The Raf-like kinase ILK1 and the high affinity K\u3csup\u3e+\u3c/sup\u3e transporter HAK5 are required for innate immunity and abiotic stress response

© 2016 American Society of Plant Biologists. All rights reserved. Plant perception of pathogen-associated molecular patterns (PAMPs) and other environmental stresses trigger transient ion fluxes at the plasma membrane. Apart from the role of Ca2+ uptake in signaling, the regulation and significance of PAMPinduced ion fluxes in immunity remain unknown. We characterized the functions of INTEGRIN-LINKED KINASE1 (ILK1) that encodes a Raf-like MAP2K kinase with functions insufficiently understood in plants. Analysis of ILK1 mutants impaired in the expression or kinase activity revealed that ILK1 contributes to plant defense to bacterial pathogens, osmotic stress sensitivity, and cellular responses and total ion accumulation in the plant upon treatment with a bacterial-derived PAMP, flg22. The calmodulin-like protein CML9, a negative modulator of flg22-triggered immunity, interacted with, and suppressed ILK1 kinase activity. ILK1 interacted with and promoted the accumulation of HAK5, a putative (H+)/K+ symporter that mediates a high-affinity uptake during K+ deficiency. ILK1 or HAK5 expression was required for several flg22 responses including gene induction, growth arrest, and plasma membrane depolarization. Furthermore, flg22 treatment induced a rapid K+ efflux at both the plant and cellular levels in wild type, while mutants with impaired ILK1 or HAK5 expression exhibited a comparatively increased K+ loss. Taken together, our results position ILK1 as a link between plant defense pathways and K+ homeostasis

Efecto antiinflamatorio de la izalpinina derivada de Chromolaena leivensis: edema de la pata inducido por λ-carragenina y modelo in silico

El flavonoide izalpinina se aisló de las partes aéreas de Chromolaena leivensis. Su determinación estructural se llevó a cabo mediante técnicas espectroscópicas de EM y RMN (1H, 13C). Se evaluó el efecto antiinflamatorio de este compuesto en un modelo de edema plantar inducido por carragenina en ratas. La inflamación de la pata se midió a intervalos de una hora durante siete horas tras la administración de -carragenano. Se evaluaron los niveles séricos de creatina quinasa (CK), obteniéndose resultados estadísticamente significativos con los tratamientos a dosis de 10 mg/kg (* p < 0,01) y 20 mg/kg (** p < 0,005). El efecto antiinflamatorio del compuesto se evaluó mediante pletismografía, y los resultados mostraron diferencias significativas en las tres concentraciones (10 mg/kg, 20 mg/kg, 40 mg/kg) en la primera y tercera hora tras el tratamiento. * p < 0,05; ** p < 0,001; **** p < 0,0001 frente al grupo de control negativo tratado con vehículo (DMSO). Por último, los análisis de acoplamiento molecular revelan que la izalpinina tiene una fuerte afinidad de unión con cinco proteínas diana implicadas en el proceso inflamatorio. El análisis mediante dinámica molecular permitió demostrar que los complejos ligando-proteína presentan una estabilidad aceptable, con valores de RMSD dentro del rango permitido.The flavonoid izalpinin was isolated from the aerial parts of Chromolaena leivensis. Its structural determination was carried out using MS and NMR spectroscopic techniques (1H, 13C). This compound was evaluated for its anti-inflammatory effect in a rat model on -carrageenan-induced plantar edema. Paw inflammation was measured at one-hour intervals for seven hours following the administration of -carrageenan. Serum creatine kinase (CK) levels were evaluated, obtaining statistically significant results with the treatments at doses of 10 mg/kg (* p < 0.01) and 20 mg/kg (** p < 0.005). The anti-inflammatory effect of the compound was evaluated by using plethysmography, and the results showed significant differences at the three concentrations (10 mg/kg, 20 mg/kg, 40 mg/kg) in the first and third hours after treatment. * p < 0.05; ** p < 0.001; **** p < 0.0001 vs. the negative control group treated with vehicle (DMSO). Lastly, molecular docking analyses reveal that izalpinin has a strong binding affinity with five target proteins involved in the inflammatory process. The analysis using molecular dynamics allowed demonstrating that the ligand–protein complexes present acceptable stability, with RMSD values within the allowed range

Theory of Functional Connections and Nelder-Mead optimization methods applied in satellite characterization

The growing population of man-made objects with the build up of mega-constellations not only increases the potential danger to all space vehicles and in-space infrastructures (including space observatories), but above all poses a serious threat to astronomy and dark skies. Monitoring of this population requires precise satellite characterization, which is is a challenging task that involves analyzing observational data such as position, velocity, and light curves using optimization methods. In this study, we propose and analyze the application of two optimization procedures to determine the parameters associated with the dynamics of a satellite: one based on the Theory of Functional Connections (TFC) and another one based on the Nelder-Mead heuristic optimization algorithm. The TFC performs linear functional interpolation to embed the constraints of the problem into a functional. In this paper, we propose to use this functional to analytically embed the observational data of a satellite into its equations of dynamics. After that, any solution will always satisfy the observational data. The second procedure proposed in this research takes advantage of the Nealder-Mead algorithm, that does not require the gradient of the objective function, as alternative solution. The accuracy, efficiency, and dependency on the initial guess of each method is investigated, analyzed, and compared for several dynamical models. These methods can be used to obtain the physical parameters of a satellite from available observational data and for space debris characterization contributing to follow-up monitoring activities in space and astronomical observatories.Comment: Submitted to Acta Astronautic

Association and Linkage Analysis of Aluminum Tolerance Genes in Maize

Aluminum (Al) toxicity is a major worldwide constraint to crop productivity on acidic soils. Al becomes soluble at low pH, inhibiting root growth and severely reducing yields. Maize is an important staple food and commodity crop in acidic soil regions, especially in South America and Africa where these soils are very common. Al exclusion and intracellular tolerance have been suggested as two important mechanisms for Al tolerance in maize, but little is known about the underlying genetics. linkage populations with approximately 200 individuals each were used to study genetic variation in this complex trait. Al tolerance was measured as net root growth in nutrient solution under Al stress, which exhibited a wide range of variation between lines. Comparative and physiological genomics-based approaches were used to select 21 candidate genes for evaluation by association analysis.). These four candidate genes are high priority subjects for follow-up biochemical and physiological studies on the mechanisms of Al tolerance in maize. Immediately, elite haplotype-specific molecular markers can be developed for these four genes and used for efficient marker-assisted selection of superior alleles in Al tolerance maize breeding programs

Worldwide comparison of survival from childhood leukaemia for 1995-2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries.

Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0-14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995-99, 2000-04, and 2005-09), sex, and age at diagnosis (&lt;1, 1-4, 5-9, and 10-14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). We analysed data from 89 828 children from 198 registries in 53 countries. During 1995-99, 5-year age-standardised net survival for all lymphoid leukaemias combined ranged from 10·6% (95% CI 3·1-18·2) in the Chinese registries to 86·8% (81·6-92·0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005-09, when age-standardised survival for lymphoid leukaemias ranged from 52·4% (95% CI 42·8-61·9) in Cali, Colombia, to 91·6% (89·5-93·6) in the German registries, and for AML ranged from 33·3% (18·9-47·7) in Bulgaria to 78·2% (72·0-84·3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000-04 and 2005-09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. Global inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood cancer survival. Canadian Partnership Against Cancer, Cancer Focus Northern Ireland, Cancer Institute New South Wales, Cancer Research UK, US Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, and the University of Kentucky

Effectiveness of alternative therapies for the management of lumbar disc disease: a descriptive research

BACKGROUND: Low back pain due to discopathy has become one of the most expensive and highest impact problems of global public health at present. AIM: To evaluate the effectiveness of alternative therapies (AT) and related factors in lumbar disk disease (LDD). METHODS: Information was collected by using a retrospective descriptive design from medical records of patients treated from January to December 2013 with LDD who were attended in a clinic specialized in AT. Sociodemographic and clinical variables included clinical diagnostic time, Visual Analog Scale at admission (V.A.S.) and post-treatment pain (0-100 points) were identifi ed. General and specifi c infl uence of the AT was measured. RESULTS: 453 medical records were identifi ed, at admission V.A.S. was 8.2 (CI95%, 7,9 to 8,3) and showed pain relief (scale 0-100) of 54,5 points (CI95%, 52.2 to 56.8). In overall, 13 types of ATs were implemented with LDD patients. The median of pain relief (p25-p75) in the general population was 60 (40-70); 8 of 13 interventions provided an estimated median of pain relief lower than the one evidenced in the general population . CONCLUSION: The AT treatment in our study showed a reduction in pain of 50-60 points and an absolute reduction of 35 points after two months of treatment, which remained over 6 or more months of follow-up. Our results suggest that the use of AT has signifi cant effect on chronic pain in patients with LDD with no response to conventional treatmen

Caracterización del HLA en una familia colombiana endogámica con síndrome de Usher

Resumen El síndrome de Usher es una enfermedad autosómica recesiva que se caracteriza por presentar retinitis pigmentosa, hipoacusia neurosensorial congénita y disfunción vestibular. El propósito de este trabajo es realizar la caracterización de hla en una familia colombiana endogámica que presenta síndrome de Usher. La metodología consiste en que con un previo consentimiento informado se realizó una genealogía de la familia y a cuatro pacientes confirmados clínicamente con síndrome de Usher y a cuatro fenotípicamente sanos se les tomó 5 ml de sangre periférica en tubos de venopunción con edta para luego realizar el aislamiento del dna por la técnica de salting out, conservados en buffer te a -8 °C y ajustada la muestra a una concentración de 8 μg/ml. Posteriormente a través de la técnica de pcr-ssp de mediana resolución se caracterizaron los antígenos de hla *a, *b, *drb1 y *dqb1. Los resultados obtenidos indican que la familia oriunda del Departamento del Huila presenta una marcada endogamia detectándose que todos los hermanos afectados, sus padres son hermanos también y una de las parejas a su vez tuvo una niña afectada, por lo que sus abuelos y padres son hermanos. En lo referente al hla, los alelos más frecuentemente encontrados fueron a30 b42 dr1 dq5 y a3 b45 dr12 y dq7, que no están asociados a la enfermedad. Estos resultados sugieren que dada la endogamia que muestra esta familia se presenta una gran acumulación de polimorfismos y mutaciones, por lo que es necesario realizar un proceso de asesoría genética para disminuir el riesgo de recurrencia. Abstract Usher syndrome is an autosomal recessive disease characterized by retinitis pigmentosa, congenital sensorineural hearing loss and vestibular dysfunction. The purpose of this work was to characterize hla in an inbred Colombian family that presents Usher Syndrome. The Methodology consisted in that a genealogy of the family was made and previous informed consent, from four patients clinically confirmed with Usher Syndrome and four phenotypically healthy patients 5 ml of peripheral blood were taken in venipuncture tubes with edta and then the dna isolation was performed with the technique of salting out, preserved in te buffer at -8 °C and adjusted the sample to a concentration of 8 μg/ml. The hla *A, *B, *DRB1 and *DQB1 antigens were then characterized by the medium-resolution pcr-ssp techniqu

