Geminiviral protein Rep interferes in PCNA sumoylation

Rep is a multifunctional protein essential for replication of geminivirus that interferes with the sumoylation of a key protein in the DNA replication, PCNA (Proliferating Cell Nuclear Antigen). It is known that Rep is capable of interacting with a plethora of plant proteins, including PCNA. Despite the biological significance remains unknown, it’s thought that this interaction should play a key role for generating new copies of the virus genome. Therefore, in order to characterize this interaction, we study which lysines are sumoylated in tomato PCNA (SlPCNA). Considering conservation, location and presence of sumoylation domain criteria, we have identified some candidate lysines and studied how its mutation affects this protein sumoylation in Escherichia coli assays. Finally, we plan to confirm and characterize the Rep interference on SlPCNA sumoylation and determine if this interference occurs in planta.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

La proteína Rep/AL1 de geminivirus altera la sumoilación de PCNA

Los geminivirus, llamados así por la forma icosaédrica de su cápside, son una familia de virus patógenos de plantas que causan algunas de las enfermedades con mayor impacto económico a nivel mundial. Estos pequeños virus de ADN se replican en el núcleo de las células vegetales utilizando la maquinaria celular del hospedador, además de requerir la presencia de la proteína viral Rep. Rep es la única proteína del genoma del virus imprescindible para su replicación y es capaz de interaccionar con una gran variedad de proteínas del huésped. Trabajos previos de nuestro grupo demostraron que dos de esas proteínas son PCNA (Proliferating cell nuclear antigen), esencial en el metabolismo del DNA, y SCE (SUMO Conjugating Enzime), enzima que interviene en la sumoilación, uno de los principales mecanismos de modificación postraduccional que está implicado en la respuesta de la planta a estrés abiótico, en el desarrollo, el crecimiento y la respuesta a patógenos. Además, otros resultados que hemos obtenido demuestran que la expresión en Escherichia coli de la proteína Rep del begomovirus TGMV (Tomato golden mosaic virus) reduce la sumoilación de PCNA en plantas y que dicha interferencia no depende de la interacción de la proteína viral con SCE1. Para profundizar en el conocimiento de la interacción Rep-PCNA nos hemos propuesto identificar las lisinas de PCNA que se sumoilan. Teniendo en cuenta criterios de conservación, localización y presencia de dominio de sumoilación se han identificado varias lisinas candidatas y se ha estudiado cómo su mutación afecta a la sumoilación de la proteína. También nos hemos planteado confirmar y caracterizar la interferencia de Rep sobre la sumoilación de PCNA y determinar si dicha interferencia se produce en la planta.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Traffic Control Magnetic Loops Electric Characteristics Variation Due to the Passage of Vehicles Over Them

"(c) 2017 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works."The effect on the buried magnetic loop response when vehicles pass over them is determined. A program is designed and used to obtain the magnetic profile of several vehicles when passing over a rectangular loop. The theoretical values are compared with the actual measurements and the accuracy of the model is checked. Besides, a new oscillator circuit, a component of which is the loop, is presented. Induction change is used to cause the oscillation frequency modification of circuit, which in turn is one of the changes used for vehicles detection, identification and classification.This work was supported in part by the City Council of Valencia in Spain and in part by Company ETRA I+D S.A.Mocholí Salcedo, A.; Arroyo Núñez, JH.; Milián Sánchez, VM.; Verdú Martín, GJ.; Arroyo Nuñez, A. (2017). Traffic Control Magnetic Loops Electric Characteristics Variation Due to the Passage of Vehicles Over Them. IEEE Transactions on Intelligent Transportation Systems. 18(6):1540-1548. doi:10.1109/TITS.2016.2612579S1540154818

Geminivirus replication protein decreases PCNA sumoylation at two acceptor sites

Geminiviruses are plant viruses with circular, single-stranded DNA (ssDNA) genomes that infect a broad range of plants causing substantial crop diseases worldwide. They replicate in nuclei of infected cells by using host DNA replication machinery and an essential protein encoded in their genome designated Rep (replication-associated protein). This multifunctional protein induces the accumulation of the host factors involved in replication and it is capable of interacting with a lot of plant proteins including PCNA (Proliferating Cell Nuclear Antigen), a processivity factor that coordinates a wide range of processes involved in maintenance, duplication and transmission of the genome, and the sumoylation enzyme that conjugates SUMO to target proteins (SUMO-conjugating enzyme- SCE). PCNA modification by SUMO, and also ubiquitin, has long been known to be of key importance for determining how DNA damage is processed by the replisome and for maintenance of overall genome integrity. In yeast, PCNA sumoylation has been associated to DNA repair involving homologous recombination (HR). Previously, we reported that Rep ectopic expression does not result in broad changes in the sumoylation pattern of plant cells, but it modifies the sumoylation state of selected host proteins. In this work, we show, using a reconstituted sumoylation system in Escherichia coli, that tomato PCNA is sumoylated at two residues, K254 and K164, and that co-expression of the Rep protein suppresses PCNA sumoylation at these lysines. Finally, we confirm that PCNA is sumoylated and that Rep also interferes with PCNA sumoylation in planta.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Mitochondrial DNA analysis of two samples from the paleolithic site of El Pirulejo

En la presente publicación se presentan los resultados del análisis del ADN mitocondrial (ADNmt) de dos individuos del nivel magdaleniense de El Pirulejo (Córdoba) (Asquerino et al., 1991). Las secuencias obtenidas se encuadran dentro de la variabilidad genética del hombre moderno actual, sin presentar similitud alguna con las secuencias de ADN mitocondrial de neandertal publicadas hasta la fecha. La distribución actual de las variantes mitocondriales encontradas en las dos muestras de El Pirulejo es similar a la encontrada en otros dos individuos Paleolíticos (Caramelli et al., 2003), y coherente con el modelo de expansión del hombre anatómicamente moderno desde África.At the present work it was studied the mitochondrial DNA (mtDNA) in two individuals from the Magdalenian level from El Pirulejo archaeological site located in Córdoba, Spain (Asquerino et al. 1991). The obtained sequences were inside the genetic variability of modern humans and did not share any similarities with published Neanderthal mtDNA sequences. The present distribution of the mtDNA lineages from El Pirulejo are similar to that found at other two Paleolithic individuals (Caramelli et al., 2003). All data are compatible with an “Out of Africa” model of dispersion of modern humans

A new role for circulating T follicular helper cells in humoral response to anti-PD-1 therapy

Background Lung cancer is one of the most frequent malignancies in humans and is a major cause of death. A number of therapies aimed at reinforcing antitumor immune response, including antiprogrammed cell death protein 1 (anti-PD-1) antibodies, are successfully used to treat several neoplasias as non-small cell lung cancer (NSCLC). However, host immune mechanisms that participate in response to anti-PD-1 therapy are not completely understood. Methods We used a syngeneic immunocompetent mouse model of NSCLC to analyze host immune response to anti-PD-1 treatment in secondary lymphoid organs, peripheral blood and tumors, by flow cytometry, immunohistochemistry and quantitative real-time PCR (qRT-PCR). In addition, we also studied specific characteristics of selected immune subpopulations in ex vivo functional assays. Results We show that anti-PD-1 therapy induces a population of circulating T follicular helper cells (cTfh) with enhanced B activation capacity, which participates in tumor response to treatment. Anti-PD-1 increases the number of tertiary lymphoid structures (TLS), which correlates with impaired tumor growth. Of note, TLS support cTfh-associated local antibody production, which participates in host immune response against tumor. Conclusion These findings unveil a novel mechanism of action for anti-PD-1 therapy and provide new targets for optimization of current therapies against lung cancer.This work was supported by grants to AA: FIS PI15/01491 and CIBER CARDIOVASCULAR from the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria del Instituto de Salud Carlos III with co-funding from the Fondo Europeo de Desarrollo Regional; FEDER

Evaluation of methods to accurately characterize the thermal conductivity of micro-and nanocellular polymers based on poly(methyl-methacrylate) (PMMA) produced at lab-scale

