Genetic indicators for disease resilience in pigs

Infectious swine diseases have the potential to decimate the health and productivity of swine farms. One of the most economically concerning diseases is caused by the Porcine Reproductive and Respiratory Syndrome (PRRS) virus. While swine producers can implement vaccines, medications, or antibiotics and antiviral drugs, many infectious pathogens such as the PRRS virus have shown these strategies to be ineffective. One complimentary strategy would be to select pigs for increased disease resistance or resilience, where disease resilience is defined as an animal’s ability to maintain performance when infected. However, the elite populations that are used for genetic improvement are typically kept in high health conditions, making it difficult and impractical for swine breeders to use phenotypic selection in an environment with exposure to disease to select for increased disease resilience. Previous research has shown that host response to PRRS virus infection has a sizable genetic component and revealed a Quantitative Trait Locus (QTL) for host response to PRRS virus infection on Sus Scrofa Chromosome (SSC) 4. A putative causative mutation in the GBP5 gene was identified for this QTL. This mutation was determined to be in complete linkage disequilibrium with the single nucleotide polymorphism (SNP) WUR10000125 (WUR) that was included on commercial SNP panels. However, this was based on data from one genetic source. The overall objective of this thesis was to determine if the WUR SNP and phenotypes obtained from in-vitro mitogen stimulation assays (MSA) of peripheral blood mononuclear cells (PBMCs) from young healthy nursery pigs can be used as genetic indicators to select for disease resilience. The two requirements for a genetic indicator are that it must be heritable and have a sizeable genetic correlation with the trait of interest, in this case, disease resilience. Data from experimental PRRS virus infection trials from the PRRS Host Genetics Consortium (PHGC) and a polymicrobial Natural Disease Challenge Model (NDCM) of grow-finish pigs were used to address these objectives. Data and SNP genotypes, including for the WUR SNP and the putative causative mutation in the GBP5 gene, were available on 1414 pigs from eight PHGC trials of ~200 commercial crossbred nursery pigs per trial from six unrelated populations. Results showed that the WUR and GBP5 SNPs were not in complete linkage disequilibrium (r2 = 0.94). Discordant genotypes were determined to be the result of recombination, rather than genotyping errors. Although it was previously speculated that the GBP5 gene is a major gene responsible for host response to PRRS, there were small but non-significant differences between the effect of GBP5 and WUR on PRRS viral load and weight gain post-infection. These results indicate that either GBP5 or the WUR SNP can be used for marker-assisted selection to increase resistance to PRRS. In the NDCM, data from 3139 crossbred nursery barrows that were genotyped using a 650 K SNP Panel (Affymetrix) were used. The 650 K panel included the WUR SNP but not the GBP5 SNP. In the NDCM, pigs were entered through a batch system of 60 or 75 pigs per batch into a facility that was seeded with multiple infectious pathogens, including PRRS, to maximize the expression of disease resilience. Disease resilience traits, including growth, feed intake, and treatment and mortality rates were recorded. Based on these data, it was determined