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The translation eukaryotic elongation factor 1alpha (eEF1A) is a monomeric GTPase involved in protein synthesis. In addition, this protein is thought to participate in other cellular functions such as actin bundling, cell cycle regulation, and apoptosis. Here we show that eEF1A is associated with the alpha2 subunit of the inhibitory glycine receptor in pulldown experiments with rat brain extracts. Moreover, additional proteins involved in translation like ribosomal S6 protein and p70 ribosomal S6 protein kinase as well as ERK1/2 and calcineurin were identified in the same pulldown approaches. Glycine receptor activation in spinal cord neurons cultured for 1 week resulted in an increased phosphorylation of ribosomal S6 protein. Immunocytochemistry showed that eEF1A and ribosomal S6 protein are localized in the soma, dendrites, and at synapses of cultured hippocampal and spinal cord neurons. Consistent with our biochemical data, immunoreactivities of both proteins were partially overlapping with glycine receptor immunoreactivity in cultured spinal cord and hippocampal neurons. After 5 weeks in culture, eEF1A immunoreactivity was redistributed to the cytoskeleton in about 45% of neurons. Interestingly, the degree of redistribution could be increased at earlier stages of in vitro differentiation by inhibition of either the ERK1/2 pathway or glycine receptors and simultaneous N-methyl-D-aspartate receptor activation. Our findings suggest a functional coupling of eEF1A with both inhibitory and excitatory receptors, possibly involving the ERK-signaling pathway.
Defects in podocyte signaling are the basis of many inherited glomerular diseases leading to glomerulosclerosis. CD2-associated protein (CD2AP) is highly expressed in podocytes and is considered to play an important role in the maintenance of the glomerular slit diaphragm. Mice deficient for CD2AP (CD2AP(-/-)) appear normal at birth but develop a rapid onset nephrotic syndrome at 3 weeks of age. We demonstrate that impaired intracellular signaling with subsequent podocyte damage is the reason for this delayed podocyte injury in CD2AP(-/-) mice. We document that CD2AP deficiency in podocytes leads to diminished signal initiation and termination of signaling pathways mediated by receptor tyrosine kinases (RTKs). In addition, we demonstrate that CIN85, a paralog of CD2AP, is involved in termination of RTK signaling in podocytes. CIN85 protein expression is increased in CD2AP(-/-) podocytes in vitro. Stimulation of CD2AP(-/-) podocytes with various growth factors, including insulin-like growth factor 1, vascular endothelial growth factor, and fibroblast growth factor, resulted in a significantly decreased phosphatidylinositol 3-kinase/AKT and ERK signaling response. Moreover, increased CIN85 protein is detectable in podocytes in diseased CD2AP(-/-) mice, leading to decreased base-line activation of ERK and decreased phosphorylation after growth factor stimulation in vivo. Because repression of CIN85 protein leads to a restored RTK signaling response, our results support an important role of CD2AP/CIN85 protein balance in the normal signaling response of podocytes.
Phosphodiesterase type 2A (PDE2A) hydrolyzes cyclic nucleotides cAMP and cGMP, thus efficiently controlling cNMP-dependent signaling pathways. PDE2A is composed of an amino-terminal region, two regulatory GAF domains, and a catalytic domain. Cyclic nucleotide hydrolysis is known to be activated by cGMP binding to GAF-B; however, other mechanisms may operate to fine-tune local cyclic nucleotide levels. In a yeast two-hybrid screening we identified XAP2, a crucial component of the aryl hydrocarbon receptor (AhR) complex, as a major PDE2A-interacting protein. We mapped the XAP2 binding site to the GAF-B domain of PDE2A. PDE assays with purified proteins showed that XAP2 binding does not change the enzymatic activity of PDE2A. To analyze whether PDE2A could affect the function of XAP2, we studied nuclear translocation of AhR, i.e. the master transcription factor controlling the expression of multiple detoxification genes. Notably, regulation of AhR target gene expression is initiated by tetrachlorodibenzodioxin (TCDD) binding to AhR and by a poorly understood cAMP-dependent pathway followed by the translocation of AhR from the cytosol into the nucleus. Binding of PDE2A to XAP2 inhibited TCDD- and cAMP-induced nuclear translocation of AhR in Hepa1c1c7 hepatocytes. Furthermore, PDE2A attenuated TCDD-induced transcription in reporter gene assays. We conclude that XAP2 targets PDE2A to the AhR complex, thereby restricting AhR mobility, possibly by a local reduction of cAMP levels. Our results provide first insights into the elusive cAMP-dependent regulation of AhR.
Identification of a lysosomal peptide transport system induced during dendritic cell development
(2007)
The delivery of protein fragments to major histocompatibility complex (MHC)-loading compartments of professional antigen-presenting cells is essential in the adaptive immune response against pathogens. Apart from the crucial role of the transporter associated with antigen processing (TAP) for peptide loading of MHC class I molecules in the endoplasmic reticulum, TAP-independent translocation pathways have been proposed but not identified so far. Based on its overlapping substrate specificity with TAP, we herein investigated the ABC transporter ABCB9, also named TAP-like (TAPL). Remarkably, TAPL expression is strongly induced during differentiation of monocytes to dendritic cells and to macrophages. TAPL does not, however, restore MHC class I surface expression in TAP-deficient cells, demonstrating that TAPL alone or in combination with single TAP subunits does not form a functional transport complex required for peptide loading of MHC I in the endoplasmic reticulum. In fact, by using quantitative immunofluorescence and subcellular fractionation, TAPL was detected in the lysosomal compartment co-localizing with the lysosome-associated membrane protein LAMP-2. By in vitro assays, we demonstrate a TAPL-specific translocation of peptides into isolated lysosomes, which strictly requires ATP hydrolysis. These results suggest a mechanism by which antigenic peptides have access to the lysosomal compartment in professional antigen-presenting cells.
The cytochrome bc1 complex is a dimeric enzyme of the inner mitochondrial membrane that links electron transfer from ubiquinol to cytochrome c by a protonmotive Q cycle mechanism in which ubiquinol is oxidized at one center in the enzyme, referred to as center P, and ubiquinone is rereduced at a second center, referred to as center N. To better understand the mechanism of ubiquinol oxidation, we have examined catalytic activities and pre-steady-state reduction kinetics of yeast cytochrome bc1 complexes with mutations in cytochrome b that we expected would affect oxidation of ubiquinol. We mutated two residues thought to be involved in proton conduction linked to ubiquinol oxidation, Tyr132 and Glu272, and two residues proposed to be involved in docking ubiquinol into the center P pocket, Phe129 and Tyr279. Substitution of Phe129 by lysine or arginine yielded a respiration-deficient phenotype and lipid-dependent catalytic activity. Increased bypass reactions were detectable for both variants, with F129K showing the more severe effects. Substitution with lysine leads to a disturbed coordination of a b heme as deduced from changes in the midpoint potential and the EPR signature. Removal of the aromatic side chain in position Tyr279 lowers the catalytic activity accompanied by a low level of bypass reactions. Pre-steady-state kinetics of the enzymes modified at Glu272 and Tyr132 confirmed the importance of their functional groups for electron transfer. Altered center N kinetics and activation of ubiquinol oxidation by binding of cytochrome c in the Y132F and E272D enzymes indicate long range effects of these mutations.
The cytochrome bc1 complex recycles one of the two electrons from quinol (QH2) oxidation at center P by reducing quinone (Q) at center N to semiquinone (SQ), which is bound tightly. We have analyzed the properties of SQ bound at center N of the yeast bc1 complex. The EPR-detectable signal, which reports SQ bound in the vicinity of reduced bH heme, was abolished by the center N inhibitors antimycin, funiculosin, and ilicicolin H, but was unchanged by the center P inhibitors myxothiazol and stigmatellin. After correcting for the EPR-silent SQ bound close to oxidized bH, we calculated a midpoint redox potential (Em) of approximately 90 mV for all bound SQ. Considering the Em values for bH and free Q, this result indicates that center N preferentially stabilizes SQ.bH(3+) complexes. This favors recycling of the electron coming from center P and also implies a >2.5-fold higher affinity for QH2 than for Q at center N, which would potentially inhibit bH oxidation by Q. Using pre-steady-state kinetics, we show that Q does not inhibit the initial rate of bH reduction by QH2 through center N, but does decrease the extent of reduction, indicating that Q binds only when bH is reduced, whereas QH2 binds when bH is oxidized. Kinetic modeling of these results suggests that formation of SQ at one center N in the dimer allows stabilization of SQ in the other monomer by Q reduction after intradimer electron transfer. This model allows maximum SQ.bH(3+) formation without inhibition of Q binding by QH2.
We have investigated the mechanism responsible for half-of-the-sites activity in the dimeric cytochrome bc(1) complex from Paracoccus denitrificans by characterizing the kinetics of inhibitor binding to the ubiquinol oxidation site at center P. Both myxothiazol and stigmatellin induced a 2-3 nm shift of the visible absorbance spectrum of the b(L) heme. The shift generated by myxothiazol was symmetric, with monophasic kinetics that indicate equal binding of this inhibitor to both center P sites. In contrast, stigmatellin generated an asymmetric shift in the b(L) spectrum, with biphasic kinetics in which each phase contributed approximately half of the total magnitude of the spectral change. The faster binding phase corresponded to a more symmetrical shift of the b(L) spectrum relative to the slower binding phase, indicating that approximately half of the center P sites bound stigmatellin more slowly and in a different position relative to the b(L) heme, generating a different effect on its electronic environment. Significantly, the slow stigmatellin binding phase was lost as the inhibitor concentration was increased. This implies that a conformational change is transmitted from one center P site in the dimer to the other upon stigmatellin binding to one monomer, rendering the second site less accessible to the inhibitor. Because the position that stigmatellin occupies at center P is considered to be analogous to that of the quinol substrate at the moment of electron transfer, these results indicate that the productive enzyme-substrate configuration is prevented from occurring in both monomers simultaneously.
Thioredoxin 1 and thioredoxin 2 have opposed regulatory functions on hypoxia-inducible factor-1α
(2007)
Hypoxia inducible factor 1 (HIF-1), a key regulator for adaptation to hypoxia, is composed of HIF-1alpha and HIF-1beta. In this study, we present evidence that overexpression of mitochondria-located thioredoxin 2 (Trx2) attenuated hypoxia-evoked HIF-1alpha accumulation, whereas cytosolic thioredoxin 1 (Trx1) enhanced HIF-1alpha protein amount. Transactivation of HIF-1 is decreased by overexpression of Trx2 but stimulated by Trx1. Inhibition of proteasomal degradation of HIF-1alpha in Trx2-overexpressing cells did not fully restore HIF-1alpha protein levels, while HIF-1alpha accumulation was enhanced in Trx1-overexpressing cells. Reporter assays showed that cap-dependent translation is increased by Trx1 and decreased by Trx2, whereas HIF-1alpha mRNA levels remained unaltered. These data suggest that thioredoxins affect the synthesis of HIF-1alpha. Trx1 facilitated synthesis of HIF-1alpha by activating Akt, p70S6K, and eIF-4E, known to control cap-dependent translation. In contrast, Trx2 attenuated activities of Akt, p70S6K, and eIF-4E and provoked an increase in mitochondrial reactive oxygen species production. MitoQ, a mitochondria specific antioxidant, reversed HIF-1alpha accumulation as well as Akt activation under hypoxia in Trx2 cells, supporting the notion of translation control mechanisms in affecting HIF-1alpha protein accumulation.
The catalytic mechanism, electron transfer coupled to proton pumping, of heme-copper oxidases is not yet fully understood. Microsecond freeze-hyperquenching single turnover experiments were carried out with fully reduced cytochrome aa(3) reacting with O(2) between 83 micros and 6 ms. Trapped intermediates were analyzed by low temperature UV-visible, X-band, and Q-band EPR spectroscopy, enabling determination of the oxidation-reduction kinetics of Cu(A), heme a, heme a(3), and of a recently detected tryptophan radical (Wiertz, F. G. M., Richter, O. M. H., Cherepanov, A. V., MacMillan, F., Ludwig, B., and de Vries, S. (2004) FEBS Lett. 575, 127-130). Cu(B) and heme a(3) were EPR silent during all stages of the reaction. Cu(A) and heme a are in electronic equilibrium acting as a redox pair. The reduction potential of Cu(A) is 4.5 mV lower than that of heme a. Both redox groups are oxidized in two phases with apparent half-lives of 57 micros and 1.2 ms together donating a single electron to the binuclear center in each phase. The formation of the heme a(3) oxoferryl species P(R) (maxima at 430 nm and 606 nm) was completed in approximately 130 micros, similar to the first oxidation phase of Cu(A) and heme a. The intermediate F (absorbance maximum at 571 nm) is formed from P(R) and decays to a hitherto undetected intermediate named F(W)(*). F(W)(*) harbors a tryptophan radical, identified by Q-band EPR spectroscopy as the tryptophan neutral radical of the strictly conserved Trp-272 (Trp-272(*)). The Trp-272(*) populates to 4-5% due to its relatively low rate of formation (t((1/2)) = 1.2 ms) and rapid rate of breakdown (t((1/2)) = 60 micros), which represents electron transfer from Cu(A)/heme a to Trp-272(*). The formation of the Trp-272(*) constitutes the major rate-determining step of the catalytic cycle. Our findings show that Trp-272 is a redox-active residue and is in this respect on an equal par to the metallocenters of the cytochrome c oxidase. Trp-272 is the direct reductant either to the heme a(3) oxoferryl species or to Cu (2+)(B). The potential role of Trp-272 in proton pumping is discussed.
In the diazotroph Klebsiella pneumoniae the flavoprotein NifL inhibits the activity of the nif-specific transcriptional activator NifA in response to molecular oxygen and combined nitrogen. Sequestration of reduced NifL to the cytoplasmic membrane under anaerobic and nitrogen-limited conditions impairs inhibition of cytoplasmic NifA by NifL. To analyze whether NifL is reduced by electrons directly derived from the reduced menaquinone pool, we studied NifL reduction using artificial membrane systems containing purified components of the anaerobic respiratory chain of Wolinella succinogenes. In this in vitro assay using proteoliposomes containing purified formate dehydrogenase and purified menaquinone (MK6) or 8-methylmenaquinone (MMK6) from W. succinogenes, reduction of purified NifL was achieved by formate oxidation. Furthermore, the respective reduction rates, which were determined using equal amounts of NifL, have been shown to be directly dependent on the concentration of both formate dehydrogenase and menaquinones incorporated into the proteoliposomes, demonstrating a direct electron transfer from menaquinone to NifL. When purified hydrogenase and MK6 from W. succinogenes were inserted into the proteoliposomes, NifL was reduced with nearly the same rate by hydrogen oxidation. In both cases reduced NifL was found to be highly associated to the proteoliposomes, which is in accordance with our previous findings in vivo. On the bases of these experiments, we propose that the redox state of the menaquinone pool is the redox signal for nif regulation in K. pneumoniae by directly transferring electrons onto NifL under anaerobic conditions.
By translocating proteasomal degradation products into the endoplasmic reticulum for loading of major histocompatibility complex I molecules, the ABC transporter TAP plays a focal role in the adaptive immunity against infected or malignantly transformed cells. A key question regarding the transport mechanism is how the quality of the incoming peptide is detected and how this information is transmitted to the ATPase domains. To identify residues involved in this process, we evolved a Trojan horse strategy in which a small artificial protease is inserted into antigenic epitopes. After binding, the TAP backbone in contact is cleaved, allowing the peptide sensor site to be mapped by mass spectrometry. Within this sensor site, we identified residues that are essential for tight coupling of peptide binding and transport. This sensor and transmission interface is restructured during the ATP hydrolysis cycle, emphasizing its important function in the cross-talk between the transmembrane and the nucleotide-binding domains. This allocrite sensor may be similarly positioned in other members of the ABC exporter family.
Sphingosylphosphorylcholine (SPC) is a bioactive lipid that binds to G protein-coupled-receptors and activates various signaling cascades. Here, we show that in renal mesangial cells, SPC not only activates various protein kinase cascades but also activates Smad proteins, which are classical members of the transforming growth factor-β (TGFβ) signaling pathway. Consequently, SPC is able to mimic TGFβ-mediated cell responses, such as an anti-inflammatory and a profibrotic response. Interleukin-1β-stimulated prostaglandin E2 formation is dose-dependently suppressed by SPC, which is paralleled by reduced secretory phospholipase A2 (sPLA2) protein expression and activity. This effect is due to a reduction of sPLA2 mRNA expression caused by inhibited sPLA2 promoter activity. Furthermore, SPC upregulates the profibrotic connective tissue growth factor (CTGF) protein and mRNA expression. Blocking TGFβ signaling by a TGFβ receptor kinase inhibitor causes an inhibition of SPC-stimulated Smad activation and reverses both the negative effect of SPC on sPLA2 expression and the positive effect on CTGF expression. In summary, our data show that SPC, by mimicking TGFβ, leads to a suppression of proinflammatory mediator production and stimulates a profibrotic cell response that is often the end point of an anti-inflammatory reaction. Thus, targeting SPC receptors may represent a novel therapeutic strategy to cope with inflammatory diseases.
2,5-Diformylbenzene-1,4-diol (5) is a well-suited starting compound for the preparation of ditopic hydroquinone-based ligands. Here, we report an optimized synthesis of 5 which improves the overall yield from published 7% to 42 %. Three new ditopic Schiff base ligands, 2,5-[iPr2N(CH2)2N=CH]2 - 1,4-(OH)2-C6H2 (8), 2,5-(pyCH2N=CH)2-1,4-(OH)2-C6H2 (9), and 2,5-[py(CH2)2N=CH]2-1,4- (OH)2-C6H2 (10), have been synthesized from 5 and structurally characterized by X-ray crystal structure analysis (py = 2-pyridyl).
The ATP-binding cassette half-transporter Mdl1 from Saccharomyces cerevisiae has been proposed to be involved in the quality control of misassembled respiratory chain complexes by exporting degradation products generated by the m-AAA proteases from the matrix. Direct functional or structural data of the transport complex are, however, not known so far. After screening expression in various hosts, Mdl1 was overexpressed 100-fold to 1% of total mitochondrial membrane protein in S. cerevisiae. Based on detergent screens, Mdl1 was solubilized and purified to homogeneity. Mdl1 showed a high binding affinity for MgATP (Kd = 0.26 μm) and an ATPase activity with a Km of 0.86 mm (Hill coefficient of 0.98) and a turnover rate of 2.6 ATP/s. Mutagenesis of the conserved glutamate downstream of the Walker B motif (E599Q) or the conserved histidine of the H-loop (H631A) abolished ATP hydrolysis, whereas ATP binding was not affected. Mdl1 reconstituted into liposomes showed an ATPase activity similar to the solubilized complex. By single particle electron microscopy, a first three-dimensional structure of the mitochondrial ATP-binding cassette transporter was derived at 2.3-nm resolution, revealing a homodimeric complex in an open conformation.
Bovine mitochondrial ATP synthase commonly is isolated as a monomeric complex that contains 16 protein subunits and the natural IF1 inhibitor protein in substoichiometric amounts. Alternatively ATP synthase can be isolated in dimeric and higher oligomeric states using digitonin for membrane solubilization and blue native or clear native electrophoresis for separation of the native mitochondrial complexes. Using blue native electrophoresis we could identify two ATP synthase-associated membrane proteins with masses smaller than 7 kDa and isoelectric points close to 10 that previously had been removed during purification. We show that in the mitochondrial membrane both proteins are almost quantitatively bound to ATP synthase. Both proteins had been identified earlier in a different context, but their association with ATP synthase was unknown. The first one had been named 6.8-kDa mitochondrial proteolipid because it can be isolated by chloroform/methanol extraction from mitochondrial membranes. The second one had been denoted as diabetes-associated protein in insulin-sensitive tissue (DAPIT), which may provide a clue for further functional and clinical investigations.
We present predictions for the pseudorapidity dependence of the azimuthal anisotropy parameters v1 and v2 of baryons and inclusive charged hadrons in Pb + Pb collisions at a LHC energy of sNN=5.5 TeV applying a microscopic transport model, namely the quark–gluon string model (QGSM) which has been recently extended for parton rearrangement and fusion processes. Pb + Pb collisions with impact parameters b=2.3 fm and b=8 fm have been simulated in order to investigate additionally the difference between central and semiperipheral configurations. In contrast to v1ch(η) at RHIC, the directed flow of charged hadrons shows a small normal flow alignment. The elliptic flow v2ch(η) turns out to be rather similar in shape for RHIC and LHC conditions, the magnitude however increases about 10–20% at the LHC, leading to the conclusion that the hydrodynamical limit will be reached.
Within a dynamical quark recombination model, we explore various proposed event-by-event observables sensitive to the microscopic structure of the QCD-matter created at RHIC energies. Charge ratio fluctuations, charge transfer fluctuations and baryon-strangeness correlations are computed from a sample of central Au + Au events at the highest RHIC energy available (sNN=200 GeV). We find that for all explored observables, the calculations yield the values predicted for a quark–gluon plasma only at early times of the evolution, whereas the final state approaches the values expected for a hadronic gas. We argue that the recombination-like hadronization process itself is responsible for the disappearance of the predicted deconfinement signals. This might explain why no fluctuation signatures for the transition between quark and hadronic matter was ever observed in the experimental data up to now.
Low concentrations of oxidized low density lipoprotein (OxLDL) are cytoprotective for phagocytes, although the underlying mechanisms remain unclear. We investigated signaling pathways used by OxLDL to attenuate apoptosis in monocytic cells. OxLDL at 25–50 μg/ml inhibited staurosporine-induced apoptosis in THP-1 cells and mouse peritoneal macrophages, and it was cytoprotective in human primary monocytes upon serum withdrawal. Attenuated cell demise was reversed by blocking extracellular signal-regulated kinase (ERK) signaling. Translocation of cytochrome c to the cytosol was attenuated by OxLDL, which again demanded ERK signaling. Analysis of Bcl-2 family proteins revealed phosphorylation of Bad at serine 112 as well as ERK-dependent inhibition of Mcl-1 degradation. Although the formation of reactive oxygen species (ROS) is an established signal generated by OxLDL, ROS scavengers did not interfere with cell protection by OxLDL. Thus, activation of the ERK signaling pathway by OxLDL is important to protect phagocytes from apoptosis.
The nuclear stopping, the elliptic flow, and the HBT interferometry are calculated by the UrQMD transport model, in which potentials for “pre-formed” particles (string fragments) from color fluxtube fragmentation as well as for confined particles are considered. This description provides stronger pressure at the early stage and describes these observables better than the default cascade mode (where the “pre-formed” particles from string fragmentation are treated to be free-streaming). It should be stressed that the inclusion of potential interactions pushes down the calculated HBT radius RO and pulls up the RS so that the HBT time-related puzzle disappears throughout the energies from AGS, SPS, to RHIC.
Clear native electrophoresis and blue native electrophoresis are microscale techniques for the isolation of membrane protein complexes. The Coomassie Blue G-250 dye, used in blue native electrophoresis, interferes with in-gel fluorescence detection and in-gel catalytic activity assays. This problem can be overcome by omitting the dye in clear native electrophoresis. However, clear native electrophoresis suffers from enhanced protein aggregation and broadening of protein bands during electrophoresis and therefore has been used rarely. To preserve the advantages of both electrophoresis techniques we substituted Coomassie dye in the cathode buffer of blue native electrophoresis by non-colored mixtures of anionic and neutral detergents. Like Coomassie dye, these mixed micelles imposed a charge shift on the membrane proteins to enhance their anodic migration and improved membrane protein solubility during electrophoresis. This improved clear native electrophoresis offers a high resolution of membrane protein complexes comparable to that of blue native electrophoresis. We demonstrate the superiority of high resolution clear native electrophoresis for in-gel catalytic activity assays of mitochondrial complexes I–V. We present the first in-gel histochemical staining protocol for respiratory complex III. Moreover we demonstrate the special advantages of high resolution clear native electrophoresis for in-gel detection of fluorescent labeled proteins labeled by reactive fluorescent dyes and tagged by fluorescent proteins. The advantages of high resolution clear native electrophoresis make this technique superior for functional proteomics analyses.
Proton pumping respiratory complex I is a major player in mitochondrial energy conversion. Yet little is known about the molecular mechanism of this large membrane protein complex. Understanding the details of ubiquinone reduction will be prerequisite for elucidating this mechanism. Based on a recently published partial structure of the bacterial enzyme, we scanned the proposed ubiquinone binding cavity of complex I by site-directed mutagenesis in the strictly aerobic yeast Yarrowia lipolytica. The observed changes in catalytic activity and inhibitor sensitivity followed a consistent pattern and allowed us to define three functionally important regions near the ubiquinone-reducing iron-sulfur cluster N2. We identified a likely entry path for the substrate ubiquinone and defined a region involved in inhibitor binding within the cavity. Finally, we were able to highlight a functionally critical structural motif in the active site that consisted of Tyr-144 in the 49-kDa subunit, surrounded by three conserved hydrophobic residues.
THE DEMAND FOR EFFICIENT MEASURES FOR PREVENTING CONSUMER CREDIT RISKS SUCH AS CREDIT SCORING IS GROWING ACROSS INDUSTRIES. IN GERMANY, SCORECALCULATIONS AND UNDERLYING CONSUMER DATA ARE STILL A WELL-GUARDEDSECRET. THE MARKET LEADER IN THE U.S. NOT ONLY DISCLOSES THE CREDIT SCORING VARIABLES TO THE CUSTOMERS BUT MOREOVER OFFERS THEM ADVICE ON HOW TO QUALIFY FOR BETTER INTEREST RATES.
Order channel management
(2007)
INSTITUTIONAL INVESTORS, I.E. HEDGE FUNDS OR TRADITIONAL FUNDS, FACE ON THE ONE HAND NEW TECHNOLOGY-ENABLED TRADING CHOICES AND ON THE OTHER HAND INCREASED PERFORMANCE PRESSURE FROM THEIR CUSTOMERS. TO BALANCE THESE OPPORTUNITIES AND CHALLENGES, NEW APPROACHES TO MANAGE THEIR TRADING DESKS AND ORDER DECISIONS ARE REQUIRED.
GERMAN BANKS ARE HIGHLY SATISFIED WITH THEIR BUSINESS PROCESS OUTSOURCING (BPO) VENTURES. BENEFITS ARE ACHIEVED THROUGH THE COMBINATION OF A CLOSE VENDOR RELATIONSHIP AND A WELL-DEFINED OUTSOURCING CONTRACT. THE OUTSOURCING OF DOMESTIC PAYMENT PROCESSES IS MOST SUCCESSFUL WHEREAS THE OUTSOURCING OF CONSUMER CREDIT PROCESSES STRUGGLES WITH QUALITY IMPROVEMENTS.
ON THE INTERNET, SEARCH ENGINES INFLUENCE THE BEHAVIOR OF AN INCREASING PART OF CUSTOMERS. BANKS MAKE USE OF SEARCH ENGINES TO PROMOTE PRODUCTS BY USING KEYWORD AUCTIONS TO PURCHASE A PLACE OF THEIR ADVERTISEMENTS IN THE SPONSORED SEARCH LISTINGS. WE DESCRIBE HOW TO BID IN KEYWORD AUCTIONS AND HOW TO MEASURE THE SUCCESS OF SEARCHENGINE MARKETING.
This article inquires the relevancy of multiple temporalisations for the discourse analysis of testimonial interviews. Step by step and by help of a range of empirical cases, the author widens the analytical scope (from questions, lines of questions, to supported interrogation by help of files and archives). He does so in order to reconstruct the efficient resources and means of forensic and administrative interrogations. The interviews turn out to be most powerful once they establish duplicity, meaning a partial separation of speech-production and speech-reception. Conclusively the author argues for a symmetrical view on scientific (qualitative) interviews and forensic interrogation. The separation of production and reception is widely ignored in qualitative methods.
The vegetation of silver fir forests in southeastern Bohemia (Czech Republic) was studied using the Braun-Blanquet approach. On the basis of 57 phytosociological relevés, three associations were subjectively distinguished: (1) oligotrophic Vaccinio vitis-idaeae-Abietetum, (2) oligo-mesotrophic Luzulo luzuloidis-Abietetum, and (3) mesotrophic Galio rotundifolii-Abietetum (all of them with drier and wetter subtypes). Each association is characterised by species composition, basic soil properties (soil type, humus form), and distribution in the study area. Ellenberg indicator values and detrended correspondence analysis were used to visualize the similarity of vegetation types and detect the main ecological factors determining the proposed classification. The syntaxonomy of fir-dominated forests is discussed.
Evidentiality is a grammatical category which has source of information as its primary meaning — whether the narrator actually saw what is being described, or made inferences about it based on some evidence, or was told about it, and so on. Evidentials are a particularly salient feature of Tibeto-Burman languages. This volume features in-depth studies of evidentiality systems in six languages: Rgyalthang, a Kham Tibetan dialect, by Krisadawan Hongladarom; Yongning Na (Naxi group; believed to be closely related to Lolo-Burmese), by Liberty Lidz; Darma (Almora branch of Western Himalayish), by Christina Willis; nDrapa (Qiangic), by Satoko Shirai; Magar (Himalayish), by Karen Grunow-Hårsta, and Tabo (or Spiti), a Tibetan dialect, by Veronika Hein. Each opens new perspectives on the composition and the semantics of evidential systems, on the marking of more than one information source in one sentence, and on the grammaticalized expression of mirativity.
The new insights on evidentiality and related issues from the Tibeto-Burman area are crucial for understanding evidentials in a cross-linguistic perspective.
This essay deals with two retellings of Genesis: Thomas Mann's "Joseph and his brothers" and Anita Diamant's "The red tent". Both authors note the presence of implicit pagan tendencies among the women of Jacob's clan (Gen 31:19; 35:2) and develop this subtext for their respective ideological purposes. Thomas Mann creates a dichotomy between the backwardness of the pagan female realm and the progressive nature of the monotheistically-oriented patriarchs. The path toward modern humanist values comes from the likes of Jacob and Joseph rather than Rachel and Leah in Mann's novel. Anita Diamant, on the other hand, adopts the opposite attitude, namely, that the paganism of Rachel, Leah, as well as other women in Jacob's family, is a humane and natural form of spirituality in contrast to the bloodthirsty Yahwism of Jacob and his sons. The latter point is illustrated by the sacking of Shechem. In order to question the patriarchal stance of the Old Testament Diamant reverses the key values informing the theology of the Bible. Thus, in "The red tent" Jacob's wives venerate the Ashera in particular. The latter constitutes a challenge to the stance of the Deuteronomic History where the cult of the Ashera is viewed as a key reason behind God's decision to let the Babylonians destroy the Southern Kingdom of Judah. And since Mann's novel upholds the patriarchal spirit of the biblical text, Diamant enters into debate with the continuity of female disempowerment which reaches all the way from Genesis to "Joseph and his brothers".
Siegfried Lenz's novel "Deutschstunde" is analyzed on the basis of work conducted by two American psychologists: Stanley Milgram and Lawrence Kohlberg. The concept of duty and obedience to authority are considered as social phenomena that go beyond personal disposition. The article uses Milgram's famous obedience experiment in order to consider the literary depiction of psychological processes underlying compliance with orders to commit reprehensible acts. A comparison is made between Jens Jepsen, the fictional obedient policeman in "Deutschstunde", and Paul Grueninger, a real policeman in wartime Switzerland, who refused to follow orders and saved many refugees at the Swiss-Austrian border.
It is commonplace to assert that the Book of Genesis in the Old Testament is based on an androcentric position. Although critics have tried to introduce some sort of female empowerment by reassessing various biblical stories (cf. Savina Teubal, 1984), Genesis remains a man's realm with only a limited female perspective. The case of Dinah's rape by Shechem in Genesis 34 illustrates the marginality of womanhood in the biblical world and theology. The pericope tells us that, while the Israelites are settled near the Hivite city of Shechem in Canaan, Jacob's and Leah's daughter Dinah goes out of the Israelite camp. She is raped by Shechem, the prince of the eponymous city, who then abducts her and makes her one of his household. A deal is concluded by Jacob's sons and the Shechemites, according to which the situation can be made legitimate through marriage if the men of Shechem circumcise themselves. While the Shechemites are weak at er the surgery, the Israelites sack the city, kill all the males and take Dinah back.
Modern retellings of the Flood pericope (Genesis 6–8) depend on the age of the targeted audience. Writing for adults, Wolfdietrich Schnurre, Brigitte Schär, Timothy Findley, and Anne Provoost ask whether universal annihilation can be justified. Their criticism of the divine notion that evil is universal and indiscriminate collective punishment is therefore justified, reveals values that are incompatible with those informing the original biblical narrative. However much modernity is aware that myths are symbolic, it apparently cannot assimilate their ethics without a critical reassessment. In this, modern writers rely on the realistic premises of modern novelistic narration. In contrast, modern retellings of the Flood story for children appear to be far more prepared to accept the ancient value system underlying the biblical narrative. Books for younger audiences seem to be much more comfortable with the notion of generalized evil and global punishment than works for adults. This becomes particularly striking in a number of picture books about Noah's ark. The narrative stance of writers ultimately depends on the way they perceive adulthood and childhood.
Information is provided on the taxonomy and distribution of 71 taxa of naturalised or naturalising plants newly recorded for the state of New South Wales during the period 1 January 2002 to 31 December 2003. Of these taxa, 32 are new records for Australia (prefaced with a †). These species are: Abutilon pictum, Acanthus mollis, †Aesculus indica (naturalising), Agapanthus praecox subsp. orientalis, Ajuga reptans, †Anigozanthos flavidus, Aquilegia vulgaris, Arbutus unedo, †Athertonia diversifolia (naturalising), †Bergenia x schmidtii (naturalising), Bromus catharticus subsp. stamineus, Bryophyllum daigremontianum, Bryophyllum fedtschenkoi, Calyptocarpus vialis, †Ceiba speciosa (naturalising), Cereus uruguayanus, †Cestrum x cultum, †Chamaecyparis lawsoniana, Cistus salviifolius, †Clematis montana, †Coprosma x cunninghamii, Coprosma robusta, Cornus capitata, Cotoneaster simonsii, Cotoneaster x watereri group, Crinum moorei, Cupressus lusitanica, †Cylindropuntia fulgida var. mamillata forma monstrosa, †Cylindropuntia prolifera, Cylindropuntia tunicata, Desmanthus virgatus, Drosanthemum candens, †Elaeagnus umbellata (naturalising), †Eragrostis trichophora, †Eupatorium lindleyanum, †Gibasis pellucida, Glechoma hederacea, †Hesperis matronalis, Hieracium aurantiacum subsp. carpathicola, †Inga edulis (naturalising), †Juniperus conferta (naturalising), †Justicia caudata, Lamium galeobdolon, Lathyrus tingitanus, †Lysimachia fortunei, †Maackia amurensis, †Monstera deliciosa, †Murdannia keisak, Odontonema tubaeforme, Oxalis vallicola, Phoenix canariensis, †Physostegia virginiana, Pinus patula, Pittosporum eugenioides, †Pittosporum ralphii, Pittosporum tenuifolium, Plectranthus ecklonii, †Potentilla vesca, †Prunus campanulata, †Rhododendron ponticum, Rosa luciae, Rubus rugosus, Ruellia squarrosa, †Senna multijuga, Stapelia gigantea, Stephanophysum longifolium, Strobilanthes anisophylla, †Tabebuia chrysotricha, †Tabebuia impetiginosa, †Tradescantia pallida and Ulmus x hollandica. Additional notes and name changes are recorded for plants first recognised as naturalised for New South Wales over the period 2000–2001. The identification of several naturalised taxa occurring in New South Wales has been corrected. Plants formerly identified as Pinus nigra var. corsicana are now considered to be Pinus halepensis; Cylindropuntia arbuscula is Cylindropuntia kleiniae, Cylindropuntia tunicata is Cylindropuntia rosea, Abrus precatorius subp. precatorius is now Abrus precatorius subsp. africanus and Cotoneaster ?horizontalis is Cotoneaster microphyllus. Further field studies have revealed that Cylindropuntia leptocaulis, Cylindropuntia spinosior, Hypericum kouytchense and Chamaesyce ophthalmica are more widespread than previously thought.
The first scientific observations on the flora of eastern Australia were made at Botany Bay in April–May 1770. We discuss the landscapes of Botany Bay and particularly of the historic landing place at Kurnell (lat 34˚ 00’ S, long 151˚ 13’ E) (about 16 km south of central Sydney), as described in the journals of Lieutenant James Cook and Joseph Banks on the Endeavour voyage in 1770. We list 132 plant species that were collected at Botany Bay by Banks and Daniel Solander, the first scientific collections of Australian flora. The list is based on a critical assessment of unpublished lists compiled by authors who had access to the collection of the British Museum (now Natural History Museum), together with species from material at National Herbarium of New South Wales that has not been previously available. The list includes Bidens pilosa which has been previously regarded as an introduced species. In 1770 the Europeans set foot on Aboriginal land of the Dharawal people. Since that time the landscape has been altered in response to a succession of different land-uses; farming and grazing, commemorative tree planting, parkland planting, and pleasure ground and tourist visitation. We describe and reconstruct the 1770 vegetation and landscape features of the Kurnell landing place site, now within Botany Bay National Park, based on primary historical sources and surviving remnants of the landscape, and suggest ways in which the remnants can be rehabilitated and enhanced to protect and focus on the botanical, historical and cultural values of this important place.
Wallum is widespread on coastal dunefields, beach ridge plains and associated sandy flats in northern NSW and southern Queensland. These sand masses contain large aquifers, and the wallum ecosystem is considered to be generally groundwater-dependent. This study describes the floristic composition and environmental relations of wallum on a Pleistocene barrier system at Nabiac (32˚ 09’S 152˚ 26’E), on the lower North Coast of NSW. Despite their minimal elevation and degraded relief, the Nabiac barriers maintain floristic patterns related to topography and hence groundwater relations. Comparative analyses identified the Nabiac wallum as representative of the ecosystem throughout large parts of its range in eastern Australia. The Nabiac wallum and nearby estuarine and alluvial vegetation supports species and communities of conservation significance. A borefield is proposed for development on the Nabiac barriers, thereby providing a valuable opportunity for research into mechanisms of groundwater utilisation by the wallum ecosystem.
Vegetation of montane bogs in east-flowing catchments of northern New England, New South Wales
(2007)
The floristics of the montane bogs in east-flowing catchments of northern New England, north-eastern New South Wales (lat 28° 47’–31° 25’ S; long 151° 50’–152° 30’ E), are described from 62 full floristic survey sites (20 x 20 m in area). Eight vegetation communities are based on flexible UPGMA analysis of cover-abundance scores of vascular plant taxa. Shrub species make up 26% of the flora and herb species 69%, with the remaining taxa trees, climbers or vines. Shrub species were of little diagnostic value, as a few common dominants were shared across most communities. The herbaceous layer was found to be of better circumscriptive value. Communities described (based on dominant herbaceous species) are: (1) Themeda australis – Gonocarpus micranthus, (2) Baumea articulata – Baloskion stenocoleum, (3) Lepidosperma limicola – Baloskion stenocoleum, (4) Baloskion fimbriatum – Lomandra longifolia, (5) Lepyrodia scariosa – Blandfordia grandiflora, (6) Lepidosperma gunnii – Lepidosperma scariosa, (7) Baloskion stenocoleum – Empodisma minus, (8) Lepidosperma limicola – Xyris operculata. The mean annual moisture index was found to account for 26% of the variation in species density. These montane bog systems are some of the richest in Australia, with a high number of rare and restricted taxa. They are vulnerable to both present landuse practices and future changes in climate, are restricted in area, and need further conservation efforts to ensure their long-term survival.
Floristic variation in Sphagnum-dominated peatland communities of the Central Highlands, Victoria
(2007)
The floristic composition of Sphagnum-dominated peatlands in the Central Highlands region of Victoria was surveyed (37º 25´ S; 145º 50´ E). NMDS ordination and cluster analysis divided the peatland sites into two broad groups with altitude being the most important factor separating these groups. Other important factors were aspect, slope and the amount of shade. Group 1 included subalpine sites that are similar to those found at higher altitudes further east in Victoria. Important species included Empodisma minus, Epacris paludosa, Richea continentis and Baeckea gunniana. The two species of Sphagnum present were Sphagnum cristatum and the more inundation-tolerant Sphagnum novozelandicum. Group 2 included montane peatlands with abundant Sphagnum cristatum. These sites range from broad wet heaths dominated by Richea victoriana and Carex appressa, to narrower cool temperate rainforest and riparian systems. The ‘rainforest’ peatlands are characterised by Leptospermum grandifolium, Nothofagus cunninghamii, Carex appressa and Blechnum penna-marina, and are in varying stages of post-fire succession regulated by sitespecific microclimate. The conservation status and catchment function of these peatlands are briefly discussed.
Based on 1222 floristic quadrat samples, 56 plant communities were identified in treeless vegetation in the Australian Alps of south-eastern Australia. (c. 35º 30´–38ºS, 146°–149°E). The study encompassed vegetation from above the upper limit of trees on mountain tops (i.e. the truly alpine environment) and below the inverted treeline in subalpine valleys. Generally, grasslands develop on deep humus soils, heathlands occur on shallower or rocky soils, and wetland communities are found in places of permanent or intermittent wetness. Duration of snow cover, lithology, altitude and exposure are also important determinants of the spatial arrangement of communities. Broadly, communities within a geographic region are more closely related to each other than to communities of similar structure or dominants from other geographic areas. Many communities are either very localised or are widespread with a small area of occupancy. Fourteen communities are probably eligible for listing as threatened, either alone or as aggregates with associated communities. A total of 710 native taxa from 82 families has been recorded. There is a high level of endemism – 30% of taxa are ± restricted to treeless vegetation in the Australia Alps and a further 14% are ± restricted to treeless vegetation but occur in mountain areas outside the Australian mainland (e.g. Tasmania and New Zealand). Thirteen taxa are listed in the Environment Protection and Biodiversity Conservation Act 1999 as threatened and a further 18 taxa are identified that may be eligible for listing as threatened nationally. 131 non-native taxa have been recorded in natural vegetation. Treeless vegetation has been intensively utilised since European settlement, initially as summer pastures for cattle and sheep but more recently as water catchments for electricity production and as tourist attractions both in winter and summer. Many communities are slowly recovering from past pressures and from the fires of 2003, which burnt most of the area for the first time since 1939. The treeless vegetation of the Australian Alps faces an uncertain future because of increased pressure from tourism and the unknown impacts of global warming.
Pre-clearing vegetation of the coastal lowlands of the Wet Tropics Bioregion, North Queensland
(2007)
A pre-clearing vegetation map and digital coverage at approximately 1:50 000 scale for the coastal lowlands (up to about 200 m elevation) of the Wet Tropics Bioregion, North Queensland is presented. The study area covers about 508 000 ha from Cooktown, 420 km south almost to Townsville (latitude 15° 30’–18° 20’ longitude 144° 50’–146° 40’). Data sources included historical aerial photography, early surveyors’ plans, explorers’ journals, previous vegetation maps, and maps of soils and geology. The pre-clearing mapping was built around the remnant vegetation mapping of Stanton & Stanton (2005), and the vegetation classification of this latter work was adopted. Vegetation units were further classified into regional ecosystems compatible with the standard State-wide system used by Queensland government. The digital coverage is part of the current Queensland Herbarium regional ecosystem coverage (Queensland Herbarium and Wet Tropics Management Authority 2005). Coloured maps (1:100 000 scale) of the pre-clearing vegetation of the Herbert, Tully, Innisfail and Macalister/Daintree subregions are on an accompanying CD-ROM. An evaluation of vegetation loss through clearing on the coastal lowlands of the Wet Tropics revealed several nearextinct vegetation communities and regional ecosystems, and many others that are drastically reduced in area. Even ecosystems occurring on poorly drained lands have suffered a surprisingly high level of loss due to the effectiveness of drainage operations. Grassland ecosystems were found to be widespread on the Herbert and Tully floodplains, but are now close to extinction. The lowlands vegetation of the Wet Tropics that remains today continues to be fragmented and degraded despite the introduction of State-wide broad-scale tree-clearing laws in 1999, and the cessation of broadscale tree-clearing in December 2006.
