Mesorhizobium olivaresii sp. nov. isolated from Lotus corniculatus nodules

16 páginas, 3 figuras, 2 tablas. -- The definitive version is available at http://www.elsevier.comIn this study four Mesorhizobium strains isolated from Lotus corniculatus nodules in Granada (Spain) were characterized. Their 16S rRNA gene sequences were closely related to those of M. albiziae LMG 23507T and M. chacoense Pr5T showing 99.4 and 99.2% similarity values, respectively. The analysis of concatenated rpoB, recA, atpD and glnII genes showed they formed a cluster with internal similarities higher than 97%. The closest species also were M. albiziae LMG 23507T and M. chacoense Pr5T showing similarity values lower than 92% in rpoB, recA and glnII genes and lower than 96.5% in the atpD gene. These results indicated that the L. corniculatus strains belong to a new species of genus Mesorhizobium which was confirmed by DNA-DNA hybridization and phenotypic characterization. Therefore a new species with the name Mesorhizobium olivaresii sp. nov. is proposed, and the type strain is CPS13T (LMG 29295T = CECT 9099T).This work was supported by the EU-INCO project LOTASSA (J.S.) and Junta de Andalucía (Spain). JDFF is recipient of a predoctoral fellowship from Universidad de Salamanca.Peer reviewe

Evolución de la agilidad y velocidad lineal en una muestra de adolescentes durante los últimos 20 años (1998-2018)

The aim of the present study was to analyse the changes in the physical capacities of agility and linear velocity in a sample of Spanish schoolchildren during a period of 20 years (1998-2018). For this purpose, a cross-sectional study was designed and the results of the 10x10 shuttle test and 45-meter dash test were analysed. The sample was configured by a total of 3056 schoolchildren between 12 and 13 years old (1792 males and 1264 females). The results showed a decrease in test performance in both sexes for the 10x10 shuttle test. On the contrary, no significant changes were obtained in relation to the performance of the test of the 45-meter dash. The increase in the sedentary lifestyles of industrialized societies, the increase in the obesity proportion, the abuse of new technologies or new social habits could explain the worsening of agility in the study sample.El objetivo del presente estudio fue analizar los cambios en las capacidades físicas de la agilidad y la velocidad lineal en una muestra de escolares españoles durante un período de 20 años (1998-2018). Para este propósito, se diseñó un estudio transversal y se analizaron los resultados de las prueba 10x10 metros y 45 metros. La muestra fue configurada por un total de 3056 escolares de entre 12 y 13 años (1792 varones y 1264 mujeres). Los resultados mostraron una disminución en el rendimiento del test en ambos sexos para la prueba de 10x10 metros. Por el contrario, no se obtuvieron cambios significativos en la prueba de 45 metros lisos. El aumento de los estilos de vida sedentarios de las sociedades industrializadas, el aumento de la proporción de obesidad, el abuso de las nuevas tecnologías o los nuevos hábitos sociales podrían explicar el empeoramiento de la agilidad en la muestra del estudio

Evaluation of micromorphological changes in tooth enamel after mechanical and ultrafast laser preparation of surface cavities

The aim of this in vitro study was to evaluate the morphological changes that occur in tooth enamel after mechanical instrumentation and after femtosecond laser irradiation with different parameters via light and scanning electron microscopy (SEM). Twelve totally impacted third molars were collected and sectioned to provide several cut surfaces. These surfaces were exposed to infrared (λ = 795 nm, 120 fs, 1-kHz repetition rate, maximum mean power 1 W) laser pulses and machined by means of a conventional mechanical technique. Two very different geometrical patterns were performed with femtosecond laser pulses: shallow rectangular cavities and deep cylindrical ones. The results of both machining procedures were examined using light and scanning electron microscopy. The SEM images show the femtosecond laser ability to produce high-precision cavities in tooth enamel. No signs of collateral damage, burning, melting, or cracks were observed despite the far different laser pulse energies used (ranging from 7 to 400 μJ), unlike what is seen with conventional mechanical techniques. The femtosecond laser has the potential to become an optimal tool for the treatment of dental decay and as an alternative to the conventional drill to reduce mechanical damage during removal of the hard dental tissue.A.G. and P.M. acknowledge the support of Spanish Ministerio de Ciencia e Innovación through the Consolider Program SAUUL (CSD2007-00013) and research project FIS2009-09522, from Junta de Castilla y León through the Program for Groups of Excellence (GR27) and of the EC Seventh Framework Programme (LASERLAB-EUROPE, grant agreement no. 228334).We also acknowledge the support of the Centro de Laseres Pulsados, CLPU, Salamanca, Spain

