Evaluation of serum galactomannan detection for diagnosis of feline upper respiratory tract aspergillosis

Measurement of serum galactomannan (GM), a polysaccharide fungal cell-wall component, is a non-invasive test for early diagnosis of invasive aspergillosis in humans. Feline upper respiratory tract (URT) aspergillosis is an emerging infectious disease in cats. Diagnosis requires biopsy for procurement of tissue specimens for cytological or histological detection of fungal hyphae and for fungal culture. The aim of this study was to evaluate serum GM measurement as a non-invasive diagnostic test for URT aspergillosis in cats. A one-stage, immunoenzymatic sandwich ELISA was used to detect serum GM in 4 groups of cats; Group 1 (URT aspergillosis) – confirmed URT aspergillosis (n=13, sinonasal aspergillosis (SNA) n=6, sino-orbital aspergillosis (SOA) n=7), Group 2 (URT other) – other URT diseases (n=15), Group 3 (β-lactam) – cats treated with β-lactam antibiotics for non-respiratory tract disease (n=14), Group 4a – healthy young cats (≤ 1y of age, n=28), Group 4b – healthy adult cats (>1 y of age, n=16). One cat with SNA and two cats with SOA caused by an Aspergillus fumigatus-mimetic species, tested positive for serum GM. For a cut-off optical density index of 1.5, the overall sensitivity and specificity of the assay was 23% and 78% respectively. False positive results occurred in 29 % of cats in Group 3 and 32% of cats in Group 4a. Specificity increased to 90% when Groups 3 and 4a were excluded from the analysis. Overall, serum GM measurement has a poor sensitivity but is a moderately specific, non-invasive screening test to rule out infection in patients with suspected feline upper respiratory tract aspergillosis.Feline Health Research Fund (FHRF

Crack-Like Processes Governing the Onset of Frictional Slip

We perform real-time measurements of the net contact area between two blocks of like material at the onset of frictional slip. We show that the process of interface detachment, which immediately precedes the inception of frictional sliding, is governed by three different types of detachment fronts. These crack-like detachment fronts differ by both their propagation velocities and by the amount of net contact surface reduction caused by their passage. The most rapid fronts propagate at intersonic velocities but generate a negligible reduction in contact area across the interface. Sub-Rayleigh fronts are crack-like modes which propagate at velocities up to the Rayleigh wave speed, VR, and give rise to an approximate 10% reduction in net contact area. The most efficient contact area reduction (~20%) is precipitated by the passage of slow detachment fronts. These fronts propagate at anomalously slow velocities, which are over an order of magnitude lower than VR yet orders of magnitude higher than other characteristic velocity scales such as either slip or loading velocities. Slow fronts are generated, in conjunction with intersonic fronts, by the sudden arrest of sub-Rayleigh fronts. No overall sliding of the interface occurs until either of the slower two fronts traverses the entire interface, and motion at the leading edge of the interface is initiated. Slip at the trailing edge of the interface accompanies the motion of both the slow and sub-Rayleigh fronts. We might expect these modes to be important in both fault nucleation and earthquake dynamics.Comment: 19 page, 5 figures, to appear in International Journal of Fractur

Visual ecology of aphids – a critical review on the role of colours in host finding

We review the rich literature on behavioural responses of aphids (Hemiptera: Aphididae) to stimuli of different colours. Only in one species there are adequate physiological data on spectral sensitivity to explain behaviour crisply in mechanistic terms. Because of the great interest in aphid responses to coloured targets from an evolutionary, ecological and applied perspective, there is a substantial need to expand these studies to more species of aphids, and to quantify spectral properties of stimuli rigorously. We show that aphid responses to colours, at least for some species, are likely based on a specific colour opponency mechanism, with positive input from the green domain of the spectrum and negative input from the blue and/or UV region. We further demonstrate that the usual yellow preference of aphids encountered in field experiments is not a true colour preference but involves additional brightness effects. We discuss the implications for agriculture and sensory ecology, with special respect to the recent debate on autumn leaf colouration. We illustrate that recent evolutionary theories concerning aphid–tree interactions imply far-reaching assumptions on aphid responses to colours that are not likely to hold. Finally we also discuss the implications for developing and optimising strategies of aphid control and monitoring

