RNA-seq analysis of the Rhizobium tropici CIAT 899 Transcripitome shows similarites in the activation patterns of symbiotic genes in the presence of apigenin and salt.

Rhizobium tropici strain CIAT 899 establishes effective symbioses with several legume species, including Phaseolus vulgaris and Leucaena leucocephala. This bacterium synthesizes a large variety of nodulation factors in response to nod-gene inducing flavonoids and, surprisingly, also under salt stress conditions. The aim of this study was to identify differentially expressed genes in the presence of both inducer molecules, and analyze the promoter regions located upstream of these genes. Results obtained by RNA-seq analyses of CIAT 899 induced with apigenin, a nod gene-inducing flavonoid for this strain, or salt allowed the identification of 19 and 790 differentially expressed genes, respectively. Fifteen of these genes were up-regulated in both conditions and were involved in the synthesis of both Nod factors and indole-3-acetic acid. Transcription of these genes was presumably activated through binding of at least one of the five NodD proteins present in this strain to specific nod box promoter sequences when the bacterium was induced by both apigenin and salt. Finally, under saline conditions, many other transcriptional responses were detected, including an increase in the transcription of genes involved in trehalose catabolism, chemotaxis and protein secretion, as well as ribosomal genes, and a decrease in the transcription of genes involved in transmembrane transport. To our knowledge this is the first time that a transcriptomic study shows that salt stress induces the expression of nodulation genes in the absence of flavonoids. Thus, in the presence of both nodulation inducer molecules, apigenin and salt, R. tropici CIAT 899 up-regulated the same set of symbiotic genes. It could be possible that the increases in the transcription levels of several genes related to nodulation under saline conditions could represent a strategy to establish symbiosis under abiotic stressing conditions

Cumplimiento, conocimiento y automedicación como factores asociados a los resultados clínicos negativos de la farmacoterapia

The patient plays a fundamental role in the attainment of good results in pharmacotherapy. Noncompliance,self-medication, or insufficient knowledge of the therapy being employed may provide asource for the causes of these negative clinical outcomes, otherwise known as medicine related problems(MRP). he Dader method was used in the evaluation, identification and classification of MRP. Theassociation of variables was established through the statistical Chi square test. Patient knowledge of themedicine, degree of compliance to therapy and self-medication were studied as causes of the negativeoutcomes encountered. 2556 patients were interviewed throughout the year that the study took place,giving a total of 2261 of valid cases. 33% presented an MRP as the cause of his/her visit to the hospitalemergency ward. Knowledge of the medicine, compliance and self-medication were only studied in thepopulation that presented an MRP and in this work it is demonstrated that these are aspects that areassociated with different dimensions of MRP. It is not possible to establish an association between theexistence or not of negative clinical outcomes in patients with the factors of knowledge of medication,compliance and self-medication. This is due to the fact that these variables are not attributable to thepatient himself, but rather are associated with the characteristics of each medicine.El paciente juega un papel primordial en la consecución de los resultados terapéuticos. El incumplimiento,la automedicación, o la falta de conocimiento del la farmacoterapia pueden ser causas de esosresultados clínicos negativos, denominados en ocasiones problemas relacionados con medicamentos(PRM). El método Dáder se utilizó para la evaluación, identificación y clasificación de PRM. Laasociación de variables se estableció mediante el estadístico chi cuadrado. El conocimiento de la medicación,el cumplimiento y la automedicación fueron estudiados como causa de estos resultados negativosde la medicación. Fueron entrevistados 2556 pacientes durante el año de estudio, resultando 2261 casosválidos. El 33 % presentaron un PRM como causa de visita a urgencias. El conocimiento de la medicación,el cumplimiento y la automedicación fueron estudiados solo en la población que presentó unPRM y se demuestra que son aspectos asociados a las distintas dimensiones de PRM. No es posibleestablecer asociación entre la existencia o no de resultados clínicos negativos en los pacientes con elconocimiento de la medicación, el cumplimiento y la automedicación, debido a que estas variables noson atributos del paciente sino que están asociadas a cada medicamento

Contexto geomorfológico y principales rasgos tecnológicos de nuevos yacimientos del Pleistoceno Medio y Superior en el Valle Inferior del Manzanares (Madrid, España)

The archaeological works developed during the years 1996 in the site of Tafesa, 2005 in the 12 de Octubre Metro Station site and 2006 in the confluence of the Butarque Stream (Villaverde-Barrio de Butarque site) located south of the Madrid City (Spain), have provided new lithic assemblages. These assemblages have been stratigraphically contextualized in the Pleistocene deposits of the Lower Manzanares river valley within the so-called “Manzanares Complex Terrace” (TCMZ). This fluvial terrace constitutes an anomalous thickened (20-15m) deposit at +22-16m above the present river thalweg mainly developed along the right (southern) valley margin. This fluvial level has been traditionally considered of middle Pleistocene age on the basis of the acheulian lithics and faunal assemblages typically located within its lower stratigraphic layers. Certainly, the Tafesa is a fluvial terrace site at +22 m with acheulian industry and middle Pleistocene faunal remains at its lower sedimentary sequence. However, the upper sedimentary levels of this same terrace in the 12 de Octubre y Villaverde-Butarque sites throw lithic assemblages of the lower and upper Paleolithic belonging to upper Pleistocene, as suggested by the available set of TL and OSL dates for the zone. The analyses developed in this study indicate that the development of this thickened fluvial terrace started during the end of the middle Pleistocene, but also comprise the whole Oxygen Isotopic Stage OIS 5 during the upper Pleistocene.Las intervenciones arqueológicas llevadas a cabo durante los años 1996 en Tafesa, 2005 en el yacimiento Hospital 12 de Octubre y 2006 en la desembocadura del arroyo Butarque (Villaverde-Barrio de Butarque) situados al sur de la ciudad de Madrid (España), han aportado nuevos conjuntos líticos contextualizados estratigráficamente en los depósitos fluviales pleistocenos correspondientes al tramo inferior del valle del río Manzanares. Los yacimientos arqueológicos analizados se sitúan geomorfológicamente en la denominada “Terraza Compleja del Manzanares” (TCMZ), la cual constituye un nivel fluvial engrosado (20-15 m de potencia) situado entre +22-16 m sobre el cauce actual del río, a lo largo de su margen derecha. Este nivel fluvial ha sido tradicionalmente considerado de edad Pleistoceno medio en base a la industria achelense y complejos faunísticos encontrados en sus niveles inferiores. Ciertamente, Tafesa es un yacimiento situado en la parte inferior-media de la terraza de +22 m con industria achelense y fauna de Pleistoceno medio. Por el contrario, los niveles superiores de esta misma terraza en los sectores del 12 de Octubre y Villaverde-Butarque se encuentran asociados a industrias del Paleolítico inferior y medio ya pertenecientes al Pleistoceno superior, como sugieren el conjunto de dataciones OSL y TL existentes para la zona. Los datos analizados en este trabajo indican que el desarrollo de este nivel de terraza engrosado comienza durante la parte final de Pleistoceno medio y abarca todo el Estadio Isotópico OIS 5, ya dentro del Pleistoceno superior

