Genomic Evolution of Two Acinetobacter baumannii Clinical Strains from ST-2 Clones Isolated in 2000 and 2010 (ST-2_clon_2000 and ST-2_clon_2010)

Acinetobacter baumannii is a successful nosocomial pathogen due to its ability to persist in hospital environments by acquiring mobile elements such as transposons, plasmids, and phages. In this study, we compared two genomes of A. baumannii clinical strains isolated in 2000 (ST-2_clon_2000) and 2010 (ST-2_clon_2010) from GenBank project PRJNA308422

The effect of divergent selection for intramuscular fat on the domestic rabbit genome

[EN] An experiment of divergent selection for intramuscular fat was carried out at Universitat Politecnica de Valencia. The high response of selection in intramuscular fat content, after nine generations of selection, and a multidimensional scaling analysis showed a high degree of genomic differentiation between the two divergent populations. Therefore, local genomic differences could link genomic regions, encompassing selective sweeps, to the trait used as selection criterion. In this sense, the aim of this study was to identify genomic regions related to intramuscular fat through three methods for detection of selection signatures and to generate a list of candidate genes. The methods implemented in this study were Wright's fixation index, cross population composite likelihood ratio and cross population - extended haplotype homozygosity. Genomic data came from the 9th generation of the two populations divergently selected, 237 from Low line and 240 from High line. A high single nucleotide polymorphism (SNP) density array, Affymetrix Axiom OrcunSNP Array (around 200k SNPs), was used for genotyping samples. Several genomic regions distributed along rabbit chromosomes (OCU) were identified as signatures of selection (SNPs having a value above cut-off of 1%) within each method. In contrast, 8 genomic regions, harbouring 80 SNPs (OCU1, OCU3, OCU6, OCU7, OCU16 and OCU17), were identified by at least 2 methods and none by the 3 methods. In general, our results suggest that intramuscular fat selection influenced multiple genomic regions which can be a consequence of either only selection effect or the combined effect of selection and genetic drift. In addition, 73 genes were retrieved from the 8 selection signatures. After functional and enrichment analyses, the main genes into the selection signatures linked to energy, fatty acids, carbohydrates and lipid metabolic processes wereACER2, PLIN2, DENND4C, RPS6, RRAGA(OCU1),ST8SIA6, VIM(OCU16),RORA, GANCandPLA2G4B(OCU17). This genomic scan is the first study using rabbits from a divergent selection experiment. Our results pointed out a large polygenic component of the intramuscular fat content. Besides, promising positional candidate genes would be analysed in further studies in order to bear out their contributions to this trait and their feasible implications for rabbit breeding programmes.The authors thank Federico Pardo, Veronica Juste and Marina Morini for technical assistance. The work was funded by project AGL2014-55921-C2-1-P and AGL2017-86083-C2-P1 from National Programme for Fostering Excellence in Scientific and Technical Research - Project I+D. B. Samuel Sosa-Madrid was supported by a FPI grant from the Economy Ministry of Spain (BES-2015-074194).Sosa-Madrid, BS.; Varona, L.; Blasco Mateu, A.; Hernández, P.; Casto-Rebollo, C.; Ibáñez-Escriche, N. (2020). The effect of divergent selection for intramuscular fat on the domestic rabbit genome. Animal. 