Politics in Spain: A Case of Monitory Democracy

Analysing the current political context in Spain is a major challenge to political theory. Spain is experiencing the accumulation of trends that in recent years have focused the attention of most theorists and political scientists: discrediting of the major parties, falling numbers of party members, disaffection, etc. In parallel, this trend has been accompanied by citizen mobilisations that, since 15 May 2011, are manifest in numerous channels and strategies. The aim of this paper was to analyse the complex Spanish context from the monitory democracy proposal. The results show how in recent years processes of public scrutiny have been consolidated through a range of citizen initiatives. The study offers an in-depth analysis of the main characteristics of the most notable cases and monitoring initiatives, and also reflects on their democratising potential.El análisis del contexto político actual en España es un reto importante para la teoría política. España está experimentando la acumulación de tendencias que en años recientes han centrado la atención de la mayor parte de teóricos y científicos políticos: desacreditación de los principales partidos, caída del número de miembros de los partidos, desafección, etc. Paralelamente, esta tendencia se ha visto acompañada por movilizaciones ciudadanas que, desde el 15 de mayo de 2011, son manifiestas en numerosos canales y estrategias. El objetivo de este documento es analizar el complejo contexto español desde la propuesta de democracia monitorizada. Los resultados muestran que en años recientes se han consolidado los procesos de escrutinio público mediante una serie de iniciativas ciudadanas. El estudio ofrece un análisis en profundidad de las principales características de los casos e iniciativas de monitorización más notables, y reflexiona también sobre su potencial democratizador

Phase 1, open-label, dose-escalation study on the safety, pharmacokinetics, and preliminary efficacy of intravenous Coxsackievirus A21 (V937), with or without pembrolizumab, in patients with advanced solid tumors

Background Oncolytic virus V937 showed activity and safety with intratumoral administration. This phase 1 study evaluated intravenous V937±pembrolizumab in patients with advanced solid tumors. Methods Patients had advanced non-small cell lung cancer (NSCLC), urothelial cancer, metastatic castration-resistant prostate cancer, or melanoma in part A (V937 monotherapy), and metastatic NSCLC or urothelial cancer in part B (V937+pembrolizumab). Prior immunotherapy was permitted >28 days before study treatment. Patients received intravenous V937 on days 1, 3, and 5 (also on day 8 in part B) of the first 21-day cycle and on day 1 of subsequent cycles for eight cycles. Three ascending dose-escalation cohorts were studied. Dose-escalation proceeded if no dose-limiting toxicities (DLTs) occurred in cycle 1 of the previous cohort. In part B, patients also received pembrolizumab 200 mg every 3 weeks from day 8 for 2 years; dose-expansion occurred at the highest-dose cohort. Serial biopsies were performed. Results No DLTs occurred in parts A (n=18) or B (n=85). Grade 3–5 treatment-related adverse events (AEs) were not observed in part A and were experienced by 10 (12%) patients in part B. The most frequent treatment-related AEs (any grade) in part B were fatigue (36%), pruritus (18%), myalgia (14%), diarrhea (13%), pyrexia (13%), influenza-like illness (12%), and nausea (12%). At the highest tested dose, median intratumoral V937 concentrations were 117,631 copies/mL on day 8, cycle 1 in part A (n=6) and below the detection limit for most patients (86% (19/22)) on day 15, cycle 1 in part B. Objective response rates were 6% (part A), 9% in the NSCLC dose-expansion cohort (n=43), and 20% in the urothelial cancer dose-expansion cohort (n=35). Conclusions Intravenous V937+pembrolizumab had a manageable safety profile. Although V937 was detected in tumor tissue, in NSCLC and urothelial cancer, efficacy was not greater than that observed in previous studies with pembrolizumab monotherapy. Trial registration number NCT02043665

Restored Agricultural Wetlands in central Iowa: Habitat Quality and Amphibian Response

Amphibians are declining throughout the United States and worldwide due, partly, to habitat loss. Conservation practices on the landscape restore wetlands to denitrify tile drainage effluent and restore ecosystem services. Understanding how water quality, hydroperiod, predation, and disease affect amphibians in restored wetlands is central to maintaining healthy amphibian populations in the region. We examined the quality of amphibian habitat in restored wetlands relative to reference wetlands by comparing species richness, developmental stress, and adult leopard frog (Lithobates pipiens) survival probabilities to a suite of environmental metrics. Although measured habitat variables differed between restored and reference wetlands, differences appeared to have sub-lethal rather than lethal effects on resident amphibian populations. There were few differences in amphibian species richness and no difference in estimated survival probabilities between wetland types. Restored wetlands had more nitrate and alkaline pH, longer hydroperiods, and were deeper, whereas reference wetlands had more amphibian chytrid fungus zoospores in water samples and resident amphibians exhibited increased developmental stress. Restored and reference wetlands are both important components of the landscape in central Iowa and maintaining a complex of fish-free wetlands with a variety of hydroperiods will likely contribute to the persistence of amphibians in this landscape

Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.

Pulmonary tuberculosis (TB), caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb), is a major world health problem. The production of reactive nitrogen species (RNS) is a potent cytostatic and cytotoxic defense mechanism against intracellular pathogens. Nevertheless, the protective role of RNS during Mtb infection remains controversial. Here we use an anti-nitrotyrosine antibody as a readout to study nitration output by the zebrafish host during early mycobacterial pathogenesis. We found that recognition of Mycobacterium marinum, a close relative of Mtb, was sufficient to induce a nitrosative defense mechanism in a manner dependent on MyD88, the central adaptor protein in Toll like receptor (TLR) mediated pathogen recognition. However, this host response was attenuated by mycobacteria via a virulence mechanism independent of the well-characterized RD1 virulence locus. Our results indicate a mechanism of pathogenic mycobacteria to circumvent host defense in vivo. Shifting the balance of host-pathogen interactions in favor of the host by targeting this virulence mechanism may help to alleviate the problem of infection with Mtb strains that are resistant to multiple drug treatments

Does practicing hatha yoga satisfy recommendations for intensity of physical activity which improves and maintains health and cardiovascular fitness?

Background: Little is known about the metabolic and heart rate responses to a typical hatha yoga session. The purposes of this study were 1) to determine whether a typical yoga practice using various postures meets the current recommendations for levels of physical activity required to improve and maintain health and cardiovascular fitness; 2) to determine the reliability of metabolic costs of yoga across sessions; 3) to compare the metabolic costs of yoga practice to those of treadmill walking. Methods: In this observational study, 20 intermediate-to-advanced level yoga practitioners, age 31.4 ± 8.3 years, performed an exercise routine inside a human respiratory chamber (indirect calorimeter) while wearing heart rate monitors. The exercise routine consisted of 30 minutes of sitting, 56 minutes of beginner-level hatha yoga administered by video, and 10 minutes of treadmill walking at 3.2 and 4.8 kph each. Measures were mean oxygen consumption (VO2), heart rate (HR), percentage predicted maximal heart rate (%MHR), metabolic equivalents (METs), and energy expenditure (kcal). Seven subjects repeated the protocol so that measurement reliability could be established. Results: Mean values across the entire yoga session for VO2, HR, %MHR, METs, and energy/min were 0.6 L/kg/min; 93.2 beats/min; 49.4%; 2.5; and 3.2 kcal/min; respectively. Results of the ICCs (2,1) for mean values across the entire yoga session for kcal, METs, and %MHR were 0.979 and 0.973, and 0.865, respectively. Conclusion: Metabolic costs of yoga averaged across the entire session represent low levels of physical activity, are similar to walking on a treadmill at 3.2 kph, and do not meet recommendations for levels of physical activity for improving or maintaining health or cardiovascular fitness. Yoga practice incorporating sun salutation postures exceeding the minimum bout of 10 minutes may contribute some portion of sufficiently intense physical activity to improve cardio-respiratory fitness in unfit or sedentary individuals. The measurement of energy expenditure across yoga sessions is highly reliable

15-PGJ2, but not thiazolidinediones, inhibits cell growth, induces apoptosis, and causes downregulation of Stat3 in human oral SCCa cells

