bluuebunny/crossref_metadata_2025 huggingface dataset:
GenoType MTBDR
plus
Assay for Molecular Detection of Rifampin and Isoniazid Resistance in
Mycobacterium tuberculosis
Strains and Clinical Samples
Authors: Lacoma A. , Garcia-Sierra N. , Prat C. , Ruiz-Manzano J. , Haba L. , Rosés S. , Maldonado J. , Domínguez J.
Published: September 2008

The purpose of this study was to evaluate the GenoType MTBDR
plus
assay (Hain Lifescience GmbH, Nehren, Germany) for its ability to detect resistance to rifampin (RIF) and isoniazid (INH) in
Mycobacterium tuberculosis
clinical strains and directly in clinical samples. A total of 62 clinical strains characterized with the Bactec 460TB system were included. For the INH-resistant strains, the MIC was measured and sequencing was performed. Sixty-five clinical samples from 28 patients (39 smear-positive samples and 26 smear-negative samples) were also tested directly. The corresponding isolates of the clinical specimens were studied with the Bactec 460TB system. The overall rates of concordance of the MTBDR
plus
assay and the Bactec 460TB system for the detection of RIF and INH susceptibility in clinical strains were 98.3% (61/62) and 79% (49/62), respectively. The rate of concordance between the Bactec 460TB system and the MTBDR
plus
test for the detection of INH resistance in the group of 27 strains with low-level resistance was 62.9% (17/27), and that for the detection of INH resistance in the group of 21 strains with high-level resistance was 85.71% (18/21). Valid test results were obtained for 78.45% (51/65) of the clinical samples tested. The rates of concordance between both assays for the detection of drug resistance in these samples were 98% (50/51) for RIF and 96.2% (49/51) for INH. Taking into account only one sample per patient, the overall rate of concordance between both tests was 92.85% (26/28). The GenoType MTBDR
plus
assay is easy to perform and is a useful tool for the management of tuberculosis, as it allows the detection of resistance to RIF and INH in
M. tuberculosis
strains and also in clinical samples.
Nonutility of Repeat Laboratory Testing for Detection of
Clostridium difficile
by Use of PCR or Enzyme Immunoassay
Authors: Aichinger Elisabeth , Schleck Cathy D. , Harmsen William S. , Nyre Lisa M. , Patel Robin
Published: September 2008

The diagnostic gains of repeat testing for
Clostridium difficile
by enzyme immunoassay and PCR (i.e., initial negative result followed by positive result) within a 7-day period were 1.9 and 1.7%, respectively. There is little value of repeat testing for
C. difficile
by enzyme immunoassay or PCR.
Comparison of Three Commercial Methods for Rapid Detection of
Clostridium difficile
Toxins A and B from Fecal Specimens
Authors: Alcalá L. , Sánchez-Cambronero L. , Catalán M. P. , Sánchez-Somolinos M. , Peláez M. T. , Marín M. , Bouza E.
Published: September 2008

Three rapid enzyme immunoassays (X/pect
Clostridium difficile
Toxin A/B test, Wampole Tox A/B Quik Chek, and ImmunoCard Toxins A&B) were compared for the diagnosis of
Clostridium difficile
infection. Of the 367 stool specimens tested, 102 (27.8%) were positive for toxigenic
C. difficile
when a combination of direct cytotoxicity assay and cytotoxic culture was used as the gold standard. Sensitivity/specificity values were 49.0%/95.8%, 54.9%/95.5%, and 66.7%/95.1%, respectively. The median times to test five stool specimens were 28, 30, and 24 min, respectively. The ImmunoCard test was the quickest and most sensitive test of the three enzyme immunoassays evaluated.
Validation of 24-Hour Fluconazole MIC Readings versus the CLSI 48-Hour Broth Microdilution Reference Method: Results from a Global
Candida
Antifungal Surveillance Program
Authors: Pfaller M. A. , Boyken L. B. , Hollis R. J. , Kroeger J. , Messer S. A. , Tendolkar S. , Diekema D. J.
Published: September 2008

We performed 24- and 48-h MIC determinations and disk diffusion testing of fluconazole against more than 11,000 clinical isolates of
Candida
species. By using the reference MIC breakpoints, the categorical agreement between the 24-h and reference 48-h broth microdilution results ranged from 93.8% (all
Candida
species) to 94.9% (all
Candida
species minus
Candida krusei
), with only 0.1% very major errors (VME). The essential agreement (within 2 log
2
dilutions) between the 24-h and 48-h results was 99.6%. The categorical agreement between the 24-h disk diffusion results and the 24-h MIC results, using the previously established breakpoints, was 94.4%, with 0.1% VME. Both the MIC and the disk diffusion results obtained for fluconazole after only 24 h of incubation may be used to determine the susceptibilities of
Candida
spp. to this widely used antifungal agent.
Sociodemographic differences in triggers to quit smoking: findings from a national survey
Authors: Vangeli E , West R
Published: September 2008

Objective:

Reasons for quitting smoking and triggers that finally precipitate a quit attempt are not necessarily the same thing. We sought to assess variation in reported triggers of attempts to stop smoking as a function of age, gender and socioeconomic status.

Methods:

Cross-sectional household survey in England. A total of 2441 smokers and ex-smokers aged 16 and over, who reported making at least one serious quit attempt in the last 12 months, were recruited. The main outcome measure was participants’ responses to the question “Whatfinallytriggered your most recent quit attempt?”. Respondents selected from a list of options or specified a trigger not on the list.

Results:

In the event, smokers typically reported as triggers similar factors as have previously been reported as “reasons”. “A concern about future health problems” (28.5%) was the most commonly cited trigger followed by “health problems I had at the time” (18%) and then “a decision that smoking was too expensive” (12.2%). The most common external trigger was advice from a health professional (5.6%). Future health concern was more common in smokers with higher socioeconomic status (SES), whereas cost and current health problems were more often cited by lower SES smokers. Younger smokers were more likely to report their quit attempt being triggered by a TV advertisement while older smokers were more likely to cite advice from a health professional. Concern about future health problems was cited less often by 16 to 24 year olds and those aged 65+ than those aged 25 to 64 years.

Conclusions:

There are significant differences in reported triggers for quit attempts as a function of sociodemographic factors. Most notably, smokers with higher SES are more likely to report concern about future health whereas those from lower SES are more likely to cite cost and current health problems.
MORSE SPECTRUM FOR NONAUTONOMOUS DIFFERENTIAL EQUATIONS
Authors: COLONIUS FRITZ , KLOEDEN PETER E. , RASMUSSEN MARTIN
Published: September 2008

The concept of a Morse decomposition consisting of nonautonomous sets is reviewed for linear cocycle mappings w.r.t. the past, future and all-time convergences. In each case, the set of accumulation points of the finite-time Lyapunov exponents corresponding to points in a nonautonomous set is shown to be an interval. For a finest Morse decomposition, the Morse spectrum is defined as the union of all of the above accumulation point intervals over the different nonautonomous sets in such a finest Morse decomposition. In addition, Morse spectrum is shown to be independent of which finest Morse decomposition is used, when more than one exists.
A COMPUTATIONAL ERGODIC THEOREM FOR INFINITE ITERATED FUNCTION SYSTEMS
Authors: CONG NGUYEN DINH , SON DOAN THAI , SIEGMUND STEFAN
Published: September 2008

Iterated function systems are examples of random dynamical systems and became popular as generators of fractals like the Sierpinski Gasket and the Barnsley Fern. In this paper we prove an ergodic theorem for iterated function systems which consist of countably many functions and which are contractive on average on an arbitrary compact metric space and we provide a computational version of this ergodic theorem in Euclidean space which allows to numerically approximate the time average together with an explicit error bound. The results are applied to an explicit example.
ON HOMOGENEOUS PINNING MODELS AND PENALIZATIONS
Authors: GRADINARU MIHAI , TINDEL SAMY
Published: September 2008

In this note, we show how the penalization method, introduced in order to describe some nontrivial changes of the Wiener measure, can be applied to the study of some simple polymer models such as the pinning model. The bulk of the analysis is then focused on the study of a martingale which has to be computed as a Markovian limit.
SOME REMARKS CONCERNING REFLECTIONLESS STURM–LIOUVILLE POTENTIALS
Authors: JOHNSON RUSSELL , ZAMPOGNI LUCA
Published: September 2008

We consider the class of reflectionless Sturm–Liouville potentials and the subclass consisting of "Sato–Segal–Wilson" potentials. We construct illustrative examples lying in these classes, in particular we adapt the constructions of Craig and Levitan to the Sturm–Liouville case. We also discuss an inverse problem of Kotani type in the context of Sato–Segal–Wilson potentials.
A QUASI-LINEAR STOCHASTIC FOKKER–PLANCK EQUATION IN σ-FINITE MEASURES
Authors: KOTELENEZ PETER M.
Published: September 2008

Solutions of quasi-linear stochastic Fokker–Planck equations for the number density of a system of solute particles in suspension are derived. The initial values and the solutions take values in a class of σ-finite Borel measures over Rd where d ≥ 1. The stochastic driving noise is defined by Itô differentials. For the special case of semi-linear stochastic Fokker–Planck equations, the solutions can be represented as solutions of first-order stochastic transport equations driven by Stratonovich differentials.
INVARIANT FOLIATIONS FOR STOCHASTIC PARTIAL DIFFERENTIAL EQUATIONS
Authors: LU KENING , SCHMALFUß BJÖRN
Published: September 2008

In this paper, we study the existence of an invariant foliation for a class of stochastic partial differential equations with a multiplicative white noise. This invariant foliation is used to trace the long term behavior of all solutions of these equations.
OPTIMAL POINTWISE APPROXIMATION OF INFINITE-DIMENSIONAL ORNSTEIN–UHLENBECK PROCESSES
Authors: MÜLLER-GRONBACH THOMAS , RITTER KLAUS , WAGNER TIM
Published: September 2008

We consider an infinite-dimensional Ornstein–Uhlenbeck process on the spatial domain ]0,1[d driven by an additive nuclear or space–time white noise, and we study the approximation of this process at a fixed point in time. We determine the order of the minimal errors as well as asymptotically optimal algorithms, both of which depend on the spatial dimension d and on the decay of the eigenvalues of the driving Wiener process W in the case of nuclear noise. In particular, the optimal order is achieved by employing drift-implicit Euler schemes with non-uniform time discretizations, while uniform time discretizations turn out to be suboptimal in general. By means of non-asymptotic error bounds and by simulation experiments, we show that the asymptotic results are predictive for the actual errors already for time discretizations with a small number of points.
STRONG PREDICTOR–CORRECTOR EULER METHODS FOR STOCHASTIC DIFFERENTIAL EQUATIONS
Authors: BRUTI-LIBERATI NICOLA , PLATEN ECKHARD
Published: September 2008

This paper introduces a new class of numerical schemes for the pathwise approximation of solutions of stochastic differential equations (SDEs). The proposed family of strong predictor–corrector Euler methods are designed to handle scenario simulation of solutions of SDEs. It has the potential to overcome some of the numerical instabilities that are often experienced when using the explicit Euler method. This is of importance, for instance, in finance where martingale dynamics arise for solutions of SDEs with multiplicative diffusion coefficients. Numerical experiments demonstrate the improved asymptotic stability properties of the proposed symmetric predictor–corrector Euler methods.
AN INTERMEDIATE REGIME FOR EXIT PHENOMENA DRIVEN BY NON-GAUSSIAN LÉVY NOISES
Authors: YANG ZHIHUI , DUAN JINQIAO
Published: September 2008

A dynamical system driven by non-Gaussian Lévy noises of small intensity is considered. The first exit time of solution orbits from a bounded neighborhood of an attracting equilibrium state is estimated. For a class of non-Gaussian Lévy noises, it is shown that the mean exit time is asymptotically faster than exponential (the well-known Gaussian Brownian noise case) but slower than polynomial (the stable Lévy noise case), in terms of the reciprocal of the small noise intensity.
Ever Since Owen: Changing Perspectives on the Early Evolution of Tetrapods
Authors: Coates Michael I. , Ruta Marcello , Friedman Matt
Published: September 2008

The traditional notion of a gap between fishes and amphibians has been closed by a wealth of fish-like fossil tetrapods, many discovered since the mid 1980s. This review summarizes these discoveries and explores their significance relative to changing ideas about early tetrapod phylogeny, biogeography, and ecology. Research emphasis can now shift to broader-based questions, including the whole of the early tetrapod radiation, from the divergence from other lobed-finned fishes to the origins of modern amphibians and amniotes. The fish-to-tetrapod morphological transition occurred within the Upper Devonian; the divergence of modern tetrapod groups is an Early Carboniferous event. Modern tetrapods emerged in the aftermath of one of the five major extinction episodes in the fossil record, but the earlier Devonian tetrapod radiation is not well understood. Tetrapod limbs, paired fins, and comparative developmental data are reviewed; again, research emphasis needs to change to explore the origins of tetrapod diversity.
New Answers for Old Questions: The Evolutionary Quantitative Genetics of Wild Animal Populations
Authors: Kruuk Loeske E.B. , Slate Jon , Wilson Alastair J.
Published: September 2008

Recent years have seen a rapid expansion in the scope of quantitative genetic analyses undertaken in wild populations. We illustrate here the potential for such studies to address fundamental evolutionary questions about the maintenance of genetic diversity and to reveal hidden genetic conflicts or constraints not apparent at the phenotypic level. Trade-offs between different components of fitness, sexually-antagonistic genetic effects, maternal effects, genotype-by-environment interactions, genotype-by-age interactions, and variation between different regions of the genome in localized genetic correlations may all prevent the erosion of genetic variance. We consider ways in which complex interactions between ecological conditions and the expression of genetic variation can be elucidated, and emphasize the benefits of conducting selection analyses within a quantitative genetic framework. We also review potential developments associated with rapid advances in genomic technology, in particular the increased availability of extensive marker information. Our conclusions highlight the complexity of processes contributing to the maintenance of genetic diversity in wild populations, and underline the value of a quantitative genetic approach in parameterizing models of life-history evolution.
Biology of the Parasitoid Melittobia (Hymenoptera: Eulophidae)
Authors: Matthews Robert W. , González Jorge M. , Matthews Janice R. , Deyrup Leif D.
Published: September 2008

As parasitoids upon solitary bees and wasps and their nest cohabitants, Melittobia have an intricate life history that involves both female cooperation and variably expressed male siblicidal conflict. Inter- and intrasexual dimorphism includes blind, flightless males and (probably nutritionally determined) short- and long-winged females. Thought to be highly inbred, Melittobia do not conform to local mate competition (LMC) theory but exhibit simple forms of many social insect traits, including overlapping adult generations, different female phenotypes, close kinship ties, parental care, and altruistic cooperative escape behaviors. Most host records and research findings are based on only 3 species—M. acasta, M. australica, and M. digitata—but any of the 12 species could have pest potential due to their polyphagy, explosive population growth, cryptic habits, and behavioral plasticity. Readily cultured in the laboratory, Melittobia offer considerable potential as a model for genetic, developmental, and behavioral studies.
Fluid and Solute Transport in Bone: Flow-Induced Mechanotransduction
Authors: Fritton Susannah P. , Weinbaum Sheldon
Published: September 2008

Much recent evidence suggests that bone cells sense their mechanical environment via interstitial fluid flow. In this review, we summarize theoretical and experimental approaches to quantify fluid and solute transport in bone, starting with the early investigations of fluid shear stress applied to bone cells. The pathways of bone interstitial fluid and solute movement are highlighted based on recent theoretical models, as well as a new generation of tracer experiments that have clarified and refined the structure and function of the osteocyte pericellular matrix. Then we trace how the fluid-flow models for mechanotransduction have evolved as new ultrastructural features of the osteocyte lacunar-canalicular porosity have been identified and how more recent in vitro fluid-flow and cell-stretch experiments have helped elucidate at the molecular level the possible pathways for cellular excitation in bone.
Turbulence, Magnetism, and Shear in Stellar Interiors
Authors: Miesch Mark S. , Toomre Juri
Published: September 2008

Stars can be fascinating settings in which to study intricate couplings among convection, rotation, magnetism, and shear, usually under distinctly nonlinear conditions that yield vigorous turbulence. The emerging flux and the rotation rates of stars can vary widely, yet there are common elements that must contribute to building and maintaining the vibrantly evolving magnetic activity they exhibit. Some of these elements, such as the rotational shear and meridional flows established by the coupling of convection with rotation, can now be studied in detail within our nearest star using helioseismology. Major three-dimensional numerical simulations help refine our intuitions about such interior dynamics, aided by rapid advances in supercomputing that are improving the fidelity of the modeling. These developments, combined with intense thrusts at new high resolution and continuous observations of solar magnetism and solar oscillations, herald a promising era for exploring such astrophysical fluid dynamics.
Antigenic Variation inPlasmodium falciparum
Authors: Scherf Artur , Lopez-Rubio Jose Juan , Riviere Loïc
Published: September 2008

The persistence of the human malaria parasite Plasmodium falciparum during blood stage proliferation in its host depends on the successive expression of variant molecules at the surface of infected erythrocytes. This variation is mediated by the differential control of a family of surface molecules termed PfEMP1 encoded by approximately 60 var genes. Each individual parasite expresses a single var gene at a time, maintaining all other members of the family in a transcriptionally silent state. PfEMP1/var enables parasitized erythrocytes to adhere within the microvasculature, resulting in severe disease. This review highlights key regulatory mechanisms thought to be critical for monoallelic expression of var genes. Antigenic variation is orchestrated by epigenetic factors including monoallelic var transcription at separate spatial domains at the nuclear periphery, differential histone marks on otherwise identical var genes, and var silencing mediated by telomeric heterochromatin. In addition, controversies surrounding var genetic elements in antigenic variation are discussed.
Host Restriction of Avian Influenza Viruses at the Level of the Ribonucleoproteins
Authors: Naffakh Nadia , Tomoiu Andru , Rameix-Welti Marie-Anne , van der Werf Sylvie
Published: September 2008

Although transmission of avian influenza viruses to mammals, particularly humans, has been repeatedly documented, adaptation and sustained transmission in the new host is a rare event that in the case of humans may result in pandemics. Host restriction involves multiple genetic determinants. Among the known determinants of host range, key determinants have been identified on the genes coding for the nucleoprotein and polymerase proteins that, together with the viral RNA segments, form the ribonucleoproteins (RNPs). The RNP genes form host-specific lineages and harbor host-associated genetic signatures. The functional significance of these determinants has been studied by reassortment and reverse genetics experiments, underlining the influence of the global genetic context. In some instances the molecular mechanisms have been approached, pointing to the importance of the polymerase activity and interaction with cellular host factors. Better knowledge of determinants of host restriction will allow monitoring of the pandemic potential of avian influenza viruses.
Cell Biology of HIV-1 Infection of Macrophages
Authors: Carter Carol A. , Ehrlich Lorna S.
Published: September 2008

HIV infection of macrophages is a critically important component of viral pathogenesis and progression to AIDS. Although the virus follows the same life cycle in macrophages and T lymphocytes, several aspects of the virus-host relationship are unique to macrophage infection. Examples of these are the long-term persistence of productive infection, sustained by the absence of cell death, and the ability of progeny virus to bud into and accumulate in endocytic compartments designated multivesicular bodies (MVBs). Recently, the hypothesis that viral exploitation of the macrophage endocytic machinery is responsible for perpetuating the chronic state of infection unique to this cell type has been challenged in several independent studies employing a variety of experimental strategies. This review examines the evidence supporting and refuting the canonical hypothesis and highlights recently identified cellular factors that may contribute to the unique aspects of the HIV-macrophage interaction.
Evolution, Population Structure, and Phylogeography of Genetically Monomorphic Bacterial Pathogens
Authors: Achtman Mark
Published: September 2008

Genetically monomorphic bacteria contain so little sequence diversity that sequencing a few gene fragments yields little or no information. As a result, our understanding of their evolutionary patterns presents greater technical challenges than exist for genetically diverse microbes. These challenges are now being met by analyses at the genomic level for diverse types of genetic variation, the most promising of which are single nucleotide polymorphisms. Many of the most virulent bacterial pathogens are genetically monomorphic, and understanding their evolutionary and phylogeographic patterns will help our understanding of the effects of infectious disease on human history.
Uric acid decreases NO production and increases arginase activity in cultured pulmonary artery endothelial cells
Authors: Zharikov Sergey , Krotova Karina , Hu Hanbo , Baylis Chris , Johnson Richard J. , Block Edward R. , Patel Jawaharlal
Published: September 2008

Elevated levels of serum uric acid (UA) are commonly associated with primary pulmonary hypertension but have generally not been thought to have any causal role. Recent experimental studies, however, have suggested that UA may affect various vasoactive mediators. We therefore tested the hypothesis that UA might alter nitric oxide (NO) levels in pulmonary arterial endothelial cells (PAEC). In isolated porcine pulmonary artery segments (PAS), UA (7.5 mg/dl) inhibits acetylcholine-induced vasodilation. The incubation of PAEC with UA caused a dose-dependent decrease in NO and cGMP production stimulated by bradykinin or Ca2+-ionophore A23187. We explored cellular mechanisms by which UA might cause reduced NO production focusing on the effects of UA on the l-arginine-endothelial NO synthase (eNOS) and l-arginine-arginase pathways. Incubation of PAEC with different concentrations of UA (2.5–15 mg/dl) for 24 h did not affect l-[3H]arginine uptake or activity/expression of eNOS. However, PAEC incubated with UA (7.5 mg/dl; 24 h) released more urea in culture media than control PAEC, suggesting that arginase activation might be involved in the UA effect. Kinetic analysis of arginase activity in PAEC lysates and rat liver and kidney homogenates demonstrated that UA activated arginase by increasing its affinity for l-arginine. An inhibitor of arginase ( S)-(2-boronoethyl)-l-cysteine prevented UA-induced reduction of A23187-stimulated cGMP production by PAEC and abolished UA-induced inhibition of acetylcholine-stimulated vasodilation in PAS. We conclude that UA-induced arginase activation is a potential mechanism for reduction of NO production in PAEC.
Inhibitory and excitatory effects of μ-, δ-, and κ-opioid receptor activation on breathing in awake turtles,Trachemys scripta
Authors: Johnson Stephen M. , Kinney Matthew E. , Wiegel Liana M.
Published: September 2008

