bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of laser intensity and applied electric field on coherent control of spin polarization by short laser pulses
Authors: Nakajima Takashi
Published: March 2006

We present a complete theory for coherent control of spin polarization through the pump-probe sequence, which is valid at arbitrary laser intensities. Anomalous intensity-dependent spin polarization has been found. Furthermore, as a new doorknob for coherent control, we propose an application of the electric field to effectively shorten the coupling time, which can be very effective for a nearly degenerate system.
Ultrafast recombination in Si-doped InN
Authors: Ascázubi Ricardo , Wilke Ingrid , Cho Shinho , Lu Hai , Schaff William J.
Published: March 2006

We report femtosecond near-infrared transient photoreflection measurements of native n-type indium nitride and silicon-doped indium nitride thin films. The overall time dependence of the ultrafast reflectivity transient is characterized by the different time scales of carrier cooling and carrier recombination. Experimental analysis demonstrates nonradiative recombination in the picosecond and subpicosecond range as the dominant recombination mechanism at room temperature even at very high carrier concentrations. Silicon-doped InN films exhibit carrier lifetimes as short as 680fs.
Local structure around Ga in ultrafine GaN∕ZnO coaxial nanorod heterostructures
Authors: Han S.-W. , Yoo H.-J. , Jin An Sung , Yoo Jinkyoung , Yi Gyu-Chul
Published: March 2006

The structure of tubular GaN coaxially grown on ZnO nanorods with thickness of 6–12nm was investigated using x-ray absorption fine structure (XAFS) at the Ga K edge. The XAFS measurements revealed that the GaN had a distorted-wurtzite structure, and that there were more distortions in the bond length of Ga–Ga pairs than in Ga–N pairs. However, no extra disorders were observed in any of the pairs. These results strongly suggest that Ga atoms first bonded to the ZnO template. Unlike other techniques, the XAFS determines structure around a selected species atom in nano-heterostructures.
Scanning tunneling microscopy for laterally resolved measurements of magnetoresistance through a point contact
Authors: Wahlström Erik , Bručas Rimantas , Hanson Maj
Published: March 2006

Using a scanning tunneling microscope for point contact measurements, we obtained laterally resolved information of the magnetoresistive properties of nanostructured spin-valve elements. A good correlation is found between magnetization and magnetoresistance curves of single-domain elliptical elements (450nm by 150nm), for magnetic fields applied along their long and short axes. In ring-shaped elements (inner and outer diameters 1.8 and 2.2μm), different magnetoresistance curves are acquired as different points around the ring are probed. The observed switching can be related to the onion state of the rings, and it clearly demonstrates a lateral resolution ⩽100nm.
Low-noise polymeric nanomechanical biosensors
Authors: Calleja Montserrat , Tamayo Javier , Nordström Maria , Boisen Anja
Published: March 2006

A sensor device based on a single polymer cantilever and optical readout has been developed for detection of molecular recognition reactions without the need of a reference cantilever for subtraction of unspecific signals. Microcantilevers have been fabricated in the photoresist SU-8 with one surface passivated with a thin fluorocarbon layer. The SU-8 surface is sensitized with biological receptors by applying silanization methods, whereas the fluorocarbon surface remains inert to these processes. The thermal and mechanical properties of the chosen materials allow overcoming the main limitations of gold-coated silicon cantilevers: the temperature, pH, and ionic strength cross sensitivities. This is demonstrated by comparing the response of SU-8 cantilevers and that of gold-coated silicon nitride cantilevers to variations in temperature and pH. The sensitivity of the developed polymeric nanomechanical sensor is demonstrated by real-time detection of the human growth hormone with sensitivity in differential surface stress of about 1mN∕m.
Proapoptotic Bid is required for pulmonary fibrosis
Authors: Budinger G. R. Scott , Mutlu Gökhan M. , Eisenbart James , Fuller Alyson C. , Bellmeyer Amy A. , Baker Christina M. , Wilson Mindy , Ridge Karen , Barrett Terrence A. , Lee Vivian Y. , Chandel Navdeep S.
Published: March 2006

The molecular mechanisms of pulmonary fibrosis are poorly understood. Previous reports indicate that activation of TGF-β1 is essential for the development of pulmonary fibrosis. Here, we report that the proapoptotic Bcl-2 family member Bid is required for the development of pulmonary fibrosis after the intratracheal instillation of bleomycin. Mice lacking Bid exhibited significantly less pulmonary fibrosis in response to bleomycin compared with WT mice. The attenuation in pulmonary fibrosis was observed despite similar levels of inflammation, lung injury, and active TGF-β1 in bronchoalveolar lavage fluid 5 days after the administration of bleomycin in mice lacking Bid and in WT controls. Bleomycin induced similar levels cell death
in vitro
in alveolar epithelial cells isolated from WT and
bid
−/−
mice. By contrast, alveolar epithelial cells from
bid
−/−
mice were resistant to TGF-β1-induced cell death. These results indicate that Bcl-2 family members are critical regulators for the development of pulmonary fibrosis downstream of TGF-β1 activation.
Cardiac hypertrophy in transgenic rats expressing a dominant-negative mutant of the natriuretic peptide receptor B
Authors: Langenickel Thomas H. , Buttgereit Jens , Pagel-Langenickel Ines , Lindner Maren , Monti Jan , Beuerlein Knut , Al-Saadi Nidal , Plehm Ralph , Popova Elena , Tank Jens , Dietz Rainer , Willenbrock Roland , Bader Michael
Published: March 2006

