bluuebunny/crossref_metadata_2025 huggingface dataset:
The Sinorhizobium meliloti chromosomal origin of replication
Authors: Sibley Christopher D. , MacLellan Shawn R. , Finan Turlough
Published: January 2006

The predicted chromosomal origin of replication (oriC) from the alfalfa symbiontSinorhizobium melilotiis shown to allow autonomous replication of a normally non-replicating plasmid withinS. meliloticells. This is the first chromosomal replication origin to be experimentally localized in theRhizobiaceaeand its location, adjacent tohemE, is the same as fororiCinCaulobacter crescentus, the only experimentally characterized alphaproteobacterialoriC. Using an electrophoretic mobility shift assay and purifiedS. melilotiDnaA replication initiation protein, binding sites for DnaA were mapped in theS. meliloti oriCregion. Mutations in these sites eliminated autonomous replication.S. melilotithat expressed DnaA from a plasmidlacpromoter was observed to form pleomorphic filamentous cells, suggesting that cell division was perturbed. Interestingly, this cell phenotype is reminiscent of differentiated bacteroids found inside plant cells in alfalfa root nodules.
SoxV transfers electrons to the periplasm of Paracoccus pantotrophus – an essential reaction for chemotrophic sulfur oxidation
Authors: Bardischewsky Frank , Fischer Jörg , Höller Bettina , Friedrich Cornelius G.
Published: January 2006

ThesoxVWgenes are located upstream of thesoxgene cluster encoding the sulfur-oxidizing ability ofParacoccus pantotrophus. SoxV is highly homologous to CcdA, which is involved in cytochromecmaturation ofP. pantotrophus. SoxV was shown to function in reduction of the periplasmic SoxW, which shows a CysXaaXaaCys motif characteristic for thioredoxins. From strain GBΩV, which carries an Ω-kanamycin-resistance-encoding interposon insoxV, and complementation analysis it was evident that SoxV but not the periplasmic SoxW was essential for lithoautotrophic growth ofP. pantotrophuswith thiosulfate. However, the thiosulfate-oxidizing activities of cell extracts from the wild-type and from strain GBΩV were similar, demonstrating that the low thiosulfate-oxidizing activity of strain GBΩVin vivowas not due to a defect in biosynthesis or maturation of proteins of the Sox system and suggesting that SoxV is part of a regulatory or catalytic system of the Sox system. Analysis of DNA sequences available from different organisms harbouring a Sox system revealed thatsoxVWgenes are exclusively present insoxoperons harbouring thesoxCDgenes, encoding sulfur dehydrogenase, suggesting that SoxCD might be a redox partner of SoxV. No complementation of theccdAmutantP. pantotrophusTP43 defective in cytochromecmaturation was achieved by expression ofsoxV in trans, demonstrating that the high identity of SoxV and CcdA does not correspond to functional homology.
Temperature-resolved study of three [M(M′O4)4(TBPO)4] complexes (MM′ = URe, ThRe, ThTc)
Authors: Helliwell Madeleine , Collison David , John Gordon H. , May Iain , Sarsfield Mark J. , Sharrad Clint A. , Sutton Andrew D.
Published: January 2006

The crystal structures of the title complexes were measured at several temperatures between room temperature and 100 K. Each sample shows reversible crystal-to-crystal phase transitions as the temperature is varied. The behaviour of [U(ReO4)4(TBPO)4] (I) and [Th(ReO4)4(TBPO)4] (II) (TBPO = tri-n-butylphosphine oxide) is very similar; at room temperature, crystals of (I) and (II) are isostructural, with space group I\bar 42m, and reducing the temperature to 100 K causes a lowering of the space-group symmetry to C-centred cells, space groups Cc for (I) and Cmc21 for (II). The variation of lattice symmetry of [Th(TcO4)4(TBPO)4] (III) was found to be somewhat different, with the body-centred cubic space group, I\bar 43m, occurring at 293 K, a reduction of symmetry at 230 K to the C-centred orthorhombic space group, Cmc21, and a further transition to the primitive orthorhombic space group, Pbc21, below 215 K. Elucidation of the correct space-group symmetry and the subsequent refinement was complicated in some cases by the twinning by pseudo-merohedry that arises from the lowering of the space-group symmetry, occurring as the temperature is reduced. All three of the crystal structures determined at room temperature have high atomic displacement parameters, particularly of the
n
Bu groups, and (III) shows disorder of some of the O atoms. The structures in the space group Cmc21, show some disorder of
n
Bu groups, but are otherwise reasonably well ordered; the structures of (I) in Cc and (III) in Pbc21 are ordered, even to the ends of the alkyl chains. Inter-comparison of the structures measured below 293 K, using the program OFIT from the SHELXTL package, showed that generally, they are remarkably alike, with weighted r.m.s. deviations of the M, M′ and P atoms of less than 0.1 Å, as are the 293 K structures of (I) and (II) with their low-temperature counterparts. However, the structure of (III) measured in the space group Cmc21 is significantly different from both the structure of (III) at 293 K and that found below 215 K, with weighted r.m.s. deviations of the Th, Tc and P atoms of 0.40 and 0.37 Å, respectively. An extensive network of weak intra- and intermolecular C—H...O hydrogen bonds found between the atoms of the
n
Bu and [M′O4] groups probably influences the packing and the overall geometry of the molecules.
Pressure-frozen benzene I revisited
Authors: Budzianowski Armand , Katrusiak Andrzej
Published: January 2006

The crystal structure of benzene, C6H6, in situ pressure-frozen in phase I, has been determined by X-ray diffraction at 0.30, 0.70 and 1.10 GPa, and 296 K. The molecular aggregation within phase I is consistent with van der Waals contacts and electrostatic attraction of the positive net atomic charges at the H atoms with the negative net charges of the C atoms. The C—H...aromatic ring centre contacts are the most prominent feature of the two experimentaly determined benzene crystal structures in phases I and III, whereas no stacking of the molecules has been observed. This specific crystal packing is a likely reason for the exceptionally high polymerization pressure of benzene. The changes of molecular arrangement within phase I on elevating the pressure and lowering the temperature are analogous.
Absence of halogen...halogen interactions in chlorotrimethylsilane polymorphs
Authors: Gajda Roman , Dziubek Kamil , Katrusiak Andrzej
Published: January 2006

The structures of in situ pressure-frozen chlorotrimethylsilane crystals, (CH3)3SiCl, have been determined at 0.23, 0.30 and 0.58 GPa. The molecular arrangements in the low-temperature and high-pressure phases are two-dimensionally isostructural, but different in the third perpendicular direction. Consequently, a striking similarity exists between the unit-cell dimensions of these polymorphs. The absence of short Cl...Cl contacts, both in the low-temperature or pressure-frozen phases of (CH3)3SiCl, has been rationalized in terms of the favoured packing patterns and comparable energies of halogen...halogen interactions and other van der Waals forces.
Structures of the cation-deficient perovskite Nd0.7Ti0.9Al0.1O3 from high-resolution neutron powder diffraction in combination with group-theoretical analysis
Authors: Zhang Zhaoming , Howard Christopher J. , Knight Kevin S. , Lumpkin Gregory R.
Published: January 2006

The crystal structures of Nd0.7Ti0.9Al0.1O3, taken to represent the ideal Nd2/3TiO3, have been elucidated from 4 to 1273 K using high-resolution neutron powder diffraction in combination with group-theoretical analysis. The room-temperature structure is monoclinic in C2/m, on a cell with a = 7.6764 (1), b = 7.6430 (1), c = 7.7114 (1) Å, β = 90.042 (2)°. Pertinent features are the layered ordering of the A-site Nd cations/vacancies along the z axis and out-of-phase tilting of the (Ti/Al)O6 octahedra around both the x and z axes. From about 750 to 1273 K, the octahedra are tilted around just one axis (x axis) perpendicular to the direction of the cation ordering, giving rise to an orthorhombic structure with space-group symmetry Cmmm.
Context‐dependent mutations predominate in an engineered high‐affinity single chain antibody fragment
Authors: Midelfort Katarina S. , Wittrup K. Dane
Published: January 2006

A mutational analysis of the femtomolar‐affinity anti‐fluorescein antibody 4M5.3, compared to its wild‐type progenitor, 4‐4‐20, indicates both context‐dependent and ‐independent mutations are responsible for the 1800‐fold affinity improvement. 4M5.3 was engineered from 4‐4‐20 by directed evolution and contains 14 mutations. The seven mutations identified as present in each of 10 final round affinity maturation clones were studied here. Affinities of the 4‐4‐20 single mutant addition and 4M5.3 single site reversion mutants were compared. These experiments identified four mutations, of these seven, that were context‐dependent in their contribution to higher affinity. A simplified mutant containing only these seven mutations was created to analyze complete double mutant cycles of selected sets of mutations. Specific mutational sets studied included the ligand contact mutations, the heavy chain CDR3 mutations, the heavy chain CDR3 mutations plus the neighboring residue at site H108, and the early and late acquired mutations on the directed evolution pathway. The heavy chain CDR3 mutational set and the ligand‐contacting mutations were shown to provide −1.4 and −2.0 kcal/mol, respectively, of the total −3.5 kcal/mol change in free energy of binding of the seven‐site consensus mutant. The mutations acquired late in the directed evolution rounds provided much of the change in free energy without the earlier acquired mutations (−3.1 kcal/mol of the total −3.5 kcal/mol). Prior structural data and electrostatic calculations presented several hypotheses for the higher affinity contributions, some of which are supported by these mutational data.
Clinical utility of quantitative RT‐PCR targeted to α1,4‐N‐acetylglucosaminyltransferase mRNA for detection of pancreatic cancer
Authors: Ishizone Satoshi , Yamauchi Kazuyoshi , Kawa Shigeyuki , Suzuki Takefumi , Shimizu Fumiaki , Harada Oi , Sugiyama Atsushi , Miyagawa Shinichi , Fukuda Minoru , Nakayama Jun
Published: January 2006

α1,4‐N‐Acetylglucosaminyltransferase (α4GnT) is a glycosyltransferase responsible for the biosynthesis of α1,4‐GlcNAc‐capped O‐glycans, and is frequently expressed in pancreatic cancer cells but not peripheral blood cells. In the present study, we tested the clinical utility of α4GnT mRNA expressed in the mononuclear cell fraction of peripheral blood as a biomarker of pancreatic cancer. Total RNA isolated from the peripheral blood mononuclear cells from 55 pancreatic cancer patients, 10 chronic pancreatitis patients, and 70 cancer‐free volunteers was analyzed quantitatively by reverse transcription‐polymerase chain reaction with primers specific for α4GnT, and the expression level of α4GnT mRNA relative to that of glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) was measured. When the ratio of α4GnT to GAPDH transcripts exceeded a defined cut‐off value, patients were considered to have pancreatic cancer. By these standards, 76.4% of the pancreatic cancer patients were detected by this assay. A strong correlation was obtained between positivity in this assay and the expression of α4GnT protein detected immunohistochemically in pancreatic cancer tissues resected subsequently, suggesting that α4GnT mRNA detected in the peripheral blood is derived from circulating pancreatic cancer cells. Although increased levels of α4GnT mRNA was detected in 40.0% of chronic pancreatitis patients and 17.1% of cancer‐free volunteers, the expression levels were significantly lower than those seen in pancreatic cancer patients. These results suggest that quantitative analysis of α4GnT mRNA expressed in the mononuclear cell fraction of peripheral blood will contribute to the detection of pancreatic cancer. (Cancer Sci 2006; 97: 119  – 126)
Modulation of the granzyme B inhibitor proteinase inhibitor 9 (PI-9) by activation of lymphocytes and monocytes in vitro and by Epstein–Barr virus and bacterial infection
Authors: Classen C F , Bird P I , Debatin K-M
Published: January 2006

Proteinase inhibitor 9 (PI-9) is an intracellular serpin expressed in lymphocytes and monocyte-derived cells. It is the only known endogenous natural antagonist of granzyme B (GrB), and its proposed function is protection of cells from misdirected GrB. We have studied the regulation of PI-9 in primary peripheral blood mononuclear cells (PBMCs) following ex-vivo stimulation, and in PBMCs from patients suffering from viral or bacterial infections. By intracellular flow cytometry, we found identical PI-9 expression in all lymphocyte subsets, lower levels in monocytes and none in granulocytes. PI-9 was stable for 48 h in the presence of cycloheximide, indicating slow protein turnover. Incubation of PBMCs with several stimuli including lipopolysaccharide (LPS) led to up-regulation in the monocyte, but not the lymphocyte fraction, within 48 h, inhibitable by the NF-κB inhibitor pyrrolidin dithiocarbamate (PTDC). Up-regulation of PI-9 was observed in lymphocytes and monocytes of patients with acute Epstein–Barr virus (EBV), but not bacterial infection. Preterm infants had similar PI-9 expression as adults in monocytes, but lower in lymphocytes, decreasing during bacterial infection. Taken together, our data indicate that PI-9 is rapidly up-regulated upon stimulation of monocytes, but not lymphocytes. By protecting monocytes and macrophages from misdirected GrB in the inflammatory process, PI-9 might be involved in the regulation of antigen presentation.
Allelopathic effect of the aquatic macrophyte, Stratiotes aloides, on natural phytoplankton
Authors: MULDERIJ GABI , SMOLDERS ALFONS J. P. , VAN DONK ELLEN
Published: January 2006

1. A survey of different Dutch Stratiotes stands showed that the density of phytoplankton (except cyanobacteria) was always higher outside S. aloides than between the rosettes of S. aloides. Analyses of water samples revealed that nutrient limitation was unlikely to have caused the lower phytoplankton biomass in the vicinity of S. aloides.

2. An in situ incubation experiment in the Danube Delta, Romania, indicated allelopathic activity against phytoplankton in S. aloides stands. The growth rate of natural phytoplankton populations exposed to water from S. aloides stands was significantly lower than that of populations that had not been in contact with S. aloides exudates.

3. A laboratory microcosm experiment showed a significantly lower phytoplankton biomass in treatments with S. aloides exudates. Nutrient concentrations and the light intensity were high enough that the lower phytoplankton biomass could not be explained by nutrient or light limitation.
Phylogeographic patterns of host‐race evolution in Tephritis conura (Diptera: Tephritidae)
Authors: DIEGISSER THORSTEN , SEITZ ALFRED , JOHANNESEN JES
Published: January 2006

Host‐race evolution is a prime candidate for sympatric speciation because host shifts must take place in the presence of both hosts. However, the geographic context in which the shift takes place may have strong allopatric or peripatric components if the primary host within a localized area is scarce or even goes extinct. Inference of the relative importance of the geographic mode of speciation may be gained from phylogeographic imprints. Here, we investigate the phylogeography of host races of the tephritid fly Tephritis conura from sympatric, parapatric and allopatric populations of Cirsium heterophyllum and Cirsium oleraceum (Asteraceae) in Europe, for addressing the age and direction, and the geographic context of host‐race formation. Haplotype networks of the host races differed significantly in molecular diversity and topology. However, host‐race haplotypes were nested within the same network, with a central haplotype H1 being the most common haplotype in both host races. C. heterophyllum flies were genetically more diverse and substructured than flies from C. oleraceum, suggesting that the latter is the derived race. The phylogeographic imprint indicates either that C. heterophyllum flies colonized C. oleraceum during range expansion or that heterophyllum flies went extinct in an area where oleraceum flies persisted (followed by re‐immigration). These imprints are in concordance with peripatric diversification, probably in the European Alps and related to the last ice age, where the host‐race diversification was largely completed before the postglacial range expansion on C. oleraceum to current areas of sympatry and parapatry with C. heterophyllum.
Dissection of a functional interaction between the DNA translocase, FtsK, and the XerD recombinase
Authors: Yates James , Zhekov Ivailo , Baker Rachel , Eklund Bjørn , Sherratt David J. , Arciszewska Lidia K.
Published: January 2006

Successful bacterial circular chromosome segregation requires that any dimeric chromosomes, which arise by crossing over during homologous recombination, are converted to monomers. Resolution of dimers to monomers requires the action of the XerCD site‐specific recombinase at dif in the chromosome replication terminus region. This reaction requires the DNA translocase, FtsKC, which activates dimer resolution by catalysing an ATP hydrolysis‐dependent switch in the catalytic state of the nucleoprotein recombination complex. We show that a 62‐amino‐acid fragment of FtsKC interacts directly with the XerD C‐terminus in order to stimulate the cleavage by XerD of BSN, a dif‐DNA suicide substrate containing a nick in the ‘bottom’ strand. The resulting recombinase–DNA covalent complex can undergo strand exchange with intact duplex dif in the absence of ATP. FtsKC‐mediated stimulation of BSN cleavage by XerD requires synaptic complex formation. Mutational impairment of the XerD–FtsKC interaction leads to reduction in the in vitro stimulation of BSN cleavage by XerD and a concomitant deficiency in the resolution of chromosomal dimers at dif in vivo, although other XerD functions are not affected.
Imaging OmpR localization in Escherichia coli
Authors: Batchelor Eric , Goulian Mark
Published: January 2006

We have used a fusion of GFP to the response regulator OmpR to image the spatial distribution of OmpR in live cells of Escherichia coli. We observed foci of increased OmpR–GFP fluorescence that appear to be due to interactions with the histidine kinase EnvZ. We also observed colocalization of OmpR–GFP with clusters of plasmids carrying OmpR binding sites, which enabled us to develop a simple method for imaging the binding of OmpR to DNA in live cells. We used the peak fluorescence intensity within cells to quantify the extent of OmpR–GFP localization either due to interactions with EnvZ or due to binding DNA. With these assays we compared the effects of osmolarity and procaine, both of which are believed to modulate EnvZ activity. Our results suggest that, at least under our growth conditions, procaine activates EnvZ–OmpR signalling whereas osmolarity has, at best, a weak effect on the EnvZ–OmpR system.
Organic anion exudation by ectomycorrhizal fungi and Pinus sylvestris in response to nutrient deficiencies
Authors: Van Schöll Laura , Hoffland Ellis , Van Breemen Nico
Published: January 2006

Low molecular weight organic anions (LMWOA) can enhance weathering of mineral grains. We tested the hypothesis that ectomycorrhizal (EcM) fungi and tree seedlings increase their exudation of LMWOA when supply of magnesium, potassium and phosphorus is low to enhance the mobilization of Mg, K and P from mineral grains.

Ectomycorrhizal fungi and Pinus sylvestris seedlings were cultured in symbiosis and in isolation on glass beads with nutrient solution or with sand as a rooting medium, with a complete nutrient supply or with Mg, K, P or N in low supply. Concentrations of all dicarboxylic LMWOA in the rooting medium were measured.

Nonmycorrhizal seedlings released predominantly malonate. Colonization with Hebeloma longicaudum decreased the amount of organic anions exuded, whereas Paxillus involutus and Piloderma croceum increased the concentration of oxalate but not the total amount of LMWOA. Phosphorus deficiency increased the concentration of LMWOA by nonmycorrhizal and EcM seedlings. Magnesium deficiency increased the concentration of oxalate by nonmycorrhizal and EcM seedlings, but not the concentration of total LMWOA. Paxillus involutus grown in pure culture responded differently to low nutrient supply compared with symbiotic growth.

Ectomycorrhizal fungi did not increase the total concentration of LMWOA compared with nonmycorrhizal seedlings but, depending on the fungal species, they affected the type of LMWOA found.
Influencing consumer purchase likelihood of organic food
Authors: Gifford Katie , Bernard John C.
Published: January 2006

Organic food is a fast‐growing niche market in the US. Information in the marketplace tends to promote organic by describing either the potential benefits from organic methods (positive framing) or the potential negative consequences of conventional agriculture (negative framing). For this research, a survey was designed to test the effect of positive and negative framing on the self‐reported change in purchase likelihood of organic food. Respondents were asked to directly evaluate whether the information in the survey made them more or less likely to purchase organic food, or if there was no change. Over 40% of the respondents reported greater likelihood of purchasing organic as a result of the survey information, and less than 4% said they would be less likely to buy it. Tobit regression results revealed that positive framing and perceived risk from conventional agricultural methods increased the influence of the survey. African‐Americans and those with more prior knowledge of organic methods reported less influence from the survey. Overall, information and knowledge variables had more effect on the impact of the survey than demographic variables.
The positive allosteric modulator GS39783 enhances GABAB receptor‐mediated inhibition of cyclic AMP formation in rat striatum in vivo
Authors: Gjoni Tina , Desrayaud Sandrine , Imobersteg Stefan , Urwyler Stephan
Published: January 2006

We studied the effects of the positive allosteric modulator GS39783 on GABAB receptors at a biochemical level in vivo. Changes in extracellular levels of cyclic AMP following GABAB receptor activation were monitored in the striatum of freely moving rats using microdialysis. Locally applied GABAB agonist R(–)‐baclofen inhibited cyclic AMP formation stimulated by a water‐soluble forskolin analogue in a concentration‐dependent manner (EC50 7.3 µm, maximal inhibition 40%). The selective GABAB antagonist CGP56999 reversed R(–)‐baclofen‐induced cyclic AMP inhibition to control levels, but not higher. Orally applied GS39783 lacked effects on its own but, together with a threshold concentration of R(–)‐baclofen (1 µm), significantly decreased cyclic AMP formation in a dose‐dependent fashion. Effects of GS39783 were revoked with CGP56999, showing dependence on GABAB receptor activation and suggesting allosteric modulation as a mechanism of action in vivo. Administered with a maximally active dose of R(–)‐baclofen, GS39783 failed to further inhibit cyclic AMP formation. The data obtained with CGP56999 and the lack of effect of GS39783 alone suggest that there is no detectable endogenous activation of GABAB receptors controlling cyclic AMP formation in rat striatum. To our knowledge, these results provide the first biochemical demonstration of in vivo activity of a G protein‐coupled receptor‐positive allosteric modulator.
Homocysteine‐induced endoplasmic reticulum protein (Herp) is up‐regulated in sporadic inclusion‐body myositis and in endoplasmic reticulum stress‐induced cultured human muscle fibers
Authors: Nogalska Anna , Engel W. King , McFerrin Janis , Kokame Koichi , Komano Hiroto , Askanas Valerie
Published: January 2006

