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Introduction Streptococcus bovis/equinus complex (SBEC) is a major cause of infective endocarditis (IE), although its incidence varies greatly depending on the geographical area. The characteristics of IE caused by Streptococcus gallolyticus susp. gallolyticus are well known; there are hardly any descriptions of IE caused by other species or biotypes. Methods Retrospective cohort study, from 1990 to 2019, of all SBEC IE in adults in three Spanish hospitals, Lugo (LH), Barcelona (BH) and Ferrol (FH) where the population is mainly rural, urban and mixed, respectively. The incidence of IE was analyzed in 3 areas. Clinical characteristics of IE (277 cases, 258 biotyped) were compared according to SBEC species and biotypes. Results There are significant differences between the incidence of SBEC IE in HL (27.9/106) vs. HF and HB (8.8 and 7,1, respectively, p Conclusions IE due to SBEC has geographical variations in incidence and different clinical characteristics among biotypes. The association with CRC was high.

Sound discrimination is essential in many species for communicating and foraging. Bats, for example, use sounds for echolocation and communication. In the bat auditory cortex there are neurons that process both sound categories, but how these neurons respond to acoustic transitions, that is, echolocation streams followed by a communication sound, remains unknown. Here, we show that the acoustic context, a leading sound sequence followed by a target sound, changes neuronal discriminability of echolocation versus communication calls in the cortex of awake bats of both sexes. Nonselective neurons that fire equally well to both echolocation and communication calls in the absence of context become category selective when leading context is present. On the contrary, neurons that prefer communication sounds in the absence of context turn into nonselective ones when context is added. The presence of context leads to an overall response suppression, but the strength of this suppression is stimulus specific. Suppression is strongest when context and target sounds belong to the same category, e.g.,echolocation followed by echolocation. A neuron model of stimulus-specific adaptation replicated our resultsin silico. The model predicts selectivity to communication and echolocation sounds in the inputs arriving to the auditory cortex, as well as two forms of adaptation, presynaptic frequency-specific adaptation acting in cortical inputs and stimulus-unspecific postsynaptic adaptation. In addition, the model predicted that context effects can last up to 1.5 s after context offset and that synaptic inputs tuned to low-frequency sounds (communication signals) have the shortest decay constant of presynaptic adaptation.SIGNIFICANCE STATEMENTWe studied cortical responses to isolated calls and call mixtures in awake bats and show that (1) two neuronal populations coexist in the bat cortex, including neurons that discriminate social from echolocation sounds well and neurons that are equally driven by these two ethologically different sound types; (2) acoustic context (i.e., other natural sounds preceding the target sound) affects natural sound selectivity in a manner that could not be predicted based on responses to isolated sounds; and (3) a computational model similar to those used for explaining stimulus-specific adaptation in rodents can account for the responses observed in the bat cortex to natural sounds. This model depends on segregated feedforward inputs, synaptic depression, and postsynaptic neuronal adaptation.

Listeria monocytogenes is a saprophytic gram-positive bacterium, and an opportunistic foodborne pathogen that can produce listeriosis in humans and animals. It has evolved an exceptional ability to adapt to stress conditions encountered in different environments, resulting in a ubiquitous distribution. Because some food preservation methods and disinfection protocols in food-processing environments cannot efficiently prevent contaminations, L. monocytogenes constitutes a threat to human health and a challenge to food safety. In the host, Listeria colonizes the gastrointestinal tract, crosses the intestinal barrier, and disseminates through the blood to target organs. In immunocompromised individuals, the elderly, and pregnant women, the pathogen can cross the blood-brain and placental barriers, leading to neurolisteriosis and materno-fetal listeriosis. Molecular and cell biology studies of infection have proven L. monocytogenes to be a versatile pathogen that deploys unique strategies to invade different cell types, survive and move inside the eukaryotic host cell, and spread from cell to cell. Here, we present the multifaceted Listeria life cycle from a comprehensive perspective. We discuss genetic features of pathogenic Listeria species, analyze factors involved in food contamination, and review bacterial strategies to tolerate stresses encountered both during food processing and along the host’s gastrointestinal tract. Then we dissect host–pathogen interactions underlying listerial pathogenesis in mammals from a cell biology and systemic point of view. Finally, we summarize the epidemiology, pathophysiology, and clinical features of listeriosis in humans and animals. This work aims to gather information from different fields crucial for a comprehensive understanding of the pathogenesis of L. monocytogenes., Graphical abstract

The nutrient content of a commercial seawater culture medium for growing the microalga Isochrysis galbana was optimized using a stochastic strategy based on genetic algorithms. For this, 210 experiments spread over seven generations were carried out. This strategy reduced the number of assays by more than 90% compared to a factorial design involving the optimization of twelve nutrients simultaneously. The optimized medium outperformed the reference medium in all aspects. The genetic algorithm strategy achieved a polyunsaturated fatty acids (PUFAs) productivity of 7.8 mg L−1 day−1 in a continuous culture of I. galbana, corresponding to an increase of 15% compared to the commercial formulation. Carotenoids, on the other hand, increased by 50% d.w. In addition, PUFA yields were significantly improved, which allowed us to reduce the requirement of several nutrients, for instance, N (25%), Mo (20%), Mn (60%), Co (60%), and Cu (60%).

Background In recent decades, increasing longevity (among other factors) has fostered a rise in Parkinson's disease incidence. Although not exhaustively studied in this devastating disease, the impact of sex represents a critical variable in Parkinson’s disease as epidemiological and clinical features differ between males and females. Methods To study sex bias in Parkinson’s disease, we conducted a systematic review to select sex-labeled transcriptomic data from three relevant brain tissues: the frontal cortex, the striatum, and the substantia nigra. We performed differential expression analysis on each study chosen. Then we summarized the individual differential expression results with three tissue-specific meta-analyses and a global all-tissues meta-analysis. Finally, results from the meta-analysis were functionally characterized using different functional profiling approaches. Results The tissue-specific meta-analyses linked Parkinson’s disease to the enhanced expression of MED31 in the female frontal cortex and the dysregulation of 237 genes in the substantia nigra. The global meta-analysis detected 15 genes with sex-differential patterns in Parkinson’s disease, which participate in mitochondrial function, oxidative stress, neuronal degeneration, and cell death. Furthermore, functional analyses identified pathways, protein–protein interaction networks, and transcription factors that differed by sex. While male patients exhibited changes in oxidative stress based on metal ions, inflammation, and angiogenesis, female patients exhibited dysfunctions in mitochondrial and lysosomal activity, antigen processing and presentation functions, and glutamic and purine metabolism. All results generated during this study are readily available by accessing an open web resource (http://bioinfo.cipf.es/metafun-pd/) for consultation and reuse in further studies. Conclusions Our in silico approach has highlighted sex-based differential mechanisms in typical Parkinson Disease hallmarks (inflammation, mitochondrial dysfunction, and oxidative stress). Additionally, we have identified specific genes and transcription factors for male and female Parkinson Disease patients that represent potential candidates as biomarkers to diagnosis.

Este documento se considera que es un capítulo de libro en lugar de un congreso, El proyecto pedagógico que aquí se presenta trata cómo los estudiantes de Arquitectura de segundo curso de la asignatura de Proyectos arquitectónicos han desarrollado una arquitectura principalmente para animales sintientes no humanos y donde los humanos entran a formar parte de ella puntualmente. Una construcción de pequeña escala en un contexto ?natural? pero fuertemente antropizado y cercano a la ciudad, el río Henares. Para alcanzar este objetivo, se destaca tanto la importancia de un aprendizaje basado en proyectos, centrado en romper hábitos preestablecidos, como de un aprendizaje cooperativo con estudiantes de otras disciplinas, -en concreto con dos asignaturas de dos grados; Zoología de Campo del grado de Biología y Fauna de la Península Ibérica del grado de Medio Ambiente, con quienes se ha trabajado para alcanzar acuerdos y resultados donde los conocimientos no propios se vean reflejados., The pedagogical project presented here deals with how architecture students in the second year of the Architectural Projects subject have developed an architecture mainly for non-human sentient animals and where humans occasionally become part of it. A small-scale construction, in a "natural" context but strongly anthropized and close to the city, the Henares River. To achieve this goal, the importance of projectbased learning, focused on breaking pre-established habits, as well as cooperative learning with students from other disciplines, specifically with two subjects of two grades, is highlighted; Zoology of the degree of Biology and Fauna of the Iberian Peninsula of the degree of Environment, with whom has been working to reach agreements and results where the knowledge of each career can be reflected.

