Jasmonate and auxin perception : how plants keep F-boxes in check

Phytohormones regulate the plasticity of plant growth and development, and responses to biotic and abiotic stresses. Many hormone signal transduction cascades involve ubiquitination and subsequent degradation of proteins by the 26S proteasome. The conjugation of ubiquitin to a substrate is facilitated by the E1 activating, E2 conjugating, and the substrate-specifying E3 ligating enzymes. The most prevalent type of E3 ligase in plants is the Cullin-RING ligase (CRL)-type, with F-box proteins (FBPs) as the substrate recognition component. The activity of these SKP-Cullin-F-box (SCF) complexes needs to be tightly regulated in time and place. Here, we review the regulation of SCF function in plants on multiple levels, with a focus on the auxin and jasmonate SCF-type receptor complexes. We discuss in particular the relevance of protein-protein interactions and post-translational modifications as mechanisms to keep SCF functioning under control. Additionally, we highlight the unique property of SCFTIR1/AFB and SCFCOI1 to recognize substrates by forming co-receptor complexes. Finally, we explore how engineered selective agonists can be used to study and uncouple the outcomes of the complex auxin and jasmonate signaling networks that are governed by these FBPs

The transcriptional repressor complex FRS7-FRS12 regulates flowering time and growth in Arabidopsis

Most living organisms developed systems to efficiently time environmental changes. The plant-clock acts in coordination with external signals to generate output responses determining seasonal growth and flowering time. Here, we show that two Arabidopsis thaliana transcription factors, FAR1 RELATED SEQUENCE 7 (FRS7) and FRS12, act as negative regulators of these processes. These proteins accumulate particularly in short-day conditions and interact to form a complex. Loss-of-function of FRS7 and FRS12 results in early flowering plants with overly elongated hypocotyls mainly in short days. We demonstrate by molecular analysis that FRS7 and FRS12 affect these developmental processes in part by binding to the promoters and repressing the expression of GIGANTEA and PHYTOCHROME INTERACTING FACTOR 4 as well as several of their downstream signalling targets. Our data reveal a molecular machinery that controls the photoperiodic regulation of flowering and growth and offer insight into how plants adapt to seasonal changes

Inactivation of nuclear factor-Y inhibits vascular smooth muscle cell proliferation and neointima formation

OBJECTIVE: Atherosclerosis and restenosis are multifactorial diseases associated with abnormal vascular smooth muscle cell (VSMC) proliferation. Nuclear factor-Y (NF-Y) plays a major role in transcriptional activation of the CYCLIN B1 gene (CCNB1), a key positive regulator of cell proliferation and neointimal thickening. Here, we investigated the role of NF-Y in occlusive vascular disease. APPROACH AND RESULTS: We performed molecular and expression studies in cultured cells, animal models, and human tissues. We find upregulation of NF-Y and cyclin B1 expression in proliferative regions of murine atherosclerotic plaques and mechanically induced lesions, which correlates with higher binding of NF-Y to target sequences in the CCNB1 promoter. NF-YA expression in neointimal lesions is detected in VSMCs, macrophages, and endothelial cells. Platelet-derived growth factor-BB, a main inductor of VSMC growth and neointima development, induces the recruitment of NF-Y to the CCNB1 promoter and augments both CCNB1 mRNA expression and cell proliferation through extracellular signal-regulated kinase 1/2 and Akt activation in rat and human VSMCs. Moreover, adenovirus-mediated overexpression of a NF-YA-dominant negative mutant inhibits platelet-derived growth factor-BB-induced CCNB1 expression and VSMC proliferation in vitro and neointimal lesion formation in a mouse model of femoral artery injury. We also detect NF-Y expression and DNA-binding activity in human neointimal lesions. CONCLUSIONS: Our results identify NF-Y as a key downstream effector of the platelet-derived growth factor-BB-dependent mitogenic pathway that is activated in experimental and human vasculoproliferative diseases. They also identify NF-Y inhibition as a novel and attractive strategy for the local treatment of neointimal formation induced by vessel denudation.This study was funded by the Spanish Ministry of Economy and Competiveness (MINECO; grants SAF2010-16044, SAF200911949), Instituto de Salud Carlos III (ISCIII; grants RD12/0042/0021, RD12/0042/0028, RD12/0042/0053), and the Dr Léon Dumont Prize 2010 by the Belgian Society of Cardiology (to Vicente Andrés). Patricia Fernández received salary support from ISCIII and Carlos Silvestre-Roig from Fundación Mario Losantos del Campo and Fundación Ferrer para la Investigación. Óscar M. Pello and Ricardo Rodríguez-Calvo hold a Juan de la Cierva contract from MINECO. Vanesa Esteban is an investigator of the Sara Borell program from ISCIII (CD06/00232). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by MINECO and Pro-CNIC Foundation.S

