bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaginismus and Dyspareunia: Automatic vs. Deliberate Disgust Responsivity
Authors: Borg Charmaine , de Jong Peter J. , Schultz Willibrord Weijmar 
Published: March 2010

ABSTRACT

Introduction
The difficulty of penetration experienced in vaginismus and dyspareunia may at least partly be due to a disgust-induced defensive response.

Aims
To examine if sex stimuli specifically elicit: (i) automatic disgust-related memory associations; (ii) physiological disgust responsivity; and/or (iii) deliberate expression of disgust/threat.

Methods
Two single target Implicit Association Task (st-IAT) and electromyography (EMG) were conducted on three groups: vaginismus (N=24), dyspareunia (N=24), and control (N=31) group.

Main Outcome Measures
st-IAT, to index their initial disgust-related associations and facial EMG for the m. levator labii and m. corrugator supercilii regions.

Results
Both clinical groups showed enhanced automatic sex-disgust associations. As a unique physiological expression of disgust, the levator activity was specifically enhanced for the vaginismus group, when exposed to a women-friendly SEX video clip. Also at the deliberate level, specifically the vaginismus group showed enhanced subjective disgust toward SEX pictures and the SEX clip, along with higher threat responses.

Conclusions
Supporting the view that disgust is involved in vaginismus and dyspareunia, for both, clinical groups’ sex stimuli automatically elicited associations with disgust. Particularly for the vaginismus group, these initial disgust associations persisted during subsequent validation processes and were also evident at the level of facial expression and self-report data. Findings are consistent with the notion that uncontrollable activated associations are involved in eliciting defensive reactions at the prospect of penetration seen in both conditions. Whereas deliberate attitudes, usually linked with the desire for having intercourse, possibly generate the distinction (e.g., severity) between these two conditions.
The discovery of two new rapidly oscillating Ap stars, HD92499 and HD143487
Authors: Elkin V. G. , Kurtz D. W. , Mathys G. , Freyhammer L. M. 
Published: March 2010

Abstract
We report the discovery of short periodic radial velocity variations in the stars HD92499 and HD143487. Both stars show strong magnetic fields and large overabundances of rare earth elements and belong to the class of cool chemically peculiar stars of the main sequence. They are therefore new rapidly oscillating Ap stars. Pulsations were detected from analysis of high time resolution spectra obtained with the European Southern Observatory Very Large Telescope by using a cross-correlation method for large spectral bands and from combinations of lines belonging to rare earth elements. The amplitudes of the pulsations are small and do not exceed several dozens of ms−1 with periods of around 10min. The detection of such low amplitudes is important for the determination of which magnetic Ap stars pulsate, and which are constant, a distinction important for the understanding of the pulsation driving mechanism in these stars.
Assessment of apparent losses in urban water systems
Authors: Mutikanga H. E. , Sharma S. K. , Vairavamoorthy K. 
Published: March 2010

AbstractApparent losses relate to water that is consumed but not paid for. Most research carried out in the last decade particularly in the United Kingdom focused mainly on leakage. Until now, there are no set procedures and guidelines for assessment of apparent losses. Much work remains to bring it to par with the available tools and methodologies for leakage management. In the absence of adequate data and proper methodology, most developed countries use default values, which tend to be lowest values for well‐managed water systems, for computation of apparent losses. These may not be appropriate for developing countries. This paper presents a methodology for the assessment of different components of apparent losses based on field audit and operational data for Kampala city's water distribution system in Uganda. Metering inaccuracies and illegal use have been found to be significant components of apparent losses. Appropriate intervention strategies have been developed based on the assessment.
Oxidation of gasoline oxygenates by closely related non‐haem‐iron alkane hydroxylases in Pseudomonas mendocina KR1 and other n‐octane‐utilizing Pseudomonas strains
Authors: Smith Christy A. , Hyman Michael R. 
Published: March 2010

Summary Pseudomonas mendocina KR1 oxidizes the gasoline oxygenate methyl tertiary butyl ether (MTBE) to tertiary butyl alcohol (TBA) during growth on C5–C8n‐alkanes. We have further explored oxidation of ether oxygenates by this strain to help identify the enzyme that catalyses these reactions. High levels of MTBE‐oxidizing activity occurred in resting cells grown on C5–C8n‐alkanes. Lower activities occurred in cells grown on longer‐chain n‐alkanes (C9–C11) and 1°‐alcohols (C5–C10). N‐octane‐grown cells also oxidized tertiary amyl methyl ether (TAME) to tertiary amyl alcohol (TAA), but did not oxidize ethyl tertiary butyl ether (ETBE), TBA or TAA. A 39 kDa polypeptide in whole cell extracts of n‐octane‐grown cells strongly cross‐reacted with an anti‐AlkB polyclonal antiserum in an SDS‐PAGE/immunoblot. This polypeptide was absent or less abundant in cells grown on dextrose, dextrose plus dicyclopropylketone or 1‐octanol. N‐octane‐grown cells of Pseudomonas aeruginosa strains KSLA‐473 and ATCC 17423 oxidized MTBE and TAME but not ETBE. N‐hexadecane‐grown cells of these strains and strain PAO1 did not oxidize any of the oxygenates tested. Our results indicate ether oxygenate‐degrading activity in alkane‐utilizing pseudomonads is consistently observed with close homologues of the GPo1 non‐haem‐iron alkane hydroxylases but is otherwise not a consistent catalytic feature of these diverse enzymes.
ramR
Mutations in Clinical Isolates of
Klebsiella pneumoniae
with Reduced Susceptibility to Tigecycline
Authors: Hentschke M. , Wolters M. , Sobottka I. , Rohde H. , Aepfelbacher M. 
Published: March 2010

ABSTRACT

Five
Klebsiella pneumoniae
isolates with reduced susceptibility to tigecycline (MIC, 2 μg/ml) were analyzed. A gene homologous to
ramR
of
Salmonella enterica
was identified in
Klebsiella pneumoniae
. Sequencing of
ramR
in the nonsusceptible
Klebsiella
strains revealed deletions, insertions, and point mutations. Transformation of mutants with wild-type
ramR
genes, but not with mutant
ramR
genes, restored susceptibility to tigecycline and repressed overexpression of
ramA
and
acrB
. Thus, this study reveals a molecular mechanism for tigecycline resistance in
Klebsiella pneumoniae
.
Role ofpfmdr1Amplification and Expression in Induction of Resistance to Artemisinin Derivatives inPlasmodium falciparum
Authors: Chavchich Marina , Gerena Lucia , Peters Jennifer , Chen Nanhua , Cheng Qin , Kyle Dennis E. 
Published: March 2010

ABSTRACTArtemisinin and its derivatives are the most rapidly acting and efficacious antimalarial drugs currently available. Although resistance to these drugs has not been documented, there is growing concern about the potential for resistance to develop. In this paper we report the selection of parasite resistance to artelinic acid (AL) and artemisinin (QHS)in vitroand the molecular changes that occurred during the selection. Exposure of threePlasmodium falciparumlines (W2, D6, and TM91C235) to AL resulted in decreases in parasite susceptibilities to AL and QHS, as well as to mefloquine, quinine, halofantrine, and lumefantrine. The changes in parasite susceptibility were accompanied by increases in the copy number, mRNA expression, and protein expression of thepfmdr1gene in the resistant progenies of W2 and TM91C235 parasites but not in those of D6 parasites. No changes were detected in the coding sequences of thepfmdr1,pfcrt,pfatp6,pftctp, andpfubcthgenes or in the expression levels ofpfatp6andpftctp. Our data demonstrate thatP. falciparumlines have the capacity to develop resistance to artemisinin derivativesin vitroand that this resistance is achieved by multiple mechanisms, to include amplification and increased expression ofpfmdr1, a mechanism that also confers resistance to mefloquine. This observation is of practical importance, because artemisinin drugs are often used in combination with mefloquine for the treatment of malaria.
Safety and Pharmacokinetics of Single Intravenous Dose of MGAWN1, a Novel Monoclonal Antibody to West Nile Virus
Authors: Beigel John H. , Nordstrom Jeffrey L. , Pillemer Stanley R. , Roncal Cory , Goldwater D. Ronald , Li Hua , Holland P. Chris , Johnson Syd , Stein Kathryn , Koenig Scott 
Published: March 2010

