Anti-IGF1R monoclonal antibody, clone 25-32

Context Selection for residual feed intake (RFI) and its impact on male reproductive development has had mixed reviews in the past. Our previous studies demonstrated earlier puberty, larger testes and greater percentage of progressively motile sperm in high-RFI bulls. However, the molecular mechanisms within testes of bulls with varying RFI remain unclear. Aims To determine the effect of RFI and pre-natal diet on the expression patterns of testicular genes and use this information to explain differences observed across RFI. Methods The study included 25 purebred-Angus bulls with a genetic background of either high or low RFI and fed either normal or low pre-natal nutrition from 30 to 150 days post conception. After slaughter (17 months), testicular tissue was recovered, and RNA was extracted and sequenced. Key results Of 19 218 expressed genes, 17 were differentially expressed for RFI (includingPLCD1,INPP4B), with no differences being observed for pre-natal diet or diet x RFI interaction (false discovery rate) < 0.1%). KEGG pathway analysis indicated that differentially expressed genes were associated with inositol phosphate metabolism, and phosphatidylinositol signalling. On the basis of a candidate gene-expression study, IGF1R was upregulated in high-RFI bulls (P< 0.1). Conclusions Increased expression of IGF1R and lowered PLCD1 and INPP4B expression could activate PI3K-Akt signalling responsible for cell growth, proliferation and steroid metabolism in high-RFI bulls. Implications Selecting bulls for feed efficiency might affect molecular networks associated with reproduction and fertility.

Aims Inflammatory myofibroblastic tumour (IMT) is a soft tissue tumour primarily affecting children and young adults. Approximately 50% of IMTs have gene fusions involving the receptor tyrosine kinase (RTK)-encoding ALK gene, providing a molecular rationale for treating IMT patients with unresectable tumours with tyrosine kinase inhibitors (TKI). However, a subset of IMT instead displays fusions affecting other RTKencoding genes, so far including NTRK3, PDGFRB and ROS1. Also, IMTs with variant RTK fusions may respond well to TKI treatment, but can be dif?cult to identify as they are negative for ALK staining at immunohistochemistry, the standard method for detection of ALK rearrangements. Materials and methods We used RNA-sequencing to search for alternate fusion events in an ALK-negative IMT. Results and conclusions We found a novel fusion gene - FN1-IGF1R. The FN1 gene, encoding ?bronectin, is thought to provide a strong promoter activity for the kinase domain of the RTK insulin-like growth factor 1 receptor, a mechanism similar to previously described RTK fusions in IMT.