The orienteering: Inclusion and sensitization from a cooperative experience

La orientación es una herramienta formativa en-caminada al desarrollo de la persona en todas sus facetas. Entre esos factores que desarrollamos están el trabajo en equipo, la empatía con el com-pañero y el fomento, a través de este tipo de acti-vidades en el medio natural, de la inclusión de per-sonas con diversidad funcional buscando un disfru-te compartido. Esto nos lleva a plantear en este taller que presentamos una propuesta de sensibili-zación, a través de la orientación, hacia las perso-nas con ceguera o deficiencia visual. La metodolo-gía más ajustada, a la propuesta sensibilizadora, es la pedagogía de la aventura, que permite la interio-rización de las experiencias desde la emoción y la reflexión de las actividades. Los contenidos que setratarán en el desarrollo del taller serán los diferen-tes sistemas de referencia, la elaboración e inter-pretación de mapas, la elección de rutas y rumbos, limitando en los participantes el sentido de la vista en alguno de los momentos de aprendizaje de la sesión. En las actividades que se plantearán, los participantes deberán resolver diferentes retos cooperativos con la ayuda de los compañeros de actividad. Entre los materiales que se utilizarán para llevar a cabo el taller estarán diferentes ele-mentos de simulación de las deficiencias visuales, mapas táctiles tridimensionales, mapas táctiles, balizas y hojas de control sensoriales. La orienta-ción dirigida a la sensibilización para la discapaci-dad visual cobra su sentido como propuesta que nos acerca a la inclusión de cualquier participanteen las actividades en el medio natural y a la refle-xión que las limitaciones y posibilidades de partici-pación, en muchos casos, está en la mano todosOrientation is a formative tool aimed at the devel-opment of the person in all its facets. Among thosefactors we develop are teamwork, empathy with the partner and the promotion, through these types of activities in the natural environment, of the inclu-sion of people with functional diversity seeking a shared enjoyment. This leads us to raise in this workshop that we present a proposal to raise awareness, through guidance, to people with blind-ness or visual impairment. The most accurate meth-odology, the sensitizing proposal, is the pedagogy of adventure, which allows the internalization of the experiences from the emotion and the reflection of the activities. The contents that will be treated in the development of the workshop will be the differ-ent systems of reference, the elaboration and inter-pretation of maps, the choice of routes and courses, limiting in the participants the sense of sight in some of the moments of learning of the session. In the activities that will be considered, the partici-pants will have to solve different cooperative chal-lenges with the help of the companions of activity.Among the materials that will be used to carry out the workshop will be different elements of simula-tion of visual deficiencies, three-dimensional tactile maps, tactile maps, beacons and sensory control sheets. The orientation directed at the sensitization for visual impairment, takes its meaning as a pro-posal that brings us closer to the inclusion of any articipant in the activities in the natural environ-ment and to the reflection that the limitations andpossibilities of participation in many cases is in the hands of all

Experience about positive development program through outdoor activities

Las actividades físicas en el medio natural son un contexto privilegiado para contribuir al desarro-llo positivo de los adolescentes. El objetivo de la comunicación es presentar una experiencia en la que se ha diseñado, aplicado y evaluado un programa de desarrollo positivo en adolescentes, basado en el modelo de responsabilidad de Helli-son y en la pedagogía de la aventura, para pro-mover el desarrollo de competencias relativas al desarrollo personal y social, así como competen-cias profesionales, propias del alumnado que cursa el ciclo formativo de conducción de activi-dades físico-deportivas en el medio natural.Outdoor physical activities are an excellent context for fostering students’ positive development. This paper presents an activity that desinged, implemented and evaluate a positive development program for teenagers based on Hellison’s model of responsibility and adventure pedagogy to work personal and social competences, with students training to lead ourdoor physical and sporting activitie

The first high-density genetic map of common cockle (Cerastoderma edule) reveals a major QTL controlling shell color variation

Shell color shows broad variation within mollusc species and despite information on the genetic pathways involved in shell construction and color has recently increased, more studies are needed to understand its genetic architecture. The common cockle ( Cerastoderma edule) is a valuable species from ecological and commercial perspectives which shows important variation in shell color across Northeast Atlantic. In this study, we constructed a high-density genetic map, as a tool for screening common cockle genome, which was applied to ascertain the genetic basis of color variation in the species. The consensus genetic map comprised 19 linkage groups (LGs) in accordance with the cockle karyotype (2n = 38) and spanned 1073 cM, including 730 markers per LG and an inter-marker distance of 0.13 cM. Five full-sib families showing segregation for several color-associated traits were used for a genome-wide association study and a major QTL on chromosome 13 associated to different color-traits was detected. Mining on this genomic region revealed several candidate genes related to shell construction and color. A genomic region previously reported associated with divergent selection in cockle distribution overlapped with this QTL suggesting its putative role on adaptationInterreg Atlantic Area | Ref. EAPA_458/2016Ministerio de Economía, Industria y Competitividad | Ref. BES2016/078166Roslin Institute | Ref. BBS/E/D/20002172Roslin Institute | Ref. BBS/E/D/30002275Roslin Institute | Ref. BBS/E/D/1000207

Golimumab as rescue therapy for refractory immune-mediated uveitis: a three-center experience

OBJECTIVE: To evaluate, in three Spanish tertiary referral centres, the short-term safety and efficacy of golimumab (GLM) for treatment of immune-mediated uveitis resistant to previous immunosuppressive therapy. METHODS: Nonrandomized retrospective interventional case series. Thirteen patients with different types of uveitis that were resistant to treatment with at least 2 previous immunosuppressors were included in this study. All included patients were treated with GLM (50 mg every four weeks) during at least 6 months. Clinical evaluation and treatment-related side effects were assessed at least four times in all included patients. RESULTS: Eight men and 5 women (22 affected eyes) with a median age of 30 years (range 20-38) and active immune-mediated uveitides were studied. GLM was used in combination with conventional immunosuppressors in 7 patients (53.8%). GLM therapy achieved complete control of inflammation in 12/13 patients (92.3%) after six months of treatment. There was a statistically significant improvement in mean BCVA (0.60 versus 0.68, P = 0.009) and mean 1 mm central retinal thickness (317 versus 261.2 µ, P = 0.05) at the six-month endpoint when compared to basal values. No major systemic adverse effects associated with GLM therapy were observed. CONCLUSIONS: GLM is a new and promising therapeutic option for patients with severe and refractory uveitis

The diguanylate cyclase AdrA regulates flagellar biosynthesis in Pseudomonas fluorescens F113 through SadB

Flagellum mediated motility is an essential trait for rhizosphere colonization by pseudomonads. Flagella synthesis is a complex and energetically expensive process that is tightly regulated. In Pseudomonas fluorescens, the regulatory cascade starts with the master regulatory protein FleQ that is in turn regulated by environmental signals through the Gac/Rsm and SadB pathways, which converge in the sigma factor AlgU. AlgU is required for the expression of amrZ, encoding a FleQ repressor. AmrZ itself has been shown to modulate c-di-GMP levels through the control of many genes encoding enzymes implicated in c-di-GMP turnover. This cyclic nucleotide regulates flagellar function and besides, the master regulator of the flagellar synthesis signaling pathway, FleQ, has been shown to bind c-di-GMP. Here we show that AdrA, a diguanylate cyclase regulated by AmrZ participates in this signaling pathway. Epistasis analysis has shown that AdrA acts upstream of SadB, linking SadB with environmental signaling. We also show that SadB binds c-di-GMP with higher affinity than FleQ and propose that c-di-GMP produced by AdrA modulates flagella synthesis through SadBThis work was supported by funding from MINECO/FEDER EU Grant RTI2018 093991-BI00 to R.R. and M.M. C.M. was funded by a FPI fellowship from MINECO. EB-R was the recipient of fellowships from Fundación Tatiana Pérez de Guzmán el Bueno (Medioambiente 2016) and the FPU program from MECD (FPU16/05513). Short stays of R.R. and C.M. at John Innes Centre were funded by MECD (Salvador de Madariaga and FPU, respectively

Distinct Roles of Mus81, Yen1, Slx1-Slx4, and Rad1 Nucleases in the Repair of Replication-Born Double-Strand Breaks by Sister Chromatid Exchange

Most spontaneous DNA double-strand breaks (DSBs) arise during replication and are repaired by homologous recombination (HR) with the sister chromatid. Many proteins participate in HR, but it is often difficult to determine their in vivo functions due to the existence of alternative pathways. Here we take advantage of an in vivo assay to assess repair of a specific replication-born DSB by sister chromatid recombination (SCR). We analyzed the functional relevance of four structure-selective endonucleases (SSEs), Yen1, Mus81-Mms4, Slx1-Slx4, and Rad1, on SCR in Saccharomyces cerevisiae. Physical and genetic analyses showed that ablation of any of these SSEs leads to a specific SCR decrease that is not observed in general HR. Our work suggests that Yen1, Mus81-Mms4, Slx4, and Rad1, but not Slx1, function independently in the cleavage of intercrossed DNA structures to reconsti-tute broken replication forks via HR with the sister chromatid. These unique effects, which have not been detected in other stud-ies unless double mutant combinations were used, indicate the formation of distinct alternatives for the repair of replication- born DSBs that require specific SSEs.Ministerio de Ciencia e Innovación FU2010-16372, CSD2007-015Junta de Andalucía BIO102 and CVI4567National Institutes of Health GM5801

Geomicrobiological heterogeneity of lithic habitats in the extreme environment of Antarctic nunataks: a potential early Mars analog

Nunataks are permanent ice-free rocky peaks that project above ice caps in polar regions, thus being exposed to extreme climatic conditions throughout the year. They undergo extremely low temperatures and scarcity of liquid water in winter, while receiving high incident and reflected (albedo) UVA-B radiation in summer. Here, we investigate the geomicrobiology of the permanently exposed lithic substrates of nunataks from Livingston Island (South Shetlands, Antarctic Peninsula), with focus on prokaryotic community structure and their main metabolic traits. Contrarily to first hypothesis, an extensive sampling based on different gradients and multianalytical approaches demonstrated significant differences for most geomicrobiological parameters between the bedrock, soil, and loose rock substrates, which overlapped any other regional variation. Brevibacillus genus dominated on bedrock and soil substrates, while loose rocks contained a diverse microbial community, including Actinobacteria, Alphaproteobacteria and abundant Cyanobacteria inhabiting the milder and diverse microhabitats within. Archaea, a domain never described before in similar Antarctic environments, were also consistently found in the three substrates, but being more abundant and potentially more active in soils. Stable isotopic ratios of total carbon (δ 13C) and nitrogen (δ 15N), soluble anions concentrations, and the detection of proteins involved in key metabolisms via the Life Detector Chip (LDChip), suggest that microbial primary production has a pivotal role in nutrient cycling at these exposed areas with limited deposition of nutrients. Detection of stress-resistance proteins, such as molecular chaperons, suggests microbial molecular adaptation mechanisms to cope with these harsh conditions. Since early Mars may have encompassed analogous environmental conditions as the ones found in these Antarctic nunataks, our study also contributes to the understanding of the metabolic features and biomarker profiles of a potential Martian microbiota, as well as the use of LDChip in future life detection missions.This project has been funded by the Spanish Ministry of Science and Innovation (MICINN)/European Regional Development Fund (FEDER) project no. RTI2018-094368-B-I00; the European Research Council Consolidator grant no. 818602; and the Spanish State Research Agency (AEI) project no. MDM-2017-0737, Unidad de Excelencia “María de Maeztu” to Centro de Astrobiología

Clastosome: a subtype of nuclear body enriched in 19S and 20S proteasomes, ubiquitin, and protein substrates of proteasome.