Soil and vegetation data were collected from a sodic-scald near Yelarbon in southern Queensland. The surface of the landscape includes relatively light textured pedestals of the A-horizon with slightly alkaline pH and slopes leading down to scalded basement representing the surface of the strongly alkaline B-horizon. The strongest gradient within the floristic patterns was associated with wetland vegetation in drainage lines, but a secondary and orthogonal gradient was related to soil pH, which was probably a function of lower alkalinity on the more stable and weathered A-horizons. There were few significant differences between soil or vegetation characteristics from plot data comparing parts of the landscape with differing historical grazing regimes. Sites included stock routes heavily grazed between the 1920s and 1970s, and subsequently almost ungrazed; and grazed paddocks that have had moderate use throughout this period. There is clear evidence that the area is naturally active in terms of erosion and deposition during flooding regardless of grazing.
Haloragis exalata F. Muell. subspecies exalata (family Haloragaceae), a perennial forb, is currently listed as Vulnerable, under both national and New South Wales threatened species conservation legislation. Very few herbarium records existed until recently. Recent discoveries of Haloragis exalata subsp. exalata in new sites on the NSW South Coast and Southern Tablelands prompted us to carry out surveys for the two varieties of the taxon, var. exalata and var. laevis. Our surveys in 2004– 2007 aimed to relocate historical collection sites and target areas of potentially suitable habitat in these areas. Our work has substantially increased the number of known localities for Haloragis exalata subsp. exalata var. exalata. It can be locally abundant. Ecologically it appears to function as a gap species whose populations are almost invariably found at sites where disturbance through temporary inundation, physical disturbance, or fire, has exposed bare earth with higher levels of light at ground level than would be present when the local vegetation community is intact. There are morphological differences between populations in disjunct areas. Haloragis exalata subsp. exalata var. laevis is much more restricted. As a result, the conservation status of Haloragis exalata subsp. exalata may need revision, considering that a) var. exalata is more widespread than previously known, but that b) there is only one known extant population of var. laevis, and that c) the population from Geehi area may be a distinct taxon.
Wollemia nobilis Jones et al. (Wollemi Pine) is restricted to four sites growing in warm temperate rainforest typical of the canyons in the Blue Mountains and Wollemi National Parks. 88 vascular plant species were recorded from four sites. The tree canopy at all sites is dominated by Wollemia nobilis, Ceratopetalum apetalum, Doryphora sassafras and Acmena smithii. A large number of fern and vine species dominate the forest floor. Site 1 contains more species than the other sites, possibly due to its diversity of topographic features. Similarity analysis indicates that sites 2 and 3 are the most similar and sites 1 and 4 are least similar in floristic composition. 54% of plant species were recorded at one site only. Ceratopetalum apetalum, Blechnum cartilagineum and Wollemia nobilis were found to contribute most to the similarity between sites.
The bryophytes (mosses, liverworts and hornworts) that occur in the Blue Mountains region of New South Wales (latitude 33˚–34˚ S, longitude 151˚–151˚40’ E) are listed and information is provided on their distribution in the region. Species lists are based on herbarium specimens and field collections. 348 bryophyte taxa have been recorded from 70 families, including 225 moss taxa (in 108 genera from 45 families), 120 liverwort taxa (in 51 genera from 24 families) and 3 hornwort taxa (in 3 genera from one family). The moss families with most taxa are the Pottiaceae (with 23 taxa in 13 genera), Bryaceae (with 15 taxa in 3 genera) and Fissidentaceae (with 13 taxa). The largest genera are Fissidens (13 taxa), Campylopus (9) and Macromitrium (8). The liverwort family with the most taxa is Lepidoziaceae, with 29 taxa in 10 genera. The largest liverwort genera are Frullania (11 taxa) and Riccardia (8). The species lists include collections from both bushland and urban areas. Natural features of the Blue Mountains, including topography, altitude, climate and vegetation appear to be important factors influencing the number of bryophyte species recorded from each location. The number of collections from particular locations has been considerably influenced by ease of access, particularly proximity to roads, public transport and railway stations. The species lists include many records from areas that were not accessible to the early collectors of the late 19th and early 20th centuries such as Wollemi National Park, Gardens of Stone National Park, Newnes Plateau and Kanangra-Boyd National Park.
The vegetation of Imbota Nature Reserve (30° 35’S, 151° 45’E) (218 ha in area), 10 km south-east of Armidale, and Yina Nature Reserve (30° 29’S, 151° 45’E), (101 ha in area), 10 km east of Armidale, on the Northern Tablelands, NSW, is described. Based on classification analyses, air photo interpretation and ground-truthing, seven vegetation communities are described and mapped : 1. Eucalyptus caliginosa (Broad-leaved Stringybark) Grassy Forest and Woodland on deep soils at Imbota; 2. Eucalyptus viminalis (Manna Gum) Grassy Forest and Woodland, Community; 3. Eucalyptus caliginosa (Broad-leaved Stringybark) Grassy Forest and Woodland on shallow soils at Imbota; 4. Eucalyptus caliginosa (Broad-leaved Stringybark) Grassy Forest and Woodland at Yina; 5. Eucalyptus blakelyi (Blakely’s Red Gum) – Eucalyptus melliodora (Yellow Box) Woodland; 6. Eucalyptus viminalis (Manna Gum) – Eucalyptus nova-anglica (New England Peppermint) Grassy Forest and Woodland and 7. Riparian Herbfields 252 vascular plant taxa (from 59 families) were recorded from the two reserves, 179 species in Imbota NR, the larger reserve and 209 in Yina NR. The lower species richness at Imbota is likely to have resulted human disturbance rather than from overall habitat heterogeneity.
The assumption that ‘soils’ and ‘vegetation’ are closely associated was tested by describing soils and vegetation along a Travelling Stock Reserve west of Grenfell, New South Wales (lat 33° 55’S, long 147° 45’E). The transect was selected on the basis of (a) minimising the effects of non-soil factors (human interference, climate and relief) on vegetation and (b) the presence of various soil and vegetation types as indicated by previous mapping. ‘Soils’ were considered at three levels: soil landscapes (a broad mapping unit widely used in central western NSW), soil types (according to a range of classifications) and soil properties (depth, pH, etc.). ‘Vegetation’ was considered in three ways: vegetation type (in various classifications), density/floristic indices (density of woody species, abundance of native species, etc.) and presence/absence of individual species. Sites along the transect were grouped according to soil landscapes or soil types and compared to vegetation types or indices recorded at the sites. Various measures indicated low associations between vegetation types and soil landscapes or soil types. Except for infrequent occurrences of a soil type or landscape, any one soil type or landscape was commonly associated with a number of vegetation types and any one vegetation type was associated with a number of soil landscapes or soil types. However, significant associations between some vegetation indices, mainly density or numbers of woody species, and some soil landscapes and soil types were evident. Although many species were relatively ubiquitous, some groups of species that were restricted to one or two soil types were identified. Canonical Correspondence Analysis provided some suggestions as to which properties (e.g. texture) of these soils were associated with the presence of particular species.
We examined differences in floristics among three regionally-threatened woodland communities in the western Riverina: Blackbox (Eucalyptus largiflorens), Bimble box-Pine (Eucalyptus populnea-Callitris glaucophylla) and Boree (Acacia pendula) between 2001 and 2004. Our aim was to examine possible relationships between the diversity and biomass of groundstorey vegetation, and remnant condition and rainfall both among communities and across years. The three woodland communities varied widely in their plant species composition, with only 22% of the 358 species common to all communities. Seven species, mainly exotic grasses and forbs, contributed 25% of the total cover across all sites and times. Blackbox communities had the greatest number of exotic and annual species. There were poor relationships between condition and diversity, richness, evenness or abundance of groundstorey plant species within 400 m2 quadrats. Overall, sites in better condition tended to support a greater cover of native plants and a lower cover of exotic plants (Blackbox only). There were only weak relationships between rainfall and biomass. The marked variation in species diversity in relation to changing seasonal conditions and within similar condition classes highlights the difficulties of developing benchmarks for separating the effects of management, and seasonal and longer-term climate change.
The aim of this study was to assess the role of currents in the dispersal of seashore species with buoyant propagules. Four introduced species which have now attained a wide distribution in southern and eastern Australia were used as indicators: Cakile edentula, Cakile maritima (Brassicaceae), Euphorbia paralias (Euphorbiaceae) and Arctotheca populifolia (Asteraceae). None arrived in Australia unaided, as all early collection localities are near ports and early long-distance dispersal within Australia was often due to shipping. Buoyancy and viability of propagules were tested to assess dispersal and colonisation potential. Propagule spread was analysed using information from herbarium specimens and fieldwork. A progression of herbarium specimen collection dates could often be explained by regional current regimes, as revealed by stranding locations of drift bottles and drift cards. The eastward spread of Euphorbia paralias from King George Sound, Western Australia, correlated well with stranding patterns of drift bottles released south of the Sound. The colonisation by Arctotheca populifolia of the southern extremity of the Eyre Peninsula and the south-east of South Australia was achieved through fruits carried from Western Australia by the Leeuwin Current. These and other congruencies between patterns of spread and the results of drifter releases are analysed and discussed.
Chemical ozone loss in winter 1991–1992 is recalculated based on observations of the HALOE satellite instrument, ER-2 aircraft measurements and balloon data. HALOE satellite observations are shown to be reliable in the lower stratosphere below 400 K, at altitudes where profiles are most likely disturbed by the enhanced sulfate aerosols, as a result of the Mt. Pinatubo eruption in June 1991. Very large chemical ozone loss was observed below 400 K from Kiruna balloon observations between December and March 1992. Additionally, for the two winters after the Mt. Pinatubo eruption, HALOE satellite observations show a stronger extent of chemical ozone loss at lower altitudes compared to other Arctic winter between 1991 and 2003. In stipe of already occurring deactivation of chlorine in March 1992, Mipas-B and LPMA balloon observations indicate still chlorine activation at lower altitudes, consistent with observed chemical ozone loss occurring between February and March and April. Enhanced chemical ozone loss in the Arctic winter 1991–1992 as calculated in earlier studies is corroborated here.
The Match method for quantification of polar chemical ozone loss is investigated mainly with respect to the impact of mixing across the vortex edge onto this estimate. We show for the winter 2002/03 that significant mixing across the vortex edge occurred and was accurately modeled by the Chemical Lagrangian Model of the Stratosphere. Observations of inert tracers and ozone in-situ from HAGAR on the Geophysica aircraft and sondes and also remote from MIPAS on ENVISAT were reproduced well. The model even reproduced a small vortex remnant that was isolated until June 2003 and was observed in-situ by a balloon-borne whole air sampler. We use this CLaMS simulation to quantify the impact of cross vortex edge mixing on the results of the Match method. It is shown that a time integration of the determined vortex average ozone loss rates as performed in Match results in larger ozone loss than the polar vortex average ozone loss in CLaMS. Also, the determination of the Match ozone loss rates can be influenced by mixing. This is especially important below 430 K, where ozone outside the vortex is lower than inside and the vortex boundary is not a strong transport barrier. This effect and further sampling effects cause an offset between vortex average ozone loss rates derived from Match and deduced from CLaMS with an even sampling for the entire vortex. Both, the time-integration of ozone loss and the determination of ozone loss rates for Match are evaluated using the winter 2002/03 CLaMS simulation. These impacts can explain the differences between CLaMS and Match column ozone loss. While the investigated effects somewhat reduce the apparent discrepancy in January ozone loss rates, a discrepancy between simulations and Match remains. However, its contribution to the accumulated ozone loss over the winter is not large.
Strong perturbations of the Arctic stratosphere during the winter 2002/2003 by planetary waves led to enhanced stretching and folding of the vortex. On two occasions the vortex in the lower stratosphere split into two secondary vortices that re-merged after some days. As a result of these strong disturbances the role of transport in and out of the vortex was stronger than usual. An advection and mixing simulation with the Chemical Lagrangian Model of the Stratosphere (CLaMS) utilising a suite of inert tracers tagging the original position of the air masses has been carried out. The results show a variety of synoptic and small scale features in the vicinity of the vortex boundary, especially long filaments peeling off the vortex edge and being slowly mixed into the mid latitude environment. The vortex folding events, followed by re-merging of different parts of the vortex led to strong filamentation of the vortex interior. During January, February, and March 2003 flights of the Russian high-altitude aircraft Geophysica were performed in order to probe the vortex, filaments and in one case the merging zone between the secondary vortices. Comparisons between CLaMS results and observations obtained from the Geophysica flights show in general good agreement.
During the APE-THESEO mission in the Indian Ocean the Myasishchev Design Bureau stratospheric research aircraft M55 Geophysica performed a flight over and within the inner core region of tropical cyclone Davina. Measurements of total water, water vapour, temperature, aerosol backscattering, ozone and tracers were made and are discussed here in comparison with the averages of those quantities acquired during the campaign time frame.
Temperature anomalies in the tropical tropopause layer (TTL), warmer than average in the lower part and colder than average in the upper TTL were observed. Ozone was strongly reduced compared to its average value, and thick cirrus decks were present up to the cold point, sometimes topped by a layer of very dry air. Evidence for meridional transport of trace gases in the stratosphere above the cyclone and the perturbed water distribution in the TTL is illustrated and discussed.
Adhesion molecules of the integrin beta1 family are thought to be involved in the malignant progression renal cell carcinoma (RCC). Still, it is not clear how they contribute to this process. Since the hematogenous phase of tumour dissemination is the rate-limiting step in the metastatic process, we explored beta1 integrin alterations on several RCC cell lines (A498, Caki1, KTC26) before and after contacting vascular endothelium in a tumour-endothelium (HUVEC) co-culture assay. Notably, alpha2, alpha3 and alpha5 integrins became down-regulated immediately after the tumour cells attached to HUVEC, followed by re-expression shortly thereafter. Integrin down-regulation on RCC cells was caused by direct contact with endothelial cells, since the isolated endothelial membrane fragments but not the cell culture supernatant contributed to the observed effects. Integrin loss was accompanied by a reduced focal adhesion kinase (FAK) expression, FAK activity and diminished binding of tumour cells to matrix proteins. Furthermore, intracellular signalling proteins RCC cells were altered in the presence of HUVEC membrane fragments, in particular 14-3-3 epsilon, ERK2, PKCdelta, PKCepsilon and RACK1, which are involved in regulating tumour cell motility. We, therefore, speculate that contact of RCC cells with the vascular endothelium converts integrin-dependent adhesion to integrin-independent cell movement. The process of dynamic integrin regulation may be an important part in tumour cell migration strategy, switching the cells from being adhesive to becoming motile and invasive.
Consequences of altered eicosanoid patterns for nociceptive processing in mPGES-1-deficient mice
(2007)
Cyclooxygenase-2 (COX-2)-dependent prostaglandin (PG) E2 synthesis in the spinal cord plays a major role in the development of inflammatory hyperalgesia and allodynia. Microsomal PGE2 synthase-1 (mPGES-1) isomerizes COX-2-derived PGH2 to PGE2. Here, we evaluated the effect of mPGES-1-deficiency on the noci-ceptive behavior in various models of nociception that depend on PGE2 synthesis. Surprisingly, in the COX-2-dependent zymosan-evoked hyperalgesia model, the nociceptive behavior was not reduced in mPGES-1-deficient mice despite a marked decrease of the spinal PGE2 synthesis. Similarly, the nociceptive behavior was unaltered in mPGES-1-deficient mice in the formalin test. Importantly, spinal cords and primary spinal cord cells derived from mPGES-1-deficient mice showed a redirection of the PGE2 synthesis to PGD2, PGF2α and 6-keto-PGF1α (stable metabolite of PGI2). Since the latter prostaglandins serve also as mediators of noci-ception they may compensate the loss of PGE2 synthesis in mPGES-1-deficient mice.
Background: In sequencing the genomes of two Xenorhabdus species, we encountered a large number of sequence repeats and assembly anomalies that stalled finishing efforts. This included a stretch of about 12 Kb that is over 99.9% identical between the plasmid and chromosome of X. nematophila.
Results: Whole genome restriction maps of the sequenced strains were produced through optical mapping technology. These maps allowed rapid resolution of sequence assembly problems, permitted closing of the genome, and allowed correction of a large inversion in a genome assembly that we had considered finished.
Conclusion: Our experience suggests that routine use of optical mapping in bacterial genome sequence finishing is warranted. When combined with data produced through 454 sequencing, an optical map can rapidly and inexpensively generate an ordered and oriented set of contigs to produce a nearly complete genome sequence assembly.
After five years of running at RHIC, and on the eve of the LHC heavy-ion program, we highlight the status of femtoscopic measurements. We emphasize the role interferometry plays in addressing fundamental questions about the state of matter created in such collisions, and present an enumerated list of measurements, analyses and calculations that are needed to advance the field in the coming years.
I discuss the physics of non-Abelian plasmas which are locally anisotropic in momentum space. Such momentum-space anisotropies are generated by the rapid longitudinal expansion of the matter created in the first 1 fm/c of an ultrarelativistic heavy ion collision. In contrast to locally isotropic plasmas anisotropic plasmas have a spectrum of soft unstable modes which are characterized by exponential growth of transverse chromo-magnetic/-electric fields at short times. This instability is the QCD analogue of the Weibel instability of QED. Parametrically the chromo-Weibel instability provides the fastest method for generation of soft background fields and dominates the short-time dynamics of the system. The existence of the chromo-Weibel instability has been proven using diagrammatic methods, transport theory, and numerical solution of classical Yang-Mills fields. I review the results obtained from each of these methods and discuss the numerical techniques which are being used to determine the late-time behavior of plasmas subject to a chromo-Weibel instability.
Introduction: Metabolic acidosis during hemorrhagic shock is common and conventionally considered to be due to hyperlactatemia. There is increasing awareness, however, that other nonlactate, unmeasured anions contribute to this type of acidosis.
Methods: Eleven anesthetized dogs were hemorrhaged to a mean arterial pressure of 45 mm Hg and were kept at this level until a metabolic oxygen debt of 120 mLO2/kg body weight had evolved. Blood pH, partial pressure of carbon dioxide, and concentrations of sodium, potassium, magnesium, calcium, chloride, lactate, albumin, and phosphate were measured at baseline, in shock, and during 3 hours post-therapy. Strong ion difference and the amount of weak plasma acid were calculated. To detect the presence of unmeasured anions, anion gap and strong ion gap were determined. Capillary electrophoresis was used to identify potential contributors to unmeasured anions.
Results: During induction of shock, pH decreased significantly from 7.41 to 7.19. The transient increase in lactate concentration from 1.5 to 5.5 mEq/L during shock was not sufficient to explain the transient increases in anion gap (+11.0 mEq/L) and strong ion gap (+7.1 mEq/L), suggesting that substantial amounts of unmeasured anions must have been generated. Capillary electrophoresis revealed increases in serum concentration of acetate (2.2 mEq/L), citrate (2.2 mEq/L), alpha-ketoglutarate (35.3 microEq/L), fumarate (6.2 microEq/L), sulfate (0.1 mEq/L), and urate (55.9 microEq/L) after shock induction.
Conclusion: Large amounts of unmeasured anions were generated after hemorrhage in this highly standardized model of hemorrhagic shock. Capillary electrophoresis suggested that the hitherto unmeasured anions citrate and acetate, but not sulfate, contributed significantly to the changes in strong ion gap associated with induction of shock.
Background: Models of isolated and perfused kidneys are used to study the effects of drugs, hazardous or toxic substances on renal functions. Since physiological and morphological parameters of small laboratory animal kidneys are difficult to compare to human renal parameters, porcine kidney perfusion models have been developed to simulate closer conditions to the human situation, but exact values of renal parameters for different collection and perfusion conditions have not been reported so far. If the organs could be used out of regular slaughtering processes animal experiments may be avoided.
Methods: To assess renal perfusion quality, we analyzed different perfusion settings in a standardized model of porcine kidney hemoperfusion with organs collected in the operating theatre (OP: groups A-D) or in a public abattoir (SLA: group E) and compared the data to in vivo measurements in living animals (CON). Experimental groups had defined preservation periods (0, 2 and 24 hrs), one with additional albumin in the perfusate (C) for edema reduction.
Results: Varying perfusion settings resulted in different functional values (mean +/- SD): blood flow (RBF [ml/min*100 g]: (A) 339.9 +/- 61.1; (C) 244.5 +/- 53.5; (D) 92.8 +/- 25.8; (E) 153.8 +/- 41.5); glomerular filtration (GFR [ml/min*100 g]: (CON) 76.1 +/- 6.2; (A) 59.2 +/- 13.9; (C) 25.0 +/- 10.6; (D) 1.6 +/- 1.3; (E) 16.3 +/- 8.2); fractional sodium reabsorption (RFNa [%] (CON) 99.8 +/- 0.1; (A) 82.3 +/- 8.1; (C) 86.8 +/- 10.3; (D) 38.4 +/- 24.5; (E) 88.7 +/- 5.8). Additionally the tubular coupling-ratio of Na-reabsorption/O2-consumption was determined (TNa/O2-cons [mmol-Na/mmol- O2] (CON) 30.1; (A) 42.0, (C) 80.6; (D) 17.4; (E) 23.8), exhibiting OP and SLA organs with comparable results.
Conclusion: In the present study functional values for isolated kidneys with different perfusion settings were determined to assess organ perfusion quality. It can be summarized that the hemoperfused porcine kidney can serve as a biological model with acceptable approximation to in vivo renal physiology, also if the organs originate from usual slaughtering processes.
Poor condition subarachnoid hemorrhage (SAH) patients present a high mortality and morbidity. In this study, we reviewed the acute interventional (surgical and endovascular) management of 109 SAH-poor condition patients, who were treated as early as logistically possible after confirming stable circulation parameters. Patients over the age of 70 years, without clinical response to painful stimulation were excluded. We recognized at least 3 different postinterventional therapeutic approaches: (1) Norm- or hypovolemic, normotensive hemodilution in 30 patients with space-occupying intracranial hematomas as well as in 31 cases with acute cerebro-spinal-fluid obstruction. (2) Normovolemic, hypertensive hemodilution after unilateral decompressive craniotomy in 23 surgical- and 2 endovascular-treated patients with focalized space occupying lesions and reduced cerebral perfusion. (3) Hypovolemic, normo-, or hypertensive hemodilution after bilateral decompressive craniotomy in 23 cases with massive brain-swelling. We observed a reduced mortality (21%). The overall late outcome was favorable in 56% and unfavorable in 23%. Selective aggressive treatment adapted to increase the cerebral perfusion, seems to be an effective therapy to improve the survival and outcome of several poor condition SAH-patients.
On the Indo-European nature of non-Indo-European animals metaphor : the case of Chinese zoosemy
(2007)
Romance suffix rivalry of action nouns from Middle English verbs in the OED textual prototypes
(2007)
Enzymes involved in tRNA maturation are essential for cytosolic, mitochondrial, and plastid protein synthesis and are therefore localized to these different compartments of the cell. Interestingly, only one isoform of tRNA nucleotidyltransferase (responsible for adding the 3′-terminal cytidine–cytidine–adenosine to tRNAs) has been identified in plants. The present study therefore explored how signals contained on this enzyme allow it to be distributed among the different cell compartments. It is demonstrated that the N-terminal portion of the protein acts as an organellar targeting signal and that differential use of multiple in-frame start codons alters the localization of the protein. Moreover, it is shown that the mature domain has a major impact on the distribution of the protein within the cell. These data indicate that regulation of dual localization involves not only specific N-terminal signals, but also additional factors within the protein or the cell.
Splicing of pre-mRNA is a critical step in mRNA maturation and disturbances cause several genetic disorders. We apply the synthetic tetracycline (tc)-binding riboswitch to establish a gene expression system for conditional tc-dependent control of pre-mRNA splicing in yeast. Efficient regulation is obtained when the aptamer is inserted close to the 5′splice site (SS) with the consensus sequence of the SS located within the aptamer stem. Structural probing indicates limited spontaneous cleavage within this stem in the absence of the ligand. Addition of tc leads to tightening of the stem and the whole aptamer structure which probably prevents recognition of the 5′SS. Combination of more then one aptamer-regulated intron increases the extent of regulation leading to highly efficient conditional gene expression systems. Our findings highlight the potential of direct RNA–ligand interaction for regulation of gene expression.
Water-filtered infrared-A radiation (wIRA) is not implicated in cellular degeneration of human skin
(2007)
Background: Excessive exposure to solar ultraviolet radiation is involved in the complex biologic process of cutaneous aging. Wavelengths in the ultraviolet-A and -B range (UV-A and UV-B) have been shown to be responsible for the induction of proteases, e. g. the collagenase matrix metalloproteinase 1 (MMP-1), which are related to cell aging. As devices emitting longer wavelengths are widely used in therapeutic and cosmetic interventions and as the induction of MMP-1 by water-filtered infrared-A (wIRA) had been discussed, it was of interest to assess effects of wIRA on the cellular and molecular level known to be possibly involved in cutaneous degeneration.
Objectives: Investigation of the biological implications of widely used water-filtered infrared-A (wIRA) radiators for clinical use on human skin fibroblasts assessed by MMP-1 gene expression (MMP-1 messenger ribonucleic acid (mRNA) expression).
Methods: Human skin fibroblasts were irradiated with approximately 88% wIRA (780-1400 nm) and 12% red light (RL, 665-780 nm) with 380 mW/cm² wIRA(+RL) (333 mW/cm² wIRA) on the one hand and for comparison with UV-A (330-400 nm, mainly UV-A1) and a small amount of blue light (BL, 400-450 nm) with 28 mW/cm² UV-A(+BL) on the other hand. Survival curves were established by colony forming ability after single exposures between 15 minutes and 8 hours to wIRA(+RL) (340-10880 J/cm² wIRA(+RL), 300-9600 J/cm² wIRA) or 15-45 minutes to UV-A(+BL) (25-75 J/cm² UV-A(+BL)). Both conventional Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and quantitative real-time RT-PCR techniques were used to determine the induction of MMP-1 mRNA at two physiologic temperatures for skin fibroblasts (30°C and 37°C) in single exposure regimens (15-60 minutes wIRA(+RL), 340-1360 J/cm² wIRA(+RL), 300-1200 J/cm² wIRA; 30 minutes UV-A(+BL), 50 J/cm² UV-A(+BL)) and in addition at 30°C in a repeated exposure protocol (up to 10 times 15 minutes wIRA(+RL) with 340 J/cm² wIRA(+RL), 300 J/cm² wIRA at each time).
Results: Single exposure of cultured human dermal fibroblasts to UV-A(+BL) radiation yielded a very high increase in MMP-1 mRNA expression (11 ±1 fold expression for RT-PCR and 76 ±2 fold expression for real-time RT-PCR both at 30°C, 75 ±1 fold expression for real-time RT-PCR at 37°C) and a dose-dependent decrease in cell survival. In contrast, wIRA(+RL) did not produce cell death and did not induce a systematic increase in MMP-1 mRNA expression (less than twofold expression, within the laboratory range of fluctuation) detectable with the sensitive methods applied. Additionally, repeated exposure of human skin fibroblasts to wIRA(+RL) did not induce MMP-1 mRNA expression systematically (less than twofold expression by up to 10 consecutive wIRA(+RL) exposures and analysis with real-time RT-PCR).
Conclusions: wIRA(+RL) even at the investigated disproportionally high irradiances does not induce cell death or a systematic increase of MMP-1 mRNA expression, both of which can be easily induced by UV-A radiation. Furthermore, these results support previous findings of in vivo investigations on collagenase induction by UV-A but not wIRA and show that infrared-A with appropriate irradiances does not seem to be involved in MMP-1 mediated photoaging of the skin. As suggested by previously published studies wIRA could even be implicated in a protective manner.
Water-filtered infrared-A (wIRA) as a special form of heat radiation with a high tissue penetration and with a low thermal load to the skin surface acts both by thermal and thermic as well as by non-thermal and non-thermic effects. wIRA produces a therapeutically usable field of heat in the tissue and increases tissue temperature, tissue oxygen partial pressure, and tissue perfusion. These three factors are decisive for a sufficient tissue supply with energy and oxygen and consequently as well for wound healing and infection defense.
wIRA can considerably alleviate the pain (with remarkably less need for analgesics) and diminish an elevated wound exudation and inflammation and can show positive immunomodulatory effects. wIRA can advance wound healing or improve an impaired wound healing both in acute and in chronic wounds including infected wounds. Even the normal wound healing process can be improved.
A prospective, randomized, controlled, double-blind study with 111 patients after major abdominal surgery at the University Hospital Heidelberg, Germany, showed with 20 minutes irradiation twice a day (starting on the second postoperative day) in the group with wIRA and visible light VIS (wIRA(+VIS), approximately 75% wIRA, 25% VIS) compared to a control group with only VIS a significant and relevant pain reduction combined with a markedly decreased required dose of analgesics: during 230 single irradiations with wIRA(+VIS) the pain decreased without any exception (median of decrease of pain on postoperative days 2-6 was 13.4 on a 100 mm visual analog scale VAS 0-100), while pain remained unchanged in the control group (p<0.001). The required dose of analgesics was 57-70% lower in the subgroups with wIRA(+VIS) compared to the control subgroups with only VIS (median 598 versus 1398 ml ropivacaine, p<0.001, for peridural catheter analgesia; 31 versus 102 mg piritramide, p=0.001, for patient-controlled analgesia; 3.4 versus 10.2 g metamizole, p=0.005, for intravenous and oral analgesia). During irradiation with wIRA(+VIS) the subcutaneous oxygen partial pressure rose markedly by approximately 30% and the subcutaneous temperature by approximately 2.7°C (both in a tissue depth of 2 cm), whereas both remained unchanged in the control group: after irradiation the median of the subcutaneous oxygen partial pressure was 41.6 (with wIRA) versus 30.2 mm Hg in the control group (p<0.001), the median of the subcutaneous temperature was 38.9 versus 36.4°C (p<0.001). The overall evaluation of the effect of irradiation, including wound healing, pain and cosmesis, assessed on a VAS (0-100 with 50 as indifferent point of no effect) by the surgeon (median 79.0 versus 46.8, p<0.001) or the patient (79.0 versus 50.2, p<0.001) was markedly better in the group with wIRA compared to the control group. This was also true for single aspects: Wound healing assessed on a VAS by the surgeon (median 88.6 versus 78.5, p<0.001) or the patient (median 85.8 versus 81.0, p=0.040, trend) and cosmetic result assessed on a VAS by the surgeon (median 84.5 versus 76.5, p<0.001) or the patient (median 86.7 versus 73.6, p=0.001). In addition there was a trend in favor of the wIRA group to a lower rate of total wound infections (3 of 46, approximately 7%, versus 7 of 48, approximately 15%, p=0.208) including late infections after discharge, caused by the different rate of late infections after discharge: 0 of 46 in the wIRA group and 4 of 48 in the control group. And there was a trend towards a shorter postoperative hospital stay: 9 days in the wIRA group versus 11 days in the control group (p=0.037). The principal finding of this study was that postoperative irradiation with wIRA can improve even a normal wound healing process.
A prospective, randomized, controlled, double-blind study with 45 severely burned children at the Children’s Hospital Park Schönfeld, Kassel, Germany, showed with 30 minutes irradiation once a day (starting on the first day, day of burn as day 1) in the group with wIRA and visible light VIS (wIRA(+VIS), approximately 75% wIRA, 25% VIS) compared to a control group with only VIS a markedly faster reduction of wound size. On the fifth day (after 4 days with irradiation) decision was taken, whether surgical debridement of necrotic tissue was necessary because of deeper (second degree, type b) burns (11 of 21 in the group with wIRA, 14 of 24 in the control group) or non-surgical treatment was possible (second degree, type a, burns). The patients treated conservatively were kept within the study and irradiated till complete reepithelialization. The patients in the group with wIRA showed a markedly faster reduction of wound area: a median reduction of wound size of 50% was reached already after 7 days compared to 9 days in the control group, a median reduction of wound size of 90% was already achieved after 9 days compared to 13 days in the control group. In addition the group with wIRA showed superior results till 3 months after the burn in terms of the overall surgical assessment of the wound, cosmesis, and assessment of effects of irradiation compared to the control group.
In a prospective, randomized, controlled study with 12 volunteers at the University Medical Center Charité, Berlin, Germany, within each volunteer 4 experimental superficial wounds (5 mm diameter) as an acute wound model were generated by suction cup technique, removing the roof of the blister with a scalpel and a sterile forceps (day 1). 4 different treatments were used and investigated during 10 days: no therapy, only wIRA(+VIS) (approximately 75% wIRA, 25% VIS; 30 minutes irradiation once a day), only dexpanthenol (= D-panthenol) cream once a day, wIRA(+VIS) and dexpanthenol cream once a day. Healing of the small experimental wounds was from a clinical point of view excellent with all 4 treatments. Therefore there were only small differences between the treatments with slight advantages of the combination wIRA(+VIS) and dexpanthenol cream and of dexpanthenol cream alone concerning relative change of wound size and assessment of feeling of the wound area. However laser scanning microscopy with a scoring system revealed differences between the 4 treatments concerning the formation of the stratum corneum (from first layer of corneocytes to full formation) especially on the days 5-7: fastest formation of the stratum corneum was seen in wounds treated with wIRA(+VIS) and dexpanthenol cream, second was wIRA(+VIS) alone, third dexpanthenol cream alone and last were untreated wounds. Bacterial counts of the wounds (taken every 2 days) showed, that wIRA(+VIS) and the combination of wIRA(+VIS) with dexpanthenol cream were able to inhibit the colonisation with physiological skin flora up to day 5 when compared with the two other groups (untreated group and group with dexpanthenol cream alone). At any investigated time, the amount of colonisation under therapy with wIRA(+VIS) alone was lower (interpreted as more suppressed) compared with the group with wIRA(+VIS) and dexpanthenol cream.
During rehabilitation after hip and knee endoprosthetic operations the resorption of wound seromas and wound hematomas was both clinically and sonographically faster and pain was reduced by irradiation with wIRA(+VIS).
wIRA can be used successfully for persistent postoperative pain e.g. after thoracotomy.
As perspectives for wIRA it seems clinically prudent to use wIRA both pre- and postoperatively, e.g. in abdominal and thoracic operations. wIRA can be used preoperatively (e.g. during 1-2 weeks) to precondition donor and recipient sites of skin flaps, transplants or partial-thickness skin grafts, and postoperatively to improve wound healing and to decrease pain, inflammation and infections at all mentioned sites. wIRA can be used to support routine pre- or intraoperative antibiotic administration or it might even be discussed to replace this under certain conditions by wIRA.
Principles and working mechanisms of water-filtered infrared-A (wIRA) in relation to wound healing
(2007)
The experience of the pleasant heat of the sun in moderate climatic zones arises from the filtering of the heat radiation of the sun by water vapor in the atmosphere of the earth. The filter effect of water decreases those parts of infrared radiation (most parts of infrared-B and -C and the absorption bands of water within infrared-A), which would cause – by reacting with water molecules in the skin – only an undesired thermal load to the surface of the skin. Technically water-filtered infrared-A (wIRA) is produced in special radiators, whose full spectrum of radiation of a halogen bulb is passed through a cuvette, containing water, which absorbs or decreases the described undesired wavelengths of the infrared radiation. Within infrared the remaining wIRA (within 780-1400 nm) mainly consists of radiation with good penetration properties into tissue and therefore allows – compared to unfiltered heat radiation – a multiple energy transfer into tissue without irritating the skin, similar to the sun’s heat radiation in moderate climatic zones. Typical wIRA radiators emit no ultraviolet (UV) radiation and nearly no infrared-B and -C radiation and the amount of infrared-A radiation in relation to the amount of visible light (380-780 nm) is emphasized.
Water-filtered infrared-A as a special form of heat radiation with a high tissue penetration and with a low thermal load to the skin surface acts both by thermal (related to heat energy transfer) and thermic (temperature depending, with a relevant change of temperature) as well as by non-thermal (without a relevant transfer of heat energy) and non-thermic (not depending on temperature, without a relevant change of temperature) effects. wIRA produces a therapeutically usable field of heat in the tissue and increases tissue temperature, tissue oxygen partial pressure, and tissue perfusion. These three factors are vital for a sufficient tissue supply with energy and oxygen. As wound healing and infection defense (e.g. granulocyte function including their antibacterial oxygen radical formation) depend decisively on a sufficient supply with energy and oxygen, one explanation for the good clinical effect of wIRA on wounds and wound infections can be the improvement of both the energy supply per time (increase of metabolic rate) and the oxygen supply. In addition wIRA has non-thermal and non-thermic effects, which are based on putting direct stimuli on cells and cellular structures.
wIRA can considerably alleviate the pain (with remarkably less need for analgesics) and diminish an elevated wound exudation and inflammation and can show positive immunomodulatory effects. wIRA can advance wound healing or improve an impaired wound healing both in acute and in chronic wounds including infected wounds. Even the normal wound healing process can be improved.
Keywords: water-filtered infrared-A (wIRA), infrared-A radiation, wound healing, thermal and non-thermal effects, thermic and non-thermic effects, energy supply, oxygen supply, tissue oxygen partial pressure, tissue temperature, tissue blood flow, reduction of pain, wound exudation, inflammation, immunomodulatory effects, acute wounds, chronic venous stasis ulcers of the lower legs, problem wounds, wound infections, infection defense, contact-free method, absent expenditure of material, quality of life, prospective, randomized, controlled, double-blind studies
Pope Benedict XVI’s Regensburg lecture has been exposed by some learned voices of 'the Muslim world' as alluding, by the means of one particular quotation, to age-old stereotypes about Islam being an essentially violent creed in which moderation through reason has no legitimate place, and of representing Muhammadas an evil and inhuman man who preached that Islam should be spread by the sword. While none of these presumably 'Muslim' voices deny that the Pope has the right to express his opinions, even when they are plainly wrong in the face of historic facts that show how Islam and Christianity were spread (or were made to spread) across the world, he is criticised for a host of omissions in terms of intellectual honesty and factual accuracy. These omissions, it is argued here, cast an unfortunate light on the compatibility of scientific and religious rationality much advocated by the Pope in his 12 September 2006 lecture. This flagrant 'performative contradiction' (Habermas) leaves room for speculation about the true aim of the speech. Is Benedict XVI's appeal to theology as a legitimate academic discipline a credible attempt to explicate Roman Catholicism's rightful place in a modern world governed by liberal democracy and ethical-political pluralism, or is it a reflection of a move to restore the age-old, intolerant, anti-scientific, and anti-democratic legacy of the pre-Vatican II Catholic Church?
Visual selective attention and visual working memory (WM) share the same capacity-limited resources. We investigated whether and how participants can cope with a task in which these 2 mechanisms interfere. The task required participants to scan an array of 9 objects in order to select the target locations and to encode the items presented at these locations into WM (1 to 5 shapes). Determination of the target locations required either few attentional resources (“popout condition”) or an attention-demanding serial search (“non pop-out condition”). Participants were able to achieve high memory performance in all stimulation conditions but, in the non popout conditions, this came at the cost of additional processing time. Both empirical evidence and subjective reports suggest that participants invested the additional time in memorizing the locations of all target objects prior to the encoding of their shapes into WM. Thus, they seemed to be unable to interleave the steps of search with those of encoding. We propose that the memory for target locations substitutes for perceptual pop-out and thus may be the key component that allows for flexible coping with the common processing limitations of visual WM and attention. The findings have implications for understanding how we cope with real-life situations in which the demands on visual attention and WM occur simultaneously. Keywords: attention, working memory, interference, encoding strategies
The majority of cells are equipped to detect and decipher physical stimuli, and then react to these stimuli in a cell type-specific manner. Ultimately, these cellular behaviors are synchronized to produce a tissue response, but how this is achieved remains enigmatic. Here, we investigated the genetic basis for mechanotransduction using the bone marrow as a model system. We found that physical stimuli produced a pattern of principal strain that precisely corresponded to the site-specific expression of sox9 and runx2, two transcription factors required for the commitment of stem cells to a skeletogenic lineage, and the arrangement and orientation of newly deposited type I collagen fibrils. To gain insights into the genetic basis for skeletal mechanotransduction we conditionally inactivated focal adhesion kinase (FAK), an intracellular component of the integrin signaling pathway. By doing so we abolished the mechanically induced osteogenic response and thus identified a critical genetic component of the molecular machinery required for mechanotransduction. Our data provide a new framework in which to consider how physical forces and molecular signals are synchronized during the program of skeletal regeneration.
The pathogenic spirochete Leptospira interrogans disseminates throughout its hosts via the bloodstream, then invades and colonizes a variety of host tissues. Infectious leptospires are resistant to killing by their hosts' alternative pathway of complement-mediated killing, and interact with various host extracellular matrix (ECM) components. The LenA outer surface protein (formerly called LfhA and Lsa24) was previously shown to bind the host ECM component laminin and the complement regulators factor H and factor H-related protein-1. We now demonstrate that infectious L. interrogans contain five additional paralogs of lenA, which we designated lenB, lenC, lenD, lenE and lenF. All six genes encode domains predicted to bear structural and functional similarities with mammalian endostatins. Sequence analyses of genes from seven infectious L. interrogans serovars indicated development of sequence diversity through recombination and intragenic duplication. LenB was found to bind human factor H, and all of the newly-described Len proteins bound laminin. In addition, LenB, LenC, LenD, LenE and LenF all exhibited affinities for fibronectin, a distinct host extracellular matrix protein. These characteristics suggest that Len proteins together facilitate invasion and colonization of host tissues, and protect against host immune responses during mammalian infection.
In this work we present a study of the influence of nucleus initializations on the event-by-event elliptic flow coefficient, v2. In most Monte-Carlo models, the initial positions of the nucleons in a nucleus are completely uncorrelated, which can lead to very high density regions. In a simple, yet more realistic model where overlapping of the nucleons is avoided, fluctuations in the initial conditions are reduced. However, v2 distributions are not very sensitive to the initialization choice.
Dynamics of relativistic heavy-ion collisions is investigated on the basis of a simple (1+1)-dimensional hydrodynamical model in light-cone coordinates. The main emphasis is put on studying sensitivity of the dynamics and observables to the equation of state and initial conditions. Low sensitivity of pion rapidity spectra to the presence of the phase transition is demonstrated, and some inconsistencies of the equilibrium scenario are pointed out. Possible non-equilibrium effects are discussed, in particular, a possibility of an explosive disintegration of the deconfined phase into quark-gluon droplets. Simple estimates show that the characteristic droplet size should decrease with increasing the collective expansion rate. These droplets will hadronize individually by emitting hadrons from the surface. This scenario should reveal itself by strong non-statistical fluctuations of observables. Critical Point and Onset of Deconfinement 4th International Workshop July 9-13 2007 GSI Darmstadt,Germany
Event-by-event multiplicity fluctuations in nucleus-nucleus collisions from low SPS up to RHIC energies have been studied within the HSD transport approach. Fluctuations of baryonic number and electric charge also have been explored for Pb+Pb collisions at SPS energies in comparison to the experimental data from NA49. We find a dominant role of the fluctuations in the nucleon participant number for the final hadron multiplicity fluctuations and a strong influence of the experimental acceptance on the final results. Critical Point and Onset of Deconfinement - 4th International Workshop July 9 - 13, 2007 Darmstadt, Germany