miR-346 controls release of TNF-alpha protein and stability of its mRNA in rheumatoid arthritis via tristetraprolin stabilization

TNF-alpha is a major cytokine implicated in rheumatoid arthritis. Its expression is regulated both at the transcriptional and posttranscriptional levels and recent data demonstrated that miRNAs are implicated in TNF-alpha response in macrophages. LPS-activated FLS isolated from RA patients express TNF-alpha mRNA but not the mature protein. This prompted us to look for miRNAs which could be implicated in this anti-inflammatory effect. Using a microarray, we found two miRNAs, miR-125b and miR-939 predicted to target the 3'-UTR of TNF-alpha mRNA, to be up-regulated in RA FLS in response to LPS, but their repression did not restore mature TNF-alpha expression in FLS. We showed previously that miR-346, which is upregulated in LPS-activated FLS, inhibited Btk expression that stabilized TNF-alpha mRNA. Blocking miR-346 reestablished TNF-alpha expression in activated FLS. Interestingly, transfection of miR-346 in LPS-activated THP-1 cells inhibited TNF-alpha secretion. We also demonstrated that TTP, a RNA binding protein which inhibited TNF-alpha synthesis, is overexpressed in activated FLS and that inhibition of miR-346 decreases its expression. Conversely, transfection of miR-346 in LPS-activated THP-1 cells increased TTP mRNA expression and inhibited TNF-alpha release. These results indicate that miR-346 controls TNF-alpha synthesis by regulating TTP expression

Da doença ao milagre: etnografia de soluções terapêuticas entre evangélicos na cidade de Boa Vista, Roraima

São várias as possibilidades de articulação entre doença, religião e cura. O artigo em questão constitui uma análise de narrativas sobre doença e cura pela religião, realizada a partir de abordagem etnográfica em 10 bairros de Boa Vista, Roraima, com indivíduos que afirmaram terem sido curados através de intervenção divina. Os resultados mostram que a doença não se reduz aos sintomas físicos universais da realidade empírica. Rituais mágicos de cura são, também, caminhos abertos à sua interpretação

The ICON Earth System Model Version 1.0

This work documents ICON-ESM 1.0, the first version of a coupled model based 19 on the ICON framework 20 • Performance of ICON-ESM is assessed by means of CMIP6 DECK experiments 21 at standard CMIP-type resolution 22 • ICON-ESM reproduces the observed temperature evolution. Biases in clouds, winds, 23 sea-ice, and ocean properties are larger than in MPI-ESM. Abstract 25 This work documents the ICON-Earth System Model (ICON-ESM V1.0), the first cou-26 pled model based on the ICON (ICOsahedral Non-hydrostatic) framework with its un-27 structured, icosahedral grid concept. The ICON-A atmosphere uses a nonhydrostatic dy-28 namical core and the ocean model ICON-O builds on the same ICON infrastructure, but 29 applies the Boussinesq and hydrostatic approximation and includes a sea-ice model. The 30 ICON-Land module provides a new framework for the modelling of land processes and 31 the terrestrial carbon cycle. The oceanic carbon cycle and biogeochemistry are repre-32 sented by the Hamburg Ocean Carbon Cycle module. We describe the tuning and spin-33 up of a base-line version at a resolution typical for models participating in the Coupled 34 Model Intercomparison Project (CMIP). The performance of ICON-ESM is assessed by 35 means of a set of standard CMIP6 simulations. Achievements are well-balanced top-of-36 atmosphere radiation, stable key climate quantities in the control simulation, and a good 37 representation of the historical surface temperature evolution. The model has overall bi-38 ases, which are comparable to those of other CMIP models, but ICON-ESM performs 39 less well than its predecessor, the Max Planck Institute Earth System Model. Problem-40 atic biases are diagnosed in ICON-ESM in the vertical cloud distribution and the mean 41 zonal wind field. In the ocean, sub-surface temperature and salinity biases are of con-42 cern as is a too strong seasonal cycle of the sea-ice cover in both hemispheres. ICON-43 ESM V1.0 serves as a basis for further developments that will take advantage of ICON-44 specific properties such as spatially varying resolution, and configurations at very high 45 resolution. 46 Plain Language Summary 47 ICON-ESM is a completely new coupled climate and earth system model that ap-48 plies novel design principles and numerical techniques. The atmosphere model applies 49 a non-hydrostatic dynamical core, both atmosphere and ocean models apply unstruc-50 tured meshes, and the model is adapted for high-performance computing systems. This 51 article describes how the component models for atmosphere, land, and ocean are cou-52 pled together and how we achieve a stable climate by setting certain tuning parameters 53 and performing sensitivity experiments. We evaluate the performance of our new model 54 by running a set of experiments under pre-industrial and historical climate conditions 55 as well as a set of idealized greenhouse-gas-increase experiments. These experiments were 56 designed by the Coupled Model Intercomparison Project (CMIP) and allow us to com-57 pare the results to those from other CMIP models and the predecessor of our model, the 58 Max Planck Institute for Meteorology Earth System Model. While we diagnose overall 59 satisfactory performance, we find that ICON-ESM features somewhat larger biases in 60 several quantities compared to its predecessor at comparable grid resolution. We empha-61 size that the present configuration serves as a basis from where future development steps 62 will open up new perspectives in earth system modellin

