bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia, not pulmonary vascular pressure, induces blood flow through intrapulmonary arteriovenous anastomoses
Authors: Tremblay Joshua C. , Lovering Andrew T. , Ainslie Philip N. , Stembridge Mike , Burgess Keith R. , Bakker Akke , Donnelly Joseph , Lucas Samuel J.E. , Lewis Nia C.S. , Dominelli Paolo B. , Henderson William R. , Dominelli Giulio S. , Sheel A. William , Foster Glen E. 
Published: November 2014

Key points
Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) is increased by acute hypoxia during rest by unknown mechanisms.
Oral administration of acetazolamide blunts the pulmonary vascular pressure response to acute hypoxia, thus permitting the observation of IPAVA blood flow with minimal pulmonary pressure change.
Hypoxic pulmonary vasoconstriction was attenuated in humans following acetazolamide administration and partially restored with bicarbonate infusion, indicating that the effects of acetazolamide on hypoxic pulmonary vasoconstriction may involve an interaction between arterial pH and .
We observed that IPAVA blood flow during hypoxia was similar before and after acetazolamide administration, even after acid–base status correction, indicating that pulmonary pressure, pH and are unlikely regulators of IPAVA blood flow.
AbstractBlood flow through intrapulmonary arteriovenous anastomoses (IPAVA) is increased with exposure to acute hypoxia and has been associated with pulmonary artery systolic pressure (PASP). We aimed to determine the direct relationship between blood flow through IPAVA and PASP in 10 participants with no detectable intracardiac shunt by comparing: (1) isocapnic hypoxia (control); (2) isocapnic hypoxia with oral administration of acetazolamide (AZ; 250 mg, three times a day for 48 h) to prevent increases in PASP; and (3) isocapnic hypoxia with AZ and 8.4% NaHCO3 infusion (AZ + HCO3–) to control for AZ‐induced acidosis. Isocapnic hypoxia (20 min) was maintained by end‐tidal forcing, blood flow through IPAVA was determined by agitated saline contrast echocardiography and PASP was estimated by Doppler ultrasound. Arterial blood samples were collected at rest before each isocapnic–hypoxia condition to determine pH, [HCO3–] and . AZ decreased pH (–0.08 ± 0.01), [HCO3–] (−7.1 ± 0.7 mmol l−1) and (−4.5 ± 1.4 mmHg; P < 0.01), while intravenous NaHCO3 restored arterial blood gas parameters to control levels. Although PASP increased from baseline in all three hypoxic conditions (P < 0.05), a main effect of condition expressed an 11 ± 2% reduction in PASP from control (P < 0.001) following AZ administration while intravenous NaHCO3 partially restored the PASP response to isocapnic hypoxia. Blood flow through IPAVA increased during exposure to isocapnic hypoxia (P < 0.01) and was unrelated to PASP, cardiac output and pulmonary vascular resistance for all conditions. In conclusion, isocapnic hypoxia induces blood flow through IPAVA independent of changes in PASP and the influence of AZ on the PASP response to isocapnic hypoxia is dependent upon the H+ concentration or .
Inositol‐1,4,5‐trisphosphate induced Ca2+ release and excitation–contraction coupling in atrial myocytes from normal and failing hearts
Authors: Hohendanner Felix , Walther Stefanie , Maxwell Joshua T. , Kettlewell Sarah , Awad Sawsan , Smith Godfrey L. , Lonchyna Vassyl A. , Blatter Lothar A. 
Published: November 2014

Key points
Impaired calcium (Ca2+) signalling is the main contributor to depressed ventricular contractile function and occurrence of arrhythmia in heart failure (HF).
Here we report that in atrial cells of a rabbit HF model, Ca2+ signalling is enhanced and we identified the underlying cellular mechanisms. Enhanced Ca2+ transients (CaTs) are due to upregulation of inositol‐1,4,5‐trisphosphate receptor induced Ca2+ release (IICR) and decreased mitochondrial Ca2+ sequestration.
Enhanced IICR, however, together with an increased activity of the sodium–calcium exchange mechanism, also facilitates spontaneous Ca2+ release in form of arrhythmogenic Ca2+ waves and spontaneous action potentials, thus enhancing the arrhythmogenic potential of atrial cells.
Our data show that enhanced Ca2+ signalling in HF provides atrial cells with a mechanism to improve ventricular filling and to maintain cardiac output, but also increases the susceptibility to develop atrial arrhythmias facilitated by spontaneous Ca2+ release.
AbstractWe studied excitation–contraction coupling (ECC) and inositol‐1,4,5‐triphosphate (IP3)‐dependent Ca2+ release in normal and heart failure (HF) rabbit atrial cells. Left ventricular HF was induced by combined volume and pressure overload. In HF atrial myocytes diastolic [Ca2+]i was increased, action potential (AP)‐induced Ca2+ transients (CaTs) were larger in amplitude, primarily due to enhanced Ca2+ release from central non‐junctional sarcoplasmic reticulum (SR) and centripetal propagation of activation was accelerated, whereas HF ventricular CaTs were depressed. The larger CaTs were due to enhanced IP3 receptor‐induced Ca2+ release (IICR) and reduced mitochondrial Ca2+ buffering, consistent with a reduced mitochondrial density and Ca2+ uptake capacity in HF. Elementary IP3 receptor‐mediated Ca2+ release events (Ca2+ puffs) were more frequent in HF atrial myoctes and were detected more often in central regions of the non‐junctional SR compared to normal cells. HF cells had an overall higher frequency of spontaneous Ca2+ waves and a larger fraction of waves (termed arrhythmogenic Ca2+ waves) triggered APs and global CaTs. The higher propensity of arrhythmogenic Ca2+ waves resulted from the combined action of enhanced IICR and increased activity of sarcolemmal Na+–Ca2+ exchange depolarizing the cell membrane. In conclusion, the data support the hypothesis that in atrial myocytes from hearts with left ventricular failure, enhanced CaTs during ECC exert positive inotropic effects on atrial contractility which facilitates ventricular filling and contributes to maintaining cardiac output. However, HF atrial cells were also more susceptible to developing arrhythmogenic Ca2+ waves which might form the substrate for atrial rhythm disorders frequently encountered in HF.
PGC‐1α mediates a rapid, exercise‐induced downregulation of glycogenolysis in rat skeletal muscle
Authors: Kim Sang Hyun , Koh Jin Ho , Higashida Kazuhiko , Jung Su Ryun , Holloszy John O. , Han Dong‐Ho 
Published: November 2014

Key points
Long‐term endurance exercise training results in a reduction in the rates of muscle glycogen depletion and lactic acid accumulation during submaximal exercise; this adaptation is mediated by an increase in muscle mitochondria.
There is evidence suggesting that short‐term training induces adaptations that downregulate glycogenolysis before there is an increase in functional mitochondria.
We discovered that a single long bout of exercise induces decreases in expression of glycogenolytic and glycolytic enzymes in rat skeletal muscle; this adaptation results in slower rates of glycogenolysis and lactic acid accumulation in muscle during contractile activity.
Two additional days of training amplified the adaptive response, which appears to be mediated by PGC‐1α; this adaptation is biologically significant, because glycogen depletion and lactic acid accumulation are major causes of muscle fatigue.
AbstractEndurance exercise training can increase the ability to perform prolonged strenuous exercise. The major adaptation responsible for this increase in endurance is an increase in muscle mitochondria. This adaptation occurs too slowly to provide a survival advantage when there is a sudden change in environment that necessitates prolonged exercise. In the present study, we discovered another, more rapid adaptation, a downregulation of expression of the glycogenolytic and glycolytic enzymes in muscle that mediates a slowing of muscle glycogen depletion and lactic acid accumulation. This adaptation, which appears to be mediated by PGC‐1α, occurs in response to a single exercise bout and is further enhanced by two additional daily exercise bouts. It is biologically significant, because glycogen depletion and lactic acid accumulation are two of the major causes of muscle fatigue and exhaustion.
Stretch‐stimulated glucose transport in skeletal muscle is regulated by Rac1
Authors: Sylow Lykke , Møller Lisbeth L. V. , Kleinert Maximilian , Richter Erik A. , Jensen Thomas E. 
Published: November 2014

Key points
Rac1 regulates stretch‐stimulated (i.e. mechanical stress) glucose transport in muscle.
Actin depolymerization decreases stretch‐induced glucose transport in skeletal muscle.
Rac1 is a required part of the mechanical stress‐component of the contraction‐stimulus to glucose transport in skeletal muscle.

AbstractAn alternative to the canonical insulin signalling pathway for glucose transport is muscle contraction/exercise. Mechanical stress is an integrated part of the muscle contraction/relaxation cycle, and passive stretch stimulates muscle glucose transport. However, the signalling mechanism regulating stretch‐stimulated glucose transport is not well understood. We recently reported that the actin cytoskeleton regulating GTPase, Rac1, was activated in mouse muscle in response to stretching. Rac1 is a regulator of contraction‐ and insulin‐stimulated glucose transport, however, its role in stretch‐stimulated glucose transport and signalling is unknown. We therefore investigated whether stretch‐induced glucose transport in skeletal muscle required Rac1 and the actin cytoskeleton. We used muscle‐specific inducible Rac1 knockout mice as well as pharmacological inhibitors of Rac1 and the actin cytoskeleton in isolated soleus and extensor digitorum longus muscles. In addition, the role of Rac1 in contraction‐stimulated glucose transport during conditions without mechanical load on the muscles was evaluated in loosely hanging muscles and muscles in which cross‐bridge formation was blocked by the myosin ATPase inhibitors BTS and Blebbistatin. Knockout as well as pharmacological inhibition of Rac1 reduced stretch‐stimulated glucose transport by 30–50% in soleus and extensor digitorum longus muscle. The actin depolymerizing agent latrunculin B similarly decreased glucose transport in response to stretching by 40–50%. Rac1 inhibition reduced contraction‐stimulated glucose transport by 30–40% in tension developing muscle but did not affect contraction‐stimulated glucose transport in muscles in which force development was prevented. Our findings suggest that Rac1 and the actin cytoskeleton regulate stretch‐stimulated glucose transport and that Rac1 is a required part of the mechanical stress‐component of the contraction‐stimulus to glucose transport in skeletal muscle.
Presynaptic and postsynaptic effects of local cathodal DC polarization within the spinal cord in anaesthetized animal preparations
Authors: Bolzoni F. , Jankowska E. 
Published: November 2014

Key points
Trans‐spinal DC stimulation affects both postsynaptic neurons and the presynaptic axons providing input to these neurons. In the present study, we show that intraspinally applied cathodal current replicates the effects of trans‐spinal direct current stimulation in deeply anaesthetized animals and affects spinal neurons both during the actual current application and during a post‐polarization period.
Presynaptic effects of local cathodal polarization were expressed in an increase in the excitability of skin afferents (in the dorsal horn) and group Ia afferents (in motor nuclei), both during and at least 30 min after DC application. However, although the postsynaptic facilitation (i.e. more effective) activation of motoneurons by stimuli applied in a motor nucleus was very potent during local DC application, it was only negligible once DC was discontinued.
The results suggest that the prolonged effects of cathodal polarization are primarily associated with changes in synaptic transmission.
AbstractThe present study aimed to compare presynaptic and postsynaptic actions of direct current polarization in the spinal cord, focusing on DC effects on primary afferents and motoneurons. To reduce the directly affected spinal cord region, a weak polarizing direct current (0.1–0.3 μA) was applied locally in deeply anaesthetized cats and rats; within the hindlimb motor nuclei in the caudal lumbar segments, or in the dorsal horn within the terminal projection area of low threshold skin afferents. Changes in the excitability of primary afferents activated by intraspinal stimuli (20–50 μA) were estimated using increases or decreases in compound action potentials recorded from the dorsal roots or peripheral nerves as their measure. Changes in the postsynaptic actions of the afferents were assessed from intracellularly recorded monosynaptic EPSPs in hindlimb motoneurons and monosynaptic extracellular field potentials (evoked by group Ia afferents in motor nuclei, or by low threshold cutaneous afferents in the dorsal horn). The excitability of motoneurons activated by intraspinal stimuli was assessed using intracellular records or motoneuronal discharges recorded from a ventral root or a muscle nerve. Cathodal polarization was found to affect motoneurons and afferents providing input to them to a different extent. The excitability of both was markedly increased during DC application, although post‐polarization facilitation was found to involve presynaptic afferents and some of their postsynaptic actions, but only negligibly motoneurons themselves. Taken together, these results indicate that long‐lasting post‐polarization facilitation of spinal activity induced by locally applied cathodal current primarily reflects the facilitation of synaptic transmission.
Measurement Systems for Cell Adhesive Forces
Authors: Zhou Dennis W. , García Andrés J. 
Published: November 2014

AbstractCell adhesion to the extracellular matrix (ECM) involves integrin receptor–ligand binding and clustering to form focal adhesion (FA) complexes, which mechanically link the cell’s cytoskeleton to the ECM and regulate fundamental cell signaling pathways. Although elucidation of the biochemical events in cell-matrix adhesive interactions is rapidly advancing, recent studies show that the forces underlying cell-matrix adhesive interactions are also critical to cell responses. Therefore, multiple measurement systems have been developed to quantify the spatial and temporal dynamics of cell adhesive forces, and these systems have identified how mechanical events influence cell phenotype and FA structure–function relationships under physiological and pathological settings. This review focuses on the development, methodology, and applications of measurement systems for probing (a) cell adhesion strength and (b) 2D and 3D cell traction forces.
Determination of the intrinsic energy dependence of LiF:Mg,Ti thermoluminescent dosimeters for 125I and 103Pd brachytherapy sources relative to 60Co
Authors: Reed J. L. , Rasmussen B. E. , Davis S. D. , Micka J. A. , Culberson W. S. , DeWerd L. A. 
Published: November 2014

Purpose:To determine the intrinsic energy dependence of LiF:Mg,Ti thermoluminescent dosimeters (TLD‐100) for 125I and 103Pd brachytherapy sources relative to 60Co.Methods:LiF:Mg,Ti TLDs were irradiated with low‐energy brachytherapy sources and with a 60Co teletherapy source. The brachytherapy sources measured were the Best 2301 125I seed, the OncoSeed 6711 125I seed, and the Best 2335 103Pd seed. The TLD light output per measured air‐kerma strength was determined for the brachytherapy source irradiations, and the TLD light output per air kerma was determined for the 60Co irradiations. Monte Carlo (MC) simulations were used to calculate the dose‐to‐TLD rate per air‐kerma strength for the brachytherapy source irradiations and the dose to TLD per air kerma for the 60Co irradiations. The measured and MC‐calculated results for all irradiations were used to determine the TLD intrinsic energy dependence for 125I and 103Pd relative to 60Co.Results:The relative TLD intrinsic energy dependences (relative to 60Co) and associated uncertainties (k = 1) were determined to be 0.883 ± 1.3%, 0.870 ± 1.4%, and 0.871 ± 1.5% for the Best 2301 seed, OncoSeed 6711 seed, and Best 2335 seed, respectively.Conclusions:The intrinsic energy dependence of TLD‐100 is dependent on photon energy, exhibiting changes of 13%–15% for 125I and 103Pd sources relative to 60Co. TLD measurements of absolute dose around 125I and 103Pd brachytherapy sources should explicitly account for the relative TLD intrinsic energy dependence in order to improve dosimetric accuracy.
Phage-Encoded Colanic Acid-Degrading Enzyme Permits Lytic Phage Infection of a Capsule-Forming Resistant Mutant Escherichia coli Strain
Authors: Kim Min Soo , Kim Young Deuk , Hong Sung Sik , Park Kwangseo , Ko Kwan Soo , Myung Heejoon 
Published: November 2014

ABSTRACT

In this study, we isolated a bacteriophage T7-resistant mutant strain of
Escherichia coli
(named S3) and then proceeded to characterize it. The mutant bacterial colonies appeared to be mucoid. Microarray analysis revealed that genes related to colanic acid production were upregulated in the mutant. Increases in colanic acid production by the mutant bacteria were observed when
l
-fucose was measured biochemically, and protective capsule formation was observed under an electron microscope. We found a point mutation in the
lon
gene promoter in S3, the mutant bacterium. Overproduction of colanic acid was observed in some phage-resistant mutant bacteria after infection with other bacteriophages, T4 and lambda. Colanic acid overproduction was also observed in clinical isolates of
E. coli
upon phage infection. The overproduction of colanic acid resulted in the inhibition of bacteriophage adsorption to the host. Biofilm formation initially decreased shortly after infection but eventually increased after 48 h of incubation due to the emergence of the mutant bacteria. Bacteriophage PBECO4 was shown to infect the colanic acid-overproducing mutant strains of
E. coli
. We confirmed that the gene product of open reading frame 547 (ORF547) of PBECO4 harbored colanic acid-degrading enzymatic (CAE) activity. Treatment of the T7-resistant bacteria with both T7 and PBECO4 or its purified enzyme (CAE) led to successful T7 infection. Biofilm formation decreased with the mixed infection, too. This procedure, using a phage cocktail different from those exploiting solely receptor differences, represents a novel strategy for overcoming phage resistance in mutant bacteria.
Adaptation Genomics of a Small-Colony Variant in a Pseudomonas chlororaphis 30-84 Biofilm
Authors: Wang Dongping , Dorosky Robert J. , Han Cliff S. , Lo Chien-chi , Dichosa Armand E. K. , Chain Patrick S. , Yu Jun Myoung , Pierson Leland S. , Pierson Elizabeth A. 
Published: November 2014

