second model, the two main conditions were parametrically modulated by the two categories, respectively (SOM, S5.1). The activation of the precuneus was higher for hard dominance-solvable games than for easy ones ( Fig. 4A and table S10). The activation of the insula was higher for the highly focal coordination games than for less focal ones ( Fig. 4B and table S11). Previous studies also found that precuneus activity increased when the number of planned moves increased (40, 41). The higher demand for memory-related imagery and memory retrieval may explain the greater precuneus activation in hard dominance-solvable games. In highly focal coordination games, the participants may have felt quite strongly that the pool students must notice the same salient feature. This may explain why insula activation correlates with NCI.Participants might have disagreed about which games were difficult. We built a third model to investigate whether the frontoparietal activation correlates with how hard a dominance-solvable game is and whether the activation in insula and ACC correlates with how easy a coordination game is. Here, the two main conditions were parametrically modulated by each participant's probability of obtaining a reward in each game (SOM, S2.2 and S5.2). We found a negative correlation between the activation of the precuneus and the participant's probability of obtaining a reward in dominance-solvable games ( Fig. 4C and table S12), which suggests that dominance-solvable games that yielded lower payoffs presented harder mental challenges. In a previous study on working memory, precuneus activity positively correlated with response times, a measure of mental effort (24). Both findings are consistent with the interpretation that subjective measures reflecting harder tasks (higher efforts) correlate with activation in precuneus. A positive correlation between insula activation and the participant's probability of obtaining a reward again suggests that coordination games with a highly salient feature strongly activated the "gut feeling" reported by many participants (Fig. 4D and table S13). A previous study found that the subjective rating of "chills intensity" in music correlates with activation of insula (42). Both findings are consistent with the interpretation that the subjective intensity of how salient a stimulus is correlates with activation in insula.As mentioned, choices were made significantly faster in coordination games than in dominancesolvable games. The results of the second and third models provide additional support for the idea that intuitive and deliberative mental processes have quite different properties. The "slow and effortful" process was more heavily taxed when the dominance-solvable games were harder. The "fast and effortless" process was more strongly activated when coordination was easy.

BackgroundInfectious disease of livestock continues to be a cause of substantial economic loss and has adverse welfare consequences in both the developing and developed world. New solutions to control disease are needed and research focused on the genetic loci determining variation in immune-related traits has the potential to deliver solutions. However, identifying selectable markers and the causal genes involved in disease resistance and vaccine response is not straightforward. The aims of this study were to locate regions of the bovine genome that control the immune response post immunisation. 195 F2 and backcross Holstein Charolais cattle were immunised with a 40-mer peptide derived from foot-and-mouth disease virus (FMDV). T cell and antibody (IgG1 and IgG2) responses were measured at several time points post immunisation. All experimental animals (F0, F1 and F2, n = 982) were genotyped with 165 microsatellite markers for the genome scan.ResultsConsiderable variability in the immune responses across time was observed and sire, dam and age had significant effects on responses at specific time points. There were significant correlations within traits across time, and between IgG1 and IgG2 traits, also some weak correlations were detected between T cell and IgG2 responses. The whole genome scan detected 77 quantitative trait loci (QTL), on 22 chromosomes, including clusters of QTL on BTA 4, 5, 6, 20, 23 and 25. Two QTL reached 5% genome wide significance (on BTA 6 and 24) and one on BTA 20 reached 1% genome wide significance.ConclusionsA proportion of the variance in the T cell and antibody response post immunisation with an FDMV peptide has a genetic component. Even though the antigen was relatively simple, the humoral and cell mediated responses were clearly under complex genetic control, with the majority of QTL located outside the MHC locus. The results suggest that there may be specific genes or loci that impact on variation in both the primary and secondary immune responses, whereas other loci may be specifically important for early or later phases of the immune response. Future fine mapping of the QTL clusters identified has the potential to reveal the causal variations underlying the variation in immune response observed.

