NMR and GC/MS investigation of the saturate and distillate fractions from the Cerro Negro heavy petroleum crude

Six fractions of the Cerro Negro heavy petroleum crude have been evaluated using nuclear magnetic resonance spectroscopy (NMR) and gas chromatography/mass spectrometry (GC/MS). The fractions include four saturated hydrocarbon distillate fractions distilling above 200/sup 0/C (200 to 425/sup 0/C (392 to 797/sup 0/F), 425 to 550/sup 0/C (797 to 1022/sup 0/F), 550 to 700/sup 0/C (1022 to 1292/sup 0/F), and >700/sup 0/C (>1292/sup 0/F)) and two distillate subfractions designated as <200/sup 0/C and >200/sup 0/C. The >700/sup 0/C and 550 to 700/sup 0/C saturated hydrocarbon fractions are not suited for analyses by combined GC/MS because their distillation ranges are higher than the upper limit of material that will elute from the gas chromatographic column. The /sup 1/H and /sup 13/C NMR spectral data for the 550 to 700/sup 0/C and >700/sup 0/C fractions indicate that normal and branched alkanes with an average carbon chainlength of C/sub 10/ are present but must be bonded to a larger molecular moiety based upon mass spectral evidence and boiling point considerations. Normal and branched alkanes were not detected in either 200 to 425/sup 0/C or 425 to 550/sup 0/C samples at concentrations of 0.01% by weight. NMR data for the 200 to 425/sup 0/C fraction give no indication of normal alkanes with C chainlengths >9. Branched alkanes possibly of the isoprenoid-like structure are present. The average molecular structural representation is an alkyl-substituted dicyclic alkane. Average molecular structural representation for the 425 to 550/sup 0/C fraction is also an alkyl-substituted dicyclic alkane. However, at least one of the alkyl substituents has a chainlength >10. Both normal and branched alkanes of C/sub 7-12/ were detected in the <200/sup 0/C subfraction. Alkanes of C/sub 12-31/ were in the >200/sup 0/C sample. /sup 1/H and /sup 13/C spectra for both subfractions indicate similar chemical composition. 12 refs., 6 figs., 8 tabs

Kepler photometry of RRc stars: peculiar double-mode pulsations and period doubling

We present the analysis of four first overtone RR Lyrae stars observed with the Kepler space telescope, based on data obtained over nearly 2.5 yr. All four stars are found to be multiperiodic. The strongest secondary mode with frequency f2 has an amplitude of a few mmag, 20–45 times lower than the main radial mode with frequency f1. The two oscillations have a period ratio of P2/P1 = 0.612–0.632 that cannot be reproduced by any two radial modes. Thus, the secondary mode is non-radial. Modes yielding similar period ratios have also recently been discovered in other variables of the RRc and RRd types. These objects form a homogenous group and constitute a new class of multimode RR Lyrae pulsators, analogous to a similar class of multimode classical Cepheids in the Magellanic Clouds. Because a secondary mode with P2/P1 ∼ 0.61 is found in almost every RRc and RRd star observed from space, this form of multiperiodicity must be common. In all four Kepler RRc stars studied, we find subharmonics of f2 at ∼1/2f2 and at ∼3/2f2. This is a signature of period doubling of the secondary oscillation, and is the first detection of period doubling in RRc stars. The amplitudes and phases of f2 and its subharmonics are variable on a time-scale of 10–200 d. The dominant radial mode also shows variations on the same time-scale, but with much smaller amplitude. In three Kepler RRc stars we detect additional periodicities, with amplitudes below 1 mmag, that must correspond to non-radial g-modes. Such modes never before have been observed in RR Lyrae variables

Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>In a previous report we have demonstrated that the chymotryptic-like serine protease kallikrein 7 (<it>KLK7</it>/hK7) is overexpressed in pancreatic cancer. In normal skin, hK7 is thought to participate in skin desquamation by contributing in the degradation of desmosomal components, such as desmogleins. Thus, the ability of hK7 to degrade desmogleins was assessed and the effect of hK7 expression on desmoglein 2 was examined in cultured pancreatic cancer cells.</p> <p>Methods</p> <p>The expression of Dsg1, Dsg2, and Dsg3 in pancreatic tissues was examined by immunohistochemistry and their expression in two pancreatic cancer cell lines, BxPC-3 and Panc-1, was determined by western blot analysis. The ability of hK7 to degrade Dsg1 and Dsg2 was investigated using <it>in vitro </it>degradation assays. BxPC-3 cells stably transfected to overexpress hK7 were used to examine the effect of hK7 on cell-surface resident Dsg2.</p> <p>Results</p> <p>The levels of immunoreactive Dsg1 and Dsg2 were reduced in pancreatic adenocarcinomas compared with both normal pancreatic and chronic pancreatitis tissues. Among the desmosomal proteins examined, Dsg2 exhibited robust expression on the surface of BxPC-3 cells. When hK7 was overexpressed in this cell line, there was a significant increase in the amount of soluble Dsg2 released into the culture medium compared with vector-transfected control cells.</p> <p>Conclusion</p> <p>A reduction in the amount of the cell adhesion components Dsg1 and Dsg2 in pancreatic tumors suggests that loss of these desmosomal proteins may play a role in pancreatic cancer invasion. Using <it>in vitro </it>degradation assays, both Dsg1 and Dsg2 could be readily proteolyzed by hK7, which is overexpressed in pancreatic adenocarcinomas. The enforced expression of hK7 in BxPC-3 cells that express significant amounts of Dsg2 resulted in a marked increase in the shedding of soluble Dsg2, which is consistent with the notion that aberrant expression of hK7 in pancreatic tumors may result in diminished cell-cell adhesion and facilitate tumor cell invasion.</p

Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis

<p>Abstract</p> <p>Background</p> <p>Clinical trials where cancer patients were treated with protease inhibitors have suggested that the serine protease, prostasin, may act as a tumour suppressor. Prostasin is proteolytically activated by the serine protease, matriptase, which has a very high oncogenic potential. Prostasin is inhibited by protease nexin-1 (PN-1) and the two isoforms encoded by the mRNA splice variants of <it>hepatocyte growth factor activator inhibitor-1 </it>(<it>HAI-1</it>), <it>HAI-1A</it>, and <it>HAI-1B</it>.</p> <p>Methods</p> <p>Using quantitative RT-PCR, we have determined the mRNA levels for <it>prostasin </it>and <it>PN-1 </it>in colorectal cancer tissue (n = 116), severe dysplasia (n = 13), mild/moderate dysplasia (n = 93), and in normal tissue from the same individuals. In addition, corresponding tissues were examined from healthy volunteers (n = 23). A part of the cohort was further analysed for the mRNA levels of the two variants of HAI-1, here denoted <it>HAI-1A </it>and <it>HAI-1B</it>. mRNA levels were normalised to <it>β-actin</it>. Immunohistochemical analysis of prostasin and HAI-1 was performed on normal and cancer tissue.</p> <p>Results</p> <p>The mRNA level of prostasin was slightly but significantly decreased in both mild/moderate dysplasia (p < 0.001) and severe dysplasia (p < 0.01) and in carcinomas (p < 0.05) compared to normal tissue from the same individual. The mRNA level of <it>PN-1 </it>was more that two-fold elevated in colorectal cancer tissue as compared to healthy individuals (p < 0.001) and elevated in both mild/moderate dysplasia (p < 0.01), severe dysplasia (p < 0.05) and in colorectal cancer tissue (p < 0.001) as compared to normal tissue from the same individual. The mRNA levels of <it>HAI-1A </it>and <it>HAI-1B </it>mRNAs showed the same patterns of expression. Immunohistochemistry showed that prostasin is located mainly on the apical plasma membrane in normal colorectal tissue. A large variation was found in the degree of polarization of prostasin in colorectal cancer tissue.</p> <p>Conclusion</p> <p>These results show that the mRNA level of <it>PN-1 </it>is significantly elevated in colorectal cancer tissue. Future studies are required to clarify whether down-regulation of prostasin activity via up regulation of PN-1 is causing the malignant progression or if it is a consequence of it.</p

Phenotypic Overlap between MMP-13 and the Plasminogen Activation System during Wound Healing in Mice

BACKGROUND: Proteolytic degradation of extracellular matrix is a crucial step in the healing of incisional skin wounds. Thus, healing of skin wounds is delayed by either plasminogen-deficiency or by treatment with the broad-spectrum metalloproteinase (MP) inhibitor Galardin alone, while the two perturbations combined completely prevent wound healing. Both urokinase-type plasminogen activator and several matrix metallo proteinases (MMPs), such as MMP-3, -9 and -13, are expressed in the leading-edge keratinocytes of skin wounds, which may account for this phenotypic overlap between these classes of proteases. METHODOLOGY: To further test that hypothesis we generated Mmp13;Plau and Mmp13;Plg double-deficient mice in a cross between Mmp13- and Plau-deficient mice as well as Mmp13- and Plg-deficient mice. These mice were examined for normal physiology in a large cohort study and in a well-characterized skin wound healing model, in which we made incisional 20 mm-long full-thickness skin wounds. PRINCIPAL FINDINGS: While mice that are deficient in Mmp13 have a mean healing time indistinguishable to wild-type mice, wound healing in both Plau- and Plg-deficient mice is significantly delayed. Histological analysis of healed wounds revealed a significant increase in keratin 10/14 immunoreactive layers of kerationcytes in the skin surface in Mmp13;Plau double-deficient mice. Furthermore, we observe, by immunohistological analysis, an aberrant angiogenic pattern during wound healing induced by Plau-deficiency, which has not previously been described. CONCLUSIONS: We demonstrate a phenotypic overlap, defined as an additional delay in wound healing in the double-deficient mice compared to the individual single-deficient mice, between MMP-13 and the plasminogen activation system in the process of wound healing, but not during gestation and in postnatal development. Thus, a dual targeting of uPA and MMP-13 might be a possible future strategy in designing therapies aimed at tissue repair or other pathological processes, such as cancer invasion, where proteolytic degradation is a hallmark

Linking genes to literature: text mining, information extraction, and retrieval applications for biology

Efficient access to information contained in online scientific literature collections is essential for life science research, playing a crucial role from the initial stage of experiment planning to the final interpretation and communication of the results. The biological literature also constitutes the main information source for manual literature curation used by expert-curated databases. Following the increasing popularity of web-based applications for analyzing biological data, new text-mining and information extraction strategies are being implemented. These systems exploit existing regularities in natural language to extract biologically relevant information from electronic texts automatically. The aim of the BioCreative challenge is to promote the development of such tools and to provide insight into their performance. This review presents a general introduction to the main characteristics and applications of currently available text-mining systems for life sciences in terms of the following: the type of biological information demands being addressed; the level of information granularity of both user queries and results; and the features and methods commonly exploited by these applications. The current trend in biomedical text mining points toward an increasing diversification in terms of application types and techniques, together with integration of domain-specific resources such as ontologies. Additional descriptions of some of the systems discussed here are available on the internet