snoRNPs Regulate Telomerase Activity in Neuroblastoma and Are Associated with Poor Prognosis

Amplification of the MYCN oncogene is strongly associated with poor prognosis in neuroblastoma (NB). In addition to MYCN amplification, many studies have focused on identifying patients with a poor prognosis based on gene expression profiling. The majority of prognostic signatures today are comprised of large gene lists limiting their clinical application. In addition, although of prognostic significance,most of these signatures fail to identify cellular processes that can explain their relation to prognosis. Here, we determined prognostically predictive genes in a data set containing 251 NBs. Gene Ontology analysis was performed on significant genes with a positive hazard ratio to search for cellular processes associated with poor prognosis. An enrichment in ribonucleoproteins (RNPs) was found. Genes involved in the stabilization and formation of the central small nucleolar RNP (snoRNP) complex were scrutinized using a backward conditional Cox regression resulting in an snoRNP signature consisting of three genes: DKC1, NHP2, and GAR1. The snoRNP signature significantly and independently predicted prognosis when compared to the established clinical risk factors. Association of snoRNP protein expression and prognosis was confirmed using tissue microarrays. Knockdown of snoRNP expression in NB cell lines resulted in reduced telomerase activity and an increase in anaphase bridge frequency. In addition, in patient material, expression of the snoRNP complex was significantly associated with telomerase activity, occurrence of segmental aberrations, and expression-based measurements of chromosomal instability. Together, these results underscore the prognostic value of snoRNP complex expression in NB and suggest a role for snoRNPs in telomere maintenance and genomic stability.     

Alta prevalencia de obesidad en una población laboral en España

Background and objectivesTo report the prevalence of obesity in a Spanish working population and its changes in recent years.Material and methodsData were collected from routine medical examinations performed on workers by a national mutual insurance society for occupational accidents and diseases (Ibermutuamur). A structured questionnaire was completed and physical examinations were performed. Overweight was defined as BMI ranging from 25 and 29.9, obesity as BMI of 30-39.9, and morbid obesity as BMI ≥ 40 kg/m².ResultsData from 1,336,055 medical examinations performed from May 2004 to November 2007 were collected. Prevalence rates in the population examined in 2004 (n = 230,684; 73% males; average age, 36.4 years) were: morbid obesity, 0.5% (0.6% males, 0.5% females); obesity, 14.5% (17.0% males, 7.7% females); overweight, 38.4% (44.8% males, 21.3% females). Prevalence rates of obesity and overweight were higher in blue-collar workers (16.4% and 40.5% respectively) as compared to white-collar workers (10.9% and 34.4% respectively). There was a progressive increase in prevalence of obesity during the 4-year study (2004-2007) in both males (17.0%, 17.6%, 17.9%, 18.2%) and females (7.6%, 8.0%, 8.4%, 8.7%).ConclusionsPrevalence of obesity and overweight in the Spanish working population is high, especially in male blue-collar workers, and is increasing. There is a need to promote early prevention programs and specific treatments for obesity.     

Assessing the effects of native plants on the pollination of an exotic herb, the blueweed Echium vulgare (Boraginaceae)

The impacts of exotic plants on the pollination and reproductive success of natives have been widely reported; however, in spite of its importance for the invasive process, the role of native plants in the pollination and reproduction of exotic plants has been less explored. To fill this gap, we compared the patterns of pollination and reproductive success in the invasive herb Echium vulgare (Boraginaceae) between monospecific patches (only E. vulgare) and mixed patches (sympatry with native herbs Schizanthus hookeri and Stachys albicaulis) in central Chile. Using sample quadrats of 1 m × 2 m, we quantified the richness, diversity and visitation rate of flower visitors in 15-min observation intervals. We conducted an assay to assess the effect of the patch types (monospecific and mixed) and the isolation of flowers to visitors on both the fruit set and seed/ovule ratio. We showed that native plants favoured the richness of visitors of E. vulgare; however, they did not lead to increases in visitation rate. The reproductive success of E. vulgare did not show differences between contrasted patches; however, the isolation of visitors decreased the fruit set, although seed production was maintained in the absence of pollinators, presumably by an autogamous mechanism. Complementary to our main research focus, we assessed changes in pollination variables and reproductive output in two coflowering native plants that occur with E. vulgare, S. hookeri and S. albicaulis. Despite the fact that our correlational study did not allow us to dissect the effects of mixed patches and relative plant abundances on variables measured for natives, we observed an increase in pollinator richness in mixed patches for the two plants studied. These results suggest a potential facilitation for visitor richness of the exotic plant in coexistence with native plants, although this facilitation does not result in changes in the visit rate or on the reproductive success of any of the studied species. This work underlines the need for additional research on community levels that assess reciprocal effects on pollination between coflowering natives and exotics.     

