Fanconi anemia protein FANCD2 inhibits TRF1 polyADP-ribosylation through tankyrase1-dependent manner

Background: Fanconi anemia (FA) is a rare autosomal recessive syndrome characterized by developmental abnormalities, progressive bone marrow failure, and predisposition to cancer. The key FA protein FANCD2 crosstalks with members of DNA damage and repair pathways that also play a role at telomeres. Therefore, we investigated whether FANCD2 has a similar involvement at telomeres. Results: We reveal that FANCD2 may perform a novel function separate to the FANCD2/BRCA pathway. This function includes FANCD2 interaction with one of the telomere components, the PARP family member tankyrase-1. Moreover, FANCD2 inhibits tankyrase-1 activity in vitro. In turn, FANCD2 deficiency increases the polyADP-ribosylation of telomere binding factor TRF1. Conclusions: FANCD2 binding and inhibiting tankyrase-1PARsylation at telomeres may provide an additional step within the FA pathway for the regulation of genomic integrity

Development of Science-Based Permitting Guidance for Geological Sequestration of CO2 in Deep Saline Aquifers Based on Modeling and Risk Assessment

Underground carbon storage may become one of the solutions to address global warming. However, to have an impact, carbon storage must be done at a much larger scale than current CO{sub 2} injection operations for enhanced oil recovery. It must also include injection into saline aquifers. An important characteristic of CO{sub 2} is its strong buoyancy--storage must be guaranteed to be sufficiently permanent to satisfy the very reason that CO{sub 2} is injected. This long-term aspect (hundreds to thousands of years) is not currently captured in legislation, even if the U.S. has a relatively well-developed regulatory framework to handle carbon storage, especially in the operational short term. This report proposes a hierarchical approach to permitting in which the State/Federal Government is responsible for developing regional assessments, ranking potential sites (''General Permit'') and lessening the applicant's burden if the general area of the chosen site has been ranked more favorably. The general permit would involve determining in the regional sense structural (closed structures), stratigraphic (heterogeneity), and petrophysical (flow parameters such as residual saturation) controls on the long-term fate of geologically sequestered CO{sub 2}. The state-sponsored regional studies and the subsequent local study performed by the applicant will address the long-term risk of the particular site. It is felt that a performance-based approach rather than a prescriptive approach is the most appropriate framework in which to address public concerns. However, operational issues for each well (equivalent to the current underground injection control-UIC-program) could follow regulations currently in place. Area ranking will include an understanding of trapping modes. Capillary (due to residual saturation) and structural (due to local geological configuration) trappings are two of the four mechanisms (the other two are solubility and mineral trappings), which are the most relevant to the time scale of interest. The most likely pathways for leakage, if any, are wells and faults. We favor a defense-in-depth approach, in which storage permanence does not rely upon a primary seal only but assumes that any leak can be contained by geologic processes before impacting mineral resources, fresh ground water, or ground surface. We examined the Texas Gulf Coast as an example of an attractive target for carbon storage. Stacked sand-shale layers provide large potential storage volumes and defense-in-depth leakage protection. In the Texas Gulf Coast, the best way to achieve this goal is to establish the primary injection level below the total depth of most wells (>2,400 m-8,000 ft). In addition, most faults, particularly growth faults, present at the primary injection level do not reach the surface. A potential methodology, which includes an integrated approach comprising the whole chain of potential events from leakage from the primary site to atmospheric impacts, is also presented. It could be followed by the State/Federal Government, as well as by the operators

Falla cardiaca avanzada por aneurismas coronarios

We present the case of a 61 years old man with hypothyroidism, hypertension, type 2 diabetes mellitus, and ischemic cardiopathy, who was admitted with a diagnosis of non-ST elevation myocardial infarction. The coronary angiography describes coronary ectasia with giant aneurysm and slow flow in the right coronary and aneurysm with slow flow anterior descending coronary. The echocardiogram shows contractility disorders with severely decreased left ventricular ejection fraction (20%) despite optimal medical management. This case presents a patient with ischemic heart disease and advanced heart failure secondary to coronary aneurysm, the proposed optimal treatment was a heart transplant given the disease’s progression.Se presenta el caso de un varón de 61 años con antecedente de hipotiroidismo, hipertensión arterial, diabetes mellitus tipo 2 y síndrome coronario crónico, que ingresa con diagnóstico de infarto de miocardio sin elevación del segmento ST. En el cateterismo se evidencia ectasia coronaria con gran aneurisma y flujo lento en arteria coronaria derecha, y aneurisma y flujo lento en arteria descendente anterior. En el ecocardiograma se encontró trastornos de motilidad, con fracción de eyección del ventrículo izquierdo severamente disminuida (20%) a pesar de manejo médico óptimo. Dado todo lo anterior, se diagnosticó como una cardiopatía isquémica y falla cardiaca avanzada secundarias a aneurismas coronarios planteándose como tratamiento definitivo el trasplante cardiaco dada la progresión de la enfermedad

Association between footwear use and neglected tropical diseases: a systematic review and meta-analysis

BACKGROUND The control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs. METHODOLOGY We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses. PRINCIPAL FINDINGS Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR=0.15; 95% CI: 0.08-0.29), CLM (OR=0.24; 95% CI: 0.06-0.96), tungiasis (OR=0.42; 95% CI: 0.26-0.70), hookworm infection (OR=0.48; 95% CI: 0.37-0.61), any STH infection (OR=0.57; 95% CI: 0.39-0.84), strongyloidiasis (OR=0.56; 95% CI: 0.38-0.83), and leptospirosis (OR=0.59; 95% CI: 0.37-0.94). No significant association between footwear use and podoconiosis (OR=0.63; 95% CI: 0.38-1.05) was found and no data were available for mycetoma, myiasis, and snakebite. The main limitations were evidence of heterogeneity and poor study quality inherent to the observational studies included. CONCLUSIONS/SIGNIFICANCE Our results show that footwear use was associated with a lower odds of several different NTDs. Access to footwear should be prioritized alongside existing NTD interventions to ensure a lasting reduction of multiple NTDs and to accelerate their control and elimination. PROTOCOL REGISTRATION PROSPERO International prospective register of systematic reviews CRD42012003338

The twilight of the Liberal Social Contract? On the Reception of Rawlsian Political Liberalism

This chapter discusses the Rawlsian project of public reason, or public justification-based 'political' liberalism, and its reception. After a brief philosophical rather than philological reconstruction of the project, the chapter revolves around a distinction between idealist and realist responses to it. Focusing on political liberalism’s critical reception illuminates an overarching question: was Rawls’s revival of a contractualist approach to liberal legitimacy a fruitful move for liberalism and/or the social contract tradition? The last section contains a largely negative answer to that question. Nonetheless the chapter's conclusion shows that the research programme of political liberalism provided and continues to provide illuminating insights into the limitations of liberal contractualism, especially under conditions of persistent and radical diversity. The programme is, however, less receptive to challenges to do with the relative decline of the power of modern states

Constitutivism

A brief explanation and overview of constitutivism

A global-scale screening of non-native aquatic organisms to identify potentially invasive species under current and future climate conditions

The threat posed by invasive non-native species worldwide requires a global approach to identify which introduced species are likely to pose an elevated risk of impact to native species and ecosystems. To inform policy, stakeholders and management decisions on global threats to aquatic ecosystems, 195 assessors representing 120 risk assessment areas across all six inhabited continents screened 819 non-native species from 15 groups of aquatic organisms (freshwater, brackish, marine plants and animals) using the Aquatic Species Invasiveness Screening Kit. This multi-lingual decision-support tool for the risk screening of aquatic organisms provides assessors with risk scores for a species under current and future climate change conditions that, following a statistically based calibration, permits the accurate classification of species into high-, medium-and low-risk categories under current and predicted climate conditions. The 1730 screenings undertaken encompassed wide geographical areas (regions, political entities, parts thereof, water bodies, river basins, lake drainage basins, and marine regions), which permitted thresholds to be identified for almost all aquatic organismal groups screened as well as for tropical, temperate and continental climate classes, and for tropical and temperate marine ecoregions. In total, 33 species were identified as posing a 'very high risk' of being or becoming invasive, and the scores of several of these species under current climate increased under future climate conditions, primarily due to their wide thermal tolerances. The risk thresholds determined for taxonomic groups and climate zones provide a basis against which area-specific or climate-based calibrated thresholds may be interpreted. In turn, the risk rankings help decision-makers identify which species require an immediate 'rapid' management action (e.g. eradication, control) to avoid or mitigate adverse impacts, which require a full risk assessment, and which are to be restricted or banned with regard to importation and/or sale as ornamental or aquarium/fishery enhancement. Decision support tools AS-ISK Hazard identification Non-native species Risk analysis Climate changepublishedVersio

A global-scale screening of non-native aquatic organisms to identify potentially invasive species under current and future climate conditions

The threat posed by invasive non-native species worldwide requires a global approach to identify which introduced species are likely to pose an elevated risk of impact to native species and ecosystems. To inform policy, stakeholders and management decisions on global threats to aquatic ecosystems, 195 assessors representing 120 risk assessment areas across all six inhabited continents screened 819 non-native species from 15 groups of aquatic organisms (freshwater, brackish, marine plants and animals) using the Aquatic Species Invasiveness Screening Kit. This multi-lingual decision-support tool for the risk screening of aquatic organisms provides assessors with risk scores for a species under current and future climate change conditions that, following a statistically based calibration, permits the accurate classification of species into high-, medium- and low-risk categories under current and predicted climate conditions. The 1730 screenings undertaken encompassed wide geographical areas (regions, political entities, parts thereof, water bodies, river basins, lake drainage basins, and marine regions), which permitted thresholds to be identified for almost all aquatic organismal groups screened as well as for tropical, temperate and continental climate classes, and for tropical and temperate marine ecoregions. In total, 33 species were identified as posing a ‘very high risk’ of being or becoming invasive, and the scores of several of these species under current climate increased under future climate conditions, primarily due to their wide thermal tolerances. The risk thresholds determined for taxonomic groups and climate zones provide a basis against which area-specific or climate-based calibrated thresholds may be interpreted. In turn, the risk rankings help decision-makers identify which species require an immediate ‘rapid’ management action (e.g. eradication, control) to avoid or mitigate adverse impacts, which require a full risk assessment, and which are to be restricted or banned with regard to importation and/or sale as ornamental or aquarium/fishery enhancement.publishedVersio