bluuebunny/crossref_metadata_2025 huggingface dataset:
Fruit and seed polymorphism and its relation to seedling growth in the genus Cakile
Authors: Maun M. A. , Payne A. M.
Published: September 2008

To ascertain the adaptive significance of dimorphism under unpredictable environments, the dimorphic fruit segments of Cakile edentula var. lacustris, Cakile edentula var. edentula, and Cakile maritima were tested for differences in size of propagules, dispersal ability, germination behaviour, and growth rate. The upper and lower fruit segments differed in some attributes but not in others. For example, the fruits, seeds, and shells of upper segments were significantly heavier than those of lower segments. However, the frequency distributions of mean mass per seed, shell, and fruit indicated a considerable zone of overlap beneath the histograms of upper and lower fruit segments. Under still conditions in a greenhouse, no differences were found in the floating ability of upper and lower fruit segments of C. edentula var. lacustris and C. maritima. Of the three taxa, C. maritima fruits had the highest shell to seed mass ratio and floated for the longest period of time. Morphological seed dimorphism was linked with a physiological seed dimorphism. The lower fruit segments of C. edentula var. lacustris germinated better than the upper fruit segments over a wider range of temperatures. Light did not alter the final germination percentage of upper or lower fruit segments but inhibited the rate of germination. The relative growth rate decreased in all three taxa with an increase in the age of a seedling, irrespective of its seed weight.
Gynodioecy in Plantago lanceolata. VI. Functions of cytokinins in growth, development, and reproduction of two sex types
Authors: Olff H. , Kuiper D. , Damme J. M. M. van , Kuiper P. J. C.
Published: September 2008

Theoretical models predict that male sterile plants of gynodioecious species should show at least some compensation for their disadvantage of not reproducing as males through female component of fitness, In this study, growth, development, and reproduction of a hermaphrodite and a male sterile family of Plantago lanceolata L. were compared under controlled conditions. The male sterile plants produced more and longer spikes and had relatively longer styles. The male sterile plants achieved their final biomass sooner, by an earlier formation of side rosettes, and flowered earlier. The hypothesis was tested as to whether cytokinins in the plants are involved as a pleiotropic factor in either or both sex expression and the various plant characteristics associated with the male sterile phenotype. The roots of the male sterile plants had higher concentrations of putative zeatin riboside than the roots of the hermaphroditic plants, as quantified by an enzyme-linked immunoassy after separation of cytokinins by high performance liquid chromatography. Spraying the plants with benzyladenine did not affect internal cytokinin concentrations or sex expression. Benzyladenine spray increased the growth rate of the main rosette and stimulated floral initiation. Our results indicate that cytokinins are possibly involved in determining the morphological differences between sex types in this species.
Taxonomic position of Gremmeniella abietina and related species: a reappraisal
Authors: Petrini Orlando , Petrini Liliane E. , Laflamme Gaston , Ouellette G. B.
Published: September 2008

A comparative study of isolates and their corresponding herbarium specimens of Gremmeniella spp. from pine, spruce, and balsam fir, of Ascocalyx laricina from larch, and of Ascocalyx abietis from balsam fir was conducted using morphological and cultural characteristics as well as electrophoresis tests on 12 and 10 – 15% gradient polyacrylamide gels. In addition, the conidia and the ascospores of the specimens were treated with 4′,6-diamino-2-phenylindole to determine the number of nuclei per cell. Ascocalyx abietis is quite distinct in the morphology of its anamorph and in its cultural characteristics from all other samples studied. The specimens from larch differ from the others by their 2-celled ascospores and their cultural characters. Among specimens from pines and from Picea and Abies, minor morphological and cultural differences were found. The electrophoresis tests confirm the differences observed in the cultural studies. The statistical analysis of the results supports the following classification of the specimens studied: within Gremmeniella abietina, two varieties are recognized, a var. typical, with the known "European" and "North American" races from Pinus and the "Asian" race from Abies sachalinensis, and a new variety, var. balsamea, comprising the isolates from Picea and Abies (Québec). A new combination is proposed in Gremmeniella for Ascocalyx laricina. Ascocalyx abietis is retained as a separate genus.
Leaf carbon isotopic composition (δ13C) and cold hardiness of wheat in relation to growth temperature and moisture stress
Authors: Macdowall F. D. H. , Lowdon J. A.
Published: September 2008

Several cultivars of spring and winter wheats were grown simultaneously several times in environmental control rooms at (i) 25:20 °C (16 h light: 8 h dark), or (ii) 4:2 °C with continuous watering, or (iii) 25:20 °C with nighttime watering and daytime wilting. The mature leaf blades of late vegetative plants were collected, and their carbon isotope ratios (13C:12C) were measured by mass spectrometry and expressed as δ13C, with an accuracy of 0.2‰, to determine if physiological effects of environmental factors other than atmospheric isotope composition could be responsible for previously observed annual cycles in plant δ13C. In (i) and (ii), the values of leaf δ13C (−31 ± 1‰) were in the low end of the C3 range, but winter wheats were about 1.2‰ less negative than spring wheat. The values obtained in (i) were 2‰ lower (more negative) than in (ii) for both wheat types. These results might be indicative of lower carboxylation resistance in winter wheat than in spring wheat and at lower temperature than at higher temperature. The effect in the growth room of temperature alone quantitatively duplicated the seasonal effect in the field. Leaf δ13C values of plants in (iii) were at or beyond the high end of the observed C3 range, presumably as a result of daytime gas exchange limitations imposed by stomatal diffusion resistance and the consequent importance of nighttime phosphoenolpyruvate carboxylase activity. This drought effect was particularly pronounced in winter wheat.
Replacement of native oak and hickory tree species by the introduced American chestnut (Castanea dentata) in southwestern Wisconsin
Authors: Paillet Frederick L. , Rutter Philip A.
Published: September 2008

American chestnut was introduced at West Salem, Wisconsin, about 1880 and had begun to replace native tree species in adjacent oak-hickory woodland before 1930. Chestnut is now an important canopy species over about 20 ha of forested ridge extending north and south of the original plantation. A smaller area of less than 5 ha is dominated by chestnut in both the canopy and understory. Chestnut seedlings and small saplings are more numerous along woodland edges and in recently disturbed soil, they are rare in the interior of ungrazed pasture and entirely absent from intensively grazed areas adjacent to chestnut-dominated woodland. Random sampling of recently established seedlings indicates that from 1 to 5 seedlings/(year ∙ ha) became established in undisturbed woodland between 1986 and 1988. The general pattern of chestnut distribution indicates the importance of woodland edges in chestnut propagation and the effects of livestock grazing in excluding chestnut. Replacement of native species by chestnut appears to have occurred in two steps: isolated groups of trees became established at favorable locations, after which many additional chestnut stems became established in the understory. The recent discovery and treatment of blight indicates that the West Salem site may not be available for study of blight-free chestnut in the future.
Characterization of the chestnut blight canker and the localization and isolation of the pathogen Cryphonectria parasitica
Authors: McManus Patricia S. , Ewers Frank W. , Fulbright Dennis W.
Published: September 2008

Naturally occurring chestnut blight cankers on Castanea dentata were categorized as virulent (sunken bark with abundant stromata) or hypovirulent (swollen bark lacking stromata). In transverse section, xylem tissue of virulent cankers was discolored and largely nonconductive. Hypovirulent cankers had anomalous secondary xylem tissue that was light in color and conducted safranin dye, although xylem of the main stem axes of hypovirulent cankers was discolored. In naturally occurring cankers, no correlation was found between canker morphology and the presence or absence of double-stranded RNA in the inciting fungus (Cryphonectria parasitica). However, a virulent strain lacking double-stranded RNA induced cankers that resembled natural virulent cankers, and inoculation with a known hypovirulent strain containing double-stranded RNA resulted in swollen cankers that resembled natural hypovirulent cankers. Cryphonectria parasitica was isolated from all growth rings of virulent cankers and from the discolored xylem tissue of hypovirulent cankers but not from the conductive anomalous xylem tissue of hypovirulent cankers. Hyphae were observed via fluorescence microscopy in the xylem of natural and induced virulent cankers but not in hypovirulent cankers, whether natural or induced by artificial means.
SURGERY DESCRIPTIONS AND VOLUMES OF BERGE KNOTS I: LARGE VOLUME BERGE KNOTS
Authors: BAKER KENNETH L.
Published: September 2008

By obtaining surgery descriptions of knots which lie on the genus one fiber of the trefoil or figure eight knot, we show that these include hyperbolic knots with arbitrarily large volume. These knots admit lens space surgeries and form two families of Berge knots. By way of tangle descriptions we also obtain surgery descriptions for these knots on minimally twisted chain links.
A NOTE ON FUNDAMENTAL GROUPS OF SYMPLECTIC TORUS COMPLEMENTS IN 4-MANIFOLDS
Authors: ETGÜ TOLGA , PARK B. DOUG
Published: September 2008

Previously, we constructed an infinite family of knotted symplectic tori representing a fixed homology class in the symplectic four-manifold E(n)K, which is obtained by Fintushel–Stern knot surgery using a nontrivial fibered knot K in S3, and distinguished the (smooth) isotopy classes of these tori by indirectly computing the Seiberg–Witten invariants of their complements. In this note, we compute the fundamental groups of the complements of these knotted tori and show that for each nontrivial fibered knot K these groups constitute an infinite collection of nonisomorphic groups. We also review some other constructions of symplectic tori in 4-manifolds and show that the fundamental groups of the complements do not distinguish homologous tori in those cases.
MODELING AND ANALYSIS OF A HARVESTING FISHERY MODEL IN A TWO-PATCH ENVIRONMENT
Authors: CAI LIMING , LI XUEZHI , SONG XINYU
Published: September 2008

In this paper, a harvesting fishery model in a two-patch environment: one free-fishing zone and the other one reserved zone where fishing is strictly prohibited, is proposed and analyzed. The existence of possible biological steady states, along with their local stability, instability and global stability is discussed. The existence of bioeconomic equilibrium is derived. An optimal harvesting policy is also given by applying pontryagin's maximum principle.
ALMOST PERIODICITY IN AN IMPULSIVE LOGISTIC EQUATION WITH INFINITE DELAY
Authors: FENG CHUNHUA , HUANG ZHENKUN
Published: September 2008

By employing a fixed point theorem in cones, this paper investigates the existence of almost periodic solutions for an impulsive logistic equation with infinite delay. A set of sufficient conditions on the existence of almost periodic solutions of the equation is obtained.
PERIODIC SOLUTION FOR NEUTRAL DELAY DIFFERENTIAL EQUATIONS MODEL OF PLANKTON ALLELOPATHY
Authors: GUI ZHANJI , ZHANG JIE
Published: September 2008

In this paper, we have proposed a modified neutral delay competitive differential equation model of the growth of two species of plankton having competitive and allelopathic effects on each other. By means of an abstract continuous theorem of k-set contractive operator and some analysis technique. Sufficient conditions are obtained for periodic solution.
REGULARITY AND GREEN'S RELATIONS OF GENERALIZED PARTIAL TRANSFORMATION SEMIGROUPS
Authors: Chinram Ronnason
Published: September 2008

Let X be any set and P(X) be the partial transformation semigroup on X. It is well-known that P(X) is regular. To generalize this, let X and Y be any sets and P(X, Y) be the set of all partial transformations from X to Y. For θ ∈ P(Y, X), let (P(X, Y), θ) be a semigroup (P(X, Y), *) where α * β = αθβ for all α, β ∈ P(X, Y). In this paper, we characterize the semigroup (P(X, Y), θ) to be regular, regular elements of the semigroup (P(X, Y), θ), [Formula: see text]-classes, [Formula: see text]-classes, [Formula: see text]-classes and [Formula: see text]-classes of the semigroup (P(X, Y), θ).
TYPE-A SEMIGROUPS WHOSE FULL SUBSEMIGROUPS FORM A CHAIN UNDER SET INCLUSION
Authors: Guo Xiaojiang , Huang Fusheng , Shum K. P.
Published: September 2008

A semigroup S is called a ∇-semigroup if the set of all its full subsemigroups forms a chain under set inclusion. In this paper, we investigate some properties of such kind of semigroups and establish several characterization theorems of type-A ∇-semigroups. Our theorems generalize the known results of P. R. Jones obtained in 1981 on inverse semigroups whose full inverse subsemigroups form a chain.
PROPERTIES OF TWO SELECTIONS IN METRIC SPACES OF NONPOSITIVE CURVATURE
Authors: Ivanshin Pyotr N.
Published: September 2008

In this article the author proves local Lipschitz properties of two selections for the space of convex hulls of n points and compacts of the complete convex Busemann metric space.
FINITE SUMS CONNECTED WITH THE INVERSES OF CENTRAL BINOMIAL NUMBERS AND CATALAN NUMBERS
Authors: Wituła R. , Słota D.
Published: September 2008

In the paper some trigonometric nature identities for finite sums of inverses of central binomial numbers and Catalan numbers are given.
2,2-Bis(4-Chlorophenyl)-1,1-Dichloroethylene Stimulates Androgen Independence in Prostate Cancer Cells through Combinatorial Activation of Mutant Androgen Receptor and Mitogen-Activated Protein Kinase Pathways
Authors: Shah Supriya , Hess-Wilson Janet K. , Webb Siobhan , Daly Hannah , Godoy-Tundidor Sonia , Kim Jae , Boldison Joanne , Daaka Yehia , Knudsen Karen E.
Published: September 2008

Therapy resistance represents a major clinical challenge in disseminated prostate cancer for which only palliative treatment is available. One phenotype of therapy-resistant tumors is the expression of somatic, gain-of-function mutations of the androgen receptor (AR). Such mutant receptors can use noncanonical endogenous ligands (e.g., estrogen) as agonists, thereby promoting recurrent tumor formation. Additionally, selected AR mutants are sensitized to the estrogenic endocrine-disrupting compound (EDC) bisphenol A, present in the environment. Herein, screening of additional EDCs revealed that multiple tumor-derived AR mutants (including T877A, H874Y, L701H, and V715M) are sensitized to activation by the pesticide 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (DDE), thus indicating that this agent may impinge on AR signaling in cancer cells. Further investigation showed that DDE induced mutant AR recruitment to the prostate-specific antigen regulatory region, concomitant with an enhancement of target gene expression, and androgen-independent proliferation. By contrast, neither AR activation nor altered cellular proliferation was observed in cells expressing wild-type AR. Activation of signal transduction pathways was also observed based on rapid phosphorylation of mitogen-activated protein kinase (MAPK) and vasodilator-stimulated phosphoprotein, although only MAPK activation was associated with DDE-induced cellular proliferation. Functional analyses showed that both mutant AR and MAPK pathways contribute to the proliferative action of DDE, as evidenced through selective abrogation of each pathway. Together, these data show that exposure to environmentally relevant doses of EDCs can promote androgen-independent cellular proliferation in tumor cells expressing mutant AR and that DDE uses both mutant AR and MAPK pathways to exert its mitogenic activity. (Mol Cancer Res 2008;6(9):1507–20)
Up-Regulation of Rho/ROCK Signaling in Sarcoma Cells Drives Invasion and Increased Generation of Protrusive Forces
Authors: Rösel Daniel , Brábek Jan , Tolde Ondřej , Mierke Claudia T. , Zitterbart Daniel P. , Raupach Carina , Bicanová Kristýna , Kollmannsberger Philip , Paňková Daniela , Veselý Pavel , Folk Petr , Fabry Ben
Published: September 2008

Tumor cell invasion is the most critical step of metastasis. Determination of the mode of invasion within the particular tumor is critical for effective cancer treatment. Protease-independent amoeboid mode of invasion has been described in carcinoma cells and more recently in sarcoma cells on treatment with protease inhibitors. To analyze invasive behavior, we compared highly metastatic sarcoma cells with parental nonmetastatic cells. The metastatic cells exhibited a functional up-regulation of Rho/ROCK signaling and, similarly to carcinoma cells, an amoeboid mode of invasion. Using confocal and traction force microscopy, we showed that an up-regulation of Rho/ROCK signaling leads to increased cytoskeletal dynamics, myosin light chain localization, and increased tractions at the leading edge of the cells and that all of these contributed to increased cell invasiveness in a three-dimensional collagen matrix. We conclude that cells of mesenchymal origin can use the amoeboid nonmesenchymal mode of invasion as their primary invading mechanism and show the dependence of ROCK-mediated amoeboid mode of invasion on the increased capacity of cells to generate force. (Mol Cancer Res 2008;6(9):1410–20)
Sphingosine-1-Phosphate and Interleukin-1 Independently Regulate Plasminogen Activator Inhibitor-1 and Urokinase-Type Plasminogen Activator Receptor Expression in Glioblastoma Cells: Implications for Invasiveness
Authors: Bryan Lauren , Paugh Barbara S. , Kapitonov Dmitri , Wilczynska Katarzyna M. , Alvarez Silvina M. , Singh Sandeep K. , Milstien Sheldon , Spiegel Sarah , Kordula Tomasz
Published: September 2008

