Characterization of Pediococcus ethanolidurans CUPV141: A b-D-glucan- and Heteropolysaccharide-Producing Bacterium

Pediococcus ethanolidurans CUPV141 is an exopolysaccharide (EPS)-producing lactic acid bacterium, first isolated from Basque Country cider (Spain). Physicochemical analysis of the EPS synthesized by the bacterium revealed that CUPV141 produces mostly a homopolysaccharide (HoPS), characterized as a 2-substituted (1,3)-beta-D-glucan, together with a small quantity of a heteropolysaccharide (HePS) composed of glucose, galactose, glucosamine, and glycerol-3-phosphate, this being the first Pediococcus strain described to produce this kind of polymer. On the contrary, an isogenic strain CUPV141NR, generated by chemical mutagenesis of CUPV141, produced the HePS as the main extracellular polysaccharide and a barely detectable amount of 2-substituted (1,3)-beta-D-glucan. This HoPS is synthesized by the transmembrane GTF glycosyltransferase (GTF), encoded by the gtf gene, which has been previously reported to be located in the pPP2 plasmid of the Pediococcus parvulus 2.6 strain. Southern blot hybridization revealed that in CUPV141 the gtf gene is located in a plasmid designated as pPE3, whose molecular mass (34.4 kbp) is different from that of pPP2 (24.5 kbp). Analysis of the influence of the EPS on the ability of the producing bacteria to adhere to the eukaryotic Caco-2 cells revealed higher affinity for the human enterocytes of CUPV141NR compared to that of CUPV141. This result indicates that, in contrast to the 2.6 strain, the presence of the HoPS does not potentiate the binding ability of P. ethanolidurans. Moreover, it supports that the phosphate-containing bacterial HePS improved the interaction between P. ethanolidurans and the eukaryotic cells.This work was supported by a grant from the Department of Environment, Territorial Planification, Agriculture and Fishing and the project no. IT 866-13 from the Basque Government and by the Spanish Ministry of Science and Innovation (AGL 2015-65010-C3-1-R)

Remote control of movement disorders using a photoactive adenosine A(2A) receptor antagonist

G protein-coupled adenosine receptors are promising therapeutic targets for a wide range of neuropathological conditions, including Parkinson's disease (PD). However, the ubiquity of adenosine receptors and the ultimate lack of selectivity of certain adenosine-based drugs have frequently diminished their therapeutic use. Photopharmacology is a novel approach that allows the spatiotemporal control of receptor function, thus circumventing some of these limitations. Here, we aimed to develop a light-sensitive caged adenosine A(2A) receptor (A(2A)R) antagonist to photocontrol movement disorders. We synthesized MRS7145 by blocking with coumarin the 5-amino position of the selective A(2A)R antagonist SCH442416, which could be photoreleased upon violet light illumination (405 nm). First, the light-dependent pharmacological profile of MRS7145 was determined in A(2A)R-expressing cells. Upon photoactivation, MRS7145 precluded A(2A)R ligand binding and agonist-induced cAMP accumulation. Next, the ability of MRS7145 to block A(2A)R in a light-dependent manner was assessed in vivo. To this end, A(2A)R antagonist-mediated locomotor activity potentiation was evaluated in brain (striatum) fiber-optic implanted mice. Upon irradiation (405 nm) of the dorsal striatum, MRS7145 induced significant hyperlocomotion and counteracted haloperidol-induced catalepsy and pilocarpine-induced tremor. Finally, its efficacy in reversing motor impairment was evaluated in a PD animal model, namely the hemiparkinsonian 6-hydroxydopamine (6-OHDA)-lesioned mouse. Photo-activated MRS7145 was able to potentiate the number of contralateral rotations induced by L-3,4-dihydroxyphenylalanine (L-DOPA). Overall, MRS7145 is a new light-operated A(2A)R antagonist with potential utility to manage movement disorders, including PD

El portafolios como herramienta facilitadora del aprendizaje en la asignatura "Procedimientos generales de intervención en fisioterapia II"

