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External ballistics of Pleistocene hand-thrown spears: experimental performance data and implications for human evolution
The appearance of weaponry - technology designed to kill - is a critical but poorly established threshold
in human evolution. It is an important behavioural marker representing evolutionary changes in
ecology, cognition, language and social behaviours. While the earliest weapons are often considered
to be hand-held and consequently short-ranged, the subsequent appearance of distance weapons is a
crucial development. Projectiles are seen as an improvement over contact weapons, and are considered
by some to have originated only with our own species in the Middle Stone Age and Upper Palaeolithic.
Despite the importance of distance weapons in the emergence of full behavioral modernity, systematic
experimentation using trained throwers to evaluate the ballistics of thrown spears during fight and at
impact is lacking. This paper addresses this by presenting results from a trial of trained javelin athletes,
providing new estimates for key performance parameters. Overlaps in distances and impact energies
between hand-thrown spears and spearthrowers are evidenced, and skill emerges as a signifcant factor in
successful use. The results show that distance hunting was likely within the repertoire of hunting strategies
of Neanderthals, and the resulting behavioural flexibility closely mirrors that of our own specie
Saturated very long-chain fatty acids regulate macrophage plasticity and invasiveness
Saturated very long-chain fatty acids (VLCFA, ≥ C22), enriched in brain myelin and innate immune cells, accumulate in X-linked adrenoleukodystrophy (X-ALD) due to inherited dysfunction of the peroxisomal VLCFA transporter ABCD1. In its severest form, X-ALD causes cerebral myelin destruction with infiltration of pro-inflammatory skewed monocytes/macrophages. How VLCFA levels relate to macrophage activation is unclear. Here, whole transcriptome sequencing of X-ALD macrophages indicated that VLCFAs prime human macrophage membranes for inflammation and increased expression of factors involved in chemotaxis and invasion. When added externally to mimic lipid release in demyelinating X-ALD lesions, VLCFAs did not activate toll-like receptors in primary macrophages. In contrast, VLCFAs provoked pro-inflammatory responses through scavenger receptor CD36-mediated uptake, cumulating in JNK signalling and expression of matrix-degrading enzymes and chemokine release. Following pro-inflammatory LPS activation, VLCFA levels increased also in healthy macrophages. With the onset of the resolution, VLCFAs were rapidly cleared in control macrophages by increased peroxisomal VLCFA degradation through liver-X-receptor mediated upregulation of ABCD1. ABCD1 deficiency impaired VLCFA homeostasis and prolonged pro-inflammatory gene expression upon LPS treatment. Our study uncovers a pivotal role for ABCD1, a protein linked to neuroinflammation, and associated peroxisomal VLCFA degradation in regulating macrophage plasticity