bluuebunny/crossref_metadata_2025 huggingface dataset:
Klebsiella pneumoniae
OmpA Confers Resistance to Antimicrobial Peptides
Authors: Llobet Enrique , March Catalina , Giménez Paloma , Bengoechea José A.
Published: November 2008

A
Klebsiella pneumoniae ompA
mutant was more susceptible to antimicrobial peptides (APs) than the wild type. Susceptibility did not result from surface changes other than the absence of OmpA. Our data suggest that OmpA is implicated in the activation of yet-unknown systems dedicated to ameliorating AP cytotoxicity.
Targeting Type III Secretion in
Yersinia pestis
Authors: Pan Ning J. , Brady Michael J. , Leong John M. , Goguen Jon D.
Published: November 2008

Yersinia pestis
, the causative agent of plague, utilizes a plasmid-encoded type III secretion system (T3SS) to aid it with its resistance to host defenses. This system injects a set of effector proteins known as Yops (
Yersinia
outer proteins) into the cytosol of host cells that come into contact with the bacteria. T3SS is absolutely required for the virulence of
Y. pestis
, making it a potential target for new therapeutics. Using a novel and simple high-throughput screening method, we examined a diverse collection of chemical libraries for small molecules that inhibit type III secretion in
Y. pestis
. The primary screening of 70,966 compounds and mixtures yielded 421 presumptive inhibitors. We selected eight of these for further analysis in secondary assays. Four of the eight compounds effectively inhibited Yop secretion at micromolar concentrations. Interestingly, we observed differential inhibition among Yop species with some compounds. The compounds did not inhibit bacterial growth at the concentrations used in the inhibition assays. Three compounds protected HeLa cells from type III secretion-dependent cytotoxicity. Of the eight compounds examined in secondary assays, four show good promise as leads for structure-activity relationship studies. They are a diverse group, with each having a chemical scaffold not only distinct from each other but also distinct from previously described candidate type III secretion inhibitors.
Real-Time Monitoring of Human Enterovirus (HEV)-Infected Cells and Anti-HEV 3C Protease Potency by Fluorescence Resonance Energy Transfer
Authors: Tsai Meng-Tian , Cheng Yun-Hsiang , Liu Yu-Ning , Liao Nien-Chien , Lu Wen-Wen , Kung Szu-Hao
Published: November 2008

A real-time assay system that allows monitoring of intracellular human enterovirus (HEV) protease activity was established using the principle of fluorescence resonance energy transfer (FRET). It was accomplished by engineering cells to constitutively express a genetically encoded FRET probe. The FRET-based probe was designed to contain an enterovirus 71 3C protease (3C
pro
) cleavage motif flanked by the FRET pair composed of green fluorescent protein 2 and red fluorescent protein 2 (DsRed2). Efficient FRET from the stable line was detected in a real-time manner by fluorescence microscopy, and the disruption of FRET was readily monitored upon HEV infection. The level of the repressed FRET was proportional to the input virus titer and the infection duration as measured by the fluorometric method. The FRET biosensor cell line was also responsive to other related HEV serotypes, but not to the phylogenetically distant herpes simplex virus, which was confirmed by Western blot analysis. The FRET biosensor was then utilized to develop a format for the determination of antiviral susceptibility, as the reduced FRET appeared to reflect viral replication. Evaluations of the FRET biosensor system with representative HEV serotypes demonstrated that their susceptibilities to a 3C
pro
inhibitor, rupintrivir, were all accurately determined. In summary, this novel FRET-based system is a means for rapid detection, quantification, and drug susceptibility testing for HEVs, with potential for the development of a high-throughput screening assay.
Discovery of a Small-Molecule Inhibitor of β-1,6-Glucan Synthesis
Authors: Kitamura Akihiro , Someya Kazuhiko , Hata Masato , Nakajima Ryohei , Takemura Makoto
Published: November 2008

It is possible that antifungal drugs with novel modes of action will provide favorable options to treat fungal infections. In the course of our screening for antifungal compounds acting on the cell wall, a pyridobenzimidazole derivative with unique activities, named D75-4590, was discovered. During treatment of
Saccharomyces cerevisiae
with D75-4590, (i) incorporation of [
14
C]glucose into the β-1,6-glucan component was selectively reduced, (ii) proteins released from the cell had lost the β-1,6-glucan moiety, and (iii) cells tended to clump, resulting in impaired cell growth. Genetic analysis of a D75-4590-resistant mutant of
S. cerevisiae
indicated that its primary target was Kre6p, which is considered to be one of the β-1,6-glucan synthases. These results strongly suggest that D75-4590 is a specific inhibitor of β-1,6-glucan synthesis. D75-4590 showed potent activities against various
Candida
species. It inhibited hyphal elongation of
C. albicans
as well.
KRE6
is conserved in various fungi, but no homologue has been found in mammalian cells. These lines of evidence indicate that D75-4590 is a promising lead compound for novel antifungal drugs. To our knowledge, this is the first report of a β-1,6-glucan inhibitor.
Characterization and Sequence Analysis of Extended-Spectrum-β-Lactamase-Encoding Genes from
Escherichia coli, Klebsiella pneumoniae
, and
Proteus mirabilis
Isolates Collected during Tigecycline Phase 3 Clinical Trials
Authors: Jones C. Hal , Tuckman Margareta , Keeney David , Ruzin Alexey , Bradford Patricia A.
Published: November 2008

