Immune response to allergens in sheep sensitized to house dust mite

<p>Abstract</p> <p>Background</p> <p>House dust mite (HDM) allergens are a major cause of allergic asthma. Most studies using animal models of allergic asthma have used rodents sensitized with the 'un-natural' allergen ovalbumin. It has only recently been recognized that the use of animal models based on HDM provide a more relevant insight into the allergen-induced mechanisms that underpin human allergic disease. We have previously described a sheep model of human allergic asthma that uses <it>Dermatophagoides pteronyssinus </it>HDM. The present study extends our understanding of the immune effects of HDM and the allergens Der p 1 and Der p 2 in the sheep model of asthma.</p> <p>Methods</p> <p>Peripheral blood sera from non-sensitized (control) sheep and sheep sensitized to HDM was collected to determine immunoglobulin (Ig) reactivities to HDM, Der p 1 and Der p 2 by ELISA. Bronchoalveolar lavage (BAL) fluid collected following allergen challenge was also assessed for the presence of HDM-specific antibodies. To examine the cellular immune response to HDM allergens, T cell proliferation and cutaneous responses were assessed in sensitized and control sheep.</p> <p>Results</p> <p>Strong HDM- and Der p 1-specific IgE, IgG₁, IgG₂and IgA serum responses were observed in sensitized sheep, while detectable levels of HDM-specific IgG₁and IgA were seen in BAL fluid of allergen-challenged lungs. In contrast, minimal antibody reactivity was observed to Der p 2. Marked T cell proliferation and late phase cutaneous responses, accompanied by the recruitment of eosinophils, indicates the induction of a cellular and delayed-type hypersensitivity (DTH) type II response by HDM and Der p 1 allergen, but not Der p 2.</p> <p>Conclusion</p> <p>This work characterizes the humoral and cellular immune effects of HDM extract and its major constituent allergens in sheep sensitized to HDM. The effects of allergen in HDM-sensitized sheep were detectable both locally and systemically, and probably mediated via enzymatic and immune actions of the major HDM allergen Der p 1. This study extends our understanding of the actions of this important allergen relevant to human allergic asthma and its effects in sheep experimentally sensitized to HDM allergens.</p

Cost-Effectiveness of Newborn Screening for Spinal Muscular Atrophy in The Netherlands

Objectives: Spinal muscular atrophy (SMA) is a rare genetic disorder that causes progressive muscle weakness and paralysis. In its most common and severe form, the majority of untreated infants die before 2 years of age. Early detection and treatment, ideally before symptom onset, maximize survival and achievement of age-appropriate motor milestones, with potentially substantial impact on health-related quality of life. Therefore, SMA is an ideal candidate for inclusion in newborn screening (NBS) programs. We evaluated the cost-effectiveness of including SMA in the NBS program in The Netherlands. Methods: We developed a cost-utility model to estimate lifetime health effects and costs of NBS for SMA and subsequent treatment versus a treatment pathway without NBS (ie, diagnosis and treatment after presentation with overt symptoms). Model inputs were based on literature, local data, and expert opinion. Sensitivity and scenario analyses were conducted to assess model robustness and validity of results. Results: After detection of SMA by NBS in 17 patients, the number of quality-adjusted life-years gained per annual birth cohort was estimated at 320 with NBS followed by treatment compared with treatment after clinical SMA diagnosis. Total healthcare costs, including screening, diagnostics, treatment, and other healthcare resource use, were estimated to be €12 014 949 lower for patients identified by NBS. Conclusions: NBS for early identification and treatment of SMA versus later symptomatic treatment after clinical diagnosis improves health outcomes and is less costly and, therefore, is a cost-effective use of resources. Results were robust in sensitivity and scenario analyses

