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

Intestinal Preparation Techniques for Histological Analysis in the Mouse

The murine intestinal tract represents a difficult organ system to study due to its long convoluted tubular structure, narrow diameter, and delicate mucosa which undergoes rapid changes after sampling prior to fixation. These features do not make for easy histological analysis as rapid fixation in situ, or after simple removal without careful dissection, results in poor postfixation tissue handling and limited options for high quality histological sections. Collecting meaningful quantitative data by analysis of this tissue is further complicated by the anatomical changes in structure along its length. This article describes two methods of intestinal sampling at necropsy that allow systematic histological analysis of the entire intestinal tract, either through examination of cross sections (circumferences) by the gut bundling technique or longitudinal sections by the adapted Swiss roll technique, together with basic methods for data collection

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

From spin coating to roll-to-roll: investigating the challenge of upscaling lead halide perovskite solar cells

Spin coating, typically used to achieve nanometre thick films, is the established method for depositing perovskite precursors at lab scale for use in solar cells. This study investigates the dynamics of spin coating perovskite. By combining experimental measurement with a semi-empirical model the evaporation rate of the dimethylformamide solvent during the spin coating of a mixed lead halide precursor is determined to be 1.2 × 10 –8 m/s. When K-bar coating the same precursor the solvent does not significantly evaporate during the deposition process and when this film is crystallised on a hot plate a rough film results which gives a power conversion efficiency (PCE) of less than 2%. By increasing the airflow of the K-bar coated perovskite film during crystallisation to 2.7 × 10 –4 m/s the PCE increases significantly to 8.5% through an improvement in short-circuit current and fill factor

Epithelial cell shedding and barrier function: a matter of life and death at the small intestinal villus tip

The intestinal epithelium is a critical component of the gut barrier. Composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, this delicate structure prevents the transfer of harmful microorganisms, antigens, and toxins from the gut lumen into the circulation. The equilibrium between the rate of apoptosis and shedding of senescent epithelial cells at the villus tip, and the generation of new cells in the crypt, is key to maintaining tissue homeostasis. However, in both localized and systemic inflammation, this balance may be disturbed as a result of pathological IEC shedding. Shedding of IECs from the epithelial monolayer may cause transient gaps or microerosions in the epithelial barrier, resulting in increased intestinal permeability. Although pathological IEC shedding has been observed in mouse models of inflammation and human intestinal conditions such as inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This process may also be an important contributor to systemic and intestinal inflammatory diseases and gut barrier dysfunction in domestic animal species. This review aims to summarize current knowledge about intestinal epithelial cell shedding, its significance in gut barrier dysfunction and host-microbial interactions, and where research in this field is directed

Autoregressive models for biomedical signal processing

Autoregressive models are ubiquitous tools for the analysis of time series in many domains such as computational neuroscience and biomedical engineering. In these domains, data is, for example, collected from measurements of brain activity. Crucially, this data is subject to measurement errors as well as uncertainties in the underlying system model. As a result, standard signal processing using autoregressive model estimators may be biased. We present a framework for autoregressive modelling that incorporates these uncertainties explicitly via an overparameterised loss function. To optimise this loss, we derive an algorithm that alternates between state and parameter estimation. Our work shows that the procedure is able to successfully denoise time series and successfully reconstruct system parameters. This new paradigm can be used in a multitude of applications in neuroscience such as brain-computer interface data analysis and better understanding of brain dynamics in diseases such as epilepsy

Size and emotion or depth and emotion? Evidence, using Matryoshka (Russian) dolls, of children using physical depth as a proxy for emotional charge

Background: The size and emotion effect is the tendency for children to draw people and other objects with a positive emotional charge larger than those with a negative or neutral charge. Here we explored the novel idea that drawing size might be acting as a proxy for depth (proximity).Methods: Forty-two children (aged 3-11 years) chose, from 2 sets of Matryoshka (Russian) dolls, a doll to represent a person with positive, negative or neutral charge, which they placed in front of themselves on a sheet of A3 paper. Results: We found that the children used proximity and doll size, to indicate emotional charge. Conclusions: These findings are consistent with the notion that in drawings, children are using size as a proxy for physical closeness (proximity), as they attempt with varying success to put positive charged items closer to, or negative and neutral charge items further away from, themselves

The Influence of Visual Feedback and Prior Knowledge About Feedback on Vertical Aiming Strategies

Two experiments were conducted to examine time and energy optimization strategies for movements made with and against gravity. In Experiment 1, we manipulated concurrent visual feedback, and knowledge about feedback. When vision was eliminated upon movement initiation, participants exhibited greater undershooting, both with their primary submovement and their final endpoint, than when vision was available. When aiming downward, participants were more likely to terminate their aiming following the primary submovement or complete a lower amplitude corrective submovement. This strategy reduced the frequency of energy-consuming corrections against gravity. In Experiment 2, we eliminated vision of the hand and the target at the end of the movement. This procedure was expected to have its greatest impact under no vision conditions where no visual feedback was available for subsequent planning. As anticipated, direction and concurrent visual feedback had a profound impact on endpoint bias. Participants exhibited pronounced undershooting when aiming downward and without vision. Differences in undershooting between vision and no vision were greater under blocked feedback conditions. When performers were uncertain about the impending feedback, they planned their movements for the worst-case scenario. Thus movement planning considers the variability in execution, and avoids outcomes that require time and energy to correct