[SPA]INTRODUCCIÓN: El portafolios es un método de enseñanza, aprendizaje y evaluación de gran utilidad educativa desde el enfoque constructivista. Su objetivo principal es que los estudiantes aprendan a buscar, relacionar y analizar información que consolide y complemente las sesiones de clase. MÉTODOS: Con el objetivo de valorar su utilidad, ventajas e inconvenientes en la asignatura “Procedimientos Generales de Intervención en Fisioterapia II” (PGIF II) pasamos una encuesta de valoración a los estudiantes. La elaboración del portafolios supone un volumen de 0,5 créditos ECTS y su calificación supone el 20% de la nota final. RESULTADOS: La encuesta fue contestada por 74 de los 100 alumnos matriculados. Las actividades realizadas que obtuvieron una mayor puntuación fueron la complementación de apuntes (8,92 ± 1,55) y la elaboración de casos clínicos (7,81 ± 1,60). El 83,8% opinó que el portafolios le había ayudado a complementar los contenidos teóricos; el 67,5% que había potenciado su pensamiento crítico y reflexivo; el 93,2% lo consideró una herramienta facilitadora del 2122 aprendizaje; el 33,1% confesó sentirse inseguro durante su realización. Sólo el 29,8% lo consideró un excesivo gasto de tiempo. CONCLUSIÓN: El portafolios es considerado por los alumnos como un método de enseñanza-aprendizaje de gran utilidad para propiciar el trabajo autónomo, completar la información de las clases teóricas y facilitar el aprendizaje de la asignatura “PGIF II”. [ENG]INTRODUCTION: The portfolio is a method of teaching, learning and evaluation. It is useful in an educational program from the constructivist approach. Its main objective is that students learn to find, correlate and analyze information to strengthen and complement the classroom sessions. METHODS: In order to assess its usefulness, advantages and disadvantages in the course "General Procedures in Physiotherapy II” (PGIF II) we carried out a closed survey with students. The development of the portfolio represents a volume of 0.5 ECTS credits and the mark is 20% of the total course marks. RESULTS: The survey was answered by 74 of the 100 students enrolled. The activities that scored highest marking (10 points, mean ± standard deviation) were notes supplementation (8.92 ± 1.55) and the development of case studies (7.81 ± 1.60). 83.8% of the students felt that the portfolio had helped to supplement the theoretical concepts, 67.5% replied that it had enhanced their critical and reflective thinking, 93.2% saw it´s a learning facilitator tool, 33,1% stated they felt unsacure during the performance. Only 29.8% of students considered it an excessive waste of time. CONCLUSION: The portfolio is considered by students as a teaching-learning method useful for promoting self-study, completing the information obtained in the classroom and facilitating learning of the course "PGIF II”.Campus Mare Nostrum, Universidad Politécnica de Cartagena, Universidad de Murcia, Región de Murci

Las prácticas de simulación como herramienta facilitadora de enseñanza-aprendizaje en fisioterapia

[SPA]INTRODUCCIÓN: Gran parte del contenido de las materias del Grado de Fisioterapia se desarrolla mediante sesiones prácticas. En ellas cobran especial importancia las prácticas de simulación: el profesor toma como modelo a un estudiante y realiza la demostración de diferentes técnicas fisioterápicas. A continuación, los estudiantes, practican hasta consolidar, mediante la repetición y la corrección de errores, lo aprendido. MÉTODOS: Para el diseño de la asignatura “Procedimientos Generales de Intervención en Fisioterapia II” (PGIF-II), se ha elegido como metodología didáctica las prácticas de simulación. Con el objetivo de valorar la utilidad, ventajas e inconvenientes de las prácticas de simulación en la asignatura al finalizar la docencia los estudiantes rellenaron una encuesta de valoración. RESULTADOS: Las prácticas de simulación constituyeron un 43,3% de las horas totales de práctica. La encuesta fue contestada por 74 de los 100 estudiantes matriculados. La pregunta sobre la utilidad de las prácticas de simulación para completar la información de las sesiones teóricas obtuvo un 7,5 ± 2,27 sobre 10 (media ± desviación estándar). Las prácticas de masaje fueron las mejor valoradas, con un puntuación media de 9,11 ± 1,14. El 98,6% opinó que les había ayudado a complementar los contenidos teóricos; el 98,6% lo consideró una herramienta facilitadora del aprendizaje y 2090 el 79,5% opinó que este tipo de prácticas había mejorado su relación con los profesores. No obstante, el 84,9% las consideraron insuficientes en cuanto a horas dedicadas. CONCLUSIÓN: Las prácticas de simulación constituyen una herramienta fundamental para la adquisición de las habilidades y destrezas específicas de la materia “PGIF II” necesarias para la adquisición de competencias. [ENG]INTRODUCTION: Much of the content of the Degree in Physiotherapy is developed through practice sessions. The simulation practices are particularly important: the professor explains physical therapy techniques and students practice to consolidate learning by repetition and error correction. METHODS: For the design of the subject "General Procedures in Physical Therapy Intervention II" (PGIF-II) a methodology based in simulation practices has been chosen. In order to evaluate the usefulness, advantages and disadvantages of this methodology studients completed a survey. RESULTS: Simulation practices constitute 43.3% of the total hours of practice. The survey was answered by 74 of the 100 students. The question of the usefulness of simulation exercises to supplement the information from the theoretical sessions obtained 7,5 ± 2,27 out of 10 (mean ± standard deviation). Practices about massage received a mean score of 9,11 ± 1,14. 98.6% of students felt that they had helped them to supplement the theoretical contents, 98,6% considered it a learning facilitator tool and 79,5% thought that such practices had improved their relationship with professors. 84,9% considered them inadequate in terms of hours spent. CONCLUSION: Simulation practices are a fundamental tool for the acquisition of specific skills and abilities of the subject "PGIF-II", necessary for the acquisition of competences.Campus Mare Nostrum, Universidad Politécnica de Cartagena, Universidad de Murcia, Región de Murci

