The effect of concurrent infections with Pasteurella multocida and Ascaridia galli on free range chickens

Pasteurella multocida and Ascaridia galli are observed with high prevalences in free range chickens in Denmark, but the impact is unknown. A study was carried out to examine the interaction between A. galli and P. multocida in chickens and the impact on production. Five groups, each with 20 18-week-old Lohmann Brown chickens were infected. Group I was orally infected with 1000 +/- 50 embryonated A. galli eggs. Group 2 received 10(4) cfu p. multocida intratracheally. Group 3 was infected with A. galli and subsequently with P. multocida. Group 4 was infected with P. multocida followed by A. galli. Group 5 was the control. The study ran for I I weeks where clinical manifestations, weight gain and egg production were recorded. Excretion of P. multocida was determined on individual basis and blood smears were made for differential counts. At the end of the study pathological lesions and the number of adult worms, larvae and eggs in the faeces were recorded. The birds were more severely affected when infected with both pathogens compared to single infections with A. galli or P. multocida, respectively. A lower weight gain and egg production was observed with dual infections. A. galli infection followed by a secondary P. multocida infection resulted in more birds with pathological lesions and continued P. multocida excretion. In conclusion a negative interaction between A. galli and R multocida was observed and it is postulated that free range chickens are at higher risk of being subjected to outbreaks of fowl cholera when they are infected with A. galli

Intake Design for an Atmosphere-Breathing Electric Propulsion System (ABEP)

Challenging space missions include those at very low altitudes, where the atmosphere is source of aerodynamic drag on the spacecraft. To extend the lifetime of such missions, an efficient propulsion system is required. One solution is Atmosphere-Breathing Electric Propulsion (ABEP) that collects atmospheric particles to be used as propellant for an electric thruster. The system would minimize the requirement of limited propellant availability and can also be applied to any planetary body with atmosphere, enabling new missions at low altitude ranges for longer times. IRS is developing, within the H2020 DISCOVERER project, an intake and a thruster for an ABEP system. The article describes the design and simulation of the intake, optimized to feed the radio frequency (RF) Helicon-based plasma thruster developed at IRS. The article deals in particular with the design of intakes based on diffuse and specular reflecting materials, which are analysed by the PICLas DSMC-PIC tool. Orbital altitudes $h=150-250$ km and the respective species based on the NRLMSISE-00 model (O, $N_2$, $O_2$, He, Ar, H, N) are investigated for several concepts based on fully diffuse and specular scattering, including hybrid designs. The major focus has been on the intake efficiency defined as $\eta_c=\dot{N}_{out}/\dot{N}_{in}$, with $\dot{N}_{in}$ the incoming particle flux, and $\dot{N}_{out}$ the one collected by the intake. Finally, two concepts are selected and presented providing the best expected performance for the operation with the selected thruster. The first one is based on fully diffuse accommodation yielding to $\eta_c<0.46$ and the second one based un fully specular accommodation yielding to $\eta_c<0.94$. Finally, also the influence of misalignment with the flow is analysed, highlighting a strong dependence of $\eta_c$ in the diffuse-based intake while, ...Comment: Accepted Versio

Intake design for an Atmosphere-Breathing Electric Propulsion System (ABEP)

Challenging space missions include those at very low altitudes, where the atmosphere is source of aerodynamic drag on the spacecraft. To extend the lifetime of such missions, an efficient propulsion system is required. One solution is Atmosphere-Breathing Electric Propulsion (ABEP) that collects atmospheric particles to be used as propellant for an electric thruster. The system would minimize the requirement of limited propellant availability and can also be applied to any planetary body with atmosphere, enabling new missions at low altitude ranges for longer times. IRS is developing, within the H2020 DISCOVERER project, an intake and a thruster for an ABEP system. The article describes the design and simulation of the intake, optimized to feed the radio frequency (RF) Helicon-based plasma thruster developed at IRS. The article deals in particular with the design of intakes based on diffuse and specular reflecting materials, which are analysed by the PICLas DSMC-PIC tool. Orbital altitudes and the respective species based on the NRLMSISE-00 model (O, , , He, Ar, H, N) are investigated for several concepts based on fully diffuse and specular scattering, including hybrid designs. The major focus has been on the intake efficiency defined as , with the incoming particle flux, and the one collected by the intake. Finally, two concepts are selected and presented providing the best expected performance for the operation with the selected thruster. The first one is based on fully diffuse accommodation yielding to and the second one based on fully specular accommodation yielding to . Finally, also the influence of misalignment with the flow is analysed, highlighting a strong dependence of in the diffuse-based intake while, for the specular-based intake, this is much lower finally leading to a more resilient design while also relaxing requirements of pointing accuracy for the spacecraft

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Divergent Pro-Inflammatory Profile of Human Dendritic Cells in Response to Commensal and Pathogenic Bacteria Associated with the Airway Microbiota

Recent studies using culture-independent methods have characterized the human airway microbiota and report microbial communities distinct from other body sites. Changes in these airway bacterial communities appear to be associated with inflammatory lung disease, yet the pro-inflammatory properties of individual bacterial species are unknown. In this study, we compared the immune stimulatory capacity on human monocyte-derived dendritic cells (DCs) of selected airway commensal and pathogenic bacteria predominantly associated with lungs of asthma or COPD patients (pathogenic Haemophillus spp. and Moraxella spp.), healthy lungs (commensal Prevotella spp.) or both (commensal Veillonella spp. and Actinomyces spp.). All bacteria were found to induce activation of DCs as demonstrated by similar induction of CD83, CD40 and CD86 surface expression. However, asthma and COPD-associated pathogenic bacteria provoked a 3–5 fold higher production of IL-23, IL-12p70 and IL-10 cytokines compared to the commensal bacteria. Based on the differential cytokine production profiles, the studied airway bacteria could be segregated into three groups (Haemophilus spp. and Moraxella spp. vs. Prevotella spp. and Veillonella spp. vs. Actinomyces spp.) reflecting their pro-inflammatory effects on DCs. Co-culture experiments found that Prevotella spp. were able to reduce Haemophillus influenzae-induced IL-12p70 in DCs, whereas no effect was observed on IL-23 and IL-10 production. This study demonstrates intrinsic differences in DC stimulating properties of bacteria associated with the airway microbiota

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation.

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities

A saturated map of common genetic variants associated with human height.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries