An assessment of histone-modification antibody quality

We have tested the specificity and utility of more than 200 antibodies raised against 57 different histone modifications in Drosophila melanogaster, Caenorhabditis elegans and human cells. Although most antibodies performed well, more than 25% failed specificity tests by dot blot or western blot. Among specific antibodies, more than 20% failed in chromatin immunoprecipitation experiments. We advise rigorous testing of histone-modification antibodies before use, and we provide a website for posting new test results (http://compbio.med.harvard.edu/antibodies/)

An assessment of histone-modification antibody quality

We have tested the specificity and utility of more than 200 antibodies raised against 57 different histone modifications in Drosophila melanogaster, Caenorhabditis elegans and human cells. Although most antibodies performed well, more than 25% failed specificity tests by dot blot or western blot. Among specific antibodies, more than 20% failed in chromatin immunoprecipitation experiments. We advise rigorous testing of histone-modification antibodies before use, and we provide a website for posting new test results (http://compbio.med.harvard.edu/antibodies/)

H4K20me1 Contributes to Downregulation of X-Linked Genes for C. elegans Dosage Compensation

The Caenorhabditis elegans dosage compensation complex (DCC) equalizes X-chromosome gene dosage between XO males and XX hermaphrodites by two-fold repression of X-linked gene expression in hermaphrodites. The DCC localizes to the X chromosomes in hermaphrodites but not in males, and some subunits form a complex homologous to condensin. The mechanism by which the DCC downregulates gene expression remains unclear. Here we show that the DCC controls the methylation state of lysine 20 of histone H4, leading to higher H4K20me1 and lower H4K20me3 levels on the X chromosomes of XX hermaphrodites relative to autosomes. We identify the PR-SET7 ortholog SET-1 and the Suv4-20 ortholog SET-4 as the major histone methyltransferases for monomethylation and di/trimethylation of H4K20, respectively, and provide evidence that X-chromosome enrichment of H4K20me1 involves inhibition of SET-4 activity on the X. RNAi knockdown of set-1 results in synthetic lethality with dosage compensation mutants and upregulation of X-linked gene expression, supporting a model whereby H4K20me1 functions with the condensin-like C. elegans DCC to repress transcription of X-linked genes. H4K20me1 is important for mitotic chromosome condensation in mammals, suggesting that increased H4K20me1 on the X may restrict access of the transcription machinery to X-linked genes via chromatin compaction

Molecular epidemiology of DFNB1 deafness in France

BACKGROUND: Mutations in the GJB2 gene have been established as a major cause of inherited non syndromic deafness in different populations. A high number of sequence variations have been described in the GJB2 gene and the associated pathogenic effects are not always clearly established. The prevalence of a number of mutations is known to be population specific, and therefore population specific testing should be a prerequisite step when molecular diagnosis is offered. Moreover, population studies are needed to determine the contribution of GJB2 variants to deafness. We present our findings from the molecular diagnostic screening of the GJB2 and GJB6 genes over a three year period, together with a population-based study of GJB2 variants. METHODS AND RESULTS: Molecular studies were performed using denaturing High Performance Liquid Chromatograghy (DHPLC) and sequencing of the GJB2 gene. Over the last 3 years we have studied 159 families presenting sensorineural hearing loss, including 84 with non syndromic, stable, bilateral deafness. Thirty families were genotyped with causative mutations. In parallel, we have performed a molecular epidemiology study on more than 3000 dried blood spots and established the frequency of the GJB2 variants in our population. Finally, we have compared the prevalence of the variants in the hearing impaired population with the general population. CONCLUSION: Although a high heterogeneity of sequence variation was observed in patients and controls, the 35delG mutation remains the most common pathogenic mutation in our population. Genetic counseling is dependent on the knowledge of the pathogenicity of the mutations and remains difficult in a number of cases. By comparing the sequence variations observed in hearing impaired patients with those sequence variants observed in general population, from the same ethnic background, we show that the M34T, V37I and R127H variants can not be responsible for profound or severe deafness

The economic impact of climate change and adaptation strategies in the water sector

In the near future, Switzerland is predicted to be affected by climate change, that is bound to impact both water demand and water supply in multiple ways. While water demand by households, firms and agriculture increases, water supply decreases (ProClim and OcCC, 2007) as climate change alters the hydrologic cycle and thus the water resources. To best face the challenges that lie ahead, an understanding of the economic impact of climate change and different adaptation strategies in the water sector is essential. This study is part of a wider research project simulating the economic impact of climate change in Switzerland, mandated by the Federal Office for the Environment (FOEN)

The economic impact of climate driven changes in water availability in Switzerland

The broad objective of this study is to estimate the economic impact of changes in water availability due to climate change in Switzerland with a 2050 time horizon. To do so, the sectoral structure of the computable general equilibrium model GEMINI-E3 is being extended. Raw water resources are introduced as a production factor into the model and a drinking water distribution sector is specified for Switzerland to allow for a precise analysis of the economic consequences of restricted water supply. Predictions of water availability in 2050 are taken from a hydrological model and alternative climate change scenarios are considered. Simulations show possible restrictions in water resource availability to increase raw water prices substantially compared to the baseline. Sectors most affected are the water distribution and agricultural sectors that use irrigation. However, the global economic impact for Switzerland is rather small due to the low price of raw water in Switzerland and its small value in the benchmark scenario. Finally, the simulation of scenarios featuring alternative levels of endogenous adaptive capacity of the economy reveals the possible economic impact of adaptation to climate change