Association of Pro-Inflammatory Cytokines and Iron Regulatory Protein 2 (IRP2) with Leishmania Burden in Canine Visceral Leishmaniasis

Leishmania infantum infection in humans and dogs can evolve with a wide range of clinical presentations, varying from asymptomatic infections to visceral leishmaniasis. We hypothesized that the immune response elicited by L. infantum infection could modulate whether the host will remain asymptomatic or progress to disease. A total of 44 dogs naturally infected with L. infantum were studied. Leishmania burden was estimated in the blood and spleen by qPCR. The expression of IFN-γ, TNF-α, IL-10 and Iron Regulatory Protein 2 (IRP2) were determined in the spleen by quantitative PCR. Sera cytokines were evaluated by ELISA. Dogs were grouped in quartiles according parasite burden. Increased expression of IFN-γ and TNF-α was associated with reduced Leishmania burden, whereas increased IL-10 and IRP2 expressions were associated with higher Leishmania load. Increased plasma albumin and IFN-γ expression explained 22.8% of the decrease in parasite burden in the spleen. These data confirm that lower IFN-γ response and higher IL-10 correlated with increased parasite load and severity of the visceral leishmaniasis in dogs. The balance between the branches of immune response and the intracellular iron availability could determine, in part, the course of Leishmania infection.     

Evaluation of Relapse-Free Survival in T3N0 Colon Cancer: The Role of Chemotherapy,a Multicentric Retrospective Analysis

Background

Adjuvant chemotherapy (AC) in Stage II Colon Cancer (CC) is still under debate. Choice should be based on patients and disease characteristics. According to guidelines AC should be considered in high-risk T3N0 patients. No data are available for better option in low-risk patients. The aim of the study is to retrospectively evaluate relapse-free survival (RFS) and disease-free survival (DFS) according to treatment received in T3N0 CC.

Methods

RFS and DFS are evaluated with Kaplan-Meier method. Multivariate Cox proportional hazard model was developed using stepwise regression, enter limit and remove limit were p = 0.10 and p = 0.15, respectively.

Results

834 patients with T3N0 CC were recruited. Median age was 69 (29–93), M/F 463/371, 335 low-risk patients (40.2%), 387 high-risk (46.4%), 112 unknown (13.4%); 127 (15.2%) patients showed symptoms at diagnosis. Median sampled lymph nodes were 15 (1–76); 353 (42.3%) patients were treated with AC. Median follow up was 5 years (range 3–24). The 5-years RFS was 78.4% and the 5-years DFS was 76.7%. At multivariate analysis symptoms, lymph nodes, and adjuvant chemotherapy were prognostic factors for RFS. AC is prognostic factor for all endpoints.In low-risk group 5-years RFS was 87.3% in treated patients and 74.7% in non-treated patients (p 0.03); in high-risk group was respectively 82.7% and 71.4% (p 0.005).

Conclusions

Data confirmed the role of known prognostic factors and suggest the relevance of adjuvant chemotherapy also in low-risk stage II T3N0 CC patients. However, the highest risk in low-risk subgroup should be identified to be submitted to AC.     

