Reconstructing past terrace fields in the Pyrenees: Insights into land management and settlement from the Bronze Age to the Early Modern era at Vilalta (1650 masl, Cerdagne, France)

© Trustees of Boston University 2015. The building of a solar power station at Thémis, at 1650 masl on the south-facing slope of the Carlit massif in the eastern Pyrenees, led to an archaeological evaluation from April-June 2009. This evaluation covered a surface of 10 ha that included a medieval village as well as the surrounding agricultural land in terraces. Non-destructive archaeological methods were used for the village. A detailed study of the 6 ha of terraces began with a fieldwalking survey, mapping every visible feature, followed by systematic trial trenches. Fifty-five trenches, 11 in the village and 44 in the fields, were opened. The stratigraphies were then compared with a series of 22 radiocarbon dates and eight relative dates provided by ceramic typologies. This combination of surface and buried evidence supported our preliminary hypothesis about the dynamics of the slope. The results suggest the existence of agrarian features beginning in the Bronze Age and reveal that the field patterns were frequently transformed, both in the Medieval and Early Modern periods. The transformations in the terrace fields after the village was abandoned are as interesting as those during occupation because, contrary to the idea of a fixed, unchanging landscape after the end of the Middle Ages, they challenge the idea that mountain zones are marginal spaces by nature, or were marginalized later.Peer Reviewe

Mouthiers-sur-Boëme, Chez les Rois

Chez les Rois est un gisement de référence de l'Aurignacien charentais et un des rares gisements aurignaciens européens à avoir livré des restes humains en place. Fouillé entre 1930 et 1939 par Potut et entre 1948 et 1952 par Mouton et Joffroy (1958), ce gisement a fait l'objet d'un sondage en 2005 et d'une fouille programmée entre 2006 et 2008 (d'Errico et Vanhaeren 2005, 2006, 2007, 2008). Cette opération de terrain a fait suite à la reprise de l'étude des restes humains et du matériel archéologique issus des fouilles Mouton et Joffroy ainsi qu'à sa datation (Ramirez Rozzi et al. sous presse). L'objectif des nouvelles fouilles était de préciser l'attribution culturelle des assemblages, la chronologie et nature de l'occupation aurignacienne ainsi que l'affiliation taxinomique des groupes humains qui ont fréquenté le site

Multidisciplinary approach to reconstructing local pastoral activities: an example from the Pyrenean Mountains (Pays Basque)

International audienceIn this study archaeology, history and palaeoecology (modern and fossil data sets of pollen and nonpollen palynomorphs) were used to reconstruct small-scale pastoral activities in the Pyrenees Mountains during the last two millennia. Modern pollen assemblages from the major vegetation units (both natural andanthropogenic) are studied on one restricted watershed area. A correlative model (RDA) of 61 modern pollen spectra and 35 external variables distinguishes two groups of taxa, providing information on the nature and spatial extent of human impact on the landscape. The first pool indicates local pastoral activities, and the second one implies regional input from outside the studied watershed, and is not characteristic of a specific land use. These pools are described as 'Local Pastoral Pollen Indicators' (LPPI) for this particular mountain region on crystalline bedrock and 'Regional Human Activities Pollen Indicators' (RHAPI). The modern data set is used to aid interpretation of the local pollen sequence of Sourzay that covers the last 2000 calendar years BP, using RDA reconstructions, and best modern analogues as a means of comparing modern and fossil spectra. The study also demonstrates agreement between the independent interpretations of two fossil proxies, LPPI and coprophilous fungi

Comparer et modéliser les sites, les territoires et les systèmes pastoraux pyrénéens dans la diachronie: présentation et premiers résultats du projet collaboratif DEPART

Le développement récent des recherches archéologiques sur les dynamiques des systèmes pastoraux d'altitude a engendré, tout au long du massif pyrénéen, la constitution d'une dizaine de zones ateliers interdisciplinaires, conçues comme autant de laboratoires d'étude des interactions entre les sociétés, leur espace et leur environnement, dans la longue durée. La quantité de données amassées permet aujourd'hui de dépasser le cadre des monographies, pour se lancer dans une véritable approche comparée des trajectoires de ces territoires d'altitude sous l’angle du pastoralisme. Ce projet, qui se fonde sur la modélisation et la création d'un Système d’Information Géographique (SIG), nécessite un important travail d'élaboration, technique et théorique, tant en termes de construction de la base de données spatialisée, que de formalisation des processus à étudier. Le réseau DEPART, créé dans cette perspective, s’est fixé comme premiers objectifs de construire et tester un SIG partagé sur un échantillon du corpus, et d'élaborer les outils et les questions structurant la comparaison. Après une présentation synthétique des différentes zones ateliers, cet article expose les résultats des discussions actuelles, sur les choix de structuration de la base et les questions appelées à sous-tendre l’analyse comparative.Peer reviewe

Dusty core disease (DuCD): expanding morphological spectrum of RYR1 recessive myopathies

