Association of Notch-1, osteopontin and stem-like cells in ENU-glioma malignant process

Notch-1 and osteopontin (OPN) mediate angiogenesis and glioma stem-like cell (GSLC) maintenance. However, the relationship between these molecules and GSLCs during the development of glioma is unknown. We investigate the expression of Notch-1, OPN and vascular endothelial growth factor (VEGF) associated to the stemness markers nestin and CD133 in three stages of murine gliomas induced by N-ethyl-N-nitrosourea (ENU). Notch-1 and OPN overexpress in the intermediate stage (II), which corresponds to the "angiogenesis switch". Nestin+ cells appear in all stages of ENU-glioma but CD133 only from stage II on. In stage III, neoplastic cells expressing nestin, CD133 and nestin/CD133 reside in spheroid-like aggregates (SAs) and in the neoangiogenic border. These aggregates show Notch-1 and VEGF+ surrounding cells and a significant size and density increase with respect to stage I (3.3 ± 1.5 to 22.4 ± 6.3 m2, n° = 0.3 ± 0.1 to 4.2 ± 0.9, from stage I to stage III, respectively). OPN expression increases in correlation to the glioma malignancy from 4.5 ± 1.8% (I) to 12.3 ± 1.2% of OPN+ cells (III). It predominates in astrocyte-like cells of the neoangiogenic border, displaying co-location with VEGF and CD133. The OPN immunopositivity distribution correlates with the CD133 distribution. In conclusion, OPN co-expressing with CD133 contributes to the identification of GSLCs in the neoangiogenic border, while Notch-1 is present around SAs in advanced stages. The ENU-glioma, mainly in stage II, is a useful tool for assessing new antitumour therapies against these molecules

Modelo algorítmico para la clasificación de una hoja de planta en base a sus características de forma y textura

A lo largo de los años, las plantas han sido consideradas parte vital e indispensable del ecosistema, ya que están presentes en todos los lugares donde vivimos y también donde no lo hacemos. Su estudio es realizado por la ciencia de la botánica, la cual se encargar del estudio de la diversidad y estructura de las mismas. La disminución y extinción de la variedad de las plantas es un tema serio, por lo cual ante el descubrimiento de nuevas especies, se propone una rápida identificación y clasificación a fin de poder monitorearlas, protegerlas y usarlas en el futuro. El problema de la clasificación de hojas es una tarea que siempre ha estado presente en la labor diaria de los botánicos, debido al gran volumen de familias y clases que existen en el ecosistema y a las nuevas especies que van apareciendo. En las últimas décadas, se han desarrollado disciplinas que necesitan de esta tarea. Por ejemplo, en la realización de estudios de impacto ambiental y en el establecimiento de niveles de biodiversidad, es de gran importancia el inventariado de las especies encontradas. Por este motivo, el presente proyecto de fin de carrera pretende obtener un modelo algorítmico mediante la comparación de cuatro modelos de clasificación de Minería de Datos, J48 Árbol de Decisión, Red Neuronal, K-Vecino más cercano y Naive Bayes o Red Bayesiana, los cuales fueron adaptados y evaluados para obtener valores de precisión. Estos valores son necesarios para realizar la comparación de los modelos mediante el método de Área bajo la curva ROC (AUC), resultando la Red Bayesiana como el modelo más apto para solucionar el problema de la Clasificación de Hojas.Tesi

Differential Exposure to N-Ethyl N-Nitrosourea During Pregnancy is Relevant to the Induction of Glioma and PNSTs in the Brain

Exposure to N-nitroso compounds (NOCs) during pregnancy has been associated with an increase in brain tumors in the progeny. This study investigated the brain tumorigenic effect of N-ethyl N-nitrosourea (ENU) after differential exposure of rats during pregnancy. Sprague Dawley rats were exposed to a single dose of ENU (80 mg/kg) in three different circumstances: 1) at first, second or third week of gestation; 2) at the 15th embryonic day (E15) in consecutive litters and 3) at E15 in three successive generations. Location and characterization of the offspring's brain tumors were performed by magnetic resonance imaging and histopathological studies. Finally, tumor incidence and latency and the animals' survival were recorded. ENU-exposure in the last two weeks of pregnancy induced intracranial tumors in over 70% of the offspring rats, these being mainly gliomas with some peripheral nerve sheath tumors (PNSTs). Tumors appeared in young adults; glioma-like small multifocal neoplasias converged on large glioblastomas in senescence and PNSTs in the sheath of the trigeminal nerve, extending to cover the brain convexity. ENU-exposure at E15 in subsequent pregnancies lead to an increase in glioma and PNST incidence. However, consecutive generational ENU-exposure (E15) decreased the animals' survival due to an early onset of both types of tumors. Moreover, PNST presented an inheritable component because progeny, which were not themselves exposed to ENU but whose progenitors were, developed PNSTs. Our results suggest that repeated exposure to ENU later in pregnancy and in successive generations favours the development of intracranial gliomas and PNSTs in the offspring.This study has been financially supported by the University of the Basque Country (UPV/EHU) (GIU 092/19 and PPG 17/51) and the Basque Government (SAN20/25

