The interplay between zinc and iron homeostasis in Aspergillus fumigatus under zinc-replete conditions relies on the iron-mediated regulation of alternative transcription units of zafA and the basal amount of the ZafA zinc-responsiveness transcription factor

[EN] Aspergillus fumigatus is a saprophyte fungus that typically grows on organic decaying matter but can also parasitize immunosuppressed hosts. This is explained, in part, by its great ability to take up Zn2+ ions from living tissues, which is induced by the ZafA transcription factor. This study shows that the ZafA-mediated regulation of fungal growth is also influenced by iron availability and that A. fumigatus is well adapted to grow in zinc-limiting and zinc-replete media with Zn:Fe ratios lower in the former than in the latter. Accordingly, this indicates that iron availability appears to be more critical for fungal growth in zinc-replete than in zinc-limiting environments. Interestingly, the cross-regulation of zinc/iron homeostasis under zinc-replete conditions relies on an unprecedented iron-mediated regulation of different zafA transcription units that, along with a limited transcript translation, allows synthesizing the right basal amount of ZafA dependent on iron availability. We posit that this regulatory strategy has evolved in fungi as a mechanism to adjust zinc intake to iron availability under zinc-replete conditions. Thus, fungal growth is enhanced in zinc- and iron-replete media but restricted by reducing zinc intake under iron starvation to prevent the noxious side effects of an intracellular zinc excess during iron deficiency

Knockdown of Dystrophin Dp71 Impairs PC12 Cells Cycle: Localization in the Spindle and Cytokinesis Structures Implies a Role for Dp71 in Cell Division

The function of dystrophin Dp71 in neuronal cells remains to be established. Previously, we revealed the involvement of this protein in both nerve growth factor (NGF)-induced neuronal differentiation and cell adhesion by isolation and characterization of PC12 neuronal cells with depleted levels of Dp71. In this work, a novel phenotype of Dp71-knockdown cells was characterized, which is their delayed growth rate. Cell cycle analyses revealed an altered behavior of Dp71-depleted cells, which consists of a delay in G0/G1 transition and an increase in apoptosis during nocodazole-induced mitotic arrest. Dp71 associates with lamin B1 and β-dystroglycan, proteins involved in aspects of the cell division cycle; therefore, we compared the distribution of Dp71 with that of lamin B1 and β-dystroglycan in PC12 cells at mitosis and cytokinesis by means of immunofluorescence and confocal microscopy analysis. All of these three proteins exhibited a similar immunostaining pattern, localized at mitotic spindle, cleavage furrow, and midbody. It is noteworthy that a drastic decreased staining in mitotic spindle, cleavage furrow, and midbody was observed for both lamin B1 and β-dystroglycan in Dp71-depleted cells. Furthermore, we demonstrated the interaction of Dp71 with lamin B1 in PC12 cells by immunoprecipitation and pull-down assays, and importantly, we revealed that knockdown of Dp71 expression caused a marked reduction in lamin B1 levels and altered localization of the nuclear envelope protein emerin. Our data indicate that Dp71 is a component of the mitotic spindle and cytokinesis multi-protein apparatuses that might modulate the cell division cycle by affecting lamin B1 and β-dystroglycan levels

High-Throughput System for the Early Quantification of Major Architectural Traits in Olive Breeding Trials Using UAV Images and OBIA Techniques

The need for the olive farm modernization have encouraged the research of more efficient crop management strategies through cross-breeding programs to release new olive cultivars more suitable for mechanization and use in intensive orchards, with high quality production and resistance to biotic and abiotic stresses. The advancement of breeding programs are hampered by the lack of efficient phenotyping methods to quickly and accurately acquire crop traits such as morphological attributes (tree vigor and vegetative growth habits), which are key to identify desirable genotypes as early as possible. In this context, an UAV-based high-throughput system for olive breeding program applications was developed to extract tree traits in large-scale phenotyping studies under field conditions. The system consisted of UAV-flight configurations, in terms of flight altitude and image overlaps, and a novel, automatic, and accurate object-based image analysis (OBIA) algorithm based on point clouds, which was evaluated in two experimental trials in the framework of a table olive breeding program, with the aim to determine the earliest date for suitable quantifying of tree architectural traits. Two training systems (intensive and hedgerow) were evaluated at two very early stages of tree growth: 15 and 27 months after planting. Digital Terrain Models (DTMs) were automatically and accurately generated by the algorithm as well as every olive tree identified, independently of the training system and tree age. The architectural traits, specially tree height and crown area, were estimated with high accuracy in the second flight campaign, i.e. 27 months after planting. Differences in the quality of 3D crown reconstruction were found for the growth patterns derived from each training system. These key phenotyping traits could be used in several olive breeding programs, as well as to address some agronomical goals. In addition, this system is cost and time optimized, so that requested architectural traits could be provided in the same day as UAV flights. This high-throughput system may solve the actual bottleneck of plant phenotyping of "linking genotype and phenotype," considered a major challenge for crop research in the 21st century, and bring forward the crucial time of decision making for breeders

