bluuebunny/crossref_metadata_2025_split huggingface dataset:
First Outbreak of a Plasmid-Mediated Carbapenem-Hydrolyzing OXA-48 β-Lactamase in Klebsiella pneumoniae in Spain
Authors: Pitart Cristina , Solé Mar , Roca Ignasi , Fàbrega Anna , Vila Jordi , Marco Francesc 
Published: July 2011

ABSTRACT

Twenty
Klebsiella pneumoniae
isolates producing OXA-48 were collected from April 2009 to September 2010. Strains were clonally related and coproduced a CTX-M-15 β-lactamase. A conjugative plasmid of circa 70 kb carrying
bla
OXA-48
was identified. Eleven isolates showed low-level resistance to carbapenems, whereas nine showed high-level resistance. Decreased expression of OmpK36 was related to high-level resistance to carbapenems. The isolates belonged to sequence type 101 (ST101). This is the first outbreak caused by an OXA-48-producing
K. pneumoniae
strain in Spain.
Sublethal Triclosan Exposure Decreases Susceptibility to Gentamicin and Other Aminoglycosides in Listeria monocytogenes
Authors: Christensen Ellen G. , Gram Lone , Kastbjerg Vicky G. 
Published: July 2011

ABSTRACT

The human food-borne pathogen
Listeria monocytogenes
is capable of persisting in food processing plants despite cleaning and sanitation and is likely exposed to sublethal biocide concentrations. This could potentially affect susceptibility of the bacterium to biocides and other antimicrobial agents. The purpose of the present study was to determine if sublethal biocide concentrations affected antibiotic susceptibility in
L. monocytogenes
. Exposure of
L. monocytogenes
strains EGD and N53-1 to sublethal concentrations of Incimaxx DES (containing peroxy acids and hydrogen peroxide) and Triquart Super (containing quaternary ammonium compound) in four consecutive cultures did not alter the frequency of antibiotic-tolerant isolates, as determined by plating on 2× the MIC for a range of antibiotics. Exposure of eight strains of
L. monocytogenes
to 1 and 4 μg/ml triclosan did not alter triclosan sensitivity. However, all eight strains became resistant to gentamicin (up to 16-fold increase in MIC) after exposure to sublethal triclosan concentrations. Gentamicin-resistant isolates of strains N53-1 and 4446 were also resistant to other aminoglycosides, such as kanamycin, streptomycin, and tobramycin. Gentamicin resistance remained at a high level also after five subcultures without triclosan or gentamicin. Aminoglycoside resistance can be caused by mutations in the target site, the 16S rRNA gene. However, such mutations were not detected in the N53-1-resistant isolates. A combination of gentamicin and ampicillin is commonly used in listeriosis treatment. The triclosan-induced resistance is, hence, of great concern. Further investigations are needed to determine the molecular mechanisms underlying the effect of triclosan.
In VitroDestruction of Streptococcus pneumoniae Biofilms with Bacterial and Phage Peptidoglycan Hydrolases
Authors: Domenech Mirian , García Ernesto , Moscoso Miriam 
Published: July 2011

ABSTRACTHost- and phage-coded cell wall hydrolases have been used to fightStreptococcus pneumoniaegrowing as planktonic cellsin vitroas well as in animal models. Until now, however, the usefulness of these enzymes in biofilm-grown pneumococci has gone untested. The antipneumococcal activity of different cell wall hydrolases produced byS. pneumoniaeand a number of its phages was examined in anin vitrobiofilm model. The major pneumococcal autolysin LytA, anN-acetylmuramoyl-l-alanine amidase, showed the greatest efficiency in disintegratingS. pneumoniaebiofilms. The phage-encoded lysozymes Cpl-1 and Cpl-7 were also very efficient. Biofilms formed by the close pneumococcal relativesStreptococcus pseudopneumoniaeandStreptococcus oraliswere also destroyed by the phage endolysins but not by theS. pneumoniaeautolysin LytA. A cooperative effect of LytA and Cpl-1 in the disintegration ofS. pneumoniaebiofilms was recorded.
Pharmacokinetic Modeling of Plasma and Intracellular Concentrations of Raltegravir in Healthy Volunteers
Authors: Wang Lingzhi , Soon Gaik Hong , Seng Kok-Yong , Li Jun , Lee Edmund , Yong Eu-Leong , Goh Boon-Cher , Flexner Charles , Lee Lawrence 
Published: July 2011