For ectothermic vertebrates, such as reptiles, the effects of opioid receptor subtype activation on breathing are poorly understood. On the basis of previous studies on mammals and lampreys, we hypothesized that μ- and δ-opioid receptor (MOR and DOR, respectively) activation would cause respiratory depression, whereas κ-opioid receptor (KOR) activation would have no effect. To address this question, we measured respiration in awake, freely swimming adult red-eared slider turtles ( Trachemys scripta) before and after injection with agonists for specific opioid receptors. Injection of the MOR agonist [d-Ala2, N-Me-Phe4,Gly5-ol]-enkephalin acetate salt (DAMGO, 1.5 or 6.5 mg/kg) decreased ventilation (V̇e) by 72 ± 9% and 95 ± 3%, respectively, 4.0 h after injection as a result of decreased breathing frequency and no change in tidal volume (Vt). DOR agonists, such as [d-Pen2,5]-enkephalin hydrate (DPDPE, 5.0 mg/kg) and [d-Ala2,d-Leu5]-enkephalin acetate salt (DADLE, 6.3 mg/kg), decreased V̇e by 44 ± 10% and 89 ± 4%, respectively, 4.0 h after injection as a result of decreased breathing frequency and no change in Vt. DADLE also increased breath duration by a maximum of 25 ± 9% at 6.0 h after injection. The KOR agonist U-50488 (6.2 mg/kg) increased Vt by a maximum of 52 ± 30% at 5.0 h after injection, with variable nonsignificant changes in V̇e and breathing frequency. Naloxone injections (0.25–0.5 mg/kg) 1.0 h before opioid agonist injections blocked all DAMGO-dependent effects, DPDPE-dependent frequency depression, and DADLE-dependent breath duration augmentation for 2.0 h after agonist injections. These results show that MOR and DOR activation causes respiratory depression as a result of decreased breathing frequency, whereas Vt is increased after KOR activation.
Effects of chronic expression of the HIV-induced protein, transactivator of transcription, on circadian activity rhythms in mice, with or without morphine
Authors: Duncan Marilyn J. , Bruce-Keller Annadora J. , Conner Clayton , Knapp Pamela E. , Xu Ruquiang , Nath Avindra , Hauser Kurt F.
Published: September 2008

Patients with human immunodeficiency virus (HIV) infection exhibit changes in sleep patterns, motor disorders, and cognitive dysfunction; these symptoms may be secondary to circadian rhythm abnormalities. Studies in mice have shown that intracerebral injection of an HIV protein, transactivator of transcription (Tat), alters the timing of circadian rhythms in a manner similar to light. Therefore, we tested the hypothesis that chronic Tat expression alters circadian rhythms, especially their entrainment to a light-dark (LD) cycle, by using transgenic mice in which Tat expression in the brain was induced via a doxycycline (DOX)-sensitive, glial fibrillary-associated, protein-restricted promoter. Because opiate substance abuse, which shares comorbidity with HIV infection, also disrupts sleep, a final experiment assessed the effects of morphine exposure on circadian rhythms in wild-type and Tat transgenic mice. Mice housed in cages equipped with running wheels were fed chow with or without DOX. Experiment 1 revealed a small but significant ( P < 0.05) difference between groups in the phase angle of entrainment and a 15% decrease in the wheel running in the DOX group ( P < 0.005). During exposure to constant darkness, DOX did not alter the endogenous period length of the circadian rhythm. Experiment 2 investigated the effect of DOX on circadian rhythms in wild-type and Tat(+) mice during exposure to a normal or phase-shifted LD cycle, or morphine treatment without any change in the LD cycle. Tat induction significantly decreased wheel running but did not affect entrainment to the normal or shifted LD cycle. Morphine decreased wheel running without altering the phase angle of entrainment, and the drug's effects were independent of Tat induction. In conclusion, these findings suggest that chronic brain expression of Tat decreases locomotor activity and the amplitude of circadian rhythms, but does not affect photic entrainment or reentrainment of the murine circadian pacemaker.
Effect of claudins 6 and 9 on paracellular permeability in MDCK II cells
Authors: Sas David , Hu Mingchang , Moe Orson W. , Baum Michel
Published: September 2008

