bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presence and axonal transport of cholinoceptor, but not adrenoceptor sites on a cat noradrenergic neurone
Authors: Alonso F. G. , Ceña V. , García A. G. , Kirpekar S. M. , Sánchez‐García P. 
Published: December 2014

1. Noradrenaline release and radioligand binding studies were carried out in the cat hypogastric nerve ligated in vito 2 cm distal to the inferior mesenteric ganglion for different time periods, and in different effector organs.2. Large quantities of noradrenaline and dopamine β‐hydroxylase (DBH) accumulated in the segments of nerve immediately proximal (P1) and distal (D1) to the ligation, with rates of about 100 and 25 mm/24 hr for the orthograde and retrograde transport, respectively.3. Nicotine evoked the release of noradrenaline from P1 and atrial slices; the secretory response to nicotine was completely antagonized by mecamylamine. [3H]α‐bungarotoxin biding to membranes from P1 allowed the estimation of a KD of 2·97 n
m and a Bmax of 1639 f‐mole/mg protein.4. Acetylcholine inhibited the release of endogenous noradrenaline evoked by high K+ stimulation in atrial slices, but not in P1 segments. Similarly, carbachol decreased [3H]noradrenaline release induced by electrical stimulation (twenty‐six shocks, 2 Hz, 5 msec) in the atrium but not in P1.5. [3H]Quinuclydinilbenzylate ([3H]QNB) specifically binds to membranes from P1 and vas deferens, following a saturation curve. In the case of P1 segments taken 48 hr after ligation a KD of 0·35 n
m and a Bmax of 129 f‐mole/mg protein were found.6. The fact that the Bmax in P1 and D1 increased with the time of ligation suggests that orthograde and retrograde axonal transports of muscarinic binding sites exist in this nerve, with approximate rates of transport of 15 and 8 mm/24 hr, respectively.7. As far as adrenoceptors are concerned, we observed that yohimbine or phentholamine did not modify transmitter release from P1, evoked by high K+ or electrical stimulation. However, yohimbine enhanced the release of [3H]noradrenaline induced by electrical stimulation from splenic slices of the same animals.8. [3H]Clonidine, [3H]dihydroergocryptine or [3H]dihydroalprenolol ([3H]DHA) did not specifically bind to membranes from P1, in spite of the fact that they showed typical saturation curves for specific binding in cortex and atrial membranes from the same cats.9. In conclusion, these data (a) further show that the ligated hypogastric nerve is a good model of noradrenergic nerve terminal free of effector cell; (b) provide direct evidence for the neural location of nicotinic receptors whose activation trigger noradrenaline release from noradrenergic neurones; (c) demonstrate the neural location and axonal transport of muscarinic receptor sites, but leave certain doubts about its functional role in this noradrenergic neurone; and (d) do not support the hypothesis that α and β‐adrenoceptors which modulate noradrenaline release from peripheral noradrenergic nerve terminals are neurally (or prejunctionally) located.
Calcium transients evoked by action potentials in frog twitch muscle fibres
Authors: Miledi R. , Parker I. , Zhu P. H. 
Published: December 2014

1. Intracellular Ca2+ transients were recorded from frog twitch muscle fibres in response to action potentials and repetitive stimulation, using ionophoretically injected arsenazo III as a Ca2+ monitor. A dual wave‐length optical system was used to measure absorbance changes of the injected dye from small areas of single fibres within the cutaneous pectoris muscle.2. The absorbance spectrum of the injected arsenazo III in a resting fibre was consistent with an intracellular free Mg2+ level of a few hundred micromolar, assuming an intracellular pH of 7·1. The resting free Ca2+ concentration was below the limit of resolution.3. The wave‐length dependence of the arsenazo light absorbance signal during twitches followed that expected for Ca2+ binding to the dye. Recordings made at wave‐lengths where the dye is maximally sensitive to pH or Mg2+ concentration changes indicated that interference from these sources is minimal at the usual wave‐length pair (650‐700 nm) used for Ca2+ recordings.4. Over a wide range of intracellular dye concentrations, the size of the arsenazo response to an action potential increased linearly with dye concentration (100‐1000 μM), although there were deviations from this relationship at low and high concentrations.5. An approximate estimate of 8 μM was obtained for the peak free Ca2+ concentration change following a single action potential. Changes in temperature (6‐25 °C) did not significantly affect the size of the free Ca2+ transient. During maximal tetanic stimulation the signal rose to about three times higher than the twitch response. An approximate minimum estimate of the increase in total cytoplasmic Ca2+ concentration during a twitch gave a value of 220 μM.6. A latency of about 1·5 ms (at 10 °C) was observed between the foot of an action potential and the onset of the arsenazo response. Recordings made using a narrow measuring light slit, placed either at the edge or the centre of a fibre, suggested that only a small part of this latency could be due to inward conduction of the action potential along the T‐tubules.7. The decay phase of the arsenazo response to an action potential followed an exponential time course, with a time constant of 71 ms at 10 °C. This time constant was strongly temperature‐dependent, with a Q10 of about 2·4. An Arrhenius plot of the decay time constant gave a straight line.8. During repetitive stimulation, the arsenazo responses evoked by successive impulses showed two changes: a progressive decrease in amplitude and a slowing of the decay. The extent to which successive responses summated during a tetanus depended upon the balance between these two effects.
The sweetness‐inducing effect of miraculin; behavioural and neurophysiological experiments in the rhesus monkey Macaca mulatta
Authors: Brouwer J. N. , Glaser D. , af Segerstad C. Hard , Hellekant G. , Ninomiya Y. , van der Wel H. 
Published: December 2014

1. The gustatory effects of miraculin, the sweetness‐inducing protein from the miracle fruit Synsepalum dulcificum, was studied in the rhesus monkey, Macaca mulatta.2. The intake of five acids was recorded in two‐bottle preference tests, one bottle containing acid and the other tap water, before and after miraculin treatment. All the acids tasted more pleasant after miraculin.3. The electrical activity of the chorda tympani nerve to stimulation of the tongue with a variety of sweeteners, acids, sodium chloride and quinine hydrochloride was recorded in anaesthetized animals.4. Pre‐treatment of the tongue with 0·3‐5 mg miraculin doubled the summated nerve response to the acids and diminished the response to sucrose by about 10%. The enhancement lasted for at least an hour and the diminution up to 20 min.5. After miraculin treatment the Spearman's rank correlation coefficient between the order of increased intake of acids and the order of enhancement of the summated nerve response was 0·99.6. A solution of 0·1 mg miraculin per ml. elicited a weak nerve response. No preference over water for this concentration of miraculin was recorded in the two‐bottle tests.7. The activity of twenty‐nine single taste fibres, selected for their responsiveness to sweetness or acids or both, was recorded after miraculin treatment. Effects were obtained in nine fibres which were similar but more pronounced than those observed in the summated recordings. Before miraculin, these fibres responded better and to a larger variety of sweeteners (81%) than the other fibres (40%). After miraculin, acids elicited on the average 2·3 times more activity than before, while the response to sweeteners was depressed. In twenty fibres no effect of miraculin was observed. These fibres responded to fewer of the sweeteners and were more stimulated by the non‐sweet stimuli than the first group.8. The results suggest that miraculin acts on those structures in the taste cell membrane that are involved in perception of the sweet taste, making them sensitive to acids. The new quality of sweetness after miraculin treatment is signalled by taste fibres which normally respond to sweet substances but which, under the influence of miraculin, are responding to acids. It is likely that the quality of a taste stimulus is conveyed by the identity of the taste fibres.
Ion currents in Drosophila flight muscles
Authors: Salkoff Lawrence B. , Wyman Robert J. 
Published: December 2014

1. The dorsal longitudinal flight muscles of Drosophila melanogaster contain three voltage‐activated ion currents, two distinct potassium currents and a calcium current. The currents can be isolated from each other by exploiting the developmental properties of the system and genetic tools, as well as conventional pharmacology.2. The fast transient potassium current (IA) is the first channel to appear in the developing muscle membrane. It can be studied in isolation between 60 and 70 hr of pupal development. The channels can be observed to carry both outward and inward currents depending on the external potassium concentration. IA is blocked by both tetraethylammonium ion (TEA) and 3‐ or 4‐aminopyridine. The inactivation and recovery properties of IA are responsible for a facilitating effect on membrane excitability.3. The delayed outward current (IK) develops after maturation of the IA system. IK can be isolated from IA by use of a mutation that removes IA from the membrane current response and can be studied before the development of Ca2+ channels. IK shows no inactivation. The channels are more sensitive to blockage by TEA than IA channels, but are not substantially blocked by 3‐ or 4‐aminopyridine.4. The calcium current (ICa) is the last of the major currents to develop and must be isolated pharmacologically with potassium‐blocking agents. ICa shows inactivation when Ca2+ is present but not when Ba2+ is the sole current carrier. When Ca2+ is the current carrier, the addition of Na+ or Li+ retards the inactivation of the net inward current. When the membrane voltage is not clamped, Ba2+ alone, or Ca2+ with Na+ (or Li+), produces a plateau response of extended duration.5. The synaptic current (IJ) evoked by motoneurone stimulation is the fastest and largest of the current systems. It has a reversal potential of approximately ‐5 mV, indicating roughly equal permeabilities of Na+ and K+. During a nerve‐driven muscle spike, IJ is the major inward current, causing a very rapid depolarization away from resting potential. An exceptionally large synaptic current is necessary to rapidly discharge the high membrane capacitance (0·03 μF/cell) in these large (0·05 × 0·1 × 0·8 mm) isopotential cells.
Calcium transients studied under voltage‐clamp control in frog twitch muscle fibres
Authors: Miledi R. , Parker I. , Zhu P. H. 
Published: December 2014

1. Intracellular calcium transients were recorded from frog twitch muscle fibres in response to voltage‐clamped depolarizing pulses, using arsenazo III as an intracellular calcium monitor. The object was to investigate the time‐ and voltage‐dependent characteristics of the coupling process between membrane depolarization and calcium release from the sarcoplasmic reticulum (s.r.)2. To examine the extent to which the T‐tubule membrane potential was controlled during clamp pulses, the dye NK 2367 was used as an optical probe of tubular potential. This indicated that the tubular time constant is about 0·6 msec.3. Strength—duration curves were obtained for depolarizing pulses required to give both threshold mechanical contraction and calcium signal. Curves measured in these two ways were closely similar.4. Changes in holding potential altered the strength—duration curve for calcium release so that at more positive holding potentials a shorter pulse was needed to obtain a response for any given pulse amplitude.5. A latency of a few milliseconds was observed between the onset of depolarization and the initial rise of the calcium signal. This became shorter with stronger depolarizations, but approached a minimum at potentials above about +25 mV.6. Subthreshold depolarizations applied before a test pulse increased the size and decreased the latency of the calcium signal. Conditioning hyperpolarizations had opposite effects.7. The rate of build‐up of potentiation or depression of response size seen with subthreshold de‐ and hyperpolarizing conditioning pulses was examined using conditioning pulses of different durations. For both pulses this process showed a time constant of about 3 msec (at 10 °C).8. The rate of decay of potentiation or depression was similarly measured, using a gap of variable duration between conditioning and test pulses. For both de‐ and hyperpolarizing pulses this showed a time constant of about 5 msec (10 °C).9. The relationship between conditioning pulse potential, and the size of calcium signal elicited by a following test pulse was non‐linear.10. Subthreshold pulses immediately following a brief test pulse affected the size of the calcium signal in a similar way to preceding conditioning pulses.11. The relationship between potential and size of the calcium signal was examined using pulses of 3 and 20 msec duration. With the long pulse the relation was roughly sigmoid, but with the short pulse continued to rise even at strongly positive potentials.12. The results are discussed in terms of a model in which the exponential build‐up of a hypothetical coupler in the excitation—contraction (e.—c.) coupling process is presumed to lead to calcium release when a threshold level is exceeded.
Dynamic Modeling of Bottomhole Assembly
Authors: Vadali Madhu , Sun Zhijie , Xue Yuzhen , Dykstra Jason 
Published: December 2014

