Eclogite or jadeitite: The two colours involved in the transfer of alpine axeheads in western Europe

During the 5th and 4th millennia BC, the Neolithic extraction of stone around Mont Viso and in the Mont Beigua massif in the north Italian Alps resulted in the production of large polished axeheads in ecologite, omphacitite, jadeitite and amphibolite - raw materials which were not only rare but which also have remarkable mechanical and aesthetic properties. These axeheads circulated around western Europe over great distances and in particular, between the Alps, the Atlantic and the North Sea. Among these Alpine jades, research suggests a tendency for different raw materials to be represented in different geographic areas. Axeheads and other items made from dark-coloured rocks from the family of eclogites and omphacitites tend to predominate in the Paris Basin, in Germany and in Great Britain and Ireland. This paper documents the manufacture, circulation and deposition of different types of Alpine axeheads over time. More specifically, it discusses observed trends in relation to variability in the supply of raw materials and finished objects, the nature of regional traditions and long-distance transfer, and ultimately, the changing significance of axeheads as socially valorized artefacts

Human Tumour Immune Evasion via TGF-β Blocks NK Cell Activation but Not Survival Allowing Therapeutic Restoration of Anti-Tumour Activity

Immune evasion is now recognized as a key feature of cancer progression. In animal models, the activity of cytotoxic lymphocytes is suppressed in the tumour microenvironment by the immunosuppressive cytokine, Transforming Growth Factor (TGF)-β. Release from TGF-β-mediated inhibition restores anti-tumour immunity, suggesting a therapeutic strategy for human cancer. We demonstrate that human natural killer (NK) cells are inhibited in a TGF-β dependent manner following chronic contact-dependent interactions with tumour cells in vitro. In vivo, NK cell inhibition was localised to the human tumour microenvironment and primary ovarian tumours conferred TGF-β dependent inhibition upon autologous NK cells ex vivo. TGF-β antagonized the interleukin (IL)-15 induced proliferation and gene expression associated with NK cell activation, inhibiting the expression of both NK cell activation receptor molecules and components of the cytotoxic apparatus. Interleukin-15 also promotes NK cell survival and IL-15 excluded the pro-apoptotic transcription factor FOXO3 from the nucleus. However, this IL-15 mediated pathway was unaffected by TGF-β treatment, allowing NK cell survival. This suggested that NK cells in the tumour microenvironment might have their activity restored by TGF-β blockade and both anti-TGF-β antibodies and a small molecule inhibitor of TGF-β signalling restored the effector function of NK cells inhibited by autologous tumour cells. Thus, TGF-β blunts NK cell activation within the human tumour microenvironment but this evasion mechanism can be therapeutically targeted, boosting anti-tumour immunity

An improved method to study NK-independent mechanisms of MTLn3 breast cancer lung metastasis

Toxicolog

Identification of short peptide sequences in the nanofiltration permeate of a bioactive whey protein hydrolysate

Short peptides in food protein hydrolysates are of significant interest as they may be highly bioactive whilst also being bioavailable. A dipeptidyl peptidase IV (DPP-IV) inhibitory whey protein hydrolysate (WPH) was fractionated using nanofiltration (NF) with a 200 Da MWCO membrane. The DPP-IV half maximal inhibitory concentration of the NF permeate (IC50 = 0.66 ± 0.08 mg protein equivalent mL− 1) was significantly more potent (P > 0.05) than that of the starting WPH (IC50 = 0.94 ± 0.24 mg protein equivalent mL− 1) and associated retentate (IC50 = 0.82 ± 0.13 mg protein equivalent mL− 1). This confirmed the contribution of short peptides within the NF permeate to the overall DPP-IV inhibitory activity. An hydrophilic interaction liquid chromatography (HILIC-) and reverse-phase (RP-) liquid chromatography tandem mass spectrometry (LC–MS/MS) strategy, based on two retention time models, allowed detection of eight free amino acids and eight di- to tetrapeptides in the NF permeate. The potential sequences of the peptides within the NF permeate were then ranked on the basis of their highest probability of occurrence. A confirmatory study with synthetic peptides showed that valine–alanine (VA), valine–leucine (VL), tryptophan–leucine (WL) and tryptophan–isoleucine (WI) displayed DPP-IV IC50 values < 170 μM. The NF and LC–MS strategies employed herein represent a new approach for the targeted identification of short peptides within bioactive food protein hydrolysates

β-lactoglobulin as a molecular carrier of linoleate: characterisation and effects on intestinal epithelial cells in vitro

S. Le Maux is currently supported by a Teagasc Walsh Fellowship and the Department of Agriculture, Fisheries and Food (FIRM project 08/RD/TMFRC/650). We also acknowledge funding from IRCSET-Ulysses Travel Grant.peer-reviewedThe dairy protein β-lactoglobulin (βlg) is known to bind hydrophobic ligands such as fatty acids. In the present work, we investigated the biological activity in vitro of linoleate once complexed to bovine βlg. Binding of linoleate (C18:2) to bovine βlg was achieved by heating at 60 °C for 30 min at pH 7.4, resulting in a linoleate/βlg molar binding stoichiometry of 1.1, 2.1, and 3.4. Two types of binding sites were determined by ITC titrations. Binding of linoleate induced the formation of covalent dimers and trimers of βlg. The LD50 on Caco-2 cells after 24 h was 58 μM linoleate. However, cell viability was unaffected when 200 μM linoleate was presented to the Caco-2 cells as part of the βlg complex. The Caco-2 cells did not increase mRNA transcript levels of long chain fatty acid transport genes, FATP4 and FABPpm, or increase levels of the cAMP signal, in response to the presence of 50 μM linoleate alone or as part of the βlg complex. Therefore, it is proposed that βlg can act as a molecular carrier and alter the bioaccessibility of linoleate/linoleic acid