that the favorable G allele for the WUR SNP was significantly associated with greater average daily gain (p=0.02) and lower numbers of treatments in the challenge nursery (p=0.05) and across the challenge nursery and finisher (p=0.01), establishing the effect of the SSC4 QTL on resilience to a polymicrobial disease challenge. For the MSAs, PBMCs were isolated from blood samples of 882 pigs from 19 batches of the NDCM, taken at 27 or 35 days of age and prior to their entry in the disease challenge. For the MSAs, PBMCs were stimulated with five unique mitogens: Concanavalin A (Con A), Phytohemagglutinin (PHA), Poke Weed Mitogen (PWM), Lipopolysaccharide (LPS), and Phorbol Myristate Acetate (PMA), and evaluated for counts of proliferated cells after 48, 72, and 96 hours compared to unstimulated samples (restcount). Proliferated cell counts were adjusted for restcount in two ways: 1) by dividing the average cell count of the stimulated wells by the average cell count of the non-stimulated wells, to compute a Blastogenic Index Score (BIS), and 2) by including the average cell count of the non-stimulated wells as a covariate in the model for analysis of the average cell count of the stimulated wells. Data on BIS and stimulated means at each time point were analyzed separately for each mitogen. For pigs that had data at all three time points for a mitogen, data across these time points were incorporated into a single phenotype called the Area Under the Curve (AUC). Differences between pairs of time points for a given mitogen (delta = 72 – 48 hrs, 96 – 72 hrs, and 96 - 48 hrs) were also analyzed as phenotypes. Genetic parameters (heritabilities and genetic correlations) were estimated for the MSA phenotypes. In general, MSA phenotypes based on BIS versus stimulated means adjusted for restcount had similar estimates of genetic parameters. Heritability estimates for the Con A, PHA, and PMA MSA phenotypes were moderate, ranging from 0.13 +0.09 to 0.37 +0.10 for Con A, from 0.10 +0.07 to 0.34 +0.09 for PHA, and from 0.05 +0.06 to 0.30 +0.10 for PMA. Heritability estimates for the PWM and LPS MSA phenotypes were low, ranging from 0.00 +0.00 to 0.15 +0.09. Disease-related phenotypes collected on these same pigs in the NDCM were then used to estimate genetic correlations of the MSA phenotypes with disease resilience phenotypes. Phenotypic correlations between MSA and disease resilience phenotypes were low. Phenotypes derived from the Con A, PHA, and PMA MSAs, however, had moderately high estimates of genetic correlations with several disease resilience traits, although none were significantly different from zero due to large standard errors. However, genetic correlation estimates were generally in the expected direction, with pigs with higher MSA response having better resilience at the genetic level. Overall, Con A presented itself as the most promising mitogen to use as a genetic indicator for disease resilience, although further studies are recommended to validate its potential and to determine the ideal time point or MSA phenotype to use. In conclusion, the use of a genetic indicator to indirectly select for increased disease resilience in swine is a viable approach. The two indicators investigated in this thesis, i.e. genotype at an SNP on chromosome 4 and results of an in vitro mitogen stimulation assay on immune cells derived from the blood of young healthy piglets, are suitable genetic indicators for disease resilience to a polymicrobial disease challenge

