The Relative Timing of Mutations in a Breast Cancer Genome

Many tumors have highly rearranged genomes, but a major unknown is the relative importance and timing of genome rearrangements compared to sequence-level mutation. Chromosome instability might arise early, be a late event contributing little to cancer development, or happen as a single catastrophic event. Another unknown is which of the point mutations and rearrangements are selected. To address these questions we show, using the breast cancer cell line HCC1187 as a model, that we can reconstruct the likely history of a breast cancer genome. We assembled probably the most complete map to date of a cancer genome, by combining molecular cytogenetic analysis with sequence data. In particular, we assigned most sequence-level mutations to individual chromosomes by sequencing of flow sorted chromosomes. The parent of origin of each chromosome was assigned from SNP arrays. We were then able to classify most of the mutations as earlier or later according to whether they occurred before or after a landmark event in the evolution of the genome, endoreduplication (duplication of its entire genome). Genome rearrangements and sequence-level mutations were fairly evenly divided earlier and later, suggesting that genetic instability was relatively constant throughout the life of this tumor, and chromosome instability was not a late event. Mutations that caused chromosome instability would be in the earlier set. Strikingly, the great majority of inactivating mutations and in-frame gene fusions happened earlier. The non-random timing of some of the mutations may be evidence that they were selected.     

Radiorespirometric studies of carbohydrate metabolism by washed spermatozoa of various species.

1. The patterns of 14CO2 evolution from specifically labeled glucose substrates by washed bull, ram, boar, rabbit, dog, rooster and turkey spermatozoa were similar and indicated the Embden-Meyerhof and Kreb's cycle pathways as the major route of energy metabolism. 2. Honey bee spermatozoa metabolized glucose-3,4-[14C], glucose-[U-14C] or fructose-[U-14C], but not glucose-1-[14C], glucose-2-[14C]or glucose-6-[14C], indicating the presence of the glycolytic pathway, but the absence of respiration via the Kreb's cycle. 3. The rate of glycolysis exceeded the rate of respiration in the spermatozoa of all the species studied. 4. A preferential utilization of glucose-1-[14C] over glucose-6-[14C] was evident in some sperm samples, but no consistent indication of pentose cycle metabolism was observed, due to considerable variability between samples within each group. 5. Fructose metabolism was greater than glucose metabolism in the rooster, less in the dog, boar and turkey, and similar in the spermatozoa from the other species examined. 6. Only ram and bull spermatozoa metabolized acetate-1-[14C] to any extent.     

A finite element evaluation of the moment arm hypothesis for altered vertebral shear failure force

The mechanism of vertebral shear failure is likely a bending moment generated about the pars interarticularis by facet contact, and the moment arm length (MAL) between the centroid of facet contact and the location of pars interarticularis failure has been hypothesised to be an influential modulator of shear failure force. To quantitatively evaluate this hypothesis, anterior shear of C3 over C4 was simulated in a finite element model of the porcine C3–C4 vertebral joint with each combination of five compressive force magnitudes (0–60% of estimated compressive failure force) and three postures (flexed, neutral and extended). Bilateral locations of peak stress within C3's pars interarticularis were identified along with the centroids of contact force on the inferior facets. These measurements were used to calculate the MAL of facet contact force. Changes in MAL were also related to shear failure forces measured from similar in vitro tests. Flexed and extended vertebral postures respectively increased and decreased the MAL by 6.6% and 4.8%. The MAL decreased by only 2.6% from the smallest to the largest compressive force. Furthermore, altered MAL explained 70% of the variance in measured shear failure force from comparable in vitro testing with larger MALs being associated with lower shear failure forces. Our results confirmed that the MAL is indeed a significant modulator of vertebral shear failure force. Considering spine flexion is necessary when assessing low-back shear injury potential because of the association between altered facet articulation and lower vertebral shear failure tolerance.     

A new respiratory quinone, 2-methyl-3-VI,VII-tetrahydroheptaprenyl-1,4-naphthoquinone isolated from Thermoleophilum album

Abstract A new menaquinone has been isolated from the Gram-negative bacterium, Thermoleophilum album , an organism obligate for thermophily and n -alkane substrates. On the basis of mass spectrometry and proton nuclear magnetic resonance (¹H-NMR) spectrometry the novel quinone is shown to correspond to 2-methyl-3-VI,VII-tetrahydroheptaprenyl-1,4-naphthoquinone.     

Nitrogen cycling and anthropogenic impact in the tropical interamerican seas

We discuss the mechanisms leading to nutrient limitation in tropical marine systems, with particular emphasis on nitrogen cycling in Caribbean ecosystems. We then explore how accelerated nutrient cycling from human activities is affecting these systems.Both nitrogen and phosphorus exert substantial influence on biological productivity and structure of tropical marine ecosystems. Offshore planktonic communities are largely nitrogen limited while nearshore ecosystems are largely phosphorus limited. For phosphorus, the ability of sediment to adsorb and store phosphorus is probably greater for tropical carbonate sediments than for most nearshore sediments in temperate coastal systems. However, the ability of tropical carbonate sediments to take up phosphorus can become saturated as phosphorus loading from human sources increases. The nature of the sediment, the mixing rate between nutrient-laden runoff waters and nutrient-poor oceanic waters and the degree of interaction of these water masses with the sediment will probably control the dynamics of this transition.Nearshore tropical marine ecosystems function differently from their temperate counterparts where coupled nitrification/denitrification serves as an important mechanism for nitrogen depuration. In contrast, nearshore tropical ecosystems are more susceptible to nitrogen loading as depurative capacity of the microbial communities is limited by the fragility of the nitrification link. At the same time, accumulation of organic matter in nearshore carbonate sediments appears to impair their capacity for phosphorus immobilization. In the absence of depurative mechanisms for either phosphorus or nitrogen, limitation for both these nutrients is alleviated and continued nutrient loading fuels the proliferation of nuisance algae.