bluuebunny/crossref_metadata_2025 huggingface dataset:
Classifying the role of trade-offs in the evolutionary diversity of pathogens
Authors: Gudelj Ivana , Coman Ciprian D , Beardmore Robert E
Published: November 2005

In this paper we use a system of non-local reaction–diffusion equations to study the effect of host heterogeneity on the phenotypic evolution of a pathogen population. The evolving phenotype is taken to be the transmission rate of the pathogen on the different hosts, and in our system there are two host populations present.

The central feature of our model is a trade-off relationship between the transmission rates on these hosts, which means that an increase in the pathogen transmission on one host will lead to a decrease in the pathogen transmission on the other. The purpose of the paper is to develop a classification of phenotypic diversity as a function of the shape of the trade-off relationship and this is achieved by determining the maximum number of phenotypes a pathogen population can support in the long term, for a given form of the trade-off. Our findings are then compared with results obtained by applying classical theory from evolutionary ecology and the more recent
adaptive dynamics method
to the same host–pathogen system. We find our work to be in good agreement with these two approaches.
The role of an astrocytic NADPH oxidase in the neurotoxicity of amyloid beta peptides
Authors: Abramov Andrey Y , Duchen Michael R
Published: November 2005

Amyloid beta peptide (Aβ) accumulates in the CNS in Alzheimer's disease. Both the full peptide (1–42) or the 25–35 fragment are toxic to neurons in culture. We have used fluorescence imaging technology to explore the mechanism of neurotoxicity in mixed asytrocyte/neuronal cultures prepared from rat or mouse cortex or hippocampus, and have found that Aβ acts preferentially on astrocytes but causes neuronal death. Aβ causes sporadic transient increases in [Ca
2+
]
c
in astrocytes, associated with a calcium dependent increased generation of reactive oxygen species (ROS) and glutathione depletion. This caused a slow dissipation of mitochondrial potential on which abrupt calcium dependent transient depolarizations were superimposed. The mitochondrial depolarization was reversed by mitochondrial substrates glutamate, pyruvate or methyl succinate, and by NADPH oxidase (NOX) inhibitors, suggesting that it reflects oxidative damage to metabolic pathways upstream of mitochondrial complex I. The Aβ induced increase in ROS and the mitochondrial depolarization were absent in cells cultured from transgenic mice lacking the NOX component, gp91
phox
. Neuronal death after 24 h of Aβ exposure was dramatically reduced both by NOX inhibitors and in gp91
phox
knockout mice. Thus, by raising [Ca
2+
]
c
in astrocytes, Aβ activates NOX, generating oxidative stress that is transmitted to neurons, causing neuronal death.
YvcK of Bacillus subtilis is required for a normal cell shape and for growth on Krebs cycle intermediates and substrates of the pentose phosphate pathway
Authors: Görke Boris , Foulquier Elodie , Galinier Anne
Published: November 2005

The HPr-like protein Crh has so far been detected only in the bacillus group of bacteria. In Bacillus subtilis, its gene is part of an operon composed of six ORFs, three of which exhibit strong similarity to genes of unknown function present in many bacteria. The promoter of the operon was determined and found to be constitutively active. A deletion analysis revealed that gene yvcK, encoded by this operon, is essential for growth on Krebs cycle intermediates and on carbon sources metabolized via the pentose phosphate pathway. In addition, cells lacking YvcK acquired media-dependent filamentous or L-shape-like aberrant morphologies. The presence of high magnesium concentrations restored normal growth and cell morphology. Furthermore, suppressor mutants cured from these growth defects appeared spontaneously with a high frequency. Such suppressing mutations were identified in a transposon mutagenesis screen and found to reside in seven different loci. Two of them mapped in genes of central carbon metabolism, including zwf, which encodes glucose-6-phosphate dehydrogenase and cggR, the product of which regulates the synthesis of glyceraldehyde-3-phosphate dehydrogenase. All these results suggest that YvcK has an important role in carbon metabolism, probably in gluconeogenesis required for the synthesis of cell wall precursor molecules. Interestingly, the Escherichia coli homologous protein, YbhK, can substitute for YvcK in B. subtilis, suggesting that the two proteins have been functionally conserved in these different bacteria.
Knockdown of LIM15/DMC1 in the mushroom Coprinus cinereus by double-stranded RNA-mediated gene silencing
Authors: Namekawa Satoshi H. , Iwabata Kazuki , Sugawara Hiroko , Hamada Fumika N. , Koshiyama Akiyo , Chiku Hiroyuki , Kamada Takashi , Sakaguchi Kengo
Published: November 2005

The basidiomyceteCoprinus cinereushas many advantages as a model organism for studying sexual development and meiosis, but it has been difficult to investigate using reverse-genetics methods, such as gene disruption by homologous recombination. Here, gene repression by dsRNA-mediated gene silencing was tried as an alternative method for reverse-genetics studies. It was shown that transformation of theLIM15/DMC1dsRNA expression construct (LIM15dsRNA) resulted in genomic insertion ofLIM15dsRNA and paucity of theLIM15/DMC1transcript. First,LIM15dsRNA was transformed into the homothallic strainAmutBmutto generate a homozygote in which both nuclei had a copy ofLIM15dsRNA. TheLIM15/DMC1-repressed strain showed abnormal homologous chromosome synapsis during meiosis. Basidiospore production was reduced to 16 % by the induction of dsRNA. However, approximately 60 % of basidiospores were viable. Next, a heterozygote was generated in which one nucleus had a copy ofLIM15dsRNA. The phenotype was similar to that of the homozygote. These results are not only the first demonstration of dsRNA-mediated gene silencing in a member of the homobasidiomycete fungi, to which 90 % of mushroom species belong, but also the first successful use of a reverse-genetics approach inC. cinereusresearch.
Identification of an upstream regulatory sequence that mediates the transcription of mox genes in Methylobacterium extorquens AM1
Authors: Zhang Meng , FitzGerald Kelly A. , Lidstrom Mary E.
Published: November 2005