An Immune Gene Expression Signature Associated With Development of Human Hepatocellular Carcinoma Identifies Mice That Respond to Chemopreventive Agents

Program (HEPCAR, reference no. 667273-2); US Department of Defense(CA150272P3); an Accelerator Award (CRUCK, AECC, AIRC) (HUNTER,reference no. C9380/A26813), NCI Cancer Center Support Grant, National Cancer Institute; Tisch Cancer Institute (P30-CA196521); Samuel Waxman Cancer Research Foundation; Spanish National Health Institute (SAF2016-76390); and the Generalitat de Catalunya/AGAUR (SGR-1358). Agrin Moeini is supported by Spanish National Health Institute. Sara Torrecilla and Judit Peix are funded by Centro de Investigación Biomedica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd-ISCIII). Carla Montironi is a recipient of Josep Font grant. Carmen Andreu-Oller is supported by "la Caixa" INPhINIT Fellowship Grant (LCF/BQ/IN17/11620024). Roser Pinyol is supported by HEPCAR and AECC. Daniela Sia is supported by the Gilead Sciences Research Scholar Program in Liver Disease. Scott L. Friedman is supported by the National Institutes of Health Research project grant (R01,DK5662) and US Department of Defense (CA150272P3). Mathias Heikenwälder was supported by an ERC Consolidator grant (HepatoMetaboPath), the SFBTR 209, 1335 and SFBTR179.Background & Aims: Cirrhosis and chronic inflammation precede development of hepatocellular carcinoma (HCC) in approximately 80% of cases. We investigated immune-related gene expression patterns in liver tissues surrounding early-stage HCCs and chemopreventive agents that might alter these patterns to prevent liver tumorigenesis. Methods: We analyzed gene expression profiles of nontumor liver tissues from 392 patients with early-stage HCC (training set, N = 167 and validation set, N = 225) and liver tissue from patients with cirrhosis without HCC (N = 216, controls) to identify changes in expression of genes that regulate the immune response that could contribute to hepatocarcinogenesis. We defined 172 genes as markers for this deregulated immune response, which we called the immune-mediated cancer field (ICF). We analyzed the expression data of liver tissues from 216 patients with cirrhosis without HCC and investigated the association between this gene expression signature and development of HCC and outcomes of patients (median follow-up, 10 years). Human liver tissues were also analyzed by histology. C57BL/6J mice were given a single injection of diethylnitrosamine (DEN) followed by weekly doses of carbon tetrachloride to induce liver fibrosis and tumorigenesis. Mice were then orally given the multiple tyrosine inhibitor nintedanib or vehicle (controls); liver tissues were collected and histology, transcriptome, and protein analyses were performed. We also analyzed transcriptomes of liver tissues collected from mice on a choline-deficient high-fat diet, which developed chronic liver inflammation and tumors, orally given aspirin and clopidogrel or the anti-inflammatory agent sulindac vs mice on a chow (control) diet. Results: We found the ICF gene expression pattern in 50% of liver tissues from patients with cirrhosis without HCC and in 60% of nontumor liver tissues from patients with early-stage HCC. The liver tissues with the ICF gene expression pattern had 3 different features: increased numbers of effector T cells; increased expression of genes that suppress the immune response and activation of transforming growth factor β signaling; or expression of genes that promote inflammation and activation of interferon gamma signaling. Patients with cirrhosis and liver tissues with the immunosuppressive profile (10% of cases) had a higher risk of HCC (hazard ratio, 2.41; 95% confidence interval, 1.21-4.80). Mice with chemically induced fibrosis or diet-induced steatohepatitis given nintedanib or aspirin and clopidogrel down-regulated the ICF gene expression pattern in liver and developed fewer and smaller tumors than mice given vehicle. Conclusions: We identified an immune-related gene expression pattern in liver tissues of patients with early-stage HCC, called the ICF, that is associated with risk of HCC development in patients with cirrhosis. Administration of nintedanib or aspirin and clopidogrel to mice with chronic liver inflammation caused loss of this gene expression pattern and development of fewer and smaller liver tumors. Agents that alter immune regulatory gene expression patterns associated with carcinogenesis might be tested as chemopreventive agents in patients with cirrhosis

Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials

The clinical utility of serum alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC) is widely recognised. However, a clear understanding of the mechanisms of AFP overexpression and the molecular traits of patients with AFP-high tumours are not known. We assessed transcriptome data, whole-exome sequencing data and DNA methylome profiling of 520 HCC patients from two independent cohorts to identify distinct molecular traits of patients with AFP-high tumours (serum concentration?>?400?ng/ml), which represents an accepted prognostic cut-off and a predictor of response to ramucirumab. Those AFP-high tumours (18% of resected cases) were characterised by significantly lower AFP promoter methylation (p?<?0.001), significant enrichment of progenitor-cell features (CK19, EPCAM), higher incidence of BAP1 oncogene mutations (8.5% vs 1.6%) and lower mutational rates of CTNNB1 (14% vs 30%). Specifically, AFP-high tumours displayed significant activation of VEGF signalling (p?<?0.001), which might provide the rationale for the reported benefit of ramucirumab in this subgroup of patients

