Contribution of the genetic background to the immune response of broilers vaccinated or challenged with LPAI H9N2

<p>Abstract</p> <p>Background</p> <p>The knowledge on the immune responses to LPAI is limited. The purpose of this study was to investigate the immune responses of two divergently selected lines of broilers, a line responding with high antibody response to antigens (HH), and a line responding with low antibody titers (LL) to antigen.</p> <p>Methods</p> <p>Day old chicks from each line were divided in two groups, one vaccinated with inactivated H9N2 vaccine and one non-vaccinated. At 21 days of age all the chicks were challenged with field isolate of H9N2, 1X10^6.5 ELD₅₀ per chick by drops to the eye, nose and beak. Twenty four hours and 14 days post challenge (PC), the chickens were weighed blood spleen and lungs were taken and leukocytes were isolated. The leukocytes were stained with monoclonal antibodies for surface markers and analyzed by flow cytometry. We used Elispot assay to identify the number of antibody producing cells in each of the organs. mRNA was extracted using TRIsol reagent in order to assess the cytokine production level by qRT-PCR using the SYBR green methods.</p> <p>Results</p> <p>Our results showed that LL-vaccinated group gained more weight than any of the other group. Using IDEXX kit, no antibody titers could be identified in vaccinated chicks 21 days post vaccination while 14 days PC vaccinated HH chickens demonstrated the highest average antibody titers. LL vaccinated chickens demonstrated higher average antibody titer than non-vaccinated LL. Using the Elispot assay no difference were found between the groups either cells producing IgA, IgM or IgY beside of a high number of IgY producing cells in the lungs of vaccinated HH birds.</p> <p>Conclusions</p> <p>Further data on leukocytes subpopulations using flow cytometry, cytokines production (IFNγ, IL-6, IL-18, IL-2 and IL-4) isotype specific antibody responses and number and functionality of NK cells are in process.</p

Kinetics of the avian influenza-specific humoral responses in lung are indicative of local antibody production

The role and kinetics of respiratory immunoglobulins in AIV infection has not been investigated. In this study we determined the numbers of both total antibody secreting cells (ASC) and virus-specific ASC in lung, spleen, blood and bone marrow (BM) following low-pathogenic AIV infection. Antiviral humoral immune responses were induced both locally in the lung and systemically in the spleen. Responses in the lung and BM preceded responses in the spleen and in blood, with virus-specific IgY ASC already detected in lung and BM from 1 week post-primary inoculation, indicating that respiratory immune responses are not induced in the spleen, but locally in the lung. ASC present in the blood of the lungs and co-isolated during lymphocyte isolation from the lungs have no major impact on the ASC detected in the lungs based on statistical correlatio

Systemic distribution of different low pathogenic avian influenza (LPAI) viruses in chicken

<p>Abstract</p> <p>Background</p> <p>Since we were able to isolate viable virus from brain and lung of H7N1 low pathogenic avian influenza virus (LPAIV) infected chickens, we here examined the distribution of different LPAIV strains in chickens by measuring the viral AI RNA load in multiple organs. Subtypes of H5 (H5N1, H5N2), H7 (H7N1, H7N7) and H9 (H9N2), of chicken (H5N2, H7N1, H7N7, H9N2), or mallard (H5N1) origin were tested. The actual presence of viable virus was evaluated with virus isolation in organs of H7N7 inoculated chickens.</p> <p>Findings</p> <p>Viral RNA was found by PCR in lung, brain, intestine, peripheral blood mononuclear cells, heart, liver, kidney and spleen from chickens infected with chicken isolated LPAIV H5N2, H7N1, H7N7 or H9N2. H7N7 virus could be isolated from lung, ileum, heart, liver, kidney and spleen, but not from brain, which was in agreement with the data from the PCR. Infection with mallard isolated H5N1 LPAIV resulted in viral RNA detection in lung and peripheral blood mononuclear cells only.</p> <p>Conclusion</p> <p>We speculate that chicken isolated LPAI viruses are spreading systemically in chicken, independently of the strain.</p

Genetics and Not Shared Environment Explains Familial Resemblance in Adult Metabolomics Data

Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term ‘metabolomics’ refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes

Application of Brownian motion theory to the analysis of membrane channel ionic trajectories calculated by molecular dynamics

This paper shows how Brownian motion theory can be used to analyze features of individual ion trajectories in channels as calculated by molecular dynamics, and that its use permits more precise determinations of diffusion coefficients than would otherwise be possible. We also show how a consideration of trajectories of single particles can distinguish between effects due to the magnitude of the diffusion coefficient and effects due to barriers and wells in the potential profile, effects which can not be distinguished by consideration of average fluxes

