Understanding the Evolutionary Relationships and Major Traits of \u3cem\u3eBacillus\u3c/em\u3e through Comparative Genomics

Background: The presence of Bacillus in very diverse environments reflects the versatile metabolic capabilities of a widely distributed genus. Traditional phylogenetic analysis based on limited gene sampling is not adequate for resolving the genus evolutionary relationships. By distinguishing between core and pan-genome, we determined the evolutionary and functional relationships of known Bacillus. Results: Our analysis is based upon twenty complete and draft Bacillus genomes, including a newly sequenced Bacillus isolate from an aquatic environment that we report for the first time here. Using a core genome, we were able to determine the phylogeny of known Bacilli, including aquatic strains whose position in the phylogenetic tree could not be unambiguously determined in the past. Using the pan-genome from the sequenced Bacillus, we identified functional differences, such as carbohydrate utilization and genes involved in signal transduction, which distinguished the taxonomic groups. We also assessed the genetic architecture of the defining traits of Bacillus, such as sporulation and competence, and showed that less than one third of the B. subtilis genes are conserved across other Bacilli. Most variation was shown to occur in genes that are needed to respond to environmental cues, suggesting that Bacilli have genetically specialized to allow for the occupation of diverse habitats and niches. Conclusions: The aquatic Bacilli are defined here for the first time as a group through the phylogenetic analysis of 814 genes that comprise the core genome. Our data distinguished between genomic components, especially core vs. pan-genome to provide insight into phylogeny and function that would otherwise be difficult to achieve. A phylogeny may mask the diversity of functions, which we tried to uncover in our approach. The diversity of sporulation and competence genes across the Bacilli was unexpected based on previous studies of the B. subtilis model alone. The challenge of uncovering the novelties and variations among genes of the non-subtilis groups still remains. This task will be best accomplished by directing efforts toward understanding phylogenetic groups with similar ecological niches

Experimental comparison between R152a and R134a working in a refrigeration facility equipped with a hermetic compressor

[EN] The EU Regulation 517/2014 has recently been approved in a further attempt to curb the effects of GlobalWarming. As a consequence, the refrigeration sector is moving towards refrigerants with a low GlobalWarming Potential (GWP100) in accordance with the limit fixed by these regulations (150). In this regard, the old refrigerant R152a attracts renewed interest due to its low GWP (138) and its similarity to R134a. The present work shows the results of using R152a in a vapour compression plant equipped with a hermetic compressor and an IHX designed for R134a. The refrigerant was replaced by a conventional drop-in process in order to carry out an energy comparison. The results have revealed an improvement in the COP with R152a up to 13% despite a reduction in the cooling capacity of about 10%. During the test campaign, R134a hermetic compressors have been shown to be capable of operating with R152a.The authors acknowledge Jaume I University of Spain, who financed partially the present study through the research project P1.B2013-10.Cabello, R.; Sanchez, D.; Llopis Doménech, R.; Armendáriz Araúzo, LM.; Torrella Alcaraz, E. (2015). Experimental comparison between R152a and R134a working in a refrigeration facility equipped with a hermetic compressor. International Journal of Refrigeration. 60:92-105. https://doi.org/10.1016/j.ijrefrig.2015.06.021S921056

Global genomic similarity and core genome sequence diversity of the Streptococcus genus as a toolkit to identify closely related bacterial species in complex environments

Background The Streptococcus genus is relevant to both public health and food safety because of its ability to cause pathogenic infections. It is well-represented (>100 genomes) in publicly available databases. Streptococci are ubiquitous, with multiple sources of isolation, from human pathogens to dairy products. The Streptococcus genus has traditionally been classified by morphology, serum types, the 16S ribosomal RNA (rRNA) gene, and multi-locus sequence types subject to in-depth comparative genomic analysis. Methods Core and pan-genomes described the genomic diversity of 108 strains belonging to 16 Streptococcus species. The core genome nucleotide diversity was calculated and compared to phylogenomic distances within the genus Streptococcus. The core genome was also used as a resource to recruit metagenomic fragment reads from streptococci dominated environments. A conventional 16S rRNA gene phylogeny reconstruction was used as a reference to compare the resulting dendrograms of average nucleotide identity (ANI) and genome similarity score (GSS) dendrograms. Results The core genome, in this work, consists of 404 proteins that are shared by all 108 Streptococcus. The average identity of the pairwise compared core proteins decreases proportionally to GSS lower scores, across species. The GSS dendrogram recovers most of the clades in the 16S rRNA gene phylogeny while distinguishing between 16S polytomies (unresolved nodes). The GSS is a distance metric that can reflect evolutionary history comparing orthologous proteins. Additionally, GSS resulted in the most useful metric for genus and species comparisons, where ANI metrics failed due to false positives when comparing different species. Discussion Understanding of genomic variability and species relatedness is the goal of tools like GSS, which makes use of the maximum pairwise shared orthologous sequences for its calculation. It allows for long evolutionary distances (above species) to be included because of the use of amino acid alignment scores, rather than nucleotides, and normalizing by positive matches. Newly sequenced species and strains could be easily placed into GSS dendrograms to infer overall genomic relatedness. The GSS is not restricted to ubiquitous conservancy of gene features; thus, it reflects the mosaic-structure and dynamism of gene acquisition and loss in bacterial genomes

La estimación de proporciones mediante técnicas Bayesianas

The estimation procedures based on Bayes' Theorem are still an unusual option in many of the environments of classic parametric inference. The aim of this paper is to show an effective scheme for the use of Bayesian estimation of unknown parameters. We have opted to focus on the estimation of parameters under the assumption of a binomial model, so that it can be followed by all those situations that meet the aforementioned probabilistic model. This approximation was studied in comparison with the classic parametric approximation, both in its point version and by means of interval estimation. On a study, by simulating samples of several sizes, we obtained empirical evidence regarding the advantage of the Bayesian procedure.ResumenLos procedimientos de estimación basados en el teorema de Bayes son inusuales en los diferentes ámbitos de aplicación de la inferencia paramétrica clásica. El objetivo de este trabajo es presentar un esquema para la estimación bayesiana de parámetros bajo los supuestos de un modelo binomial. El procedimiento Bayes se estudia en comparación con la aproximación paramétrica cl??sica, ambas opciones, en su versión puntual y mediante intervalos de estimación. Se presenta también un estudio de simulación con diferentes tamaños muestrales en el que se ponen de manifiesto las ventajas del procedimiento bayesiano.AbstractThe estimation procedures based on Bayes' Theorem are still an unusual option in many of the environments of classic parametric inference. The aim of this paper is to show an effective scheme for the use of Bayesian estimation of unknown parameters. We have opted to focus on the estimation of parameters under the assumption of a binomial model, so that it can be followed by all those situations that meet the aforementioned probabilistic model. This approximation was studied in comparison with the classic parametric approximation, both in its point version and by means of interval estimation. On a study, by simulating samples of several sizes, we obtained empirical evidence regarding the advantage of the Bayesian procedure

Hereditary renal adysplasia, pulmonary hypoplasia and Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: a case report

<p>Abstract</p> <p>Background</p> <p>Hereditary renal adysplasia is an autosomal dominant trait with incomplete penetrance and variable expression that is usually associated with malformative combinations (including Müllerian anomalies) affecting different mesodermal organs such as the heart, lung, and urogenital system.</p> <p>Case report</p> <p>A case showing pulmonary hypoplasia, hip dysplasia, hereditary renal adysplasia, and Mayer-Rokitansky-Kuster-Hauser syndrome in adulthood is reported here. The i.v. pyelography showed right renal agenesis with a normal left kidney and ureter. Ultrasound and Magnetic Resonance Imaging also showed right renal agenesis with multicystic embryonary remnants in the right hemipelvis probably corresponding to a dysgenetic kidney. An uretrocystoscopy showed absence of ectopic ureter and of the right hemitrigone. She was scheduled for a diagnostic laparoscopy and creation of a neovagina according to the McIndoe technique with a prosthesis and skin graft. Laparoscopy confirmed the absence of the uterus. On both sides, an elongated, solid, rudimentary uterine horn could be observed. Both ovaries were also elongated, located high in both abdominal flanks and somewhat dysgenetics. A conventional cytogenetic study revealed a normal female karyotype 46, XX at a level of 550 GTG bands. A CGH analysis was performed using a 244K oligoarray CGH detecting 11 copy number variants described as normal variants in the databases. The 17q12 and 22q11.21 microdeletions described in other MRKH patients were not present in this case. Four years after operation her evolution is normal, without symptoms and the neovagina is adequately functional. The geneticists have studied her family history and the pedigree of the family is shown.</p> <p>Conclusions</p> <p>We suggest that primary damage to the mesoderm (paraaxil, intermediate, and lateral) caused by mutations in a yet unidentified gene is responsible for: 1) skeletal dysplasia, 2) inappropriate interactions between the bronchial mesoderm and endodermal lung bud as well as between the blastema metanephric and ureteric bud, and eventually 3) Müllerian anomalies (peritoneal mesothelium) at the same level. These anomalies would be transmitted as an autosomal dominant trait with incomplete penetrance and variable expressivity.</p

Reporte de atención clínica integral

El Proyecto de Aplicación Profesional en Atención Clínica Interdisciplinaria tuvo como objetivo general ofrecer servicios de atención y orientación profesional a los consultantes que la solicitaron para encontrar respuesta a los diferentes motivos de consulta psicológica y nutricional. Se les brindó el acompañamiento psicológico y nutricional a niños, adolescentes, adultos y familias en los siguientes escenarios: el Centro de Atención Psicológica, Centros de Desarrollo Comunitario del DIF Zapopan como DIF Arenales Tapatíos, DIF Santa María del Pueblito, DIF Santa Ana Tepetitlán Centro Polanco, Bufete Jurídico Clínica Ignacio Ellacuría y Clínica Nutricia. El proyecto ofreció principalmente espacios de atención en modalidad presencial y algunos en línea, donde se atendieron problemáticas tales como: consecuencias tras vivir la Pandemia de Covid-19, diferentes tipos de violencia, TCAS, problemas relacionales, depresión, ideación suicida, situaciones postraumáticas, y complicaciones en el desarrollo de una vida saludable tanto en los aspectos nutricionales como en el acceso a la justicia. Asimismo, se describen los múltiples aprendizajes tanto personales como profesionales, a través de las experiencias e intervenciones a lo largo del Proyecto de Aplicación Profesional.ITESO, A.C

Phylogenetic Distribution and Evolutionary History of Bacterial DEAD-Box Proteins

DEAD-box proteins are found in all domains of life and participate in almost all cellular processes that involve RNA. The presence of DEAD and Helicase_C conserved domains distinguish these proteins. DEAD-box proteins exhibit RNA-dependent ATPase activity in vitro, and several also show RNA helicase activity. In this study, we analyzed the distribution and architecture of DEAD-box proteins among bacterial genomes to gain insight into the evolutionary pathways that have shaped their history. We identified 1,848 unique DEAD-box proteins from 563 bacterial genomes. Bacterial genomes can possess a single copy DEAD-box gene, or up to 12 copies of the gene, such as in Shewanella. The alignment of 1,208 sequences allowed us to perform a robust analysis of the hallmark motifs of DEAD-box proteins and determine the residues that occur at high frequency, some of which were previously overlooked. Bacterial DEAD-box proteins do not generally contain a conserved C-terminal domain, with the exception of some members that possess a DbpA RNA-binding domain (RBD). Phylogenetic analysis showed a separation of DbpA-RBD-containing and DbpA-RBD-lacking sequences and revealed a group of DEAD-box protein genes that expanded mainly in the Proteobacteria. Analysis of DEAD-box proteins from Firmicutes and γ-Proteobacteria, was used to deduce orthologous relationships of the well-studied DEAD-box proteins from Escherichia coli and Bacillus subtilis. These analyses suggest that DbpA-RBD is an ancestral domain that most likely emerged as a specialized domain of the RNA-dependent ATPases. Moreover, these data revealed numerous events of gene family expansion and reduction following speciation

Rationally Designed Interfacial Peptides Are Efficient In Vitro Inhibitors of HIV-1 Capsid Assembly with Antiviral Activity

Virus capsid assembly constitutes an attractive target for the development of antiviral therapies; a few experimental inhibitors of this process for HIV-1 and other viruses have been identified by screening compounds or by selection from chemical libraries. As a different, novel approach we have undertaken the rational design of peptides that could act as competitive assembly inhibitors by mimicking capsid structural elements involved in intersubunit interfaces. Several discrete interfaces involved in formation of the mature HIV-1 capsid through polymerization of the capsid protein CA were targeted. We had previously designed a peptide, CAC1, that represents CA helix 9 (a major part of the dimerization interface) and binds the CA C-terminal domain in solution. Here we have mapped the binding site of CAC1, and shown that it substantially overlaps with the CA dimerization interface. We have also rationally modified CAC1 to increase its solubility and CA-binding affinity, and designed four additional peptides that represent CA helical segments involved in other CA interfaces. We found that peptides CAC1, its derivative CAC1M, and H8 (representing CA helix 8) were able to efficiently inhibit the in vitro assembly of the mature HIV-1 capsid. Cocktails of several peptides, including CAC1 or CAC1M plus H8 or CAI (a previously discovered inhibitor of CA polymerization), or CAC1M+H8+CAI, also abolished capsid assembly, even when every peptide was used at lower, sub-inhibitory doses. To provide a preliminary proof that these designed capsid assembly inhibitors could eventually serve as lead compounds for development of anti-HIV-1 agents, they were transported into cultured cells using a cell-penetrating peptide, and tested for antiviral activity. Peptide cocktails that drastically inhibited capsid assembly in vitro were also able to efficiently inhibit HIV-1 infection ex vivo. This study validates a novel, entirely rational approach for the design of capsid assembly interfacial inhibitors that show antiviral activity

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

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