In concert with the development of novel β-lactams and broad-spectrum cephalosporins, bacterially encoded β-lactamases have evolved to accommodate the new agents. This study was designed to identify, at the sequence level, the genes responsible for the extended-spectrum-β-lactamase (ESBL) phenotypes of
Escherichia coli, Klebsiella pneumoniae
, and
Proteus mirabilis
isolates collected during the global tigecycline phase 3 clinical trials. PCR assays were developed to identify and clone the
bla
TEM
,
bla
SHV
,
bla
OXA
, and
bla
CTX
genes from clinical strains. Isolates were also screened for AmpC genes of the
bla
CMY
,
bla
ACT
,
bla
FOX
, and
bla
DHA
families as well as the
bla
KPC
genes encoding class A carbapenemases.
E. coli, K. pneumoniae
, and
P. mirabilis
isolates with ceftazidime MICs of ≥2 μg/ml were designated possible ESBL-producing pathogens and were then subjected to a confirmatory test for ESBLs by use of Etest. Of 272 unique patient isolates, 239 were confirmed by PCR and sequencing to carry the genes for at least one ESBL, with 44% of the positive isolates harboring the genes for multiple ESBLs. In agreement with current trends for ESBL distribution,
bla
CTX-M
-type β-lactamase genes were found in 83% and 71% of the ESBL-positive
E. coli
and
K. pneumoniae
isolates, respectively, whereas
bla
SHV
genes were found in 41% and 28% of the ESBL-positive
K. pneumoniae
and
E. coli
isolates, respectively. Ninety-seven percent of the
E. coli
and
K. pneumoniae
isolates were tigecycline susceptible (MIC
90
= 2 μg/ml), warranting further studies to define the therapeutic utility of tigecycline against strains producing ESBLs in a clinical setting.
Multiple-Dose Pharmacokinetic Behavior of Elvucitabine, a Nucleoside Reverse Transcriptase Inhibitor, Administered over 21 Days with Lopinavir-Ritonavir in Human Immunodeficiency Virus Type 1-Infected Subjects
Authors: Colucci Philippe , Pottage John C. , Robison Heather , Turgeon Jacques , Schürmann Dirk , Hoepelman I. M. , Ducharme Murray P.
Published: November 2008

The purpose of this study was to describe the plasma pharmacokinetics (PK) of elvucitabine at different doses when administered daily or every other day for 21 days with lopinavir-ritonavir (Kaletra) in human immunodeficiency virus (HIV)-infected subjects. Three different dosing regimens of elvucitabine were administered with lopinavir-ritonavir to 24 subjects with moderate levels of HIV. Plasma samples were collected over 35 days. Elvucitabine concentrations were analyzed using a validated liquid chromatography-tandem mass spectrometry assay. The PK of elvucitabine was determined using both noncompartmental and compartmental analyses. Models were developed and tested using ADAPT II, while a population analysis was performed using IT2S. The PK behavior of elvucitabine was best described by a two-compartment linear model using two absorption rates and an increase in the bioavailability after day 1. The augmentation in the bioavailability after day 1 was variable, with some subjects demonstrating a major increase while others had little or no increase. Elvucitabine has a long half-life of approximately 100 h. The increase in elvucitabine bioavailability may be due to ritonavir inhibiting an efflux gut transporter with activity present in various levels between subjects. The proposed PK model may be utilized and improved further by linking the PK behavior of elvucitabine to various markers of efficacy.
Variations in Amino Acid Composition of Antisense Peptide-Phosphorodiamidate Morpholino Oligomer Affect Potency against
Escherichia coli
In Vitro and In Vivo
Authors: Mellbye Brett L. , Puckett Susan E. , Tilley Luke D. , Iversen Patrick L. , Geller Bruce L.
Published: November 2008

The potency of antisense peptide-phosphorodiamidate morpholino oligomers (PPMOs) was improved by varying the peptide composition. An antisense phosphorodiamidate morpholino oligomer (PMO) complementary to the mRNA of the essential gene
acpP
(which encodes the acyl carrier protein required for lipid biosynthesis) in
Escherichia coli
was conjugated to the 5′ ends of various cationic membrane-penetrating peptides. Each peptide had one of three repeating sequence motifs: C-N-N (motif 1), C-N (motif 2), or C-N-C (motif 3), where C is a cationic residue and N is a nonpolar residue. Variations in the cationic residues included arginine, lysine, and ornithine (O). Variations in the nonpolar residues included phenylalanine, valine, β-alanine (B), and 6-aminohexanoic acid (X). The MICs of the PPMOs varied from 0.625 to >80 μM (about 3 to 480 μg/ml). Three of the most potent were the (RX)
6
B-, (RXR)
4
XB-, and (RFR)
4
XB-AcpP PMOs, which were further tested in mice infected with
E. coli
. The (RXR)
4
XB-AcpP PMO was the most potent of the three conjugates tested in mice. The administration of 30 μg (1.5 mg/kg of body weight) (RXR)
4
XB-AcpP PMO at 15 min postinfection reduced CFU/ml in blood by 10
2
to 10
3
within 2 to 12 h compared to the numbers in water-treated controls. All mice treated with 30 μg/dose of (RXR)
4
XB-AcpP PMO survived infection, whereas all water-treated mice died 12 h postinfection. The reduction in CFU/ml in blood was proportional to the dose of PPMO from 30 to 300 μg/ml. In summary, the C-N-C motif was more effective than the other two motifs, arginine was more effective than lysine or ornithine, phenylalanine was more effective than 6-aminohexanoic acid in vitro but not necessarily in vivo, and (RXR)
4
XB-AcpP PMO reduced bacterial infection and promoted survival at clinically relevant doses.
Comparison of the Performances of Two In-House Rapid Methods for Antitubercular Drug Susceptibility Testing
Authors: de la Iglesia Agustina I. , Stella Emma J. , Morbidoni Héctor R.
Published: November 2008

