bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outbreak of Meropenem-ResistantSerratia marcescensComediated by Chromosomal AmpC β-Lactamase Overproduction and Outer Membrane Protein Loss
Authors: Suh Borum , Bae Il Kwon , Kim Juwon , Jeong Seok Hoon , Yong Dongeun , Lee Kyungwon 
Published: September 2010

ABSTRACTThe aim of this study was to investigate the mechanisms involved in the meropenem resistance ofSerratia marcescensclinical isolates. Meropenem-resistant (MIC range, 16 to 32 μg/ml)S. marcescensisolates were recovered from nine patients in a tertiary hospital in Seoul, South Korea, from June to November 2005. All the isolates shared identical or similar (>85% similarity) SpeI macrorestriction patterns, indicating clonal spread. PCR experiments did not detect any carbapenemase in those isolates. They carried theblaCTX-M-22gene located on a 150-kbp plasmid of the incompatibility group L/M; however, the addition of clavulanic acid exhibited few effects on meropenem MICs. Although meropenem MICs were reduced 4- to 16-fold with the addition of boronic acid, no plasmid-borne AmpC β-lactamase gene was detected in PCR experiments. Real-time quantitative PCR experiments showed that expression levels of the chromosomalampCgene in those isolates were 87.06 to 155.76 times higher than that of the reference strain ATCC 8100. SDS-PAGE showed a lack of the 42-kDa outer membrane protein (OmpF). In combination with the overproduction of the chromosomal AmpC enzyme, the loss of OmpF may have played a role in the acquisition of meropenem resistance in our isolates.
Improved Detection of Mutated Human Cytomegalovirus UL97 by Pyrosequencing
Authors: Schindele Birgit , Apelt Luise , Hofmann Jörg , Nitsche Andreas , Michel Detlef , Voigt Sebastian , Mertens Thomas , Ehlers Bernhard 
Published: September 2010

ABSTRACTGanciclovir (GCV) resistance frequently occurs upon prolonged treatment of ongoing active human cytomegalovirus (HCMV) infection in individuals with immature or compromised immune functions (e.g., recipients of solid-organ and hematopoietic stem cell transplants). Using pyrosequencing (PSQ), we established fast and sensitive detection of GCV resistance-associated mutations occurring in the HCMV open reading frame UL97. These mutations have been repeatedly associated with clinical treatment failure. We designed four PSQ assays and evaluated them by analyzing mixtures of plasmids or bacterial artificial chromosome-derived viruses containing UL97 wild-type and mutant sequences. A minimum level of 6% mutant sequence variants could be detected in these mixtures. In order to further evaluate the novel PSQ assays, we tested clinical specimens from patients with active HCMV infections. The results were compared with those obtained by conventional dideoxy chain terminator sequencing. As the PSQ method was more sensitive in detecting minor HCMV mutant fractions in a wild-type population, it is suggested that pyrosequencing is a useful tool for the early detection of emerging GCV-resistant HCMV in GCV-treated patients.
Novel Apramycin Resistance Gene
apmA
in Bovine and Porcine Methicillin-Resistant
Staphylococcus aureus
ST398 Isolates
Authors: Feßler Andrea T. , Kadlec Kristina , Schwarz Stefan 
Published: September 2010

ABSTRACT

A novel apramycin resistance gene,
apmA
, was detected on the ca.-40-kb resistance plasmid pAFS11 from bovine methicillin-resistant
Staphylococcus aureus
(MRSA) of sequence type 398 (ST398). The
apmA
gene coded for a protein of 274 amino acids that was related only distantly to acetyltransferases involved in chloramphenicol or streptogramin A resistance. NsiI deletion of
apmA
resulted in a 16- to 32-fold decrease in the apramycin MICs. An
apmA
-specific PCR identified this gene in one additional bovine and four porcine MRSA ST398 isolates.
How Innate Immune Mechanisms Contribute to Antibody-Enhanced Viral Infections
Authors: Ubol Sukathida , Halstead Scott B. 
Published: September 2010