14(11):2225-2235. https://doi.org/10.1017/S1751731120001263S222522351411Beissinger, T. M., Rosa, G. J., Kaeppler, S. M., Gianola, D., & de Leon, N. (2015). Defining window-boundaries for genomic analyses using smoothing spline techniques. Genetics Selection Evolution, 47(1). doi:10.1186/s12711-015-0105-9Carneiro, M., Albert, F. W., Afonso, S., Pereira, R. J., Burbano, H., Campos, R., … Ferrand, N. (2014). The Genomic Architecture of Population Divergence between Subspecies of the European Rabbit. PLoS Genetics, 10(8), e1003519. doi:10.1371/journal.pgen.1003519Carneiro M, Rubin CJ, Di Palma F, Albert FW, Alföldi J, Barrio AM, Pielberg G, Rafati N, Sayyab S, Turner-Maier J, Younis S, Afonso S, Aken B, Alves JM, Barrell D, Bolet G, Boucher S, Burbano HA, Campos R, Chang JL, Duranthon V, Fontanesi L, Garreau H, Heiman D, Johnson J, Mage RG, Peng Z, Queney G, Rogel-Gaillard C, Ruffier M, Searle S, Villafuerte R, Xiong A, Young S, Forsberg-Nilsson K, Good JM, Lander ES, Ferrand N, Lindblad-Toh K and Andersson L 2014b. Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication. Science 345, 1074–1079.Cesar, A. S., Regitano, L. C., Mourão, G. B., Tullio, R. R., Lanna, D. P., Nassu, R. T., … Coutinho, L. L. (2014). Genome-wide association study for intramuscular fat deposition and composition in Nellore cattle. BMC Genetics, 15(1). doi:10.1186/1471-2156-15-39Chen, H., Patterson, N., & Reich, D. (2010). Population differentiation as a test for selective sweeps. Genome Research, 20(3), 393-402. doi:10.1101/gr.100545.109Damon, M., Wyszynska-Koko, J., Vincent, A., Hérault, F., & Lebret, B. (2012). Comparison of Muscle Transcriptome between Pigs with Divergent Meat Quality Phenotypes Identifies Genes Related to Muscle Metabolism and Structure. PLoS ONE, 7(3), e33763. doi:10.1371/journal.pone.0033763Gandolfi, G., Mazzoni, M., Zambonelli, P., Lalatta-Costerbosa, G., Tronca, A., Russo, V., & Davoli, R. (2011). Perilipin 1 and perilipin 2 protein localization and gene expression study in skeletal muscles of European cross-breed pigs with different intramuscular fat contents. Meat Science, 88(4), 631-637. doi:10.1016/j.meatsci.2011.02.020Gol, S., Ros-Freixedes, R., Zambonelli, P., Tor, M., Pena, R. N., Braglia, S., … Davoli, R. (2015). Relationship between perilipin genes polymorphisms and growth, carcass and meat quality traits in pigs. Journal of Animal Breeding and Genetics, 133(1), 24-30. doi:10.1111/jbg.12159González-Rodríguez, A., Munilla, S., Mouresan, E. F., Cañas-Álvarez, J. J., Díaz, C., Piedrafita, J., … Varona, L. (2016). On the performance of tests for the detection of signatures of selection: a case study with the Spanish autochthonous beef cattle populations. Genetics Selection Evolution, 48(1). doi:10.1186/s12711-016-0258-1Grams, V., Wellmann, R., Preuß, S., Grashorn, M. A., Kjaer, J. B., Bessei, W., & Bennewitz, J. (2015). Genetic parameters and signatures of selection in two divergent laying hen lines selected for feather pecking behaviour. Genetics Selection Evolution, 47(1). doi:10.1186/s12711-015-0154-0Gurgul, A., Jasielczuk, I., Ropka-Molik, K., Semik-Gurgul, E., Pawlina-Tyszko, K., Szmatoła, T., … Krupiński, J. (2018). A genome-wide detection of selection signatures in conserved and commercial pig breeds maintained in Poland. BMC Genetics, 19(1). doi:10.1186/s12863-018-0681-0Johansson, A. M., Pettersson, M. E., Siegel, P. B., & Carlborg, Ö. (2010). Genome-Wide Effects of Long-Term Divergent Selection. PLoS Genetics, 6(11), e1001188. doi:10.1371/journal.pgen.1001188Kim, E.-S., Ros-Freixedes, R., Pena, R. N., Baas, T. J., Estany, J., & Rothschild, M. F. (2015). Identification of signatures of selection for intramuscular fat and backfat thickness in two Duroc populations1. Journal of Animal Science, 93(7), 3292-3302. doi:10.2527/jas.2015-8879Kuleshov, M. V., Jones, M. R., Rouillard, A. D., Fernandez, N. F., Duan, Q., Wang, Z., … Ma’ayan, A. (2016). Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Research, 44(W1), W90-W97. doi:10.1093/nar/gkw377Li, X., Lee, C.-K., Choi, B.-H., Kim, T.-H., Kim, J.-J., & Kim, K.