Harvest time: Crop-reaping technologies and the Neolithisation of the Central Mediterranean

Neolithic societies were defined by the development of agricultural economies not only because part of their diet was obtained from cultivated plants, but also because crophusbandry practices strongly affected people’s lifestyles in a variety of ways. It is therefore unsurprising that the development and diffusion of agriculture can be studied from diverse perspectives and with different approaches, by analysing, for example, the macro- and micro-botanical remains of fruits and grains for morphometric and taxonomic variation (Colledge & Conolly 2007) and genetic history (Mascher et al. 2016). Conversely, agriculture can be indirectly assessed through its impact on the environment and subsequent landscape modifications (Zanchetta et al. 2013; Mercuri 2014). Yet another approach explores crop-husbandry practices as reflected in changing technology. New agricultural tasks required the adaptation of existing technologies and the adoption of new tools and practices, including querns, millstones and other grain-grinding equipment, as well as artefacts and structures for grain storage, cooking and processing. The most evident innovation in flaked stone technology associated with the Neolithisation phenomenon concerns the so-called ‘glossy blades’. Early experimental and use-wear studies of these blades fed debate about the mechanisms responsible for polish formation (Anderson 1982; Unger-Hamilton 1984). More recently, however, renewed attention towards these tools and their technological, functional and geographic variability (Ibáñez et al. 2008; Maeda et al. 2016) has considered their significance in relation to economic organisation, cultural boundaries and processes of technological innovation

The time is ripe for a change. The evolution of harvesting technologies in Central Dalmatia during the Neolithic period (6th millennium cal BC)

The Dalmatian coast has been occupied by Neolithic seafaring communities since the beginning of the 6th millennium BC. On the basis of pottery styles, a transition between the Impressed Ware and Danilo culture is defined, around 5300 cal BC. Nevertheless, bioarchaeological and archaeological data indicate general continuity between the two periods. In the current paper, we present an integrated technological and use-wear study of a large selection of lithics from several sites of both inland and insular Dalmatia. The results provide strong evidence for a change in harvesting techniques between the Impressed Ware and Danilo cultural phases. This change can be related to the pursuit of better performing inserts that could be used for longer periods and would be quicker to resharpen. Such a switch may have been associated with an initial increase in agricultural production during the Middle Neolithic

Role of serotonin 5-HT2A receptors in the development of cardiac hypertrophy in response to aortic constriction in mice.

International audienceSerotonin, in addition to its fundamental role as a neurotransmitter, plays a critical role in the cardiovascular system, where it is thought to be involved in the development of cardiac hypertrophy and failure. Indeed, we recently found that mice with deletion of monoamine oxidase A had enhanced levels of blood and cardiac 5-HT, which contributed to exacerbation of hypertrophy in a model of experimental pressure overload. 5-HT2A receptors are expressed in the heart and mediate a hypertrophic response to 5-HT in cardiac cells. However, their role in cardiac remodeling in vivo and the signaling pathways associated are not well understood. In the present study, we evaluated the effect of a selective 5-HT2A receptor antagonist, M100907, on the development of cardiac hypertrophy induced by transverse aortic constriction (TAC). Cardiac 5-HT2A receptor expression was transiently increased after TAC, and was recapitulated in cardiomyocytes, as observed with 5-HT2A in situ labeling by immunohistochemistry. Selective blockade of 5-HT2A receptors prevented the development of cardiac hypertrophy, as measured by echocardiography, cardiomyocyte area and heart weight-to-body weight ratio. Interestingly, activation of calmodulin kinase (CamKII), which is a core mechanism in cardiac hypertrophy, was reduced in cardiac samples from M100907-treated TAC mice compared to vehicle-treated mice. In addition, phosphorylation of histone deacetylase 4 (HDAC4), a downstream partner of CamKII was significantly diminished in M100907-treated TAC mice. Thus, our results show that selective blockade of 5-HT2A receptors has beneficial effect in the development of cardiac hypertrophy through inhibition of the CamKII/HDAC4 pathway

Ephrin-B1 Is a Novel Specific Component of the Lateral Membrane of the Cardiomyocyte and Is Essential for the Stability of Cardiac Tissue Architecture Cohesion

International audienceRATIONALE: Cardiac tissue cohesion relying on highly ordered cardiomyocytes (CM) interactions is critical because most cardiomyopathies are associated with tissue remodeling and architecture alterations. OBJECTIVE: Eph/ephrin system constitutes a ubiquitous system coordinating cellular communications which recently emerged as a major regulator in adult organs. We examined if eph/ephrin could participate in cardiac tissue cyto-organization. METHODS AND RESULTS: We reported the expression of cardiac ephrin-B1 in both endothelial cells and for the first time in CMs where ephrin-B1 localized specifically at the lateral membrane. Ephrin-B1 knock-out (KO) mice progressively developed cardiac tissue disorganization with loss of adult CM rod-shape and sarcomeric and intercalated disk structural disorganization confirmed in CM-specific ephrin-B1 KO mice. CMs lateral membrane exhibited abnormal structure by electron microscopy and notably increased stiffness by atomic force microscopy. In wild-type CMs, ephrin-B1 interacted with claudin-5/ZO-1 complex at the lateral membrane, whereas the complex disappeared in KO/CM-specific ephrin-B1 KO mice. Ephrin-B1 deficiency resulted in decreased mRNA expression of CM basement membrane components and disorganized fibrillar collagen matrix, independently of classical integrin/dystroglycan system. KO/CM-specific ephrin-B1 KO mice exhibited increased left ventricle diameter and delayed atrioventricular conduction. Under pressure overload stress, KO mice were prone to death and exhibited striking tissue disorganization. Finally, failing CMs displayed downregulated ephrin-B1/claudin-5 gene expression linearly related to the ejection fraction. CONCLUSIONS: Ephrin-B1 is necessary for cardiac tissue architecture cohesion by stabilizing the adult CM morphology through regulation of its lateral membrane. Because decreased ephrin-B1 is associated with molecular/functional cardiac defects, it could represent a new actor in the transition toward heart failure