Challenges and opportunities in polysaccharides research and technology: The EPNOE views for the next decade in the areas of materials, food and health care

International audienceThe European Polysaccharide Network of Excellence (EPNOE) is a research and education network connecting 16 academic and research institutions and a large number of companies with its focus on polysaccharide expertise development and polysaccharide-related research for innovation in business and industry. EPNOE has two main missions in the field of polysaccharide applications in materials, food, and pharmacy/medicine, which are to organise education in polysaccharide science and to perform basic and applied research for the development of new products derived from polysaccharides. In 2009, the EPNOE network prepared a research road map vision to 2020 focussed on polysaccharide use in material structuring, food and health, taking both research and education into consideration. The research road map was prepared from various social, political, industrial and scientific inputs coming from within and outside EPNOE: (1) results of four brain-storming sessions by EPNOE scientists and students, (2) individual contributions of EPNOE scientists and (3) individual contributions of scientists outside EPNOE through an internet review. The result is described in this article

Síntesis de la cronoestratigrafía y evolución sedimentaria de los sistemas lacustres evaporíticos y carbonatados neógenos de la Cuenca de Calatayud-Montalbán.

La Cuenca terciaria de Calatayud-Montalbán consta de dos subcuencas diferentes separadas por el umbral de Daroca (Cuenca de Calatayud en el sector septentrional y Cuenca de Montalbán en el sector meridional). Estas cuencas presentan una evolución sedimentaria muy similar de los sistemas lacustres neógenos evaporíticos y carbonáticos, que generalmente ocupan los sectores centrales de ambas depresiones. En la Cuenca de Calatayud, se reconocen tradicionalmente en el Neógeno tres unidades sedimentarias mayores denominadas Unidad Inferior, Intermedia y Superior separadas por dos rupturas sedimentarias principales. Las dos primeras tienen carácter evaporítico, mientras que la última tiene un carácter fluviolacustre. En los sectores centrales de la Cuenca de Montalbán, el sondeo Barrachina-l y las secciones estratigráficas complementarias han permitido apreciar una evolución sedimentaria muy similar para las unidades neógenas, con facies evaporíticas y carbonáticas muy parecidas, aunque con una cronoestratigrafía diferente y la ausencia del registro sedimentario del Mioceno medio a Plioceno. En este trabajo también se describe por vez primera la presencia de un nivel volcanoclástico intercalado entre las facies evaporíticas del Mioceno inferior de la Cuenca de Montalbán. Las asociaciones minerales identificadas en los depósitos lacustres del Mioceno inferiormedio de ambos sectores de la cuenca, muestran una secuencia que evoluciona desde facies lacustres evaporíticas de alto grado de hipersalinidad, hacia facies lacustres evaporíticas de baja-moderada salinidad. Solamente, el registro sedimentario de la Cuenca de Calatayud permite asegurar que esta evolución sedimentaria se completa con la presencia de facies carbonáticas fluviolacustres características de aguas dulces en el Mioceno superior. Esta secuencia de precipitación salina responde a un cambio progresivo en la hidroquímica de los sistemas lacustres relacionado con un cambio gradual de las condiciones climáticas que comenzaría en el Rambliense y se extendería, al menos, durante todo el Mioceno medio. Las diferencias cronoestratigráficas entre los dos sectores de la misma depresión deben estar relacionados con los diferentes condicionantes tectónicos y/o geomorfológicos a los que se han visto sometidas ambas cuencas durante el Mioceno. [ABSTRACT] The Tertiary Calatayud-Montalbán Basin consists of two distinct sub-basins separated by the Daroca High (Calatayud Basin in the northern sector and Montalbán Basin in the southern sector). These basins present a quite similar sedimentary evolution of the Neogene evaporitic and carbonatic lacustrine systems, that generally occupy central locations in both basins. Three main sedimentary units (Lower, Intermediate and Upper units) divided by two main sedimentary breaks are traditionally described in the Calatayud Basin. The Lower and Intermediate units have evaporitic sedimentation, whilst the Upper Unit is tipically freshwater fluviolacustrine sedimentation. In the central areas of the Montalbán basin, the Barrachina-l drill hole and complementary stratigraphic sections showed a very similar sedimentary evolution of the Neogene units, with similar evaporitic and carbonatic facies, but different chronostratigraphy. The Upper MiocenePliocene sedimentary record of the Montalbán Basin is absent. In addition, this work presents the first occurrence of a volcanoclastic layer interbedded in the Lower Miocene evaporitic facies of the Montalbán Basin. The identified mineral assemblages of the lacustrine deposits of both sectors of the basin, show an evolutionary sequence during the Lower-Middle Miocene from hypersaline to lower moderated salinity lacustrine facies. This evolutionary trend is only complete in the sedimentary record of the Calatayud Basin, where freshwater carbonatic fluviolacustrine facies are described in the Upper Miocene. This precipitation sequence is the result of a progressive hydrochemical change of the lacustrine systems related to a climatic change from the Ramblian to the Middle Miocene. Differences in the chronostratigraphy of both basins should be related to distinct tectonic scenarios and/or geomorphologic features during the Miocene