Musical Robots For Children With ASD Using A Client-Server Architecture

Presented at the 22nd International Conference on Auditory Display (ICAD-2016)People with Autistic Spectrum Disorders (ASD) are known to have difficulty recognizing and expressing emotions, which affects their social integration. Leveraging the recent advances in interactive robot and music therapy approaches, and integrating both, we have designed musical robots that can facilitate social and emotional interactions of children with ASD. Robots communicate with children with ASD while detecting their emotional states and physical activities and then, make real-time sonification based on the interaction data. Given that we envision the use of multiple robots with children, we have adopted a client-server architecture. Each robot and sensing device plays a role as a terminal, while the sonification server processes all the data and generates harmonized sonification. After describing our goals for the use of sonification, we detail the system architecture and on-going research scenarios. We believe that the present paper offers a new perspective on the sonification application for assistive technologies

UNLV Financial Aid Forecasting

With an increasing population of students enrolling into UNLV each year, it is important to be able to predict the financial aid funding for future years. We were able to predict how many students would apply for aid and whether or not they would receive any, or enough need-based financial aid, from the years 2019-2023

Star formation history and transition epoch of cluster galaxies based on the Horizon-AGN simulation

Cluster galaxies exhibit substantially lower star formation rates than field galaxies today, but it is conceivable that clusters were sites of more active star formation in the early universe. Herein, we present an interpretation of the star formation history (SFH) of group/cluster galaxies based on the large-scale cosmological hydrodynamic simulation, Horizon-AGN. We find that massive galaxies in general have small values of e-folding timescales of star formation decay (i.e., ``mass quenching'') regardless of their environment, whilst low-mass galaxies exhibit prominent environmental dependence. In massive host halos (i.e., clusters), the e-folding timescales of low-mass galaxies are further decreased if they reside in such halos for a longer period of time. This ``environmental quenching'' trend is consistent with the theoretical expectation from ram pressure stripping. Furthermore, we define a ``transition epoch'' as where cluster galaxies become less star-forming than field galaxies. The transition epoch of group/cluster galaxies varies according to their stellar and host cluster halo masses. Low-mass galaxies in massive clusters show the earliest transition epoch of $\sim 7.6$ Gyr ago in lookback time. However, it decreases to $\sim 5.2$ Gyr for massive galaxies in low-mass clusters. Based on our findings, we can describe cluster galaxy's SFH with regard to the cluster halo-to-stellar mass ratio.Comment: 17 pages, 10 figures, resubmitted to ApJ following first referee repor

An SREBP-Responsive microRNA Operon Contributes to a Regulatory Loop for Intracellular Lipid Homeostasis

SummarySterol regulatory element-binding proteins (SREBPs) have evolved as a focal point for linking lipid synthesis with other pathways that regulate cell growth and survival. Here, we have uncovered a polycistrionic microRNA (miRNA) locus that is activated directly by SREBP-2. Two of the encoded miRNAs, miR-182 and miR-96, negatively regulate the expression of Fbxw7 and Insig-2, respectively, and both are known to negatively affect nuclear SREBP accumulation. Direct manipulation of this miRNA pathway alters nuclear SREBP levels and endogenous lipid synthesis. Thus, we have uncovered a mechanism for the regulation of intracellular lipid metabolism mediated by the concerted action of a pair of miRNAs that are expressed from the same SREBP-2-regulated miRNA locus, and each targets a different protein of the multistep pathway that regulates SREBP function. These studies reveal an miRNA “operon” analogous to the classic model for genetic control in bacterial regulatory systems

Dehydration entropy drives liquid-liquid phase separation by molecular crowding

Liquid-liquid phase separation occurs in cells and can be induced in artificial systems, but the mechanism of the effect of molecular crowders is unclear. Here dehydration entropy-driven phase separation of model charged polymers lacking any chemical complexity or hydrophobicity is shown to be enhanced by polyethylene glycol. Complex coacervation driven liquid-liquid phase separation (LLPS) of biopolymers has been attracting attention as a novel phase in living cells. Studies of LLPS in this context are typically of proteins harboring chemical and structural complexity, leaving unclear which properties are fundamental to complex coacervation versus protein-specific. This study focuses on the role of polyethylene glycol (PEG)-a widely used molecular crowder-in LLPS. Significantly, entropy-driven LLPS is recapitulated with charged polymers lacking hydrophobicity and sequence complexity, and its propensity dramatically enhanced by PEG. Experimental and field-theoretic simulation results are consistent with PEG driving LLPS by dehydration of polymers, and show that PEG exerts its effect without partitioning into the dense coacervate phase. It is then up to biology to impose additional variations of functional significance to the LLPS of biological systems.11Ysciescopu

Perinatal Docosahexaenoic Acid Supplementation Improves Cognition and Alters Brain Functional Organization in Piglets.

Epidemiologic studies associate maternal docosahexaenoic acid (DHA)/DHA-containing seafood intake with enhanced cognitive development; although, it should be noted that interventional trials show inconsistent findings. We examined perinatal DHA supplementation on cognitive performance, brain anatomical and functional organization, and the brain monoamine neurotransmitter status of offspring using a piglet model. Sows were fed a control (CON) or a diet containing DHA (DHA) from late gestation throughout lactation. Piglets underwent an open field test (OFT), an object recognition test (ORT), and magnetic resonance imaging (MRI) to acquire anatomical, diffusion tensor imaging (DTI), and resting-state functional MRI (rs-fMRI) at weaning. Piglets from DHA-fed sows spent 95% more time sniffing the walls than CON in OFT and exhibited an elevated interest in the novel object in ORT, while CON piglets demonstrated no preference. Maternal DHA supplementation increased fiber length and tended to increase fractional anisotropy in the hippocampus of offspring than CON. DHA piglets exhibited increased functional connectivity in the cerebellar, visual, and default mode network and decreased activity in executive control and sensorimotor network compared to CON. The brain monoamine neurotransmitter levels did not differ in healthy offspring. Perinatal DHA supplementation may increase exploratory behaviors, improve recognition memory, enhance fiber tract integrity, and alter brain functional organization in offspring at weaning