Biosynthesis and secretion of a complex extracellular matrix (EM) is a hallmark of Salmonella biofilm formation, impacting on its relationship with both the environment and the host. Cellulose is a major component of Salmonella EM. It is considered an anti-virulence factor because it interferes with Salmonella proliferation inside macrophages and virulence in mice. Its synthesis is stimulated by CsgD, the master regulator of biofilm formation in enterobacteria, which in turn is under the control of MlrA, a MerR-like transcription factor. In this work, we identified a SPI-2-encoded Salmonella-specific transcription factor homolog to MlrA, MlrB, that represses transcription of its downstream gene, orf319, and of csgD inside host cells. MlrB is induced in laboratory media mimicking intracellular conditions and inside macrophages, and it is required for intramacrophage proliferation. An increased csgD expression is observed in the absence of MlrB inside host cells. Interestingly, inactivation of the CsgD-controlled cellulose synthase-coding gene restored intramacrophage proliferation to rates comparable to wild-type bacteria in the absence of MlrB. These data indicate that MlrB represses CsgD expression inside host cells and suggest that this repression lowers the activation of the cellulose synthase. Our findings provide a novel link between biofilm formation and Salmonella virulence, Agencia Nacional de Promoción Científica y Tecnológica, Grant/Award Number: PICT-2015-2056; Spanish Ministry of Science and Innovation, Grant/Award Number: BIO2016-77639-P

18 páginas, 7 figuras, 2 tablas, RcsB is a transcriptional regulator that controls expression of numerous genes in enteric bacteria. RcsB accomplishes this role alone or in combination with auxiliary transcriptional factors independently or dependently of phosphorylation. To understand the mechanisms by which RcsB regulates such large number of genes, we performed structural studies as well as in vitro and in vivo functional studies with different RcsB variants. Our structural data reveal that RcsB binds promoters of target genes such as rprA and flhDC in a dimeric active conformation. In this state, the RcsB homodimer docks the DNA-binding domains into the major groove of the DNA, facilitating an initial weak read-out of the target sequence. Interestingly, comparative structural analyses also show that DNA binding may stabilize an active conformation in unphosphorylated RcsB. Furthermore, RNAseq performed in strains expressing wild-type or several RcsB variants provided new insights into the contribution of phosphorylation to gene regulation and assign a potential role of RcsB in controlling iron metabolism. Finally, we delimited the RcsB box for homodimeric active binding to DNA as the sequence TN(G/A)GAN4TC(T/C)NA. This RcsB box was found in promoter, intergenic and intragenic regions, facilitating both increased or decreased gene transcription., Spanish Government (Ministerio de Econom´ıa y Competitividad y Ministerio de Ciencia e Innovacion) ´ [BIO2016-78571-P, PID2019-108541GB-I00 to A.M., BFU2016-78606-P, PID2019-110630GB-I00 to P.C., BIO2016-77639-P to F.G.-dP.]; Valencian Government grant PROMETEO/2020/012 to A.M. P.C. is recipient of a Ramon y Cajal contract from the Ministry of Economy and ´ Competitiveness. Funding for open access charge: Spanish government.

espanolIntroduccion: El dia 7 de febrero de 1937 se produjo un desplazamiento de poblacion desde Malaga hacia Almeria por la carretera de la costa, cuyas dificultades y penurias dejaron un profundo recuerdo en quienes lo vivieron y en sus descendientes.Metodo: Este estudio pretende identificar los elementos que actuaron como detonantes de esa huida, masiva y coincidente en el tiempo, mediante analisis cualitativo de contenidos de prensa, radio local y rumores en 1937.Resultados: Los continuos bombardeos sobre una ciudad sometida a una intensa campana de propaganda de guerra, sin informacion fiable sobre la situacion del frente y del propio Estado y con intensa comunicacion informal de rumores, propiciaron un episodio de panico colectivo.Discusion y Conclusion: Cuando los milicianos se repliegan y anuncian la llegada del enemigo, el miedo compartido desencadena la reaccion defensiva de huida masiva. EnglishIntroduction:On February 7, 1937 a population displacement occurred from Malaga to Almeria traversing the coastal roads, whose difficulties and hardship left a profound memory in those who lived it and their descendants.Methods:This study aims to identify the elements that acted as triggers for the dis-placement, massive and concurrent in time, through qualitative content analysis of press, radio and rumors recorded in 1937.Results:The continuous bombardments over a city subjected to an intense war propa-ganda campaign, with lack of reliable information regarding the situation at the front and the State itself; combined with the rampant spread of rumors, propitiated a collec-tive episode of collective herd-like panic.Discussion and Conclusion:When militiamen retreated and announced the arrival of the enemy, the shared fear triggers the defensive reaction of mass exodus.

Las estimaciones indican que 148 especies de aves en Norteamérica enfrentan amenaza alta o severa, pues sus poblaciones están disminuyendo. El gorrión de Baird (Centronyx bairdii) es una de las especies con declive poblacional, presenta plumaje monomórfico y su sexo no se puede determinar a simple vista. La determinación del sexo de las aves permite conocer su comportamiento social y proporción en la dinámica de sus poblaciones. Un método de clasificación es el de redes neuronales artificiales y se ha utilizado en diversos campos, como la clasificación de plantas y semillas y la diferenciación de especies productoras de madera. En el ámbito de la ornitología se ha utilizado poco. Por lo tanto, el objetivo de este estudio fue desarrollar una red neuronal artificial para diferenciar el sexo de los gorriones de la especie Centronyx bairdii, con datos zoométricos obtenidos en campo. La hipótesis fue que las redes neuronales artificiales pueden predecir el sexo de las aves de la especie Centronyx bairdii. La red neuronal construida a partir de los datos de peso, cuerda alar, longitud de cola, culmen, ancho del pico y profundidad del pico de 111 aves, permitió diferenciar el sexo de la especie con grado de certeza de 92.3%.

This paper describes molecular and functional characterization of a novel dioxygenase enzyme from the aquatic cyanobacterium Anabaena cylindrica. The enzyme showed a strong inhibition by excess of the precursor L‐DOPA. However, its heterologous expression has allowed detecting the formation of the main compounds in the biosynthetic pathway of betalains. The discovery of this novel dioxygenase in the phylum cyanobacteria shows that betalains' formation is more diverse than expected., Summary The biosynthesis of betalamic acid, the structural unit of pigments betalains, is performed by enzymes with 4,5‐DOPA‐extradiol‐dioxygenase activity. These enzymes were believed to be limited to plants of the order Caryophyllales and to some fungi. However, the discovery of Gluconacetobacter diazotrophicus as the first betalain‐forming bacterium opened a new field in the search for novel biological systems able to produce betalains. This paper describes molecular and functional characterization of a novel dioxygenase enzyme from the aquatic cyanobacterium Anabaena cylindrica. The enzyme was found to be a homodimer of a polypeptide of 17.8 kDa that, opposite to previous related enzymes, showed a strong inhibition by excess of the precursor L‐DOPA. However, its heterologous expression has allowed detecting the formation of the main compounds in the biosynthetic pathway of betalains. In addition, phylogenetic analysis has shown that this enzyme is not close related to enzymes from plants, fungi or proteobacteria such as G. diazotrophicus. The presence of enzymes that produce these health‐promoting compounds is more diverse than expected. The discovery of this novel dioxygenase in the phylum cyanobacteria expands the presence of betalamic acid‐forming enzymes in organisms of different nature with no apparent relationship among them.

We studied the laccase-catalysed oxygenation of methoxyphenolic food ingredients, such as 2-methoxyphenol (guaiacol) and 2,6-dimethoxyphenol (syringol), isomers such as 3- and 4-methoxyphenol, and 2,3-, 3,4- and 3,5-dimethoxyphenol. These methoxyphenolic substrates generate unstable free radicals, which leads to the erroneous determination of steady state rates. The addition of small quantities of ascorbic acid as coupling reagent generates a lag period because it reduces free radicals to methoxyphenols. Measurement of the length of the lag period provides the reliable determination of true steady state rates. We describe the application of this chronometric method to the kinetic characterization of the oxidation of the above methoxyphenolic substrates by Trametes versicolor laccase.

'El Palmeral' apartments (1968-1970) located in Aguadulce, a tourist town in Almería, in the Andalusian region of southern Spain are the best work by the architect Fernando Cassinello (Almería, 1928-Madrid, 1975). The urban planning regulations of the development, which required the ground floor to be diaphanous, made possible the original solution of the three great reduced arches with the upper structure of porticos on each block. Hence, the apartments rest on six large arches, producing an image similar to that of an inhabited bridge. Fernando Cassinello, in his dual capacity as professor at the School of Architecture in Madrid and researcher at the Eduardo Torroja Institute of Construction Sciences (IETcc), always positioned himself in the median that unites Architecture and Engineering. In some of his works, an infrastructural derivative can be appreciated. Therein lays the interest of his architectural work. He was able to introduce singular structural aspects, even in private housing projects, both single family and collective. This could be in the way his buildings were related to the ground, or the way he dealt with stairs, which have so often been excluded from the built volume, and which served functions beyond facilitating vertical movement.

© 2020 The Authors., The peptidoglycan (PG), as the exoskeleton of most prokaryotes, maintains a defined shape and ensures cell integrity against the high internal turgor pressure. These important roles have attracted researchers to target PG metabolism in order to control bacterial infections. Most studies, however, have been performed in bacteria grown under laboratory conditions, leading to only a partial view on how the PG is synthetized in natural environments. As a case in point, PG metabolism and its regulation remain poorly understood in symbiotic and pathogenic bacteria living inside eukaryotic cells. This review focuses on the PG metabolism of intracellular bacteria, emphasizing the necessity of more in vivo studies involving the analysis of enzymes produced in the intracellular niche and the isolation of PG from bacteria residing within eukaryotic cells. The review also points to persistent infections caused by some intracellular bacterial pathogens and the extent at which the PG could contribute to establish such physiological state. Based on recent evidences, I speculate on the idea that certain structural features of the PG may facilitate attenuation of intracellular growth. Lastly, I discuss recent findings in endosymbionts supporting a cooperation between host and bacterial enzymes to assemble a mature PG., Work in my laboratory is supported by grants BIO2016‐77639‐P and PCIN‐2016‐082 from the Spanish Ministry of Science, Innovation and Universities.