Caracterización del HLA en una familia colombiana endogámica con síndrome de Usher

El síndrome de Usher es una enfermedad autosómica recesiva que se caracteriza por presentar retinitis pigmentosa, hipoacusia neurosensorial congénita y disfunción vestibular. El propósito de este trabajo es realizar la caracterización de hla en una familia colombiana endogámica que presenta síndrome de Usher. La metodología consiste en que con un previo consentimiento informado se realizó una genealogía de la familia y a cuatro pacientes confirmados clínicamente con síndrome de Usher y a cuatro fenotípicamente sanos se les tomó 5 ml de sangre periférica en tubos de venopunción con edta para luego realizar el aislamiento del dna por la técnica de salting out, conservados en buffer te a -8 °C y ajustada la muestra a una concentración de 8 μg/ml. Posteriormente a través de la técnica de pcr-ssp de mediana resolución se caracterizaron los antígenos de hla *a, *b, *drb1 y *dqb1. Los resultados obtenidos indican que la familia oriunda del Departamento del Huila presenta una marcada endogamia detectándose que todos los hermanos afectados, sus padres son hermanos también y una de las parejas a su vez tuvo una niña afectada, por lo que sus abuelos y padres son hermanos. En lo referente al hla, los alelos más frecuentemente encontrados fueron a30 b42 dr1 dq5 y a3 b45 dr12 y dq7, que no están asociados a la enfermedad. Estos resultados sugieren que dada la endogamia que muestra esta familia se presenta una gran acumulación de polimorfismos y mutaciones, por lo que es necesario realizar un proceso de asesoría genética para disminuir el riesgo de recurrencia

Caracterización del HLA en una familia colombiana endogámica con síndrome de Usher

Resumen El síndrome de Usher es una enfermedad autosómica recesiva que se caracteriza por presentar retinitis pigmentosa, hipoacusia neurosensorial congénita y disfunción vestibular. El propósito de este trabajo es realizar la caracterización de hla en una familia colombiana endogámica que presenta síndrome de Usher. La metodología consiste en que con un previo consentimiento informado se realizó una genealogía de la familia y a cuatro pacientes confirmados clínicamente con síndrome de Usher y a cuatro fenotípicamente sanos se les tomó 5 ml de sangre periférica en tubos de venopunción con edta para luego realizar el aislamiento del dna por la técnica de salting out, conservados en buffer te a -8 °C y ajustada la muestra a una concentración de 8 μg/ml. Posteriormente a través de la técnica de pcr-ssp de mediana resolución se caracterizaron los antígenos de hla *a, *b, *drb1 y *dqb1. Los resultados obtenidos indican que la familia oriunda del Departamento del Huila presenta una marcada endogamia detectándose que todos los hermanos afectados, sus padres son hermanos también y una de las parejas a su vez tuvo una niña afectada, por lo que sus abuelos y padres son hermanos. En lo referente al hla, los alelos más frecuentemente encontrados fueron a30 b42 dr1 dq5 y a3 b45 dr12 y dq7, que no están asociados a la enfermedad. Estos resultados sugieren que dada la endogamia que muestra esta familia se presenta una gran acumulación de polimorfismos y mutaciones, por lo que es necesario realizar un proceso de asesoría genética para disminuir el riesgo de recurrencia. Abstract Usher syndrome is an autosomal recessive disease characterized by retinitis pigmentosa, congenital sensorineural hearing loss and vestibular dysfunction. The purpose of this work was to characterize hla in an inbred Colombian family that presents Usher Syndrome. The Methodology consisted in that a genealogy of the family was made and previous informed consent, from four patients clinically confirmed with Usher Syndrome and four phenotypically healthy patients 5 ml of peripheral blood were taken in venipuncture tubes with edta and then the dna isolation was performed with the technique of salting out, preserved in te buffer at -8 °C and adjusted the sample to a concentration of 8 μg/ml. The hla *A, *B, *DRB1 and *DQB1 antigens were then characterized by the medium-resolution pcr-ssp techniqu