bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steady-State Intrapulmonary Pharmacokinetics and Pharmacodynamics of Posaconazole in Lung Transplant Recipients
Authors: Conte John E. , DeVoe Catherine , Little Emily , Golden Jeffrey A. 
Published: June 2010

ABSTRACT

This prospective study evaluated the plasma and intrapulmonary pharmacokinetics and pharmacodynamics (PKPD) of posaconazole (POS) in lung transplant recipients. Twenty adult lung transplant patients were instructed to take a 400-mg POS oral suspension twice daily (BID) with a high-fat meal for a total of 14 doses. Pulmonary epithelial lining fluid (ELF) and alveolar cell (AC) samples were obtained via bronchoalveolar lavage, and blood samples were collected at the approximate time of bronchoscopy. POS concentrations were assayed using liquid chromatography with tandem mass spectrometry. The maximum concentrations (
C
max
) (mean ± standard deviation [SD]) in plasma, ELF, and AC were 1.3 ± 0.4, 1.3 ± 1.7, and 55.4 ± 44.0 μg/ml. POS concentrations in plasma, ELF, and AC did not decrease significantly, indicating slow elimination after multiple dosing. Mean concentrations of POS in plasma, ELF, and AC were above the MIC
90
(0.5 μg/ml) for
Aspergillus
species over the 12-h dosing interval and for 24 h following the last dose. Area under the concentration-time curve from 0 to 12 h (AUC
0-12
)/MIC
90
ratios in plasma, ELF, and AC were 21.98, 22.42, and 1,060. We concluded that a dose of 400 mg BID resulted in sustained plasma, ELF, and AC concentrations above the MIC
90
for
Aspergillus
spp. during the dosing interval. Confirmation of the therapeutic value of these observations requires further investigation. The intrapulmonary PKPD of POS may be favorable for treatment or prevention of aspergillosis, although further research on the relevant PKPD parameters and the effect of POS protein binding is required.
Efficacy of Amphiphilic Core-Shell Nanostructures Encapsulating Gentamicin in an
In Vitro Salmonella
and
Listeria
Intracellular Infection Model
Authors: Ranjan A. , Pothayee N. , Vadala T. P. , Seleem M. N. , Restis E. , Sriranganathan N. , Riffle J. S. , Kasimanickam R. 
Published: June 2010

ABSTRACT

Core-shell nanostructures with nonionic amphiphilic shells and ionic cores encapsulating gentamicin were designed for therapy against intracellular pathogens, including
Salmonella
and
Listeria
. Flow cytometry and confocal microscopy showed that their uptake into J774A.1 macrophages proceeded mainly by fluid-phase endocytosis and clathrin-mediated pathways. The nanostructures were nontoxic
in vitro
at doses of 50 to 250 μg/ml, and they significantly reduced the amounts of intracellular
Salmonella
(0.53 log) and
Listeria
(3.16 log), thereby suggesting effective transport into the cells.
qnrVC-Like Gene Located in a Novel Complex Class 1 Integron Harboring the ISCR1Element in anAeromonas punctataStrain from an Aquatic Environment in Shandong Province, China
Authors: Xia Ruirui , Guo Xianhu , Zhang Yuzhen , Xu Hai 
Published: June 2010

ABSTRACTAqnrVC-like gene,qnrVC4, was found in a novel complex class 1 integron gene cassette array following the ISCR1element andblaPER-1in a multidrug-resistant strain of the aquatic bacteriumAeromonas punctata. The deduced QnrVC4 protein sequence shares 45% to 81% amino acid identity with quinolone resistance determinants QnrB6, QnrA1, QnrS1, QnrC, QnrVC1, and QnrVC3. A Ser-83 to Ile amino acid substitution in gyrase A may be mainly responsible for ciprofloxacin resistance in this strain.
Growth in a Biofilm Induces a Hyperinfectious Phenotype inVibrio cholerae
Authors: Tamayo Rita , Patimalla Bharathi , Camilli Andrew 
Published: June 2010

