CircRNA-5335 Regulates the Differentiation and Proliferation of Sheep Preadipocyte via the miR-125a-3p/STAT3 Pathway.

The content of intramuscular fat (IMF) from preadipocytes is proportional to meat quality in livestock. However, the roles of circRNAs in IMF deposition in sheep are not well known. In this study, we show that circRNA-5335/miR-125a-3p/STAT3 play a crucial adjective role in the proliferation and differentiation of sheep preadipocytes. In this study, we characterized the roles of differentially expressed circRNA-5335/miR-125a-3p/STAT3, which were screened from sheep of different months of age and based on sequencing data. Firstly, the expression profiles of circRNA-5335/miR-125a-3p/STAT3 were identified during the differentiation of preadipocytes in vitro by RT-qPCR and WB. Then, the targeting relationship of the circRNA-5335/miR-125a-3p/STAT3 was verified by dual-luciferase reporter assays. The results of RT-qPCR, CCK8, EdU and Oil Red O staining assay showed that miR-125a-3p suppressed the differentiation and raised the proliferation of preadipocytes by targeting STAT3. As a competing endogenous RNA, the downregulation of circRNA-5335 decreased the expression of STAT3 by increasing miR-125a-3p, which inhibited the differentiation of preadipocytes and promoted proliferation. Our present study demonstrates the functional significance of circRNA-5335/miR-125a-3p/STAT3 in the differentiation of sheep preadipocytes, and provides novel insights into exploring the mechanism of IMF.

Robust structured light 3D measurement method based on polarization-encoded projection patterns.

Fringe projection profilometry (FPP) is widely used in 3D vision measurement because of its high robustness and measurement accuracy. In the case of HDR objects, due to the problem of surface reflectivity, the obtained image will be overexposed. This will cause the sinusoidality of the fringes projected on the surface of the object in the acquired image to be interfered, resulting in a phase error in the calculated wrapped phase. Therefore, a polarization-encoded sinusoidal structured light is proposed to enhance the sinusoidality of the fringe. The phase information contained in the polarized sinusoidal structured light fringe is only related to the polarization state, not to the light intensity. A polarization coding assisted structured light measurement strategy (PASM) is proposed. This method uses polarization coding assisted polarization phase-shifting fringes for phase unwrapping. The angle of the linear polarizer is set to zero in this method, and it does not require rotating the polarizer. It only needs a single exposure to improve the fringe quality and obtain a more stable unwrapping phase. The experimental results show that the obtained polarization fringes have better sinusoidality, and the phase unwrapping can be more accurate. The reconstructed 3D point cloud also does not appear missing and has better accuracy. It is a reliable method for vision measurement of HDR objects.

The role of miR-369-3p in proliferation and differentiation of preadipocytes in Aohan fine-wool sheep.

MicroRNAs (miRNAs) are a large class of non-coding RNAs that play important roles in the proliferation and differentiation of adipocytes. Our previous sequencing analysis revealed higher expression of miR-369-3p in the longissimus muscle of 2-month-old Aohan fine-wool sheep (AFWS) compared to 12-month-old sheep (P<0.05), suggesting that miR-369-3p may regulate fat deposition in AFWS. To test this, miR-369-3p mimics, inhibitors, and negative controls (NCs) were constructed and transfected into AFWS preadipocytes. After transfection with miR-369-3p mimics, we found a decrease (P<0.05) in the expression of genes and proteins related to cell proliferation and differentiation, detected by RT-qPCR (quantitative reverse transcription PCR) and western blot analyses. Moreover, EdU (5-ethynyl-2'-deoxyuridine) detection and Oil Red O staining showed a decrease (P<0.05) in cell proliferation and lipid accumulation, respectively. The opposite trends (P<0.05) were obtained after transfection with miR-369-3p inhibitors. In conclusion, the results showed that miR-369-3p can inhibit the proliferation and differentiation of AFWS preadipocytes, providing a theoretical basis to further explore the molecular mechanism of fat deposition in sheep and other domestic animals.

A bioactive dextran-based hydrogel promote the healing of infected wounds via antibacterial and immunomodulatory.

