PEST sequences from a cactus dehydrin regulate its proteolytic degradation

Dehydrins (DHNs) are intrinsically disordered proteins expressed under cellular dehydration-related stresses. In this study, we identified potential proteolytic PEST sequences located at the central and C-terminal regions from the Opuntia streptacantha OpsDHN1 protein. In order to evaluate these PEST sequences as proteolytic tags, we generated a translational fusion with the GUS reporter protein and OpsDHN1 coding sequence. We found a GUS degradation effect in tobacco agro-infiltrated leaves and Arabidopsis transgenic lines that expressed the fusion GUS::OpsDHN1 full-length. Also, two additional translational fusions between OpsDHN1 protein fragments that include the central (GUS::PEST-1) or the C-terminal (GUS::PEST-2) PEST sequences were able to decrease the GUS activity, with PEST-2 showing the greatest reduction in GUS activity. GUS signal was abated when the OpsDHN1 fragment that includes both PEST sequences (GUS::PEST-1-2) were fused to GUS. Treatment with the MG132 proteasome inhibitor attenuated the PEST-mediated GUS degradation. Point mutations of phosphorylatable residues in PEST sequences reestablished GUS signal, hence these sequences are important during protein degradation. Finally, in silico analysis identified potential PEST sequences in other plant DHNs. This is the first study reporting presence of PEST motifs in dehydrins

Influence of MUC5B gene on antisynthetase syndrome

ABSTRACT: MUC5B rs35705950 (G/T) is strongly associated with idiopathic pulmonary fibrosis (IPF) and also contributes to the risk of interstitial lung disease (ILD) in rheumatoid arthritis (RA-ILD) and chronic hypersensitivity pneumonitis (CHP). Due to this, we evaluated the implication of MUC5B rs35705950 in antisynthetase syndrome (ASSD), a pathology characterised by a high ILD incidence. 160 patients with ASSD (142 with ILD associated with ASSD [ASSD-ILD+]), 232 with ILD unrelated to ASSD (comprising 161 IPF, 27 RA-ILD and 44 CHP) and 534 healthy controls were genotyped. MUC5B rs35705950 frequency did not significantly differ between ASSD-ILD+ patients and healthy controls nor when ASSD patients were stratified according to the presence/absence of anti Jo-1 antibodies or ILD. No significant differences in MUC5B rs35705950 were also observed in ASSD-ILD+ patients with a usual interstitial pneumonia (UIP) pattern when compared to those with a non-UIP pattern. However, a statistically significant decrease of MUC5B rs35705950 GT, TT and T frequencies in ASSD-ILD+ patients compared to patients with ILD unrelated to ASSD was observed. In summary, our study does not support a role of MUC5B rs35705950 in ASSD. It also indicates that there are genetic differences between ILD associated with and that unrelated to ASSD.We are indebted to the patients and healthy controls for their essential collaboration to this study. We also thank the National DNA Bank Repository (Salamanca) for supplying part of the control samples. This study was partially supported by grants from the Foundation for Research in Rheumatology (FOREUM). RL-M is a recipient of a Miguel Servet type I programme fellowship from the ‘Instituto de Salud Carlos III’ (ISCIII), co-funded by the European Social Fund (ESF, ‘Investing in your future’) (grant CP16/00033). SR-M is supported by funds of the RETICS Program (RD16/0012/0009), co-funded by the European Regional Development Fund (ERDF). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). VM is supported by funds of a Miguel Servet type I programme (grant CP16/00033) (ISCIII, co-funded by ESF). LL-G is supported by funds of PI18/00042 (ISCIII, co-funded by ERDF). OG is Staff Personnel of Xunta de Galicia (Servizo Galego de Saude, SERGAS) through a research-staff stabilization contract (ISCIII/SERGAS). OG,is member of RETICS Programme, RD16/0012/0014 (RIER: Red de Investigación en Inflamación y Enfermedades Reumáticas) via Instituto de Salud Carlos III (ISCIII) and FEDER. The work of OG (PI17/00409), was funded by Instituto de Salud Carlos III and FEDER. OG is a beneficiary of a project funded by Research Executive Agency of the European Union in the framework of MSCA-RISE Action of the H2020 Programme (Project number 734899). OG is beneficiary of a grant funded by Xunta de Galicia, Consellería de Educación, Universidade e Formación Profesional and Consellería de Economía, Emprego e Industria (GAIN), GPC IN607B2019/10

Ética profesional en educación superior : finalidades, estrategias y desafíos de la formación

Todo proyecto educativo que no responde a su época se expone a problemas de legitimidad y al duro escrutinio y sanción de los usuarios. Las instituciones de educación superior no son la excepción de esta premisa clásica, incluso más validada por eldinamismos, la versatilidad y ojo crítico en el mundo contemporáneo. La ética se ha convertido en el baremo principal para someter a juicio a las instituciones y a las personas que ahí actuan, como a las finalidades que se pretenden en sus acciones. En esta perspectiva, debe examinarse la función de las instituciones de educación superior.Este libro es el esfuerzo colectivo por acercarnos a esa problemática, en especial a las finalidades, estrategias y relaciones en juego para cumplir la tarea de la formación y sus nexos inevitables con la ética profesional

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

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

Çédille, revista de estudios franceses

Presentació

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Oral Manifestations Associated with HIV/AIDS Patients

Oral manifestations are early and important clinical indicators of Human Immunodeficiency Virus (HIV) infection since they can occur in up to 50% of HIV-infected patients and in up to 80% of patients at the AIDS stage (&lt;200 CD4+ T lymphocytes). Oral health is related to physical and mental well-being because the presence of some lesions can compromise dental aesthetics, and alter speech, chewing, and swallowing, thus impacting the quality of life of patients. For this reason, it is necessary to integrate, as part of the medical treatment of HIV-positive patients, the prevention, diagnosis, and control of oral health. It is essential that health professionals have the power to identify, diagnose, and treat oral pathologies through clinical characteristics, etiological agents, and risk factors, both local and systemic. A diagnosis at an early stage of injury allows optimizing and prioritizing oral treatments, especially in acute pathologies, such as gingivitis and necrotizing periodontitis. In this group of patients, the development of strategies for the prevention, control, and reduction of these pathologies must be prioritized in order to reduce morbidity and mortality in this group of patients