The neonatal proximal tubule has a lower permeability to chloride, higher resistance, and higher relative sodium-to-chloride permeability (PNa/PCl) than the adult tubule, which may be due to maturational changes in the tight junction. Claudins are tight-junction proteins between epithelial cells that determine paracellular permeability characteristics of epithelia. We have previously described the presence of two claudin isoforms, claudins 6 and 9, in the neonatal proximal tubule and subsequent reduction of these claudins during postnatal maturation. The question is whether changes in claudin expression are related to changes in functional characteristics in the neonatal tubule. We transfected claudins 6 and 9 into Madin-Darby canine kidney II (MDCK II) cells and performed electrophysiological studies to determine the resultant changes in physiological characteristics of the cells. Expression of claudins 6 and 9 resulted in an increased transepithelial resistance, decreased chloride permeability, and decreased PNa/PCl and PHCO3/PCl. These findings constitute the first characterization of the permeability characteristics of claudins 6 and 9 in a cell model and may explain why the neonatal proximal tubule has lower permeability to chloride and higher resistance than the adult proximal tubule.
Intrarenal RAS activity and urinary angiotensinogen excretion in anti-thymocyte serum nephritis rats
Authors: Ohashi Naro , Yamamoto Tatsuo , Huang Yanjie , Misaki Taro , Fukasawa Hirotaka , Suzuki Hiroyuki , Togawa Akashi , Suzuki Sayuri , Fujigaki Yoshihide , Nakagawa Tsutomu , Nakamura Yukio , Suzuki Fumiaki , Kitagawa Masatoshi , Hishida Akira
Published: September 2008

The differential roles of circulating and intrarenal renin-angiotensin system (RAS) in glomerulonephritis have not been elucidated. In this study, we investigated the levels of circulating and intrarenal RAS activity and urinary angiotensinogen (AGT) excretion in anti-thymocyte serum (ATS) nephritis induced by an ATS injection (ATS group). The effect of olmesartan, an angiotensin II (ANG II) type 1 receptor blocker (ARB), on the development of nephritis was also examined (ATS+ARB group). In addition, the rats received a saline injection instead of ATS (control group). Mesangial proliferation with transient proteinuria, which peaked at day 7, was significantly increased in the ATS group compared with the control group. The levels of glomerular AGT mRNA, intrarenal ANG II, and urinary AGT excretion in the ATS group were increased significantly at day 7 compared with the control group. Administration of olmesartan (ATS+ARB group) significantly decreased the levels of renal lesions, proteinuria, and intrarenal RAS activity compared with the ATS group. In addition, the levels of urinary AGT excretion correlated with the levels of glomerular damage, urinary protein excretion, and immunoreactivity for AGT and ANG II in kidney. On the other hand, plasma renin activity was significantly lower in the ATS group compared with the control group and significantly higher in the ATS+ARB group than in the ATS group. These data suggest that an increase in kidney-specific RAS activity, which parallels urinary AGT excretion, plays an important role in the development of ATS nephritis.
Single-channel analysis of functional epithelial sodium channel (ENaC) stability at the apical membrane of A6 distal kidney cells
Authors: Yu Ling , Helms My N. , Yue Qiang , Eaton Douglas C.
Published: September 2008

Epithelial sodium channels (ENaC) play an essential role in maintaining total body fluid and electrolyte homeostasis. As such, abnormal expression of ENaC at the cell surface is linked to several important human diseases. Although the stability of ENaC subunits has been extensively studied by protein biochemical analysis, the half-life of the functional channel in the apical membrane remains controversial. Because the functional stability of the multisubunit channel may be more physiologically relevant than the stability of individual subunit proteins, we performed studies of functional ENaC channels using A6 epithelial cells, a Xenopus laevis distal nephron cell line. We recorded single-channel activity in over 400 cells with the translation blockers cycloheximide (CHX) or puromycin, as well as the intracellular protein trafficking inhibitors brefeldin A (BFA) or nocodazole. Our cell-attached, single-channel recordings allow us to quantify the channel density in the apical membrane, as well as to determine channel open probability ( Po) from control (untreated) cells and from cells at different times of drug treatment. The data suggest that the half-life of ENaC channels is ∼3.5 h following puromycin, BFA, and nocodazole treatment. Furthermore, these three drugs had no significant effect on the Poof ENaC for at least 6 h after exposure. A decrease in apical channel number and Powas observed following 2 h of CHX inhibition of protein synthesis, and the apparent channel half-life was closer to 1.5 h following CHX treatment. Treatment of cells with the translation inhibitors does not alter the expression of the protease furin, and therefore changes in protease activity cannot explain changes in ENaC Po. Confocal images show that BFA and nocodazole both disrupt most of the Golgi apparatus after 1-h exposure. In cells with the Golgi totally disrupted by overnight exposure to BFA, 20% of apical ENaC channels remained functional. This result suggests that ENaC is delivered to the apical membrane via a pathway that might bypass the Golgi vesicular trafficking pathway, or that there might be two pools of channels with markedly different half-lives in the apical membrane.
MDM2 E3 ubiquitin ligase mediates UT-A1 urea transporter ubiquitination and degradation
Authors: Chen Guangping , Huang Haidong , Fröhlich Otto , Yang Yuan , Klein Janet D. , Price S. Russ , Sands Jeff M.
Published: September 2008

UT-A1 is the primary urea transporter in the apical plasma membrane responsible for urea reabsorption in the inner medullary collecting duct. Although the physiological function of UT-A1 has been well established, the molecular mechanisms that regulate its activity are less well understood. Analysis of the UT-A1 amino acid sequence revealed a potential MDM2 E3 ubiquitin ligase-binding motif in the large intracellular loop of UT-A1, suggesting that UT-A1 urea transporter protein may be regulated by the ubiquitin-proteasome pathway. Here, we report that UT-A1 is ubiquitinated and degraded by the proteasome but not the lysosome proteolytic pathway. Inhibition of proteasome activity causes UT-A1 cell surface accumulation and concomitantly increases urea transport activity. UT-A1 interacts directly with MDM2; the binding site is located in the NH2-terminal p53-binding region of MDM2. MDM2 mediates UT-A1 ubiquitination both in vivo and in vitro. Overexpression of MDM2 promotes UT-A1 degradation. The mechanism is likely to be physiologically important as UT-A1 ubiquitination was identified in kidney inner medullary tissue. The ubiquitin-proteasome degradation pathway provides an important novel mechanism for UT-A1 regulation.
Predictors of increased PaCO2 during immersed prone exercise at 4.7 ATA
Authors: Cherry A. D. , Forkner I. F. , Frederick H. J. , Natoli M. J. , Schinazi E. A. , Longphre J. P. , Conard J. L. , White W. D. , Freiberger J. J. , Stolp B. W. , Pollock N. W. , Doar P. O. , Boso A. E. , Alford E. L. , Walker A. J. , Ma A. C. , Rhodes M. A. , Moon R. E.
Published: September 2008

