Involvement of miRNAs in the Differentiation of Human Glioblastoma Multiforme Stem-Like Cells

Glioblastoma multiforme (GBM)-initiating cells (GICs) represent a tumor subpopulation with neural stem cell-like properties that is responsible for the development, progression and therapeutic resistance of human GBM. We have recently shown that blockade of NFκB pathway promotes terminal differentiation and senescence of GICs both in vitro and in vivo, indicating that induction of differentiation may be a potential therapeutic strategy for GBM. MicroRNAs have been implicated in the pathogenesis of GBM, but a high-throughput analysis of their role in GIC differentiation has not been reported. We have established human GIC cell lines that can be efficiently differentiated into cells expressing astrocytic and neuronal lineage markers. Using this in vitro system, a microarray-based high-throughput analysis to determine global expression changes of microRNAs during differentiation of GICs was performed. A number of changes in the levels of microRNAs were detected in differentiating GICs, including over-expression of hsa-miR-21, hsa-miR-29a, hsa-miR-29b, hsa-miR-221 and hsa-miR-222, and down-regulation of hsa-miR-93 and hsa-miR-106a. Functional studies showed that miR-21 over-expression in GICs induced comparable cell differentiation features and targeted SPRY1 mRNA, which encodes for a negative regulator of neural stem-cell differentiation. In addition, miR-221 and miR-222 inhibition in differentiated cells restored the expression of stem cell markers while reducing differentiation markers. Finally, miR-29a and miR-29b targeted MCL1 mRNA in GICs and increased apoptosis. Our study uncovers the microRNA dynamic expression changes occurring during differentiation of GICs, and identifies miR-21 and miR-221/222 as key regulators of this process.     

Anthropometric and Micronutrient Status of School-Children in an Urban West Africa Setting: A Cross-Sectional Study in Dakar (Senegal)

Background

Urban areas in West Africa are not immune to undernutrition with recent urbanization and high food prices being important factors. School children often have a poor nutritional status, potentially affecting their health and schooling performance. Yet, generally school children do not benefit from nutrition programs. The objective of the study was to assess the anthropometric and micronutrient status of children from state schools in the Dakar area.

Methods

School children (n = 604) aged from 5 to 17 y (52.5% girls, 47.5% ≥10 y) were selected through a two-stage random cluster sample of children attending urban primary state schools in the Dakar area (30 schools × 20 children). The prevalence of stunting (height-for-age<−2 z-scores) and thinness (BMI-for-age<−2 z-scores, WHO 2006, and three grades of thinness corresponding to BMI of 18.5, 17.0 and 16.0 kg/m2 in adults) were calculated from weight and height. Hemoglobin, plasma concentrations of ferritin (FER), transferrin receptors (TfR), retinol binding protein (RBP), and zinc, and urinary iodine concentrations were measured. Correction factors were used for FER and RBP in subjects with inflammation determined with C-reactive protein and α1-acid-glycoprotein.

Results

4.9% of children were stunted, 18.4% were thin, 5.6% had severe thinness (BMI-for-age<−3 z-scores). Only one child had a BMI-for-age>2 z-scores. Prevalence of anemia, iron deficiency and iron deficiency anemia was 14.4%, 39.1% and 10.6% respectively. 3.0% had vitamin A deficiency, 35.9% a marginal vitamin A status, and 25.9% zinc deficiency. Urinary iodine was <50 µg/L in 7.3% of children and ≥200 µg/L in 22.3%. The prevalence of marginal vitamin A, zinc deficiency, high TfR was significantly higher in boys than in girls (P<0.05). Height-for-age and retinol were significantly lower in participants ≥10 y and <10 y respectively.

Conclusion

Undernutrition, especially thinness, iron and zinc deficiencies in school children in the Dakar area requires special targeted nutrition interventions.     

Do Shade-Grown Coffee Plantations Pose a Disease Risk for Wild Birds?

Shade-grown coffee plantations are often promoted as a conservation strategy for wild birds. However, these agro-ecosystems are actively managed for food production, which may alter bird behaviors or interactions that could change bird health, compared to natural forest. To examine whether there is a difference between the health parameters of wild birds inhabiting shade-grown coffee plantations and natural forest, we evaluated birds in Costa Rica for (1) their general body condition, (2) antibodies to pathogens, (paramyxovirus and Mycoplasma spp.), and (3) the prevalence and diversity of endo-, ecto-, and hemoparasites. We measured exposure to Mycoplasma spp. and paramyxovirus because these are pathogens that could have been introduced with domestic poultry, one mechanism by which these landscapes could be detrimental to wild birds. We captured 1,561 birds representing 75 species. Although seasonal factors influenced body condition, we did not find bird general body condition to be different. A total of 556 birds of 31 species were tested for antibodies against paramyxovirus-1. Of these, five birds tested positive, four of which were from shade coffee. Out of 461 other tests for pathogens (for antibodies and nucleotide detection), none were positive. Pterolichus obtusus, the feather mite of chickens, was found on 15 birds representing two species and all were from shade-coffee plantations. Larvated eggs of Syngamus trachea, a nematode typically associated with chickens, were found in four birds captured in shade coffee and one captured in forest. For hemoparasites, a total of 1,121 blood smears from 68 bird species were examined, and only one species showed a higher prevalence of infection in shade coffee. Our results indicate that shade-coffee plantations do not pose a significant health risk to forest birds, but at least two groups of pathogens may deserve further attention: Haemoproteus spp. and the diversity and identity of endoparasites.     

A Type IV Pilus Mediates DNA Binding during Natural Transformation in Streptococcus pneumoniae

Natural genetic transformation is widely distributed in bacteria and generally occurs during a genetically programmed differentiated state called competence. This process promotes genome plasticity and adaptability in Gram-negative and Gram-positive bacteria. Transformation requires the binding and internalization of exogenous DNA, the mechanisms of which are unclear. Here, we report the discovery of a transformation pilus at the surface of competent Streptococcus pneumoniae cells. This Type IV-like pilus, which is primarily composed of the ComGC pilin, is required for transformation. We provide evidence that it directly binds DNA and propose that the transformation pilus is the primary DNA receptor on the bacterial cell during transformation in S. pneumoniae. Being a central component of the transformation apparatus, the transformation pilus enables S. pneumoniae, a major Gram-positive human pathogen, to acquire resistance to antibiotics and to escape vaccines through the binding and incorporation of new genetic material.     

In Vivo Study of Spherical Gold Nanoparticles: Inflammatory Effects and Distribution in Mice

Objectives

Gold nanoparticles (AuNPs) of 21 nm have been previously well characterized in vitro for their capacity to target macrophages via active uptake. However, the short-term impact of such AuNPs on physiological systems, in particular resident macrophages located in fat tissue in vivo, is largely unknown. This project investigated the distribution, organ toxicity and changes in inflammatory cytokines within the adipose tissue after mice were exposed to AuNPs.

Methods

Male C57BL/6 mice were injected intraperitoneally (IP) with a single dose of AuNPs (7.85 μg AuNPs/g). Body weight and energy intake were recorded daily. Tissues were collected at 1 h, 24 h and 72 h post-injection to test for organ toxicity. AuNP distribution was examined using electron microscopy. Proinflammatory cytokine expression and macrophage number within the abdominal fat pad were determined using real-time PCR.

Results

At 72 hours post AuNP injection, daily energy intake and body weight were found to be similar between Control and AuNP treated mice. However, fat mass was significantly smaller in AuNP-treated mice. Following IP injection, AuNPs rapidly accumulated within the abdominal fat tissue and some were seen in the liver. A reduction in TNFα and IL-6 mRNA levels in the fat were observed from 1 h to 72 h post AuNP injection, with no observable changes in macrophage number. There was no detectable toxicity to vital organs (liver and kidney).

Conclusion

Our 21 nm spherical AuNPs caused no measurable organ or cell toxicity in mice, but were correlated with significant fat loss and inhibition of inflammatory effects. With the growing incidence of obesity and obesity-related diseases, our findings offer a new avenue for the potential development of gold nanoparticles as a therapeutic agent in the treatment of such disorders.     

Direct and Indirect Effects of Climate on Demography and Early Growth of Pinus sylvestris at the Rear Edge: Changing Roles of Biotic and Abiotic Factors

Global change triggers shifts in forest composition, with warming and aridification being particularly threatening for the populations located at the rear edge of the species distributions. This is the case of Scots pine (Pinus sylvestris) in the Mediterranean Basin where uncertainties in relation to its dynamics under these changing scenarios are still high. We analysed the relative effect of climate on the recruitment patterns of Scots pine and its interactions with local biotic and abiotic variables at different spatial scales. Number of seedlings and saplings was surveyed, and their annual shoot growth measured in 96 plots located across altitudinal gradients in three different regions in the Iberian Peninsula. We found a significant influence of climate on demography and performance of recruits, with a non-linear effect of temperature on the presence of juveniles, and a positive effect of precipitation on their survival. Abundance of juveniles of P. sylvestris that underwent their first summer drought was skewed towards higher altitudes than the altitudinal mean range of the conspecific adults and the optimum elevation for seedlings'' emergence. At local level, light availability did not influence juveniles'' density, but it enhanced their growth. Biotic interactions were found between juveniles and the herb cover (competition) and between the number of newly emerged seedlings and shrubs (facilitation). Results also highlighted the indirect effect that climate exerts over the local factors, modulating the interactions with the pre-existing vegetation that were more evident at more stressful sites. This multiscale approach improves our understanding of the dynamics of these marginal populations and some management criteria can be inferred to boost their conservation under the current global warming.     

Expression of the Legume-Specific Nod Factor Receptor Proteins Alters Developmental and Immune Responses in Rice

Plant Molecular Biology Reporter - Legumes form symbiosis with rhizobia, which fix nitrogen for the benefit of host plant in return for carbon resources. Development of this unique symbiosis in...     

The interplay between local and landscape scales on the density of pond-dwelling anurans in subtropical grasslands

We investigated the role of local and landscape environmental variables on anurans density classified as habitat specialists and generalists in grassland landscapes, known as South Brazilian grasslands (SBG). In this region, we surveyed 187 ponds distributed over 40 landscape sampling units. For each pond, 31 local environmental variables were measured. Each landscape sampling unit was embedded within a larger regional sampling unit with different landscape properties. For each landscape and regional sampling units, 16 landscape metrics were extracted from a land cover and use map. We recorded 35 species, eleven of which are specialists in the SBG. The specialists were affected by 11 local and 2 landscape environmental variables, while generalists were affected by 14 local and one landscape environmental variable. Thus, specialists and generalists presented different relationships with local and landscape variables, but in general local variables had a greater influence on the density of anurans than the landscape variables. However, the landscape indirectly influenced local variables because higher quality ponds were in landscapes with higher percentages of natural habitat. In conclusion, reproductive sites with higher local quality and located within landscapes with higher percentages of natural grasslands are essential to conserve anurans in this habitat. Effective conservation of such sites would benefit from further studies that assess effects of land use and biotic integrity of ponds, which can help to determine (a) the relative effects of local habitat quality of ponds and (b) the effectiveness of protecting ponds and their local surroundings for anuran conservation in SBG. Abstract in Portuguese is available with online material.