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Background: Genome-wide association studies of asthma have identified associations with variants in type-2 related genes. Also, specific interactions between genetic variants and viral bronchiolitis in the development of asthma has been suggested. Objective: To conduct a gene-based analysis of genetic variants in type 2 cytokine related genes as risk factors for allergic asthma at school age, and further, to study their interaction with specific viral infections in early childhood. Methods: A prospectively investigated cohort of children with previous bronchiolitis and controls came for follow-up at school age. The research visit, blinded to viral exposure, included detailed lung function tests, laboratory investigation, and questionnaires. Allergic asthma was defined as typical symptoms plus objective variable airway obstruction, in addition to laboratory verified atopy (elevated eosinophil count or sensitization to an allergen). Targeted and complete sequencing was performed for nine type 2 cytokine candidate genes: IL4, 5, 13, 25, 33 and 37, IL17RB, CRLF2 and TSLP. Results: At follow-up, there were 109 children with genetic data, 91 with a history of bronchiolitis (46% respiratory syncytial virus, 24% human rhinovirus, 15% human metapneumovirus and 14% mixed viral etiology) and 18 without. The median age was 9.4 years (range 6–13) and 41 (38%) had laboratory verified atopy. Twenty-one children (19%) met the definition of allergic asthma. After adjusting for age, sex and five viral categories, IL33 achieved nominal significance (p = 0.017) for a positive association with allergic asthma development. In the gene-virus interaction analysis, the variant set in IL17RB demonstrated a nominally significant positive interaction with human metapneumovirus infection (p=0.05). Conclusion: The results highlight the multifactorial nature of allergic asthma risk, with both viral infection and inherited genetic variants contributing to increasing risk. Results for IL33

In salmon aquaculture, the sustainable management of salmon lice (Lepeophtheirus salmonis) is limited by the adaptive capacity of the parasite. This is evident in the repeated evolution of pesticide resistance in the salmon louse population. To better prepare for resistance, we constructed a numerical metapopulation model that predicts the evolutionary dynamics of lice across an interconnected farm network. This model integrates within-farm population dynamics and between-farm louse dispersal, the latter using outputs from a state-of-the-art particle-tracking model. Distinct from previous metapopulation models, it also simulates spatial and temporal genetic variation arising from selection. The model was parameterized to simulate the evolution of resistance to the pesticide azamethiphos on farms in southern Norway. It successfully reproduced the rapid (within 10 years) evolution of azamethiphos resistance following extensive delousing treatments. It also identified strong spatial patterns in resistance, with regions of high farm connectivity being potential hotspots of louse adaptation. Rates of infestation and evolution were significantly reduced when highly connected farms were excluded from the simulation, compared to when low-connectivity or random sites were excluded. This model can be a valuable tool for coordinating pest management at a regional scale, in a way that slows or prevents the spread of resistance.

Identification of fetal kidney anomalies invites questions about underlying causes and recurrence risk in future pregnancies. We therefore investigated the diagnostic yield of next-generation sequencing in fetuses with bilateral kidney anomalies and the correlation between disrupted genes and fetal phenotypes. Fetuses with bilateral kidney anomalies were screened using an in-house-designed kidney-gene panel. In families where candidate variants were not identified, whole-exome sequencing was performed. Genes uncovered by this analysis were added to our kidney panel. We identified likely deleterious variants in 11 of 56 (20%) families. The kidney-gene analysis revealed likely deleterious variants in known kidney developmental genes in 6 fetuses and TMEM67 variants in 2 unrelated fetuses. Kidney histology was similar in the latter 2 fetuses-presenting a distinct prenatal form of nephronophthisis. Exome sequencing identified ROBO1 variants in one family and a GREB1L variant in another family. GREB1L and ROBO1 were added to our kidney-gene panel and additional variants were identified. Next-generation sequencing substantially contributes to identifying causes of fetal kidney anomalies. Genetic causes may be supported by histological examination of the kidneys. This is the first time that SLIT-ROBO signaling is implicated in human bilateral kidney agenesis.

The present study is part of a larger work aiming at establishing the knowledge basis needed to develop cost-effective processes for producing high-bright mechanical and chemimechanical pulps. The influence of process conditions (time, pH, temperature, consistency) on the optical properties during pulp storage of a well-washed hydrogen peroxide bleached Norway spruce pulp has been examined. The general effect of storage was darkening of the pulp due to an increase in light absorption, especially at shorter wavelengths. Time and temperature were found to be the process variables that had the largest impact, the trends were similar independent of pH and pulp consistency. The light scattering ability increased initially, giving a positive contribution to brightness. This indicates that the storage also resulted in a change in sheet structure.

Udgivelsesdato: 2008/8