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Abstract The cultivation of grapevines has spanned millennia, leading to thousands of varieties through exchanges, mutations, and crosses between genotypes, as well probably as gene flow from wild populations. These varieties are typically categorized by regional origin and primary use, either for wine production or fruit consumption. France, within the Western European group, hosts many of the world’s renowned wine grape varieties. However, the historical development of cultivated grapevines in France and in the world remains poorly understood. This study applies morphometry on 19,377 charred and waterlogged archaeological grape pips to investigate the evolutionary history of grapevine in France over the last 10,000 years. The study compares seed outlines and lengths, corrected for taphonomic distortions, with a reference collection of 80 wild and 466 modern domestic grapevine accessions. Findings reveal a shift from wild grapevine exploitation to the expansion of domestic varieties around 600–500 BCE, coinciding with Mediterranean cultural influences and the introduction of eastern grape types. The identification of the East-Table group, a group of varieties of eastern origin for fruit consumption, indicates that grapes were also grown for food, especially in Mediterranean regions and near urban areas, alongside wine production. Early French viticulture featured a notable presence of Western European wine-type grapevines. The abundance of pips with wild-like morphology suggests early cultivation involved plants at an initial domestication stage and gene flow between introduced and wild grapevines. As viticulture spread northward, wild and Eastern morphotypes declined, leading to the dominance of Western European wine types in inner France during the Middle Ages.

The use and socio-environmental importance of fruits dramatically changed after the emergence of arboriculture and fruit domestication in the eastern Mediterranean, between the 5th and the 3rd millennia BCE. Domesticated fruits together with cultivation techniques apparently reached the western Mediterranean via colonial activities during the 1st millennium BCE – early 1st millennium CE. However, the pace and chronology of this diffusion as well as the recompositions in diversity, to adapt to new socio-environmental conditions, remain poorly known. In this study we investigate archaeobotanical records in Southern France from the Neolithic to the end of the Roman empire (ca. 5,800 BCE – 500 CE) to assess changes in fruit use as well as the emergence, spread and evolution of fruit cultivation. We explore changes in native traditions faced with innovations brought by Mediterranean colonization and how domesticated fruit cultivation spread from the Mediterranean to more temperate areas. Archaeobotanical data from 577 assemblages were systematically analyzed distinguishing two datasets according to preservation of plant remains (charred vs. uncharred), as this impacts on the quantity and diversity of taxa. The 47 fruit taxa identified were organized in broad categories according to their status and origin: exotic, allochtonous cultivated, indigenous cultivated, wild native. We also analyzed diversity, quantity of fruits compared to the total of economic plants and spatio-temporal variations in the composition of fruit assemblages using correspondence factor analyses. Archaeobotanical data reflect variations and continuities in the diversity of species used through time and space. In the Mediterranean area, significant changes related to the arrival of new plants and development of fruit cultivation occurred mainly, first during the Iron Age (6th-5th c. BCE), then in the beginning of the Roman period. Large cities played a major role in this process. In agreement with archeological information, archaeobotanical data reveal the predominance of viticulture in both periods. However, arboriculture also included other fruit species that have been subject to less intensive and specialized cultivation practices. Most significantly, this study pinpoints the continuous contribution of native, supposedly wild fruits throughout the chronology. Despite the homogenizing Roman influence, results reveal clear differences between the Mediterranean and temperate regions.

Glial cells are mechanosensitive, and thus, engineered systems have taken a step forward to design mechanotransduction platforms in order to impart diverse mechanical stresses to cells. Mechanical strain encountered in the central nervous system can arise from diverse mechanisms, such as tissue reorganization, fluid flow, and axon growth, as well as pathological events including axon swelling or mechanical trauma. Biomechanical relevance of the in vitro mechanical testing requires to be placed in line with the physiological and mechanical changes in central nervous tissues that occur during the progression of neurodegenerative diseases. Mechanotransduction signaling utilized by glial cells and the recent approaches intended to model altered microenvironment adapted to pathological context are discussed in this review. New insights in systems merging substrate's stiffness and topography should be considered for further glial mechanotransduction studies, while testing platforms for drug discoveries promise great advancements in pharmacotherapy. Potential leads and strategies for clinical outcomes are expected to be developed following the exploration of these glial mechanosensitive signaling pathways.