Herp is a stress‐response protein localized in the endoplasmic reticulum (ER) membrane. Herp was proposed to improve ER‐folding, decrease ER protein load, and participate in ER‐associated degradation (ERAD). Intra‐muscle‐fiber ubiquitinated multiprotein‐aggregates containing, among other proteins, either amyloid‐β (Aβ) or phosphorylated tau are characteristic of sporadic inclusion‐body myositis (s‐IBM). ER stress and proteasome inhibition appear to play a role in s‐IBM pathogenesis. We have now studied Herp in s‐IBM muscle fibers and in ER‐stress‐induced or proteasome‐inhibited cultured human muscle fibers. In s‐IBM muscle fibers: (i) Herp was strongly immunoreactive in the form of aggregates, which co‐localized with Aβ, GRP78, and β2 proteasome subunit; (ii) Herp mRNA and protein were increased. In ER‐stress‐induced cultured human muscle fibers: (i) Herp immunoreactivity was diffusely increased; (ii) Herp mRNA and protein were increased. In proteasome‐inhibited cultured human muscle fibers: (i) Herp immunoreactivity was in the form of aggregates; (ii) Herp protein was increased, but its mRNA was not. Accordingly, in s‐IBM muscle fibers: (i) increase of Herp might be due to both ER‐stress and proteasome inhibition; (ii) co‐localization of Herp with Aβ, proteasome, and ER‐chaperone GRP78 could reflect its possible role in processing and degradation of cytotoxic proteins in ER.
INTANGIBLE ASSETS, BOOK‐TO‐MARKET, AND COMMON STOCK RETURNS
Authors: Nelson James M.
Published: January 2006

I examine two anomalies where the Fama and French three‐factor model fails to adequately explain monthly industry and index returns. Both anomalies are consistent with a bad model problem where the book‐to‐market factor introduces a negative bias in the intercepts. I propose the intangibles model as an alternative where the three‐factor model is known to have difficulty. This alternative model, which replaces the book‐to‐market factor with zero investment portfolio returns based on prior investments in intangible assets, is well specified in random samples, has comparable power, and fully explains both anomalies.
SECURITIES PRICE EFFECTS OF UNIONIZATION LEGISLATION
Authors: Naiker Vic , Navissi Farshid
Published: January 2006

Prior studies document that firms experience negative stock price effects in response to unionization. We study the economic effects of a radical change in unionization legislation in New Zealand and hypothesize that the stock price effect of unionization is a function of prior unionization status of firms. We provide evidence that legislative events that increase the likelihood of introducing more stringent legislation do not affect stock prices of high‐unionized firms, whereas low‐unionized firms are affected negatively and significantly. Legislative events that signal less stringent unionization legislation result in significant stock price increases for all firms.
Multidrug resistance 1 genotype and disposition of budesonide in early primary biliary cirrhosis
Authors: Dilger Karin , Cascorbi Ingolf , Grünhage Frank , Hohenester Simon , Sauerbruch Tilman , Beuers Ulrich
Published: January 2006

Abstract: Background: Budesonide, which is a dual substrate of P‐glycoprotein, the product of the multidrug resistance 1 (MDR1) gene, and cytochrome P450 3A (CYP3A) has been proposed for treatment of early primary biliary cirrhosis (PBC). Recently, MDR1 gene polymorphisms have been discussed as a potential cause of glucocorticoid resistance. We tested the hypothesis that MDR1 gene polymorphisms affect absorption of oral budesonide.

Methods: In 21 patients with histologically proven early‐stage (I/II) PBC and nine healthy subjects, we evaluated the impact of MDR1 single nucleotide polymorphisms (2677G>T,A and 3435C>T) on disposition of a single oral dose of 3 mg budesonide. CYP3A5 gene polymorphisms (6986A>G) were analyzed in parallel.

Results: In MDR1 2677 GG and 3435 CC genotypes, absorption and elimination of budesonide were not significantly different from those in corresponding homozygous variants. Peak plasma levels and areas under the plasma concentration time curves (AUC) of budesonide were not lower in MDR1 3435 CC with putatively high intestinal expression of P‐glycoprotein than in MDR1 3435 TT. Interestingly, in two CYP3A5*1/*3 carriers with high enzyme activity, lower AUC was noted than in 28 CYP3A5*3/*3 carriers with a deficient enzyme.

Conclusion: Common MDR1 gene polymorphisms do not affect disposition of budesonide in early PBC.
Adnexal masses in pregnancy: A 5‐year review
Authors: KUMARI Ibha , KAUR Shanujeet , MOHAN Harsh , HURIA Anju
Published: January 2006

A retrospective analysis of all pregnant women who had an adnexal mass surgically resected at the Government Medical College and Hospital, Chandigarh, over a 5‐year period found an incidence of 20 in 16 260 deliveries during the study period. The most frequent complication was torsion (25% of the cases) and the majority of cases occurred in the first trimester of pregnancy. Two of the women had malignant ovarian tumours. There was no difference in gestational age at delivery or birth weight in patients undergoing emergency surgery versus elective surgery.
Self‐Perceived Gender Typicality and the Peer Context During Adolescence
Authors: Smith Tara E. , Leaper Campbell
Published: January 2006

This research examined adolescents' gender identity in relation to the peer context and their self‐concept. Participants were 229 adolescents who completed questionnaire measures of self‐concept and multidimensional gender identity. Regression analysis indicated peer acceptance partially mediated the relation between self‐perceived gender typicality and self‐worth. Cluster analysis revealed four groups of adolescents with differing profiles of self‐perceived gender typicality, felt peer pressure for gender conformity, and peer acceptance. Findings highlight the inherently social and contextual nature of gender identity. Also, the pathologizing of gender‐nonconforming youth is discussed.
The Dynamics of Incrementalism: Subsystems, Politics, and Public Lands
Authors: Wood Robert S.
Published: January 2006

A host of research has been produced in the decade since Baumgartner and Jones’ theory of punctuated equilibrium first drew attention to the dynamics of policy change over time. Much of this research follows a topic across time, highlighting the shift from negative to positive feedback as challengers push an issue from subsystem to institutional level. Far less attention has been paid to the periods between major punctuations, neglecting key questions about whether incremental periods reflect an absence of challengers or the successful defense of established subsystem interests.

This research is a comparison of policy change across two segments of environmental policy. The breakup of the timber subsystem was a clear victory for environmentalists, yet these same actors have been largely unsuccessful at dislodging established grazing interests. These findings highlight the strategic value of venue shifting for bypassing entrenched interests and illustrate the potential for successful challenges to occur in judicial venues.
Andalucia (n. gen.)—the Deepest Branch Within Jakobids (Jakobida; Excavata), Based on Morphological and Molecular Study of a New Flagellate from Soil
Authors: LARA ENRIQUE , CHATZINOTAS ANTONIS , SIMPSON ALASTAIR G. B.
Published: January 2006

ABSTRACT. A new heterotrophic flagellate (Andalucia godoyi n. gen. n. sp.) is described from soil. Earlier preliminary 18S rRNA analyses had indicated a relationship with the phylogenetically difficult‐to‐place jakobid Jakoba incarcerata. Andalucia godoyi is a small (3–5 μm) biflagellated cell with a ventral feeding groove. It has tubular mitochondrial cristae. There are two major microtubular roots (R1, R2) and a singlet root associated with basal body 1 (posterior). The microtubular root R1 is associated with non‐microtubular fibres “I,”“B,” and “A,” and divides in two parts, while R2 is associated with a “C” fibre. These structures support the anterior portion of the groove. Several features of A. godoyi are characteristic of jakobids: (i) there is a single dorsal vane on flagellum 2; (ii) the C fibre has the jakobid multilaminate substructure; (iii) the dorsal fan of microtubules originates in very close association with basal body 2; and (iv) there is no “R4” microtubular root associated with basal body 2. Morphological analyses incorporating the A. godoyi data strongly support the monophyly of all jakobids. Our 18S rRNA phylogenies place A. godoyi and J. incarcerata as a strong clade, which falls separately from other jakobids. Statistical tests do not reject jakobid monophyly, but a specific relationship between Jakoba libera and J. incarcerata and/or A. godoyi is rejected. Therefore, we have established a new genus Andalucia n. gen. with the type species Andalucia godoyi n. sp., and transfer Jakoba incarcerata to Andalucia as Andalucia incarcerata n. comb.
Generic normalization method for real‐time PCR
Authors: Argyropoulos Dimitris , Psallida Charoula , Spyropoulos Caroline G.
Published: January 2006

A generic sample normalization method applicable in relative comparison of mRNAs quantified with real‐time polymerase chain reaction (PCR) is proposed. The method was applied in samples obtained from tomato seeds after osmopriming and aging treatments and from untreated seeds at early imbibition stage, when seeds had not completed germination. Normalization in sample variations was accomplished by detecting synthetic DNA sequences tailing cDNA after second strand reverse transcription synthesis, while the use of the common normalizer GAPDH proved unreliable. Results, obtained from the new method and having a standard error less than 10%, verified the expression profile of a germination‐specific mannanase gene that was closely recorded at different time intervals in relation to seed germination.
Role of the Extended α4 Domain of
Staphylococcus aureus
Gyrase A Protein in Determining Low Sensitivity to Quinolones
Authors: Strahilevitz Jacob , Robicsek Ari , Hooper David C.
Published: January 2006

Fluoroquinolones target two bacterial type II topoisomerases, DNA gyrase and topoisomerase IV. Acquired resistance to quinolones occurs stepwise, with the first mutation occurring in the more sensitive target enzyme. To limit the emergence of resistance, quinolones should ideally possess dual activities against the two enzymes. For reasons that are as yet unclear,
Staphylococcus aureus
gyrase is less sensitive to quinolones than topoisomerase IV, counter to its greater sensitivity in
Escherichia coli
, thereby limiting the use of quinolones for the treatment of staphylococcal infections. Mutations in the α4-helix domain of the GyrA subunit of gyrase are important in determining quinolone resistance. We replaced an extended region encompassing the α4 domain in the
E. coli
GyrA protein with its homolog in
S. aureus
and tested for its ability to complement a thermosensitive gyrase and its catalytic and noncatalytic properties. Purified gyrase reconstituted with chimeric GyrA was more resistant to ciprofloxacin than wild-type gyrase at both inhibition of catalytic activity and stimulation of cleavage complexes, and this difference was more apparent in the presence of K
+
-glutamate. The chimeric GyrA subunit was able to complement thermosensitive gyrase, similar to wild-type GyrA. Without supplemental K
+
-glutamate the MICs of ciprofloxacin for thermosensitive
E. coli
complemented with chimeric DNA gyrase were equal to those for
E. coli
complemented with wild-type gyrase but were twofold higher in the presence of K
+
-glutamate. Our findings suggest that the extended α4 domain of
S. aureus
GyrA is responsible, at least in part, for the increased resistance of
S. aureus
gyrase to quinolones and that this effect is modulated by K
+
-glutamate.
Emergence of DHA-1-Producing
Klebsiella
spp. in the Parisian Region: Genetic Organization of the
ampC
and
ampR
Genes Originating from
Morganella morganii
Authors: Verdet Charlotte , Benzerara Yahia , Gautier Valérie , Adam Olivier , Ould-Hocine Zahia , Arlet Guillaume
Published: January 2006

