Impaired Translesion Synthesis in Xeroderma Pigmentosum Variant Extracts

Xeroderma pigmentosum variant (XPV) cells are characterized by a cellular defect in the ability to synthesize intact daughter DNA strands on damaged templates. Molecular mechanisms that facilitate replication fork progression on damaged DNA in normal cells are not well defined. In this study, we used single-stranded plasmid molecules containing a single N-2-acetylaminofluorene (AAF) adduct to analyze translesion synthesis (TLS) catalyzed by extracts of either normal or XPV primary skin fibroblasts. In one of the substrates, the single AAF adduct was located at the 3' end of a run of three guanines that was previously shown to induce deletion of one G by a slippage mechanism. Primer extension reactions performed by normal cellular extracts from four different individuals produced the same distinct pattern of TLS, with over 80% of the products resulting from the elongation of a slipped intermediate and the remaining 20% resulting from a nonslipped intermediate. In contrast, with cellular extracts from five different XPV patients, the TLS reaction was strongly reduced, yielding only low amounts of TLS via the nonslipped intermediate. With our second substrate, in which the AAF adduct was located at the first G in the run, thus preventing slippage from occurring, we confirmed that normal extracts were able to perform TLS 10-fold more efficiently than XPV extracts. These data demonstrate unequivocally that the defect in XPV cells resides in translesion synthesis independently of the slippage proces

Cost-effectiveness of irbesartan in diabetic nephropathy: a systematic review of published studies

Background. To review published studies on the cost-effectiveness of the use of irbesartan for treatment of advance overt nephropathy in patients with type 2 diabetes and hypertension. Methods. Articles were identified based on a search of the PubMed databases using the keywords ‘irbesartan', ‘ESRD', ‘cost-effectiveness', ‘nephropathy' and ‘costs', and by personal communication with the authors. Only studies published in the last 10 years were included. All costs data from the cost-effectiveness studies were inflated to 2003 Euros using published governmental conversion tables. Results. Seven published studies were identified, spanning the following country settings: the US, Belgium and France, Germany, Hungary, Italy, Spain, and the UK. In each, the same pharmacoeconomic model was adapted using country-specific data to project and evaluate the clinical and cost outcomes of the treatment arms of the Irbesartan in Diabetic Nephropathy Trial (IDNT) (irbesartan, amlodipine or standard blood pressure control). Mean time to onset of ESRD was 8.23 years for irbesartan, 6.82 years for amlodipine and 6.88 years for the control (values were the same for Belgium, France, Germany, Hungary, Italy and Spain as transition probabilities for progression to ESRD were all derived from the IDNT). Mean cumulative incidence of ESRD was 36% with irbesartan, 49% with amlodipine and 45% with control treatment. Treatment with irbesartan was projected to improve life expectancy compared to both amlodipine and control in all seven published studies. Analysis of total lifetime costs showed that irbesartan treatment was cost saving compared to the other two treatment regimens, due to the associated reduction in ESRD cases. Cost savings with irbesartan became evident very early; after 2-3 years of treatment in most settings. Conclusions. Modelling studies based on the IDNT published to date suggest that irbesartan treatment in patients with type 2 diabetes, hypertension and advanced nephropathy is both life- and cost-saving compared to amlodipine or contro

Forêts de montagne et changement climatique : impacts et adaptation

This review identifies the main impacts of climate change on mountain forests, mainly in Europe, and the management practices proposed for forest adaption. The rise in temperatures, more frequent droughts and the multiplication of extreme events should lead, especially below 1000m in altitude, to the disappearance of highly drought-intolerant tree species (spruce, Scots pine) and their replacement by deciduous trees. In addition, recruitment of some species (fir, beech) is observed at higher altitudes and the duration of the growing season is increasing. Management recommendations for forest adaptation to climate change focus on reducing tree species' vulnerability to water stress and pests, as well as increasing their resilience and ability to respond to extreme weather events. They require genetic improvements and practices that encourage the establishment of suitable species, reduce water consumption and reduce the exposure of stands to risk.Les impacts du changement climatique sur les forêts de montagne sont déjà perceptibles et les prévisions nous montrent, par leurs contradictions, la complexité des phénomènes en jeu. L'objectif de cette étude bibliographique est d'abord de caractériser les principaux effets du changement climatique, principalement dans les forêts alpines, puis de présenter différentes options d'adaptation devant permettre de conserver les services actuellement fournis par la forêt. L'épicéa, le sapin et le hêtre, dominants dans les Alpes françaises, y sont privilégiés

MAGIC-SPP: a database-driven DNA sequence processing package with associated management tools

BACKGROUND: Processing raw DNA sequence data is an especially challenging task for relatively small laboratories and core facilities that produce as many as 5000 or more DNA sequences per week from multiple projects in widely differing species. To meet this challenge, we have developed the flexible, scalable, and automated sequence processing package described here. RESULTS: MAGIC-SPP is a DNA sequence processing package consisting of an Oracle 9i relational database, a Perl pipeline, and user interfaces implemented either as JavaServer Pages (JSP) or as a Java graphical user interface (GUI). The database not only serves as a data repository, but also controls processing of trace files. MAGIC-SPP includes an administrative interface, a laboratory information management system, and interfaces for exploring sequences, monitoring quality control, and troubleshooting problems related to sequencing activities. In the sequence trimming algorithm it employs new features designed to improve performance with respect to concerns such as concatenated linkers, identification of the expected start position of a vector insert, and extending the useful length of trimmed sequences by bridging short regions of low quality when the following high quality segment is sufficiently long to justify doing so. CONCLUSION: MAGIC-SPP has been designed to minimize human error, while simultaneously being robust, versatile, flexible and automated. It offers a unique combination of features that permit administration by a biologist with little or no informatics background. It is well suited to both individual research programs and core facilities

Forêts de montagne et changement climatique : impacts et adaptations

This review identifies the main impacts of climate change on mountain forests, mainly in Europe, and the management practices proposed for forest adaption. The rise in temperatures, more frequent droughts and the multiplication of extreme events should lead, especially below 1000m in altitude, to the disappearance of highly drought-intolerant tree species (spruce, Scots pine) and their replacement by deciduous trees. In addition, recruitment of some species (fir, beech) is observed at higher altitudes and the duration of the growing season is increasing. Management recommendations for forest adaptation to climate change focus on reducing tree species' vulnerability to water stress and pests, as well as increasing their resilience and ability to respond to extreme weather events. They require genetic improvements and practices that encourage the establishment of suitable species, reduce water consumption and reduce the exposure of stands to risk.Cette étude bibliographique recense les principaux impacts du changement climatique sur les forêts de montagne, principalement européennes, ainsi que les pratiques de gestion proposées pour adapter les forêts à ces changements. La hausse des températures, les sécheresses plus fréquentes et la multiplication des évènements extrêmes devraient entrainer, surtout en-deçà de 1000m d'altitude, une réduction des essences les moins tolérantes à la sécheresse (épicéa, pin sylvestre) et leur remplacement par des feuillus. D'ores et déjà, le recrutement de certaines essences (sapin, hêtre) est observé à des altitudes plus élevées et la durée de la saison de végétation augmente. Les préconisations de gestion pour l'adaptation des forêts au changement climatique s'attachent à réduire la vulnérabilité des essences au stress hydrique et aux parasites, ainsi qu'à renforcer leur résilience et leur capacité de réponse aux évènements climatiques extrêmes. Elles passent par des améliorations génétiques et des pratiques qui favorisent l'installation d'espèces adaptées, réduisent la consommation d'eau et l'exposition des peuplements aux risques