bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of Arabidopsis ACBP3 Enhances NPR1-Dependent Plant Resistance to Pseudomonas syringe pv tomato DC3000
Authors: Xiao Shi , Chye Mee-Len
Published: June 2011

ACBP3 is one of six Arabidopsis (Arabidopsis thaliana) genes, designated ACBP1 to ACBP6, that encode acyl-coenzyme A (CoA)-binding proteins (ACBPs). These ACBPs bind long-chain acyl-CoA esters and phospholipids and are involved in diverse cellular functions, including acyl-CoA homeostasis, development, and stress tolerance. Recombinant ACBP3 binds polyunsaturated acyl-CoA esters and phospholipids in vitro. Here, we show that ACBP3 plays a role in the plant defense response to the bacterial pathogen Pseudomonas syringae pv tomato DC3000. ACBP3 mRNA was up-regulated upon pathogen infection and treatments using pathogen elicitors and defense-related phytohormones. Transgenic Arabidopsis ACBP3 overexpressors (ACBP3-OEs) showed constitutive expression of pathogenesis-related genes (PR1, PR2, and PR5), cell death, and hydrogen peroxide accumulation in leaves. Consequently, ACBP3-OEs displayed enhanced resistance to the bacterial pathogen P. syringae DC3000. In contrast, the acbp3 T-DNA insertional mutant was more susceptible and exhibited lower PR gene transcript levels upon infection. Using the ACBP3 OE-1 line in combination with nonexpressor of PR genes1 (npr1-5) or coronatine-insensitive1 (coi1-2), we concluded that the enhanced PR gene expression and P. syringae DC3000 resistance in the ACBP3-OEs are dependent on the NPR1-mediated, but not the COI1-mediated, signaling pathway. Given that ACBP3-OEs showed greater susceptibility to infection by the necrotrophic fungus Botrytis cinerea while the acbp3 mutant was less susceptible, we suggest that ACBP3 plays a role in the plant defense response against biotrophic pathogens that is distinct from necrotrophic pathogens. ACBP3 function in plant defense was supported further by bioinformatics data showing up-regulation of many biotic and abiotic stress-related genes in ACBP3 OE-1 in comparison with the wild type.
Normal prostate‐derived stromal cells stimulate prostate cancer development
Authors: Peng Yu‐Bing , Zhou Juan , Gao Yan , Li Yu‐Hua , Wang Hao , Zhang Ming , Ma Li‐Ming , Chen Qi , Da Jun , Wang Zhong , Li Runsheng
Published: June 2011

Stromal cells play a decisive role in regulating tumor progression. In this study, we assessed the significance of normal prostate‐derived stromal cells (PSCs) in prostate cancer development. An in vivo s.c. tumor model was established as follows: Group 1, DU145 cells alone; Group 2, DU145 + PSCs; Group 3, DU145 cells alone injected into pre‐castrated mice; and Group 4, DU145 + PSCs injected into pre‐castrated mice. Following injection, tumors were only detectable in the first two groups, with more aggressive growth in Group 2 than in Group 1 (P < 0.05). Immunohistochemical analysis revealed significantly higher proliferation (P < 0.05), but not apoptosis or altered expression of androgen receptor in Group 2, as compared with Group 1. In vitro, DU145 cells isolated from Group 1 tumors showed lower viability and migratory capability than those from Group 2. cDNA microarray on isolated DU145 cells from Groups 1 and 2 revealed the differential expression of genes regulating cell cycle progression and cell mobility, including GADD45A, RHOV, KLK11, and PCK1. Our results suggest that stromal cells derived from normal prostate potentiate the development of tumor growth in vivo, which is achieved at least in part through the regulation of cell‐cycle‐ and migration‐related gene expression within the tumor cells. (Cancer Sci 2011; 102: 1630–1635)
The large‐scale dynamics of grain‐size variation in alluvial basins, 1: Theory
Authors: Paola Chris , Heller Paul L. , Angevine Charles L.
Published: June 2011

We study the interplay of various factors causing vertical grain‐size changes in alluvial basins using a simple coupled model for sediment transport and downstream partitioning of grain sizes. The sediment‐transport model is based on the linear diffusion equation; by deriving this from first principles we show that the main controls on the diffusivity are water discharge and stream type (braided or single‐thread). The grain‐size partitioning model is based on the assumption that the deposit is dominated by gravel until all gravel in transport has been exhausted, at which point deposition of the finer fractions begins.