Glioblastoma multiforme is an invasive primary brain tumor, which evades the current standard treatments. The invasion of glioblastoma cells into healthy brain tissue partly depends on the proteolytic and nonproteolytic activities of the plasminogen activator system proteins, including the urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1), and a receptor for uPA (uPAR). Here we show that sphingosine-1-phosphate (S1P) and the inflammatory mediator interleukin-1 (IL-1) increase the mRNA and protein expression of PAI-1 and uPAR and enhance the invasion of U373 glioblastoma cells. Although IL-1 enhanced the expression of sphingosine kinase 1 (SphK1), the enzyme that produces S1P, down-regulation of SphK1 had no effect on the IL-1–induced uPAR or PAI-1 mRNA expression, suggesting that these actions of IL-1 are independent of S1P production. Indeed, the S1P-induced mRNA expression of uPAR and PAI-1 was blocked by the S1P2 receptor antagonist JTE013 and by the down-regulation of S1P2 using siRNA. Accordingly, the inhibition of mitogen-activated protein kinase/extracellular signal–regulated kinase kinase 1/2 and Rho-kinase, two downstream signaling cascades activated by S1P2, blocked the activation of PAI-1 and uPAR mRNA expression by S1P. More importantly, the attachment of glioblastoma cells was inhibited by the addition of exogenous PAI-1 or siRNA to uPAR, whereas the invasion of glioblastoma cells induced by S1P or IL-1 correlated with their ability to enhance the expression of PAI-1 and uPAR. Collectively, these results indicate that S1P and IL-1 activate distinct pathways leading to the mRNA and protein expression of PAI-1 and uPAR, which are important for glioblastoma invasiveness. (Mol Cancer Res 2008;6(9):1469–77)
The Retinoblastoma Protein Tumor Suppressor Is Important for Appropriate Osteoblast Differentiation and Bone Development
Authors: Berman Seth D. , Yuan Tina L. , Miller Emily S. , Lee Eunice Y. , Caron Alicia , Lees Jacqueline A.
Published: September 2008

Mutation of the retinoblastoma (RB) tumor suppressor gene is strongly linked to osteosarcoma formation. This observation and the documented interaction between the retinoblastoma protein (pRb) and Runx2 suggests that pRb is important in bone development. To assess this hypothesis, we used a conditional knockout strategy to generate pRb-deficient embryos that survive to birth. Analysis of these embryos shows that Rb inactivation causes the abnormal development and impaired ossification of several bones, correlating with an impairment in osteoblast differentiation. We further show that Rb inactivation acts to promote osteoblast differentiation in vitro and, through conditional analysis, establish that this occurs in a cell-intrinsic manner. Although these in vivo and in vitro differentiation phenotypes seem paradoxical, we find that Rb-deficient osteoblasts have an impaired ability to exit the cell cycle both in vivo and in vitro that can explain the observed differentiation defects. Consistent with this observation, we show that the cell cycle and the bone defects in Rb-deficient embryos can be suppressed by deletion of E2f1, a known proliferation inducer that acts downstream of Rb. Thus, we conclude that pRb plays a key role in regulating osteoblast differentiation by mediating the inhibition of E2F and consequently promoting cell cycle exit. (Mol Cancer Res 2008;6(9):1440–51)
Development of a Genetic System for the Denitrifying Bacterium ‘Aromatoleum aromaticum’ Strain EbN1
Authors: Wöhlbrand Lars , Rabus Ralf
Published: September 2008

Members of the betaproteobacterial ‘Aromatoleum’/Azoarcus/Thauera cluster contribute to the biodegradation of aromatic and other recalcitrant compounds in anoxic soils and sediments. The metabolically versatile ‘Aromatoleumaromaticum’ strain EbN1 represents a model organism for this cluster, having already been studied on the physiological, proteogenomic and biochemical level. Here we report the development of a genetic system for ‘A. aromaticum’ strain EbN1 enabling unmarked deletion mutagenesis by heterologous recombination and subsequent complementation. The antibiotic sensitivity of strain EbN1 was characterized and optimal conditions for efficient cultivation on solid medium were established. A procedure for introducing foreign DNA into strain EbN1 by conjugation was developed. The effectiveness of the genetic system was demonstrated by unmarked in-frame deletion of ebdC2, encoding the γ-subunit of a paralogous ethylbenzene dehydrogenase.
A Genomic View on Nitrogen Metabolism and Nitrogen Control in Mycobacteria
Authors: Amon Johannes , Titgemeyer Fritz , Burkovski Andreas
Published: September 2008

Knowledge about nitrogen metabolism and control in the genus Mycobacterium is sparse, especially compared to the state of knowledge in related actinomycetes like Streptomyces coelicolor or the close relative Corynebacterium glutamicum. Therefore, we screened the published genome sequences of Mycobacterium smegmatis, Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium avium ssp. paratuberculosis and Mycobacterium leprae for genes encoding proteins for uptake of nitrogen sources, nitrogen assimilation and nitrogen control systems, resulting in a detailed comparative genomic analysis of nitrogen metabolism-related genes for all completely sequenced members of the genus. Transporters for ammonium, nitrate, and urea could be identified, as well as enzymes crucial for assimilation of these nitrogen sources, i.e. glutamine synthetase, glutamate dehydrogenase, glutamate synthase, nitrate reductase, nitrite reductase, and urease proteins. A reduction of genes encoding proteins for nitrogen transport and metabolism was observed for the pathogenic mycobacteria, especially for M. leprae. Signal transduction components identified for the different species include adenylyl- and uridylyltransferase and a PII-type signal transduction protein. Exclusively for M. smegmatis, two homologs of putative nitrogen regulatory proteins were found, namely GlnR and AmtR, while in other mycobacteria, AmtR was absent and GlnR seems to be the nitrogen transcription regulator protein.
Notch3 Is a Major Regulator of Vascular Tone in Cerebral and Tail Resistance Arteries
Authors: Belin de Chantemèle E.J. , Retailleau K. , Pinaud F. , Vessières E. , Bocquet A. , Guihot A.L. , Lemaire B. , Domenga V. , Baufreton C. , Loufrani L. , Joutel A. , Henrion D.
Published: September 2008

Objective—Notch3, a member of the evolutionary conserved Notch receptor family, is primarily expressed in vascular smooth muscle cells. Genetic studies in human and mice revealed a critical role for Notch3 in the structural integrity of distal resistance arteries by regulating arterial differentiation and postnatal maturation.

Methods and Results—We investigated the role of Notch3 in vascular tone in small resistance vessels (tail and cerebral arteries) and large (carotid) arteries isolated fromNotch3-deficient mice using arteriography. Passive diameter and compliance were unaltered in mutant arteries. Similarly, contractions to phenylephrine, KCl, angiotensin II, and thromboxane A2 as well as dilation to acetylcholine or sodium nitroprusside were unaffected. However,Notch3deficiency induced a dramatic reduction in pressure-induced myogenic tone associated with a higher flow (shear stress)-mediated dilation in tail and cerebral resistance arteries only. Furthermore, RhoA activity and myosin light chain phosphorylation, measured in pressurized tail arteries, were significantly reduced inNotch3KO mice. Additionally, myogenic tone inhibition by the Rho kinase inhibitor Y27632 was attenuated in mutant tail arteries.

Conclusions—Notch3 plays an important role in the control of vascular mechano-transduction, by modulating the RhoA/Rho kinase pathway, with opposite effects on myogenic tone and flow-mediated dilation in the resistance circulation.
Advanced Glycation End-Product of Low Density Lipoprotein Activates the Toll-Like 4 Receptor Pathway Implications for Diabetic Atherosclerosis
Authors: Hodgkinson Conrad P. , Laxton Ross C. , Patel Kunal , Ye Shu
Published: September 2008

Objective—

Diabetes is a major risk factor for coronary heart disease. Accumulation of advanced glycation end-products (AGEs) attributable to hyperglycemia in diabetics promotes the development of atherosclerosis. However, the underlying mechanisms remain unclear.

Methods and Results—

The advanced glycation end-product of low-density-lipoprotein (AGE-LDL) induced proinflammatory cytokine production in human coronary artery endothelial cells and human- and mouse-macrophages. AGE-LDL stimulated cytokine synthesis was markedly reduced in mouse macrophages with a TLR4 loss-of-function mutation. Coimmunoprecipitation experiments indicated AGE-LDL interacts with TLR4, RAGE, and CD36. Incubation of cultured macrophages with TLR4, RAGE, or CD36 antibodies inhibited AGE-LDL stimulation of tumor necrosis factor (TNF)α production. A competitive binding inhibitor of TLR4 blocked AGE-LDL binding to the receptor. After transfection of a HEK293 cell system with wild-type TLR4, AGE-LDL activated a signaling pathway including p38α, JNK, and ERK1 kinases and AP1, Elk1, and NF–κB transcription factors; the net result being increased cytokine production. These effects were absent when cells were transfected with empty plasmid. Two common polymorphisms in TLR4, D299G and T399I, reduced the response of TLR4 to lipopolysaccharide (LPS) but had no effect on AGE-LDL signaling.

Conclusions—

These results indicate that AGE-LDL activates a TLR4-mediated signaling pathway, thus inducing proinflammatory cytokine production. This mechanism may partly explain the increased risk of atherosclerosis observed in diabetics.
VEGF-A Stimulates ADAM17-Dependent Shedding of VEGFR2 and Crosstalk Between VEGFR2 and ERK Signaling
Authors: Swendeman Steven , Mendelson Karen , Weskamp Gisela , Horiuchi Keisuke , Deutsch Urban , Scherle Peggy , Hooper Andrea , Rafii Shahin , Blobel Carl P.
Published: September 2008

Vascular endothelial growth factor (VEGF)-A and the VEGF receptors are critical for regulating angiogenesis during development and homeostasis and in pathological conditions, such as cancer and proliferative retinopathies. Most effects of VEGF-A are mediated by the VEGFR2 and its coreceptor, neuropilin (NRP)-1. Here, we show that VEGFR2 is shed from cells by the metalloprotease disintegrin ADAM17, whereas NRP-1 is released by ADAM10. VEGF-A enhances VEGFR2 shedding by ADAM17 but not shedding of NRP-1 by ADAM10. VEGF-A activates ADAM17 via the extracellular signal-regulated kinase (ERK) and mitogen-activated protein kinase pathways, thereby also triggering shedding of other ADAM17 substrates, including tumor necrosis factor α, transforming growth factor α, heparin-binding epidermal growth factor–like growth factor, and Tie-2. Interestingly, an ADAM17-selective inhibitor shortens the duration of VEGF-A–stimulated ERK phosphorylation in human umbilical vein endothelial cells, providing evidence for an ADAM17-dependent crosstalk between the VEGFR2 and ERK signaling. Targeting the sheddases of VEGFR2 or NRP-1 might offer new opportunities to modulate VEGF-A signaling, an already-established target for treatment of pathological neovascularization.
Inducible Nitric Oxide Synthase Expression and Cardiomyocyte Dysfunction During Sustained Moderate Ischemia in Pigs
Authors: Heinzel Frank R. , Gres Petra , Boengler Kerstin , Duschin Alexej , Konietzka Ina , Rassaf Tienush , Snedovskaya Julia , Meyer Stephanie , Skyschally Andreas , Kelm Malte , Heusch Gerd , Schulz Rainer
Published: September 2008

