Mitochondrial DNA disturbances and deregulated expression of oxidative phosphorylation and mitochondrial fusion proteins in sporadic inclusion body myositis

Sporadic inclusion body myositis (sIBM) is one of the most common myopathies in elderly people. Mitochondrial abnormalities at the histological level are present in these patients. We hypothesize that mitochondrial dysfunction may play a role in disease aetiology. We took the following measurements of muscle and peripheral blood mononuclear cells (PBMCs) from 30 sIBM patients and 38 age-and gender-paired controls: mitochondrial DNA (mtDNA) deletions, amount of mtDNA and mtRNA, mitochondrial protein synthesis, mitochondrial respiratory chain (MRC) complex I and IV enzymatic activity, mitochondrial mass, oxidative stress and mitochondrial dynamics (mitofusin 2 and optic atrophy 1 levels). Depletion of mtDNA was present in muscle from sIBM patients and PBMCs showed deregulated expression of mitochondrial proteins in oxidative phosphorylation. MRC complex IV/citrate synthase activity was significantly decreased in both tissues and mitochondrial dynamics were affected in muscle. Depletion of mtDNA was significantly more severe in patients with mtDNA deletions, which also presented deregulation of mitochondrial fusion proteins. Imbalance in mitochondrial dynamics in muscle was associated with increased mitochondrial genetic disturbances (both depletion and deletions), demonstrating that proper mitochondrial turnover is essential for mitochondrial homoeostasis and muscle function in these patients

Indicadors d'avaluació de les cures infermeres

Avaluació; Cures; InfermeriaEvaluation; Cares; NursingEvaluación; Cuidados; EnfermeríaEls professionals d’infermeria, pel rol significatiu que els atorguen les seves competències, han de poder avaluar de manera clara i transparent l’impacte de les cures que porten a terme sobre les persones, fent visible l’aportació professional a la salut de la població. Per això, és necessari que hi hagi informació suficient i contrastada per elaborar uns indicadors clau amb una visió comuna per a tot el sistema, que permetin conèixer els resultats sensibles a les accions pròpies dels infermers i les infermeres

Repeat-associated siRNAs cause chromatin silencing of retrotransposons in the Drosophila melanogaster germline

Silencing of genomic repeats, including transposable elements, in Drosophila melanogaster is mediated by repeat-associated short interfering RNAs (rasiRNAs) interacting with proteins of the Piwi subfamily. rasiRNA-based silencing is thought to be mechanistically distinct from both the RNA interference and microRNA pathways. We show that the amount of rasiRNAs of a wide range of retroelements is drastically reduced in ovaries and testes of flies carrying a mutation in the spn-E gene. To address the mechanism of rasiRNA-dependent silencing of retrotransposons, we monitored their chromatin state in ovaries and somatic tissues. This revealed that the spn-E mutation causes chromatin opening of retroelements in ovaries, resulting in an increase in histone H3 K4 dimethylation and a decrease in histone H3 K9 di/trimethylation. The strongest chromatin changes have been detected for telomeric HeT-A elements that correlates with the most dramatic increase of their transcript level, compared to other mobile elements. The spn-E mutation also causes depletion of HP1 content in the chromatin of transposable elements, especially along HeT-A arrays. We also show that mutations in the genes controlling the rasiRNA pathway cause no derepression of the same retrotransposons in somatic tissues. Our results provide evidence that germinal Piwi-associated short RNAs induce chromatin modifications of their targets

New environment, new invaders - repeated horizontal transfer of LINEs to sea snakes

While numerous studies have found horizontal transposon transfer (HTT) to be widespread across metazoans, few have focused on HTT in marine ecosystems. To investigate potential recent HTTs into marine species we searched for novel repetitive elements in sea snakes, a group of elapids which transitioned to a marine habitat at most 18 Mya. Our analysis uncovered repeated HTTs into sea snakes following their marine transition. The 7 subfamilies of horizontally transferred LINE retrotransposons we identified in the olive sea snake (Aipysurus laevis) are transcribed, and hence are likely still active and expanding across the genome. A search of 600 metazoan genomes found all 7 were absent from other amniotes, including terrestrial elapids, with the most similar LINEs present in fish and marine invertebrates. The one exception was a similar LINE found in sea kraits, a lineage of amphibious elapids which independently transitioned to a marine environment 25 Mya. Our finding of repeated horizontal transfer events into marine snakes greatly expands past findingst that the marine environment promotes the transfer of transposons. Transposons are drivers of evolution as sources of genomic sequence and hence genomic novelty. We identified 13 candidate genes for HTT-induced adaptive change based on internal or neighbouring HTT LINE insertions. One of these, ADCY4, is of particular interest as a part of the KEGG adaptation pathway "Circadian Entrainment". This provides evidence of the ecological interactions between species influencing evolution of metazoans not only through specific selection pressures, but also by contributing novel genomic material

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Differential clinical characteristics and prognosis of intraventricular conduction defects in patients with chronic heart failure