Inscuteable Regulates the Pins-Mud Spindle Orientation Pathway

During asymmetric cell division, alignment of the mitotic spindle with the cell polarity axis ensures that the cleavage furrow separates fate determinants into distinct daughter cells. The protein Inscuteable (Insc) is thought to link cell polarity and spindle positioning in diverse systems by binding the polarity protein Bazooka (Baz; aka Par-3) and the spindle orienting protein Partner of Inscuteable (Pins; mPins or LGN in mammals). Here we investigate the mechanism of spindle orientation by the Insc-Pins complex. Previously, we defined two Pins spindle orientation pathways: a complex with Mushroom body defect (Mud; NuMA in mammals) is required for full activity, whereas binding to Discs large (Dlg) is sufficient for partial activity. In the current study, we have examined the role of Inscuteable in mediating downstream Pins-mediated spindle orientation pathways. We find that the Insc-Pins complex requires Gαi for partial activity and that the complex specifically recruits Dlg but not Mud. In vitro competition experiments revealed that Insc and Mud compete for binding to the Pins TPR motifs, while Dlg can form a ternary complex with Insc-Pins. Our results suggest that Insc does not passively couple polarity and spindle orientation but preferentially inhibits the Mud pathway, while allowing the Dlg pathway to remain active. Insc-regulated complex assembly may ensure that the spindle is attached to the cortex (via Dlg) before activation of spindle pulling forces by Dynein/Dynactin (via Mud)

The Role of Spatially Controlled Cell Proliferation in Limb Bud Morphogenesis

Oriented cell behaviors likely have a more important role in limb bud elongation during development than previously suggested by the “growth-based morphogenesis” hypothesis

Dynamics and Mechanical Stability of the Developing Dorsoventral Organizer of the Wing Imaginal Disc

Shaping the primordia during development relies on forces and mechanisms able to control cell segregation. In the imaginal discs of Drosophila the cellular populations that will give rise to the dorsal and ventral parts on the wing blade are segregated and do not intermingle. A cellular population that becomes specified by the boundary of the dorsal and ventral cellular domains, the so-called organizer, controls this process. In this paper we study the dynamics and stability of the dorsal-ventral organizer of the wing imaginal disc of Drosophila as cell proliferation advances. Our approach is based on a vertex model to perform in silico experiments that are fully dynamical and take into account the available experimental data such as: cell packing properties, orientation of the cellular divisions, response upon membrane ablation, and robustness to mechanical perturbations induced by fast growing clones. Our results shed light on the complex interplay between the cytoskeleton mechanics, the cell cycle, the cell growth, and the cellular interactions in order to shape the dorsal-ventral organizer as a robust source of positional information and a lineage controller. Specifically, we elucidate the necessary and sufficient ingredients that enforce its functionality: distinctive mechanical properties, including increased tension, longer cell cycle duration, and a cleavage criterion that satisfies the Hertwig rule. Our results provide novel insights into the developmental mechanisms that drive the dynamics of the DV organizer and set a definition of the so-called Notch fence model in quantitative terms

Restos de caballos fósiles cuaternarios en la depresión Prados-Guatén (Pantoja de la Sagra, Toledo)

Durante la primera reunión de campo del Grupo Madrileño de Cuaternario (GQM-AEQUA) se localizaron restos fragmentarios de dentición de caballos fósiles en los antiguos areneros de Pantoja de La Sagra (Toledo), actualmente en proceso de desmantelamiento y relleno. Ante la posibilidad de deterioro y pérdida los restos fueron recolectados y trasladados al Museo Nacional de Ciencias Naturales (CSIC, Madrid) donde se ha procedido a su análisis. Las piezas fósiles analizadas responden a un maxilar izquierdo con tres piezas dentales in situ (molares y premolares), y otras siete más aisladas. Todos los dientes aislados, junto con el fragmento de maxilar existente, corresponden a un adulto joven. Los restos fósiles se encontraban asociados a un nivel de arenas fluviales situado unos cuatro metros por debajo de la superficie de la Terraza de +15 m de la Depresión Prados-Guatén definida como un nivel perteneciente al tránsito Pleistoceno inferior-medio, del antiguo Sistema fluvial Manzanares-Guatén por Silva (1988). En concreto los niveles superiores de esta terraza han sido interpretados como resultado de la superposición de los últimos depósitos del antiguo sistema fluvial y los primeros asociados al relleno de la Depresión por tributarios de área fuente más local tras su abandono como consecuencia del proceso de captura del valle inferior del Manzanares por parte del Río Jarama al SW de la Ciudad de Madrid (Silva et al., 1988). Los caracteres morfológicos y morfométricos de las piezas dentarias permiten identificarlos como Equus ferus cf. mosbachensis cuya distribución bioestratigráfica abarca la parte final del Pleistoceno Medio (c.a. 500-200 ka B.P.). Junto a los restos fósiles aparecieron también escasos fragmentos líticos correspondientes a productos de lascado en sílex de difícil atribución tecnológica. Los restos fósiles analizados, indican que el depósito extensivo de arenas fluviales en el eje de la Depresión, culminó durante el final del Pleistoceno medio, y que la dinámica fluvial de la Depresión tras su proceso de abandono fue de hecho más activa de lo que se pensaba con la instalación de sistemas de arroyos relevantes alimentados por cabeceras locales antes del encajamiento definitivo actual de los arroyos Prados y Guatén.Peer reviewe

