bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosomal loci that influence oral nicotine consumption in C57BL/6J × C3H/HeJ F2 intercross mice
Authors: Li X. C. , Karadsheh M. S. , Jenkins P. M. , Brooks J. C. , Drapeau J. A. , Shah M. S. , Lautner M. A. , Stitzel J. A.
Published: September 2006

Several studies have demonstrated that there are genetic influences on free‐choice oral nicotine consumption in mice. In order to establish the genetic architecture that underlies individual differences in free‐choice nicotine consumption, quantitative trait loci (QTL) mapping was used to identify chromosomal regions that influence free‐choice nicotine consumption in male and female F2 mice derived from a cross between C57BL/6J and C3H/HeJ mice. These two mouse strains were chosen not only because they differ significantly for oral nicotine consumption, but also because they are at or near phenotypic extremes for all measures of nicotine sensitivity that have been reported. A four‐bottle choice paradigm was used to assess nicotine consumption over an 8‐day period. The four bottles contained water or water supplemented with 25, 50 or 100 μg/ml of nicotine base. Using micrograms of nicotine consumed per milliliter of total fluid consumed per day as the nicotine consumption phenotype, four significant QTL were identified. The QTL with the largest LOD score was located on distal chromosome 1 (peak LOD score = 15.7). Other chromosomes with significant QTL include central chromosome 4 (peak LOD score = 4.1), proximal chromosome 7 (peak LOD score = 6.1) and distal chromosome 15 (peak LOD score = 4.8). These four QTL appear to be responsible for up to 62% of the phenotypic variance in oral nicotine consumption.
Eliciting Patient Treatment Preferences: A Strategy to Integrate Evidence‐Based and Patient‐Centered Care
Authors: Sidani Souraya , Epstein Dana , Miranda Joyal
Published: September 2006

Background: The integrated patient‐centered evidence‐based approach to care is integral to guide practice and enhance the quality of care. In this paper, a strategy to operationalize the integrated approach is described.

Description of strategy: The strategy flows from the processes used to synthesize the best available evidence for interventions that address a clinical problem, and to elicit patient preferences for treatment options, which is an important step in patient‐centered care. The strategy consists of three phases: (1) synthesis of evidence about the effectiveness and relevance of interventions derived from research and practice; (2) generation of written material describing the nature, dose, effectiveness, and risks associated with the evidence‐based interventions; and (3) using the written descriptions to elicit patient preferences. Examples from an ongoing study are presented to illustrate the implementation of the strategy within the context of research.

Implications: Nurses are invited to apply the strategy in practice and to evaluate its feasibility and utility in enhancing the quality of care.
Sympathoexcitatory response to peripheral chemoreflex activation is enhanced in juvenile rats exposed to chronic intermittent hypoxia
Authors: Braga Valdir A. , Soriano Renato N. , Machado Benedito H.
Published: September 2006

In the present study, we tested the hypothesis that chronic intermittent hypoxia (CIH) produces changes in the autonomic and respiratory responses to acute peripheral chemoreflex activation. To attain this goal, 3‐week‐old rats were exposed to 10 days of CIH (6% O2 for 40 s at 9 min intervals; 8 h day−1). They were then used to obtain a working heart–brainstem preparation and, using this unanaesthetized experimental preparation, the chemoreflex was activated with potassium cyanide (0.05%, injected via the perfusion system), and the thoracic sympathetic nerve activity (tSNA), heart rate and phrenic nerve discharge (PND) were recorded. Rats subjected to CIH (n= 12), when compared with control animals (n= 12), presented the following significant changes in response to chemoreflex activation: (a) an increase in tSNA (78 ± 4 versus 48 ± 3%); (b) a long‐lasting increase in the frequency of the PND at 20 (0.52 ± 0.03 versus 0.36 ± 0.03 Hz) and 30 s (0.40 ± 0.02 versus 0.31 ± 0.02 Hz) after the stimulus; and (c) a greater bradycardic response (−218 ± 20 versus−163 ± 16 beats min−1). These results indicate that the autonomic and respiratory responses to chemoreflex activation in juvenile rats previously submitted to CIH are greatly increased.
Enteric‐formulated lactoferrin was more effectively transported into blood circulation from gastrointestinal tract in adult rats
Authors: Takeuchi Takashi , Jyonotsuka Takahiro , Kamemori Nao , Kawano Genji , Shimizu Hirohiko , Ando Kunio , Harada Etsumori
Published: September 2006

We have previously demonstrated that intestinally infused bovine lactoferrin (bLF) is transported into the blood circulation via the lymphatic pathway, not via the portal circulation. Therefore, in the present study, we further investigated whether intragastrically infused enteric‐formulated bLF (EF‐bLF) was more efficiently absorbed than bLF from the intestine in adult rats. The rats were randomly divided into three groups: 30 and 300 mg kg−1 non‐enteric‐formulated bLF (non‐EF‐bLF) groups and a 30 mg kg−1 EF‐bLF group. Thoracic lymph was collected from a thoracic lymph duct under general anaesthesia. Bovine lactoferrin was infused into the stomach or duodenal lumen via a needle for a period of over 1 min in a volume of 1 ml kg−1. The bLF transported into the lymph was assayed quantitatively by double‐antibody enzyme‐linked immunosorbent assay (ELISA). Following the intragastric administration of bLF, the three groups showed almost the same lymph flow, but the bLF concentration in the lymph fluid in the EF‐bLF group increased significantly and peaked 3 h after administration. With intraduodenal administration, the bLF concentration in the lymph fluid of the higher non‐EF‐bLF group was significantly higher than those of the other groups. The amount of absorbed bLF in the EF‐bLF group was, however, about 10 times higher than that in the lower non‐EF‐bLF group, when it was administered intragastrically. These data show that enteric‐formulated bLF is less susceptible to gastric pepsin and is more efficiently absorbed from the intestine than is non‐enteric‐formulated bLF.
Alternative splicing of P2X6 receptors in developing mouse brain and during in vitro neuronal differentiation
Authors: Da Silva Rogério L. , Resende Rodrigo R. , Ulrich Henning
Published: September 2006