The economic impact of climate driven changes in water availability in Switzerland

The broad objective of this study is to estimate the economic impact of changes in water availability due to climate change in Switzerland with a 2050 time horizon. To do so, the sectoral structure of the computable general equilibrium model GEMINI-E3 is being extended. Raw water resources are introduced as a production factor into the model and a drinking water distribution sector is specified for Switzerland to allow for a precise analysis of the economic consequences of restricted water supply. Predictions of water availability in 2050 are taken from a hydrological model and alternative climate change scenarios are considered. Simulations show possible restrictions in water resource availability to increase raw water prices substantially compared to the baseline. Sectors most affected are the water distribution and agricultural sectors that use irrigation. However, the global economic impact for Switzerland is rather small due to the low price of raw water in Switzerland and its small value in the benchmark scenario. Finally, the simulation of scenarios featuring alternative levels of endogenous adaptive capacity of the economy reveals the possible economic impact of adaptation to climate change

Ralentissement de l'activité mondiale et crise du Golfe : quels ajustements pour l'économie française ?

Die Verlangsamung des weltweiten Wirtschaftswachstums und der Ölschock: welche Anpassungsmaßnahmen sind für die französische Wirtschaft erforderlich? von Mireille Assouline, Anne Epaulard, Patrick Fève, Marc Vielle. Die deutliche Verlangsamung des Wirtschafjtswachstums in den westlichen Ländern, verbunden mit den jüngsten durch die Golfkrise bedingten Ereignissen (Unsicherheit des Ölpreises) konnte auf eine neue Phase der Rezession in der Weltwirtschaft schließen lassen. Mit der anhand des Hermès-France-Modells vorgenommenen Analyse sollen nicht nur die Rückwirkungen dieser extemen Schocks auf die französische Wirtschaft beziffert, sondern ebenfalls die Folgen der möglichen Veränderungen im Verhalten der Wirtschaftssubjekte angesichts einer solchen Situation bewertet werden: sofortige Überwälzung der Kostensteigerungen auf die Preise, Vorwegnahme des Abschwungs durch die Unternehmer und Änderung der Lohnindexierungsregeln. Daneben werden verschiedene Anpassungspolitiken (Senkung der Sozialbeiträge der Arbeitgeber und Haushaltskürzungen) für den Fall eines extemen Schocks großen Ausmaßes in Erwägung gezogen.The Slump in World Activity and the Oil Crisis : Adjustments the French Economy Must Make, by Mireille Assouline, Anne Epaulard, Patrick Fève and Marc Vielle. The marked slowdown in the growth of Western economies stemming from the recent Gulf Crisis and the uncertainty over oil prices leads us to believe there will be a new recessionary phase in world economy. The analysis made using the Hermès-France model aims not only to quantify the impact of these external factors on the French economy, but also to assess the consequences possible changes in the behaviour of the economic agents could have under such circumstances, the immediate result being that higher costs would raise prices and that firms would expect a slowdown in activity and modify their salary scales accordingly. Various adjustment policies, (including lower social contributions for employers and budgetary cutbacks) are also to be expected in the event we are faced with a large-scale external crisis.Ralentissement de l'activité mondiale et crise du Golfe : quels ajustements pour l'économie française ? par Mireille Assouline, Anne Epaulard, Patrick Fève, Marc Vielle. Le ralentissement marqué de la croissance des économies occidentales associé aux événements récents de la crise du Golfe (incertitude sur le prix du pétrole ) a pu laisser présager une nouvelle phase de récession pour l'économie mondiale. L'analyse effectuée à l'aide du modèle Hermès-France cherche non seulement à chiffrer l'impact de ces chocs externes sur l'économie française, mais aussi à évaluer les conséquences des modifications possibles de comportement des agents économiques dans un tel contexte : répercussion immédiate des hausses de coûts dans les prix, anticipations à la baisse des entrepreneurs et modifications des règles d'indexation des salaires. Enfin différentes politiques d'ajustement (diminution des cotisations sociales employeurs et restriction budgétaire) sont envisagées dans le cas d'un choc externe de grande ampleur.Moderación de la actividad mundial y la crisis del petróleo : ¿ que reajustes para la economía francesa ?. Mireille Assouline, Anne Epaulard, Patrick Fève y Marc Vielle. La notable disminución del crecimiento de las economías occidentales y los recientes acontecimientos de la crisis del Golfo (incertidumbre en relación con los precios del petróleo) dejaban presumir una nueva etapa de recesiôn para la economía mundial. El análisis efectuado con el modelo Hermès-France trata de evaluar el impacto de estas crisis externas con respecta a la economía francesa y las consecuencias de las posibles modificaciones de comportamiento de los agentes económicos en dicho contexto: repercusión inmediata del aumento de los costes en los precios, anticipaciones reduccionistas por parte de los empresarios y modificaciones de las reglas de reajuste de salarios. Por último, se contemplan diversas políticas de reajuste (disminución de las cotizaciones sociales de las empresas y restricción presupuestaria) en el caso de una crisis externa de gran envergadura.Assouline Mireille, Epaulard Anne, Fève Patrick, Vielle Marc. Ralentissement de l'activité mondiale et crise du Golfe : quels ajustements pour l'économie française ?. In: Économie & prévision, n°96, 1990-5. pp. 33-44