-S. (2010). Quantitative gene expression analysis on chromosome 6 between Korean native pigs and Yorkshire breeds for fat deposition. Genes & Genomics, 32(4), 385-393. doi:10.1007/s13258-010-0009-6Lillie, M., Sheng, Z., Honaker, C. F., Dorshorst, B. J., Ashwell, C. M., Siegel, P. B., & Carlborg, Ö. (2017). Genome-wide standing variation facilitates long-term response to bidirectional selection for antibody response in chickens. BMC Genomics, 18(1). doi:10.1186/s12864-016-3414-7Ma, H., Zhang, S., Zhang, K., Zhan, H., Peng, X., Xie, S., … Ma, Y. (2019). Identifying Selection Signatures for Backfat Thickness in Yorkshire Pigs Highlights New Regions Affecting Fat Metabolism. Genes, 10(4), 254. doi:10.3390/genes10040254Mallick, S., Gnerre, S., Muller, P., & Reich, D. (2009). The difficulty of avoiding false positives in genome scans for natural selection. Genome Research, 19(5), 922-933. doi:10.1101/gr.086512.108Martínez-Álvaro, M., Hernández, P., & Blasco, A. (2016). Divergent selection on intramuscular fat in rabbits: Responses to selection and genetic parameters1. Journal of Animal Science, 94(12), 4993-5003. doi:10.2527/jas.2016-0590Mauch E, Servin B, Gilbert H and Dekkers J 2018. Signatures of selection in two independent populations of pigs divergently selected for feed efficiency. Animal Industry Report AS 664, ASL R3274.Oleksyk, T. K., Smith, M. W., & O’Brien, S. J. (2010). Genome-wide scans for footprints of natural selection. Philosophical Transactions of the Royal Society B: Biological Sciences, 365(1537), 185-205. doi:10.1098/rstb.2009.0219Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., … Sham, P. C. (2007). PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses. The American Journal of Human Genetics, 81(3), 559-575. doi:10.1086/519795Qanbari, S., & Simianer, H. (2014). Mapping signatures of positive selection in the genome of livestock. Livestock Science, 166, 133-143. doi:10.1016/j.livsci.2014.05.003Sabeti, P. C., Varilly, P., Fry, B., Lohmueller, J., Hostetter, E., … Lander, E. S. (2007). Genome-wide detection and characterization of positive selection in human populations. Nature, 449(7164), 913-918. doi:10.1038/nature06250Sargolzaei, M., Chesnais, J. P., & Schenkel, F. S. (2014). A new approach for efficient genotype imputation using information from relatives. BMC Genomics, 15(1), 478. doi:10.1186/1471-2164-15-478Sosa-Madrid BS, Hernández P, Blasco A, Haley CS, Fontanesi L, Santacreu MA, Pena RN, Navarro P and Ibáñez-Escriche N 2020. Genomic regions influencing intramuscular fat in divergently selected rabbit lines. Animal Genetics 51, 58–69.Sosa-Madrid BS, Ibañez-Escriche N, Santacreu MA, Varona L and Blasco A 2017. Huellas de selección en un experimento de seleccion divergente para capacidad uterina en conejo. In Proceedings of the XVII Jornadas sobre Producción Animal, 30–31 May 2017, Zaragoza, Spain, pp. 558–560.Szpiech ZA and Hernandez RD 2014. selscan: an efficient multithreaded program to perform EHH-based scans for positive selection. Molecular Biology and Evolution 31, 2824–2827.Utsunomiya, Y. T., Pérez O’Brien, A. M., Sonstegard, T. S., Van Tassell, C. P., do Carmo, A. S., Mészáros, G., … Garcia, J. F. (2013). Detecting Loci under Recent Positive Selection in Dairy and Beef Cattle by Combining Different Genome-Wide Scan Methods. PLoS ONE, 8(5), e64280. doi:10.1371/journal.pone.0064280Walter, M., Chen, F. W., Tamari, F., Wang, R., & Ioannou, Y. A. (2009). Endosomal lipid accumulation in NPC1 leads to inhibition of PKC, hypophosphorylation of vimentin and Rab9 entrapment. Biology of the Cell, 101(3), 141-153. doi:10.1042/bc20070171Wang, Z., Ma, H., Xu, L., Zhu, B., Liu, Y., Bordbar, F., … Li, J. (2019). 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Mechanisms of Tolerance and Resistance to Chlorhexidine in Clinical Strains of Klebsiella pneumoniae Producers of Carbapenemase: Role of New Type II Toxin-Antitoxin System, PemIK

Although the failure of antibiotic treatment is normally attributed to resistance, tolerance and persistence display a significant role in the lack of response to antibiotics. Due to the fact that several nosocomial pathogens show a high level of tolerance and/or resistance to chlorhexidine, in this study we analyzed the molecular mechanisms associated with chlorhexidine adaptation in two clinical strains of Klebsiella pneumoniae by phenotypic and transcriptomic studies. These two strains belong to ST258-KPC3 (high-risk clone carrying β-lactamase KPC3) and ST846-OXA48 (low-risk clone carrying β-lactamase OXA48). Our results showed that the K. pneumoniae ST258-KPC3CA and ST846-OXA48CA strains exhibited a different behavior under chlorhexidine (CHLX) pressure, adapting to this biocide through resistance and tolerance mechanisms, respectively. Furthermore, the appearance of cross-resistance to colistin was observed in the ST846-OXA48CA strain (tolerant to CHLX), using the broth microdilution method. Interestingly, this ST846-OXA48CA isolate contained a plasmid that encodes a novel type II toxin/antitoxin (TA) system, PemI/PemK. We characterized this PemI/PemK TA system by cloning both genes into the IPTG-inducible pCA24N plasmid, and found their role in persistence and biofilm formation. Accordingly, the ST846-OXA48CA strain showed a persistence biphasic curve in the presence of a chlorhexidine-imipenem combination, and these results were confirmed by the enzymatic assay (WST-1).The State Plan for R+D+I 2013–2016 National Plan for Scientific Research, Technological Development and Innovation 2008–2011 PI16/01163 and PI19/00878ISCIII-Deputy General Directorate for Evaluation and Promotion of Research - European Regional Development Fund “A way of Making Europe” and Instituto de Salud Carlos III FEDER, Spanish Network for the Research in Infectious Diseases REIPI, RD16/0016/0001, RD16/CIII/0004/0002 and RD16/0016/0006The Study Group on Mechanisms of Action and Resistance to Antimicrobials, GEMAR

