Progress in cardiovascular anastomoses: will the vascular join replace Carrel's technique?

BACKGROUND: Vascular reconstructions are becoming challenging due to the comorbidity of the aging population and since the introduction of minimally invasive approaches. Many sutureless anastomosis devices have been designed to facilitate the cardiovascular surgeon's work and the vascular join (VJ) is one of these. We designed an animal study to assess its reliability and long-term efficacy. METHODS: VJ allows the construction of end-to-end and end-to-side anastomoses. It consists of two metallic crowns fixed to the extremity of the two conduits so that vessel edges are joined layer by layer. There is no foreign material exposed to blood. In adult sheep both carotid arteries were prepared and severed. End-to-end anastomoses were performed using the VJ device on one side and the classical running suture technique on the other side. Animals were followed-up with Duplex-scan every 3 months and sacrificed after 12 months. Histopathological analysis was carried out. RESULTS: In 20 animals all 22 sutureless anastomoses were successfully completed in less than 2 min versus 6 +/- 3 min for running suture. Duplex showed the occlusion of three controls and one sutureless anastomosis. Two controls and one sutureless had stenosis >50%. Histology showed very thin layer of myointimal hyperplasia (50 +/- 10 microm) in the sutureless group versus 300 +/- 27 microm in the control. No significant inflammatory reaction was detected. CONCLUSIONS: VJ provides edge-to-edge vascular repair that can be considered the most physiological way to restore vessel continuity. For the first time, in healthy sheep, an anastomotic device provided better results than suture technique.

Identification of a key lysine residue in heat shock protein 90 required for azole and echinocandin resistance in Aspergillus fumigatus.

Heat shock protein 90 (Hsp90) is an essential chaperone involved in the fungal stress response that can be harnessed as a novel antifungal target for the treatment of invasive aspergillosis. We previously showed that genetic repression of Hsp90 reduced Aspergillus fumigatus virulence and potentiated the effect of the echinocandin caspofungin. In this study, we sought to identify sites of posttranslational modifications (phosphorylation or acetylation) that are important for Hsp90 function in A. fumigatus. Phosphopeptide enrichment and tandem mass spectrometry revealed phosphorylation of three residues in Hsp90 (S49, S288, and T681), but their mutation did not compromise Hsp90 function. Acetylation of lysine residues of Hsp90 was recovered after treatment with deacetylase inhibitors, and acetylation-mimetic mutations (K27A and K271A) resulted in reduced virulence in a murine model of invasive aspergillosis, supporting their role in Hsp90 function. A single deletion of lysine K27 or an acetylation-mimetic mutation (K27A) resulted in increased susceptibility to voriconazole and caspofungin. This effect was attenuated following a deacetylation-mimetic mutation (K27R), suggesting that this site is crucial and should be deacetylated for proper Hsp90 function in antifungal resistance pathways. In contrast to previous reports in Candida albicans, the lysine deacetylase inhibitor trichostatin A (TSA) was active alone against A. fumigatus and potentiated the effect of caspofungin against both the wild type and an echinocandin-resistant strain. Our results indicate that the Hsp90 K27 residue is required for azole and echinocandin resistance in A. fumigatus and that deacetylase inhibition may represent an adjunctive anti-Aspergillus strategy.

Determinants of economic growth: Will data tell?

Many factors inhibiting and facilitating economic growth havebeen suggested. Can agnostics rely on international incomedata to tell them which matter? We find that agnostic priorslead to conclusions that are sensitive to differences acrossavailable income estimates. For example, the PWT 6.2 revisionof the 1960-96 income estimates in the PWT 6.1 leads tosubstantial changes regarding the role of government,international trade, demography, and geography. We concludethat margins of error in international income estimates appeartoo large for agnostic growth empirics.

Will endoscopists soon replace pathologists in the diagnosis of (pre-)neoplastic and inflammatory mucosal lesions?

This short review addresses the question whether pathologists will continue to play a central role in the diagnosis of mucosal lesions of the gastrointestinal tract or whether their role will soon be assumed by clinical colleagues equipped with modern high-resolution endoscopes. In order to support the raison d'etre of the pathologist - at least for the time being and the near future - the author lists three arguments, related to (i) the differences in the orientation of the plane of view (histology: perpendicular to the mucosal surface vs. endoscopy: parallel to the mucosal surface), (ii) the advantages of staining and immunostaining tissue sections, and (iii) the possibility to perform deeper sections and to consul with colleagues in the case of difficult diagnoses.

Will the Convention on Biological Diversity put an end to biological control?