ABSTRACT

West Nile Virus (WNV) is a neurotropic flavivirus that can cause debilitating diseases, such as encephalitis, meningitis, or flaccid paralysis. We report the safety, pharmacokinetics, and immunogenicity of a recombinant humanized monoclonal antibody (MGAWN1) targeting the E protein of WNV in a phase 1 study, the first to be performed on humans. A single intravenous infusion of saline or of MGAWN1 at escalating doses (0.3, 1, 3, 10, or 30 mg/kg of body weight) was administered to 40 healthy volunteers (30 receiving MGAWN1; 10 receiving placebo). Subjects were evaluated on days 0, 1, 3, 7, 14, 21, 28, 42, 56, 91, 120, and 180 by clinical assessments, clinical laboratory studies, electrocardiograms (ECGs), and pharmacokinetic and immunogenicity assays. All 40 subjects tolerated the infusion of the study drug, and 39 subjects completed the study. One serious adverse event of schizophrenia occurred in the 0.3-mg/kg cohort. One grade 3 neutropenia occurred in the 3-mg/kg cohort. Six MGAWN1-treated subjects experienced 11 drug-related adverse events, including diarrhea (1 subject), chest discomfort (1), oral herpes (1), rhinitis (1), neutropenia (2), leukopenia (1), dizziness (1), headache (2), and somnolence (1). In the 30-mg/kg cohort, MGAWN1 had a half-life of 26.7 days and a maximum concentration in serum (
C
max
) of 953 μg/ml. This study suggests that single infusions of MGAWN1 up to 30 mg/kg appear to be safe and well tolerated in healthy subjects. The
C
max
of 953 μg/ml exceeds the target level in serum estimated from hamster studies by 28-fold and should provide excess WNV neutralizing activity and penetration into the brain and cerebrospinal fluid (CSF). Further evaluation of MGAWN1 for the treatment of West Nile virus infections is warranted.
Effect of Vicriviroc on the QT/Corrected QT Interval and Central Nervous System in Healthy Subjects
Authors: O'Mara Edward , Kasserra Claudia , Huddlestone John Robert , Wan Yuntao , Soni Peter , Caceres Maria , Medlock Matthew , Morrison Royce , Devinsky Orrin 
Published: March 2010