We then examine the response of an alluvial basin to sinusoidal variation in each of four basic governing variables: input sediment flux, subsidence rate, supplied gravel fraction, and diffusivity (controlled mainly by water flux). We find that, except in the case of variable gravel fraction, the form of the basin response depends strongly on the time‐scale over which the variation occurs. There is a natural time‐scale for any basin, which we call the ‘equilibrium time’, defined as the square of basin length divided by the diffusivity. We define ‘slow’ variations in imposed independent variables as those whose period is long compared with the equilibrium time. We find that slow variation in subsidence produces smoothly cyclic gravel‐front migration, with progradation during times of low sedimentation rate, while slow variation in sediment flux produces gravel progradation during times of high sedimentation rate. Slow variation in diffusivity produces no effect. Conversely, we define ‘rapid’ variations as those whose period is short compared with the equilibrium time. Our model results suggest that basins respond strongly to rapid variation in either sediment flux or diffusivity; in both cases, deep proximal unconformities are associated with abrupt gravel progradation. This progradation occurs during times of either low sediment flux or high diffusivity. On the other hand, basin response to variation in subsidence rate gradually diminishes as the time scale becomes short relative to the equilibrium time. Each of the four variables we have considered ‐ input sediment flux, subsidence, gravel fraction, and diffusivity ‐ is associated with a characteristic response pattern. In addition, the time scale of imposed variations relative to the equilibrium time acts in its own right as a fundamental control on the form of the basin response.
Adult age and ex vivo protein binding of lorazepam, oxazepam and temazepam in healthy subjects
Authors: Chin Paul K. L. , Jensen Berit P. , Larsen Helle S. , Begg Evan J.
Published: June 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The hypothesis that protein binding decreases with ageing has been used to explain studies that have not found a decline in total clearance in relation to age of highly protein bound drugs, cleared by capacity limited metabolism.

• Lorazepam, oxazepam and temazepam are highly protein bound to albumin and are cleared by capacity limited metabolism.

• There is conflicting or little data concerning the relationship between the protein binding of these drugs and age.

WHAT THIS PAPER ADDS

• In an ex vivo study of 60 healthy subjects (19–87 years), no clinically significant change was seen in the protein binding of these benzodiazepines with age, arguing against the hypothesis, at least in healthy subjects. The study was adequately powered to show a change of at least 7–10%.

AIM To see if adult age correlates with ex vivo protein binding of lorazepam, oxazepam and temazepam in healthy subjects.

METHODS Sixty healthy drug free subjects were recruited in the age groups 18–39, 40–64 and ≥65 years. Plasma albumin concentrations were determined. Ex vivo unbound fractions (fu) were assessed by spiking samples and measuring the free and total concentrations.

RESULTS No correlation of age with fu was seen. The study was powered to demonstrate a change in fu of ≥7–10%. A decline in plasma albumin concentration of ∼0.03 g l−1 year−1 was seen with increasing age (P= 0.032) and was associated with increased fu of lorazepam (P= 0.009) and oxazepam (P= 0.014).

CONCLUSIONS There was no association of adult age with ex vivo fu of lorazepam, oxazepam or temazepam in healthy subjects.
What’s new in skin cancer? An analysis of guidelines and systematic reviews published in 2008–2009
Authors: Macbeth A. E. , Grindlay D. J. C. , Williams H. C.
Published: June 2011

This review summarizes clinically important findings from 17 systematic reviews and 2 guidelines on skin cancer indexed between April 2008 and April 2009. Melanoma primary-prevention measures, such as education, are more likely to be successful in younger children than adolescents, and general population screening for melanoma by whole-body examination is not currently supported by the evidence. A large systematic review of melanoma and pregnancy concluded that pregnancy does not affect prognosis. Two systematic reviews imply that sunburn later in life also increases the risk of melanoma, and that it is just as important as sunburn early in life. Three systematic reviews discussed the role of positron emission tomography and sentinel lymph-node biopsy for melanoma staging, but produced conflicting results. Superior diagnostic accuracy of dermatoscopy over naked-eye examination for melanoma was found in one review, while a second implied nonsignificantly higher sensitivity of computer-based diagnostic methods over dermatoscopy for melanoma but with reduced specificity. There were no identified randomized controlled trials of treatments for unresectable recurrent melanoma, and a review of immunotherapy with vaccines for melanoma failed to prove improved overall and disease-free survival. Guidelines for the management of basal cell carcinoma call for risk stratification, based on numerous factors including tumour size, site and histological subtype. Squamous cell carcinoma of the ear has been shown to spread to regional lymph nodes more commonly than to other sites, and may be predicted by depth of invasion, tumour size, cellular differentiation and completeness of excision.
A coherent geostatistical approach for combining choropleth map and field data in the spatial interpolation of soil properties
Authors: Goovaerts P.
Published: June 2011

Information available for mapping continuous soil attributes often includes point field data and choropleth maps such as soil or geology maps that model the spatial distribution of soil attributes as the juxtaposition of polygons (areas) with constant values. This paper presents two approaches to incorporate both point and areal data in the spatial interpolation of continuous soil attributes. In the first instance, area‐to‐point kriging is used to map the variability within soil units while ensuring the coherence of the prediction so that the average of disaggregated estimates is equal to the original areal datum. The resulting estimates are then used as local means in residual kriging. The second approach proceeds in one step and capitalizes on (i) a general formulation of kriging that allows the combination of both point and areal data through the use of area‐to‐area, area‐to‐point and point‐to‐point covariances in the kriging system, (ii) the availability of Geographical Information Systems (GIS) to discretize polygons of irregular shape and size and (iii) knowledge of the point‐support variogram model that can be inferred directly from point measurements, thereby eliminating the need for deconvolution procedures. The two approaches are illustrated using the geological map and heavy metal concentrations recorded in the topsoil of the Swiss Jura. Sensitivity analysis indicates that the new procedures improve prediction over ordinary kriging and traditional residual kriging based on the assumption that the local mean is constant within each mapping unit.
Lognormal block kriging for contaminated soil
Authors: Paul R. , Cressie N.
Published: June 2011