Natriuretic peptides (NP) mediate their effects by activating membrane-bound guanylyl cyclase-coupled receptors A (NPR-A) or B (NPR-B). Whereas the pathophysiological role of NPR-A has been widely studied, only limited knowledge on the cardiovascular function of NPR-B is available.
In vitro
studies suggest antiproliferative and antihypertrophic actions of the NPR-B ligand C-type NP (CNP). Because of the lack of a specific pharmacological inhibitor, these effects could not clearly be attributed to impaired NPR-B signaling. Recently, gene deletion revealed a predominant role of NPR-B in endochondral ossification and development of female reproductive organs. However, morphological abnormalities and premature death of NPR-B-deficient mice preclude detailed cardiovascular phenotyping. In the present study, a dominant-negative mutant (NPR-BΔKC) was used to characterize CNP-dependent NPR-B signaling
in vitro
and in transgenic rats. Here we demonstrate that reduced CNP- but not atrial NP-dependent cGMP response attenuates antihypertrophic potency of CNP
in vitro
. In transgenic rats, NPR-BΔKC expression selectively reduced NPR-B but not NPR-A signaling. NPR-BΔKC transgenic rats display progressive, blood pressure-independent cardiac hypertrophy and elevated heart rate. The hypertrophic phenotype is further enhanced in chronic volume overload-induced congestive heart failure. Thus, this study provides evidence linking NPR-B signaling to the control of cardiac growth.
Free radical production requires both inducible nitric oxide synthase and xanthine oxidase in LPS-treated skin
Authors: Nakai Kozo , Kadiiska Maria B. , Jiang Jin-Jie , Stadler Krisztian , Mason Ronald P.
Published: March 2006

Free radical formation has been investigated in diverse experimental models of LPS-induced inflammation. Here, using electron spin resonance (ESR) and the spin trap α-(4-pyridyl-1-oxide)-
N-tert
-butylnitrone, we have detected an ESR spectrum of α-(4-pyridyl-1-oxide)-
N-tert
-butylnitrone radical adducts in the lipid extract of mouse skin treated with LPS for 6 h. The ESR spectrum was consistent with the trapping of lipid-derived radical adducts. In addition, a secondary radical-trapping technique using dimethyl sulfoxide (DMSO) demonstrated methyl radical formation, revealing the production of hydroxyl radical. Radical adduct formation was suppressed by aminoguanidine,
N
-(3-aminomethyl)benzylacetamidine (1400W), or allopurinol, suggesting a role for both inducible nitric oxide synthase (iNOS) and xanthine oxidase (XO) in free radical formation. The radical formation was also suppressed in iNOS knockout (iNOS
−/−
) mice, demonstrating the involvement of iNOS. NADPH oxidase was not required in the formation of these radical adducts because the ESR signal intensity was increased by LPS treatment in NADPH oxidase knockout (gp91
phox−/−
) mice as much as it was in the wild-type mouse. Nitric oxide (
•
NO) end products were increased in LPS-treated skin. As expected, the
•
NO end products were not suppressed by allopurinol but were by aminoguanidine. Interestingly, nitrotyrosine formation in LPS-treated skin was also suppressed by aminoguanidine and allopurinol independently. Pretreatment with the ferric iron chelator Desferal had no effect on free radical formation. Our results imply that both iNOS and XO, but neither NADPH oxidase nor ferric iron, work synergistically to form lipid radical and nitrotyrosine early in the skin inflammation caused by LPS.
Gestation stage-dependent mechanisms of invariant natural killer T cell-mediated pregnancy loss
Authors: Boyson Jonathan E. , Nagarkatti Nisha , Nizam Leena , Exley Mark A. , Strominger Jack L.
Published: March 2006

Stimulation of CD1d-restricted semiinvariant natural killer T cells by using the CD1d ligand α-galactosylceramide (αGalCer) induces pregnancy loss in mice through an ill-defined mechanism involving TNF, IFN-γ, and perforin. In this article, we demonstrate that during early gestation, αGalCer efficiently induced pregnancy loss in C57BL/6J and BALB/cJ mice in a perforin-dependent manner. In contrast, during midgestation perforin was no longer required for pregnancy loss. Concomitant with the loss of a perforin requirement at midgestation was the emergence of strain-dependent variations in susceptibility to αGalCer-induced pregnancy loss. Whereas pregnant C57BL/6J mice remained susceptible to αGalCer at midgestation, pregnant BALB/cJ mice were resistant to its effects. Pregnancy loss during midgestation was correlated with dramatically higher serum cytokine levels, including TNF and IL-2, in the susceptible C57BL/6J strain compared with the resistant BALB/cJ strain. Thus, the stage of gestation defined two distinct mechanisms of pregnancy loss: a perforin-dependent mechanism operating at early gestation and a perforin-independent, cytokine-dominated mechanism operating after midgestation.
Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level
Authors: Ilany Jacob , Bilan Philip J. , Kapur Sonia , Caldwell James S. , Patti Mary-Elizabeth , Marette Andre , Kahn C. Ronald
Published: March 2006

Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad
in vivo
, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter–enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose–response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes.
A method for evaluating the structural quality of protein models by using higher-order φ–ψ pairs scoring
Authors: Sims Gregory E. , Kim Sung-Hou
Published: March 2006

A method is presented for scoring the model quality of experimental and theoretical protein structures. The structural model to be evaluated is dissected into small fragments via a sliding window, where each fragment is represented by a vector of multiple φ–ψ angles. The sliding window ranges in size from a length of 1–10 φ–ψ pairs (3–12 residues). In this method, the conformation of each fragment is scored based on the fit of multiple φ–ψ angles of the fragment to a database of multiple φ–ψ angles from high-resolution x-ray crystal structures. We show that measuring the fit of predicted structural models to the allowed conformational space of longer fragments is a significant discriminator for model quality. Reasonable models have higher-order φ–ψ score fit values (
m
) > −1.00.
SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons
Authors: Rumbaugh Gavin , Adams J. Paige , Kim Jee H. , Huganir Richard L.
Published: March 2006

