bak deletion stimulates gastric epithelial proliferation and enhances Helicobacter felis-induced gastric atrophy and dysplasia in mice

Helicobacter infection causes a chronic superficial gastritis that in some cases progresses via atrophic gastritis to adenocarcinoma. Proapoptotic bak has been shown to regulate radiation-induced apoptosis in the stomach and colon and also susceptibility to colorectal carcinogenesis in vivo. Therefore we investigated the gastric mucosal pathology following H. felis infection in bak-null mice at 6 or 48 wk postinfection. Primary gastric gland culture from bak-null mice was also used to assess the effects of bak deletion on IFN-γ-, TNF-α-, or IL-1β-induced apoptosis. bak-null gastric corpus glands were longer, had increased epithelial Ki-67 expression, and contained fewer parietal and enteroendocrine cells compared with the wild type (wt). In wt mice, bak was expressed at the luminal surface of gastric corpus glands, and this increased 2 wk post-H. felis infection. Apoptotic cell numbers were decreased in bak-null corpus 6 and 48 wk following infection and in primary gland cultures following cytokine administration. Increased gastric epithelial Ki-67 labeling index was observed in C57BL/6 mice after H. felis infection, whereas no such increase was detected in bak-null mice. More severe gastric atrophy was observed in bak-null compared with C57BL/6 mice 6 and 48 wk postinfection, and 76% of bak-null compared with 25% of C57BL/6 mice showed evidence of gastric dysplasia following long-term infection. Collectively, bak therefore regulates gastric epithelial cell apoptosis, proliferation, differentiation, mucosal thickness, and susceptibility to gastric atrophy and dysplasia following H. felis infection

Mice lacking NF-κB1 exhibit marked DNA damage responses and more severe gastric pathology in response to intraperitoneal tamoxifen administration

Tamoxifen (TAM) has recently been shown to cause acute gastric atrophy and metaplasia in mice. We have previously demonstrated that the outcome of Helicobacter felis infection, which induces similar gastric lesions in mice, is altered by deletion of specific NF-κB subunits. Nfkb1-/- mice developed more severe gastric atrophy than wild-type (WT) mice 6 weeks after H. felis infection. In contrast, Nfkb2-/- mice were protected from this pathology. We therefore hypothesized that gastric lesions induced by TAM may be similarly regulated by signaling via NF-κB subunits. Groups of five female C57BL/6 (WT), Nfkb1-/-, Nfkb2-/- and c-Rel-/- mice were administered 150 mg/kg TAM by IP injection. Seventy-two hours later, gastric corpus tissues were taken for quantitative histological assessment. In addition, groups of six female WT and Nfkb1-/- mice were exposed to 12 Gy γ-irradiation. Gastric epithelial apoptosis was quantified 6 and 48 h after irradiation. TAM induced gastric epithelial lesions in all strains of mice, but this was more severe in Nfkb1-/- mice than in WT mice. Nfkb1-/- mice exhibited more severe parietal cell loss than WT mice, had increased gastric epithelial expression of Ki67 and had an exaggerated gastric epithelial DNA damage response as quantified by γH2AX. To investigate whether the difference in gastric epithelial DNA damage response of Nfkb1-/- mice was unique to TAM-induced DNA damage or a generic consequence of DNA damage, we also assessed gastric epithelial apoptosis following γ-irradiation. Six hours after γ-irradiation, gastric epithelial apoptosis was increased in the gastric corpus and antrum of Nfkb1-/- mice. NF-κB1-mediated signaling regulates the development of gastric mucosal pathology following TAM administration. This is associated with an exaggerated gastric epithelial DNA damage response. This aberrant response appears to reflect a more generic sensitization of the gastric mucosa of Nfkb1-/- mice to DNA damage