During diving, arterial Pco2 (PaCO2) levels can increase and contribute to psychomotor impairment and unconsciousness. This study was designed to investigate the effects of the hypercapnic ventilatory response (HCVR), exercise, inspired Po2, and externally applied transrespiratory pressure (Ptr) on PaCO2 during immersed prone exercise in subjects breathing oxygen-nitrogen mixes at 4.7 ATA. Twenty-five subjects were studied at rest and during 6 min of exercise while dry and submersed at 1 ATA and during exercise submersed at 4.7 ATA. At 4.7 ATA, subsets of the 25 subjects (9–10 for each condition) exercised as Ptr was varied between +10, 0, and −10 cmH2O; breathing gas Po2 was 0.7, 1.0, and 1.3 ATA; and inspiratory and expiratory breathing resistances were varied using 14.9-, 11.6-, and 10.2-mm-diameter-aperture disks. During exercise, PaCO2 (Torr) increased from 31.5 ± 4.1 (mean ± SD for all subjects) dry to 34.2 ± 4.8 ( P = 0.02) submersed, to 46.1 ± 5.9 ( P < 0.001) at 4.7 ATA during air breathing and to 49.9 ± 5.4 ( P < 0.001 vs. 1 ATA) during breathing with high external resistance. There was no significant effect of inspired Po2 or Ptr on PaCO2 or minute ventilation (V̇e). V̇e (l/min) decreased from 89.2 ± 22.9 dry to 76.3 ± 20.5 ( P = 0.02) submersed, to 61.6 ± 13.9 ( P < 0.001) at 4.7 ATA during air breathing and to 49.2 ± 7.3 ( P < 0.001) during breathing with resistance. We conclude that the major contributors to increased PaCO2 during exercise at 4.7 ATA are increased depth and external respiratory resistance. HCVR and maximal O2 consumption were also weakly predictive. The effects of Ptr, inspired Po2, and O2 consumption during short-term exercise were not significant.
Corticospinal-evoked responses in lower limb muscles during voluntary contractions at varying strengths
Authors: Oya T. , Hoffman B. W. , Cresswell A. G.
Published: September 2008

This study investigated corticospinal-evoked responses in lower limb muscles during voluntary contractions at varying strengths. Similar investigations have been made on upper limb muscles, where evoked responses have been shown to increase up to ∼50% of maximal force and then decline. We elicited motor-evoked potentials (MEPs) and cervicomedullary motor-evoked potentials (CMEPs) in the soleus (Sol) and medial gastrocnemius (MG) muscles using magnetic stimulation over the motor cortex and cervicomedullary junction during voluntary plantar flexions with the torque ranging from 0 to 100% of a maximal voluntary contraction. Differences between the MEP and CMEP were also investigated to assess whether any changes were occurring at the cortical or spinal levels. In both Sol and MG, MEP and CMEP amplitudes [normalized to maximal M wave (Mmax)] showed an increase, followed by a plateau, over the greater part of the contraction range with responses increasing from ∼0.2 to ∼6% of Mmax for Sol and from ∼0.3 to ∼10% of Mmax for MG. Because both MEPs and CMEPs changed in a similar manner, the observed increase and lack of decrease at high force levels are likely related to underlying changes occurring at the spinal level. The evoked responses in the Sol and MG increase over a greater range of contraction strengths than for upper limb muscles, probably due to differences in the pattern of motor unit recruitment and rate coding for these muscles and the strength of the corticospinal input.
Expression of growth-related genes in young and older human skeletal muscle following an acute stimulation of protein synthesis
Authors: Drummond Micah J. , Miyazaki Mitsunori , Dreyer Hans C. , Pennings Bart , Dhanani Shaheen , Volpi Elena , Esser Karyn A. , Rasmussen Blake B.
Published: September 2008

Muscle growth is associated with an activation of the mTOR signaling pathway and satellite cell regulators. The purpose of this study was to determine whether 17 selected genes associated with mTOR/muscle protein synthesis and the satellite cells/myogenic program are differentially expressed in young and older human skeletal muscle at rest and in response to a potent anabolic stimulus [resistance exercise + essential amino acid ingestion (RE+EAA)]. Twelve male subjects (6 young, 6 old) completed a bout of heavy resistance exercise. Muscle biopsies were obtained before and at 3 and 6 h post RE+EAA. Subjects ingested leucine-enriched essential amino acids at 1 h postexercise. mRNA expression was determined using qRT-PCR. At rest, hVps34 mRNA was elevated in the older subjects ( P < 0.05) while there was a tendency for levels of myoD, myogenin, and TSC2 mRNA to be higher than young. The anabolic stimulus (RE+EAA) altered mRNAs associated with mTOR regulation. Notably, REDD2 decreased in both age groups ( P < 0.05) but the expression of Rheb mRNA increased only in the young. Finally, cMyc mRNA was elevated ( P < 0.05) in both young and old at 6 h post RE+EAA. Furthermore, RE+EAA also increased expression of several mRNAs associated with satellite function in the young ( P < 0.05), while expression of these mRNAs did not change in the old. We conclude that several anabolic genes in muscle are more responsive in young men post RE+EAA. Our data provide new insights into the regulation of genes important for transcription and translation in young and old human skeletal muscle post RE+EAA.
Top-Down Regulation of Plasticity in the Birdsong System: “Premotor” Activity in the Nucleus HVC Predicts Song Variability Better Than It Predicts Song Features
Authors: Day Nancy F. , Kinnischtzke Amanda K. , Adam Murtaza , Nick Teresa A.
Published: September 2008