Emerging Hyalomma lusitanicum: From identification to vectorial role and integrated control

In the Mediterranean basin, the tick species Hyalomma lusitanicum Koch stands out among other species of the Hyalomma genus due to its wide distribution, and there is great concern about its potential role as a vector and/or reservoir and its continuous expansion to new areas because of climate warming and human and other animal movements. This review aims to consolidate all the information on H. lusitanicum, including taxonomy and evolution, morphological and molecular identification, life cycle, sampling methods, rearing under laboratory conditions, ecology, hosts, geographical distribution, seasonality, vector role and control methods. The availability of adequate data is extremely relevant to the development of appropriate control strategies in areas where this tick is currently distributed as well as in new areas where it could become established in the near future.This work was partially supported by the COST Action CA21170 “Prevention, anticipation and mitigation of tick-borne disease risk applying the DAMA protocol (PRAGMATICK)”.Peer reviewe

Switching to Glycerol Phenylbutyrate in 48 Patients with Urea Cycle Disorders: Clinical Experience in Spain

Background and objectives: Glycerol phenylbutyrate (GPB) has demonstrated safety and efficacy in patients with urea cycle disorders (UCDs) by means of its clinical trial program, but there are limited data in clinical practice. In order to analyze the efficacy and safety of GPB in clinical practice, here we present a national Spanish experience after direct switching from another nitrogen scavenger to GPB. Methods: This observational, retrospective, multicenter study was performed in 48 UCD patients (age 11.7 ± 8.2 years) switching to GPB in 13 centers from nine Spanish regions. Clinical, biochemical, and nutritional data were collected at three different times: prior to GPB introduction, at first follow-up assessment, and after one year of GPB treatment. Number of related adverse effects and hyperammonemic crisis 12 months before and after GPB introduction were recorded. Results: GPB was administered at a 247.8 ± 102.1 mg/kg/day dose, compared to 262.6 ± 126.1 mg/kg/day of previous scavenger (46/48 Na-phenylbutyrate). At first follow-up (79 ± 59 days), a statistically significant reduction in ammonia (from 40.2 ± 17.3 to 32.6 ± 13.9 μmol/L, p < 0.001) and glutamine levels (from 791.4 ± 289.8 to 648.6 ± 247.41 μmol/L, p < 0.001) was observed. After one year of GPB treatment (411 ± 92 days), we observed an improved metabolic control (maintenance of ammonia and glutamine reduction, with improved branched chain amino acids profile), and a reduction in hyperammonemic crisis rate (from 0.3 ± 0.7 to less than 0.1 ± 0.3 crisis/patients/year, p = 0.02) and related adverse effects (RAE, from 0.5 to less than 0.1 RAEs/patients/year p < 0.001). Conclusions: This study demonstrates the safety of direct switching from other nitrogen scavengers to GPB in clinical practice, which improves efficacy, metabolic control, and RAE compared to previous treatments.This study was funded by AECOM (Spanish Association for the Study of Inborn Errors of Metabolism). Immedica Pharma Spain funded medical writing support and article processing charges

Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1α but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients

Epidemiological associations linking between obstructive sleep apnea and poorer solid malignant tumor outcomes have recently emerged. Putative pathways proposed to explain that these associations have included enhanced hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) cell expression in the tumor and altered immune functions via intermittent hypoxia (IH). Here, we examined relationships between HIF-1α and VEGF expression and nocturnal IH in cutaneous melanoma (CM) tumor samples. Prospectively recruited patients with CM tumor samples were included and underwent overnight polygraphy. General clinical features, apnea-hypopnea index (AHI), desaturation index (DI4%), and CM characteristics were recorded. Histochemical assessments of VEGF and HIF-1α were performed, and the percentage of positive cells (0, 75%) was blindly tabulated for VEGF expression, and as 0, 0-5.9, 6.0-10.0, >10.0% for HIF-1α expression, respectively. Cases with HIF-1α expression >6% (high expression) were compared with those 75% of cells was compared with those with <75%. 376 patients were included. High expression of VEGF and HIF-1α were seen in 88.8 and 4.2% of samples, respectively. High expression of VEGF was only associated with increasing age. However, high expression of HIF-1α was significantly associated with age, Breslow index, AHI, and DI4%. Logistic regression showed that DI4% [OR 1.03 (95% CI: 1.01-1.06)] and Breslow index [OR 1.28 (95% CI: 1.18-1.46)], but not AHI, remained independently associated with the presence of high HIF-1α expression. Thus, IH emerges as an independent risk factor for higher HIF-1α expression in CM tumors and is inferentially linked to worse clinical CM prognostic indicators.IA is supported by SEPAR (086/2014 and 595/2017). MM-G is supported by the Instituto de Salud Carlos III (PI16/01772) and cofinanced by the European Development Regional Find “A way to achieve Europe” (ERDF) and SEPAR (211/2012). ER-F is the recipient of a postdoctoral fellowship from “Fundación Científica de la Asociación Española Contra el Cáncer” and supported by FMM-2013/0075 of “Fundación Mutua Madrileña.” JR-P is supported by FIS 2014/1737 from the Spanish Ministry of Health. RF is supported in part by the Spanish Ministry of Economy and Competitiveness—Instituto de Salud Carlos III (FIS-PI14/00004); DG is supported by National Institutes of Health grant 1R01HL130984 and by the Herbert T. Abelson Chair in Pediatrics

<i>Gaia</i> Data Release 1. Summary of the astrometric, photometric, and survey properties

Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ∼3000 Cepheid and RR-Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr−1 for the proper motions. A systematic component of ∼0.3 mas should be added to the parallax uncertainties. For the subset of ∼94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr−1. For the secondary astrometric data set, the typical uncertainty of the positions is ∼10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ∼0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data

Use of tocilizumab in kidney transplant recipients with COVID-1

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed