Modeling ANXA2-overexpressing circulating tumor cells homing and high throughput screening for metastasis impairment in endometrial carcinomas

Cèl·lules tumorals circulants; Micrometàstasi; DaunorrubicinaCélulas tumorales circulantes; Micrometástasis; DaunorrubicinaCirculating tumor cells; Micrometastasis; DaunorubicinEndometrial cancer (EC) is the most common neoplasm of the female reproductive tract in the developed world. Patients usually are diagnosed in early stage having a good prognosis. However, up to 20–25% of patients are diagnosed in advanced stages and have a higher risk of recurrence, making the prognosis worse. Previously studies identified ANXA2 as a predictor of recurrent disease in EC even in low risk patients. Furthermore, Circulating Tumor Cells (CTC) released from the primary tumor into the bloodstream, are plasticity entities responsible of the process of metastasis, becoming into an attractive clinical target. In this work we validated ANXA2 expression in CTC from high-risk EC patients. After that, we modelled in vitro and in vivo the tumor cell attachment of ANXA2-expressing CTC to the endothelium and the homing for the generation of micrometastasis. ANXA2 overexpression does not provide an advantage in the adhesion process of CTC, but it could be playing an important role in more advanced steps, conferring a greater homing capacity. We also performed a high-throughput screening (HTS) for compounds specifically targeting ANXA2, and selected Daunorubicin as candidate hit. Finally, we validated Daunorubicin in a 3D transendothelial migration system and also in a in vivo model of advanced EC, demonstrating the ability of Daunorubicin to inhibit the proliferation of ANXA2-overexpressing tumor cells.This work was supported by grants from the Instituto de Salud Carlos III ( ISCIII ), grant PI17/01919 and PI20/00969 , co-financed by the European Regional Development Fund (FEDER); from Fundación Científica de la Asociación Española Contra el Cáncer (AECC), Grupos Clínicos Coordinados 2018; Xunta de Galicia ( ED431C 2018/21 ); Ministry of Economy and Competiveness (Innopharma Project) and from CIBERONC ( CB16/12/00328 ); Carolina Herrero is supported by a predoctoral i-PFIS fellowship from Instituto de Salud Carlos III ( IFI17/00047 )

Sequencing of diverse mandarin, pummelo and orange genomes reveals complex history of admixture during citrus domestication

Cultivated citrus are selections from, or hybrids of, wild progenitor species whose identities and contributions to citrus domestication remain controversial. Here we sequence and compare citrus genomes-a high-quality reference haploid clementine genome and mandarin, pummelo, sweet-orange and sour-orange genomes-and show that cultivated types derive from two progenitor species. Although cultivated pummelos represent selections from one progenitor species, Citrus maxima, cultivated mandarins are introgressions of C. maxima into the ancestral mandarin species Citrus reticulata. The most widely cultivated citrus, sweet orange, is the offspring of previously admixed individuals, but sour orange is an F1 hybrid of pure C. maxima and C. reticulata parents, thus implying that wild mandarins were part of the early breeding germplasm. A Chinese wild 'mandarin' diverges substantially from C. reticulata, thus suggesting the possibility of other unrecognized wild citrus species. Understanding citrus phylogeny through genome analysis clarifies taxonomic relationships and facilitates sequence-directed genetic improvement

Sequencing of diverse mandarin, pummelo and orange genomes reveals complex history of admixture during citrus domestication

Cultivated citrus are selections from, or hybrids of, wild progenitor species whose identities and contributions to citrus domestication remain controversial. Here we sequence and compare citrus genomes-a high-quality reference haploid clementine genome and mandarin, pummelo, sweet-orange and sour-orange genomes-and show that cultivated types derive from two progenitor species. Although cultivated pummelos represent selections from one progenitor species, Citrus maxima, cultivated mandarins are introgressions of C. maxima into the ancestral mandarin species Citrus reticulata. The most widely cultivated citrus, sweet orange, is the offspring of previously admixed individuals, but sour orange is an F1 hybrid of pure C. maxima and C. reticulata parents, thus implying that wild mandarins were part of the early breeding germplasm. A Chinese wild 'mandarin' diverges substantially from C. reticulata, thus suggesting the possibility of other unrecognized wild citrus species. Understanding citrus phylogeny through genome analysis clarifies taxonomic relationships and facilitates sequence-directed genetic improvement. (Résumé d'auteur

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Ahora / Ara

La cinquena edició del microrelatari per l’eradicació de la violència contra les dones de l’Institut Universitari d’Estudis Feministes i de Gènere «Purificación Escribano» de la Universitat Jaume I vol ser una declaració d’esperança. Aquest és el moment en el qual les dones (i els homes) hem de fer un pas endavant i eliminar la violència sistèmica contra les dones. Ara és el moment de denunciar el masclisme i els micromasclismes començant a construir una societat més igualitària. Cadascun dels relats del llibre és una denúncia i una declaració que ens encamina cap a un món millor

Acta Horticulturae

In recent years we have generated various collections of citrus mutants. One objective of these collections is the selection of genotypes of commercial interest. In the present communication we describe 3 lines derived from clementine (Citrus clementina) through physical mutagenesis, named ‘Clemenverd’, ‘Nero’ and ‘Neufina’. These lines that show enhanced agronomic traits as related to the parental genotype have been registered. ‘Clemenverd’ shows delayed external maturation. ‘Nero’ is an early cultivar of seedless clementine that maintains the excellence of clementine quality. On the other hand, ‘Neufina’ holds well into February the commercial organoleptic qualities of the parental cultivar. ‘Neufina’ also has excellent perdurability in the tree, making it an ideal option to extend the supply of clementines during winter

Acta Horticulturae

The survival of the citrus industry is critically dependent on genetically superior cultivars. Improvements in these traits through traditional techniques are unfortunately extremely difficult due to the unusual combination of biological characteristics of citrus. Genomic science holds promise of improvements in breeding and the main goal of our group is to develop genomics tools for the generation of new genotypes. We pursue the identification of candidate genes, alleles and genotypes improving citrus fruit quality and performance, correlating phenotypic analyses, metabolic profiling and gene expression. At completion, genes and alleles with major functions in nutritional quality and stress tolerance could be selected and genotypes with improved fruit composition searched among existing or generated collections. This goal is supported by two complementary strategies the identification of genes of agricultural interest by the use of mutants and microarrays and the elucidation of the citrus genome sequence. In this communication the efforts we are developing in this first approach are revised while the other strategy will be resumed elsewhere

CITRUS GENOMICS AND BREEDING: IDENTIFICATION OF CANDIDATE GENES BY THE USE OF MUTANTS AND MICROARRAYS

The survival of the citrus industry is critically dependent on genetically superior cultivars. Improvements in these traits through traditional techniques are unfortunately extremely difficult due to the unusual combination of biological characteristics of citrus. Genomic science holds promise of improvements in breeding and the main goal of our group is to develop genomics tools for the generation of new genotypes. We pursue the identification of candidate genes, alleles and genotypes improving citrus fruit quality and performance, correlating phenotypic analyses, metabolic profiling and gene expression. At completion, genes and alleles with major functions in nutritional quality and stress tolerance could be selected and genotypes with improved fruit composition searched among existing or generated collections. This goal is supported by two complementary strategies the identification of genes of agricultural interest by the use of mutants and microarrays and the elucidation of the citrus genome sequence. In this communication the efforts we are developing in this first approach are revised while the other strategy will be resumed elsewhere