Bacterial infection will attack the wound and aggravate inflammation, which is the main reason for the difficulty in wound healing. Here, we reported a dextran-based hydrogel composed of methacrylated gelatin (GelMA) and oxidized dextran (oDex), which loaded with black phosphorus (BP) nanosheets and zinc oxide nanoparticles (ZnO NPs). The hydrogel exhibited synergistic antibacterial activity of photothermal and zinc ions with an irradiation of 808 nm NIR laser. Meanwhile, trace zinc released from the hydrogel reduced polarization of macrophages towards the M2 phenotype. A larger proportion of M2 macrophages secreted anti-inflammatory factors and cytokines to reduce inflammation and facilitate neovascularization. Under the combined treatment of photothermal stimulation and immune factors, more neovascularization and shorter inflammation appeared in infected full-thickness defect wounds of mouse, which greatly accelerated wounds closure. Therefore, the combined treatment of antibacterial activity and anti-inflammatory properties of hydrogel Gel/BP/ZnO + NIR is suggested to be a hopeful approach for chronic wounds.

miR-27a Targeting PIK3R3 Regulates the Proliferation and Apoptosis of Sheep Hair Follicle Stem Cells.

Micro RNAs are regulatory factors in tissue development, organ formation, cell growth, apoptosis and other biological processes. In particular, several miRNAs are related to the development of hair follicles. Here, we investigated the effect of the targeting of PIK3R3 by miR-27a on the AKT/MTOR pathway and on the proliferation and apoptosis of hair follicle stem cells (HFSCs) in sheep. Knockdown of the expression of PIK3R3 was found to significantly inhibit the proliferation and promote the apoptosis of HFSCs. Similarly, a miR-27a mimic significantly inhibited the proliferation and promoted the apoptosis of HFSCs. The miR-27a mimic was also shown to significantly inhibit the expression of PIK3R3, AKT, and MTOR and the phosphorylation of AKT and MTOR, while a miR-27a inhibitor increased the expression of these genes. The presence of an miR-27a binding site in the 3' UTR of PIK3R3 was identified by a bioinformatics analysis, and the interaction was verified with a dual-luciferase reporter assay. The expression of PIK3R3 mRNA and protein was negatively correlated with the presence of miR-27a, which suggests that this interaction may be involved in the biological impacts on proliferation and apoptosis. Thus, this study demonstrates that miR-27a plays a potential role in the proliferation and apoptosis of sheep hair follicle stem cells by targeting PIK3R3, which can be used to design new methods to improve sheep wool.

Identification and Characterization of Circular RNAs in Association With the Deposition of Intramuscular Fat in Aohan Fine-Wool Sheep.

Aohan fine-wool sheep (AFWS) is a high-quality fine-wool sheep breed that supplies wool and meat. Research is needed on the molecular mechanism behind intramuscular fat (IMF) deposition that greatly improves mutton quality. The widely expressed non-coding RNA is physiologically used in roles such as competitive endogenous RNA (ceRNA) that includes circular RNAs (circRNAs). Although circRNAs were studied in many fields, little research was devoted to IMF in sheep. We used the longissimus dorsi muscle of 2 and 12-month-old AWFS as research material to identify circRNAs related to IMF deposition in these sheep by RNA-seq screening for differentially expressed circRNAs in the two age groups. A total of 11,565 candidate circRNAs were identified, of which the 104 differentially expressed circRNAs in the two age groups were analyzed. Enrichment analysis was performed using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. The enriched pathways included lipid transport (GO:0006869), negative regulation of canonical Wnt signaling pathway (GO:0090090), fat digestion and absorption (ko04975), and sphingolipid metabolism (ko00600). The differentially expressed circRNAs included ciRNA455, circRNA9086, circRNA7445, circRNA4557, and others. The source genes involved in these pathways might regulate IMF deposition. We used the TargetScan and miRanda software for interaction analysis, and a network diagram of circRNA-miRNA interactions was created. CircRNA455-miR-127, circRNA455-miR-29a, circRNA455-miR-103, circRNA4557-mir149-5p, and circRNA2440-mir-23a might be involved in the IMF deposition process. The targeting relationship of circRNA4557-miR-149-5p was verified by a dual-luciferase reporter assay. The RT-qPCR results of seven randomly selected circRNAs were consistent with the sequencing results. This study provides additional information on circRNA regulation of IMF deposition in AFWS and is a useful resource for future research on this sheep breed.