Farming economy was first introduced to the coastal areas of Southern France by Impressa groups (ca. 5850-5650 cal BC), originating from Italy, and subsequently spread to the hinterland by Cardial/Epicardial communities (ca. 5400-4500 cal BC). Fruit and seed remains preserved in archaeological sites provide direct evidence of the botanical resources cultivated and collected by these ancient social groups. But the transition from hunter-gathering to agricultural subsistence strategies is still poorly known in the area, due to insufficient and sometimes outdated archaeobotanical studies. Here we present new results and a critical review of all the available archaeobotanical data, in order to characterize food plant resources, cultivation practices and their variations in time and space. The archaeological dataset is composed of 19 sites (20 site/phases) mostly located in the Mediterranean lowlands. Our results demonstrate that farming economy of the Impressa groups was focused on the cultivation of hulled wheats, with only slight differences compared to their South Italian origins. The contribution of naked cereals increased in the Cardial/Epicardial agriculture, in agreement with the situation in other areas of the Western Mediterranean. The subsistence economy of hinterland sites seems to include a wider contribution of wild fruits and more limited contribution of crops. However, the poor evidence of cultivation activities in the hinterland is likely due first to the difficulties to find and excavate the sites and perform large-scale archaeobotanical sampling. It is likely that agriculture played a significant but variable role between sites and territories.

This paper presents the history of the introduction and expansion of arboriculture during the 1st millennium BC from the South of the Iberian Peninsula to the South of France. The earliest evidence of arboriculture at the beginning of the 1st millennium hails from the south of the Iberia from where it spread northward along the peninsula’s eastern edge. The different fruits (grape, olive, fig, almond, pomegranate and apple/pear) arrived together in certain areas in spite of uneven distribution and acceptance by local communities. Grape was the crop with the greatest diffusion. The greater diversity of crops in the southern half of the peninsula is also noteworthy. Their development paved the way for a commercial agricultural model in some territories where fruits and their derivatives, such as wine and oil, played vital roles.

Induction of angiogenesis is a potential treatment for chronic ischemia. Low molecular weight fucoidan (LMWF), the sulfated polysaccharide from brown seaweeds, has been shown to promote revascularization in a rat limb ischemia, increasing angiogenesis in vivo. We investigated the potential role of two heparan sulfate (HS) metabolism enzymes, exostosin-2 (EXT2) and heparanase (HPSE), and of two HS-membrane proteoglycans, syndecan-1 and -4 (SDC-1 and SDC-4), in LMWF induced angiogenesis. Our results showed that LMWF increases human vascular endothelial cell (HUVEC) migration and angiogenesis in vitro. We report that the expression and activity of the HS-degrading HPSE was increased after LMWF treatment. The phenotypic tests of LMWF-treated and EXT2- or HPSE-siRNA-transfected cells indicated that EXT2 or HPSE expression significantly affect the proangiogenic potential of LMWF. In addition, LMWF increased SDC-1, but decreased SDC-4 expressions. The effect of LMWF depends on SDC-4 expression. Silencing EXT2 or HPSE leads to an increased expression of SDC-4, providing the evidence that EXT2 and HPSE regulate the SDC-4 expression. Altogether, these data indicate that EXT2, HPSE, and SDC-4 are involved in the proangiogenic effects of LMWF, suggesting that the HS metabolism changes linked to LMWF-induced angiogenesis offer the opportunity for new therapeutic strategies of ischemic diseases.

Grapevine (Vitis vinifera), one of the most important fruit species in the Classical Mediterranean world, is thought to have been domesticated first in South-Western Asia, during the Neolithic. However, the domestication process remains largely unknown. Crucial unanswered questions concern the duration of the process (rapid or slow?) and the related geographical area (single or multiple-origins?). Seeds from domesticated grapevine and from its wild ancestor are reported to differ according to shape. Our work aims, first, to confirm this difference and secondly to identify the extent of domestication in the grapes cultivated by Romans in Southern France during the period 50 BCE-500 CE. We had the opportunity to analyze uncharred waterlogged grape pips from 17 archaeological sites. Based on an extended reference sample of modern wild grapevines and cultivars our work shows that both subspecies can be discriminated using simple measurements. The elongation gradient of the pip's body and stalk may be regarded as an indicator of the strength of the selection pressures undergone by domesticated grapes. Grapevines cultivated during the Roman period included a mix of morphotypes comprising wild, intermediate and moderately selected domesticated forms. Our data point to a relative shift towards more selected types during the Roman period. Domestication of the grapevine appears to have been a slow process. This could result from the recurrent incorporation into cultivation of plants originating from sexual reproduction, when grape cultivation essentially relies on vegetative propagation.

