Characterization of SMG-9, an essential component of the nonsense-mediated mRNA decay SMG1C complex

SMG-9 is part of a protein kinase complex, SMG1C, which consists of the SMG-1 kinase, SMG-8 and SMG-9. SMG1C mediated phosphorylation of Upf1 triggers nonsense-mediated mRNA decay (NMD), a eukaryotic surveillance pathway that detects and targets for degradation mRNAs harboring premature translation termination codons. Here, we have characterized SMG-9, showing that it comprises an N-terminal 180 residue intrinsically disordered region (IDR) followed by a well-folded C-terminal domain. Both domains are required for SMG-1 binding and the integrity of the SMG1C complex, whereas the C-terminus is sufficient to interact with SMG-8. In addition, we have found that SMG-9 assembles in vivo into SMG-9:SMG-9 and, most likely, SMG-8:SMG-9 complexes that are not constituents of SMG1C. SMG-9 self-association is driven by interactions between the C-terminal domains and surprisingly, some SMG-9 oligomers are completely devoid of SMG-1 and SMG-8. We propose that SMG-9 has biological functions beyond SMG1C, as part of distinct SMG-9-containing complexes. Some of these complexes may function as intermediates potentially regulating SMG1C assembly, tuning the activity of SMG-1 with the NMD machinery. The structural malleability of IDRs could facilitate the transit of SMG-9 through several macromolecular complexes

Caracterização dos quintais agroflorestais urbanos na cidade de Alta Floresta-MT

O presente estudo teve por objetivo caracterizar os quintais agroflorestais urbanos, no município de Alta Floresta-MT, Brasil. Foram entrevistados 30 mantenedores utilizando entrevistas semiestruturadas. Os quintais possuem área média de 1,28 ha. O tempo médio de ocupação dos quintais é de 15 anos. Nenhum informante soube responder o que é um quintal agroflorestal. As espécies vegetais nos quintais possuem diversas origens. A periodicidade da manutenção dos quintais é diária. As tratos culturas são poda, desbrota, adubação, controle de formigas e cupins. Utilizam-se adubos químicos e agrotóxicos para o controle de espécies espontâneas, de insetos e doenças. Há criação de animais, além da presença de animais silvestres. Observou-se heterogeneidade na caracterização dos quintais agroflorestais urbanos.This study aimed to characterize urban agroforestry gardens and the profile of the maintainers of these, in the municipality of Alta Floresta-MT, Brazil. Thirty maintainers were interviewed using semi-structured interviews. The gardens have an average area of 1.28 ha. The average time of occupancy of the yards is 15 years. No informant could answer what is an agroforestry yard. Plant species in backyards have diverse origins. The frequency of maintenance of gardens is daily. Culture treatments are pruning, thinning, fertilization, ant control and termites. Chemical fertilizers and pesticides are used for the control of spontaneous species of insects and diseases. There are farm animals and the presence of wild animals. There was heterogeneity in the characterization of urban agroforestry yards.Eje A5: Sistemas de conocimientoFacultad de Ciencias Agrarias y Forestale

Caracterização dos quintais agroflorestais urbanos na cidade de Alta Floresta-MT

O presente estudo teve por objetivo caracterizar os quintais agroflorestais urbanos, no município de Alta Floresta-MT, Brasil. Foram entrevistados 30 mantenedores utilizando entrevistas semiestruturadas. Os quintais possuem área média de 1,28 ha. O tempo médio de ocupação dos quintais é de 15 anos. Nenhum informante soube responder o que é um quintal agroflorestal. As espécies vegetais nos quintais possuem diversas origens. A periodicidade da manutenção dos quintais é diária. As tratos culturas são poda, desbrota, adubação, controle de formigas e cupins. Utilizam-se adubos químicos e agrotóxicos para o controle de espécies espontâneas, de insetos e doenças. Há criação de animais, além da presença de animais silvestres. Observou-se heterogeneidade na caracterização dos quintais agroflorestais urbanos.This study aimed to characterize urban agroforestry gardens and the profile of the maintainers of these, in the municipality of Alta Floresta-MT, Brazil. Thirty maintainers were interviewed using semi-structured interviews. The gardens have an average area of 1.28 ha. The average time of occupancy of the yards is 15 years. No informant could answer what is an agroforestry yard. Plant species in backyards have diverse origins. The frequency of maintenance of gardens is daily. Culture treatments are pruning, thinning, fertilization, ant control and termites. Chemical fertilizers and pesticides are used for the control of spontaneous species of insects and diseases. There are farm animals and the presence of wild animals. There was heterogeneity in the characterization of urban agroforestry yards.Eje A5: Sistemas de conocimientoFacultad de Ciencias Agrarias y Forestale

Measurement of the Lifetime Difference Between B_s Mass Eigenstates

We present measurements of the lifetimes and polarization amplitudes for B_s --> J/psi phi and B_d --> J/psi K*0 decays. Lifetimes of the heavy (H) and light (L) mass eigenstates in the B_s system are separately measured for the first time by determining the relative contributions of amplitudes with definite CP as a function of the decay time. Using 203 +/- 15 B_s decays, we obtain tau_L = (1.05 +{0.16}/-{0.13} +/- 0.02) ps and tau_H = (2.07 +{0.58}/-{0.46} +/- 0.03) ps. Expressed in terms of the difference DeltaGamma_s and average Gamma_s, of the decay rates of the two eigenstates, the results are DeltaGamma_s/Gamma_s = (65 +{25}/-{33} +/- 1)%, and DeltaGamma_s = (0.47 +{0.19}/-{0.24} +/- 0.01) inverse ps.Comment: 8 pages, 3 figures, 2 tables; as published in Physical Review Letters on 16 March 2005; revisions are for length and typesetting only, no changes in results or conclusion

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Liming on picloram leaching in dystrophic Red Yellow Latosol

ABSTRACT The practice of liming may influence the leaching of herbicides in soils, especially those with weak acid character, such as picloram. The study on leaching, preserving soil structure, is an important factor when one intends to understand the dynamics of herbicides and environmental impacts. Thus, the effect of liming on picloram leaching in a dystrophic Red Yellow Latosol under field conditions was studied using a bioindicator plant. The experiment was set up in a completely randomized design (CRD), in split-plot scheme, with factorial in the plot. The factors of the plot corresponded to two soil conditions (presence and absence of liming) and 5 picloram concentrations (0; 384; 768; 1152; 1536 g ha-1), and the factor of the subplot was 5 soil depths (0-8, 8-16, 16-24, 24-32 and 32-40 cm), with four replicates. Pipes were introduced into the soil and, in part of the treatments, limestone was applied superficially. After ninety days, the different doses of picloram were applied on the surface of each pipe and these pipes were withdrawn after an accumulated rainfall of 128 mm, to perform the bioassay using cucumber plants (Cucumis sativus). Evaluations of plant development (phytotoxicity and shoot biomass) were carried out 21 days after sowing. It was concluded that picloram showed high leaching rate under all studied conditions and liming increased picloram leaching at doses lower than 768 g ha-1