Adenosine triphosphate acts as a fast excitatory neurotransmitter by binding to and activating seven structurally related subtypes of purinergic P2X receptors, which act as ligand‐gated ion channels. Besides its role in neurotransmission, ATP also has trophic functions during development of the neuronal system. P2X receptor expression, mainly of P2X4 and P2X6 subtypes, has been detected in adult brain and also during neuronal development. We have used the mouse teratocarcinoma P19 cell line as an in vitro model to study P2X6 receptor expression during early neuronal differentiation. We have detected a full‐length and an alternatively spliced form of the mouse P2X6 receptor gene in P19 cells using reverse transcriptase‐polymerase chain reaction. The alternatively spliced form was already present at the stage of pluripotent undifferentiated P19 cells, and was predominant compared to the full‐length form during the whole course of neuronal differentiation of P19 cells. Alternative splicing of P2X6 receptor subunits was also confirmed during postnatal development of mouse brain. During postnatal development, however, the full‐length form was predominant compared to the spliced form. Alternative splicing is suggested to regulate P2X6 receptor function during neuronal differentiation.
Manually controlled human balancing using visual, vestibular and proprioceptive senses involves a common, low frequency neural process
Authors: Lakie Martin , Loram Ian D.
Published: September 2006

Ten subjects balanced their own body or a mechanically equivalent unstable inverted pendulum by hand, through a compliant spring linkage. Their balancing process was always characterized by repeated small reciprocating hand movements. These bias adjustments were an observable sign of intermittent alterations in neural output. On average, the adjustments occurred at intervals of ∼400 ms. To generate appropriate stabilizing bias adjustments, sensory information about body or load movement is needed. Subjects used visual, vestibular or proprioceptive sensation alone and in combination to perform the tasks. We first ask, is the time between adjustments (bias duration) sensory specific? Vision is associated with slow responses. Other senses involved with balance are known to be faster. Our second question is; does bias duration depend on sensory abundance? An appropriate bias adjustment cannot occur until unplanned motion is unambiguously perceived (a sensory threshold). The addition of more sensory data should therefore expedite action, decreasing the mean bias adjustment duration. Statistical analysis showed that (1) the mean bias adjustment duration was remarkably independent of the sensory modality and (2) the addition of one or two sensory modalities made a small, but significant, decrease in the mean bias adjustment duration. Thus, a threshold effect can alter only a very minor part of the bias duration. The bias adjustment duration in manual balancing must reflect something more than visual sensation and perceptual thresholds; our suggestion is that it is a common central motor planning process. We predict that similar processes may be identified in the control of standing.
Regional variations in the glial influence on synapse development in the mouse CNS
Authors: Steinmetz C. C. , Buard I. , Claudepierre T. , Nägler K. , Pfrieger F. W.
Published: September 2006

There is increasing evidence that synapse function depends on interactions with glial cells, namely astrocytes. Studies on specific neurons of the central nervous system (CNS) indicated that glial signals also control synapse development, but it remained unclear whether this is a general principle that applies to other neuronal cell types. To address this question, we developed new methods to immunoisolate neurons from different brain regions of postnatal mice and to culture them in a chemically defined medium. Electrophysiological recordings and immunocytochemical staining revealed vigorous synaptogenesis in hippocampal and cerebellar neurons, but not in retinal ganglion cells (RGCs) in the absence of glial cells. Co‐culture with glia promoted synapse formation in RGCs as indicated by a strong increase in the incidence and frequency of action potential‐independent miniature synaptic currents, but showed no such effects in hippocampal or cerebellar neurons. On the other hand, glial signals promoted the efficacy of excitatory synapses in all regions as indicated by an increase in the size of spontaneous synaptic events in cerebellar cultures and of miniature synaptic currents in hippocampal neurons and RGCs. Inhibitory synaptic currents remained largely unaffected by glia. Our results indicate that in the mammalian CNS, the way that glial signals promote the development of excitatory synapses depends on the type of neuron.
Evidence for Novel pH-Dependent Regulation of
Candida albicans
Rim101, a Direct Transcriptional Repressor of the Cell Wall β-Glycosidase Phr2
Authors: Baek Yong-Un , Martin Samuel J. , Davis Dana A.
Published: September 2006

Candida albicans
is a commensal fungus of mucosal surfaces that can cause disease in susceptible hosts. One aspect of the success of
C. albicans
as both a commensal and a pathogen is its ability to adapt to diverse environmental conditions, including dramatic variations in environmental pH. The response to a neutral-to-alkaline pH change is controlled by the Rim101 signal transduction pathway. In neutral-to-alkaline environments, the zinc finger transcription factor Rim101 is activated by the proteolytic removal of an inhibitory C-terminal domain. Upon activation, Rim101 acts to induce alkaline response gene expression and repress acidic response gene expression. Previously, recombinant Rim101 was shown to directly bind to the alkaline-pH-induced gene
PHR1
. Here, we demonstrate that endogenous Rim101 also directly binds to the alkaline-pH-repressed gene
PHR2
. Furthermore, we find that of the three putative binding sites, only the −124 site and, to a lesser extent, the −51 site play a role in vivo. In
C. albicans
, the predicted Rim101 binding site was thought to be CCAAGAA, divergent from the GCCAAG site defined in
Aspergillus nidulans
and
Saccharomyces cerevisiae
. Our results suggest that the Rim101 binding site in
C. albicans
is GCCAAGAA, but slight variations are tolerated in a context-dependent fashion. Finally, our data suggest that Rim101 activity is governed not only by proteolytic processing but also by an additional mechanism not previously described.
Evolutionary Origins of the Eukaryotic Shikimate Pathway: Gene Fusions, Horizontal Gene Transfer, and Endosymbiotic Replacements
Authors: Richards Thomas A. , Dacks Joel B. , Campbell Samantha A. , Blanchard Jeffrey L. , Foster Peter G. , McLeod Rima , Roberts Craig W.
Published: September 2006

Currently the shikimate pathway is reported as a metabolic feature of prokaryotes, ascomycete fungi, apicomplexans, and plants. The plant shikimate pathway enzymes have similarities to prokaryote homologues and are largely active in chloroplasts, suggesting ancestry from the plastid progenitor genome.Toxoplasma gondii, which also possesses an alga-derived plastid organelle, encodes a shikimate pathway with similarities to ascomycete genes, including a five-enzyme pentafunctionalarom. These data suggests that the shikimate pathway and the pentafunctionalaromeither had an ancient origin in the eukaryotes or was conveyed by eukaryote-to-eukaryote horizontal gene transfer (HGT). We expand sampling and analyses of the shikimate pathway genes to include the oomycetes, ciliates, diatoms, basidiomycetes, zygomycetes, and the green and red algae. Sequencing of cDNA fromTetrahymena thermophilaconfirmed the presence of a pentafusedarom, as in fungi andT. gondii. Phylogenies and taxon distribution suggest that thearomgene fusion event may be an ancient eukaryotic innovation. Conversely, the Plantae lineage (represented here by both Viridaeplantae and the red algae) acquired different prokaryotic genes for all seven steps of the shikimate pathway. Two of the phylogenies suggest a derivation of the Plantae genes from the cyanobacterial plastid progenitor genome, but if the full Plantae pathway was originally of cyanobacterial origin, then the five other shikimate pathway genes were obtained from a minimum of two other eubacterial genomes. Thus, the phylogenies demonstrate both separate HGTs and shared derived HGTs within the Plantae clade either by primary HGT transfer or secondarily via the plastid progenitor genome. The shared derived characters support the holophyly of the Plantae lineage and a single ancestral primary plastid endosymbiosis. Our analyses also pinpoints a minimum of 50 gene/domain loss events, demonstrating that loss and replacement events have been an important process in eukaryote genome evolution.
Saccharomyces cerevisiae
a
-Factor Mutants Reveal Residues Critical for Processing, Activity, and Export
Authors: Huyer Gregory , Kistler Amy , Nouvet Franklin J. , George Carolyn M. , Boyle Meredith L. , Michaelis Susan
Published: September 2006

The
Saccharomyces cerevisiae
mating pheromone
a
-factor
provides a paradigm for understanding the biogenesis of prenylated
fungal pheromones. The biogenesis of
a
-factor involves multiple
steps: (i) C-terminal CAAX modification (where C is cysteine, A is
aliphatic, and X is any residue) which includes prenylation,
proteolysis, and carboxymethylation (by Ram1p/Ram2p, Ste24p or Rce1p,
and Ste14p, respectively); (ii) N-terminal processing, involving two
sequential proteolytic cleavages (by Ste24p and Axl1p); and (iii)
nonclassical export (by Ste6p). Once exported, mature
a
-factor
interacts with the Ste3p receptor on
MATα
cells to
stimulate mating. The
a
-factor biogenesis machinery is well
defined, as is the CAAX motif that directs C-terminal modification;
however, very little is known about the sequence determinants within
a
-factor required for N-terminal processing, activity, and
export. Here we generated a large collection of
a
-factor mutants
and identified residues critical for the N-terminal processing steps
mediated by Ste24p and Axl1p. We also identified mutants that fail to
support mating but do not affect biogenesis or export, suggesting a
defective interaction with the Ste3p receptor. Mutants significantly
impaired in export were also found, providing evidence that the Ste6p
transporter recognizes sequence determinants as well as CAAX
modifications. We also performed a phenotypic analysis of the entire
set of isogenic
a
-factor biogenesis machinery mutants, which
revealed information about the dependency of biogenesis steps upon one
another, and demonstrated that export by Ste6p requires the completion
of all processing events. Overall, this comprehensive analysis will
provide a useful framework for the study of other fungal pheromones, as
well as prenylated metazoan proteins involved in development and
aging.
SYNCHRONIZING CHAOTIC ATTRACTORS OF CHUA'S CANONICAL CIRCUIT: THE CASE OF UNCERTAINTY IN CHAOS SYNCHRONIZATION
Authors: KYPRIANIDIS I. M. , BOGIATZI A. N. , PAPADOPOULOU M. , STOUBOULOS I. N. , BOGIATZIS G. N. , BOUNTIS T.
Published: September 2006

