Discovery of lost genes in the genome of Acinetobacter baumannii using Anablast

Motivation: Microbial resistance to antibiotics is currently one of the greatest threats in global health. Multiple outbreaks of multi-resistant Acinetobacter baumannii strains have been documented [1] and it is necessary to find new drugs against it, and the finding of new genes in the bacteria could help in this fighting. As A. baumannii is a highly studied organism, it is difficult to find new genes by homology with traditional predictors.For this reason we have chosen the AnABlast program which is a new bioinformatics tool which has been successful in finding out new genes in eukaryotes. This program generates profiles of accumulated alignments in query amino acid sequences using a low-stringency BLAST strategy [2], which highlight regions with evolutionary meaning.Methods: First, we used AnAblast to locate new coding regions in the A. baumannii genome. After that we analyzed the regions found by AnABlast comparing them with known sequences from the GenBank database to look for the genes found in intergenic regions and we obtain a series of candidates that we need to analyze, characterize and validate.Results: We obtained nine candidates that have been characterized analyzing both its evolutionary conservation and function annotation. Eight of them were also found in other strains of A. baumannii and one could be a gene not found until now that needs to be validated.Conclusions: Using the AnABlast program we have found nine possible coding regions not detected by other methods in the reference strain of A. baumannii. Although they need validation, AnAblast has proven itself useful for gene detection in prokaryote

Searching for novel genes and pseudogenes in the human Y chromosome based on ancestral coding signals

Motivation: Human Y chromosome has several features that contribute to an extreme variation due to the lack of a homologous partner for crossing over, high rate of sequence amplification and low evolutionary pressure [1]. For these reasons, we think that the Y chromosome could be a perfect candidate in order to discover new coding and fossil regions such as pseudogenes.Genome finding is one of the greatest hits in modern biology. However, in silico identification of small and complex coding sequences is still challenging. Jiménez et al [2] developed AnAblast, a computer tool which has been successful in uncovering new genes, as well as fossil-coding sequences. This program generates profiles of accumulated alignments of conserved coding signals using a low-stringency BLAST strategy [2]. Methods: We have used AnAblast to localizate new coding regions in the chromosome Y. After that, AnAblast-generated profiles were introduced into a genome browser, along with other informative data such as repeats and RNA expression data. The candidate's list obtained was complemented by careful BLAST, InterPro and peaks analysis. Moreover, we performed a search on the tool Genome Data Viewer (GDV) to check each result.Results: We have been able to identify some chromosome Y regions that fulfill different requirements: (1) regions without previous annotations as pseudogenes, genes or non-coding regions (Ensembl track); (2) regions without previous annotations as interspersed repeats and low complexity (RepeatMasker track); and (3) regions with expression profiles (RNA-seq of testis).The best candidate to be a new coding region was localized at Y:9912876-9919657 (-). Blast and InterPro analysis indicated similarity with serine-proteases which are found in rodents and another organism such as Rousettus aegyptiacus (Egyptian fruit bat). After the search on GDV, we observed that only the first bat´s exon was not found in our candidate. In spite of this, we found a methionine codon in our candidate (more specifically in the first exon). Furthermore, the Y chromosome has a 5´-truncated copy of this region.Conclusions: We have found some chromosome Y regions which could be new coding genes or pseudogenes. Thus, this in silico research provides a powerful protocol to search novel genes and fossil regions in the whole human genome. Although we added several RNA-seq tracks that showed the expression of these regions, clinical trials should be performed to verify our candidates

L-arginine ameliorates defective autophagy in GM2 gangliosidoses by mTOR modulation

Aims: Tay–Sachs and Sandhoff diseases (GM2 gangliosidosis) are autosomal recessive disorders of lysosomal function that cause progressive neurodegeneration in infants and young children. Impaired hydrolysis catalysed by β-hexosaminidase A (HexA) leads to the accumulation of GM2 ganglioside in neuronal lysosomes. Despite the storage phenotype, the role of autophagy and its regulation by mTOR has yet to be explored in the neuropathogenesis. Accordingly, we investigated the effects on autophagy and lysosomal integrity using skin fibroblasts obtained from patients with Tay–Sachs and Sandhoff diseases. Results: Pathological autophagosomes with impaired autophagic flux, an abnormality confirmed by electron microscopy and biochemical studies revealing the accelerated release of mature cathepsins and HexA into the cytosol, indicating increased lysosomal permeability. GM2 fibroblasts showed diminished mTOR signalling with reduced basal mTOR activity. Accordingly, provision of a positive nutrient signal by L-arginine supplementation partially restored mTOR activity and ameliorated the cytopathological abnormalities. Innovation: Our data provide a novel molecular mechanism underlying GM2 gangliosidosis. Impaired autophagy caused by insufficient lysosomal function might represent a new therapeutic target for these diseases. Conclusions: We contend that the expression of autophagy/lysosome/mTOR-associated molecules may prove useful peripheral biomarkers for facile monitoring of treatment of GM2 gangliosidosis and neurodegenerative disorders that affect the lysosomal function and disrupt autophagy