Silent synapses, or excitatory synapses that lack functional α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), are thought to be critical for regulation of neuronal circuits and synaptic plasticity. Here, we report that SynGAP, an excitatory synapse-specific RasGAP, regulates AMPAR trafficking, silent synapse number, and excitatory synaptic transmission in hippocampal and cortical cultured neurons. Overexpression of SynGAP in neurons results in a remarkable depression of AMPAR-mediated miniature excitatory postsynaptic currents, a significant reduction in synaptic AMPAR surface expression, and a decrease in the insertion of AMPARs into the plasma membrane. This change is specific for AMPARs because no change is observed in synaptic NMDA receptor expression or total synapse density. In contrast to these results, synaptic transmission is increased in neurons from SynGAP knockout mice as well as in neuronal cultures treated with SynGAP small interfering RNA. In addition, activation of the extracellular signal-regulated kinase, ERK, is significantly decreased in SynGAP-overexpressing neurons, whereas P38 mitogen-activated protein kinase (MAPK) signaling is potentiated. Furthermore, ERK activation is up-regulated in neurons from SynGAP knockout mice, whereas P38 MAPK function is depressed. Taken together, these data suggest that SynGAP plays a critical role in the regulation of neuronal MAPK signaling, AMPAR membrane trafficking, and excitatory synaptic transmission.
Modeling the role of bacteriophage in the control of cholera outbreaks
Authors: Jensen Mark A. , Faruque Shah M. , Mekalanos John J. , Levin Bruce R.
Published: March 2006

Cholera is a waterborne diarrheal disease that continues to plague the developing world. Individuals become infected by consuming water from reservoirs contaminated by virulent strains of the bacteriumVibrio cholerae. Epidemiological and environmental observations of a cholera outbreak in Dhaka, Bangladesh, suggest that lytic bacteriophage specific forV. choleraemay limit the severity of cholera outbreaks by killing bacteria present in the reservoir and in infected individuals. To quantify this idea and generate testable hypotheses, we analyzed a mathematical model that combines the epidemiology of cholera with the population dynamics of the bacteria and phage. Under biologically reasonable conditions, we found that vibriophage can ameliorate cholera outbreaks. If phage predation limits bacterial density before an outbreak, a transient reduction in phage density can disrupt that limitation, and subsequent bacterial growth can initiate a cholera outbreak. The severity of the outbreak depends on the density of phage remaining in the reservoir. If the outbreak is initiated instead by a rise in bacterial density, the introduction of phage can reduce the severity of the outbreak and promote its decline. In both situations, the magnitude of the phage effect depends mainly on vibrio growth and phage mortality rates; the lower the rates, the greater the effect. Our analysis also suggests that either bacteria in the environmental reservoir are hyperinfectious or most victims ingest bacteria amplified in food or drinking water contaminated by environmental water carrying few viableV. cholerae. Our theoretical results make a number of empirically testable predictions.
Self-synthesizing DNA transposons in eukaryotes
Authors: Kapitonov Vladimir V. , Jurka Jerzy
Published: March 2006

Eukaryotes contain numerous transposable or mobile elements capable of parasite-like proliferation in the host genome. All known transposable elements in eukaryotes belong to two types: retrotransposons and DNA transposons. Here we report a previously uncharacterized class of DNA transposons called
Polintons
that populate genomes of protists, fungi, and animals, including entamoeba, soybean rust, hydra, sea anemone, nematodes, fruit flies, beetle, sea urchin, sea squirt, fish, lizard, frog, and chicken.
Polintons
from all these species are characterized by a unique set of proteins necessary for their transposition, including a protein-primed DNA polymerase B, retroviral integrase, cysteine protease, and ATPase. In addition,
Polintons
are characterized by 6-bp target site duplications, terminal-inverted repeats that are several hundred nucleotides long, and 5′-AG and TC-3′ termini. Analogously to known transposable elements,
Polintons
exist as autonomous and nonautonomous elements. Our data suggest that
Polintons
have evolved from a linear plasmid that acquired a retroviral integrase at least 1 billion years ago. According to the model of
Polinton
transposition proposed here, a
Polinton
DNA molecule excised from the genome serves as a template for extrachromosomal synthesis of its double-stranded DNA copy by the
Polinton
-encoded DNA polymerase and is inserted back into genome by its integrase.
Incidental Mononuclear Cell Infiltrate in the Uvea of Cynomolgus Monkeys
Authors: Sinha Dinesh P. , Cartwright Mark E. , Johnson Robert C.
Published: March 2006

Mononuclear cell infiltrate (MCI) in the uvea was observed in naïve, untreated (control group) cynomolgus monkeys in approximately 25% of drug safety evaluation studies. The total incidence of MCI in the choroid and the ciliary body was 29% of 342 males and 25% of 306 female monkeys. In the studies in which MCI was present in the ciliary body or choroid, the incidence was as high as 75%. There were no other ocular histopathologic findings in these monkeys. All monkeys were clinically healthy and the eyes were not remarkable when examined ophthalmoscopically.
Mechanisms and Biomarkers of Cardiovascular Injury Induced by Phosphodiesterase Inhibitor III SK&F 95654 in the Spontaneously Hypertensive Rat
Authors: Zhang Jun , Herman Eugene H. , Robertson Donald G. , Reily Michael D. , Knapton Alan , Ratajczak Helen V. , Rifai Nader , Honchel Ronald , Blanchard Kerry T. , Stoll Raymond E. , Sistare Frank D.
Published: March 2006