ABSTRACTBiofilm formation plays a multifaceted role in the life cycles of a wide variety of microorganisms. In the case of pathogenicVibrio cholerae, biofilm formation in its native aquatic habitats is thought to aid in persistence during interepidemic seasons and to enhance infectivity upon oral ingestion. The structure ofV. choleraebiofilms has been hypothesized to protect the bacteria during passage through the stomach. Here, we directly test the role of biofilm architecture in the infectivity ofV. choleraeby comparing the abilities of intact biofilms, dispersed biofilms, and planktonic cells to colonize the mouse small intestine. Not only wereV. choleraebiofilms better able to colonize than planktonic cells, but the structure of the biofilm was also found to be dispensable: intact and dispersed biofilms colonized equally, and both vastly out-colonized planktonic cells. The infectious dose for biofilm-derivedV. choleraewas orders of magnitude lower than that of planktonic cells. This biofilm-induced hyperinfectivity may be due in part to a higher growth rate of biofilm-derived cells during infection. These results suggest that the infectious dose of naturally occurring biofilms ofV. choleraemay be much lower than previously estimated using cells grown planktonicallyin vitro. Furthermore, this work implies the existence of factors specifically induced during growth in a biofilm that augment infection byV. cholerae.
Delineation of Regions of theYersiniaYopM Protein Required for Interaction with the RSK1 and PRK2 Host Kinases and Their Requirement for Interleukin-10 Production and Virulence
Authors: McPhee Joseph B. , Mena Patricio , Bliska James B. 
Published: June 2010

ABSTRACTThe YopM protein ofYersiniasp. is a type III secreted effector that is required for virulence in murine models of infection. YopM has previously been shown to contain leucine-rich repeats (LRRs) and to interact with two host kinases, RSK1 and PRK2, although the consequence of these interactions is unknown. A series of YopM proteins missing different numbers of LRRs or a C-terminal domain were produced and used forin vitrobinding reactions to map domains required for interaction with RSK1 and PRK2. A C-terminal domain of YopM (from LRR12 to the C terminus) was shown to be required for interaction with RSK1, while an internal portion encompassing LRR6 to LRR15 was shown to be required for interaction with PRK2. The virulence of aYersinia pseudotuberculosisΔyopMmutant in mice via an intravenous route of infection was significantly attenuated. At day 4 postinfection, there were significantly increased levels of gamma interferon and reduced levels of interleukin-18 (IL-18) and IL-10 in the serum of the ΔyopM-infected mice compared to that of mice infected with the wild type, suggesting that YopM action alters the balance of these key cytokines to promote virulence. The PRK2 and RSK1 interaction domains of YopM were both required for IL-10 inductionin vivo, irrespective of splenic colonization levels. In an orogastric model ofY. pseudotuberculosisinfection, a ΔyopMmutant was defective in dissemination from the intestine to the spleen and significantly reduced in virulence. In addition,Y. pseudotuberculosismutants expressing YopM proteins unable to interact with either RSK1 (YopMΔ12-C) or PRK2 (YopMΔ6-15) were defective for virulence in this assay, indicating that both interaction domains are important for YopM to promote pathogenesis.
Avian-Pathogenic
Escherichia coli
Strains Are Similar to Neonatal Meningitis
E. coli
Strains and Are Able To Cause Meningitis in the Rat Model of Human Disease
Authors: Tivendale Kelly A. , Logue Catherine M. , Kariyawasam Subhashinie , Jordan Dianna , Hussein Ashraf , Li Ganwu , Wannemuehler Yvonne , Nolan Lisa K. 
Published: June 2010

ABSTRACT

Escherichia coli
strains causing avian colibacillosis and human neonatal meningitis, urinary tract infections, and septicemia are collectively known as extraintestinal pathogenic
E. coli
(ExPEC). Characterization of ExPEC strains using various typing techniques has shown that they harbor many similarities, despite their isolation from different host species, leading to the hypothesis that ExPEC may have zoonotic potential. The present study examined a subset of ExPEC strains: neonatal meningitis
E. coli
(NMEC) strains and avian-pathogenic
E. coli
(APEC) strains belonging to the O18 serogroup. The study found that they were not easily differentiated on the basis of multilocus sequence typing, phylogenetic typing, or carriage of large virulence plasmids. Among the APEC strains examined, one strain was found to be an outlier, based on the results of these typing methods, and demonstrated reduced virulence in murine and avian pathogenicity models. Some of the APEC strains tested in a rat model of human neonatal meningitis were able to cause meningitis, demonstrating APEC's ability to cause disease in mammals, lending support to the hypothesis that APEC strains have zoonotic potential. In addition, some NMEC strains were able to cause avian colisepticemia, providing further support for this hypothesis. However, not all of the NMEC and APEC strains tested were able to cause disease in avian and murine hosts, despite the apparent similarities in their known virulence attributes. Thus, it appears that a subset of NMEC and APEC strains harbors zoonotic potential, while other strains do not, suggesting that unknown mechanisms underlie host specificity in some ExPEC strains.
Importance of Conserved Residues of the Serine Protease Autotransporter β-Domain in Passenger Domain Processing and β-Barrel Assembly
Authors: Yen Yihfen T. , Tsang Casey , Cameron Todd A. , Ankrah Dennis O. , Rodou Athina , Stathopoulos Christos 
Published: June 2010