Activation of peroxisome proliferator-activated receptor gamma (PPARγ) has been linked to induction of differentiation, cell growth inhibition and apoptosis in several types of human cancer. However, the possible effects of PPARγ agonists on human oral squamous cell carcinoma have not yet been reported. In this study, treatment with 15-deoxy-Δ12,14-PGJ2 (15-PGJ2), a natural PPARγ ligand, induced a significant reduction of oral squamous cell carcinoma cell growth, which was mainly attributed to upregulation of apoptosis. Interestingly, rosiglitazone and ciglitazone, two members of the thiazolidinedione family of PPARγ activators, did not exert a growth inhibitory effect. Given the critical role that the oncogene signal transducer and activator of transcription 3 (Stat3) plays in head and neck carcinogenesis, its potential regulation by PPARγ ligands was also examined. Treatment of oral squamous cell carcinoma cells with 15-PGJ2 induced an initial reduction and eventual elimination of both phosphorylated and unphosphorylated Stat3 protein levels. In contrast, other PPARγ did not induce similar effects. Our results provide the first evidence of significant antineoplastic effects of 15-PGJ2 on human oral squamous cell carcinoma cells, which may be related to downmodulation of Stat3 and are at least partly mediated through PPARγ-independent events

Endophyte Microbiome Diversity in Micropropagated Atriplex canescens and Atriplex torreyi var griffithsii

Microbial diversity associated with micropropagated Atriplex species was assessed using microscopy, isolate culturing, and sequencing. Light, electron, and confocal microscopy revealed microbial cells in aseptically regenerated leaves and roots. Clone libraries and tag-encoded FLX amplicon pyrosequencing (TEFAP) analysis amplified sequences from callus homologous to diverse fungal and bacterial taxa. Culturing isolated some seed borne endophyte taxa which could be readily propagated apart from the host. Microbial cells were observed within biofilm-like residues associated with plant cell surfaces and intercellular spaces. Various universal primers amplified both plant and microbial sequences, with different primers revealing different patterns of fungal diversity. Bacterial and fungal TEFAP followed by alignment with sequences from curated databases revealed 7 bacterial and 17 ascomycete taxa in A. canescens, and 5 bacterial taxa in A. torreyi. Additional diversity was observed among isolates and clone libraries. Micropropagated Atriplex retains a complex, intimately associated microbiome which includes diverse strains well poised to interact in manners that influence host physiology. Microbiome analysis was facilitated by high throughput sequencing methods, but primer biases continue to limit recovery of diverse sequences from even moderately complex communities

Host-Adaptation of Francisella tularensis Alters the Bacterium's Surface-Carbohydrates to Hinder Effectors of Innate and Adaptive Immunity

The gram-negative bacterium Francisella tularensis survives in arthropods, fresh water amoeba, and mammals with both intracellular and extracellular phases and could reasonably be expected to express distinct phenotypes in these environments. The presence of a capsule on this bacterium has been controversial with some groups finding such a structure while other groups report that no capsule could be identified. Previously we reported in vitro culture conditions for this bacterium which, in contrast to typical methods, yielded a bacterial phenotype that mimics that of the bacterium's mammalian, extracellular phase.SDS-PAGE and carbohydrate analysis of differentially-cultivated F. tularensis LVS revealed that bacteria displaying the host-adapted phenotype produce both longer polymers of LPS O-antigen (OAg) and additional HMW carbohydrates/glycoproteins that are reduced/absent in non-host-adapted bacteria. Analysis of wildtype and OAg-mutant bacteria indicated that the induced changes in surface carbohydrates involved both OAg and non-OAg species. To assess the impact of these HMW carbohydrates on the access of outer membrane constituents to antibody we used differentially-cultivated bacteria in vitro to immunoprecipitate antibodies directed against outer membrane moieties. We observed that the surface-carbohydrates induced during host-adaptation shield many outer membrane antigens from binding by antibody. Similar assays with normal mouse serum indicate that the induced HMW carbohydrates also impede complement deposition. Using an in vitro macrophage infection assay, we find that the bacterial HMW carbohydrate impedes TLR2-dependent, pro-inflammatory cytokine production by macrophages. Lastly we show that upon host-adaptation, the human-virulent strain, F. tularensis SchuS4 also induces capsule production with the effect of reducing macrophage-activation and accelerating tularemia pathogenesis in mice.F. tularensis undergoes host-adaptation which includes production of multiple capsular materials. These capsules impede recognition of bacterial outer membrane constituents by antibody, complement, and Toll-Like Receptor 2. These changes in the host-pathogen interface have profound implications for pathogenesis and vaccine development