Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Background Cl channels in neurons and skeletal muscle are significantly permeable for alkali cations when tested with asymmetrical concentrations of the same salt. Both anion and cation permeation were proposed to require binding of an alkali cation with the pore (Franciolini, F., and W. Nonner. 1987. Journal of General Physiology. 90:453-478). We tested this hypothesis by bilaterally substituting large alkali cations for Na and found no significant changes of unitary conductance at 300 mM symmetrical concentrations. In addition, all organic cations examined were permeant in a salt gradient test (1,000 mM internal@300 mM external), including triethanolamine, benzyltrimethylamine, and bis-tris-propane (BTP, which is divalent at the tested pH of 6.2). Inward currents were detected following substitution of internal NaCl by the Na salts of the divalent anions of phosphoric, fumaric, and malic acid. Zero-current potentials in gradients of the Na and BTP salts of varied anions (propionate, F, Br, nitrate) that have different permeabilities under bi-ionic conditions, were approximately constant, as if the permeation of either cation were coupled to the permeation of the anion. These results rule out our earlier hypothesis of anion permeation dependent on a bound alkali cation, but they are consistent with the idea that the tested anions and cations form mixed complexes while traversing the Cl channel.
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PMID:Anion-cation interactions in the pore of neuronal background chloride channels. 783 38

Transport of a divalent cation (Ca2+) and three DNA indicators [ethidium bromide (EB), propidium iodide (PI), and ethidium homodimer (EthD-1)] across electroporated membranes of several mammalian cell lines was found to be selective and asymmetrical. In low salt medium, Ca2+ and EB were preferentially transported across the anodefacing cell membrane while PI and EthD-1 predominately entered at the site facing the cathode. In high salt medium, the entry site for Ca2+ and EB was reversed to the cathode-facing hemisphere while it remained unchanged for PI and EthD-1. In all these experiments, the observed transport patterns remained unaffected whether the dyes (or ion) were present during or added after the electroporating pulse. The data suggest that asymmetric pores are created on both sides of the membrane facing the electrodes, with smaller pore size (but greater in number) on the anode side and larger pores (with a lower population) on the cathode side. Furthermore, the rate of resealing of the membrane pores is significantly enhanced in high ionic strength medium, thus affecting the entry site. The asymmetric transport pattern is neither caused by electrophoresis induced by the externally applied electric field nor due to one-sided membrane breakdown as previously believed.
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PMID:Selective and asymmetric molecular transport across electroporated cell membranes. 797 93

'Halophilic adaptation' of proteins, i.e. the requirement for high concentrations of monovalent ions for thermodynamic stability of proteins from halophilic organisms, is not fully understood. In this work, an explanation for the halophilic behavior of dihydrofolate reductase (h-DHFR) from Halobacterium volcanii is attempted, based on a model structure derived from comparative modeling to dihydrofolate reductase from Escherichia coli. The model structure of h-DHFR shows an unique asymmetrical charge distribution over the protein surface, with positively charged amino acids centered around the active site and negative charges on the opposite side of the enzyme. This particular charge distribution and the correlated molecular dipole are functionally relevant. The negative charges on the surface form clusters which are shielded at high salt concentrations; at low salt, they repulse each other, thus destabilizing the protein. Results are in accordance with denaturation data and, thus, provide an explanation for the exceptional stability properties of h-DHFR.
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PMID:A structure-based model for the halophilic adaptation of dihydrofolate reductase from Halobacterium volcanii. 817 Sep 25