Identification and validation of a regulatory mutation upstream of the BMP2 gene associated with carcass length in pigs.

BACKGROUND: Carcass length is very important for body size and meat production for swine, thus understanding the genetic mechanisms that underly this trait is of great significance in genetic improvement programs for pigs. Although many quantitative trait loci (QTL) have been detected in pigs, very few have been fine-mapped to the level of the causal mutations. The aim of this study was to identify potential causal single nucleotide polymorphisms (SNPs) for carcass length by integrating a genome-wide association study (GWAS) and functional assays. RESULTS: Here, we present a GWAS in a commercial Duroc × (Landrace × Yorkshire) (DLY) population that reveals a prominent association signal (P = 4.49E-07) on pig chromosome 17 for carcass length, which was further validated in two other DLY populations. Within the detected 1 Mb region, the BMP2 gene stood out as the most likely causal candidate because of its functions in bone growth and development. Whole-genome gene expression studies showed that the BMP2 gene was differentially expressed in the cartilage tissues of pigs with extreme carcass length. Then, we genotyped an additional 267 SNPs in 500 selected DLY pigs, followed by further whole-genome SNP imputation, combined with deep genome resequencing data on multiple pig breeds. Reassociation analyses using genotyped and imputed SNP data revealed that the rs320706814 SNP, located approximately 123 kb upstream of the BMP2 gene, was the strongest candidate causal mutation, with a large association with carcass length, with a ~ 4.2 cm difference in length across all three DLY populations (N = 1501; P = 3.66E-29). This SNP segregated in all parental lines of the DLY (Duroc, Large White and Landrace) and was also associated with a significant effect on body length in 299 pure Yorkshire pigs (P = 9.2E-4), which indicates that it has a major value for commercial breeding. Functional assays showed that this SNP is likely located within an enhancer and may affect the binding affinity of transcription factors, thereby regulating BMP2 gene expression. CONCLUSIONS: Taken together, these results suggest that the rs320706814 SNP on pig chromosome 17 is a putative causal mutation for carcass length in the widely used DLY pigs and has great value in breeding for body size in pigs.

Identification of miRNA in Sheep Intramuscular Fat and the Role of miR-193a-5p in Proliferation and Differentiation of 3T3-L1.

Intramuscular fat (IMF) is one of the most critical parameters affecting meat quality and mainly affected by genetic factors. MicroRNA as an important regulatory factor, which is still a lack of research in the development of sheep IMF deposition. We used RNA sequencing (RNA-seq) and cell-level validation to explore the role of miRNA in IMF deposition. As for this purpose, longissimus thoracis et lumborum (LTL) samples of 2 month-old (Mth-2) and 12 months-old (Mth-12) Aohan fine-wool sheep (AFWS) were used to identified miRNAs expression. We found 59 differentially expressed miRNAs (DE-miRNA) between these age groups and predicted their 1,796 target genes. KEGG functional enrichment analysis revealed eight pathways involved in lipid metabolism-related processes, including fatty acid elongation and the AMPK signaling pathway. A highly expressed DE-miRNA, miR-193a-5p, was found to serve a function in 3T3-L1 preadipocyte differentiation. Luciferase assay demonstrated that miR-193a-5p directly binds to the 3'-UTR region of ACAA2. By constructing mimics and inhibitor vector transfecting into 3T3-L1 cells to explore the effect of miR-193a-5p on cell proliferation and differentiation, we demonstrated that overexpression of miR-193a-5p inhibited 3T3-L1 preadipocyte proliferation, as evidenced by decreased mRNA and protein expression of CDK4 and CyclinB. CCK-8 assay showed that miR-193a-5p significantly inhibited cell proliferation. Similarly, the overexpression of miR-193a-5p inhibited 3T3-L1 preadipocyte differentiation and adipocyte-specific molecular markers' expression, leading to a decrease in PPARγ and C/EBPα and ACAA2. Inhibition of miR-193a-5p had the opposite effects. Our study lists the miRNAs associated with intramuscular lipid deposition in sheep and their potential targets, striving to improve sheep meat quality.

