bluuebunny/crossref_metadata_2025 huggingface dataset:
Propagation of bovine coronavirus in clones of the Caco‐2 cell line showing different levels of alkaline phosphatase activity
Authors: MORI Kenichi , INOUE Yuuki , MUKAI Takao , OHORI Hitoshi
Published: March 2006

The aim of the present study was to determine whether bovine coronavirus (BCV) has the ability to initiate infection in a human colon carcinoma cell line, Caco‐2, that has been established to spontaneously differentiate after confluence. When Caco‐2 cells were infected with BCV, a titer of 5.5 × 106 plaque‐forming units (p.f.u.)/mL was found in the culture supernatant at 5 days postinfection. Two clones, Caco‐2/CA1 and Caco‐2/CA2, were then isolated by monitoring alkaline phosphatase (ALP) and cell proliferation activities. The ALP activity level of CA1 cells was significantly higher than that of CA2 cells, while the level of cell proliferation activity of CA1 was significantly lower than that of CA2. When CA1 and CA2 cells were infected with BCV at confluence, virus hemagglutination (HA) was detected in the culture supernatant at 5 days postinfection for CA1 cells and at 8 days postinfection for CA2 cells. Thus, BCV propagation was substantially delayed in CA2 cells, suggesting that a cellular factor(s) that appears at the differentiation stage may control BCV propagation. BCV‐susceptible CA1 and CA2 cells showing different levels of ALP activity would be useful for further experiments to elucidate the mechanism of BCV propagation.
Species of Bursaphelenchus Fuchs, 1937 (Nematoda: Parasitaphelenchidae) and other nematode genera associated with insects from Pinus pinaster in Portugal
Authors: Penas A.C. , Bravo M.A. , Naves P. , Bonifácio L. , Sousa E. , Mota M.
Published: March 2006

Insects associated with maritime pine, Pinus pinaster, in Portugal were collected and screened for the presence of Bursaphelenchus species. Nematodes were identified using Internal Transcribed Spacers‐Restriction Fragment Length Polymorphism (ITS‐RFLP) analysis of dauer juveniles and morphological identification of adults that developed from dauer juveniles on fungal cultures or on cultures in pine wood segments at 26°C. Several associations are described: Bursaphelenchus teratospicularis and Bursaphelenchus sexdentati are associated with Orthotomicus erosus; Bursaphelenchus tusciae, B. sexdentati and/or Bursaphelenchus pinophilus with Hylurgus ligniperda and Bursaphelenchus hellenicus with Tomicus piniperda, Ips sexdentatus and H. ligniperda. An unidentified Bursaphelenchus species is vectored by Hylobius sp. The previously reported association of Bursaphelenchus xylophilus with Monochamus galloprovincialis was confirmed. The association of Bursaphelenchus leoni with Pityogenes sp. is not definitively established and needs further studies for clarification. Other nematode genera besides Bursaphelenchus were found to be associated with the insects sampled, including two different species of Ektaphelenchus, Parasitorhabditis sp., Parasitaphelenchus sp., Contortylenchus sp. and other unidentified nematodes. The Ektaphelenchus species found in O. erosus is morphologically similar to B. teratospicularis found in the same insect; adults of both the species are found in cocoon‐like structures under the elytra of the insects.
Response of different forms of propagules of Rhizoctonia solani AG2‐1 (ZG5) exposed to the volatiles produced in soil amended with green manures
Authors: Yulianti T. , Sivasithamparam K. , Turner D.W.
Published: March 2006

The sensitivity of different forms of propagules of Rhizoctonia solani anastomosis group (AG)2‐1/zymogram group (ZG)5 to volatile compounds produced in soil amended with green manure will influence the efficacy of green manures used to manage the disease. In laboratory experiments, we determined the impact of volatiles arising from residues of five species of Brassicaceae, and Avena sativa (oat), a non‐Brassicaceae species, and volatiles of pure allyl isothiocyanate (AITC) or 2‐phenylethyl isothiocyanate (2‐PEITC) in either their soluble or vapour phase on the hyphal growth of R. solani arising from different propagules. The brassicaceous species were Brassica napus var. Karoo, B. napus B1, B. napus B2, B. nigra and Diplotaxis tenuifolia (a brassicaceous weed). Colony growth and hyphal density on water agar were measured up to 7 days. The amendment of a sandy soil with green manures at a high (100 g kg−1, 10%) concentration generally suppressed the growth of the pathogen, but at a low (10 g kg−1, 1%) concentration, the amendment had little effect on the radial fungal growth of the pathogen but increased the density of hyphae through more branching. The inhibition by volatiles from the residues of Brassicaceae species at 10% concentration was stronger (82–86%) than that by volatiles from oat (64%) amendment at the same rate. Hyphae arising from sclerotia and precolonised ryegrass seed were less sensitive than hyphae growing out of potato dextrose agar plugs. This indicates that thick‐pigmented cell walls may have protected the fungus from these unfavourable conditions. Pure AITC and 2‐PEITC in the range of 0.5–2.0 mM inhibited the growth of R. solani from all forms of propagules, but hyphae originating from agar plugs were the most vulnerable compared with the two others. Thus, hyphae arising from the medulla of the sclerotia may be relatively tolerant to volatile compounds emanating from decomposing Brassica green manure amendments in the field and in vitro inhibition of the vegetative growth of the pathogen may not reflect its response to the amendments in the field.
The Future of Tropical Forest Species1
Authors: Wright S. Joseph , Muller‐Landau Helene C.
Published: March 2006

Deforestation and habitat loss are widely expected to precipitate an extinction crisis among tropical forest species. Humans cause deforestation, and humans living in rural settings have the greatest impact on extant forest area in the tropics. Current human demographic trends, including slowing population growth and intense urbanization, give reason to hope that deforestation will slow, natural forest regeneration through secondary succession will accelerate, and the widely anticipated mass extinction of tropical forest species will be avoided. Here, we show that the proportion of potential forest cover remaining is closely correlated with human population density among countries, in both the tropics and the temperate zone. We use United Nations population projections and continent‐specific relationships between both total and rural population density and forest remaining today to project future tropical forest cover. Our projections suggest that deforestation rates will decrease as population growth slows, and that a much larger area will continue to be forested than previous studies suggest. Tropical forests retracted to smaller areas during repeated Pleistocene glacial events in Africa and more recently in selected areas that supported large prehistoric human populations. Despite many caveats, these projections and observations provide hope that many tropical forest species will be able to survive the current wave of deforestation and human population growth. A strategy to preserve tropical biodiversity might include policies to improve conditions in tropical urban settings to hasten urbanization and preemptive conservation efforts in countries with large areas of extant forest and large projected rates of future human population growth. We hope that this first attempt inspires others to produce better models of future tropical forest cover and associated policy recommendations.
Quality control for daily observational rainfall series in the UK
Authors: Yang C. , Chandler R. E. , Isham V. S. , Wheater H. S.
Published: March 2006

Daily rainfall sequences in the UK need careful quality control before use. This issue is discussed using data from two rain gauge networks. In particular, changes in recording resolution or inconsistencies between different types of recording device may result in biases, for which allowance should be made when these data are used for modelling. Model fitting is shown to be an effective way of investigating unexplained spatial or temporal inconsistencies. Generalized linear models are fitted to data from the Blackwater catchment to illustrate model‐based data checking. Some apparently unexplained spatial inconsistencies are related to trace values in the data set. By applying a simple threshold to the data, the inconsistencies can be removed.
Descartes's Passions of the Soul
Authors: Shapiro Lisa
Published: March 2006

While Descartes's Passions of the Soul has been taken to hold a place in the history to human physiology, until recently philosophers have neglected the work. In this research summary, I set Descartes's last published work in context and then sketch out its philosophical significance. From it, we gain further insight into Descartes's solution to the Mind–Body Problem – that is, to the problem of the ontological status of the mind–body union in a human being, to the nature of body–mind causation, and to the way body‐caused thoughts represent the world. In addition, the work contains Descartes's developed ethics, in his account of virtue and of the passion of générosité in particular. Through his taxonomy of the passions and the account of their regulation, we also learn more about his moral psychology.
Optimal Contact Force Distribution for Multi-Limbed Robots
Authors: Hong Dennis W. , Cipra Raymond J.
Published: March 2006

One of the inherent problems of multi-limbed mobile robotic systems is the problem of multi-contact force distribution; the contact forces and moments at the feet required to support it and those required by its tasks are indeterminate. A new strategy for choosing an optimal solution for the contact force distribution of multi-limbed robots with three feet in contact with the environment in three-dimensional space is presented. The incremental strategy of opening up the friction cones is aided by using the “force space graph” which indicates where the solution is positioned in the solution space to give insight into the quality of the chosen solution and to provide robustness against disturbances. The “margin against slip with contact point priority” approach is also presented which finds an optimal solution with different priorities given to each foot contact point. Examples are presented to illustrate certain aspects of the method and ideas for other optimization criteria are discussed.
Optical Response of High-Dielectric-Constant Perovskite-Related Oxide
Authors: Homes C. C. , Vogt T. , Shapiro S. M. , Wakimoto S. , Ramirez A. P.
Published: March 2006

Optical conductivity measurements on the perovskite-related oxide CaCu
3
Ti
4
O
12
provide a hint of the physics underlying the observed giant dielectric effect in this material. A low-frequency vibration displays anomalous behavior, implying that there is a redistribution of charge within the unit cell at low temperature. At infrared frequencies (terahertz), the value for the dielectric constant is ∼80 at room temperature, which is far smaller than the value of ∼10
5
obtained at lower radio frequencies (kilohertz). This discrepancy implies the presence of a strong absorption at very low frequencies due to dipole relaxation. At room temperature, the characteristic relaxation times are fast (≲500 nanoseconds) but increase dramatically at low temperature, suggesting that the large change in dielectric constant may be due to a relaxor-like dynamical slowing down of dipolar fluctuations in nanosize domains.
Cenozoic Plant Diversity in the Neotropics
Authors: Jaramillo Carlos , Rueda Milton J. , Mora Germán
Published: March 2006

Several mechanisms have been proposed to explain the high levels of plant diversity in the Neotropics today, but little is known about diversification patterns of Neotropical floras through geological time. Here, we present the longest time series compiled for palynological plant diversity of the Neotropics (15 stratigraphic sections, 1530 samples, 1411 morphospecies, and 287,736 occurrences) from the Paleocene to the early Miocene (65 to 20 million years ago) in central Colombia and western Venezuela. The record shows a low-diversity Paleocene flora, a significantly more diverse early to middle Eocene flora exceeding Holocene levels, and a decline in diversity at the end of the Eocene and early Oligocene. A good correlation between diversity fluctuations and changes in global temperature was found, suggesting that tropical climate change may be directly driving the observed diversity pattern. Alternatively, the good correspondence may result from the control that climate exerts on the area available for tropical plants to grow.
Significant Warming of the Antarctic Winter Troposphere
Authors: Turner J. , Lachlan-Cope T. A. , Colwell S. , Marshall G. J. , Connolley W. M.
Published: March 2006

We report an undocumented major warming of the Antarctic winter troposphere that is larger than any previously identified regional tropospheric warming on Earth. This result has come to light through an analysis of recently digitized and rigorously quality controlled Antarctic radiosonde observations. The data show that regional midtropospheric temperatures have increased at a statistically significant rate of 0.5° to 0.7°Celsius per decade over the past 30 years. Analysis of the time series of radiosonde temperatures indicates that the data are temporally homogeneous. The available data do not allow us to unambiguously assign a cause to the tropospheric warming at this stage.
Rotational Coherence and a Sudden Breakdown in Linear Response Seen in Room-Temperature Liquids
Authors: Moskun Amy C. , Jailaubekov Askat E. , Bradforth Stephen E. , Tao Guohua , Stratt Richard M.
Published: March 2006

Highly energized molecules normally are rapidly equilibrated by a solvent; this finding is central to the conventional (linear-response) view of how chemical reactions occur in solution. However, when a reaction initiated by 33-femtosecond deep ultraviolet laser pulses is used to eject highly rotationally excited diatomic molecules into alcohols and water, rotational coherence persists for many rotational periods despite the solvent. Molecular dynamics simulations trace this slow development of molecular-scale friction to a clearly identifiable molecular event: an abrupt liquid-structure change triggered by the rapid rotation. This example shows that molecular relaxation can sometimes switch from linear to nonlinear response.
Impact of
Enterococcus faecalis
on the Bactericidal Activities of Arbekacin, Daptomycin, Linezolid, and Tigecycline against Methicillin-Resistant
Staphylococcus aureus
in a Mixed-Pathogen Pharmacodynamic Model
Authors: LaPlante Kerry L. , Rybak Michael J. , Leuthner Kimberly D. , Chin Judy N.
Published: March 2006

We inoculated an in vitro pharmacodynamic model simultaneously with clinical isolates of methicillin-resistant
Staphylococcus aureus
and an enterocin-producing enterococcus (vancomycin-resistant
Enterococcus faecalis
, ampicillin susceptible) at 7 log
10
CFU/ml to examine enterocin effects and antimicrobial activity on staphylococci. The investigated antimicrobial regimens were 100 mg arbekacin every 12 h (q12h), 6 mg daptomycin per kg of body weight/day, 600 mg linezolid q12h, and 100 mg tigecycline q24h alone and in combination (daptomycin, linezolid, and tigecycline) with arbekacin. Simulations were performed in triplicate; bacterial quantification occurred over 48 h, and development of resistance was evaluated throughout. When we evaluated the impact of antimicrobial activity against
S. aureus
alone, daptomycin demonstrated bactericidal activity (≥3 log
10
CFU/ml kill), whereas arbekacin, linezolid, and tigecycline displayed bacteriostatic activities (<3 log
10
CFU/ml kill). In the mixed-pathogen model, early and distinctive stunting of
S. aureus
growth was noted (1.5 log CFU/ml difference) in the presence of enterocin-producing
E. faecalis
compared to growth controls run individually (
P
= 0.02). Most noteworthy was that in the presence of enterocin-producing
E. faecalis
, bactericidal activity was observed with arbekacin and tigecycline and with the addition of arbekacin to linezolid. Antagonism was noted for the combination of tigecycline and arbekacin against
S. aureus
in the presence of enterocin-producing
E. faecalis
. Our research demonstrates that the inhibitory effect of
E. faecalis
contributed significantly to its overall antimicrobial impact on
S. aureus
. This contribution was enhanced or improved compared to the activity of each antimicrobial alone. Further research is warranted to determine the impact of polymicrobial infections on antimicrobial activity.
Candida glabrata PDR1
, a Transcriptional Regulator of a Pleiotropic Drug Resistance Network, Mediates Azole Resistance in Clinical Isolates and Petite Mutants
Authors: Tsai Huei-Fung , Krol Anna A. , Sarti Kelly E. , Bennett John E.
Published: March 2006

Candida glabrata
, a yeast with intrinsically low susceptibility to azoles, frequently develops increased azole resistance during prolonged treatment. Transposon mutagenesis revealed that disruption of Cg
PDR1
resulted in an 8- to 16-fold increase in fluconazole susceptibility of
C. glabrata
. Cg
PDR1
is a homolog of
Saccharomyces cerevisiae PDR1
, which encodes a transcriptional regulator of multidrug transporters. Northern blot analyses indicated that Cg
PDR1
regulated both constitutive and drug-induced expression of Cg
CDR1
, a multidrug transporter gene. In agreement with the Northern analysis, the Cg
pdr1
mutant had increased rhodamine accumulation, in contrast to the decreased accumulation in the Cg
PDR1
-overexpressing strain. Northern analyses also indicated the importance of Cg
PDR1
in fluconazole resistance arising during therapy. Two clinically resistant isolates had higher expression of Cg
PDR1
and Cg
CDR1
compared to their paired susceptible isolates. Integrative transformation of Cg
PDR1
from the two resistant isolates converted the Cg
pdr1
mutant into azole-resistant strains with upregulated Cg
PDR1
expression. Two different amino acid substitutions, W297S in one isolate and F575L in the other, accounted for the upregulated Cg
PDR1
expression and the resistance. Finally, Cg
PDR1
was shown to be required for the azole resistance due to mitochondrial deficiency. Thus, Cg
PDR1
encodes a transcriptional regulator of a pleiotropic drug resistance network and contributes to the azole resistance of clinical isolates and petite mutants.
Sialidase Fusion Protein as a Novel Broad-Spectrum Inhibitor of Influenza Virus Infection
Authors: Malakhov Michael P. , Aschenbrenner Laura M. , Smee Donald F. , Wandersee Miles K. , Sidwell Robert W. , Gubareva Larisa V. , Mishin Vasiliy P. , Hayden Frederick G. , Kim Do Hyong , Ing Alice , Campbell Erin R. , Yu Mang , Fang Fang
Published: March 2006

Influenza is a highly infectious disease characterized by recurrent annual epidemics and unpredictable major worldwide pandemics. Rapid spread of the highly pathogenic avian H5N1 strain and escalating human infections by the virus have set off the alarm for a global pandemic. To provide an urgently needed alternative treatment modality for influenza, we have generated a recombinant fusion protein composed of a sialidase catalytic domain derived fromActinomyces viscosusfused with a cell surface-anchoring sequence. The sialidase fusion protein is to be applied topically as an inhalant to remove the influenza viral receptors, sialic acids, from the airway epithelium. We demonstrate that a sialidase fusion construct, DAS181, effectively cleaves sialic acid receptors used by both human and avian influenza viruses. The treatment provides long-lasting effect and is nontoxic to the cells. DAS181 demonstrated potent antiviral and cell protective efficacies against a panel of laboratory strains and clinical isolates of IFV A and IFV B, with virus replication inhibition 50% effective concentrations in the range of 0.04 to 0.9 nM. Mouse and ferret studies confirmed significant in vivo efficacy of the sialidase fusion in both prophylactic and treatment modes.
New Approach for High-Throughput Screening of Drug Activity onPlasmodiumLiver Stages
Authors: Gego Audrey , Silvie Olivier , Franetich Jean-François , Farhati Khemaïs , Hannoun Laurent , Luty Adrian J. F. , Sauerwein Robert W. , Boucheix Claude , Rubinstein Eric , Mazier Dominique
Published: March 2006

Plasmodiumliver stages represent potential targets for antimalarial prophylactic drugs. Nevertheless, there is a lack of molecules active on these stages. We have now developed a new approach for the high-throughput screening of drug activity onPlasmodiumliver stages in vitro, based on an infrared fluorescence scanning system. This method allowed us to count automatically and rapidlyPlasmodium-infected hepatocytes, using different hepatic cells and differentPlasmodiumspecies, includingPlasmodium falciparum. This new technique is well adapted for high-throughput drug screening and should facilitate the identification of new antimalarial compounds active onPlasmodiumliver stages.
In defence of moral imperialism: four equal and universal prima facie principles
Authors: Dawson A , Garrard E
Published: March 2006

Raanan Gillon is a noted defender of the four principles approach to healthcare ethics. His general position has always been that these principles are to be considered to be both universal and prima facie in nature. In recent work, however, he has made two claims that seem to present difficulties for this view. His first claim is that one of these four principles, respect for autonomy, has a special position in relation to the others: he holds that it is first among equals. We argue that this claim makes little sense if the principles are to retain their prima facie nature. His second claim is that cultural variation can play an independent normative role in the construction of our moral judgments. This, he argues, enables us to occupy a middle ground between what he sees as the twin pitfalls of moral relativism and (what he calls) moral imperialism. We argue that there is no such middle ground, and while Gillon ultimately seems committed to relativism, it is some form of moral imperialism (in the form of moral objectivism) that will provide the only satisfactory construal of the four principles as prima facie universal moral principles.
EXTREMAL FUNCTIONS FOR A SHARP MOSER–TRUDINGER INEQUALITY
Authors: YANG YUNYAN
Published: March 2006

Let Ω be a bounded smooth domain in ℝ2, and λ1(Ω) the first eigenvalue of the Laplacian with Dirichlet boundary condition in Ω. Then Adimurthi and Druet show that for any 0 ≤ α < λ1(Ω)[Formula: see text] We prove in this paper that there exist extremal functions for the above inequality. In other words, we show that [Formula: see text] is attained for any 0 ≤ α < λ1(Ω).
Pollutant particles enhanced H2O2 production from NAD(P)H oxidase and mitochondria in human pulmonary artery endothelial cells
Authors: Li Zhuowei , Hyseni Xhevahire , Carter Jacqueline D. , Soukup Joleen M. , Dailey Lisa A. , Huang Yuh-Chin T.
Published: March 2006

Particulate matter (PM) induces oxidative stress and cardiovascular adverse health effects, but the mechanistic link between the two is unclear. We hypothesized that PM enhanced oxidative stress in vascular endothelial cells and investigated the enzymatic sources of reactive oxygen species and their effects on mitogen-activated protein kinase (MAPK) activation and vasoconstriction. We measured the production of extracellular H2O2, activation of extracellular signal-regulated kinases1/2 (ERK1/2) and p38 MAPKs in human pulmonary artery endothelial cells (HPAEC) treated with urban particles (UP; SRM1648), and assessed the effects of H2O2 on vasoconstriction in pulmonary artery ring and isolated perfused lung. Within minutes after UP treatment, HPAEC increased H2O2 production that could be inhibited by diphenyleneiodonium (DPI), apocynin (APO), and sodium azide (NaN3). The water-soluble fraction of UP as well as its two transition metal components, Cu and V, also stimulated H2O2 production. NaN3 inhibited H2O2 production stimulated by Cu and V, whereas DPI and APO inhibited only Cu-stimulated H2O2 production. Inhibitors of other H2O2-producing enzymes, including Nω-methyl-l-argnine, indomethacin, allopurinol, cimetidine, rotenone, and antimycin, had no effects. DPI but not NaN3 attenuated UP-induced pulmonary vasoconstriction and phosphorylation of ERK1/2 and p38 MAPKs. Knockdown of p47phox gene expression by small interfering RNA attenuated UP-induced H2O2 production and phosphorylation of ERK1/2 and p38 MAPKs. Intravascular administration of H2O2 generated by glucose oxidase increased pulmonary artery pressure. We conclude that UP induce oxidative stress in vascular endothelial cells by activating NAD(P)H oxidase and the mitochondria. The endothelial oxidative stress may be an important mechanism for PM-induced acute cardiovascular health effects.
Transcriptional repression of Na-K-2Cl cotransporter NKCC1 by hypoxia-inducible factor-1
Authors: Ibla Juan C. , Khoury Joseph , Kong Tianqing , Robinson Andreas , Colgan Sean P.
Published: March 2006

Tissue edema is commonly associated with hypoxia. Generally, such episodes of fluid accumulation are self-limiting. At present, little is known about mechanisms to compensate excessive fluid transport. Here we describe an adaptive mechanism to dampen fluid loss during hypoxia. Initial studies confirmed previous observations of attenuated electrogenic Cl− secretion after epithelial hypoxia. A screen of known ion transporters in Cl−-secreting epithelia revealed selective downregulation of Na-K-2Cl cotransporter NKCC1 mRNA, protein, and function. Subsequent studies identified transcriptional repression of NKCC1 mediated by hypoxia-inducible factor (HIF). Chromatin immunoprecipitation analysis identified a functional HIF binding site oriented on the antisense strand of genomic DNA downstream of the transcription start site corresponding to the NKCC1 5′-untranslated region. Additional in vivo studies using conditional Hif1a-null mice revealed that the loss of HIF-1α in Cl−-secreting epithelia results in a loss of NKCC1 repression. These studies describe a novel regulatory pathway for NKCC1 transcriptional repression by hypoxia. These results suggest that HIF-dependent repression of epithelial NKCC1 may provide a compensatory mechanism to prevent excessive fluid loss during hypoxia.
Targeted disruption of the murine CCK1 receptor gene reduces intestinal lipid-induced feedback inhibition of gastric function
Authors: Whited K. L. , Thao D. , Lloyd K. C. Kent , Kopin A. S. , Raybould H. E.
Published: March 2006

Cholecystokinin (CCK), acting at CCK1 receptors (CCK1Rs) on intestinal vagal afferent terminals, has been implicated in the control of gastrointestinal function and food intake. Using CCK1R−/− mice, we tested the hypothesis that lipid-induced activation of the vagal afferent pathway and intestinal feedback of gastric function is CCK1R dependent. In anesthetized CCK1R+/+ (“wild type”) mice, meal-stimulated gastric acid secretion was inhibited by intestinal lipid infusion; this was abolished in CCK1R−/− mice. Gastric emptying of whole egg, measured by nuclear scintigraphy in awake mice, was significantly faster in CCK1R−/− than CCK1R+/+ mice. Gastric emptying of chow was significantly slowed in response to administration of CCK-8 (22 pmol) in CCK1R+/+ but not CCK1R−/− mice. Activation of the vagal afferent pathway was measured by immunohistochemical localization of Fos protein in the nucleus of the solitary tract (NTS; a region where vagal afferents terminate). CCK-8 (22 pmol ip) increased neuronal Fos expression in the NTS of fasted CCK1R+/+ mice; CCK-induced Fos expression was reduced by 97% in CCK1R−/− compared with CCK1R+/+ mice. Intralipid (0.2 ml of 20% Intralipid and 0.04 g lipid), but not saline, gavage increased Fos expression in the NTS of fasted CCK1R+/+ mice; lipid-induced Fos expression was decreased by 47% in CCK1R−/− compared with CCK1R+/+mice. We conclude that intestinal lipid activates the vagal afferent pathway, decreases gastric acid secretion, and delays gastric emptying via a CCK1R-dependent mechanism. Thus, despite a relatively normal phenotype, intestinal feedback in response to lipid is severely impaired in these mice.
Mesangial cells initiate compensatory renal tubular hypertrophy via IL-10-induced TGF-β secretion: effect of the immunomodulator AS101 on this process
Authors: Sinuani Inna , Averbukh Zhan , Gitelman Inna , Rapoport Micha J. , Sandbank Judit , Albeck Michael , Sredni Benjamin , Weissgarten Joshua
Published: March 2006

The present study investigated the role of IL-10 produced by the mesangial cells in postnephrectomy compensatory renal growth and the effect of the immunomodulator AS101 on this process. One hundred forty unilateral nephrectomized and sham-operated male Sprague-Dawley rats were treated by AS101 or PBS before and after surgery. The results show that secretion of IL-10 and TGF-β by mesangial cells isolated from the remaining kidneys was increased significantly, compared with those of control and sham animals. Moreover, TGF-β secretion by mesangial cells was increased after the addition of exogenous recombinant IL-10 and inhibited in the presence of neutralizing anti-IL-10 antibodies. In vivo, compensatory growth of the remaining kidneys was associated with significant increase in IL-10 content in renal tissues and plasma. Immunohistochemical studies show that IL-10 was produced by mesangial cells. Elevated IL-10 levels were followed by the rise in TGF-β content in plasma and renal tissue. AS101 treatment decreased IL-10 and TGF-β expression in plasma and kidney tissues and results in 25% reduction in the fresh and fractional kidney weight and decreased hypertrophy of tubular cells (protein/DNA ratio, morphometric analysis). Taken together, these data demonstrate that TGF-β production by mesangial cells is IL-10 dependent. Mesangial cells are the major source of IL-10 in kidneys. AS101, by inhibiting the activity of IL-10, decreases TGF-β production by mesangial cells, thus limiting compensatory tubular cell hypertrophy.
Somatostatin Presynaptically Inhibits Both GABA and Glutamate Release Onto Rat Basal Forebrain Cholinergic Neurons
Authors: Momiyama Toshihiko , Zaborszky Laszlo
Published: March 2006

A whole cell patch-clamp study was carried out in slices obtained from young rat brain to elucidate the roles of somatostatin in the modulation of synaptic transmission onto cholinergic neurons in the basal forebrain (BF), a region that contains cholinergic and GABAergic corticopetal neurons and somatostatin (SS)-containing local circuit neurons. Cholinergic neurons within the BF were identified by in vivo prelabeling with Cy3 IgG. Because in many cases SS is contained in GABAergic neurons in the CNS, we investigated whether exogenously applied SS can influence GABAergic transmission onto cholinergic neurons. Bath application of somatostatin (1 μM) reduced the amplitude of the evoked GABAergic inhibitory presynaptic currents (IPSCs) in cholinergic neurons. SS also reduced the frequency of miniature IPSCs (mIPSCs) without affecting their amplitude distribution. SS-induced effect on the mIPSC frequency was significantly larger in the solution containing 7.2 mM Ca2+ than in the standard (2.4 mM Ca2+) external solution. Similar effects were observed in the case of non-NMDA glutamatergic excitatory postsynaptic currents (EPSCs). SS inhibited the amplitude of evoked EPSCs and reduced the frequency of miniature EPSCs dependent on the external Ca2+ concentration with no effect on their amplitude distribution. Pharmacological analyses using SS-receptor subtype–specific drugs suggest that SS-induced action of the IPSCs is mediated mostly by the sst2 subtype, whereas sst subtypes mediating SS-induced inhibition of EPSCs are mainly sst1 or sst4. These findings suggest that SS presynaptically inhibits both GABA and glutamate release onto BF cholinergic neurons in a Ca2+-dependent way, and that SS-induced effect on IPSCs and EPSCs are mediated by different sst subtypes.
ET-1 Lys198Asn and ETA Receptor H323H Polymorphisms in Heart Failure
Authors: Colombo Maria Giovanna , Ciofini Enrica , Paradossi Umberto , Bevilacqua Stefano , Biagini Andrea
Published: March 2006

Background: The endothelin (ET) system plays a central role in the control of myocardial function and its pathophysiology. The aim of the present study was to explore whether genetic variations of ET-1 (G/T substitution that predicts an Lys/Asn change at codon 198) and its receptor ETA (T/C in exon 6, H323H) could predispose carriers to heart failure (HF). Methods: Genotyping at these two loci was done in 122 patients with HF [echocardiographic left ventricular ejection fraction (LVEF) ≤40%] and 216 age-matched subjects without HF. Causes of HF included ischemic (n = 96) and idiopathic cardiomyopathies (n = 26). Results: The ET-1 Lys198Asn was significantly associated with the occurrence of HF (p = 0.005). The risk of HF was independently increased among Asn/Asn in comparison to Lys carriers (OR = 3.2, p = 0.03). Moreover, homozygous carriers of both ET-1 and ETA variants showed a marked increase in the risk of HF (adjusted OR = 8.6, p = 0.005), displayed significantly lower LVEF (p = 0.002) and higher left ventricular end-diastolic (p = 0.03) and end-systolic diameters (p = 0.04; for Asn/Asn and TT vs. Lys and C carriers of the ET-1 and ETA polymorphisms, respectively). Furthermore, the extent of coronary artery disease (r = –0.62, p < 0.0001) and the Asn/Asn and TT double genotype (r = –0.30, p = 0.0001) were the only significant and independent predictors of LVEF by multivariate analysis. Conclusions: The ET-1 Lys198Asn and ETA receptor H323H polymorphisms seem to act synergistically to increase the risk of HF.
Medical and Ventilatory Treatment of Acute Heart Failure: New Insights
Authors: Hodt Anders , Steine Kjetil , Atar Dan
Published: March 2006

