Transcription factor NRF2 protects mice against dietary iron-induced liver injury by preventing hepatocytic cell death

BACKGROUND & AIMS: The liver, being the major site of iron storage, is particularly exposed to the toxic effects of iron. Transcription factor NRF2 is critical for protecting the liver against disease by activating the transcription of genes encoding detoxification/antioxidant enzymes. We aimed to determine if the NRF2 pathway plays a significant role in the protection against hepatic iron overload.METHODS: Wild-type and Nrf2(-/-) mouse primary hepatocytes were incubated with ferric ammonium citrate. Wild-type and Nrf2(-/-) mice were fed standard rodent chow or iron-rich diet for 2weeks, with or without daily injection of the antioxidant mito-TEMPOL.RESULTS: In mouse hepatocytes, iron induced the nuclear translocation of NRF2 and the expression of cytoprotective genes in an NRF2-dependent manner. Moreover, Nrf2(-/-) hepatocytes were highly susceptible to iron-induced cell death. Wild-type and Nrf2(-/-) mice fed iron-rich diet accumulated similar amounts of iron in the liver and were equally able to increase the expression of hepatic hepcidin and ferritin. Nevertheless, in Nrf2-null mice the iron loading resulted in progressive liver injury, ranging from mild confluent necrosis to severe necroinflammatory lesions. Hepatocytic cell death was associated with gross ultrastructural damage to the mitochondria. Notably, liver injury was prevented in iron-fed animals that received mito-TEMPOL.CONCLUSIONS: NRF2 protects the mouse liver against the toxicity of dietary iron overload by preventing hepatocytic cell death. We identify NRF2 as a potential modifier of liver disease in iron overload pathology and show the beneficial effect of the antioxidant mito-TEMPOL in a mouse model of dietary iron-induced liver injury.This work is funded by FEDER Funds through the Operational Competitiveness Programme - COMPETE and by National Funds through FCT - Fundacao para a Ciencia e a Tecnologia under the project FCOMP-01-0124-FEDER-011062 (PTDC/SAU-FCF/101177/2008). TLD is supported by "Programa Ciencia - financiado pelo POPH - QREN - Tipologia 4.2 - Promocao do Emprego Cientifico, comparticipado pelo Fundo Social Europeu e por fundos nacionais do MCTES''

16th International Congress on Antiphospholipid Antibodies Task Force Report on Antiphospholipid Syndrome Treatment Trends

Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent antiphospholipid antibodies. The 16th International Congress on Antiphospholipid Antibodies Task Force on APS Treatment Trends reviewed the current status with regard to existing and novel treatment trends for APS, which is the focus of this Task Force report. The report addresses current treatments and developments since the last report, on the use of direct oral anticoagulants in patients with APS, antiplatelet agents, adjunctive therapies (hydroxychloroquine, statins and vitamin D), targeted treatment including rituximab, belimumab, and anti-TNF agents, complement inhibition and drugs based on peptides of beta-2-glycoprotein I. In addition, the report summarises potential new players, including coenzyme Q10, adenosine receptor agonists and adenosine potentiation. In each case, the report provides recommendations for clinicians, based on the current state of the art, and suggests a clinical research agenda. The initiation and development of appropriate clinical studies requires a focus on devising suitable outcome measures, including a disease activity index, an optimal damage index, and a specific quality of life index

Projecting coral responses to intensifying marine heatwaves under ocean acidification

Over this century, coral reefs will run the gauntlet of climate change, as marine heatwaves (MHWs) become more intense and frequent, and ocean acidification (OA) progresses. However, we still lack a quantitative assessment of how, and to what degree, OA will moderate the responses of corals to MHWs as they intensify throughout this century. Here, we first projected future MHW intensities for tropical regions under three future greenhouse gas emissions scenario (representative concentration pathways, RCP2.6, RCP4.5 and RCP8.5) for the near-term (2021-2040), mid-century (2041-2060) and late-century (2081-2100). We then combined these MHW intensity projections with a global data set of 1,788 experiments to assess coral attribute performance and survival under the three emissions scenarios for the near-term, mid-century and late-century in the presence and absence of OA. Although warming and OA had predominately additive impacts on the coral responses, the contribution of OA in affecting most coral attributes was minor relative to the dominant role of intensifying MHWs. However, the addition of OA led to greater decreases in photosynthesis and survival under intermediate and unrestricted emissions scenario for the mid- and late-century than if intensifying MHWs were considered as the only driver. These results show that role of OA in modulating coral responses to intensifying MHWs depended on the focal coral attribute and extremity of the scenario examined. Specifically, intensifying MHWs and OA will cause increasing instances of coral bleaching and substantial declines in coral productivity, calcification and survival within the next two decades under the low and intermediate emissions scenario. These projections suggest that corals must rapidly adapt or acclimatize to projected ocean conditions to persist, which is far more likely under a low emissions scenario and with increasing efforts to manage reefs to enhance resilience

The role of the freshwater shrimp atyaephyra desmarestii in leaf litter breakdown in streams

