Passenger deletions generate therapeutic vulnerabilities in cancer

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.     

Genome-wide association study identifies susceptibility loci for dengue shock syndrome at MICB and PLCE1

Hypovolemic shock (dengue shock syndrome (DSS)) is the most common life-threatening complication of dengue. We conducted a genome-wide association study of 2,008 pediatric cases treated for DSS and 2,018 controls from Vietnam. Replication of the most significantly associated markers was carried out in an independent Vietnamese sample of 1,737 cases and 2,934 controls. SNPs at two loci showed genome-wide significant association with DSS. We identified a susceptibility locus at MICB (major histocompatibility complex (MHC) class I polypeptide-related sequence B), which was within the broad MHC region on chromosome 6 but outside the class I and class II HLA loci (rs3132468, P(meta) = 4.41 × 10(-11), per-allele odds ratio (OR) = 1.34 (95% confidence interval: 1.23-1.46)). We identified associated variants within PLCE1 (phospholipase C, epsilon 1) on chromosome 10 (rs3765524, P(meta) = 3.08 × 10(-10), per-allele OR = 0.80 (95% confidence interval: 0.75-0.86)). We identify two loci associated with susceptibility to DSS in people with dengue, suggesting possible mechanisms for this severe complication of dengue.     

Summer monsoon and dust signals recorded in the Dasuopu firn core, central Himalayas

In September 1997, a 15-m firn core was recovered from an elevation of 7 000 m a. s.l. from the Dasuopu Glacier in the central Himalayas. The analysis of δ18O values and major ion (Ca2+ , Mg2+ , NH4+ , SO42- and NO3-) concentrations shows that average annual accumulation is 0.75 m (water equivalent) in the Dasuopu firn core. The seasonal variations of δ18O values and major ion concentrations in the core indicate that present summer monsoon and dust signals are recorded with high-resolution in the Dasuopu Glacier. δ18O in precipitation are controlled by amount effect in summer monsoon season, more negative δ18O is representative of summer monsoon signal in snow layers. Higher concentrations of Ca2+ , Mg2+ , SO42- and NO3-are dominated by spring dust storm imput derived from the arid and semi-arid desert regions in central Asia. Also EOF analysis verifies that high spring concentrations of major ions are consistent. Due to the possibly different sources, the secondary variations of NH4+ and NO3- are negatively relevant with that of Ca2+ and Mg2+ .     

Alloglossidium anomophagis sp. n. (Trematoda: Plagiorchiidae) exhibiting progenesis in water fleas (Anomopoda: Daphniidae)

The trematode,Alloglossidium anomophagis sp. n. (Digenea: Plagiorchiidae) exhibits progenesis in water fleas of the genusDaphnia (Anomopoda: Daphniidae) occurring in temporary rainwater-filled ditches near Houston, Texas, USA. We assume thatA. anomophagis has achieved its truncated life cycle by eliminating the vertebrate which originally served as the definitive host. The adults ofA. anomophagis represent the smallest trematodes in the family Plagiorchiidae, measuring less than 0.5 mm in length.     

Diagnosis of Vocal Cord Paralysis in Anaesthesia

Vocal cord paralysis can occur as a complication o surgery or anaesthesia,if permanent is a significant clinica problem.Early detection is important to optimize the chance o repair,and avoid complications associated with an impaired swallow.An algorithm to detect altered vocal cord function was presented based on wavelet packet analysis(WPA) and suppor vector machines(SVM),and compared with the Hoarseness Diagram method(HDm),which was reported as an objective voice quality evaluation approach and could be u...     

A putative lipid transfer protein involved in systemic resistance signalling in Arabidopsis

Localized attack by a necrotizing pathogen induces systemic acquired resistance (SAR) to subsequent attack by a broad range of normally virulent pathogens. Salicylic acid accumulation is required for activation of local defenses, such as pathogenesis-related protein accumulation, at the initial site of attack, and for subsequent expression of SAR upon secondary, distant challenge. Although salicylic acid moves through the plant, it is apparently not an essential mobile signal. We screened Agrobacterium tumefaciens transfer DNA (tDNA) tagged lines of Arabidopsis thaliana for mutants specifically compromized in SAR. Here we show that Defective in induced resistance 1-1 (dir1-1) exhibits wild-type local resistance to avirulent and virulent Pseudomonas syringae, but that pathogenesis-related gene expression is abolished in uninoculated distant leaves and dir1-1 fails to develop SAR to virulent Pseudomonas or Peronospora parasitica. Petiole exudate experiments indicate that dir1-1 is defective in the production or transmission from the inoculated leaf of an essential mobile signal. DIR1 encodes a putative apoplastic lipid transfer protein and we propose that DIR1 interacts with a lipid-derived molecule to promote long distance signalling.     

Extinction risk from climate change

Climate change over the past approximately 30 years has produced numerous shifts in the distributions and abundances of species and has been implicated in one species-level extinction. Using projections of species' distributions for future climate scenarios, we assess extinction risks for sample regions that cover some 20% of the Earth's terrestrial surface. Exploring three approaches in which the estimated probability of extinction shows a power-law relationship with geographical range size, we predict, on the basis of mid-range climate-warming scenarios for 2050, that 15-37% of species in our sample of regions and taxa will be 'committed to extinction'. When the average of the three methods and two dispersal scenarios is taken, minimal climate-warming scenarios produce lower projections of species committed to extinction ( approximately 18%) than mid-range ( approximately 24%) and maximum-change ( approximately 35%) scenarios. These estimates show the importance of rapid implementation of technologies to decrease greenhouse gas emissions and strategies for carbon sequestration.