Chromosomal mapping of rRNA genes, core histone genes and telomeric sequences in Brachidontes puniceus and Brachidontes rodriguezi (Bivalvia, Mytilidae)

<p>Abstract</p> <p>Background</p> <p>Chromosome rearrangements are an important part of the speciation process in many taxa. The study of chromosome evolution in bivalves is hampered by the absence of clear chromosomal banding patterns and the similarity in both chromosome size and morphology. For this reason, obtaining good chromosome markers is essential for reliable karyotypic comparisons. To begin this task, the chromosomes of the mussels <it>Brachidontes puniceus </it>and <it>B. rodriguezi </it>were studied by means of fluorochrome staining and fluorescent <it>in situ </it>hybridization (FISH).</p> <p>Results</p> <p><it>Brachidontes puniceus </it>and <it>B. rodriguezi </it>both have 2n = 32 chromosomes but differing karyotype composition. Vertebrate-type telomeric sequences appear at both ends of every single chromosome. <it>B. puniceus </it>presents a single terminal major rRNA gene cluster on a chromosome pair while <it>B. rodriguezi </it>shows two. Both mussels present two 5S rDNA and two core histone gene clusters intercalary located on the long arms of two chromosome pairs. Double and triple-FISH experiments demonstrated that one of the 5S rDNA and one of the major rDNA clusters appear on the same chromosome pair in <it>B. rodriguezi </it>but not in <it>B. puniceus</it>. On the other hand, the second 5S rDNA cluster is located in one of the chromosome pairs also bearing one of the core histone gene clusters in the two mussel species.</p> <p>Conclusion</p> <p>Knowledge of the chromosomal distribution of these sequences in the two species of <it>Brachidontes </it>is a first step in the understanding of the role of chromosome changes on bivalve evolution.</p

Promiscuous Speciation with Gene Flow in Silverside Fish Genus Odontesthes (Atheriniformes, Atherinopsidae) from South Western Atlantic Ocean Basins

The present paper integrates phylogenetic and population genetics analyses based on mitochondrial and nuclear molecular markers in silversides, genus Odontesthes, from a non-sampled area in the SW Atlantic Ocean to address species discrimination and to define Managements Units for sustainable conservation. All phylogenetic analyses based on the COI mitochondrial gene were consistent to support the monophyly of the genus Odontesthes and to include O. argentinensis, O. perugiae-humensis and some O. bonariensis haplotypes in a basal polytomy conforming a major derivative clade. Microsatellites data revealed somewhat higher genetic variability values in the O. argentinensis-perugia populations than in O. bonariensis and O. perugia-humensis taxa. Contrasting population genetics structuring emerged from mitochondrial and microsatellites analyses in these taxa. Whereas mitochondrial data supported two major groups (O. argentinensis-perugia-humensis vs. O. bonariensis-perugiae-humensis populations), microsatellite data detected three major genetic entities represented by O. bonariensis, O. perugiae-humensis and an admixture of populations belonging to O. argentinensis-perugiae respectively. Therefore, the star COI polytomy in the tree topology involving these taxa could be interpreted by several hypothetic scenarios such as the existence of shared ancestral polymorphisms, incomplete lineage sorting in a radiating speciation process and/or reticulation events. Present findings support that promiscuous and recent contact between incipient species sharing asymmetric gene flow exchanges, blurs taxa boundaries yielding complicated taxonomy and Management Units delimitation in silverside genus Odontesthes from SW Atlantic Ocean basins.This research received financial support from the project Fondo María Viñas_2009_1_2793 (FMV_2009_1_2793_Project) granted by the Agencia Nacional de Investigación e Inovación (ANII) of UruguayS

The Potential of Zebrafish as a Model Organism for Improving the Translation of Genetic Anticancer Nanomedicines

