MPI-blastn and NCBI-TaxCollector: improving metagenomic analysis with high performance classification and wide taxonomic attachment.

Metagenomic sequencing technologies are advancing rapidly and the size of output data from high-throughput genetic sequencing has increased substantially over the years. This brings us to a scenario where advanced computational optimizations are requested to perform a metagenomic analysis. In this paper, we describe a new parallel implementation of nucleotide BLAST (MPI-blastn) and a new tool for taxonomic attachment of Basic Local Alignment Search Tool (BLAST) results that supports the NCBI taxonomy (NCBI-TaxCollector). MPI-blastn obtained a high performance when compared to the mpiBLAST and ScalaBLAST. In our best case, MPI-blastn was able to run 408 times faster in 384 cores. Our evaluations demonstrated that NCBI-TaxCollector is able to perform taxonomic attachments 125 times faster and needs 120 times less RAM than the previous TaxCollector. Through our optimizations, a multiple sequence search that currently takes 37 hours can be performed in less than 6 min and a post processing with NCBI taxonomic data attachment, which takes 48 hours, now is able to run in 23 min.

ACTH inhibits the capsaicin-evoked release of CGRP from rat adrenal afferent nerves.

The adrenal cortex is innervated by afferent fibers that have been implicated in affecting cortical steroidogenesis. Modulation of neurotransmitter release from afferents may represent a regulatory system for the control of adrenal cortical function. The present studies validate an in vitro superfusion technique for adrenal capsules employing the drug capsaicin, which activates a subset of afferent fibers and induces the release of calcitonin gene-related peptide (CGRP). Capsaicin-evoked CGRP release from adrenal afferents was blocked by capsazepine, a competitive antagonist for the capsaicin receptor, or by removal of extracellular calcium. Exogenous ACTH prevented capsaicin-evoked CGRP release, elevated basal aldosterone release, and prevented capsaicin-induced reduction in aldosterone release. Immunolabeling for the recently cloned capsaicin vanilloid receptor 1 demonstrated its presence in adrenal nerves. These results show that in vitro superfusion of adrenal capsules can be used to characterize factors that modulate neurotransmitter release from adrenal afferents. Furthermore, the results suggest that activation of adrenal afferents in vivo may attenuate aldosterone steroidogenesis and that high levels of ACTH may prevent this phenomenon.

Tobacco addiction and pharmacological interventions.

Even though its health consequences are well known, tobacco use continues to kill millions of smokers worldwide every year. In the US alone, tobacco use kills > 430,000 people each year. The global mortality toll is approximately 5 million annually and this is increasing. It is the powerful grip of tobacco addiction that sustains high levels of daily smoke intake and persistent smoking, with > 90% of all cigarette smokers who quit, resuming smoking within 1 year. Tobacco addiction, which places tremendous health and economic burdens on individual societies, is also becoming a global epidemic. Although tobacco addiction is a complex phenomenon, it is treatable and several effective medications are now available. In the mid-1980s, the US FDA approved nicotine gum, the first of these effective pharmacological aids. Other effective medications have subsequently become available, including nicotine transdermal patches, nasal spray, oral vapour inhaler, sublingual nicotine tablets and bupropion. These medications and the potential for development of new medications will be reviewed.

Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations.

PURPOSE: To evaluate the diagnostic value of positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) for the diagnosis of primary breast cancer. PATIENTS AND METHODS: Preoperatively, 144 patients with masses suggestive of breast cancer underwent PET imaging of the breast. To identify breast cancer by increased metabolic activity, parametric FDG-PET images were analyzed for increased tracer uptake applying conventional image reading (CIR) and sensitive image reading (SIR). One hundred eighty-five breast tumors were evaluated by histology, revealing 132 breast carcinomas and 53 benign masses. RESULTS: Breast carcinomas were identified with an overall sensitivity of 64.4% (CIR) and 80.3% (SIR). The increase in sensitivity (SIR) resulted in a noticeable decrease in specificity, from 94.3% (CIR) to 75.5% (SIR). At stage pT1, only 30 (68.2%) of 44 breast carcinomas were detected, compared with 57 (91.9%) of 62 at stage pT2. A higher percentage of invasive lobular carcinomas were false-negative (65.2%) compared with invasive ductal carcinomas (23.7%). Nevertheless, positive PET scans provided a high positive-predictive value (96.6%) for breast cancer. CONCLUSION: Partial volume effects and varying metabolic activity (dependent on tumor type) seem to represent the most significant limitations for the routine diagnostic application of PET. The number of invasive procedures is therefore unlikely to be significantly reduced by PET imaging in patients presenting with abnormal mammography. However, the high positive-predictive value, resulting from the increased metabolic activity of malignant tissue, may be used with carefully selected subsets of patients as well as to determine the extent of disease or to assess therapy response.

The effects of nicotine on the immune system.

Although considerable work has been done on the potential health effects of smoking, little is known about the contribution of nicotine to those effects. This paper presents an overview of the immune system, and a discussion of the existing literature on the effects of tobacco smoke and nicotine on immunity. Treatment with nicotine has been shown to influence all aspects of the immune system, including alterations in humoral and cellular immunity. In addition, preliminary data suggest that gender and genetic factors impact on the immunological effects of nicotine. Finally, the possible mechanisms that might mediate the effects of nicotine are discussed.

Precipitation of insulinotropin in the presence of protamine: effect of phenol and zinc on the isophane ratio and the insulinotropin concentration in the supernatant.

PURPOSE: The purpose of this study is to determine the minimum quantity of protamine required for the completion of insulinotropin precipitation under different precipitation conditions. METHODS: The experiments involved combining insulinotropin with varying concentrations of protamine in pH 7.2 phosphate buffered saline and analyzing the concentrations of both proteins in the supernatant. Isophane ratio (the protamine/insulinotropin molar ratio that results in a minimum total protein concentration in the supernatant) was determined for different precipitation conditions. RESULTS: When neutral solutions of insulinotropin (pI 5.3) and protamine (pI 13.8) were combined, precipitation did not occur. However, in the presence of phenol and/or zinc, insulinotropin co-precipitated with protamine. In the presence of phenol, the isophane ratio and the insulinotropin concentration in the supernatant were determined to be 0.08 and 0.18 mg/ml, respectively. In the presence of zinc, the isophane ratio increased with zinc concentration, apparently from the precipitation of protamine in the presence of zinc. The isophane ratio and the insulinotropin concentration in the supernatant were 0.13 and 0.13 mg/ml, respectively, when the zinc/insulinotropin molar ratio was one. In the presence of phenol and zinc with the zinc/insulinotropin molar ratio of 1.0, the isophane ratio and the insulinotropin concentration in the supernatant were 0.11 and 1 microgram/ml, respectively. CONCLUSIONS: A method to determine the isophane ratio of protamine/insulinotropin precipitation was developed to determine the minimum quantity of protamine required for the completion of insulinotropin precipitation under different precipitation conditions. A synergistic effect between phenol and zinc on the precipitation of insulinotropin in the presence of protamine was found.

FT-IR and near-infrared FT-Raman studies of the secondary structure of insulinotropin in the solid state: alpha-helix to beta-sheet conversion induced by phenol and/or by high shear force.

Insulinotropin (glucagon-like peptide I) is a peptide containing 31 amino acid residues. It stimulates the secretion of the hormone insulin. The solubility of this peptide is highly dependent on its environment and the treatment that it has undergone. For instance, synthetic insulinotropin is highly soluble in neutral phosphate-buffered saline (1 mg/mL). However, the application of shear force by stirring renders it extremely insoluble (1 micrograms/mL). This property may be explained in terms of a change in peptide secondary structure with no alteration in primary structure. In order to understand this phenomenon, FT-IR and near-IR FT-Raman were employed to examine four samples prepared under different experimental conditions. It was found that solubility decreases as the alpha-helix is converted to an antiparallel beta-sheet structure.