. IUGR induces an exaggerated Th2 response in the developing rat brain, including upregulation of several Th2 cytokines. Of these, IL-4 is significantly increased during the period corresponding to robust developmental myelination. We show that neutralizing IL-4 antibody therapy given in the newborn period ameliorates inflammation and restores myelin protein expression and oligodendrocyte cell number in the IUGR brain to control levels, demonstrating a novel role for Th2 responses and IL-4 in IUGR and white matter injury. In addition, IL-4 directly affects oligodendrocytes in vitro decreasing differentiation.ConclusionsIn this study, we have identified inflammation as a factor in the decrease in myelin seen in an animal model of IUGR. IL-4, an inflammatory protein often thought to be protective in the adult, is specifically increased, and treatment of these animals to prevent this increase ameliorates white matter damage. Our results suggest that the immune system plays a role in IUGR that is different in the perinatal period than in the adult and preventing this exaggerated Th2 response may be a potential therapeutic target.

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