This version does not correspond to the published one. To access the final version go to: http://www.springerlink.com/content/a31518u452m03286/In aquatic ecosystems, microorganisms and invertebrates provide critical links between plant detritus and higher trophic levels. Atyaephyra desmarestii is an omnivorous decapod that inhabits freshwaters and exhibits high tolerance to temperature oscillations and high ability to colonize new habitats. Although A. desmarestii is able to ingest a variety of foods, few studies have been conducted to elucidate the role of this freshwater shrimp on detritus breakdown in streams. In this study, A. desmarestii was allowed to feed on conditioned or unconditioned alder and eucalyptus leaves in microcosms with or without access to its fecal pellets. At the end of the experiment, total body length of the animals was measured, and the remaining leaves and fecal pellets were used for dry mass quantification and assessment of bacterial and fungal diversity by denaturing gradient gel electrophoresis (DGGE). Cluster analyses of DGGE fingerprints indicated that the major differences in microbial communities on leaves were between leaf types, while on fecal pellets were between conditioned and unconditioned leaves. However, the consumption rate by the shrimp did not differ between leaf types, and was significantly higher on leaves conditioned by microorganisms and in treatments without access to feces. In treatments without access to feces, the production of feces and fine particulate organic matter was also significantly higher for conditioned leaves. Overall, our results support the feeding plasticity of A. desmarestii and its potential role in plant litter breakdown in streams. This might have implications for maintaining stream ecosystem functioning, particularly if more vulnerable shredders decline.The Portuguese Foundation for the Science and Technology supported S. Duarte (SFRH/BPD/47574/2008

Effect of Dysglycemia on Urinary Lipid Mediator Profiles in Persons With Pulmonary Tuberculosis

Background: Oxidized lipid mediators such as eicosanoids play a central role in the inflammatory response associated with tuberculosis (TB) pathogenesis. Diabetes mellitus (DM) leads to marked changes in lipid mediators in persons with TB. However, the associations between diabetes-related changes in lipid mediators and clearance of M. tuberculosis (Mtb) among persons on anti-TB treatment (ATT) are unknown. Quantification of urinary eicosanoid metabolites can provide insights into the circulating lipid mediators involved in Mtb immune responses. // Methods: We conducted a multi-site prospective observational study among adults with drug-sensitive pulmonary TB and controls without active TB; both groups had sub-groups with or without dysglycemia at baseline. Participants were enrolled from RePORT-Brazil (Salvador site) and RePORT-South Africa (Durban site) and stratified according to TB status and baseline glycated hemoglobin levels: a) TB-dysglycemia (n=69); b) TB-normoglycemia (n=64); c) non-TB/dysglycemia (n=31); d) non-TB/non-dysglycemia (n=29). We evaluated the following urinary eicosanoid metabolites: 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (major urinary metabolite of prostaglandin E2, PGE-M), tetranor-PGE1 (metabolite of PGE2, TN-E), 9α-hydroxy-11,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (metabolite of PGD2, PGD-M), 11-dehydro-thromboxane B2 (11dTxB2), 2,3-dinor-6-keto-PGF1α (prostaglandin I metabolite, PGI-M), and leukotriene E4 (LTE4). Comparisons between the study groups were performed at three time points: before ATT and 2 and 6 months after initiating therapy. // Results: PGE-M and LTE4 values were consistently higher at all three time-points in the TB-dysglycemia group compared to the other groups (p<0.001). In addition, there was a significant decrease in PGI-M and LTE4 levels from baseline to month 6 in the TB-dysglycemia and TB-normoglycemia groups. Finally, TB-dysglycemia was independently associated with increased concentrations of PGD-M, PGI-M, and LTE4 at baseline in a multivariable model adjusting for age, sex, BMI, and study site. These associations were not affected by HIV status. // Conclusion: The urinary eicosanoid metabolite profile was associated with TB-dysglycemia before and during ATT. These observations can help identify the mechanisms involved in the pathogenesis of TB-dysglycemia, and potential biomarkers of TB treatment outcomes, including among persons with dysglycemia

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

A study on the construct validity of the Parent-Child Conflict Tactics Scale (CTSPC) in an urban population in Northeast Brazil

The Parent-Child Conflict Tactics Scale (CTSPC) is one of the most widely used instruments in the world for investigating domestic violence against children, but targeted use has proven inadequate given the phenomenon's complexity. This study focused on the factor structure of CTSPC scales in an urban population in Northeast Brazil. We conducted a cross-sectional study in a cohort of 1,370 children in Salvador, Bahia State. Factor analysis with promax oblique rotation was performed, and the Kuder-Richardson coefficient was calculated. Factor analysis showed a different distribution of items in the factors as compared to the original instrument. Violence showed a gradual profile in each factor. The Kuder-Richardson coefficient was 0.63 for factor 1, 0.59 for factor 2, and 0.42 for factor 3. The items behaved differently from the original instrument, corroborating international studies. These findings support proposing a resizing of the CTSPC