ABSTRACT

Raltegravir is a potent inhibitor of HIV integrase. Persistently high intracellular concentrations of raltegravir may explain sustained efficacy despite high pharmacokinetic variability. We performed a pharmacokinetic study of healthy volunteers. Paired blood samples for plasma and peripheral blood mononuclear cells (PBMCs) were collected predose and 4, 8, 12, 24, and 48 h after a single 400-mg dose of raltegravir. Samples of plasma only were collected more frequently. Raltegravir concentrations were determined using liquid chromatography-mass spectrometry. The lower limits of quantitation for plasma and PBMC lysate raltegravir were 2 nmol/liter and 0.225 nmol/liter, respectively. Noncompartmental analyses were performed using WinNonLin. Population pharmacokinetic analysis was performed using NONMEM. Six male subjects were included in the study; their median weight was 67.4 kg, and their median age was 33.5 years. The geometric mean (GM) (95% confidence interval shown in parentheses) maximum concentration of drug (
C
max
), area under the concentration-time curve from 0 to 12 h (AUC
0–12
), and area under the concentration-time curve from 0 h to infinity (AUC
0–∞
) for raltegravir in plasma were 2,246 (1,175 to 4,294) nM, 10,776 (5,770 to 20,126) nM · h, and 13,119 (7,235 to 23,788) nM · h, respectively. The apparent plasma raltegravir half-life was 7.8 (5.5 to 11.3) h. GM intracellular raltegravir
C
max
, AUC
0–12
, and AUC
0–∞
were 383 (114 to 1,281) nM, 2,073 (683 to 6,290) nM · h, and 2,435 (808 to 7,337) nM · h (95% confidence interval shown in parentheses). The apparent intracellular raltegravir half-life was 4.5 (3.3 to 6.0) h. Intracellular/plasma ratios were stable for each patient without significant time-related trends over 48 h. Population pharmacokinetic modeling yielded an intracellular-to-plasma partitioning ratio of 11.2% with a relative standard error of 35%. The results suggest that there is no intracellular accumulation or persistence of raltegravir in PBMCs.
Origin of OXA-181, an Emerging Carbapenem-Hydrolyzing Oxacillinase, as a Chromosomal Gene in Shewanella xiamenensis
Authors: Potron Anaïs , Poirel Laurent , Nordmann Patrice 
Published: July 2011

ABSTRACT

Plasmid-mediated carbapenem-hydrolyzing β-lactamases are becoming emerging threats with
Enterobacteriaceae
. In particular, the carbapenem-hydrolyzing class D β-lactamase OXA-48 and its derivative OXA-181 have been reported increasingly worldwide. Using a PCR-based strategy, environmental samples were screened for
bla
OXA-48
-like genes.
Shewanella xiamenensis
, an environmental species from marine and freshwater, was identified as the progenitor of the
bla
OXA-181
gene. This work identifies the reservoir of an emerging carbapenemase gene that is clinically significant.
Identification of a Novel Virulence Factor in Clostridium Difficile That Modulates Toxin Sensitivity of Cultured Epithelial Cells
Authors: Miura Masashi , Kato Haru , Matsushita Osamu 
Published: July 2011

ABSTRACT

Two glucosylating toxins named toxins A and B play a role in the pathogenesis of
Clostridium Difficile
infection. The interaction of the toxins with host cell factors proceeds to downstream stages of cytotoxic effects in cells, in which involvement of other
C. difficile
factors remains unknown. We utilized culture filtrate of
C. difficile
with a low dilution to characterize the influence of putative minor proteins on the organization of the actin cytoskeleton in cultured epithelial cells and found a previously uncharacterized F-actin aggregated structure, termed “actin aggregate,” at the juxtanuclear region. We reasoned that formation of actin aggregate was due to an additional factor(s) in the culture filtrate rather than the glucosylating toxins, because treatment of purified toxins rarely caused actin aggregate in cells. We focused on a previously uncharacterized hypothetical protein harboring a KDEL-like sequence as a candidate. The product of the candidate gene was detected in culture filtrate of
C. difficile
ATCC 9689 and was renamed Srl. Purified glutathione
S
-transferase-tagged Srl triggered formation of actin aggregate in the cells in the presence of either toxin A or B and enhanced cytotoxicity of each of the two toxins, including decreases in both cell viability and transepithelial resistance of cultured epithelial monolayer, although the recombinant Srl alone did not show detectable cytotoxicity. Srl-neutralized culture filtrate partially inhibited morphological changes of the cells in parallel with decreased actin aggregate formation in the cells. Thus, Srl might contribute to the modulation of toxin sensitivity of intestinal epithelial cells by enhancing cytotoxicity of
C. difficile
toxins.
Role of Interleukin-23-Dependent Antifungal Immune Responses in Dendritic Cell-Vaccinated Mice
Authors: Zheng Mingquan , Rapaka Rekha R. , Yu Amy C. , Shellito Judd E. , Kolls Jay K. 
Published: July 2011

