Fluxes and distribution of dissolved iron in the eastern (sub-) tropical North Atlantic Ocean

Aeolian dust transport from the Saharan/Sahel desert regions is considered the dominant external input of iron (Fe) to the surface waters of the eastern (sub-) tropical North Atlantic Ocean. To test this hypothesis, we investigated the sources of dissolved Fe (DFe) and quantified DFe fluxes to the surface ocean in this region. In winter 2008, surface water DFe concentrations varied between <0.1 nM and 0.37 nM, with an average of 0.13 ± 0.07 nM DFe (n = 194). A strong correlation between mixed layer averaged concentrations of dissolved aluminum (DAl), a proxy for dust input, and DFe indicated dust as a source of DFe to the surface ocean. The importance of Aeolian nutrient input was further confirmed by an increase of 0.1 nM DFe and 0.05 ?M phosphate during a repeat transect before and after a dust event. An exponential decrease of DFe with increasing distance from the African continent, suggested that continental shelf waters were a source of DFe to the northern part of our study area. Relatively high Fe:C ratios of up to 3 × 10?5 (C derived from apparent oxygen utilization (AOU)) indicated an external source of Fe to these African continental shelf waters. Below the wind mixed layer along 12°N, enhanced DFe concentrations (>1.5 nM) correlated positively with apparent oxygen utilization (AOU) and showed the importance of organic matter remineralization as an DFe source. As a consequence, vertical diffusive mixing formed an important Fe flux to the surface ocean in this region, even surpassing that of a major dust event

Alternate bar response to sediment supply termination

Sediment supply is widely held to be one of the primary controls on bar topography in alluvial channels, yet quantitative linkages between sediment supply and bar topography are not well developed. We explore the conditions under which alternate bars form and how they respond to the elimination of sediment supply in two linked laboratory experiments. The first set of experiments was conducted in a 28 m long, 0.86 m wide flume channel using a unimodal sand‐gravel mix. The second set of experiments was conducted at field scale in a 55 m long, 2.74 m wide channel using a unimodal gravel mixture. In both experiments, alternate bars and patchy surface grain‐size distributions developed under steady flow and sediment supply conditions. The cessation of the sediment supply induced a reduction in the surface grain‐size heterogeneity and the bars were eliminated. In both flumes, mean boundary shear stress had declined, but were capable of moving sediments after the bars disappeared, albeit at relatively small rates compared to when the bars were present. In the smaller flume, the previously stationary bars migrated out of the flume and were not replaced with new bars. A nearly featureless bed formed with limited surface grain‐size heterogeneity, a slightly coarsened surface and a slightly reduced slope. In the larger flume, the formation of alternate bars was induced by an imposed upstream flow constriction and as such, the bars did not migrate. Termination of sediment supply led to progressive erosion of bed topography and loss of the bars, coarsening of the bed surface, loss of bed texture patchiness and significant slope reduction. The original alternate bar topography redeveloped when the sediment supply was restored once sufficient deposition had occurred to reconstruct the original channel slope. This shows that the bar loss was reversible by establishing the previous conditions and highlights the importance of sediment supply for bar formation. The role of sediment supply in bar formation and stability is not often recognized in stream restoration. Our results suggest that the loss of sediment supply can significantly affect alternate bar topography and that considerable volumes of sediment may be needed restore channel bars

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

BRCA1 and BRCA2 Germline Mutations in Malaysian Women with Early-Onset Breast Cancer without a Family History

BACKGROUND: In Asia, breast cancer is characterised by an early age of onset: In Malaysia, approximately 50% of cases occur in women under the age of 50 years. A proportion of these cases may be attributable, at least in part, to genetic components, but to date, the contribution of genetic components to breast cancer in many of Malaysia's ethnic groups has not been well-characterised. METHODOLOGY: Given that hereditary breast carcinoma is primarily due to germline mutations in one of two breast cancer susceptibility genes, BRCA1 and BRCA2, we have characterised the spectrum of BRCA mutations in a cohort of 37 individuals with early-onset disease (<or=40 years) and no reported family history. Mutational analysis of BRCA1 and BRCA2 was conducted by full sequencing of all exons and intron-exon junctions. CONCLUSIONS: Here, we report a total of 14 BRCA1 and 17 BRCA2 sequence alterations, of which eight are novel (3 BRCA1 and 5 BRCA2). One deleterious BRCA1 mutation and 2 deleterious BRCA2 mutations, all of which are novel mutations, were identified in 3 of 37 individuals. This represents a prevalence of 2.7% and 5.4% respectively, which is consistent with other studies in other Asian ethnic groups (4-9%)