Resistance to rifampin (rifampicin), isoniazid, and streptomycin of 69
Mycobacterium tuberculosis
isolates was analyzed by an in-house method based on mycobacteriophage D29 and a colorimetric micromethod. Both methods showed sensitivity and specificity values ranging from 93% to 100%. These simple methods offer an option for drug resistance assessment of
M. tuberculosis
.
Reconstruction of the Phenotypes of Methicillin-Resistant
Staphylococcus aureu
s by Replacement of the Staphylococcal Cassette Chromosome
mec
with a Plasmid-Borne Copy of
Staphylococcus sciuri pbpD
Gene
Authors: Antignac Aude , Tomasz Alexander
Published: November 2008

The
mecA
gene, the central determinant of methicillin (meticillin)-resistant
Staphylococcus aureus
(MRSA), is not native to this bacterial species but may have originated in the animal commensal species
Staphylococcus sciuri
. All
S. sciuri
strains carry a close homologue of
mecA
in the form of
pbpD
, the genetic determinant of penicillin binding protein 4 (PBP 4) of
S. sciuri
. Here we describe an experimental system that could be used for additional tests for this proposition. The
S. sciuri pbpD
gene was cloned into a shuttle plasmid and introduced into methicillin-susceptible
S. aureus
strain COL-S derived from parental MRSA strain COL from which the resistance cassette staphylococcal cassette chromosome
mec
was excised. The
S. sciuri pbpD
determinant was transcribed and translated in the
S. aureus
transductants producing large amounts of the 84-kDa
S. sciuri
PBP 4 and was then deposited in the plasma membrane of the host bacterium. Transductants carrying the heterologous
S. sciuri pbpD
gene exhibited properties typical of those of parental MRSA strain COL, including broad-spectrum, high-level, and homogeneous resistance to structurally different β-lactams. Antibiotic resistance was dependent on the functioning of
S. aureus
PBP 2 and was suppressed by the specific regulatory genes
mecI
and
mecR
and by inhibitors of an early step in cell wall biosynthesis.
S. sciuri
PBP 4 was also able to replace the essential physiological function(s) of the native PBP 2 of
S. aureus
and produce peptidoglycan typical of that of parental MRSA strain COL. Our results provide further support for the proposition that the resistance determinant
mecA
of MRSA strains has evolved from
S. sciuri pbpD
.
Variety of Antiprion Compounds Discovered through an In Silico Screen Based on Cellular-Form Prion Protein Structure: Correlation between Antiprion Activity and Binding Affinity
Authors: Hosokawa-Muto Junji , Kamatari Yuji O. , Nakamura Hironori K. , Kuwata Kazuo
Published: November 2008

Transmissible spongiform encephalopathies are associated with the conformational conversion of the prion protein from the cellular form (PrP
C
) to the scrapie form. This process could be disrupted by stabilizing the PrP
C
conformation, using a specific ligand identified as a chemical chaperone. To discover such compounds, we employed an in silico screen that was based on the nuclear magnetic resonance structure of PrP
C
. In combination, we performed ex vivo screening using the Fukuoka-1 strain-infected neuronal mouse cell line at a compound concentration of 10 μM and surface plasmon resonance. Initially, we selected 590 compounds according to the calculated docked energy and finally discovered 24 efficient antiprion compounds, whose chemical structures are quite diverse. Surface plasmon resonance studies showed that the binding affinities of compounds for PrP
C
roughly correlated with the compounds' antiprion activities, indicating that the identification of chemical chaperones that bind to the PrP
C
structure and stabilize it is one efficient strategy for antiprion drug discovery. However, some compounds possessed antiprion activities with low affinities for PrP
C
, indicating a mechanism involving additional modulation factors. We classified the compounds roughly into five categories: (i) binding and effective, (ii) low binding and effective, (iii) binding and not effective, (iv) low binding and not effective, and (v) acceleration. In conclusion, we found a spectrum of compounds, many of which are able to modulate the pathogenic conversion reaction. The appropriate categorization of these diverse compounds would facilitate antiprion drug discovery and help to elucidate the pathogenic conversion mechanism.
Identification of a Novel Trimethoprim Resistance Gene,
dfrK
, in a Methicillin-Resistant
Staphylococcus aureus
ST398 Strain and Its Physical Linkage to the Tetracycline Resistance Gene
tet
(L)
Authors: Kadlec Kristina , Schwarz Stefan
Published: November 2008

A novel trimethoprim resistance gene, designated
dfrK
, was detected in close proximity to the tetracycline resistance gene
tet
(L) on the ca. 40-kb plasmid pKKS2187 in a porcine methicillin (meticillin)-resistant
Staphylococcus aureus
isolate of sequence type 398. The
dfrK
gene encodes a 163-amino-acid dihydrofolate reductase that differs from all so-far-known dihydrofolate reductases.
In Vitro Evaluation of the Antimicrobial Activity of Ceftaroline against Cephalosporin-Resistant Isolates of
Streptococcus pneumoniae
Authors: McGee Lesley , Biek Donald , Ge Yigong , Klugman Magderie , du Plessis Mignon , Smith Anthony M. , Beall Bernard , Whitney Cynthia G. , Klugman Keith P.
Published: November 2008