The cardiovascular injury of the type III selective PDE inhibitor SK&F 95654 was investigated in SHR. Twenty-four hours after a single sc injection of 100 or 200 mg/kg of the drug, rats exhibited cardiomyocyte necrosis and apoptosis, interstitial inflammation, hemorrhage and edema, as well as mesenteric arterial hemorrhage and necrosis, periarteritis, EC and VSMC apoptosis, EC activation, and MC activation and degranulation. Elevated serum levels of cTnT and decreased cTnT immunoperoxidase staining on cardiomyocytes were detected in the drug-treated rats. Serum levels of α2-macroglobulin and IL-6 were significantly elevated following drug treatment. NMR spectral patterns of urine samples are significantly different between the drug-treated and control rats. These results indicate that measurement of serum cTnT, acute phase proteins, and cytokines as well as metabonomic urine profiles may serve as potential biomarkers for drug-induced cardiovascular injury in rats. Increased expression of CD63 on MC (tissue biomarker of MC), of nitrotyrosine on MC and EC (an indirect indicator of NO in vivo), and of iNOS on MC and EC (source of NO) suggest that NO produced by activated and degranulated MC as well as activated EC play an important role in SK&F 95654-induced mesenteric vascular injury.
Review of the Effects of Anti-Angiogenic Compounds on the Epiphyseal Growth Plate
Authors: Hall Anthony P. , Westwood F. Russell , Wadsworth Peter F.
Published: March 2006

The formation of new blood vessels from a pre-existing vascular bed, termed “angiogenesis,” is of critical importance for the growth and development of the animal since it is required for the growth of the skeleton during endochondral ossification, development and cycling of the corpus luteum and uterus, and for the repair of tissues during wound healing. “Vasculogenesis,” the de novo formation of blood vessels is also important for the proper function and development of the vascular system in the embryo. New blood vessel formation is a prominent feature and permissive factor in the relentless progression of many human diseases, one of the most important examples of which is neoplasia. It is for this reason that angiogenesis is considered to be one of the hallmarks of cancer. The development of new classes of drugs that inhibit the growth and proper functioning of new blood vessels in vivo is likely to provide significant therapeutic benefit in the treatment of cancer, as well as other conditions where angiogenesis is a strong driver to the disease process. During the preclinical safety testing of these drugs, it is becoming increasingly clear that their in vivo efficacy is reflected in the profile of “expected toxicity” (resulting from pharmacology) observed in laboratory animals, so much so, that this profile of “desired” toxicity may act as a signature for their anti-angiogenic effect. In this article we review the major mechanisms controlling angiogenesis and its role during endochondral ossification. We also review the effects of perturbation of endochondral ossification through four mechanisms—inhibition of vascular endothelial growth factor (VEGF), pp60 c-Src kinase and matrix metalloproteinases as well as disruption of the blood supply with vascular targeting agents. Inhibition through each of these mechanisms appears to have broadly similar effects on the epiphyseal growth plate characterised by thickening due to the retention of hypertrophic chondrocytes resulting from the inhibition of angiogenesis. In contrast, in the metaphysis there are differing effects reflecting the specific role of these targets at this site.
Playing the Trump Card
Authors: Stoppard Tom
Published: March 2006

FREE SPEECH WILL PREVAIL WHEN WE ACCORD IT TO OTHERS
Rebirth of Russian Nationalism
Authors: Panfilov Oleg , Tait Arch
Published: March 2006

STATE CONTROL OF THE MASS MEDIA IS THE PRINCIPAL CAUSE OF THE GROWTH OF XENOPHOBIA IN RUSSIA, WITH TELEVISION THE MAIN WEAPON IN THE PROPAGANDA ARMOURY
Law and a Sort of Order
Authors: Hudson Anthony
Published: March 2006

WHAT TO DO WHEN FREE SPEECH IS CONFRONTED BY BAD LAWS
When Speech Became Treason
Authors: Kenny Mary
Published: March 2006

WILLIAM JOYCE, THE LAST MAN TO BE EXECUTED FOR TREASON IN THE UK, DIED FOR HIS WORDS NOT HIS DEEDS, SAYS HIS LATEST BIOGRAPHER
Lessons in Legislation
Authors: Butler Amir
Published: March 2006

AUSTRALIAN LAWS AGAINST INCITEMENT TO RELIGIOUS HATRED HAVE SOWN DIVISION AND UNDERMINED FREEDOM OF SPEECH, THOUGHT AND CONSCIENCE
Reduced To a Sideshow
Authors: Moorehead Caroline
Published: March 2006

AFGHANISTAN IS STILL IN A STATE OF PERPETUAL CIVIL WAR, BUT THE CAMERAS HAVE ALL MOVED ON TO THE BIG SHOW IN IRAQ
Chad in the Firing Line
Authors: De Waal Alex
Published: March 2006

CHAD’S LONG-RUNNING WAR SPILLED OVER INTO DARFUR AND SET IN MOTION THE CRISIS THERE. NOW IT LOOKS AS IF IT’S RETURNING ACROSS THE BORDER, SOWING MAYHEM IN ITS WAKE
Peace or a Lasting Truce?
Authors: Dizdarevic Srdjan , Pribichevich Zoric Christina
Published: March 2006

TEN YEARS AFTER THE INTERNATIONAL COMMUNITY INTERVENED TO END THE WAR, BOSNIA-HERZEGOVINA IS STILL RIVEN BY RELIGIOUS AND ETHNIC DIVIDES
Missing in Action
Authors: Fisher Mark
Published: March 2006

