bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fixed-Dose Isosorbide Dinitrate-Hydralazine: Race-Based Cardiovascular Medicine Benefit or Mirage?
Authors: Ferdinand Keith C. 
Published: August 2008

The goal of this paper is to present a succinct overview, from a clinician’s perspective, of the importance and implications of research on heart failure in African Americans. It first gives a brief outline of the rationale and results of the African-American Heart Failure Trial (A-HeFT), which showed evidence for the effectiveness of fixed-dose combination of isosorbide dinitrate and hydralazine (ISDN/Hyd), marketed as BiDil (NitroMed Inc.), in this population. Finally, it underscores the necessity of treating African Americans with evidence-based medicine given that humanistic physicians and other clinicians strive to provide holistic treatment to their patients.Most researchers and clinicians recognize the difficulty with utilizing race as a category for inclusion in trials. While race lacks any true biologic definition, it is potentially beneficial as a consideration in clinical studies, based on prior evidence of certain potential differences across self-identified racial/ethnic groups in morbidity and mortality and responses to medicine. Even though use of race as a classification is a problematic distinction, it should not be ignored. If clinical trials demonstrate significant improvement with targeted treatment in African Americans, clinicians should not withhold life-saving drugs that result from such studies.
Understanding Race at the Frontier of Pharmaceutical Regulation: An Analysis of the Racial Difference Debate at the ICH
Authors: Kuo Wen-Hua 
Published: August 2008

Reflecting on the tension of which he was aware between the imperial West and the still-mysterious East, Victorian writer Rudyard Kipling (1865-1936) penned the above phrase to express the incommensurable situation wherein the Westerner never understands the Asian, as the latter’s culture differs too greatly from his own. However, aware that East and West nevertheless cannot remain separated forever, the author ends the poem with an eventual encounter between the two.Over 100 years have passed since this poem was written, yet the ambivalent encounter between East and West that it depicts still exists and is currently playing out within the field of pharmaceuticals. On one side of the divide are the many people in the industry who want to standardize global acceptance of drugs; on the other are the local authorities who want to maintain the overruling legal need not to compromise on health care at a national level. In this sense, the divergence and unity that Kipling captures is what this paper aims to discuss as it addresses how race is debated at the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).
Characterization of DegQ
Vh
, a Serine Protease and a Protective Immunogen from a Pathogenic
Vibrio harveyi
Strain
Authors: Zhang Wei-wei , Sun Kun , Cheng Shuang , Sun Li 
Published: August 2008

ABSTRACT

Vibrio harveyi
is an important marine pathogen that can infect a number of aquaculture species.
V. harveyi degQ
(

degQ
Vh

), the gene encoding a DegQ homologue, was cloned from T4, a pathogenic
V. harveyi
strain isolated from diseased fish. DegQ
Vh
was closely related to the HtrA family members identified in other
Vibrio
species and could complement the temperature-sensitive phenotype of an
Escherichia coli
strain defective in
degP
. Expression of

degQ
Vh

in T4 was modulated by temperature, possibly through the σ
E
-like factor. Enzymatic analyses demonstrated that the recombinant DegQ
Vh
protein expressed in and purified from
E. coli
was an active serine protease whose activity required the integrity of the catalytic site and the PDZ domains. The optimal temperature and pH of the recombinant DegQ
Vh
protein were 50°C and pH 8.0. A vaccination study indicated that the purified recombinant DegQ
Vh
was a protective immunogen that could confer protection upon fish against infection by
V. harveyi
. In order to improve the efficiency of DegQ
Vh
as a vaccine, a genetic construct in the form of the plasmid pAQ1 was built, in which the DNA encoding the processed DegQ
Vh
protein was fused with the DNA encoding the secretion region of AgaV, an extracellular β-agarase. The
E. coli
strain harboring pAQ1 could express and secrete the chimeric DegQ
Vh
protein into the culture supernatant. Vaccination of fish with viable
E. coli
expressing chimeric

degQ
Vh

significantly (
P
< 0.001) enhanced the survival of fish against
V. harveyi
challenge, which was possibly due to the relatively prolonged exposure of the immune system to the recombinant antigen produced constitutively, albeit at a gradually decreasing level, by the carrier strain.
The Genome of
Polaromonas
sp. Strain JS666: Insights into the Evolution of a Hydrocarbon- and Xenobiotic-Degrading Bacterium, and Features of Relevance to Biotechnology
Authors: Mattes Timothy E. , Alexander Anne K. , Richardson Paul M. , Munk A. Christine , Han Cliff S. , Stothard Paul , Coleman Nicholas V. 
Published: August 2008

