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Inactivation of tumour-suppressor genes by homozygous deletion is a prototypic event in the cancer genome, yet such deletions often encompass neighbouring genes. We propose that homozygous deletions in such passenger genes can expose cancer-specific therapeutic vulnerabilities when the collaterally deleted gene is a member of a functionally redundant family of genes carrying out an essential function. The glycolytic gene enolase 1 ( ENO1 ) in the 1p36 locus is deleted in glioblastoma (GBM), which is tolerated by the expression of ENO2 . Here we show that short-hairpin-RNA-mediated silencing of ENO2 selectively inhibits growth, survival and the tumorigenic potential of ENO1 -deleted GBM cells, and that the enolase inhibitor phosphonoacetohydroxamate is selectively toxic to ENO1 -deleted GBM cells relative to ENO1 -intact GBM cells or normal astrocytes. The principle of collateral vulnerability should be applicable to other passenger-deleted genes encoding functionally redundant essential activities and provide an effective treatment strategy for cancers containing such genomic events. The ‘collateral’ homozygous deletion of essential redundant housekeeping genes in cancer genomes is shown to confer therapeutic vulnerability on cancer cells with the deletion, without affecting genomically intact normal non-cancerous cells, suggesting new therapeutic opportunities. A new type of anticancer target This Article introduces the concept of 'collateral damage' in cancer genomes as a possible basis for therapeutic strategies. Ronald DePinho and colleagues examine pairs of functionally redundant 'passenger' genes with 'housekeeping' roles, for example in cellular metabolism. They hypothesize that genetic deletions in cancer that encompass one such gene (as collateral damage caused by proximity to tumour-suppressor genes) may expose a selective vulnerability of cancer cells, but not normal cells, to pharmacological inhibition of the protein encoded by the second gene. They demonstrate this concept for the glycolytic enzymes ENO1 and ENO2. There is often homozygous deletion of the ENO1 gene on chromosome 1p36 in glioblastomas, which is shown here to render glioma cells sensitive to knockdown of ENO2 or to a small-molecule enolase inhibitor. The authors further analyse existing cancer genomics data sets for other examples of pairs of redundant housekeeping genes, one of which resides close to frequently deleted tumour-suppressor genes. They suggest that this concept may be generally applicable and could offer new therapeutic opportunities.

[...]Fig. 2 of this Corrigendum shows the corrected Fig. 3a, in which for the cell line U87, an additional non-targeting short hairpin RNA control (original lanes 7 and 8) was excised with the remaining halves of the blot and merged, which is now indicated by a dashed line.

Nature 488, 337–342 (2012); doi:10.1038/nature11331 In this Article, during the preparation of Figures 2d and 3a, we processed digital western blot scans to remove duplicate or otherwise irrelevant lanes from single-blot images. Although all excisions/mergers originated from the same gel, these figure constructions should have been explicitly pointed out.

Stenhelmoides Grouvelle is a Neotropical genus of Elmidae and although it exhibits a wide distribution, until now no larvae had been associated with adults of this genus. Larvae, very likely belonging to this genus, were associated based on co-occurrence with adults. Eleven larvae and nine adults were examined from ten localities at altitudes between 30 and 682 m a.s.l. in the Andean, Caribbean and Pacific regions in Colombia. Mature larvae of the Stenhelmoides rufulus (Hinton) are described and illustrated for the first time. A larval diagnosis for the genus is presented; body shape, distribution and form of setae and number of pleural sclerites are diagnostic characters for larvae of this genus. Comparative notes with similar larvae of other Elmidae genera are presented. The existing generic keys are updated to include larvae of Stenhelmoides . Comments on distribution and habitat of Stenhelmoides larvae are also provided. This work contributes to enhance the knowledge of Neotropical larvae, which have been described for only approximately 56% of genera and 8% of species of Elmidae.

Fil: Izquierdo, Andrea Elisa. Universidad Nacional de Tucumán. Instituto de Ecología Regional. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Ecología Regional; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentina

Background.  Five neuroinvasive Bacillus cereus infections (4 fatal) occurred in hospitalized patients with acute myelogenous leukemia (AML) during a 9-month period, prompting an investigation by infection control and public health officials. Methods.  Medical records of case-patients were reviewed and a matched case-control study was performed. Infection control practices were observed. Multiple environmental, food, and medication samples common to AML patients were cultured. Multilocus sequence typing was performed for case and environmental B cereus isolates. Results.  All 5 case-patients received chemotherapy and had early-onset neutropenic fevers that resolved with empiric antibiotics. Fever recurred at a median of 17 days (range, 9–20) with headaches and abrupt neurological deterioration. Case-patients had B cereus identified in central nervous system (CNS) samples by (1) polymerase chain reaction or culture or (2) bacilli seen on CNS pathology stains with high-grade B cereus bacteremia. Two case-patients also had colonic ulcers with abundant bacilli on autopsy. No infection control breaches were observed. On case-control analysis, bananas were the only significant exposure shared by all 5 case-patients (odds ratio, 9.3; P = .04). Five environmental or food isolates tested positive for B cereus, including a homogenized banana peel isolate and the shelf of a kitchen cart where bananas were stored. Multilocus sequence typing confirmed that all case and environmental strains were genetically distinct. Multilocus sequence typing-based phylogenetic analysis revealed that the organisms clustered in 2 separate clades. Conclusions.  The investigation of this neuroinvasive B cereus cluster did not identify a single point source but was suggestive of a possible dietary exposure. Our experience underscores the potential virulence of B cereus in immunocompromised hosts.

La Familia Elmidae incluye coleópteros acuáticos de tamaño pequeño a mediano. Suelen ser comunes en aguas corrientes con buen contenido de oxígeno, por lo cual se las utiliza como indicadoras de calidad de agua. Los élmidos tienen una distribución mundial, aunque se encuentran muy diversificados en la región Neotropical, con 46 géneros descriptos hasta la actualidad y aproximadamente 435 especies. En este trabajo se presenta un resumen de toda la información conocida de Elmidae para la región Neotropical. Se actualiza la distribución de los géneros y el número de especies conocidas para cada uno. Se provee el número de especies por países y una lista actualizada de especies con larvas conocidas. PALABRAS CLAVE. Coleópteros acuáticos. Elminae. Larainae. América del Sur. Elmidae, commonly called riffle beetles, includes small to medium sized aquatic beetles. Elmids are common in running waters with high oxygen content, making them good indicators of water quality. This family shows a worldwide distribution, being more diverse in the Neotropical region, with 46 described genera and about 435 species. This paper summarizes all known information about Elmidae from the Neotropical Region. This contribution presents updated data on the distribution of riffles beetles, the number of species described by genera and country, and a list of species with known larvae. KEY WORDS. Aquatic beetles. Elminae. Larainae. South America.

Elmidae, commonly called riffle beetles, includes small to medium sized aquatic beetles. Elmids are common in running waters with high oxygen content, making them good indicators of water quality. This family shows a worldwide distribution, being more diverse in the Neotropical region, with 46 described genera and about 435 species. This paper summarizes all known information about Elmidae from the Neotropical Region. This contribution presents updated data on the distribution of riffles beetles, the number of species described by genera and country, and a list of species with known larvae.Original Abstract: La Familia Elmidae incluye coleopteros acuaticos de tamano pequeno a mediano. Suelen ser comunes en aguas corrientes con buen contenido de oxigeno, por lo cual se las utiliza como indicadoras de calidad de agua. Los elmidos tienen una distribucion mundial, aunque se encuentran muy diversificados en la region Neotropical, con 46 generos descriptos hasta la actualidad y aproximadamente 435 especies. En este trabajo se presenta un resumen de toda la informacion conocida de Elmidae para la region Neotropical. Se actualiza la distribucion de los generos y el numero de especies conocidas para cada uno. Se provee el numero de especies por paises y una lista actualizada de especies con larvas conocidas.

Inactivation of tumour-suppressor genes by homozygous deletion is a prototypic event in the cancer genome, yet such deletions often encompass neighbouring genes. We propose that homozygous deletions in such passenger genes can expose cancer-specific therapeutic vulnerabilities when the collaterally deleted gene is a member of a functionally redundant family of genes carrying out an essential function. The glycolytic gene enolase 1 (ENO1) in the 1p36 locus is deleted in glioblastoma (GBM), which is tolerated by the expression of ENO2. Here we show that short-hairpin-RNA-mediated silencing of ENO2 selectively inhibits growth, survival and the tumorigenic potential of ENO1-deleted GBM cells, and that the enolase inhibitor phosphonoacetohydroxamate is selectively toxic to ENO1-deleted GBM cells relative to ENO1-intact GBM cells or normal astrocytes. The principle of collateral vulnerability should be applicable to other passenger-deleted genes encoding functionally redundant essential activities and provide an effective treatment strategy for cancers containing such genomic events.