The survival of microbial cells under changing environmental conditions requires an efficient reprogramming of transcription, often mediated by alternative sigma factors. The Gram-positive human pathogen Listeria monocytogenes senses and responds to environmental stress mainly through the alternative sigma factor σB (SigB), which controls expression of the general stress response regulon. SigB activation is achieved through a complex series of phosphorylation/dephosphorylation events culminating in the release of SigB from its anti-sigma factor RsbW. At the top of the signal transduction pathway lies a large multi-protein complex known as the stressosome that is believed to act as a sensory hub for stresses. Following signal detection, stressosome proteins become phosphorylated. Resetting of the stressosome is hypothesized to be exerted by a putative phosphatase, RsbX, which presumably removes phosphate groups from stressosome proteins post-stress. We addressed the role of the RsbX protein in modulating the activity of the stressosome and consequently regulating SigB activity in L. monocytogenes. We show that RsbX is required to reduce SigB activation/levels under non-stress conditions and that it is required for appropriate SigB mediated stress-adaptation. A strain lacking RsbX displayed impaired motility and biofilm formation, but also an increased survival at low pH. Our results could suggest that absence of RsbX alter the multi-protein composition of the stressosome without dramatically affecting its phosphorylation status. Overall the data show that RsbX plays a critical role in modulating the signal transduction pathway by blocking SigB activation under non-stressed conditions. Importance Pathogenic bacteria need to sense and respond to stresses to survive harsh environments but also be able to turn off the response when no longer facing stress. Activity of the stress-sigma factor SigB in the human pathogen Listeria monocytogenes is controlled by a hierarchic system having a large stress-sensing multiprotein complex known as the stressosome at the top. Following stress exposure, proteins in the stressosome become phosphorylated leading to SigB activation. We have studied the role of a putative phosphatase, RsbX, which is hypothesized to dephosphorylate stressosome proteins. RsbX is not only critical to switch off the stress response post-stress but also to keep the activity of SigB low at non-stressed conditions to prevent unnecessary gene-expression and save energy.

Biostimulants have become highly important in agriculture. For these products to be efficient, they need to be formulated, for a specific crop, according to the mineral nutrients and metabolites requirements in each phenological phase of the crops. In this study, the agronomical behavior of 10 tomato varieties was evaluated (‘Cherry’, ‘Corazón de Buey’, ‘Green Zebra’, ‘Marglobe’, ‘Marmande VR’, ‘Montserrat’, ‘Muchamiel’, ‘Óptima’, ‘Roma VF’ and ‘Tres Cantos’), in other to select four varieties with the greatest agronomical differences between them to be analyzed by omics tools. So, the varieties ‘Cherry’, ‘Green Zebra’, ‘Montserrat’, and ‘Tres Cantos’ were selected for an ionomic, metabolic, and hormone study to determine the predominant nutrients and metabolites in the different phenological phases, and to relate it with its agronomic characteristics. It was observed that the variability of the results could be mainly explained by the different phenological phases during the development of the crop, rather than by the variety. The major compounds were N (4.71 g 100 g dw), K (3.86 g 100 g dw), P (0.53 mg g dw), glutamate (5.21 mg g dw), glutamine (2.89 mg g dw), aspartate (1.54 mg g dw), tyrosine (2.36 mg g dw), phenylalanine (1.70 mg g dw), sucrose (14.4 mg g dw), malate (13.2 mg g dw), and isopentenyladenine (iP) (2.65 ng g dw). No correlation was found between any specific compound and an agronomic characteristic. But, it can be concluded that Biostimulant products must contain these compounds in other to stimulate growth and increase the production of tomatoes plants, as they comprise most of the metabolites and nutrients needed in some or all of the phenological phases., Acknowledgments This research was funded by State R&D Program Oriented to the Challenges of the Society, Innovation and Science Ministerial (Spain Government), grant number RTC-2016–4568–2. We acknowledge the support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).

Dinoflagellates of the genus Karlodinium are ichthyotoxic species that produce karlotoxins. Karlotoxins show hemolytic and cytotoxic activities and have been associated with fish mortality. This study evaluated the effect of toxins released into the environment of Karlodinium veneficum strain K10 (Ebro Delta, NW Mediterranean) on the early stages of Danio rerio (zebrafish). Extracts of supernatant of K10 contained KmTx-10, -11, -12, -13, and a sulfated form of KmTx-10. Total egg mortality was observed for karlotoxins concentration higher than 2.69 µg L−1 and the 1.35 µg L−1, 87% of development anomalies were evidenced (concentrations expressed as KmTx-2 equivalent). Larvae of 8 days post-fertilization exposed to 1.35 µg L−1 presented epithelial damage with 80% of cells in the early apoptotic stage. Our results indicate that supernatants with low concentration of KmTxs produce both lethal and sublethal effects in early fish stages. Moreover, apoptosis was induced at concentrations as low as 0.01 µg L−1. This is of great relevance since detrimental long-term effects due to exposure to low concentrations of these substances could affect wild and cultured fish.

Essential peptidoglycan synthases, like penicillin binding proteins 2 and 3 (PBP2/PBP3) of Escherichia coli, define shape by orchestrating cell elongation and division, respectively. Despite being intensively studied as drug targets, the regulatory rules governing their production remain poorly understood. During infection, the closely related pathogen Salmonella enterica serovar Typhimurium downregulates PBP2/PBP3 production and replace them with alternative peptidoglycan synthases, PBP2SAL/PBP3SAL, absent in E. coli. The bases for such switch in morphogenetic proteins are unknown. Here, we show that the S. Typhimurium regulator OmpR triggers PBP2SAL and PBP3SAL expression responding solely to acid pH and define a shared motif present in upstream regions of the PBP2SAL- and PBP3SAL-coding genes sufficient for such control. The elimination of PBP2/PBP3 in infection conditions is however multifactorial, requiring acidity, high osmolarity and being favoured by OmpR and the Prc protease. Remarkably, we found that E. coli loses the essential PBP3 required for cell division when exposed to both acidity and high osmolarity, the environmental cues encountered by intracellular S. Typhimurium. Therefore, OmpR played a central role in the evolution of this pathogen when co-opting the regulation of PBP2SAL/PBP3SAL and, consequently, promoting a new morphogenetic cycle that made possible increasing progeny inside acidic eukaryotic phagosomes.SignificanceSome enzymes that participate in peptidoglycan metabolism are present exclusively in bacterial pathogens and modify its structure to limit immune recognition. The intracellular pathogen Salmonella enterica serovar Typhimurium is the only example known to date in which a “substitution” of essential peptidoglycan enzymes involved in cell division and elongation takes place during infection. The data presented here support instability of PBP3 in environments with acidity and high osmolarity as a probable selective pressure that promoted the fixation of alternative morphogenetic enzymes. This was possible due to the control that OmpR exerted over these new foreign functions. The acquisition of enzymes like PBP2SAL and PBP3SAL therefore represent a “quantum leap” evolutionary event in S. Typhimurium that made possible the colonization of acidic intracellular niches.

Climate change exacerbates flooding problems due to hurricanes followed by heavy rains, particularly in sub-tropical regions. Consequently, submerged plants experience hypoxia stress which limits agronomic and horticultural crop growth and production. Hypoxia causes oxidative damage by accelerating the lipid peroxidation associated with O2- and H2O2 levels. Additionally, hypoxia increases the accumulation of organic osmoprotectants and antioxidant activity, whereas it decreases the macronutrient (N, P, K, and Zn) uptake. This study aimed at investigating the effects of flooding-induced hypoxia stress on the growth and the physiological, biochemical, and nutritional characteristics of the hydroponically grown southern highbush blueberry (cv. Jewel) plants. In addition, the hypoxia-mitigating effects of conventional silicon (Si-C) and silicon nanoparticles (SiNPs) and their application methods (foliar vs. foliar and rootzone application) were also appraised. Both the Si-C and the SiNPs efficiently alleviated hypoxia-induced oxidative and osmotic damage to cells by enhancing the activities of the enzymatic antioxidants (ascorbate peroxidase, catalase, dehydroascorbate reductase, superoxide dismutase, peroxidase, guaiacol peroxidase, monodehydroascorbate, reductase), the non-enzymatic antioxidants (ascorbic acid and glutathione contents), and the accumulation of compatible solutes (proline and glycinebetaine) in leaves and roots. However, the SiNPs were more effective than Si-C at improving antioxidant activities and osmolytes formation. A strong negative correlation between the antioxidant activities and the lipid peroxidation rate was observed in the SiNP-treated plants under hypoxia stress. The SiNPs also regulated nutrient uptake by increasing the K, N, P, and Zn concentrations while decreasing Fe and Mn concentrations to a less toxic level. Blueberry plants treated with SiNPs responded more effectively to hypoxia stress by maintaining higher antioxidant and osmoprotectant concentrations than blueberry plants treated with Si-C. Additionally, the foliar and rootzone applications yielded better results than the foliar applications only.