Routine management of locally advanced cervical cancer with concurrent radiation and cisplatin. Five-year results

BACKGROUND: Globally, cervical cancer primarily affects socially disadvantaged women. Five randomized trials were the foundation for adopting cisplatin-based chemotherapy during radiation as the standard of care for high-risk patients after primary radical hysterectomy who require adjuvant radiation and for locally advanced patients treated with definitive radiation. These results were obtained in clinical trials performed in carefully prepared academic centers; hence, we sought to determine whether these results could be reproduced when patients were treated on an out-of-protocol basis. METHODS: We reviewed the files of 294 patients with locally advanced cervical cancer who received radiation plus weekly cisplatin as routine management between 1999 to 2003, and analyzed treatment compliance, response rate, toxicity, and survival. RESULTS: A total of 294 patients who received radiation and cisplatin were analyzed. Mean age was 43.8 years (range, 26–68 years). The majority of cases were squamous cell carcinoma (87.8%), and distribution according to International Federation of Gynecology and Obstetrics (FIGO) stage was as follows: IB2-IIA, 23%; IIB, 53.3%, and IIIB, 23%; there were only two IVA cases. Overall, 96% of patients completed external beam, and intracavitary therapy. The majority of patients (67%) received the planned six courses of weekly cisplatin. Complete responses were achieved in 243 (83%) patients, whereas 51 (17%) had either persistent (32 patients, 10.8%) or progressive (19 patients, 6.4%) disease. At median follow-up (28 months; range, 2–68 months), 36 patients (12.2%) have relapsed (locally 30.5, and systemically, 69.5%). The most common toxicities were hematologic and gastrointestinal, in the majority of cases considered mild-moderate. At median follow-up (28 months; range, 2–68 months), overall and progression-free survival are 76.5 and 67%, respectively. CONCLUSION: Our results support use of chemoradiation with six weekly applications of cisplatin at 40 mg/m(2 )during external radiation for routine management of locally advanced cervical cancer

Inhibition of inflammatory signaling in Pax5 mutant cells mitigates B-cell leukemogenesis

Altres ajuts: We would like to thank the "Fundación Ramón Areces," a Research Contract with the "Fundación Síndrome de Wolf-Hirschhorn o 4p-", and institutional grants from the "Fundación Ramón Areces" and "Banco de Santander" to the CBMSO. Research in the ISG group is partially supported by by Junta de Castilla y León (UIC-017, CSI001U16, and CSI234P18), and by the German Jose Carreras Foundation (DJCLS R13/26; DJCLS 07R/2019). AC-G and M.I.-H. are supported by FSE-Conserjería de Educación de la Junta de Castilla y León 2019 and 2020 (ESF- European Social Fund) fellowship, respectively. J.R.-G. is supported by a scholarship from University of Salamanca co-financed by Banco Santander and ESF.PAX5 is one of the most frequently mutated genes in B-cell acute lymphoblastic leukemia (B-ALL), and children with inherited preleukemic PAX5 mutations are at a higher risk of developing the disease. Abnormal profiles of inflammatory markers have been detected in neonatal blood spot samples of children who later developed B-ALL. However, how inflammatory signals contribute to B-ALL development is unclear. Here, we demonstrate that Pax5 heterozygosis, in the presence of infections, results in the enhanced production of the inflammatory cytokine interleukin-6 (IL-6), which appears to act in an autocrine fashion to promote leukemia growth. Furthermore, in vivo genetic downregulation of IL-6 in these Pax5 heterozygous mice retards B-cell leukemogenesis, and in vivo pharmacologic inhibition of IL-6 with a neutralizing antibody in Pax5 mutant mice with B-ALL clears leukemic cells. Additionally, this novel IL-6 signaling paradigm identified in mice was also substantiated in humans. Altogether, our studies establish aberrant IL6 expression caused by Pax5 loss as a hallmark of Pax5-dependent B-ALL and the IL6 as a therapeutic vulnerability for B-ALL characterized by PAX5 loss