A multiple A-tract sequence has been identified in the promoter regions for the mxaF, pqqA, mxaW, mxbD and mxcQ genes involved in methanol oxidation in Methylobacterium extorquens AM1, a facultative methylotroph. Site-directed mutagenesis was exploited to delete or change this conserved sequence. Promoter-xylE transcriptional fusions were used to assess promoter activity in these mutants. A fiftyfold drop in the XylE activity was observed for the mxaF and pqqA promoters without this sequence, and a five- to sixfold drop in the XylE activity was observed for the mxbD and mxcQ promoters without this sequence. Mutants were generated in the chromosomal copies in which this sequence was either deleted or altered, and these mutants were unable to grow on methanol. When one of these sequences was added to Plac of Escherichia coli, which is a weak constitutive promoter in M. extorquens AM1, the activity increased two- to threefold. These results suggest that this sequence is essential for normal expression of these genes in M. extorquens AM1, and may serve as a general enhancer element for genetic constructs in this bacterium.
Methylcrotonyl-CoA and geranyl-CoA carboxylases are involved in leucine/isovalerate utilization (Liu) and acyclic terpene utilization (Atu), and are encoded by liuB/liuD and atuC/atuF, in Pseudomonas aeruginosa
Authors: Höschle Birgit , Gnau Volker , Jendrossek Dieter
Published: November 2005

Pseudomonas aeruginosa is able to grow on acyclic monoterpenes (citronellol, citronellate, geraniol and geranylate), and on other methyl-branched compounds such as leucine or isovalerate. The catabolic pathway of citronellol (Atu, acyclic terpene utilization) enters that of leucine/isovalerate (Liu, leucine and isovalerate utilization) at the level of methylcrotonyl-CoA. Key enzymes of the combined pathways are geranyl-CoA carboxylase (GCase) and methylcrotonyl-CoA carboxylase (MCase). In this study, isovalerate-grown cells specifically expressed MCase (apparent molecular mass of the biotin-containing subunit, 74 kDa) only, and the GCase biotin-containing subunit (71 kDa) was not detected. Citronellol- or citronellate-grown cells produced both carboxylases. Biotin-dependent proteins were purified from crude extracts by avidin-affinity chromatography, and assigned to the corresponding coding genes by trypsin fingerprint analysis. The two subunits of MCase corresponded to liuB/liuD (PA2014/PA2012) of the P. aeruginosa genome database, and atuC/atuF (PA2888/PA2891) encoded GCase subunits. This finding is contrary to that reported by others. The identified genes are part of two separate gene clusters [liuRABCDE (PA2011–PA2016) and atuABCDEFGH (PA2886–PA2893)] that are thought to encode most of the genes of the Atu and Liu pathways.
Regulation of nitrate reductase activity in Mycobacterium tuberculosis by oxygen and nitric oxide
Authors: Sohaskey Charles D.
Published: November 2005

Nitrate reduction byMycobacterium tuberculosisis regulated by control of the transport of nitrate into the cell by NarK2. When oxygen was introduced into hypoxic cultures, nitrite production was quickly inhibited. The nitrate-reducing enzyme itself is relatively insensitive to oxygen, suggesting that the inhibition of nitrite production by oxygen was a result of interference with nitrate transport. This was not due to degradation of NarK2, as the inhibition was reversed by the removal of oxygen although chloramphenicol prevented new synthesis of NarK2. The oxidant potassium ferricyanide was added to anaerobic cultures to produce a positive redox potential in the absence of oxygen. Nitrite production decreased, signifying that oxidizing conditions, rather than oxygen itself, were responsible for the inhibition of nitrate transport. Nitric oxide added to cultures allowed NarK2 to be active even in the presence of oxygen. A similar result was obtained with hydroxylamine and ethanol, both of which interfere with oxygen utilization and the electron transport chain. It is proposed that NarK2 senses the redox state of the cell, possibly by monitoring the flow of electrons to cytochrome oxidase, and adjusts its activity so that nitrate is transported under reducing, but not under oxidizing, conditions.
Evaluation of O-antigen inactivation on Pla activity and virulence of Yersinia pseudotuberculosis harbouring the pPla plasmid
Authors: Pouillot Flavie , Derbise Anne , Kukkonen Maini , Foulon Jeannine , Korhonen Timo K. , Carniel Elisabeth
Published: November 2005

