The beginning of high mountain occupations in the Pyrenees. Human settlements and mobility from 10,500 cal BP to 4500 cal BP

During the last two decades, the archaeological research carried out in the Pyrenees challenged the traditional images of the past in this mountain area. The archaeological sequence of the range goes back and sites like Balma Margineda, treated until recently as an exception, now are seen as part of more global process. Actual data suggest that main valleys of the Pyrenean frequented by humans at the end of the last glacial period, with sites slightly over 1000 o.s.l. After the Younger Dryas, the human presence ascended to alpine and subalpine areas, in accordance with current archaeological data. The Neolisitation process was early in some hillsides, with intense remains of farming and pastoralism in many sites from dated in the second half of the 6th millennia cal BC. Human settlements like Coro Tracito, Els Trocs and El Sardo confirm the full introduction of agrarian activity in the central part of the Pyrenees between 5300 and 4600 cal BC. After 3500/3300 cal BC the indices oh sheepherding rises to alpine areas, with an abrupt increase of known archaeological sites in alpine areas, above the current timberline. This phenomena, as well as the signs of anthropic disturbance of the alpine environment in sedimentary sequences, suggests a more stable and ubiquitous human presence, probably largely associated with the development of mobile herding practices

Circulación e intercambio en el poblamiento y la explotación de la alta montaña del Pirineo en los milenios V-IV ANE

Los datos arqueológicos que presentamos indican que las áreas de alta montaña del Pirineo axial fueron objeto de un proceso de ocupación y explotación económica continuada a lo largo del Neolítico. La reiterada ocupación de la Cueva del Sardo de Boí, situada a 1790 m de altitud, en el Parque Nacional de Aigüestortes i Estany de Sant Maurici, desde inicios del V hasta mediados del III milenio ANE, nos permite apoyar esta hipótesis. El estudio de los materiales líticos amortizados en el yacimiento parece indicar la existencia de patrones de movilidad regional de los grupos neolíticos pirenaicos, así como el contacto con otros grupos al exterior de la cordillera

Single-Cell Analysis of Blood-Brain Barrier Response to Pericyte Loss

Rationale: Pericytes are capillary mural cells playing a role in stabilizing newly formed blood vessels during development and tissue repair. Loss of pericytes has been described in several brain disorders, and genetically induced pericyte deficiency in the brain leads to increased macromolecular leakage across the blood-brain barrier (BBB). However, the molecular details of the endothelial response to pericyte deficiency remain elusive. Objective: To map the transcriptional changes in brain endothelial cells resulting from lack of pericyte contact at single-cell level, and to correlate them with regional heterogeneities in BBB function and vascular phenotype. Methods and Results: We reveal transcriptional, morphological and functional consequences of pericyte absence for brain endothelial cells using a combination of methodologies, including single-cell RNA sequencing, tracer analyses and immunofluorescent detection of protein expression in pericyte-deficient adult Pdgfbret/ret mice. We find that endothelial cells without pericyte contact retain a general BBB-specific gene expression profile, however, they acquire a venous-shifted molecular pattern and become transformed regarding the expression of numerous growth factors and regulatory proteins. Adult Pdgfbret/ret brains display ongoing angiogenic sprouting without concomitant cell proliferation providing unique insights into the endothelial tip cell transcriptome. We also reveal heterogeneous modes of pericyte-deficient BBB impairment, where hotspot leakage sites display arteriolar-shifted identity and pinpoint putative BBB regulators. By testing the causal involvement of some of these using reverse genetics, we uncover a reinforcing role for angiopoietin 2 at the BBB. Conclusions: By elucidating the complexity of endothelial response to pericyte deficiency at cellular resolution, our study provides insight into the importance of brain pericytes for endothelial arterio-venous zonation, angiogenic quiescence and a limited set of BBB functions. The BBB-reinforcing role of ANGPT2 is paradoxical given its wider role as TIE2 receptor antagonist and may suggest a unique and context-dependent function of ANGPT2 in the brain

Interacción entre clima y ocupación humana en la configuración del paisaje vegetal del Parque Nacional de Aigüestortes i Estany de Sant Maurici a lo largo de los últimos 15.000 años

The vegetation of the National Park of Aigüestortes i Estany de St Maurici is the result of an interaction between climate, plant community dynamics and the human occupation of the territory. The OCUPAproject aimed to reconstruct this interaction across the last millennia combining methods from palaeoecology and archaeology. The study focused primarily on the Sant Nicolau valley and built on the multidisciplinary analysis of the sedimentary archive of two lakes (Llebreta and Redó) and a number of archaeological sites located in shelters and outdoors. There is archaeological evidence of human presencesince 9000 yr cal BP, and a continuous record since 7500 yr cal BP. At early stages, humans transformed the surroundings of the shelters occupied and lithic tools indicate contacts with locations far away (i.e.,the Ebro plains). Since more than 3000 years ago, there has been human impact on the vegetation withoutinterruption until present. Initially, the impacts were mostly related to livestock: use of fire to open grazing lands, soil erosion and, during the medieval period, forestry and eutrophication of lakes. The agriculture impact in the lower part of the valley (e.g., Llebreta) occurred about 2100 yr ago, although some cereal grains and tools for harvesting have been found for the Neolithic. In the medieval period, the impact was higher than during the last centuries. In general, the changes in the human land use approximately follow the major changes in climate, but the specific causal link is likely related to the social and cultural dynamics of a broader territory since the Neolithic

MS-based lipidomics of human blood plasma: a community-initiated position paper to develop accepted guidelines

Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent

A mutation of EPT1 (SELENOI) underlies a new disorder of Kennedy pathway phospholipid biosynthesis.