In this paper, we have studied the dynamics of two identical resistively coupled Chua's canonical circuits and have found that it is strongly affected by initial conditions, coupling strength and the presence of coexisting attractors. Depending on the coupling variable, chaotic synchronization has been observed both numerically and experimentally. Anti-phase synchronization has also been studied numerically clarifying some aspects of uncertainty in chaos synchronization.
UNSUPERVISED CLUSTERING USING FRACTAL DIMENSION
Authors: TASOULIS D. K. , VRAHATIS M. N.
Published: September 2006

Clustering can be defined as the process of "grouping" a collection of objects into subsets or clusters. The clustering problem has been addressed in numerous contexts and by researchers in different disciplines. This reflects its broad appeal and usefulness as an exploratory data analysis approach. Unsupervised clustering algorithms have been developed to address real world problems in which the number of clusters present in the dataset is unknown. These algorithms approximate the number of clusters while performing the clustering procedure. This paper is a first step towards the development of unsupervised clustering algorithms capable of identifying clusters within clusters. To this end, an unsupervised clustering algorithm is modified so as to take into consideration the fractal dimension of the data. The experimental results indicate that this approach can provide further qualitative information compared to the unsupervised clustering algorithm.
APPROACHES TO ADAPTIVE STOCHASTIC SEARCH BASED ON THE NONEXTENSIVE q-DISTRIBUTION
Authors: MAGOULAS GEORGE D. , ANASTASIADIS ARISTOKLIS
Published: September 2006

This paper explores the use of the nonextensive q-distribution in the context of adaptive stochastic searching. The proposed approach consists of generating the "probability" of moving from one point of the search space to another through a probability distribution characterized by the q entropic index of the nonextensive entropy. The potential benefits of this technique are investigated by incorporating it in two different adaptive search algorithmic models to create new modifications of the diffusion method and the particle swarm optimizer. The performance of the modified search algorithms is evaluated in a number of nonlinear optimization and neural network training benchmark problems.
(MULTI)FRACTALITY OF PHYSIOLOGICAL TIME-SERIES
Authors: KNEŽEVIĆ ANDREA , MARTINIS MLADEN
Published: September 2006

This paper contains the application of fractal concept in analyzing heartbeat (RR interval) fluctuations measured under controlled physical activity for subjects with stable angina pectoris (SAP). Results that illustrate the separation ability of the nonlinear methods, such as the Hurst R/S method, the detrended fluctuation analysis, DFA, and the method of G-moments, in distinguishing healthy from SAP subjects in scaling parameter space are presented.
The Developmental, Physiological, Neural, and Genetical Causes and Consequences of Frequency-Dependent Selection in the Wild
Authors: Sinervo Barry , Calsbeek Ryan
Published: September 2006

We outline roles of frequency-dependent selection (FDS) in coadaptation and coevolutionary change. Coadaptation and coevolution occur because correlational selection (CS) and correlated evolution couple many traits. CS arises from causal interactions between traits expressed in two or more interactors, which invariably involve different traits (signalers-receivers). Thus, the causes of CS are due to FDS acting on trait interactions. Negative FDS, a rare advantage, is often coupled to positive FDS generating complex dynamics and FD cycles. Neural mechanisms of learning and perception create analogous routes by which traits are reinforced in cognitive and perceptual systems of interactors, substituting for positive FDS. FDS across all levels of biological organization is thus best understood as proximate causes that link interactors and shape genetic correlations within and among interactors on long timescales, or cognitive trait correlations within interactors on short timescales. We find rock-paper-scissors dynamics are common in nature.
Clinical phenotype and gene expression profile in Crohn's disease
Authors: Csillag Claudio , Nielsen Ole Haagen , Borup Rehannah , Nielsen Finn Cilius , Olsen Jørgen
Published: September 2006

The clinical course varies significantly among patients with Crohn's disease (CD). This study investigated whether gene expression profiles generated by DNA microarray technology might predict disease progression. Biopsies from the descending colon were obtained colonoscopically from 40 CD patients. Gene profiling analyses were performed using a Human Genome U133 Plus 2.0 GeneChip Array, and summarization into a single expression measure for each probe set was performed using the robust multiple array procedure. Principal component analysis demonstrated that three components explain two-thirds of the total variation. The most important parameters for the determination of the colonic gene expression patterns were the presence of disease (CD) and presence of inflammation. Superimposition of clinical phenotype data revealed a grouping of the samples from patients with stenosis toward negative values on the axis of the second principal component. The functional annotation analysis suggested that the expression of genes involved in intracellular transport and cytoskeletal organization might influence the development of stenosis. In conclusion, even though most variation in the colonic gene expression patterns is due to presence or absence of CD and inflammation status, the development of stenosis is a parameter that affects colonic gene expression to some extent.
Body temperature changes induced by huddling in breeding male emperor penguins
Authors: Gilbert Caroline , Maho Yvon Le , Perret Martine , Ancel André
Published: September 2006

Huddling is the key energy-saving mechanism for emperor penguins to endure their 4-mo incubation fast during the Antarctic winter, but the underlying physiological mechanisms of this energy saving have remained elusive. The question is whether their deep body (core) temperature may drop in association with energy sparing, taking into account that successful egg incubation requires a temperature of about 36°C and that ambient temperatures of up to 37.5°C may be reached within tight huddles. Using data loggers implanted into five unrestrained breeding males, we present here the first data on body temperature changes throughout the breeding cycle of emperor penguins, with particular emphasis on huddling bouts. During the pairing period, core temperature decreased progressively from 37.5 ± 0.4°C to 36.5 ± 0.3°C, associated with a significant temperature drop of 0.5 ± 0.3°C during huddling. In case of egg loss, body temperature continued to decrease to 35.5 ± 0.4°C, with a further 0.9°C decrease during huddling. By contrast, a constant core temperature of 36.9 ± 0.2°C was maintained during successful incubation, even during huddling, suggesting a trade-off between the demands for successful egg incubation and energy saving. However, such a limited drop in body temperature cannot explain the observed energy savings of breeding emperor penguins. Furthermore, we never observed any signs of hyperthermia in huddling birds that were exposed to ambient temperatures as high as above 35°C. We suggest that the energy savings of huddling birds is due to a metabolic depression, the extent of which depends on a reduction of body surface areas exposed to cold.
Effects of pulse lung inflation on chest wall expiratory motor activity
Authors: Romaniuk Jaroslaw R. , Dick Thomas E. , Kowalski Krzysztof E. , DiMarco Anthony F.
Published: September 2006

The effects of pulse lung inflation (LI) on expiratory muscle activity and phase duration (Te) were determined in anesthetized, spontaneously breathing dogs ( n = 20). A volume syringe was used to inflate the lungs at various times during the expiratory phase. The magnitude of lung volume was assessed by the corresponding change in airway pressure (Paw; range 2–20 cmH2O). Electromyographic (EMG) activities were recorded from both thoracic and abdominal muscles. Parasternal muscle EMG was used to record inspiratory activity. Expiratory activity was assessed from the triangularis sterni (TS), internal intercostal (IIC), and transversus abdominis (TA) muscles. Lung inflations <7 cmH2O consistently inhibited TS activity but had variable effects on TA and IIC activity and expiratory duration. Lung inflations resulting in Paw values >7 cmH2O, however, inhibited expiratory EMG activity of each of the expiratory muscles and lengthened Te in all animals. The responses of expiratory EMG and Te were directly related to the magnitude of the lung inflation. The inhibition of expiratory motor activity was independent of the timing of pulse lung inflation during the expiratory phase. The inhibitory effects of lung inflation were eliminated by bilateral vagotomy and could be reproduced by electrical stimulation of the vagus nerve. We conclude that pulse lung inflation resulting in Paw between 7 and 20 cmH2O produces a vagally mediated inhibition of expiratory muscle activity that is directly related to the magnitude of the inflation. Lower inflation pressures produce variable effects that are muscle specific.
Dependence of lung injury on surface tension during low-volume ventilation in normal open-chest rabbits
Authors: D’Angelo Edgardo , Pecchiari Matteo , Gentile Guendalina
Published: September 2006

To evaluate the role of pulmonary surfactant in the prevention of lung injury caused by mechanical ventilation (MV) at low end-expiratory volumes, lung mechanics and morphometry were assessed in three groups of eight normal, open-chest rabbits ventilated for 3–4 h at zero end-expiratory pressure (ZEEP) with physiological tidal volumes (Vt = 10 ml/kg). One group was left untreated ( group A); the other two received surfactant intratracheally ( group B) or aerosolized dioctylsodiumsulfosuccinate ( group C) before MV on ZEEP. Relative to initial MV on positive end-expiratory pressure (PEEP; 2.3 cmH2O), quasi-static elastance (Est) and airway (Rint) and viscoelastic resistance (Rvisc) increased on ZEEP in all groups. After restoration of PEEP, only Rint (124%) remained elevated in group A, only Est (36%) was significantly increased in group B, whereas in group C, Est, Rint, and Rvisc were all markedly augmented (274, 253, and 343%). In contrast, prolonged MV on PEEP had no effect on lung mechanics of eight open-chest rabbits ( group D). Lung edema developed in group C (wet-to-dry ratio = 7.1), but not in the other groups. Relative to group D, both groups A and C, but not B, showed histological indexes of bronchiolar injury, whereas all groups exhibited an increased number of polymorphonuclear leukocytes in alveolar septa, which was significantly greater in group C. In conclusion, administration of exogenous surfactant largely prevents the histological and functional damage of prolonged MV at low lung volumes, whereas surfactant dysfunction worsens the functional alterations, also because of edema formation and, possibly, increased inflammatory response.
Focal warming in the nucleus of the solitary tract prolongs the laryngeal chemoreflex in decerebrate piglets
Authors: Xia L. , Damon T. A. , Leiter J. C. , Bartlett D.
Published: September 2006