Efeitos tecnológicos e estruturais nas emissões brasileiras de CO2 para o período 2000 a 2005: uma abordagem de análise de decomposição estrutural (SDA)

Este artigo objetiva mensurar a influência de mudanças na estrutura produtiva sobre as variações nas emissões de dióxido de carbono brasileiras. O método utilizado foi o de análise de decomposição estrutural (SDA - Structural Decomposition Analysis). Trata-se de um método de insumo-produto, logo de estática comparativa, que permite detalhar as mudanças tanto tecnológicas quanto no processo produtivo em termos setoriais. As emissões setoriais foram obtidas junto ao balanço de emissões, energias equivalente e final, e as matrizes IBGE de insumo-produto são provenientes do Sistema de Contas Nacionais do IBGE, ambas para os anos de 2000 e 2005, sendo adaptadas para 15 setores econômicos brasileiros. Os principais resultados indicam que: os setores de transportes, siderurgia e alimentos e bebidas são aqueles que se mostraram mais propensos ao aumento de emissões quando considerada a variação na demanda final, enquanto os setores indústria do cimento, de minerais não metálicos e papel e celulose se destacam por redução de emissões devido à mudança tecnológica

Variation in response to Alternaria carthami infection by a range of safflower (Carthamus tinctorius) varieties

Abstract Twenty safflower (Carthamus tinctorius) varieties were tested for their response to the fungal pathogen Alternaria carthami. The varieties tested represented a selection of domestic and international varieties, both hybrid and open pollinated, including the standard Australian variety Sironaria. An isolate of Alternaria carthami was selected from the New South Wales fungal germplasm bank at Tamworth as representing the region where most safflower is currently grown. The plants were inoculated using agar slabs at the sixth leaf stage. Leaf lesions were assessed six and twelve days after inoculation. Variation in the level of infection was observed among the varieties tested. Two varieties, namely UC1 and 120045 had a 100% mortality rate, whilst the lowest levels of infection were recorded in S501, Saffire, C01, Sironaria, S555 and S8154. Of these varieties Sironaria, Saffire and S555 have been reported as having promising marketability characteristics, and therefore have good potential for south-eastern Australia. The variation in infection levels present within the varieties tested also demonstrates that different levels of resistance are present within the plant population. Breeding for resistance in the future should be a priority if infection by A. carthami is to be minimised in commercial production

Size-Dependent Lipid Content in Human Milk Fat Globules Characterized by Laser Trap Raman Spectroscopy

Argov N, Wachsmann-Hogui S, Freeman SL, Huser T, Lebrilla CB, German JB. Size-Dependent Lipid Content in Human Milk Fat Globules Characterized by Laser Trap Raman Spectroscopy. J. Agric. Food Chem. 2008;56(16):7446-7450