Mutations in genes involved in lipid metabolism have increasingly been associated with various subtypes of hereditary spastic paraplegia, a highly heterogeneous group of neurodegenerative motor neuron disorders characterized by spastic paraparesis. Here, we report an unusual autosomal recessive neurodegenerative condition, best classified as a complicated form of hereditary spastic paraplegia, associated with mutation in the ethanolaminephosphotransferase 1 (EPT1) gene (now known as SELENOI), responsible for the final step in Kennedy pathway forming phosphatidylethanolamine from CDP-ethanolamine. Phosphatidylethanolamine is a glycerophospholipid that, together with phosphatidylcholine, constitutes more than half of the total phospholipids in eukaryotic cell membranes. We determined that the mutation defined dramatically reduces the enzymatic activity of EPT1, thereby hindering the final step in phosphatidylethanolamine synthesis. Additionally, due to central nervous system inaccessibility we undertook quantification of phosphatidylethanolamine levels and species in patient and control blood samples as an indication of liver phosphatidylethanolamine biosynthesis. Although this revealed alteration to levels of specific phosphatidylethanolamine fatty acyl species in patients, overall phosphatidylethanolamine levels were broadly unaffected indicating that in blood EPT1 inactivity may be compensated for, in part, via alternate biochemical pathways. These studies define the first human disorder arising due to defective CDP-ethanolamine biosynthesis and provide new insight into the role of Kennedy pathway components in human neurological function

Deciphering lipid structures based on platform-independent decision rule sets

We developed decision rule sets for Lipid Data Analyzer (LDA; http://genome.tugraz.at/lda2), enabling automated and reliable annotation of lipid species and their molecular structures in high-throughput data from chromatography-coupled tandem mass spectrometry. Platform independence was proven in various mass spectrometric experiments, comprising low- and high-resolution instruments and several collision energies. We propose that this independence and the capability to identify novel lipid molecular species render current state-of-the-art lipid libraries now obsolete

The Human Occupation of the Mountain Environment: the contribution of microwear analysis to the study of the Cova del Sardo site (Spanish Pyrenees)

In this report we assess the results of the microwear study of the Cova del Sardo (Catalan Pyrenees). The site is located at an altitude of 1780 m.a.s.l and presents a sequence of prehistoric occupations with radiocarbon dates from the VI millennium to III millennium cal BC. Our data indicate that lithic resources were used for both subsistence and crafting activities. Pastoralism was not the only economic activity practiced by local populations

The Beginning of High Mountain Occupations in the Pyrenees. Human Settlements and Mobility from 18,000 cal BC to 2000 cal BC

During the last two decades, the archaeological research carried out in the Pyrenees challenged the traditional images of the past in this mountain area. The archaeological sequence of the range goes back and sites like Balma Margineda, treated until recently as an exception, now are seen as part of more global process. Actual data suggest that main valleys of the Pyrenean frequented by humans at the end of the last glacial period, with sites slightly over 1000 o.s.l. After the Younger Dryas, the human presence ascended to alpine and subalpine areas, in accordance with current archaeological data. The Neolisitation process was early in some hillsides, with intense remains of farming and pastoralism in many sites from dated in the second half of the 6th millennia cal BC. Human settlements like Coro Tracito, Els Trocs and El Sardo confirm the full introduction of agrarian activity in the central part of the Pyrenees between 5300 and 4600 cal BC. After 3500/3300 cal BC the indices oh sheepherding rises to alpine areas, with an abrupt increase of known archaeological sites in alpine areas, above the current timberline. This phenomena, as well as the signs of anthropic disturbance of the alpine environment in sedimentary sequences, suggests a more stable and ubiquitous human presence, probably largely associated with the development of mobile herding practices.This paper has been carried out in the frame of the GAAM/AGREST research activity. More specifically, this study is part of the projects “Análisi ecológico de la culturización del paisaje de alta montaña desde el Neolítico: los Parques Nacionales de montaña como modelo (CUL-PA)” funded by the Ministry of Agriculture, Food and Environment (Spain) and directed by J. Catalán and “Modelización de los espacios prehistóricos de montaña. Un SIG del patrimonio arqueológico y los territorios pastoriles” (HAR2015-66780-P, MINECO/FEDER) funded by the Ministry of Economy and Competitiveness (Spain) and directed by E. Gassiot.Peer reviewe