Herein we investigate the structure/function relationships of fucoidans from Ascophyllum nodosum to analyze their pro-angiogenic effect and cellular uptake in native and glycosaminoglycan-free (GAG-free) human endothelial cells (HUVECs). Fucoidans are marine sulfated polysaccharides, which act as glycosaminoglycans mimetics. We hypothesized that the size and sulfation rate of fucoidans influence their ability to induce pro-angiogenic processes independently of GAGs. We collected two fractions of fucoidans, Low and Medium Molecular Weight Fucoidan (LMWF and MMWF, respectively) by size exclusion chromatography and characterized their composition (sulfate, fucose and uronic acid) by colorimetric measurement and Raman and FT-IR spectroscopy. The high affinities of fractionated fucoidans to heparin binding proteins were confirmed by Surface Plasmon Resonance. We evidenced that LMWF has a higher pro-angiogenic (2D-angiogenesis on Matrigel) and pro-migratory (Boyden chamber) potential on HUVECs, compared to MMWF. Interestingly, in a GAG-free HUVECs model, LMWF kept a pro-angiogenic potential. Finally, to evaluate the association of LMWF-induced biological effects and its cellular uptake, we analyzed by confocal microscopy the GAGs involvement in the internalization of a fluorescent LMWF. The fluorescent LMWF was mainly internalized through HUVEC clathrin-dependent endocytosis in which GAGs were partially involved. In conclusion, a better characterization of the relationships between the fucoidan structure and its pro-angiogenic potential in GAG-free endothelial cells was required to identify an adapted fucoidan to enhance vascular repair in ischemia.

La réflexion sur les temporalités des liens nature-société a occasionné de riches travaux au sein des différentes disciplines des sciences humaines et sociales (SHS) dès les années 1970. En dressant une historiographie des temps de la nature dans les SHS, en insistant sur les controverses et sur les résultats conceptuels (anthroposystème, héritage, crise, résilience…) de cette historiographie, c’est une épistémologie du temps qui apparaît, scandée en trois étapes : la construction interdisciplinaire des temps de l’environnement, la crise opérationnelle des temporalités pour lesquelles le rapport au vivant constitue un creuset d’engagement, enfin l’affirmation de la contribution des sciences géohistoriques à la gouvernance de l’environnement.

Fucoidans are natural sulfated polysaccharides used as glycosaminoglycans (GAG) mimetics. Both GAGs and chemokines are important to regulate angiogenesis and wound healing. Fucoidans interacts with pro-angiogenic chemokines, such as RANTES and SDF-1, leads to revascularization and increases endothelial cell migration. However this pro-angiogenic activity remains unclear and depends of the type of fucoidan. Innovative vascular therapies based on GAG mimetic should be developed. Upstream of developing a tissue engineering therapy, we propose to understand the beneficial effect of fucoidans on angiogenesis by a structure-function study. We hypothesize that the size and sulfation level could regulate the chemokines affinity and modulate its beneficial properties. We purified and characterized 5 fractions of fucoidans according to their sulfation rate. We tested their affinity to chemokines (Surface Plasmon Resonance), the effect on endothelial cells (HUVEC) migration (Boyden chamber) and their pro-angiogenic properties (Microvascular network formation). We also analyzed the effect of fucoidans on endogen proteoglycans and GAG expression (qRT-PCR, FACS). The structural analysis of fucoidans resulted in fractions (5-27kDa) composed of fucose, sulfate and uronic acid. The most sulfated fraction (5kDa with the ratio sulfate/fucose at 1.87) presented high affinity to biotinylated-SDF-1 and RANTES. Furthermore, this 5kDa fucoidan significantly increased HUVEC migration and microvascular network formation compared to other fractions. The 5 kDa fucoidan shows the highest pro-angiogenic effects on HUVEC. Sulfate-rich 5kDa fucoidan confirmed our hypothesis than small and highly sulfated fucoidan is attractive candidate to develop therapies based on revascularization. We now focus to develop regenerative cell therapy of ischemic heart based on the injection of progenitors cells coupled with pro-angiogenic fucoidan and chemokines. [ABSTRACT FROM AUTHOR]

The authors attempt to specify the diffusion pattern of the Impressed-Ware Neolithic (Im­presso-cardial complex, ICC), from south-eastern Italy onto the French Mediterranean coasts. Using ChronoModel® software, a Bayesian model was built with sets of dates obtained on well-contextualised, short-lived samples. The results highlight a clear tightening of the chronology in the so-called nuclear area (Apulia, Basilicata, Calabria) and a pioneer dispersal at record speed in the Tyrrhe­nian Basin. Moreover, they question the origins and initial developments of the Impressed-Wares techno-complex.