Producción CientíficaThe characterization of the thermal conductivity of new and enhanced thermal insulators developed at lab-scale is a challenge. The small dimensions of the prototypes make impossible the use of the conventional techniques because steady-state methods require large samples. Furthermore, the accuracy of transient methods to measure the thermal conductivity is not clear. In this work, we compare four different approaches to measure the thermal conductivity of small prototypes of nanocellular poly(methyl-methacrylate) (PMMA). Both steady-state and transient techniques are used. Results show that the transient plane source method is not suitable for the characterization of these materials (the deviation from the steady-state methods is on average higher than 15%). In addition, two different approaches for measuring the thermal conductivity of small samples via a steady-state technique are proposed and validated.Junta de Castilla y León (grant VA202P20)Ministerio de Ciencia, Innovación y Universidades (projects RTI2018-098749-B-I00 and PTQ2019-010560)Instituto para la Competitividad Empresarial de Castilla y León - Fondo Europeo de Desarrollo Regional (projects PAVIPEX. 04/18/VA/008 and FICACEL. 11/20/VA/0001

Neuralgia Occipital: uma abordagem terapêutica não invasiva

Objetivo: avaliar a aplicação de uma intervenção não invasiva que consiste em uma modificação postural usando modelos personalizados e osteopatia em pessoas com neuralgia occipital. Método: estudo retrospectivo da intervenção realizada em população adulta com neuralgia occipital que consiste de modificação postural empregando órteses plantares personalizadas e osteopatia, em um período de estudo de quatro anos. As variáveis observadas foram: persistência de cefaleia, alinhamento dos eixos, apoio plantar, centro de gravidade e centro de massa; dados da entrevista médica, escala visual analógica, sistema de análise de marcha Win-Track e o software Kinovea para análise de vídeo (instrumentos de avaliação clínica utilizados). Resultados: foram estudados no total 34 registros de pessoas com neuralgia occipital. Uma fração de 58,8% dos pacientes informou apresentar melhoria após a intervenção. Os dados da escala visual analógica foram fornecidos para 64,7% dos registros, encontrando diferenças significativas (p<0,001) entre as médias antes (8,4±1,7) e depois da intervenção (2,6±2,7). Conclusão: a modificação postural empregando órteses personalizadas e osteopatia melhora substancialmente a sintomatologia dos pacientes com neuralgia occipital.Objective: to evaluate the application of a noninvasive intervention consisting of a postural modification using personalized models and osteopathy in people with occipital neuralgia. Method: retrospective study of the intervention performed in adult population with occipital neuralgia, consisting of postural modification using personalized plantar orthoses and osteopathy, in a study period of four years. The observed variables were: persistence of headache, alignment of the axes, plantar support, center of gravity and center of mass; medical interview data, visual analogue scale, Win-Track gait analysis system and Kinovea software for video analysis (clinical assessment instruments used). Results: a total of 34 records of people with occipital neuralgia were studied. A fraction of 58.8% of the patients reported improvement after the intervention. The visual analogue scale data were provided for 64.7% of the records and significant differences (p <0.001) between the means before (8.4 ± 1.7) and after the intervention (2.6 ± 2.7) were found. Conclusion: postural modification using personalized orthoses and osteopathy substantially improves the symptomatology of patients with occipital neuralgia.Objetivo: evaluar la aplicación de una intervención no invasiva consistente en una modificación postural empleando plantillas personalizadas y osteopatía en personas con neuralgia occipital. Método: estudio retrospectivo de la intervención llevada a cabo en población adulta con neuralgia occipital, de modificación postural empleando órtesis plantares personalizadas y osteopatía, en un período de estudio de cuatro años. Las variables observadas fueron: persistencia de cefalea, alineación de los ejes, apoyo plantar, centro de gravedad y centro de masa; datos de la entrevista médica, la escala visual análoga, el sistema de análisis de la marcha Win-Track y el software Kinovea para análisis de vídeo (instrumentos de valoración clínica utilizados). Resultados: un total de 34 registros de personas con neuralgia occipital fueron estudiados. Un 58,8% refería presentar mejoría tras la intervención. Los datos de la escala visual análoga eran proporcionados un 64,7% de los registros, encontrándose diferencias significativas (p<0,001) entre las medias previas a la intervención (8,4±1,7) y aquellas posteriores (2,6±2,7). Conclusión: la modificación postural empleando órtesis personalizadas y osteopatía mejora sustancialmente la sintomatología de los pacientes con neuralgia occipital