Many soil properties are lognormally distributed over a spatial domain of interest, 𝒟, including contaminants caused by anthropogenic activity. Remediation of contaminated soil is often made at the block level, where the contaminant is averaged over pre‐specified spatial regions of 𝒟 called blocks. During the period 1954–1963, devices composed of radioactive material were blown apart by chemical explosives at Area 13 of the Nevada Test Site in the United States. A consequence of the testing was the contamination of the immediately surrounding soil and vegetation with americium (Am). The concentrations are clearly lognormally distributed, and ex situ soil remediation requires prediction of average Am concentration over blocks. Recent developments in geostatistical methodology and computation make optimal lognormal block kriging appealing and tractable. In this article, we apply these to obtain an optimal spatial predictor of block‐averaged Am contamination in soil at the Nevada Test Site. The dataset that we analyse has multiple Am observations for certain spatial locations, for which we develop kriging equations that are often unavailable in kriging software. We also show how these multiple observations can be used to obtain an estimate of the measurement error.
On the soil information content of visible–near infrared reflectance spectra
Authors: Viscarra Rossel R. A. , Chappell A. , De Caritat P. , McKenzie N. J.
Published: June 2011

We describe the information content of soil visible–near infrared (vis–NIR) reflectance spectra and map their spatial distribution across Australia. The spectra of 4030 surface soil samples from across the country were measured with a vis–NIR spectrometer in the range 350 to 2500 nm. The spectra were compressed by a principal component analysis (PCA) and the resulting scores were mapped by ordinary point kriging. The largely dominant and common feature in the maps was the difference between the more expansive, older and more weathered landscapes in the centre and west of Australia and the generally younger, more complex landscapes in the east. A surface soil class map derived from the clustering of the principal components was similar to an existing soil classification map. We show that vis–NIR reflectance spectra (i) provide a rapid and efficient integrative measure of the composition of the soil, (ii) can replace the use of traditional soil properties to describe the soil and make pedological interpretations of its spatial distribution and (iii) can be used to classify soil objectively.
The assessment of point‐source and diffuse soil metal pollution using robust geostatistical methods: a case study in Swansea (Wales, UK)
Authors: Marchant B. P. , Tye A. M. , Rawlins B. G.
Published: June 2011

The spatial variation of soil metal content arising from diffuse pollution in industrial regions cannot be analysed by conventional geostatistical methods because predictions are influenced by metal content from natural sources and extreme values from point‐source pollution. We analyse a survey of soil arsenic, copper, lead, and tin at 372 locations around Swansea (Wales, UK). We use the approach of Hamon et al. (2004) to determine the natural metal concentrations in contaminated regions from the iron content. However, we find that this indicator is not appropriate to the area around Swansea because the iron content is elevated across the contaminated region. Therefore the natural concentration of each metal is approximated by the median concentration on nearby uncontaminated rural soils on the same parent material. We divide the remaining variation between diffuse pollution and point‐source pollution by the robust winsorizing algorithm of Hawkins & Cressie (1984). This leads to a plausible log‐Gaussian model with a constant mean which represents the diffuse pollution and estimates of the contribution of point‐source pollution at each observation site. Point‐source pollution occurs at sites historically associated with production, transport and disposal of industrial wastes. The pattern of diffuse pollution is consistent with emissions from multiple smelters located throughout urban Swansea and the effects of prevailing wind and topography are evident.
A risk map for gully locations in central Queensland, Australia
Authors: Eustace A. H. , Pringle M. J. , Denham R. J.
Published: June 2011

In central Queensland, Australia, relatively little is known about where gullies occur (‘gully presence’). This is despite a general acceptance among scientists and politicians that gully erosion in the region is an ecologically important process, exacerbated by grazing pressure. We aimed to create a risk map of gully presence for a 4.86 × 106‐ha area of central Queensland dominated by grazing and thought to be particularly prone to gully erosion. We achieved this by using (i) light detection and ranging (lidar) technology (vertical accuracy < 0.15 m; spatial resolution 0.5 m) to observe topography on transects at eight selected sites within the study area, (ii) object‐oriented classification to derive gully presence from lidar observations and (iii) a random forest to model the relationship between gully presence and a set of readily available explanatory variables (comprising soil, topography, and vegetation information; finest spatial resolution 25 m) and (iv) extrapolating the model to unsampled locations. Cross‐validation indicated that the predictive ability of the model was modest, with an average area under the receiver operating characteristic curve of 0.62 (where 1.0 is a perfect model and 0.5 is no better than chance). The greatest risk of gully presence was associated with areas of large topographic variation, and where, coincidentally, there was relatively little long‐term vegetation cover. Ultimately, however, we acknowledge that the quality of the map is limited by the small area of observed lidar data relative to the study area, the relatively coarse spatial resolution of the explanatory variables and the possibility that gully presence is the result of different processes at different locations.
Mortality in juvenile salmonids passed through an agricultural Hidrostal pump
Authors: THOMPSON A. M. , GLASGOW J. , BUEHRENS T. , DRUCKER E. G.
Published: June 2011

