A European competence framework for industrial pharmacy practice in biotechnology

Project Report: The PHAR-IN ("Competences for industrial pharmacy practice in biotechnology") looked at whether there is a difference in how industrial employees and academics rank competences for practice in the biotechnological industry. A small expert panel consisting of the authors of this paper produced a biotechnology competence framework by drawing up an initial list of competences then ranking them in importance using a three-stage Delphi process. The framework was next evaluated and validated by a large expert panel of academics (n = 37) and industrial employees (n = 154). Results show that priorities for industrial employees and academics were similar. The competences for biotechnology practice that received the highest scores were mainly in: . "Research and Development", . "Upstream" and "Downstream" Processing', " . "Product development and formulation", " . "Aseptic processing", ."Analytical methodology", . "Product stability", and . "Regulation". The main area of disagreement was in the category "Ethics and drug safety" where academics ranked competences higher than did industrial employees.

Immunoregulatory soluble CTLA-4 modifies effector T cell responses in systemic lupus erythematosus

Acknowledgments This work was supported by Arthritis Research UK (Grant no. 19282). We are grateful to Dr. Nick Fluck for his invaluable support in recruiting patients for the study, and Mrs. Vivien Vaughan for her invaluable expertise in recruiting study participants and maintaining ethical documentation.

The management of bone tools from the Bronze Age site of El Portalón of Cueva Mayor, Sierra de Atapuerca, Burgos

In this paper we analyze the set of Bronze Age bone tools recovered at the archaeological site of El Portalón of Cueva Mayor in the Sierra de Atapuerca (Burgos). The Bronze Age cultural period is the best represented in the cavity and its study has forced us to unify the different excavation and stratigraphical criteria undertaken from the earliest archaeological excavations developed by J.M. Apellániz during the 70s until the excavations of the current research team (EIA) since 2000. We propose here for the first time a relationship between the initial system of “beds” used by Apellániz and our recent sedimentary sequence that recognizes eleven stratigraphic levels radiometrically dated from the late Upper Pleistocene to the Middle Age. Within the bone industry assemblage we recognize a large variety of utensils and ornamental elements, with native and allochthonous features, that make evident a regional as well as long distance relationships of these populations of the interior of the Iberian Peninsula during the recent Prehistory.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes

Lipoprotein-associated phospholipase A2 (Lp-PLA2) hydrolyses oxidized low-density lipoproteins into proinflammatory products, which can have detrimental effects on vascular function. As a specific inhibitor of Lp-PLA2, darapladib has been shown to be protective against atherogenesis and vascular leakage in diabetic and hypercholesterolemic animal models. This study has investigated whether Lp-PLA2 and its major enzymatic product, lysophosphatidylcholine (LPC), are involved in blood-retinal barrier (BRB) damage during diabetic retinopathy. We assessed BRB protection in diabetic rats through use of species-specific analogs of darapladib. Systemic Lp-PLA2 inhibition using SB-435495 at 10 mg/kg (i.p.) effectively suppressed BRB breakdown in streptozotocin-diabetic Brown Norway rats. This inhibitory effect was comparable to intravitreal VEGF neutralization, and the protection against BRB dysfunction was additive when both targets were inhibited simultaneously. Mechanistic studies in primary brain and retinal microvascular endothelial cells, as well as occluded rat pial microvessels, showed that luminal but not abluminal LPC potently induced permeability, and that this required signaling by the VEGF receptor 2 (VEGFR2). Taken together, this study demonstrates that Lp-PLA2 inhibition can effectively prevent diabetes-mediated BRB dysfunction and that LPC impacts on the retinal vascular endothelium to induce vasopermeability via VEGFR2. Thus, Lp-PLA2 may be a useful therapeutic target for patients with diabetic macular edema (DME), perhaps in combination with currently administered anti-VEGF agents.

Phosphomimetic Mutation of the N-Terminal Lid of MDM2 Enhances the Polyubiquitination of p53 through Stimulation of E2-Ubiquitin Thioester Hydrolysis.

Mouse double minute 2 (MDM2) has a phosphorylation site within a lid motif at Ser17 whose phosphomimetic mutation to Asp17 stimulates MDM2-mediated polyubiquitination of p53. MDM2 lid deletion, but not Asp17 mutation, induced a blue shift in the λmax of intrinsic fluorescence derived from residues in the central domain including Trp235, Trp303, Trp323, and Trp329. This indicates that the Asp17 mutation does not alter the conformation of MDM2 surrounding the tryptophan residues. In addition, Phe235 mutation enhanced MDM2 binding to p53 but did not stimulate its ubiquitination function, thus uncoupling increases in p53 binding from its E3 ubiquitin ligase function. However, the Asp17mutation inMDM2 stimulated its discharge of the UBCH5a-ubiquitin thioester adduct (UBCH5a is a ubiquitin-conjugating enzyme E2D 1 UBC4/5 homolog yeast). This stimulation of ubiquitin discharge fromE2 was independent of the p53 substrate. There are now four known effects of the Asp17 mutation on MDM2: (i) it alters the conformation of the isolated N-terminus as defined by NMR; (ii) it induces increased thermostability of the isolated N-terminal domain; (iii) it stimulates the allosteric interaction ofMDM2 with the DNA-binding domain of p53; and (iv) it stimulates a novel protein–protein interaction with the E2-ubiquitin complex in the absence of substrate p53 that, in turn, increases hydrolysis of theE2-ubiquitin thioester bond. These data also suggest a new strategy to disrupt MDM2 function by targeting the E2-ubiquitin discharge reaction.