Transient inhibition of the JAK/STAT pathway prevents B-ALL development in genetically predisposed mice

Preventing development of childhood B-cell acute lymphoblastic leukemia (B-ALL), a disease with devastating effects, is a longstanding and unsolved challenge. Heterozygous germline alterations in the PAX5 gene can lead to B-ALL upon accumulation of secondary mutations affecting the JAK/STAT signaling pathway. Preclinical studies have shown that this malignant transformation occurs only under immune stress such as exposure to infectious pathogens. Here we show in Pax5+/− mice that transient, early-life administration of clinically relevant doses of ruxolitinib, a JAK1/2 inhibitor, significantly mitigates the risk of B-ALL following exposure to infection; 1 of 29 animals treated with ruxolitinib developed B-ALL versus 8 of 34 untreated mice. Ruxolitinib treatment preferentially targeted Pax5+/− versus wild-type B-cell progenitors and exerted unique effects on the Pax5+/− B-cell progenitor transcriptional program. These findings provide the first in vivo evidence for a potential strategy to prevent B-ALL development.C. Cobaleda and C. Vicente-Dueñas labs are members of the EU COST Action LEGEND (CA16223). Research in C. Vicente-Dueñas group has been funded by Instituto de Salud Carlos III through the project " PI17/00167 and by a “Miguel Servet Grant” [CPII19/00024 - AES 2017-2020; co-funded by European Regional Development Fund (ERDF)/European Social Fund (ESF) "A way to make Europe"/"Investing in your future"]. J.J. Yang and K.E. Nichols receive funding from the American Lebanese Syrian Associated Charities (ALSAC) and R01CA241452 from the NCI. Research in ISG group is partially supported by FEDER and by SAF2015-64420-R MINECO/FEDER, UE, RTI2018-093314-B-I00 MCIU/AEI/FEDER, UE, 9659122185-122185-4-21 MCIU/AEI/FEDER, UE, by Junta de Castilla y León (UIC-017, CSI001U16, CSI234P18, and CSI144P20). M. Ramírez-Orellana and I. Sánchez-García have been supported by the Fundacion Unoentrecienmil (CUNINA project). C. Cobaleda, M. Ramírez-Orellana, and I. Sánchez-García have been supported by the Fundación Científica de la Asociación Española contra el Cáncer (PRYCO211305SANC). A. Casado-García (CSI067-18) and M. Isidro-Hernández (CSI021-19) are supported by FSE-Conserjería de Educación de la Junta de Castilla y León 2019 and 2020 (ESF, European Social Fund) fellowship, respectively. J. Raboso-Gallego is supported by a scholarship from University of Salamanca co-financed by Banco Santander and ESF. S. Alemán-Arteaga is supported by an Ayuda para Contratos predoctorales para la formación de doctores (PRE2019-088887)

Moda sostenible. Diseñando modelos de economía circular en la región

El PAP Moda Sostenible: Diseñando modelos de economía circular en la región, tiene como objetivo general: activar economías locales, involucrando a los pequeños productores de la región en el sistema de la moda, desde una perspectiva sostenible. Como metodología se utiliza un modelo circular de moda sostenible1 basado en los tres pilares de la sostenibilidad: desarrollo económico, cuidado ambiental y cohesión social, con el que se busca incrementar los ingresos de los artesanos y productores de la comunidad destino, fortalecer el tejido social de los involucrados, gestionar de manera adecuada los recursos naturales con los que se trabaje y generar vínculos entre los consumidores y los productores. Durante este primer periodo se plantearon tres objetivos clave, que permitieron obtener resultados favorables: 1. Se realizaron manuales y fichas derivadas del análisis de los recursos naturales y humanos de la organización destino, que permitieron generar las primeras líneas de acción y propuestas de mejora. 2. Se creó una línea de productos viable y asequible para incrementar ingresos inmediatos en la comunidad destino que permitirá invertir en los desarrollos de mejora posteriores. Se creo @parakata una marca con identidad que ofrece los productos de los artesanos productores, con una línea de accesorios que ya se encuentra en fase de testeo dentro del mercado meta y una propuesta museográfica que se implementará para atraer nuevos clientes y aliados al lugar de origen de la producción artesanal (Casita de Piedra Cetcaser). 3. Se fortalecieron habilidades de los artesanos y productores tras detectar áreas de oportunidad para posibles mejoras integrales que se abordaron bajo manuales y capacitaciones en línea. Ofreciendo con esto a los beneficiarios, herramientas para prepararse y apropiarse de los productos y servicios diseñados en colaboración con las alumnas del PAP, permitiendo así su sostenibilidad a lo largo del tiempoITESO, A.C