Ludificación de la Historia de Veterinaria

En este proyecto se han realizado ocho interpretaciones histórico-teatrales de personajes relevantes en la historia de la veterinaria, realizada por los propios alumnos matriculados y profesores, para facilitar el conocimiento de aspectos personales, profesionales y sociales de la Veterinaria en distintas épocas

Thirty-day outcomes in frail older patients discharged home from the emergency department with acute heart failure: effects of high-risk criteria identified by the DEED FRAIL-AHF trial

Objectives: To study the effect of high-risk criteria on 30-day outcomes in frail older patients with acute heart failure (AHF) discharged from an emergency department (ED) or an ED's observation and short-stay areas. Material and methods: Secondary analysis of discharge records in the Older AHF Key Data registry. We selected frail patients (aged > 70 years) discharged with AHF from EDs. Risk factors were categorized as modifiable or nonmodifiable. The outcomes were a composite endpoint for a cardiovascular event (revisits for AHF, hospitalization for AHF, or cardiovascular death) and the number of days alive out-of-hospital (DAOH) within 30 days of discharge. Results: We included 380 patients with a mean (SD) age of 86 (5.5) years (61.2% women). Modifiable risk factors were identified in 65.1%, nonmodifiable ones in 47.8%, and both types in 81.6%. The 30-day cardiovascular composite endpoint occurred in 83 patients (21.8%). The mean 30-day DAOH observed was 27.6 (6.1) days. Highrisk factors were present more often in patients who developed the cardiovascular event composite endpoint: the rates for patients with modifiable, nonmodifiable, or both types of risk were, respectively, as follows in comparison with patients not at high risk: 25.0% vs 17.2%, P = .092; 27.6% vs 16.7%, P = .010; and 24.7% vs 15.2%, P = .098). The 30-day DAOH outcome was also lower for at-risk patients, according to type of risk factor present: modifiable, 26.9 (7.0) vs 28.4 (4.4) days, P = .011; nonmodifiable, 27.1 (7.0) vs 28.0 (5.0) days, P = .127; and both, 27.1 (6.7) vs 28.8 (3.4) days, P = .005). After multivariate analysis, modifiable risk remained independently associated with fewer days alive (adjusted absolute difference in 30-day DAOH, -1.3 days (95% CI, -2.7 to -0.1 days). Nonmodifiable factors were associated with increased risk for the 30-day cardiovascular composite endpoint (adjusted absolute difference, 10.4%; 95% CI, -2.1% to 18.7%). Conclusion: Risk factors are common in frail elderly patients with AHF discharged home from hospital ED areas. Their presence is associated with a worse 30-day prognosis

Deliverable 3.6 zoning plan of case studies : evaluation of spatial management options for the case studies

