Polyploid lineages in the genus Porphyra

Whole genome duplication is now accepted as an important evolutionary force, but the genetic factors and the life history implications affecting the existence and abundance of polyploid lineages within species are still poorly known. Polyploidy has been mainly studied in plant model species in which the sporophyte is the dominant phase in their life history. In this study, we address such questions in a novel system (Porphyra, red algae) where the gametophyte is the dominant phase in the life history. Three Porphyra species (P. dioica, P. umbilicalis, and P. linearis) were used in comparisons of ploidy levels, genome sizes and genetic differentiation using flow cytometry and 11 microsatellite markers among putative polyploid lineages. Multiple ploidy levels and genome sizes were found in Porphyra species, representing different cell lines and comprising several cytotype combinations among the same and different individuals. In P. linearis, genetic differentiation was found among three polyploid lineages: triploid, tetraploid and mixoploids, representing different evolutionary units. We conclude that the gametophytic phase (n) in Porphyra species is not haploid, contradicting previous theories. New hypotheses for the life histories of Porphyra species are discussed.FCT (Fundacao para a Ciencia e a Tecnologia, Portugal) [SFRH/BPD/109452/2015, NORIGENOMICS - PTDC/MAR/099698/2008, UID/Multi/04326/2013, BIODIVERSA/004/2015-MARFOR

Automatic detection of EEG arousals

[Abstract] Fragmented sleep is commonly caused by arousals that can be detected with the observation of electroencephalographic (EEG) signals. As this is a time consuming task, automatization processes are required. A method using signal processing and machine learning models, for arousal detection, is presented. Relevant events are identified in the EEG signals and in the electromyography, during the signal processing phase. After discarding those events that do not meet the required characteristics, the resulting set is used to extract multiple parameters. Several machine learning models — Fisher’s Linear Discriminant, Artificial Neural Networks and Support Vector Machines — are fed with these parameters. The final proposed model, a combination of the different individual models, was used to conduct experiments on 26 patients, reporting a sensitivity of 0.72 and a specificity of 0.89, while achieving an error of 0.13, in the arousal events detection.Galicia. Consellería de Cultura, Educación e Ordenación Universitaria; GRC2014/035Ministerio de Economía y Competitividad; TIN2013-40686

Mediterranean species of Caulerpa are polyploid with smaller genomes in the invasive ones

Caulerpa species are marine green algae, which often act as invasive species with rapid clonal proliferation when growing outside their native biogeographical borders. Despite many publications on the genetics and ecology of Caulerpa species, their life history and ploidy levels are still to be resolved and are the subject of large controversy. While some authors claimed that the thallus found in nature has a haplodiplobiontic life cycle with heteromorphic alternation of generations, other authors claimed a diploid or haploid life cycle with only one generation involved. DAPI-staining with image analysis and microspectrophotometry were used to estimate relative nuclear DNA contents in three species of Caulerpa from the Mediterranean, at individual, population and species levels. Results show that ploidy levels and genome size vary in these three Caulerpa species, with a reduction in genome size for the invasive ones. Caulerpa species in the Mediterranean are polyploids in different life history phases; all sampled C. taxifolia and C. racemosa var. cylindracea were in haplophasic phase, but in C. prolifera, the native species, individuals were found in both diplophasic and haplophasic phases. Different levels of endopolyploidy were found in both C. prolifera and C. racemosa var. cylindracea. Life history is elucidated for the Mediterranean C. prolifera and it is hypothesized that haplophasic dominance in C. racemosa var. cylindracea and C. taxifolia is a beneficial trait for their invasive strategies

Distinctive accumulation patterns of trace elements in sediments of bedrock rivers (Miño river, NW Iberian Peninsula)

Sediment compositions and enrichment patterns are investigated in an urban reach of a bedrock river, the Miño River passing through Ourense City, Spain. This study focuses on the trace element distribution in different fractions to gain insights into trace element enrichment. To assess enrichment, a context-specific approach was employed, based on the mean, the standard deviation of the estimated background, and the empirical rule, avoiding the pitfalls of general and arbitrary thresholds. Notably, the <0.063 mm and <2 mm fractions showed differential accumulation patterns. Both fractions serve to detect enrichments that can be indicative of contamination, but they measure different things, the maturity of sediments and postdepositional processes being key factors in understanding the sediment composition and enrichments. These findings also highlight the role of rock cavities, particularly those hosting permanent deposits, as traps for trace elements and their potential significance in assessing environmental enrichment. This work contributes to understanding sediment compositions and enrichment dynamics in bedrock rivers. It also underscores the significance of considering site-specific approaches for enrichment assessment and the necessity for further research to unravel the mechanisms driving differential accumulation within distinct depositional environments.Universidade de Vigo | Ref. INOU15-02Deputación de Ourense | Ref. INOU15-02Xunta de Galicia | Ref. ED481D-2023/00

Looking for combination of benznidazole and trypanosoma cruzitriosephosphate isomerase inhibitors for chagas disease treatment