Avocado (Persea americana Mill.) is a subtropical tree, particularly sensitive to either an excess or a lack of water. Understanding this balance is crucial to determine the optimum water supply and enhance crop productivity. The rising shortage of water resources in semiarid producing regions and the need for irrigation optimization call for sustainable water savings. A 3-year monitoring study with avocado cv. “Hass” tested sustained-deficit irrigation strategies supplying 33, 50 or 75% of the estimated crop water demand. They were compared with a control strategy supplying 100% of the estimated crop water demand. The leaf water potential, stomatal conductance, tree growth, yield and several fruit quality parameters were evaluated. The yield, tree growth and fruit size were significantly and proportionally lessened by deficit irrigation treatments. Over the study, the average yields amounted to 31.6, 38.3 and 43.8 kg tree−1 in the 33, 50 and 75% treatments respectively, which were significantly less than the yield of 47.5 kg tree−1 measured in the control. The 33% and 75% sustained-deficit irrigation treatments increased the omega 3 and omega 6 fatty acids as well as the unsaturated fatty acids (oleic); however, the 33% deficit irrigation treatment significantly reduced the yield, size and fruit weight. We consider, therefore, that approximately 25% of the irrigation water can be saved without adversely affecting the avocado tree performance in short and medium terms and we recommend implementing the 75% sustained-deficit irrigation strategy. Here we show for the first time the key role of redesigning irrigation strategies in Mediterranean areas, focusing on the benefits of sustained-deficit irrigation, which can save water, encourage water use efficiency and enhance fruit quality. In order to save water, it is critical and necessary to implement such novel water shortage strategies, at the affordable cost of reducing fruit yield while enhancing its quality.

Cadmium is absorbed by plants rapidly and without control through the same channels as other essential metals, interfering with their transport and utilization. Many studies have shown that selenium could be utilized as a way to avoid this unwanted transport and other negative effects of Cd. For this reason, the present research study was conducted with four treatments (−Cd/−Se, +Cd/−Se, +Cd/+SeF, and +Cd/+SeR) to determine the type of application of Se that is best (foliarly and/or via the root) as regards the reduction of the toxic effects of Cd on plants. Our results showed that the Cd excess in the nutrient solution resulted in a decrease in the total dry biomass of the plants grown under these conditions, and this decrease was due to the reduction of the growth of the shoot (48% +Cd/−Se, 45% +Cd/+SeF, and 38% +Cd/+SeR, relative to −Cd/−Se). This reduction in growth was due to: (i) the toxicity of Cd itself and (ii) the nutritional disequilibrium suffered by the plants. It seems that under hydroponic conditions, the addition of Se to the nutrient solution, and therefore its absorption through the roots (lower antioxidant activity, superoxide dismutase, H2O2 concentration and higher catalase activity), greatly delayed and reduced the toxic effects of Cd on the pepper plants, as opposed to the foliar application of this element.

There is growing interest in finding microalgae species that efficiently convert dissolved nutrients contained in aquaculture effluents into highly valuable biomass. The different nitrogen forms that are present in aquaculture effluents are particularly concerning. This study demonstrated that the dinoflagellate Amphidinium carterae can acclimate to both combined and sole nitrogen sources such as nitrate, ammonium, and urea over a wide concentration range. As far as is known, it is the first time that a species of the genus Amphidinium has been successfully cultured with urea as the sole source of nitrogen. In the presence of 882 μM of nitrate, A. carterae tolerated urea concentrations up to 5000 μM. With respect to ammonium-N tolerance, it has been observed that it is lethal at concentrations higher than 441 μM. A robust laboratory experimental design was critical for accurately assessing this acclimation. Alternative N sources did not affect the production of high-value specific polyketide secondary metabolites from A. carterae, such as amphidinols, with an average concentration of 0.435 ± 0.038% biomass d.w. An analysis of the symbiotic microbial assemblages developed in a long-term A. carterae culture in an open raceway pond, and the fact that it is able to metabolize all three nitrogen sources simultaneously, supports the idea that this microalga has the potential to be successfully cultured with aquaculture effluents.

Background and aim In Mexican traditional medicine, Montanoa tomentosa (Mt) has been used as a remedy for reproductive impairments and mood swings. In pre-clinical research, both the extract and some of its active metabolites have produced oxytocinergic-like effects on female reproductive organs; however, there are no detailed studies of its effects on mood swing and brain structures. The aim of this study, was to analyze the behavioral effects of acute administration of a Mt infusion on male rats, during the Open Field (OFT) and Forced Swim (FST) Tests, and their association with the activation of oxytocin (OXT) cells, indicated by Fos protein (Fos/OXT) in the paraventricular (PVN) and supraoptic nuclei (SON). Experimental procedure 52 adult male Wistar rats were assigned to two conditions; with FST (n = 8), or without (n = 5). Each integrated condition included four groups [Control, Vehicle, Fluoxetine (Flx; 10 mg/kg), and Mt (50 mg/kg), p.o.]. Results and conclusion Mt and Flx treatment produced an anti-despair-like effect on the FST, but no significant changes in locomotor activity. Also, the Mt infusion -but not Flx-significantly increased the number of Fos/OXT cells in the PVN and SON, regardless of the condition, compared to the control and vehicle groups. These results show that Mt, but not Flx, produces an anti-despair-like effect that could be associated with the activation of OXT cells in PVN and SON. This study thus contributes to our knowledge of the pharmacological activity of Mt infusions, which could be a natural antidepressant agent with future clinical relevance., Graphical abstract Image 1, Highlights 1 An anti-despair-like effect. 2 Activation of oxytocin neurons in the Paraventricular and Supraoptic Nuclei. 3 Could be exerting a protective effect against stress in short-term.

In order to understand photosynthetic responses of pomegranate plants (Punica granatum L.) to salinity, an experiment was conducted with three varieties, 'Mollar de Elche', 'Valenciana', and 'Wonderful', irrigated with seven salt concentrations (0, 40, 60, 80, 100, 120, and 140 mM NaCl). At the end of the experiment, parameters of gas exchange, chlorophyll fluorescence, water relations, and sugar and chloride concentrations were measured in leaves. As the concentration of NaCl increased, the concentration of Cl- in leaves was elevated, and the CO2 assimilation rate, stomatal conductance, variable fluorescence/maximum fluorescence ratio, PSII quantum yield, and total soluble sugars decreased. In 'Valenciana', the decrease of the net assimilation of CO2 could occur due to the closure of stomata, while in 'Mollar' and 'Wonderful', this was due to damage caused by Cl- toxicity. The study of carbohydrates also suggests a different behavior of carbon metabolism in the three varieties.

Background Cystic fibrosis (CF) is an endotoxin tolerance (ET)-related disease. Given that increased PD-L1 has been reported in ET, its expression and physiological effects on cystic fibrosis monocytes should be studied. Methods We analyzed the phenotype and ex vivo response of immune system cells in 32 patients with CF, 19 of them colonized by Pseudomonas aeruginosa. An in vitro model was developed of Pseudomonas aeruginosa colonization using purified lipopolysaccharides (LPS) from one of the most prevalent strains in patients with CF (a CF-adapted Pseudomonas aeruginosa ST395 clone). Changes in the immune response, including cytokine production and T-lymphocyte proliferation, as well as expression of PD-L1, were evaluated. Results PD-L1 was overexpressed in the monocytes of patients with CF compared with healthy volunteers, and levels of this immune checkpoint were associated with Pseudomonas aeruginosa colonization. In addition, patients with Pseudomonas aeruginosa colonization showed a patent ET status, including poor inflammatory response, reduced HLA-DR expression and T-lymphocyte proliferation impairment. PD-L1/PD-1 blocking assays reverted the impaired adaptive response. Ultimately, monocytes from healthy volunteers cultured in the presence of the clinically relevant strain of Pseudomonas aeruginosa or serum collected from patients with CF colonized by Pseudomonas aeruginosa reproduced the previous observed features. Conclusions Pseudomonas aeruginosa colonization in patients with CF was associated with PD-L1 overexpression and impaired T cell response, and LPS from this pathogen induced the observed phenotype. Our findings open new avenues for the use of anti-PD-1/PD-L1 immunotherapy in patients with CF who are colonized by Pseudomonas aeruginosa.

Empirical evidence suggests that, in the auditory cortex (AC), the phase relationship between spikes and local-field potentials (LFPs) plays an important role in the processing of auditory stimuli. Nevertheless, unlike the case of other sensory systems, it remains largely unexplored in the auditory modality whether the properties of the cortical columnar microcircuit shape the dynamics of spike-LFP coherence in a layer-specific manner. In this study, we directly tackle this issue by addressing whether spike-LFP and LFP-stimulus phase synchronization are spatially distributed in the AC during sensory processing, by performing laminar recordings in the cortex of awake short-tailed bats (Carollia perspicillata) while animals listened to conspecific distress vocalizations. We show that, in the AC, spike-LFP and LFP-stimulus synchrony depend significantly on cortical depth, and that sensory stimulation alters the spatial and spectral patterns of spike-LFP phase-locking. We argue that such laminar distribution of coherence could have functional implications for the representation of naturalistic auditory stimuli at a cortical level.

Aims To discern the differences in expression profiling of two histological subtypes of colorectal carcinoma (CRC) arising from the serrated route (serrated adenocarcinoma (SAC) and CRC showing histological and molecular features of a high level of microsatellite instability (hmMSI-H) both sharing common features (female gender, right-sided location, mucinous histology, and altered CpG methylation), but dramatically differing in terms of prognosis, development of an immune response, and treatment options. Methods and results Molecular signatures of SAC and hmMSI-H were obtained by the use of transcriptomic arrays; quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were used to validate differentially expressed genes. An over-representation of innate immunity functions (granulomonocytic recruitment, chemokine production, Toll-like receptor signalling, and antigen processing and presentation) was obtained from this comparison, and intercellular cell adhesion molecule-1 (ICAM1) was more highly expressed in hmMSI-H, whereas two genes [those encoding calcitonin gene-related peptide-receptor component protein and C-X-C motif chemokine ligand 14 (CXCL14)] were more highly expressed in SAC. These array results were subsequently validated by qPCR, and by IHC for CXCL14 and ICAM1. Information retrieved from public databanks confirmed our findings. Conclusions Our findings highlight specific functions and genes that provide a better understanding of the role of the immune response in the serrated pathological route and may be of help in identifying actionable molecules.