Design and Feasibility of an Intervention to Support Cancer Genetic Counselees in Informing their At-Risk Relatives

Cancer genetic counselees receive individualized information regarding heightened risks and medical recommendations which is also relevant for their at-risk relatives. Unfortunately, counselees often insufficiently inform these relatives. We designed an intervention aimed at improving counselees' knowledge regarding which at-risk relatives to inform and what information to disclose, their motivation to disclose, and their self-efficacy. The intervention, offered by telephone by trained psychosocial workers, is based on the principles of Motivational Interviewing. Phase 1 of the intervention covers agenda setting, exploration, and evaluation, and phase 2 includes information provision, enhancing motivation and self-efficacy, and brainstorming for solutions to disseminate information within the family. Fidelity and acceptability of the intervention were assessed using recordings of intervention sessions and by counselee self-report. A total of 144 counselees participated. Psychosocial workers (n = 5) delivered the intervention largely as intended. Counselees highly appreciated the content of the intervention and the psychosocial workers who delivered the intervention. In the sessions, psychosocial workers provided additional and/or corrective information, and brainstorming for solutions was performed in 70 %. These results indicate that this intervention is feasible and warrants testing in clinical practice. For this, a randomized controlled trial is currently in progress to test the intervention's efficacy

[F-18]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules:a blinded, randomised controlled multicentre trial

Purpose To assess the impact of an [F-18]FDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with indeterminate cytology. Methods In this double-blinded, randomised controlled multicentre trial, 132 adult euthyroid patients with scheduled diagnostic surgery for a Bethesda III or IV thyroid nodule underwent [F-18]FDG-PET/CT and were randomised to an [F-18] FDG-PET/CT-driven or diagnostic surgery group. In the [F-18]FDG-PET/CT-driven group, management was based on the [F-18]FDG-PET/CT result: when the index nodule was visually [F-18]FDG-positive, diagnostic surgery was advised; when [F-18]FDG-negative, active surveillance was recommended. The nodule was presumed benign when it remained unchanged on ultrasound surveillance. In the diagnostic surgery group, all patients were advised to proceed to the scheduled surgery, according to current guidelines. The primary outcome was the fraction of unbeneficial patient management in one year, i.e., diagnostic surgery for benign nodules and active surveillance for malignant/borderline nodules. Intention-to-treat analysis was performed. Subgroup analyses were performed for non-Hurthle cell and Hurthle cell nodules. Results Patient management was unbeneficial in 42% (38/91 [95% confidence interval [CI], 32-53%]) of patients in the [F-18] FDG-PET/CT-driven group, as compared to 83% (34/41 [95% CI, 68-93%]) in the diagnostic surgery group (p < 0.001). [F-18]FDG-PET/CT-driven management avoided 40% (25/63 [95% CI, 28-53%]) diagnostic surgeries for benign nodules: 48% (23/48 [95% CI, 33-63%]) in non-Hurthle cell and 13% (2/15 [95% CI, 2-40%]) in I-Liable cell nodules (p = 0.02). No malignant or borderline tumours were observed in patients under surveillance. Sensitivity, specificity, negative and positive predictive value, and benign call rate (95% CI) of [F-18]FDG-PET/CT were 94.1% (80.3-99.3%), 39.8% (30.0-50.2%), 95.1% (83.5-99.4%), 35.2% (25.4-45.9%), and 31.1% (23.3-39.7%), respectively. Conclusion An [F-18]FDG-PET/CT-driven diagnostic workup of indeterminate thyroid nodules leads to practice changing management, accurately and oncologically safely reducing futile surgeries by 40%. For optimal therapeutic yield, application should be limited to non-Hurthle cell nodules

Определение скорости перемещения деформаций растяжений в массиве при подземной выемке угля

Приведена швидкість переміщення деформацій в непорушеному масиві. Встановлено, що швидкість в породах середнього ступеня метаморфізму складає 15 м/добу. Середня швидкість переміщення деформацій в сланцях – 10 м/добу, в піщаниках – 15 м/добу. При повторній підробці швидкість переміщення деформацій складає 17 м/добу.Deformation’s speed travel in the virgin rock massif is given in this article. It has been determined that deformation’s speed in the rocks of medium-scale metamorphism was 15 meters over the entire circadian period. The average speed of deformation’s travel in the shale rocks is 10 meters over the entire circadian period and in the sandstone is 15 meters over the entire circadian period. During the recurring undermining the speed travel of deformations is 17 meters over the entire circadian period