Yersinia pestis is a species that emerged recently from Yersinia pseudotuberculosis and gained an exceptional pathogenicity potential. Among the major genetic differences between the plague bacillus and its ancestor is the acquisition of the pPla plasmid, which has been associated with the increased virulence of Y. pestis. In a previous study, introduction of pPla into Y. pseudotuberculosis did not lead to any modification of the virulence of the host bacterium. However, it was subsequently demonstrated that the presence of smooth lipopolysaccharide (LPS) inhibits the activity of Pla. In this study, pPla was introduced into a Y. pseudotuberculosis strain expressing smooth LPS, and into a variant in which a mutation that abrogates the formation of O-antigen (O-Ag) repeats (as in natural isolates of Y. pestis) was generated. It was found that in both strains, Pla was synthesized, exported to the bacterial membrane and processed as in Y. pestis. However, the ability of Pla to activate plasminogen was weak and observed only at 37 °C in the smooth strain, while this activity was similar to that of Y. pestis and expressed at both 28 and 37 °C in the O-Ag mutant strain. Similarly, Pla-mediated inactivation of the antiprotease α
2-antiplasmin was not detected in the smooth Y. pseudotuberculosis strain grown at 28 °C, but was expressed at both temperatures in the O-Ag mutant strain. Despite the more efficient activity of Pla, the Y. pseudotuberculosis O-Ag mutant strain exhibited a lower pathogenicity upon subcutaneous infection of mice. The results thus indicate that, although abrogation of O side chain synthesis in a Y. pseudotuberculosis strain harbouring pPla potentiates the two proteolytic activities of Pla, this is not sufficient to confer to Y. pseudotuberculosis a higher pathogenicity potential. These results also suggest that acquisition of pPla may not have been sufficient to confer an immediate higher pathogenic potential to the ancestor Y. pestis strain.
The putative lytic transglycosylase VirB1 from Brucella suis interacts with the type IV secretion system core components VirB8, VirB9 and VirB11
Authors: Höppner Christoph , Carle Anna , Sivanesan Durga , Hoeppner Sabine , Baron Christian
Published: November 2005

VirB1-like proteins are believed to act as lytic transglycosylases, which facilitate the assembly of type IV secretion systems via localized lysis of the peptidoglycan. This paper presents the biochemical analysis of interactions of purified Brucella suis VirB1 with core components of the type IV secretion system. Genes encoding VirB1, VirB8, VirB9, VirB10 and VirB11 were cloned into expression vectors; the affinity-tagged proteins were purified from Escherichia coli, and analyses by gel filtration chromatography showed that they form monomers or homo-multimers. Analysis of protein–protein interactions by affinity precipitation revealed that VirB1 bound to VirB9 and VirB11. The results of bicistron expression experiments followed by gel filtration further supported the VirB1–VirB9 interaction. Peptide array mapping identified regions of VirB1 that interact with VirB8, VirB9 and VirB11 and underscored the importance of the C-terminus, especially for the VirB1–VirB9 interaction. The binding sites were localized on a structure model of VirB1, suggesting that different portions of VirB1 may interact with other VirB proteins during assembly of the type IV secretion machinery.
Functional interactions between type IV secretion systems involved in DNA transfer and virulence
Authors: de Paz Héctor D. , Sangari Félix J. , Bolland Silvia , García-Lobo Juan M. , Dehio Christoph , de la Cruz Fernando , Llosa Matxalen
Published: November 2005

This paper reports an analysis of the functional interactions between type IV secretion systems (T4SS) that are part of the conjugative machinery for horizontal DNA transfer (cT4SS), and T4SS involved in bacterial pathogenicity (pT4SS). The authors' previous work showed that a conjugative coupling protein (T4CP) interacts with the VirB10-type component of the T4SS in order to recruit the protein–DNA complex to the transporter for conjugative DNA transfer. This study now shows by two-hybrid analysis that conjugative T4CPs also interact with the VirB10 element of the pT4SS of Agrobacterium tumefaciens (At), Bartonella tribocorum (Bt) and Brucella suis (Bs). Moreover, the VirB10 component of a cT4SS (protein TrwE of plasmid R388) could be partially substituted by that of a pT4SS (protein TrwE of Bt) for conjugation. This result opens the way for the construction of hybrid T4SS that deliver DNA into animal cells. Interestingly, in the presence of part of the Bs T4SS the R388 T4SS protein levels were decreased and R388 conjugation was strongly inhibited. Complementation assays between the Trw systems of R388 and Bt showed that only individual components from the so-called ‘core complex’ could be exchanged, supporting the concept that this core is the common scaffold for the transport apparatus while the other ‘peripheral components' are largely system-specific.
Hydrogen bonding in brucinium dihydrogen citrate trihydrate at 130 K
Authors: Smith Graham , Wermuth Urs D. , White Jonathan M.
Published: November 2005

The structure of brucinium dihydrogen citrate trihydrate (systematic name: 2,3-dimethoxy-10-oxostrychnidinium dihydrogen citrate trihydrate), C23H27N2O4
+·C6H7O7
−·3H2O, has been determined at 130 K. The crystallographic asymmetric unit comprises two brucinium cations, two dihydrogen citrate anions and six water molecules of solvation. The two citrate anions, which are conformationally dissimilar, associate through extensive hydrogen-bonding interactions with the common undulating brucinium cation layer substructures and the water molecules, forming a three-dimensional framework polymer.
O—H...O-bridged dimers linked via C—H...O and C—H...π interactions in 4,6-di-O-benzyl-myo-inositol 1,3,5-orthoformate
Authors: Manoj K. , Devaraj S. , Gonnade R. G. , Bhadbhade M. M. , Shashidhar M. S.
Published: November 2005