Intraventricular conduction defects (IVCDs) can impair prognosis of heart failure (HF), but their specific impact is not well established. This study aimed to analyse the clinical profile and outcomes of HF patients with LBBB, right bundle branch block (RBBB), left anterior fascicular block (LAFB), and no IVCDs. Clinical variables and outcomes after a median follow-up of 21 months were analysed in 1762 patients with chronic HF and LBBB (n = 532), RBBB (n = 134), LAFB (n = 154), and no IVCDs (n = 942). LBBB was associated with more marked LV dilation, depressed LVEF, and mitral valve regurgitation. Patients with RBBB presented overt signs of congestive HF and depressed right ventricular motion. The LAFB group presented intermediate clinical characteristics, and patients with no IVCDs were more often women with less enlarged left ventricles and less depressed LVEF. Death occurred in 332 patients (interannual mortality = 10.8%): cardiovascular in 257, extravascular in 61, and of unknown origin in 14 patients. Cardiac death occurred in 230 (pump failure in 171 and sudden death in 59). An adjusted Cox model showed higher risk of cardiac death and pump failure death in the LBBB and RBBB than in the LAFB and the no IVCD groups. LBBB and RBBB are associated with different clinical profiles and both are independent predictors of increased risk of cardiac death in patients with HF. A more favourable prognosis was observed in patients with LAFB and in those free of IVCDs. Further research in HF patients with RBBB is warranted

Minimum Bayes’ risk subsequence combination for machine translation

The final publication is available at Springer via http://dx.doi.org/10.1007/s10044-014-0387-5System combination has proved to be a successful technique in the pattern recognition field. However, several difficulties arise when combining the outputs of tasks, e.g. machine translation, that generate structured patterns. So far, machine translation system combination approaches either implement sophisticated classifiers to select one of the provided translations, or generate new sentences by combining the "best" subsequences of the provided translations. We present minimum Bayes' risk system combination (MBRSC), a system combination method for machine translation that gathers together the advantages of sentence-selection and subsequence-combination methods. MBRSC is able to detect and utilize the "best" subsequences of the provided translations to generate the optimal consensus translation with respect to a particular performance met- ric. Experiments show that MBRSC yields significant improvements in translation quality.Work supported by the EC (FEDER/FSE) and the Spanish MEC/MICINN under the MIPRCV "Consolider Ingenio 2010'' program (CSD2007-00018), the iTrans2 (TIN2009-14511) project, the UPV under Grant 20091027, the Spanish MITyC under the erudito.com (TSI-020110-2009-439) project and by the General-itat Valenciana under grant Prometeo/2009/014.Gonzalez Rubio, J.; Casacuberta Nolla, F. (2015). Minimum Bayes’ risk subsequence combination for machine translation. Pattern Analysis and Applications. 18(3):523-533. https://doi.org/10.1007/s10044-014-0387-5S52353318

The promoter of the TLC1.1 retrotransposon from Solanum chilense is activated by multiple stress-related signaling molecules

Marcela Salazar, Enrique González, José A. Casaretto, and Simón Ruiz-Lara. Instituto de Biología Vegetal y Biotecnología, Universidad de Talca, Casilla 747, Talca, ChileThe LTR retrotransposons are the most abundant mobile elements in the plant genome and seem to play an important role in genome reorganization induced by environmental challenges. Their success in this function depends on the ability of their promoters to respond to different signaling pathways that regulate plant adaptation to biotic and abiotic stresses. The promoter of the TLC1.1 retrotransposon from Solanum chilense contains two primary ethylene-responsive elements (PERE boxes) that are essential for its response to ethylene and for the stress-induced expression. Here, we describe that a 270 bp fragment (P270), derivative of this retroelement promoter, is also able to activate the transcription of the GUS reporter gene in transgenic plants in response to salicylic acid (SA), abscisic acid (ABA), methyl jasmonate (MeJA), hydrogen peroxide (H2O2) and the synthetic auxin 2,4-D. PERE box-dependent and independent routes are involved in the response of P270 to these signal molecules. MeJA, H2O2 and 2,4-D activate this promoter through cis-acting elements other than PERE boxes, whereas ABA and SA act via a PERE box-independent pathway but require this element for maximal activation. Three putative cis-acting elements MRE, GCN4 and GT1/TCA identified in the P270 promoter may be involved in the PERE box-independent activation pathway. These results suggest that the promoter of TLC1.1 may act as an integrator of different signal transduction pathways, allowing this member of the TLC1 retrotransposon family to be activated in response to multiples challenges

Indicadors d'avaluació de les cures infermeres

Avaluació; Cures; InfermeriaEvaluation; Cares; NursingEvaluación; Cuidados; EnfermeríaEls professionals d’infermeria, pel rol significatiu que els atorguen les seves competències, han de poder avaluar de manera clara i transparent l’impacte de les cures que porten a terme sobre les persones, fent visible l’aportació professional a la salut de la població. Per això, és necessari que hi hagi informació suficient i contrastada per elaborar uns indicadors clau amb una visió comuna per a tot el sistema, que permetin conèixer els resultats sensibles a les accions pròpies dels infermers i les infermeres