Farm animals remain at risk of endemic, exotic and newly emerging viruses. Vaccination is often promoted as the best possible solution, and yet for many pathogens, either there are no appropriate vaccines or those that are available are far from ideal. A complementary approach to disease control may be to identify genes and chromosomal regions that underlie genetic variation in disease resistance and response to vaccination. However, identification of the causal polymorphisms is not straightforward as it generally requires large numbers of animals with linked phenotypes and genotypes. Investigation of genes underlying complex traits such as resistance or response to viral pathogens requires several genetic approaches including candidate genes deduced from knowledge about the cellular pathways leading to protection or pathology, or unbiased whole genome scans using markers spread across the genome.Evidence for host genetic variation exists for a number of viral diseases in cattle including bovine respiratory disease and anecdotally, foot and mouth disease virus (FMDV). We immunised and vaccinated a cattle cross herd with a 40-mer peptide derived from FMDV and a vaccine against bovine respiratory syncytial virus (BRSV). Genetic variation has been quantified. A candidate gene approach has grouped high and low antibody and T cell responders by common motifs in the peptide binding pockets of the bovine major histocompatibility complex (BoLA) DRB3 gene. This suggests that vaccines with a minimal number of epitopes that are recognised by most cattle could be designed. Whole genome scans using microsatellite and single nucleotide polymorphism (SNP) markers has revealed many novel quantitative trait loci (QTL) and SNP markers controlling both humoral and cell-mediated immunity, some of which are in genes of known immunological relevance including the toll-like receptors (TLRs).The sequencing, assembly and annotation of livestock genomes and is continuing apace. In addition, provision of high-density SNP chips should make it possible to link phenotypes with genotypes in field populations without the need for structured populations or pedigree information. This will hopefully enable fine mapping of QTL and ultimate identification of the causal gene(s). The research could lead to selection of animals that are more resistant to disease and new ways to improve vaccine efficacy.

Bovine respiratory disease (BRD) is the most economically important disease in U.S. feedlots. Infection can result in morbidity, mortality, and reduced average daily gain. Cheap and reliable genetic methods of prediction and protection from BRD would be highly advantageous to the industry. The immune response may correlate with BRD incidence. Cattle (n = 2,182) were vaccinated against common viral and bacterial pathogens of BRD. Two blood samples were collected, one during booster vaccination and one 21d later, enabling 3 phenotypes for each trait [prebooster (pre), postbooster (post), and delta (post minus pre)]. From the blood samples innate and adaptive responses [counts of white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, and basophils] were measured. In addition, feedlot ADG and binary traits [health records (HR; 0 = healthy, 1 = ill) and lung scores (LS; collected at harvest; 0 = no lesions, 1 = lesions)] were also recorded. Traits ADG, HR, and LS have all been significantly correlated with infection to BRD. In this investigation we aimed to find correlations between the immune response and ADG, HR, and LS to find an easily measurable trait that would be a good predictor of BRD resistance after vaccination. The results showed an average positive delta for the innate immune response (eosinophils, basophils, neutrophils), whereas the adaptive immune response had an average negative delta (lymphocytes). Overall, we discovered that the immune responses had moderately high heritabilities (h(2); lowest: delta monocytes, 0.21 ± 0.05; greatest: pre lymphocytes: 0.5 ± 0.05), with lymphocytes having the greatest h(2) throughout the study (h(2) ≥ 0.41). All genetic correlations were calculated using bivariate REML models. Although LS did not significantly correlate with any of the immune phenotypes, both ADG (post lymphocytes, -0.24 ± 0.12) and HR (pre eosinophils, -0.67 ± 0.29; delta WBC, -0.5 ± 0.24, and delta lymphocytes, -0.67 ± 0.21) did. All the significant genetic correlations with HR were negative; resistance to BRD appears to be a function of greater delta lymphocytes and WBC. The increase in eosinophils may potentially link its role in decreasing lymphocytes. These results may enable producers to predict if revaccination, quarantine, and breeding of animals is required to reduce the incidence of BRD postvaccination. In addition, immunological phenotypes maybe used to aid genomic selection indices to select animals with greater rates of protection after BRD vaccination.

Infectious disease is an important problem for animal breeders, farmers and governments worldwide. One approach to reducing disease is to breed for resistance. This linkage study used a Charolais-Holstein F2 cattle cross population (n = 501) which was genotyped for 165 microsatellite markers (covering all autosomes) to search for associations with phenotypes for Bovine Respiratory Syncytial Virus (BRSV) specific total-IgG, IgG1 and IgG2 concentrations at several time-points pre- and post-BRSV vaccination. Regions of the bovine genome which influenced the immune response induced by BRSV vaccination were identified, as well as regions associated with the clearance of maternally derived BRSV specific antibodies. Significant positive correlations were detected within traits across time, with negative correlations between the pre- and post-vaccination time points. The whole genome scan identified 27 Quantitative Trait Loci (QTL) on 13 autosomes. Many QTL were associated with the Thymus Helper 1 linked IgG2 response, especially at week 2 following vaccination. However the most significant QTL, which reached 5% genome-wide significance, was on BTA 17 for IgG1, also 2 weeks following vaccination. All animals had declining maternally derived BRSV specific antibodies prior to vaccination and the levels of BRSV specific antibody prior to vaccination were found to be under polygenic control with several QTL detected. Heifers from the same population (n = 195) were subsequently immunised with a 40-mer Foot-and-Mouth Disease Virus peptide (FMDV) in a previous publication. Several of these QTL associated with the FMDV traits had overlapping peak positions with QTL in the current study, including the QTL on BTA23 which included the bovine Major Histocompatibility Complex (BoLA), and QTL on BTA9 and BTA24, suggesting that the genes underlying these QTL may control responses to multiple antigens. These results lay the groundwork for future investigations to identify the genes underlying the variation in clearance of maternal antibody and response to vaccination.

No abstract

Background: Reproductive performance is critical for efficient swine production. Recent results indicated that vulva size (VS) may be predictive of reproductive performance in sows. Study objectives were to estimate genetic parameters, identify genomic regions associated, and estimate genomic prediction accuracies (GPA) for VS traits. Results: Heritability estimates of VS traits, vulva area (VA), height (VH), and width (VW) measurements, were moderately to highly heritable in Yorkshire, with 0.46 ± 0.10, 0.55 ± 0.10, 0.31 ± 0.09, respectively, whereas these estimates were low to moderate in Landrace, with 0.16 ± 0.09, 0.24 ± 0.11, and 0.08 ± 0.06, respectively. Genetic correlations within VS traits were very high for both breeds, with the lowest of 0.67 ± 0.29 for VH and VW for Landrace. Genome-wide association studies (GWAS) for Landrace, reveled genomic region associated with VS traits on Sus scrofa chromosome (SSC) 2 (154-157 Mb), 7 (107-110 Mb), 8 (4-6 Mb), and 10 (8-19 Mb). For Yorkshire, genomic regions on SSC 1 (87-91 and 282-287 Mb) and 5 (67 Mb) were identified. All regions explained at least 3.4% of the genetic variance. Accuracies of genomic prediction were moderate in Landrace, ranging from 0.30 (VH) to 0.61 (VA), and lower for Yorkshire, with 0.07 (VW) to 0.11 (VH). Between-breed and multi-breed genomic prediction accuracies were low. Conclusions: Our findings suggest that VS traits are heritable in Landrace and Yorkshire gilts. Genomic analyses show that major QTL control these traits, and they differ between breed. Genomic information can be used to increase genetic gains for these traits in gilts. Additional research must be done to validate the GWAS and genomic prediction results reported in our study.

Advancing age and chronic health conditions, significant risk factors for severe COVID-19, are associated with a pro-inflammatory state, termed inflamm-aging. CXCR6+ T cells are known to traffic to the lung and have been reported to increase with age. The ligand of CXCR6, CXCL16, is constitutively expressed in the lung and upregulated during inflammatory responses and the CXCR6/CXCL16 axis is associated with severe lung disease and pneumonia. Genome-wide association studies have also recently identified 3p21.31, encompassing the CXCR6 gene, as a susceptibility locus for severe COVID-19. We assessed numbers T cells expressing the chemokine receptor CXCR6 and plasma levels of CXCL16, in control and COVID-19 patients. Results demonstrated that circulating CD8+CXCR6+ T cells were significantly elevated with advancing age, yet virtually absent in patients with severe COVID-19. Peripheral levels of CXCL16 were significantly upregulated in severe COVID-19 patients compared to either mild COVID-19 patients or SARS-CoV-2 negative controls. This study supports a significant role of the CXCR6/CXCL16 axis in the immunopathogenesis of severe COVID-19.