Modelling creativity: identifying key components through a corpus-based approach

Creativity is a complex, multi-faceted concept encompassing a variety of related aspects, abilities, properties and behaviours. If we wish to study creativity scientifically, then a tractable and well-articulated model of creativity is required. Such a model would be of great value to researchers investigating the nature of creativity and in particular, those concerned with the evaluation of creative practice. This paper describes a unique approach to developing a suitable model of how creative behaviour emerges that is based on the words people use to describe the concept. Using techniques from the field of statistical natural language processing, we identify a collection of fourteen key components of creativity through an analysis of a corpus of academic papers on the topic. Words are identified which appear significantly often in connection with discussions of the concept. Using a measure of lexical similarity to help cluster these words, a number of distinct themes emerge, which collectively contribute to a comprehensive and multi-perspective model of creativity. The components provide an ontology of creativity: a set of building blocks which can be used to model creative practice in a variety of domains. The components have been employed in two case studies to evaluate the creativity of computational systems and have proven useful in articulating achievements of this work and directions for further research

Lipid Modifications of Sonic Hedgehog Ligand Dictate Cellular Reception and Signal Response

Sonic hedgehog (Shh) signaling regulates cell growth during embryonic development, tissue homeostasis and tumorigenesis. Concentration-dependent cellular responses to secreted Shh protein are essential for tissue patterning. Shh ligand is covalently modified by two lipid moieties, cholesterol and palmitate, and their hydrophobic properties are known to govern the cellular release and formation of soluble multimeric Shh complexes. However, the influences of the lipid moieties on cellular reception and signal response are not well understood.We analyzed fully lipidated Shh and mutant forms to eliminate one or both adducts in NIH3T3 mouse embryonic fibroblasts. Quantitative measurements of recombinant Shh protein concentration, cellular localization, and signaling potency were integrated to determine the contributions of each lipid adduct on ligand cellular localization and signaling potency. We demonstrate that lipid modification is required for cell reception, that either adduct is sufficient to confer cellular association, that the cholesterol adduct anchors ligand to the plasma membrane and that the palmitate adduct augments ligand internalization. We further show that signaling potency correlates directly with cellular concentration of Shh ligand.The findings of this study demonstrate that lipid modification of Shh determines cell concentration and potency, revealing complementary functions of hydrophobic modification in morphogen signaling by attenuating cellular release and augmenting reception of Shh protein in target tissues

An Amphioxus Gli Gene Reveals Conservation of Midline Patterning and the Evolution of Hedgehog Signalling Diversity in Chordates

Background. Hedgehog signalling, interpreted in receiving cells by Gli transcription factors, plays a central role in the development of vertebrate and Drosphila embryos. Many aspects of the signalling pathway are conserved between these lineages, however vertebrates have diverged in at least one key aspect: they have evolved multiple Gli genes encoding functionally-distinct proteins, increasing the complexity of the hedgehog-dependent transcriptional response. Amphioxus is one of the closest living relatives of the vertebrates, having split from the vertebrate lineage prior to the widespread gene duplication prominent in early vertebrate evolution. Principal findings. We show that amphioxus has a single Gli gene, which is deployed in tissues adjacent to sources of hedgehog signalling derived from the midline and anterior endoderm. This shows the duplication and divergence of the Gli family, and hence the origin of vertebrate Gli functional diversity, was specific to the vertebrate lineage. However we also show that the single amphioxus Gli gene produces two distinct transcripts encoding different proteins. We utilise three tests of Gli function to examine the transcription regulatory capacities of these different proteins, demonstrating one has activating activity similar to Gli2, while the other acts as a weak repressor, similar to Gli3. Conclusions. These data show that the vertebrates and amphioxus have evolved functionally-similar repertoires of Gli proteins using parallel molecular routes; vertebrates via gene duplication and divergence, and amphioxus via alternate splicing of a single gene. Our results demonstrate that similar functional complexity of intercellular signalling can be achieved via different evolutionary pathways

