Cryo-EM studies of Phosphatidylinositol-3-kinase related kinase (PIKK) structures from yeast: Transcription-associated protein 1 (Tra1) and Mitosis-entry checkpoint 1 (Mec1), and their role as conserved genomic regulators

The regulation of the genome is an essential biological task. In eukaryotes, fundamental nuclear processes such as DNA replication, transcription and repair require a large variety of protein effectors to ensure the correct transmission of genetic information, for regulated gene expression and to maintain genome integrity. The phosphatidylinositol 3-kinase-related kinase (PIKK) protein family represents a group of very large and highly conserved Ser/Thr-protein kinases, where most function in genome regulation processes. S. cerevisiae proteins Tra1 and Mec1 (known as TRRAP and ATR in humans) are two essential PIKKs found in the nucleus. Tra1 is a 3,744-residue protein and a shared subunit between the chromatin modifying complexes SAGA and NuA4. Tra1 stimulates transcriptional activation by directly interacting with transcription activators and is also involved in DNA repair. Here, I present the near-atomic resolution cryo-EM structure of the full-length Tra1 polypeptide. A “de novo” atomic model was built from the map, revealing the unique arrangement of Tra1 alpha-solenoid, which is organised into an N-terminal Finger segment inserted into a circular Cradle region before the Kinase domain. Structural interpretation of previously published Tra1 mutants allowed to identify a Gal4 binding region. Mec1 is a 2,368-residue protein that forms a complex with Ddc2 (ATRIP in humans), and participates in the DNA-Damage-Response, Replication-Stress-Response, in telomere maintenance and meiosis, and its kinase activity influences cell cycle progression. Here, I present the high-resolution cryo-EM structure of the heterodimeric Mec1-Ddc2 complex, providing the first complete atomic model of Mec1. The structure reveals how the complex is assembled, showing extensive interactions between Ddc2 solenoid region and Mec1. The map also shows the integration point of Ddc2 N-terminal region into the complex, and together with existing structural data for the interaction of Ddc2 coiled-coil with RPA, an integrative model shed light in the understanding of Mec1 recruitment to RPA-coated ssDNA

Neuroplasticity and Healthy Lifestyle: How Can We Understand This Relationship?

Our brain has this extraordinary ability to experience functional and structural changes before environmental stimuli, cognitive demand, or our experience itself. Exercise, diet, an appropriate sleep pattern, and reading habits are among those activities proposed to induce effects on cerebral architecture—an active lifestyle seems to induce changes in the brain function that favour welfare and better quality of life. This special issue is intended to extend the knowledge about the relationship between neuroplasticity and a healthy lifestyleFil: Begega, Azucena. Universidad de Oviedo; EspañaFil: Santín, Luis J.. Universidad de Málaga; EspañaFil: Galeano, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Cutuli, Debora. Universita Di Roma; ItaliaFil: Sampedro Piquero, Patricia. Universidad Autonoma de Madrid. Facultad de Psicología. Departamento de Psicología Biológica y de la Salud; Españ

Evaluación de la calidad de servicios de la empresa Proyectos Obras e Inmobiliaria Cáceres S.A.C. - 2017

El mundo competitivo empresarial hoy exige mayores prestaciones de servicio, busca encontrar nuevas experiencias y los mercados no tradicionales como la construcción no son la excepción. Ante esto, la investigación pretendió evaluar la calidad de servicio con la que viene operando en el mercado pues, la empresa en estudio ha experimentado crecimiento en su cartera de clientes con respecto a años anteriores; sin embargo, los indicadores de servicio mostraron ciertos problemas que están deteniendo el crecimiento y que afecta en especial la calidad de la atención. El objetivo general del estudio fue determinar la calidad de servicio prestado por la empresa Proyectos Obras e Inmobiliaria Cáceres S.A.C., el análisis tuvo un enfoque cuantitativo descriptivo y se ha tomado a un grupo de 30 clientes (público y privado) en los departamentos donde opera: Lambayeque, Piura y Cajamarca. Se les aplicó un cuestionario bajo la escala de Likert previamente validado y a través del Alpha de Cronbach se corroboró la consistencia del instrumento. Los resultados mostraron que la empresa tiene buena aceptación sobre sus servicios prestados, pero falencias respecto al servicio preventa y la claridad de la comunicación con los clientes. Se hizo un análisis de las brechas de servicio para finalmente mostrar las conclusiones del estudio, que principalmente muestra una media obtenida general de 6.16 en la escala de 7 de Likert

Aberrant Brain Neuroplasticity and Function in Drug Addiction: A Focus on Learning-Related Brain Regions

