2,458 research outputs found
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Direct iminization of PEEK
Semi-crystalline poly(ether ketone)s are important high-temperature engineering thermoplastics, but are difficult to characterize at the molecular level because of their insolubility in conventional organic solvents. Here we report that polymers of this type, including PEEK, react cleanly at high temperatures with low-volatility aralkyl amines to afford stable, noncrystalline poly(ether-imine)s, which are readily soluble in solvents such as chloroform, THF and DMF and so characterizable by conventional size-exclusion chromatography
The activation mechanism of alpha 1 homomeric glycine receptors
The glycine receptor mediates fast synaptic inhibition in the spinal cord and brainstem. Its activation mechanism is not known, despite the physiological importance of this receptor and the fact that it can serve as a prototype for other homopentameric channels. We analyzed single-channel recordings from rat recombinant alpha1 glycine receptors by fitting different mechanisms simultaneously to sets of sequences of openings at four glycine concentrations (10-1000 muM). The adequacy of the mechanism and the rate constants thus fitted was judged by examining how well these described the observed dwell-time distributions, open-shut correlation, and single-channel P-open dose-response curve. We found that gating efficacy increased as more glycine molecules bind to the channel, but maximum efficacy was reached when only three (of five) potential binding sites are occupied. Successive binding steps are not identical, implying that binding sites can interact while the channel is shut. These interactions can be interpreted in the light of the topology of the binding sites within a homopentamer
Openings of the rat recombinant alpha1 homomeric glycine receptor as a function of the number of sgonist molecules bound
The functional properties of rat homomeric {alpha}1 glycine receptors were investigated using whole-cell and outside-out recording from human embryonic kidney cells transfected with rat {alpha}1 subunit cDNA. Whole-cell dose-response curves gave EC50 estimates between 30 and 120 µM and a Hill slope of ~3.3. Single channel recordings were obtained by steady-state application of glycine (0.3, 1, or 10 µM) to outside-out patches. Single channel conductances were mostly 60–90 pS, but smaller conductances of ~40 pS were also seen (10% of the events) with a relative frequency that did not depend on agonist concentration. The time constants of the apparent open time distributions did not vary with agonist concentration, but short events were more frequent at low glycine concentrations. There was also evidence of a previously missed short-lived open state that was more common at lower glycine concentrations. The time constants for the different components of the burst length distributions were found to have similar values at different concentrations. Nevertheless, the mean burst length increased with increasing glycine. This was because the relative area of each burst-length component was concentration dependent and short bursts were favored at lower glycine concentrations. Durations of adjacent open and shut times were found to be strongly (negatively) correlated. Additionally, long bursts were made up of longer than average openings separated by short gaps, whereas short bursts usually consisted of single isolated short openings. The most plausible explanation for these findings is that long bursts are generated when a higher proportion of the five potential agonist binding sites on the receptor is occupied by glycine. On the basis of the concentration dependence and the intraburst structure we provide a preliminary kinetic scheme for the activation of the homomeric glycine receptor, in which any number of glycine molecules from one to five can open the channel, although not with equal efficiency
The QT interval in lightning injury with implications for the cessation of metabolism hypothesis
An hypothesis is presented to provide an alternative to the Cessation of Metabolism hypothesis often invoked in lightning injury. Cessation of Metabolism has been proposed to explain the observation of good recovery after a prolonged period in cardiac arrest in some lightning injured patients. Reevaluation of EEGs from lightning injured patients show a high incidence of QT prolongation. Reexamination of the cases used to support Cessation of Metabolism also reveals little evidence to justify the hypothesis. The finding of QT prolongation coupled with the hyperadrenergic state said to exist in lightning injury, may promote a state of episodic induction of and recovery from Torsade de Pointes Ventricular Tachycardia (VT). Histological examination of the myocardium supports the new hypothesis. This the first concerted description of lightning injury as one of the general causes of QT prolongation. It appears to occur frequently after lightning injury, is a prerequisite of and predisposes to episodes of Torsade de Pointes VT. These electrocardiographic abnormalities explain Cessation of Metabolism and recognition may change management and lead to greater survival
Single-channel behavior of heteromeric α1β glycine receptors: an attempt to detect a conformational change before the channel opens
The α1β heteromeric receptors are likely to be the predominant synaptic form of glycine receptors in the adult. Their activation mechanism was investigated by fitting putative mechanisms to single-channel recordings obtained at four glycine concentrations (10-1000 µM) from rat {alpha}1{beta} receptors, expressed in human embryonic kidney 293 cells. The adequacy of each mechanism, with its fitted rate constants, was assessed by comparing experimental dwell time distributions, open-shut correlations, and the concentration-open probability (Popen) curve with the predictions of the model. A good description was obtained only if the mechanism had three glycine binding sites, allowed both partially and fully liganded openings, and predicted the presence of open-shut correlations. A strong feature of the data was the appearance of an increase in binding affinity as more glycine molecules bind, before the channel opens. One interpretation of this positive binding cooperativity is that binding sites interact, each site sensing the state of ligation of the others. An alternative, and novel, explanation is that agonist binding stabilizes a higher affinity form of the receptor that is produced by a conformational change ("flip") that is separate from, and precedes, channel opening. Both the "interaction" scheme and the flip scheme describe our data well, but the latter has fewer free parameters and above all it offers a mechanism for the affinity increase. Distinguishing between the two mechanisms will be important for our understanding of the structural dynamics of activation in the nicotinic superfamily and is important for our understanding of mutations in these receptors
Limits of sensing temporal concentration changes by single cells
Berg and Purcell [Biophys. J. 20, 193 (1977)] calculated how the accuracy of
concentration sensing by single-celled organisms is limited by noise from the
small number of counted molecules. Here we generalize their results to the
sensing of concentration ramps, which is often the biologically relevant
situation (e.g. during bacterial chemotaxis). We calculate lower bounds on the
uncertainty of ramp sensing by three measurement devices: a single receptor, an
absorbing sphere, and a monitoring sphere. We contrast two strategies, simple
linear regression of the input signal versus maximum likelihood estimation, and
show that the latter can be twice as accurate as the former. Finally, we
consider biological implementations of these two strategies, and identify
possible signatures that maximum likelihood estimation is implemented by real
biological systems.Comment: 11 pages, 2 figure
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Synthesis, x-ray structure and anion binding properties of a cryptand-like hybrid calixpyrrole
The novel cryptand in/out-3, containing two tripyrrolemethane units briged by three 1,3- diisopropylidenbenzene arms was readily synthesized by a convergent three-step synthesis. It binds fluoride by inclusion with excellent selectivity with respect to a number of other tested anions. The structure of the free receptor and that of its fluoride complex were investigated in solution by NMR spectroscopy. The solid state X-ray structure of the free cryptand 3 was also determined
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Conformational modulation of sequence recognition in synthetic macromolecules
The different triplet sequences in high molecular weight aromatic copolyimides comprising pyromellitimide units ("I") flanked by either ether-ketone ("K") or ether-sulfone residues ("S") show different binding strengths for pyrene-based tweezer-molecules. Such molecules bind primarily to the diimide unit through complementary π-π-stacking and hydrogen bonding. However, as shown by the magnitudes of 1H NMR complexation shifts and tweezer-polymer binding constants, the triplet "SIS" binds tweezer-molecules more strongly than "KIS" which in turn bind such molecules more strongly than "KIK". Computational models for tweezer-polymer binding, together with single-crystal X-ray analyses of tweezer-complexes with macrocyclic ether-imides, reveal that the variations in binding strength between the different triplet sequences arise from the different conformational preferences of aromatic rings at diarylketone and diarylsulfone linkages. These preferences determine whether or not chain-folding and secondary π−π-stacking occurs between the arms of the tweezermolecule and the 4,4'-biphenylene units which flank the central diimide residue
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Trifluoromethylation of carbonyl groups in aromatic poly(ether ketone)s: formation of strongly polar yet surface-hydrophobic poly(arylenenecarbinol)s
Fluoride-catalyzed reactions of trimethyl(trifluoromethyl)silane with a range of aromatic poly(ether ketone)s, both amorphous and semi-crystalline, proceed quantitatively in THF to yield soluble, amorphous polymers in which the carbon-silicon bond of CF3SiMe3 has added across the carbonyl-oxygen double bond of each carbonyl group. When the starting poly(ether ketone) is amorphous and soluble in THF the reaction is fairly rapid (hours), but is much slower (days) when the starting polymer is semi-crystalline, with only low solubility in THF. Quantitative desilylation of the resulting polymers is achieved by reaction with excess fluoride ion, affording poly(arylene-trifluoromethylcarbinol)s. These extremely polar polymers are readily soluble in protic solvents such as methanol or ethanol, to give solutions from which tough, coherent films may be cast by evaporation in air. Despite the evidently high polarity of the bulk polymers, the surfaces of cast films are relatively hydrophobic, with static water contact angles of ~ 90°. Surface analyses by XPS are consistent with enrichment of the polymer-air interface in CF3 groups
A study of certain factors affecting reproduction in the mare
This thesis describes a study of the behavioural, hormonal and ovarian changes recorded in groups of housed mares during late autumn / spring over three years. In the first year the investigations concerned larger mares but these were replaced by pony mares during the subsequent two years. In the third year, mares demonstrating positive oestrous behaviour were mated. Variations from normal cyclical activity are discussed. Incorporated in this study was an investigation into the effects of different environmental lighting on melatonin patterns and on reproductive activity in the pony mares. A radioimmunoassay for the estimation of plasma melatonin concentration was established and the assay validated by recognised reliability criteria. No correlation was found between environmental lighting, patterns of melatonin secretion and reproductive activity in these mares. Factors which may have affected reproductive activity in this study, other than light and plasma melatonin concentration, are suggested and discussed
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