Copper supply during the Final Neolithic at the Saint-Blaise/Bains des Dames site (Neuchâtel, Switzerland)

The Saint-Blaise/Bains des Dames stratified site in Neuchâtel, Switzerland, contains several occupations that span the Late through Final Neolithic, including the Horgen, Lüscherz, and Auvernier-Cordé periods. As part of a study on prehistoric metallurgy in western Switzerland, we compare the lead isotope ratios (multicollector inductively coupled plasma mass spectrometer) and elemental compositions (instrumental neutron activation analysis) of the site's numerous copper finds to a database of corresponding measurements for copper ores throughout Europe. The results show a considerable variation in copper compositions present at the site, suggesting complex economic relationships and multiple chaînes opératoires during the time in question. Specifically, during the Final Neolithic, we distinguished ten coherent clusters, confirmed by both the elemental compositions and lead isotope ratios. When compared to the Europe-wide database of copper ores, we observed significant changes in the provenance of the copper through time that reflect equally significant changes in social, cultural, and economic interactions

Anne E. Perkins, MD Correspondence

Entries include brief biographical information, a typed biographical letter, and handwritten biographical letters on personal stationery from her relatives

Bericht zur Großen Exkursion nach Polen vom 24. Juli bis 06. August 2006

Das Institut für Geographie der Justus-Liebig-Universität Gießen veranstaltet seit dem Jahre 2002 in regelmäßiger Folge Exkursionen nach Polen. Diese Exkursionen sind in die über 25 Jahre bestehende Partnerschaft der Universitäten Gießen und Lódz eingebunden. Der Bericht zur Großen Exkursion nach Polen vom 24. Juli bis 06. August 2006 dient zum einen dazu, die unterschiedlichen Exkursionsziele in ihrer ökologischen, soziokulturellen, historischen und ökonomischen Dimension zu charakterisieren. Zum anderen gibt er die persönlichen Eindrücke und Erlebnisse der Studierenden während der Exkursion wider. Dies ist umso wichtiger, wenn man bedenkt, dass es ein wesentliches Ziel dieser Fahrt war, das Nachbarland im Osten in möglichst großer Breite auch in seiner Widersprüchlichkeit kennen zu lernen. Die Fahrtroute verlief durch die ehemals deutschen Gebiete in Schlesien, in das "polnische Ruhrgebiet" rund um Kattowitz und Gleiwitz, führte nach Krakau und Kielce bis östlich der Weichsel. Von Kazimierz Dolny ging es über Lódz, wo die 35 Studierenden die Untersuchungsgebiete eines von Dr. Michael Link und Dr. Jaroslaw Sieradzki geleiteten, gemeinsamen Projektes beider Universitäten zur Erforschung der biologischen Vielfalt in einer gewachsenen Kulturlandschaft kennen lernten, und über Breslau wieder zurück nach Gießen. Das gegenseitige Verständnis der durch den geschichtlichen Verlauf zeitweise entzweiten Nachbarvölker kann nur über gegenseitiges Kennen lernen verbessert werden. Die Exkursionen sollen in Zukunft verstärkt im Rahmen eines Studierendenaustauschs stattfinden. Dem Exkursionsbericht sind verschiedene Pressestimmen beigefügt.The Institute of Geography of the University of Giessen organizes since 2002 regularly fieldtrips to Poland. These excursions are part of the over 25 year lasting partnership between the Universities of Giessen and Lódz. The report about the fieldtrip to Poland from 24th of July to 6th of August 2006 characterizes the ecological, socio cultural, historical and economical dimension of the different points of the fieldtrip. Furthermore, the report reflects the personal impressions and experiences of the students. This is very important because one of the main aims of this trip to Poland was to understand the wide spread spectrum of culture and living conditions of our neighbour country. The route of the excursion went through the former German parts of Poland in Silesia to the upper Silesian coal mining and steel factoring area (Katowice and Gliwice). From this place we went to Kraków and Kielce. Coming from a little town east of the river Wisla named Kazimierz Dolny the route followed in western direction to Lódz. In the Central Poland area the 35 students visited a bilateral scientific project on "Biodiversity of Agricultural used Landscapes" between both universities leaded by Dr. Michael Link and Dr. Jaroslaw Sieradzki. At the end of the fieldtrip the study group went to Breslau. The understanding between both neighbour countries can only be improved by a better knowledge of each other. In the future the excursions should be organized more in the frame of student exchange programs. he report includes also some newspaper articles about the fieldtrip to Poland

Modelling collective axon growth from in vivo data reveals the importance of physical axon-axon interactions

International audienceNeurite extension is essential to establish complex neuronal circuits during brain development. Neurons extend their axons in a crowded environment to reach target territories and connect to specific partners. Much work has been performed on cultured isolated neurons, focusing on the response of axon growing ends to chemical guidance cues. However, the cellular mechanisms involved in the growth of axon groups in their natural environment (the brain), are still poorly understood. Our objective is to shed light on collective axon growth and branching processes in a complex environment, considering axon-axon mechanical interactions. To do so, we propose a simple mathematical model for axonal elongation that we simulate embedded in a realistic environment

The Ig cell adhesion molecule Basigin controls compartmentalization and vesicle release at Drosophila melanogaster synapses

Synapses can undergo rapid changes in size as well as in their vesicle release function during both plasticity processes and development. This fundamental property of neuronal cells requires the coordinated rearrangement of synaptic membranes and their associated cytoskeleton, yet remarkably little is known of how this coupling is achieved. In a GFP exon-trap screen, we identified Drosophila melanogaster Basigin (Bsg) as an immunoglobulin domain-containing transmembrane protein accumulating at periactive zones of neuromuscular junctions. Bsg is required pre- and postsynaptically to restrict synaptic bouton size, its juxtamembrane cytoplasmic residues being important for that function. Bsg controls different aspects of synaptic structure, including distribution of synaptic vesicles and organization of the presynaptic cortical actin cytoskeleton. Strikingly, bsg function is also required specifically within the presynaptic terminal to inhibit nonsynchronized evoked vesicle release. We thus propose that Bsg is part of a transsynaptic complex regulating synaptic compartmentalization and strength, and coordinating plasma membrane and cortical organization

SPADE: A Small Particle Detection Method Using A Dictionary Of Shapes Within The Marked Point Process Framework

International audienc

An image based high throughput screen to identify regulators of Imp containing RNP granules

International audienceIn vivo, RNAs and proteins are frequently packaged into diverse dynamic macromolecular structures named mRNP granules. These assemblies form upon phase separation of individual RNA and protein components, a process involving the establishment of multivalent weak interactions and their regulations via post-translational modifications. Defects in their properties have been associated with several human pathologies. However, our knowledge of these dynamic structures relies essentially on the study of P bodies and stress granules. We are interested in the highly conserved RNA binding protein Imp whose mammalian counterpart's overexpression correlates with poor prognosis in several cancers. In vivo, Imp is present in cytoplasmic RNP granules, distinct from P-bodies and visible both in neuronal cell bodies and axons. They are also detected in Drosophila S2R + cultured cells. Taking advantage of this cellular model, we have undertaken a genome-wide RNAi-based visual screen to identify factors that regulate the properties of Imp-containing granules. This implies combining high throughput microscopy with the development of a computational pipeline for automatic image analysis. This pipeline first segments and discriminates healthy from dead nuclei, storing this information in an interactive SQLite database that enables experimental quality control. Then, GFP-Imp granules are detected using the SPADE algorithm in the cytoplasm of healthy cells. Data from the pilot screen we have performed to validate the experimental design and develop our pipeline for data mining are presented

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)