ABSTRACT

The rhizosphere-colonizing bacterium
Pseudomonas chlororaphis
30-84 is an effective biological control agent against take-all disease of wheat. In this study, we characterize a small-colony variant (SCV) isolated from a
P. chlororaphis
30-84 biofilm. The SCV exhibited pleiotropic phenotypes, including small cell size, slow growth and motility, low levels of phenazine production, and increased biofilm formation and resistance to antimicrobials. To better understand the genetic alterations underlying these phenotypes, RNA and whole-genome sequencing analyses were conducted comparing an SCV to the wild-type strain. Of the genome's 5,971 genes, transcriptomic profiling indicated that 1,098 (18.4%) have undergone substantial reprograming of gene expression in the SCV. Whole-genome sequence analysis revealed multiple alterations in the SCV, including mutations in
yfiR
(cyclic-di-GMP production),
fusA
(elongation factor), and
cyoE
(heme synthesis) and a 70-kb deletion. Genetic analysis revealed that the
yfiR
locus plays a major role in controlling SCV phenotypes, including colony size, growth, motility, and biofilm formation. Moreover, a point mutation in the
fusA
gene contributed to kanamycin resistance. Interestingly, the SCV can partially switch back to wild-type morphologies under specific conditions. Our data also support the idea that phenotypic switching in
P. chlororaphis
is not due to simple genetic reversions but may involve multiple secondary mutations. The emergence of these highly adherent and antibiotic-resistant SCVs within the biofilm might play key roles in
P. chlororaphis
natural persistence.
Alternative Fecal Indicators and Their Empirical Relationships with Enteric Viruses, Salmonella enterica, and Pseudomonas aeruginosa in Surface Waters of a Tropical Urban Catchment
Authors: Liang L. , Goh S. G. , Vergara G. G. R. V. , Fang H. M. , Rezaeinejad S. , Chang S. Y. , Bayen S. , Lee W. A. , Sobsey M. D. , Rose J. B. , Gin K. Y. H. 
Published: November 2014

ABSTRACT

The suitability of traditional microbial indicators (i.e.,
Escherichia coli
and enterococci) has been challenged due to the lack of correlation with pathogens and evidence of possible regrowth in the natural environment. In this study, the relationships between alternative microbial indicators of potential human fecal contamination (
Bacteroides thetaiotaomicron
,
Methanobrevibacter smithii
, human polyomaviruses [HPyVs], and F+ and somatic coliphages) and pathogens (
Salmonella
spp.,
Pseudomonas aeruginosa
, rotavirus, astrovirus, norovirus GI, norovirus GII, and adenovirus) were compared with those of traditional microbial indicators, as well as environmental parameters (temperature, conductivity, salinity, pH, dissolved oxygen, total organic carbon, total suspended solids, turbidity, total nitrogen, and total phosphorus). Water samples were collected from surface waters of urban catchments in Singapore.
Salmonella
and
P. aeruginosa
had significant positive correlations with most of the microbial indicators, especially
E. coli
and enterococci. Norovirus GII showed moderately strong positive correlations with most of the microbial indicators, except for HPyVs and coliphages. In general, high geometric means and significant correlations between human-specific markers and pathogens suggest the possibility of sewage contamination in some areas. The simultaneous detection of human-specific markers (i.e.,
B. thetaiotaomicron
,
M. smithii
, and HPyVs) with
E. coli
and enterococcus supports the likelihood of recent fecal contamination, since the human-specific markers are unable to regrow in natural surface waters. Multiple-linear-regression results further confirm that the inclusion of
M. smithii
and HPyVs, together with traditional indicators, would better predict the occurrence of pathogens. Further study is needed to determine the applicability of such models to different geographical locations and environmental conditions.