High-sensitivity C-reactive protein (hsCRP) and homocysteine (Hcy) are inflammation markers but are also related to cardiovascular diseases, disability, or higher risk of death. Although inflammation is considered to be associated with frailty, data regarding the association between hsCRP or Hcy and frailty are controversial or scarce, especially with respect to their association with prefrailty. Thus, our objective was to study the association of hsCRP and Hcy with prefrailty and frailty in 1,211 Spanish men and women aged 65â 98 years from the Toledo Study for Healthy Aging (TSHA) cohort, classified according to Friedâ s criteria. Hcy was independently associated with frailty (odds ratio [OR] = 1.06; 95% confidence interval [CI]: 1.01â 1.12), whereas hsCRP was independently associated with both prefrailty (OR = 1.03; 95% CI: 1.01â 1.06) and frailty (OR = 1.07; 95% CI: 1.02â 1.12). Furthermore, both markers were positively correlated with the number of Friedâ s criteria that were met and were independently associated with the criteria of exhaustion (Hcy: OR = 1.03, 95% CI: 1.00â 1.06), weakness (hsCRP: OR = 1.03, 95% CI: 1.01â 1.05), and low physical activity (hsCRP: OR = 1.04, 95% CI: 1.02â 1.06). Thus, our results highlight the importance of inflammation in age-related physical decline and, in particular, its association with fatigue, low strength, and decreased physical activity., This study was supported by the Instituto de Salud Carlos III (Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad; RD06/0013/0001, and RD12/0043/0012). Ministerio de Ciencia e Innovación; PI07/90175). NA-S was supported by fellowships from the Instituto de Salud Carlos III (Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad; RD06/0013/0001 and RD12/0043/0012) and by a fellowship from the Consejería de Salud, Junta de Andalucía (PC-0111-2016-0111). IC-C was supported by fellowships from the Ministerio de Educación, Cultura y Deporte (FPU13/01210) and Junta de Andalucía (CTS160).

Sustainable dinoflagellate microalgae-based bioprocess designed to produce secondary metabolites (SMs) with interesting bioactivities are attracting increasing attention. However, dinoflagellates also produce other valuable bioproducts (e.g polyunsaturated fatty acids, carotenoids, etc.) that could be recovered and should therefore be taken into account in the bioprocess. In this study, biomass of the marine dinoflagellate microalga Amphidinium carterae was used to assess and optimise three different methods in order to obtain three families of high-value biochemical compounds present in the biomass. The existing processes encompassed a multi-step extraction process for carotenoids, fatty acids and APDs individually and are optimized for the integral valorization of raw A. carterae biomass, with SMs being the primary target compounds. Total process recovery yields were 97% for carotenoids, 80% for total fatty acids and 100% for an extract rich in APDs (not purified).

Quinoa (Chenopodium quinoa Willd.) is native to South America; it is characterized by its high nutrient contents and high adaptation capacity to diverse edapho-climatic conditions, which highlights it's genetic variability expressed as multiple physiological and phenological responses. The objective of this research was to evaluate the physiological response and proximal composition of the grain to three types of fertilization under the environmental conditions of the municipality of Oicata (Boyaca, Colombia) located at 2,875 m a.s.l. The white Soracá variety was planted using a completely randomized design with four treatments and four replicates. It was observed that the fertilization sources have an effect on the physiological and phenological behavior, mainly on the number of leaves, length of stem and chlorophyll content. The reproductive stage and the proximal composition of seeds changed, which is attributed to the application of mineral organic fertilizer that improves the production of quinoa grains, while N-P-K contribution shows greater growth and vegetable development, but less yield. RESUMEN La quinua (Chenopodium quinoa Willd.) es originaria de América del Sur, y está caracterizada por la alta composición nutricional y su fácil adaptabilidad a condiciones edafoclimáticas, lo que resalta su amplia variabilidad genética que se expresa en múltiples respuestas fisiologías y fenológicas. El objetivo de este estudio fue evaluar la respuesta fisiológica y la composición proximal del grano a tres tipos de fertilización bajo condiciones de clima y suelo propias del municipio de Oicatá (Boyacá, Colombia), localizado a 2.875 msnm. Se sembró quinua variedad blanca de Soracá, utilizando un diseño completamente al azar con cuatro tratamientos y cuatro repeticiones. Se observó que las fuentes de fertilización tienen efecto sobre el comportamiento fisiológico y fenológico, principalmente en el número de hojas, longitud de tallo y contenido de clorofila. Las etapas reproductivas y la composición proximal de las semillas también mostraron cambios, lo que se atribuye al aporte de abono orgánico-mineral que mejora la producción de granos de quinua, mientras que el aporte de N-P-K muestra mayor crecimiento y desarrollo vegetativo, pero menor rendimiento.

This study explores the possibility of using mycorrhization as a novel technique for diminishing the negative effects of boron (B) in the nutrient solution on seedlings of Carrizo citrange rootstock plants. For this, an experiment was planned for studying the physiological (gas exchange and chlorophyll fluorescence parameters), morphological (vegetative growth parameters), nutritional (organic solutes, carbohydrates) and oxidative stress responses of seedlings that were either mycorrhized (+AM, Rhizophagus irregularis; previously known as Glomus intraradices) or not mycorrhized (-AM), and irrigated with water containing different concentrations of B (0.5, 5 and 10 mg L−1). It was observed that an excess of B in the nutrient solution decreased the vegetative growth in both +AM and -AM plants, but this decrease was greater in -AM plants. Mycorrhized plants (+AM) under high B concentration accumulated less B in the leaves, and had a smaller reduction of net assimilation rate of CO2 and lower MDA concentration than non-mycorrhized plants. Thus, it can be concluded that mycorrhization increased the tolerance to high boron concentration in the irrigation water of citrange Carrizo seedlings by reducing both the B concentration in the plant tissue and the B toxicity in the physiological processes. The study of organic solutes and carbohydrates also pointed to a different response model between +AM and -AM plants that could be related to the different tolerance observed between these plants.

Summary Background Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three cancer‐prone genodermatoses whose causal genetic mutations cannot fully explain, on their own, the array of associated phenotypic manifestations. Recent evidence highlights the role of the stromal microenvironment in the pathology of these disorders. Objectives To investigate, by means of comparative gene expression analysis, the role played by dermal fibroblasts in the pathogenesis of RDEB, KS and XPC. Methods We conducted RNA‐Seq analysis, which included a thorough examination of the differentially expressed genes, a functional enrichment analysis and a description of affected signalling circuits. Transcriptomic data were validated at the protein level in cell cultures, serum samples and skin biopsies. Results Interdisease comparisons against control fibroblasts revealed a unifying signature of 186 differentially expressed genes and four signalling pathways in the three genodermatoses. Remarkably, some of the uncovered expression changes suggest a synthetic fibroblast phenotype characterized by the aberrant expression of extracellular matrix (ECM) proteins. Western blot and immunofluorescence in situ analyses validated the RNA‐Seq data. In addition, enzyme‐linked immunosorbent assay revealed increased circulating levels of periostin in patients with RDEB. Conclusions Our results suggest that the different causal genetic defects converge into common changes in gene expression, possibly due to injury‐sensitive events. These, in turn, trigger a cascade of reactions involving abnormal ECM deposition and underexpression of antioxidant enzymes. The elucidated expression signature provides new potential biomarkers and common therapeutic targets in RDEB, XPC and KS. What's already known about this topic? Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three genodermatoses with high predisposition to cancer development.Although their causal genetic mutations mainly affect epithelia, the dermal microenvironment likely contributes to the physiopathology of these disorders. What does this study add? We disclose a large overlapping transcription profile between XPC, KS and RDEB fibroblasts that points towards an activated phenotype with high matrix‐synthetic capacity.This common signature seems to be independent of the primary causal deficiency, but reflects an underlying derangement of the extracellular matrix via transforming growth factor‐β signalling activation and oxidative state imbalance. What is the translational message? This study broadens the current knowledge about the pathology of these diseases and highlights new targets and biomarkers for effective therapeutic intervention.It is suggested that high levels of circulating periostin could represent a potential biomarker in RDEB., Linked Comment: https://doi.org/10.1111/bjd.18104. https://doi.org/10.1111/bjd.18271 available online