Nuclear bodies represent a heterogeneous class of nuclear structures. Herein, we describe that a subset of nuclear bodies is highly enriched in components of the ubiquitin-proteasome pathway of proteolysis. We coined the term clastosome (from the Greek klastos, broken and soma, body) to refer to this type of nuclear body. Clastosomes contain a high concentration of 1) ubiquitin conjugates, 2) the proteolytically active 20S core and the 19S regulatory complexes of the 26S proteasome, and 3) protein substrates of the proteasome. Although detected in a variety of cell types, clastosomes are scarce under normal conditions; however, they become more abundant when proteasomal activity is stimulated. In contrast, clastosomes disappear when cells are treated with proteasome inhibitors. Protein substrates of the proteasome that are found concentrated in clastosomes include the short-lived transcription factors c-Fos and c-Jun, adenovirus E1A proteins, and the PML protein. We propose that clastosomes are sites where proteolysis of a variety of protein substrates is taking place

Somatostatin Receptor Splicing Variant sst5TMD4 Overexpression in Glioblastoma Is Associated with Poor Survival, Increased Aggressiveness Features and Somatostatin Analogs Resistance

Glioblastoma (GBM) is the most malignant and lethal brain tumor. Current standard treatment consists of surgery followed by radiotherapy/chemotherapy; however, this is only a palliative approach with a mean post-operative survival of scarcely ~12–15 months. Thus, the identification of novel therapeutic targets to treat this devastating pathology is urgently needed. In this context, the truncated splicing variant of the somatostatin receptor subtype 5 (sst5TMD4), which is produced by aberrant alternative splicing, has been demonstrated to be overexpressed and associated with increased aggressiveness features in several tumors. However, the presence, functional role, and associated molecular mechanisms of sst5TMD4 in GBM have not been yet explored. Therefore, we performed a comprehensive analysis to characterize the expression and pathophysiological role of sst5TMD4 in human GBM. sst5TMD4 was significantly overexpressed (at mRNA and protein levels) in human GBM tissue compared to non-tumor (control) brain tissue. Remarkably, sst5TMD4 expression was significantly associated with poor overall survival and recurrent tumors in GBM patients. Moreover, in vitro sst5TMD4 overexpression (by specific plasmid) increased, whereas sst5TMD4 silencing (by specific siRNA) decreased, key malignant features (i.e., proliferation and migration capacity) of GBM cells (U-87 MG/U-118 MG models). Furthermore, sst5TMD4 overexpression in GBM cells altered the activity of multiple key signaling pathways associated with tumor aggressiveness/progression (AKT/JAK-STAT/NF-κB/TGF-β), and its silencing sensitized GBM cells to the antitumor effect of pasireotide (a somatostatin analog). Altogether, these results demonstrate that sst5TMD4 is overexpressed and associated with enhanced malignancy features in human GBMs and reveal its potential utility as a novel diagnostic/prognostic biomarker and putative therapeutic target in GBMs

Peutz-Jeghers syndrome and duodeno-jejunal adenocarcinoma-therapeutic implications

The Peutz-Jeghers syndrome (PJS) is an autosomal dominant hamartomatous poliposis describred in 1921. Hemminki in 1997 described the presence of LKB-1 mutation tumor-suppressor gen.The patients with PJS develop a higher cumulative incidence of gastrointestinal, pancreas and extraintestinal tumors, being occasion of a renew interest on hamartomatous polyposis syndromes regarding the clinical care, cancer surveillance treatment and long term follow-up.We report the case of a 38 years old male, diagnosed of PJS who developed a multiple adenocarcinoma in duodenum and yeyunum. Surgically treated and with a long-term free disease survival of 11 years represents the sixth case reported in the spanish literature of PJS associated with a gastrointestinal tumor.A critical review, molecular alterations and the established criteria of tumor screening and surveillance are reviewed