WARS PUT CIVILISATIONS AS WELL AS PEOPLE TO THE SWORD BUT MUCH OF THE RECENT DESTRUCTION OF IRAQ’S ANCIENT CULTURE COULD HAVE BEEN AVOIDED
Appearance and Reality
Authors: Petley Julian
Published: March 2006

THERE HAS BEEN PRECIOUS LITTLE CONSULTATION ON THE UK’S CONSULTATION ON THE POSSESSION OF EXTREME PORNOGRAPHIC MATERIAL THOUGH THERE ARE SERIOUS GROUNDS FOR ALARM
Moving On
Authors: Hilsum Lindsey
Published: March 2006

AUDIENCES WANT TO SEE WARS THAT FEATURE ‘OUR BOYS’. JOURNALISTS NEED WARS THEY CAN UNDERSTAND AND COMMUNICATE. THE GRUBBY CONFLICTS THAT OFTEN FOLLOW THE MAIN ACTION HOLD LITTLE INTEREST FOR EITHER
…And One You May Have Missed
Authors: Rumpf Roger , Chagnon Jacquelyn
Published: March 2006

LAOS WAS OFFICALLY NEUTRAL THROUGHOUT THE VIETNAM WAR BUT THIS DID NOT PREVENT INTERVENTION BY EITHER PARTY TO THE CONFLICT
Exosomes and HIV Gag bud from endosome-like domains of the T cell plasma membrane
Authors: Booth Amy M. , Fang Yi , Fallon Jonathan K. , Yang Jr-Ming , Hildreth James E.K. , Gould Stephen J.
Published: March 2006

Exosomes are secreted, single membrane organelles of ∼100 nm diameter. Their biogenesis is typically thought to occur in a two-step process involving (1) outward vesicle budding at limiting membranes of endosomes (outward = away from the cytoplasm), which generates intralumenal vesicles, followed by (2) endosome–plasma membrane fusion, which releases these internal vesicles into the extracellular milieu as exosomes. In this study, we present evidence that certain cells, including Jurkat T cells, possess discrete domains of plasma membrane that are enriched for exosomal and endosomal proteins, retain the endosomal property of outward vesicle budding, and serve as sites of immediate exosome biogenesis. It has been hypothesized that retroviruses utilize the exosome biogenesis pathway for the formation of infectious particles. In support of this, we find that Jurkat T cells direct the key budding factor of HIV, HIV Gag, to these endosome-like domains of plasma membrane and secrete HIV Gag from the cell in exosomes.
Osteoblast differentiation and skeletal development are regulated by Mdm2–p53 signaling
Authors: Lengner Christopher J. , Steinman Heather A. , Gagnon James , Smith Thomas W. , Henderson Janet E. , Kream Barbara E. , Stein Gary S. , Lian Jane B. , Jones Stephen N.
Published: March 2006

Mdm2 is required to negatively regulate p53 activity at the peri-implantation stage of early mouse development. However, the absolute requirement for Mdm2 throughout embryogenesis and in organogenesis is unknown. To explore Mdm2–p53 signaling in osteogenesis, Mdm2-conditional mice were bred with Col3.6-Cre–transgenic mice that express Cre recombinase in osteoblast lineage cells. Mdm2-conditional Col3.6-Cre mice die at birth and display multiple skeletal defects. Osteoblast progenitor cells deleted for Mdm2 have elevated p53 activity, reduced proliferation, reduced levels of the master osteoblast transcriptional regulator Runx2, and reduced differentiation. In contrast, p53-null osteoprogenitor cells have increased proliferation, increased expression of Runx2, increased osteoblast maturation, and increased tumorigenic potential, as mice specifically deleted for p53 in osteoblasts develop osteosarcomas. These results demonstrate that p53 plays a critical role in bone organogenesis and homeostasis by negatively regulating bone development and growth and by suppressing bone neoplasia and that Mdm2-mediated inhibition of p53 function is a prerequisite for Runx2 activation, osteoblast differentiation, and proper skeletal formation.
Analysis of kinesin motor function at budding yeast kinetochores
Authors: Tytell Jessica D. , Sorger Peter K.
Published: March 2006

Accurate chromosome segregation during mitosis requires biorientation of sister chromatids on the microtubules (MT) of the mitotic spindle. Chromosome–MT binding is mediated by kinetochores, which are multiprotein structures that assemble on centromeric (CEN) DNA. The simple CENs of budding yeast are among the best understood, but the roles of kinesin motor proteins at yeast kinetochores have yet to be determined, despite evidence of their importance in higher eukaryotes. We show that all four nuclear kinesins in Saccharomyces cerevisiae localize to kinetochores and function in three distinct processes. Kip1p and Cin8p, which are kinesin-5/BimC family members, cluster kinetochores into their characteristic bilobed metaphase configuration. Kip3p, a kinesin-8,-13/KinI kinesin, synchronizes poleward kinetochore movement during anaphase A. The kinesin-14 motor Kar3p appears to function at the subset of kinetochores that become detached from spindle MTs. These data demonstrate roles for structurally diverse motors in the complex processes of chromosome segregation and reveal important similarities and intriguing differences between higher and lower eukaryotes.
The Drosophila melanogaster Apaf-1 homologue ARK is required for most, but not all, programmed cell death
Authors: Mills Kathryn , Daish Tasman , Harvey Kieran F. , Pfleger Cathie M. , Hariharan Iswar K. , Kumar Sharad
Published: March 2006