The secondary structures of the 5'-untranslated region (5'-UTR) of five different tymoviruses have been determined by structure probing, computer prediction and sequence comparison. Despite large sequence differences, there are remarkable similarities in the secondary structure. In all viruses two or four hairpins are found, most of which contain a symmetrical internal loop consisting of adjacent C-C or C-A mismatches. Since it is known that such mismatches can be protonated and protonated cytosines play an important role in RNA-protein interactions in tymoviral virions, the influence of pH on the conformation of the internal loop was studied. UV melting experiments and 1-dimensional proton NMR at varying pH values and salt concentrations confirm that the hairpins can be protonated under relatively mild conditions. The hairpin found in the 5'-UTR of erysimum latent virus, which has an asymmetrical internal loop consisting of cytosines and uridines, shows comparable behaviour. It is concluded that all tymoviral RNAs contain protonatable hairpins in the 5'-UTR. Binding experiments with empty viral capsids, however, do not yet establish a role in capsid protein binding.
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PMID:Protonatable hairpins are conserved in the 5'-untranslated region of tymovirus RNAs. 901 60

The participation of apical membranes of uterine epithelial cells in the process of blastocyst adhesion makes them an interesting object in the study of changes occurring during early pregnancy. In the study of these changes alkaline phosphatase (AIP), a typical brush border enzyme, was chosen for demonstration with the scanning electron microscope (SEM) by means of a backscatter detector. Thus the temporal and spatial pattern of enzyme activity on the uterine luminal surface was made visible with lead salt procedures. AIP activity was shown to be located on apical membranes and microvilli of endometrial epithelial cells with high activity on day 2 of pregnancy decreasing to virtually no activity on day 5. This decrease in overall AIP activity was shown to be asymmetrical with respect to the uterine cavity. It begins on the antimesometrial half of the uterine lining on day 2. A distribution pattern demarcating a presumptive implantation site along the uterine horn was not found. However, on day 5 of pregnancy, a characteristic pattern of surface folds was found, dividing the uterine horn into 'implantation segments'. In addition, SEM investigation revealed a marked variation of AIP activity from one individual cell to the next on day 2 of pregnancy resulting in a mosaic-like pattern. This pattern is lost with the decrease of AIP activity on day 5. Thus heterogeneity of uterine epithelial cells in AIP activity is apparently a feature of nonreceptive epithelium in contrast to the homogeneous epithelium on day 5. It is proposed that epithelial cell homogeneity could be a marker for uterine receptivity.
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PMID:Alkaline phosphatase distribution in rat endometrial epithelium during early pregnancy: a scanning electron-microscopic study. 941 54

We have reconstituted oligonucleosome complexes containing histone H1 starting from a synthetic DNA template, consisting of 12 tandemly arranged 208-base pair fragments of the 5 S rRNA gene, purified HeLa histone octamers, and histone H1. A ratio of histone H1 per histone octamer used in the reconstitution (0.8-0.9 mol of histone H1/mol of histone octamer) similar to that observed in vivo was used. The reconstituted chromatin complexes exhibit a salt-dependent folding, which is almost indistinguishable from that exhibited by chromatin fragments obtained from nuclease digestion of native chromatin. The folding of this reconstituted chromatin complex seems to be rather independent of the symmetrical or asymmetrical position occupied by H1 in the individual nucleosomes. Binding of histone H1 to the oligonucleosome complexes, under the stoichiometric binding conditions used, had no inhibitory effect on the transcriptional potential of these complexes.
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PMID:Folding of chromatin in the presence of heterogeneous histone H1 binding to nucleosomes. 956 81

The summer flounder (Paralichthys dentatus) undergoes a true metamorphosis during which the bilaterally symmetrical larva transforms into an asymmetrical juvenile. This study addresses the influence of manipulating thyroid status on larval development and growth. Development was assessed by categorizing larvae in stages based on the position of the translocating eye and growth was assessed as a change in total length. Larvae were raised in seawater or in seawater containing thyroxine-sodium salt (100 ppb, T4) or thiourea (30 ppm, TU). Ambient T4 raised whole-animal T4 concentration almost threefold, whereas treatment with TU reduced whole-animal T4 concentration by 95%. The whole-animal T4 concentrations of untreated larvae increased during metamorphic climax (MC) and were related to developmental stage rather than age. Altering thyroid status of larvae in different stages had different consequences. T4 treatment of late premetamorphic (late pre-M) larvae accelerated their rate of development to prometamorphosis (pro-M), early MC, and mid MC, whereas TU treatment at this stage caused developmental stasis in early MC. T4 treatment of pro-M larvae accelerated development to early MC only and, unlike the response of late pre-M larvae, some of the pro-M larvae treated with TU slowly developed to late MC. TU treatment could inhibit completion of metamorphosis in early MC and mid MC, but not in late MC. Thyroid status of larvae had no effect on growth. However, starting at an age when most untreated and T4-treated larvae were in late MC, they began to grow longer than TU-treated larvae in developmental stasis at early MC and mid MC. Thus, T4 is necessary and sufficient for metamorphosis in summer flounder and, at this single dose, has a more pronounced effect on development at earlier stages.
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PMID:Metamorphosis in the summer flounder (Paralichthys dentatus): stage-specific developmental response to altered thyroid status. 967 87

