bluuebunny/crossref_metadata_2025 huggingface dataset:
Corrosion resistance of titanium ion implanted AZ91 magnesium alloy
Authors: Liu Chenglong , Xin Yunchang , Tian Xiubo , Zhao J. , Chu Paul K.
Published: May 2007

Degradable metal alloys constitute a new class of materials for load-bearing biomedical implants. Owing to their good mechanical properties and biocompatibility, magnesium alloys are promising in degradable prosthetic implants. The objective of this study is to improve the corrosion behavior of surgical AZ91 magnesium alloy by titanium ion implantation. The surface characteristics of the ion implanted layer in the magnesium alloys are examined. The authors’ results disclose that an intermixed layer is produced and the surface oxidized films are mainly composed of titanium oxide with a lesser amount of magnesium oxide. X-ray photoelectron spectroscopy reveals that the oxide has three layers. The outer layer which is 10nm thick is mainly composed of MgO and TiO2 with some Mg(OH)2. The middle layer that is 50nm thick comprises predominantly TiO2 and MgO with minor contributions from MgAl2O4 and TiO. The third layer from the surface is rich in metallic Mg, Ti, Al, and Ti3Al. The effects of Ti ion implantation on the corrosion resistance and electrochemical behavior of the magnesium alloys are investigated in simulated body fluids at 37±1°C using electrochemical impedance spectroscopy and open circuit potential techniques. Compared to the unimplanted AZ91 alloy, titanium ion implantation significantly shifts the open circuit potential (OCP) to a more positive potential and improves the corrosion resistance at OCP. This phenomenon can be ascribed to the more compact surface oxide film, enhanced reoxidation on the implanted surface, as well as the increased β-Mg12Al17 phase.
Cytoplasmic-Membrane Anchoring of a Class A β-Lactamase and Its Capacity in Manifesting Antibiotic Resistance
Authors: Suvorov Maxim , Vakulenko Sergei B. , Mobashery Shahriar
Published: May 2007

Bacterial β-lactamases are the major causes of resistance to β-lactam antibiotics. Three classes of these enzymes are believed to have evolved from ancestral penicillin-binding proteins (PBPs), enzymes responsible for bacterial cell wall biosynthesis. Both β-lactamases and PBPs are able to efficiently form acyl-enzyme species with β-lactam antibiotics. In contrast to β-lactamases, PBPs are unable to efficiently turn over antibiotics and therefore are susceptible to inhibition by β-lactam compounds. Although both PBPs and gram-negative β-lactamases operate in the periplasm, PBPs are anchored to the cytoplasmic membrane, but β-lactamases are not. It is believed that β-lactamases shed the membrane anchor in the course of evolution. The significance of this event remains unclear. In an attempt to demonstrate any potential influence of the membrane anchor on the overall biological consequences of β-lactamases, we fused the TEM-1 β-lactamase to the C-terminal membrane-anchor of penicillin-binding protein 5 (PBP5) of
Escherichia coli
. The enzyme was shown to express well in
E. coli
and was anchored to the cytoplasmic membrane. Expression of the anchored enzyme did not result in any changes in antibiotic resistance pattern of bacteria or growth rates. However, in the process of longer coincubation, the organism that harbored the plasmid for the anchored TEM-1 β-lactamase lost out to the organism transformed by the plasmid for the nonanchored enzyme over a period of 8 days of continuous growth. The effect would appear to be selection of a variant that eliminates the problematic protein through elimination of the plasmid that encodes it and not structural or catalytic effects at the protein level. It is conceivable that an evolutionary outcome could be the shedding of the sequence for the membrane anchor or alternatively evolution of these enzymes from nonanchored progenitors.
Efficacy of a Novel Rifamycin Derivative, ABI-0043, against
Staphylococcus aureus
in an Experimental Model of Foreign-Body Infection
Authors: Trampuz Andrej , Murphy Christopher K. , Rothstein David M. , Widmer Andreas F. , Landmann Regine , Zimmerli Werner
Published: May 2007

We compared the efficacy of a novel rifamycin derivative, ABI-0043, with that of rifampin, alone and in combination with levofloxacin, against methicillin-susceptible
Staphylococcus aureus
ATCC 29213 in a guinea pig tissue-cage infection model. The MIC, logarithmic-growth-phase minimal bactericidal concentration, and stationary-growth-phase minimal bactericidal concentration of ABI-0043 were 0.001, 0.008, and 0.25 μg/ml, respectively; the corresponding concentrations of rifampin were 0.016, 0.8, and 3.6 μg/ml, respectively. After a single intraperitoneal dose of 12.5 mg/kg of body weight, the peak concentration in cage fluid was 1.13 μg/ml of ABI-0043 and 0.98 μg/ml of rifampin. Five days after completion of treatment, levofloxacin administered alone (5 mg/kg/12 h) resulted in bacterial counts in cage fluid that were similar to those for untreated controls (>8.0 log
10
CFU/ml), whereas rifampin and ABI-0043 administered alone (12.5 mg/kg/12 h) decreased the mean titers of bacteria ± standard deviations to 1.43 ± 0.28 log
10
and 1.57 ± 0.53 log
10
CFU/ml, respectively, in cage fluid. In combination with levofloxacin, both rifamycins cleared bacteria from the cage fluid. The cure rates of cage-associated infections with rifampin and ABI-0043 administered alone were 46% and 58%, respectively, and increased to 88% and 92% in combination with levofloxacin. Emergence of rifamycin resistance was observed in 42% of cages after ABI-0043 therapy and in 38% of cages after rifampin therapy; no emergence of resistance occurred with combination treatment with levofloxacin. In conclusion, ABI-0043 had cure rates comparable to that of rifampin. ABI-0043 in combination with a quinolone has the potential for treatment of implant-associated infections caused by susceptible strains of
S. aureus
, potentially without drug-drug interactions.
Dual Targeting of DNA Gyrase and Topoisomerase IV: Target Interactions of Heteroaryl Isothiazolones in
Staphylococcus aureus
Authors: Cheng Jijun , Thanassi Jane A. , Thoma Christy L. , Bradbury Barton J. , Deshpande Milind , Pucci Michael J.
Published: May 2007

Heteroaryl isothiazolones (HITZs) are antibacterial agents that display excellent in vitro activity against
Staphylococcus aureus
. We recently identified a series of these compounds that show potent bactericidal activities against methicillin-resistant
Staphylococcus aureus
(MRSA). We report here the results of in vitro resistance studies that reveal potential underlying mechanisms of action. HITZs selected
gyrA
mutations exclusively in first-step mutants of wild-type
S. aureus
, indicating that in contrast to the case with most quinolones, DNA gyrase is the primary target. The compounds displayed low mutation frequencies (10
−9
to 10
−10
) at concentrations close to the MICs and maintained low MICs (≤0.016 μg/ml) against mutants with single mutations in either
gyrA
or
grlA
(
parC
). These data suggested that HITZs possess significant inhibitory activities against target enzymes, DNA gyrase and topoisomerase IV. This dual-target inhibition was supported by low 50% inhibitory concentrations against topoisomerase IV as measured in a decatenation activity assay and against DNA gyrase as measured in a supercoiling activity assay. Good antibacterial activities (≤1 μg/ml) against staphylococcal
gyrA grlA
double mutants, as well as low frequencies (10
−9
to 10
−10
) of selection of still higher-level mutants, also suggested that HITZs remained active against mutant enzymes. We further demonstrated that HITZs exhibit good inhibition of both
S. aureus
mutant enzymes and thus continue to possess a novel dual-targeting mode of action against these mutant strains. In stepwise acquisition of mutations, HITZs selected quinolone resistance determining region mutations
gyrA
(
Ser84Leu
),
grlA
(
Ser80Phe
),
grlA
(
Ala116Val
), and
gyrA
(
Glu88Lys
) sequentially, suggesting that the corresponding amino acids are key amino acids involved in the binding of HITZs to topoisomerases. The overall profile of these compounds suggests the potential utility of HITZs in combating infections caused by
S. aureus
, including multidrug-resistant MRSA.
Pyrophosphorolytic Excision of Nonobligate Chain Terminators by Hepatitis C Virus NS5B Polymerase
Authors: Deval Jérôme , Powdrill Megan H. , D'Abramo Claudia M. , Cellai Luciano , Götte Matthias
Published: May 2007

Nonobligate chain terminators, such as 2′-C-methylated nucleotides, block RNA synthesis by the RNA-dependent RNA polymerase (RdRp) of hepatitis C virus (HCV). Previous studies with related viral polymerases have shown that classical chain terminators lacking the 3′-hydroxyl group can be excised in the presence of pyrophosphate (PP
i
), which is detrimental to the inhibitory activity of these compounds. Here we demonstrate that the HCV RdRp enzyme is capable of removing both obligate and clinically relevant nonobligate chain terminators. Pyrimidines are more efficiently excised than are purines. The presence of the next complementary templated nucleotide literally blocks the excision of obligate chain terminators through the formation of a dead-end complex (DEC). However, 2′-C-methylated CMP is still cleaved efficiently under these conditions. These findings show that a 2′-methylated primer terminus impedes nucleotide binding. The S282T mutation, associated with resistance to 2′-C-methylated nucleotides, does not affect the excision patterns. Thus, the decreased susceptibility to 2′-C-methylated nucleotides appears to be based solely on improved discrimination between the inhibitor and its natural counterpart. In conclusion, our data suggest that the phosphorolytic excision of nonobligate, pyrimidine-based chain terminators can diminish their potency. The templated nucleotide does not appear to provide protection from excision through DEC formation.
Interaction of the GraRS Two-Component System with the VraFG ABC Transporter To Support Vancomycin-Intermediate Resistance in
Staphylococcus aureus
Authors: Meehl Michael , Herbert Silvia , Götz Friedrich , Cheung Ambrose
Published: May 2007

Current treatment for serious infections caused by methicillin-resistant
Staphylococcus aureus
relies heavily upon the glycopeptide antibiotic vancomycin. Unfortunately, this practice has led to an intermediate resistance phenotype that is particularly difficult to treat in invasive staphylococcal diseases, such as septicemia and its metastatic complications, including endocarditis. Although the vancomycin-intermediate resistance phenotype has been linked to abnormal cell wall structures and autolytic rates, the corresponding genetic changes have not been fully elucidated. Previously, whole-genome array studies listed numerous genes that are overexpressed in vancomycin-intermediate sensitive strains, including
graRS
(SACOL0716 to -0717), encoding a two-component regulatory system (TCRS), as well as the adjacent
vraFG
(SACOL0718 to -0720), encoding an ATP-binding cassette (ABC) transporter; but the exact contribution of these genes to increased vancomycin resistance has not been defined. In this study, we showed that isogenic strains with mutations in genes encoding the GraRS TCRS and the VraFG ABC transporter are hypersensitive to vancomycin as well as polymyxin B. Moreover, GraRS regulates the expression of the adjacent VraFG pump, reminiscent of gram-positive bacteriocin-immunity regulons. Mutations of
graRS
and
vraFG
also led to increased autolytic rates and a more negative net surface charge, which may explain, in part, to their increased sensitivity to cationic antimicrobial peptides. Taken together, these data reveal an important genetic mediator to the vancomycin-intermediate
S. aureus
phenotype and may hold clues to the selective pressures on staphylococci upon exposure to selective cationic peptide antibiotics used in clinical practice.
Lack of an Effect of Antibiotic Treatment on Prolonged Detection of Chlamydial DNA in Murine Genital Tract Infection
Authors: Reeves Dawn M. , Nagarajan Uma , O'Connell Catherine , Andrews Charles W. , Darville Toni
Published: May 2007

Mice treated with antibiotics early or late after active infection had resolved were examined for chlamydial DNA in endocervical swabs. The early eradication of infection limited oviduct pathology, despite the continued detection of chlamydial DNA by nested PCR. Late antibiotic treatment had no effect on the ability to detect DNA or oviduct pathology.
gyrA
and
parC
Mutations and Associated Quinolone Resistance in
Vibrio anguillarum
Serotype O2b Strains Isolated from Farmed Atlantic Cod (
Gadus morhua
) in Norway
Authors: Colquhoun D. J. , Aarflot L. , Melvold C. F.
Published: May 2007

MIC testing of
Vibrio anguillarum
isolates recovered from diseased farmed Atlantic cod revealed oxolinic acid MICs of ≤0.001, 0.06, and 16 μg ml
−1
. Single
gyrA
Ser-Ile substitutions were identified at position 83 of the intermediate and resistant strains, while a
parC
Ser-Leu substitution at position 85 was found only in the resistant strain.
Promoter and Transcription Analysis of Penicillin-Binding Protein Genes in
Streptococcus gordonii
Authors: Haenni Marisa , Moreillon Philippe , Lazarevic Vladimir
Published: May 2007

An optimally cross-linked peptidoglycan requires both transglycosylation and transpeptidation, provided by class A and class B penicillin-binding proteins (PBPs).
Streptococcus gordonii
possesses three class A PBPs (PBPs 1A, 1B, and 2A) and two class B PBPs (PBPs 2B and 2X) that are important for penicillin resistance. High-level resistance (MIC, ≥2 μg/ml) requires mutations in class B PBPs. However, although unmutated, class A PBPs are critical to facilitate resistance development (M. Haenni and P. Moreillon, Antimicrob. Agents Chemother. 50:4053-4061, 2006). Thus, their overexpression might be important to sustain the drug. Here, we determined the promoter regions of the
S. gordonii
PBPs and compared them to those of other streptococci. The extended −10 box was highly conserved and complied with a σ
A
-type promoter consensus sequence. In contrast, the −35 box was poorly conserved, leaving the possibility of differential PBP regulation. Gene expression in a penicillin-susceptible parent (MIC, 0.008 μg/ml) and a high-level-resistant mutant (MIC, 2 μg/ml) was monitored using luciferase fusions. In the absence of penicillin, all PBPs were constitutively expressed, but their expression was globally increased (1.5 to 2 times) in the resistant mutant. In the presence of penicillin, class A PBPs were specifically overexpressed both in the parent (PBP 2A) and in the resistant mutant (PBPs 1A and 2A). By increasing transglycosylation, class A PBPs could promote peptidoglycan stability when transpeptidase is inhibited by penicillin. Since penicillin-related induction of class A PBPs occurred in both susceptible and resistant cells, such a mutation-independent facilitating mechanism could be operative at each step of resistance development.
Role for Cell Density in Antifungal Drug Resistance in
Candida albicans
Biofilms
Authors: Perumal Palani , Mekala Satish , Chaffin W. LaJean
Published: May 2007

Biofilms of
Candida albicans
are less susceptible to many antifungal drugs than are planktonic yeast cells. We investigated the contribution of cell density to biofilm phenotypic resistance. Planktonic yeast cells in RPMI 1640 were susceptible to azole-class drugs, amphotericin B, and caspofungin at 1 × 10
3
cells/ml (standard conditions) using the XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt] assay. As reported by others, as the cell concentration increased to 1 × 10
8
cells/ml, resistance was observed with 10- to 20-fold-greater MICs. Biofilms that formed in microtiter plate wells, like high-density planktonic organisms, were resistant to drugs. When biofilms were resuspended before testing, phenotypic resistance remained, but organisms, when diluted to 1 × 10
3
cells/ml, were susceptible. Drug-containing medium recovered from high-cell-density tests inhibited low-cell-density organisms. A fluconazole-resistant strain showed greater resistance at high planktonic cell density, in biofilm, and in resuspended biofilm than did low-density planktonic or biofilm organisms. A strain lacking drug efflux pumps
CDR1
,
CDR2
, and
MDR1
, while susceptible at a low azole concentration, was resistant at high cell density and in biofilm. A strain lacking
CHK1
that fails to respond to the quorum-sensing molecule farnesol had the same response as did the wild type. FK506, reported to abrogate tolerance to azole drugs at low cell density, had no effect on tolerance at high cell density and in biofilm. These observations suggested that cell density has a role in the phenotypic resistance of biofilm, that neither the drug efflux pumps tested nor quorum sensing through Chk1p contributes to resistance, and that azole drug tolerance at high cell density differs mechanistically from tolerance at low cell density.
Purine Salvage Pathways among
Borrelia
Species
Authors: Pettersson Jonas , Schrumpf Merry E. , Raffel Sandra J. , Porcella Stephen F. , Guyard Cyril , Lawrence Kevin , Gherardini Frank C. , Schwan Tom G.
Published: May 2007