ABSTRACTSerine protease autotransporters of the familyEnterobacteriaceae(SPATE) comprise a family of virulence proteins secreted by enteric Gram-negative bacteria via the autotransporter secretion pathway. A SPATE polypeptide contains a C-terminal translocator domain that inserts into the bacterial outer membrane as a β-barrel structure and mediates secretion of the passenger domain to the extracellular environment. In the present study, we examined the role of conserved residues located in the SPATE β-barrel-forming region in passenger domain secretion. Thirty-nine fully conserved residues in Tsh were mutated by single-residue substitution, and defects in their secretion phenotypes were assessed by cell fractionation and immunochemistry. A total of 22 single mutants exhibited abnormal phenotypes in different cellular compartments. Most mutants affecting secretion are charged residues with side chains pointing into the β-barrel interior. Seven mutants showed notable abnormalities in processing (constructs with the E1231A, E1249A, and R1374A mutations) and β-barrel assembly or insertion into the outer membrane (constructs with the G1158Y, F1360A, Y1375A, and F1377A mutations). The phenotypes of the β-barrel assembly/insertion mutants and the presence of a processed Tsh passenger domain in the periplasm support the possibility that the translocator domain must undergo extensive folding prior to insertion into the outer membrane. Results from double-mutation experiments further demonstrate that F1360 and F1377 affect β-barrel insertion/assembly at different times. In light of these new data, a more refined model for the mechanism of SPATE secretion is presented.
Coxiella burnetii
Phase I and II Variants Replicate with Similar Kinetics in Degradative Phagolysosome-Like Compartments of Human Macrophages
Authors: Howe Dale , Shannon Jeffrey G. , Winfree Seth , Dorward David W. , Heinzen Robert A. 
Published: June 2010

ABSTRACT

Coxiella burnetii
infects mononuclear phagocytes, where it directs biogenesis of a vacuolar niche termed the parasitophorous vacuole (PV). Owing to its lumenal pH (∼5) and fusion with endolysosomal vesicles, the PV is considered phagolysosome-like. However, the degradative properties of the mature PV are unknown, and there are conflicting reports on the maturation state and growth permissiveness of PV harboring virulent phase I or avirulent phase II
C. burnetii
variants in human mononuclear phagocytes. Here, we employed infection of primary human monocyte-derived macrophages (HMDMs) and THP-1 cells as host cells to directly compare the PV maturation kinetics and pathogen growth in cells infected with the Nine Mile phase I variant (NMI) or phase II variant (NMII) of
C. burnetii
. In both cell types, phase variants replicated with similar kinetics, achieving roughly 2 to 3 log units of growth before they reached stationary phase. HMDMs infected by either phase variant secreted similar amounts of the proinflammatory cytokines interleukin-6 and tumor necrosis factor alpha. In infected THP-1 cells, equal percentages of NMI and NMII PVs decorate with the early endosomal marker Rab5, the late endosomal/lysosomal markers Rab7 and CD63, and the lysosomal marker cathepsin D at early (8 h) and late (72 h) time points postinfection (p.i.). Mature PVs (2 to 4 days p.i.) harboring NMI or NMII contained proteolytically active cathepsins and quickly degraded
Escherichia coli
. These data suggest that
C. burnetii
does not actively inhibit phagolysosome function as a survival mechanism. Instead, NMI and NMII resist degradation to replicate in indistinguishable digestive PVs that fully mature through the endolysosomal pathway.
Triassic ammonoid biostratigraphy: an overview
Authors: Balini Marco , Lucas Spencer G. , Jenks James F. , Spielmann Justin A. 
Published: June 2010