In the last few decades, the field of nanomedicine applied to cancer has revolutionized cancer treatment: several nanoformulations have already reached the market and are routinely being used in the clinical practice. In the case of genetic nanomedicines, i.e., designed to deliver gene therapies to cancer cells for therapeutic purposes, advances have been less impressive. This is because of the many barriers that limit the access of the therapeutic nucleic acids to their target site, and the lack of models that would allow for an improvement in the understanding of how nanocarriers can be tailored to overcome them. Zebrafish has important advantages as a model species for the study of anticancer therapies, and have a lot to offer regarding the rational development of efficient delivery of genetic nanomedicines, and hence increasing the chances of their successful translation. This review aims to provide an overview of the recent advances in the development of genetic anticancer nanomedicines, and of the zebrafish models that stand as promising tools to shed light on their mechanisms of action and overall potential in oncologyThis work was supported by the Xunta de Galicia, Spain (Competitive Reference Groups, GRC2014/010), the Carlos III Health Institute/FEDER (PI15/00828), and the Spanish Ministry of Education, Culture and Sport (FPU15/06595)S

Cell senescence contributes to tissue regeneration in zebrafish

Cellular senescence is a stress response that limits the proliferation of damaged cells by establishing a permanent cell cycle arrest. Different stimuli can trigger senescence but excessive production or impaired clearance of these cells can lead to their accumulation during aging with deleterious effects. Despite this potential negative side of cell senescence, its physiological role as a pro‐regenerative and morphogenetic force has emerged recently after the identification of programmed cell senescence during embryogenesis and during wound healing and limb regeneration. Here, we explored the conservation of tissue injury‐induced senescence in a model of complex regeneration, the zebrafish. Fin amputation in adult fish led to the appearance of senescent cells at the site of damage, and their removal impaired tissue regeneration. Despite many conceptual similarities, this tissue repair response is different from developmental senescence. Our results lend support to the notion that cell senescence is a positive response promoting tissue repair and homeostasis.Funding at the laboratory of M.C. is provided by the Ministerio de Ciencia, Innovación y Universidades, Fondos Europeos de Desarrollo Regional (FEDER) (RTI2018‐095818‐B‐100). Work in the laboratory of A.B.‐I. was funded by grants from the Xunta de Galicia (2016‐PG008) and the crowdfunding platform Precipita (FECYT; 2017‐CP081). The laboratory of L.S. is supported by the Regional Government Xunta de Galicia (ED431C 2018/28)S

Developmentally-programmed cellular senescence is conserved and widespread in zebrafish

Cellular senescence is considered a stress response imposing a stable cell cycle arrest to restrict the growth of damaged cells. More recently however, cellular senescence was identified during mouse embryo development at particular structures during specific periods of time. This programmed cell senescence has been proposed to serve developmental and morphogenetic functions and to potentially represent an evolutionary origin of senescence. Cellular senescence has also been described to take place during bird (chick and quail) and amphibian (xenopus and axoltl) development. Fish however, have been described to show a very narrow and restricted pattern of developmental cell senescence. Here we carried out a detailed characterization of senescence during zebrafish development and found it to be conserved and widespread. Apart from yolk and cloaca, previously described structures, we also identified senescence in the developing central nervous system, intestine, liver, pronephric ducts, and crystalline. Interestingly, senescence at these developing structures disappeared upon treatment with senolytic compound ABT-263, supporting their senescent identity and opening the possibility of studying the contribution of this process to development. In summary, our findings extend the description of developmentally-programmed cell senescence to lower vertebrates contributing to the notion of the relevance of this process for embryo developmentFunding at the laboratory of M.C. is provided by the Ministerio de Ciencia, Innovación y Universidades, Fondos Europeos de Desarrollo Regional (FEDER) (RTI2018-095818-B-100). Work in the laboratory of A.B.-I. was funded by grants from the Xunta de Galicia (2016-PG008) and the crowdfunding platform Precipita (FECYT; 2017-CP081). Funding at laboratory of L.S. is provided by Xunta de Galicia (ED431C2018/28)S

Danio Rerio as Model Organism for Adenoviral Vector Evaluation

Viral vector use is wide-spread in the field of gene therapy, with new clinical trials starting every year for different human pathologies and a growing number of agents being approved by regulatory agencies. However, preclinical testing is long and expensive, especially during the early stages of development. Nowadays, the model organism par excellence is the mouse (Mus musculus), and there are few investigations in which alternative models are used. Here, we assess the possibility of using zebrafish (Danio rerio) as an in vivo model for adenoviral vectors. We describe how E1/E3-deleted adenoviral vectors achieve efficient transduction when they are administered to zebrafish embryos via intracranial injection. In addition, helper-dependent (high-capacity) adenoviral vectors allow sustained transgene expression in this organism. Taking into account the wide repertoire of genetically modified zebrafish lines, the ethical aspects, and the affordability of this model, we conclude that zebrafish could be an efficient alternative for the early-stage preclinical evaluation of adenoviral vectorsThis research was funded by Xunta de Galicia, Local Government, grant number ED431C 2018/28, and Gobierno de Navarra, Local Government, grant numbers 0011-1383-2018-000011 PT038 and 0011-1383-2019-000006 PT013 (XANTOGEN)S

Glycosylated Cell Penetrating Peptides, GCPPs

This is the peer reviewed version of the following article: Gallego, I. , Rioboo, A. , Reina, J. ., Díaz, B. , Canales, Á., Cañada, F. ., Guerra-Varela, J. , Sánchez, L. and Montenegro, J. (2019), Glycosylated Cell Penetrating Peptides, GCPPs. ChemBioChem. doi:10.1002/cbic.201800720, which has been published in final form at https://doi.org/10.1002/cbic.201800720. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsThe cell membrane regulates the exchange of molecules and information with the external environment. However, this control barrier hinders the delivery of exogenous bioactive molecules that can be applied to correct cellular malfunctions. Therefore, the traffic of macromolecules across the cell membrane represents a great challenge for the development of the next generation of therapies and diagnostic methods. Cell penetrating peptides are short peptide sequences capable of delivering a broad range of biomacromolecules across the cellular membrane. However, penetrating peptides still suffer from limitations mainly related with their lack of specificity and potential toxicity. Glycosylation has emerged as a potential promising strategy for the biological improvement of synthetic materials. In this work we have developed a new convergent strategy for the synthesis of penetrating peptides functionalized with glycan residues by an oxime bond connection. We have systematically characterized the uptake efficiency and the intracellular distribution of these glycopeptides by flow cytometry, confocal microscopy and in zebrafish animal models. The incorporation of these glycan residues into the peptide structure influenced the internalization efficiency and the cellular toxicity of the resulting glycopeptide hybrids in the different cell lines tested. The results reported here highlight the potential of the glycosylation of penetrating peptides to modulate their activityWe acknowledge funding from the Spanish Agencia Estatal de Investigación (AEI) [CTQ2014-59646-R, SAF2017-89890-R, CTQ2016-76263-P, CTQ2015-64597-C2-2P], the Xuntade Galicia (ED431G/09, ED431C 2017/25 and 2016-AD031) and the ERDF. I. G. received a predoctoral fellowship from the Xunta de Galicia (ED481A-2018/116). A. R. received a predoctoral fellowship from the Fundación Segundo Gil Dávila. J.G.-V. and L.S. acknowledge the financial support received from the Xunta de Galicia (Galicia, Spain) under the Grupos de Referencia Competitiva Programme: Project GRC2014/010. J. M. received a Ramón y Cajal (RYC-2013-13784), an ERC Starting Investigator Grant (DYNAP-677786) and a Young Investigator Grant from the HFSP (RGY0066/2017)S

Evaluation of the in vitro and in vivo efficacy of ruthenium polypyridyl compounds against breast cancer

[Abstract] The clinical success of cisplatin, carboplatin, and oxaliplatin has sparked the interest of medicinal inorganic chemistry to synthesize and study compounds with non-platinum metal centers. Despite Ru(II)–polypyridyl complexes being widely studied and well established for their antitumor properties, there are not enough in vivo studies to establish the potentiality of this type of compound. Therefore, we report to the best of our knowledge the first in vivo study of Ru(II)–polypyridyl complexes against breast cancer with promising results. In order to conduct our study, we used MCF7 zebrafish xenografts and ruthenium complexes [Ru(bipy)2(C12H8N6-N,N)][CF3SO3]2Ru1 and [{Ru(bipy)2}2(μ-C12H8N6-N,N)][CF3SO3]4Ru2, which were recently developed by our group. Ru1 and Ru2 reduced the tumor size by an average of 30% without causing significant signs of lethality when administered at low doses of 1.25 mg·L−1. Moreover, the in vitro selectivity results were confirmed in vivo against MCF7 breast cancer cells. Surprisingly, this work suggests that both the mono- and the dinuclear Ru(II)–polypyridyl compounds have in vivo potential against breast cancer, since there were no significant differences between both treatments, highlighting Ru1 and Ru2 as promising chemotherapy agents in breast cancer therapy.Xunta de Galicia; ED431C 2018/39Portugal. Fundação para a Ciência e a Tecnologia; PEst 2015-2020Portugal. Fundação para a Ciência e a Tecnologia; UID/Multi/04349/2013Portugal. Fundação para a Ciência e a Tecnologia; RECI/QEQ-QIN/0189/2012Portugal. Fundação para a Ciência e a Tecnologia; UID/QUI/00100/2020Portugal. Fundação para a Ciência e a Tecnologia; UIDP/04378/2020Portugal. Fundação para a Ciência e a Tecnologia; UIDB/04378/2020Portugal. Fundação para a Ciência e a Tecnologia; LA/P/0140/202

Asymmetric data acquisition system for an endoscopic PET-US detector

According to current prognosis studies of pancreatic cancer, survival rate nowadays is still as low as 6% mainly due to late detections. Taking into account the location of the disease within the body and making use of the level of miniaturization in radiation detectors that can be achieved at the present time, EndoTOFPET-US collaboration aims at the development of a multimodal imaging technique for endoscopic pancreas exams that combines the benefits of high resolution metabolic information from time-of- flight (TOF) positron emission tomography (PET) with anatomical information from ultrasound (US). A system with such capabilities calls for an application-specific high-performance data acquisition system (DAQ) able to control and readout data from different detectors. The system is composed of two novel detectors: a PET head extension for a commercial US endoscope placed internally close to the region-of-interest (ROI) and a PET plate placed over the patient's abdomen in coincidence with the PET head. These two detectors will send asymmetric data streams that need to be handled by the DAQ system. The approach chosen to cope with these needs goes through the implementation of a DAQ capable of performing multi-level triggering and which is distributed across two different on-detector electronics and the off-detector electronics placed inside the reconstruction workstation. This manuscript provides an overview on the design of this innovative DAQ system and, based on results obtained by means of final prototypes of the two detectors and DAQ, we conclude that a distributed multi-level triggering DAQ system is suitable for endoscopic PET detectors and it shows potential for its application in different scenarios with asymmetric sources of data

Creativity and emerging technologies in Education

La creatividad es un valor en alza debido a su estrecha relación con la solución de problemas y el emprendimiento. Es conveniente que esta creatividad sea fomentada desde los primeros años de escolarización cuando el mundo de fantasía y simbólico del niño está en plena ebullición y dónde todo es posible. Así, el fomento de la creatividad, aparece convenientemente contemplado en el currículum de la etapa. Por otro lado, desde las administraciones educativas se está promoviendo el uso de metodologías didácticas en las que el alumnado, como protagonista de su aprendizaje, participa de forma activa en la creación de contenidos y materiales educativos. Este nuevo escenario está generando nuevos retos y aprendizajes para los docentes. Se hace imprescindible conocer y dominar qué herramientas y estrategias son necesarias en el mundo de la información y conocimiento. El profesorado ya no puede seguir siendo el mismo que en el pasado dado que desempeña otra tarea muy distinta: la de enseñar a aprender con los medios que están al alcance de su alumnado y no enseñar contenidos como antaño. Los resultados consistentes con la literatura hacen imposible concebir un currículo que promueva la creatividad sin educación para los medios y sin las tecnologías emergentes que se puedan aplicar en el aula.Creativity is a rising value due to its close relationship with problem solving and entrepreneurship. It is convenient that this creativity be fostered from the first years of schooling when the fantasy and symbolic world of the child is in full boiling and where everything is possible. Thus, the promotion of creativity is conveniently contemplated in the curriculum of the stage. On the other hand, the educational administrations are promoting the use of didactic methodologies in which the students, as protagonists of their learning, participate actively in the creation of content and educational materials. This new scenario is generating new challenges and learning for teachers. It is essential to know and master what tools and strategies are necessary in the world of information and knowledge. The teaching staff can no longer be the same as in the past given that they perform another very different task: that of teaching to learn with the means available to their students and not teaching content as in the past. The results consistent with the literature make it impossible to conceive a curriculum that promotes creativity without education for the media and without the emerging technologies that can be applied in the classroom.peerReviewe