The Apaf-1 protein is essential for cytochrome c–mediated caspase-9 activation in the intrinsic mammalian pathway of apoptosis. Although Apaf-1 is the only known mammalian homologue of the Caenorhabditis elegans CED-4 protein, the deficiency of apaf-1 in cells or in mice results in a limited cell survival phenotype, suggesting that alternative mechanisms of caspase activation and apoptosis exist in mammals. In Drosophila melanogaster, the only Apaf-1/CED-4 homologue, ARK, is required for the activation of the caspase-9/CED-3–like caspase DRONC. Using specific mutants that are deficient for ark function, we demonstrate that ARK is essential for most programmed cell death (PCD) during D. melanogaster development, as well as for radiation-induced apoptosis. ark mutant embryos have extra cells, and tissues such as brain lobes and wing discs are enlarged. These tissues from ark mutant larvae lack detectable PCD. During metamorphosis, larval salivary gland removal was severely delayed in ark mutants. However, PCD occurred normally in the larval midgut, suggesting that ARK-independent cell death pathways also exist in D. melanogaster.
Drosophila Cajal bodies: accessories not included
Authors: Matera A. Gregory
Published: March 2006

Cajal bodies are nuclear sites of small ribonucleoprotein (RNP) remodeling and maturation. A recent study describes the discovery of the Drosophila Cajal body, revealing some interesting insights into the subnuclear organization of RNA processing machineries among different species.
Assessment of the Compliance of Nigerian Dentists With Infection Control: A Preliminary Study
Authors: Sofola Oyinkansola Olulola , Savage Kofo Olaide
Published: March 2006

Objective:

To assess the compliance of a group of Nigerian dentists with standard infection control practices.

Method:

A confidential self-administered questionnaire survey was conducted among dentists engaged in active clinical practices in public hospitals in Lagos, Nigeria (n = 185).

Results:

One hundred forty-six questionnaires were returned (response rate, 78.9%). Most (70.6%) of the dentists always wore gloves when treating patients, whereas 29.4% sometimes did. Regarding facemasks, 45.9% always wore them, 52.7% sometimes wore them, and 1.4% never wore them. Protective eye wear was always worn by 4.8% of the dentists, sometimes worn by 52.7%, and never worn by 42.5%. Approximately half (50.7%) of the respondents had received hepatitis B vaccination. Sterilization was performed using a combination of methods, including auto-claving (84.1%), boiling (19.3%), dry heat (17.5%), and chemicals (29.7%). Nonavailability of materials was the major reason for noncompliance with infection control practices.

Conclusions:

Nigerian dentists need continuous education regarding infection control. Also, Nigerian hospitals urgently need adequate funding for up-to-date and functional equipment and materials.
Activity of Three Disinfectants and Acidified Nitrite AgainstClostridium difficileSpores
Authors: Wullt Marlene , Odenholt Inga , Walder Mats
Published: March 2006

Objective:

To identify environmentally safe, rapidly acting agents for killing spores ofClostridium difficilein the hospital environment.

Design:

Three classic disinfectants (2% glutaraldehyde, 1.6% peracetyl ions, and 70% isopropanol) and acidified nitrite were compared for activity againstC. difficilespores. Four strains ofC. difficilebelonging to different serogroups were tested using a dilution–neutralization method according to preliminary European Standard prEN 14347. For peracetyl ions and acidified nitrite, the subjective cleaning effect and the sporicidal activity was also tested in the presence of organic load.

Results:

Peracetyl ions were highly sporicidal and yielded a minimum 4 log10reduction of germinating spores already at short exposure times, independent of organic load conditions. Isopropanol 70% showed low or no inactivation at all exposure times, whereas glutaraldehyde and acidified nitrite each resulted in an increasing inactivation factor (IF) over time, from an IF greater than 1.4 at 5 minutes of exposure time to greater than 4.1 at 30 minutes. Soiling conditions did not influence the effect of acidified nitrite. There was no difference in the IF among the 4 strains tested for any of the investigated agents. Acidified nitrite demonstrated a good subjective cleaning effect and peracetyl ions demonstrated a satisfactory effect.

Conclusions:

Cidal activity was shown againstC. difficilespores by glutaraldehyde, peracetyl ions, and acidified nitrite. As acidified nitrite and peracetyl ions are considered to be environmentally safe chemicals, these agents seem well suited for the disinfection ofC. difficilespores in the hospital environment.
Theoretical Risk for Occupational Blood-Borne Infections in Forensic Pathologists
Authors: Nolte Kurt B. , Yoon Steven S.
Published: March 2006

Using a cumulative probability analysis and published data, we calculated the theoretical career risk of occupational HIV (2.4%) and HCV (39%; possible range, 13% to 94%) infections for forensic pathologists. Serologic studies of these physicians are needed to clarify occupational exposure and infection risks. Autopsy personnel should wear cut-resistant undergloves to decrease percutaneous injuries.
Ten-Year Persistence of Antibody to Hepatitis B Surface Antigen in Healthcare Workers Vaccinated Against Hepatitis B Virus, and Response to Booster Vaccination
Authors: Durlach Ricardo , Laugas Stella , Freuler Cristina B. , Rodríguez Viviana E. , Costa Marta
Published: March 2006

This study estimated the number of HCWs with protective antibody levels 5 and 10 years after HBV vaccination. Kaplan-Meier probabilities of protective levels were 0.95 at 60 days after vaccination, 0.87 at 5 years, and 0.79 at 10 years. Those without protective levels displayed good response 7 and 30 days after a booster
Elevated Preoperative Fasting Serum Glucose Levels Increase the Risk of Postoperative Mediastinitis in Patients Undergoing Open Heart Surgery
Authors: Wilson Stephen J. , Sexton Daniel J.
Published: March 2006

We conducted a case-control study to investigate the relationship between preoperative fasting serum glucose and postoperative mediastinitis in patients undergoing open heart surgery. Multivariate analysis revealed that a glucose level of 126 mg/dL or greater was associated with a significantly increased risk of mediastinitis (OR, 5.25;P= .002).
Meningitis Due to Enterobacter aerogenes Subsequent to Resection of Acoustic Neuroma and Percutaneous Endoscopic Gastrostomy Tube Placement: A Rare Nosocomial Event
Authors: Poetker David M. , Edmiston Charles E. , Smith Michelle M. , Meyer Glenn A. , Wackym Phillip A.
Published: March 2006

We present a case of meningitis after percutaneous endoscopic gastrostomy (PEG) tube placement subsequent to acoustic neuroma resection and cranioplasty. Four days following PEG tube placement the patient developed Enterobacter aerogenes meningitis, requiring explantation of infected cranioplasty material. His condition subsequently improved. Etiology and future intervention strategies are discussed (Infect Control Hosp Epidemiol 2003;24:780-782).
Relative Versus Absolute Noncontagiousness of Respiratory Tuberculosis on Treatment
Authors: Long Richard , Bochar Karen , Chomyc Sylvia , Talbot James , Barrie James , Kunimoto Dennis , Tilley Peter
Published: March 2006

Objective:

To assess the validity of current estimates of the noncontagiousness of sputum smear-positive respiratory tuberculosis (TB) on treatment.

Design:

A descriptive analysis of the mycobacteriologic response to treatment.

Setting:

A TB inpatient unit of a Canadian hospital.

Patients:

Thirty-two HIV-seronegative patients with moderate to advanced sputum smear-positive respiratory TB were treated with uninterrupted, directly observed, weight-adjusted isoniazid, rifampin, and pyrazinamide. Each patient's initial isolate was drug susceptible and each patient's sputum mycobacteriology was systematically followed until 3 consecutive sputum smears were negative on 3 separate days.

Results:

The time to smear conversion varied remarkably (range, 8 to 115 days; average, 46 days) and was influenced by sputum sampling frequency. Only 3 patients (9.4%) had smear conversions by 14 days and only 8 (25%) had smear conversions by 21 days, the average time it took for drug susceptibility test results to become available. During the first 21 days of treatment, the semiquantitative sputum smear score decreased rapidly and the time to detection of positive cultures doubled. Within the time to smear conversion, virtually all smear-positive specimens (98%) were culture positive and only 34% of the patients had culture conversions (ie, 3 consecutive negative cultures).

Conclusion:

Current estimates of the noncontagiousness of sputum smear-positive respiratory TB on treatment (for 14 days, for 21 days, or until smear conversion) are estimates of relative noncontagiousness. They do not signal absolute noncontagiousness (culture conversion). Semiquantitative smear and time-to-detection data suggest that respiratory isolation beyond 21 days of optimal treatment should be selective.
Outcomes of Nosocomial Bloodstream Infections in Adult Neutropenic Patients: A Prospective Cohort and Matched Case-Control Study
Authors: Wisplinghoff Hilmar , Cornely Oliver A. , Moser Susanne , Bethe Ullrich , Stützer Hartmut , Salzberger Bernd , Fätkenheuer Gerd , Seifert Harald
Published: March 2006

Objective:

To examine the clinical and epidemiologic features, excess length of stay, extra costs, and mortality attributable to bloodstream infection (BSI) in neutropenic patients with hematologic malignancies.

Design:

Prospective cohort and matched case-control study.

Patients:

All adult neutropenic patients with hematologic malignancies admitted to Cologne University Hospital between May 1, 1997, and April 30, 1998, were prospectively observed. Case-patients were defined as patients with nosocomial BSI; control-patients were selected among patients without BSI.

Results:

During the study period, the BSI rate in neutropenic patients was 14.3 per 100 neutropenic episodes. Eighty-four case-patients were included. Matching was successful for 96% of the cohort; 81 matched pairs were studied. The mean total length of stay was significantly longer for patients with BSI than for control-patients (37 vs 29 days;P= .002). Extra costs attributable to the infection averaged $3,200 (U.S.) per patient. The crude mortality rates of case-patients and control-patients were 16% and 4%, respectively (P= .013), with an attributable mortality of 12% (odds ratio, 11). Eighty-seven percent of patients met the criteria for sepsis according to the American College of Chest Physicians/Society of Critical Care Medicine. Severe sepsis or septic shock occurred in 13% of patients and was correlated with mortality (55% vs 10% in patients without severe sepsis or septic shock;P=.01).

Conclusions:

Nosocomial BSI in neutropenic patients is significantly associated with an excess length of hospital stay, extra costs, and excess mortality. Severe sepsis and septic shock are closely correlated with an adverse outcome.
Preventing Central Venous Catheter-Associated Primary Bloodstream Infections: Characteristics of Practices Among Hospitals Participating in the Evaluation of Processes and Indicators in Infection Control (EPIC) Study
Authors: Braun Barbara I. , Kritchevsky Stephen B. , Wong Edward S. , Solomon Steve L. , Steele Lynn , Richards Cheryl L. , Simmons Bryan P. ,   Evaluation of Processes and Indicators in Infection Control (EPIC) Study Group
Published: March 2006

Objectives:

To describe the conceptual framework and methodology of the Evaluation of Processes and Indicators in Infection Control (EPIC) study and present results of CVC insertion characteristics and organizational practices for preventing BSIs. The goal of the EPIC study was to evaluate relationships among processes of care, organizational characteristics, and the outcome of BSI.