Within MESMA, nine case studies (CS) represent discrete marine European spatial entities, at different spatial scales, where a spatial marine management framework is in place, under development or considered. These CS (described in more details below) are chosen in such a way (MESMA D. 3.1 ) that they encompass the complexity of accommodating the various user functions of the marine landscape in various regions of the European marine waters. While human activities at sea are competing for space, there is also growing awareness of the possible negative effects of these human activities on the marine ecosystem. As such, system specific management options are required, satisfying current and future sectoral needs, while safeguarding the marine ecosystem from further detoriation. This integrated management approach is embedded in the concept of ecosystem based management (EBM). The goal of marine EBM is to maintain marine ecosystems in a healthy, productive and resilient condition, making it possible that they sustain human use and provide the goods and services required by society (McLeod et al. 2005). Therefore EBM is an environmental mangagement approach that recognises the interactions within a marine ecosystem, including humans. Hence, EBM does not consider single issues, species or ecosystems good and services in isolation. Operationalisation of EBM can be done through place-based or spatial management approaches (Lackey 1998), such as marine spatial planning (MSP). MSP is a public process of analysing and allocating the spatial and temporal distribution of human activities aiming at achieving ecological, economic and social objectives. These objectives are usually formulated through political processes (Douvere et al. 2007, Douvere 2008). Within MESMA, a spatially managed area (SMA) is then defined as “a geographical area within which marine spatial planning initiatives exist in the real world”. Marine spatial planning initiatives refer to existing management measures actually in place within a defined area, or in any stage of a process of putting management in place, e.g. plans or recommendations for a particular area. Management can include management for marine protection (e.g. in MPAs), or management for sectoral objectives (e.g. building a wind farm to meet renewable energy objectives). Within MESMA, SMAs can have different spatial scales. A SMA can be a small, specific area that is managed/planned to be managed for one specific purpose, but it can also be a larger area within which lots of plans or ‘usage zones’ exist. This definition is different from the definition mentioned in the DoW (page 60). The original definition was adapted during a CS leader workshop (2-4 May 2012 in Gent, Belgium) and formally accepted by the MESMA ExB during the ExB meeting in Cork (29-30 May 2012). MSP should result in a marine spatial management plan that will produce the desired future trough explicit decisions about the location and timing of human activities. Ehler & Douvere (2009) consider this spatial management as a beginning toward the the implementation of desired goals and objectives. They describe the spatial management plan as a comprehensive, strategic document that provides the framework and direction for marine spatial management decisions. The plan should identify when, where and how goals and objectives will be met. Zoning (the development of zoning plans) is often an important management measure to implement spatial management plans. The purpose of a zoning plan (Ehler & Douvere 2009) is: To provide protection for biologically and ecologically important habitats, ecosystems, and ecological processes. To seperate conflicting human activities, or to combine compatible activities. To protect the natural values of the marine management area (in MESMA terminology: the SMA) while allowing reasonable human uses of the area. To allocate areas for reasonable human uses while minimising the effects of these human uses on each other, and nature. To preserve some areas of the SMA in their natural state undisturbed by humans except for scientific and educational purposes.peer-reviewe

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: A nationwide study in Spain

Objective To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. Settings The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. Participants This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. Interventions An exploratory factorial analysis was performed to select the most relevant variables of the sample. Primary and secondary outcome measures Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. Results Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/10 5 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade =3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/10 5 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. Conclusions Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/10 5 people/week) was a statistically independent predictor of mortality. Trial registration number CEIM 20/217

Jardins per a la salut

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia. Assignatura: Botànica farmacèutica. Curs: 2014-2015. Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són el recull de les fitxes botàniques de 128 espècies presents en el Jardí Ferran Soldevila de l’Edifici Històric de la UB. Els treballs han estat realitzats manera individual per part dels estudiants dels grups M-3 i T-1 de l’assignatura Botànica Farmacèutica durant els mesos de febrer a maig del curs 2014-15 com a resultat final del Projecte d’Innovació Docent «Jardins per a la salut: aprenentatge servei a Botànica farmacèutica» (codi 2014PID-UB/054). Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pels professors de l’assignatura. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica. També s’ha pretès motivar els estudiants a través del retorn de part del seu esforç a la societat a través d’una experiència d’Aprenentatge-Servei, deixant disponible finalment el treball dels estudiants per a poder ser consultable a través d’una Web pública amb la possibilitat de poder-ho fer in-situ en el propi jardí mitjançant codis QR amb un smartphone

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline