Wig-1, a novel regulator of N-Myc mRNA and N-Myc-driven tumor growth

Wig-1 is a transcriptional target of the p53 tumor suppressor and encodes an mRNA stability-regulating protein. We show here that Wig-1 knockdown causes a dramatic inhibition of N-Myc expression and triggers differentiation in neuroblastoma cells carrying amplified N-Myc. Transient Wig-1 knockdown significantly delays development of N-Myc-driven tumors in mice. We also show that N-Myc expression is induced upon moderate p53-activating stress, suggesting a role of the p53-Wig-1-N-Myc axis in promoting cell cycle re-entry upon p53-induced cell cycle arrest and DNA repair. Moreover, our findings raise possibilities for the improved treatment of poor prognosis neuroblastomas that carry amplified N-Myc

A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease

Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology

Interactive Effect of UVR and Phosphorus on the Coastal Phytoplankton Community of the Western Mediterranean Sea: Unravelling Eco- Physiological Mechanisms

Versión del editor4,411

Rubber-toughened epoxy loaded with carbon nanotubes: structure-property relationships

The paper reports on the preparation, structure and properties of ternary thermosetting blends, based on DGEBA epoxy, cured with 3,3′-DDS and modified by the addition of CTBN reactive liquid rubber and/or 0.3wt% of commercial multi- walled carbon nanotubes. The toughening effect of the phase-separated rubber particles is enhanced by the presence of the nanotubes, through a change in the morphology. In the absence of the rubber, the nanotubes alone produce a minimal effect upon the thermo-mechanical characteristics of the resin. However, the electrical conductivity of the cured resin samples is found to increase by five orders of magnitude, up to 3.6×10-3 S/m in the ternary bl

Consistently dated records from the Greenland GRIP, GISP2 and NGRIP ice cores for the past 104ka reveal regional millennial-scale δ18O gradients with possible Heinrich event imprint

We present a synchronization of the NGRIP, GRIP and GISP2 ice cores onto a master chronology extending back to 104ka before present, providing a consistent chronological framework for these three Greenland records. The synchronization aligns distinct peaks in volcanic proxy records and other impurity records (chemo-stratigraphic matching) and assumes that these layers of elevated impurity content represent the same, instantaneous event in the past at all three sites. More than 900 marker horizons between the three cores have been identified and our matching is independently confirmed by 24 new and previously identified volcanic ash (tephra) tie-points. Using the reference horizons, we transfer the widely used Greenland ice-core chronology, GICC05modelext, to the two Summit cores, GRIP and GISP2. Furthermore, we provide gas chronologies for the Summit cores that are consistent with the GICC05modelext timescale by utilizing both existing and new gas data (CH4 concentration and δ15N of N2). We infer that the accumulation contrast between the stadial and interstadial phases of the glacial period was ~10% greater at Summit compared to at NGRIP. The δ18O temperature-proxy records from NGRIP, GRIP, and GISP2 are generally very similar and display synchronous behaviour at climate transitions. The δ18O differences between Summit and NGRIP, however, changed slowly over the Last Glacial-Interglacial cycle and also underwent abrupt millennial-to-centennial-scale variations. We suggest that this observed latitudinal δ18O gradient in Greenland during the glacial period is the result of 1) relatively higher degree of precipitation with a Pacific signature at NGRIP, 2) increased summer bias in precipitation at Summit, and 3) enhanced Rayleigh distillation due to an increased source-to-site distance and a potentially larger source-to-site temperature gradient. We propose that these processes are governed by changes in the North American Ice Sheet (NAIS) volume and North Atlantic sea-ice extent and/or sea-surface temperatures (SST) on orbital timescales, and that changing sea-ice extent and SSTs are the driving mechanisms on shorter timescales. Finally, we observe that maxima in the Summit-NGRIP δ18O difference are roughly coincident with prominent Heinrich events. This suggests that the climatic reorganization that takes place during stadials with Heinrich events, possibly driven by a southward expansion of sea ice and low SSTs in the North Atlantic, are recorded in the ice-core records