ABSTRACT

Polaromonas
sp. strain JS666 can grow on
cis
-1,2-dichloroethene (cDCE) as a sole carbon and energy source and may be useful for bioremediation of chlorinated solvent-contaminated sites. Analysis of the genome sequence of JS666 (5.9 Mb) shows a bacterium well adapted to pollution that carries many genes likely to be involved in hydrocarbon and xenobiotic catabolism and metal resistance. Clusters of genes coding for haloalkane, haloalkanoate,
n
-alkane, alicyclic acid, cyclic alcohol, and aromatic catabolism were analyzed in detail, and growth on acetate, catechol, chloroacetate, cyclohexane carboxylate, cyclohexanol, ferulate, heptane, 3-hydroxybenzoate, hydroxyquinol, gentisate, octane, protocatechuate, and salicylate was confirmed experimentally. Strain JS666 also harbors diverse putative mobile genetic elements, including retrons, inteins, a miniature inverted-repeat transposable element, insertion sequence transposases from 14 families, eight genomic islands, a Mu family bacteriophage, and two large (338- and 360-kb) plasmids. Both plasmids are likely to be self-transferable and carry genes for alkane, alcohol, aromatic, and haloacid metabolism. Overall, the JS666 genome sequence provides insights into the evolution of pollutant-degrading bacteria and provides a toolbox of catabolic genes with utility for biotechnology.
Gram-Negative Bacterial Lipopolysaccharide Retention by a Positively Charged New-Generation Filter
Authors: Bononi Ilaria , Balatti Veronica , Gaeta Soccorso , Tognon Mauro 
Published: August 2008

ABSTRACT
Removing endotoxins is an important target in the pharmaceutical industry and in clinical practice. A filter introduced into an intravenous line prevents microbiological contamination, but to date no filters have retained bacterial endotoxins. In our study, we assayed a new-generation filter which is able to capture endotoxins from solutions.
Factors Associated with Cross-Contamination of Hides of Scottish Cattle by
Escherichia coli
O157
Authors: Mather A. E. , Reid S. W. J. , McEwen S. A. , Ternent H. E. , Reid-Smith R. J. , Boerlin P. , Taylor D. J. , Steele W. B. , Gunn G. J. , Mellor D. J. 
Published: August 2008

ABSTRACT

The putative source of hide contamination for 236 cattle in Scotland followed from the farm through to slaughter was determined using phage and verocytotoxin type data. The majority of cattle (84%) were found to have subtypes of
Escherichia coli
O157 on their hide that had not been found previously in any animal from the farm of origin, strongly suggesting that contamination occurred once animals had left the farm of origin. Using logistic regression analysis, several variables and factors were found to be strongly associated (
P
< 0.01) with cross-contamination of cattle hides at the univariate level; commercial transport to slaughter, transport with other animals, use of a crush, line automation, and increasing slaughterhouse throughput were all risk factors, while feeding hay in lairage, processing an animal earlier in a slaughter cohort, and cleaning the landing area poststunning were protective. In the multivariable model, with the slaughterhouse and the farm group included as random effects, factors associated with the cross-contamination of cattle hides were identified. Transport to the slaughterhouse by a commercial hauler had a borderline-significant association with increased odds of an animal having a cross-contaminated hide (odds ratio [OR] [95% confidence interval {CI}] = 5.7 [0.99, 33.0];
P
= 0.05). At the slaughterhouse, providing hay to cattle waiting in lairage (OR [95% CI] = 0.04 [<0.01, 1.04];
P
= 0.05) and cleaning the landing area (OR [95% CI] = 0.03 [<0.01, 1.15,];
P
= 0.06) also had a borderline-significant association with decreased odds of an animal having a cross-contaminated hide. Although the prevalence of carcass contamination remains very low, targeted intervention at the preslaughter stage may have the potential to reduce further the risk to public health.
Extensive Genome Rearrangements and Multiple Horizontal Gene Transfers in a Population of
Pyrococcus
Isolates from Vulcano Island, Italy
Authors: White James R. , Escobar-Paramo Patricia , Mongodin Emmanuel F. , Nelson Karen E. , DiRuggiero Jocelyne 
Published: August 2008

ABSTRACT

The extent of chromosome rearrangements in
Pyrococcus
isolates from marine hydrothermal vents in Vulcano Island, Italy, was evaluated by high-throughput genomic methods. The results illustrate the dynamic nature of the genomes of the genus
Pyrococcus
and raise the possibility of a connection between rapidly changing environmental conditions and adaptive genomic properties.
Identification and Characterization of Lactococcal-Prophage-Carried Superinfection Exclusion Genes
Authors: Mahony Jennifer , McGrath Stephen , Fitzgerald Gerald F. , van Sinderen Douwe 
Published: August 2008

ABSTRACT

Superinfection exclusion (Sie) proteins are prophage-encoded phage resistance systems. In this study, genes encoding Sie systems were identified on the genomes of
Lactococcus lactis
subsp.
cremoris
MG1363 and
L. lactis
subsp.
lactis
IL1403. These Sie systems are genetically distinct and yet were shown to act specifically against a particular subset of the 936 phage group. Each of the systems allows normal phage adsorption while affecting plasmid transduction and intracellular phage DNA replication, which points to the blocking of phage DNA injection as their common mode of action. Sie-specifying genes found on the MG1363 prophages are also present in various lactococcal strains, whereas the prophage-encoded Sie systems of IL1403 do not appear to be as widely disseminated.
Genetic Structure and Aggressiveness of
Erysiphe necator
Populations during Grapevine Powdery Mildew Epidemics
Authors: Montarry Josselin , Cartolaro Philippe , Delmotte François , Jolivet Jérôme , Willocquet Laetitia 
Published: August 2008

ABSTRACT

Isolates of the causal ascomycete of grapevine powdery mildew,
Erysiphe necator
, correspond to two genetically differentiated groups (A and B) that coexist on the same host. This coexistence was analyzed by investigating temporal changes in the genetic and phenotypic structures of
E. necator
populations during three epidemics. Group A was present only at the start of the growing season, whereas group B was present throughout all three epidemics. Group A was less aggressive in terms of germination and infection efficiency but was more aggressive than group B in terms of the latency period, lesion diameter, and spore production. Our results are consistent with a temporal differentiation of niches, preventing recombination, and suggest an association between the disease level and the frequencies of genetic groups.
Genetic Tools for Studying
Capnocytophaga canimorsus
Authors: Mally Manuela , Cornelis Guy R. 
Published: August 2008

ABSTRACT

Capnocytophaga canimorsus
, a commensal bacterium from canine oral flora, has been isolated throughout the world from severe human infections caused by dog bites. Due to the low level of evolutionary relationship to
Proteobacteria
, genetic methods suitable for the genus
Capnocytophaga
needed to be established. Here, we show that Tn
4351
, derived from
Bacteroides fragilis
, could be introduced by conjugation into
C. canimorsus
and conferred resistance to erythromycin. By mapping and sequencing a naturally occurring plasmid isolated from a clinical isolate of
C. canimorsus
, we identified a
repA
gene that allowed us to construct
Escherichia coli-Capnocytophaga
shuttle vectors. Most commonly used antibiotic markers were not functional in
C. canimorsus
, but cefoxitin (
cfxA
), tetracycline (
tetQ
), and erythromycin (
ermF
) resistances could be used as markers for plasmid maintenance in
C. canimorsus
and even in some other
Capnocytophaga
spp. Shuttle vectors were introduced into
C. canimorsus
either by conjugation using the origin of transfer (
oriT
) of RP4 or by electrotransformation. Taking advantage of the promoter of
ermF
, an expression vector was constructed. Finally, a method that allows site-directed mutagenesis is described. All these genetic tools pave the way, not only for molecular studies of the pathogenesis of
C. canimorsus
, but also for studies of other oral
Capnocytophaga
species.
The Deep-Sea Bacterium
Photobacterium profundum
SS9 Utilizes Separate Flagellar Systems for Swimming and Swarming under High-Pressure Conditions
Authors: Eloe Emiley A. , Lauro Federico M. , Vogel Rudi F. , Bartlett Douglas H. 
Published: August 2008

