Subgroup-specific structural variation across 1,000 medulloblastoma genomes

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4 alpha. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kappa B signalling in Group 4, suggest future avenues for rational, targeted therapy.

Two new genera, ten new species and new records of Amazonian Stygnidae Simon, 1879 (Opiliones: Laniatores)

As a result of recent expeditions to two mountains in the Amazon basin, Tapirapeco and Pico da Neblina, two new genera of Stygnidae, Imeri g. nov. (type species Imeri lomanhungae sp. nov.) and Jime g. nov. (type species Jime chifrudo sp. nov.), and ten new species are described: Auranus hehu sp. nov., Auranus tepui sp. nov., Imeri lomanhungae sp. nov.; Jime chifrudo sp. nov.; Stygnoplus ianomami sp. nov.; Stygnus magalhaesi sp. nov.; Stygnoplus neblina sp. nov.; Stygnoplus tapirapeco sp. nov.; Stygnus nogueirai sp. nov., Stygnus kuryi sp. nov.. Additionally, new distributional records in Amazonas (Brazil) are presented for Stygnidius guerinii Soerensen, 1932, Minax tetraspinosus Pinto-da-Rocha, 1997 and Protimesius longipalpis (Roewer, 1943). Keys for genera of Heterostygninae and Stygninae are provided.

An Extreme Case of Plant-Insect Codiversification: Figs and Fig-Pollinating Wasps

It is thought that speciation in phytophagous insects is often due to colonization of novel host plants, because radiations of plant and insect lineages are typically asynchronous. Recent phylogenetic comparisons have supported this model of diversification for both insect herbivores and specialized pollinators. An exceptional case where contemporaneous plant-insect diversification might be expected is the obligate mutualism between fig trees (Ficus species, Moraceae) and their pollinating wasps (Agaonidae, Hymenoptera). The ubiquity and ecological significance of this mutualism in tropical and subtropical ecosystems has long intrigued biologists, but the systematic challenge posed by >750 interacting species pairs has hindered progress toward understanding its evolutionary history. In particular, taxon sampling and analytical tools have been insufficient for large-scale cophylogenetic analyses. Here, we sampled nearly 200 interacting pairs of fig and wasp species from across the globe. Two supermatrices were assembled: on an average, wasps had sequences from 77% of 6 genes (5.6 kb), figs had sequences from 60% of 5 genes (5.5 kb), and overall 850 new DNA sequences were generated for this study. We also developed a new analytical tool, Jane 2, for event-based phylogenetic reconciliation analysis of very large data sets. Separate Bayesian phylogenetic analyses for figs and fig wasps under relaxed molecular clock assumptions indicate Cretaceous diversification of crown groups and contemporaneous divergence for nearly half of all fig and pollinator lineages. Event-based cophylogenetic analyses further support the codiversification hypothesis. Biogeographic analyses indicate that the present-day distribution of fig and pollinator lineages is consistent with a Eurasian origin and subsequent dispersal, rather than with Gondwanan vicariance. Overall, our findings indicate that the fig-pollinator mutualism represents an extreme case among plant-insect interactions of coordinated dispersal and long-term codiversification.

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous gamma H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the alpha-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-alpha primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.

An ancient founder mutation in PROKR2 impairs human reproduction

Congenital gonadotropin-releasing hormone (GnRH) deficiency manifests as absent or incomplete sexual maturation and infertility. Although the disease exhibits marked locus and allelic heterogeneity, with the causal mutations being both rare and private, one causal mutation in the prokineticin receptor, PROKR2 L173R, appears unusually prevalent among GnRH-deficient patients of diverse geographic and ethnic origins. To track the genetic ancestry of PROKR2 L173R, haplotype mapping was performed in 22 unrelated patients with GnRH deficiency carrying L173R and their 30 first-degree relatives. The mutations age was estimated using a haplotype-decay model. Thirteen subjects were informative and in all of them the mutation was present on the same approximate to 123 kb haplotype whose population frequency is 10. Thus, PROKR2 L173R represents a founder mutation whose age is estimated at approximately 9000 years. Inheritance of PROKR2 L173R-associated GnRH deficiency was complex with highly variable penetrance among carriers, influenced by additional mutations in the other PROKR2 allele (recessive inheritance) or another gene (digenicity). The paradoxical identification of an ancient founder mutation that impairs reproduction has intriguing implications for the inheritance mechanisms of PROKR2 L173R-associated GnRH deficiency and for the relevant processes of evolutionary selection, including potential selective advantages of mutation carriers in genes affecting reproduction.

A magia desencantada: Henry James e o caso de "Os amigos dos amigos"

Por meio do exame do conto "Os amigos dos amigos" ("The friends of the friends"), de Henry James, bem como de seu processo de criação, este trabalho investiga a categoria do duplo confrontando as suas fontes primitivas com sua adoção na narrativa moderna - um confronto que nos permite sugerir uma chave de interpretação para a ficção jamesiana, e ainda discutir a presença do sobrenatural numa sociedade que privilegia o espetáculo, a publicidade, a novidade, o consumo e o progresso.

Tentativa de balanço: entrevista com Iumna Maria Simon

Narrando a sua formação intelectual, Iumna Maria Simon analisa a situação da crítica literária na universidade e fora dela, a poesia contemporânea e as condições da leitura da obra literária hoje. A entrevista expõe o modo como desenvolveu sua compreensão da literatura brasileira mais recente e como organiza seu foco crítico e suas referências teóricas, enquanto professora e crítica.

O modelo keynesiano de James Meade

Este artigo reavalia o "modelo simplificado" da Teoria Geral de Keynes elaborado por James Meade e procura complementar alguns dos argumentos teóricos que Meade deixou apenas indicados. O artigo também responde às solicitações de Frisch a Meade, quanto à explicação do significado de estabilidade e à explicitação dos pressupostos que garantem suas conclusões. Além disso, apresenta alguns dos cálculos não desenvolvidos por Meade, e, quando necessário, suas devidas correções.