Abstract
The Triassic chronostratigraphic scale was built on two centuries of research on ammonoid biostratigraphy and biochronology. Two Triassic stage bases and all of the Triassic substages are currently defined by ammonoid bioevents. The study of Triassic ammonoids began during the late 1700s, and in 1895, Edmund von Mojsisovics, Wilhelm Waagen and Carl Diener published an essentially complete Triassic chronostratigraphic scale based on ammonoid biostratigraphy. This scale introduced many of the Triassic stage and substage names still used today, and all terminology of stages and substages subsequently introduced has been based on ammonoid biostratigraphy. Early Triassic ammonoids show a trend from cosmopolitanism (Induan) to latitudinal differentiation (Olenekian), and the four Lower Triassic substage (Griesbachian, Dinerian, Smithian and Spathian) boundaries are globally correlated by widespread ammonoid biotic events. Middle Triassic ammonoids have provinciality similar to that of the Olenekian and provide a basis for recognizing six Middle Triassic substages. Late Triassic ammonoids provide a basis for recognizing three stages divided into five substages. The main uncertainty for the future of Triassic ammonoid biostratigraphy is not the decline of the ammonoids as a tool for dating and correlation of Triassic strata but, rather, the dramatic decrease in the number of specialists, due to the lack of replacement of experienced palaeontologists who started their activity in the 1950s and 1960s.
Triassic palynology of central and northwestern Europe: a review of palynofloral diversity patterns and biostratigraphic subdivisions
Authors: Kürschner Wolfram M. , Herngreen G. F. Waldemaar 
Published: June 2010

Abstract
We document palynofloral trends through the Triassic in the Germanic and Alpine facies with an emphasis on diversity trends and possibly related palaeoenvironmental changes. As a first order approximation of palynofloral diversity, we used the range through method of the software package PAST based on a range chart compiled from several Triassic palynological studies and reviews. Our analysis suggests that during the entire Triassic the diversity of plants producing spores was largely controlled by the availability of water, while diversity among gymnosperms was also affected by other environmental and biotic factors. In general, palynofloral diversity declines by some 50% between the early Carnian and the Norian, mainly as a result of a decrease in the number of pollen species. This is the second most severe loss in pollen species after the Permian–Triassic biotic crisis. In comparison to the marked palynofloral turnover at the Permian–Triassic transition and the end-Carnian decrease in palynofloral diversity, the end-Triassic biotic crisis appears to have little affected palynofloral species diversity in Europe. A study of the palynostratigraphy of NW Europe recognizes nine zones (and nine subzones) that encompass the Triassic, most of which have their boundaries based on the first occurrences of marker species. The palynostratigraphic zones and subzones in Europe are correlated to the marine Triassic stages based on various data, including numerous palynological records in marine Alpine Triassic strata.
The Triassic timescale: new constraints and a review of geochronological data
Authors: Mundil Roland , Pálfy József , Renne Paul R. , Brack Peter 
Published: June 2010

Abstract

A review of geochronological data underlying the geological timescale for the Triassic yields a significantly different timescale calibration than that published in the most recent compilation (Geologic TimeScale 2004). This is partly due to the availability of new radio–isotopic data, but mostly because strict selection criteria are applied and complications arising from biases (both systematic and random) are accounted for in this contribution. The ages for the base and the top of the Triassic are constrained by U–Pb ages to 252.3 and 201.5 Ma, respectively. These dates also constrain the ages of major extinction events at the Permian–Triassic and Triassic–Jurassic boundaries, and are statistically indistinguishable from ages obtained for the Siberian Traps and volcanic products from the Central Atlantic Magmatic Province, respectively, suggesting a causal link. Ages for these continental volcanics, however, are mostly from the K–Ar (
40
Ar/
39
Ar) system, which requires accounting and correcting for a systematic bias of
c
. 1% between U–Pb and
40
Ar/
39
Ar isotopic ages (the
40
Ar/
39
Ar ages being younger).

Robust age constraints also exist for the Induan–Olenekian boundary (251.2 Ma) and the Early–Middle Triassic (Olenekian–Anisian) boundary (247.2 Ma), resulting in a surprisingly short duration of the Early Triassic, which has implications for the timing of biotic recovery and major changes in ocean chemistry during this time. Furthermore, the Anisian–Ladinian boundary is constrained to 242.0 Ma by new U–Pb and
40
Ar/
39
Ar ages. Radio–isotopic ages for the Late Triassic are scarce, and the only reliable and biostratigraphically-controlled age is from an upper Carnian tuff dated to 230.9 Ma, yielding a duration of more than 35 Ma for the Late Triassic. All of these ages are from U–Pb analyses applied to zircons with uncertainties at the permil level or better. The resulting compilation can only serve as a guideline and must be considered a snapshot, resolving some of the issues mainly associated with inaccurate and misinterpreted data in previous publications. However, further advances will require revision of some of the data presented here.
Biochronology of Triassic bivalves
Authors: McRoberts Christopher A. 
Published: June 2010

AbstractSubstantial advances by numerous researchers over the past 20 years have made it possible to develop a composite biochronological scheme for the Triassic based on the bivalvesClaraia,Peribositria,Enteropleura,Daonella,Halobia,EomonotisandMonotis. These bivalves exhibit temporal durations nearly equal to ammonoids and conodonts. Widely distributed across the Tethys, Panthalassa and Boreal regions, these bivalves occur in a wide variety of marine facies and water depths, but are most notable for their thick shell accumulation in deeper-water oxygen deficient environments. They were most likely resting or reclining benthos, may have housed chemosymbionts, and were part of episodic opportunistic palaeocommunities in or near oxygen deficient settings.A new biochronological zonation for bivalves is presented that encompasses the entire Triassic and is integrated with standard ammonoid schemes. The Lower Triassic is characterized by 2–3 zones ofClaraia, most notably from the eastern Tethys representing the entire Induan and lower portion of the Olenekian. Later in the Olenekian, and most notably from the Boreal realm, species ofPeribositria(included by some workers withinBositra) provide useful zonal indexes. The Middle Triassic is well represented byEnteropleura(Middle Anisian) andDaonella(Upper Anisian through Ladinian) in the Tethys and North America with significant occurrences throughout the circum-Pacific and Boreal realms. The Upper Triassic can be subdivided into 8–13 bivalve zones based on the succession ofHalobia,EomonotisandMonotis sensu latospecies with best representation in the Tethys, Boreal and eastern Panthalassa regions.
Using probabilistic confidence models for trust inference in Web-based social networks
Authors: Kuter Ugur , Golbeck Jennifer 
Published: June 2010

In this article, we describe a new approach that gives an explicit probabilistic interpretation for social networks. In particular, we focus on the observation that many existing Web-based trust-inference algorithms conflate the notions of “trust” and “confidence,” and treat the amalgamation of the two concepts to compute the trust value associated with a social relationship. Unfortunately, the result of such an algorithm that merges trust and confidence is not a trust value, but rather a new variable in the inference process. Thus, it is hard to evaluate the outputs of such an algorithm in the context of trust inference.
This article first describes a formal probabilistic network model for social networks that allows us to address that issue. Then we describe SUNNY, a new trust inference algorithm that uses probabilistic sampling to separately estimate trust information and our confidence in the trust estimate and use the two values in order to compute an estimate of trust based on only those information sources with the highest confidence estimates.
We present an experimental evaluation of SUNNY. In our experiments, SUNNY produced more accurate trust estimates than the well-known trust inference algorithm TidalTrust, demonstrating its effectiveness. Finally, we discuss the implications these results will have on systems designed for personalizing content and making recommendations.
Breast Cancer Cells in Three-dimensional Culture Display an Enhanced Radioresponse after Coordinate Targeting of Integrin α5β1 and Fibronectin
Authors: Nam Jin-Min , Onodera Yasuhito , Bissell Mina J. , Park Catherine C. 
Published: June 2010

Abstract
Tactics to selectively enhance cancer radioresponse are of great interest. Cancer cells actively elaborate and remodel their extracellular matrix (ECM) to aid in survival and progression. Previous work has shown that β1-integrin inhibitory antibodies can enhance the growth-inhibitory and apoptotic responses of human breast cancer cell lines to ionizing radiation, either when cells are cultured in three-dimensional laminin-rich ECM (3D lrECM) or grown as xenografts in mice. Here, we show that a specific α heterodimer of β1-integrin preferentially mediates a prosurvival signal in human breast cancer cells that can be specifically targeted for therapy. 3D lrECM culture conditions were used to compare α-integrin heterodimer expression in malignant and nonmalignant cell lines. Under these conditions, we found that expression of α5β1-integrin was upregulated in malignant cells compared with nonmalignant breast cells. Similarly, we found that normal and oncofetal splice variants of fibronectin, the primary ECM ligand of α5β1-integrin, were also strikingly upregulated in malignant cell lines compared with nonmalignant acini. Cell treatment with a peptide that disrupts the interactions of α5β1-integrin with fibronectin promoted apoptosis in malignant cells and further heightened the apoptotic effects of radiation. In support of these results, an analysis of gene expression array data from breast cancer patients revealed an association of high levels of α5-integrin expression with decreased survival. Our findings offer preclinical validation of fibronectin and α5β1-integrin as targets for breast cancer therapy. Cancer Res; 70(13); 5238–48. ©2010 AACR.