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Macrophages are tissue resident innate phagocytic cells that take on contrasting phenotypes, or polarization states, in response to the changing combination of microbial and cytokine signals at sites of infection. During the opening stages of an infection, macrophages adopt the proinflammatory, highly antimicrobial M1 state, later shifting to an anti-inflammatory, pro-tissue repair M2 state as the infection resolves. The changes in gene expression underlying these transitions are primarily governed by nuclear factor kappaB (NF-kB), Janus kinase (JAK)/signal transducer and activation of transcription (STAT), and hypoxia-inducible factor 1 (HIF1) transcription factors, the activity of which must be carefully controlled to ensure an effective yet spatially and temporally restricted inflammatory response. While much of this control is provided by pathway-specific feedback loops, recent work has shown that the transcriptional co-regulators of the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxy-terminal domain (CITED) family serve as common controllers for these pathways. In this review, we describe how CITED proteins regulate polarization-associated gene expression changes by controlling the ability of transcription factors to form chromatin complexes with the histone acetyltransferase, CBP/p300. We will also cover how differences in the interactions between CITED1 and 2 with CBP/p300 drive their contrasting effects on pro-inflammatory gene expression. [ABSTRACT FROM AUTHOR]

BackgroundThe news media facilitated the rapid dissemination of the findings from the estrogen plus progestin therapy arm of the Women's Health Initiative (EPT-WHI).ObjectiveTo examine the relationship between the potential exposure to newspaper coverage and subsequent hormone therapy (HT) use. DESIGN/POPULATION: Population-based cohort of women receiving mammography at 7 sites (327,144 postmenopausal women).MeasurementsThe outcome was the monthly prevalence of self-reported HT use. Circulation data for local, regional, and national newspapers was used to create zip-code level measures of the estimated average household exposure to newspaper coverage that reported the harmful effects of HT in July 2002.ResultsWomen had an average potential household exposure of 1.4 articles. There was substantial variation in the level of average household exposure to newspaper coverage; women from rural sites received less than women from urban sites. Use of HT declined for all average potential exposure groups after the publication of the EPT-WHI. HT prevalence among women who lived in areas where there was an average household exposure of at least 3 articles declined significantly more (45 to 27%) compared to women who lived in areas with

Published evaluations of career preparation of alumni from long-standing postdoctoral fellowship programs in the biomedical sciences are limited and often focus on quantitative analysis of data from extant publicly available sources. Qualitative methods provide the opportunity to gather robust information about specific program elements from structured postdoctoral training programs and the influence of this training on subsequent career paths of alumni. In-depth interviews with a subset of the National Cancer Institute's Cancer Prevention Fellowship Program (CPFP) alumni (n = 27), representing more than 25 years of the program's history and multiple career sectors, were conducted to assess alumni reflections on the training environment and career preparation during their time in the CPFP. NVivo software was used to analyze data and identify major themes. Four main themes emerged from these interviews, including: the value of structured training curriculum, mentorship, transdisciplinary environment, and professional identity. Even when reflecting on training that occurred one to two decades earlier, alumni were able to highlight specific components of a structured postdoctoral training program as influencing their research and career trajectories. These results may have relevance for those interested in assessing how postdoctoral training can influence fellows throughout their careers and understanding salient features of structured programs.

Neisseria meningitidis and N. gonorrhoeae are exclusive human pathogens. N. meningitidis is a leading cause of sepsis and meningitis, whereas N. gonorrhoeae (gonococcus) traditionally causes gonorrhea, a sexually transmitted infection [...]

Macrophages serve as a first line of defense against microbial pathogens. Exposure to interferon-γ (IFNγ) increases interferonstimulated gene (ISG) expression in these cells, resulting in enhanced antimicrobial and proinflammatory activity. Although this response must be sufficiently vigorous to ensure the successful clearance of pathogens, it must also be carefully regulated to prevent tissue damage. This is controlled in part by CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2), a transcriptional coregulator that limits ISG expression by inhibiting STAT1 and IRF1. Here, we show that the closely related Cited1 is an ISG, which is expressed in a STAT1-dependent manner, and that IFNγ stimulates the nuclear accumulation of CITED1 protein. In contrast to CITED2, ectopic CITED1 enhanced the expression of a subset of ISGs, including Ccl2, Ifit3b, Isg15 and Oas2. This effect was reversed in a Cited1-null cell line produced by CRISPR-based genomic editing. Collectively, these data show that CITED1 maintains proinflammatory gene expression during periods of prolonged IFNγ exposure and suggest that there is an antagonistic relationship between CITED proteins in the regulation of macrophage inflammatory function. [ABSTRACT FROM AUTHOR]