Proceedings of the National Academy of Sciences of the United States of America
-
Proc. Natl. Acad. Sci. U.S.A. · Oct 2012
Recruitment of medial prefrontal cortex neurons during alcohol withdrawal predicts cognitive impairment and excessive alcohol drinking.
Chronic intermittent access to alcohol leads to the escalation of alcohol intake, similar to binge drinking in humans. Converging lines of evidence suggest that impairment of medial prefrontal cortex (mPFC) cognitive function and overactivation of the central nucleus of the amygdala (CeA) are key factors that lead to excessive drinking in dependence. However, the role of the mPFC and CeA in the escalation of alcohol intake in rats with a history of binge drinking without dependence is currently unknown. ⋯ The results showed that abstinence from alcohol in rats with a history of escalation of alcohol intake specifically recruited GABA and corticotropin-releasing factor (CRF) neurons in the mPFC and produced working memory impairments associated with excessive alcohol drinking during acute (24-72 h) but not protracted (16 -68 d) abstinence. Moreover, abstinence from alcohol was associated with a functional disconnection of the mPFC and CeA but not mPFC and nucleus accumbens. These results show that recruitment of a subset of GABA and CRF neurons in the mPFC during withdrawal and disconnection of the PFC-CeA pathway may be critical for impaired executive control over motivated behavior, suggesting that dysregulation of mPFC interneurons may be an early index of neuroadaptation in alcohol dependence.
-
Proc. Natl. Acad. Sci. U.S.A. · Oct 2012
Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes.
Adaptive features of innate immunity, recently described as "trained immunity," have been documented in plants, invertebrate animals, and mice, but not yet in humans. Here we show that bacille Calmette-Guérin (BCG) vaccination in healthy volunteers led not only to a four- to sevenfold increase in the production of IFN-γ, but also to a twofold enhanced release of monocyte-derived cytokines, such as TNF and IL-1β, in response to unrelated bacterial and fungal pathogens. ⋯ In experimental studies, BCG vaccination induced T- and B-lymphocyte-independent protection of severe combined immunodeficiency SCID mice from disseminated candidiasis (100% survival in BCG-vaccinated mice vs. 30% in control mice). In conclusion, BCG induces trained immunity and nonspecific protection from infections through epigenetic reprogramming of innate immune cells.
-
Proc. Natl. Acad. Sci. U.S.A. · Oct 2012
Misconduct accounts for the majority of retracted scientific publications.
A detailed review of all 2,047 biomedical and life-science research articles indexed by PubMed as retracted on May 3, 2012 revealed that only 21.3% of retractions were attributable to error. In contrast, 67.4% of retractions were attributable to misconduct, including fraud or suspected fraud (43.4%), duplicate publication (14.2%), and plagiarism (9.8%). ⋯ The percentage of scientific articles retracted because of fraud has increased ∼10-fold since 1975. Retractions exhibit distinctive temporal and geographic patterns that may reveal underlying causes.
-
Proc. Natl. Acad. Sci. U.S.A. · Oct 2012
ReviewPreventing abusive head trauma resulting from a failure of normal interaction between infants and their caregivers.
Head trauma from abuse, including shaken baby syndrome, is a devastating and potentially lethal form of infant physical abuse first recognized in the early 1970s. What has been less recognized is the role of the early increase in crying in otherwise normal infants in the first few months of life as a trigger for the abuse. In part, this is because infant crying, especially prolonged unsoothable crying, has been interpreted clinically as something wrong with the infant, the infant's caregiver, or the interactions between them. ⋯ Together, these findings point to a conceptualization of AHT as the consequence of a failure in an otherwise common, iterative, and developmentally normal infant-caregiver interaction. They also imply that there is a window of opportunity for prevention of AHT, and potentially other forms of infant abuse, through a public health primary universal prevention strategy aimed at changing knowledge and behaviors of caregivers and society in general concerning normal development of infants and the significance of early increased infant crying. If effective, there may be important implications for prevention of infant abuse nationally and internationally.