Relational agency: Relational sociology, agency and interaction

yesThis article explores how the concept of agency in social theory changes when it is conceptualised as a relational rather than an individual phenomenon. I begin with a critique of the structure/agency debate, particularly of how this emerges in the critical realist approach to agency typified by Margaret Archer. It is argued that this approach, and the critical realist version of relational sociology that has grown from it, reifies social relations as a third entity to which agents have a cognitive, reflexive relation, playing down the importance of interaction. This upholds the Western moral and political view of agents as autonomous, independent, and reflexive individuals. Instead of this I consider agency from a different theoretical tradition in relational sociology in which agents are always located in manifold social relations. From this I create an understanding of agents as interactants, ones who are interdependent, vulnerable, intermittently reflexive, possessors of capacities that can only be practiced in joint actions, and capable of sensitive responses to others and to the situations of interaction. Instead of agency resting on the reflexive monitoring of action or the reflexive deliberation on structurally defined choices, agency emerges from our emotional relatedness to others as social relations unfold across time and space

Oral iron exacerbates colitis and influences the intestinal microbiome

Inflammatory bowel disease (IBD) is associated with anaemia and oral iron replacement to correct this can be problematic, intensifying inflammation and tissue damage. The intestinal microbiota also plays a key role in the pathogenesis of IBD, and iron supplementation likely influences gut bacterial diversity in patients with IBD. Here, we assessed the impact of dietary iron, using chow diets containing either 100, 200 or 400 ppm, fed ad libitum to adult female C57BL/6 mice in the presence or absence of colitis induced using dextran sulfate sodium (DSS), on (i) clinical and histological severity of acute DSS-induced colitis, and (ii) faecal microbial diversity, as assessed by sequencing the V4 region of 16S rRNA. Increasing or decreasing dietary iron concentration from the standard 200 ppm exacerbated both clinical and histological severity of DSS-induced colitis. DSS-treated mice provided only half the standard levels of iron ad libitum (i.e. chow containing 100 ppm iron) lost more body weight than those receiving double the amount of standard iron (i.e. 400 ppm); p<0.01. Faecal calprotectin levels were significantly increased in the presence of colitis in those consuming 100 ppm iron at day 8 (5.94-fold) versus day-10 group (4.14-fold) (p<0.05), and for the 400 ppm day-8 group (8.17-fold) versus day-10 group (4.44-fold) (p<0.001). In the presence of colitis, dietary iron at 400 ppm resulted in a significant reduction in faecal abundance of Firmicutes and Bacteroidetes, and increase of Proteobacteria, changes which were not observed with lower dietary intake of iron at 100 ppm. Overall, altering dietary iron intake exacerbated DSS-induced colitis; increasing the iron content of the diet also led to changes in intestinal bacteria diversity and composition after colitis was induced with DSS

Retrospective evaluation of the seasonality of canine tetanus in England (2006-2017):49 dogs

Objective&nbsp;To evaluate the seasonality of canine tetanus in England.Methods&nbsp;Medical records of a single referral hospital in England were reviewed. Dogs diagnosed with localized or generalized tetanus between January 2006 and June 2017 were studied.Results&nbsp;Forty-nine cases were included. The prevalence of tetanus in England was significantly higher in the winter when compared with the summer (P&nbsp;=&nbsp;0.002) and autumn (P&nbsp;=&nbsp;0.024), with the highest number of cases recorded in February.Conclusions&nbsp;The prevalence of canine tetanus in England was significantly higher in winter months, especially in February

The Body Dances: Carnival Dance and Organization

Building on the work of Pierre Bourdieu and Maurice Merleau-Ponty we seek to open up traditional categories of thought surrounding the relation `body-organization' and elicit a thought experiment: What happens if we move the body from the periphery to the centre? We pass the interlocking theoretical concepts of object-body/subject-body and habitus through the theoretically constructed empirical case of `carnival dance' in order to re-evaluate such key organizational concepts as knowledge and learning. In doing so, we connect with an emerging body of literature on `sensible knowledge'; knowledge that is produced and preserved within bodily practices. The investigation of habitual appropriation in carnival dance also allows us to make links between repetition and experimentation, and reflect on the mechanism through which the principles of social organization, whilst internalized and experienced as natural, are embodied so that humans are capable of spontaneously generating an infinite array of appropriate actions. This perspective on social and organizational life, where change and permanence are intricately interwoven, contrasts sharply with the dominant view in organization studies which juxtaposes change/ creativity and stability