Modelling haematopoietic malignancies using zebrafish

Primitive and definitive haematopoiesis were studied during embryonic and larval development in three zebrafish models of human haematological diseases: TEL-AML1 expressing acute lymphoblastic leukaemia (ALL), GATA2 haploinsufficient disorders, and MDS with isolated del(5q) (MDS5q). The t(12;21)(p13;q22) chromosomal translocation resulting in the TEL-AML1 fusion gene is the most common translocation in childhood ALL. The translocation arises in utero and can be found in approximately 1% of new-born infants. However, less than 1% of these children develop leukaemia and this translocation is not observed in adult ALL. This suggests that the cell of origin resulting in the eventual transformation to BCP-ALL is present and disrupted early during development. Early developmental haematopoiesis was studied in transgenic zebrafish expressing the human TEL-AML1 fusion protein. The numbers of granulocytes are transiently increased by the expression of TEL-AML1 fusion protein in these animals. The GATA2 gene encodes a transcription factor that plays a major role in haematopoiesis. Recently, germline GATA2 mutations have been identified as the cause of a range of haemato-vascular disorders including Emberger syndrome, Monomac and DCML deficiency all with predisposition to MDS. We took advantage of the presence of two GATA2 paralogs (gata2a and gata2b) in zebrafish to dissect the role of GATA2 in early haematopoietic and vascular development. Gata2a and Gata2b were shown to have different functions in haematopoiesis. Gata2a regulates primitive myeloid cell development and vascular morphogenesis. The first wave of lymphocytes and haematopoietic progenitors derived from the dorsal aorta are also affected. A novel role for the Gata2b was identified, in the development of myeloid cells in the caudal haematopoietic tissue. Double heterozygous fish carrying mutations in both gata2a and gata2b were used to model germinal mutations in GATA2 found in patients. Ribosomal protein gene 14 (RPS14), located on 5q, has been shown to be the likely genetic determinant of anaemia in patients with MDS5q. Our group has used TALENs to generate an rps14 mutant zebrafish. Fish carrying a heterozygous mutation in rps14 gene show defects in erythropoiesis and granulopoiesis, and the severity of these defects is enhanced by haemolytic or cold stress. The rescuing effects of a TLR7/8 agonist, imiquimod, identified previously in a small molecule screen for modifiers of the anaemia phenotype associated with Rps14 loss, were studied in rps14 mutant fish. Pharmacological evidence suggests a role for TLR7 in erythroid development, as exposure to a TLR7 agonist partially rescues the phenotype of heterozygous rps14 mutant fish, while treatment with a TLR8 agonist has no effect

Accurate quantitative determination of the total amounts of Strecker aldehydes contained in wine. Assessment of their presence in table wines

Strecker aldehydes (SAs) are key determinants of wine shelf-life and can be present in unoxidized wines in odorless forms, such as hydroxyalkylsulfonates, imines or acetals. A robust and accurate method for the determination of total forms of SAs, based on the classical derivatization with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) and in the selective solid phase extraction of derivatives has been optimized and validated. Matrix effects have been solved by the use of adequate internal standards and by large-enough equilibration times under anoxic conditions. Method figures of merit are highly satisfactory in terms of detection limits ( 0.997), reproducibility (5–13%) and recoveries (RSDs, between 2 and 10%, for 3-methylbutanal, 14%). The analysis of total SAs in 108 Spanish wines revealed that between 52% and 70% of unoxidized red wines and likely a similar fraction of white wines, contain levels of SAs high enough to cause oxidative aromas if bound forms of SAs cleave

Purificadora para el acceso a agua potable

Este proyecto, parte del PAP: San Pedro de Valencia: renovación urbana, saneamiento ambiental y emprendimientos turísticos, se trata de la Gestión de la estandarización de la Purificadora Ahuisculco, el cual es un trabajo colaborativo que se lleva a cabo junto con el comité del agua del poblado de Ahuisculco, en el que se busca como objetivo principal el establecimiento de una purificadora comunitaria, que se propuso en el PAP de primavera 2022, que pueda brindar a la comunidad la oportunidad de consumir su recurso tan abundante que es el agua, de una manera segura y saludable. Se genera un proyecto arquitectónico y ejecutivo, con el objetivo de generar una correcta gestión del agua, a través de la construcción de una planta potabilizadora de agua. Se va avanzando parcialmente, en comunicación y colaboración con la Mesa directiva del Colectivo Ahisculco Defiende su Agua y Comité del Agua potable Ahuisculco. También se genera una proyección de cuantificación y costos, en la que se pueden ver plasmados los estimados de inversión, teniendo la oportunidad de realizar comparaciones y ajustes del presupuesto.ITESO, A.C