Long non-coding RNA TP73-AS1 promotes pancreatic cancer growth and metastasis through miRNA-128-3p/GOLM1 axis.

BACKGROUND: Previous studies have suggested that long non-coding RNAs (lncRNA) TP73-AS1 is significantly upregulated in several cancers. However, the biological role and clinical significance of TP73-AS1 in pancreatic cancer (PC) remain unclear. AIM: To investigate the role of TP73-AS1 in the growth and metastasis of PC. METHODS: The expression of lncRNA TP73-AS1, miR-128-3p, and GOLM1 in PC tissues and cells was detected by quantitative real-time polymerase chain reaction. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of miR-128-3p. The regulatory roles of TP73-AS1 and miR-128-3p in cell proliferation, migration, and invasion abilities were verified by Cell Counting Kit-8, wound-healing, and transwell assays, as well as flow cytometry and Western blot analysis. The interactions among TP73-AS1, miR-128-3p, and GOLM1 were explored by bioinformatics prediction, luciferase assay, and Western blot. RESULTS: The expression of TP73-AS1 and miRNA-128-3p was dysregulated in PC tissues and cells. High TP73-AS1 expression was correlated with a poor prognosis. TP73-AS1 silencing inhibited PC cell proliferation, migration, and invasion in vitro as well as suppressed tumor growth in vivo. Mechanistically, TP73-AS1 was validated to promote PC progression through GOLM1 upregulation by competitively binding to miR-128-3p. CONCLUSION: Our results demonstrated that TP73-AS1 promotes PC progression by regulating the miR-128-3p/GOLM1 axis, which might provide a potential treatment strategy for patients with PC.

Whole-exome sequencing identifies genes associated with Tourette's disorder in multiplex families.

Tourette's Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein-protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.

Effects of Litter Size and Parity on Farrowing Duration of Landrace × Yorkshire Sows.

Litter size has increased and farrowing duration has also prolonged in recent years. The aim of this study was to analyze the effect of litter size and parity on farrowing duration (FAR) to estimate the possibility of selecting a short farrowing duration. We recorded 32,200 parturitions of 8420 Landrace × Yorkshire sows, determined farrowing duration, litter size, parity, gestation length. Results showed that total number of born (TNB) and parity obeyed a cubic (p = 0.0004, p = 0.004) relationship while number born alive (NBA) and number born dead (NBD) obeyed a linear (p = 0.0239, p = 0.0035) relationship with FAR. Gestation length obeyed a linear (p = 0.02) relationship with FAR. FAR of sows with stillbirth was longer than that of sows without stillbirth. Stillbirth rate increased rapidly from about 2% to 4%, especially when FAR was over 240 min. FAR gradually prolonged with the parities. FAR of 7th parity sows was longer than that of 1st~6th parity sows (p < 0.05), but different parity sows had little difference in the same FAR interval except for gilts. Results indicated it was possible and necessary to consider FAR into pig breeding without worrying about decreasing of live litter size or negative effect of parity if FAR was shorter than 300 min.

The effect of purine content on sensory quality of pork.

Although high level of purine in foods is considered a risk factor for hyperuricemia and gout, purine-rich foods continue to be popular for their delicious taste. The main objective of this study was to investigate the effects of purine bases on the sensory quality of pork. A total of 406 longissimus thoracis et lumborum samples were collected from a heterogeneous F6 pig population to determine purine composition and its correlation to sensory quality of pork. The contents of total purine and two major uricogenic bases (adenine and hypoxanthine) were negatively correlated with tenderness, juiciness, oiliness and overall liking (r < -0.2, P < 0.05), but they were not significantly correlated with umami. In contrast, guanine content, which accounts for only about 10% of the total purine content, was positively correlated with umami (r = 0.15, P < 0.05), and had no significant relationships with other sensory indicators. These results imply that purine bases with different uricogenic effects also influence different sensory quality indices of pork.

