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Fernandez, H.

Publications and source records attributed to Fernandez, H..

6 recordsLinked to original sources

Unveiling the Toxicological and Allelopathic Effects of Pteridium aquilinum: Chemical Profiling and Biological Assays

The fern Pteridium aquilinum (bracken) is among the world most widespread plants and poses serious ecological and health risks due to the presence of illudane glycosides (IGs), carcinogenic compounds that particularly affect grazing livestock. This study determined the presence of IGs in plant extracts and in water samples from the Asturias region (northern Spain), an area characterized by intensive cattle farming, and assessed the genotoxic potential, and allelopathic effects of these samples. The glycosides ptaquiloside (PTA) and ptesculentoside (PTE), together with the degradation products pterosin A and pterosin B, were quantified in in vitro-cultured gametophytes and young sporophytes, spring-collected croziers, and autumn water samples from several bracken-infested sites. All sampling locations contained IGs in both plant and water samples, with particularly high concentrations of PTA detected in croziers from Brana Vieja (Somiedo), where cattle deaths had been reported. In vivo genotoxicity assays, using Drosophila melanogaster, revealed induction of somatic mutations and recombination events by aqueous plant extracts and of somatic mutations by water samples. The genotoxic activity of plant extracts, but not that of water samples, was associated with pterosins A and B. Moreover, comet assays in cultured human cells confirmed the genotoxic activity of plant extracts. Unexpectedly, allelopathic bioassays indicated a possible phytostimulatory rather than inhibitory effect of bracken extracts on the germination of meadow species. These findings underscore the widespread presence and biological activity of bracken in northern Spain and highlight the urgent need for management strategies to mitigate the ecological and toxicological threats posed by bracken proliferation.

pharmacology and toxicology↗

Comprehensive analysis of proteins associated with light responses and stress tolerance in the gametophyte of the fern Dryopteris affinis ssp. affinis

The fern gametophyte, despite its crucial role as the pioneer stage ensuring the successful establishment of the fern, has remained largely neglected as a subject of research, being particularly evident at the molecular level. In this study, based on an RNA-sequenced gametophyte transcriptome from the apogamous fern Dryopteris affinis ssp. affinis, 1,160 proteins functionally associated with light responses, transport processes, and stress mechanisms were identified. Light-responsive proteins are linked to photosynthesis, photorespiration, xanthophyll metabolism, and photomorphogenesis. Among them are several HIGH CHLOROPHYLL FLUORESCENCE (HCF 136, 173 and 244), which participate in the formation of photosystem II, and ENHANCER OF VARIEGATION 3 (EVR3), which is involved in chloroplast biogenesis. Regarding photomorphogenesis, the protein list includes the photoreceptors PHYTOCHROME B (PHYB), CRYPTOCHROMES 1 and 2 (CRY1 and 2), PHOTOTROPIN 2 (PHOT2), and UV RESISTANCE LOCUS 2, 3 and 8 (UVR2, 3 and 8). Likewise, related to transport, 659 proteins were found either in membranes and cytoplasm, moving a wide range of molecules, such as PERMEASE 2 and 3 (AAP2 and 3), SUCROSE TRANSPORTER 4 (SUC4), AMMONIUM TRANSPORTER 1 (AMT1), MECHANOSENSITIVE ION CHANNEL PROTEIN 1 (MSL1), among others. Furthermore, our results comprised an extensive arsenal of proteins to battle against both biotic and abiotic stress, or involved in plant immunity, such as BRASSINOSTEROID-SIGNALLING KINASE 1 (BSK1), NON-RESPONDING TO OXYLIPINS 7 (NOXY7), and CALLOSE SYNTHASE 12 (CALS12); whereas -MANNOSIDASE 2 (GMII), PALMITOYL-MONOGALACTOSYLDIACYLGLYCEROL {Delta}-7 DESATURASE (ADS3), and FORGETTER 1 (FGT1) are linked to salt, cold or heat stresses, respectively. Analysis of protein-protein interactions revealed MODIFIED TRANSPORT TO THE VACUOLE 17 (MTV17) as the most connected protein, with 19 interactions, mainly supported by text-mining and database evidence. These findings contribute to expanding the limited knowledge at the molecular level of ferns overall, paving the way for future experimental investigations.

plant biology↗

Transcriptomic analyses in the gametophyte ofDryopteris affinis: apomixis and more