Abstract  Hidrostal pumps have been successfully employed in live fish transport, yet their effectiveness in fish passage is incompletely understood. This study investigates juvenile salmonid mortality in experimental passage trials through Hidrostal pumps at an agricultural pump facility in Washington State, USA. The effects of impeller pitch, rotational speed and fish body size on passage survival were examined. Hatchery‐reared salmonids [Oncorhynchus mykiss (Walbaum) and Oncorhynchus kisutch (Walbaum)] were introduced to low‐ and high‐pitch impeller assemblies operating at two speeds. Instantaneous mortality rates ranged from 0 to 4% for high‐pitch trials and from 3 to 10% for low‐pitch trials. Larger fish experienced sublethal injury at higher rates (approximately 60% injured) than smaller fish (approximately 23% injured) and exhibited greater susceptibility to injury at higher pump speed. Injury between trials was compared by ranking according to severity and summed for each treatment; greater injury severity was found for the low‐pitch impeller and from higher rotational speeds. Although injury and mortality rates to fish passing through Hidrostal pumps may be reduced through the use of higher‐pitch impellers and lower operational speeds, the use of pump‐bypass facilities may be warranted where acceptable impact thresholds are low.
Short chain xylooligosaccharides: a potential prebiotic used to improve batter fermentation and its effect on the quality attributes of idli, a cereal–legume‐based Indian traditional food
Authors: Aachary Ayyappan Appukuttan , Gobinath Duraiswamy , Prapulla Siddalingaiya Gurudutt
Published: June 2011

Xylooligosaccharides (XOS), a potential prebiotic exhibits important technological characteristics and interesting nutritional properties. The major fraction in XOS produced enzymatically from corncob was characterised as β‐d‐xylopyranosyl‐(1,4)‐d‐xylanopyranose (xylobiose) using 13C and 2D‐HSQC NMR. The use of this XOS as a prebiotic in idli, a cereal/legume‐based fermented cake, and its effect on texture, fermentation and sensory characteristics was investigated. Idli batter was fermented with different concentrations of XOS (0, 0.2, 0.4 and 0.6% w/v) for 4–18 h conventionally. The addition of XOS markedly increased lactic acid bacteria number (9.88 ± 0.08 log cfu g−1) which resulted in rapid reduction in pH (4.61 ± 0.03) and specific gravity after 6 h of fermentation when compared to conventional batter fermentation for 18 h without XOS (9.46 ± 0.06 log cfu g−1). Instrumental (colour and texture) and sensory evaluation indicated that the optimum conditions were 0.4% XOS and 6 h fermentation. Idlis with XOS had higher moisture content and a softer texture. Addition of XOS benefits both fermentation and idli quality.
The anxiety of Taiwanese women with or without continuity treatment after previous in vitro fertilisation failure
Authors: Su Tsann‐Juu , Tzeng Ya‐Ling , Kuo Pi‐Chao
Published: June 2011

Aims and objectives.  To compare the anxiety levels of Taiwanese women who continued with in vitro fertilisation treatment and those who discontinued treatment post‐in vitro fertilisation failure.

Background.  In vitro fertilisation is perceived as the last resort of infertility treatment. The impact of unsuccessful in vitro fertilisation treatment on psychological function has been documented; however, research comparing the levels of anxiety of women who cease and those who continue in vitro fertilisation post‐failure is scant.

Design.  A cross‐sectional comparative study design was used.

Method.  Fifty‐eight women in whom in vitro fertilisation had failed within the previous year were recruited to this study from a medical centre in northern Taiwan; 34 women continued treatment and 24 discontinued treatment. The State‐Trait Anxiety Inventory was used to assess their levels of anxiety.

Results.  Women in the group who continued treatment exhibited higher state and trait anxiety (TA) than women in the group who discontinued treatment (p < 0·005). The number and frequency of in vitro fertilisation cycles were significantly higher in the group who continued treatment than in those who did not. A strong positive correlation between state and TA (r = 0·8, p < 0·01) existed in both groups.

Conclusions.  Both groups exhibited considerable levels of anxiety; however, the women who continued in vitro fertilisation treatment had higher levels of anxiety than those who discontinued treatment.

Relevance to clinical practice.  The level of anxiety of women who decide to continue in vitro fertilisation treatment should be assessed as early as possible and counselling services provided to women who experience in vitro fertilisation failure should concentrate more on relieving psychological distress. One year after discontinuing treatment, some women still experience considerable anxiety; therefore, the care and assistance provided to these women need to be continually evaluated.
Family quality of life: adult school children with intellectual disabilities in Bosnia and Herzegovina
Authors: Svraka E. , Loga S. , Brown I.
Published: June 2011

Aims  This study endeavours to provide initial data on quality of life for families with adult children who have intellectual disabilities (ID) in the Canton of Sarajevo.

Methods  The principal measure used was the Family Quality of life Survey 2006 – main caregivers of people with intellectual or developmental disabilities. The sample consisted of the main caregivers of 35 families with adult school children with ID who attended classes in a specially adapted programme in the Center of Vladimir Nazor and in the Vocational Secondary School in Sarajevo. Of the 35 participants, 21 were male and 14 female. Students with disabilities ranged from 19 to 32 years old (mean 21.45).

Results  Consistent with previous research, the nine domains measured by the scale were all rated high for Importance. Opportunities were considered to be particularly low for Financial Well‐Being and Support from Others. These domains were also rated lowest for Attainment and Satisfaction. Initiative was relatively high across all domains, and Stability (the degree to which things were seen as likely to improve or decline) varied slightly across domains but the means indicated that things are expected to stay almost the same or improve slightly.

Conclusions  This research provides initial data for family quality of life in Bosnia and Herzegovina. It also provides suggestions for improving quality of life for families that have one or more members with ID. The results should also contribute to rejecting stereotypes and promoting inclusion of children with ID as well as the rights of their families.
High levels of IgM against methylglyoxal‐modified apolipoprotein B100 are associated with less coronary artery calcification in patients with type 2 diabetes
Authors: Engelbertsen D. , Anand D. V. , Fredrikson G. N. , Hopkins D. , Corder R. , Shah P. K. , Lahiri A. , Nilsson J. , Bengtsson E.
Published: June 2011

Abstract.  Engelbertsen D, Anand DV, Fredrikson GN, Hopkins D, Corder R, Shah PK, Lahiri A, Nilsson J, Bengtsson E (Skåne University Hospital, Lund University, Malmö, Sweden; Cardiac Imaging and Research Centre, Wellington Hospital, London, UK; Malmö University, Malmö, Sweden; King’s College Hospital, London, UK; William Harvey Research Institute, London, UK; Cedars‐Sinai Medical Center, Los Angeles, CA, USA; David Geffen School of Medicine, UCLA School of Medicine, Los Angeles, CA, USA). High levels of IgM against methylglyoxal‐modified apolipoprotein B100 is associated with less coronary artery calcification in patients with type 2 diabetes. J Intern Med 2012; 271: 82–89.

Objective.  Advanced glycation end products (AGE) have been implicated in diabetic vascular complications through activation of pro‐inflammatory genes. AGE‐modified proteins are also targeted by the immune system resulting in the generation of AGE‐specific autoantibodies, but the association of these immune responses with diabetic vasculopathy remains to be fully elucidated. The aim of this study was to determine whether antibodies against apolipoprotein B100 modified by methylglyoxal (MGO‐apoB100) are associated with coronary atherosclerosis in patients with type 2 diabetes.

Methods.  We measured antibodies against MGO‐apoB100 in plasma from 497 type 2 diabetic patients without clinical signs of cardiovascular disease. Severity of coronary disease was assessed as coronary artery calcium (CAC) imaging. Immunoglobulin (Ig)M and IgG levels recognizing MGO‐apoB100 were determined by enzyme‐linked immunosorbent assay.

Results.  Anti‐MGO‐apoB100 IgM antibody levels were higher in subjects with a low to moderate CAC score (≤400 Agatston units) than in subjects with a high score (>400 Agatston units; 136.8 ± 4.4 vs. 101.6 ± 7.4 arbitrary units (AU), P < 0.0001) and in subjects demonstrating no progression of CAC during 30 months of follow‐up (136.4 ± 5.7 vs. 113.9 ± 6.2 AU in subjects with progression, P < 0.0001). Subjects with a family history of premature myocardial infarction had lower levels of anti‐MGO‐apoB100 IgM. Female subjects had higher levels of anti‐MGO‐apoB100 antibodies and lower CAC than men. Accordingly, high levels of IgM against MGO‐apoB100 are associated with less severe and a lower risk of progression of coronary disease in subjects with type 2 diabetes.

Conclusions.  Although conclusions regarding causal relationships based on epidemiological observations need to be made with caution, our findings suggest the possibility that anti‐MGO‐apoB100 IgM may be protective in diabetic vasculopathy.
Heritability not missing—genetic basis of sexual weaponry uncovered
Authors: SCOTT McCAIRNS R. J. , MERILÄ JUHA
Published: June 2011

The chase to uncover the genetic underpinnings of quantitative traits of ecological and evolutionary importance has been on for a good while. However, the potential power of genome‐wide association studies (GWAS) as an approach to identify genes of interest in wild animal populations has remained untapped. Setting technical and economic explanations aside, the sobering lack of success in human GWAS might have fed this restraint. Namely, while GWAS have successfully identified genetic variants associated with hundreds of complex traits (e.g. Ku et al. 2010), these variants have generally captured only a low percentage of variance in traits known to be highly heritable—an observation came to be known as the ‘missing heritability’ (Maher 2008; Aulchenko et al. 2009). Hence, if the vastly resourced human studies have been unsuccessful (but see: Yang et al. 2010), why should we expect that less resourced studies of wild animal populations would be able do better? In this issue of Molecular Ecology, Johnston et al. (2011) prove this line of thinking wrong. In an impressive and what may well be the most advanced gene mapping study ever performed in a wild population, they identify a single locus (RXFP2) responsible for explaining horn phenotype in feral domestic sheep from St Kilda (Fig. 1). This same locus is also shown to account for up to 76% of additive genetic variance in horn size in male sheep: this contrasts sharply with most human GWAS where mapped loci explain only a modest proportion of genetic variation in a given trait.

 The Soay sheep of the St Kilda archipelago are a primitive feral breed of domestic sheep. Pictured are a male with vestigial horns (=‘scurred’; left) and two normal‐horned males (centre and right). Photograph courtesy of Peter Korsten.

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The significance of environmental exposure on the progression of allergic diseases
Authors: Wahn U.
Published: June 2011

To cite this article: Wahn U. The significance of environmental exposure on the progression of allergic diseases. Allergy 2011; 66 (Suppl. 95):7–9.

