Genetic parameters and genomic regions associated with piglet response to vaccination for porcine reproductive and respiratory syndrome (PRRS) virus and co-infection with PRRS virus and porcine circovirus type 2b (PCV2b)

Citation: Dunkelberger, J. R., Serao, N. V. L., Kerrigan, M. A., Lunney, J. K., Rowland, R. R. R., & Dekkers, J. C. M. (2016). Genetic parameters and genomic regions associated with piglet response to vaccination for porcine reproductive and respiratory syndrome (PRRS) virus and co-infection with PRRS virus and porcine circovirus type 2b (PCV2b). Journal of Animal Science, 94, 52-53. doi:10.2527/msasas2016-112Objectives of this research were to estimate genetic parameters and to identify genomic regions associated with PRRS viral load (VL), PCV2b VL, and average daily gain (ADG) in nursery pigs vaccinated or non-vaccinated for PRRS virus (PRRSV), followed by co-infection with PRRSV and PCV2b. Data used included 396 commercial crossbred pigs from two PRRS Host Genetics Consortium trials, all from the same genetic supplier. Pigs were sent to Kansas State University after weaning and randomly sorted into two rooms. All pigs in one room were vaccinated for PRRS, and 28 d later, pigs in both rooms were co-infected with PRRSV and PCV2b, followed for 42 d, and genotyped using the 80K BeadChip. PRRS VL after vaccination and post co-infection and PCV2b VL were calculated as area under the curve of serum viremia from ?28 to 0, 0 to 21, and 0 to 42 d post co-infection, respectively. Genetic parameters were estimated by fitting multivariate animal models in ASReml4 with litter and pen (trial) as additional random effects. Trait-specific fixed effects of trial and weight and age at vaccination were also fitted. Genome-wide association (GWA) studies were performed by fitting SNPs as fixed effects one at a time in bivariate animal models for the non-vaccinated (Non-Vx) and vaccinated (Vx) groups for each trait. Heritability estimates following vaccination were 0.31, 0.07, and 0.10 for ADG Non-Vx, ADG Vx, and PRRS Vx, respectively. During the co-infection period, heritability estimates were slightly higher at 0.53, 0.57, 0.56, 0.20, 0.18, and 0.15 for ADG Non-Vx, ADG Vx, PRRS Non-Vx, PRRS Vx, PCV2b Non-Vx, and PCV2b Vx, respectively. Standard errors ranged from 0.14 to 0.22. A strong, positive genetic correlation (0.95 ± 1.01) was observed for PRRS VL post-vaccination with PRRS VL Non-Vx. Unique genomic regions were identified between Vx and Non-Vx pigs for each trait, the most significant of which was identified for PCV2b VL and located near the major histocompatibility complex, an important region for response to infection. The chromosome 4 region, which has been associated with VL following PRRSV-only infection, was associated with PRRS VL Non-Vx but not PRRS Vx or PRRS VL post-vaccination. Together, these results suggest that selection for improved performance under co-infection of PRRS and PCV2b is possible. Additionally, identification of unique genomic regions between Vx and Non-Vx pigs may enable selection of pigs with better response to vaccination. This research was supported by USDA-NIFA grants 2012–38420–19286 and 2013–68004–20362

Identification of a putative quantitative trait nucleotide in guanylate binding protein 5 for host response to PRRS virus infection

Citation: Koltes, J. E., Fritz-Waters, E., Eisley, C. J., Choi, I., Bao, H., Kommadath, A., . . . Reecy, J. M. (2015). Identification of a putative quantitative trait nucleotide in guanylate binding protein 5 for host response to PRRS virus infection. Bmc Genomics, 16, 13. doi:10.1186/s12864-015-1635-9Background: Previously, we identified a major quantitative trait locus (QTL) for host response to Porcine Respiratory and Reproductive Syndrome virus (PRRSV) infection in high linkage disequilibrium (LD) with SNP rs80800372 on Sus scrofa chromosome 4 (SSC4). Results: Within this QTL, guanylate binding protein 5 (GBP5) was differentially expressed (DE) (p < 0.05) in blood from AA versus AB rs80800372 genotyped pigs at 7,11, and 14 days post PRRSV infection. All variants within the GBP5 transcript in LD with rs80800372 exhibited allele specific expression (ASE) in AB individuals (p < 0.0001). A transcript re-assembly revealed three alternatively spliced transcripts for GBP5. An intronic SNP in GBP5, rs340943904, introduces a splice acceptor site that inserts five nucleotides into the transcript. Individuals homozygous for the unfavorable AA genotype predominantly produced this transcript, with a shifted reading frame and early stop codon that truncates the 88 C-terminal amino acids of the protein. RNA-seq analysis confirmed this SNP was associated with differential splicing by QTL genotype (p < 0.0001) and this was validated by quantitative capillary electrophoresis (p < 0.0001). The wild-type transcript was expressed at a higher level in AB versus AA individuals, whereas the five-nucleotide insertion transcript was the dominant form in AA individuals. Splicing and ASE results are consistent with the observed dominant nature of the favorable QTL allele. The rs340943904 SNP was also 100 % concordant with rs80800372 in a validation population that possessed an alternate form of the favorable B QTL haplotype. Conclusions: GBP5 is known to play a role in inflammasome assembly during immune response. However, the role of GBP5 host genetic variation in viral immunity is novel. These findings demonstrate that rs340943904 is a strong candidate causal mutation for the SSC4 QTL that controls variation in host response to PRRSV.Additional Authors: Lunney, J. K.;Liu, P.;Carpenter, S.;Rowland, R. R. R.;Dekkers, J. C. M.;Reecy, J. M

