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The goal of this study was to identify genetic variants, genes, or genomic regions that modulate MC disease. A genome-wide association study was performed using a single-locus mixed linear model of 1967 genotypes (624,460 SNPs) and metritis complex records. Then, in-silico functional analyses were performed to detect biological mechanisms and pathways associated with the development of MC. The ATP8A2, COX16, AMN, and TRAF3 genes, located on chromosomes 12, 10, and 21, were associated with MC at p \u2264 0.0001. These genes are involved in the regulation of cholesterol metabolism in the stromal tissue of the uterus, which can be directly associated with the mode of transmission for pathogens causing the metritis complex. The modulation of cholesterol abundance alters the efficiency of virulence factors and may affect the susceptibility of the host to infection. The SIPA1L1, DEPDC5, and RNF122 genes were also significantly associated with MC at p \u2264 0.0001 and are involved in the PI3k-Akt pathway, responsible for activating the autophagic processes. Thus, the dysregulation of these genes allows for unhindered bacterial invasion, replication, and survival within the endometrium.<\/jats:p>","DOI":"10.3390\/genes15040439","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T13:42:30Z","timestamp":1711892550000},"page":"439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Molecular Mechanisms Associated with the Development of the Metritis Complex in Dairy Cattle"],"prefix":"10.3390","volume":"15","author":[{"given":"Leanna","family":"Sanchez","sequence":"first","affiliation":[{"name":"Department of Animal Science, California Polytechnic State University, 1 Grand Ave., San Luis Obispo, CA 93407, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Campos-Chillon","sequence":"additional","affiliation":[{"name":"Department of Animal Science, California Polytechnic State University, 1 Grand Ave., San Luis Obispo, CA 93407, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Sargolzaei","sequence":"additional","affiliation":[{"name":"Select Sires Inc., 11740 US-42, Plain City, OH 43064, USA"},{"name":"Center for Genetic Improvement of Livestock, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Animal Science, California Polytechnic State University, 1 Grand Ave., San Luis Obispo, CA 93407, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim A.","family":"Sprayberry","sequence":"additional","affiliation":[{"name":"Department of Animal Science, California Polytechnic State University, 1 Grand Ave., San Luis Obispo, CA 93407, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garry","family":"McArthur","sequence":"additional","affiliation":[{"name":"Swinging Udders Veterinary Services, 8418 Liberty Rd, Galt, CA 95632, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Software Engineering, California Polytechnic State University, 1 Grand Ave., San Luis Obispo, CA 93407, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Golden","sequence":"additional","affiliation":[{"name":"Theta Solutions LLC, Olympia, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siroj","family":"Pokharel","sequence":"additional","affiliation":[{"name":"Department of Animal Science, California Polytechnic State University, 1 Grand Ave., San Luis Obispo, CA 93407, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed K.","family":"Abo-Ismail","sequence":"additional","affiliation":[{"name":"Department of Animal Science, California Polytechnic State University, 1 Grand Ave., San Luis Obispo, CA 93407, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.tvjl.2007.12.031","article-title":"Uterine Diseases in Cattle after Parturition","volume":"176","author":"Sheldon","year":"2008","journal-title":"Vet. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13937","DOI":"10.1038\/s41598-022-18347-w","article-title":"Evaluation of Antimicrobial Resistance and Risk Factors for Recovery of Intrauterine Escherichia Coli from Cows with Metritis on California Commercial Dairy Farms","volume":"12","author":"Basbas","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3158","DOI":"10.3168\/jds.2020-19125","article-title":"The Economic Cost of Metritis in Dairy Herds","volume":"104","author":"Silva","year":"2021","journal-title":"J. Dairy Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7056","DOI":"10.3168\/jds.2020-19661","article-title":"Failure of Clinical Cure in Dairy Cows Treated for Metritis Is Associated with Reduced Productive and Reproductive Performance","volume":"104","author":"Figueiredo","year":"2021","journal-title":"J. Dairy Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3621","DOI":"10.3168\/jds.2012-5922","article-title":"Metritis in Dairy Cows: Risk Factors and Reproductive Performance","volume":"96","author":"Giuliodori","year":"2013","journal-title":"J. Dairy Sci."