Optimization and Pharmacological Validation of a Leukocyte Migration Assay in Zebrafish Larvae for the Rapid In Vivo Bioactivity Analysis of Anti-Inflammatory Secondary Metabolites

Over the past decade, zebrafish (Danio rerio) have emerged as an attractive model for in vivo drug discovery. In this study, we explore the suitability of zebrafish larvae to rapidly evaluate the anti-inflammatory activity of natural products (NPs) and medicinal plants used in traditional medicine for the treatment of inflammatory disorders. First, we optimized a zebrafish assay for leukocyte migration. Inflammation was induced in four days post-fertilization (dpf) zebrafish larvae by tail transection and co-incubation with bacterial lipopolysaccharides (LPS), resulting in a robust recruitment of leukocytes to the zone of injury. Migrating zebrafish leukocytes were detected in situ by myeloperoxidase (MPO) staining, and anti-inflammatory activity was semi-quantitatively scored using a standardized scale of relative leukocyte migration (RLM). Pharmacological validation of this optimized assay was performed with a panel of anti-inflammatory drugs, demonstrating a concentration-responsive inhibition of leukocyte migration for both steroidal and non-steroidal anti-inflammatory drugs (SAIDs and NSAIDs). Subsequently, we evaluated the bioactivity of structurally diverse NPs with well-documented anti-inflammatory properties. Finally, we further used this zebrafish-based assay to quantify the anti-inflammatory activity in the aqueous and methanolic extracts of several medicinal plants. Our results indicate the suitability of this LPS-enhanced leukocyte migration assay in zebrafish larvae as a front-line screening platform in NP discovery, including for the bioassay-guided isolation of anti-inflammatory secondary metabolites from complex NP extracts.     

Microbial Volatile Organic Compounds Produced by Bacillus amyloliquefaciens GB03 Ameliorate the Effects of Salt Stress in Mentha piperita Principally Through Acetoin Emission

Journal of Plant Growth Regulation - We investigated the effects of microbial volatile organic compounds (mVOC) emitted by Bacillus amyloliquefaciens GB03 on Mentha piperita growing under different...     

Role of Sonic hedgehog signaling in cell cycle,oxidative stress,and autophagy of temozolomide resistant glioblastoma

The first-line chemotherapy treatment for Glioblastoma (GBM) - the most aggressive and frequent brain tumor - is temozolomide (TMZ). The Sonic hedgehog (SHH) pathway is involved with GBM tumorigenesis and TMZ chemoresistance. The role of SHH pathway inhibition in the potentiation of TMZ's effects using T98G, U251, and GBM11 cell lines is investigated herein. The combination of GANT-61 and TMZ over 72 hr suggested a synergistic effect. All TMZ-resistant cell lines displayed a significant decrease in cell viability, increased DNA fragmentation and loss of membrane integrity. For T98G cells, G₂/M arrest was observed, while U251 cells presented a significant increase in reactive oxygen species production and catalase activity. All the cell lines presented acidic vesicles formation correlated to Beclin-1 overexpression. The combined treatment also enhanced GLI1 expression, indicating the presence of select resistant cells. The selective inhibition of the SHH pathway potentiated the cytotoxic effect of TMZ, thus becoming a promising in vitro strategy for GBM treatment.     

Species delimitation based on integrative approach suggests reallocation of genus in Hypostomini catfish (Siluriformes,Loricariidae)

Hydrobiologia - Integrative approaches are particularly useful to resolve taxonomic uncertainties in species-rich groups that have undergone explosive radiation, such as Hypostomini (suckermouth...     

Catalytic activity of iron phthalocyanine for the oxidation of thiocyanate and L-cysteine anchored on Au(111) clusters

ABSTRACT

We studied the oxidation reactions of thiocyanate and L-cysteine on iron phthalocyanine (FePc) coupled via a bridging ligand of the 4-mercatopyridine (4MP) type to a gold cluster (Au₂₆), aiming to simulate a modified gold electrode. Theoretical models have been used based on the framework of density functional theory. Several mechanistic pathways are explored for the study of these reactions, finding that the most favorable mechanism involves an electron transfer process as the rate-determining step. Along the process, the ability of the gold cluster to act as an electron acceptor facilitating the reactions was detected. In addition, the proposed models presented a correlation between the energy obtained for the rate-determining step of the reaction and the experimental oxidation potentials of the thiocyanate and L-cysteine.