In Vivo IS6110 profile changes in a Mycobacterium tuberculosis strain as determined by tracking over 14 years

Transposition and homologous recombination of IS6110 appear in Mycobacterium tuberculosis along in vivo sequential infec- tions. These events were checked in different clones of a successful strain, M. tuberculosis Zaragoza, with the focus on a variant in which integration of a copy of IS6110 in the origin of replication (oriC) region occurred

An integrative "omics" apprach identifies new candidate genes to impact aroma volatiles in peach fruit

[EN] Background: Ever since the recent completion of the peach genome, the focus of genetic research in this area has turned to the identification of genes related to important traits, such as fruit aroma volatiles. Of the over 100 volatile compounds described in peach, lactones most likely have the strongest effect on fruit aroma, while esters, terpenoids, and aldehydes have minor, yet significant effects. The identification of key genes underlying the production of aroma compounds is of interest for any fruit-quality improvement strategy. Results: Volatile (52 compounds) and gene expression (4348 genes) levels were profiled in peach fruit from a maturity time-course series belonging to two peach genotypes that showed considerable differences in maturation characteristics and postharvest ripening. This data set was analyzed by complementary correlation-based approaches to discover the genes related to the main aroma-contributing compounds: lactones, esters, and phenolic volatiles, among others. As a case study, one of the candidate genes was cloned and expressed in yeast to show specificity as an omega-6 Oleate desaturase, which may be involved in the production of a precursor of lactones/esters. Conclusions: Our approach revealed a set of genes (an alcohol acyl transferase, fatty acid desaturases, transcription factors, protein kinases, cytochromes, etc.) that are highly associated with peach fruit volatiles, and which could prove useful in breeding or for biotechnological purposes.We are grateful to Cristina Besada, PhD (Instituto Valenciano de Investigaciones Agrarias, IVIA, Spain) for her help with the fruit quality parameter analyses. We are also thankful to Cristina Marti and Clara Pons (Instituto de Biologia Molecular y Celular de Plantas, IBMCP, Spain) for their advice on microarray analyses. Jesus Garcia Brunton, PhD for providing the fruits used in this study (Instituto Murciano de Investigacion y Desarrollo Agrario, IMIDA, Spain). HS-SPME-GC-MS analyses were performed at the Metabolomic lab facilities at the IBMCP (CSIC) in Spain. GS has financial support from INTA (Instituto Nacional de Tecnologia Agropecuaria, Argentine). This project has been funded by the Ministry of Economy and Competitivity grant AGL2010-20595.Sánchez, G.; Venegas Calerón, M.; Salas, J.; Monforte Gilabert, AJ.; Badenes, M.; Granell Richart, A. (2013). An integrative "omics" apprach identifies new candidate genes to impact aroma volatiles in peach fruit. BMC Genomics. 14(343):1-23. https://doi.org/10.1186/1471-2164-14-343S1231434

The peach volatilome modularity is reflected at the genetic and environmental response levels in a QTL mapping population

Background: The improvement of fruit aroma is currently one of the most sought-after objectives in peach breeding programs. To better characterize and assess the genetic potential for increasing aroma quality by breeding, a quantity trait locus (QTL) analysis approach was carried out in an F-1 population segregating largely for fruit traits. Results: Linkage maps were constructed using the IPSC peach 9 K Infinium (R) II array, rendering dense genetic maps, except in the case of certain chromosomes, probably due to identity-by-descent of those chromosomes in the parental genotypes. The variability in compounds associated with aroma was analyzed by a metabolomic approach based on GC-MS to profile 81 volatiles across the population from two locations. Quality-related traits were also studied to assess possible pleiotropic effects. Correlation-based analysis of the volatile dataset revealed that the peach volatilome is organized into modules formed by compounds from the same biosynthetic origin or which share similar chemical structures. QTL mapping showed clustering of volatile QTL included in the same volatile modules, indicating that some are subjected to joint genetic control. The monoterpene module is controlled by a unique locus at the top of LG4, a locus previously shown to affect the levels of two terpenoid compounds. At the bottom of LG4, a locus controlling several volatiles but also melting/non-melting and maturity-related traits was found, suggesting putative pleiotropic effects. In addition, two novel loci controlling lactones and esters in linkage groups 5 and 6 were discovered. Conclusions: The results presented here give light on the mode of inheritance of the peach volatilome confirming previously loci controlling the aroma of peach but also identifying novel ones.GS has financial support from INTA (Instituto Nacional de Tecnologia Agropecuaria, Argentina). HS-SPME-GC-MS analyses were performed at the Metabolomic lab facilities at the IBMCP (CSIC) in Spain. This project has been funded by the Ministry of Economy and Competitivity grant AGL2010-20595.Sánchez, G.; Martinez, J.; Romeu, J.; Garcia, J.; Monforte Gilabert, AJ.; Badenes, M.; Granell Richart, A. (2014). The peach volatilome modularity is reflected at the genetic and environmental response levels in a QTL mapping population. BMC Plant Biology. 14(137):1-16. https://doi.org/10.1186/1471-2229-14-137S11614137Klee, H. J., & Giovannoni, J. J. (2011). Genetics and Control of Tomato Fruit Ripening and Quality Attributes. Annual Review of Genetics, 45(1), 41-59. doi:10.1146/annurev-genet-110410-132507Sánchez, G., Besada, C., Badenes, M. L., Monforte, A. J., & Granell, A. (2012). A Non-Targeted Approach Unravels the Volatile Network in Peach Fruit. PLoS ONE, 7(6), e38992. doi:10.1371/journal.pone.0038992Eduardo, I., Chietera, G., Bassi, D., Rossini, L., & Vecchietti, A. (2010). Identification of key odor volatile compounds in the essential oil of nine peach accessions. Journal of the Science of Food and Agriculture, 90(7), 1146-1154. doi:10.1002/jsfa.3932Derail, C., Hofmann, T., & Schieberle, P. (1999). Differences in Key Odorants of Handmade Juice of Yellow-Flesh Peaches (Prunus persicaL.) Induced by the Workup Procedure. Journal of Agricultural and Food Chemistry, 47(11), 4742-4745. doi:10.1021/jf990459gGreger, V., & Schieberle, P. (2007). Characterization of the Key Aroma Compounds in Apricots (Prunus armeniaca) by Application of the Molecular Sensory Science Concept. Journal of Agricultural and Food Chemistry, 55(13), 5221-5228. doi:10.1021/jf0705015Zhang, B., Shen, J., Wei, W., Xi, W., Xu, C.-J., Ferguson, I., & Chen, K. (2010). Expression of Genes Associated with Aroma Formation Derived from the Fatty Acid Pathway during Peach Fruit Ripening. Journal of Agricultural and Food Chemistry, 58(10), 6157-6165. doi:10.1021/jf100172eAubert, C., Günata, Z., Ambid, C., & Baumes, R. (2003). Changes in Physicochemical Characteristics and Volatile Constituents of Yellow- and White-Fleshed Nectarines during Maturation and Artificial Ripening. Journal of Agricultural and Food Chemistry, 51(10), 3083-3091. doi:10.1021/jf026153iXI, W.-P., ZHANG, B., LIANG, L., SHEN, J.-Y., WEI, W.-W., XU, C.-J., … CHEN, K.