},{"key":"ref_6","unstructured":"Overton, M., and Fetrow, J. (2008, January 7). Economics of Postpartum Uterine Health. Proceedings of the Dairy Cattle Reproduction Council Convention Annual Meet, Omaha, NE, USA."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1095\/biolreprod.109.077370","article-title":"Defining Postpartum Uterine Disease and the Mechanisms of Infection and Immunity in the Female Reproductive Tract in Cattle1","volume":"81","author":"Sheldon","year":"2009","journal-title":"Biol. Reprod."},{"key":"ref_8","first-page":"131","article-title":"The Effect of Retained Placenta and Metritis Complex on Reproductive Performance in Dairy Cattle A Case Control Study","volume":"20","author":"Sandals","year":"1979","journal-title":"Can. Vet. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1017\/S1751731114002614","article-title":"Invited Review: Overview of New Traits and Phenotyping Strategies in Dairy Cattle with a Focus on Functional Traits","volume":"9","author":"Cole","year":"2015","journal-title":"Animal"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Freebern, E., Santos, D.J.A., Fang, L., Jiang, J., Parker Gaddis, K.L., Liu, G.E., VanRaden, P.M., Maltecca, C., Cole, J.B., and Ma, L. (2020). GWAS and Fine-Mapping of Livability and Six Disease Traits in Holstein Cattle. BMC Genom., 21.","DOI":"10.1186\/s12864-020-6461-z"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/s41576-018-0016-z","article-title":"From Genome-Wide Associations to Candidate Causal Variants by Statistical Fine-Mapping","volume":"19","author":"Schaid","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nrg1521","article-title":"Genome-Wide Association Studies for Common Diseases and Complex Traits","volume":"6","author":"Hirschhorn","year":"2005","journal-title":"Nat. Rev. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"509","DOI":"10.3168\/jds.2021-20685","article-title":"Genomic Loci and Genetic Parameters for Uterine Diseases in First-Parity Holstein Cows and Associations with Milk Production and Fertility","volume":"105","author":"May","year":"2022","journal-title":"J. Dairy Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3190","DOI":"10.3168\/jds.2013-7543","article-title":"Genomic Selection for Producer-Recorded Health Event Data in US Dairy Cattle","volume":"97","author":"Cole","year":"2014","journal-title":"J. Dairy Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.3168\/jds.2018-15038","article-title":"Genetics and Genomics of Reproductive Disorders in Canadian Holstein Cattle","volume":"102","author":"Guarini","year":"2019","journal-title":"J. Dairy Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10030","DOI":"10.3168\/jds.2018-16026","article-title":"Genetic and Environmental Analysis of Diseases with Major Economic Impact in Israeli Holsteins","volume":"102","author":"Weller","year":"2019","journal-title":"J. Dairy Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1111\/age.12661","article-title":"Genomic Breeding Values, SNP Effects and Gene Identification for Disease Traits in Cow Training Sets","volume":"49","author":"Naderi","year":"2018","journal-title":"Anim. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1007\/s00439-012-1199-6","article-title":"Heritability in the Genome-Wide Association Era","volume":"131","author":"Zaitlen","year":"2012","journal-title":"Hum. Genet."},{"key":"ref_19","unstructured":"Noakes, D.E., and Parkinson, T.J. (2019). Veterinary Reproduction and Obstetrics, England GCW."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1016\/j.theriogenology.2005.08.021","article-title":"Defining Postpartum Uterine Disease in Cattle","volume":"65","author":"Sheldon","year":"2006","journal-title":"Theriogenology"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Snelling, W.M., Hoff, J.L., Li, J.H., Kuehn, L.A., Keel, B.N., Lindholm-Perry, A.K., and Pickrell, J.K. (2020). Assessment of Imputation from Low-Pass Sequencing to Predict Merit of Beef Steers. Genes, 11.","DOI":"10.3390\/genes11111312"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-Generation PLINK: Rising to the Challenge of Larger and Richer Datasets","volume":"4","author":"Chang","year":"2015","journal-title":"GigaScience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v008.i11","article-title":"Scatterplot3d\u2014An R Package for Visualizing Multivariate Data","volume":"8","author":"Ligges","year":"2003","journal-title":"J. Stat. Softw."},{"key":"ref_24","unstructured":"R Core Team (2021). 2021 R: A Language and Environment for Statistical Computing 2021, R Core Team."},{"key":"ref_25","unstructured":"Wickham, H., and Chang, W. (2023, April 18). Package \u2018Ggplot2\u2019. Create Elegant Data Visualisations Using the Grammar of Graphics. 2016, Version 2.1. pp. 1\u2013189. Available online: https:\/\/citeseerx.ist.psu.edu\/document?repid=rep1&type=pd."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ajhg.2010.11.011","article-title":"GCTA: A Tool for Genome-Wide Complex Trait Analysis","volume":"88","author":"Yang","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s00251-018-1088-9","article-title":"A Genome-Wide Association Study for Mastitis Resistance in Phenotypically Well-Characterized Holstein Dairy Cattle Using a Selective Genotyping Approach","volume":"71","author":"Kurz","year":"2019","journal-title":"Immunogenetics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10332","DOI":"10.3168\/jds.2020-18339","article-title":"Genetic and Nongenetic Profiling of Milk \u03b2-Hydroxybutyrate and Acetone and Their Associations with Ketosis in Holstein Cows","volume":"103","author":"Klein","year":"2020","journal-title":"J. Dairy Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6420","DOI":"10.3168\/jds.2015-10444","article-title":"Explorations in Genome-Wide Association Studies and Network Analyses with Dairy Cattle Fertility Traits","volume":"99","author":"Null","year":"2016","journal-title":"J. Dairy Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3389\/fgene.2018.00141","article-title":"Genome-Wide Association Study for Susceptibility to and Recoverability From Mastitis in Danish Holstein Cows","volume":"9","author":"Welderufael","year":"2018","journal-title":"Front. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Turner, S.D. (2014). qqman: An R package for visualizing GWAS results using QQ and manhattan plots. Biorxiv.","DOI":"10.1101\/005165"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Da, Y., Wang, C., Wang, S., and Hu, G. (2014). Mixed Model Methods for Genomic Prediction and Variance Component Estimation of Additive and Dominance Effects Using SNP Markers. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087666"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"D988","DOI":"10.1093\/nar\/gkab1049","article-title":"Ensembl 2022","volume":"50","author":"Cunningham","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"W169","DOI":"10.1093\/nar\/gkm415","article-title":"DAVID Bioinformatics Resources: Expanded Annotation Database and Novel Algorithms to Better Extract Biology from Large Gene Lists","volume":"35","author":"Huang","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"D871","DOI":"10.1093\/nar\/gks1150","article-title":"Animal QTLdb: An Improved Database Tool for Livestock Animal QTL\/Association Data Dissemination in the Post-Genome Era","volume":"41","author":"Hu","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11786","DOI":"10.3168\/jds.2019-17106","article-title":"Symposium Review: The Uterine Microbiome Associated with the Development of Uterine Disease in Dairy Cows","volume":"102","author":"Bicalho","year":"2019","journal-title":"J. Dairy Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1530\/REP-19-0564","article-title":"Uterine Infection Alters the Transcriptome of the Bovine Reproductive Tract Three Months Later","volume":"160","author":"Horlock","year":"2020","journal-title":"Reproduction"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e20200063","DOI":"10.1590\/1984-3143-ar2020-0063","article-title":"de Recent Advances and Future Directions for Uterine Diseases Diagnosis, Pathogenesis, and Management in Dairy Cows","volume":"17","year":"2020","journal-title":"Anim. Reprod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"87","DOI":"10.17555\/jvc.2016.04.33.2.87","article-title":"Effects of Dystocia on the Postpartum Complications, Milk Production and Reproductive Performance in Dairy Cows","volume":"33","author":"Kim","year":"2016","journal-title":"J. Vet. Clin."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.tvjl.2007.12.019","article-title":"Postpartum Uterine Disease and Dairy Herd Reproductive Performance: A Review","volume":"176","author":"LeBlanc","year":"2008","journal-title":"Vet. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.3168\/jds.2006-295","article-title":"Impacts of Dystocia on Health and Survival of Dairy Calves","volume":"90","author":"Lombard","year":"2007","journal-title":"J. Dairy Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1186\/1751-0147-49-S1-S3","article-title":"Causes of Bovine Abortion, Stillbirth and Neonatal Death in Finland 1999\u20132006","volume":"49","author":"Anttila","year":"2007","journal-title":"Acta Vet. Scand."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1590\/S0100-204X2011000600011","article-title":"Factors Associated with 56-Day Non-Return Rate in Dairy Cattle","volume":"46","author":"Fouz","year":"2011","journal-title":"Pesqui. Agropecu\u00e1ria Bras."