Weighing ependymoma as an epigenetic disease.

INTRODUCTION: Ependymoma is the third most common malignant pediatric brain tumor. Although the biology that drives ependymoma is slowly being unraveled, the ability to translate these findings to clinical care remains an ongoing challenge. Epigenetic alterations appear to play a central role in the development of molecular classification of ependymoma. METHODS: We reviewed the published literature available describing genetic and epigenetic underpinnings of ependymoma that have been reported to date and have summarized the information regarding genetic drivers of ependymoma that may point us toward therapeutic strategies. RESULTS: Ependymoma is a molecularly heterogeneous disease which has now been divided into at least nine distinct molecular subtypes based on DNA methylation and gene expression profiling. DNA methylation has emerged as an effective tool for classification of brain tumors alongside histopathology and other molecular diagnostics. There have been large retrospective cohorts describing molecular subgroup identity as a powerful independent predictor of outcome. There is limited published data on prospective trials to date however this is forthcoming which will lead to molecular stratification in the next generation of clinical studies. CONCLUSION: This is a review of recent advancements in our understanding of the epigenetic basis of ependymoma and discussion of how these findings reveal potential therapeutic opportunities.

Invited Review: The role and contribution of transcriptional enhancers in brain cancer.

Genetic alterations identified across several paediatric and adult brain tumours reveal recurrent disruption of active chromatin landscapes and dysregulation of transcriptional programmes. Noncoding elements, specifically enhancers, are central to these mechanisms, and are influenced by developmental and neural gene regulatory signatures. Epigenomic and transcriptomic methods and techniques have facilitated detection of active enhancers, and characterization of brain tumours integrated with genomic structural information. These datasets have provided new insights into the mechanisms of transcriptional control that are profoundly altered in childhood and adult brain cancer; offering new ideas and molecular targets for therapeutic intervention. This review summarizes recent advances in our understanding of active transcriptional programmes of brain cancer, their impact on tumour development, and research areas for further exploration.

Are aposematic signals honest? A review.

We explore the relevance of honest signalling theory to the evolution of aposematism. We begin with a general consideration of models of signal stability, with a focus on the Zahavian costly signalling framework. Next, we review early models of signalling in the context of aposematism (some that are consistent and some inconsistent with costly honest signalling). We focus on controversies surrounding the idea that aposematic signals are handicaps in a Zahavian framework. Then, we discuss how the alignment of interests between signaller and predator influences the evolution of aposematism, highlight the distinction between qualitative and quantitative honesty and review theory and research relevant to these categories. We also review recent theoretical treatments of the evolution of aposematism that have focused on honest signalling as well as empirical research on a variety of organisms, including invertebrates and frogs. Finally, we discuss future directions for empirical and theoretical research in this area.

The Chinese hamster FANCG/XRCC9 mutant NM3 fails to express the monoubiquitinated form of the FANCD2 protein, is hypersensitive to a range of DNA damaging agents and exhibits a normal level of spontaneous sister chromatid exchange.

Fanconi anemia (FA) is a human autosomal disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinking agents such as mitomycin C and diepoxybutane. Six FA genes have been cloned including a gene designated XRCC9 (for X-ray Repair Cross Complementing), isolated using a mitomycin C-hypersensitive Chinese hamster cell mutant termed UV40, and subsequently found to be identical to FANCG. A nuclear complex containing the FANCA, FANCC, FANCE, FANCF and FANCG proteins is needed for the activation of a sixth FA protein FANCD2. When monoubiquitinated, the FANCD2 protein co-localizes with the breast cancer susceptibility protein BRCA1 in DNA damage induced foci. In this study, we have assigned NM3, a nitrogen mustard-hypersensitive Chinese hamster mutant to the same genetic complementation group as UV40. NM3, like human FA cell lines (but unlike UV40) exhibits a normal spontaneous level of sister chromatid exchange. We show that both NM3 and UV40 are also hypersensitive to other DNA crosslinking agents (including diepoxybutane and chlorambucil) and to non-crosslinking DNA damaging agents (including bleomycin, streptonigrin and EMS), and that all these sensitivities are all corrected upon transfection of the human FANCG/XRCC9 cDNA. Using immunoblotting, NM3 and UV40 were found not to express the active monoubiquitinated isoform of the FANCD2 protein, although expression of the FANCD-L isoform was restored in the FANCG cDNA transformants, correlating with the correction of mutagen-sensitivity. These data indicate that cellular resistance to these DNA damaging agents requires FANCG and that the FA gene pathway, via its activation of FANCD2 and that protein's subsequent interaction with BRCA1, is involved in maintaining genomic stability in response not only to DNA interstrand crosslinks but also a range of other DNA damages including DNA strand breaks. NM3 and other "FA-like" Chinese hamster mutants should provide an important resource for the study of these processes in mammalian cells.

Caracterizaçao e perfil de sensibilidade de 45 amostras de Staphylococcus coagulase negativa de origem hospitalar / Sensitivity and characteristics of 45 strains coagulase-negative Staphylococcus sp isolated from clinical specimens

No presente trabalho foram analisadas 45 amostras de Staphylococcus coagulase negativa isoladas de especimes clinicos, quanto a diversas caracteristicas e propriedades biologicas. Alem da classificaçao em especies, foram efetuados estudos sobre a sensibilidade a antimicrobianos e determinada a concentraçao minima inibitoria destas amostras frente a vancomicina e a oxacilina. Cinco especies foram identificadas pelo metodo convencional (Kloos & Schleifer, 1975) associado a alguns testes do Micrometodo Bactrey, e corresponderam: S.saprohyticus (6); S. epidermidis (20); S. hominis (4); S. haemolyticus (7); S. warnery (5). Tres amostras nao foram identificadas. Uma percentagem elevada (84,4 por cento ) de amostras apresentaram resistencia a penicilina, em menor grau, a canamicina (55,6 por cento ), gentamicina (48,9 por cento ), fosfomicina (44,4 por cento ) e, oxacilina e sulfametoxazol-trimetoprim (37,8 por cento ). Foram encontradas amostras (66,6 por cento ) multi-resistentes. Todas as amostras foram testadas quanto a produçao de beta-lactamase, 35 tiveram resultado positivo, das quais 20 eram S. epidermidis. Na determinaçao da concentraçao minima inibitoria a oxacilina apresentou uma percentagem de amostras resistentes (72,1 por cento ) bem maior que no teste de sensibilidade a antimicrobianos por difusao em agar frente a este antibiotico (39,5 por cento )

Calponin. Developmental isoforms and a low molecular weight variant.

Two-dimensional gel analysis of basic proteins in developing human smooth muscle identifies calponin as a prominent marker of the differentiated phenotype. Adult tissue (human and mouse) typically expresses up to four calponin isoforms, three of which appear sequentially during fetal development: adult myometrial cells express the same three isoforms in primary culture in vitro and these are down-regulated, in reverse order, during the subsequent modulation of phenotype. Monospecific, polyclonal antibodies against calponin identify a lower molecular weight variant of calponin (L-calponin) that is strongly and specifically expressed in adult smooth muscles of the human urogenital tract. L-calponin is down-regulated in benign smooth muscle derived tumors (leiomyoma) and is not expressed in primary cultures of normal uterine tissue.