Immunohistochemical analysis of the mechanistic target of rapamycin and hypoxia signalling pathways in basal cell carcinoma and trichoepithelioma

Background: Basal cell carcinoma (BCC) is the most common cancer in Caucasians. Trichoepithelioma (TE) is a benign neoplasm that strongly resembles BCC. Both are hair follicle (HF) tumours. HFs are hypoxic microenvironments, therefore we hypothesized that hypoxia-induced signalling pathways could be involved in BCC and TE as they are in other human malignancies. Hypoxia-inducible factor 1 (HIF1) and mechanistic/mammalian target of rapamycin (mTOR) are key players in these pathways. Objectives: To determine whether HIF1/mTOR signalling is involved in BCC and TE. Methods: We used immunohistochemical staining of formalin-fixed paraffin-embedded BCC (n = 45) and TE (n = 35) samples to assess activity of HIF1, mTORC1 and their most important target genes. The percentage positive tumour cells was assessed manually in a semi-quantitative manner and categorized (0%, 80%). Results: Among 45 BCC and 35 TE examined, expression levels were respectively 81% and 57% (BNIP3), 73% and 75% (CAIX), 79% and 86% (GLUT1), 50% and 19% (HIF1 alpha), 89% and 88% (pAKT), 55% and 61% (pS6), 15% and 25% (pMTOR), 44% and 63% (PHD2) and 44% and 49% (VEGF-A). CAIX, Glut1 and PHD2 expression levels were significantly higher in TE when only samples with at least 80% expression were included. Conclusions: HIF and mTORC1 signalling seems active in both BCC and TE. There are no appreciable differences between the two with respect to pathway activity. At this moment immunohistochemical analyses of HIF, mTORC1 and their target genes does not provide a reliable diagnostic tool for the discrimination of BCC and TE

An Individual-Oriented Model on the Emergence of Support in Fights, Its Reciprocation and Exchange

Complex social behaviour of primates has usually been attributed to the operation of complex cognition. Recently, models have shown that constraints imposed by the socio-spatial structuring of individuals in a group may result in an unexpectedly high number of patterns of complex social behaviour, resembling the dominance styles of egalitarian and despotic species of macaques and the differences between them. This includes affiliative patterns, such as reciprocation of grooming, grooming up the hierarchy, and reconciliation. In the present study, we show that the distribution of support in fights, which is the social behaviour that is potentially most sophisticated in terms of cognitive processes, may emerge in the same way. The model represents the spatial grouping of individuals and their social behaviour, such as their avoidance of risks during attacks, the self-reinforcing effects of winning and losing their fights, their tendency to join in fights of others that are close by (social facilitation), their tendency to groom when they are anxious, the reduction of their anxiety by grooming, and the increase of anxiety when involved in aggression. Further, we represent the difference in intensity of aggression apparent in egalitarian and despotic macaques. The model reproduces many aspects of support in fights, such as its different types, namely, conservative, bridging and revolutionary, patterns of choice of coalition partners attributed to triadic awareness, those of reciprocation of support and ‘spiteful acts’ and of exchange between support and grooming. This work is important because it suggests that behaviour that seems to result from sophisticated cognition may be a side-effect of spatial structure and dominance interactions and it shows that partial correlations fail to completely omit these effects of spatial structure. Further, the model is falsifiable, since it results in many patterns that can easily be tested in real primates by means of existing data

The release and uptake of metals from potential biofilm inhibition products during spiny lobster (Sagmariasus verreauxi, H. Milne Edwards 1851) culture

Zinc (Zn) and copper (Cu) are strong inhibitors of bacterial biofilms in aqueous solutions, but are known toxins of crustaceans. A new metal application method; cold-sprayed metal embedment, known to modulate metal release, was tested for its applications in crustacean larval culture systems. Cold-spray technology allows metal particles to bond to plastics, while modulating metal ion release and biocide activity to the substrate boundary. In this study, Eastern spiny lobster (Sagmariasus verreauxi) larvae (phyllosoma) were cultured in the presence of cold-sprayed Zn and Cu metal surfaces. Metal loss was monitored gravimetrically on embedded surfaces, assessment of water ion concentrations and analysis of phyllosoma body content were undertaken. Phyllosoma moulting, deformity and mortality patterns were monitored. Cold-sprayed Zn- and Cu-embedded surfaces were depleted with losses of 0.69% and 31.2% noted respectively. Culture water concentrations of these metals were elevated and accumulation by phyllosoma occurred. Water Zn concentrations of 18.5 μg L−1 were associated with chronic eyestalk moult deformities; the first report of Zn causing a non-lethal moult deformity in crustacean larvae. The Cu surface lost a third of its metal mass with a water concentration of 40 μg L−1 causing acute toxicity and localization of composite granules in the midgut gland. Cu associated mortality was noted by Day 2 of culture with a LD 50 experienced by Day 9. Future work on the use of bioactive metals in aquaculture systems will focus on a range of different metal alloys, and improved modulation of ion release mechanisms through increased particle embedment depth and separation