BACKGROUND The current chemotherapy for Chagas disease is based on monopharmacology with low efficacy and drug tolerance. Polypharmacology is one of the strategies to overcome these limitations. OBJECTIVES Study the anti-Trypanosoma cruzi activity of associations of benznidazole (Bnz) with three new synthetic T. cruzi-triosephosphate isomerase inhibitors, 2, 3, and 4, in order to potentiate their actions. METHODS The in vitro effect of the drug combinations were determined constructing the corresponding isobolograms. In vivo activities were assessed using an acute murine model of Chagas disease evaluating parasitaemias, mortalities and IgG anti-T. cruzi antibodies. FINDINGS The effect of Bnz combined with each of these compounds, on the growth of epimastigotes, indicated an additive action or a synergic action, when combining it with 2 or 3, respectively, and an antagonic action when combining it with 4. In vivo studies, for the two chosen combinations, 2 or 3 plus one fifth equivalent of Bnz, showed that Bnz can also potentiate the in vivo therapeutic effects. For both combinations a decrease in the number of trypomastigote and lower levels of anti-T. cruzi IgG-antibodies were detected, as well clear protection against death. MAIN CONCLUSIONS These results suggest the studied combinations could be used in the treatment of Chagas disease

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

Genetic diversity and biogeographical patterns of Caulerpa prolifera across the Mediterranean and Mediterranean/Atlantic transition zone

© 2015, Springer-Verlag Berlin Heidelberg. Knowledge of spatial patterns of genetic differentiation between populations is key to understanding processes in evolutionary history of biological species. Caulerpa is a genus of marine green algae, which has attracted much public attention, mainly because of the impacts of invasive species in the Mediterranean. However, very little is known about the ecological and evolutionary history of the Mediterranean native Caulerpa prolifera, a species which is currently found at sites distributed worldwide. C. prolifera provides a good model to explore the patterns of genetic diversity at different scales across the Mediterranean and Atlantic area. This study aims to investigate the biogeographical patterns of diversity and differentiation of C. prolifera in the Mediterranean, with special focus on the Mediterranean/Atlantic transition zone. We used two nuclear (ITS rDNA and the hypervariable microsatellite locus CaPr_J2) and one chloroplast (tufA) DNA markers on samples of C. prolifera from its entire range. Analyses of 51 sequences of the cpDNA tufA of C. prolifera, 87 ITS2 sequences and genotypes of 788 ramets of C. prolifera for the locus CaPr_J2 revealed three different biogeographical areas: West Atlantic, East Atlantic and a larger area representing the Mediterranean, the Mediterranean/Atlantic transition zone and a Pacific site (Bali). It was found out that the Mediterranean/Atlantic transition zone is a biogeographical boundary for C. prolifera. A lack of connectivity was revealed between Atlantic and Mediterranean types, and identical sequences found in the Mediterranean and Indo-Pacific suggest either recent gene flow along the Red Sea connection or a possible ancient Indo-Pacific origin.Financial support for this study was provided by several research projects: CAULERPA_GENETICS (PTDC/MAR/70921/2006) by FCT (Portuguese Science Foundation) co-funded by FEDER and a postdoctoral fellowship (SFRH/BPD/17206/2004) from FCT, Portugal, co-funded by FSE, both to EVA, EXCL/AAG-GLO/0661/2012 to ES, CAULEXPAN (Spanish Ministry of Education, REN2002-00701) to NM, MedVeg (EU contract no. Q5RS-2001-02456), PRADERAS by the Foundation BBVA (Banco Bilbao Vizcaya Argentaria) to CDPeer Reviewe

The association of germline variants with chronic lymphocytic leukemia outcome suggests the implication of novel genes and pathways in clinical evolution

Background Chronic Lymphocytic Leukemia (CLL) is the most frequent lymphoproliferative disorder in western countries and is characterized by a remarkable clinical heterogeneity. During the last decade, multiple genomic studies have identified a myriad of somatic events driving CLL proliferation and aggressivity. Nevertheless, and despite the mounting evidence of inherited risk for CLL development, the existence of germline variants associated with clinical outcomes has not been addressed in depth. Methods Exome sequencing data from control leukocytes of CLL patients involved in the International Cancer Genome Consortium (ICGC) was used for genotyping. Cox regression was used to detect variants associated with clinical outcomes. Gene and pathways level associations were also calculated. Results Single nucleotide polymorphisms in PPP4R2 and MAP3K4 were associated with earlier treatment need. A gene-level analysis evidenced a significant association of RIPK3 with both treatment need and survival. Furthermore, germline variability in pathways such as apoptosis, cell-cycle, pentose phosphate, GNα13 and Nitric oxide was associated with overall survival. Conclusion Our results support the existence of inherited conditionants of CLL evolution and points towards genes and pathways that may results useful as biomarkers of disease outcome. More research is needed to validate these findings.S

Zonation of Ribosomal DNA Transcription Defines a Stem Cell Hierarchy in Colorectal Cancer

Colorectal cancers (CRCs) are composed of an amalgam of cells with distinct genotypes and phenotypes. Here, we reveal a previously unappreciated heterogeneity in the biosynthetic capacities of CRC cells. We discover that the majority of ribosomal DNA transcription and protein synthesis in CRCs occurs in a limited subset of tumor cells that localize in defined niches. The rest of the tumor cells undergo an irreversible loss of their biosynthetic capacities as a consequence of differentiation. Cancer cells within the biosynthetic domains are characterized by elevated levels of the RNA polymerase I subunit A (POLR1A). Genetic ablation of POLR1A-high cell population imposes an irreversible growth arrest on CRCs. We show that elevated biosynthesis defines stemness in both LGR5+ and LGR5− tumor cells. Therefore, a common architecture in CRCs is a simple cell hierarchy based on the differential capacity to transcribe ribosomal DNA and synthesize proteins