In addition to strong genetic influences on atopic sensitization and disease development in infancy and childhood, a number of environmental factors modulate clinical and immunological phenotypes early in life and even prenatally. These factors include gastrointestinal or skin exposure to food allergens; respiratory exposure to indoor and outdoor allergens; presence of environmental pollutants such as tobacco smoke; and exposure to microbial compounds.
Allergic diseases, gene–environment interactions
Authors: Renz H. , Conrad M. , Brand S. , Teich R. , Garn H. , Pfefferle P. I.
Published: June 2011

To cite this article: Renz H, Conrad M, Brand S, Teich R, Garn H, Pfefferle PI. Allergic diseases, gene–environment interactions. Allergy 2011; 66 (Suppl. 95): 10–12.

Allergic asthma develops in part from dysregulation of the innate and adaptive immune functions, particularly an imbalance in the Th2‐driven adaptive immune response. This dysregulation is the result of complex interactions between genes and environment. These interactions occur both pre‐ and postnatally, providing opportunities for early interventions in immunological programming.
Allergen structures and epitopes
Authors: Meno K. H.
Published: June 2011

To cite this article: Meno KH. Allergen structures and epitopes. Allergy 2011; 66 (Suppl. 95): 19–21.

Human type 1 hypersensitivity diseases such as allergic rhinoconjunctivitis are characterized by allergen‐specific IgE antibodies produced in allergic individuals after allergen exposure. IgE antibodies bound to receptors on the surface of effector cells trigger an allergic response by interacting with three‐dimensional (conformational) epitopes on the allergen surface. Crystal structures are available for complexes of antibody specifically bound to five allergens, from birch pollen, bee venom, cockroach, cow’s milk and timothy grass pollen. The details of the antibody–allergen interaction extending all the way to atomic resolution are available from such complexes. In vitro investigations using recombinant monoclonal antibodies and human basophils show that binding affinity is a key to triggering the allergic response. Continued molecular characterization of antibody–allergen interactions is paving the way for the use of recombinant allergens in allergen‐specific diagnosis and immunotherapy.
Mucosal dendritic cells in allergy and immunotherapy
Authors: Novak N. , Allam J.‐P.
Published: June 2011

To cite this article: Novak N, Allam J‐P. Mucosal dendritic cells in allergy and immunotherapy. Allergy 2011; 66 (Suppl. 95): 22–24.

The oral epithelium contains oral mucosal Langerhans cells (oLCs) that constitutively express the high‐affinity IgE‐receptor FcεRI, the lipopolysaccharide receptor CD14 and toll‐like receptor (TLR)4. The distribution of oLCs profoundly differs at distinct oral mucosal sites, with higher numbers of oLCs detectable in the vestibulum compared with the sublingual region. The oLC response to activation of TLR4 and FcεRI and to binding of allergen suggests that these cells are involved in the maintenance of tolerance towards bacterial components and allergens. Thus, oLCs are important targets for allergens and adjuvants during sublingual immunotherapy, and characterizing them is crucial for improving allergen‐specific immunotherapy.
Anaphylaxis caused by Hymenoptera stings: from epidemiology to treatment
Authors: Bilò M. B.
Published: June 2011

To cite this article: Bilò MB. Anaphylaxis caused by Hymenoptera stings: from epidemiology to treatment. Allergy 2011; 66 (Suppl. 95): 35–37.

Hymenoptera venom allergy occasionally causes fatal reactions. The prevalence of systemic reactions (SRs) is 0.3–8.9%, with anaphylaxis in 0.3–42.8% of cases. Factors contributing to reaction severity include older age, insect type, a previous less severe SR, preexisting diseases, concomitant treatments, mast cell diseases and elevated baseline tryptase serum concentration. Venom immunotherapy (VIT) is highly effective, as shown by sting challenge and spontaneous field stings. Indications for VIT are based on history of an SR, positive diagnostic tests, natural history and established risk factors for a severe outcome. Current strategies for reducing adverse reactions include anti‐IgE monoclonal antibody pretreatment, and purified aqueous and purified aluminium hydroxide adsorbed preparations. New strategies for VIT, mostly using recombinant allergen, are in development. Further improvements will increase the safety and efficacy of VIT.
Dosing and efficacy in specific immunotherapy
Authors: Demoly P. , Calderon M. A.
Published: June 2011

To cite this article: Demoly P, Calderon MA. Dosing and efficacy in specific immunotherapy. Allergy 2011; 66 (Suppl. 95): 38–40.

Allergen‐specific immunotherapy is used to treat allergic rhinoconjuctivitis and asthma worldwide. The clinical efficacy of the most common routes, subcutaneous (SCIT) and sublingual (SLIT) immunotherapy, is documented for respiratory allergy by double‐blind, placebo‐controlled, randomised clinical trials (DB PC RCT). However, dose–effect relationships are not available for all extracts. The 1998 WHO Consensus Report on Allergen Immunotherapy found SCIT ineffective at low doses, with high doses more likely to result in an unacceptably high level of systemic reactions. Recent large well‐designed DB PC RCTs using SLIT grass pollen tablets have undergone phase II–III studies in adults with allergic rhinitis, yielding proper dose–response studies. These were analysed by the European Academy of Allergy and Clinical Immunology Immunotherapy Interest Group task force on dose effect. In general, low doses (5–7 μg of allergen Phl p 5 per day) are ineffective. Daily doses of 15–25 μg of the major allergen protein are required for significant clinical improvement measured by symptom scores. A higher dose (33–40 μg of Phl p 5 per day) was not more effective than 15–25 μg. Optimization of the allergen/adjuvant ratio may allow for lower allergen doses, increase the safety/efficacy profile and allow for shorter updosing. However, our analysis of the available studies concluded that every product requires its own dose–response relationship study.
Safety and tolerability of immunotherapy using various updosing schedules of a new SCIT product with an optimised allergen/aluminium hydroxide ratio
Authors: Jung K.
Published: June 2011

To cite this article: Jung K. Safety and tolerability of immunotherapy using various updosing schedules of a new SCIT product with an optimised allergen/aluminium hydroxide ratio. Allergy 2011; 66 (Suppl. 95): 41–43.