Impact of gastrointestinal side effects on patients’ reported quality of life trajectories after radiotherapy for prostate cancer: Data from the prospective, observational pros-it CNR study

Radiotherapy (RT) represents an important therapeutic option for the treatment of localized prostate cancer. The aim of the current study is to examine trajectories in patients’ reported quality of life (QoL) aspects related to bowel function and bother, considering data from the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study, analyzed with growth mixture models. Data for patients who underwent RT, either associated or not associated with androgen deprivation therapy, were considered. QoL outcomes were assessed over a 2-year period from the diagnosis, using the Italian version of the University of California Los Angeles-Prostate Cancer Index (Italian-UCLA-PCI). Three trajectories were identified for the bowel function; having three or more comorbidities and the use of 3D-CRT technique for RT were associated with the worst trajectory (OR = 3.80, 95% CI 2.04–7.08; OR = 2.17, 95% CI 1.22–3.87, respectively). Two trajectories were identified for the bowel bother scores; diabetes and the non-Image guided RT method were associated with being in the worst bowel bother trajectory group (OR = 1.69, 95% CI 1.06–2.67; OR = 2.57, 95% CI 1.70–3.86, respectively). The findings from this study suggest that the absence of comorbidities and the use of intensity modulated RT techniques with image guidance are related with a better tolerance to RT in terms of bowel side effects

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care

Genomewide association of piglet responses to infection with one of two porcine reproductive and respiratory syndrome virus isolates.

Porcine reproductive and respiratory syndrome (PRRS) is a devastating disease in the swine industry. Identification of host genetic factors that enable selection for improved performance during PRRS virus (PRRSV) infection would reduce the impact of this disease on animal welfare and production efficiency. We conducted genomewide association study (GWAS) analyses of data from 13 trials of approximately 200 commercial crossbred nursery-age piglets that were experimentally infected with 1 of 2 type 2 isolates of PRRSV (NVSL 97-7985 [NVSL] and KS2006-72109 [KS06]). Phenotypes analyzed were viral load (VL) in blood during the first 21 d after infection (dpi) and weight gain (WG) from 0 to 42 dpi. We accounted for the previously identified QTL in the region on SSC4 in our models to increase power to identify additional regions. Many regions identified by single-SNP analyses were not identified using Bayes-B, but both analyses identified the same regions on SSC3 and SSC5 to be associated with VL in the KS06 trials and on SSC6 in the NVSL trials ( < 5 x 10); for WG, regions on SSC5 and SSC17 were associated in the NVSL trials ( < 3 x 10). No regions were identified with either method for WG in the KS06 trials. Except for the region on SSC4, which was associated with VL for both isolates (but only with WG for NVSL), identified regions did not overlap between the 2 PRRSV isolate data sets, despite high estimates of the genetic correlation between isolates for traits based on these data. We also identified genomic regions whose associations with VL or WG interacted with either PRRSV isolate or with genotype at the SSC4 QTL. Gene ontology (GO) annotation terms for genes located near moderately associated SNP ( < 0.003) were enriched for multiple immunologically (VL) and metabolism- (WG) related GO terms. The biological relevance of these regions suggests that, although it may increase the number of false positives, the use of single-SNP analyses and a relaxed threshold also increased the identification of true positives. In conclusion, although only the SSC4 QTL was associated with response to both PRRSV isolates, genes near associated SNP were enriched for the same GO terms across PRRSV isolates, suggesting that host responses to these 2 isolates are affected by the actions of many genes that function together in similar biological processes

Strong Women and Nontraditional Mothers: The Female Figures in Napoli Milionaria! and Filumena Marturano by Eduardo de Filippo

A study of the feminine figures in Napoli Milionaria! and Filumena Marturano by Eduardo de Filippo

Treatment paths for localised prostate cancer in Italy: The results of a multidisciplinary, observational, prospective study (Pros-IT CNR)

