A novel, high-welfare methodology for evaluating poultry red mite interventions in vivo

Optimisation and use of a device for the on-hen in vivo feeding of all hematophagous stages of Dermanyssus gallinae is described. The sealed mesh device contains the mites and is applied to the skin of the hen’s thigh where mites can feed on the bird through a mesh which has apertures large enough to allow the mites’ mouth-parts to access to the bird but small enough to contain the mites. By optimising the depth and width of the mesh aperture size we have produced a device which will lead to both reduction and refinement in the use of animals in research, allowing the pre-screening of new vaccines and systemic acaricides/insecticides which have been developed for the control of these blood-feeding parasites before progressing to large field trials. For optimal use,the device should be constructed from 105μm aperture width, 63 μm depth, polyester mesh and the mites (irrespective of life stage) should be conditioned with no access to food for 3 weeks at 4 °C for optimal feeding and post-feeding survival

Addressing Barriers to Universal Screening for Social, Emotional, and Behavioral Risk in Elementary Schools

Early identification of students in need of additional support in the classroom is an important structure for school districts to have in place. Universal screening for social-emotional and behavioral (SEB) risk is one method that schools can use to identify students in need of SEB support and to begin early intervention programing. Unfortunately, recommendations about universal screening and resources for universal screening for SEB risk are limited. As a result, barriers to screening are increased and interventions are delayed – sometimes indefinitely -- for those who need them most. This paper discusses the barriers and challenges experienced by elementary schools (grades K-5) in one school district in the South across a three-year consultative study. This district was supported by the researchers in identifying an appropriate SEB screener, in disseminating the screener, and in ensuring accuracy in its completion. Across the three years, data were evaluated from previous years, and recommendations to improve the district’s screening initiative were made by the lead consultant and school psychology graduate students. Over time, positive changes were noted in screening practices, but it is evident that more work needs to be done. Specific solutions and future implications for early childhood are discussed

Serum and acute phase protein changes in laying hens, infested with poultry red mite

The poultry red mite (PRM) is one of the most economically important ectoparasites of laying hens globally. This mite can have significant deleterious effects on its fowl host including distress, anemia, reduced egg production, and reduced egg quality. This study was conducted to evaluate the influence of PRM on the serum protein profile in laying hens and its effect on the acute phase proteins (APPs) to assess their potential as biomarkers for mite infestation. Three APPs: alpha-1 acid glycoprotein (AGP), serum amyloid-A (SAA), and ceruloplasmin (CP) were measured in serum samples collected from laying hens at 12 and 17 wk of age, and then for up to 4 mo after a challenge with PRM (starting at 18.5 wk of age). The serum protein profile (SDS-PAGE/nanoflow HPLC electrospray tandem mass spectrometry) and concentration of individual serum proteins (SDS-PAGE-band densitometry) were also compared. Post challenge there was a positive correlation (r = 0.489; P < 0.004) between the levels of SAA and the PRM numbers. The levels of SAA steadily increased after the PRM challenge and were significantly different than the pre-challenge levels at 28, 32, and 36 wk of age (P < 0.01). The PRM numbers also peaked around 31-33 wk of age. The results for AGP and CP in comparison were inconsistent. Proteomics revealed the presence of 2 high molecular weight proteins in the serum between 12 and 17 wk of age. These were identified as Apolipoprotein-B and Vitellogenin-2, and their increase was commensurate with the onset of lay. No other major differences were detected in the protein profiles of blood sera collected pre and post challenge. We conclude that SAA could be used as a useful biomarker to monitor PRM infestation in commercial poultry flocks and that PRM infestation does not disrupt the production of the major proteins in the serum that are associated with egg formation

Negative Regulation of Immunoglobulin E–dependent Allergic Responses by Lyn Kinase

