p62/SQSTM1 expression in canine mammary tumours: Evolutionary notes

Recent studies highlighted the role of autophagy as a cardinal regulatory system for homeostasis and cancer‐related signalling pathways. In this context, the deregulated expression of p62 – Sequestosome1 (p62/SQSTM1) – a protein acting both as an autophagy receptor and signalling hub, has been associated with tumour development and chronic inflammation. Multiple clinical studies test drugs targeting autophagy, and even more research is on the way to clinical trials. However, no comparative investigations have been carried out to identify adequate preclinical models to assess p62‐based medicine. In veterinary oncology the role of p62 in cancer‐related pathways has been largely ignored. We compared p62 sequences in multiple organisms and found that canine p62 significantly diverges from the humans and from other animals sequences. Then, we chart by immunohistochemistry the expression levels of p62 in canine mammary tumours. A total of 66 tumours and 10 non‐neoplastic mammary samples were examined. The expression of p62 was higher in normal tissue and adenomas than carcinomas, with lowest levels of p62 protein detected in high grade carcinomas. In all cases examined the tumour stroma appeared to be p62‐negative. Taken together our results would suggest that in dogs the association between p62 expression and cancer cells overturns that reported in human breast carcinoma, where p62 accumulates in malignant cells as compared to normal epithelium. Thus, at least in canine mammary tumours, p62 should be not considered a tumour‐rejection antigen for an anti‐cancer immunotherapy.     

Conformational and intramolecular hydrogen bonding effects on post-emergence and pre-emergence selectivities of herbicidal pyrrole dicarboxylates

Dimethyl 2-methyl-5-(chloropyridin-2-yl)pyrrole-3,4-dicarboxylates in which the chlorine atom is substituted at different positions of the pyridine ring have widely varying biological properties. The 3-chloro analog (I) is a post-emergence and pre-emergence herbicide, the 4- and 5-chloro analogs (II, III) are post-emergence herbicides but not pre-emergence, and the 6-chloro analog (IV) is inactive. Computer graphic and molecular mechanics analyses of their molecular conformations showed that the 4- and 5-chloro analogs adopt a coplanar, intramolecularly hydrogen bonded conformation whereas the 3-chloro analog does not. High-level quantum mechanical calculations of the conformational preferences of related model systems were in agreement with these results. Based on this, II and III were predicted to have higher octanol/water partition coefficients relative to I, leading to higher soil binding and weaker xylem transport, hence their observed weaker pre-emergence activities. Experimental measurements of octanol/water partition coefficients, soil binding, and infrared hydrogen bonding studies verified these predictions. Molecular modeling techniques are usually used for designing compounds to fit enzyme active sites and designing putative receptor models. This study demonstrates the usefulness of these techniques for dealing with transport problems.     

胸膜肺炎放线杆菌的全球新动态

胸膜肺炎放线杆菌(actinobacillus pleuropneumoniae,APP)的感染在全世界范围内都有发生。尽管该病最先报道于1957年,但该病依然吸引着全球的研究机构对其进行研究。在一些主要的大型会议,如在丹麦哥本哈根的丹麦国际