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Whooping cough is resurging in the United States despite high vaccine coverage. The rapid rise of Bordetella pertussis isolates lacking pertactin (PRN), a key vaccine antigen, has led to concerns about vaccine-driven evolution. Previous studies showed that pertactin can mediate binding to mammalian cells in vitro and act as an immunomodulatory factor in resisting neutrophil-mediated clearance. To further investigate the role of PRN in vivo, we examined the functions of pertactin in the context of a more naturally low dose inoculation experimental system using C3H/HeJ mice that is more sensitive to effects on colonization, growth and spread within the respiratory tract, as well as an experimental approach to measure shedding and transmission between hosts. A B. bronchiseptica pertactin deletion mutant was found to behave similarly to its wild-type (WT) parental strain in colonization of the nasal cavity, trachea, and lungs of mice. However, the pertactin-deficient strain was shed from the nares of mice in much lower numbers, resulting in a significantly lower rate of transmission between hosts. Histological examination of respiratory epithelia revealed that pertactin-deficient bacteria induced substantially less inflammation and mucus accumulation than the WT strain and in vitro assays verified the effect of PRN on the induction of TNF-α by murine macrophages. Interestingly, only WT B. bronchiseptica could be recovered from the spleen of infected mice and were further observed to be intracellular among isolated splenocytes, indicating that pertactin contributes to systemic dissemination involving intracellular survival. These results suggest that pertactin can mediate interactions with immune cells and augments inflammation that contributes to bacterial shedding and transmission between hosts. Understanding the relative contributions of various factors to inflammation, mucus production, shedding and transmission will guide novel strategies to interfere with the reemergence of pertussis. Author summary: B. pertussis strains lacking pertactin have been rising in prevalence especially in countries using acellular vaccines containing pertactin as a key, membrane-associated surface antigen. Previous in vivo studies revealed immunomodulatory properties of pertactin in conventional B. pertussis infection models in which roughly one million bacteria are delivered into lungs, leading to severe pneumonic disease and a strong immune response. However, natural infections begin in the nasopharyngeal region, progress slowly during a prolonged catarrhal stage, only later reaching the trachea and rarely involve the lungs. In this study, a more natural experimental system takes advantage of the ability of B. bronchiseptica, a closely related species, to naturally colonize mice with inocula as low as 5 colony forming units (CFU). In this system B. bronchiseptica can be observed to efficiently colonize, grow, spread within the respiratory tract, is shed from the nares, and transmits between hosts, allowing each of these steps to be measured and studied. Under these conditions, an isogenic pertactin deletion strain was indistinguishable from its parental strain in its abilities to colonize, grow in numbers and spread within the respiratory tract. However, the pertactin-deficient mutant was shed from these mice in lower numbers than wild type, and was defective in transmission between mice. These assays reveal novel roles of pertactin in the induction of inflammation, mucus production, shedding and transmission. [ABSTRACT FROM AUTHOR]

The article investigates the question of women's collective action emergence in the 1956-1979 period with an eye toward testing hypotheses about the mobilization of resources and the political opportunity structure. It is hoped to illuminate two important dimensions of the political opportunity structure, the level of institutional access and the presence of elite allies as they pertain to the U.S. women's movement. The second goal was to examine one potential consequence of collective action. The findings show mixed support for arguments about how the political opportunity structure affects collective action. The presence of a Democratic president, arguably an elite ally to the women's movement, actually decreases the amount of insider and outsider collective action. Because the women's movement emerged during a period of Democratic control of the presidency, and flourished during a long period of Democratic control of the U.S. Congress, it had hypothesized that a Democratic president would increase rates of collective action. -

Background: To analyze global trends in focus and funding of research related to high tibial osteotomy (HTO) and to identify the 100 most cited articles in this field., Methods: A Web of Science search was used to identify HTO publications in English-language scientific journals from January 1967 till February 3th, 2021. Results were filtered to the 100 most cited articles by reading the abstract or full-text paper. Information of these articles was recorded for further analysis. The 10 top-cited articles during the last 5 years and the 10 top-cited articles about HTO ranked by average citations per year were selected to predict research trends., Results: In all, 48 out of the 100 top-cited articles were published between 2000 and 2010. The United States of America was the primary contributor (n = 29) followed by Germany (n = 17) and Japan (n = 11). The total number of citations per article ranged from 65 to 563, median 108, mean 135 (standard deviation = 84). The American Journal of Bone and Joint Surgery accounted for 23 out of the 100 top-cited articles. Koshino T was the most cited author (603 citations). The most frequently highlighted study theme was prognostic research. Patient-based clinical research was the dominant study design (85%). The majority of articles (48 out of 100) were level IV evidence with a mean of 141 (standard deviation = 97) citations. Top-cited articles in the last 5 years focused on open wedge osteotomy., Conclusion: Technical optimization of open wedge osteotomy has emerged as the main area of research in HTO. More specifically, recent publications focus on the surgical technology, cartilage repair and new fixation devices. Besides, papers with a high level of evidence are needed for the development of HTO., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The PhoP-PhoQ two-component regulation system of Salmonella enterica serovar Typhimurium is involved in the response to various environmental stresses and is essential for bacterial virulence. Our previous studies showed that acetylation plays an important role in regulating the activity of PhoP, which consequently mediates the change in virulence of S Typhimurium. Here, we demonstrate that a conserved lysine residue, K88, is crucial for the function of PhoP and its acetylation-downregulated PhoP activities. K88 could be specifically acetylated by acetyl phosphate (AcP), and the acetylation level of K88 decreased significantly after phagocytosis of S Typhimurium by macrophages. Acetylation of K88 inhibited PhoP dimerization and DNA-binding abilities. In addition, mutation of K88 to glutamine, mimicking the acetylated form, dramatically attenuated intestinal inflammation and systemic infection of S Typhimurium in the mouse model. These findings indicate that nonenzymatic acetylation of PhoP by AcP is a fine-tuned mechanism for the virulence of S Typhimurium and highlights that virulence and metabolism in the host are closely linked., (Copyright © 2021 American Society for Microbiology.)