Michael Christensen

Cholinergic neurotransmission links solitary chemosensory cells to nasal inflammation

Significance Millions of people worldwide suffer from chronic nasal inflammation involving obstructed airflow and nasal discharge. Although nasal inflammation is often considered to be a reaction to allergens, approximately one-quarter of all cases are nonallergic rhinitis. The causes of this disease are unknown, but symptoms may be triggered or exacerbated by a variety of inhaled irritants or even seemingly innocuous odors. We report here that specialized chemosensory cells of the nasal epithelium of mice detect potential irritants and transmit this information to pain-sensing nerve terminals, which then release bioactive peptides to trigger an inflammatory response—all without the necessity for activity of the adaptive immune system. This previously unidentified pathway may offer therapeutic targets for intervention in nonallergic rhinitis. Solitary chemosensory cells (SCCs) of the nasal cavity are specialized epithelial chemosensors that respond to irritants through the canonical taste transduction cascade involving Gα-gustducin and transient receptor potential melastatin 5. When stimulated, SCCs trigger peptidergic nociceptive (or pain) nerve fibers, causing an alteration of the respiratory rate indicative of trigeminal activation. Direct chemical excitation of trigeminal pain fibers by capsaicin evokes neurogenic inflammation in the surrounding epithelium. In the current study, we test whether activation of nasal SCCs can trigger similar local inflammatory responses, specifically mast cell degranulation and plasma leakage. The prototypical bitter compound, denatonium, a well-established activator of SCCs, caused significant inflammatory responses in WT mice but not mice with a genetic deletion of elements of the canonical taste transduction cascade, showing that activation of taste signaling components is sufficient to trigger local inflammation. Chemical ablation of peptidergic trigeminal fibers prevented the SCC-induced nasal inflammation, indicating that SCCs evoke inflammation only by neural activity and not by release of local inflammatory mediators. Additionally, blocking nicotinic, but not muscarinic, acetylcholine receptors prevents SCC-mediated neurogenic inflammation for both denatonium and the bacterial signaling molecule 3-oxo-C12-homoserine lactone, showing the necessity for cholinergic transmission. Finally, we show that the neurokinin 1 receptor for substance P is required for SCC-mediated inflammation, suggesting that release of substance P from nerve fibers triggers the inflammatory events. Taken together, these results show that SCCs use cholinergic neurotransmission to trigger peptidergic trigeminal nociceptors, which link SCCs to the neurogenic inflammatory pathway.

Collaborative augmented reality environments: integrating VR, working materials, and distributed work spaces

In this work, we present a new method for displaying stereo scenes, which speeds up the rendering time of complex geometry. We first discuss a scene splitting strategy, allowing us to partition objects to the distant background or the near foreground. Furthermore, wededuce a computation rule for positioning a cutting plane in the scene.

Uncovered Interest Parity and Policy Behavior New Evidence

McCallum (1994a) introduces policy behavior to resolve previous empirical rejections of the uncovered interest parity (UIP) theory. In this note, we reexamine his policy behavior argument. First, we extend the data set used by McCallum to include the recent 8 years, and contrary to the analysis provided by McCallum, we make a thorough econometric analysis of his UIP specification. It is shown that in most cases his theory is upported by the data as well as it passes conventional econometric tests. We then take a closer look at his policy behavioral relationship, but unfortunately it turns out that this specification is inconsistent with the UIP specification suggested by McCallum (1994a).

Danish mutual fund performance

This article provides the first independent performance analysis of Danish mutual funds. We analyse selectivity and market timing abilities for 71 mutual funds that have been in operation from 2001 to 2010. The results show great fund performance diversity. Half the funds have performed neutrally, whereas 42% of the funds have shown significantly negative performance and only 7% of the funds have over-performed their benchmark. Furthermore, 14% of the funds analysed possess market timing abilities, but for 8 out of 10 funds, their market timing ability has been unsuccessful.

Renoprotective Effects of Metformin are Independent of Organic Cation Transporters 1 &2 and AMP-activated Protein Kinase in the Kidney.

The type-2 diabetes drug metformin has proven to have protective effects in several renal disease models. Here, we investigated the protective effects in a 3-day unilateral ureteral obstruction (3dUUO) mouse model. Compared with controls, ureteral obstructed animals displayed increased tubular damage and inflammation. Metformin treatment attenuated inflammation, increased the anti-oxidative response and decreased tubular damage. Hepatic metformin uptake depends on the expression of organic cation transporters (OCTs). To test whether the effects of metformin in the kidney are dependent on these transporters, we tested metformin treatment in OCT1/2−/− mice. Even though exposure of metformin in the kidney was severely decreased in OCT1/2−/− mice when evaluated with [11C]-Metformin and PET/MRI, we found that the protective effects of metformin were OCT1/2 independent when tested in this model. AMP-activated protein kinase (AMPK) has been suggested as a key mediator of the effects of metformin. When using an AMPK-β1 KO mouse model, the protective effects of metformin still occurred in the 3dUUO model. In conclusion, these results show that metformin has a beneficial effect in early stages of renal disease induced by 3dUUO. Furthermore, these effects appear to be independent of the expression of OCT1/2 and AMPK-β1, the most abundant AMPK-β isoform in the kidney.