ABSTRACT

CD40 ligand (CD40L) transduction of antigen-pulsed dendritic cells (DCs) can result in antigen-specific humoral immune responses even in CD4
+
T-cell-depleted settings. Here, we show that CD40L transduction of DCs results in the induction of interleukin-12p40 (IL-12p40), IL-12p70, and IL-23. Using DCs that were deficient in IL-12p40, IL-12p35, or IL-23p19, we show that these molecules are dispensable for primary IgG1 responses to
Pneumocystis
, but IgG2c was dependent on IL-12p40 and IL-23p19 but not IL-12p35. Antigen-specific recall responses in CD4-deficient mice were critically dependent on IL-12p40 and IL-23p19 expression in DCs and were not affected by the lack of IL-12p35. To confirm that this defect in recall was due to IL-23, transduction of IL-12p40
−/−
DCs with a recombinant adenovirus expressing functional IL-23 restored recall responses in DC-vaccinated CD4-deficient mice. These data show that DC-produced IL-23 is critical for vaccine-induced antigen-specific IgG2c and recall antibody responses in the setting of CD4
+
T-cell depletion.
Geology of the Chenier Plain of Cameron Parish, southwestern Louisiana
Authors: Owen Donald E. 
Published: July 2011

Abstract
The Chenier Plain of southwestern coastal Louisiana is a Holocene strand plain composed of wooded beach ridges (cheniers) and intervening mudflat grassy wetlands. The mudflats form as prograding tidal flats along the open, but low-energy Gulf of Mexico coast; cheniers form from winnowing of sand and shells from the mudflats by waves during transgression. Mudflats are deposited when a Mississippi River delta lobe is nearby to the east, and cheniers are formed when distributaries switch to a more distant location farther east. All of the cheniers have formed within approximately the past 3000 yr or less and are progressively younger toward the present coastline. Spits are attached to the cheniers at estuaries; they grow westward in response to the dominant longshore currents. Currently, mudflats are prograding in Vermillion Parish to the east, while cheniers form in eastern Cameron Parish along with some regressive beach ridge development in western Cameron Parish.
This coast is microtidal with low wave energy. A high rate of subsidence as well as sea-level rise characterizes the Chenier Plain, which is subject to increased wave energy and mud transport every year during many cold-front passages and periodic storm surges associated with tropical cyclones of much lower frequency. Major storm surges can inundate the entire Chenier Plain, wreaking havoc on human settlements.
Neogene drainage development of Marsh and Portneuf valleys, eastern Idaho
Authors: Thackray Glenn D. , Rodgers David W. , Drabick Andrew 
Published: July 2011

Abstract
Neogene drainage development in southeastern Idaho has been influenced by drainage capture, Basin and Range faulting, volcanism, and the Late Pleistocene Lake Bonneville overflow and Bonneville Flood. In Marsh Valley, the Middle to Late Pleistocene sedimentary sequence is dominated by alternating lacustrine/paludal and alluvial sediments, which have yielded new 40Ar/39Ar, amino acid racemization, and luminescence age estimates. The pattern of sedimentation through time indicates poor drainage integration of southern Marsh Valley through most of the last ca. 640 ka and suggests slow basin subsidence along Quaternary faults mapped on the basin edges. Marsh Valley initially incised into that valley fill sequence ca. 19 ka, shortly before the Bonneville Flood. Marsh Creek is a markedly underfit stream occupying a meandering, broad valley carved into the valley fill sequence. These geomorphic and sedimentologic patterns suggest non-catastrophic Lake Bonneville overflow before and after the Bonneville Flood.
In Portneuf Valley, ca. 8.5–7.4 Ma basin fill and a bedrock pediment are perched 800 m above the modern valley floor. Major incision of basin fill and bedrock by the ancestral Portneuf drainage system occurred prior to the Middle to Late Pleistocene, when two cut-fill events resulted in accumulation of alluvial fan deposits extending ~10–60 m above the modern valley floor and basalt extending ~10 m below to 20 m above the modern valley floor. Final incision by Lake Bonneville overflow is evident but relatively minor in comparison to the cumulative downcutting. Overall, incision is attributed to isostatic subsidence of the eastern Snake River Plain, which served as base level for the Portneuf drainage system after passage of the Yellowstone hot spot in late Miocene time.
Impact of learning HIV status on contraceptive use in the MIRA trial
Authors: Blanchard Kelly , Holt Kelsey , Bostrom Alan , van der Straten Ariane , Ramjee Gita , de Bruyn Guy , Chipato Tsungai , Montgomery Elizabeth T , Padian Nancy S 
Published: July 2011

Background and methodologyWe examined the effect of becoming HIV-positive on contraceptive practices in a Phase III randomised controlled trial of the diaphragm for HIV prevention. We coded self-reported contraceptive use into seven categories of methods in order of effectiveness. We compared the proportion using each category of contraception at baseline and last visit between women who did and did not become HIV-positive. We compared changes in the proportion using each category of contraception from baseline to last visit and calculated the percentage of women that moved to a more or less effective method category or stayed the same. We examined immediate and long-term changes in contraceptive use category after learning HIV-positive status.ResultsA total of 4645 women remained HIV-negative and 309 became HIV-positive. The proportion using each category of contraception was similar between groups at baseline and last visit. In both groups approximately one-fifth changed to a less effective method category between baseline and last visit. Few women reported using long-acting methods. Among HIV-positive women, shorter-term changes in the proportion using each category of contraception were similar to longer-term changes, though somewhat more women were using a method in the same category 3 months after seroconversion.Discussion and conclusionsLearning about HIV-positive status did not appear to significantly change patterns of use of effective contraceptives or the probability of switching to a more or less effective method. Information about, and access to, long-acting methods should receive more attention and be a routine part of family planning programmes and prevention trials.
Increased gonorrhoea and chlamydia testing did not increase case detection in an HIV clinical cohort 1999–2007
Authors: Berry Stephen A , Ghanem Khalil G , Page Kathleen R , Gange Stephen J , Thio Chloe L , Moore Richard D , Gebo Kelly A 
Published: July 2011

ObjectivesSince 2003, US organisations have recommended universal screening, rather than targeted screening, of HIV-infected persons for gonorrhoea and chlamydia. The objective of this study was to determine whether wider testing resulting from these guidelines would produce an increase in gonorrhoea/chlamydia diagnoses.Methods3283 patients receiving HIV care in 1999–2007 in the Johns Hopkins Hospital HIV clinic were studied. The two primary outcomes were the occurrence of any gonorrhoea/chlamydia testing in each year of care and the occurrence of any positive result(s) in years of testing. The proportion of all patients in care who were diagnosed with gonorrhoea/chlamydia was defined as the number of patients with positive results divided by the number of patients in care. Trends were analysed with repeated measures logistic regression.ResultsThe proportion of patients tested for gonorrhoea/chlamydia increased steadily from 0.12 in 1999 to 0.33 in 2007 (OR per year for being tested 1.17, 95% CI 1.15 to 1.19). The proportion positive among those tested decreased significantly after 2003 (OR per year 0.67, 95% CI 0.55 to 0.81). The proportion of all patients in care diagnosed with gonorrhoea/chlamydia therefore remained generally stable in 1999–2007 (OR per year 0.97, 95% CI 0.91 to 1.04).ConclusionsUniversal annual screening, as implemented, did not increase the proportion of all patients in care who were diagnosed with gonorrhoea/chlamydia. Similarly low implementation rates have been reported in cross-sectional studies. If future efforts to enhance implementation do not yield increases in diagnoses, then guidelines focusing on targeted screening of high-risk groups rather than universal screening may be warranted.
Insulin Increases De Novo Steroidogenesis in Prostate Cancer Cells
Authors: Lubik Amy A. , Gunter Jennifer H. , Hendy Stephen C. , Locke Jennifer A. , Adomat Hans H. , Thompson Vanessa , Herington Adrian , Gleave Martin E. , Pollak Michael , Nelson Colleen C. 
Published: July 2011

Abstract
Androgen-dependent pathways regulate maintenance and growth of normal and malignant prostate tissues. Androgen deprivation therapy (ADT) exploits this dependence and is used to treat metastatic prostate cancer; however, regression initially seen with ADT gives way to development of incurable castration-resistant prostate cancer (CRPC). Although ADT generates a therapeutic response, it is also associated with a pattern of metabolic alterations consistent with metabolic syndrome including elevated circulating insulin. Because CRPC cells are capable of synthesizing androgens de novo, we hypothesized that insulin may also influence steroidogenesis in CRPC. In this study, we examined this hypothesis by evaluating the effect of insulin on steroid synthesis in prostate cancer cell lines. Treatment with 10 nmol/L insulin increased mRNA and protein expression of steroidogenesis enzymes and upregulated the insulin receptor substrate insulin receptor substrate 2 (IRS-2). Similarly, insulin treatment upregulated intracellular testosterone levels and secreted androgens, with the concentrations of steroids observed similar to the levels reported in prostate cancer patients. With similar potency to dihydrotestosterone, insulin treatment resulted in increased mRNA expression of prostate-specific antigen. CRPC progression also correlated with increased expression of IRS-2 and insulin receptor in vivo. Taken together, our findings support the hypothesis that the elevated insulin levels associated with therapeutic castration may exacerbate progression of prostate cancer to incurable CRPC in part by enhancing steroidogenesis. Cancer Res; 71(17); 5754–64. ©2011 AACR.
Definition of the Landscape of Promoter DNA Hypomethylation in Liver Cancer
Authors: Stefanska Barbara , Huang Jian , Bhattacharyya Bishnu , Suderman Matthew , Hallett Michael , Han Ze-Guang , Szyf Moshe 
Published: July 2011

Abstract
We use hepatic cellular carcinoma (HCC), one of the most common human cancers, as a model to delineate the landscape of promoter hypomethylation in cancer. Using a combination of methylated DNA immunoprecipitation and hybridization with comprehensive promoter arrays, we have identified approximately 3,700 promoters that are hypomethylated in tumor samples. The hypomethylated promoters appeared in clusters across the genome suggesting that a high-level organization underlies the epigenomic changes in cancer. In normal liver, most hypomethylated promoters showed an intermediate level of methylation and expression, however, high-CpG dense promoters showed the most profound increase in gene expression. The demethylated genes are mainly involved in cell growth, cell adhesion and communication, signal transduction, mobility, and invasion; functions that are essential for cancer progression and metastasis. The DNA methylation inhibitor, 5-aza-2′-deoxycytidine, activated several of the genes that are demethylated and induced in tumors, supporting a causal role for demethylation in activation of these genes. Previous studies suggested that MBD2 was involved in demethylation of specific human breast and prostate cancer genes. Whereas MBD2 depletion in normal liver cells had little or no effect, we found that its depletion in human HCC and adenocarcinoma cells resulted in suppression of cell growth, anchorage-independent growth and invasiveness as well as an increase in promoter methylation and silencing of several of the genes that are hypomethylated in tumors. Taken together, the findings define the potential functional role of hypomethylation in cancer. Cancer Res; 71(17); 5891–903. ©2011 AACR.
Potent Antitumor Immunity Generated by a CD40-Targeted Adenoviral Vaccine
Authors: Hangalapura Basav N. , Oosterhoff Dinja , de Groot Jan , Boon Louis , Tüting Thomas , van den Eertwegh Alfons J. , Gerritsen Winald R. , van Beusechem Victor W. , Pereboev Alexander , Curiel David T. , Scheper Rik J. , de Gruijl Tanja D. 
Published: July 2011

AbstractIn situ delivery of tumor-associated antigen (TAA) genes into dendritic cells (DC) has great potential as a generally applicable tumor vaccination approach. Although adenoviruses (Ad) are an attractive vaccine vehicle in this regard, Ad-mediated transduction of DCs is hampered by the lack of expression of the Ad receptor CAR on the DC surface. DC activation also requires interaction of CD40 with its ligand CD40L to generate protective T-cell–mediated tumor immunity. Therefore, to create a strategy to target Ads to DCs in vivo, we constructed a bispecific adaptor molecule with the CAR ectodomain linked to the CD40L extracellular domain via a trimerization motif (CFm40L). By targeting Ad to CD40 with the use of CFm40L, we enhanced both transduction and maturation of cultured bone marrow–derived DCs. Moreover, we improved transduction efficiency of DCs in lymph node and splenic cell suspensions in vitro and in skin and vaccination site–draining lymph nodes in vivo. Furthermore, CD40 targeting improved the induction of specific CD8+ T cells along with therapeutic efficacy in a mouse model of melanoma. Taken together, our findings support the use of CD40-targeted Ad vectors encoding full-length TAA for in vivo targeting of DCs and high-efficacy induction of antitumor immunity. Cancer Res; 71(17); 5827–37. ©2011 AACR.