Comparison of Cobb Angles Measured Manually,Calculated from 3-D Spinal Reconstruction,and Estimated from Torso Asymmetry

While scoliotic spinal deformity is traditionally measured by the Cobb angle, we seek to estimate scoliosis severity from the torso surface without X-ray radiation. Here, we measured the Cobb angle in three ways: by protractor from postero-anterior X-ray, by computer from a 3-D digitized model of the vertebral body line, and by neural-network estimation from indices of torso surface asymmetry. The estimates of the Cobb angle by computer and by neural network were equally accurate in 153 records from 52 patients (standard deviation of 6° from the Cobb angle, r =0.93 ), showing that torso asymmetry reliably predicted spinal deformity. Further improvements in predictive accuracy may require estimation of other 3-D indices of spinal deformity besides the Cobb angle with its wide measurement variability.     

Metagenomics reveals sediment microbial community response to Deepwater Horizon oil spill

The Deepwater Horizon (DWH) oil spill in the spring of 2010 resulted in an input of ∼4.1 million barrels of oil to the Gulf of Mexico; >22% of this oil is unaccounted for, with unknown environmental consequences. Here we investigated the impact of oil deposition on microbial communities in surface sediments collected at 64 sites by targeted sequencing of 16S rRNA genes, shotgun metagenomic sequencing of 14 of these samples and mineralization experiments using ¹⁴C-labeled model substrates. The 16S rRNA gene data indicated that the most heavily oil-impacted sediments were enriched in an uncultured Gammaproteobacterium and a Colwellia species, both of which were highly similar to sequences in the DWH deep-sea hydrocarbon plume. The primary drivers in structuring the microbial community were nitrogen and hydrocarbons. Annotation of unassembled metagenomic data revealed the most abundant hydrocarbon degradation pathway encoded genes involved in degrading aliphatic and simple aromatics via butane monooxygenase. The activity of key hydrocarbon degradation pathways by sediment microbes was confirmed by determining the mineralization of ¹⁴C-labeled model substrates in the following order: propylene glycol, dodecane, toluene and phenanthrene. Further, analysis of metagenomic sequence data revealed an increase in abundance of genes involved in denitrification pathways in samples that exceeded the Environmental Protection Agency (EPA)''s benchmarks for polycyclic aromatic hydrocarbons (PAHs) compared with those that did not. Importantly, these data demonstrate that the indigenous sediment microbiota contributed an important ecosystem service for remediation of oil in the Gulf. However, PAHs were more recalcitrant to degradation, and their persistence could have deleterious impacts on the sediment ecosystem.     

Definition of a small core transcriptional circuit regulated by AML1-ETO

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Fumarate reductase of Escherichia coli. Elucidation of the covalent-flavin component.

Fumarate reductase is a membrane-bound terminal oxidase which is induced when Escherichia coli is grown anaerobically. The purified enzyme is composed of two polypeptide chains of 69,000 and 24,000 daltons and contains 1 mol of covalently bound flavin adenine dinucleotide per mol of enzyme. Fluorescence scanning of SDS-polyacrylamide gels of the protein shows that the flavin is attached to the large subunit. The hypsochromic shift of the 372 nm band of riboflavin to 350 nm in both native fumarate reductase and a flavin peptide released by proteolytic digestion indicates that the flavin is attached via position 8 alpha of riboflavin. Based on the spectral properties and pH-fluorescence dependence we have identified the linkage as 8 alpha-[N(3)-histidyl]FAD.     

BRCA1 and BRCA2 associated breast cancer and the roles of current modelling systems in drug discovery

For a drug candidate to be fully developed takes years and investment of hundreds of millions of dollars. There is no doubt that drug development is difficult and risky, but vital to protecting against devastating disease. This difficulty is clearly evident in BRCA1 and BRCA2 related breast cancer, with current treatment options largely confined to invasive surgical procedures, as well as chemotherapy and radiotherapy regimes which damage healthy tissue and can leave remnant disease. Consequently, patient survival and relapse rates are far from ideal, and new candidate treatments are needed. The preclinical stages of drug discovery are crucial to get right for translation to hospital beds. Disease models must take advantage of current technologies and be accurate for rapid and translatable treatments. Careful selection of cell lines must be coupled with high throughput techniques, with promising results trialled further in highly accurate humanised patient derived xenograft models. Traditional adherent drug screening should transition to 3D culture systems amenable to high throughput techniques if the gap between in vitro and in vivo studies is to be partially bridged. The possibility of organoid, induced pluripotent stem cell, and conditionally reprogrammed in vitro models is tantalising, however protocols are yet to be fully established. This review of BRCA1 and BRCA2 cancer biology and current modelling systems will hopefully guide the design of future drug discovery endeavours and highlight areas requiring improvement.     

Impacts of invasive riparian knotweed on litter decomposition,aquatic fungi,and macroinvertebrates

Bohemian knotweed (Polygonum × bohemicum), the hybrid between Japanese and giant knotweed, is the most common invasive knotweed species in western North America and the most difficult to control. Invasive knotweed congeners spread aggressively along streams and establish dense monotypic stands, reducing riparian plant species diversity. Allochthonous organic matter inputs from riparian plants are an important source of energy and nutrients for organisms in small streams. However, little information exists concerning the influence of knotweed on stream processes. This study examines the quality of Bohemian knotweed leaves compared to native red alder and black cottonwood leaves, along with leaf-associated fungal biomass accumulation, macroinvertebrate communities, and decay rates from three forested streams in western Washington State. Senesced knotweed leaves were lower in nitrogen and phosphorus, and higher in cellulose, fiber, and lignin content than alder leaves, but were more similar to cottonwood leaves. Fungal biomass differed among species and changed over time. Macroinvertebrate shredders collected from leaf packs after 31 days were proportionately more abundant on alder leaves than knotweed and cottonwood. Decay rates were not significantly different among leaf species, but during the first 31 days alder broke down faster than knotweed. After 56 days, all of the leaf packs were mostly decomposed. Overall, these findings do not show major discrepancies between leaf species except those related to initial litter structural and chemical quality. However, changes in the timing and quantity of litter inputs are also important factors to be considered in understanding the impact of invasive knotweed on stream ecosystem processes.