Bernardino Alcázar-Navarrete,1,2 Francisco García-Rio,2,3 Guadalupe Sánchez,4 Esther Mariscal,5 Andrea García,5 Maribel Cuesta,6 Estefany Uría,6 Marc Miravitlles2,7 1Respiratory Department. Hospital Universitario Virgen de las Nieves, Granada, Spain; 2CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain; 3Hospital Universitario La Paz, IdiPAZ, Madrid, Spain; 4Medical Department, GSK, Madrid, Spain; 5Market Access Department, GSK, Madrid, Spain; 6Oblikue Consulting, Barcelona, Spain; 7Pneumology Department, Hospital Universitari Vall d’Hebron, Vall D’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, SpainCorrespondence: Francisco García-RioHospital Universitario La Paz, Idipaz, Paseo de la Castellana, 261, Madrid, 28046, SpainTel +34 917 27 70 00Email fgr01m@gmail.comBackground: The cost of chronic obstructive pulmonary disease (COPD) in Spain has been studied from different perspectives, but parameters such as the patient’s phenotype have seldom been considered. Our aim was to describe the disease burden of COPD patients with frequent exacerbator phenotype, treated with triple therapy.Methods: An observational, multicenter study was carried out from December 2017 to November 2018 in pulmonology services among patients ≥ 40 years with COPD confirmed diagnosis receiving triple therapy (ICS/LAMA/LABA) and history of ≥ 2 moderate or ≥ 1 severe exacerbation in the 12 months prior to the inclusion visit. COPD-related healthcare resources were collected over a 12-months period prior to the inclusion visit: pharmacological and non-pharmacological treatments, medical and ER visits, hospitalizations, tests and productivity loss. Costs were updated to € 2019. Patients were classified according to blood eosinophil levels: < 150 cells/μL and ≥ 150 cells/μL.Results: A total of 306 patients were included (77.1% men), with mean age of 69.9 years. Mean COPD exacerbation rate was 2.5/patient/year and 51.3% of patients had ≥ 150 cells/μL eosinophil level. On average, for the total population, COPD-related visits/patients/year were 6.2. Resource use in moderate exacerbation was higher in patients with eosinophils ≥ 150 cells/μL, whereas in severe exacerbation was higher in patients with eosinophils < 150cells/μL. According to eosinophil levels, total annual mean (SD) costs/patient accounted for € 8382 (9863) and € 5144 (5444) for patients with eosinophils < 150 cells/μL and ≥ 150 cells/μL, respectively.Conclusion: The impact of exacerbating COPD patients treated with triple therapy in Spain is large, especially among those with eosinophils < 150 cells/μL.Keywords: frequent exacerbation, triple therapy, cost, eosinophil, health care resources, COPD

Se remite un caballo (Equus caballus), sexo macho, de raza Pinto y 8 años de edad. Con historia de balanopostitis nodular exudativa crónica complicada con infección bacteriana secundaria data de 4 años. Emaciación crónica severa. Oliguria, estranguria y polidipsia. Linfadenomegalia de nódulos linfáticos inguinales y femurales preescapulares. Se le practicó eutanasia. Posteriormente se le prácticó necropsia por las técnicas sistemáticas descritas para equinos. Se tomaron secciones de tejido para estudio histopatológico y fueron procesadas por los métodos convencionales de procesamiento histológico. Fueron tomadas muestras de heces para estudios parasitológicos. El examen macroscópico reveló emaciación crónica severa. Balanopostitis exudativa crónica severa con infección bacteriana secundaria. Se evidencio hidroperitoneo marcado. Linfadenomegalia de nódulos mesentéricos. Los cortes histológicos evidenciaron: Balanopostitis crónica severa, con focos de proliferación de células escamosas espinocelulares con abundante acantosis, pleomorfismo, hipercromasia nuclear, anaplasia, figuras mitóticas típicas y atípicas constantes, presencia de perlas corneas abundantes. En algunas zonas se observaron granulomas con formas parasitarias tipo Habronema. Los resultados del estudio coprológico fueron consistentes con huevos de Habronema muscae. En conclusión: la historia clínica, los hallazgos macroscópicos e histológicos evidencian un síndrome de balanopostitis crónica y carcinoma epidermoide metastásico.

Biofuels have been obtained from vegetable oils, animal fats and recently from microorganisms such as algae, bacteria or yeasts that present a significant content of triacylglycerols through a transesterification reaction. Technical problems with biodiesel or agrodiesel (Term recently used, in this work we will use biodiesel), include oxidative stability, cold flow, and increased NOx emissions. The solution to these problems involves the use of additives on the one hand or modifying the fatty acid composition of the microorganisms alternatively, either through changes in the cultivation temperature, addition of nanomaterials, or through genetic modification, to obtain high-quality biofuels. In this work, two species of microalgae with high fatty acid content were obtained, Botryococcus braunii originating from Cuzco, Peru and Coccomyxa subellipsoidea C-169, from Marble Point, Antarctica, both were cultivated under optimal conditions and later direct transesterification was performed to obtaining biodiesel. The main objective was to develop an economical and viable process that allows it to compete with fossil fuels, based on obtaining biomass and the transesterification method. Here, direct transesterification was effective and allows to significantly reduce the problems associated with the increase in costs of obtaining biodiesel, because reduces critical steps, also the biodiesel thus obtained represents an advance in the development of high-quality biofuels, large-scale and inexpensive. Resumen. Los biocombustibles se han obtenido desde finales del siglo XIX a partir de aceites vegetales, grasas animales y recientemente a partir de microorganismos como algas, bacterias o levaduras que presentan un contenido significativo en triacilgliceroles mediante una reacción de transesterificación. Algunos de los problemas técnicos con el biodiésel o agrodiesel (término usado recientemente, en este trabajo usaremos biodiesel) son: estabilidad oxidativa, flujo en frío y aumento de emisiones de NOx. La solución a estos problemas incluye el uso de aditivos, por un lado, o modificar la composición de ácidos grasos de los microorganismos por otro, ya sea mediante cambios en la temperatura de cultivo, adición de nanomateriales, o mediante modificación genética, para obtener biocombustibles de alta calidad. En este trabajo se utilizaron dos especies de microalgas con gran contenido en ácidos grasos, Botryococcus braunii originaria de Cuzco, Perú y Coccomyxa subellipsoidea C-169, de Punta Mármol, Antártida, ambas fueron cultivadas en óptimas condiciones y posteriormente se realizó la transesterificación directa para obtener el biodiésel. El principal objetivo fue desarrollar un proceso económico y viable, que permita competir con los combustibles fósiles, a partir de la obtención de biomasa y el proceso de transesterificación. La transesterificación directa fue exitosa y permitió reducir significativamente los problemas asociados con el aumento de costos de obtención de biodiésel, ya que reduce pasos críticos del proceso, además el biodiésel así obtenido representa un avance en el desarrollo de biocombustibles de alta calidad, a gran escala y de bajo costo.

Se registró un caso de miositis parasitaria en el oso palmero Myrmecophaga trydactila en el parque zoológico “El Pinar” Caracas Venezuela. Con historia de claudicación de miembros posteriores, dermatitis crónica supurada recurrente en región femoral, cervical y axilar, bacteriemia y septicemia. Se le práctico necropsia por las técnicas sistemática descrita para animales domésticos. Se tomaron secciones de tejido para estudio histopatológico y fueron procesadas por los métodos de procesamiento histológico. Fueron tomadas muestras de contenido gástrico y heces para estudios parasitológicos mediante la técnica de flotación. El examen macroscópico reveló emaciación crónica marcada, dermatitis exudativa crónica severa con infección bacteriana secundaria. Se evidencio hidroperitoneo marcado y gastritis erosiva focal crónica nodular. Enteritis duodenal mucosa segmental y colitis crónica. Hepatomegalia con focos de fibrosis en el parénquima. Hemorragia petequial cortical en glándulas adrenales, bilateral. Miositis nodular en músculos semi membranoso y semi tendinoso de miembros posteriores. Los cortes histológicos evidenciaron: dermatitis crónica caracterizada por un infiltrado mixto polimorfonuclear neutrofílico abundantes eosinófilos degenerados e infiltrado mononuclear linfocitico y plasmocitario. Se observa miositis linfocitaria focal con la presencia de quistes intermiofibrilares con formas larvarias de aproximadamente 800 a 900 μm, enrolladas sobre si mismas, con cordones laterales, rodeadas de una capsula densa de tejido fibroso, respuesta fibroplasica y calcificación focal. El estudio coprológico fue consistente con huevos de Trichinella sp

Se estudiaron 3 equinos (Equus asinus Linnaeus, 1758), dos de sexo macho y una hembra, entre 5-8 años de edad, en actividad atlética, en Choroni, Estado Aragua, Venezuela. El examen clínico evidenció pelo hirsuto y condición corporal moderada. Las lesiones cutáneas tipo dermatitis nodular eritematosa a costrosas crónica presentaron un centro ulcerado con bordes de reepitelización complicadas. Fueron tomadas secciones de tejido tegumentario en los límites de las lesiones afectadas descritas anteriormente, mediante la técnica de biopsia por escisión. Las muestras fueron fijadas en formol al 10% y analizadas por los métodos convencionales de procesamiento histológico y coloreadas con Hematoxilina y Eosina. Adicionalmente se emplearon las coloraciones especiales PAS, Giemsa y Grocott. Los cortes histológicos revelaron dermatitis nodular erosiva ulcerativa costrosa. Dermatitis perivascular tipo I y un infiltrado inflamatorio fueron observados. Se observaron linfocitarios mononucleares y plasmocitarios e infiltrados polimorfonucleares neutrofílicos con abundantes macrófagos reactivos. Las coloraciones especiales PAS, Giemsa y Grocott evidenciaron formas de amastigotes flageladas y abundantes bacterias y hongos secundarios. En conclusión, se registran tres casos de dermatitis nodular eritematosa asociada a la infestación crónica por Leishmania sp. en los asnos estudiados de Choroni, estado de Aragua, Venezuela.