Testing Swampland Conjectures with Machine Learning

We consider Type IIB compactifications on an isotropic torus $T^6$ threaded by geometric and non geometric fluxes. For this particular setup we apply supervised machine learning techniques, namely an artificial neural network coupled to a genetic algorithm, in order to obtain more than sixty thousand flux configurations yielding to a scalar potential with at least one critical point. We observe that both stable AdS vacua with large moduli masses and small vacuum energy as well as unstable dS vacua with small tachyonic mass and large energy are absent, in accordance to the Refined de Sitter Conjecture. Moreover, by considering a hierarchy among fluxes, we observe that perturbative solutions with small values for the vacuum energy and moduli masses are favored, as well as scenarios in which the lightest modulus mass is much greater than the corresponding AdS vacuum scale. Finally we apply some results on Random Matrix Theory to conclude that the most probable mass spectrum derived from this string setup is that satisfying the Refined de Sitter and AdS scale conjectures.Comment: 30 pages, 14 Figures. (v2) References adde

Consumo energético, eficiencia de campo y cobertura vegetal en labranza-siembra de maíz en el valle del cauca, colombia

En el Centro de Investigaciones Palmira de la Corporación Colombiana de Investigación Agropecuaria, Corpoica, se realizó un estudio de auditoría energética en cuatro métodos de labranza-siembra (vertisol) de maíz en rotación con algodón. El mayor consumo de energía fósil correspondió a labranza convencional (LC), en la cual más del 70% se invirtió en las labores de labranza primaria y secundaria, seguida de cincel vibratorio (CV) con un 65% y de mulch-tiller (MT) con 54%; siembra directa (SD) sólo empleó combustible fósil en la operación de desbroce de la soca y en la siembra; LC requirió casi 4 veces más energía que SD, CV casi 3 veces más y MT 2.7 veces más; el costo del combustible estuvo en igual proporción, lo mismo que el costo ambiental; en LC, MT y CV el primer pase del implemento de labranza consumió entre 1.5 y 3 veces más energía que el segundo y tercer pases, en suelos tenaces como los vertisoles del CI Palmira. Los altos valores de eficiencia de campo en LC contrastaron con el elevado consumo energético, en comparación con SD, y éste mostró diferencias notorias con respecto a los demás métodos de labranza-siembra en lo relacionado con la conservación de la cobertura vegetal del suelo. ABSTRACT Energy consumption, field efficiency and on ground vegetal cover in corn till-planting systems on Valle del Cauca, Colombia. Corn-cotton energy audit in four tillage-planting systems was carried out at the Colombian Corporation of Agricultural Research Center branch Palmira. The highest consumption of fossil energy corresponded to conventional tillage (LC), in which more than 70% of this consumption corresponded to primary and secondary tillage, followed by vibratory chisel (CV) with 65% and mulch-tiller (MT) with 54%, whereas no-till planting (SD) observed the lowest energy consumption, because it suppressed itself primary and secondary tillage and only used fossil fuel to prepare the soca of the previous culture. Referred to SD, LC required about 4 times more energy, CV about 3 times and MT 2.7 times more, respectively. The cost of the fuel was in equal proportion, just like the environmental cost. In LC, MT and CV, the first one run of tillage consumed between 1.5 and 3 times more energy than the second and third runs, in hard soils like vertisols of the Palmira Research Center. The highest field efficiency in LC contrasted with the elevated energy consumption, in comparison with SD. SD showed well-known differences with regard to the other till-planting systems, concerning on ground vegetal cover conservation. Key words: Zea mays, cotton, tillage energy audit, live mulches

Distanciamiento social ante la COVID-19: Simulación del aforo máximo de personas mediante PHP

Population confluence in internal or external areas considerably increases transmission of COVID-19, due to not respecting the social distancing established by the health system. The objective of this work was to make use of programming techniques, using the PHP language (hypertext preprocessor), for the development of an application that simulates the maximum capacity of people who can enter an internal or external area. The methodology allowed recognizing common internal and external areas, configurating to the development environment, coding, simulation proposing and executing of the simulator where a practical case and ten places were evaluated to determine its reliability. The simulator provided the maximum capacity of people who can enter an internal or external area, complying with the social distancing of 2 m. The results made it possible to know that the use of information technologies through programming techniques and the PHP language contributed to being a technological alternative for the fight against the spread of the virus.La confluencia poblacional en áreas internas o externas incrementa considerablemente la trasmisión de la COVID-19, por no respetar el distanciamiento social que establece el sistema de salud. El objetivo de este trabajo fue hacer uso de técnicas de programación, empleando el lenguaje PHP (preprocesador de hipertexto), para el desarrollo de una aplicación que simule el aforo máximo de personas que pueden ingresar a un área interna o externa. La metodología permitió el reconocimiento de áreas internas y externas comunes, configuración al entorno de desarrollo, codificación, propuesta de simulación y ejecución del simulador donde se ha evaluado un caso práctico y diez lugares para determinar su confiabilidad. El simulador brindó el aforo máximo de personas que pueden ingresar a un lugar de área interna o externa cumpliendo el distanciamiento social de 2 m. Los resultados permitieron conocer que el uso de las tecnologías de información a través de las técnicas de programación y el lenguaje PHP contribuyó en ser una alternativa tecnológica para la lucha contra la propagación del virus

Management of the oral hemangiomas in infants and children : scoping review

Pediatric oral hemangiomas are benign vascular tumors that can be seen from birth, particularly in females. Hemangiomas are most frequent located in the lips and usually regress spontaneously, thus they do not require any type of treatment in most cases. The present scoping review pretended to synthesize the most relevant and currently available information from the international dental literature published in the last 25 years, regarding the management of pediatric oral hemangiomas. An exhaustive literature search was performed in four electronic databases (PubMed, Embase, Google Scholar, and Cochrane). Initially, 241 related titles and abstracts were found. After the duplication removal, screening, and assessment processes, 37 records were included for full-text reading. Finally, 20 articles in the English language were included in the scoping review for data extraction and assessment. We identified and subsequently discussed three fundamental issues associated to the management of pediatric oral hemangiomas: (i) clinical characteristics, differential diagnosis, and histopathological findings; (ii) evolution and complications; and (iii) current available treatment modalities. Although these like-tumor lesions are uncommon, pediatric dentistry practitioners must be familiar with the inherent clinical characteristics, diagnosis approaches, and currently available treatment options. Nowadays, surgical removal and non-invasive medical/pharmacologic therapies are the best management modalities for pediatric oral hemangiomas

A high-throughput chemically induced inflammation assay in zebrafish

Artículo de publicación ISIBackground: Studies on innate immunity have benefited from the introduction of zebrafish as a model system. Transgenic fish expressing fluorescent proteins in leukocyte populations allow direct, quantitative visualization of an inflammatory response in vivo. It has been proposed that this animal model can be used for high-throughput screens aimed at the identification of novel immunomodulatory lead compounds. However, current assays require invasive manipulation of fish individually, thus preventing high-content screening. Results: Here we show that specific, noninvasive damage to lateral line neuromast cells can induce a robust acute inflammatory response. Exposure of fish larvae to sublethal concentrations of copper sulfate selectively damages the sensory hair cell population inducing infiltration of leukocytes to neuromasts within 20 minutes. Inflammation can be assayed in real time using transgenic fish expressing fluorescent proteins in leukocytes or by histochemical assays in fixed larvae. We demonstrate the usefulness of this method for chemical and genetic screens to detect the effect of immunomodulatory compounds and mutations affecting the leukocyte response. Moreover, we transformed the assay into a high-throughput screening method by using a customized automated imaging and processing system that quantifies the magnitude of the inflammatory reaction. Conclusions: This approach allows rapid screening of thousands of compounds or mutagenized zebrafish for effects on inflammation and enables the identification of novel players in the regulation of innate immunity and potential lead compounds toward new immunomodulatory therapies. We have called this method the chemically induced inflammation assay, or ChIn assay.This work was supported by grants to MA from Fondecyt (1070867), FONDAP (15090007), ICM (P06-039F), CORFO-Innova (09MCSS-6705), DFG-Conicyt 075-2009; to CD from UNAB (DI- 01-09/1) and Fondecyt (24090004); to UL from Dopaminet (EU FP7 223744); and to CG by a Marie Curie International Reintegration Grant (EU FP7; PIRG07-GA-2010-267552)

