Evaluation of the mutagenic effects of SV40 in mouse, hamster, and mouse-human hybrid cells

We have examined the ability of SV40 to induce changes in drug or temperature resistance in mouse, hamster, and mouse-human hybrid cells. SV40 induced a substantial increase of cells resistant to 5-bromodeoxyuridine + trifluorothymidine in Balb/c 3T3 cells and induced an increase of hybrid cells resistant to 6-thioguanine. SV40 was found to be nonmutagenic or weakly mutagenic in other test systems. The 3T3 cells were T-antigen positive, exhibited a marked reduction in TK activity, were heterogeneous for [ 3 H]BrdU incorporation by autoradiography, and exhibited instability of the drug-resistance phenotype, suggesting that SV40 may be inducing resistance by an epigenetic process. SV40-induced 6-thioguanine resistance in the hybrids appears to occur predominantly by chromosome loss.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45539/1/11188_2005_Article_BF01233058.pd

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Active faulting on the Ninetyeast Ridge and its relation to deformation of the Indo-Australian plate

The ~4500 km long Ninetyeast Ridge (NER) in the northeastern Indian Ocean crosses a broad zone of deformation where the Indo-Australian plate is fracturing into three smaller plates (India, Capricorn, Australia) separated by diffuse boundaries whose extents are poorly defined. New multichannel seismic reflection profiles image active faults along the entire length of the NER and show spatial changes in the style of deformation along the ridge. The northern NER (0°N–5°N) displays transpressional motion along WNW-ESE faults. Observed fault patterns confirm strike-slip motion at the western extent of the April 2012 Wharton Basin earthquake swarm. In the central NER (5°S–8°S), deformation on WNW-ESE-trending thrust faults implies nearly N-S compression. An abrupt change in fault style occurs between 8° and 11°S, with modest, extension characterizing the southern NER (11°S–27°S). Although extension is dominant, narrow zones of faults with strike-slip or compressional character also occur in the southern NER, suggesting a complex combination of fault motions. At all sites, active faulting is controlled by the reactivation of original, spreading-center formed, normal faults, implying that deformation is opportunistic and focused along existing zones of weakness, even when original fault trend is oblique to the direction of relative plate motion. Observed faulting can be interpreted as India-Australia deformation in the northern NER and Capricorn-Australia deformation in the southern NER. The India-Capricorn boundary is directly adjacent to the northern NER and this juxtaposition combined with a different style of faulting to the east of the NER imply that the ridge is a tectonic boundary

Palaeointensity determinations and rock magnetic properties on basalts from Shatsky Rise: new evidence for a Mesozoic dipole low

International audienceIODP Expedition 324 cored igneous rocks from Shatsky Rise, an oceanic plateau in the northwest Pacific Ocean that formed mainly during late Jurassic and Early Cretaceous times. We selected 60 samples from 3 different holes for Thellier-Thellier palaeointensity determinations. Induced and remanent magnetization curves measured at low- and high-temperature suggest a diverse and complex magnetic mineralogy, with large variations in Ti content and oxidation state. Hysteresis and FORC measurements show that most samples contain singledomain magnetic grains. After carrying out the palaeointensity determinations, only 9 samples satisfied all reliability criteria. These gave palaeointensity values between 16.5 and 21.5 μT, which correspond to average VDM values of (4.9 ± 0.2) × 1022 Am2 for an estimated age of 140-142 Ma. This value is lower than that for the recent field, which agrees with the hypothesis of a Mesozoic Dipole Low