The centrosymmetric O—H...O-bonded head-to-head dimers of the title compound, C21H22O6, are linked together via bifurcated C—H...O interactions along the a axis and via favourable C—H...π interactions along the b axis in the crystal structure.
Gallium tris(iodate), Ga(IO3)3
Authors: Chen Xue-An , Xue Hai-Ping , Chang Xin-An , Zang He-Gui , Xiao Wei-Qiang
Published: November 2005

Ga(IO3)3 crystallizes in the space group P63, with the Ga atom at a site with imposed threefold symmetry. The crystal structure consists of slightly distorted GaO6 octahedra that are bridged by I atoms of IO3
− groups, giving rise to a three-dimensional polar network. The framework contains unoccupied hexagonal channels running parallel to the hexagonal [001] direction. The iodate groups have their stereochemically active non-bonded electron pairs pointing in the same direction along [001], which creates the polarity in the structure. The I—O bond distances and O—I—O angles are normal, being in the ranges 1.783 (3)–1.847 (2) Å and 94.68 (11)–99.61 (12)°, respectively.
Contrasting three-dimensional framework structures in the isomeric pair 2-iodo-N-(2-nitrophenyl)benzamide and N-(2-iodophenyl)-2-nitrobenzamide
Authors: Wardell James L. , Skakle Janet M. S. , Low John N. , Glidewell Christopher
Published: November 2005

In 2-iodo-N-(2-nitrophenyl)benzamide, C13H9IN2O3, the molecules are linked into a three-dimensional framework structure by a combination of a C—H...O hydrogen bond, and iodo–nitro, carbonyl–carbonyl and aromatic π–π stacking interactions. In the isomeric compound N-(2-iodophenyl)-2-nitrobenzamide, the framework structure is built from N—H...O, C—H...O and C—H...π(arene) hydrogen bonds and an iodo–nitro interaction.
2,6-Di-tert-butylphenol revisited at 110 K
Authors: Lutz Martin , Spek Anthony L.
Published: November 2005

The title compound, C14H22O, was studied at 110 K. The phenolic hydroxy group was found to be coplanar with the benzene ring and, due to steric hindrance from the tert-butyl groups, this hydroxy group does not form hydrogen bonds. The shortest intermolecular O...O distance is 3.1008 (11) Å, with an O—H...O angle of 117.3 (16)°. There are no significant intermolecular π–π stacking or C—H...π interactions.
N-Benzylethylammonium nitrate: a three-dimensional hydrogen-bonded framework comprising substructures in zero, one and two dimensions
Authors: Abonia Rodrigo , Rengifo Emerson , Cobo Justo , Low John N. , Glidewell Christopher
Published: November 2005

The title compound is a salt, C9H14N+·NO3
−, in which two N—H...O hydrogen bonds and two C—H...O hydrogen bonds generate a three-dimensional framework structure. The combination of one N—H...O hydrogen bond and one C—H...O hydrogen bond generates a finite (zero-dimensional) centrosymmetric R
4
4(14) aggregate containing two cations and two anions; the combination of the two N—H...O hydrogen bonds generates a one-dimensional C
2
2(6) chain of alternating cations and anions, and the combination of one N—H...O hydrogen bond and two C—H...O hydrogen bonds generates a two-dimensional sheet of alternating R
4
4(14) and R
8
6(34) rings.
Two phosphate–imidazole complexes with and without a hydrogen-bonded guest molecule
Authors: Pavan Kumar K. V. P. , Kumara Swamy K. C.
Published: November 2005

The molecular structures of the complexes imidazolium 6,6′-di-tert-butyl-4,4′-dimethyl-2,2′-thiodiphenyl phosphate, C3H5N2
+·C22H28O4PS−, (I), and imidazolium 6,6′-di-tert-butyl-4,4′-dimethyl-2,2′-thiodiphenyl phosphate diisopropyl hydrazodicarboxylate hemisolvate, C3H5N2
+·C22H28O4PS−·0.5C8H16N2O4, (II), have been determined. While (I) forms the expected hydrogen-bonded chain utilizing the two imidazole N-bound H atoms, in (II), the substituted hydrazine solvent molecule inserts itself between the chains. Compound (I) exhibits a strong N—H...O hydrogen bond, with an N...O distance of 2.603 (2) Å. The hydrazine solvent molecule in (II) lies about a twofold axis and the N-bound H atoms are involved in bifurcated hydrogen bonds with phosphate O atoms. A C-bound H atom of the imidazolium cation is involved in a C—H...O interaction with a carbonyl O atom of the hydrazine solvent molecule.
Characterization of human NSCLC cell line with innate etoposide‐resistance mediated by cytoplasmic localization of topoisomerase II alpha
Authors: de Lucio Bautista , Manuel Victor , Barrera‐Rodríguez Raul
Published: November 2005

Topoisomerase (topo) II alpha is a target for many chemotherapeutic agents in clinical use. In tumor cells resistant to topo II poisons, there have been descriptions of quantitative and qualitative alterations involved in this enzyme. More recently, the cytoplasmic localization of topo II alpha has been described as a mechanism to confer drug resistance. Here, we report the characterization of a human non‐small‐cell lung cancer cell line, INER‐37, which shows an innate resistance to etoposide. In this cell line, etoposide resistance was directly associated with the expression of topo II alpha resident mainly in the cytoplasmic region. At the molecular level, INER‐37 cells carry on a heterozygous gene deletion, transcribing two different topo II alpha mRNAs: 4.8 kb and 2.0 kb. The bigger 4.8 kb mRNA (missing 1.3 kb of 3′ mRNA and including the untranslated region) is translated into a truncated cytoplasmic protein of approximately 160 kDa. The protein truncation affects at least 96 amino acids in the COOH‐terminal region where the more proximal bipartite nuclear localization signal is located. The INER‐37 cell line is the first cancer cell line reported with an innate mutation affecting the 3′‐end region of the topo II alpha gene that confers a cytoplasmic localization of the enzyme and therefore an increased resistance to etoposide. (Cancer Sci 2005; 96: 774–783)
Targeting Id1 and Id3 inhibits peritoneal metastasis of gastric cancer
Authors: Tsuchiya Takeshi , Okaji Yurai , Tsuno Nelson H. , Sakurai Daisuke , Tsuchiya Naoyuki , Kawai Kazushige , Yazawa Kentaro , Asakage Masahiro , Yamada Jun , Yoneyama Satomi , Kitayama Joji , Osada Takuya , Watanabe Toshiaki , Tokunaga Katsushi , Takahashi Koki , Nagawa Hirokazu
Published: November 2005

Inhibitor of DNA binding (Id) proteins are essential for cell differentiation, proliferation, migration, invasion and angiogenesis. Recently, they have been shown to correlate with less differentiated phenotypes, high malignant potential and poor clinical outcome in various kinds of tumors. In an attempt to develop new strategies for the treatment of peritoneal metastasis of gastric cancer, we prepared an Id1, 3 double‐knockdown gastric cancer cell line, MKN45, by RNA interference and investigated its effects on the development of metastatic nodules in the peritoneal cavity. Both cell proliferation and migration capabilities were decreased in Id1, 3 double‐knockdown cells, as was their ability to bind to laminin, which could be explained by the decreased expression of integrin α6. These are important steps in the metastatic process. In a mouse model, the number of peritoneal metastatic nodules formed by Id1, 3 double‐knockdown cells was reduced compared to mock‐transfected control cells, as was the size of individual tumors. In this study, we clearly demonstrated that Id1, 3 double‐knockdown significantly impaired the ability of gastric cancer cells to form peritoneal metastasis. Id should be considered an ideal target for the treatment and prevention of gastric cancer, and RNA interference is an attractive and promising strategy to achieve it. (Cancer Sci 2005; 96: 784–790)
Porphyromonas gingivalis-induced inflammatory mediator profile in anex vivohuman whole blood model
Authors: Bodet C , Chandad F , Grenier D
Published: November 2005

Periodontitis is characterized by an accumulation of inflammatory cells in periodontal tissue and subgingival sites. Leukocytes play a major role in the host response to Porphyromonas gingivalis, a major aetiological agent of chronic periodontitis. Secretion of high levels of inflammatory mediators, including cytokines and prostaglandins, by leucocytes is believed to contribute to periodontal tissue destruction. The aim of this study was to investigate the inflammatory response of an ex vivo whole blood model to P. gingivalis stimulation. The production of interleukin-1 beta (IL-1β), IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumour necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), IFN-γ-inducible protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), Regulated on Activation Normal T cell Expressed and Secreted (RANTES) and prostaglandin E2 (PGE2) were quantified by enzyme-linked immunosorbent assays. P. gingivalis induced the secretion of the pro-inflammatory cytokines IL-1β, TNF-α, IL-6 and IFN-γ, the chemokines IL-8, RANTES and MCP-1 and the inflammatory mediator PGE2 in an ex vivo human whole blood model. The secretion levels were dependent on the strain and the infectious dose used. While the mediator profiles were comparable between six healthy subjects, a high interindividual variability in the levels of secreted mediators was observed. This study supports the view that P. gingivalis, by inducing high levels of inflammatory mediators from a mixed leucocyte population, can contribute to the progression of periodontitis.
1,25-Dihydroxyvitamin D3 inhibits lipopolysaccharide-induced immune activation in human endothelial cells
Authors: Equils O , Naiki Y , Shapiro A M , Michelsen K , Lu D , Adams J , Jordan S
Published: November 2005

In addition to its well-known role in mineral and skeletal homeostasis, 1,25-dihydroxyvitamin D3[1,25-(OH)2, D3] regulates the differentiation, growth and function of a broad range of immune system cells, including monocytes, dendritic cells, T and B lymphocytes. Vascular endothelial cells play a major role in the innate immune activation during infections, sepsis and transplant rejection; however, currently there are no data on the effect of 1,25-(OH)2 D3 on microbial antigen-induced endothelial cell activation. Here we show that 1,25-(OH)2 D3 pretreatment of human microvessel endothelial cells (HMEC) inhibited the enteric Gram-negative bacterial lipopolysaccharide (LPS) activation of transcription factor NF-κB and interleukin (IL)-6, IL-8 and regulated upon activation normal T cell exposed and secreted (RANTES) release. The effect of 1,25-(OH)2 D3 was not due to increased cell death or inhibition of endothelial cell proliferation. 1,25-(OH)2 D3 pretreatment of HMEC did not block MyD88-independent LPS-induced interferon (IFN)-β promoter activation. 1,25-(OH)2 D3 pretreatment of HMEC did not modulate Toll-like receptor 4 (TLR4) or MD-2 expression. These data suggest that 1,25-(OH)2 D3 may play a role in LPS-induced immune activation of endothelial cells during Gram-negative bacterial infections, and a suggest a potential role for 1,25-(OH)2 D3 and its analogues as an adjuvant in the treatment of Gram-negative sepsis.
Differential regulation of interleukin-12 and tumour necrosis factor-α by phosphatidylinositol 3-kinase and ERK 1/2 pathways duringMycobacterium tuberculosisinfection
Authors: Yang C-S , Lee J-S , Jung S-B , Oh J-H , Song C-H , Kim H-J , Park J-K , Paik T-H , Jo E-K
Published: November 2005