Genome sequencing projects on two relapsing fever spirochetes,
Borrelia hermsii
and
Borrelia turicatae
, revealed differences in genes involved in purine metabolism and salvage compared to those in the Lyme disease spirochete
Borrelia burgdorferi
. The relapsing fever spirochetes contained six open reading frames that are absent from the
B. burgdorferi
genome. These genes included those for hypoxanthine-guanine phosphoribosyltransferase (
hpt
), adenylosuccinate synthase (
purA
), adenylosuccinate lyase (
purB
), auxiliary protein (
nrdI
), the ribonucleotide-diphosphate reductase alpha subunit (
nrdE
), and the ribonucleotide-diphosphate reductase beta subunit (
nrdF
). Southern blot assays with multiple
Borrelia
species and isolates confirmed the presence of these genes in the relapsing fever group of spirochetes but not in
B. burgdorferi
and related species. TaqMan real-time reverse transcription-PCR demonstrated that the chromosomal genes (
hpt
,
purA
, and
purB
) were transcribed in vitro and in mice. Phosphoribosyltransferase assays revealed that, in general,
B. hermsii
exhibited significantly higher activity than did the
B. burgdorferi
cell lysate, and enzymatic activity was observed with adenine, hypoxanthine, and guanine as substrates.
B. burgdorferi
showed low but detectable phosphoribosyltransferase activity with hypoxanthine even though the genome lacks a discernible ortholog to the
hpt
gene in the relapsing fever spirochetes.
B. hermsii
incorporated radiolabeled hypoxanthine into RNA and DNA to a much greater extent than did
B. burgdorferi
. This complete pathway for purine salvage in the relapsing fever spirochetes may contribute, in part, to these spirochetes achieving high cell densities in blood.
Unique Gene Expression Profiles in Infants Vaccinated with Different Strains ofMycobacterium bovisBacille Calmette-Guérin
Authors: Wu Bo , Huang Chunhong , Garcia Lourdes , de Leon Alfredo Ponce , Osornio Jose Sifuentes , Bobadilla-del-Valle Miriam , Ferreira Leticia , Canizales Sergio , Small Peter , Kato-Maeda Midori , Krensky Alan M. , Clayberger Carol
Published: May 2007

Vaccination withMycobacterium bovisbacille Calmette-Guérin (BCG) has variable efficacy in preventing tuberculosis. We hypothesized that some of this variation might be due to differences among BCG strains. To test this, neonates in Orizaba, Mexico, were vaccinated with one of three different BCG strains (BCG-Brazil [BBCG], BCG-Denmark [DBCG], or BCG-Japan [JBCG]). One year after vaccination, peripheral blood mononuclear cells (PBMC) were obtained and recall immune responses to culture filtrate proteins (CFP) ofMycobacterium tuberculosiswere evaluated using quantitative real-time PCR. CFP-activated PBMC from BBCG- and DBCG-immunized children expressed high levels of cytokines characteristic of an adaptive immune response (gamma interferon, interleukin-2β [IL-12β], and IL-27), while those from children immunized with JBCG did not. In contrast, vaccination with JBCG resulted in significantly greater expression of cytokines characteristic of a proinflammatory immune response (IL-1α, IL-1β, IL-6, and IL-24) in PBMC activated with CFP compared to PBMC from children vaccinated with BBCG or DBCG. Thus, different strains of BCG can activate different immune pathways, which may affect long-term vaccine efficacy.
Possible Correlates of Long-Term Protection againstHelicobacter pylorifollowing Systemic or Combinations of Mucosal and Systemic Immunizations
Authors: Taylor Jennifer M. , Ziman Melanie E. , Fong Julie , Solnick Jay V. , Vajdy Michael
Published: May 2007

The ability to induce long-term immunity toHelicobacter pyloriis necessary for an effective vaccine. This study was designed to establish the most efficient route(s) (systemic, mucosal, or a combination) of immunization for induction of long-term immunity and to define correlates of protection. Mice were immunized orally alone (oral group), intramuscularly (i.m.) alone (i.m. group), orally followed by i.m. (oral/i.m. group), or i.m. followed by orally (i.m./oral group). Long-term protective immunity to oralH. pylorichallenge was observed 3 months after immunization through the i.m. or oral/i.m. route. Protection correlated with an increase inH. pylori-specific interleukin-12 and both immunoglobulin G1 (IgG1) and IgG2a serum titers following challenge. Mice that were not protected (oral or i.m./oral) had increased levels of IgA in both sera and Peyer's patches. This study demonstrates the ability to induce long-term immunity againstH. pylori, provides correlates of protection, and illustrates the crucial role of the immunization route(s).
Survival ofChlamydia muridarumwithin Dendritic Cells
Authors: Rey-Ladino Jose , Jiang Xiaozhou , Gabel Brent R. , Shen Caixia , Brunham Robert C.
Published: May 2007

Immune responses toChlamydia trachomatisunderlay both immunity and immunopathology. Immunopathology in turn has been attributed to chronic persistent infection with persistence being defined as the presence of organisms in the absence of replication. We hypothesized that dendritic cells (DCs) play a central role inChlamydiaimmunity and immunopathology by favoring the long-term survival ofC. muridarum. This hypothesis was examined based on (i) direct staining ofChlamydiain infected DCs to evaluate the development of inclusions, (ii) titration of infected DCs on HeLa cells to determine cultivability, and (iii) transfer ofChlamydia-infected DCs to naive mice to evaluate infectivity. The results show thatChlamydiasurvived within DCs and developed both typical and atypical inclusions that persisted in a subpopulation of DCs for more than 9 days after infection. Since the cultivability ofChlamydiafrom DCs onto HeLa was lower than that estimated by the number of inclusions in DCs, this suggests that the organisms may be in state of persistence. Intranasal transfer of long-term infected DCs or DCs purified from the lungs of infected mice caused mouse lung infection, suggesting that in addition to persistent forms, infectiveChlamydiaorganisms also developed within chronically infected DCs. Interestingly, after in vitro infection withChlamydia, most DCs died. However,Chlamydiaappeared to survive in a subpopulation of DCs that resisted infection-induced cell death. Surviving DCs efficiently presentedChlamydiaantigens toChlamydia-specific CD4+T cells, suggesting that the bacteria are able to both direct their own survival and still allow DC antigen-presenting function. Together, these results raise the possibility thatChlamydia-infected DCs may be central to the maintenance of T-cell memory that underlies both immunity and immunopathology.
Differential Stability and Trade-Off Effects of Pathoadaptive Mutations in the
Escherichia coli
FimH Adhesin
Authors: Weissman Scott J. , Beskhlebnaya Viktoriya , Chesnokova Veronika , Chattopadhyay Sujay , Stamm Walter E. , Hooton Thomas M. , Sokurenko Evgeni V.
Published: May 2007