In acute myocardial ischemia, regional blood flow and function are proportionally reduced. With prolongation of ischemia, function further declines at unchanged blood flow. We studied the involvement of an inflammatory signal cascade in such progressive dysfunction and whether dysfunction is intrinsic to cardiomyocytes. In 10 pigs, ischemia was induced by adjusting inflow into the cannulated left anterior coronary artery to reduce coronary arterial pressure to 45 mm Hg (ISCH); 4 pigs received the inducible nitric oxide synthase (iNOS) inhibitors aminoguanidine or
l
-
N
6
-(1-iminoethyl)-lysine during ISCH (ISCH+iNOS-Inhib); 6 pigs served as controls (SHAM). Anterior (AW) and posterior (PW) systolic wall thickening (sonomicrometry) were measured. After 6 hours, nitric oxide (NO) synthase (NOS) protein expression, NOS activity, and NO metabolites (nitrite/nitrate/nitroso species) were quantified in biopsies isolated from AW and PW. Cardiomyocyte shortening and intracellular calcium (Indo-1 acetoxymethyl ester) were measured without and with the NOS substrate
l-
arginine (100 μmol/L). In ISCH, AW wall thickening decreased from 42±4% (baseline) to 16±3% (6 hours). Wall thickening remained unchanged in ISCH-PW and SHAM-AW/PW. NOS2 (iNOS) protein expression and activity, but not NOS3 (endothelial NO synthase), were increased in ISCH-AW and ISCH-PW. iNOS expression correlated with increased nitrite contents. Cardiomyocyte shortening was reduced in ISCH-AW versus SHAM-AW (4.4±0.3% versus 5.6±0.3%).
l-
Arginine reduced cardiomyocyte shortening further in ISCH-AW (to 2.8±0.2%) and ISCH-PW (3.4±0.4% versus 5.4±0.4%) but not in SHAM or in ISCH+iNOS-Inhib; intracellular [Ca
2+
] remained unchanged. With
l-
arginine, in vitro AW cardiomyocyte shortening correlated with in vivo AW wall thickening (
r
=0.72). In conclusion, sustained regional ischemia induces myocardial iNOS expression in pigs, which contributes to contractile dysfunction at the cardiomyocyte level.
Engaging the South: Ming China and Southeast Asia in the Fifteenth Century
Authors: Wade Geoff
Published: September 2008

The fifteenth century witnessed Ming China expanding its interactions with areas to the south—areas which we today refer to as Southeast Asia. This involved overland political expansion, the gradual incorporation of Tai polities, as well as their economic exploitation. The twenty-year incorporation of the Dai Viêt policy was also part of this process. In the maritime realm, following the early fifteenth-century sending of massive armadas in an attempt to achieve a pax Ming in the region, the Ming court made efforts to ban maritime commerce by non-state players. This paper examines the effects that these various Ming policies had on Southeast Asia in the political, economic, technological, and cultural spheres. Le XVIème siècle vit la multiplication des interventions de la Chine des Ming dans la région aujourd'hui dénommée Asie du Sud-Est. Elles entraînèrent une expansion politique terrestre, l'annexion progressive des royaumes Thaïs et leur exploitation économique. L'incorporation du royaume de Dai Viêt à la Chine durant vingt années, s'inscrit dans le même développement. Dans le domaine maritime, le début du XVIème siècle est marqué par l'envoi d'armadas qui tentèrent d'imposer la pax Ming dans l'Asie du Sud-Est., la cour Ming s'efforçant d'exclure le négoce privé du commerce maritime. Cette contribution étudie les effets de l'ensemble des stratégies des Ming en Asie du Sud-Est dans la sphère politique, économique, technologique et culturelle.
The Rise and Fall of the Tujjār Councils of Representatives in Iran, 1884–85
Authors: Gilbar Gad
Published: September 2008

In July 1884 Nāsir al-Dīn Shāh approved the establishment of councils of representatives of the big merchants (majālis-i wukalā-yi tujjār) in the main commercial centers of Iran. Within three to four months, the tujjār elected their councils in eighteen cities and towns in the country. These councils were to supervise commercial activities in Iran, encourage investments in new projects by big local merchants, and above all limit the involvement and interference of both the provincial governors and the local religious leaders in business matters. The establishment of the councils prompted hostility and resistance by both governors and ‘ulamā’ from the very beginning. Events in Tabrīz in November-December 1884 struck a decisive blow to the councils. The institution at that town disbanded in late December, and several weeks later most of the other councils followed suit. In light of these developments, the shah, in February or March 1885, nullified his instructions concerning the establishment of the councils. This article analyzes the conditions and circumstances that prompted the shah and the tujjār to take a step that was without precedent in nineteenth-century Iran or elsewhere in the Middle East. It also studies in detail the events that brought about the end of a promising and significant development. En juillet 1884 Nāsir al-Dīn Shāh approuva l'établissement des conseils représentant les grands marchands (majālis-i wukalā-yi tujjār) dans les principaux centres commerciaux de l'Iran. Ces conseils devaient surveiller les activités commerciales en Iran, encourager les grands marchands locaux à investir dans des projets nouveaux, et tout d'abord restreindre l'influence et les interventions des gouverneurs provinciaux et des autorités religieuses locales dans leurs affaires. Cette initiative provoqua aussitôt l'hostilité et l'opposition des gouverneurs et des ‘Ulamā’.Cette contribution analyse les conditions et les circonstances qui poussèrent le Schah et les tujjār à cette démarche sans précédent dans l'Iran du XIXième siècle et ailleurs dans le Moyen-Orient à cette époque et détaille les événements qui menèrent à l'échec de ce développement prometteur et important.
From Autonomy to Integration? International Law, Free Trade and the Environment
Authors: Mehling Michael , Lindroos Anja
Published: September 2008

Our current understanding of so-called “self-contained regimes” is based on an overly simplistic appreciation of how such regimes interact with each other and with the larger body of international law. Drawing on an analysis of WTO case law, this article highlights two distinct normative relations, addressing the relationship of international trade law vis-à-vis general international law and international environmental law. As the analysis reveals, further differentiation of normative relationships is needed to better understand how such seemingly independent regimes operate in a fragmented legal system. It also shows that a recently proposed interpretative tool, systemic integration, raises new questions and challenges traditional conceptions of international treaty law.
Fairness, Promptness and Effectiveness: How the Openness of Good Faith Limits the Flexibility of the DSU
Authors: Panizzon Marion
Published: September 2008

The World Trade Organization Appellate Body has drawn from international legal principles to intensify the normative impact of good faith duties vaguely described in Articles 3(10) and 4(3) of the Dispute Settlement Understanding. In the context of the Appellate Body's repeated rejection of good faith principles in the “substantive” WTO law of the General Agreement on Tariffs and Trade, the General Agreement on Trade in Services and the Agreement on Trade-Related Aspects of Intellectual Property Rights, the development of “procedural” good faith adjudication stands out. Relating procedural good faith adjudication to the level of fairness, the WTO judiciary thus relegates to the past power-oriented, diplomacy-based structures of WTO dispute settlement.This article will show how the general good faith principle served to reduce the flexibility remaining in the WTO's Member-driven dispute settlement procedure, often abused by powerful WTO Members to draw out disputes at the expense of developing country Members. One will also describe how the Appellate Body derived a due process standard, the one of requiring a “fair, prompt and effective” resolution of WTO trade disputes from the good faith obligation in Article 3(10) DSU, while keeping due process distinct from good faith duties.This due process standard enables the Appellate Body to review (and restrict) the use of procedural rights by WTO Members even when the exercise of these rights appears – on its face – consistent with DSU norms.The article finds that the due process standard is a first-time judicial assertion in Appellate Body practice of a broader enforceability of good faith.
Open Method of Coordination: A New Stepping Stone in the Legal Order of International and European Relations
Authors: Haar Beryl ter
Published: September 2008

The open method of coordination is characterised by the combined use of modes of governance and soft law instruments, a combination that is uncommon since they usually are sequentially related to each other: governance leads to soft law. The focus of this paper is therefore on the significance of this combined use for the position of the OMC in the legal order of international and European relations. To determine the OMC's position, the paper first substantiates the soft law aspects of the ideal-type OMC, based on the international relations concept of legalisation, an ideal-type European Community law and the terminology of the gap-thesis. Furthermore, the paper examines the internal and external functioning of the OMC, the latter having focus on, in particular, its relations with Community hard law. The paper concludes by showing that the OMC adds in two ways a new stepping stone into the legal order of international and European relations.
Iamblichus' Egyptian Neoplatonic Theology in De Mysteriis
Authors: Clark Dennis
Published: September 2008

In De Mysteriis VIII Iamblichus gives two orderings of first principles, one in purely Neoplatonic terms drawn from his own philosophical system, and the other in the form of several Egyptian gods, glossed with Neoplatonic language again taken from his own system. The first ordering or taxis includes the Simple One and the One Existent, two of the elements of Iamblichus' realm of the One. The second taxis includes the Egyptian (H)eikton, which has now been identified with the god of magic, Heka, glossed as the One Existent. The Egyptian god Kmeph is also a member of this taxis, and is the Egyptian Kematef, a god of creation associated with the solar Amun-Re. Iamblichus refers to this god also as the Hegemon of the celestial gods, which should be equated to Helios, specifically the noeric Helios as described by Julian in his Hymn to Helios. Iamblichus describes Kmeph as an “intellect knowing himself”, and so the noeric Kmeph/Helios should also be seen as the Paternal Demiurgic Zeus, explicitly described also by Proclus as an intellect knowing himself. This notion of a self-thinking intellect may offer a solution to the problematic formulation by Proclus in his Timaeus commentary of Iamblichus' view of the Demiurgy encompassing all the noeric realm. The identification of Kmeph as the noeric Helios now also allows the first direct parallels to de Mysteriis to be found in extant Hermetica. In addition it can be inferred from the specific Neoplatonic terminology employed that the noetic Father of Demiurges, Kronos, appears, as well as the secondary Demiurgic triad of Zeus, Poseidon, and Pluto, in the forms of the Egyptian Amun, Ptah, and Osiris, thus raising the question that much of the theology documented only in Proclus might appear already to have been established by Iamblichus.
Plotinus on the Soul's Omnipresence in Body
Authors: Gurtler, S.J. Gary
Published: September 2008

In examining Ennead VI 4[22], we find Plotinus in conflict with modern, i.e., Cartesian or Kantian, assumptions about the relation of soul and body and the identification of the self with the subject. Curiously, his images and exposition are more in tune with Twentieth Century notions such as wave and field. With these as keys, we are in a position to unlock the subtlety of Plotinus' analysis of the way soul and body are present together, with sensation structured through the body and judgment coming from the soul. The problem of the self concerns not only the unity of the self in terms of body and soul, but also how the self is constituted in relation to other selves, both keeping its individuality and sharing its experiences at the same time.
From Plato's Good to Platonic God
Authors: Gerson Lloyd
Published: September 2008

One of the major puzzling themes in the history of Platonism is how theology is integrated with philosophy. In particular, one may well wonder how Plato's superordinate first principle of all, Idea of the Good, comes to be understood by his disciples as a mind or in some way possessing personal attributes. In what sense is the Good supposed to be God? In this paper I explore some Platonic accounts of the first principle of all in order to understand where the integration of the personal into the metaphysical is organic and where it is not. I conclude that the “ontological” and the “henological” construals of the first principle of all differ in their openness to “intellectualizing” that principle.
Cell Therapy in Peripheral Arterial Disease
Authors: Al Mheid Ibhar , Quyyumi Arshed A.
Published: September 2008

Management of advanced obstructive vascular disease affecting the extremities poses tremendous challenges for physicians and patients. Peripheral arterial disease is often a consequence of obstructive atherosclerosis affecting the ileofemoral circulation but is also rarely a result of nonatherosclerotic conditions such as thromboangiitis obliterans (Buerger's disease). Consequences range from the presence of asymptomatic obstruction to intermittent claudication, development of rest pain, ulceration, gangrene, and amputation. A relatively new and promising approach using cell therapy has recently been developed to treat intractable symptoms related to ischemia in subjects with peripheral arterial disease in whom conventional medical therapy and revascularization modalities have been exhausted.
Risk Factors for Abdominal Aortic Aneurysm and the Influence of Social Deprivation
Authors: Badger Stephen A. , O'Donnell Mark E. , Sharif Muhammed A. , Boyd Christopher S. , Hannon Raymond J. , Lau Louis L. , Lee Bernard , Soong Chee V.
Published: September 2008

Introduction: the objective of this abdominal aortic aneurysm (AAA) screening study was to determine attendance and disease prevalence patterns in Northern Ireland and the role of deprivation and other risk factors. Patients and methods: patients from primary care practices from Belfast, Lisburn, and Saintfield were screened. Past medical history and deprivation details were determined. Results: 2264 men from Belfast, 1104 men in Lisburn, and 284 in Saintfield were invited to attend. Overall, 1659 (45.3%) men attended, with 40.6% from Belfast, 55.0% from Lisburn, and 45.8% from Saintfield ( P < .0001). Ninety-two (5.5%) new AAAs were diagnosed, with 6.5%, 3.8%, and 6.2% in the 3 areas ( P = .055). As deprivation decreased, attendance increased and prevalence decreased. Smoking, peripheral arterial disease, number of medications prescribed, and geographical origin were independent risk factors for AAAs. Conclusion: aneurysm prevalence is influenced by geographical origin and deprivation, which should, therefore, be important factors in health care planning and screening provision.
Predictors of Long-Term Major Adverse Cardiac Events and Clinical Restenosis following Elective Percutaneous Coronary Stenting
Authors: Cai Qiangjun , Skelding Kimberly , Arthur Armstrong , Desai Dipan , Wood G. Craig , Blankenship James
Published: September 2008

Limited data exist regarding the predictors of long-term clinical outcomes following elective percutaneous coronary intervention (PCI) in the current era of stenting. The authors investigated the predictors of major adverse cardiac events (MACE) and clinical restenosis in 740 consecutive patients who underwent successful elective PCI with bare metal stents (BMSs) or drug-eluting stents (DESs). At 30-month follow -up, compared with BMS recipients, DES recipients had a significantly lower rate of MACE, which was mainly driven by a decreased repeat target vessel PCI. The rate of 30-month clinical restenosis was significantly lower in DES recipients. The authors conclude that baseline clinical, angiographic, and procedural characteristics determine long-term MACE and clinical restenosis after elective PCI, with DES being the independent predictor for both.
Benefits of Low-Intensity Pain-Free Treadmill Exercise on Functional Capacity of Individuals Presenting with Intermittent Claudication Due to Peripheral Arterial Disease
Authors: Barak Sharon , Stopka Christine Boyd , Martinez Coleen Archer , Carmeli Eli
Published: September 2008

Patients with intermittent claudication due to peripheral arterial disease (PAD) experience muscle aching during walking secondary to ischemia. The purpose of this study was to examine the effects of low-intensity pain-free exercise (LIPFE) on functional capacity of individuals with PAD. A total of 12 participants with PAD underwent training on treadmill for 6 weeks, twice a week, for about 45 minutes. Outcome measures included walking distance (WDI), walking duration (WDU), mean walking rate (WR), estimated oxygen consumption (EVO2), metabolic equivalent (MET), estimated total energy expenditure (ETEE), and estimated rate of energy expenditure (EREE). Mean improvement of WDI, WDU, and MWR were 104% (an addition of 1.0 km), 55% (an addition of 13.3 minutes), and 41% (0.9 km/h faster), respectively. Mean improvement of EVO2, MET, ETEE, and EREE, were 20%, 20%, 80%, and 20%, respectively. In conclusion, it appears that LIPFE training is an effective intervention for individuals presenting with PAD.