Estudio fenológico y caracterización morfológica de variedades tradicionales de manzano y melocotonero

Las variedades locales de frutales seleccionadas a lo largo de los años por los agricultores, son muy interesantes para preservar la biodiversidad y los recursos fitogenéticos, ya que presentan unas características organolépticas peculiares y un valor cultural irremplazable. En 2007 se inició un trabajo de recuperación de variedades tradicionales de frutales en Andalucía (Proyecto INIA, RF2007-00027- C06-05) que contempla su prospección, localización, recogida de material vegetal, caracterización morfológica y molecular, multiplicación, documentación y mantenimiento en colección. En este trabajo se han caracterizado morfológicamente mediante caracteres UPOV las flores, hojas y ramos de un año, de cinco variedades tradicionales de manzano (Malus x domestica Borkh.) y dos de melocotonero [Prunus persica (L) Batsch], no estudiadas con anterioridad. Se ha evaluado la floración en la campaña 2011 y se han realizado los fenogramas correspondientesMICINN, INIA y Fondos FEDE

The complemented mutant (compl)Delta Bcstc7(niaD), in the STC7 of Botrytis cinerea led to the characterization of 11,12,13-tri-nor-eremophilenols derivatives

Botrytis cinerea has high potential for the production of specialized metabolites. The recent resequencing of the genome of the B05.10 strain using PacBio technology and the resulting update of the Ensembl Fungi (2017) database in the genome sequence have been instrumental in identifying new genes that could be involved in secondary metabolism. Thus, a new sesquiterpene cyclase (STC) coding gene (Bcstc7) has been included in the gene list from this phytopathogenic fungus. We recently constructed the null and complement transformants in STC7 which enabled us to functionally characterize this STC. Deletion of the Bcstc7 gene abolished (+)-4-epi-eremophilenol biosynthesis, and could then be re-established by complementing the null mutant with the Bcstc7 gene. Chemical analysis of the complemented transformant suggests that STC7 is the principal enzyme responsible for the key cyclization step of farnesyl diphosphate (FDP) to (+)-4-epi-eremophil-9-en-11-ols. A thorough analysis of the metabolites produced by two wild-type strains, B05.10 and UCA992, and the complemented mutant (compl)Delta Bcstc7(niaD), revealed the isolation and structural characterization of six 11,12,13-tri-nor-eremophilene derivatives, in addition to a large number of known eremophilen-11-ol derivatives. The structural characterization was carried out by extensive spectroscopic techniques. The biosynthesis of these compounds is explained by a retroaldol reaction or by dehydration and oxidative cleavage of C11-C13 carbons. This is the first time that this interesting family of degraded eremophilenols has been isolated from the phytopathogenous fungus B. cinerea.This research was supported by grants from MICINN-ERDF (RTI 2018-097356-B-C21 and -B-C22). Use of NMR facilities at the Servicio Centralizado de Ciencia y Tecnologia (SCCYT) of the University of Cadiz is acknowledged

Therapeutic approach with commercial supplements for pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels

[Background]: Neurodegeneration with brain iron accumulation (NBIA) is a group of rare neurogenetic disorders frequently associated with iron accumulation in the basal nuclei of the brain characterized by progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. Pantothenate kinase-associated neurodegeneration (PKAN) is one of the most widespread NBIA subtypes. It is caused by mutations in the gene of pantothenate kinase 2 (PANK2) that result in dysfunction in PANK2 enzyme activity, with consequent deficiency of coenzyme A (CoA) biosynthesis, as well as low levels of essential metabolic intermediates such as 4′-phosphopantetheine, a necessary cofactor for essential cytosolic and mitochondrial proteins. [Methods]: In this manuscript, we examined the therapeutic effectiveness of pantothenate, panthetine, antioxidants (vitamin E and omega 3) and mitochondrial function boosting supplements (L-carnitine and thiamine) in mutant PANK2 cells with residual expression levels. [Results]: Commercial supplements, pantothenate, pantethine, vitamin E, omega 3, carnitine and thiamine were able to eliminate iron accumulation, increase PANK2, mtACP, and NFS1 expression levels and improve pathological alterations in mutant cells with residual PANK2 expression levels. [Conclusion]: Our results suggest that several commercial compounds are indeed able to significantly correct the mutant phenotype in cellular models of PKAN. These compounds alone or in combinations are of common use in clinical practice and may be useful for the treatment of PKAN patients with residual enzyme expression levels.This work was supported by FIS PI16/00786 and PI19/00377 grants, Instituto de Salud Carlos III, Spain and Fondo Europeo de Desarrollo Regional (FEDER-Unión Europea), Proyectos de Investigación de Excelencia de la Junta de Andalucía CTS-5725 and PY18-850