FimH is the tip adhesin of mannose-specific type 1 fimbriae of
Escherichia coli
, which are critical to the pathogenesis of urinary tract infections. Point FimH mutations increasing monomannose (1M)-specific uroepithelial adhesion are commonly found in uropathogenic strains of
E. coli
. Here, we demonstrate the emergence of a mixed population of clonally identical
E. coli
strains in the urine of a patient with acute cystitis, where half of the isolates carried a glycine-to-arginine substitution at position 66 of the mature FimH. The R66 mutation induced an unusually strong 1M-binding phenotype and a 20-fold advantage in mouse bladder colonization. However,
E. coli
strains carrying FimH-R66, but not the parental FimH-G66, had disappeared from the patient's rectal and urine samples collected from 29 to 44 days later, demonstrating within-host instability of the R66 mutation. No FimH variants with R66 were identified in a large (>600 strains) sequence database of
fimH
-positive
E. coli
strains. However, several strains carrying genes encoding FimH with either S66 or C66 mutations appeared to be relatively stable in the
E. coli
population. Relative to FimH-R66, the FimH-S66 and FimH-C66 variants mediated only moderate increases in 1M binding but preserved the ability to enhance binding under flow-induced shear conditions. In contrast, FimH-R66 completely lost shear-enhanced binding properties, with bacterial adhesion being inhibited by shear forces and lacking a rolling mode of binding. These functional trade-offs may determine the natural populational instability of this mutation or other pathoadaptive FimH mutations that confer dramatic increases in 1M binding strength.
Conjugated Polyunsaturated Oxacyclic Carbene Complexes: Synthesis, Structure, and Properties
Authors: Fischer Helmut , Rädler Michael , Mosbacher Alexander , Drexler Matthias , Hübner Eike , Weibert Bernhard , Heck Jürgen , Wittenburg Christian , Steffens Stefan
Published: May 2007

The reaction of [(CO)5M(thf)] with but-3-yn-1-ols in the presence of NEt3 offers a convenient route to 2-oxacyclopentylidene complexes [(CO)5M=C-O-CH2CH2CH2] (M = Cr (1a), W (1b)) in yields up to 96%. Furthermore, the reaction of 1 with ω-(dimethylamino)- substituted enals, Me2N-(CH=CH)n-C(=O)H, activated by Me3SiCl/NEt3 or POCl3/NEt3 gives via aldol condensation the unsaturated oxacyclic push-pull carbene complexes [(CO)5M=C-O-CH2CH2C{=CH-(CH=CH)n-NMe2}] (n = 0 (2), 1 (3), 2 (4), 3 (5)). In 2-5, the amino group acts as an electron-donor unit and the oxacyclic carbene pentacarbonyl moiety as an electron acceptor. The aminometallaenes 2-5 have been characterized spectroscopically, the chromium complexes 2a-5a additionally by X-ray structure analysis. For some complexes, their nonlinear optical properties (second harmonic generation) have been studied and β values up to 58 × 10-30 esu have been determined. The results of DFT calculations on chromium complexes 2a-5a show that on lengthening of the unsaturated chain the influence of the carbonyl-metal fragment on the polyunsaturated chain strongly decreases.
Synthesis and Characterization of Ni(II) and Pd(II) Complexes Bearing Achiral and Chiral Bidentate Aminophosphine Ligands
Authors: Benito-Garagorri David , Mereiter Kurt , Kirchner Karl
Published: May 2007

The synthesis of a range of achiral and chiral bidentate aminophosphine ligands and their complexes with nickel(II) and palladium(II) has been investigated. The ligands and the complexes have been characterized by NMR spectroscopy, and X-ray structures of representative compounds have been determined. In addition, DFT calculations have been performed to investigate different geometries of the nickel(II) complexes in the solid state and in solution.
Commercialization of automated RNA synthesis - Twenty years on
Authors: Zon Gerald
Published: May 2007

Following the introduction of the first successful automated DNA synthesizer by Applied Biosystems Inc. (ABI) in 1983, the company was in a position to consider the commercialization of additional chemistries to enable the automated synthesis of RNA oligonucleotides or other analogs. This retrospective account provides a personal view of how ABI collaborated with Professor Kelvin K. Ogilvie in 1986 to commercialize automated RNA synthesis, using the 2′-O-alkylsilyl-protected monomers that he pioneered. The influence of end-user scientific applications on this decision-making process is highlighted, together with the influence of such applications on subsequent commoditization of RNA. Hopefully, these perspectives will provide chemists with further appreciation of the sometime complex and unpredictable interplay between academically interesting chemistry and evolving scientific applications that influence commercialization, and vice versa.Key words: RNA, synthesis, automated, 2′-O-alkylsilyl phosphoramidite, siRNA.
Synthesis and structure of fluoroindole nucleosides
Authors: Božilović Jelena , Bats Jan W , Engels Joachim W
Published: May 2007

Chemically modified bases are frequently used to stabilize nucleic acids, to study the driving forces for nucleic acid structure formation, and to tune DNA and RNA hybridization conditions. Nucleoside analogues are chemical means to investigate hydrogen bonds, base stacking, and solvation as the three predominant forces that are responsible for the stability of nucleic acids. To obtain deeper insight into the contributions of these interactions to RNA stability, we decided to synthesize some novel nucleic acid analogues where the nucleobases are replaced by fluoroindoles. Fluorinated indoles can be compared with fluorinated benzimidazoles to determine the role of nitrogen in five-membered ring systems. The synthesis of fluoroindole ribonucleosides as well as the X-ray crystal structures of all synthesized fluoroindole ribonucleosides are reported here. These compounds could also be building blocks for a variety of biologically active RNA analogues.Key words: indoles, nucleosides, crystal structure, glycosilation, indole-synthesis.
High-quality oligo-RNA synthesis using the new 2′-O-TEM protecting group by selectively quenching the addition of p-tolyl vinyl sulphone to exocyclic amino functions
Authors: Zhou Chuanzheng , Pathmasiri Wimal , Honcharenko Dmytro , Chatterjee Subhrangsu , Barman Jharna , Chattopadhyaya Jyoti
Published: May 2007

During the F–-promoted deprotection of the oligo–RNA, synthesized using our 2′-O-(4-tolylsulfonyl)ethoxymethyl (2′-O-TEM) group [Org. Biomol. Chem. 5, 333 (2007)], p-tolyl vinyl sulphone (TVS) is formed as a by-product. The TVS formed has been shown to react with the exocyclic amino functions of adenosine (A), guanosine (G), and cytidine (C) of the fully deprotected oligo–RNA to give undesirable adducts, which are then purified by HPLC and unambiguously characterized by 1H, 13C Heteronuclear Multiple Bond Correlation (HMBC) NMR and mass spectroscopic analysis. The relative nucleophilic reactivities of the nucleobases toward TVS have been found to be the following: N6–A > N4–C > N2–G > > N3–U. This reactivity of TVS toward RNA nucleobases to give various Michael adducts could, however, be suppressed by using various amines as scavengers. Among all these amines, morpholine and piperidine are the most efficient scavenger for TVS, which gave highly pure oligo–RNA even in the crude form and can be used directly in RNA chemical biology studies.Key words: RNA synthesis, RNA alkylation, p-tolyl vinyl sulphone, Michael addition.
Topological Aspects of Quantum Hall Effect in Graphene
Authors: Aoki Hideo , Fukui Takahiro , Hatsugai Yasuhiro
Published: May 2007

We study the recently observed quantum Hall effect (QHE) in graphene from a theoretical viewpoint of topological nature of the QHE to pose questions: (i) The zero-mass Dirac dispersion, which is the origin of the anomalous QHE, exists only around the zero gap, so a natural question is what happens to the QHE topological numbers over the entire energy spectrum. (ii) How the property that the bulk QHE topological number is equal to the edge QHE topological number, shown for the ordinary QHE, applies to the honeycomb lattice. We have shown that (a) the anomalous QHE ∝ (2N + 1) persists, surprisingly, all the way up to the van-Hove singularities, at which the normal behaviour abruptly takes over. (b) The edge-bulk correspondence persists as shown from the result for finite systems. All these properties hold for the entire sequence of lattice Hamiltonians that interpolate between square↔honeycomb↔ π-flux lattices, so the anomalous QHE is on a quantum critical line.
SPECTROSCOPIC STUDIES OF SEMICONDUCTOR STRUCTURES IN MAGNETIC FIELDS
Authors: POTEMSKI MAREK
Published: May 2007

The aptitude of magneto-spectroscopic methods for studying the electronic and spin properties of semiconductor structures is demonstrated with a few examples of our recent work on two-dimensional electron gases and semiconductor quantum dots, on bulk GaAs and GaN , as well as on thin graphitic layers.
RANGE-DEPENDENT DISORDER EFFECTS ON THE PLATEAU-WIDTHS CALCULATED WITHIN THE SCREENING THEORY OF THE IQHE
Authors: SIDDIKI AFIF , GERHARDTS ROLF R.
Published: May 2007

We summarize the screening theory of the integer quantized Hall effect (IQHE) and emphasize its two key mechanisms: first, the existence, in certain magnetic field intervals, of incompressible strips, with integer values of the local filling factor and quantized values of longitudinal and Hall resistivity, and second, the confinement of an imposed dissipative current to these strips, leading to the quantization of the global resistances. We demonstrate that, without any localization assumption, this theory explains the enormous experimental reproducibility of the quantized resistance values, as well as experimental results on the potential distribution in narrow Hall bars. We further demonstrate that inclusion of long-range potential fluctuations allows to apply the theory to wider Hall bars, and can lead to a broadening of the quantum Hall plateaus, whereas short-range disorder tends to narrow the plateaus.
ANDERSON-FANO TRANSITIONS IN PHOTOLUMINESCENCE OF A TWO DIMENSIONAL ELECTRON GAS
Authors: BRYJA L. , WÓJS A. , RYCZKO K. , WÓJCIK K. , MISIEWICZ J. , POTEMSKI M. , REUTER D. , WIECK A.
Published: May 2007

The many body interaction are investigated in polarization resolved photoluminescence in the magnetic field up to 23 T. The Fermi edge singularity, Anderson-Fano transition and neutral and negatively charged excitons (trions) are detected in the photoluminescence spectra. The experimental results are supplemented by realistic calculations.
POINT CONTACT SPECTROSCOPY OF MAGNETIC EDGE STATES
Authors: LAMBERT N. J. , NOGARET A. R. , SASSINE S. , PORTAL J. C. , BEERE H. E. , RITCHIE D. A.
Published: May 2007

We report on a novel ballistic electron spectrometer that images the k-space structure of open orbits confined by a magnetic field gradient. Magnetoresistance measurements were performed on a AlGaAs/GaAs/Dy device which supported magnetic edge states. Point contacts were used to ensure the commensurability of edge state period to the length of the waveguide. Periodic oscillations in the non-local magnetoresistance were observed, which we ascribe to the discrete nature of the orbits. A semi-classical model is used to describe the device, and gives good agreement with experimental results.
COMPREHENSIVE STUDY OF SPIN-FLIP EXCITATIONS IN CdZnTe/CdZnMnTe QUANTUM WELLS
Authors: FUKUOKA DAISUKE , ARAHARA KOUSHIRO , KOYAMA TAKAAKI , TANAKA NAOKI , OTO KENICHI , MURO KIYOFUMI , TAKEYAMA SHOJIRO , KARCZEWSKI GREGOSZ , WOJTOWICZ THOMASZ , KOSSUT JACEK
Published: May 2007