Impact of Liver Inflammation on Bile Acid Side Chain Shortening and Amidation

Bile acid; Inflammation; Oncostatin MÀcid biliar; Inflamació; Oncostatina MÁcido biliar; Inflamación; Oncostatina MBile acid (BA) synthesis from cholesterol by hepatocytes is inhibited by inflammatory cytokines. Whether liver inflammation also affects BA side chain shortening and conjugation was investigated. In human liver cell lines (IHH, HepG2, and HepaRG), agonists of nuclear receptors including the farnesoid X receptor (FXR), liver X receptor (LXR), and peroxisome proliferator-activated receptors (PPARs) did not affect the expression of BA-related peroxisomal enzymes. In contrast, hepatocyte nuclear factor 4α (HNF4α) inhibition down-regulated acyl-CoA oxidase 2 (ACOX2). ACOX2 was repressed by fibroblast growth factor 19 (FGF19), which was prevented by extracellular signal-regulated kinase (ERK) pathway inhibition. These changes were paralleled by altered BA synthesis (HPLC-MS/MS). Cytokines able to down-regulate cholesterol-7α-hydroxylase (CYP7A1) had little effect on peroxisomal enzymes involved in BA synthesis except for ACOX2 and bile acid-CoA:amino acid N-acyltransferase (BAAT), which were down-regulated, mainly by oncostatin M (OSM). This effect was prevented by Janus kinase (JAK) inhibition, which restored BA side chain shortening and conjugation. The binding of OSM to the extracellular matrix accounted for a persistent effect after culture medium replacement. In silico analysis of four databases (n = 201) and a validation cohort (n = 90) revealed an inverse relationship between liver inflammation and ACOX2/BAAT expression which was associated with changes in HNF4α levels. In conclusion, BA side chain shortening and conjugation are inhibited by inflammatory effectors. However, other mechanisms involved in BA homeostasis counterbalance any significant impact on the serum BA profile.This study was supported by the CIBERehd (EHD15PI05/2016) and Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI19/00819, PI20/00189, and PI20/01663 co-funded by European Regional Development Fund/European Social Fund, “Investing in your future”); Junta de Castilla y Leon (SA074P20); Fundació Marato TV3 (Ref. 201916/31), Spain; AECC Scientific Foundation (2017/2020), Spain; Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of Wuerzburg, Germany (Project A-E-384 to H.M.H.); grants PID2019-111669-RB-I00, PID2020-115055RB-I00 from Agencia Estatal de Investigación (AEI), Spain; the AGAUR of the Generalidad de Cataluña SGR-2017-1112, Spain; and European Cooperation in Science & Technology (COST) Action CA17112. R.E.E was recipient of a predoctoral fellowship from “Junta de Castilla y León” and “Fondo Social Europeo” (EDU/574/2018). J.A. was recipient of a grant from Fundación Echebano (2020–2022)

Differential Requirement of Gata2a and Gata2b for Primitive and Definitive Myeloid Development in Zebrafish

Germline loss or mutation of one copy of the transcription factor GATA2 in humans leads to a range of clinical phenotypes affecting hematopoietic, lymphatic and vascular systems. GATA2 heterozygous mice show only a limited repertoire of the features observed in humans. Zebrafish have two copies of the Gata2 gene as a result of an additional round of ancestral whole genome duplication. These genes, Gata2a and Gata2b, show distinct but overlapping expression patterns, and between them, highlight a significantly broader range of the phenotypes observed in GATA2 deficient syndromes, than each one alone. In this manuscript, we use mutants for Gata2a and Gata2b to interrogate the effects on hematopoiesis of these two ohnologs, alone and in combination, during development in order to further define the role of GATA2 in developmental hematopoiesis. We define unique roles for each ohnolog at different stages of developmental myelopoiesis and for the emergence of hematopoietic stem and progenitor cells. These effects are not additive in the haploinsufficient state suggesting a redundancy between these two genes in hematopoietic stem and progenitor cells. Rescue studies additionally support that Gata2b can compensate for the effects of Gata2a loss. Finally we show that adults with loss of combined heterozygosity show defects in the myeloid compartment consistent with GATA2 loss in humans. These results build on existing knowledge from other models of GATA2 deficiency and refine our understanding of the early developmental effects of GATA2. In addition, these studies shed light on the complexity and potential structure-function relationships as well as sub-functionalization of Gata2 genes in the zebrafish model