Interleukin (IL)-12 and tumour necrosis factor (TNF)-α are both thought to be critical factors in the defence against mycobacteria but are known to play different roles. In this study, we investigated the regulatory pathways for IL-12 and TNF-α expression in human monocyte-derived macrophages (MDMs) after treatment with Mycobacterium tuberculosis H37Rv or the Triton X-100 solubilized proteins (TSP) purified from M. tuberculosis. We found a rapid phosphorylation of Akt and extracellular signal-regulated kinase (ERK), albeit with differential activation kinetics, in human MDMs treated with M. tuberculosis or TSP. Studies using inhibitors selective for phosphatidylinositol 3-kinase (PI 3-K) and ERK 1/2 show that both pathway plays an essential role in the induction of TNF-α at both the transcriptional and translational levels in human MDMs. In contrast, blockade of the PI 3-K/Akt or ERK 1/2 pathways significantly increased M. tuberculosis- or TSP-induced IL-12 p40 and p35 mRNA and bioactive p70 protein. The enhancement of IL-12 levels by inhibition of PI 3-K and ERK 1/2 was not reversed by neutralization of TNF-α or addition of rhTNF-α, suggesting that the negative regulation of IL-12 is not mediated by concomitant TNF-α suppression. Further, PI 3-K activity is required for the M. tuberculosis- or TSP-induced phosphorylation of ERK 1/2 activation. TSP from M. tuberculosis shows a similar dependency on the PI 3-K and ERK 1/2 pathways to those by M. tuberculosis. Collectively, these data suggest that the Th1-driving cytokine IL-12 and proinflammatory cytokine TNF-α are differentially regulated by PI 3-K and ERK 1/2 pathways in human MDMs during mycobacterial infection. These results may provide therapeutic targets for precise and specific fine-tuning of cytokine responses.
Biological Flora of the British Isles: Rubus vestitus Weihe
Authors: TAYLOR K.
Published: November 2005

This account reviews information on all aspects of the biology of Rubus vestitus that are relevant to understanding its ecological characteristics and behaviour. The main topics are presented within the standard framework of the Biological Flora of the British Isles: distribution, habitat, communities, responses to biotic factors, responses to environment, structure and physiology, phenology, floral and seed characters, hervbivores and disease, history, and conservation.

Rubus vestitus is a widespread member of the series Vestiti, one of 11 rather ill‐defined series of largely apomictic microspecies in the section Glandulosus of Rubus subg. Rubus. Each of the series represents a main node in the spectrum of variation within this section. Its species (usually with those from sections Rubus and Corylifolii) are commonly included in the Rubus fruticosus L. aggregate (brambles or blackberries). More than 320 microspecies have been recognized in this aggregate in Britain.

Rubus vestitus is typical of shady woodlands, wood margins, scrub and hedgebanks. Often abundant on calcareous or clay soils, it is rarer on acid soils of heaths and moors.

Rubus vestitus is placed in its ecological context, relative to the other widespread and important bramble species in Britain. Where possible, information specific to R. vestitus is provided but much of the relevant literature does not distinguish it within the broader R. fruticosus agg. As this is the first account of a bramble in the Biological Flora of the British Isles, an inclusive approach incorporates data for the species aggregate where appropriate (e.g. in lists of pollinators and phytophagous insects).
A feeling of well‐being accompanied by a period of prosperity and birthweight in Chile: a possible link?
Authors: Amigo Hugo , Vargas Claudio , Rona Roberto J.
Published: November 2005

The aims of the study were to describe the trend in birthweight from 1985 to 2000 in Chile and ascertain the possible factors that may explain the changes in birthweight during the period. We used time series of birthweight and length at birth of all live births (n > 4 000 000). Multivariable regression analyses were carried out to assess whether the gender of the newborn, maternal education, maternal age and marital status could explain the trend in the total time series and by period. Birthweight adjusted for gestational age was analysed in terms of grams and Z scores. There was an increase in birthweight of 100 g between 1989 and 1994 that coincided with the re‐establishment of democracy and economic growth in Chile. The changes in birthweight were not explained by the available independent variables and trends of caesarean section, maternal obesity and post‐mature deliveries over the period. The birthweight difference between mothers with university education and those with primary education was 0.2 Z scores (equivalent to 110 g) in 1985 and was greatly reduced by 2000 (equivalent to 40 g). A positive sense of social well‐being and economic growth may have influenced an increase in birthweight between 1989 and 1994 as socio‐economic growth preceded and continued after the period of increasing birthweight. Our study showed a remarkable decrease in the differences in birthweight by educational level not shown in other countries of similar wealth.
Hypospadias and maternal exposures to cigarette smoke
Authors: Carmichael Suzan L. , Shaw Gary M. , Laurent Cecile , Lammer Edward J. , Olney Richard S. ,   The National Birth Defects Prevention Study
Published: November 2005

The few previous studies of hypospadias and smoking have suggested either no association or a reduced risk. This study, which uses data from the National Birth Defects Prevention Study, a multi‐state, population‐based case–control study, includes data on males born with severe hypospadias (i.e. the urethra opens at the penile shaft, scrotum or perineum) from 1997 to 2000. Non‐malformed, liveborn male controls were selected randomly from birth certificates or from birth hospitals. Maternal interviews were completed by telephone with 453 case mothers and 1267 control mothers. Maternal smoking was not associated with hypospadias risk. For example, during the third month of pregnancy, smoking < 0.5 pack/day had an odds ratio (OR) of 1.1 [95% CI 0.6, 1.9]; 0.5 pack/day, 0.6 [0.4, 1.1]; and ≥ 1 pack/day, 0.8 [0.4, 1.6]. Exposure to any secondhand smoke at home during the third month of pregnancy showed an OR of 0.6 [95% CI 0.4, 1.0], and exposure at work or school, an OR of 0.7 [0.5, 1.1]. Similar risks were observed for other months during the periconceptional period, and adjustment for several potential confounders did not substantially alter results. This analysis does not confirm a recent report suggesting that maternal smoking is associated with a reduced risk of having offspring with hypospadias.
Economic behaviour and the norms of capitalism
Authors: Demeulenaere Pierre
Published: November 2005

The idea of moralising the capitalist economy presupposes an idea of morality or justice. If we confine ourselves intuitively to the principle of freedom or non‐domination – often connected with a defence of market institutions as well as broader moral justifications – two questions must be asked. Firstly, can profit‐oriented economic behaviour secure principles of non‐domination? The answer is no, for there is a structural interest in cheating in a prisoner's dilemma situation. Additional normative considerations must be introduced in order to ensure that market norms are respected. The second question is, then, whether moral regard for the principle of non‐domination can in itself justify free‐trade institutions. Here again the answer is no, inasmuch as various typical features of social existence prevent us from thinking that respect for the pure norms of free trade can be consonant with direct application of this non‐domination principle. In fact, actual social existence introduces other norms reflecting other social objectives that may also be derived from a non‐domination principle.
The ethics of competition
Authors: Pharo Patrick
Published: November 2005

This paper on moral sociology first examines the moral aspect of criticisms traditionally levelled at capitalism and then analyses the attempted response and justification of capitalism based on the supposed naturally beneficial effects of competition. Social contests inherent in human ways of life are not restricted to economics and are unlikely to possess spontaneously the moral virtue attached to them. The article thus explores more specifically the ethical nature of producer and consumer competition and concludes by proposing that the level and quality of self‐esteem engendered or fostered by a socio‐economic order be taken as a sort of moral yardstick.
The morality of belief in the profits of virtue
Authors: Colonomos Ariel
Published: November 2005

This article deals with a business ethic which requires multinationals to observe, in the countries in which they set up, the rules of justice, accountability, and human rights. This model rethinks the conception of corporate ethics, and the reasons for its propagation have to do with the transformation of international relations after the Cold War. Underpinning its development are the language games which the moral entrepreneurs decide to use, and finance is the social space in which the various elements of this communication link up. The present inquiry is both explanatory and normative in its aim. The text discusses the morality of “honesty pays”, placing it in the context of the culturally and historically situated forms of utilitarianism that it espouses. The inquiry concludes by stressing the deeply religious character of its appeal, the effectiveness and validity of which rest on self‐fulfilling prophecies.
Capitalism and ethics: how conflicts‐of‐interest legislation can be used to handle moral dilemmas in the economy*
Authors: Swedberg Richard
Published: November 2005

In this article I look at the way that conflict of interest‐legislation is used to handle moral dilemmas in the US economy. The key idea of this type of laws is that it is possible to prevent a certain type of moral conflicts from arising by forbidding all the actors who have been set to guard ageneral interestto enter into a situation where their behaviour may be influenced by theirprivate interests. In an attempt to better understand how this type of legislation works in reality, I use as my empirical case what happened when the US bull market of the 1990s fell apart and a number of corporate scandals broke out. The reason for using just this example is that conflicts of interest figured very prominently in the scandals that followed the bull market, especially in the accounting industry which this article covers in detail. An effort is also made to see how suggestions were made, in response to the scandals, to improve upon the existing conflicts of interest‐legislation in various ways.
When firms behave “responsibly”, are the roots national or global?
Authors: Reich Simon
Published: November 2005

The article proposes to assess the extent to which corporate codes of conduct are converging or, conversely, remain distinctly national in character. This approach makes it possible to assess whether purportedly global firms are influenced by global norms or domestic factors. The empirical basis for the analysis includes field research interviewing senior corporate and government officials as well as a wealth of aggregate statistical data. Three areas of corporate activity were systematically examined: governance and finance; research and development; and trade and direct investment. The research revealed three discernable clusters of behaviour across the operational areas, epitomised by the cases of the three largest national economies – Germany, Japan, and the USA. It follows that, if the world's largest corporations (purportedly the progenitors of globalization) are not converging in terms of behaviour in the activities that they adjudge to be most strategically important to them, then the proponents (and indeed prophets) of globalization are obviously clearly overstating their case. National champions may have been disappearing like the dinosaurs, but national patterns of behaviour are not.
What's wrong with business ethics
Authors: Rodin David
Published: November 2005

The field of business ethics is trapped between two competing and flawed conceptions of corporate responsibility. On the one hand is the shareholder value model, championed by Nobel Prize winning economist Milton Friedman, which claims that corporations owe positive moral obligations only to their shareholders. On the other hand is the normative stakeholder theory, which claims that corporations are morally obliged to secure the interests of a broad range of groups, of which shareholders are only one. In this paper I will argue that if it is to generate a viable account of corporate moral responsibility, business ethics will need to abandon both canonical approaches and adopt a new approach based on a more concrete conception of the business corporation. At the end of the paper I sketch what such a theoretical approach would look like. The argument is not only relevant to business ethics; it also has important consequences for Michael Porter's influential approach to competitive strategy.
Inference gaps in moral assessment: capitalism, corporations and individuals
Authors: French Peter A.
Published: November 2005

The paper is divided into three parts. In the first an argument is made that negative moral assessments of institutions are insufficient bases from which to infer similar negative moral assessments of the actions of the organizations that embody those institutions or the individuals that perform institution‐constituted actions within those institutions. The second part re‐examines arguments for organizational intentionality and hence organizational membership in the moral community that the author had presented over two decades ago and offers a revision of the author's position on organizational intentionality that is intended to be more intuitively pleasing than his former account that was based on understanding intentionality on the desire/belief complex model. The third part draws some of the consequences of the inference gaps in moral assessment for understanding the complexity of the elements of the moral world.
Probing the “moralization of capitalism” problem: Democratic experimentalism and the co‐evolution of norms
Authors: Arnsperger Christian
Published: November 2005

The most fundamental issue raised by any discussion around the ‘moralization of capitalism’ is the puzzle of second‐order morality: How exactly is it possible to pass a moral judgement on our categories of moral judgement? How can our norms of morality be said to be immoral, thus calling for (re‐)moralization? The answer depends on the observation that norms and interaction structures in capitalism have co‐evolved, and hence can be taken neither as autonomous with respect to one another nor as obeying a hidden functionality. This implies that, paradoxically, the moralization problem cannot be solved in moral terms, but calls for a political approach, to make best use of which we need to come to terms with capitalism as a fully fledged cultural system. The ideology inherent in that cultural system can only be attacked from within the system itself, through decentralized processes of democratic decision‐making rather than by mere prophetic denunciation or moral invectives. Because the particular version of the capitalist culture in which we live now is a radically contingent result of history, it makes sense to support a framework of democratic experimentalism which embeds multiple institutional experimentation within a system of experience‐building and experience‐formation analogous to the system of information‐utilisation and information‐dissemination offered by the Hayekian market. Only by thus creating the real and concrete democratic presuppositions for alternative capitalist practices can we begin to make sense of the puzzle inherent in the “moralization of capitalism” problem.
Christian economic morality: the medieval turning point
Authors: Erner Guillaume
Published: November 2005

It is one of history's paradoxical commonplaces that capitalism came into being within a Christian culture that was hostile to money. Little thought has, however, been given to the reasons for that hostility, though they are not self‐evident. While it is true that the Church Fathers displayed great hostility towards material things, medieval theologians had no qualms about revising the theses of the Early Church to suit the needs of the moment. We seek to explain the virulence of this early form of anti‐capitalism by the connection that was made between material concerns in the broad sense – money, but also sex – and an anti‐world that was supposed to be dominated by the Jews. A study of the discourse of thirteenth‐century Christian theologians enables us to highlight the links between hostility towards money and hatred of outsiders, which may help to explain the continuing prevalence of this rejection within various modern forms of discourse.
Saints, Stalwarts, and Slackers: State Financial Contributions to Welfare Reform
Authors: Rodgers Harrell R.
Published: November 2005

Considerable literature finds that spending levels are important predictors of poverty rates, both in the American states and in western European nations. Those jurisdictions with the most generous support programs generally have lower poverty rates. This article examines state Temporary Assistance for Needy Families (TANF) spending levels in relation to national norms, the spending ability of the state as predicted by their total taxable revenue base, and the state's poverty rate. The analysis shows enormous variation in state per capita TANF spending, with many states spending far less than the national mean and their fiscal capacity. Most of the low‐spending states have the fiscal ability to fund more vigorous programs but at optimal levels; some would still fall below the national mean. In return for improved funding, these states would be candidates for increased federal assistance. A few states with a high poverty rate and usually with large numbers of poor citizens are generous spenders, indicating that funding is one component of effective programs.
Adaptation without Pressure? European Legislation and British Merger Policy
Authors: Zahariadis Nikolaos
Published: November 2005

European legislation exercises an important influence on national policy even in areas where there is no pressure or need to incorporate in national legislation directives or regulations agreed upon in Brussels. In this article, I apply insights from the literature on sociological institutionalism and policy framing to explore statistically the impact of the 1989 European Merger Control Regulation on British merger policy during the period from 1984 to 2000. The findings address two issues in the broader literature of European integration. First, the study undermines the point, which is widely accepted in the Europeanization literature, that pressure emanating from the incompatibility between European and national institutions, norms, or policies is a necessary condition for national adaptation. Second, Euroskeptics and other proponents of British “exceptionalism” have much to fear from European integration. Even in the absence of regulations emanating from Brussels, European ideas and norms seep into national practice by way of policy framing and institutional isomorphism.