The four horses of an Iron Age apocalypse: war-horses from the third-century weapon sacrifice at Illerup Aadal (Denmark)

The Illerup Aadal weapon sacrifice mirrors the material world of a Germanic army from c. AD 210. Apart from the personal equipment and the weaponry of more than 400 warriors, it comprises four horses. The present paper gives the first conclusive analysis of the skeletal remains of these animals, involving osteological investigation and strontium isotope analysis. The results shed new light on the character of the sacrificial ceremonies which unfolded in the aftermath of Iron Age battles; on the nature of cavalry and its significance in Iron Age warfare; and on the much debated question as to where the army of Illerup Aadal had originally come from

Loss of ADAM9 expression impairs beta 1 integrin endocytosis, focal adhesion formation and cancer cell migration

The transmembrane protease ADAM9 is frequently upregulated in human cancers, and it promotes tumour progression in mice. In vitro, ADAM9 regulates cancer cell adhesion and migration by interacting with integrins. However, how ADAM9 modulates integrin functions is not known. We here show that ADAM9 knockdown increases beta 1 integrin levels through mechanisms that are independent of its protease activity, in ADAM9-silenced cells, adhesion to collagen and fibronectin is reduced, suggesting an altered function of the accumulated integrins. Mechanistically, ADAM9 co-immunoprecipitates with beta 1 integrin, and both internalization and subsequent degradation of beta 1 integrin are significantly decreased in ADAM9-silenced cells, with no effect on beta 1 integrin recycling. Accordingly, the formation of focal adhesions and actin stress fibres in ADAM9-silenced cells is altered, possibly explaining the reduction in cell adhesion and migration in these cells. Taken together, our data provide mechanistic insight into the ADAM9-integrin interaction, demonstrating that ADAM9 regulates beta 1 integrin endocytosis. Moreover, our findings indicate that the reduced migration of ADAM9-silenced cells is, at least in part, caused by the accumulation and altered activity of beta 1 integrin at the cell surface

PKCα and PKCδ Regulate ADAM17-Mediated Ectodomain Shedding of Heparin Binding-EGF through Separate Pathways

Epidermal growth factor receptor (EGFR) signalling is initiated by the release of EGFR-ligands from membrane-anchored precursors, a process termed ectodomain shedding. This proteolytic event, mainly executed by A Disintegrin And Metalloproteases (ADAMs), is regulated by a number of signal transduction pathways, most notably those involving protein kinase C (PKC). However, the molecular mechanisms of PKC-dependent ectodomain shedding of EGFR-ligands, including the involvement of specific PKC isoforms and possible functional redundancy, are poorly understood. To address this issue, we employed a cell-based system of PMA-induced PKC activation coupled with shedding of heparin binding (HB)-EGF. In agreement with previous studies, we demonstrated that PMA triggers a rapid ADAM17-mediated release of HB-EGF. However, PMA-treatment also results in a protease-independent loss of cell surface HB-EGF. We identified PKCα as the key participant in the activation of ADAM17 and suggest that it acts in parallel with a pathway linking PKCδ and ERK activity. While PKCα specifically regulated PMA-induced shedding, PKCδ and ERK influenced both constitutive and inducible shedding by apparently affecting the level of HB-EGF on the cell surface. Together, these findings indicate the existence of multiple modes of regulation controlling EGFR-ligand availability and subsequent EGFR signal transduction

Effect of local TGF-β1 and IGF-1 release on implant fixation: comparison with hydroxyapatite coating: A paired study in dogs

Background and purpose Hydroxyapatite (HA) coating stimulates the osseointegration of cementless orthopedic implants. Recently, locally released osteogenic growth factors have also been shown experimentally to stimulate osseointegration so that bone fills gaps around orthopedic implants. Here, we have compared the effect of local release of TGF-β 1 and IGF-1 with that of hydroxyapatite coating on implant fixation

Effects of Heparin and Enoxaparin on APP Processing and Aβ Production in Primary Cortical Neurons from Tg2576 Mice

Alzheimer's disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of β-amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1) and γ-secretase. Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower Aβ plaque deposition and improve cognitive function in AD transgenic mice

Korsformede benknapper fra yngre bronzealder

This article presents species identifications by ZooMS (Zooarchaeology by Mass spectrometry of a number of unburned cross-shaped buttons from Bronze age cremation graves in Denmark