The laryngeal chemoreflex (LCR), elicited by a drop of water in the larynx, is exaggerated by mild hyperthermia (body temperature = 40–41°C) in neonatal piglets. We tested the hypothesis that thermal prolongation of the LCR results from heating the nucleus of the solitary tract (NTS), where laryngeal afferents first form synapses in the brain stem. Three- to 13-day-old piglets were decerebrated and vagotomized and studied without anesthesia while paralyzed and ventilated. Phrenic nerve activity and rectal temperature were recorded. A thermode was placed in the medulla, and the brain tissue temperature was recorded with a thermistor ∼1 mm from the tip of the thermode. When the thermode was inserted into the brain stem, respiratory activity was arrested or greatly distorted in eight animals. However, the thermode was inserted in nine animals without disrupting respiratory activity, and in these animals, warming the medullary thermode (thermistor temperature = 40–41°C) while holding rectal temperature constant reversibly exaggerated the LCR. The caudal raphé was warmed focally by ∼2°C in four additional animals; this did not alter the duration of the LCR in these animals. Thermodes placed in the NTS did not disrupt respiratory activity, but they did prolong the LCR when warmed. Thermodes that were placed deep to the NTS in the region of the nucleus ambiguus disrupted respiratory activity, which precluded any analysis of the LCR. We conclude that prolongation of the laryngeal chemoreflex by whole body hyperthermia originates from the elevation of brain tissue temperature within in the NTS.
Evidence for the Presence of Histamine Uptake into the Synaptosomes of Rat Brain
Authors: Sakurai Eiko , Sakurai Eiichi , Oreland L. , Nishiyama S. , Kato M. , Watanabe T. , Yanai K.
Published: September 2006

Histamine has many physiological roles in the brain and periphery. Neuronal histamine is metabolized almost exclusively by histamine N-methyltransferase. Although several neurotransmitter systems such as dopamine and 5-hydroxytryptamine have their specific reuptake system in their neurons and glial cells, a specific histamine reuptake system into the corresponding nerve terminals or glial cells has not yet been clearly elucidated. We characterized the uptake of histamine into the P2 fractions of rat brain homogenized in 0.32 mol/l sucrose using in vitro uptake techniques. [3H]histamine uptake increased with the increment of added protein amount and elapsed time. [3H]histamine uptake was also temperature-dependent. The uptake of [3H]histamine into the P2 fractions occurs by two saturable processes, a high-affinity and a low-affinity, characterized by Km values of 0.16 and 1.2 µmol/l, respectively. Na+, Cl– and HCO3– ions were essential for the uptake of histamine in P2 fractions. [3H]histamine uptake was inhibited in the presence of several tricyclic antidepressants. In accordance with this, the endogenous release of histamine from brain slices evoked by 100 mmol/l K+ was augmented in the presence of 20 µmol/l imipramine. These results further support the existence of a specific histamine uptake system in the brain, although the precise molecular entities have not been identified until now.
Different Effects of Growth Factors on Human Renal Early Distal Tubular Cells in vitro
Authors: Baer Patrick C. , Geiger Helmut
Published: September 2006

Background: In the kidney, recovery from tubular damage requires regenerative mechanisms leading to re-epithelialization of the injured tubules. Current evidence supports the para- or autocrine role of growth factors in repair and regeneration of ischemic or nephrotoxic experimental acute renal failure. Methods: We evaluated the effects of EGF, HGF, IGF-1, and bFGF on human renal thick ascending limb and distal convoluted cells (TALDC) in vitro. TALDC were isolated by immunomagnetic separation and cultured. Signal transduction of the growth factors was evaluated by Western blot of ERK1/2 MAP-K phosphorylation. Cell proliferation was measured by MTT assay and a fluorometric assay. Results: A significant, dose- and time-dependent phosphorylation of ERK1/2 could be detected exclusively after stimulation with EGF. No other growth factor induced a significant MAPK phosphorylation. In the same manner, proliferation assays showed a significant growth-promoting effect of EGF. Neither HGF, nor IGF-1 or bFGF showed a stimulative effect on TALDC proliferation. Conclusion: The present study highlights the effects of growth factors on cultured TALDC and supports the hypothesis that in vivo EGF plays a para- or autocrine role during renal repair mechanisms.
Sphingosine-1 Phosphate Prevents Monocyte/Endothelial Interactions in Type 1 Diabetic NOD Mice Through Activation of the S1P1 Receptor
Authors: Whetzel Angela M. , Bolick David T. , Srinivasan Suseela , Macdonald Timothy L. , Morris Margaret A. , Ley Klaus , Hedrick Catherine C.
Published: September 2006

Monocyte recruitment and adhesion to vascular endothelium are key early events in atherosclerosis. We examined the role of sphingosine-1-phosphate (S1P) on modulating monocyte/endothelial interactions in the NOD/LtJ (NOD) mouse model of type 1 diabetes. Aortas from nondiabetic and diabetic NOD mice were incubated in the absence or presence of 100 nmol/L S1P. Fluorescently labeled monocytes were incubated with the aortas. Aortas from NOD diabetic mice bound 7-fold more monocytes than nondiabetic littermates (10±1 monocytes bound/field for nondiabetic mice vs 74±12 monocytes bound/field for diabetic mice,
P
<0.0001). Incubation of diabetic aortas with 100 nmol/L S1P reduced monocyte adhesion to endothelium by 90%. We found expression of S1P1, S1P2, and S1P3 receptors on NOD aortic endothelial cells. The S1P1 receptor-specific agonist SEW2871 inhibited monocyte adhesion to diabetic aortas. Studies in diabetic S1P3-deficient mice revealed that the S1P3 receptor did not play a pivotal role in this process. S1P reduced endothelial VCAM-1 induction in type 1 diabetic NOD mice, most likely through inhibition of nuclear factor κB translocation to the nucleus. Thus, S1P activation of the S1P1 receptor functions in an antiinflammatory manner in type 1 diabetic vascular endothelium to prevent monocyte/endothelial interactions. S1P may play an important role in the prevention of vascular complications of type 1 diabetes.
Mitochondrial PKCε and Mitochondrial ATP-Sensitive K
+
Channel Copurify and Coreconstitute to Form a Functioning Signaling Module in Proteoliposomes
Authors: Jabůrek Martin , Costa Alexandre D.T. , Burton Jana R. , Costa Cinthia L. , Garlid Keith D.
Published: September 2006