Computed Tomography Measurement of Rib Cage Morphometry in Emphysema

Background: Factors determining the shape of the human rib cage are not completely understood. We aimed to quantify the contribution of anthropometric and COPD-related changes to rib cage variability in adult cigarette smokers. Methods: Rib cage diameters and areas (calculated from the inner surface of the rib cage) in 816 smokers with or without COPD, were evaluated at three anatomical levels using computed tomography (CT). CTs were analyzed with software, which allows quantification of total emphysema (emphysema%). The relationship between rib cage measurements and anthropometric factors, lung function indices, and %emphysema were tested using linear regression models. Results: A model that included gender, age, BMI, emphysema%, forced expiratory volume in one second (FEV1)%, and forced vital capacity (FVC)% fit best with the rib cage measurements (R2  = 64% for the rib cage area variation at the lower anatomical level). Gender had the biggest impact on rib cage diameter and area (105.3 cm2; 95% CI: 111.7 to 98.8 for male lower area). Emphysema% was responsible for an increase in size of upper and middle CT areas (up to 5.4 cm2; 95% CI: 3.0 to 7.8 for an emphysema increase of 5%). Lower rib cage areas decreased as FVC% decreased (5.1 cm2; 95% CI: 2.5 to 7.6 for 10 percentage points of FVC variation). Conclusions: This study demonstrates that simple CT measurements can predict rib cage morphometric variability and also highlight relationships between rib cage morphometry and emphysema

Sensing of Fatty Acids for Octanoylation of Ghrelin Involves a Gustatory G-Protein

Ghrelin is an important regulator of energy--and glucose homeostasis. The octanoylation at Ser(3) is essential for ghrelin's biological effects but the mechanisms involved in the octanoylation are unknown. We investigated whether the gustatory G-protein, α-gustducin, and the free fatty acid receptors GPR40 and GPR120 are involved in the fatty acid sensing mechanisms of the ghrelin cell.Wild-type (WT) and α-gustducin knockout (gust(-/-)) mice were fed a glyceryl trioctanoate-enriched diet (OD) during 2 weeks. Ghrelin levels and gastric emptying were determined. Co-localization between GPR40, GPR120 and ghrelin or α-gustducin/α-transducin was investigated by immunofluorescence staining. The role of GPR120 in the effect of medium and long chain fatty acids on the release of ghrelin was studied in the ghrelinoma cell line, MGN3-1. The effect of the GPR40 agonist, MEDICA16, and the GPR120 agonist, grifolic acid, on ghrelin release was studied both in vitro and in vivo.Feeding an OD specifically increased octanoyl ghrelin levels in the stomach of WT mice but not of gust(-/-) mice. Gastric emptying was accelerated in WT but not in gust(-/-) mice. GPR40 was colocalized with desoctanoyl but not with octanoyl ghrelin, α-gustducin or α-transducin positive cells in the stomach. GPR120 only colocalized with ghrelin in the duodenum. Addition of octanoic acid or α-linolenic acid to MGN3-1 cells increased and decreased octanoyl ghrelin levels, respectively. Both effects could not be blocked by GPR120 siRNA. MEDICA16 and grifolic acid did not affect ghrelin secretion in vitro but oral administration of grifolic acid increased plasma ghrelin levels.This study provides the first evidence that α-gustducin is involved in the octanoylation of ghrelin and shows that the ghrelin cell can sense long- and medium-chain fatty acids directly. GPR120 but not GPR40 may play a role in the lipid sensing cascade of the ghrelin cell