ABSTRACTPreexisting antibodies may enhance viral infections. In dengue, nonneutralizing antibodies raised by natural infection with one of four dengue viruses (DENVs) may enhance infection with a different virus by a process we term “intrinsic antibody-dependent enhancement” (iADE). In addition, nonprotective antibodies raised by formalin-inactivated respiratory syncytial virus (RSV) and measles virus vaccines have led to enhanced disease during breakthrough infections. Infections under iADE conditions not only facilitate the process of viral entry into monocytes and macrophages but also modify innate and adaptive intracellular antiviral mechanisms, suppressing type 1 interferon (IFN) production and resulting in enhanced DENV replication. The suppression observedin vitrohas been documented in patients with severe (dengue hemorrhagic fever [DHF]) but not in patient with mild (dengue fever [DF]) secondary dengue virus infections. Important veterinary viral infections also may exhibit iADE. It is thought that use of formalin deconforms viral epitopes of RSV, resulting in poor Toll-like receptor (TLR) stimulation; suboptimal maturation of dendritic cells with reduced production of activation factors CD40, CD80, and CD86; decreased germinal center formation in lymph nodes; and the production of nonprotective antibodies. These antibodies fail to neutralize RSV, allowing replication with secondary stimulation of RSV-primed Th2 cells producing more low-avidity antibody, resulting in immune complexes deposited into affected tissue. However, when formalin-inactivated RSV was administered with a TLR agonist to mice, they were protected against wild-type virus challenge. Safe and effective vaccines against RSV/measles virus and dengue virus may benefit from a better understanding of how innate immune responses can promote production of protective antibodies.
Alternative Endogenous Protein Processing via an Autophagy-Dependent Pathway Compensates forYersinia-Mediated Inhibition of Endosomal Major Histocompatibility Complex Class II Antigen Presentation
Authors: Rüssmann Holger , Panthel Klaus , Köhn Brigitte , Jellbauer Stefan , Winter Sebastian E. , Garbom Sara , Wolf-Watz Hans , Hoffmann Sigrid , Grauling-Halama Silke , Geginat Gernot 
Published: September 2010

ABSTRACTExtracellularYersinia pseudotuberculosisemploys a type III secretion system (T3SS) for translocating virulence factors (Yersiniaouter proteins [Yops]) directly into the cytosol of eukaryotic cells. Recently, we used YopE as a carrier molecule for T3SS-dependent secretion and translocation of listeriolysin O (LLO) fromListeria monocytogenes. We demonstrated that translocation of chimeric YopE/LLO into the cytosol of macrophages byYersiniaresults in the induction of a codominant antigen-specific CD4 and CD8 T-cell response in orally immunized mice. In this study, we addressed the requirements for processing and major histocompatibility complex (MHC) class II presentation of chimeric YopE proteins translocated into the cytosol of macrophages by theYersiniaT3SS. Our data demonstrate the ability ofYersiniato counteract exogenous MHC class II antigen presentation of secreted hybrid YopE by the action of wild-type YopE and YopH. In the absence of exogenous MHC class II antigen presentation, an alternative pathway was identified for YopE fusion proteins originating in the cytosol. This endogenous antigen-processing pathway was sensitive to inhibitors of phagolysosomal acidification and macroautophagy, but it did not require the function either of the proteasome or of transporters associated with antigen processing. Thus, by an autophagy-dependent mechanism, macrophages are able to compensate for the YopE/YopH-mediated inhibition of the endosomal MHC class II antigen presentation pathway for exogenous antigens. This is the first report demonstrating that autophagy might enable the host to mount an MHC class II-restricted CD4 T-cell response against translocated bacterial virulence factors. We provide critical new insights into the interaction between the mammalian immune system and a human pathogen.
Transcriptomic and Innate Immune Responses toYersinia pestisin the Lymph Node during Bubonic Plague
Authors: Comer Jason E. , Sturdevant Daniel E. , Carmody Aaron B. , Virtaneva Kimmo , Gardner Donald , Long Dan , Rosenke Rebecca , Porcella Stephen F. , Hinnebusch B. Joseph 
Published: September 2010