Eficiencia espectral y capacidad en un canal MIMO masivo con alta densidad de usuarios

[EN] This paper presents an analysis of the massive MIMO channel in an indoor picocell with a high number of active user terminals. The analysis is based on the results of a measurement campaign carried out in the 3.2 to 4 GHz band in a scenario of reduced size, in which users (up to 20) are placed in an orderly manner. In order to evaluate the performance of the resulting massive MIMO channel, results concerning both the sum capacity as well as the spectral efficiency are included. Furthermore and concerning the channel spectral efficiency, an analysis showing the spread and differences between the individual contributions of each active user is reported and discussed.Este trabajo ha sido financiado por los proyectos del Plan Estatal de Investigación Científica y Técnica y de Innovación TEC2017-86779-C2-1-R y TEC2017-86779-C2-2-R.Alejandro Rodríguez Aparicio; Jesús R. Pérez; Luis Valle; Torres Jiménez, RP.; Rubio Arjona, L.; Rodrigo Peñarrocha, VM.; Reig, J. (2021). Eficiencia espectral y capacidad en un canal MIMO masivo con alta densidad de usuarios. Íñigo Cuiñas Gómez. 1-4. http://hdl.handle.net/10251/1910821

Space and time in the tectonic evolution of the northwestern Iberian Massif: Implications for the Variscan belt.

Recent advances in geochemical studies of igneous rocks, isotopic age data for magmatism and metamorphism, quantitative pressure-temperature (P-T) estimates of metamorphic evolution, and structural geology in the northwestern Iberian Massif are integrated into a synthesis of the tectonic evolution that places the autochthonous and allochthonous terranes in the framework of Paleozoic plate tectonics. Because northwestern Iberia is free from strike-slip faults of continental scale, it is retrodeformable and preserves valuable information about the orthogonal component of convergence of Gondwana with Laurentia and/or Baltica, and the opening and closure of the Rheic Ocean. The evolution deduced for northwest Iberia is extended to the rest of the Variscan belt in an attempt to develop a three-dimensional interpretation that assigns great importance to the transcurrent components of convergence. Dominant Carboniferous dextral transpression following large Devonian and Early Carboniferous thrusting and recumbent folding is invoked to explain the complexity of the belt without requiring a large number of peri-Gondwanan terranes, and its ophiolites and highpressure allochthonous units are related to a single oceanic closure. Palinspastic reconstruction of the Variscan massifs and zones cannot be achieved without restoration of terrane transport along the colliding plate margins. A schematic reconstruction is proposed that involves postcollisional strike-slip displacement of ~3000 km between Laurussia and Gondwana during the Carboniferous

Comparison of seven prognostic tools to identify low-risk pulmonary embolism in patients aged <50 years

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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

Short-term changes in klotho and FGF23 in heart failure with reduced ejection fraction—a substudy of the DAPA-VO2 study

The klotho and fibroblast growth factor 23 (FGF-23) pathway is implicated in cardiovascular pathophysiology. This substudy aimed to assess the changes in klotho and FGF-23 levels 1-month after dapagliflozin in patients with stable heart failure and reduced ejection fraction (HFrEF). The study included 29 patients (32.2% of the total), with 14 assigned to the placebo group and 15 to the dapagliflozin, as part of the double-blind, randomized clinical trial [DAPA-VO2 (NCT04197635)]. Blood samples were collected at baseline and after 30 days, and Klotho and FGF-23 levels were measured using ELISA Kits. Between-treatment changes (raw data) were analyzed by using the Mann-Whitney test and expressed as median (p25%–p75%). Linear regression models were utilized to analyze changes in the logarithm (log) of klotho and FGF-23. The median age was 68.3 years (60.8–72.1), with 79.3% male and 81.5% classified as NYHA II. The baseline medians of left ventricular ejection fraction, glomerular filtration rate, NT-proBNP, klotho, and FGF-23 were 35.8% (30.5–37.8), 67.4 ml/min/1.73 m2 (50.7–82.8), 1,285 pg/ml (898–2,305), 623.4 pg/ml (533.5–736.6), and 72.6 RU/ml (62.6–96.1), respectively. The baseline mean peak oxygen uptake was 13.1 ± 4.0 ml/kg/min. Compared to placebo, patients on dapagliflozin showed a significant median increase of klotho [Δ+29.5, (12.9–37.2); p = 0.009] and a non-significant decrease of FGF-23 [Δ−4.6, (−1.7 to −5.4); p = 0.051]. A significant increase in log-klotho (p = 0.011) and a decrease in log-FGF-23 (p = 0.040) were found in the inferential analysis. In conclusion, in patients with stable HFrEF, dapagliflozin led to a short-term increase in klotho and a decrease in FGF-23

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6&nbsp;years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P &lt; 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100&nbsp;years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe