Stem cells: implications in the development of brain tumors

Stem cells are characterized by their capacity for self-renewal, for giving rise to new cells in specific tissues, and for maintaining this capacity throughout the entire life of their host. Stem cells are pluripotent and maintain continuous production of neurons, astrocytes, and oligodendrocytes. Stem cells in brain tumors also proliferate, undergo self-renewal, and give rise to other poorly differentiated cells. Unlike non-tumor stem cells, tumor stem cells lack the normal mechanisms that regulate proliferation and differentiation, resulting in uncontrolled production and incomplete differentiation of tumor cells. Discovering the role of tumor stem cells in the brain has given us a new perspective about the molecular pathways involved in signaling and about oncogenesis in the central nervous system; it can also help us explain the high rate of recurrence of some tumors and the diffuse nature of glioblastomas. Ideally, this perspective can be expected to lead to better treatments. This article reviews the characteristics of non-tumor and tumor stem cells, emphasizing the importance of brain tumor stem cells in the pathogenesis of common brain tumors.     

Radiographic and Laser Fluorescence Methods Have No Benefits for Detecting Caries in Primary Teeth

Clinical guidelines advise that dentists take radiographs in children to detect caries lesions missed by visual inspection; however, due to the current low caries prevalence in most countries, we hypothesized that the adjunct methods of caries detection would not significantly improve the detection of primary molar lesions in comparison to visual inspection alone. We evaluated the performance of visual inspection, alone or in combination with radiographic and laser fluorescence pen (LFpen) methods, in detecting occlusal and approximal caries lesions in primary molars. Two examiners evaluated children who had sought dental treatment with these diagnostic strategies. The reference standard involved the temporary separation of approximal and operative interventions for occlusal surfaces. The sensitivity, specificity, accuracy and utility of diagnostic strategies were calculated. Simultaneous combined strategies increased sensitivities but decreased specificities. Furthermore, no differences were observed in accuracy and utility, parameters more influenced by caries prevalence. In conclusion, adjunct radiographic and laser fluorescence methods offer no benefits to the detection of caries in primary teeth in comparison to visual inspection alone; hence, present clinical guidelines should be re-evaluated.     

Molecular and epidemiological aspects of hepatitis C virus infection among crack cocaine users

The aim is to investigate the prevalence, risk factors, and hepatitis C virus (HCV) genotypes/subtypes among crack users in-treatment in Central Brazil. A cross-sectional survey in which 600 in-treatment crack users were interviewed and tested for anti-HCV Ab by enzyme-linked immunosorbent assay was conducted between August 2012 and April 2013. Anti-HCV-positive samples were also submitted for HCV RNA detection by polymerase chain reaction. Positive HCV RNA samples were genotyped by direct sequencing analysis of the NS5B region of the viral genome, followed by phylogenetic analysis. Of the total, 3.7% (95.0% CI, 2.4%-5.6%) were anti-HCV positive. Age over 40 years and history of injecting drugs were risk factors for HCV, while snorting cocaine was a protector variable. HCV RNA was detected in 14 of 22 anti-HCV-positive samples, and the genotypes 1 (n = 10) and 3 (n = 2), subtypes 1a (n = 7), 1b (n = 3), and 3a (n = 2) were identified. The HCV prevalence found among crack users is almost threefold that observed in the general population in Brazil supporting that this population is at higher risk for HCV. The findings of cocaine insufflation as a protective behavior for HCV infection in this population should be explored.     

Structural basis for targeting the chromatin repressor Sfmbt to Polycomb response elements

Polycomb group (PcG) protein complexes repress developmental regulator genes by modifying their chromatin. How different PcG proteins assemble into complexes and are recruited to their target genes is poorly understood. Here, we report the crystal structure of the core of the Drosophila PcG protein complex Pleiohomeotic (Pho)-repressive complex (PhoRC), which contains the Polycomb response element (PRE)-binding protein Pho and Sfmbt. The spacer region of Pho, separated from the DNA-binding domain by a long flexible linker, forms a tight complex with the four malignant brain tumor (4MBT) domain of Sfmbt. The highly conserved spacer region of the human Pho ortholog YY1 binds three of the four human 4MBT domain proteins in an analogous manner but with lower affinity. Comparison of the Drosophila Pho:Sfmbt and human YY1:MBTD1 complex structures provides a molecular explanation for the lower affinity of YY1 for human 4MBT domain proteins. Structure-guided mutations that disrupt the interaction between Pho and Sfmbt abolish formation of a ternary Sfmbt:Pho:DNA complex in vitro and repression of developmental regulator genes in Drosophila. PRE tethering of Sfmbt by Pho is therefore essential for Polycomb repression in Drosophila. Our results support a model where DNA tethering of Sfmbt by Pho and multivalent interactions of Sfmbt with histone modifications and other PcG proteins create a hub for PcG protein complex assembly at PREs.