Use of an orthovoltage X-ray treatment unit as a radiation research system in a small-animal cancer model

<p>Abstract</p> <p>Background</p> <p>We explore the use of a clinical orthovoltage X-ray treatment unit as a small-animal radiation therapy system in a tumoral model of cervical cancer.</p> <p>Methods</p> <p>Nude mice were subcutaneously inoculated with 5 × 10⁶HeLa cells in both lower limbs. When tumor volume approximated 200 mm³treatment was initiated. Animals received four 2 mg/kg intraperitoneal cycles (1/week) of cisplatin and/or 6.25 mg/kg of gemcitabine, concomitant with radiotherapy. Tumors were exposed to 2.5 Gy/day nominal surface doses (20 days) of 150 kV X-rays. Lead collimators with circular apertures (0.5 to 1.5 cm diameter) were manufactured and mounted on the applicator cone to restrict the X-ray beam onto tumors. X-ray penetration and conformality were evaluated by measuring dose at the surface and behind the tumor lobe by using HS GafChromic film. Relative changes in tumor volume (RTV) and a clonogenic assay were used to evaluate the therapeutic response of the tumor, and relative weight loss was used to assess toxicity of the treatments.</p> <p>Results</p> <p>No measurable dose was delivered outside of the collimator apertures. The analysis suggests that dose inhomogeneities in the tumor reach up to ± 11.5% around the mean tumor dose value, which was estimated as 2.2 Gy/day. Evaluation of the RTV showed a significant reduction of the tumor volume as consequence of the chemoradiotherapy treatment; results also show that toxicity was well tolerated by the animals.</p> <p>Conclusion</p> <p>Results and procedures described in the present work have shown the usefulness and convenience of the orthovoltage X-ray system for animal model radiotherapy protocols.</p

Prevalence and genetic diversity of Avipoxvirus in house sparrows in Spain

Avipoxvirus (APV) is a fairly common virus affecting birds that causes morbidity and mortality in wild and captive birds. We studied the prevalence of pox-like lesions and genetic diversity of APV in house sparrows (Passer domesticus) in natural, agricultural and urban areas in southern Spain in 2013 and 2014 and in central Spain for 8 months (2012±2013). Overall, 3.2% of 2,341 house sparrows visually examined in southern Spain had cutaneous lesions consistent with avian pox. A similar prevalence (3%) was found in 338 birds from central Spain. Prevalence was higher in hatch-year birds than in adults. We did not detect any clear spatial or temporal patterns of APV distribution. Molecular analyses of poxvirus-like lesions revealed that 63% of the samples were positive. Molecular and phylogenetic analyses of 29 DNA sequences from the fpv167 gene, detected two strains belonging to the canarypox clade (subclades B1 and B2) previously found in Spain. One of them appears predominant in Iberia and North Africa and shares 70% similarity to fowlpox and canarypox virus. This APV strain has been identified in a limited number of species in the Iberian Peninsula, Morocco and Hungary. The second one has a global distribution and has been found in numerous wild bird species around the world. To our knowledge, this represents the largest study of avian poxvirus disease in the broadly distributed house sparrow and strongly supports the findings that Avipox prevalence in this species in South and central Spain is moderate and the genetic diversity low.This study was funded by the Spanish Ministry of Science and Innovation (Project CGL2010-15734/BOS), the Spanish Ministry of Economy and Competitiveness (Project CGL2013-41642-P/BOS) and the Innovation and Development Agency of Andalusia (Spain) (P11-RNM-7038). Grants were awarded to JMP (Juan de la Cierva- JCI-2012-11868) and MAJM (FPIBES-2011-047609), Spanish Ministry of Economy and Competitiveness; RAJW (CEI-PICATA2012), CEI Campus of International Excellence; MM (FPU12/0568), Spanish Ministry of Education, Culture and Sports. RAJW was supported by the Craaford Foundation (grant 20160971) during the writing of this publication. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript