The Effect of PRRS Virus Outbreak on Genetic Parameters of Reproductive Performance in Pigs

PRRSV is a significant economic problem for producers in the US and around the world. The genetic basis for reproductive performance in sow herds has been poorly understood

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

Morbid obesity and thyroid cancer rate. A review of literature

In the past three decades, several recent studies have analyzed the alarming increase of obesity worldwide, and it has been well established that the risk of many types of malignancies is increased in obese individuals; in the same period, thyroid cancer has become the fastest growing cancer of all malignancies. We investigated the current literature to underline the presence of a connection between excess body weight or Body Mass Index (BMI) and risk of thyroid cancer. Previous studies stated that the contraposition between adipocytes and adipose-resident immune cells enhances immune cell production of multiple pro-inflammatory factors with subsequent induction of hyperlipidemia and vascular injury; these factors are all associated with oxidative stress and cancer development and/or progression. Moreover, recent studies made clear the mitogenic and tumorigenic action of insulin, carried out through the stimulation of mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase/AKT (PI3K/AKT) pathways, which is correlated to the hyperinsulinemia and hyperglycemia found in obese population. Our findings suggest that obesity and excess body weight are related to an increased risk of thyroid cancer and that the mechanisms that combine overweight with this cancer should be searched for in the adipokine pathways and chronic inflammation onset

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

Field Mixing in Curved Spacetime and Dark Matter

An extensive review of recent results concerning the quantum field theory of particle mixing in curved spacetime is presented. The rich mathematical structure of the theory for both fermions and bosons, stemming from the interplay of curved space quantization and field mixing, is discussed, and its phenomenological implications are shown. Fermionic and bosonic oscillation formulae for arbitrary globally hyperbolic spacetimes are derived and the transition probabilities are explicitly computed on some metrics of cosmological and astrophysical interest. The formulae thus obtained are characterized by a pure QFT correction to the amplitudes, which is absent in quantum mechanics, where only the phase of the oscillations is affected by the gravitational background. Their deviation from the flat space probabilities is demonstrated, with the aid of numerical analyses. The condensate structure of the flavor vacuum of mixed fermions is studied, assessing its role as a possible dark matter component in a cosmological context. It is shown that the flavor vacuum behaves as a barotropic fluid, satisfying the equation of the state of cold dark matter. New experiments on the cosmic neutrino background, as PTOLEMY, may validate these theoretical results

Laboratory markers in ulcerative colitis: Current insights and future advances.

Ulcerative colitis (UC) and Crohn’s disease (CD) are the major forms of inflammatory bowel diseases (IBD) in man. Despite some common features, these forms can be distinguished by different genetic predisposition, risk factors and clinical, endoscopic and histological characteristics. The aetiology of both CD and UC remains unknown, but several evidences suggest that CD and perhaps UC are due to an excessive immune response directed against normal constituents of the intestinal bacterial flora. Tests sometimes invasive are routine for the diagnosis and care of patients with IBD. Diagnosis of UC is based on clinical symptoms combined with radiological and endoscopic investigations. The employment of non-invasive biomarkers is needed. These biomarkers have the potential to avoid invasive diagnostic tests that may result in discomfort and potential complications. The ability to determine the type, severity, prognosis and response to therapy of UC, using biomarkers has long been a goal of clinical researchers. We describe the biomarkers assessed in UC, with special reference to acute-phase proteins and serologic markers and thereafter, we describe the new biological markers and the biological markers could be developed in the future: (1) serum markers of acute phase response: The laboratory tests most used to measure the acute-phase proteins in clinical practice are the serum concentration of C-reactive protein and the erythrocyte sedimentation rate. Other biomarkers of inflammation in UC include platelet count, leukocyte count, and serum albumin and serum orosomucoid concentrations; (2) serologic markers/antibodies: In the last decades serological and immunologic biomarkers have been studied extensively in immunology and have been used in clinical practice to detect specific pathologies. In UC, the presence of these antibodies can aid as surrogate markers for the aberrant host immune response; and (3) future biomarkers: The development of biomarkers in UC will be very important in the future. The progress of molecular biology tools (microarrays, proteomics and nanotechnology) have revolutionised the field of the biomarker discovery. The advances in bioinformatics coupled with cross-disciplinary collaborations have greatly enhanced our ability to retrieve, characterize and analyse large amounts of data generated by the technological advances. The techniques available for biomarkers development are genomics (single nucleotide polymorphism genotyping, pharmacogenetics and gene expression analyses) and proteomics. In the future, the addition of new serological markers will add significant benefit. Correlating serologic markers with genotypes and clinical phenotypes should enhance our understanding of pathophysiology of UC