A large-scale comparison of meat quality and intramuscular fatty acid composition among three Chinese indigenous pig breeds.

Derived from the long historical natural and artificial selection, Chinese indigenous pigs have formed their own special meat characteristics. We herein systematically evaluated 14 meat characteristics and 15 fatty acid composition traits on three Chinese local pig breeds. The experimental pigs were produced by crossing design covering all sire genealogy and most of dam genealogy in each of the three breeds' seed conservation farms. All animals were reared in the same standardized housing and feeding conditions. A Comparison study showed that most of the investigated meat quality traits present significant differences among Bamaxiang, Erhualian and Laiwu breeds. While Erhualian pigs outperformed pH traits, the Laiwu pigs showed extremely high intramuscular fat content, better meat color and lower drip loss (P < .05). The highest contents of total saturated fatty acids and total polyunsaturated fatty acids were found in Laiwu and Erhualian, respectively. These results will benefit the future breeding utilization of these genetic resources for worldwide swine meat quality improvement.

Transcriptome sequencing analysis of porcine MDM response to FSL-1 stimulation.

Mycoplasma infection can cause many diseases in pigs, resulting in great economic losses in pork production. Innate immune responses are thought to play critical roles in the pathogenesis of mycoplasma disease. However, the molecular events involved in immune responses remain to be determined. Hence, the object of this study was to use RNA-Seq to investigate the gene expression profiles of the innate immune response mediated by FSL-1 in pig monocyte-derived macrophages (MDMs). The results revealed that 1442 genes were differentially expressed in the FSL-1 group compared with the control groups, of which 777 genes were upregulated and 665 genes were downregulated. KEGG pathway analysis showed that the upregulated genes were mainly involved in innate immune-related pathways including the TNF signaling pathway, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, Jak-STAT signaling pathway, chemokine signaling pathway, NOD-like receptor signaling pathway and NF-kappa B signaling pathway. The downregulated genes were only involved in the cGMP-PKG signaling pathway and glycerophospholipid metabolism. Our results showed that FSL-1 stimulation activated the TLR2 signaling pathway and resulted in diverse inflammatory responses. FSL-1 induced the transcription of numerous protein-coding genes involved in a complex network of innate immune-related pathways. We speculate that TNF, IL1B, IL6, NFKB1, NFKBIA, CXCL2, CXCL8, CXCL10, CCL2, CCL4 and CCL5 were the most likely hub genes that play important roles in the above pathways. This study identified the differentially expressed genes and their related signaling pathways, contributing to the comprehensive understanding of the mechanisms underlying host-pathogen interactions during mycoplasma infection and providing a reference model for further studies.

Sevoflurane Inhibited Osteosarcoma Cell Proliferation And Invasion Via Targeting miR-203/WNT2B/Wnt/ß-Catenin Axis.

BACKGROUND: Osteosarcoma is one of the most common primary bone cancers with predominant occurrence in children and adolescents. This study aimed to determine the effects of sevoflurane treatment on the osteosarcoma progression and to explore the underlying molecular mechanisms. MATERIALS AND METHODS: The mRNA and protein expression levels were determined by qPCR and Western blot, respectively. Osteosarcoma cell proliferation, apoptosis and invasion were determined by MTT, caspase-3 activity, colony formation and Transwell invasion assays, respectively. The interaction between miR-203 and WNT2B 3' untranslated region was confirmed by luciferase reporter assay. RESULTS: Sevoflurane treatment for 6 hrs concentration-dependently suppressed cell viability, increased caspase-3 activity and up-regulated miR-203 expression in both U2OS and MG63 cells. MiR-203 overexpression suppressed cell viability, increased caspase-3 activity and suppressed cell growth and invasion of osteosarcoma cells. In addition, miR-203 knockdown attenuated the tumor-suppressive effects of sevoflurane treatment on osteosarcoma cells. Mechanistic studies showed that miR-203 repressed the expression of WNT2B in U2OS cells, and inhibition of miR-203 attenuated the suppressive effects of sevoflurane on WNT2B expression. More importantly, WNT2B overexpression attenuated the effects of sevoflurane treatment on cell viability, caspase-3 activity, cell growth and invasion of U2OS cells. MiR-203 overexpression suppressed Wnt/ß-catenin signalling. Similarly, sevoflurane suppressed the activity of Wnt/ß-catenin signalling, which was partially reversed by miR-203 knockdown and WTN2B overexpression. CONCLUSION: Our data showed the tumor-suppressive effects of sevoflurane on osteosarcoma cells, and mechanistic studies revealed that sevoflurane inhibited osteosarcoma cell proliferation and invasion partly via targeting the miR-203/WNT2B/Wnt/ß-catenin axis.