Increasing pneumococcal resistance to extended-spectrum cephalosporins warrants the search for novel agents with activity against such resistant strains. Ceftaroline, a parenteral cephalosporin currently in phase 3 clinical development, has demonstrated potent in vitro activity against resistant gram-positive organisms, including penicillin-resistant
Streptococcus pneumoniae.
In this study, the activity of ceftaroline was evaluated against highly cefotaxime-resistant isolates of pneumococci from the Active Bacterial Core surveillance program of the Centers for Disease Control and Prevention and against laboratory-derived cephalosporin-resistant mutants of
S. pneumoniae
. The MICs of ceftaroline and comparators were determined by broth microdilution. In total, 120 U.S. isolates of cefotaxime-resistant (MIC ≥ 4 μg/ml)
S. pneumoniae
were tested along with 18 laboratory-derived R6 strains with known penicillin-binding protein (PBP) mutations. Clinical isolates were characterized by multilocus sequence typing, and the DNAs of selected isolates were sequenced to identify mutations affecting
pbp
genes. Ceftaroline (MIC
90
= 0.5 μg/ml) had greater in vitro activity than penicillin, cefotaxime, or ceftriaxone (MIC
90
= 8 μg/ml for all comparators) against the set of highly cephalosporin-resistant clinical isolates of
S. pneumoniae
. Ceftaroline was also more active against the defined R6 PBP mutant strains, which suggests that ceftaroline can overcome common mechanisms of PBP-mediated cephalosporin resistance. These data indicate that ceftaroline has significant potency against
S. pneumoniae
strains resistant to existing parenteral cephalosporins and support its continued development for the treatment of infections caused by resistant
S. pneumoniae
strains.
Mycoplasma suis
Invades Porcine Erythrocytes
Authors: Groebel K. , Hoelzle K. , Wittenbrink M. M. , Ziegler U. , Hoelzle L. E.
Published: November 2008

Mycoplasma suis
belongs to the hemotrophic mycoplasma group and causes infectious anemia in pigs. According to the present state of knowledge, this organism adheres to the surface of erythrocytes but does not invade them. We found a novel
M. suis
isolate that caused severe anemia in pigs with a fatal disease course. Interestingly, only marginal numbers of the bacteria were visible on and between the erythrocytes in acridine orange-stained blood smears for acutely diseased pigs, whereas very high loads of
M. suis
were detected in the same blood samples by quantitative PCR. These findings indicated that
M. suis
is capable of invading erythrocytes. By use of fluorescent labeling of
M. suis
and examination by confocal laser scanning microscopy, as well as scanning and transmission electron microscopy, we proved that the localization of
M. suis
was intracellular. This organism invades erythrocytes in an endocytosis-like process and is initially surrounded by two membranes, and it was also found floating freely in the cytoplasm. In conclusion, we were able to prove for the first time that a member of the hemotrophic mycoplasma group is able to invade the erythrocytes of its host. Such colonization should protect the bacterial cells from the host's immune response and hamper antibiotic treatment. In addition, an intracellular life cycle may explain the chronic nature of hemotrophic mycoplasma infections and should serve as the foundation for novel strategies in hemotrophic mycoplasma research (e.g., treatment or prophylaxis).
Effect of a different caeruloplasmin assay method on the relationship between serum copper and caeruloplasmin
Authors: Twomey P J
Published: November 2008

Background

The assessment of copper status is difficult. When investigating excess and deficient copper states, healthcare professionals usually assume that the locally available caeruloplasmin and copper assay results are comparable to data from the literature.

Objective

To investigate the effect of different caeruloplasmin assays on the relationship between copper and caeruloplasmin.

Methods

Caeruloplasmin and copper results were obtained retrospectively from the laboratory information system before and after a change in the caeruloplasmin assay method. The central tendencies and population confidence intervals for copper and caeruloplasmin were compared. Linear regression analysis was carried out to determine the exact relationship (slope and intercept) between caeruloplasmin and copper. The graph of copper versus caeruloplasmin was also examined to see if the confidence intervals overlapped or not. Finally, the χ2 test was used to determine if there was a difference with respect to the lower reference intervals for the caeruloplasmin assays.

Results

There were 338 and 461 patients in the first and second methods, respectively. None of the patients had Wilson disease. There was no difference between the central tendency copper concentrations or the 95% confidence intervals for the population copper concentrations for the two periods. However, there were differences between the two caeruloplasmin assay methods for both the central tendencies and the population confidence intervals. The data show a statistically significant difference in the relationship between caeruloplasmin and copper associated with the change in the caeruloplasmin assay. There were seven and 100 patients with caeruloplasmin concentrations <200 mg/l with the first and second methods, respectively, which was a significant difference (χ2 test; p<<0.001).