-S. (2011). Postharvest temperature influences volatile lactone production via regulation of acyl-CoA oxidases in peach fruit. Plant, Cell & Environment, 35(3), 534-545. doi:10.1111/j.1365-3040.2011.02433.xBrandi, F., Bar, E., Mourgues, F., Horváth, G., Turcsi, E., Giuliano, G., … Rosati, C. (2011). Study of «Redhaven» peach and its white-fleshed mutant suggests a key role of CCD4 carotenoid dioxygenase in carotenoid and norisoprenoid volatile metabolism. BMC Plant Biology, 11(1), 24. doi:10.1186/1471-2229-11-24Sánchez, G., Venegas-Calerón, M., Salas, J. J., Monforte, A., Badenes, M. L., & Granell, A. (2013). An integrative «omics» approach identifies new candidate genes to impact aroma volatiles in peach fruit. BMC Genomics, 14(1), 343. doi:10.1186/1471-2164-14-343Verde, I., Abbott, A. G., Scalabrin, S., Jung, S., Shu, S., … Grimwood, J. (2013). The high-quality draft genome of peach (Prunus persica) identifies unique patterns of genetic diversity, domestication and genome evolution. Nature Genetics, 45(5), 487-494. doi:10.1038/ng.2586Verde, I., Bassil, N., Scalabrin, S., Gilmore, B., Lawley, C. T., Gasic, K., … Peace, C. (2012). Development and Evaluation of a 9K SNP Array for Peach by Internationally Coordinated SNP Detection and Validation in Breeding Germplasm. PLoS ONE, 7(4), e35668. doi:10.1371/journal.pone.0035668Zorrilla-Fontanesi, Y., Rambla, J.-L., Cabeza, A., Medina, J. J., Sánchez-Sevilla, J. F., Valpuesta, V., … Amaya, I. (2012). Genetic Analysis of Strawberry Fruit Aroma and Identification of O-Methyltransferase FaOMT as the Locus Controlling Natural Variation in Mesifurane Content. Plant Physiology, 159(2), 851-870. doi:10.1104/pp.111.188318Zanor, M. I., Rambla, J.-L., Chaïb, J., Steppa, A., Medina, A., Granell, A., … Causse, M. (2009). Metabolic characterization of loci affecting sensory attributes in tomato allows an assessment of the influence of the levels of primary metabolites and volatile organic contents. Journal of Experimental Botany, 60(7), 2139-2154. doi:10.1093/jxb/erp086Romeu, J. F., Monforte, A. J., Sánchez, G., Granell, A., García-Brunton, J., Badenes, M. L., & Ríos, G. (2014). Quantitative trait loci affecting reproductive phenology in peach. BMC Plant Biology, 14(1), 52. doi:10.1186/1471-2229-14-52Lander, E. S., Green, P., Abrahamson, J., Barlow, A., Daly, M. J., Lincoln, S. E., & Newburg, L. (1987). MAPMAKER: An interactive computer package for constructing primary genetic linkage maps of experimental and natural populations. Genomics, 1(2), 174-181. doi:10.1016/0888-7543(87)90010-3Voorrips, R. E. (2002). MapChart: Software for the Graphical Presentation of Linkage Maps and QTLs. Journal of Heredity, 93(1), 77-78. doi:10.1093/jhered/93.1.77Tikunov, Y., Lommen, A., de Vos, C. H. R., Verhoeven, H. A., Bino, R. J., Hall, R. D., & Bovy, A. G. (2005). A Novel Approach for Nontargeted Data Analysis for Metabolomics. Large-Scale Profiling of Tomato Fruit Volatiles. Plant Physiology, 139(3), 1125-1137. doi:10.1104/pp.105.068130Shannon, P. (2003). Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks. Genome Research, 13(11), 2498-2504. doi:10.1101/gr.1239303Yang, J., Hu, C., Hu, H., Yu, R., Xia, Z., Ye, X., & Zhu, J. (2008). QTLNetwork: mapping and visualizing genetic architecture of complex traits in experimental populations. Bioinformatics, 24(5), 721-723. doi:10.1093/bioinformatics/btm494Elshire, R. J., Glaubitz, J. C., Sun, Q., Poland, J. A., Kawamoto, K., Buckler, E. S., & Mitchell, S. E. (2011). A Robust, Simple Genotyping-by-Sequencing (GBS) Approach for High Diversity Species. PLoS ONE, 6(5), e19379. doi:10.1371/journal.pone.0019379Quilot, B., Wu, B. H., Kervella, J., G�nard, M., Foulongne, M., & Moreau, K. (2004). QTL analysis of quality traits in an advanced backcross between Prunus persica cultivars and the wild relative species P. davidiana. Theoretical and Applied Genetics, 109(4), 884-897. doi:10.1007/s00122-004-1703-zDirlewanger, E., Quero-García, J., Le Dantec, L., Lambert, P., Ruiz, D., Dondini, L., … Arús, P. (2012). Comparison of the genetic determinism of two key phenological traits, flowering and maturity dates, in three Prunus species: peach, apricot and sweet cherry. Heredity, 109(5), 280-292. doi:10.1038/hdy.2012.38Dirlewanger, E., Graziano, E., Joobeur, T., Garriga-Caldere, F., Cosson, P., Howad, W., & Arus, P. (2004). Comparative mapping and marker-assisted selection in Rosaceae fruit crops. Proceedings of the National Academy of Sciences, 101(26), 9891-9896. doi:10.1073/pnas.030793710

Analysis of Mycobacterium africanum in the last 17 years in Aragon identifies a specific location of IS6110 in Lineage 6

The purpose of this study was to increase our knowledge about Mycobacterium africanum and report the incidence and characteristics of tuberculosis (TB) due to their lineages in Aragon, Spain, over the period 2003–2019. The study includes all the cases in our region, where all the M. tuberculosis complex isolates are systematically characterised. We detected 31 cases of M. africanum among 2598 cases of TB in the period studied. TB caused by M. africanum is rare (1.19%) in our population, and it affects mainly men of economically productive age coming from West African countries. Among the isolates, Lineage (L) 6 was more frequent than L5. The genotyping of these strains identified five clusters and 13 strains with a unique pattern. The isolates’ characterisation identified a copy of IS6110 within the moaX gene, which turned out to be specific for L6. It will allow the differentiation of this lineage from the rest of MTBC with a simple PCR reaction. It remains to be established whether this polymorphism may limit M. africanum transmission. Furthermore, a mutation in the mutT2 promoter was found as specific for L6 strains, which could be related to the high variability found for L6 compared to L5. © 2021, The Author(s)

Quantitative trait loci affecting reproductive phenology in peach

Background: The reproductive phenology of perennial plants in temperate climates is largely conditioned by the duration of bud dormancy, and fruit developmental processes. Bud dormancy release and bud break depends on the perception of cumulative chilling and heat during the bud development. The objective of this work was to identify new quantitative trait loci (QTLs) associated to temperature requirements for bud dormancy release and flowering and to fruit harvest date, in a segregating population of peach. Results: We have identified QTLs for nine traits related to bud dormancy, flowering and fruit harvest in an intraspecific hybrid population of peach in two locations differing in chilling time accumulation. QTLs were located in a genetic linkage map of peach based on single nucleotide polymorphism (SNP) markers for eight linkage groups (LGs) of the peach genome sequence. QTLs for chilling requirements for dormancy release and blooming clustered in seven different genomic regions that partially coincided with loci identified in previous works. The most significant QTL for chilling requirements mapped to LG1, close to the evergrowing locus. QTLs for heat requirement related traits were distributed in nine genomic regions, four of them co-localizing with QTLs for chilling requirement trait. Two major loci in LG4 and LG6 determined fruit harvest time. Conclusions: We identified QTLs associated to nine traits related to the reproductive phenology in peach. A search of candidate genes for these QTLs rendered different genes related to flowering regulation, chromatin modification and hormone signalling. A better understanding of the genetic factors affecting crop phenology might help scientists and breeders to predict changes in genotype performance in a context of global climate change.We thank Matilde Gonzalez for technical assistance. 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Theoretical and Applied Genetics, 109(4), 884-897. doi:10.1007/s00122-004-1703-zDirlewanger, E., Quero-García, J., Le Dantec, L., Lambert, P., Ruiz, D., Dondini, L., … Arús, P. (2012). Comparison of the genetic determinism of two key phenological traits, flowering and maturity dates, in three Prunus species: peach, apricot and sweet cherry. Heredity, 109(5), 280-292. doi:10.1038/hdy.2012.38Olukolu, B. A., Trainin, T., Fan, S., Kole, C., Bielenberg, D. G., Reighard, G. L., … Holland, D. (2009). Genetic linkage mapping for molecular dissection of chilling requirement and budbreak in apricot (Prunus armeniacaL.). Genome, 52(10), 819-828. doi:10.1139/g09-050Fan, S., Bielenberg, D. G., Zhebentyayeva, T. N., Reighard, G. L., Okie, W. R., Holland, D., & Abbott, A. G. (2009). Mapping quantitative trait loci associated with chilling requirement, heat requirement and bloom date in peach (Prunus persica). 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Burden and risk factors for Pseudomonas aeruginosa community-acquired pneumonia:a Multinational Point Prevalence Study of Hospitalised Patients

