We proposed to investigate the genomic basis of antibody response to porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) vaccination and its relationship to reproductive performance in non-PRRSV-infected commercial sows. Nine hundred and six F1 replacement gilts (139 ± 17 days old) from two commercial farms were vaccinated with a commercial modified live PRRSV vaccine. Blood samples were collected about 52 days after vaccination to measure antibody response to PRRSV as sample-to-positive (S/P) ratio and for single-nucleotide polymorphism (SNP) genotyping. Reproductive performance was recorded for up to 807 sows for number born alive (NBA), number of piglets weaned, number born mummified (MUM), number of stillborn (NSB), and number of pre-weaning mortality (PWM) at parities (P) 1-3 and per sow per year (PSY). Fertility traits such as farrowing rate and age at first service were also analyzed. BayesC0 was used to estimate heritability and genetic correlations of S/P ratio with reproductive performance. Genome-wide association study (GWAS) and genomic prediction were performed using BayesB. The heritability estimate of S/P ratio was 0.34 ± 0.05. High genetic correlations (r g) of S/P ratio with farrowing performance were identified for NBA P1 (0.61), PWM P2 (-0.70), NSB P3 (-0.83), MUM P3 (-0.84), and NSB PSY (-0.90), indicating that genetic selection for increased S/P ratio would result in improved performance of these traits. A quantitative trait locus was identified on chromosome 7 (∼25 Mb), at the major histocompatibility complex (MHC) region, explaining ∼30% of the genetic variance for S/P ratio, mainly by SNPs ASGA0032113, H3GA0020505, and M1GA0009777. This same region was identified in the bivariate GWAS of S/P ratio and reproductive traits, with SNP H3GA0020505 explaining up to 10% (for NBA P1) of the genetic variance of reproductive performance. The heterozygote genotype at H3GA0020505 was associated with greater S/P ratio and NBA P1 (P = 0.06), and lower MUM P3 and NSB P3 (P = 0.07). Genomic prediction
Studies have shown that intramuscular adipogenesis and fibrogenesis may concomitantly occur in skeletal muscle of beef cattle. Thus, we hypothesized that the discrepancy of intramuscular fat content in beef from Nellore and Angus was associated with differences in intramuscular adipogenesis and fibrogenesis during the finishing phase. To test our hypothesis, longissimus muscle samples of Nellore (n = 6; BW = 372.5 ± 37.3 kg) and Angus (n = 6; BW = 382.8 ± 23.9 kg) cattle were collected for analysis of gene and protein expression, and quantification of intramuscular fat and collagen. Least-squares means were estimated for the effect of Breed and differences were considered at P ≤ 0.05. A greater intramuscular fat content was observed in skeletal muscle of Angus compared to Nellore cattle (P≤0.05). No differences were observed for mRNA expression of lipogenic and lipolytic markers ACC, FAS, FABP4, SERBP–1, CPT–2, LPL, and ACOX (P > 0.05) in skeletal muscle of Nellore and Angus cattle. Similarly, no differences were observed in mRNA expression of adipogenic markers Zfp423, PPARγ, and C/EBPα (P>0.05) However, a greater PPARγ protein content was observed in skeletal muscle of Angus compared to Nellore cattle (P≤0.05). A greater abundance of adipo/fibrogenic cells, evaluated by the PDGFRα content, was observed in skeletal muscle of Angus than Nellore cattle (P≤0.05). No differences in fibrogenesis were observed in skeletal muscle of Angus and Nellore cattle, which is in accordance with the lack of differences in intramuscular collagen content in beef from both breeds (P>0.05). These findings demonstrate that difference in intramuscular fat content is associated with a slightly enhanced adipogenesis in skeletal muscle of Angus compared to Nellore cattle, while no difference in fibrogenesis.
BackgroundMaternal nutrition has been highlighted as one of the main factors affecting intra-uterine environment. The increase in nutritional requirements by beef cows during late gestation can cause nutritional deficiency in the fetus and impact the fetal regulation of genes associated with myogenesis and immune response.MethodsForty days before the expected calving date, cows were assigned to one of two diets: 100% (control) or 70% (restricted group) of the daily energy requirement. Muscle samples were collected from 12 heifers and 12 steers, and blood samples were collected from 12 steers. The objective of this work was to identify and to assess the biological relevance of differentially expressed genes (DEG) in the skeletal muscle and blood of beef calves born from cows that experienced [or not] a 30% energy restriction during the last 40 days of gestation.ResultsA total of 160, 164, and 346 DEG (q-value< 0.05) were identified in the skeletal muscle for the effects of diet, sex, and diet-by-sex interaction, respectively. For blood, 452, 1392, and 155 DEG were identified for the effects of diet, time, and diet-by-time interaction, respectively. For skeletal muscle, results based on diet identified genes involved in muscle metabolism. In muscle, from the 10 most DEG down-regulated in the energy-restricted group (REST), we identified 5 genes associated with muscle metabolism and development: SLCO3A1, ATP6V0D1, SLC2A1, GPC4, and RASD2. In blood, among the 10 most DEG, we found genes related to response to stress up-regulated in the REST after weaning, such as SOD3 and INO80D, and to immune response down-regulated in the REST after vaccination, such as OASL, KLRF1, and LOC104968634.ConclusionIn conclusion, maternal energy restriction during late gestation may limit the expression of genes in the muscle and increase expression in the blood of calves. In addition, enrichment analysis showed that a short-term maternal energy restriction during pregnancy affects the expression of genes related to energy metabolism and muscle contraction, and immunity and stress response in the blood. Therefore, alterations in the intra-uterine environment can modify prenatal development with lasting consequences to adult life.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5089-8) contains supplementary material, which is available to authorized users.
Phytochemicals play an important role in cancer therapy. Hispolon and 26 of its analogs (9 known and 17 new) were synthesized and evaluated for their antiproliferative activities in a panel of six independent human cancer cell lines using the in vitro cell-based MTT assay. Among the hispolon analogs tested, Compound VA-2, the most potent overall, produced its most significant effect in the colon cancer cell lines HCT-116 (IC50 1.4±1.3 μM) and S1 (IC50 1.8±0.9 μM) compared to its activity in the normal HEK293/pcDNA3.1 cell line (IC50 15.8±3.7 μM; p<0.01 for each comparison). Based on our results, VA-2 was about 9- to 11-times more potent in colon cancer cells and 2- to 3-times more potent in prostate cancer cells compared to HEK293/pcDNA3.1 cells. Morphological analysis of VA-2 showed significant reduction of cell number, while the cells’ sizes were also markedly increased and were obvious at 68 h of treatment with 1 μM in HCT-116 (colon) and PC-3 (prostate) cancer cells. A known analog, Compound VA-4, prepared by simple modifications on the aromatic functional groups of hispolon, inhibited prostate and colon cancer cell lines with IC50 values < 10 μM. In addition, hispolon isoxazole and pyrazole analogs, VA-7 and VA-15 (known), respectively, have shown significant activity with the mean IC50 values in the range 3.3 to 10.7 μM in all the cancer cell lines tested. Activity varied among the analogs in which aromatic functional groups and β-diketone functional groups are modified. But the activity of analogs VA-16 to VA-27 was completely lost when the side chain double-bond was hydrogenated indicating the crucial role of this functionality for anticancer activity. Furthermore, many of the compounds synthesized were not substrates for the ABCB1-transporter, the most common cause of multidrug resistance in anti-cancer drugs, suggesting they may be more effective anticancer agents.
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