We have developed a new analytical ultracentrifugal micromethod for the determination of serum low-density lipoprotein (LDL) subclasses directly from ultracentrifugal Schlieren scans. We have used special software for the analysis of this type of single-spin density-gradient ultracentrifugation. The flotation of LDL patterns was obtained by underlayering a physiological salt solution with serum or isolated lipoprotein fractions raised to a density of 1.3 g/mL in the spinning ultracentrifugation capillary band-forming cell. The repeated analysis of Schlieren curves of the same sample from 10 to 100 microL in the 60-100 min full-speed interval time resulted in quite reproducible results. We obtained quantitative results by measuring the Schlieren areas between the sample curves and the reference baseline curve by using computerised numerical and graphic techniques. The decomposition of the integrated curve was carried out using a nonlinear regression program followed by deconvolution algorithm analysis in order to determine the parameters of the composing Gaussian subclasses. The LDL particle concentrations were calculated from the area under the integral of the Gaussian curve using a calibration data constant. The flotation range of the LDL Schlieren curves in the cell was identified with serum from which LDL had been removed by means of precipitation reagents and with centrifugation of isolated LDL aliquots. With this technique, we measured the concentration of LDL and analysed its polydispersity without the need for preceding sequential isolation of the LDL. On the basis of the Schlieren curves, the LDL samples were either physically paucidisperse, having a symmetrical peak within a narrow density range, or were polydisperse, showing an asymmetrical pattern distributed over a broader density region. The described method proved to be useful for a clear and immediate visual presentation of the concentration values of the LDL and for the identification of the heterogeneity of LDL variants without the need for the preparative isolation of that density class.
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PMID:A short-run new analytical ultracentrifugal micromethod for determining low-density lipoprotein sub-fractions using Schlieren refractometry. 1128 37

Temporomandibular joint (TMJ) pain conditions are poorly understood. Since formalin is a noxious stimulus widely used in animal behavioral experiments for studying pain mechanisms, the aim of this study was to develop a behavioral model to study the TMJ pain conditions by characterizing the nociceptive behavioral responses induced by the injection of formalin into the TMJ region of rats. NaCl (0.9%) or different concentrations of formalin (0.5, 1.5, 2.5 or 5%) were administrated into the TMJ region. The formalin-induced behavioral responses characterized by moving the mandible, rubbing the orofacial region and flinching the head quickly were quantified for 45 min. The TMJ injection of formalin significantly increased the asymmetrical orofacial rubbing and head flinching behaviors, but not the movement of the mandible with concentrations of 1.5% and above (P<0.05, Dunn's test) when compared with the NaCl (0.9%) injection. These responses were significantly reduced (P<0.05, Mann-Whitney test) by the co-application of lidocaine N-ethyl bromide quaternary salt, QX-314 (2%), and by the administration of intraperitoneal morphine (4 mg/kg) 30 min prior to the TMJ formalin injection. This study demonstrates that the injection of formalin into the TMJ region of rats produces quantitative nociceptive behaviors constituting a novel behavioral model for TMJ pain.
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PMID:Development of a behavioral model of TMJ pain in rats: the TMJ formalin test. 1169 Jul 32