ABSTRACTA delayed inflammatory response is a prominent feature of infection withYersinia pestis, the agent of bubonic and pneumonic plague. Using a rat model of bubonic plague, we examined lymph node histopathology, transcriptome, and extracellular cytokine levels to broadly characterize the kinetics and extent of the host response toY. pestisand how it is influenced by theYersiniavirulence plasmid (pYV). Remarkably, dissemination and multiplication of wild-typeY. pestisduring the bubonic stage of disease did not induce any detectable gene expression or cytokine response by host lymph node cells in the developing bubo. Only after systemic spread had led to terminal septicemic plague was a transcriptomic response detected, which included upregulation of several cytokine, chemokine, and other immune response genes. Although an initial intracellular phase ofY. pestisinfection has been postulated, a Th1-type cytokine response associated with classical activation of macrophages was not observed during the bubonic stage of disease. However, elevated levels of interleukin-17 (IL-17) were present in infected lymph nodes. In the absence of pYV, sustained recruitment to the lymph node of polymorphonuclear leukocytes (PMN, or neutrophils), the major IL-17 effector cells, correlated with clearance of infection. Thus, the ability to counteract a PMN response in the lymph node appears to be a majorin vivofunction of theY. pestisvirulence plasmid.
A 32-Kilodalton Hydrolase Plays an Important Role in
Paracoccidioides brasiliensis
Adherence to Host Cells and Influences Pathogenicity
Authors: Hernández Orville , Almeida Agostinho J. , Gonzalez Angel , Garcia Ana Maria , Tamayo Diana , Cano Luz Elena , Restrepo Angela , McEwen Juan G. 
Published: September 2010

ABSTRACT

One of the most crucial events during infection with the dimorphic fungus
Paracoccidioides brasiliensis
is adhesion to pulmonary epithelial cells, a pivotal step in the establishment of disease. In this study, we have evaluated the relevance of a 32-kDa protein, a putative adhesion member of the haloacid dehalogenase (HAD) superfamily of hydrolases, in the virulence of this fungus. Protein sequence analyses have supported the inclusion of PbHad32p as a hydrolase and have revealed a conserved protein only among fungal dimorphic and filamentous pathogens that are closely phylogenetically related. To evaluate its role during the host-pathogen interaction, we have generated mitotically stable
P. brasiliensis HAD32
(
PbHAD32
) antisense RNA (aRNA) strains with consistently reduced gene expression. Knockdown of
PbHAD32
did not alter cell vitality or viability but induced morphological alterations in yeast cells. Moreover, yeast cells with reduced
PbHAD32
expression were significantly affected in their capacity to adhere to human epithelial cells and presented decreased virulence in a mouse model of infection. These data support the hypothesis that PbHad32p binds to extracellular matrix (ECM) proteins and modulates the initial immune response for evasion of host defenses. Our findings point to
PbHAD32
as a novel virulence factor active during the initial interaction with host cells in
P. brasiliensis
.
Comparison of the Regulation, Metabolic Functions, and Roles in Virulence of the Glyceraldehyde-3-Phosphate Dehydrogenase Homologues
gapA
and
gapB
in
Staphylococcus aureus
Authors: Purves Joanne , Cockayne Alan , Moody Peter C. E. , Morrissey Julie A. 
Published: September 2010

ABSTRACT

The Gram-positive bacterium
Staphylococcus aureus
contains two glyceraldehyde-3-phosphate dehydrogenase (GAPDH) homologues known as GapA and GapB. GapA has been characterized as a functional GAPDH protein, but currently there is no biological evidence for the role of GapB in metabolism in
S. aureus
. In this study we show through a number of complementary methods that
S. aureus
GapA is essential for glycolysis while GapB is essential in gluconeogenesis. These proteins are reciprocally regulated in response to glucose concentrations, and both are influenced by the glycolysis regulator protein GapR, which is the first demonstration of the role of this regulator in
S. aureus
and the first indication that GapR homologues control genes other than those within the glycolytic operon. Furthermore, we show that both GapA and GapB are important in the pathogenesis of
S. aureus
in a
Galleria mellonella
model of infection, showing for the first time in any bacteria that both glycolysis and gluconeogenesis have important roles in virulence.
Reproducible Science
Authors: Casadevall Arturo , Fang Ferric C. 
Published: September 2010

ABSTRACT
The reproducibility of an experimental result is a fundamental assumption in science. Yet, results that are merely confirmatory of previous findings are given low priority and can be difficult to publish. Furthermore, the complex and chaotic nature of biological systems imposes limitations on the replicability of scientific experiments. This essay explores the importance and limits of reproducibility in scientific manuscripts.
Epidemiology of fall related forearm and wrist fractures among adults treated in US hospital emergency departments
Authors: Orces Carlos H , Martinez Fidel J 
Published: September 2010