Mitochondria are key mediators of the cardioprotective signal and the mitochondrial ATP-sensitive K
+
channel (mitoK
ATP
) plays a crucial role in originating and transmitting that signal. Recently, protein kinase C ε (PKCε) has been identified as a component of the mitoK
ATP
signaling cascade. We hypothesized that PKCε and mitoK
ATP
interact directly to form functional signaling modules in the inner mitochondria membrane. To examine this possibility, we studied K
+
flux in liposomes containing partially purified mitoK
ATP
. The reconstituted proteins were obtained after detergent extraction of isolated mitochondria, 200-fold purification by ion exchange chromatography, and reconstitution into lipid vesicles. Immunoblot analysis revealed the presence of PKCε in the reconstitutively active fraction. Addition of the PKC activators 12-phorbol 13-myristate acetate, hydrogen peroxide, and the specific PKCε peptide agonist, ψεRACK, each activated mitoK
ATP
-dependent K
+
flux in the reconstituted system. This effect of PKCε was prevented by chelerythrine, by the specific PKCε peptide antagonist, εV
1-2
, and by the specific mitoK
ATP
inhibitor 5-hydroxydecanoate. In addition, the activating effect of PKC agonists was reversed by exogenous protein phosphatase 2A. These results demonstrate persistent, functional association of mitochondrial PKCε and mitoK
ATP
.
Association of Serial Biochemical Markers With Acute Ischemic Stroke
Authors: Jauch Edward C. , Lindsell Christopher , Broderick Joseph , Fagan Susan C. , Tilley Barbara C. , Levine Steven R.
Published: September 2006

Background and Purpose—

Biochemical markers of acute neuronal injury may aid in the diagnosis and management of acute ischemic stroke. Serum samples from the National Institute for Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen activator Stroke Study were analyzed for the presence of 4 biochemical markers of neuronal, glial, and endothelial cell injury. These biochemical markers, myelin basic protein (MBP), neuron-specific enolase (NSE), S100β, and soluble thrombomodulin, were studied for an association with initial stroke severity, infarct volume, and functional outcome.

Methods—

In the original NINDS study, serum samples were drawn from all patients on presentation to the Emergency Department and at ≈2 and 24 hours after initiation of study therapy. In this analysis, stored serum samples were available for 359 patients; 107 patients had samples for all 3 time points. Serum marker concentrations were measured by ELISA techniques. We examined the relation between serum concentrations of each marker and the degree of baseline neurological deficit, functional outcome, and infarct size on computed tomography at 24 hours and the effect of fibrinolytic therapy.

Results—

Higher 24-hour peak concentrations of MBP, NSE, and S100β were associated with higher National Institutes of Health Stroke Scale baseline scores (
r
=0.186,
P
<0.0001;
r
=0.117,
P
=0.032; and
r
=0.263,
P
<0.0001, respectively). Higher peak concentrations of MBP and S100β (
r
=0.209,
P
<0.0001;
r
=0.239,
P
<0.0001) were associated with larger computed tomography lesion volumes. Patients with favorable outcomes had smaller changes in MBP and S100β (
P
<0.05) concentrations in the first 24 hours. Soluble thrombomodulin was not associated with any severity or outcome measure.

Conclusions—

This study corroborates previous work demonstrating correlations of MBP, NSE, and S100β with clinical and radiographic features in acute stroke. Despite significantly better outcomes in the tissue plasminogen activator–treated group, we found no difference in the early release of the 4 biomarkers between treatment groups. Further study will define the role of biomarkers in acute stroke management and prognostication.
Safety, Feasibility, and Short-Term Follow-Up of Drug-Eluting Stent Placement in the Intracranial and Extracranial Circulation
Authors: Gupta Rishi , Al-Ali Firas , Thomas Ajith J. , Horowitz Michael B. , Barrow Thomas , Vora Nirav A. , Uchino Ken , Hammer Maxim D. , Wechsler Lawerence R. , Jovin Tudor G.
Published: September 2006

Background and Purpose—

The use of bare metal stents to treat symptomatic intracranial stenosis may be associated with significant restenosis rates. The advent of drug-eluting stents (DESs) in the coronary circulation has resulted in a reduction of restenosis rates. We report our technical success rate and short-term restenosis rates after stenting with DESs in the intracranial and extracranial circulation.

Methods—

This study was a retrospective review of the period between April 1, 2004, and April 15, 2006, of 59 patients with 62 symptomatic intracranial or extracranial atherosclerotic lesions at 2 medical centers (University of Pittsburgh and Borgess Medical Center).

Results—

The mean age of our cohort was 61±12 years. The location of the 62 lesions was as follows: extracranial vertebral artery 31 (50%), intracranial vertebral artery or basilar artery 18 (29%), extracranial internal carotid artery (ICA) near the petrous bone 5 (8%), and intracranial ICA 8 (13%). There were 2 (3%) periprocedural complications: 1 non—flow-limiting dissection and 1 disabling stroke. Fifty vessels were available for follow-up angiography or computed tomography angiography at a median time of 4.0±2 months. A total of 2 of 36 extracranial stents (7%) and 1 of 26 intracranial stents (5%) were found to have restenosis ≥50% at follow-up.