The use and socio-environmental importance of fruits dramatically changed after the emergence of arboriculture and fruit domestication in the eastern Mediterranean, between the 5th and the 3rd millennia BCE. Domesticated fruits together with cultivation techniques apparently reached the western Mediterranean via colonial activities during the 1st millennium BCE - early 1st millennium CE. However, the pace and chronology of this diffusion as well as the recompositions in diversity, to adapt to new socio-environmental conditions, remain poorly known. In this study we investigate archaeobotanical records in Southern France from the Neolithic to the end of the Roman empire (ca. 5,800 BCE - 500 CE) to assess changes in fruit use as well as the emergence, spread and evolution of fruit cultivation. We explore changes in native traditions faced with innovations brought by Mediterranean colonization and how domesticated fruit cultivation spread from the Mediterranean to more temperate areas. Archaeobotanical data from 577 assemblages were systematically analyzed distinguishing two datasets according to preservation of plant remains (charred vs . uncharred), as this impacts on the quantity and diversity of taxa. The 47 fruit taxa identified were organized in broad categories according to their status and origin: exotic, allochtonous cultivated, indigenous cultivated, wild native. We also analyzed diversity, quantity of fruits compared to the total of economic plants and spatio-temporal variations in the composition of fruit assemblages using correspondence factor analyses. Archaeobotanical data reflect variations and continuities in the diversity of species used through time and space. In the Mediterranean area, significant changes related to the arrival of new plants and development of fruit cultivation occurred mainly, first during the Iron Age (6th-5th c. BCE), then in the beginning of the Roman period. Large cities played a major role in this process. In agreement with archeological information, archaeobotanical data reveal the predominance of viticulture in both periods. However, arboriculture also included other fruit species that have been subject to less intensive and specialized cultivation practices. Most significantly, this study pinpoints the continuous contribution of native, supposedly wild fruits throughout the chronology. Despite the homogenizing Roman influence, results reveal clear differences between the Mediterranean and temperate regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bouby, Bonhomme, Cabanis, Durand, Figueiral, Flottes, Marinval, Martin, Paradis, Pinaud, Ros, Rovira and Tillier.)

Farming economy was first introduced to the coastal areas of Southern France by Impressa groups (ca. 5850-5650 cal BC), originating from Italy, and subsequently spread to the hinterland by Cardial/Epicardial communities (ca. 5400-4500 cal BC). Fruit and seed remains preserved in archaeological sites provide direct evidence of the botanical resources cultivated and collected by these ancient social groups. But the transition from hunter-gathering to agricultural subsistence strategies is still poorly known in the area, due to insufficient and sometimes outdated archaeobotanical studies. Here we present new results and a critical review of all the available archaeobotanical data, in order to characterize food plant resources, cultivation practices and their variations in time and space. The archaeological dataset is composed of 19 sites (20 site/phases) mostly located in the Mediterranean lowlands. Our results demonstrate that farming economy of the Impressa groups was focused on the cultivation of hulled wheats, with only slight differences compared to their South Italian origins. The contribution of naked cereals increased in the Cardial/Epicardial agriculture, in agreement with the situation in other areas of the Western Mediterranean. The subsistence economy of hinterland sites seems to include a wider contribution of wild fruits and more limited contribution of crops. However, the poor evidence of cultivation activities in the hinterland is likely due first to the difficulties to find and excavate the sites and perform large-scale archaeobotanical sampling. It is likely that agriculture played a significant but variable role between sites and territories., Competing Interests: The authors have declared that no competing interests exist.

Grapevine (Vitis vinifera), one of the most important fruit species in the Classical Mediterranean world, is thought to have been domesticated first in South-Western Asia, during the Neolithic. However, the domestication process remains largely unknown. Crucial unanswered questions concern the duration of the process (rapid or slow?) and the related geographical area (single or multiple-origins?). Seeds from domesticated grapevine and from its wild ancestor are reported to differ according to shape. Our work aims, first, to confirm this difference and secondly to identify the extent of domestication in the grapes cultivated by Romans in Southern France during the period 50 BCE-500 CE. We had the opportunity to analyze uncharred waterlogged grape pips from 17 archaeological sites. Based on an extended reference sample of modern wild grapevines and cultivars our work shows that both subspecies can be discriminated using simple measurements. The elongation gradient of the pip's body and stalk may be regarded as an indicator of the strength of the selection pressures undergone by domesticated grapes. Grapevines cultivated during the Roman period included a mix of morphotypes comprising wild, intermediate and moderately selected domesticated forms. Our data point to a relative shift towards more selected types during the Roman period. Domestication of the grapevine appears to have been a slow process. This could result from the recurrent incorporation into cultivation of plants originating from sexual reproduction, when grape cultivation essentially relies on vegetative propagation.