ObjectiveTo examine national estimates of forearm and wrist fractures among adults treated in US emergency departments.MethodsThe National Electronic Injury Surveillance System All Injury Program was used to estimate emergency department visits for unintentional fall related forearm and/or wrist fractures among adults aged 50 years or older between 2001 and 2007. Census population estimates were used as the denominator to calculate age-specific and age-adjusted fracture rates per 100 000 persons.ResultsBased on 14 771 cases, an estimated 1 045 008 adults aged ≥50 years were treated in US hospital emergency departments for fall related forearm and/or wrist fractures during the study period. Of these, an estimated 832 591 (80%) fractures occurred among women. The incidence of fractures among women increased gradually with age from the age of 50 years. In men, fracture rates remained low until later in life. Between 2001 and 2007, fracture rates increased predominantly among women in the age group 50–59 years at an annual rate of 3.9% (95% CI −0.1 to 8.2).ConclusionsThe study indicates marked gender differences in unintentional fall related forearm and/or wrist fractures among adults aged ≥50 years treated in US hospital emergency departments. Interventions aimed at preventing falls might be effective in reducing the incidence of this injury, particularly in those women who already have diminished bone mineral.
Chromitites from the Fiskenæsset anorthositic complex, West Greenland: clues to late Archaean mantle processes
Authors: Rollinson Hugh , Reid Claire , Windley Brian 
Published: September 2010

Abstract
Chromitites in the late Archaean Fiskenæsset anorthosite complex are characterized by a most unusual mineral assemblage: highly calcic plagioclase, iron-rich aluminous chromites and primary amphibole. In particular, the chromite compositions are atypical of chromitites in layered igneous intrusions. However, rare occurrences of this mineral assemblage are found in modern arcs and it is proposed here that the late Archaean calcic anorthositic chromitites formed by the partial melting of unusually aluminous harzburgite in a mantle wedge above a subduction zone. This melting process produced a hydrous, aluminous basalt, which fractionated at depth in the crust to produce a variety of high-alumina basalt compositions, from which the anorthosite complex with its chromitite horizons formed as a cumulate within the continental crust. The principal trigger for the late precipitation of chromite is thought to have been the removal of Al from the basaltic melt through plagioclase crystallization, and the build-up of Cr through an absence of clinopyroxene. It is proposed that the aluminous mantle source of the parent magma was produced by the melting of a harzburgitic mantle refertilized by small-volume, aluminous slab melts. This process ceased at the end of the Archaean because the dominant mechanism of crust generation changed such that melt production shifted from the slab into the mantle wedge, thus explaining why highly calcic anorthosites are almost totally restricted to the Archaean.
Roles of strike-slip faults during continental deformation: examples from the active Arabia–Eurasia collision
Authors: Allen Mark B. 
Published: September 2010

Abstract

This paper concerns the kinematics of active strike-slip faults in the Arabia–Eurasia collision zone, and how they accommodate plate convergence. Several roles are discernible:
(1) collision zone boundaries
, the left-lateral Dead Sea Fault System and right-lateral faults in eastern Iran form the western and eastern boundaries of the collision zone;
(2) tectonic escape structures
, the North and East Anatolian faults transport intervening crust westwards, out of the path of the Arabia;
(3) strain partitioning
, right-lateral slip on the Zagros Main Recent Fault and NW–SE-striking thrusts to its SW produce north–south convergence, parallel to the plate vector; left-lateral slip along the Alborz range and thrusts across it produce oblique left-lateral shortening;
(4) shortening arrays
, arrays of strike-slip faults (e.g. Kopeh Dagh and eastern Iranian faults) rotate about vertical axes, producing north–south shortening without crustal thickening;
(5) transfer zones
, fold trends and earthquake slip vectors change orientation across strike-slip faults in the Zagros, suggesting that these faults allow for changes in thrust transport along strike in the orogen. These different roles emphasize the complex behaviour of continental crust, and the advantages of studying active tectonics rather than ancient examples.
Was Late Cretaceous–Paleocene obduction of ophiolite complexes the primary cause of crustal thickening and regional metamorphism in the Pakistan Himalaya?
Authors: Searle M. P. , Treloar P. J. 
Published: September 2010

