Protease-activated receptor 2 mediates eosinophil infiltration and hyperreactivity in allergic inflammation of the airway

Trypsin and mast cell tryptase can signal to epithelial cells, myocytes, and nerve fibers of the respiratory tract by cleaving proteinase-activated receptor 2 (PAR2). Since tryptase inhibitors are under development to treat asthma, a precise understanding of the contribution of PAR2 to airway inflammation is required. We examined the role of PAR2 in allergic inflammation of the airway by comparing OVA-sensitized and -challenged mice lacking or overexpressing PAR2. In wild-type mice, immunoreactive PAR2 was detected in airway epithelial cells and myocytes, and intranasal administration of a PAR2 agonist stimulated macrophage infiltration into bronchoalveolar lavage fluid. OVA challenge of immunized wild-type mice stimulated infiltration of leukocytes into bronchoalveolar lavage and induced airway hyperreactivity to inhaled methacholine. Compared with wild-type animals, eosinophil infiltration was inhibited by 73% in mice lacking PAR2 and increased by 88% in mice overexpressing PAR2. Similarly, compared with wild-type animals, airway hyperreactivity to inhaled methacholine (40 micro g/ml) was diminished 38% in mice lacking PAR2 and increased by 52% in mice overexpressing PAR2. PAR2 deletion also reduced IgE levels to OVA sensitization by 4-fold compared with those of wild-type animals. Thus, PAR2 contributes to the development of immunity and to allergic inflammation of the airway. Our results support the proposal that tryptase inhibitors and PAR2 antagonists may be useful therapies for inflammatory airway disease.

Effect of cinnamon on gastric emptying, arterial stiffness, postprandial lipemia, glycemia, and appetite responses to high-fat breakfast

Abstract BACKGROUND: Cinnamon has been shown to delay gastric emptying of a high-carbohydrate meal and reduce postprandial glycemia in healthy adults. However, it is dietary fat which is implicated in the etiology and is associated with obesity, type 2 diabetes and cardiovascular disease. We aimed to determine the effect of 3 g cinnamon (Cinnamomum zeylanicum) on GE, postprandial lipemic and glycemic responses, oxidative stress, arterial stiffness, as well as appetite sensations and subsequent food intake following a high-fat meal. METHODS: A single-blind randomized crossover study assessed nine healthy, young subjects. GE rate of a high-fat meal supplemented with 3 g cinnamon or placebo was determined using the 13C octanoic acid breath test. Breath, blood samples and subjective appetite ratings were collected in the fasted and during the 360 min postprandial period, followed by an ad libitum buffet meal. Gastric emptying and 1-day fatty acid intake relationships were also examined. RESULTS: Cinnamon did not change gastric emptying parameters, postprandial triacylglycerol or glucose concentrations, oxidative stress, arterial function or appetite (p < 0.05). Strong relationships were evident (p < 0.05) between GE Thalf and 1-day palmitoleic acid (r = -0.78), eiconsenoic acid (r = -0.84) and total omega-3 intake (r = -0.72). The ingestion of 3 g cinnamon had no effect on GE, arterial stiffness and oxidative stress following a HF meal. CONCLUSIONS: 3 g cinnamon did not alter the postprandial response to a high-fat test meal. We find no evidence to support the use of 3 g cinnamon supplementation for the prevention or treatment of metabolic disease. Dietary fatty acid intake requires consideration in future gastrointestinal studies.

Mulsemedia: state of the art, perspectives, and challenges

Mulsemedia—multiple sensorial media—captures a wide variety of research efforts and applications. This article presents a historic perspective on mulsemedia work and reviews current developments in the area. These take place across the traditional multimedia spectrum—from virtual reality applications to computer games—as well as efforts in the arts, gastronomy, and therapy, to mention a few. We also describe standardization efforts, via the MPEG-V standard, and identify future developments and exciting challenges the community needs to overcome.

Temperature regulation of extracellular proteases in ectomycorrhizal fungi (Hebeloma spp.) grown in axenic culture

Strains of Hebeloma representative of different climatic zones were grown in axenic culture at either 2 °C and 22° or 6° and 22°. Culture filtrates were assayed for proteolytic activity using FITC labelled BSA as a substrate. Assays were run between 0–37°. Growth at low temperature induced greater proteolytic activity (g−1 D.W. mycelium). Many of the strains produced protease(s) which retained significant activity at temperatures as low as 0°, and a thermal optimum between 0–6° with a second optimum at higher temperature. The results are discussed in relation the nutrient acquisition potential of ectomycorrhizal fungi at low temperature and the contribution such cold active proteases might make to the soil enzyme pool.

Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study

Background: The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. Objective: We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics. Design: A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD). Results: Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P < 0.001). A small improvement in the aortic pulse wave velocity (i.e., a decrease of 0.22 m/s; 95% CI: −0.4, −0.3 m/s) was evident in the nitrate group, showing a trend (P = 0.06) to improvement in comparison with the placebo group. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P < 0.05) but no significant changes in unstimulated expression. No adverse effects of dietary nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P < 0.01). The proportions of 78 bacterial taxa were different after the nitrate treatment; of those taxa present, 2 taxa were responsible for >1% of this change, with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens (P < 0.01) increased after nitrate treatment relative to after placebo treatment. Conclusions: Sustained dietary nitrate ingestion improves vascular function in hypercholesterolemic patients. These changes are associated with alterations in the oral microbiome and, in particular, nitrate-reducing genera. Our findings provide additional support for the assessment of the potential of dietary nitrate as a preventative strategy against atherogenesis in larger cohorts. This trial was registered at clinicaltrials.gov as NCT01493752.

Texture, realism, performance: exploring the intersection of transtexts and the contemporary sitcom

Contemporary US sitcom is at an interesting crossroads: it has received an increasing amount of scholarly attention (e.g. Mills 2009; Butler 2010; Newman and Levine 2012; Vermeulen and Whitfield 2013), which largely understands it as shifting towards the aesthetically and narratively complex. At the same time, in the post-broadcasting era, US networks are particularly struggling for their audience share. With the days of blockbuster successes like Must See TV’s Friends (NBC 1994-2004) a distant dream, recent US sitcoms are instead turning towards smaller, engaged audiences. Here, a cult sensibility of intertextual in-jokes, temporal and narrational experimentation (e.g. flashbacks and alternate realities) and self-reflexive performance styles have marked shows including Community (NBC 2009-2015), How I Met Your Mother (CBS 2005-2014), New Girl (Fox 2011-present) and 30 Rock (NBC 2006-2013). However, not much critical attention has so far been paid to how these developments in textual sensibility in contemporary US sitcom may be influenced by, and influencing, the use of transmedia storytelling practices, an increasingly significant industrial concern and rising scholarly field of enquiry (e.g. Jenkins 2006; Mittell 2015; Richards 2010; Scott 2010; Jenkins, Ford and Green 2013). This chapter investigates this mutual influence between sitcom and transmedia by taking as its case studies two network shows that encourage invested viewership through their use of transtexts, namely How I Met Your Mother (hereafter HIMHM) and New Girl (hereafter NG). As such, it will pay particular attention to the most transtextually visible character/actor from each show: HIMYM’s Barney Stinson, played by Neil Patrick Harris, and NG’s Schmidt, played by Max Greenfield. This chapter argues that these sitcoms do not simply have their particular textual sensibility and also (happen to) engage with transmedia practices, but that the two are mutually informing and defining. This chapter explores the relationships and interplay between sitcom aesthetics, narratives and transmedia storytelling (or industrial transtexts), focusing on the use of multiple delivery channels in order to disperse “integral elements of a fiction” (Jenkins, 2006 95-6), by official entities such as the broadcasting channels. The chapter pays due attention to the specific production contexts of both shows and how these inform their approaches to transtexts. This chapter’s conceptual framework will be particularly concerned with how issues of texture, the reality envelope and accepted imaginative realism, as well as performance and the actor’s input inform and illuminate contemporary sitcoms and transtexts, and will be the first scholarly research to do so. It will seek out points of connections between two (thus far) separate strands of scholarship and will move discussions on transtexts beyond the usual genre studied (i.e. science-fiction and fantasy), as well as make a contribution to the growing scholarship on contemporary sitcom by approaching it from a new critical angle. On the basis that transmedia scholarship stands to benefit from widening its customary genre choice (i.e. telefantasy) for its case studies and from making more use of in-depth close analysis in its engagement with transtexts, the chapter argues that notions of texture, accepted imaginative realism and the reality envelope, as well as performance and the actor’s input deserve to be paid more attention to within transtext-related scholarship.