ABSTRACT

Motility is a critical function needed for nutrient acquisition, biofilm formation, and the avoidance of harmful chemicals and predators. Flagellar motility is one of the most pressure-sensitive cellular processes in mesophilic bacteria; therefore, it is ecologically relevant to determine how deep-sea microbes have adapted their motility systems for functionality at depth. In this study, the motility of the deep-sea piezophilic bacterium
Photobacterium profundum
SS9 was investigated and compared with that of the related shallow-water piezosensitive strain
Photobacterium profundum
3TCK, as well as that of the well-studied piezosensitive bacterium
Escherichia coli
. The SS9 genome contains two flagellar gene clusters: a polar flagellum gene cluster (PF) and a putative lateral flagellum gene cluster (LF). In-frame deletions were constructed in the two flagellin genes located within the PF cluster (
flaA
and
flaC
), the one flagellin gene located within the LF cluster (
flaB
), a component of a putative sodium-driven flagellar motor (
motA2
), and a component of a putative proton-driven flagellar motor (
motA1
). SS9 PF
flaA
,
flaC
, and
motA2
mutants were defective in motility under all conditions tested. In contrast, the
flaB
and
motA1
mutants were defective only under conditions of high pressure and high viscosity.
flaB
and
motA1
gene expression was strongly induced by elevated pressure plus increased viscosity. Direct swimming velocity measurements were obtained using a high-pressure microscopic chamber, where increases in pressure resulted in a striking decrease in swimming velocity for
E. coli
and a gradual reduction for 3TCK which proceeded up to 120 MPa, while SS9 increased swimming velocity at 30 MPa and maintained motility up to a maximum pressure of 150 MPa. Our results indicate that
P. profundum
SS9 possesses two distinct flagellar systems, both of which have acquired dramatic adaptations for optimal functionality under high-pressure conditions.
Bacteriophages Reduce Experimental Contamination of Hard Surfaces, Tomato, Spinach, Broccoli, and Ground Beef by
Escherichia coli
O157:H7
Authors: Abuladze Tamar , Li Manrong , Menetrez Marc Y. , Dean Timothy , Senecal Andre , Sulakvelidze Alexander 
Published: August 2008

ABSTRACT

A bacteriophage cocktail (designated ECP-100) containing three
Myoviridae
phages lytic for
Escherichia coli
O157:H7 was examined for its ability to reduce experimental contamination of hard surfaces (glass coverslips and gypsum boards), tomato, spinach, broccoli, and ground beef by three virulent strains of the bacterium. The hard surfaces and foods contaminated by a mixture of three
E. coli
O157:H7 strains were treated with ECP-100 (test samples) or sterile phosphate-buffered saline buffer (control samples), and the efficacy of phage treatment was evaluated by comparing the number of viable
E. coli
organisms recovered from the test and control samples. Treatments (5 min) with the ECP-100 preparation containing three different concentrations of phages (10
10
, 10
9
, and 10
8
PFU/ml) resulted in statistically significant reductions (
P =
<0.05) of 99.99%, 98%, and 94%, respectively, in the number of
E. coli
O157:H7 organisms recovered from the glass coverslips. Similar treatments resulted in reductions of 100%, 95%, and 85%, respectively, in the number of
E. coli
O157:H7 organisms recovered from the gypsum board surfaces; the reductions caused by the two most concentrated phage preparations were statistically significant. Treatment with the least concentrated preparation that elicited significantly less contamination of the hard surfaces (i.e., 10
9
PFU/ml) also significantly reduced the number of viable
E. coli
O157:H7 organisms on the four food samples. The observed reductions ranged from 94% (at 120 ± 4 h posttreatment of tomato samples) to 100% (at 24 ± 4 h posttreatment of spinach samples). The data suggest that naturally occurring bacteriophages may be useful for reducing contamination of various hard surfaces, fruits, vegetables, and ground beef by
E. coli
O157:H7.
TOR1 and TOR2 Have Distinct Locations in Live Cells
Authors: Sturgill Thomas W. , Cohen Adiel , Diefenbacher Melanie , Trautwein Mark , Martin Dietmar E. , Hall Michael N. 
Published: August 2008

ABSTRACT

TOR is a structurally and functionally conserved Ser/Thr kinase found in two multiprotein complexes that regulate many cellular processes to control cell growth. Although extensively studied, the localization of TOR is still ambiguous, possibly because endogenous TOR in live cells has not been examined. Here, we examined the localization of green fluorescent protein (GFP) tagged, endogenous TOR1 and TOR2 in live
S. cerevisiae
cells. A DNA cassette encoding three copies of green fluorescent protein (3XGFP) was inserted in the
TOR1
gene (at codon D330) or the
TOR2
gene (at codon N321). The TORs were tagged internally because TOR1 or TOR2 tagged at the N or C terminus was not functional. The
TOR1
D330-3XGFP
strain was not hypersensitive to rapamycin, was not cold sensitive, and was not resistant to manganese toxicity caused by the loss of Pmr1, all indications that TOR1-3XGFP was expressed and functional. TOR2-3XGFP was functional, as
TOR2
is an essential gene and
TOR2
N321-3XGFP
haploid cells were viable. Thus, TOR1 and TOR2 retain function after the insertion of 748 amino acids in a variable region of their noncatalytic domain. The localization patterns of TOR1-3XGFP and TOR2-3XGFP were documented by imaging of live cells. TOR1-3XGFP was diffusely cytoplasmic and concentrated near the vacuolar membrane. The TOR2-3XGFP signal was cytoplasmic but predominately in dots at the plasma membrane. Thus, TOR1 and TOR2 have distinct localization patterns, consistent with the regulation of cellular processes as part of two different complexes.
Copper Distributed by Atx1 Is Available to Copper Amine Oxidase 1 in
Schizosaccharomyces pombe
Authors: Peter Chardeen , Laliberté Julie , Beaudoin Jude , Labbé Simon 
Published: August 2008

