The lipopolysaccharide outer core of Yersinia enterocolitica serotype O:3 is required for virulence and plays a role in outer membrane integrity

Lipopolysaccharide (LPS) of Yersinia enterocolitica O:3 has an inner core linked to both the O-antigen and to an outer core hexasaccharide that forms a branch. The biological role of the outer core was studied using polar and non-polar mutants of the outer core biosynthetic operon. Analysis of O-antigen- and outer core-deficient strains suggested a critical role for the outer core in outer membrane properties relevant in resistance to antimicrobial peptides and permeability to hydrophobic agents, and indirectly relevant in resistance to killing by normal serum. Wild-type bacteria but not outer core mutants killed intragastrically infected mice, and the intravenous lethal dose was approximately 10(4)-fold higher for outer core mutants. After intragastric infection, outer core mutants colonized Peyer's patches and invaded mesenteric lymph nodes, spleen and liver, and induced protective immunity against wild-type bacteria. In mice co-infected intragastrically with an outer core mutant-wild type mixture, both strains colonized Peyer's patches similarly during the first 2 days, but the mutant was much less efficient in colonizing deeper organs and was cleared faster from Peyer's patches. The results demonstrate that outer core is required for Y. enterocolitica O:3 full virulence, and strongly suggest that it provides resistance against defence mechanisms (most probably those involving bactericidal peptides).

Patriotism or Integrity?:Constitutional Community in Divided Societies

Some commentators worry that a plurinational constitutional order can only ever be an inherently unstable modus vivendi. They fear that the accommodation of sub-state nationalism will tend to undermine the viability of constitutional democracies. This article enlists Ronald Dworkin’s theory of ‘law as integrity’ to show how these concerns might be assuaged. My central claim is that the expressive value of integrity can drive a divided society in the direction of an eventual community of principle, even in the absence of a common political identity. I argue that this model of political community is a more plausible prescription for divided societies than the theory that competing nationalisms might be superseded by constitutional patriotism. I go on to explain, however, that integrity has a better chance of realizing this potential if the generally judge-centric focus of Dworkin’s theory is expanded to make greater room for non-judicial interpretative responsibility. Occasional references are made to the example of Northern Ireland to illustrate my points.

Tool life and hole surface integrity studies for hole-making of Ti6Al4V Alloy

With a significant growth in the use of titanium alloys in the aviation manufacturing industry, the key challenge of making high-quality holes in the aircraft assembly process needs to be addressed. In this work, case studies deploying traditional drilling and helical milling technologies are carried out to investigate the tool life and hole surface integrity for hole-making of titanium alloy. Results show that the helical milling process leads to much longer tool life, generally lower hole surface roughness, and higher hole subsurface microhardness. In addition, no plastically deformed layer or white layer has been observed in holes produced by helical milling. In contrast, a slightly softened region was always present on the drilled surface. The residual stress distributions within the hole surface, including compressive and tensile residual stress, have also been investigated in detail.

Bringing practice closer to research - seeking integrity, sincerity and authenticity

This article tackles the abundance of inconsistent terminologies that surround the discourse on practice and research. The text builds on recent debates on creative practice and education, sparked through the EU funded project SHARE. I argue that a shift in contemporary continental philosophy in the 1970s, which nudged the body into a more central position, allowed for creative practice and with it ‘embodied knowing’ to slowly push open the doors of the academies. I will show that practice today is already well embedded in some UK institutions, and I put forward that rather than thinking of an apologetic Practice as..., Performance as .., we should refer more resolutely to what I here term ‘Practice Research’. I demystify notions of validation of creative practice by re-emphasising the artistic qualities of ‘integrity, sincerity and authenticity’, borrowed from the 2013 BBC Reith lecturer and artist/potter Grayson Perry.

Insulin and insulin-like growth factor signaling increases proliferation and hyperplasia of the ovarian surface epithelium and decreases follicular integrity through upregulation of the PI3-kinase pathway

BACKGROUND: The ovarian surface epithelium responds to cytokines and hormonal cues to initiate proliferation and migration following ovulation. Although insulin and IGF are potent proliferative factors for the ovarian surface epithelium and IGF is required for follicle development, increased insulin and IGF activity are correlated with at least two gynecologic conditions: polycystic ovary syndrome and epithelial ovarian cancer. Although insulin and IGF are often components of in vitro culture media, little is known about the effects that these growth factors may have on the ovarian surface epithelium morphology or how signaling in the ovarian surface may affect follicular health and development.

METHODS: Ovaries from CD1 mice were cultured in alginate hydrogels in the presence or absence of 5 μg/ml insulin or IGF-I, as well as small molecule inhibitors of IR/IGF1R, PI 3-kinase signaling, or MAPK signaling. Tissues were analyzed by immunohistochemistry for expression of cytokeratin 8 to mark the ovarian surface epithelium, Müllerian inhibiting substance to mark secondary follicles, and BrdU incorporation to assess proliferation. Changes in gene expression in the ovarian surface epithelium in response to insulin or IGF-I were analyzed by transcription array. Extracellular matrix organization was evaluated by expression and localization of collagen IV.

RESULTS: Culture of ovarian organoids with insulin or IGF-I resulted in formation of hyperplastic OSE approximately 4-6 cell layers thick with a high rate of proliferation, as well as decreased MIS expression in secondary follicles. Inhibition of the MAPK pathway restored MIS expression reduced by insulin but only partially restored normal OSE growth and morphology. Inhibition of the PI 3-kinase pathway restored MIS expression reduced by IGF-I and restored OSE growth to a single cell layer. Insulin and IGF-I altered organization of collagen IV, which was restored by inhibition of PI 3-kinase signaling.

CONCLUSIONS: While insulin and IGF are often required for propagation of primary cells, these cytokines may act as potent mitogens to disrupt cell growth, resulting in formation of hyperplastic OSE and decreased follicular integrity as measured by MIS expression and collagen deposition. This may be due partly to altered collagen IV deposition and organization in the ovary in response to insulin and IGF signaling mediated by PI 3-kinase.