A role for Lyn kinase as a positive regulator of immunoglobulin (Ig)E-dependent allergy has long been accepted. Contrary to this belief, Lyn kinase was found to have an important role as a negative regulator of the allergic response. This became apparent from the hyperresponsive degranulation of lyn−/− bone marrow–derived mast cells, which is driven by hyperactivation of Fyn kinase that occurs, in part, through the loss of negative regulation by COOH-terminal Src kinase (Csk) and the adaptor, Csk-binding protein. This phenotype is recapitulated in vivo as young lyn−/− mice showed an enhanced anaphylactic response. In vivo studies also demonstrated that as lyn−/− mice aged, their serum IgE increased as well as occupancy of the high affinity IgE receptor (FcεRI). This was mirrored by increased circulating histamine, increased mast cell numbers, increased cell surface expression of the high affinity IgE receptor (FcεRI), and eosinophilia. The increased IgE production was not a consequence of increased Fyn kinase activity in lyn−/− mice because both lyn−/− and lyn−/− fyn−/− mice showed high IgE levels. Thus, lyn−/− mice and mast cells thereof show multiple allergy-associated traits, causing reconsideration of the possible efficacy in therapeutic targeting of Lyn in allergic disease

Linking protein to phenotype with Mendelian Randomization detects 38 proteins with causal roles in human diseases and traits

To efficiently transform genetic associations into drug targets requires evidence that a particular gene, and its encoded protein, contribute causally to a disease. To achieve this, we employ a three-step proteome-by-phenome Mendelian Randomization (MR) approach. In step one, 154 protein quantitative trait loci (pQTLs) were identified and independently replicated. From these pQTLs, 64 replicated locally-acting variants were used as instrumental variables for proteome-by-phenome MR across 846 traits (step two). When its assumptions are met, proteome-by-phenome MR, is equivalent to simultaneously running many randomized controlled trials. Step 2 yielded 38 proteins that significantly predicted variation in traits and diseases in 509 instances. Step 3 revealed that amongst the 271 instances from GeneAtlas (UK Biobank), 77 showed little evidence of pleiotropy (HEIDI), and 92 evidence of colocalization (eCAVIAR). Results were wide ranging: including, for example, new evidence for a causal role of tyrosine-protein phosphatase non-receptor type substrate 1 (SHPS1; SIRPA) in schizophrenia, and a new finding that intestinal fatty acid binding protein (FABP2) abundance contributes to the pathogenesis of cardiovascular disease. We also demonstrated confirmatory evidence for the causal role of four further proteins (FGF5, IL6R, LPL, LTA) in cardiovascular disease risk

Gender Differences in Russian Colour Naming

In the present study we explored Russian colour naming in a web-based psycholinguistic experiment (http://www.colournaming.com). Colour singletons representing the Munsell Color Solid (N=600 in total) were presented on a computer monitor and named using an unconstrained colour-naming method. Respondents were Russian speakers (N=713). For gender-split equal-size samples (NF=333, NM=333) we estimated and compared (i) location of centroids of 12 Russian basic colour terms (BCTs); (ii) the number of words in colour descriptors; (iii) occurrences of BCTs most frequent non-BCTs. We found a close correspondence between females’ and males’ BCT centroids. Among individual BCTs, the highest inter-gender agreement was for seryj ‘grey’ and goluboj ‘light blue’, while the lowest was for sinij ‘dark blue’ and krasnyj ‘red’. Females revealed a significantly richer repertory of distinct colour descriptors, with great variety of monolexemic non-BCTs and “fancy” colour names; in comparison, males offered relatively more BCTs or their compounds. Along with these measures, we gauged denotata of most frequent CTs, reflected by linguistic segmentation of colour space, by employing a synthetic observer trained by gender-specific responses. This psycholinguistic representation revealed females’ more refined linguistic segmentation, compared to males, with higher linguistic density predominantly along the redgreen axis of colour space

‘Instead of fetching flowers, the youths brought in flakes of snow’: exploring extreme weather history through English parish registers

Parish registers provide organized, dated and located population data and as such, are routinely among the most frequently consulted documents within the holdings of county record offices and archives. Throughout history, extreme weather has had significant impacts on the church, its congregation, and local landscape. It is for these reasons that extreme weather events have been deemed worthy of official note by authors of many registers. Although isolated entries have been used as supporting evidence for the occurrence of a number of historic extreme weather events, the information that parish registers contain relating to weather history has not been studied in its own right. Parish register narratives add new events to existing chronologies of extreme weather events and contribute to our understanding of their impacts at the local level. As public and well used documents they also function to keep the memory of particular events alive. The examples in this paper cover a wide range of weather types, places, and time periods, also enabling recording practice to be explored. Finally, as the number of digitized registers increases, we highlight the risks of weather narratives being obscured, and reflect on how the weather history contained within might be systematically captured

Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases