bluuebunny/crossref_metadata_2025 huggingface dataset:
Apremilast, a cAMP phosphodiesterase‐4 inhibitor, demonstrates anti‐inflammatory activity in vitro and in a model of psoriasis
Authors: Schafer PH , Parton A , Gandhi AK , Capone L , Adams M , Wu L , Bartlett JB , Loveland MA , Gilhar A , Cheung Y‐F , Baillie GS , Houslay MD , Man H‐W , Muller GW , Stirling DI
Published: December 2009

Background and purpose:  Apremilast is an orally administered phosphodiesterase‐4 inhibitor, currently in phase 2 clinical studies of psoriasis and other chronic inflammatory diseases. The inhibitory effects of apremilast on pro‐inflammatory responses of human primary peripheral blood mononuclear cells (PBMC), polymorphonuclear cells, natural killer (NK) cells and epidermal keratinocytes were explored in vitro, and in a preclinical model of psoriasis.

Experimental approach:  Apremilast was tested in vitro against endotoxin‐ and superantigen‐stimulated PBMC, bacterial peptide and zymosan‐stimulated polymorphonuclear cells, immunonoglobulin and cytokine‐stimulated NK cells, and ultraviolet B light‐activated keratinocytes. Apremilast was orally administered to beige‐severe combined immunodeficient mice, xenotransplanted with normal human skin and triggered with human psoriatic NK cells. Epidermal skin thickness, proliferation index and inflammation markers were analysed.

Key results:  Apremilast inhibited PBMC production of the chemokines CXCL9 and CXCL10, cytokines interferon‐γ and tumour necrosis factor (TNF)‐α, and interleukins (IL)‐2, IL‐12 and IL‐23. Production of TNF‐α by NK cells and keratinocytes was also inhibited. In vivo, apremilast significantly reduced epidermal thickness and proliferation, decreased the general histopathological appearance of psoriasiform features and reduced expression of TNF‐α, human leukocyte antigen‐DR and intercellular adhesion molecule‐1 in the lesioned skin.

Conclusions and implications:  Apremilast displayed a broad pattern of anti‐inflammatory activity in a variety of cell types and decreased the incidence and severity of a psoriasiform response in vivo. Inhibition of TNF‐α, IL‐12 and IL‐23 production, as well as NK and keratinocyte responses by this phosphodiesterase‐4 inhibitor suggests a novel approach to the treatment of psoriasis.
Public versus Private Managers: How Public and Private Managers Differ in Leadership Behavior
Authors: Andersen Jon Aarum
Published: December 2009

This article aims to find out whether there are behavioral differences between public and private sector managers. Two groups of public managers (managers of social insurance agencies and public school principals) and a group of private managers (two samples) are investigated. Behavioral dimensions are investigated including leadership style (task, relationship, and change orientation), decision‐making style (the functions of sensing, intuition, thinking, and feeling), and motivation profile (achievement, affiliation, and power motivation). An analysis of data from 459 managers in four organizations in Sweden reveal significant differences in behavior between public and private managers. However, no significant differences in leadership behavior are discovered among public managers. Possible explanations for such differences and similarities are explored.
Nutrient supply and bird predation additively control insect herbivory and tree growth in two contrasting forest habitats
Authors: Garibaldi Lucas A. , Kitzberger Thomas , Noemí Mazía C. , Chaneton Enrique J.
Published: December 2009

It has been suggested that bottom–up and top–down forces interactively control food web dynamics. While top–down effects would increase with resource availability to plants, bottom–up effects would be stronger under low predator abundance. These predictions, however, have rarely been tested at contrasting sites while keeping the dominant plant species unchanged. Furthermore, few studies have factorially manipulated both types of forces in forest communities. For two years, we evaluated the effects of fertiliser (NPK) addition and bird exclusion on tree growth, leaf traits, insect abundance, and folivory rates in a dry/warm and a wet/cold Nothofagus pumilio forest in Patagonia, Argentina. Overall, we found no interaction between nutrient supply and bird predation, although the strength of bottom–up and top–down forces differed markedly between forest sites. Treatment effects were generally weak in the wet forest, where tree growth rates and insect herbivory were low relative to the dry forest. In the dry forest, fertilisation increased sapling growth, insect abundance and folivory, whereas bird exclusion increased leaf damage and reduced tree growth. In the wet forest, fertilisation enhanced leaf nutrient contents and folivore abundance but not sapling growth, while bird exclusion had little impact on insects or trees. These results imply that factors other than nutrients and birds were important in controlling tree growth and folivore activity in the wet forest. While treatment effect sizes varied widely among feeding guilds, in general, nutrient effects on folivores were stronger than predator effects. We conclude that, within the time‐frame of this study, tree growth and herbivory were additively affected by soil nutrients and predator presence, as bird exclusion effects did not change with elevated folivore activity on fertilised trees. We also show that both top–down and bottom–up cascades were weaker in a forest site characterised by slow‐growing juvenile trees subjected to low folivore pressure.
Second lineage of heart forming region provides new understanding of conotruncal heart defects
Authors: Nakajima Yuji
Published: December 2009

Abnormal heart development causes various congenital heart defects. Recent cardiovascular biology studies have elucidated the morphological mechanisms involved in normal and abnormal heart development. The primitive heart tube originates from the lateral‐most part of the heart forming mesoderm and mainly gives rise to the left ventricle. Then, during the cardiac looping, the outflow tract is elongated by the addition of cardiogenic cells from the both pharyngeal and splanchnic mesoderm (corresponding to anterior and secondary heart field, respectively), which originate from the mediocaudal region of the heart forming mesoderm and are later located anteriorly (rostrally) to the dorsal region of the heart tube. Therefore, the heart progenitors that contribute to the outflow tract region are distinct from those that form the left ventricle. The knowledge that there are two different lineages of heart progenitors in the four‐chambered heart provides new understanding of the morphological and molecular etiology of conotruncal heart defects.
Antimicrobial Resistance of Enterococci Isolated from Mastitic Bovine Milk Samples in Korea
Authors: Nam H. M. , Lim S. K. , Moon J. S. , Kang H. M. , Kim J. M. , Jang K. C. , Kim J. M. , Kang M. I. , Joo Y. S. , Jung S. C.
Published: December 2009

The aim of this study was to determine the antimicrobial resistance of various species of enterococci isolated from mastitic bovine milk samples. A total of 105 enterococci isolates were examined: Enterococcus faecalis (n = 47), Enterococcus faecium (n = 39), Enterococcus gallinarum (n = 6), Enterococcus avium (n = 6), Enterococcus hirae (n = 5) and Enterococcus durans (n = 2). All the isolates were susceptible to ampicillin, gentamicin and vancomycin, and only a single E. hirae isolate was resistant to ampicillin. In general, the most frequently observed resistance among the enterococcal isolates was to tetracycline (69.5%), followed by penicillin (64.7%), erythromycin (57.1%) and cephalothin (44.7%). A similar antimicrobial resistance pattern was observed among individual species except E. durans, which exhibited only tetracycline resistance. Resistance observed among isolates of E. hirae and E. gallinarum was almost as high as E. faecium and E. faecalis. Of 105 isolates, only six (5.7%) strains of E. faecium were susceptible to all the antimicrobials tested and about 52% (55/105) showed resistance to more than three antimicrobials. The most common multiple resistance pattern was penicillin, tetracycline and erythromycin, which was observed in 32 of 105 (30.4%) isolates. This study demonstrates that enterococcal isolates belonging to minor species showed antimicrobial resistance rates as high as those of E. faecium and E. faecalis, and that monitoring of antimicrobial resistance should not be restricted only to those two major species.
The European Rabbit (Oryctolagus cuniculus), a Source of Zoonotic Cryptosporidiosis
Authors: Robinson G. , Chalmers R. M.
Published: December 2009

Cryptosporidium spp. have been found in the faeces of over 150 mammalian host species, but the risks to public health from wildlife are poorly understood. In summer 2008, the Cryptosporidium sp. rabbit genotype was identified as the aetiological agent in an outbreak of waterborne human cryptosporidiosis. The source was a wild rabbit that had entered a treated water tank. To establish current knowledge about Cryptosporidium spp. infecting lagomorphs, especially the host range and biological characteristics of the rabbit genotype, and the potential risks to public health that rabbits may pose in the transmission of zoonotic cryptosporidiosis, we undertook a literature and data review. The literature returned demonstrates that although the European rabbit (Oryctolagus cuniculus) has been the most widely studied lagomorph, few large scale studies were found. The prevalence of Cryptosporidium spp. in wild rabbit populations in the two large scale studies was 0.9% (95%CI 0.2–5.0) and 0.0% (95%CI 0.0–1.6). Neither study provided age nor sex profiles nor typing of Cryptosporidium isolates. The infecting Cryptosporidium species was confirmed in just four other studies of rabbits, all of which showed the rabbit genotype. Human‐infectious Cryptosporidium species including Cryptosporidium parvum have caused experimental infections in rabbits and it is likely that this may also occur naturally. No published studies of the host range and biological features of the Cryptosporidium rabbit genotype were identified, but information was generated on the identification and differentiation of the rabbit genotype at various genetic loci. Both pet and wild rabbits are a potential source of human cryptosporidiosis and as such, good hygiene practices are recommended during and after handling rabbits or exposure to their faeces, or potentially contaminated surfaces. Water supplies should be protected against access by wildlife, including rabbits.
Sushi in Pregnancy, Parasitic Diseases – Obstetrician Survey
Authors: Jones J. L. , Anderson B. , Schulkin J. , Parise M. E. , Eberhard M. L.
Published: December 2009

Parasites from raw fish can lead to a wide range of clinical manifestations and can be challenging to treat in pregnancy as result of medication exposure of the foetus. We surveyed obstetrician‐gynecologists (ob‐gyns) in the U.S. to determine their knowledge about the consumption of raw fish during pregnancy. In March 2007, a questionnaire was mailed to members of the American College of Obstetricians and Gynecologists (ACOG) randomly selected to represent all members. Non‐responding physicians were sent two additional mailings. Of the 606 ACOG members surveyed, 305 (50%) responded. Most (82%) respondents indicated that eating raw fish is not safe during pregnancy. However, few (19%) knew that thorough freezing kills parasites in fish. Nearly all (94%) respondents thought that parasitic infections can be more challenging to treat in pregnancy. U.S. ob‐gyns believe that eating raw fish during pregnancy is not safe; most would benefit from information about how to prevent infection and about treatment.
Vaccination of Poultry Workers: Delivery and Uptake of Seasonal Influenza Immunization
Authors: Vivancos R. , Showell D. , Keeble B. , Goh S. , Kroese M. , Lipp A. , Battersby J.
Published: December 2009

Avian influenza is a highly infectious disease in poultry and although the risk of human infection is low, concerns exist that it could evolve into a new human strain of pandemic potential if reassortment with a human influenza virus occurs. In January 2007, the UK government introduced a programme to vaccinate poultry workers to reduce the potential of such an event. This study evaluates the delivery, uptake and costs of the programme in three counties of England. A questionnaire survey was completed by consultants in public health in all the Primary Care Trusts in Norfolk, Suffolk and Cambridgeshire in May 2007. The delivery of the programme varied between Primary Care Trusts, including being delivered in some cases by clinics in primary care, by general practitioners and occupational health services in others. The uptake of vaccination was low ranging from 7% to 29% at a cost of £29 to £132 per person vaccinated. Vaccination of poultry workers as a public health measure to prevent an influenza pandemic is likely to be ineffective with the level of coverage found in this evaluation in our region.
The Borrelial Fibronectin-Binding Protein RevA Is an Early Antigen of Human Lyme Disease
Authors: Brissette Catherine A. , Rossmann Evelyn , Bowman Amy , Cooley Anne E. , Riley Sean P. , Hunfeld Klaus-Peter , Bechtel Michael , Kraiczy Peter , Stevenson Brian
Published: December 2009

Previous studies using small numbers of serum samples from human patients and experimentally infected animals identified the frequent presence of antibodies recognizing RevA, a borrelial fibronectin-binding outer surface protein. We now demonstrate that most examined Lyme disease spirochetes from North America and Europe contain genes encoding RevA proteins, some with extensive regions of conservation and others with moderate diversity. Line blot analyses using recombinant RevA from two diverse Lyme disease spirochetes of RevA and serum samples from culture-confirmed human Lyme disease patients from the United States (n= 46, mainly with early Lyme disease) and Germany (>500, with early and late manifestations of Lyme disease) were performed. The results indicated that a sizable proportion of patients produced antibodies that recognized recombinant RevA. Overall, RevA-based serological studies were less sensitive and less specific than other assay types, such as the VlsE-based C6 peptide assay. However, sera from patients in the initial stages of Lyme disease contained antibodies against RevA, demonstrating that this protein is expressed early in human infection. Thus, RevA may be a useful target for preventative or curative therapies.
Immunologic Indicators of Clinical Progression during CanineLeishmania infantumInfection
Authors: Boggiatto Paola M. , Ramer-Tait Amanda E. , Metz Kyle , Kramer Erin E. , Gibson-Corley Katherine , Mullin Kathleen , Hostetter Jesse M. , Gallup Jack M. , Jones Douglas E. , Petersen Christine A.
Published: December 2009

In both dogs and humansLeishmania infantuminfection is more prevalent than disease, as infection often does not equate with clinical disease. Previous studies additively indicate that advanced clinical visceral leishmaniasis is characterized by increased production of anti-Leishmaniaantibodies,Leishmania-specific lymphoproliferative unresponsiveness, and decreased production of gamma interferon (IFN-γ) with a concomitant increase of interleukin-10 (IL-10). In order to differentiate infection versus progressive disease for better disease prognostication, we temporally evaluated humoral and cellular immunologic parameters of naturally infected dogs. The work presented here describes for the first time the temporal immune response to natural autochthonousL. infantuminfection in foxhounds within the United States. Several key changes in immunological parameters should be considered when differentiating infection versus clinical disease, including a dramatic rise in IgG production, progressive increases in antigen-specific peripheral blood mononuclear cell proliferation, and IFN-γ production. Polysymptomatic disease is precluded by increased IL-10 production and consistent detection of parasite kinetoplast DNA in whole blood. This clinical presentation and the immuno-dysregulation mirror those observed in human patients, indicating that this animal model will be very useful for testing immunomodulatory anti-IL-10 and other therapies.
Corynebacterium accolens
-Associated Pelvic Osteomyelitis
Authors: Wong Jenny S. J. , Seaward Lois M. , Ho Carmen P. , Anderson Trevor P. , Lau Esther O. C. , Amodeo Matthew R. , Metcalf Sarah C. L. , Pithie Alan D. , Murdoch David R.
Published: December 2009

Corynebacterium accolens
is a rare human pathogen. We encountered a case of
C. accolens
isolated from a thigh collection in a man with osteomyelitis of the adjacent pubic symphysis.
Evaluation of Diagnostic Tests for
Clostridium difficile
Infection
Authors: Swindells Jonathan , Brenwald Nigel , Reading Nathan , Oppenheim Beryl
Published: December 2009

We evaluated toxigenic
Clostridium difficile
detection by a lateral flow assay for antigen and toxin, an enzyme immunoassay, and two commercial PCR methods. Compared to the cell cytotoxicity neutralization assay and toxigenic culture, both toxin detection methods lacked sensitivity. PCR following combined antigen and toxin detection provided the most useful diagnostic information.
First Case of Human Infection Due to
Pseudomonas fulva
, an Environmental Bacterium Isolated from Cerebrospinal Fluid
Authors: Almuzara Marisa N. , Vazquez Miryam , Tanaka Naoto , Turco Marisa , Ramirez Maria S. , Lopez Eduardo L. , Pasteran Fernando , Rapoport Melina , Procopio Adriana , Vay Carlos A.
Published: December 2009

We report the first case of human infection due to
Pseudomonas fulva. P. fulva
caused acute meningitis following the placement of a drainage system in a 2-year-old female. Additionally, the isolate displayed a VIM-2 carbapenemase in a class 1 integron context.
Herpes Simplex Virus Type 1 Immediate-Early Protein ICP22 Is Required for VICE Domain Formation during Productive Viral Infection
Authors: Bastian Thomas W. , Livingston Christine M. , Weller Sandra K. , Rice Stephen A.
Published: December 2009

During productive infection, herpes simplex virus type 1 (HSV-1) induces the formation of discrete nuclear foci containing cellular chaperone proteins, proteasomal components, and ubiquitinated proteins. These structures are known as VICE domains and are hypothesized to play an important role in protein turnover and nuclear remodeling in HSV-1-infected cells. Here we show that VICE domain formation in Vero and other cells requires the HSV-1 immediate-early protein ICP22. Since ICP22 null mutants replicate efficiently in Vero cells despite being unable to induce VICE domain formation, it can be concluded that VICE domain formation is not essential for HSV-1 productive infection. However, our findings do not exclude the possibility that VICE domain formation is required for viral replication in cells that are nonpermissive for ICP22 mutants. Our studies also show that ICP22 itself localizes to VICE domains, suggesting that it could play a role in forming these structures. Consistent with this, we found that ICP22 expression in transfected cells is sufficient to reorganize the VICE domain component Hsc70 into nuclear inclusion bodies that resemble VICE domains. An N-terminal segment of ICP22, corresponding to residues 1 to 146, is critical for VICE domain formation in infected cells and Hsc70 reorganization in transfected cells. We previously found that this portion of the protein is dispensable for ICP22's effects on RNA polymerase II phosphorylation. Thus, ICP22 mediates two distinct regulatory activities that both modify important components of the host cell nucleus.
Evidence of Early B-Cell Dysregulation in Simian Immunodeficiency Virus Infection: Rapid Depletion of Naïve and Memory B-Cell Subsets with Delayed Reconstitution of the Naïve B-Cell Population
Authors: Kuhrt David , Faith Seth A. , Leone Amanda , Rohankedkar Mukta , Sodora Donald L. , Picker Louis J. , Cole Kelly Stefano
Published: December 2009

Despite eliciting a robust antibody response in humans, several studies in human immunodeficiency virus (HIV)-infected patients have demonstrated the presence of B-cell deficiencies during the chronic stage of infection. While several explanations for the HIV-induced B-cell deficit have been proposed, a clear mechanistic understanding of this loss of B-cell functionality is not known. This study utilizes simian immunodeficiency virus (SIV) infection of rhesus macaques to assess B-cell population dynamics beginning at the acute phase and continuing through the chronic phase of infection. Flow cytometric assessment demonstrated a significant early depletion of both naïve and memory B-cell subsets in the peripheral blood, with differential kinetics for recovery of these populations. Furthermore, the altered numbers of naïve and memory B-cell subsets in these animals corresponded with increased B-cell activation and altered proliferation profiles during the acute phase of infection. Finally, all animals produced high titers of antibody, demonstrating that the measurement of virus-specific antibody responses was not an accurate reflection of alterations in the B-cell compartment. These data indicate that dynamic B-cell population changes in SIV-infected macaques arise very early after infection at the precise time when an effective adaptive immune response is needed.
Spectrum-generating bialgebra of the hexagonal-lattice dimer model
Authors: Schmidt Jeffrey R.
Published: December 2009

The method of constructing a complete set of “zero-operator” identities preserved by the matrix coproduct is shown to be general, and is used to build the operator bialgebra for the hexagonal-lattice dimer model. This technique is complementary to the RTT-equation, and does not require a solution to the Yang–Baxter equation. The resulting bialgebra in the case of hexagonal lattice dimers has a distinctly Yangian structure, but has no R-matrix or antipode.
Exploration of perturbed dyonic theories
Authors: Joshi S. C.
Published: December 2009

By extending the study of dyonic harmonic oscillator and dyonium in the presence of an external magnetic field, the possibility of observation of dyons has been explored. The splitting in energy levels of dyonium under the influence of a weak magnetic field has been undertaken with inclusion of spin-orbit interaction, and it is observed that the energy level splits into nondegenerate as well doubly degenerate states. The effect of a strong magnetic field on dyonium has also been carried out by treating spin-orbit interaction as a perturbation, leading to interesting results.
CONTROLLED FABRICATION OF Nb2O5 HOLLOW NANOSPHERES AND NANOTUBES
Authors: LIU FEI , XUE DONGFENG
Published: December 2009

A simple procedure for one-step growing Nb 2 O 5 hollow nanospheres and nanotubes was proposed. The final products were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and transmission electron microscopy (TEM). The as-obtained hollow spheres present a polycrystal surface while the nanotubes possess single crystal walls. Moreover, the factors that could impact the product morphology and crystal structure were discussed, and the corresponding mechanism was proposed accordingly. The crystal structure and morphology of products can be easily tuned by adjusting the molar ratio of Nb / Ti used, which determines the amount of F - ions existing in the reaction system. The as-obtained Nb 2 O 5 hollow nanospheres and nanotubes may exhibit enhanced applications in a wide range of areas. Additionally, it is rational to expect that this simple method can be extended to systems of other inorganic materials with desired morphologies.
INFLUENCES OF THE MEDIUM ON PREPARATION OF COPPER NANOFLUIDS BY WIRE EXPLOSION PROCESS
Authors: BAC L. H. , YUN G. S. , KIM J. S. , KIM J. C. , RHEE C. K.
Published: December 2009

This paper presents a novel single-step method for preparation copper nanofluids by electrical explosion of wire in liquid. Three types of fluids were used as a medium of the wire explosion process: deionised water, cetyl trimethyl ammonium bromide (CTAB) solution 0.001 M and ethylene glycol. The X-ray diffraction (XRD), field emission scanning electron microscope (FE-SEM), energy dispersive spectroscopy (EDS) and UV-vis spectroscopy were used to investigate the properties of the nanofluids. Pure copper phase was detected in the nanofluids using ethylene glycol and mixture of copper and oxide phase was observed in the nanofluids using water and CTAB solution. FE-SEM analysis showed that size of particles formed in ethylene glycol was about 90 nm, the smallest in three samples.
POLYMORPH SELECTION OF CALCIUM CARBONATE BY THE MORPHOLOGY OF BIOMACROMOLECULES: FROM ARAGONITE, VATERITE TO CALCITE
Authors: XIAO JUNWU , ZHU YINGCHUN , YUAN JIANHUI , RUAN QICHAO , ZENG YI , CHENG LIFANG , WANG LIANZHOU , XU FANGFANG
Published: December 2009

The selective polymorph synthesis of aragonite, vaterite and calcite was done by changing the conformation of chitosan molecules. Aragonite crystals in hexagonal prism-like shape were obtained in chitosan precipitates, vaterite crystals in hexagonal symmetrical plate-like shape were prepared in chitosan gel, and calcite nanoparticles were obtained in chitosan sol. The phenomenon of polymorph selection of biominerals by the morphology of biomacromolecules indicates that the studies on the relation between biominerals and biomacromelecules have general interest not only in bionics, but also in biometrics and related fields.
Retinal metabolic state of the proline-23-histidine rat model of retinitis pigmentosa
Authors: Acosta Monica L. , Shin Yea-Seul , Ready Sarah , Fletcher Erica L. , Christie David L. , Kalloniatis Michael
Published: December 2009

We determined the metabolic changes that precede cell death in the dystrophic proline-23-histidine (P23H) line 3 (P23H-3) rat retina compared with the normal Sprague-Dawley (SD) rat retina. Metabolite levels and metabolic enzymes were analyzed early in development and during the early stages of degeneration in the P23H-3 retina. Control and degenerating retinas showed an age-dependent change in metabolite levels and enzymatic activity, particularly around the time when phototransduction was activated. However, lactate dehydrogenase (LDH) activity was significantly higher in P23H-3 than SD retina before the onset of photoreceptor death. The creatine/phosphocreatine system did not contribute to the increase in ATP, because phosphocreatine levels, creatine kinase, and expression of the creatine transporter remained constant. However, Na+-K+-ATPase and Mg2+-Ca2+-ATPase activities were increased in the developing P23H-3 retina. Therefore, photoreceptor apoptosis in the P23H-3 retina occurs in an environment of increased LDH, ATPase activity, and higher-than-normal ATP levels. We tested the effect of metabolic challenge to the retina by inhibiting monocarboxylate transport with α-cyano-4-hydroxycinnamic acid or systemically administering the phosphodiesterase inhibitor sildenafil. Secondary to monocarboxylate transport inhibition, the P23H-3 retina did not demonstrate alterations in metabolic activity. However, administration of sildenafil significantly reduced LDH activity in the P23H-3 retina and increased the number of terminal deoxynucleotidyl transferase biotin-dUPT nick end-labeled photoreceptor cells. Photoreceptor cells with a rhodopsin mutation display an increase in apoptotic markers secondary to inhibition of a phototransduction enzyme (phosphodiesterase), suggesting increased susceptibility to altered cation entry.
Continuous estimates of dynamic cerebral autoregulation during transient hypocapnia and hypercapnia
Authors: Dineen N. E. , Brodie F G. , Robinson T. G. , Panerai R. B.
Published: December 2009

Dynamic cerebral autoregulation (CA) is the transient response of cerebral blood flow (CBF) to rapid blood pressure changes: it improves in hypocapnia and becomes impaired during hypercapnia. Batch-processing techniques have mostly been used to measure CA, providing a single estimate for an entire recording. A new approach to increase the temporal resolution of dynamic CA parameters was applied to transient hypercapnia and hypocapnia to describe the time-varying properties of dynamic CA during these conditions. Thirty healthy subjects (mean ± SD: 25 ± 6 yr, 9 men) were recruited. CBF velocity was recorded in both middle cerebral arteries (MCAs) with transcranial Doppler ultrasound. Arterial blood pressure (Finapres), end-tidal CO2 (ETCO2; infrared capnograph), and a three-lead ECG were also measured at rest and during repeated breath hold and hyperventilation. A moving window autoregressive moving average model provided continuous values of the dynamic CA index [autoregulation index (ARI)] and unconstrained gain. Breath hold led to significant increase in ETCO2 (+5.4 ± 6.1 mmHg), with concomitant increase in CBF velocity in both MCAs. Continuous dynamic CA parameters showed highly significant changes ( P < 0.001), with a temporal pattern reflecting a delayed dynamic response of CA to changes in arterial Pco2 and a maximal reduction in ARI of −5.1 ± 2.4 and −5.1 ± 2.3 for the right and left MCA, respectively. Hyperventilation led to a marked decrease in ETCO2 (−7.2 ± 4.1 mmHg, P < 0.001). Unexpectedly, CA efficiency dropped significantly with the inception of the metronome-controlled hyperventilation, but, after ∼30 s, the ARI increased gradually to show a maximum change of 5.7 ± 2.9 and 5.3 ± 3.0 for the right and left MCA, respectively ( P < 0.001). These results confirm the potential of continuous estimates of dynamic CA to improve our understanding of human cerebrovascular physiology and represent a promising new approach to improve the sensitivity of clinical applications of dynamic CA modeling.
Rectification of the EMG Signal Impairs the Identification of Oscillatory Input to the Muscle
Authors: Neto Osmar Pinto , Christou Evangelos A.
Published: December 2009

Rectification of EMG signals is a common processing step used when performing electroencephalographic–electromyographic (EEG–EMG) coherence and EMG–EMG coherence. It is well known, however, that EMG rectification alters the power spectrum of the recorded EMG signal (interference EMG). The purpose of this study was to determine whether rectification of the EMG signal influences the capability of capturing the oscillatory input to a single EMG signal and the common oscillations between two EMG signals. Several EMG signals were reconstructed from experimentally recorded EMG signals from the surface of the first dorsal interosseus muscle and were manipulated to have an oscillatory input or common input (for pairs of reconstructed EMG signals) at various frequency bands (in Hz: 0–12, 12–30, 30–50, 50–100, 100–150, 150–200, 200–250, 250–300, and 300–400), one at a time. The absolute integral and normalized integral of power, peak power, and peak coherence (for pairs of EMG signals) were quantified from each frequency band. The power spectrum of the interference EMG accurately detected the changes to the oscillatory input to the reconstructed EMG signal, whereas the power spectrum of the rectified EMG did not. Similarly, the EMG–EMG coherence between two interference EMG signals accurately detected the common input to the pairs of reconstructed EMG signals, whereas the EMG–EMG coherence between two rectified EMG signals did not. The frequency band from 12 to 30 Hz in the power spectrum of the rectified EMG and the EMG–EMG coherence between two rectified signals was influenced by the input from 100 to 150 Hz but not from the input from 12 to 30 Hz. The study concludes that the power spectrum of the EMG and EMG–EMG coherence should be performed on interference EMG signals and not on rectified EMG signals because rectification impairs the identification of the oscillatory input to a single EMG signal and the common oscillatory input between two EMG signals.
Inhibitory Odorant Signaling in Mammalian Olfactory Receptor Neurons
Authors: Ukhanov Kirill , Corey Elizabeth A. , Brunert Daniela , Klasen Katharina , Ache Barry W.
Published: December 2009

Odorants inhibit as well as excite olfactory receptor neurons (ORNs) in many species of animals. Cyclic nucleotide-dependent activation of canonical mammalian ORNs is well established but it is still unclear how odorants inhibit these cells. Here we further implicate phosphoinositide-3-kinase (PI3K), an indispensable element of PI signaling in many cellular processes, in olfactory transduction in rodent ORNs. We show that odorants rapidly and transiently activate PI3K in the olfactory cilia and in the olfactory epithelium in vitro. We implicate known G-protein–coupled isoforms of PI3K and show that they modulate not only the magnitude but also the onset kinetics of the electrophysiological response of ORNs to complex odorants. Finally, we show that the ability of a single odorant to inhibit another can be PI3K dependent. Our collective results provide compelling support for the idea that PI3K-dependent signaling mediates inhibitory odorant input to mammalian ORNs and at least in part contributes to the mixture suppression typically seen in the response of ORNs to complex natural odorants.
Forecasts of Tropical Pacific Sea Surface Temperatures by Neural Networks and Support Vector Regression
Authors: Aguilar-Martinez Silvestre , Hsieh William W.
Published: December 2009

Two nonlinear regression methods, Bayesian neural network (BNN) and support vector regression (SVR), and linear regression (LR), were used to forecast the tropical Pacific sea surface temperature (SST) anomalies at lead times ranging from 3 to 15 months, using sea level pressure (SLP) and SST as predictors. Datasets for 1950–2005 and 1980–2005 were studied, with the latter period having the warm water volume (WWV) above the 20∘C isotherm integrated across the equatorial Pacific available as an extra predictor.

The forecasts indicated that the nonlinear structure is mainly present in the second PCA (principal component analysis) mode of the SST field. Overall, improvements in forecast skills by the nonlinear models over LR were modest.
Although SVR has two structural advantages over neural network models, namely (a) no multiple minima in the optimization process and (b) an error norm robust to outliers in the data, it did not give better overall forecasts than BNN.
Addition of WWV as an extra predictor generally increased the forecast skills slightly; however, the influence of WWV on SST anomalies in the tropical Pacific appears to be linear.
Treatment for Recurrent Ovarian Cancer—At First Relapse
Authors: Ushijima Kimio
Published: December 2009

Recurrent ovarian cancer is a lethal disease, and few patients can be cured. Although most patients receive standardized surgery and chemotherapy, the status of recurrent disease is heterogeneous. The site of recurrence and the survival intervals after recurrence are also widely distributed. Among a number of factors, many clinical trials identified time to recurrence was the factor most related to chemosensitivity at first relapse. The current recommendation for platinum sensitive ovarian cancer is a carboplatin containing combination chemotherapy. Generally, a single agent is chosen for platinum resistant ovarian cancer. Patients with single site recurrence and a long disease free interval are candidates for secondary cytoreduction, which may provide longer survival. There are several treatment choices at first relapse, and disease status, chemotherapy-free interval, and the patient's condition play a major role in the decision making process.
Weak and Strong Convergence of an Implicit Iteration Process for an Asymptotically Quasi-"Equation missing" -Nonexpansive Mapping in Banach Space
Authors: Mukhamedov Farrukh , Saburov Mansoor
Published: December 2009

We prove the weak and strong convergence of the implicit iterative process to a common fixed point of an asymptotically quasi-"Equation missing"-nonexpansive mapping "Equation missing" and an asymptotically quasi-nonexpansive mapping "Equation missing", defined on a nonempty closed convex subset of a Banach space.
Pedunculopontine Nucleus Deep Brain Stimulation in a Patient with Primary Progressive Freezing Gait Disorder
Authors: Ostrem Jill L. , Christine Chadwick W. , Glass Graham A. , Schrock Lauren E. , Starr Philip A.
Published: December 2009

Background: Pedunculopontine nucleus (PPN) deep brain stimulation (DBS) has recently been suggested for treatment of medication-unresponsive gait and axial symptoms in Parkinson’s disease. Patients with the rare primary progressive freezing gait disorder (PPFG) have similar disabling symptoms and few therapeutic options. We report here on our experience with PPN DBS in treating a 76-year-old man with medication-refractory PPFG. Methods: The patient was treated with staged PPN DBS and underwent careful pre- and postoperative clinical evaluations up to 12 months after surgery. Results: PPN DBS resulted in only mild improvement in symptoms after 12 months of stimulation. Conclusion: In this single case of a patient with PPFG, PPN DBS served only a limited role in treating his symptoms and adds to the very limited published literature describing patients treated with DBS at this brain target.
The Independent Evolution of the Enlargement of the Principal Sensory Nucleus of the Trigeminal Nerve in Three Different Groups of Birds
Authors: Gutiérrez-Ibáñez Cristián , Iwaniuk Andrew N. , Wylie Douglas R.
Published: December 2009

In vertebrates, sensory specializations are usually correlated with increases in the brain areas associated with that specialization. This correlation is called the ‘principle of proper mass’ whereby the size of a neural structure is a reflection of the complexity of the behavior that it subserves. In recent years, several comparative studies have revealed examples of this principle in the visual and auditory system of birds, but somatosensory specializations have largely been ignored. Many species rely heavily on tactile information during feeding. Input from the beak, tongue and face, conveyed via the trigeminal, facial, glossopharyngeal and hypoglossal nerves, is first processed in the brain by the principal sensory nucleus of the trigeminal nerve (PrV) in the brainstem. Previous studies report that PrV is enlarged in some species that rely heavily on tactile input when feeding, but no extensive comparative studies have been performed. In this study, we assessed the volume of PrV in 73 species of birds to present a detailed analysis of the relative size variation of PrV using both conventional and phylogenetically based statistics. Overall, our results indicate that three distinct groups of birds have a hypertrophied PrV: waterfowl (Anseriformes), beak-probing shorebirds (Charadriiformes), and parrots (Psittaciformes). These three groups have different sensory requirements from the orofacial region. For example, beak-probing shorebirds use pressure information from the tip of the beak to find buried prey in soft substrates, whereas waterfowl, especially filter-feeding ducks, use information from the beak, palate, and tongue when feeding. Parrots likely require increased sensitivity in the tongue to manipulate food items. Thus, despite all sharing an enlarged PrV and feeding behaviors dependent on tactile input, each group has different requirements that have led to the independent evolution of a large PrV.
Enhancement of Antiviral Activity of Collectin Trimers through Cross-Linking and Mutagenesis of the Carbohydrate Recognition Domain
Authors: White Mitchell R. , Boland Patrick , Tecle Tesfaldet , Gantz Donald , Sorenson Grith , Tornoe Ida , Holmskov Uffe , McDonald Barbara , Crouch Erika C. , Hartshorn Kevan L.
Published: December 2009

Surfactant protein D (SP-D) plays important roles in innate defense against respiratory viruses [including influenza A viruses (IAVs)]. Truncated trimers composed of its neck and carbohydrate recognition domains (NCRDs) bind various ligands; however, they have minimal inhibitory activity for IAV. We have sought to find ways to increase the antiviral activity of collectin NCRDs. Cross-linking of the SP-D NCRD with nonblocking monoclonal antibodies (mAbs) markedly potentiates antiviral activity. In the present report, we demonstrate that F(ab’)2 [but not F(ab’)1] fragments of a cross-linking mAb have similar effects. Hence, cross-linking activity, but not the Fc domain of the mAb, is needed for increased antiviral activity. In contrast, the Fc domain of the mAb was important for increasing viral uptake or respiratory burst responses of human neutrophils. Our NCRD constructs contain an S protein binding site. Herein, we show that a multivalent S protein complex caused cross-linking and also increased the antiviral activity of NCRDs. NCRDs of conglutinin and CL43 had greater intrinsic antiviral activity than those of SP-D or mannose-binding lectin. Based on motifs found in these serum collectins, we have constructed mutant versions of the human SP-D NCRD that have increased antiviral activity. These mutant NCRDs also had potentiated activity after cross-linking with F(ab’)2 fragments or S protein complexes. Hence, the antiviral activity of NCRDs can be increased by 2 distinct, complementary strategies, namely cross-linking of NCRDs through various means and mutagenesis of CRD residues to increase viral binding. These findings may be relevant for antiviral therapy.
Koexistenz nervaler Proliferate mit frühen epithelialen Neoplasien und benignen Ektopien der Cervix uteri
Authors: Bajardi F.
Published: December 2009

Fragestellung: Anlass der Studie war die Hypothese, dass Stromasysteme die DignitÄt des Epithels beeinflussen kÖnnten. Methode: Bei Zervixkonisaten wurde wie das Epithel auch das Stroma fÄchendeckend histologisch untersucht. Ergebnisse: Es wurden Neurome, Neurofibrome und vaskulÄre Neurofibromatosen gefunden. Sie waren hÄufig bei epithelialen Neoplasien (168 von 203 FÄllen) und seltener (8 von 21 FÄllen) bei benignen Ektopien. Schlussfolgerung: Somit korreliert die Frequenz der neuralen Proliferate mit der QualitÄt des Epithels. Diese Beziehung wird als Argument gegen die Vorstellung des autonomen Wachstums des neoplastischen OberflÄchenepithels gewertet.
Immunhistologischer Tumorzellnachweis an Lymphknoten beim nodal-negativen Mammakarzinom: Korrelation mit “etablierten" und “neueren" Prognosefaktoren
Authors: Gerber B. , Krause Annette , Kimmig R.
Published: December 2009