Design:

This was a multicenter prospective observational study of variation in hospital practices related to preventing CVC-associated BSIs. Process of care information (eg, barrier use during insertions and experience of the inserting practitioner) was collected for a random sample of approximately 5 CVC insertions per month per hospital during November 1998 to December 1999. Organization demographic and practice information (eg, surveillance activities and staff and ICU nurse staffing levels) was also collected.

Setting:

Medical, surgical, or medical-surgical ICUs from 55 hospitals (41 U.S. and 14 international sites).

Participants:

Process information was obtained for 3,320 CVC insertions with an average of 58.2 (± 16.1) insertions per hospital. Fifty-four hospitals provided policy and practice information.

Results:

Staff spent an average of 13 hours per week in study ICU surveillance. Most patients received nontunneled, multiple lumen CVCs, of which fewer than 25% were coated with antimicrobial material. Regarding barriers, most clinicians wore masks (81.5%) and gowns (76.8%); 58.1% used large drapes. Few hospitals (18.1%) used an intravenous team to manage ICU CVCs.

Conclusions:

Substantial variation exists in CVC insertion practice and BSI prevention activities. Understanding which practices have the greatest impact on BSI rates can help hospitals better target improvement interventions.
Bloodstream Infections in a Community Hospital: A 25-Year Follow-Up
Authors: Scheckler William E. , Bobula James A. , Beamsley Mark B. , Hadden Scott T.
Published: March 2006

Objective:

To examine the current status of bloodstream infections (BSIs) in a community hospital as part of a 25-year longitudinal study.

Design:

Retrospective descriptive epidemiologic study.

Setting:

Community teaching hospital.

Patients:

All inpatients in 1998 with a positive blood culture who met the CDC NNIS System case definition of BSI.

Methods:

Cases were stratified by underlying illness category using case mix adjustment categories (after McCabe) and reviewed for associations among mortality, underlying illness severity, and multiple clinical and laboratory parameters.

Results:

Of 19,289 patients discharged in 1998,185 had an episode of infection documented by blood culture (96 cases per 10,000 inpatients). BSI was twice as frequent in patients 65 years and older compared with younger patients. BSIs caused or contributed to the deaths of 22 patients for an overall case-fatality rate of 11.9% compared with 20.7% in 1982 (P = .02). Striking decreases were noted for in-hospital patient mortality in 1998 for BSIs with ultimately and rapidly fatal underlying illnesses (P = .02 and P < .10, respectively). Primary bacteremia decreased compared with 1982. Antibiotic use was vigorous, but resistance was modest in both nosocomial and community-acquired organisms and had changed little from 1982 and 1987.

Conclusions:

Compared with previous studies, case-fatality rates in patients with BSI were substantially lower in rapidly fatal and ultimately fatal underlying illness categories. Antibiotic use was extensive but prompt and appropriate. Microorganism resistance to antibiotics changed little from the 1980s.
Community-Acquired Methicillin-Resistant Staphylococcus aureus Infection in Singapore Is Usually “Healthcare Associated”
Authors: Tambyah Paul A. , Habib Abdulrazaq G. , Ng Toon-Mae , Goh Helen , Kumarasinghe Gamini
Published: March 2006

Objecttve:

To assess the frequency of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections.

Setting:

A teaching hospital in Singapore.

Methods:

Prospectively collected surveillance data were reviewed during a 1-year period to determine the extent and origin of community-acquired MRSA infections.

Results:

Whereas 32% of 383 MRSA infections were detected less than 48 hours after hospital admission and would, by convention, be classified as “community acquired,” all but one of these were among patients who had been exposed to outpatient centers including dialysis or chemotherapy clinics, visiting nurses, community hospitals, or all three.

Conclusions:

With health care increasingly being delivered in an outpatient setting, community-acquired MRSA infections are often acquired in hospital-related sites and most may be more accurately described as “healthcare acquired.” Infection control measures need to move beyond the traditional paradigm of acute care hospitals to effectively control the spread of resistant pathogens.
Rates of Carriage of Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus in an Outpatient Population
Authors: Kenner Julie , O'Connor Tasha , Piantanida Nicholas , Fishbain Joel , Eberly Bardwell , Viscount Helen , Uyehara Catherine , Hospenthal Duane
Published: March 2006

Objectives:

To assess the prevalence of and the clinical features associated with asymptomatic Staphylococcus aureus colonization in a healthy outpatient population, and to compare the characteristics of colonizing methicillin-resistant S. aureus (MRSA) strains with those of strains causing infection in our community and hospital.

Setting:

Outpatient military clinics.

Methods:

Specimens were obtained from the nares, pharynx, and axillae of 404 outpatients, and a questionnaire was administered to obtain demographic and risk factor information. MRSA strains were typed by pulsed-field gel electrophoresis (PFGE) and evaluated for antibiotic susceptibility. Antibiograms of study MRSA strains were compared with those of MRSA strains causing clinical illness during the same time period.

Results:

Methicillin-susceptible S. aureus (MSSA) colonization was present in 153 (38%) of the 404 asymptomatic outpatients, and MRSA colonization was present in 8 (2%). Detection of colonization was highest from the nares. No clinical risk factor was significantly associated with MRSA colonization; however, a tendency was noted for MRSA to be more common in men and in those who were older or who had been recently hospitalized. All colonizing MRSA strains had unique patterns on PFGE. In contrast to strains responsible for hospital infections, most colonizing isolates of MRSA were susceptible to oral antibiotics.

Conclusions:

MRSA and MSSA colonization is common in our outpatient population. Colonization is best detected by nares cultures and most carriers of MRSA are without apparent predisposing risk factors for acquisition. Colonizing isolates of MRSA are heterogeneous and, unlike nosocomial isolates, often retain susceptibility to other non-beta-lactam antibiotics.