ABSTRACT
Vicriviroc is a CCR5 antagonist in clinical development for the treatment of HIV-1. Two phase I studies were conducted to assess the safety of vicriviroc. One study characterized the drug's potential to prolong the QT/corrected QT (QTc) interval and to induce arrhythmia. In this partially blind, parallel-group study, 200 healthy subjects aged 18 to 50 years were randomized in equal groups to the following regimens: (i) placebo for 9 days and a single dose of moxifloxacin at 400 mg on day 10, (ii) placebo, (iii) vicriviroc-ritonavir (30 and 100 mg), (iv) vicriviroc-ritonavir (150 and 100 mg), and (v) ritonavir (100 mg). The second study characterized the effects of a range of vicriviroc doses on the central nervous system (CNS). In this third-party-blind, parallel-group study, 30 healthy subjects aged 18 to 48 years were randomized to receive a single dose of either vicriviroc at 200, 250, or 300 mg or placebo, followed by multiple (seven) once-daily doses of either vicriviroc at 150, 200, or 250 mg or placebo, respectively. In the first study, vicriviroc produced no clinically meaningful effect on the QT/QTc interval when administered at a supratherapeutic or therapeutic dose concurrently with ritonavir. In the second study, vicriviroc produced no observable seizure activity, nor was it held to be associated with any clinically relevant changes in brain waveforms in the final consensus of reviewers. These findings showed that vicriviroc produced no clinically relevant QTc prolongation cardiac or epileptogenic effects in healthy individuals at exposures as high as five times those expected for HIV-infected patients receiving therapeutic doses of vicriviroc in a ritonavir-boosted protease inhibitor-containing regimen.
Preclinical Evaluation of the Antifolate QN254, 5-Chloro-N′6′-(2,5-Dimethoxy-Benzyl)-Quinazoline-2,4,6-Triamine, as an Antimalarial Drug Candidate
Authors: Nzila Alexis , Rottmann Matthias , Chitnumsub Penchit , Kiara Stevens M. , Kamchonwongpaisan Sumalee , Maneeruttanarungroj Cherdsak , Taweechai Supannee , Yeung Bryan K. S. , Goh Anne , Lakshminarayana Suresh B. , Zou Bin , Wong Josephine , Ma Ngai Ling , Weaver Margaret , Keller Thomas H. , Dartois Veronique , Wittlin Sergio , Brun Reto , Yuthavong Yongyuth , Diagana Thierry T. 
Published: March 2010

ABSTRACTDrug resistance against dihydrofolate reductase (DHFR) inhibitors—such as pyrimethamine (PM)—has now spread to almost all regions where malaria is endemic, rendering antifolate-based malaria treatments highly ineffective. We have previously shown that the di-amino quinazoline QN254 [5-chloro-N′6′-(2,5-dimethoxy-benzyl)-quinazoline-2,4,6-triamine] is active against the highly PM-resistantPlasmodium falciparumV1S strain, suggesting that QN254 could be used to treat malaria in regions with a high prevalence of antifolate resistance. Here, we further demonstrate that QN254 is highly active againstPlasmodium falciparumclinical isolates, displaying various levels of antifolate drug resistance, and we provide biochemical and structural evidence that QN254 binds and inhibits the function of both the wild-type and the quadruple-mutant (V1S) forms of the DHFR enzyme. In addition, we have assessed QN254 oral bioavailability, efficacy, and safetyin vivo. The compound displays favorable pharmacokinetic properties after oral administration in rodents. The drug was remarkably efficacious againstPlasmodium bergheiand could fully cure infected mice with three daily oral doses of 30 mg/kg. In the course of these efficacy studies, we have uncovered some dose limiting toxicity at higher doses that was confirmed in rats. Thus, despite its relativein vitroselectivity toward thePlasmodiumDHFR enzyme, QN254 does not show the adequate therapeutic index to justify its further development as a single agent.
Molecular Epidemiology, Sequence Types, and Plasmid Analyses of KPC-Producing
Klebsiella pneumoniae
Strains in Israel
Authors: Leavitt Azita , Carmeli Yehuda , Chmelnitsky Inna , Goren Moran G. , Ofek Itzhak , Navon-Venezia Shiri 
Published: March 2010

ABSTRACT

Sporadic isolates of carbapenem-resistant KPC-2-producing
Klebsiella pneumoniae
were isolated in Tel Aviv Medical Center during 2005 and 2006, parallel to the emergence of the KPC-3-producing
K. pneumoniae
sequence type 258 (ST 258). We aimed to study the molecular epidemiology of these isolates and to characterize their
bla
KPC
-carrying plasmids and their origin. Ten isolates (8 KPC-2 and 2 KPC-3 producing) were studied. All isolates were extremely drug resistant. They possessed the
bla
KPC
gene and varied in their additional beta-lactamase contents. The KPC-2-producing strains belonged to three different sequence types: ST 340 (
n
= 2), ST 277 (
n
= 2), and a novel sequence type, ST 376 (
n
= 4). Among KPC-3-producing strains, a single isolate (ST 327) different from ST 258 was identified, but both strains carried the same plasmid (pKpQIL). The KPC-2-encoding plasmids varied in size (45 to 95 kb) and differed among each of the STs. Two of the
Klebsiella bla
KPC-2
-carrying plasmids were identical to plasmids from
Escherichia coli
, suggesting a common origin of these plasmids. These data indicate that KPC evolution in
K. pneumoniae
is related to rare events of interspecies spread of
bla
KPC-2
-carrying plasmids from
E. coli
followed by limited clonal spread, whereas KPC-3 carriage in this species is related almost strictly to clonal expansion of ST 258 carrying pKpQIL.
Mitogen-Activated Protein Kinase Phosphatase 2 Regulates the Inflammatory Response in Sepsis
Authors: Cornell Timothy T. , Rodenhouse Paul , Cai Qing , Sun Lei , Shanley Thomas P. 
Published: March 2010

ABSTRACT

Sepsis results from a dysregulation of the regulatory mechanisms of the pro- and anti-inflammatory response to invading pathogens. The mitogen-activated protein (MAP) kinase cascades are key signal transduction pathways involved in the cellular production of cytokines. The dual-specific phosphatase 1 (DUSP 1), mitogen-activated protein kinase phosphatase-1 (MKP-1), has been shown to be an important negative regulator of the inflammatory response by regulating the p38 and Jun N-terminal protein kinase (JNK) MAP kinase pathways to influence pro- and anti-inflammatory cytokine production. MKP-2, also a dual-specific phosphatase (DUSP 4), is a phosphatase highly homologous with MKP-1 and is known to regulate MAP kinase signaling; however, its role in regulating the inflammatory response is not known. We hypothesized a regulatory role for MKP-2 in the setting of sepsis. Mice lacking the MKP-2 gene had a survival advantage over wild-type mice when challenged with intraperitoneal lipopolysaccharide (LPS) or a polymicrobial infection via cecal ligation and puncture. The MKP-2
−/−
mice also exhibited decreased serum levels of both pro-inflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-1β [IL-1β], IL-6) and anti-inflammatory cytokines (IL-10) following endotoxin challenge. Isolated bone marrow-derived macrophages (BMDMs) from MKP-2
−/−
mice showed increased phosphorylation of the extracellular signal-regulated kinase (ERK), decreased phosphorylation of JNK and p38, and increased induction of MKP-1 following LPS stimulation. The capacity for cytokine production increased in MKP-2
−/−
BMDMs following MKP-1 knockdown. These data support a mechanism by which MKP-2 targets ERK deactivation, thereby decreasing MKP-1 and thus removing the negative inhibition of MKP-1 on cytokine production.
Genome-Wide Transposon Mutagenesis Reveals a Role for pO157 Genes in Biofilm Development in
Escherichia coli
O157:H7 EDL933
Authors: Puttamreddy Supraja , Cornick Nancy A. , Minion F. Chris 
Published: March 2010

ABSTRACT

Enterohemorrhagic
Escherichia coli
O157:H7, a world-wide human food-borne pathogen, causes mild to severe diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome. The ability of this pathogen to persist in the environment contributes to its dissemination to a wide range of foods and food processing surfaces. Biofilms are thought to be involved in persistence, but the process of biofilm formation is complex and poorly understood in
E. coli
O157:H7. To better understand the genetics of this process, a mini-Tn
5
transposon insertion library was constructed in strain EDL933 and screened for biofilm-negative mutants using a microtiter plate assay. Ninety-five of 11,000 independent insertions (0.86%) were biofilm negative, and transposon insertions were located in 51 distinct genes/intergenic regions that must be involved either directly or indirectly in biofilm formation. All of the 51 biofilm-negative mutants showed reduced biofilm formation on both hydrophilic and hydrophobic surfaces. Thirty-six genes were unique to this study, including genes on the virulence plasmid pO157. The type V secreted autotransporter serine protease EspP and the enterohemolysin translocator EhxD were found to be directly involved in biofilm formation. In addition, EhxD and EspP were also important for adherence to T84 intestinal epithelial cells, suggesting a role for these genes in tissue interactions
in vivo
.
Cooperation between Multiple Microbial Pattern Recognition Systems Is Important for Host Protection against the Intracellular PathogenLegionella pneumophila
Authors: Archer Kristina A. , Ader Florence , Kobayashi Koichi S. , Flavell Richard A. , Roy Craig R. 
Published: March 2010

ABSTRACTMultiple pattern recognition systems have been shown to initiate innate immune responses to microbial pathogens. The degree to which these detection systems cooperate with each other to provide host protection is unknown. Here, we investigated the importance of several immune surveillance pathways in protecting mice against lethal infection by the intracellular pathogenLegionella pneumophila, the causative agent of a severe pneumonia called Legionnaires' disease. Rip2 and Naip5/NLRC4 signaling was found to contribute to the innate immune response generated againstL. pneumophilain the lung. Elimination of Rip2 or Naip5/NLRC4 signaling in MyD88-deficient mice resulted in increased replication and dissemination ofL. pneumophilaand higher rates of mortality. Irradiated wild-type mice receiving bone marrow cells from pattern recognition receptor-deficient mice displayedL. pneumophilainfection phenotypes similar to those of donor mice. Rip2 and Naip5/NLRC4 signaling provided additive effects in protecting MyD88-deficient mice from lethal infection byL. pneumophila, with the contribution of Naip5/NLRC4 being slightly greater than that of Rip2. Thus, activation of the Rip2, MyD88, and Naip5/NLRC4 signaling pathways triggers a coordinated and synergistic response that protects the host against lethal infection byL. pneumophila. These data provide new insight into how different pattern recognition systems interact functionally to generate innate immune responses that protect the host from lethal infection by activating cellular pathways that restrict intracellular replication ofL. pneumophilaand by recruiting to the site of infection additional phagocytes that eliminate extracellular bacteria.
Global Transcriptional Response of Macrophage-Like THP-1 Cells to Shiga Toxin Type 1
Authors: Leyva-Illades Dinorah , Cherla Rama P. , Galindo Cristi L. , Chopra Ashok K. , Tesh Vernon L. 
Published: March 2010

ABSTRACTShiga toxins (Stxs) are bacterial cytotoxins produced by the enteric pathogensShigella dysenteriaeserotype 1 and some serotypes ofEscherichia colithat cause bacillary dysentery and hemorrhagic colitis, respectively. To date, approaches to studying the capacity of Stxs to alter gene expression in intoxicated cells have been limited to individual genes. However, it is known that many of the signaling pathways activated by Stxs regulate the expression of multiple genes in mammalian cells. To expand the scope of analysis of gene expression and to better understand the underlying mechanisms for the various effects of Stxs on host cell functions, we carried out comparative microarray analyses to characterize the global transcriptional response of human macrophage-like THP-1 cells to Shiga toxin type 1 (Stx1) and lipopolysaccharides. The data were analyzed by using a rigorous combinatorial approach with three separate statistical algorithms. A total of 36 genes met the criteria of upregulated expression in response to Stx1 treatment, with 14 genes uniquely upregulated by Stx1. Microarray data were validated by real-time reverse transcriptase PCR for genes encoding early growth response 1 (Egr-1) (transcriptional regulator), cyclooxygenase 2 (COX-2; inflammation), and dual specificity phosphatase 1 (DUSP1), DUSP5, and DUSP10 (regulation of mitogen-activated protein kinase signaling). Stx1-mediated signaling through extracellular signal-regulated kinase 1/2 and Egr-1 appears to be involved in the increased expression and production of the proinflammatory mediator tumor necrosis factor alpha. Activation of COX-2 is associated with the increased production of proinflammatory and vasoactive eicosanoids. However, the capacity of Stx1 to increase the expression of genes encoding phosphatases suggests that mechanisms to dampen the macrophage proinflammatory response may be built into host response to the toxins.