Eleven
Klebsiella pneumoniae
clinical isolates and one
Klebsiella oxytoca
clinical isolate showing various pulsed-field gel electrophoresis types and producing an inducible DHA-1 class C β-lactamase were isolated in the Parisian region between 1998 and 2003. The aim of this study was to compare the genetic organization of the
bla
DHA-1
genes in this collection of clinical isolates. In four isolates, the
Morganella morganii
-derived genomic region containing
bla
DHA-1
was inserted in an entire complex
sul1
-type integron, including a region common to In6-In7 (CR1), as previously described in a
bla
DHA-1
-producing
Salmonella enterica
serovar Enteritidis KF92 isolate from Saudi Arabia in 1992. Different gene cassette arrays were characterized in each of these integrons. In two of them, an additional 10-kb fragment was inserted between the CR1 and the
M. morganii
-derived region and was similar to the
sap
(ABC transporter family) and
psp
(phage shock protein) operons originated from
Salmonella enterica
serovar Typhimurium. The length of the
M. morganii
region was variable, suggesting that several independent recombination events have occurred and that open reading frame
orf513
encodes a recombinase involved in the mobilization of the resistance genes. The genetic organization of
bla
DHA-1
was identical in the eight other isolates. This structure is likely derived from a complex integron following the insertion of IS
26
, leading to the deletion of the first part of integron. The horizontal transfer of one plasmid carrying that truncated integron was shown for seven of these isolates.
Linezolid in Prophylaxis against Experimental Aortic Valve Endocarditis Due to
Streptococcus oralis
or
Enterococcus faecalis
Authors: Athanassopoulos George , Pefanis Angelos , Sakka Vissaria , Iliopoulos Dimitrios , Perrea Despina , Giamarellou Helen
Published: January 2006

There are no experimental studies regarding the prophylactic efficacy of linezolid against infective endocarditis. Nonbacterial thrombotic endocarditis of the aortic valve was induced in rabbits by the insertion of a polyethylene catheter. Twenty-four hours later, animals were randomly assigned to a control group, and groups receiving either ampicillin (two doses of 40 mg/kg of body weight each, given intravenously, 2 h apart) or linezolid (a single per os dose of 75 mg/kg). The first dose of ampicillin and the single dose of linezolid were administered 0.5 and 1 h, respectively, prior to the intravenous inoculation of ∼10
7
CFU of
Streptococcus oralis
or
Enterococcus faecalis
. Linezolid peak levels in rabbit serum were similar to the peak serum levels in humans following a 600-mg oral dose of linezolid. Linezolid prevented endocarditis in 87% of
S. oralis
-challenged rabbits (
P
< 0.001 versus controls;
P
= 0.026 versus ampicillin). In rabbits challenged with
E. faecalis
, linezolid prevented endocarditis in 73% (
P
= 0.003 versus controls;
P
= 0.049 versus ampicillin). Ampicillin prevented endocarditis due to
S. oralis
or due to
E. faecalis
in 47% (
P
= 0.005 versus controls) and in 30% (
P
= not significant versus controls) of the challenged animals, respectively. In conclusion, linezolid was effective as prophylaxis against endocarditis caused by a strain of
S. oralis
and to a lesser degree against that caused by a strain of
E. faecalis
. Its prophylactic efficacy was superior to that of ampicillin.
Efficacy of Quinolones against Secondary Pneumococcal Pneumonia after Influenza Virus Infection in Mice
Authors: Hayashi Katsuhiko , Kadowaki Shin-etsu , Takei Masaya , Fukuda Hideyuki
Published: January 2006

We established a mouse model of secondary pneumococcal pneumonia after influenza virus infection and investigated the efficacy of several quinolones against pneumonia in this model. Gatifloxacin exhibited the highest efficacy among the quinolones examined and is probably useful for the treatment of secondary bacterial pneumonia.
Potentiation of Catechin Gallate-Mediated Sensitization of
Staphylococcus aureus
to Oxacillin by Nongalloylated Catechins
Authors: Stapleton Paul D. , Shah Saroj , Hara Yukihiko , Taylor Peter W.
Published: January 2006

(−)−Epicatechin gallate (ECg) and (−)−epigallocatechin gallate (EGCg) reduce oxacillin resistance in
mecA
-containing strains of
Staphylococcus aureus
. Their binding to staphylococcal cells is enhanced by the nongalloyl analogues (−)−epicatechin (EC) and (−)−epigallocatechin (EGC). EC and EGC significantly increased the capacity of ECg and EGCg to reduce levels of staphylococcal oxacillin resistance.
In117, an Unusual In0-Like Class 1 Integron Containing CR1 and
bla
CTX-M-2
and Associated with a Tn
21
-Like Element
Authors: Valverde Aránzazu , Cantón Rafael , Galán Juan Carlos , Nordmann Patrice , Baquero Fernando , Coque Teresa M.
Published: January 2006

An unusual In0-like class 1 integron containing a common region that includes the putative recombinase gene named orf513 (CR1) and
bla
CTX-M-2
was characterized from
Escherichia coli
. The integron contained an unusual gene cassette array,
estX-aadA1
, embedded between the 5′-conserved segment (5′-CS) and 3′-CS1 regions and was flanked by
mer
-Tn
21
sequences downstream of the
tni
truncated module. This element constitutes one of the few examples of CR1-bearing class 1 integrons that has been fully characterized.
Trematocidal Activity of Praziquantel and Artemisinin Derivatives: In Vitro and In Vivo Investigations with Adult
Echinostoma caproni
Authors: Keiser Jennifer , Brun Reto , Fried Bernard , Utzinger Jürg
Published: January 2006

We examined the effects of praziquantel and the artemisinins on adult
Echinostoma caproni
. In vitro, both praziquantel and the artemisinins exhibited exposure-response relationships. In vivo, worm burden reductions of 100% were achieved with single oral doses of praziquantel, artesunate, and artemether at 50, 700, and 1,100 mg/kg of body weight, respectively.
In Vitro Bactericidal Activity of Human β-Defensin 3 against Multidrug-Resistant Nosocomial Strains
Authors: Maisetta Giuseppantonio , Batoni Giovanna , Esin Semih , Florio Walter , Bottai Daria , Favilli Flavia , Campa Mario
Published: January 2006

The antimicrobial activity of human β-defensin 3 (hBD-3) against multidrug-resistant clinical isolates of
Staphylococcus aureus
,
Enterococcus faecium
,
Pseudomonas aeruginosa
,
Stenotrophomonas maltophilia
, and
Acinetobacter baumannii
was evaluated. A fast bactericidal effect (within 20 min) against all bacterial strains tested was observed. The presence of 20% human serum abolished the bactericidal activity of hBD-3 against gram-negative strains and reduced the activity of the peptide against gram-positive strains.
Pulsatile Delivery of Clarithromycin Alone or in Combination with Amoxicillin against
Streptococcus pneumoniae
Authors: Leuthner Kimberly D. , Cheung Chrissy M. , Rybak Michael J.
Published: January 2006

We evaluated pulsatile dosing of clarithromycin and amoxicillin alone or combined against
Streptococcus pneumoniae
with various susceptibilities. When combined, pulsatile amoxicillin with clarithromycin was superior to either 8- or 12-h dosing against the intermediate strain and was identical for the susceptible strain. Pulse dosing of antimicrobials warrants further investigation.
Streptococcus pyogenes
Isolates with High-Level Macrolide Resistance and Reduced Susceptibility to Telithromycin Associated with 23S rRNA Mutations
Authors: Farrell David J. , Shackcloth Jemma , Barbadora Karen A. , Green Michael D.
Published: January 2006

Seven high-level macrolide-resistant
Streptococcus pyogenes
isolates had reduced activity to telithromycin but were negative for methylation and efflux genes. All were of the constitutive phenotype, were clonally related (
emm
type 12 and MLST type 36), and had identical dual mutations (A2058G and U2166C) in domain V of 23S rRNA.
Levels of toxins in oral tobacco products in the UK: Table 1
Authors: McNeill A , Bedi R , Islam S , Alkhatib M N , West R
Published: January 2006

Objective:This study examined the constituents of smokeless tobacco products available in the UK and compared them with products available in India, Sweden, and the USA

Methods:Seven UK brands of smokeless tobacco, including a tooth cleaning powder, and four international brands of smokeless tobacco were tested for a range of toxins and known carcinogens, such as tobacco specific N-nitrosamines (TSNA), as well as nicotine availability.

Results:Ten of the 11 brands tested had detectable levels of tobacco specific nitrosamines, which are proven carcinogens, and levels varied 130-fold. All had detectable levels of benzo(a)pyrene, another proven carcinogen (with around 175-fold variation) and several toxic metals (with nearly 150-fold variation). Nicotine availability varied in the UK products from 0.1 mg/g to 63.2 mg/g. All the tobacco products tested are likely to be hazardous to users’ health, but the data indicate that it should be possible to reduce key toxins to non-detectable levels.

Conclusions:Smokeless tobacco products should be regulated and standards set for maximum levels of toxins and carcinogens.
CARRIER MOBILITY IN A SEMICONDUCTOR QUANTUM WELL WIRE–EFFECTS OF EXTERNAL PERTURBATIONS
Authors: REKHA B. , NAVANEETHAKRISHNAN K.
Published: January 2006

Carrier mobility in a narrow GaAs semiconductor quantum well wire embedded in the GaAlAs matrix is investigated using a simple model developed by Lee and Spector. Five different screening functions with three different impurity distributions are used in the calculations. The results show that (i) the choice of the screening function is important as the mobility values vary by two orders of magnitude, and (ii) the mobility values not only depend on the impurity distribution but also vary differently with the wire radius. While hydrostatic pressure reduces the mobility values, temperature increases the values. The polaronic effect decreases the mobility values irrespective of temperature and pressure, the maximum contribution being 9%.
THE BOSTON ROUTE 128 MODEL OF HIGH-TECH INDUSTRY DEVELOPMENT
Authors: WONGLIMPIYARAT JARUNEE
Published: January 2006

This study applies the concept of industrial clusters to explain the development of technologically sophisticated region of Boston Route 128. It is argued that the success of Boston, Massachusetts, is rooted in innovation, entrepreneurial management and the policy towards technology commercialisation. To consider the argument, the paper proposes the cluster model to capture the specific features of Boston Route 128. It represents a model of the universities working with industries to form a cluster of high-technology-based firms. The venture capital accelerates the process of technology commercialisation, giving rise to a new Boston model of innovation management. Policy makers may use the Boston model as a benchmark to evaluate their performance in supporting high-tech industries.
Control of Alignment Regularity and Density of Nanodots by Changing Concentration and Molecular Weight of Self-Assembling Diblock Copolymer
Authors: Matsuyama Tsuyoshi , Kawata Yoshimasa
Published: January 2006

We show that nanodots can be regularly aligned on a glass substrate using poly(styrene)-block-poly(2-vinylpyridine) (PS-P2VP) for application in high-density optical media. The alignment regularity and density of the nanodots are determined using the PS-P2VP concentration in solution and the PS-P2VP molecular weight. By optimizing the PS-P2VP concentration in toluene, a distance of 61 nm ±8.8% between the nanodots and a data density of 0.20 Tbits/in.2 are achieved with a molecular weight of 57,500–57,000. With a molecular weight of 25,500–23,500, we demonstrate a dot interval of 46 nm while keeping similar standard deviation and a data density of 0.35 Tbits/in.2.