Will the Convention on Biological Diversity put an end to biological control? Under the Convention on Biological Diversity countries have sovereign rights over their genetic resources. Agreements governing the access to these resources and the sharing of the benefits arising from their use need to be established between involved parties. This also applies to species collected for potential use in biological control. Recent applications of access and benefit sharing principles have already made it difficult or impossible to collect and export natural enemies for biological control research in several countries. If such an approach is widely applied it would impede this very successful and environmentally safe pest management method based on the use of biological diversity. The International Organization for Biological Control of Noxious Animals and Plants has, therefore, created the "Commission on Biological Control and Access and Benefit Sharing". This commission is carrying out national and international activities to make clear how a benefit sharing regime might seriously frustrate the future of biological control. In addition, the IOBC Commission members published information on current regulations and perceptions concerning exploration for natural enemies and drafted some 30 case studies selected to illustrate a variety of points relevant to access and benefit sharing. In this article, we summarize our concern about the effects of access and benefit sharing systems on the future of biological control.

Will EMU increase eurosclerosis?

In this paper we study the relationship between labor market institutions and monetary policy. We use a simple macroeconomic framework to show how optimal monetary policy rules depend on labor institutions (labor adjustment costs, and nominal and real wage rigitidy) and social preferences regarding inflation, employment, and real wages. We also calibrate our model tocompute how the change in social welfare brought about by giving up monetary policy as a result of joining the Economic and Monetary Union (EMU) depends on institutions and preferences. We then use the calibrated model to analyze how EMU affects the incentives for labor market reform, both for reformsthat increase the economy's adjustment potential and for those that affect the long-run unemployment rate.

Nanotechnology: What is it and how will it affect us?

A non-technical review of nanotechnology from a Catalan perspective – its potential economic and social impacts and the potential role of public policy.

PROTEOMICS OF OXIDATIVE LESIONS OCCURRING DURING TRANSFUSION-PURPOSED STORAGE OF ERYTHROCYTE CONCENTRATES

Erythrocyte concentrates (ECs) are the major labile blood product being transfused worldwide, aiming at curing anemia of diverse origins. In Switzerland, ECs are stored at 4 °C up to 42 days in saline-adenine-glucose-mannitol (SAGM). Such storage induces cellular lesions, altering red blood cells (RBCs) metabolism, protein content and rheological properties. A hot debate exists regarding the impact of the storage lesions, thus the age of ECs on transfusion-related clinical adverse outcomes. Several studies tend to show that poorer outcomes occur in patients receiving older blood products. However, no clear association was demonstrated up to date. While metabolism and early rheological changes are reversible through transfusion of the blood units, oxidized proteins cannot be repaired, and it is likely such irreversible damages would affect the quality of the blood product and the efficiency of the transfusion. In vivo, RBCs are constantly exposed to oxygen fluxes, and are thus well equipped to deal with oxidative challenges. Moreover, functional 20S proteasome complexes allow for recognition and proteolysis of fairly oxidized protein, and some proteins can be eliminated from RBCs by the release of microvesicles. The present PhD thesis is involved in a global research project which goal is to characterize the effect of processing and storage on the quality of ECs. Assessing protein oxidative damages during RBC storage is of major importance to understand the mechanisms of aging of stored RBCs. To this purpose, redox proteomic-based investigations were conducted here. In a first part, cysteine oxidation and protein carbonylation were addressed via 2D-DIGE and derivatization-driven immunodetection approaches, respectively. Then, the oxidized sub- proteomes were characterized through LC-MS/MS identification of proteins in spots of interest (cysteine oxidation) or affinity-purified carbonylated proteins. Gene ontology annotation allowed classifying targets of oxidation according to their molecular functions. In a third part, the P20S activity was evaluated throughout the storage period of ECs, and its susceptibility to highly oxidized environment was investigated. The potential defensive role of microvesiculation was also addressed through the quantification of eliminated carbonylated proteins. We highlighted distinct protein groups differentially affected by cysteine oxidation, either reversibly or irreversibly. In addition, soluble extracts showed a decrease in carbonylation at the beginning of the storage and membrane extracts revealed increasing carbonylation after 4 weeks of storage. Engaged molecular functions revealed that antioxidant (AO) are rather reversibly oxidized at their cysteine residue(s), but are irreversibly oxidized through carbonylation. In the meantime, the 20S proteasome activity is decreased by around 40 % at the end of the storage period. Incubation of fresh RBCs extracts with exogenous oxidized proteins showed a dose-dependent and protein-dependent inhibitory effect. Finally, we proved that the release of microvesicles allows the elimination of increasing quantities of carbonylated proteins. Taken together, these results revealed an oxidative pathway model of RBCs storage, on which further investigation towards improved storage conditions will be based. -- Les concentrés érythrocytaires (CE) sont le produit sanguin le plus délivré au monde, permettant de traiter différentes formes d'anémies. En Suisse, les CE sont stocké à 4 °C pendant 42 jours dans une solution saline d'adénine, glucose et mannitol (SAGM). Une telle conservation induit des lésions de stockage qui altèrent le métabolisme, les protéines et les propriétés rhéologique du globule rouge (GR). Un débat important concerne l'impact du temps de stockage des CE sur les risques de réaction transfusionnelles, certaines études tentant de démontrer que des transfusions de sang vieux réduiraient l'espérance de vie des patients. Cependant, aucune association concrète n'a été prouvée à ce jour. Alors que les modifications du métabolisme et changement précoces des propriétés rhéologiques sont réversibles suite à la transfusion du CE, les protéines oxydées ne peuvent être réparées, et il est probable que de telles lésions affectent la qualité et l'efficacité des produits sanguins. In vivo, les GR sont constamment exposés à l'oxygène, et sont donc bien équipés pour résister aux lésions oxydatives. De plus, les complexes fonctionnels de proteasome 20S reconnaissent et dégradent les protéines modérément oxydées, et certaines protéines peuvent être éliminées par les microparticules. Cette thèse de doctorat est imbriquée dans un projet de recherche global ayant pour objectif la caractérisation des effets de la préparation et du stockage sur la qualité des GR. Evaluer les dommages oxydatifs du GR pendant le stockage est primordial pour comprendre les mécanismes de vieillissement des produits sanguin. Dans ce but, des recherches orientées redoxomique ont été conduites. Dans une première partie, l'oxydation des cystéines et la carbonylation des protéines sont évaluées par électrophorèse bidimensionnelle différentielle et par immunodétection de protéines dérivatisées. Ensuite, les protéines d'intérêt ainsi que les protéines carbonylées, purifiées par affinité, sont identifiées par spectrométrie de masse en tandem. Les protéines cibles de l'oxydation sont classées selon leur fonction moléculaire. Dans une troisième partie, l'activité protéolytique du protéasome 20S est suivie durant la période de stockage. L'impact du stress oxydant sur cette activité a été évalué en utilisant des protéines exogènes oxydées in vitro. Le potentiel rôle défensif de la microvesiculation a également été étudié par la quantification des protéines carbonylées éliminées. Dans ce travail, nous avons observé que différents groupes de protéines sont affectés par l'oxydation réversible ou irréversible de leurs cystéines. De plus, une diminution de la carbonylation en début de stockage dans les extraits solubles et une augmentation de la carbonylation après 4 semaines dans les extraits membranaires ont été montrées. Les fonctions moléculaires engagées par les protéines altérées montrent que les défenses antioxydantes sont oxydées de façon réversible sur leurs résidus cystéines, mais sont également irréversiblement carbonylées. Pendant ce temps, l'activité protéolytique du protéasome 20S décroit de 40 % en fin de stockage. L'incubation d'extraits de GR en début de stockage avec des protéines oxydées exogènes montre un effet inhibiteur « dose-dépendant » et « protéine-dépendant ». Enfin, les microvésicules s'avèrent éliminer des quantités croissantes de protéines carbonylées. La synthèse de ces résultats permet de modéliser une voie oxydative du stockage des GRs, à partir de laquelle de futures recherches seront menées avec pour but l'amélioration des conditions de stockage.