Background: The traditional medical treatment of acute heart failure (AHF) has remained unchanged for many years. It has been based on oxygen supplementation and mechanical ventilatory support as well as the administration of morphine, diuretics, nitrates and inotropic agents. In 2005 the European Society of Cardiology (ESC) published new guidelines on the diagnosis and treatment of AHF. Also, new therapies have been introduced recently, giving rise to changes in therapeutic concepts. Material/Method: Based on these new guidelines and recent studies selected from the literature we here describe the new ESC classification of AHF including its epidemiology and pathophysiology. We further present a state-of-the-art status of the choices of medical treatment for patients with acute decompensated heart failure and pulmonary edema. Results: Mechanical ventilatory support reduces the number of patients who require endotracheal intubation.Nitrates in dosages higher than employed today appear to be beneficiary to patients with pulmonary congestion, probably because of the pronounced afterload-reducing effect. Nesiritide, a synthetic brain natriuretic peptide, has shown better hemodynamic effects than common nitrate dosages in patients with congestive heart failure. Tezosentan, an endothelin antagonist, was tested in the biggest AHF trial ever, which, however, was terminated prematurely because it was futile to proceed given the endpoints dyspnea and death. The β1-adrenergic drug dobutamine and the phosphodiestherase inhibitor milrinone are associated with increased mortality in patients with pronounced chronic and acute congestive heart failure. Levosimendan, a new inotropic drug, has shown lower mortality compared to dobutamine in patients with acute congestive heart failure. Conclusion: New concepts have finally emerged, including the application of old drugs such as nitrates in new (i.e., higher) dosages, as well as the novel compound levosimendan, recommended for patients with AHF and hypoperfused organs. The new ESC classification of AHF provides a valuable and long-awaited guideline to diagnose and treat this severe condition.
Nanobacteria, HIV and Magic Bullets – Update of Perspectives 2005
Authors: Sommer Andrei P. , Milankovits Marton , Mester Adam R.
Published: March 2006

In 1997 a Finnish group speculated on the presence of nanobacteria in vaccines. In 2001, a report on the identification of nanobacteria in a number of vaccines attracted much attention. Experiments indicated that viable nanobacteria are excreted via urine. Their extreme survivability suggests that prior to discussing any possible contamination of vaccines, sources and routes of natural infection need to be examined. In view of 30,000,000 HIV infections in sub-Saharan Africa, the recently reported occurrence of nanobacteria in HIV-infected patients deserves concern. Clearly, it could indicate the origin of a giant reservoir and dissemination cycle. Here we discuss novel therapeutic strategies to prevent or reduce nanobacterial infection. In regard of the rapid progress in this field, we start with a brief introductory summary, and analyze possible implications.
BAY 41-2272, a Direct Activator of Soluble Guanylate Cyclase, Reduces Right Ventricular Hypertrophy and Prevents Pulmonary Vascular Remodeling during Chronic Hypoxia in Neonatal Rats
Authors: Deruelle Philippe , Balasubramaniam Vivek , Kunig Anette M. , Seedorf Gregory J. , Markham Neil E. , Abman Steven H.
Published: March 2006

Exposure to hypoxia during the first weeks of life in newborn rats decreases vascular growth and alveolarization and causes pulmonary hypertension (PH). BAY 41-2272 is a novel direct activator of soluble guanylate cyclase independent of nitric oxide, effective as an acute pulmonary vasodilator in an animal model of persistent pulmonary hypertension of the newborn, but whether prolonged BAY 41-2272 therapy is effective in the setting of chronic PH is unknown. We hypothesize that BAY 41-2272 would prevent PH induced by chronic exposure to neonatal hypoxia. At 2 days of age, newborn rats were randomly exposed to hypoxia (FiO2, 0.12) or room air, and received daily intramuscular treatment with BAY 41-2272 (1 mg/kg) or saline. After 2 weeks, rats were killed for assessment of right ventricular hypertrophy (RVH), wall thickness of small pulmonary arteries, vessels density, radial alveolar counts and mean linear intercepts. In comparison with control, hypoxia increased RVH and artery wall thickness, reduced vessels density, decreased radial alveolar counts and increased mean linear intercepts. In comparison with hypoxic controls, prolonged BAY 41-2272 treatment during chronic hypoxia reduced RVH (0.67 ± 0.03 vs. 0.52 ± 0.05; p < 0.05), and attenuated artery wall thickness (48.2 ± 2.8% vs. 35.7 ± 4.1 µm; p < 0.01). However, BAY 41-2272 did not change vessels density, radial alveolar counts or mean linear intercepts. We conclude that BAY 41-2272 prevents the vascular structural effects of PH and reduces RVH but does not protect from hypoxia-induced inhibition of alveolarization and vessel growth. We speculate that BAY 41-2272 may provide a new therapy for chronic PH.
Vesicular Trafficking of Tyrosine Kinase Receptors and Associated Proteins in the Regulation of Signaling and Vascular Function
Authors: Mukherjee Sanchita , Tessema Mathewos , Wandinger-Ness Angela
Published: March 2006