Abstract

Regional metamorphic rocks in the Pakistan Himalaya include both UHP coesite eclogite-facies and MP/T kyanite–sillimanite-grade Barrovian metamorphic rocks. Age data show that peak metamorphism of both was
c.
47 Ma.
40
Ar–
39
Ar hornblende cooling ages date post-peak metamorphic cooling of both through 500 °C by 40 Ma, some 20 Ma earlier than for metamorphic rocks in the central and eastern Himalaya. Typically these ages have been explained by obduction of the Kohistan arc onto the Indian plate at about 50 Ma and India–Asia collision. We suggest instead that the earlier metamorphic and cooling ages of the Pakistani Barrovian metamorphic sequence could be partially explained by Late Cretaceous to Early Paleocene crustal thickening linked to obduction of an ophiolite thrust sheet onto the leading edge of the Indian plate, similar to the Spontang Ophiolite in Ladakh. Heating following on from this Paleocene crustal thickening explains peak Barrovian metamorphism within 5–10 Ma of subsequent obduction of Kohistan. Remnants of the ophiolite sheet, and underlying Tethyan sediments, are preserved in NW India and in western Pakistan but not in northern Pakistan. Tectonic erosion removed all cover sequences (including the ophiolites) from the Indian plate basement.
Landscape development of the Himalayan–Tibetan orogen: a review
Authors: Owen Lewis A. 
Published: September 2010

Abstract
The Himalayan–Tibetan orogen provides one of the best natural laboratories in which to examine the nature and dynamics of landscape development within continent–continent collision zones. Many new tectonic–climatic–geomorphological theories and models have emerged and/or have been greatly influenced as a consequence of the study of the region and the quest to understand its geomorphological development. These include models of the interactions between tectonics, climate and surfice processes, notably, the influence of climate on surface uplift by denudational unloading; the limiting of topography by glaciation (the glacial buzz-saw model); localized uplift at syntaxes by enhanced fluvial and glacial erosion that, in turn, weaken the lithosphere, enhancing surface uplift and exhumation (the tectonic aneurysm model); climate-driven out-of-sequence thrusting and crustal channel flow; glacial damming leading to differential erosion and uplift; paraglaciation; and the influence of extreme events such as earthquakes, landslides, and floods as major formative processes. The development of new technologies, including satellite remote sensing and global positioning systems, and analytical methods such as numerical dating is now allowing these theories and models to be tested and will inevitably lead to new paradigms.
The anatomy and ontogeny of modern intra-oceanic arc systems
Authors: Stern Robert J. 
Published: September 2010

Abstract

Intra-oceanic arc systems (IOASs) represent the oceanic endmember of arc–trench systems and have been the most important sites of juvenile continental crust formation for as long as plate tectonics has operated. IOASs' crustal profiles are wedge-shaped, with crust up to 20–35 km thick; a more useful definition is that IOASs occur as chains of small islands, generally just the tops of the largest volcanoes. A very small fraction of IOASs lie above sea level, but advancing marine technologies allow their most important features to be defined. Modern IOASs subduct old, dense oceanic lithosphere and so tend to be under extension. They consist of four parallel components: trench, forearc, volcanic–magmatic arc, and back-arc, occupying a ≥200 km zone along the leading edge of the overriding plate. These components form as a result of hydrous melting of the mantle and reflect the strongly asymmetric nature of subduction processes. Forearcs preserve infant arc lithosphere whereas magmatism in mature IOASs is concentrated along the volcanic–magmatic front. Mature IOASs often have minor rear-arc volcanism and, because most IOASs are strongly extensional, sea-floor spreading often forms back-arc basins. Sub-IOAS mantle is also asymmetric, with serpentinized harzburgite beneath the forearc, pyroxene-rich low-
V
p
mantle beneath the magmatic front, and lherzolite–harzburgite beneath back-arc basins. Because most IOASs are far removed from continents, they subduct oceanic lithosphere with thin sediments and have naked forearcs subject to tectonic erosion. IOASs evolve from broad zones of very high degrees of melting and sea-floor spreading during their first 5–10 Ma, with the volcanic–magmatic front retreating to its ultimate position
c.
200 km from the trench.