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S0093-691X(00)00234-X","article-title":"Risk Factors for Post Partum Ovarian Dysfunction in High Producing Dairy Cows in Belgium: A Field Study","volume":"53","author":"Opsomer","year":"2000","journal-title":"Theriogenology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.3168\/jds.2015-10337","article-title":"Carryover Effect of Postpartum Inflammatory Diseases on Developmental Biology and Fertility in Lactating Dairy Cows","volume":"99","author":"Ribeiro","year":"2016","journal-title":"J. Dairy Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5764","DOI":"10.3168\/jds.2010-3429","article-title":"Risk Factors for Postpartum Uterine Diseases in Dairy Cows","volume":"93","author":"Dubuc","year":"2010","journal-title":"J. Dairy Sci."},{"key":"ref_47","first-page":"228","article-title":"Uterine Diseases in Dairy Cows: Understanding the Causes and Seeking Solutions","volume":"10","year":"2013","journal-title":"Anim. Reprod."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6836","DOI":"10.1038\/s41598-022-10435-1","article-title":"Identifying Key Genes in Milk Fat Metabolism by Weighted Gene Co-Expression Network Analysis","volume":"12","author":"Mu","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Xing, Y., Peng, K., Yi, Q., Yu, D., Shi, H., Yang, G., and Yin, S. (2023). TMEM30A Is Essential for Hair Cell Polarity Maintenance in Postnatal Mouse Cochlea. Cell. Mol. Biol. Lett., 28.","DOI":"10.1186\/s11658-023-00437-w"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1093\/biolre\/ioy099","article-title":"Isoprenoids Increase Bovine Endometrial Stromal Cell Tolerance to the Cholesterol-Dependent Cytolysin from Trueperella Pyogenes","volume":"99","author":"Griffin","year":"2018","journal-title":"Biol. Reprod."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13046-017-0490-8","article-title":"Pro-Inflammation NF-\u03baB Signaling Triggers a Positive Feedback via Enhancing Cholesterol Accumulation in Liver Cancer Cells","volume":"36","author":"He","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.mcp.2017.06.002","article-title":"MicroRNA-214 Regulates Immunity-Related Genes in Bovine Mammary Epithelial Cells by Targeting NFATc3 and TRAF3","volume":"35","author":"Song","year":"2017","journal-title":"Mol. Cell. Probes"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1080\/15384101.2016.1207840","article-title":"The Hippo Pathway, P53 and Cholesterol","volume":"15","author":"Aylon","year":"2016","journal-title":"Cell Cycle"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Prusinkiewicz, M.A., Gameiro, S.F., Ghasemi, F., Dodge, M.J., Zeng, P.Y.F., Maekebay, H., Barrett, J.W., Nichols, A.C., and Mymryk, J.S. (2020). Survival-Associated Metabolic Genes in Human Papillomavirus-Positive Head and Neck Cancers. Cancers, 12.","DOI":"10.3390\/cancers12010253"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0092-8674(00)80213-5","article-title":"The SREBP Pathway: Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor","volume":"89","author":"Brown","year":"1997","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.rvsc.2017.08.002","article-title":"Role of Lipid Mediators in the Regulation of Oxidative Stress and Inflammatory Responses in Dairy Cattle","volume":"116","author":"Mavangira","year":"2018","journal-title":"Res. Vet. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Str\u00fcve, K., Herzog, K., Magata, F., Piechotta, M., Shirasuna, K., Miyamoto, A., and Bollwein, H. (2013). The Effect of Metritis on Luteal Function in Dairy Cows. BMC Vet. Res., 9.","DOI":"10.1186\/1746-6148-9-244"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e12895","DOI":"10.1111\/acel.12895","article-title":"Reactive Oxygen Species-induced Changes in Glucose and Lipid Metabolism Contribute to the Accumulation of Cholesterol in the Liver during Aging","volume":"18","author":"Seo","year":"2019","journal-title":"Aging Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"748","DOI":"10.3390\/ani5030382","article-title":"Relationships between Circulating Urea Concentrations and Endometrial Function in Postpartum Dairy Cows","volume":"5","author":"Cheng","year":"2015","journal-title":"Animals"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s00210-006-0043-8","article-title":"The Solute Carrier Family SLC10: More than a Family of Bile Acid Transporters Regarding Function and Phylogenetic Relationships","volume":"372","author":"Geyer","year":"2006","journal-title":"Naunyn. Schmiedebergs Arch. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1002\/mrd.20174","article-title":"Immunolocalization of Cubilin, Megalin, Apolipoprotein J, and Apolipoprotein A-I in the Uterus and Oviduct","volume":"69","author":"Argraves","year":"2004","journal-title":"Mol. Reprod. Dev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"10158","DOI":"10.1073\/pnas.96.18.10158","article-title":"Cubilin, the Endocytic Receptor for Intrinsic Factor-Vitamin B 12 Complex, Mediates High-Density Lipoprotein Holoparticle Endocytosis","volume":"96","author":"Hammad","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Pleckaityte, M. (2020). Cholesterol-Dependent Cytolysins Produced by Vaginal Bacteria: Certainties and Controversies. Front. Cell. Infect. Microbiol., 9.","DOI":"10.3389\/fcimb.2019.00452"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"9410","DOI":"10.1038\/s41598-022-12681-9","article-title":"IFN-\u03c4 Mediated miR-26a Targeting PTEN to Activate PI3K\/AKT Signalling to Alleviate the Inflammatory Damage of bEECs","volume":"12","author":"Liu","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Huang, X., Tan, J., Chen, X., Liu, M., Zhu, H., Li, W., He, Z., Han, J., and Ma, C. (2021). Akt Phosphorylation Influences Persistent Chlamydial Infection and Chlamydia-Induced Golgi Fragmentation Without Involving Rab14. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.675890"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Pantazi, I., Papafragkos, I., Kolliniati, O., Lapi, I., Tsatsanis, C., and Vergadi, E. (2022). Akt Inhibition Promotes Autophagy and Clearance of Group B Streptococcus from the Alveolar Epithelium. Pathogens, 11.","DOI":"10.3390\/pathogens11101134"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/s41392-022-01152-2","article-title":"The RING Finger Protein Family in Health and Disease","volume":"7","author":"Cai","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1128\/MCB.19.1.733","article-title":"The E6 Oncoproteins of High-Risk Papillomaviruses Bind to a Novel Putative GAP Protein, E6TP1, and Target It for Degradation","volume":"19","author":"Gao","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Zou, Z., Tao, T., Li, H., and Zhu, X. (2020). mTOR Signaling Pathway and mTOR Inhibitors in Cancer: Progress and Challenges. Cell Biosci., 10.","DOI":"10.1186\/s13578-020-00396-1"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Dossou, A.S., and Basu, A. (2019). The Emerging Roles of mTORC1 in Macromanaging Autophagy. Cancers, 11.","DOI":"10.3390\/cancers11101422"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1093\/carcin\/bgm263","article-title":"Downregulation of HER2 by RIG1 Involves the PI3K\/Akt Pathway in Ovarian Cancer Cells","volume":"29","author":"Ou","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41419-022-04598-y","article-title":"SGSM2 Inhibits Thyroid Cancer Progression by Activating RAP1 and Enhancing Competitive RAS Inhibition","volume":"13","author":"Su","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Andrade, G.M., Da Silveira, J.C., Perrini, C., Del Collado, M., Gebremedhn, S., Tesfaye, D., Meirelles, F.V., and Perecin, F. (2017). The Role of the PI3K-Akt Signaling Pathway in the Developmental Competence of Bovine Oocytes. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0185045"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1161\/01.RES.0000022200.71892.9F","article-title":"Role of Akt Signaling in Vascular Homeostasis and Angiogenesis","volume":"90","author":"Shiojima","year":"2002","journal-title":"Circ. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.3168\/jds.2019-17307","article-title":"The Effect of Ex Vivo Lipopolysaccharide Stimulation and Nutrient Availability on Transition Cow Innate Immune Cell AKT\/mTOR Pathway Responsiveness","volume":"103","author":"Sipka","year":"2020","journal-title":"J. Dairy Sci."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Wang, Y., Wang, X., Wang, M., Zhang, L., Zan, L., and Yang, W. (2021). Bta-miR-34b Controls Milk Fat Biosynthesis via the Akt\/mTOR Signaling Pathway by Targeting RAI14 in Bovine Mammary Epithelial Cells. J. Anim. Sci. Biotechnol., 12.","DOI":"10.1186\/s40104-021-00598-8"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s12711-015-0124-6","article-title":"Impact of QTL Properties on the Accuracy of Multi-Breed Genomic Prediction","volume":"47","author":"Wientjes","year":"2015","journal-title":"Genet. Sel. Evol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1365-2052.2010.02148.x","article-title":"Exploration of Relationships between Production and Fertility Traits in Dairy Cattle via Association Studies of SNPs within Candidate Genes Derived by Expression Profiling: Relationships between Production and Fertility at the Genomic Level","volume":"42","author":"Pimentel","year":"2011","journal-title":"Anim. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"18275","DOI":"10.1038\/s41598-020-75104-7","article-title":"Qualitative and Quantitative Differences in Endometrial Inflammatory Gene Expression Precede the Development of Bovine Uterine Disease","volume":"10","author":"Brewer","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1146\/annurev-animal-020518-115227","article-title":"Tolerance and Innate Immunity Shape the Development of Postpartum Uterine Disease and the Impact of Endometritis in Dairy Cattle","volume":"7","author":"Sheldon","year":"2019","journal-title":"Annu. Rev. Anim. 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