Receptor tyrosine kinases (RTKs) play a pivotal role in the development and function of the cardiovascular system. Ligand-activated RTKs promote numerous downstream signal transduction pathways that lead to vascular permeability, as well as proliferation, migration, and differentiation of vascular endothelia and smooth muscle cells. Ligand binding also promotes internalization of the activated receptors either to downregulate the signaling via degradation of the ligand/receptor complex or to signal from endosomes. However, the outcomes of receptor internalization via clathrin-dependent or caveolar pathways and trafficking mechanisms are incompletely clarified in vascular systems. Activity modulation through endocytosis and vesicular trafficking significantly impacts downstream targets of RTKs such as endothelial nitric oxide synthase (eNOS) and VE-cadherin. RTKs and their associated targets are also transported to the nucleus, where they may directly impact nuclear signaling. Although the nuclear transport pathways are just beginning to be unraveled, it appears that endocytosis and vesicular trafficking are involved. In this review, we discuss the mechanisms by which activated RTKs and the downstream targets eNOS and VE-cadherin may be internalized and transported to various intracellular compartments. How localization and interacting proteins impact protein function and influence signaling is an important theme, as is the potential for modulating signaling through therapeutic targeting of activated receptors and components of the endocytic machinery.
Clinical Stress Testing in the Pediatric Age Group
Authors: Paridon Stephen M. , Alpert Bruce S. , Boas Steven R. , Cabrera Marco E. , Caldarera Laura L. , Daniels Stephen R. , Kimball Thomas R. , Knilans Timothy K. , Nixon Patricia A. , Rhodes Jonathan , Yetman Angela T.
Published: March 2006

This statement is an updated report of the American Heart Association’s previous publications on exercise in children. In this statement, exercise laboratory requirements for environment, equipment, staffing, and procedures are presented. Indications and contraindications to stress testing are discussed, as are types of testing protocols and the use of pharmacological stress protocols. Current stress laboratory practices are reviewed on the basis of a survey of pediatric cardiology training programs.
Jesuit Pastoral Theater on an Urban Stage: Lisbon, 1588-1593
Authors: Brockey Liam
Published: March 2006

In the late sixteenth century, the Society of Jesus became one of the most influential religious groups in Catholic Europe and beyond. Yet specifically how the meteoric rise of the Jesuits occurred has remained an enigma, especially in light of the entrenched complex of interests that comprised contemporary society. Based on manuscript correspondence and other under-exploited archival material, this article analyzes the actions of senior members of this religious order in the city of Lisbon in late 1580s and early 1590s in order to show how the Society gained its prestige through a host of pastoral activities directed at a variety of audiences. By avoiding a focus on colleges or missions, this study offers a new perspective on the Jesuits' attempts to win their place among ecclesiastical elites, as well as the respect of both nobles and plebeians in one of the largest and most ethnically diverse cities in Europe.
Confronting Decline in Early Modern Arabic Thought
Authors: Matar Nabil
Published: March 2006

This article argues that Arabic thinkers of the seventeenth century failed to confront the problem of decline in their societies in the manner that Ottoman and Spanish writers did. Arabic writers, from Alexandria in Egypt to Miknas in Morocco, refused to concede decline and instead declared the nasr (victory) of their deen (religion) of Islam over Europe, or used Ibn Khaldun to determine the fall of the European dunya (world). Only the Moriscos, who had been exposed to the empiricism of European thought, believed that war technology—and manuals about it and about other technologies—was needed to bridge the gap between a modernizing Europe and a stagnant Islamic West.
Korea’s Global City
Authors: Shin Kyoung-ho , Timberlake Michael
Published: March 2006

Seoul, South Korea has risen remarkably in the global hierarchy of cities since the mid-1970s, and arguably it is now among an elite group of about 15 of the most globally central cities in the world. While it is increasingly the object of urban studies research, few efforts have specifically focused on linking social structural changes within the city to its increasingly intense participation in the global economy. The globalization and world cities perspective suggests that as cities achieve global prominence, they should experience certain social structural transformations, some of which are problematic, such as increasing polarization and marginalization. But critics of this view argue that the ‘globalizationists’ ignore the role of the state, which, to them, has a more profound influence over urban transformations. This article surveys some of the research and data on Seoul’s recent social transformation and compares these changes to the expectations of the globalization perspective and to the counter-argument that state policies are more important. We also discuss the likelihood that the Korean capital will improve or even maintain its prominence in the world-systems city system.
Statistically Equivalent Representative Volume Elements for Unidirectional Composite Microstructures: Part II - With Interfacial Debonding
Authors: Swaminathan Shriram , Ghosh Somnath
Published: March 2006

In this sequel to the study on microstructures without damage, methods for evaluating the statistically equivalent representative volume element (SERVE) are proposed for fiber-reinforced microstructures undergoing initiation and propagation of damage in the form of interfacial debonding. The microstructural analysis is executed using the Voronoi cell finite element model (VCFEM) in which the interface is modeled using a bilinear cohesive zone law. As introduced in the first article, a combination of statistical and computational tools is proposed to capture the evolving nature of the SERVE with increased loading. The effectiveness of alternative definitions and methods of characterizing the damaging microstructure is examined through numerical simulations.
Training, Morale and Modern War
Authors: Strachan Hew
Published: March 2006

Since 1945, theories of combat motivation have been shaped primarily by the argument that soldiers fight for their comrades. This emphasis on the primary group, advanced particularly by Americans, has been challenged from two directions. First, those who point to the heavy losses sustained in fighting on fronts such as the Russian in the second world war argue that ideology or ‘legitimate demand’ must play a role. Second, evidence from both world wars suggests that disciplinary systems also need to be taken into account. This article seeks to incorporate a fourth explanation, the function of realistic training, a point made by one of the most important post-1945 American books on combat motivation, S.L.A. Marshall’s Men Against Fire, but subsequently overlooked.