4550. The beautiful Church of S. Sebastian, built of steel, Manila / [photogr. Underwood & Underwood]

Donateur : Vassal, Gabrielle Maud (1880-1959)

Networks of people in specialty production: family firms in the iron and steel Wire industries in Spain (1870-2000)

Capital intensive industries in specialized niches of production have constituted solid ground for family firms in Spain , as evidenced by the experience of the iron and steel wire industries between 1870 and 2000. The embeddedness of these firms in their local and regional environments have allowed the creation of networks that, together with favourable institutional conditions, significantly explain the dominance of family entrepreneurship in iron and steel wire manufacturing in Spain, until the end of the 20 th century. Dominance of family firms at the regional level has not been not an obstacle for innovation in wire manufacturing in Spain, which has taken place even when institutional conditions blocked innovation and traditional networking. Therefore, economic theories about the difficulties dynastic family firms may have to perform appropriately in science-based industries must be questioned

Neotropical woodlice (isopoda) colonizing leaf-litter of pioneer plants in a coal residue disposal environment

The irregular disposal of coal combustion residues has adverse impacts on terrestrial ecosystems. Pioneer plants and soil invertebrates play an important role in the recovery of these areas. The goal of this study was to investigate the colonization patterns of terrestrial isopods (Oniscidea) in leaf litter of three spontaneous pioneer plants (grass - Poaceae, shrub - Euphorbiaceae, tree - Anarcadiaceae) at sites used for fly ash or boiler slag disposal. The experiment consisted of eight blocks (four per disposal site) of 12 litter bags each (four per plant species) that were randomly removed after 6, 35, 70 or 140 days of field exposure. Three isopod species were found in the litter bags: Atlantoscia floridana (van Name, 1940) (Philosciidae; n = 116), Benthana taeniata Araujo & Buckup, 1994 (Philosciidae; n = 817) and Balloniscus sellowii (Brandt, 1833) (Balloniscidae; n = 48). The isopods colonized the three leaf-litter species equally during the exposure period. However, the pattern of leaf-litter colonization by these species suggests a conflict of objectives between high quality food and shelter availability. The occurrence of A. floridana and the abundance and fecundity of B. taeniata were influenced by the residue type, indicating that the isopods have different degrees of tolerance to the characteristics of the studied sites. Considering that terrestrial isopods are abundant detritivores and stimulate the humus-forming processes, it is suggested that they could have an indirect influence on the soil restoration of this area.