Neuroeducación en los ambientes escolares. Un despertar desde el binomio: emoción-aprendizaje

Education is and must be assumed as a constantly changing system, whose socio-constructive process enables the development of comprehensive skills in the personality of the being, their cognitive, psychological, and emotional skills, involving soft skills such as sociability and emotional awareness, endowing the subject, as an agent that reconfigures, modifying or influencing its context to vice versa; in how the proxemic reality conditions or consolidates mechanisms of cognitive apprehension, gestating a learning located in the characteristics of neurodivergence. With this, it alludes to a reorientation of the teaching practice, aimed at a new formation horizon, where the validity is assumed from the synapse and school stimuli. For this reason, it is proposed to interpret the epistemic notions of neuroeducation in school environments, assumed as that awakening, which overcomes emotion-learning relational sleepiness. Determining a heartfelt involvement in knowledge, understanding the student as an emotional subject, thus, their willingness to learn is conditioned by their state of mind.La educación es y debe ser asumida como un sistema en constante cambio, cuyo proceso socioconstructivo, posibilita el desarrollo de competencias integrales en la personalidad del ser, sus competencias cognitivas, psicológicas, emocionales, implicando, las habilidades blandas como la sociabilidad y conciencia emocional, dotando al sujeto, como un agente que se reconfigura, modificando o incidiendo en su contexto a viceversa; en cómo la realidad proxémica, condiciona o consolida mecanismos de aprehensión cognitiva, gestando un aprendizaje situado en las características de la neurodivergencia. Con ello, se alude a una reorientación de la práctica docente, dirigida a un nuevo horizonte de formación, donde la vigencia sea asumida desde la sinapsis y estímulos escolares. Por ello, se plantea interpretar las nociones epistémicas de la neuroeducación en los ambientes escolares, asumidos como ese despertar, superador de la somnolencia relacional emoción-aprendizaje. Determinándose una sentida implicación en el conocimiento, al entender al escolar como sujeto emocional, así, su disposición por aprender, se condiciona por su estado de ánimo

Pantothenate and L-Carnitine supplementation improves pathological alterations in cellular models of KAT6A syndrome

Mutations in several genes involved in the epigenetic regulation of gene expression have been considered risk alterations to different intellectual disability (ID) syndromes associated with features of autism spectrum disorder (ASD). Among them are the pathogenic variants of the lysine-acetyltransferase 6A (KAT6A) gene, which causes KAT6A syndrome. The KAT6A enzyme participates in a wide range of critical cellular functions, such as chromatin remodeling, gene expression, protein synthesis, cell metabolism, and replication. In this manuscript, we examined the pathophysiological alterations in fibroblasts derived from three patients harboring KAT6A mutations. We addressed survival in a stress medium, histone acetylation, protein expression patterns, and transcriptome analysis, as well as cell bioenergetics. In addition, we evaluated the therapeutic effectiveness of epigenetic modulators and mitochondrial boosting agents, such as pantothenate and L-carnitine, in correcting the mutant phenotype. Pantothenate and L-carnitine treatment increased histone acetylation and partially corrected protein and transcriptomic expression patterns in mutant KAT6A cells. Furthermore, the cell bioenergetics of mutant cells was significantly improved. Our results suggest that pantothenate and L-carnitine can significantly improve the mutant phenotype in cellular models of KAT6A syndrome.This research was funded by FIS PI16/00786 (2016) and FIS PI19/00377 (2019) grants, the Ministerio de Sanidad, Spain, and the Fondo Europeo de Desarrollo Regional (FEDER Unión Europea), Spanish Ministry of Education, Culture and Sport. This activity has been co-financed by the European Regional Development Fund (ERDF) and by the Regional Ministry of Economic Transformation, Industry, Knowledge and Universities of the Junta de Andalucía, within the framework of the ERDF Andalusia operational program 2014–2020 Thematic objective “01-Reinforcement of research, technological development and innovation” through the reference research project CTS-5725 and PY18-850.Peer reviewe