Fragestellung: Die Bedeutung von immunhistologisch detektierten Tumorzellen in axillÄren Lymphknoten und ihre Beziehung zu anderen Prognoseparametern werden untersucht. Methoden: 1807 axÍllÄre Lymphknoten von 122 pT1-2N₀M₀-Patientinnen wurden mit einem Panzytokeratin-AntikÖrper untersucht. Klinische Daten, histologische Befunde, etablierte und neuere Prognoseparameter wurden zudem bestimmt. Die mittlere Nachbeobachtungszeit betrÄgt 50 Monate. Ergebnisse: Der immunhistologische Tumorzellnachweis in den Lymphknoten von 16 der 122 (13,1 %) Patientinnen war mit einem kÜrzerem krankheitsfreien Über-leben (p = 0,03) verbunden. In der multivariaten Analyse mit dem Cox-Regressionsmodell wurden TumorgrÖΒe, Grading, GefÄΒinvasion und S-Phase als unabhÄngige Prognoseparameter, nicht jedoch der Tumorzellachweis bestÄtigt. SchluΒfolgerung: Immunhistologisch nachgewiesene Tumorzellen in axillÄren Lymphknoten sind prognostisch und therapeutisch bedeutsam, stellen jedoch keinen unabhÄngigen Prognoseparameter dar.
Uncoupling Protein-2 Negatively Regulates Polymorphonuclear Leukocytes Chemotaxis via Modulating [Ca
2+
] Influx
Authors: Liu Dan-Qing , Guo Ya-Lan , Bian Zhen , Chen Yuan-Yuan , Chen Xi , Liu Yuan , Zhang Chen-Yu , Zen Ke
Published: December 2009

Objective—

Previous studies demonstrated that uncoupling protein 2 (UCP2) plays a negative role in modulating leukocyte inflammatory responses. The mechanism underneath the role of UCP2 in modulating leukocyte inflammatory responses, however, is incompletely understood. Here, we investigated the effect of UCP2 in polymorphonuclear leukocyte (PMN) chemotaxis.

Methods and Results—

First, we assessed PMN chemotaxis in zymosan-induced murine peritonitis and found that UCP2
−/−
mice had significantly more migrated PMN in peritoneal lavage compared to their wild-type littermates. In vitro transmigration assays using isolated PMN also showed that PMN from UCP2
−/−
mice migrated faster than those from wild-type mice in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP). Second, in supporting an inhibitory role of UCP2 in PMN transmigration, migrated PMN had a decreased UCP2 expression compared to nonmigrated PMN. In contrast, in streptozotocin-induced diabetic mice in which UCP2 expression was enhanced, PMN chemotaxis was reduced. Third, comparing to UCP2
+/+
PMN, UCP2
−/−
PMN had a stronger upregulation of fMLP-induced surface CD11b/CD18 and CD11a/CD18. Finally, UCP2
−/−
PMN showed a quicker and larger fMLP-triggered intracellular calcium mobilization compared to UCP2
+/+
PMN.

Conclusion—

Our study demonstrates that UCP2 serves as a brake in controlling PMN chemotaxis and that the effect of UCP2 on PMN chemotaxis may be through modulating calcium influx.
Association of Plasma Sphingomyelin Levels and Incident Coronary Heart Disease Events in an Adult Population
Authors: Yeboah Joseph , McNamara Coleen , Jiang Xian-Cheng , Tabas Ira , Herrington David M. , Burke Gregory L. , Shea Steven
Published: December 2009

Objective—

A high plasma sphingomyelin level has been associated with subclinical atherosclerosis, coronary artery disease, and worse prognosis in subjects with acute coronary syndromes. We wanted to assess the predictive value of plasma sphingomyelin levels for incident coronary heart disease (CHD) events in the Multi-Ethnic Study of Atherosclerosis.

Methods and Results—

The plasma sphingomyelin level was measured in 6809 of 6814 subjects (age, mean±SD, 62.2±10.2 years) participating in the Multi-Ethnic Study of Atherosclerosis, a population-based cohort study of adults free of clinical cardiovascular disease at baseline recruited at 6 clinic sites in the United States. The subjects consisted of 52.8% females, 38.5% whites, 11.8% Chinese, 27.8% blacks, and 21.9% Hispanics. Cox proportional hazard analysis was used to examine the association between plasma sphingomyelin level and 5 years of adjudicated incident CHD events, including myocardial infarction, resuscitated cardiac arrest, angina, CHD-related death, and revascularization (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty). The mean±SD plasma sphingomyelin level was 48.0±16.0 mg/dL. A total of 189 subjects had an adjudicated CHD event during the 5 years of follow-up. In the Kaplan-Meier analysis, subjects with a plasma sphingomyelin level higher than the sex-specific median had a similar event-free survival rate compared with subjects with a plasma sphingomyelin level at or less than the sex-specific median (97.16% versus 97.00%; log rank
P
=0.71). In the univariate Cox proportional hazard analysis, the plasma sphingomyelin level was not a predictor of an incident CHD event (hazard ratio, 0.992 [0.982–1.004];
P
=0.09). In our multistage multivariate Cox proportional hazard models, a higher plasma sphingomyelin level had a modest negative association with incident CHD events when total cholesterol, high-density lipoprotein, and triglycerides were included in the model (hazard ratio, 0.985 [0.973–0.996];
P
=0.008) and also in our full model after adjusting for age, sex, total cholesterol, high-density lipoprotein, triglycerides, diabetes mellitus, cigarette smoking, systolic and diastolic blood pressure, medication use for blood pressure, and 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitor use (hazard ratio, 0.984 [0.973–0.996];
P
=0.002). In other models, the plasma sphingomyelin level was not associated with incident CHD events.

Conclusion—

A high plasma sphingomyelin level is not associated with an increased risk of incident CHD in population-based adults free of clinical cardiovascular disease at baseline.