Conclusions

This study shows that that the relationship between copper and caeruloplasmin depends on the caeruloplasmin assay used. A caeruloplasmin assay that reads too high may miss cases of Wilson disease (false negatives), and an assay that reads too low (false positives) may result in further investigations to exclude Wilson disease. Assay-based cut-offs are essential for the investigation of copper excess and deficiency states in the absence of proper assay standardisation. Each laboratory should verify their caeruloplasmin assay reference interval to avoid false positives and/or false negative results.
Cardiovascular risk in South Asians
Authors: Ramaraj R , Chellappa P
Published: November 2008

Cardiovascular disease (CVD) has become a major clinical and public health problem. South Asian countries, namely India, Pakistan, Sri Lanka, Bangladesh and Nepal, not only represent a quarter of the world's population but also contribute to the highest proportion of CVD burden when compared with any other regions globally. This population carries the increased risk even if they migrate to other countries and have increased mortality due to CVD at a younger age in comparison to the local population. In this review, the risk factors and reasons for the higher rate of CVD in South Asians are discussed.
Exercise induced bronchoconstriction and sports
Authors: Billen A , Dupont L
Published: November 2008

Exercise induced bronchoconstriction (EIB) describes the acute transient airway narrowing that occurs during and most often after exercise, and is prevalent in elite athletes. Prolonged hyperventilation of dry or cold air and increased inhalation of pollutants or allergens could account for the bronchoconstrictive reaction. The subsequent airway inflammation seems to differ from typical asthma. Objective measures of lung function and provocation tests should be used for an accurate and reliable diagnosis. EIB is currently treated with inhalation of β2-agonists or, as second choice, sodium cromoglycate approximately 15 min before exercise. If this proves to be insufficient then inhaled steroids should be added. Leukotriene receptor antagonists can be used in patients whose symptoms do not respond to inhaled steroids. The screening of high risk populations such as swimmers, cyclists, rowers and winter athletes is recommended by some authors. Drug doping regulations and practical recommendations for competitive athletes and their health care providers are explained.
Recent advances in the management of type 2 diabetes mellitus: a review
Authors: Srinivasan B T , Jarvis J , Khunti K , Davies M J
Published: November 2008

Type 2 diabetes mellitus (T2DM) is a progressive disorder caused by a combination of insulin resistance and β cell dysfunction. It is associated with an increased and premature risk of cardiovascular disease as well as specific microvascular complications such as retinopathy, nephropathy and neuropathy. In the last 5 years new glucose lowering drugs acting on novel pathways have been developed, licensed and launched, such as the glucagon-like peptide (GLP-1) agonists (exenatide) and dipeptidyl peptidase (DPP-IV) inhibitors such as sitagliptin and vildagliptin. This review looks at these new agents in terms of their mode of action, pharmacokinetics and use in clinical practice. This review also includes new agents in the area of weight loss that may have a positive effect for glucose management—for example, rimonabant.
Pseudo-hypertriglyceridaemia: a measurement artefact due to glycerol kinase deficiency
Authors: Walmsley T A , Potter H C , George P M , Florkowski C M
Published: November 2008

A man presented with elevated plasma triglycerides and was commenced on fibrate treatment. The triglycerides did not fall and compliance was questioned. The triglyceride elevation was inconsistent with the observed lack of turbidity in the plasma sample. Triglyceride elevation was not confirmed by a different analytical method and lipoprotein electrophoresis showed a normal very low density lipoprotein (VLDL) band pattern. Glycerol kinase deficiency was suspected and was supported by elevated urine glycerol, and confirmed by reduced leucocyte enzyme activity and mutational analysis of the GK gene which showed a novel three base pair deletion. Demonstration of a point mutation also excludes a contiguous gene deletion syndrome.
Correlation of Grassy Lake and Cedar Lake ambers using infrared spectroscopy, stable isotopes, and palaeoentomology
Authors: McKellar Ryan C. , Wolfe Alexander P. , Tappert Ralf , Muehlenbachs Karlis
Published: November 2008

The Late Cretaceous Grassy Lake and Cedar Lake amber deposits of western Canada are among North America’s most famous amber-producing localities. Although it has been suggested for over a century that Cedar Lake amber from western Manitoba may be a secondary deposit having originated from strata in Alberta, this hypothesis has not been tested explicitly using geochemical fingerprinting coupled to comparative analyses of arthropod faunal content. Although there are many amber-containing horizons associated with Cretaceous coals throughout Alberta, most are thermally mature and brittle, thus lacking the resilience to survive long distance transport while preserving intact biotic inclusions. One of the few exceptions is the amber found in situ at Grassy Lake. We present a suite of new analyses from these and other Late Cretaceous ambers from western Canada, including stable isotopes (H and C), Fourier transform infrared (FTIR) spectra, and an updated faunal compendium for the Grassy and Cedar lakes arthropod assemblages. When combined with amber’s physical properties and stratigraphic constraints, the results of these analyses confirm that Cedar Lake amber is derived directly from the Grassy Lake amber deposit or an immediate correlative equivalent. This enables the palaeoenvironmental context of Grassy Lake amber to be extended to the Cedar Lake deposit, making possible a more inclusive survey of Cretaceous arthropod faunas.
Lower Silurian subduction-related volcanic rocks in the Chaleurs Group, northern New Brunswick, CanadaGeological Survey of Canada, Contribution No. 2008-0166.Contribution to Natural Resources Canada’s Targeted Geoscience Initiative 3 (2005–2010).
Authors: Wilson R. A. , van Staal C. R. , Kamo S.
Published: November 2008

Early Silurian volcanic and subvolcanic rocks are preserved in the lower part of the Chaleurs Group at two locations in northern New Brunswick. At Quinn Point, mafic to intermediate rocks are hosted by sedimentary rocks of the Weir Formation, and at Pointe Rochette, a bed of felsic tuff occurs near the base of the Weir. These rocks are interpreted as the first evidence in New Brunswick of magmatism associated with Late Ordovician – Early Silurian subduction of Tetagouche–Exploits back-arc oceanic crust. At Quinn Point, mafic rocks include a thick basaltic flow or sill and intermediate to mafic cobbles in overlying conglomerate beds. The in situ mafic rocks and the conglomerate clasts are chemically alike and display subduction-related affinities on tectonic discrimination diagrams. At Pointe Rochette, fine-grained felsic tuff contains elevated Th and U and depleted high-field-strength elements, consistent with a subduction-influenced setting, although rare-earth element (REE) abundances are low and the REE profile is relatively flat. A U–Pb (zircon) age of 429.2 ± 0.5 Ma was obtained from the tuff, consistent with the late Llandovery to early Wenlock age of the overlying La Vieille Formation and coinciding with the latter stages of development of the Brunswick subduction complex. Volcanic rocks were emplaced in the arc to arc-trench gap region, probably reflecting local step-back of the magmatic axis due to accretion of continental back-arc ribbons. The low volume of Early Silurian subduction-influenced rocks is probably related to the relatively narrow width of the back-arc basin and the young, “warm” character of back-arc crust.
FORMATION OF RELATIVISTIC MHD JETS: STATIONARY STATE SOLUTIONS AND NUMERICAL SIMULATIONS
Authors: FENDT CHRISTIAN , MEMOLA ELISABETTA
Published: November 2008

We discuss numerical results of relativistic magnetohydrodynamic (MHD) jet formation models. We first review some examples of stationary state solutions treating the collimation and acceleration process of relativistic MHD jets. We provide an a posteriori check for the MHD condition in highly magnetized flows, namely the comparison of particle density to Goldreich–Julian density. Using the jet dynamical parameters calculated from the MHD model, we show the rest-frame thermal X-ray spectra of the jet, from which we derive the overall spectrum taking into account a variation of Doppler boosting and Doppler shift of emission lines along the outflow. Finally, we present preliminary results of relativistic MHD simulations of jet formation demonstrating the acceleration of a low velocity (0.01 c) disk wind to a collimated high velocity (0.8 c).
MAGNETIC COLLIMATION AND MAGNETOHYDRODYNAMIC KINK INSTABILITY DRIVEN BY DIFFERENTIAL ROTATION
Authors: CAREY C. S. , SOVINEC C. R. , HEINZ S. , EVERETT J. E.
Published: November 2008

We investigate the launching and stability of extragalactic jets through magnetohydrodynamic simulations of jet evolution. In these simulations, a small scale equilibrium magnetic corona is twisted by a differentially rotating accretion disk. Two-dimensional calculations show the formation of a collimated outflow. This outflow is divided into two regions by the Alfvén surface: a magnetically dominated Poynting region, and a kinetically dominated region. Three-dimensional calculations show that the outflow is unstable to the m = 1 kink instability, and that the growth rate of the kink instability decreases as the rotation rate of the accretion disk increases.
ON COSMIC RAY ACCELERATION IN RELATIVISTIC JETS
Authors: OSTROWSKI MICHAL
Published: November 2008

We review the theoretical progress in the field of cosmic-ray first-order Fermi acceleration at relativistic shock fronts, showing that recent results change our knowledge about these processes substantially. In particular, relativistic shocks are unlikely to form particle distributions extending to very high energies. Instead, recent simulations give particle distributions where a shock-compressed injected component is followed by a more or less extended high energy tail. An increase of the Lorentz factor of the shock usually leads to steepening and a decrease of the energetic tail, so that fitted spectral indices to the high energy part can substantially deviate from the "universal power law index" σ ≈ 2.2.

We report on observational findings from the hot spots in Cygnus A, showing that the derived electron spectra (with a very flat, σ ≈ 1.5, low energy part up to ~ 1 GeV, followed by a much steeper, σ > 3, part at higher energies) indeed deviate from the standard expectation for relativistic shocks.

We conclude with a short discussion of some qualitative features of shear and second-order Fermi acceleration in turbulent relativistic plasmas.
Vascular Endothelial Function and Leisure-Time Physical Activity in Adolescents
Authors: Pahkala Katja , Heinonen Olli J. , Lagström Hanna , Hakala Paula , Simell Olli , Viikari Jorma S.A. , Rönnemaa Tapani , Hernelahti Miika , Sillanmäki Lauri , Raitakari Olli T.
Published: November 2008

Background—

Exercise training improves endothelial function in high-risk adolescents, but the influence of habitual leisure-time physical activity on endothelial function in healthy adolescents is unknown.

Methods and Results—

Brachial artery flow-mediated endothelial function and physical activity habits were assessed in 483 adolescents (13 years of age) participating in an atherosclerosis prevention study (Special Turku Coronary Risk Factor Intervention Project for Children [STRIP]). Endothelial function was examined with ultrasound; physical activity was assessed with self-administered questionnaires. A leisure-time physical activity index was calculated by multiplying mean weekly leisure-time exercise intensity, duration, and frequency [boys, 31.2±23.0 MET h/wk (mean±SD); girls, 24.0±20.9 MET h/wk;
P
for gender difference=0.0003]. Maximum flow-mediated dilatation (FMD) and total FMD response (the area under the dilatation curve 40 to 180 seconds after hyperemia) were calculated. In boys, maximum FMD and area under the dilatation curve 40 to 180 seconds after hyperemia were directly associated with leisure-time physical activity index in regression analyses adjusted for brachial artery diameter (maximum FMD,
P
=0.020; area under the dilatation curve 40 to 180 seconds after hyperemia,
P
=0.0055). These associations remained significant after further adjustments for body mass index, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein, and systolic blood pressure. A difference of ≈50 MET h/wk corresponding to ≈10 hours of moderate intensity activity weekly between sedentary and active boys was associated with an ≈1% unit difference in maximum FMD.