Conclusions—

This report demonstrates that DES delivery in the intracranial and extracranial circulation is technically feasible. A small percentage of patients developed short-term in-stent restenosis. Longer-term follow-up is required in the setting of a prospective study to determine the late restenosis rates for DESs in comparison with bare metal stents.
Defining the Diaspora: Appalachians in the Great Migration
Authors: Alexander J. Trent
Published: September 2006

New scholarship on southern white out-migration challenges long-held views regarding the economic difficulties experienced by Appalachian white migrants in the North. A comparison of the experiences of Appalachian white migrants and other southern white migrants during a forty-year period, using the Integrated Public Use Microdata Series files (IPUMS), shows that Appalachian migrants were significantly more impoverished than were other southern white migrants. As recent research suggests, migrants from the non-Appalachian South made a smooth economic transition, but migrants from the southern Appalachian region were nearly as impoverished as southern African-American migrants and international immigrants from the poorest developing countries. For these groups, the economic transition was a slow and difficult process.
The Massacres of Ottoman Armenians and the Writing of Ottoman History
Authors: Quataert Donald
Published: September 2006

Little of the writing about the massacres of Armenians, which occurred in 1915, not long before the Ottoman Empire's demise, has utilized Ottoman-language materials. Yet, Ottomanists have a responsibility to research these events and their origins to promote a more complete understanding of them. Providing explanations of the violence that states organize against their own subjects and citizens should be the task of historians able to read the documentary record of the states concerned.
An Investigation of Collective Human Behavior in Large-Scale Mixed Reality Spaces
Authors: Eng Kynan , Mintz Matti , Delbrück Tobi , Douglas Rodney J , Whatley Adrian M , Manzolli Jônatas , Verschure Paul F. M. J
Published: September 2006

Future mixed reality systems will need to support large numbers of simultaneous, nonexpert users at reasonable per-user costs if the systems are to be widely deployed within society in the short to medium term. We have constructed a prototype of such a system, an interactive entertainment space called Ada that was designed to behave like a simple organism. Using Ada we conducted two studies: the first assessing the effect of varying the operating parameters of the space on the collective behavior and attitudes of its users, and the second assessing the relationships among user demographics, behavior, and attitudes. Our results showed that small changes in the ambient settings of the environment have a significant effect on both user attitudes and behavior, and that the changes in user attitudes do not necessarily correspond to the environmental changes. We also found that individual user opinions are affected by demographics and reflected in overt behavior. Using these results, we propose some tentative guidelines for the design of future shared mixed reality spaces.
The Impact of Military Lifestyle Demands on Well-Being, Army, and Family Outcomes
Authors: Burrell Lolita M. , Adams Gary A. , Durand Doris Briley , Castro Carl Andrew
Published: September 2006

Adopting M. Segal’s framework, we focused on examining four military lifestyle demands—(1) risk of service member injury or death, (2) frequent relocations, (3) periodic separations, and (4) foreign residence—and their relationships to psychological and physical well-being, satisfaction with the Army, and marital satisfaction. Questionnaire results from 346 spouses living overseas indicated that the impact of separations was negatively related to all four outcomes, while foreign residence was negatively related to physical and psychological well-being, fear for soldier safety was negatively related to physical well-being, and the impact of moving was negatively related to satisfaction with the Army. The results further indicated that perceptions of moving and separations were more important in determining outcomes than were the actual number of moves or separations.
Appraisal Antecedents of Shame and Guilt: Support for a Theoretical Model
Authors: Tracy Jessica L. , Robins Richard W.
Published: September 2006

Four studies used experimental and correlational methods to test predictions about the antecedents of shame and guilt derived from an appraisal-based model of self-conscious emotions (Tracy & Robins, 2004). Results were consistent with the predicted relations between appraisals (i.e., causal attributions) and emotions. Specifically, (a) internal attributions were positively related to both shame and guilt; (b) the chronic tendency to make external attributions was positively related to the tendency to experience shame; and (c) internal, stable, uncontrollable attributions for failure were positively related to shame, whereas internal, unstable, controllable attributions for failure were positively related to guilt. Emotions and attributions were assessed using a variety of methods, so converging results across studies indicate the robustness of the findings and provide support for the theoretical model.
Governmental Context Determines Institutional Value: Independently Certified Performance and Failure in the Spanish Newspaper Industry
Authors: Núñez-Nickel Manuel , Gutiérrez Isabel , Carmona Salvador
Published: September 2006

Many societies demand that independent professionals (e.g. auditors) certify the performance of firms. The value placed on such certification (i.e. the public perception of reliability/unreliability that may impact on an organization's success/failure) is not uniform, however, but contingent upon changing political contexts. This study presents and analyses data on the entire population of newspapers in Spain from 1966 to 1993, a time of peaceful transition from military dictatorship to capitalist democracy. Our results highlight the contingent nature of institutional life, demonstrating how changes in political contexts are associated with varying understandings of institutions. In particular, our findings support the prediction that, under a dictatorship, independently certified performance is not instrumental in organizational success or failure whereas, in a modern democracy, the certification process has a positive effect on the survival chances of firms.