Gliometako zelula nestina-positiboen banaketa

Zelula ama tumoralak (ZAT), ze lula amen ezaugarriak dituzten eta tumore bat birsortzeko gaitasuna duten tumore-ze1ulak dira. Bai anima1ietan eta bai gizakietan ere , multzoka agertzen dira eremu peribaskularrean, askotan egitura berezietan multzokatuta. Azken urteotan , ZATak kimio-erradio terapiekiko erresistenteak direla ikusi da, baita berreritzearen eragileak direla ere. Nerbio Sistema Zentraleko glioma tumoreetan, ehuna infiltratzeko eta angiogenesia pizteko gai dira zelula hauek. Lan honen helburua, gliomaren garapenaren zeharreko tumore-ama zelulen agerpena eta banaketa aztertzea da, batez ere multzoka agertzen direnenen kasuan.Horretarako, etilnitrosourearen (ENU) bitartez arratoiei glioma tumoreak induzitzen zaizkie eta nestinaren markaketaren bidez bertako zelula amak izan daitezkeen zelulak identifikatzen ditugu. Datuen arabera. nestina-positibo diren zelula multzoen tamaina eta kantitatea gliomaren garapenarekin batera handitzen doa. Taldekatze hauek, eremu peribaskularrean eta baita tumore barruan ere agertzen dira eta in vitro agertzen diren neurosferen antzeko morfologia erakutsi dute. Multzoek eta neurosferek in vitro azaltzen dituzten parekotasun hauek, in vivo agertzen dituztenen seinale izan daitezke. Egitura berezi hauek, kontra duten mikroingurune batetik ihes egiteko ZATek sortzen duten gordailua izatea proposatu da

Fetal sex modulates developmental response to maternal malnutrition

The incidence of obesity and metabolic diseases is dramatically high in rapidly developing countries. Causes have been related to intrinsic ethnic features with development of a thrifty genotype for adapting to food scarcity, prenatal programming by undernutrition, and postnatal exposure to obesogenic lifestyle. Observational studies in humans and experimental studies in animal models evidence that the adaptive responses of the offspring may be modulated by their sex. In the contemporary context of world globalization, the new question arising is the existence and extent of sex-related differences in developmental and metabolic traits in case of mixed-race. Hence, in the current study, using a swine model, we compared male and female fetuses that were crossbred from mothers with thrifty genotype and fathers without thrifty genotype. Female conceptuses evidence stronger protective strategies for their adequate growth and postnatal survival. In brief, both male and female fetuses developed a brain-sparing effect but female fetuses were still able to maintain the development of other viscerae than the brain (mainly liver, intestine and kidneys) at the expense of carcass development. Furthermore, these morphometric differences were reinforced by differences in nutrient availability (glucose and cholesterol) favoring female fetuses with severe developmental predicament. These findings set the basis for further studies aiming to increase the knowledge on the interaction between genetic and environmental factors in the determination of adult phenotype

Obesity and Metabolic Traits after High-Fat Diet in Iberian Pigs with Low Birth Weight of Placental Origin

Intrauterine growth restriction (IUGR) and later obesity and metabolic disorders have classically been associated with maternal malnutrition, but most cases of IUGR are related to placental insufficiency. The current study, using a swine model for IUGR and obesity, aimed to determine the interaction of birth weight (categorized as low birth weight [LBW] or normal birth-weight [NBW]) and postnatal diet (categorized as maintenance diet [MD] or fattening diet [FD]) on body weight, adiposity and metabolic traits. FD induced higher body weight and adiposity (both p < 0.0001), with higher fructosamine levels (p < 0.005) and a trend toward higher HOMA-β index (p = 0.05). NBW pigs remained heavier than LBW pigs during the early juvenile period (p < 0.005), but there were no differences at later stages. There were no differences in metabolic traits during juvenile development, but there were differences in adulthood, when LBW pigs showed higher glucose and lower insulin levels than NBW pigs (both p < 0.05). These results suggest that (a) FD allows LBW offspring to achieve similar obesity in adulthood as NBW offspring, and (b) glucose metabolism is more compromised in obese LBW than obese NBW pigs. The comparison of our data with previous studies highlights significant differences between offspring with LBW induced by maternal malnutrition or placental insufficiency, which should be considered when studying the condition

Impact of genotype, body weight and sex on the prenatal muscle transcriptome of Iberian pigs

Growth is dependent on genotype and diet, even at early developmental stages. In this study, we investigated the effects of genotype, sex, and body weight on the fetal muscle transcriptome of purebred Iberian and crossbred Iberian x Large White pigs sharing the same uterine environment. RNA sequencing was performed on 16 purebred and crossbred fetuses with high body weight (340±14g and 415±14g, respectively) and 16 with low body weight (246±14g and 311±14g, respectively), on gestational day 77. Genotype had the greatest effect on gene expression, with 645 genes identified as differentially expressed (DE) between purebred and crossbred animals. Functional analysis showed differential regulation of pathways involved in energy and lipid metabolism, muscle development, and tissue disorders. In purebred animals, fetal body weight was associated with 35 DE genes involved in development, lipid metabolism and adipogenesis. In crossbred animals, fetal body weight was associated with 60 DE genes involved in muscle development, viability, and immunity. Interestingly, the results suggested an interaction genotype∗weight for some DE genes. Fetal sex had only a modest effect on gene expression. This study allowed the identification of genes, metabolic pathways, biological functions and regulators related to fetal genotype, weight and sex, in animals sharing the same uterine environment. Our findings contribute to a better understanding of the molecular events that influence prenatal muscle development and highlight the complex interactions affecting transcriptional regulation during development.</p