Background There are several treatments available to newly diagnosed prostate cancer (PCA) patients. Although surgery and radiotherapy (RT) with or without androgen deprivation therapy (ADT) are widely adopted treatment options for localized PCA together with active surveillance (AS), there is no consensus nor randomised trials on treatment selection, prospective quality of life (QOL), along with toxicity outcomes and according to treatment modality in the Italian population. The current study aimed to describe clinical-therapeutic features and QOL at PCA diagnosis, according to different treatment patterns in a large prospective, Italian population, enrolled in the Pros-IT CNR study. Methods The Pros-IT CNR is an on-going national, multicenter, observational, prospective study on patients affected by PCA who have been referred by 97 Italian Urology, Radiation Oncology and Medical Oncology facilities participating in the project. The possible relationships between the treatment patterns reported in the 6 month follow-up case report form and patients\u2019 features at diagnosis were evaluated using exploratory multiple correspondence analysis (MCA) and other data analysis method. Results At diagnosis, surgery and AS patients were significantly younger, had fewer comorbidities, lower PSA levels and Gleason Score (GS) values; they were also diagnosed at an earlier stage of disease with respect to the RT or ADT patients who showed significantly worse QoL scores at the time of diagnosis. Conclusions An analysis of the data collected at baseline and 6 months later uncovered substantial differences in ages, comorbidities, clinical and QOL features in the various treatment groups. These findings do not fully reflect the current PCA treatment guidelines and suggest the need for a multidisciplinary consensus guideline to ameliorate both the counselling and treatments of PCA patients

Cerebellum Transcriptome of Mice Bred for High Voluntary Activity Offers Insights into Locomotor Control and Reward-Dependent Behaviors

The role of the cerebellum in motivation and addictive behaviors is less understood than that in control and coordination of movements. High running can be a self-rewarding behavior exhibiting addictive properties. Changes in the cerebellum transcriptional networks of mice from a line selectively bred for High voluntary running (H) were profiled relative to an unselected Control (C) line. The environmental modulation of these changes was assessed both in activity environments corresponding to 7 days of Free (F) access to running wheel and to Blocked (B) access on day 7. Overall, 457 genes exhibited a significant (FDR-adjusted P-value < 0.05) genotype-by-environment interaction effect, indicating that activity genotype differences in gene expression depend on environmental access to running. Among these genes, network analysis highlighted 6 genes (Nrgn, Drd2, Rxrg, Gda, Adora2a, and Rab40b) connected by their products that displayed opposite expression patterns in the activity genotype contrast within the B and F environments. The comparison of network expression topologies suggests that selection for high voluntary running is linked to a predominant dysregulation of hub genes in the F environment that enables running whereas a dysregulation of ancillary genes is favored in the B environment that blocks running. Genes associated with locomotor regulation, signaling pathways, reward-processing, goal-focused, and reward-dependent behaviors exhibited significant genotype-by-environment interaction (e.g. Pak6, Adora2a, Drd2, and Arhgap8). Neuropeptide genes including Adcyap1, Cck, Sst, Vgf, Npy, Nts, Penk, and Tac2 and related receptor genes also exhibited significant genotype-by-environment interaction. The majority of the 183 differentially expressed genes between activity genotypes (e.g. Drd1) were under-expressed in C relative to H genotypes and were also under-expressed in B relative to F environments. Our findings indicate that the high voluntary running mouse line studied is a helpful model for understanding the molecular mechanisms in the cerebellum that influence locomotor control and reward-dependent behaviors

Evaluation of an alternative dosing regimen with tadalafil, three times per week, for men with erectile dysfunction: SURE study in Italy

AIM: To examine the preference for two dosing regimens of 20 mg of tadalafil, on demand or three times per week, in men affected with erectile dysfunction (ED) in Italy. METHODS: Scheduled Use versus on demand Regimen Evaluation (SURE) is a multicenter, crossover and open-label study, involving 94 urology centers in Italy. Patients aged 18 years or older affected with ED for at least 3 months were enrolled and randomized to 20 mg of tadalafil treatment on demand or three times per week for 5-6 weeks. After a 1-week washout, patients were crossed over to the alternate regimen for 5-6 weeks. A treatment preference question was used to determine the preferred treatment regimen. International Index of Erectile Function (IIEF) and Sexual Encounter Profile (SEP) questionnaire were used as efficacy measures. RESULTS: A total of 1 058 men (mean age 54.8 years), were randomized to treatment. Overall, 59.1% of patients preferred the on-demand regimen and 41.9% preferred the three times per week dosing. Both regimens were efficacious and well tolerated. Although a statistically higher improvement of the IIEF erectile function (IIEF-EF) domain score and the SEP questionnaire was reported for the three times per week compared to the on-demand treatment regimen, this difference was numerically minimal and lacking in clinical significance. CONCLUSION: Tadalafil is effective and well tolerated whether used on demand or three times per week. Patients should be given the option to choose the best treatment regimen according to personal needs and preferences