Chronic Delivery of Antibody Fragments Using Immunoisolated Cell Implants as a Passive Vaccination Tool

BACKGROUND: Monoclonal antibodies and antibody fragments are powerful biotherapeutics for various debilitating diseases. However, high production costs, functional limitations such as inadequate pharmacokinetics and tissue accessibility are the current principal disadvantages for broadening their use in clinic. METHODOLOGY AND PRINCIPAL FINDINGS: We report a novel method for the long-term delivery of antibody fragments. We designed an allogenous immunoisolated implant consisting of polymer encapsulated myoblasts engineered to chronically release scFv antibodies targeted against the N-terminus of the Aβ peptide. Following a 6-month intracerebral therapy we observed a significant reduction of the production and aggregation of the Aβ peptide in the APP23 transgenic mouse model of Alzheimer's disease. In addition, functional assessment showed prevention of behavioral deficits related to anxiety and memory traits. CONCLUSIONS AND SIGNIFICANCE: The chronic local release of antibodies using immunoisolated polymer cell implants represents an alternative passive vaccination strategy in Alzheimer's disease. This novel technique could potentially benefit other diseases presently treated by local and systemic antibody administration

Microarray-Based Oncogenic Pathway Profiling in Advanced Serous Papillary Ovarian Carcinoma

Introduction: The identification of specific targets for treatment of ovarian cancer patients remains a challenge. The objective of this study is the analysis of oncogenic pathways in ovarian cancer and their relation with clinical outcome. Methodology: A meta-analysis of 6 gene expression datasets was done for oncogenic pathway activation scores: AKT, β-Catenin, BRCA, E2F1, EGFR, ER, HER2, INFα, INFγ, MYC, p53, p63, PI3K, PR, RAS, SRC, STAT3, TNFα, and TGFβ and VEGF-A. Advanced serous papillary tumours from uniformly treated patients were selected (N = 464) to find differences independent from stage-, histology- and treatment biases. Survival and correlations with documented prognostic signatures (wound healing response signature WHR/genomic grade index GGI/invasiveness gene signature IGS) were analysed. Results: The GGI, WHR, IGS score were unexpectedly increased in chemosensitive versus chemoresistant patients. PR and RAS activation scor

Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation

OBJECTIVES: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with Vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet) METHODS: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. RESULTS: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (aHR 2.74, 95% confidence interval 1.76 - 4.26) and ischemic stroke (aHR 1.29, 95% confidence interval 1.04 - 1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleeds burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2-4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥11 microbleeds (94 vs 48 per 1,000 patient-years). INTERPRETATION: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. This article is protected by copyright. All rights reserved

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data