Se remite un equino Pura Sangre de Carrera, de 2 años de edad y de sexo masculino. Con historia de emaciación severa, pelo hirsuto y diarrea crónica esporádica. Los exámenes coprológicos previos evidenciaron 1850 HPG (huevos por g de heces) de Strongylus spp. El tratamiento empleado fue con Ivermectina 0,2 mg. kg-1 a una dosis única vía oral. Se le practicó necropsia y fueron tomadas muestras de tejidos para estudio histopatológico, las mismas que fueron procesadas por los métodos convencionales. Adicionalmente se tomaron muestras de contenido intestinal para estudios parasitológicos. Los hallazgos de macroscópicos fueron de emaciación severa, pelo hirsuto y mucosas pálidas. Se evidenció síndrome ulceroso gástrico, enteritis en intestino delgado hemorrágico focal crónico con presencia de formas parasitarias de 3-5 cm y tipo quistes, así como hemomelasma ilei. Los cortes histológicos mostraron enteritis proliferativa caracterizada por un infiltrado linfocitario y eosinofilos escasos. Se observaron quistes parasitarios en la porción secretora (lamina propia). El estudio coprológico evidenció 1050 HPG de Strongylus spp. y las formas parasitarias observadas fueron identificadas como Strongylus vulgaris (Looss, 1900). En conclusión los hallazgos de necropsia evidenciaron un síndrome de parasitosis severa asociada a la infestación crónica por vulgaris.

Background Cancer is a major health problem which presents a high heterogeneity. In this work we explore omics data from Breast, Kidney and Lung cancers at different levels as signalling pathways, functions and miRNAs, as part of the CAMDA 2019 Hi-Res Cancer Data Integration Challenge. Our goal is to find common functional patterns which give rise to the generic microenvironment in these cancers and contribute to a better understanding of cancer pathogenesis and a possible clinical translation down further studies. Results After a tumor versus normal tissue comparison of the signaling pathways and cell functions, we found 828 subpathways, 912 Gene Ontology terms and 91 Uniprot keywords commonly significant to the three studied tumors. Such features interestingly show the power to classify tumor samples into subgroups with different survival times, and predict tumor state and tissue of origin through machine learning techniques. We also found cancer-specific alternative activation subpathways, such as the ones activating STAT5A in ErbB signaling pathway. miRNAs evaluation show the role of miRNAs, such as mir-184 and mir-206, as regulators of many cancer pathways and their value in prognoses. Conclusions The study of the common functional and pathway activities of different cancers is an interesting approach to understand molecular mechanisms of the tumoral process regardless of their tissue of origin. The existence of platforms as the CAMDA challenges provide the opportunity to share knowledge and improve future scientific research and clinical practice.

The oxidation of oleuropein and 3-hydroxytyrosol by oxidases laccase, tyrosinase, and peroxidase has been studied. The use of a spectrophotometric method and another spectrophotometric chronometric method has made it possible to determine the kinetic parameters Vmax and KM for each enzyme. The highest binding affinity was shown by laccase. The antioxidant capacities of these two molecules have been characterized, finding a very similar primary antioxidant capacity between them. Docking studies revealed the optimal binding position, which was the same for the two molecules and was a catalytically active position. PRACTICAL APPLICATIONS: One of the biggest environmental problems in the food industry comes from olive oil mill wastewater with a quantity of approximately 30 million tons per year worldwide. In addition, olive pomace, the solid residue obtained from the olive oil production, is rich in hydroxytyrosol and oleuropein and the action of enzymatic oxidases can give rise to products in their reactions that can lead to polymerization. This polymerization can have beneficial effects because it can increase the antioxidant capacity with potential application on new functional foods or as feed ingredients. Tyrosinase, peroxidase, and laccase are the enzymes degrading these important polyphenols. The application of a spectrophotometric method for laccase and a chronometric method, for tyrosinase and peroxidase, allowed us to obtain the kinetic information of their reactions on hydroxytyrosol and oleuropein. The kinetic information obtained could advance in the understanding of the mechanism of these important industrial enzymes.

The mammalian frontal and auditory cortices are important for vocal behaviour. Here, using local field potential recordings, we demonstrate for the first time that the timing and spatial pattern of oscillations in the fronto-auditory cortical network of vocalizing bats (Carollia perspicillata) predict the purpose of vocalization: echolocation or communication. Transfer entropy analyses revealed predominantly top-down (frontal-to-auditory cortex) information flow during spontaneous activity and pre-vocal periods. The dynamics of information flow depended on the behavioural role of the vocalization and on the timing relative to vocal onset. Remarkably, we observed the emergence of predominantly bottom-up (auditory-to-frontal cortex) information transfer patterns specific echolocation production, leading to self-directed acoustic feedback. Electrical stimulation of frontal areas selectively enhanced responses to echolocation sounds in auditory cortex. These results reveal unique changes in information flow across sensory and frontal cortices, potentially driven by the purpose of the vocalization in a highly vocal mammalian model.

Simple Summary We investigated the influence of autophagy-related variants in modulating colorectal cancer (CRC) risk through a meta-analysis of genome-wide association study (GWAS) data from four large European cohorts. We found that genetic variants within the DAPK2 and ATG5 loci were associated with CRC risk. This study also shed some light onto the functional mechanisms behind the observed associations and demonstrated the impact of DAPK2rs11631973 and ATG5rs546456 polymorphisms on the modulation of host immune responses, blood derived-cell counts and serum inflammatory protein levels, which might be involved in promoting cancer development. No effect of the DAPK2 and ATG5 polymorphisms on the autophagy flux was observed, Acknowledgments: We kindly thank all individuals who agreed to participate in the DACHS, CRCGen, CORSA and Czech Republic Colorectal Cancer studies, as well as all cooperating physicians and students. We thank Hugo Sousa for the collection of healthy donors for the autophagy in vitro studies, Data Availability Statement: The genotype data used in the present study are available from the corresponding authors upon reasonable request. Functional data used in this project have been meticulously catalogued and archived in the BBMRI-NL data infrastructure (https://hfgp.bbmri.nl/, accessed on 13 December 2019) using the MOLGENIS open-source platform for scientific data [52]. This allows flexible data querying and download, including sufficiently rich metadata and interfaces for machine processing (R statistics, REST API) and using FAIR principles to optimise findability, accessibility, interoperability and reusability [53,54]., Funding: This work was partially supported by grants from the Instituto de Salud Carlos III (Madrid, Spain; PI12/02688 and PI17/02256). CORSA was funded by the Austrian Research Promotion Agency (FFG) BRIDGE grant (no. 829675, to Andrea Gsur), the “Herzfelder’sche Familienstiftung” (grant to Andrea Gsur). Czech Republic CCS was funded by GACR grants (18–09709S, 19–10543S and 20–03997S), ProgresQ28/1.LF and UNCE/MED/006 grants. This article is based upon work from COST Action CA17118, supported by COST (European Cooperation in Science and Technology). A.K. is a recipient of a Ramalingaswami Re-Retry Faculty Fellowship (Grant; BT/RLF/Re-entry/38/2017) from the Department of Biotechnology (DBT), Government of India (GOI). V.M. received funding from the Agency for Management of University and Research Grants (AGAUR) of the Catalan Government grant 2017SGR723, the Instituto de Salud Carlos III, co-funded by FEDER funds–a way to build Europe–grants PI14-00613, PI17-00092 and the Spanish Association Against Cancer (AECC) Scientific Foundation grant GCTRA18022MORE. K.H. was supported by European Union Horizon 2020 grant No. 856620. We thank the CERCA Programme, Generalitat de Catalunya for institutional support., The role of genetic variation in autophagy-related genes in modulating autophagy and cancer is poorly understood. Here, we comprehensively investigated the association of autophagy-related variants with colorectal cancer (CRC) risk and provide new insights about the molecular mechanisms underlying the associations. After meta-analysis of the genome-wide association study (GWAS) data from four independent European cohorts (8006 CRC cases and 7070 controls), two loci, DAPK2 (p = 2.19 × 10−5) and ATG5 (p = 6.28 × 10−4) were associated with the risk of CRC. Mechanistically, the DAPK2rs11631973G allele was associated with IL1 β levels after the stimulation of peripheral blood mononuclear cells (PBMCs) with Staphylococcus aureus (p = 0.002), CD24 + CD38 + CD27 + IgM + B cell levels in blood (p = 0.0038) and serum levels of en-RAGE (p = 0.0068). ATG5rs546456T allele was associated with TNF α and IL1 β levels after the stimulation of PBMCs with LPS (p = 0.0088 and p = 0.0076, respectively), CD14+CD16− cell levels in blood (p = 0.0068) and serum levels of CCL19 and cortisol (p = 0.0052 and p = 0.0074, respectively). Interestingly, no association with autophagy flux was observed. These results suggested an effect of the DAPK2 and ATG5 loci in the pathogenesis of CRC, likely through the modulation of host immune responses., Instituto de Salud Carlos III (Madrid, Spain; PI12/02688 and PI17/02256), CORSA was funded by the Austrian Research Promotion Agency (FFG), BRIDGE grant (no. 829675, to Andrea Gsur), Czech Republic CCS was funded by GACR grants (18–09709S, 19–10543S and 20–03997S), ProgresQ28/1.LF and UNCE/MED/006 grants, COST Action CA17118, supported by COST (European Cooperation in Science and Technology), A.K. is a recipient of a Ramalingaswami Re-Retry Faculty Fellowship (Grant; BT/RLF/Re-entry/38/2017) from the Department of Biotechnology (DBT), Government of India (GOI), Agency for Management of University and Research Grants (AGAUR) of the Catalan Government grant 2017SGR723, the Instituto de Salud Carlos III, co-funded by FEDER funds–a way to build Europe–grants PI14-00613, PI17-00092 and the Spanish Association Against Cancer (AECC) Scientific Foundation grant GCTRA18022MORE., European Union Horizon 2020 grant No. 856620, CERCA Programme, Generalitat de Catalunya for institutional support