This paper presents a comprehensive 4D dynamic model of a bottomhole assembly (BHA) used for directional drilling of oil and gas wells. Although directional drilling has been in practice for some time, it still poses several challenges, particularly related to building an autonomous drilling system. The difficulty with drilling automation derives from the complexity of the process that includes interaction with the borehole and fluid (mud) flow and complex downhole vibrations, such as bit-bounce (axial), whirl (lateral), and stick/slip (torsional). Moreover, the measurements from a limited number of downhole sensors are usually contaminated with high noise levels, and can only be transmitted at low rates with long transmission delays using mud pulsing, or at a high cost using wired pipe. Therefore, it is preferable that the directional drilling system work autonomously with limited communication to the surface. To facilitate this, a compressive physics-based model of the BHA behavior was created to be used in control system development.
In this work, the 4D dynamic model of the BHA accounts for the dynamics in rotation, axial motion, and bending along two lateral directions. The model uses a lumped mass-spring system and the system parameters (mass and stiffness) are derived from the shear beam theory of a flexible beam under certain boundary conditions.
Simulation results of the model were successful in qualitatively replicating the three types of downhole vibrations, namely bit-bounce, whirl, and stick/slip, and are discussed in this paper. The model is shown to qualitatively replicate downhole conditions and can be implemented in real-time, thereby making it suitable for autonomous directional drilling control.
Complete Genome Sequence of a Betanodavirus Isolated from Half-Smooth Tongue Sole (
Cynoglossus semilaevis
)
Authors: Li Jin , Shi Cheng Yin , Huang Jie , Geng Wei Guang , Wang Sheng Qiang , Su Zi Dan 
Published: December 2014

ABSTRACT

Betanodavirus, commonly called nervous necrosis virus (NNV) of fish, has emerged as a major constraint on marine aquaculture worldwide. Here, we report the complete genome sequence of a betanodavirus (strain CsCN128) isolated from diseased half-smooth tongue sole (
Cynoglossus semilaevis
) in China. The genome sequence of strain CsCN128 shares ≥98.7% similarity with seven-band grouper nervous necrosis virus from Japan. Phylogenetic analysis indicates that strain CsCN128 belongs to the red-spotted grouper nervous necrosis virus (RGNNV) genotype of betanodavirus. The genome of the strain CsCN128 will facilitate further study on the molecular epidemiology and natural susceptible host range of betanodaviruses.
Draft Genome Sequence of Pseudomonas aeruginosa Strain WS394, a Multidrug-Resistant and Highly Cytotoxic Wound Isolate from Chronic Ulcus Cruris
Authors: Vorhölter Frank-Jörg , Arnold Martin , Wibberg Daniel , Blom Jochen , Winkler Anika , Viehoever Prisca , Albersmeier Andreas , Goesmann Alexander , Zange Sabine , Heesemann Jürgen , Pühler Alfred , Hogardt Michael 
Published: December 2014

ABSTRACT

Pseudomonas aeruginosa
is a frequent human pathogen that increasingly causes chronic infections of nonhealing wounds. Here we present the 6.8 Mb draft genome of strain WS394, a multidrug-resistant chronic ulcer isolate that exhibited outstanding high cell cytotoxicity despite defective secretion of exotoxin U, suggesting a habitat-dependent adaptation process.
Platelet adhesion on endothelium early after vein grafting mediates leukocyte recruitment and intimal hyperplasia in a murine model
Authors: Tseng Chi-Nan , Chang Ya-Ting , Lengquist Mariette , Kronqvist Malin , Hedin Ulf , Eriksson Einar E. 
Published: December 2014

SummaryIntimal hyperplasia (IH) is the substrate for accelerated atherosclerosis and limited patency of vein grafts. However, there is still no specific treatment targeting IH following graft surgery. In this study, we used a mouse model of vein grafting to investigate the potential for early intervention with platelet function for later development of graft IH. We transferred the inferior vena cava (IVC) from donor C57BL/6 mice to the carotid artery in recipients using a cuff technique. We found extensive endothelial injury and platelet adhesion one hour following grafting. Adhesion of leukocytes was distinct in areas of platelet adhesion. Platelet and leukocyte adhesion was strongly reduced in mice receiving a function-blocking antibody against the integrin αIIbβ3. This was followed by a reduction of IH one month following grafting. Depletion of platelets using antiserum also reduced IH at later time points. These findings indicate platelets as pivotal to leukocyte recruitment to the wall of vein grafts. In conclusion, the data also highlight early intervention of platelets and inflammation as potential treatment for later formation of IH and accelerated atherosclerosis following bypass surgery.
Estimation of dabigatran plasma concentrations in the perioperative setting
Authors: Dincq Anne-Sophie , Hjemdahl Paul , Rönquist-Nii Yuko , Pohanka Anton , Gourdin Maximilien , Chatelain Bernard , Dogné Jean-Michel , Mullier François , Douxfils Jonathan , Lessire Sarah 
Published: December 2014