ABSTRACT

Copper amine oxidases (CAOs) have been proposed to be involved in the metabolism of xenobiotic and biogenic amines. The requirement for copper is absolute for their activity. In the fission yeast
Schizosaccharomyces pombe
,
cao1

+

and
cao2

+

genes are predicted to encode members of the CAO family. While both genes are expressed in wild-type cells, we determined that the expression of only
cao1

+

but not
cao2

+

results in the production of an active enzyme. Site-directed mutagenesis identified three histidine residues within the C-terminal region of Cao1 that are necessary for amine oxidase activity. By use of a
cao1

+

-
GFP
allele that retained wild-type function, Cao1-GFP was localized in the cytosol (GFP is green fluorescent protein). Under copper-limiting conditions, disruption of
ctr4

+

,
ctr5

+

, and
cuf1

+

produced a defect in amine oxidase activity, indicating that a functionally active Cao1 requires Ctr4/5-mediated copper transport and the transcription factor Cuf1. Likewise,
atx1
null cells exhibited substantially decreased levels of amine oxidase activity. In contrast, deletion of
ccc2
,
cox17
, and
pccs
had no significant effect on Cao1 activity. Residual amine oxidase activity in cells lacking
atx1

+

can be restored to normal levels by returning an
atx1

+

allele, underscoring the critical importance of the presence of Atx1 in cells. Using two-hybrid analysis, we demonstrated that Cao1 physically interacts with Atx1 and that this association is comparable to that of Atx1 with the N-terminal region of Ccc2. Collectively, these results describe the first example of the ability of Atx1 to act as a copper carrier for a molecule other than Ccc2 and its critical role in delivering copper to Cao1.
Trade-Off between Iron Uptake and Protection against Oxidative Stress: Deletion ofcueOPromotes UropathogenicEscherichia coliVirulence in a Mouse Model of Urinary Tract Infection
Authors: Tree Jai J. , Ulett Glen C. , Ong Cheryl-Lynn Y. , Trott Darren J. , McEwan Alastair G. , Schembri Mark A. 
Published: August 2008

ABSTRACTThe periplasmic multicopper oxidase (CueO) is involved in copper homeostasis and protection against oxidative stress. Here, we show that the deletion ofcueOin uropathogenicEscherichia coliincreases its colonization of the urinary tract despite its increased sensitivity to hydrogen peroxide. ThecueOdeletion mutant accumulated iron with increased efficiency compared to its parent strain; this may account for its advantage in the iron-limited environment of the urinary tract.
ESAT-6-Like Protein Secretion inBacillus anthracis
Authors: Garufi Gabriella , Butler Emily , Missiakas Dominique 
Published: August 2008

ABSTRACTProteins of the WXG100 family represent the prototypical substrates of bacterial type VII secretion systems that typically encompass 100 residues, lack canonical signal peptides, and form helix-turn-helix hairpin structures with WXG positioned in the turn element.Bacillus anthracisencodes six WXG100 proteins, herein referred to as EsxB, EsxL, EsxP, EsxQ, EsxV, and EsxW. With the exception of EsxB,B. anthracisproteins harbor C-terminal extensions that are appended to canonical WXG domains. When cultured in liquid broth,B. anthracissecretes two substrates, EsxB and EsxW, into the extracellular environment. EsxB is required for the stability and secretion of EsxW; however, EsxW is dispensable for EsxB secretion. In agreement with the hypothesis that EsxB binding to substrates promotes recognition and secretion by the type VII pathway, EsxB is reported to interact with EsxB and EsxW. Unlike deletions in mycobacterial EsxB, deletion of five N- or C-terminal residues does not affect the ability of mutantB. anthracisEsxB to travel the type VII pathway and initiate secretion of EsxW. Translational fusion of ubiquitin to the N or C terminus of EsxB also had no effect, while ubiquitin insertion into the center turn abrogated secretion. Anthrax-infected guinea pigs mounted humoral immune responses to EsxB, EsxP, and EsxW, which suggests thatB. anthracisactivates the type VII secretion pathway during infection.