Pseudornonas aeruginosa is a challenging bacterium to treat due to its intrinsic resistance to the antibiotics used most frequently in patients with community-acquired pneumonia (CAP). Data about the global burden and risk factors associated with P. aeruginosa-CAP are limited. We assessed the multinational burden and specific risk factors associated with P. aeruginosa-CAP. We enrolled 3193 patients in 54 countries with confirmed diagnosis of CAP who underwent microbiological testing at admission. Prevalence was calculated according to the identification of P. aeruginosa. Logistic regression analysis was used to identify risk factors for antibiotic-susceptible and antibiotic-resistant P. aeruginosa-CAP. The prevalence of P. aeruginosa and antibiotic-resistant P. aeruginosa-CAP was 4.2% and 2.0%, respectively. The rate of P. aeruginosa CAP in patients with prior infection/colonisation due to P. aeruginosa and at least one of the three independently associated chronic lung diseases (i.e. tracheostomy, bronchiectasis and/or very severe chronic obstructive pulmonary disease) was 67%. In contrast, the rate of P. aeruginosa-CAP was 2% in patients without prior P. aeruginosa infection/colonisation and none of the selected chronic lung diseases. The multinational prevalence of P. aeruginosa-CAP is low. The risk factors identified in this study may guide healthcare professionals in deciding empirical antibiotic coverage for CAP patients

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Analysis of the full-length integrase DNA complex by a modified approach for DNA docking

A model of the full-length HIV-1 integrase dimer was constructed assembling the experimentally determined structures of the single domains. Subsequently, the three-domain protein-viral DNA complex was generated for the first time through an automated docking algorithm, obtained modifying the ESCHER program, a well-known method for protein-protein docking. A detailed study of the contacts established with DNA by the enzyme revealed that the predicted model reproduced the results of mutagenesis and cross-linking experiments, confirming the validity of our docking approach in predicting the base specificity in the DNA-protein interaction

Litiasis en divertículo de uretra de localización intraescrotal

Los divertículos uretrales en el varón son una patología rara que aparece, en su mayoría, después de realizar manipulaciones uretrales. Desde el punto de vista clínico, pueden ser sintomáticos o no sintomáticos. Las complicaciones ocurren en un 10% de los casos, siendo la más frecuente la litiasis. Cuando el divertículo está ocupado por cálculos, suele presentar una sintomatología mucho más evidente. La cistouretrografía es la técnica de elección en estos casos, ya que permite diferenciar los divertículos uretrales del resto de las lesiones quísticas parauretrales. El tratamiento de elección es la exéresis del divertículo y la uretroplastia. La abstención quirúrgica puede estar indicada solo en los divertículos asintomáticos de muy pequeño volumen. Presentamos un paciente de 44 años de edad que acudió al servicio de Urgencias por el desarrollo de una masa escrotal de gran tamaño con signos inflamatorios locales. Se confirmó quirúrgicamente el diagnóstico presuntivo de divertículo uretral gigante con litiasis en su interior, efectuado tras la evaluación imagenológica con radiografía simple, ecografía, tomografía computada y uretrografía retrógrada