Élaboration d’un matériel pédagogique pour l’éducation à la paix basé sur des modèles de paix

L’éducation à la paix s’est développée juste après la Deuxième Guerre mondiale, notamment avec la création de l’UNESCO. D’ailleurs, son Acte constitutif commence avec l’énoncé du principe suivant: « Les guerres prenant naissance dans l’esprit des hommes, c’est dans l’esprit des hommes que doivent être élevées les défenses de la paix. » (Unesco, 1945, 2014, p. 5) Après des recherches sur l’idéal de paix et sur les conceptions de l’éducation à la paix, nous avons posé quelques questions: Quelles sont les différentes stratégies d’éducation à la paix formelles, informelles et non formelles mises en place à travers le monde? À partir de l’inventaire des stratégies d’éducation à la paix, quelles sont celles qui participent le plus à l’objectif de construire un artisan de paix en chaque individu, peu importe son âge, sa classe sociale, sa culture et sa société? La recension des écrits a permis de mettre en évidence quelques pratiques: le dialogue pour la réconciliation, l’éducation interculturelle et aux droits humains, la médiation des conflits. Mais on ne relève pas de pratiques d’éducation à la paix basée sur les modèles. C’est pourquoi, nous avons énoncé la question générale de recherche en ces termes: En quoi les vies des figures de paix en tant que modèles de paix peuvent-elles contribuer à l’éducation à la paix? Nous avons mis en relief le lien possible entre le modèle de paix et la pédagogie basée sur le modèle (Gardner, 1999) dans le but de faire de l’éducation à la paix. Puis, nous avons pu poser deux objectifs de recherche: 1. Élaborer un matériel pédagogique à partir de la vie de modèles de paix pour servir à l’éducation à la paix dans des contextes éducatifs non formels; 2. Faire valider le matériel par des experts. Selon la démarche méthodologique de la recherche de développement (Van der Maren, 2014), nous avons élaboré le prototype du matériel pédagogique. Pour cela, nous avons sélectionné cinq modèles de paix: le Mahatma Gandhi, Mère Teresa, Martin Luther King, Wangari Maathai et Cheikh Ahmadou Bamba. Pour chaque modèle, nous avons créé des scénarios pédagogiques et élaboré du matériel d’accompagnement en fonction d’événements marquants dans leurs vies. Sept experts ont évalué le matériel produit et ont fait des suggestions pour l’améliorer. L’analyse de leur évaluation et leurs recommandations nous a permis de rédiger une nouvelle version que nous avons appelée la version validée du matériel. Le matériel pédagogique produit est intitulé La vie de modèles de paix: Outils d’éducation à la paix. La visée de ce matériel est de donner la possibilité à l’être humain d’identifier son potentiel en tant qu’artisan de paix et de l’amener à développer la paix en lui-même afin de semer la paix autour de lui. Les retombées de cette recherche concernent tant la communauté scientifique que la communauté professionnelle. Nous avons développé une approche pédagogique nouvelle pour faire de l’éducation à la paix et avons dégagé ses fondements théoriques, en plus de produire pour des intervenants socioéducatifs un matériel pédagogique qui a fait l’objet d’une évaluation rigoureuse.

The Proceedings of the South Carolina Historical Association

Annually, the association publishes a journal, The Proceedings, which consists of papers presented at the annual meeting. The United States and Austria, 1918-1919: The Problem of National Self-Determination by Duane Myers The German Economy during World War II: Petroleum by Peter W. Becker Tillman’s Lieutenant: John Laurens Manning Irby by Jerry Slaunwhite Tillman’s Lieutenant: John Lowndes McLaurin by Rodger Stroup

Climate seasonality limits leaf carbon assimilation and wood productivity in tropical forests.

The seasonal climate drivers of the carbon cy- cle in tropical forests remain poorly known, although these forests account for more carbon assimilation and storage than any other terrestrial ecosystem. Based on a unique combina- tion of seasonal pan-tropical data sets from 89 experimental sites (68 include aboveground wood productivity measure- ments and 35 litter productivity measurements), their asso- ciated canopy photosynthetic capacity (enhanced vegetation index, EVI) and climate, we ask how carbon assimilation and aboveground allocation are related to climate seasonal- ity in tropical forests and how they interact in the seasonal carbon cycle. We found that canopy photosynthetic capacity seasonality responds positively to precipitation when rain- fall is < 2000 mm yr-1 (water-limited forests) and to radia- tion otherwise (light-limited forests). On the other hand, in- dependent of climate limitations, wood productivity and lit- terfall are driven by seasonal variation in precipitation and evapotranspiration, respectively. Consequently, light-limited forests present an asynchronism between canopy photosyn- thetic capacity and wood productivity. First-order control by precipitation likely indicates a decrease in tropical forest pro- ductivity in a drier climate in water-limited forest, and in cur- rent light-limited forest with future rainfall < 2000 mm yr-1.

Los indígenas y la conservación de la Biodiversidad: 500 años de Resistencia

IntroducciónEn la actualidad, los indígenas costarricenses representan un 1% del total de la población de nuestro país. Sin embargo, este pequeño, pero importante sector de nuestra nación, ha podido conservar para sí, para los costarricenses y la humanidad, una parte importante del territorio deonde se resguarda nuestro patrimonio natural. Cerca del 85% de los indígenas vivien a ambos lados de la cordillera de Talamanca, asiento histórico de las dos etnias numéricamente más importantes de los indígenas costarricenses contemporáneos: los bribris y los cabécares. Aproximadamente el 75% del territorio es bosque natural y un 15% se encuentra en el presente literalmente alterado...