Rapid screening of 4000 individuals for germ-line variations in the BRAF gene

Background: The BRAF gene is frequently somatically altered in malignant melanoma. A majority of variations are at the valine 600 residue leading to a V600E substitution that constitutively activates the kinase. We screened 4000 patient and control DNAs for germ-line variations at the valine 600 residue. Methods: We developed a novel assay by adapting single-base variation assays and software for MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry to screen for all 5 reported variants at codon 600 of the BRAF gene. We screened a case-control collection comprising samples from 1082 melanoma patients and 154 of their unaffected relatives from 1278 families and from 2744 individuals from 659 unselected twin families with no history of melanoma. A panel of 66 melanoma cell lines was used for variation-positive controls. Results: All melanoma cell lines that we had found previously to carry a codon 600 variation were verified in this study. Three of the 4 possible variants (V600E n = 47, V600K n = 2, V600R n = 1) were detected, but no case of V600D was available. No germ-line variants were found in the samples from the 3980 melanoma patients or from the control individuals. Conclusions: This new assay is a high-throughput, automated alternative to standard sequencing and can be used as a rapid initial screen for somatic variants associated with melanoma. Germ-line variants at valine 600 are unlikely to exist and do not contribute to the reported role of the BRAF gene in melanoma predisposition. (c) 2006 American Association for Clinical Chemistry.

Pumice rafting and faunal dispersion during 2001-2002 in the Southwest Pacific: record of a dacitic submarine explosive eruption from Tonga

A new influx of sea-rafted pumice reached the eastern coast of Australia in October 2002, approximately 1 year after a felsic, shallow-marine explosive eruption at a previously unknown volcano (0403-091) along the Tofua volcanic arc (Tonga). The eruption produced floating pumice rafts that first became stranded in Fiji in November 2001, approximately I month after the eruption. Strandings of sea-rafted pumice along shorelines have been the only record of products from this submarine explosive eruption at the remote, submerged volcano. Computed drift trajectories of the sea-rafted pumice using numerical models of southwest Pacific surface wind fields and ocean currents indicate two cyclonic systems disturbed the drift of pumice to eastern Australia, as well as the importance of the combined wave and direct wind effect on pumice trajectory. Pumice became stranded along at least two-thirds (>2000 km) of the coastline of eastern Australia, being deposited on beaches during a sustained period of fresh onshore winds. Typical amounts of pumice initially stranded on beaches were 500-4000 individual clasts per in, and a minimum volume estimate of pumice that arrived to eastern Australia is 1.25 x 10(5) m(3). Pumice was beached below maximum tidal/storm surge levels and was quickly reworked back into the ocean, such that the concentration of beached pumice rapidly dissipated within weeks of the initial stranding, and little record of this stranding event now exists. Most stranded pumice clasts ranged in size from 2 to 5 cm in diameter; the largest measured clasts were 10 cm in Australia and 20 cm in Fiji. The pumice has a low phenocryst content (3500 km) and period of pumice floatation (greater than or equal to1 year), confirm the importance of sea-rafted pumice as a long-distance dispersal mechanism for marine organisms including marine pests and harmful invasive species. Billions of individual rafting pumice clasts can be generated in a single small-volume eruption, such as observed here, and the geological implications for the transport of sessile taxa over large distances are significant. An avenue for future research is to examine whether speciation events and volcanicity are linked; the periodic development of globalism for some taxa (e.g., corals, gastropods, bryozoa) may correlate in time and/or space with voluminous silicic igneous events capable of producing >10(6) km(3) of silicic pumice-rich pyroclastic material and emplaced into ocean basins. (C) 2004 Elsevier B.V. All rights reserved.

High-precision TIMS U-series and AMS C-14 dating of a coral reef lagoon sediment core from southern South China Sea

Accurate dating of lagoon sediments has been a difficult problem, although lagoon profiles, usually with high deposition rates, have a great potential for high-resolution climate reconstruction. We report 26 high-precision TIMS U-series dates (on 25 coral branches) and five AMS C-14 dates (on foraminifera) for a 15.4-m long lagoon core from Yongshu Reef, Nansha area, southern South China Sea. All the dates are in the correct stratigraphical sequence, providing the best chronology so far reported for lagoon deposits. The results reveal a similar to 4000-a continuous depositional history, with sedimentation rates varying from 0.8 to 24.6 mm a(-1), with an average of 3.85 mm a(-1), which corresponds to an average net carbonate accumulation rate of similar to 2700 g CaCO3 m(-2) a(-1), significantly higher than the mean value (800 +/- 400 g CaCO3 m(-2) a(-1)) used for lagoons in general in previous studies of global carbonate budget. Episodes of accelerated depositions within the last 1000 years correlate well with strong storm events identified by U-series dates of storm-transported coral blocks in the area. However, in the longer term, the sedimentation rates during the past 1000 years were much higher than earlier on, probably due to more vigorous wave-reef interaction as a result of relative sea-level fall since 500 AD and expansion of reef flat area, supplying more sediments. The coral TIMS U-series ages and foraminifera AMS 14C dates reveal intriguing apparent radiocarbon reservoir ages (R) from 572 to 1052 years, which are much higher than global mean values of similar to 400 years. (c) 2006 Elsevier Ltd. All rights reserved.

Brisbane Airport: An alluvial landscape veiled by marine sediments

At Brisbane Airport, the construction of a diversion channel for Kedron Brook exposed a former beach, low cliff and sand spit, which, with their associated sediments and acid sulfate soils, demonstrate a postglacial high sea-level 1.3 - 1.4 m above present mean sea-level. The beach appears to date from 4000 to 5000 y BP. It varies in level where it lies above soft ground; these variations, and sag depressions that follow buried streamlines, indicate sediment consolidation since withdrawal of the sea from the former shore. Most of the area consists of former estuarine deposits, mangrove and saline marshes, and stranded tidal flats on which acid sulfate soils are widely developed. The modern landforms mostly reproduce subsurface features, to the extent that the surface relief replicates the landscape transgressed by the sea 7000 years ago. A small rise of sea-level possibly to +0.65 m occurred about 2000-3000 years ago. Foredunes near the present shore that are related to a slightly lower level 1000 - 500 years ago (-0.25 m) are currently subject to wave erosion.

Gene expression in human alcoholism: Microarray analysis of frontal cortex

Background: Changes in brain gene expression are thought to be responsible for the tolerance, dependence, and neurotoxicity produced by chronic alcohol abuse, but there has been no large scale study of gene expression in human alcoholism. Methods: RNA was extracted from postmortem samples of superior frontal cortex of alcoholics and nonalcoholics. Relative levels of RNA were determined by array techniques. We used both cDNA and oligonucleotide microarrays to provide coverage of a large number of genes and to allow cross-validation for those genes represented on both types of arrays. Results: Expression levels were determined for over 4000 genes and 163 of these were found to differ by 40% or more between alcoholics and nonalcoholics. Analysis of these changes revealed a selective reprogramming of gene expression in this brain region, particularly for myelin-related genes which were downregulated in the alcoholic samples. In addition, cell cycle genes and several neuronal genes were changed in expression. Conclusions: These gene expression changes suggest a mechanism for the loss of cerebral white matter in alcoholics as well as alterations that may lead to the neurotoxic actions of ethanol.