The effects of different intensities of long-term grazing on the direction and strength of plant–soil feedback in a semiarid grassland of Northwest China

AimsPlant–soil feedbacks (PSFs) and grazing drive community dynamics in grasslands. We examined how the intensity of grazing and PSF interact to affect plant growth and explored what drives the observed feedback effects.MethodsThree dominant perennial plant species; Artemisia capillaris, Lespedeza davurica, and Stipa bungeana were grown in field-conditioned soil (sterilized or unsterilized) collected from four grazing intensities in a semiarid grassland of northwest China. Soil nutrient concentrations and root fungal communities were determined.ResultsPlant biomass increased with grazing intensity for the three plant species. Within each grazing intensity, plant growth in sterilized soil relative to unsterilized soil differed markedly among species. Soil inorganic nitrogen (N) concentration tended to increase with increasing grazing intensity. Arbuscular mycorrhizal fungi (AMF) colonization was high for all grazing intensities for L. davurica. Fusarium tricinctum, the most common pathogenic Fusarium species, had the highest frequency from the control for A. capillaris and tended to increase with increasing grazing intensity for S. bungeana.ConclusionsOur results suggest that in grasslands plant growth can be modified by the intensity of grazing via grazing-induced changes in soil nutrient availability and fungal communities. Additional studies are needed to determine how grazing intensity affects species co-existence through PSFs to mixed communities.

Quality Management in a Danish Business School - A Head of Department Perspective

The global change in the dominant idea of public higher education from a social institution to an industry has had a dramatic influence on the way that universities are organised and managed. Focus on efficiency and effectiveness has led to increasing demand for performance measures. In Denmark the tendency has been the same and in this article we discuss the latest proposed set of performance measures from the Ministry of Science. The purpose is to use the measures to allocate resources across universities. But it is obvious that these performance measures will have important behavioural consequence both across faculties, departments and within departments at a university. We are focusing on these aspects in this article.

Real Supply Shocks and the Money Growth-Inflation Relationship

Abstract This paper analyzes how real supply shocks affect monetary policy. Although it is widely accepted that money growth and inflation are one-to-one related in the long run, short run deviations are usually the case. Theoretically, we analyze whether such short run deviations can be attributed to global real supply shocks impinging on the economy, and empirically we provide evidence in favor of this hypothesis as well confirming that the money growth rate and inflation is one-to-one related in the long run for the United States.

A toxic endophyte-infected grass helps reverse degradation and loss of biodiversity of over-grazed grasslands in northwest China.

Overgrazing of China’s grasslands is increasingly causing biodiversity to decline. In degenerated grasslands of northwest China endophyte (Epichloё gansuensis) infected Achnatherum inebrians (drunken horse grass) is becoming widely distributed because of its toxicity to livestock. In this study, we investigated the ecological consequences of endophyte toxicity in this native grass, at three sites in northwest China, by comparing seed production of plant species and arthropod abundance in overgrazed grasslands with and without the presence of A. inebrians. Our findings demonstrate that the presence of endophyte infected A. inebrians reduces the loss of plant and arthropod biodiversity by providing a protected nursery free of animal grazing. Therefore, A. inebrians, typically regarded as an unwanted toxic invader by pastoralists, should be viewed as beneficial for grasslands as its presence maintains plant and arthropod biodiversity, and provides a foundation stone in the reconstruction and restoration of these grassland ecosystems.

Design and evolution of software architecture in practice

With special focus on software architectural issues, we report from the first two major phases of a software development project. Our experience suggests that explicit focus on software architecture in these phases was an important key to success. More specifically: Demands for stability, flexibility and proper work organisation in an initial prototyping phase of a project are facilitated by having an explicit architecture. However, the architecture should also allow for certain degrees of freedom for experimentation. Furthermore, in a following evolutionary development phase, architectural redesign is necessary and should be firmly based on experience gained from working within the prototype architecture. Finally, to get it right, the architecture needs to be prototyped, or iterated upon, throughout evolutionary development cycles. In this architectural prototyping process, we address the difficult issue of identifying and evolving functional components in the architecture and point to an architectural strategy a set of architectures, their context and evolution-that was helpful in this respect.