Spin-flip excitations in non-doped Cd 0.93 Zn 0.07 Te/Cd 0.48 Zn 0.04 Mn 0.48 Te quantum wells have been comprehensively studied by spin-flip Raman scattering (SFRS) spectroscopy and time-resolved Kerr rotation (TRKR) spectroscopy. In 4 nm quantum well, two spin-flip Raman peaks were observed in addition to the multiple Mn 2+ spin-flip scatterings. The spin-flip energies are isotropic against the magnetic field direction and well described by modified Brillouin functions. Based on the circumstantial analysis, they are assigned to the spin-flip of residual electrons and the electron spin-flip in the localized exciton, respectively, even though the large energy difference between the two electron spin-flip processes is a puzzle. While, in 9 nm quantum well a strange spin-flip excitation was observed together with a very weak Mn 2+ spin-flip scattering. The spin-flip energy changed strangely up to the magnetic field 4T, and then linearly increased with field (| g *|=1.15). A high-resolution TRKR spectroscopy revealed an unusual temperature dependence, which resembled "softening mode" of spin resonance observed in p-doped ferromagnetic CdMnTe quantum wells. However, these behaviors are well understood by an "inverted spin configuration", which results from a negative g*-factor and a very weak s-d interaction between the electrons and the manganese ions in the barrier.
NUCLEAR HYPERPOLARIZATION AND POLARIZATION TRANSFER SYSTEM FOR SEMICONDUCTORS
Authors: GOTO ATSUSHI , HASHI KENJIRO , SHIMIZU TADASHI , OHKI SHINOBU
Published: May 2007

We have been developing a nuclear hyperpolarization and polarization transfer system for semiconductors. It enables successive transfers of polarization (angular momentum) from photons to nuclear spins via photo-excited electrons in semiconductors using laser, microwave and multi-channel radio-frequency fields, resulting in the nuclear hyperpolarization in a target material. A part of the system has been completed and successfully applied to the hyperpolarization and polarization transfer experiments in InP and GaAs . The current status of the system is presented together with some preliminary data.
INTERFERENCE INDUCED MAGNETORESISTANCE BEYOND THE DIFFUSION REGIME IN 2D SYSTEMS WITH SPIN-ORBIT COUPLING
Authors: GERMANENKO A. V. , MINKOV G. M. , RUT O. E. , SHERSTOBITOV A. A.
Published: May 2007

The interference quantum correction to the conductivity and its temperature and magnetic-field dependence with taking into account the spin relaxation processes is investigated. The results of numerical and real physical experiments are reported. We show that the shape of the magnetoresistance is nonuniversal beyond the diffusion regime, when the close trajectories with small number of collisions are of importance. It is sensitive to anisotropy of scattering and correlation of impurity distribution.
SPIN BALLISTIC TRANSPORT AND SPIN CURRENT OSCILLATIONS IN MESOSCOPIC LOOP STRUCTURES
Authors: TRALLE IGOR , PAŚKO WIOLETTA
Published: May 2007

In the paper a theory of quantum interference in a loop structure caused by spin coherent transport and the Larmor precession of the electron spin is presented. The 'spin ballistic' regime is supposed to occur when the phase relaxation length of the spin part of electron wave function is much greater than the phase relaxation length of the 'orbital' part. If magnetic fields in two arms of the structure are different, the spin part of the wave function acquires a phase shift due to spin precession around the field. If the structure length L is chosen to be [Formula: see text], It is possible to 'wash out' the quantum interference related to the phase coherence of the 'orbital part' of the wave function, retaining at the same time that related to the phase coherence of the spin part and to reveal the corresponding conductance oscillations. Different mechanisms of spin relaxation as well as their influence on the spin transport are considered. The quantum interference in the time-dependent magnetic field is also discussed and similarities between this effect and Josephson one, as well as their differences are considered.
OPTIMIZATION AND THE MIRANDA APPROACH IN DETECTING HORSESHOE-TYPE CHAOS BY COMPUTER
Authors: BÁNHELYI BALÁZS , CSENDES TIBOR , GARAY BARNABAS M.
Published: May 2007

We report on experiences with an adaptive subdivision method supported by interval arithmetic that enables us to prove subset relations of the form [Formula: see text], and thus check certain sufficient conditions for chaotic behavior of dynamical systems in a rigorous way.

Our proof of the underlying abstract theorem avoids referring to any results of applied algebraic topology and relies only on the Brouwer fixed point theorem.

The second novelty is that the process of gaining the subset relations to be checked is, to a large extent, also automatized. The promising subset relations come from solving a constrained optimization problem via the penalty function approach.

Abstract results and computational methods are demonstrated by finding embedded copies of the standard horseshoe dynamics in iterates of the classical Hénon mapping.
METHODS FOR QUANTIFYING THE CAUSAL STRUCTURE OF BIVARIATE TIME SERIES
Authors: LUNGARELLA M. , ISHIGURO K. , KUNIYOSHI Y. , OTSU N.
Published: May 2007

In the study of complex systems one of the major concerns is the detection and characterization of causal interdependencies and couplings between different subsystems. The nature of such dependencies is typically not only nonlinear but also asymmetric and thus makes the use of symmetric and linear methods ineffective. Moreover, signals sampled from real world systems are noisy and short, posing additional constraints on the estimation of the underlying couplings. In this article, we compare a set of six recently introduced methods for quantifying the causal structure of bivariate time series extracted from systems with complex dynamical behavior. We discuss the usefulness of the methods for detecting asymmetric couplings and directional flow of information in the context of uni- and bidirectionally coupled deterministic chaotic systems.
A genome-scale map of expression for a mouse brain section obtained using voxelation
Authors: Chin Mark H. , Geng Alex B. , Khan Arshad H. , Qian Wei-Jun , Petyuk Vladislav A. , Boline Jyl , Levy Shawn , Toga Arthur W. , Smith Richard D. , Leahy Richard M. , Smith Desmond J.
Published: May 2007

Gene expression signatures in the mammalian brain hold the key to understanding neural development and neurological diseases. We have reconstructed two-dimensional images of gene expression for 20,000 genes in a coronal slice of the mouse brain at the level of the striatum by using microarrays in combination with voxelation at a resolution of 1 mm3. Good reliability of the microarray results were confirmed using multiple replicates, subsequent quantitative RT-PCR voxelation, mass spectrometry voxelation, and publicly available in situ hybridization data. Known and novel genes were identified with expression patterns localized to defined substructures within the brain. In addition, genes with unexpected patterns were identified, and cluster analysis identified a set of genes with a gradient of dorsal/ventral expression not restricted to known anatomical boundaries. The genome-scale maps of gene expression obtained using voxelation will be a valuable tool for the neuroscience community.
Masquerader: High Mobility Group Box-1 and Cancer
Authors: Ellerman Jessica E. , Brown Charles K. , de Vera Michael , Zeh Herbert J. , Billiar Timothy , Rubartelli Anna , Lotze Michael T.
Published: May 2007

Since its identification a third of a century ago, the high-mobility group box-1 (HMGB1) protein has been linked to varied diverse cellular processes, including release from necrotic cells and secretion by activated macrophages engulfing apoptotic cells. Initially described as solely chromatin-associated, HMGB1 was additionally discovered in the cytoplasm of several types of cultured mammalian cells 6 years later. In addition to its intracellular role, HMGB1 has been identified extracellularly as a putative leaderless cytokine and differentiation factor. In the years since its discovery, HMGB1 has also been implicated in disease states, including Alzheimer's, sepsis, ischemia-reperfusion, arthritis, and cancer. In cancer, overexpression of HMGB1, particularly in conjunction with its receptor for advanced glycation end products, has been associated with the proliferation and metastasis of many tumor types, including breast, colon, melanoma, and others. This review focuses on current knowledge and speculation on the role of HMGB1 in the development of cancer, metastasis, and potential targets for therapy.
Heat Shock Protein 27 Protects L929 Cells from Cisplatin-Induced Apoptosis by Enhancing Akt Activation and Abating Suppression of Thioredoxin Reductase Activity
Authors: Zhang Yong , Shen Xun
Published: May 2007

Purpose: Heat shock protein 27 (Hsp27) is up-regulated in multiple malignancies and implicated in cisplatin resistance. It is attempted to know how Hsp27 endues cell with cisplatin resistance by interfering with upstream of both apoptosis signal–regulating kinase 1 (ASK1)/p38 mitogen-activated protein kinase–activated apoptotic signaling and serine/threonine kinase Akt-dependent survival signaling.

Experimental Design: The mouse L929 cells stably transfected with human Hsp27 or its dominant-negative mutant and the human cervical cancer HeLa cells transfected with Hsp27 siRNA were used. The cisplatin-induced apoptosis and activation of ASK1, p38, and Akt were compared in control cells, cells overexpressing Hsp27, and cells with their endogenous Hsp27 knocked down.

Results: Hsp27 effectively protected the cells from cisplatin-induced DNA fragmentation. The p38 inhibitors obviously decreased whereas Akt inhibitors markedly increased the apoptotic fraction in cisplatin-treated cells. Overexpression of Hsp27 doubly enhanced the drug-induced Akt activation while substantially depressing the drug-induced activation of ASK1 and p38. Knockdown of the endogenous Hsp27 in HeLa cells resulted in the effects opposite to that observed in the Hsp27-overexpressing cells. Enhancement of Akt activation is associated with complex formation between Akt and Hsp27, whereas depression of ASK1/p38 activation is attributed to a reversion of the drug-induced inhibition of thioredoxin reductase activity and subsequent oxidation of thioredoxin.

Conclusions: Hsp27 endues cells with cisplatin resistance via depression of the drug-induced ASK1/p38 activation and enhancement of the drug-induced Akt activation. This study revealed the intervention of Hsp27 in upstream of both ASK1/p38 apoptotic signaling and phosphatidylinositol 3-kinase/Akt survival signaling. Therefore, the inhibition of Hsp27 may be a novel strategy of cancer chemotherapy.
Utility of Osteopontin and Serum Mesothelin in Malignant Pleural Mesothelioma Diagnosis and Prognosis Assessment
Authors: Grigoriu Bogdan-Dragos , Scherpereel Arnaud , Devos Patrick , Chahine Bachar , Letourneux Marc , Lebailly Pierre , Grégoire Marc , Porte Henri , Copin Marie-Christine , Lassalle Philippe
Published: May 2007

Purpose: Malignant mesothelioma is a highly aggressive tumor and is often diagnosed too late for a curative treatment. We compared diagnostic and prognostic values of mesothelin and osteopontin in 172 patients suspected of malignant pleural mesothelioma (MPM) and in a control group of 112 asymptomatic asbestos-exposed subjects.

Experimental Design: Osteopontin and mesothelin were assayed with commercial ELISA kits in a series of 43 patients with pleural metastases of various carcinomas, 33 patients with benign pleural lesions associated with asbestos exposure, 96 patients with MPMs, and 112 asbestos-exposed healthy subjects. Results were correlated with patient's diagnosis and survival.

Results: Serum osteopontin level was higher in MPM patients compared with healthy asbestos-exposed subjects and had a good capability to distinguish between these two populations. However, osteopontin was unable to distinguish between MPM and pleural metastatic carcinoma or benign pleural lesions associated with asbestos exposure. Neither plasma nor pleural fluid osteopontin were more powerful in this respect. Serum mesothelin had a good ability for diagnosing MPM but was unable to identify patients with nonepithelioid mesothelioma subtypes. Survival analysis identified tumor histologic subtype along with serum osteopontin and serum mesothelin as independent prognostic factors in mesothelioma patients.

Conclusions: Osteopontin has a lower diagnostic accuracy than mesothelin in patients suspected of MPM. Insufficient specificity limits osteopontin utility as diagnostic marker. Both molecules have a potential value as prognostic markers.