Several morphological phenotypes have been associated to RYR1-recessive myopathies. We recharacterized the RYR1-recessive morphological spectrum by a large monocentric study performed on 54 muscle biopsies from a large cohort of 48 genetically confirmed patients, using histoenzymology, immunohistochemistry, and ultrastructural studies. We also analysed the level of RyR1 expression in patients' muscle biopsies. We defined "dusty cores" the irregular areas of myofibrillar disorganisation characterised by a reddish-purple granular material deposition with uneven oxidative stain and devoid of ATPase activity, which represent the characteristic lesion in muscle biopsy in 54% of patients. We named Dusty Core Disease (DuCD) the corresponding entity of congenital myopathy. Dusty cores had peculiar histological and ultrastructural characteristics compared to the other core diseases. DuCD muscle biopsies also showed nuclear centralization and type1 fibre predominance. Dusty cores were not observed in other core myopathies and centronuclear myopathies. The other morphological groups in our cohort of patients were: Central Core (CCD: 21%), Core-Rod (C&R:15%) and Type1 predominance "plus" (T1P+:10%). DuCD group was associated to an earlier disease onset, a more severe clinical phenotype and a lowest level of RyR1 expression in muscle, compared to the other groups. Variants located in the bridge solenoid and the pore domains were more frequent in DuCD patients. In conclusion, DuCD is the most frequent histopathological presentation of RYR1-recessive myopathies. Dusty cores represent the unifying morphological lesion among the DuCD pathology spectrum and are the morphological hallmark for the recessive form of disease

Baseline observations from the POSSIBLE EU® study: characteristics of postmenopausal women receiving bone loss medications

Summary: Prospective Observational Scientific Study Investigating Bone Loss Experience in Europe (POSSIBLE EU®) is an ongoing longitudinal cohort study that utilises physician- and patient-reported measures to describe the characteristics and management of postmenopausal women on bone loss therapies. We report the study design and baseline characteristics of 3,402 women recruited from general practice across five European countries. Purpose The POSSIBLE EU® is a study describing the characteristics and management of postmenopausal women receiving bone loss medications. Methods: Between 2005 and 2008, general practitioners enrolled postmenopausal women initiating, switching or continuing treatment with bone loss treatment in France, Germany, Italy, Spain and the UK. Patients and physicians completed questionnaires at study entry and at 3-month intervals, for 1 year. Results: Of 3,402 women enrolled (mean age 68.2 years [SD] 9.83), 96% were diagnosed with low bone mass; 55% of these using dual energy X-ray absorptiometry. Most women (92%) had comorbidities. Mean minimum T score (hip or spine) at diagnosis was −2.7 (SD 0.89; median −2.7 [interquartile range, −3.2, −2.2]) indicating low bone mineral density. Almost 40% of the women had prior fractures in adulthood, mostly non-vertebral, non-hip in nature, 30% of whom had at least two fractures and more than half experienced moderate/severe pain or fatigue. Bisphosphonates were the most common type of bone loss treatment prescribed in the 12 months preceding the study. Conclusions POSSIBLE EU® characterises postmenopausal women with low bone mass, exhibiting a high rate of prevalent fracture, substantial bone fragility and overall comorbidity burden. Clinical strategies for managing osteoporosis in this population varied across the five participating European countries, reflecting their different guidelines, regulations and standards of care

Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores

The myosin-directed chaperone UNC-45B is essential for sarcomeric organization and muscle function from Caenorhabditis elegans to humans. The pathological impact of UNC-45B in muscle disease remained elusive. We report ten individuals with bi-allelic variants in UNC45B who exhibit childhood-onset progressive muscle weakness. We identified a common UNC45B variant that acts as a complex hypomorph splice variant. Purified UNC-45B mutants showed changes in folding and solubility. In situ localization studies further demonstrated reduced expression of mutant UNC-45B in muscle combined with abnormal localization away from the A-band towards the Z-disk of the sarcomere. The physiological relevance of these observations was investigated in C. elegans by transgenic expression of conserved UNC-45 missense variants, which showed impaired myosin binding for one and defective muscle function for three. Together, our results demonstrate that UNC-45B impairment manifests as a chaperonopathy with progressive muscle pathology, which discovers the previously unknown conserved role of UNC-45B in myofibrillar organization

In Silico Screening Based on Predictive Algorithms as a Design Tool for Exon Skipping Oligonucleotides in Duchenne Muscular Dystrophy

The use of antisense 'splice-switching' oligonucleotides to induce exon skipping represents a potential therapeutic approach to various human genetic diseases. It has achieved greatest maturity in exon skipping of the dystrophin transcript in Duchenne muscular dystrophy (DMD), for which several clinical trials are completed or ongoing, and a large body of data exists describing tested oligonucleotides and their efficacy. The rational design of an exon skipping oligonucleotide involves the choice of an antisense sequence, usually between 15 and 32 nucleotides, targeting the exon that is to be skipped. Although parameters describing the target site can be computationally estimated and several have been identified to correlate with efficacy, methods to predict efficacy are limited. Here, an in silico pre-screening approach is proposed, based on predictive statistical modelling. Previous DMD data were compiled together and, for each oligonucleotide, some 60 descriptors were considered. Statistical modelling approaches were applied to derive algorithms that predict exon skipping for a given target site. We confirmed (1) the binding energetics of the oligonucleotide to the RNA, and (2) the distance in bases of the target site from the splice acceptor site, as the two most predictive parameters, and we included these and several other parameters (while discounting many) into an in silico screening process, based on their capacity to predict high or low efficacy in either phosphorodiamidate morpholino oligomers (89% correctly predicted) and/or 2'O Methyl RNA oligonucleotides (76% correctly predicted). Predictions correlated strongly with in vitro testing for sixteen de novo PMO sequences targeting various positions on DMD exons 44 (R² 0.89) and 53 (R² 0.89), one of which represents a potential novel candidate for clinical trials. We provide these algorithms together with a computational tool that facilitates screening to predict exon skipping efficacy at each position of a target exon