Muscle glycogen level and occurrence of acid meat in commercial hybrid pigs are regulated by two low-frequency causal variants with large effects and multiple common variants with small effects.

BACKGROUND: Meat production from the commercial crossbred Duroc × (Landrace × Yorkshire) (DLY) pig is predominant in the pork industry, but its meat quality is often impaired by low ultimate pH (pHu). Muscle glycogen level at slaughter is closely associated with pHu and meat technological quality, but its genetic basis remains elusive. The aim of this study was to identify genes and/or causative mutations associated with muscle glycogen level and other meat quality traits by performing a genome-wide association study (GWAS) and additional analyses in a population of 610 DLY pigs. RESULTS: Our initial GWAS identified a genome-wide significant (P = 2.54e-11) quantitative trait locus (QTL) on SSC15 (SSC for Sus scrofa chromosome) for the level of residual glycogen and glucose (RG) in the longissimus muscle at 45 min post-mortem. Then, we demonstrated that a low-frequency (minor allele frequency = 0.014) R200Q missense mutation in the PRKAG3 (RN) gene caused this major QTL effect on RG. Moreover, we showed that the 200Q (RN-) allele was introgressed from the Hampshire breed into more than one of the parental breeds of the DLY pigs. After conditioning on R200Q, re-association analysis revealed three additional QTL for RG on SSC3 and 4, and on an unmapped scaffold (AEMK02000452.1). The SSC3 QTL was most likely caused by a splice mutation (g.8283C>A) in the PHKG1 gene that we had previously identified. Based on functional annotation, the genes TMCO1 on SSC4 and CKB on the scaffold represent promising candidate genes for the other two QTL. There were significant interaction effects of the GWAS tag SNPs at those two loci with PRKAG3 R200Q on RG. In addition, a number of common variants with potentially smaller effects on RG (P < 10-4) were uncovered by a second conditional GWAS after adjusting for the two causal SNPs, R200Q and g.8283C>A. CONCLUSIONS: We found that the RN- allele segregates in the parental lines of our DLY population and strongly influences its meat quality. Our findings also indicate that the genetic basis of RG in DLY can be mainly attributed to two major genes (PRKAG3 and PHKG1), along with many minor genes.

Pharmacy students' attitudes and perceptions toward pharmacogenomics education.

PURPOSE: To evaluate final-year pharmacy students' perceptions toward pharmacogenomics education, their attitudes on its clinical relevance, and their readiness to use such knowledge in practice. METHODS: A 19-question survey was developed and modified from prior studies and was pretested on a small group of pharmacogenomics faculty and pharmacy students. The final survey was administered to 978 final-year pharmacy students in 8 school/colleges of pharmacy in New York and New Jersey between January and May 2017. The survey targeted 3 main themes: perceptions toward pharmacogenomics education, attitudes toward the clinical relevance of this education, and the students' readiness to use knowledge of pharmacogenomics in practice. RESULTS: With a 35% response rate, the majority (81%) of the 339 student participants believed that pharmacogenomics was a useful clinical tool for pharmacists, yet only 40% felt that it had been a relevant part of their training. Almost half (46%) received only 1-3 lectures on pharmacogenomics and the majority were not ready to use it in practice. Survey results pointed toward practice-based trainings such as pharmacogenomics rotations as the most helpful in preparing students for practice. CONCLUSIONS: Final-year student pharmacists reported varying exposure to pharmacogenomics content in their pharmacy training and had positive attitudes toward the clinical relevance of the discipline, yet they expressed low confidence in their readiness to use this information in practice.