This chapter will review the altered brain structure and function associated to drug addiction, with a focus on brain regions involved in learning and motivated behavior. As evidenced by both clinical and preclinical studies, repeated drug exposure affects whole brain neuroplasticity including the mesolimbic system which is a main locus for reward, an action-control center such as the dorsal striatum, and limbic brain regions such as the prefrontal cortex, the hippocampus, and the amygdala that are involved in behavioral control, memory, and mood. In this way, the drug-seeking actions that were initially intentional responses become involuntary habits governed by the dorsal striatum. Drug addiction may also curse with a reduced ability to experience rewards that are unrelated to drugs and emotional dysregulation, while the impairment on limbic regions contributes to generate cognitive symptoms. These entail persistent memories for previous experiences with the drug contrasting with a global cognitive decline that may hamper the acquisition of new, adaptive learnings. Overall, these features promote a desire for the drug, leading to relapse in drug use. Further drug exposure, in turn, aggravates its consequences on the brain and behavior, creating the harmful “addiction cycle.

Tillage effects on weed seed bank with wheat monoculture and rotational

El banco de semillas de malas hierbas presente en el suelo es una demostración de la existencia de una comunidad de malas hierbas y está vinculado a las fases de crecimiento de un ecosistema. Las prácticas agronómicas pueden ocasionar cambios en el banco de semillas de los suelos agrícolas. Nuestro objetivo fue comparar la influencia del laboreo de conservación (mínimo laboreo y siembra directa) frente al laboreo convencional, sobre la densidad y riqueza específica del banco de semillas persistente de un suelo agrícola, en parcelas con dos sistemas de cultivo: monocultivo y rotación de trigo de invierno. Se tomaron muestras de suelo en parcelas con los tres sistemas de laboreo, a 3 profundidades: 0-7 cm, 7-15 cm y 15-30 cm. Los resultados obtenidos en este estudio mostraron que el efecto acumulativo del laboreo en parcelas con trigo en monocultivo no tuvo efectos en la densidad de semillas, aunque sí en su distribución, cuantificadas mayoritariamente a mayor profundidad (P3). Por otro lado, se observó una clara influencia del laboreo y la profundidad en la densidad y riqueza específica del banco de semillas de tipo persistente del suelo, en las parcelas con rotación de trigo. Nuestros resultados confirman que una variedad de cultivos puede ir asociada a una mayor variedad de especies de malas hierbas presentes en el banco de semillas del suelo.The weed seedbank into the soil is a demonstration of the existence of a weed community and it is linked to ecosystem growth phases. Agronomic practices can cause changes in the seed bank of agricultural soils. Our objective was to compare the influence of conservation tillage (mínimum tillage and direct seeding) with conventional tillage on weed seed density and species richness of persistent seedbank, with two cropping systems: wheat monoculture and wheat rotation. Soil samples were taken in plots with three tillage systems, at 3 depths: P1 (0-7 cm), P2 (7-15cm) and P3 (15-30 cm). The results of this study showed that cumulative effects of tillage systems, in wheat monoculture plots, had no effect on seed density, and the seed species were concentrated in deepest section of soil (P3). On the other hand, we observed a clear influence of tillage and depth on weed density and species richness of the persistent weed seed bank in wheat rotation plots. Our results confirm that a variety of crops could be associated to a variety of weed species present into soil seedbank

Role of the 5-HT1A receptors in the effect of Galanin(1-15) on Fluoxetine-mediated action in the forced swimming test

Galanin N-terminal fragment (1-15) [GAL(1-15)] modulates the antidepressant effects induced by the 5-HT1A receptor (5-HT1AR) agonist in the forced swimming test (FST) and the binding characteristics and mRNA levels of 5-HT1AR in the dorsal hippocampus and dorsal raphe (DR). Recently, we observed that GAL(1-15) enhanced the antidepressant-like effects induced by Fluoxetine (FLX) in the FST. In this work, we have studied whether the effects of GAL(1–15) on FLX action were mediated via 5-HT1AR, analyzing the effect of the 5-HT1AR antagonist WAY100635 in this effect and if the binding characteristics and mRNA levels of 5-HT1AR in the DR and dorsal hippocampus are modified by GAL(1-15)+FLX. Groups of rats (n=6-8) received three injections of sc FLX(10mg/kg) and 15 minutes before the FST a single icv injection of GAL(1-15) (1nmol) and 5HT1AR antagonist WAY100635(6nmol) icv alone or in combination. We also analyzed the effects of GAL(1-15)+FLX in the binding characteristics of the 5-HT1AR agonist [H3]-8-OH-DPAT and 5-HT1A mRNA levels in the DR, CA1 and Dentate Gyrus (DG). WAY100635 significantly blocked the reduction in immobility time (p<0.05), and the increase in swimming time (p<0.01) induced by GAL(1-15)+FLX in the FST. GAL(1-15)+FLX produced a significant increase in the 5HT1AR mRNA levels in CA1 (p<0.05) and DG (p<0.05). This effect was not observed in the DR. Moreover, GAL(1-15)+FLX produced a significant decrease in the Kd value (p<0.01) and in the Bmax value (p<0.05) of [3H]-8-OH-DPAT in the DG. These effects were not observed in the CA1 or in the DR. These results indicate that 5HT1AR participates in the GAL(1-15)/FLX interactions in the FST and the mechanism underlying affected the binding characteristics and the mRNA levels of 5-HT1AR specifically in the dorsal hippocampus. The heteroreceptor 5-HT1AR-GALR1-GALR2 located in the dorsal hippocampus may be the target for GAL(1-15). This work was supported by SAF2016-79008-P; PSI2013-44901-P.SAF2016-79008-P; PSI2013-44901-P. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

The Competitive Ability of Weed Community with Selected Crucifer Oilseed Crops

Dedicated production of energy crops on agricultural land is expected to be a crucial source of biomass to be exploited in order to achieve the renewable energy targets in the European Union. Vegetable oils are the main source for the production of biofuel; therefore, an alternative is to use oils from non-food oilseed crops. Oilseed crops examples include rapeseed, crambe and camelina

Long-term consequences of alcohol use in early adolescent mice: Focus on neuroadaptations in GR, CRF and BDNF.

Our aim was to assess the cognitive and emotional state, as well as related-changes in the glucocorticoid receptor (GR), the corticotropin-releasing factor (CRF) and the brain-derived neurotrophic factor (BDNF) expression of adolescent C57BL/6J male mice after a 5-week two-bottle choice protocol (postnatal day [pd]21 to pd52). Additionally, we wanted to analyse whether the behavioural and neurobiological effects observed in late adolescence (pd62) lasted until adulthood (pd84). Behavioural testing revealed that alcohol during early adolescence increased anxiety-like and compulsive-related behaviours, which was maintained in adulthood. Concerning cognition, working memory was only altered in late adolescent mice, whereas object location test performance was impaired in both ages. In contrast, novel object recognition remained unaltered. Immunohistochemical analysis showed that alcohol during adolescence diminished BDNF+ cells in the cingulate cortex, the hippocampal CA1 layer and the central amygdala. Regarding hypothalamic-pituitary-adrenal axis (HPA) functioning, alcohol abuse increased the GR and CRF expression in the hypothalamic paraventricular nucleus and the central amygdala. Besides this, GR density was also higher in the prelimbic cortex and the basolateral amygdala, regardless of the animals' age. Our findings suggest that adolescent alcohol exposure led to long-term behavioural alterations, along with changes in BDNF, GR and CRF expression in limbic brain areas involved in stress response, emotional regulation and cognition.post-print4591 K

The competitive ability of weed communities in selected crucifer oilseed crops under different water and nitrogen

Durante los años 2012 y 2013, se llevó a cabo un experimento en el centro de la península cuyo objetivo fue el estudio de la flora arvense en 3 especies de “Brassica” (“B. carinata”, “B. juncea” y “B. nigra”). Las malas hierbas se evaluaron con 2 niveles de riego, con y sin aporte de agua, y con tres dosis de fertilización diferentes: 0, 75 y 150 kg N ha-1. El establecimiento del cultivo de las tres especies de “Brassica” varió en función del año. Las escasas lluvias de 2012 redujeron la densidad y biomasa de la flora arvense en comparación con el año 2013 en el que la pluviometría fue mayor. Los resultados sugieren que la especie “B. nigra” no estaba bien adaptada a nuestras condiciones climáticas continentales, mostrando un rendimiento más bajo que el resto de los cultivares. Por otro lado, la infestación de malas hierbas fue menor en todas las parcelas donde se cultivaba “B. carinata”.A field study was undertaken to examine the interaction and relationships between weeds and three “Brassica” species (“B. carinata”, “B. juncea” and “B. nigra”) grown in 2012 and 2013. We evaluated the weed density, fresh and dry biomass of weeds with 2 water regimes: with and without irrigation, and three different doses of fertilization: 0, 75 and 150 kg N ha-1. Crop establishment of “Brassica” species varied significantly each year. Lower rainfall in 2012 led to lower density, fresh and dry biomass of weeds compared to 2013. The results confirmed that “B. nigra” was not well adapted to our continental climatic conditions, and thus the yield was lower than the other cultivars. The lowest weed infestation occurred in plots where “B. carinata” was grown in all cases