We studied real-time changes in brain activity during active vocal learning in the zebra finch songbird. The song nucleus HVC is required for the production of learned song. To quantify the relationship of HVC activity and behavior, HVC population activity during repeated vocal sequences (motifs) was recorded and temporally aligned relative to the motif, millisecond by millisecond. Somewhat surprisingly, HVC activity did not reliably predict any vocal feature except amplitude and, to a lesser extent, entropy and pitch goodness (sound periodicity). Variance in “premotor” HVC activity did not reliably predict variance in behavior. In contrast, HVC activity inversely predicted the variance of amplitude, entropy, frequency, pitch, and FM. We reasoned that, if HVC was involved in song learning, the relationship of HVC activity to learned features would be developmentally regulated. To test this hypothesis, we compared the HVC song feature relationships in adults and juveniles in the sensorimotor “babbling” period. We found that the relationship of HVC activity to variance in FM was developmentally regulated, with the greatest difference at an HVC vocalization lag of 50 ms. Collectively, these data show that, millisecond by millisecond, bursts in HVC activity predict song stability on-line during singing, whereas decrements in HVC activity predict plasticity. These relationships between neural activity and plasticity may play a role in vocal learning in songbirds by enabling the selective stabilization of parts of the song that match a learned tutor model.
Functional Inequalities Associated with Additive Mappings
Authors: Roh Jaiok , Chang Ick-Soon
Published: September 2008

The functional inequality ∥f(x) + 2f(y) + 2f(z)∥ ≤ ∥2f(x/2 + y + z)∥ + ϕ  (x, y, z) (x, y, z ∈ G) is investigated, where G is a group divisible by 2, f : G → X and ϕ : G3 → [0, ∞) are mappings, and X is a Banach space. The main result of the paper states that the assumptions above together with (1) ϕ(2x, −x, 0) = 0 = ϕ(0, x, −x) (x ∈ G) and (2) limn→∞(1/2n)ϕ(2n+1x, 2ny, 2nz) = 0, or limn→∞2nϕ(x/2n−1, y/2n, z/2n) = 0  (x, y, z ∈ G), imply that f is additive. In addition, some stability theorems are proved.
Photodynamic Therapy and the Development of Metal-Based Photosensitisers
Authors: Josefsen Leanne B. , Boyle Ross W.
Published: September 2008

Photodynamic therapy (PDT) is a treatment modality that has been used in the successful treatment of a number of diseases and disorders, including age-related macular degeneration (AMD), psoriasis, and certain cancers. PDT uses a combination of a selectively localised light-sensitive drug (known as a photosensitiser) and light of an appropriate wavelength. The light-activated form of the drug reacts with molecular oxygen to produce reactive oxygen species (ROS) and radicals; in a biological environment these toxic species can interact with cellular constituents causing biochemical disruption to the cell. If the homeostasis of the cell is altered significantly then the cell enters the process of cell death. The first photosensitiser to gain regulatory approval for clinical PDT was Photofrin. Unfortunately, Photofrin has a number of associated disadvantages, particularly pro-longed patient photosensitivity. To try and overcome these disadvantages second and third generation photosensitisers have been developed and investigated. This Review highlights the key photosensitisers investigated, with particular attention paid to the metallated and non-metallated cyclic tetrapyrrolic derivatives that have been studiedin vitroandin vivo; those which have entered clinical trials; and those that are currently in use in the clinic for PDT.
Monitoring Neonatal Regional Cerebral Oxygen Saturation in Clinical Practice: Value and Pitfalls
Authors: van Bel Frank , Lemmers Petra , Naulaers Gunnar
Published: September 2008

This review focuses on the clinical use of near infrared spectroscopy (NIRS) to assess brain oxygenation by the tissue oxygenation index (TOI), and monitoring regional cerebral oxygen saturation (rScO2), cerebral fractional tissue oxygen extraction (cFTOE), which is derived from rScO2, and systemic oxygen saturation. Its precision and pitfalls are discussed. At this stage, it is clear that NIRS-monitored oxygenation of the brain by rScO2 or TOI lacks the precision required to be used as a robust quantitative variable to monitor cerebral oxygenation. Intra- and especially interpatient variability are too large for this aim. On the other hand, when used merely as a trend monitor in the individual patient, substantial changes in rScO2 or TOI and consequently of cFTOE, larger than the limits of agreement, can yield important clinical information that suggest an intervention. Since neonatal intensive care is for a substantial part ‘brain orientated’ this approach seems conceivable. This gives rise to the conclusion that NIRS-monitored TOI, rScO2 and cFTOE increasingly will have a role in clinical practice as semiquantitative indicators of changes in cerebral oxygenation and oxygen extraction. Combination with other (cerebral) parameters such as amplitude-integrated EEG and blood pressure seems promising for further optimization of monitoring the immature brain.