The gametophyte of the fern Dryopteris affinis ssp. affinis represents a good model to explore the molecular basis of vegetative and reproductive development, as well as stress responses. Specifically, this fern reproduces asexually by apogamy, a peculiar case of apomixis whereby a sporophyte forms directly from a gametophytic cell without fertilization. Using an RNA-sequencing approach, we have previously annotated more than six thousand transcripts. Here, we selected one hundred of the inferred proteins that seemed particularly interesting for a detailed study of their potential functions, protein-protein interactions, and molecular phylogenies. As expected, a plethora of proteins associated with gametogenesis and embryogenesis in angiosperms, such as FERONIA (FER) and CHROMATING REMODELING 11 (CHR11) were identified, and more than a dozen candidates potentially involved in apomixis, such as ARGONAUTE4 (AGO4), AGO9, and AGO10, BABY BOOM (BBM), FASCIATED STEM4 (FAS4), FERTILIZATION-INDEPENDENT ENDOSPERM (FIE), and MATERNAL EFFECT EMBRYO ARREST29 (MEE29). In addition, proteins involved in the response to biotic and abiotic stresses were widely represented, as shown by the enrichment of heat-shock proteins. Using the String platform, studying interactomes revealed that most of the protein-protein interactions were predicted based on experimental, database, and text mining datasets, with MULTICOPY SUPPRESSOR OF IRA4 (MSI4) showing the highest number of 16 interactions. Lastly, some proteins were studied from a phylogenetic point of view, comparing the alignments with respect to more distantly or closely related plant groups, identifying AGO1 as the evolutionarily most similar to that other ferns and the most distant to the predicted common ancestor. This work sets the stage for future functional characterizations in relation to gametophyte development including apomictic reproduction.

plant biology↗

Loss of the mitochondrial citrate carrier, SLC25A1/CIC disrupts embryogenesis via 2-Hydroxyglutarate

Germline inactivating mutations of the SLC25A1 gene contribute to various human developmental disorders, including combined D/L-2-hydroxyglutaric aciduria (D/L-2HGA), a severe systemic syndrome characterized by the accumulation of both enantiomers of 2-hydroxyglutaric acid (2HG). The mechanisms by which SLC25A1 deficiency leads to this disease and the role of 2HG are unclear and no therapies exist. We now show that mice lacking both Slc25a1 alleles display a spectrum of alterations that resemble human D/L-2HGA. Mechanistically, SLC25A1 loss results in a proliferation defect and activates two distinct senescence pathways, oncogene-induced senescence (OIS) and mitochondrial dysfunction-induced senescence (MiDAS), both involving the p53 tumor suppressor and driven by two discernible signals: the accumulation of 2HG, inducing OIS, and mitochondrial dysfunction, triggering MiDAS. Inhibiting these senescence programs or blocking p53 activity reverses the growth defect caused by SLC25A1 dysfunction and restores proliferation. These findings reveal novel pathogenic roles of senescence in human disorders and suggest potential strategies to correct the molecular alterations caused by SLC25A1 loss.

developmental biology↗

Variational autoencoders learn universal latent representations of metabolomics data

Dimensionality reduction approaches are commonly used for the deconvolution of high-dimensional metabolomics datasets into underlying core metabolic processes. However, current state-of-the-art methods are widely incapable of detecting nonlinearities in metabolomics data. Variational Autoencoders (VAEs) are a deep learning method designed to learn nonlinear latent representations which generalize to unseen data. Here, we trained a VAE on a large-scale metabolomics population cohort of human blood samples consisting of over 4,500 individuals. We analyzed the pathway composition of the latent space using a global feature importance score, which showed that latent dimensions represent distinct cellular processes. To demonstrate model generalizability, we generated latent representations of unseen metabolomics datasets on type 2 diabetes, schizophrenia, and acute myeloid leukemia and found significant correlations with clinical patient groups. Taken together, we demonstrate for the first time that the VAE is a powerful method that learns biologically meaningful, nonlinear, and universal latent representations of metabolomics data.

bioinformatics↗

MicroExonator enables systematic discovery and quantification of microexons across mouse embryonic development

Microexons, exons that are [≤]30 nucleotides, were shown to play key roles in neuronal development, but are difficult to detect and quantify using standard RNA-Seq alignment tools. Here, we present MicroExonator, a novel pipeline for reproducible de novo discovery and quantification of microexons. We processed 289 RNA-seq datasets from eighteen mouse tissues corresponding to nine embryonic and postnatal stages, providing the most comprehensive survey of microexons available for mouse. We detected 2,984 microexons, 332 of which are differentially spliced throughout mouse embryonic brain development, including 29 that are not present in mouse transcript annotation databases. Unsupervised clustering of microexons alone segregates brain tissues by developmental time and further analysis suggest a key function for microexon inclusion in axon growth and synapse formation. Finally, we analysed single-cell RNA-seq data from the mouse visual cortex and we report differential inclusion between neuronal subpopulations, suggesting that some microexons could be cell-type specific.

genomics↗