Whole genome sequence association with E-selectin levels reveals loss-of-function variant in African Americans.

E-selectin mediates the rolling of circulating leukocytes during inflammatory processes. Previous genome-wide association studies in European and Asian individuals have identified the ABO locus associated with E-selectin levels. Using Trans-Omics for Precision Medicine whole genome sequencing data in 2249 African Americans (AAs) from the Jackson Heart Study, we examined genome-wide associations with soluble E-selectin levels. In addition to replicating known signals at ABO, we identified a novel association of a common loss-of-function, missense variant in Fucosyltransferase 6 (FUT6; rs17855739,p.Glu274Lys, P = 9.02 × 10-24) with higher soluble E-selectin levels. This variant is considerably more common in populations of African ancestry compared to non-African ancestry populations. We replicated the association of FUT6 p.Glu274Lys with higher soluble E-selectin in an independent population of 748 AAs from the Women's Health Initiative and identified an additional pleiotropic association with vitamin B12 levels. Despite the broad role of both selectins and fucosyltransferases in various inflammatory, immune and cancer-related processes, we were unable to identify any additional disease associations of the FUT6 p.Glu274Lys variant in an electronic medical record-based phenome-wide association scan of over 9000 AAs.

A whole-genome sequence based association study on pork eating quality traits and cooking loss in a specially designed heterogeneous F6 pig population.

To determine the genetic basis of pork eating quality traits and cooking loss, we herein performed a genome-wide association study (GWAS) for tenderness, juiciness, oiliness, umami, overall liking and cooking loss by using whole genome sequences of heterogeneous stock F6 pigs which were generated by crossing 4 typical western pig breeds (Duroc, Landrace, Large White and Pietrain) and 4 typical Asian pig breeds (Erhualian, Laiwu, Bamaxiang and Tibetan). We identified 50 associated loci (QTLs) and most of them are novel. Seven loci also showed pleiotropic associations with different traits. In addition, we identified multiple promising candidate genes for these traits, including PAK1 and AQP11 for cooking loss, EP300 for tenderness, SDK1 for juiciness, FITM2 and 5-linked MYH genes for oiliness, and TNNI2 and TNNT3 for overall liking. Our results provide not only a better understanding of the genetic basis for meat quality, but also a potential application in future breeding for these complex traits.

Investigation of Eph-ephrin A1 in the regulation of embryo implantation in sows.

Eph A1 and ephrin A1 (Eph-ephrin A1) is a key receptor-ligand pair of Eph-ephrin system, which plays important roles in the migration and adhesion of cells, tissue morphogenesis and vasculogenesis in mammals. In order to investigate the regulation of Eph-ephrin A1 during porcine embryo implantation, the expressions of mRNA and protein of Eph-ephrin A1 were detected in different reproductive tissues from twelve sows during embryo implantation period on pregnancy day 13, 18 and 24, respectively. Functions of Eph-ephrin A1 on the migration and adhesion of porcine endometrial epithelial cells were analysed by RNA interference (RNAi), transwell migration assays and MTT assays. Results showed that mRNA levels of Eph-ephrin A1 were highly expressed in endometrial attachment site when compared to other reproductive tissues (p < 0.05) and were peaked on pregnancy day 18 during embryo implantation (p < 0.05). Protein levels of Eph-ephrin A1 were highly expressed in endometrial attachment site and were peaked on pregnancy day 18 (p < 0.05). Eph-ephrin A1 proteins were located in endometrial luminal epithelium, stroma of attachment site and inter-attachment site during embryo implantation, and the protein levels were higher during implantation compared to pre-implantation or post-implantation. Furthermore, silencing ephrin A1 gene significantly reduced the migration and adhesion capacity of porcine endometrial epithelial cells. These findings suggest that the Eph-ephrin A1 protein likely targets endometrial attachment site to enhance the migration and adhesion of porcine endometrial epithelial cells around pregnancy day 18 during pregnancy in sows.