Defining the Rhizobium leguminosarum Species Complex

Bacteria currently included in Rhizobium leguminosarum are too diverse to be considered a single species, so we can refer to this as a species complex (the Rlc). We have found 429 publicly available genome sequences that fall within the Rlc and these show that the Rlc is a distinct entity, well separated from other species in the genus. Its sister taxon is R. anhuiense. We constructed a phylogeny based on concatenated sequences of 120 universal (core) genes, and calculated pairwise average nucleotide identity (ANI) between all genomes. From these analyses, we concluded that the Rlc includes 18 distinct genospecies, plus 7 unique strains that are not placed in these genospecies. Each genospecies is separated by a distinct gap in ANI values, usually at approximately 96% ANI, implying that it is a ‘natural’ unit. Five of the genospecies include the type strains of named species: R. laguerreae, R. sophorae, R. ruizarguesonis, “R. indicum” and R. leguminosarum itself. The 16S ribosomal RNA sequence is remarkably diverse within the Rlc, but does not distinguish the genospecies. Partial sequences of housekeeping genes, which have frequently been used to characterize isolate collections, can mostly be assigned unambiguously to a genospecies, but alleles within a genospecies do not always form a clade, so single genes are not a reliable guide to the true phylogeny of the strains. We conclude that access to a large number of genome sequences is a powerful tool for characterizing the diversity of bacteria, and that taxonomic conclusions should be based on all available genome sequences, not just those of type strains

Defining the Rhizobium leguminosarum Species Complex

Bacteria currently included in Rhizobium leguminosarum are too diverse to be considered a single species, so we can refer to this as a species complex (the Rlc). We have found 429 publicly available genome sequences that fall within the Rlc and these show that the Rlc is a distinct entity, well separated from other species in the genus. Its sister taxon is R. anhuiense. We constructed a phylogeny based on concatenated sequences of 120 universal (core) genes, and calculated pairwise average nucleotide identity (ANI) between all genomes. From these analyses, we concluded that the Rlc includes 18 distinct genospecies, plus 7 unique strains that are not placed in these genospecies. Each genospecies is separated by a distinct gap in ANI values, usually at approximately 96% ANI, implying that it is a ‘natural’ unit. Five of the genospecies include the type strains of named species: R. laguerreae, R. sophorae, R. ruizarguesonis, “R. indicum” and R. leguminosarum itself. The 16S ribosomal RNA sequence is remarkably diverse within the Rlc, but does not distinguish the genospecies. Partial sequences of housekeeping genes, which have frequently been used to characterize isolate collections, can mostly be assigned unambiguously to a genospecies, but alleles within a genospecies do not always form a clade, so single genes are not a reliable guide to the true phylogeny of the strains. We conclude that access to a large number of genome sequences is a powerful tool for characterizing the diversity of bacteria, and that taxonomic conclusions should be based on all available genome sequences, not just those of type strains

Results of combined treatment of anaplastic thyroid carcinoma (ATC)

<p>Abstract</p> <p>Background</p> <p>Anaplastic thyroid carcinoma (ATC) is among the most aggressive human malignancies. It is associated with a high rate of local recurrence and with poor prognosis.</p> <p>Methods</p> <p>We retrospectively reviewed 44 consecutive patients treated between 1996 and 2010 at Leon Berard Cancer Centre, Lyon, France. The combined treatment strategy derived from the one developed at the Institut Gustave Roussy included total thyroidectomy and cervical lymph-node dissection, when feasible, combined with 2 cycles of doxorubicin (60 mg/m2) and cisplatin (100 mg/m2) Q3W, hyperfractionated (1.2 Gy twice daily) radiation to the neck and upper mediastinum (46-50 Gy), and then four cycles of doxorubicin-cisplatin.</p> <p>Results</p> <p>Thirty-five patients received the three-phase combined treatment. Complete response after treatment was achieved in 14/44 patients (31.8%). Eight patients had a partial response (18.2%). Twenty-two (50%) had progressive disease. All patients with metastases at diagnosis died shortly afterwards. Thirteen patients are still alive. The median survival of the entire population was 8 months.</p> <p>Conclusion</p> <p>Despite the ultimately dismal prognosis of ATC, multimodality treatment significantly improves local control and appears to afford long-term survival in some patients. There is active ongoing research, and results obtained with new targeted systemic treatment appear encouraging.</p

Historia de la investigación en la simbiosis leguminosa-bacteria: una perspectiva didáctica

After cereals, legumes constitute the second most important family of crops for human and animal consumption. However, in contrast to the former, legumes are capable of growing in arid soils of low fertility, due to their ability to establish symbiotic associations with soil bacteria called rhizobia. These microorganisms form special organs in the roots of legumes called nodules, where atmospheric dinitrogen (N₂) is transformed into ammonium that is exported to the plant for growth. Since their discovery in legume nodules until today, knowledge of the bacteria capable of establishing symbiosis with these plants has advanced in many aspects. Especially, advances in molecular techniques for bacterial identification and access to unexplored places have confirmed that the interaction of legumes with rhizobia is older, and that N₂-fixing bacteria are more abundant and diverse, than considered previously. Here, we attempt to relate the history of an association whose development is key in the history of mankind as we know it now.<br><br>Después de los cereales, las leguminosas constituyen la segunda familia en importancia para la alimentación humana y animal. Sin embargo, en contraste con ellos, las leguminosas son capaces de crecer en suelos áridos, de escasa fertilidad, lo que se debe a su capacidad para establecer asociaciones simbióticas con bacterias del suelo llamadas rhizobia. Estos microorganismos forman unos órganos especiales en las raíces de las leguminosas, los nódulos, donde el dinitrógeno (N₂) atmosférico se transforma en amonio que se exporta a la planta para su crecimiento. Desde su descubrimiento en los nódulos de las leguminosas hasta nuestros días, el conocimiento de las bacterias capaces de establecer simbiosis con estas plantas ha avanzado en múltiples aspectos. Sobre todo, los avances en las técnicas moleculares de identificación bacteriana y el acceso a lugares inexplorados ha permitido confirmar que la interacción de las leguminosas con los rhizobia es más antigua de lo que se creía y que las bacterias fijadoras de dinitrógeno (N₂) son más abundantes y diversas de lo que se había pensado. Trataremos de describir la historia de una asociación cuyo desarrollo ha sido, y es, clave en la historia de la humanidad tal como la conocemos ahora

Molecular characterization of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis

Background and aims: Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is increasing globally, but its molecular features are not well defined. We aimed to identify unique molecular traits characterising NASH-HCC compared to other HCC aetiologies. Methods: We collected 80 NASH-HCC and 125 NASH samples from 5 institutions. Expression array (n = 53 NASH-HCC; n = 74 NASH) and whole exome sequencing (n = 52 NASH-HCC) data were compared to HCCs of other aetiologies (n = 184). Three NASH-HCC mouse models were analysed by RNA-seq/expression-array (n = 20). Activin A receptor type 2A (ACVR2A) was silenced in HCC cells and proliferation assessed by colorimetric and colony formation assays. Results: Mutational profiling of NASH-HCC tumours revealed TERT promoter (56%), CTNNB1 (28%), TP53 (18%) and ACVR2A (10%) as the most frequently mutated genes. ACVR2A mutation rates were higher in NASH-HCC than in other HCC aetiologies (10% vs. 3%, p <0.05). In vitro, ACVR2A silencing prompted a significant increase in cell proliferation in HCC cells. We identified a novel mutational signature (MutSig-NASH-HCC) significantly associated with NASH-HCC (16% vs. 2% in viral/alcohol-HCC, p = 0.03). Tumour mutational burden was higher in non-cirrhotic than in cirrhotic NASH-HCCs (1.45 vs. 0.94 mutations/megabase; p <0.0017). Compared to other aetiologies of HCC, NASH-HCCs were enriched in bile and fatty acid signalling, oxidative stress and inflammation, and presented a higher fraction of Wnt/TGF-β proliferation subclass tumours (42% vs. 26%, p = 0.01) and a lower prevalence of the CTNNB1 subclass. Compared to other aetiologies, NASH-HCC showed a significantly higher prevalence of an immunosuppressive cancer field. In 3 murine models of NASH-HCC, key features of human NASH-HCC were preserved. Conclusions: NASH-HCCs display unique molecular features including higher rates of ACVR2A mutations and the presence of a newly identified mutational signature. Lay summary: The prevalence of hepatocellular carcinoma (HCC) associated with non-alcoholic steatohepatitis (NASH) is increasing globally, but its molecular traits are not well characterised. In this study, we uncovered higher rates of ACVR2A mutations (10%) - a potential tumour suppressor - and the presence of a novel mutational signature that characterises NASH-related HCC