Flavonoids are potential nutraceutical compounds present in diary food. They are considered health-promoting compounds and promising drugs for different diseases, such as neurological and inflammatory diseases, diabetes and cancer. Therefore, toxicological and mechanistic studies should be done to assert the biological effects and identify the molecular targets of these compounds. In this work we describe the effects of six structurally-related flavonoids—baicalein, chrysin, scutellarein, 6-hydroxyflavone, 6,7-dihydroxyflavone and 7,8-dihydroxyflavone—on Caenorhabditis elegans’ lifespan and stress resistance. The results showed that chrysin, 6-hydroxyflavone and baicalein prolonged C. elegans’ lifespan by up to 8.5%, 11.8% and 18.6%, respectively. The lifespan extensions caused by these flavonoids are dependent on different signaling pathways. The results suggested that chrysin’s effects are dependent on the insulin signaling pathway via DAF-16/FOXO. Baicalein and 6-hydroxyflavone’s effects are dependent on the SKN-1/Nfr2 pathway. In addition, microarray analysis showed that baicalein downregulates important age-related genes, such as mTOR and PARP.

Horizontal gene transfer has shaped the evolution of Salmonella enterica as pathogen. Some functions acquired by this mechanism include enzymes involved in peptidoglycan (PG) synthesis and remodeling. Here, we report a novel serovar Typhimurium protein that is absent in non-pathogenic bacteria and bears a LprI functional domain, first reported in a Mycobacterium tuberculosis lipoprotein conferring lysozyme resistance. Based on the presence of such domain, we hypothesized a role of this S. Typhimurium protein in PG metabolism. This protein, which we named ScwA for Salmonella cell wall-related regulator-A, controls positively the levels of the murein lytic transglycosylase MltD. In addition, the levels of other enzymes that cleave bonds in the PG lattice were affected in a mutant lacking ScwA, including a soluble lytic tranglycosylase (Slt), the amidase AmiC, and a few endo- and carboxypeptidases (NlpC, PBP4, and AmpH). The scwA gene has lower G+C content than the genomic average (43.1 vs. 52.2%), supporting acquisition by horizontal transfer. ScwA is located in the periplasm, stabilized by two disulfide bridges, produced preferentially in stationary phase and down-regulated following entry of the pathogen into eukaryotic cells. ScwA deficiency, however, results in a hypervirulent phenotype in the murine typhoid model. Based on these findings, we conclude that ScwA may be exploited by S. Typhimurium to ensure cell envelope homeostasis along the infection and to prevent host overt damage. This role could be accomplished by controlling the production or stability of a reduced number of peptidoglycan hydrolases whose activities result in the release of PG fragments., Ministry of Science and Innovation

Background In this review, we were interested to identify the wide universe of enzymes associated with epigenetic modifications, whose gene expression is regulated by miRNAs with a high relative abundance in Crohn's disease (CD) affected tissues, with the aim to determine their impact in the pathogenesis and evolution of the disease. Methods We used HMDD and Bibliometrix R-package in order to identify the miRNAs overexpressed in CD. The identified enzymes associated with epigenetic mechanisms and post-translational modifications, regulated by miRNAs upregulated in CD, were analyzed using String v11 database. Results We found 190 miRNAs with great abundance in patients with CD, of which 26 miRNAs regulate the gene expression of enzymes known to catalyze epigenetic modifications involved in essentials pathophysiological processes, such as chromatin architecture reorganization, immune response regulation including CD4+ T cells polarization, integrity of gut mucosa, gut microbiota composition and tumorigenesis. Conclusion The integrated analysis of miRNAs with a high relative abundance in patients with CD showed a combined and superimposed gene expression regulation of enzymes associated with relevant epigenetic mechanisms and that could explain, in part, the pathogenesis of CD.

Betalains are the nitrogenous pigments that replace anthocyanins in the plant order Caryophyllales. Here, we describe unconventional decarboxylated betalains in quinoa (Chenopodium quinoa) grains. Decarboxylated betalains are derived from a previously unconsidered activity of the 4,5-DOPA-extradiol-dioxygenase enzyme (DODA), which has been identified as the key enzymatic step in the established biosynthetic pathway of betalains. Here, dopamine is fully characterized as an alternative substrate of the DODA enzyme able to yield an intermediate and structural unit of plant pigments: 6-decarboxy-betalamic acid, which is proposed and described. To characterize this activity, quinoa grains of different colors were analyzed in depth by chromatography, time-of-flight mass spectrometry, and reactions were performed in enzymatic assays and bioreactors. The enzymatic-chemical scheme proposed leads to an uncharacterized family of 6-decarboxylated betalains produced by a hitherto unknown enzymatic activity. All intermediate compounds as well as the final products of the dopamine-based biosynthetic pathway of pigments have been unambiguously determined and the reactions have been characterized from the enzymatic and functional perspectives. Results evidence a palette of molecules in quinoa grains of physiological relevance and which explain minor betalains described in plants of the Caryophyllales order. An entire family of betalains is anticipated.

Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Posttranslational modifications (PTMs) have been extensively studied in malignancies due to its relevance in tumor pathogenesis and therapy. This review is focused on the dysregulation of glycosyltransferase expression in CRC and its impact in cell function and in several biological pathways associated with CRC pathogenesis, prognosis and therapeutic approaches. Glycan structures act as interface molecules between cells and their environment and in several cases facilitate molecule function. CRC tissue shows alterations in glycan structures decorating molecules, such as annexin-1, mucins, heat shock protein 90 (Hsp90), 1 integrin, carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR), insulin-like growth factor-binding protein 3 (IGFBP3), transforming growth factor beta (TGF- ) receptors, Fas (CD95), PD-L1, decorin, sorbin and SH3 domain-containing protein 1 (SORBS1), CD147 and glycosphingolipids. All of these are described as key molecules in oncogenesis and metastasis. Therefore, glycosylation in CRC can affect cell migration, cell–cell adhesion, actin polymerization, mitosis, cell membrane repair, apoptosis, cell differentiation, stemness regulation, intestinal mucosal barrier integrity, immune system regulation, T cell polarization and gut microbiota composition; all such functions are associated with the prognosis and evolution of the disease. According to these findings, multiple strategies have been evaluated to alter oligosaccharide processing and to modify glycoconjugate structures in order to control CRC progression and prevent metastasis. Additionally, immunotherapy approaches have contemplated the use of neo-antigens, generated by altered glycosylation, as targets for tumor-specific T cells or engineered CAR (Chimeric antigen receptors) T cells.

While studies have established the existence of differences in the epidemiological and clinical patterns of lung adenocarcinoma between male and female patients, we know relatively little regarding the molecular mechanisms underlying such sex-based differences. In this study, we explore said differences through a meta-analysis of transcriptomic data. We performed a meta-analysis of the functional profiling of nine public datasets that included 1366 samples from Gene Expression Omnibus and The Cancer Genome Atlas databases. Meta-analysis results from data merged, normalized, and corrected for batch effect show an enrichment for Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways related to the immune response, nucleic acid metabolism, and purinergic signaling. We discovered the overrepresentation of terms associated with the immune response, particularly with the acute inflammatory response, and purinergic signaling in female lung adenocarcinoma patients, which could influence reported clinical differences. Further evaluations of the identified differential biological processes and pathways could lead to the discovery of new biomarkers and therapeutic targets. Our findings also emphasize the relevance of sex-specific analyses in biomedicine, which represents a crucial aspect influencing biological variability in disease, This work was supported by Fondo de Investigación Sanitaria (ISCIII PI15-00209), GV/2020/ 186, and ISCIII PT17/0009/0015 FEDER

[EN] The tree tomato (Solanum betaceum Cav.) is an underutilized fruit crop native to the Andean region and phylogenetically related to the tomato and potato. Tree tomato fruits have a high amount of nutrients and bioactive compounds. However, so far there are no studies at the genome or transcriptome level for this species. We performed a de novo assembly and transcriptome annotation for purple-fruited (A21) and an orange-fruited (A23) accessions. A total of 174,252 (A21) and 194,417 (A23) transcripts were assembled with an average length of 851 and 849 bp. A total of 34,636 (A21) and 36,224 (A23) transcripts showed a significant similarity to known proteins. Among the annotated unigenes, 22,096 (A21) and 23,095 (A23) were assigned to the Gene Ontology (GO) term and 14,035 (A21) and 14,540 (A23) were found to have Clusters of Orthologous Group (COG) term classifications. Furthermore, 22,096 (A21) and 23,095 (A23) transcripts were assigned to 155 and 161 (A23) KEGG pathways. The carotenoid biosynthetic process GO terms were significantly enriched in the purple-fruited accession A21. Finally, 68,647 intraspecific single-nucleotide variations (SNVs) and almost 2 million interspecific SNVs were identified. The results of this study provide a wealth of genomic data for the genetic improvement of the tree tomato., Pietro Gramazio is grateful to the Spanish Ministerio de Ciencia e Innovacion for a Juan de laCierva-Formacion post-doctoral grant FJC2019-038921-I funded by MCIN/AEI/10.13039/501100011033)