Morphologies of AGN host galaxies using HST/ACS in the CDFS-GOODS field

Using HST/ACS images in four bands F435W, F606W, F775W and F850LP, we identify optical counterparts to the X-ray sources in the Chandra Deep Field South in the GOODS South field. A detailed study has been made of these sources to study their morphological types. We use methods like decomposition of galaxy luminosity profiles, color maps and visual inspection of 192 galaxies which are identified as possible optical counterparts of Chandra X-ray sources in the CDFS-GOODS field. We find that most moderate luminosity AGN hosts are bulge dominated in the redshift range (z \approx 0.4-1.3), but not merging/interacting galaxies. This implies probable fueling of the moderate luminosity AGN by mechanisms other than those merger driven.Comment: pdflatex, accepted in ApSS. revisions in tex

Wind energy development can lead to guild‐specific habitat loss in boreal forest bats

Forest management rarely considers protecting bats in Fennoscandian regions although all species rely on forest habitat at some point in their annual cycle. This issue is especially evident as wind parks have increasingly been developed inside Fennoscandian forests, against the advice of international bat conservation guidelines. In this study, we aimed to describe and explain bat community dynamics at a Norwegian wind park located in a boreal forest, especially to understand potential avoidance or attraction effects. The bat community was sampled acoustically and described using foraging guilds (short, medium, and long-range echolocators; SRE, MRE, LRE) as well as behavior (commuting, feeding and social calls). Sampling was undertaken at two locations per turbine: 1) the turbine pad and 2) a paired natural habitat at ground level, as well as from a meteorological tower. We used a recently developed method for camera trapping nocturnal flying insects synchronously with bat acoustic activity. Our results reveal trends in feeding and general bat activity across foraging guilds in relation to insect availability, habitat type, wind, temperature, and seasonality. We show how seasonal patterns in behavior across guilds were affected by habitat type, temperature, and wind. We found that SRE commuting and especially feeding activity was highest in natural habitats, whereas LRE overall activity at habitats more season dependent. We found that nocturnal insect availability was positively correlated with total bat feeding activity throughout the night. Our results provide evidence for both direct and indirect risks to bat communities by wind parks: SRE bat habitat is lost to wind energy infrastructure and LRE bat may have an increased risk of fatality. Our findings provide important insights on seasonal and spatial variability in bat activity, which can inform standardizing monitoring of bats acoustically in boreal forests, at wind parks, and in combination with non-invasive insect monitoring

Carcinoembryonic Antigen Gene Family

The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin supergene family and can be divided into two main subgroups based on sequence comparisons. In humans it is clustered on the long arm of chromosome 19 and consists of approximately 20 genes. The CEA subgroup genes code for CEA and its classical crossreacting antigens, which are mainly membrane-bound, whereas the other subgroup genes encode the pregnancy-specific glycoproteins (PSG), which are secreted. Splice variants of individual genes and differential post-translational modifications of the resulting proteins, e.g., by glycosylation, indicate a high complexity in the number of putative CEA-related molecules. So far, only a limited number of CEA-related antigens in humans have been unequivocally assigned to a specific gene. Rodent CEA-related genes reveal a high sequence divergence and, in part, a completely different domain organization than the human CEA gene family, making it difficult to determine individual gene counterparts. However, rodent CEA-related genes can be assigned to human subgroups based on similarity of expression patterns, which is characteristic for the subgroups. Various functions have been determined for members of the CEA subgroup in vitro, including cell adhesion, bacterial binding, an accessory role for collagen binding or ecto-ATPases activity. Based on all that is known so far on its biology, the clinical outlook for the CEA family has been reassessed

Perceptual judgment and saccadic behavior in a spatial distortion with briefly presented stimuli.

When observers are asked to localize the peripheral position of a small probe with respect to the mid-position of a spatially extended comparison stimulus, they tend to judge the probe as being more peripheral than the mid-position of the comparison stimulus. This relative mislocalization seems to emerge from differences in absolute localization, that is the comparison stimulus is localized more towards the fovea than the probe. The present study compared saccadic behaviour and relative localization judgements in three experiments and determined the quantitative relationship between both measures. The results showed corresponding effects in localization errors and saccadic behaviour. Moreover, it was possible to estimate the amount of the relative mislocalization by means of the saccadic amplitude