Metabolic adaptation of two in silico mutants of Mycobacterium tuberculosis during infection

ABSTRACT: Background: Up to date, Mycobacterium tuberculosis (Mtb) remains as the worst intracellular killer pathogen. To establish infection, inside the granuloma, Mtb reprograms its metabolism to support both growth and survival, keeping a balance between catabolism, anabolism and energy supply. Mtb knockouts with the faculty of being essential on a wide range of nutritional conditions are deemed as target candidates for tuberculosis (TB) treatment. Constraint-based genome-scale modeling is considered as a promising tool for evaluating genetic and nutritional perturbations on Mtb metabolic reprogramming. Nonetheless, few in silico assessments of the effect of nutritional conditions on Mtb’s vulnerability and metabolic adaptation have been carried out. Results: A genome-scale model (GEM) of Mtb, modified from the H37Rv iOSDD890, was used to explore the metabolic reprogramming of two Mtb knockout mutants (pfkA- and icl-mutants), lacking key enzymes of central carbon metabolism, while exposed to changing nutritional conditions (oxygen, and carbon and nitrogen sources). A combination of shadow pricing, sensitivity analysis, and flux distributions patterns allowed us to identify metabolic behaviors that are in agreement with phenotypes reported in the literature. During hypoxia, at high glucose consumption, the Mtb pfkA-mutant showed a detrimental growth effect derived from the accumulation of toxic sugar phosphate intermediates (glucose-6-phosphate and fructose-6-phosphate) along with an increment of carbon fluxes towards the reductive direction of the tricarboxylic acid cycle (TCA). Furthermore, metabolic reprogramming of the icl-mutant (icl1&icl2) showed the importance of the methylmalonyl pathway for the detoxification of propionyl-CoA, during growth at high fatty acid consumption rates and aerobic conditions. At elevated levels of fatty acid uptake and hypoxia, we found a drop in TCA cycle intermediate accumulation that might create redox imbalance. Finally, findings regarding Mtb-mutant metabolic adaptation associated with asparagine consumption and acetate, succinate and alanine production, were in agreement with literature reports. Conclusions: This study demonstrates the potential application of genome-scale modeling, flux balance analysis (FBA), phenotypic phase plane (PhPP) analysis and shadow pricing to generate valuable insights about Mtb metabolic reprogramming in the context of human granulomas

A school-based physical activity promotion intervention in children: rationale and study protocol for the PREVIENE Project

The lack of physical activity and increasing time spent in sedentary behaviours during childhood place importance on developing low cost, easy-toimplement school-based interventions to increase physical activity among children. The PREVIENE Project will evaluate the effectiveness of five innovative, simple, and feasible interventions (active commuting to/from school, active Physical Education lessons, active school recess, sleep health promotion, and an integrated program incorporating all 4 interventions) to improve physical activity, fitness, anthropometry, sleep health, academic achievement, and health-related quality of life in primary school children. The PREVIENE Project will provide the information about the effectiveness and implementation of different school-based interventions for physical activity promotion in primary school children.The PREVIENE Project was funded by the Spanish Ministry of Economy and Competitiveness (DEP2015-63988-R, MINECO-FEDER). MAG is supported by grants from the Spanish Ministry of Economy and Competitivenes