SummaryThe perioperative management of dabigatran is challenging, and recommendations based on activated partial thromboplastin time (aPTT) and thrombin time (TT) are unsatisfactory. Dedicated coagulation tests have limitations at plasma concentrations < 50 ng/ml. Therefore, a more sensitive test, which is available 24/7, is required. It was the aim of this study to investigate the performance of the Hemoclot Thrombin Inhibitors® LOW (HTI LOW) kit, a diluted thrombin time, and the STA® – ECA II (ECA-II) kit, a chromogenic variant of the ecarin clotting time, that were developed to measure low dabigatran concentrations, compared to reference dabigatran analysis by liquid chromatography tandem mass-spectrometry (LC-MS/MS). This study included 33 plasma samples from patients treated with dabigatran etexilate who had plasma concentrations < 200 ng/ml. HTI LOW and ECA-II were performed along with HTI, aPTT (STA®-C. K.Prest® and SynthasIL ®) and TT (STA® – Thrombin). All procedures were performed according to recommendations by the manufacturers. Linear (or curvilinear) correlations and Bland-Altman analyses were calculated. For free dabigatran concentrations < 50 ng/ml, the R2 of linear correlations were 0.69, 0.84 and 0.61, with HTI, HTI LOW and ECA-II, respectively. The R2 for TT, STA®-C. K.Prest® and SynthasIL® were 0.67, 0.42 and 0.15. For HTI, HTI LOW and ECA-II, Bland-Altman analyses revealed mean differences of –6 ng/ml (95 %CI: –25–14 ng/ml), 1 ng/ml (95 %CI: –18–19 ng/ml) and –1 ng/ml (95 %CI: –25–23 ng/ml), demonstrating that tests dedicated to measuring low concentrations are more accurate than HTI. In conclusion, the use of HTI LOW or ECA-II to assess low plasma dabigatran concentrations is supported by our findings.
Molecular Controls of Lymphatic VEGFR3 Signaling
Authors: Deng Yong , Zhang Xi , Simons Michael 
Published: December 2014

Objectives—
Vascular endothelial growth factor receptor 3 (VEGFR3) plays important roles both in lymphangiogenesis and angiogenesis. On stimulation by its ligand VEGF-C, VEGFR3 is able to form both homodimers as well as heterodimers with VEGFR2 and activates several downstream signal pathways, including extracellular signal-regulated kinases (ERK)1/2 and protein kinase B (AKT). Despite certain similarities with VEGFR2, molecular features of VEGFR3 signaling are still largely unknown.

Approach and Results—
Human dermal lymphatic endothelial cells were used to examine VEGF-C–driven activation of signaling. Compared with VEGF-A activation of VEGFR2, VEGF-C–induced VEGFR3 activation led to a more extensive AKT activation, whereas activation of ERK1/2 displayed a distinctly different kinetics. Furthermore, VEGF-C, but not VEGF-A, induced formation of VEGFR3/VEGFR2 complexes. Silencing VEGFR2 or its partner neuropilin 1 specifically abolished VEGF-C–induced AKT but not ERK activation, whereas silencing of neuropilin 2 had little effect on either signaling pathway. Finally, suppression of vascular endothelial phosphotyrosine phosphatase but not other phosphotyrosine phosphatases enhanced VEGF-C–induced activation of both ERK and AKT pathways. Functionally, both ERK and AKT pathways are important for lymphatic endothelial cells migration.

Conclusions—
VEGF-C activates AKT signaling via formation of VEGFR3/VEGFR2 complex, whereas ERK is activated by VEGFR3 homodimer. Neuropilin 1 and vascular endothelial phosphotyrosine phosphatase are involved in regulation of VEGFR3 signaling.
Are Special Processes at Work in the Rapid Intensification of Tropical Cyclones?
Authors: Kowch Roman , Emanuel Kerry 
Published: December 2014

Abstract
Probably not. Frequency distributions of intensification and dissipation developed from synthetic open-ocean tropical cyclone data show no evidence of significant departures from exponential distributions, though there is some evidence for a fat tail of dissipation rates. This suggests that no special factors govern high intensification rates and that tropical cyclone intensification and dissipation are controlled by statistically random environmental and internal variability.