Characteristics of small breast and/or ovarian cancer families with germline mutations in BRCA1 and BRCA2

For families with a small number of cases of breast and/or ovarian cancer, limited data are available to predict the likelihood of genetic predisposition due to mutations in BRCA1 or BRCA2. In 104 families with three or more affected individuals (average 3.8) seeking counselling at family cancer clinics, mutation analysis was performed in the open reading frame of BRCA1 and BRCA2 by the protein truncation test and mutation-specific assays. In 31 of the 104 families tested, mutations were detected (30%). The majority of these mutations (25) occurred in BRCA1. Mutations were detected in 15 out of 25 families (60%) with both breast and ovarian cancer and in 16 out of 79 families (20%) with exclusively cases of breast cancer. Thus, an ovarian cancer case strongly predicted finding a mutation (P < 0.001). Within the group of small breast-cancer-only families, a bilateral breast cancer case or a unilateral breast cancer case diagnosed before age 40 independently predicted finding a BRCA1 or BRCA2 mutation (P = 0.005 and P = 0.02, respectively). Therefore, even small breast/ovarian cancer families with at least one case of ovarian cancer, bilateral breast cancer, or a case of breast cancer diagnosed before age 40, should be referred for mutation screening. © 1999 Cancer Research Campaig

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability

Genome co-amplification upregulates a mitotic gene network activity that predicts outcome and response to mitotic protein inhibitors in breast cancer.

BACKGROUND: High mitotic activity is associated with the genesis and progression of many cancers. Small molecule inhibitors of mitotic apparatus proteins are now being developed and evaluated clinically as anticancer agents. With clinical trials of several of these experimental compounds underway, it is important to understand the molecular mechanisms that determine high mitotic activity, identify tumor subtypes that carry molecular aberrations that confer high mitotic activity, and to develop molecular markers that distinguish which tumors will be most responsive to mitotic apparatus inhibitors. METHODS: We identified a coordinately regulated mitotic apparatus network by analyzing gene expression profiles for 53 malignant and non-malignant human breast cancer cell lines and two separate primary breast tumor datasets. We defined the mitotic network activity index (MNAI) as the sum of the transcriptional levels of the 54 coordinately regulated mitotic apparatus genes. The effect of those genes on cell growth was evaluated by small interfering RNA (siRNA). RESULTS: High MNAI was enriched in basal-like breast tumors and was associated with reduced survival duration and preferential sensitivity to inhibitors of the mitotic apparatus proteins, polo-like kinase, centromere associated protein E and aurora kinase designated GSK462364, GSK923295 and GSK1070916, respectively. Co-amplification of regions of chromosomes 8q24, 10p15-p12, 12p13, and 17q24-q25 was associated with the transcriptional upregulation of this network of 54 mitotic apparatus genes, and we identify transcription factors that localize to these regions and putatively regulate mitotic activity. Knockdown of the mitotic network by siRNA identified 22 genes that might be considered as additional therapeutic targets for this clinically relevant patient subgroup. CONCLUSIONS: We define a molecular signature which may guide therapeutic approaches for tumors with high mitotic network activity

Development and demonstration of a Lagrangian dispersion modeling system for real‐time prediction of smoke haze pollution from biomass burning in Southeast Asia

Abstract Transboundary smoke haze caused by biomass burning frequently causes extreme air pollution episodes in maritime and continental Southeast Asia. With millions of people being affected by this type of pollution every year, the task to introduce smoke haze related air quality forecasts is urgent. We investigate three severe haze episodes: June 2013 in Maritime SE Asia, induced by fires in central Sumatra, and March/April 2013 and 2014 on mainland SE Asia. Based on comparisons with surface measurements of PM10 we demonstrate that the combination of the Lagrangian dispersion model NAME with emissions derived from satellite‐based active‐fire detection provides reliable forecasts for the region. Contrasting two fire emission inventories shows that using algorithms to account for fire pixel obscuration by cloud or haze better captures the temporal variations and observed persistence of local pollution levels. Including up‐to‐date representations of fuel types in the area and using better conversion and emission factors is found to more accurately represent local concentration magnitudes, particularly for peat fires. With both emission inventories the overall spatial and temporal evolution of the haze events is captured qualitatively, with some error attributed to the resolution of the meteorological data driving the dispersion process. In order to arrive at a quantitative agreement with local PM10 levels, the simulation results need to be scaled. Considering the requirements of operational forecasts, we introduce a real‐time bias correction technique to the modeling system to address systematic and random modeling errors, which successfully improves the results in terms of reduced normalized mean biases and fractional gross errors