Conclusions—

Leisure-time physical activity is directly associated with brachial artery FMD responses in 13-year-old boys, providing evidence that physical activity beneficially influences endothelial function in healthy male adolescents. Lack of association in girls may reflect their overall lower physical activity level.
Semantic Priming in a Cortical Network Model
Authors: Brunel Nicolas , Lavigne Frédéric
Published: November 2008

Contextual recall in humans relies on the semantic relationships between items stored in memory. These relationships can be probed by priming experiments. Such experiments have revealed a rich phenomenology on how reaction times depend on various factors such as strength and nature of associations, time intervals between stimulus presentations, and so forth. Experimental protocols on humans present striking similarities with pair association task experiments in monkeys. Electrophysiological recordings of cortical neurons in such tasks have found two types of task-related activity, “retrospective” (related to a previously shown stimulus), and “prospective” (related to a stimulus that the monkey expects to appear, due to learned association between both stimuli). Mathematical models of cortical networks allow theorists to understand the link between the physiology of single neurons and synapses, and network behavior giving rise to retrospective and/or prospective activity. Here, we show that this type of network model can account for a large variety of priming effects. Furthermore, the model allows us to interpret semantic priming differences between the two hemispheres as depending on a single association strength parameter.
Motion on Numbers: Transcranial Magnetic Stimulation on the Ventral Intraparietal Sulcus Alters Both Numerical and Motion Processes
Authors: Salillas Elena , Basso Demis , Baldi Maurizia , Semenza Carlo , Vecchi Tomaso
Published: November 2008

It has often been proposed that there is a close link between representation of number and space. In the present work, single-pulse transcranial magnetic stimulation (TMS) was applied to the ventral intraparietal sulcus (VIPS) to determine effects on performance in motion detection and number comparison tasks. Participants' reaction times and thresholds for perception of laterally presented coherent motion in random dot kinematograms increased significantly when the contralateral VIPS was stimulated in contrast to the interhemispheric sulcus (Experiment 1) and to the ipsilateral VIPS (Experiment 2). In number comparison tasks, participants compared the magnitude of the laterally presented numbers 1–9 with the number 5. Again, reaction times significantly increased when TMS was applied to the contralateral VIPS in contrast to control sites. The finding that VIPS-directed TMS results in impaired efficiency in both motion perception and number comparison suggests that these processes share a common neural substrate.
When Elephants Fly: Differential Sensitivity of Right and Left Inferior Frontal Gyri to Discourse and World Knowledge
Authors: Menenti Laura , Petersson Karl Magnus , Scheeringa René , Hagoort Peter
Published: November 2008

Both local discourse and world knowledge are known to influence sentence processing. We investigated how these two sources of information conspire in language comprehension. Two types of critical sentences, correct and world knowledge anomalies, were preceded by either a neutral or a local context. The latter made the world knowledge anomalies more acceptable or plausible. We predicted that the effect of world knowledge anomalies would be weaker for the local context. World knowledge effects have previously been observed in the left inferior frontal region (Brodmann's area 45/47). In the current study, an effect of world knowledge was present in this region in the neutral context. We also observed an effect in the right inferior frontal gyrus, which was more sensitive to the discourse manipulation than the left inferior frontal gyrus. In addition, the left angular gyrus reacted strongly to the degree of discourse coherence between the context and critical sentence. Overall, both world knowledge and the discourse context affect the process of meaning unification, but do so by recruiting partly different sets of brain areas.
Both a Nicotinic Single Nucleotide Polymorphism (SNP) and a Noradrenergic SNP Modulate Working Memory Performance when Attention is Manipulated
Authors: Greenwood Pamela M. , Sundararajan Ramya , Lin Ming-Kuan , Kumar Reshma , Fryxell Karl J. , Parasuraman Raja
Published: November 2008

We investigated the relation between the two systems of visuospatial attention and working memory by examining the effect of normal variation in cholinergic and noradrenergic genes on working memory performance under attentional manipulation. We previously reported that working memory for location was impaired following large location precues, indicating the scale of visuospatial attention has a role in forming the mental representation of the target. In one of the first studies to compare effects of two single nucleotide polymorphisms (SNPs) on the same cognitive task, we investigated the neurotransmission systems underlying interactions between attention and memory. Based on our previous report that the CHRNA4 rs#1044396 C/T nicotinic receptor SNP affected visuospatial attention, but not working memory, and the DBH rs#1108580 G/A noradrenergic enzyme SNP affected working memory, but not attention, we predicted that both SNPs would modulate performance when the two systems interacted and working memory was manipulated by attention. We found the scale of visuospatial attention deployed around a target affected memory for location of that target. Memory performance was modulated by the two SNPs. CHRNA4 C/C homozygotes and DBH G allele carriers showed the best memory performance but also the greatest benefit of visuospatial attention on memory. Overall, however, the CHRNA4 SNP exerted a stronger effect than the DBH SNP on memory performance when visuospatial attention was manipulated. This evidence of an integrated cholinergic influence on working memory performance under attentional manipulation is consistent with the view that working memory and visuospatial attention are separate systems which can interact.
Priming Letters by Colors: Evidence for the Bidirectionality of Grapheme–Color Synesthesia
Authors: Weiss Peter H. , Kalckert Andreas , Fink Gereon R.
Published: November 2008

In synesthesia, stimulation of one sensory modality leads to a percept in another nonstimulated modality, for example, graphemes trigger an additional color percept in grapheme–color synesthesia, which encompasses the variants letter–color and digit–color synesthesia. Until recently, it was assumed that synesthesia occurs strictly unidirectional: Although the perception of a letter induces a color percept in letter–color synesthetes, they typically do not report that colors trigger the percept of a letter. Recent data on number processing in synesthesia suggest, however, that colors can implicitly elicit numerical representations in digit–color synesthetes, thereby questioning unidirectional models of synesthesia. Using a word fragment completion paradigm in 10 letter–color synesthetes, we show here for the first time that colors can implicitly influence lexical search. Our data provide strong support for a bidirectional nature of grapheme–color synesthesia and, in general, may allude to the mechanisms of cross-modality interactions in the human brain.
EEG Activity Underlying Successful Study of Associative and Order Information
Authors: Caplan Jeremy B. , Glaholt Mackenzie G. , McIntosh Anthony R.
Published: November 2008

Two of the most well studied and ecologically relevant memory paradigms are memory for pairs (“associations”) and ordered sequences (“serial lists”). Behavioral theories comprise two classes: those that use common mechanisms and those that use distinct mechanisms for study and retrieval of associations versus serial lists. We tested the common-mechanisms hypothesis by recording electroencephalographic activity related to successful study (“subsequent memory effect” [SME]) of pairs and short lists (triples) of nouns. Multivariate analysis identified four distributed patterns of brain activity: (1) right parietal activity throughout most of the study period that differentiated study of pairs from triples within subjects as well as exhibiting an SME that was significant for pairs but not for triples; (2) a left parietal and fronto-polar activity pattern that was reliable around 500 msec and later in the study trial, exhibiting an SME for pairs and a weaker, nonsignificant SME for triples; (3) a left frontal/right parietal topography in the middle of the study interval which covaried with speed and accuracy across subjects; and (4) a pattern resembling the late positive component preceded by an early potential which together covaried with accuracy in triples but slow response times for both pairs and triples. These patterns point to the relevance of three classic SME components (early, late positive, and slow components) from single-item memory to memory for structured information, but suggest that they reflect subsets of more complex spatio-temporal patterns. Our findings support common underlying mechanisms for study and recall of pairs and lists. However, existing models must be modified to account for differences in both the presence of certain study-relevant processes and in the relevance of these processes to performance measures for pairs versus serial lists.
The Question of Becoming: Islamic Reform Movements in Contemporary Ethiopia
Authors: Østebø Terje
Published: November 2008

Facilitated by a new (since 1991) political climate, enhancing Muslim opportunities for religious expression, several Islamic reform movements have surfaced in Ethiopia. Under consideration here are the Salafi movement, the Tabligh movement and an Intellectualist revivalist movement, each of which was crucial for the reconfiguration of religious affiliation, and served as a channel in the search for belonging and coherent meaning. Discussing the movements' socio-cultural composition and their particular features, this paper pays attention to how issues of locality interact with translocal ideological currents and affect one another. Of particular interest in the Ethiopian case is the explicit avoidance of any political agenda, a distinct intermarriage with a discourse on ethnicity, where the latter has contributed to complex processes of constructing and demarcating religious- and ethnic-based boundaries. The paper thus seeks to demonstrate the complex interrelationship between global currents and local factors, all contributing to the heterogenisation of contemporary Islam.
Restorative Justice under the ICC Penalty Regime
Authors: Radosavljevic Dragana
Published: November 2008

This paper investigates the International Criminal Court's prosecutorial and sentencing strategies in supplying durable international, and through complementarity, national accountability mechanisms with clearly defined sentencing objectives. By scrutinising the scope of plea agreements as a validated trial strategy for international crimes and the sentencing rationale of the same, this work evaluates the impact these have on restorative and reconciliatory justice. An overview of this practice as well as that of amnesties aims to illustrate the ideologically ambivalent model of international justice under the ICC Statute and its detrimental outcome, or impartial approach to international justice and, importantly, to the quest for truth. This results in potential distortion of the historical record accompanying conflict, which in turn is fundamental to any peace building and reconciliation process.
Withdrawing from Participating in a Biobank — A Comparative Study
Authors: Gertz Renate
Published: November 2008

The development of biobanks worldwide is considered to hold great promise for the provision of new insights into the connection between genes and environment and to have a positive impact on public health. There is, however, a constant tension between the rights of individuals on one hand and the progress of research on the other hand. One of the rights developed to protect the autonomy and free will of participants and reflecting the basic principles regulating medical research according to the Nuremberg Code and the Declaration of Helsinki is the right to be able to withdraw from the biobank at any time as an expression of the participant's free will and autonomy. There are two important problems to withdrawing, namely the 'what' and 'when' — what can be withdrawn and when can it be withdrawn.