Allergen extracts for subcutaneous specific immunotherapy (SCIT) may be adsorbed to aluminium hydroxide for adjuvant effect and to delay allergen discharge. A product with an optimised allergen‐to‐aluminium hydroxide ratio enables a lower allergen dose and shorter introduction phase. The new therapeutic product Avanz (ALK, Denmark) has an optimised allergen‐to‐aluminium hydroxide ratio. A multicentre, randomised, phase II clinical trial evaluated the immunological effects and tolerability of two different five‐step updosing schedules for Avanz in 400 patients with grass pollen‐induced rhinoconjunctivitis with or without asthma, randomised into two groups. Group 1 were administered weekly, and group 2 were administered every 3 to 4 days. After updosing, patients received two maintenance injections after 2 and 4 weeks. In the updosing phase, local and systemic reactions were significantly more frequent in group 2 than group 1. In the maintenance phase, adverse reactions were less common in both groups. No generalised reactions with hypotension or fatal reactions occurred. An increase in allergen‐specific immunoglobulin G4 (IgG4) and IgE antibodies was established one week after the last injection. Avanz is a SCIT product with an optimised allergen‐to‐aluminium hydroxide ratio that enables a shorter updosing phase. We established an improved safety profile with weekly updosing compared with 3–4‐day intervals. Clinical trials are needed to confirm clinical efficacy.
Immunological measures as potential markers of dose
Authors: Kleine‐Tebbe J.
Published: June 2011

To cite this article: Kleine‐Tebbe J. Immunological measures as potential markers of dose. Allergy 2011; 66 (Suppl. 95): 44–46.

Specific immunotherapy (SIT) induces immunological changes leading to a decrease in allergen‐driven symptoms and medication use. However, the use of arbitrary and variable assay formats and units hampers comparisons between SIT studies. The magnitude of IgG response induced by SIT is not directly linked to clinical improvement, so an increase in allergen‐specific IgG4 should be considered a necessary but not sufficient marker of clinical efficacy. Dose‐dependent IgG4 immune responses should be demonstrated by the manufacturer, not by doctors. Symptom and medication scores are essential end‐points for immunotherapy studies, but are subjective, so close association with objective assay measurements will be difficult. Nonetheless, blocking antibody assays combining serology and cellular function may provide a solution for relating immunological assay measurements to clinical outcomes.
Effect of AIT in children including potential to prevent the development of asthma
Authors: Valovirta E.
Published: June 2011

To cite this article: Valovirta E. Effect of AIT in children including potential to prevent the development of asthma. Allergy 2011; 66 (Suppl. 95): 53–54.

Allergy specific immunotherapy may alter the natural course of allergic disease. Thus, it is of significant importance, particularly in paediatric populations. Four studies using the grass allergy immunotherapy tablet (AIT) for allergic rhinoconjunctivitis in children showed good clinical outcomes and good safety profiles. Allergic rhinoconjunctivitis often precedes asthma, and treatment with specific immunotherapy has the potential to reduce the development of asthma in children suffering from rhinoconjunctivitis. Since Grazax® AIT has been shown to induce disease modification the prevention of asthma might be hypothesised. The GAP (Grazax® Asthma Prevention) trial is investigating the asthma preventive effect of standardised grass AIT in grass allergic children with rhinoconjunctivitis without asthma. The trial is a 5‐year, multicentre, multinational, randomised, double‐blind, placebo‐controlled, prospective trial for children aged 5–12 years. In a few years, the results will show if grass AIT with Grazax® can prevent the development of asthma in children suffering from allergic rhinoconjunctivitis.
Immunotherapy concepts under investigation
Authors: Kündig T. M.
Published: June 2011

To cite this article: Kündig TM. Immunotherapy concepts under investigation. Allergy 2011; 66 (Suppl. 95): 60–62.

Allergen‐specific immunotherapy (SIT) is effective, but used by only 5% of allergy patients, partly because it requires several years. Intralymphatic immunotherapy (ILIT) administers allergen directly into a subcutaneous lymph node and requires only three injections and a lower allergen dose than subcutaneous administration. ILIT was further improved using a recombinant allergen with enhanced uptake and decreased degradation by antigen‐presenting cells. Another interesting route is transcutaneous/epicutaneous immunotherapy (TCIT, EPIT), which administers allergen by a skin patch. Clinical trials show that TCIT, EPIT is safe and comparably effective to conventional immunotherapy. Implementation of these new methods would increase the spectrum of SIT options, allowing greater individual choice of SIT.
Clinical and molecular analysis of UAE fibrochondrogenesis patients expands the phenotype and reveals two COL11A1 homozygous null mutations
Authors: Akawi NA , Al‐Gazali L , Ali BR
Published: June 2011

Akawi NA, Al‐Gazali L, Ali BR. Clinical and molecular analysis of UAE fibrochondrogenesis patients expands the phenotype and reveals two COL11A1 homozygous null mutations.

Fibrochondrogenesis is documented to be a neonatally lethal rare recessively inherited disorder characterized by short‐limbed skeletal dysplasia. Here we report two patients from two unrelated consanguineous Emirati families who have unexpectedly survived till the ages of 3 and 6 years. These patients show additional symptoms which include developmental delay, profound sensory–neural deafness, severe myopia and progressive severe skeletal abnormalities. Linkage of fibrochondrogenesis in the Emirati families to chromosome 1 has been established using homozygosity mapping confirming recent findings by Tompson et al. in 2010. Screening of the COL11A1 gene revealed two null homozygous mutations [c.4084C>T (p.R1362X) and c.3708+437T>G] in the aforementioned two families. The c.4084C>T mutation is predicted to introduce a stop codon at position Arg1362, whereas the c.3708+437T>G mutation causes the activation of an intronic pseudoexon between exons 48 and 49. This resulted in the insertion of 50 nucleotides into the mRNA. The carriers of these mutations display ocular defects with normal hearing. In conclusion, our data shall improve the overall understanding of fibrochondrogenesis especially in surviving homozygous patients and, at least partly, explain the phenotypic variability associated with COL11A1 gene mutations.
A case of progressive thrombotic microangiopathy after ABO‐incompatible renal transplantation
Authors: Miura Masayoshi , Fujita Hiromi , Suzuki Akira , Kubota Kanako C. , Fukasawa Yuichiro , Shimoda Naohiko , Tsuchihashi Seiichiro , Tamaki Tohru
Published: June 2011

Miura M, Fujita H, Suzuki A, Kubota KC, Fukasawa Y, Shimoda N, Tsuchihashi S, Tamaki T. A case of progressive thrombotic microangiopathy after ABO‐incompatible renal transplantation. Clin Transplant 2011: 25 (Suppl. 23): 19–22. © 2011 John Wiley & Sons A/S.

Abstract:  A 21‐yr‐old man of blood type O receiving hemodialysis for IgA nephropathy underwent living‐related ABO‐incompatible (ABOI) renal transplantation from his mother, whose blood type is A. He was negative for flow cross‐match, anti‐human leukocyte antigen (HLA) antibody, and anti‐MICA antibody. Pre‐treatment anti‐A IgG titer was 1:256. Desensitization consisted of tacrolimus, mycophenolate mofetil, methylprednisolone, rituximab, and plasmapheresis. He developed acute antibody rejection at day 2 post‐transplant, which was successfully treated. After renal artery reconstruction surgery at day 91 for renovascular hypertension caused by renal artery stricture, the patient suffered from acute prostatitis, which subsequently induced type III acute antibody‐mediated rejection. Even after recovery from the rejection after temporary hemodialysis, graft function progressively deteriorated and consecutive allograft biopsy showed progressive thrombotic microangiopathy (TMA) without any evidence of donor‐specific antibody other than anti‐A antibody. The tacrolimus dose was kept low for fear of tacrolimus‐induced TMA. Despite these efforts, the patient resumed hemodialysis six months’ post‐transplant.
A case of recurrent focal segmental glomerulosclerosis (FSGS) involving massive proteinuria (>50 g/day) immediately after renal transplantation
Authors: Okamoto Masahiko , Koshino Katsuhiro , Sakai Kazuki , Nobori Shuji , Matsuyama Masahide , Ushigome Hidetaka , Okajima Hideaki , Masuzawa Naoko , Yoshimura Norio
Published: June 2011

Okamoto M, Koshino K, Sakai K, Nobori S, Matsuyama M, Ushigome H, Okajima H, Masuzawa N, Yoshimura N. A case of recurrent focal segmental glomerulosclerosis (FSGS) involving massive proteinuria (>50 g/d) immediately after renal transplantation. Clin Transplant 2011: 25 (Suppl. 23): 53–58. © 2011 John Wiley & Sons A/S.

Abstract:  A 15‐yr‐old girl with end‐stage kidney disease caused by primary focal segmental glomerulosclerosis (FSGS) underwent a living‐related donor kidney transplantation. The allograft functioned well immediately after reperfusion, but massive proteinuria exceeding 50 g/d appeared on day 3. Treatment with rituximab and plasma exchange (PE) successfully decreased the proteinuria to 10 g/d. A biopsy specimen on day 30 showed no segmental glomerulosclerosis but partial interstitial infiltration of inflammatory cells. An increased number of podocytes showed intracytoplasmic vacuolization, and an electron micrograph showed diffuse mild subendothelial edema and foot process effacement. The podocytes were hypertrophied but were not detached from the basement membrane. As the therapies used to reduce the patient’s proteinuria were having a limited effect, intravenous steroid pulse therapy followed by low‐density lipoprotein apheresis was performed. A biopsy specimen taken on day 120 showed no segmental glomerulosclerosis. Thrombus formation in one glomerulus and packed lymphocytes in the capillary loop of another glomerulus were detected. The patient’s clinical course was compatible with FSGS recurrence. Although the early pathological changes were not typical of FSGS, they might be indicative of the primary lesion that subsequently progresses to typical FSGS.