The Value of Procalcitonin and the SAPS II and APACHE III Scores in the Differentiation of Infectious and Non-infectious Fever in the ICU: A Prospective, Cohort Study

Early and accurate differentiation between infectious and non-infectious fever is vitally important in the intensive care unit (ICU). In the present study, patients admitted to the medical ICU were screened daily from August 2008 to February 2009. Within 24 hr after the development of fever (>38.3℃), serum was collected for the measurement of the procalcitonin (PCT) and high mobility group B 1 levels. Simplified Acute Physiology Score (SAPS) II and Acute Physiology And Chronic Health Evaluation (APACHE) III scores were also analyzed. Sixty-three patients developed fever among 448 consecutive patients (14.1%). Fever was caused by either infectious (84.1%) or non-infectious processes (15.9%). Patients with fever due to infectious causes showed higher values of serum PCT (7.8±10.2 vs 0.5±0.2 ng/mL, P=0.026), SAPS II (12.0±3.8 vs 7.6±2.7, P=0.006), and APACHE III (48±20 vs 28.7±13.3, P=0.039) than those with non-infectious fever. In receiver operating characteristic curve analysis, the area under the curve was 0.726 (95% CI; 0.587-0.865) for PCT, 0.759 (95% CI; 0.597-0.922) for SAPS II, and 0.715 (95% CI; 0.550-0.880) for APACHE III. Serum PCT, SAPS II, and APACHE III are useful in the differentiation between infectious and non-infectious fever in the ICU

Characterization of in-barn heat processed swine mortalities

In-barn heat processing of mass swine mortalities to inactivate pathogens could facilitate more carcass disposal options and reduce the risk of pathogen spread in the event of a foreign animal disease (FAD) outbreak. A 12.2 × 12.2 × 2.4 m (W × L × H) heat processing room was created using a temporary wall inside a de-commissioned commercial gestation barn in northwest Iowa. Eighteen swine carcasses (six per group) divided into three weight groups (mean ± SD initial carcass weights: 31.8 ± 3.3, 102.7 ± 8.1, and 226.3 ± 27.6 kg) were randomly assigned a location inside the room. Three carcasses per weight group were placed directly on concrete slats and on a raised platform. One carcass per weight group and placement (n=6) was instrumented with five temperature sensors, inserted into the brain, pleura, peritoneal, ham, and bone marrow of the femur, and a sensor was attached directly to the skin surface. Environmental conditions (ambient and room) and carcass temperatures were collected at 15-min intervals. Carcasses were subjected to an average room temperature of 57.3 ± 1.2°C for 14 days. The average (±SD) reduction from initial weight for the carcasses on slats was 45.0 ± 4.70% (feeder), 33.0 ± 8.30% (market), and 34.0 ± 15.80% (sow), and for the carcasses on a raised platform, it was 39.0 ± 6.80% (feeder), 49.0 ± 11.30% (market), and 45.0 ± 6.70% (sow). There was a significant interaction between carcass placement (slats and raised) and carcass weight loss for the market weight group. When average carcass surface temperature was at 40.6, 43.3, and 46.1°C (data grouped for analysis), the average internal carcass temperature for most measurement locations was significantly different across carcass weight groups and between the carcasses on a raised platform and those on slats. This preliminary analysis of carcass weight loss, leachate production, and temperature variation in carcasses of different sizes can be used for planning and evaluating mass swine mortality management strategies