Monosubstituted [M(N)Cl(2)(POP)] [M = Tc, 1; Re, 2] and [M(N)Cl(2)(PNP)] [M = Tc, 3; Re, 4] complexes were prepared by reaction of the precursors [M(N)Cl(4)](-) and [M(N)Cl(2)(PPh(3))(2)] (M = Tc, Re) with the diphosphine ligands bis(2-diphenylphosphinoethyl)ether (POP) and bis(2-diphenylphosphinoethyl)methoxyethylamine (PNP) in refluxing dichloromethane/methanol solutions. In these compounds, the diphosphine acted as a chelating ligand bound to the metal center through the two phosphorus atoms. Considering also the weak interaction of the heteroatom (N or O) located in the middle of the carbon backbone connecting the two P atoms, we found that the coordination arrangement of the diphosphine ligand could be viewed as either meridional (m) or facial (f), and the resulting geometry as pseudooctahedral. The heteroatom of the diphosphine ligand was invariably located trans to the nitrido linkage, as established by X-ray diffraction analysis of the representative compounds 2m and 4f. Density functional theoretical calculations showed that in POP-type complexes the mer form is favored by approximately 6 kcal mol(-1), whereas mer and fac isomers are almost isoenergetic in PNP-type complexes. A possible role of noncovalent interactions between the phosphinic phenyl substituents in stabilizing the fac-isomer was also highlighted. The existence of fac-mer isomerism in this class of complexes was attributed to the strong tendency of the two phosphorus atoms to occupy a reciprocal trans-position within the pseudooctahedral geometry. The switching of P atoms between cis- and trans-configurations was confirmed by the observation that the fac isomers, 1f and 2f, were irreversibly transformed, in solution, into the corresponding mer isomers, 1m and 2m, thus suggesting that fac complexes are more reactive species. Theoretical calculations supported this view by showing that the lowest unoccupied orbitals of the fac isomers are more accessible to a nucleophilic attack with respect to those of the mer ones. Furthermore, the large participation of the Cl orbitals to the HOMO, which is a metal-ligand pi* antibonding in the complex basal plane, shows that the Tc-Cl bonds are labile. As a consequence, facial isomers could be considered as highly electrophilic intermediates that were selectively reactive toward substitution by electron-rich donor ligands. Experimental evidence was in close agreement with this description. It was found that fac-[M(N)Cl(2)(PXP)] complexes easily underwent ligand-exchange reactions with bidentate donor ligands such as mercaptoacetic acid (NaHL(1)), S-methyl 2-methyldithiocarbazate (H(2)L(2)), diethyldithiocarbamate sodium salt (NaL(3)), and N-acetyl-L-cysteine (H(2)L(4)) to afford stable asymmetrical heterocomplexes of the type fac-[M(N)(L(n))(POP)](+/0) (5-8) and fac-[M(N)(L(n))(PNP)](+/0) (9-14) comprising two different polydentate chelating ligands bound to the same metal center. In these reactions, the bidentate ligand replaced the two chloride atoms on the equatorial plane of the distorted octahedron, leaving the starting fac-[M(N)(PXP)](2+) (X = O, N) moieties untouched. No formation of the corresponding symmetrical complexes containing two identical bidentate ligands was detected over a broad range of experimental conditions. Solution-state NMR studies confirmed that the structure in solution of these heterocomplexes was identical to that established in the solid state by X-ray diffraction analysis of the prototype complexes fac-[M(N)(HL(2))(POP)][BF(4)] [M = Tc, 7; Re, 8] and fac-[Tc(N)(HL(2))(PNP)][BF(4)], 11. In conclusion, the novel metal fragment fac-[M(N)(PXP)](2+) could be utilized as an efficient synthon for the preparation of a large class of asymmetrical, nitrido heterocomplexes incorporating a particular diphosphine ligand and a variety of bidentate chelating molecules.
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PMID:Chemistry of the strong electrophilic metal fragment [(99)Tc(N)(PXP)](2+) (PXP = diphosphine ligand). A novel tool for the selective labeling of small molecules. 1223 61


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