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At least 955 records · Page 53Linked to original sources
PubMed1996

Mirror-image RNA that binds D-adenosine.

A 58-mer L-RNA ligand that binds to naturally occurring D-adenosine with a dissociation constant of 1.7 microM in solution was identified from a combinatorial library employing mirror-design. The corresponding D-RNA ligand shows identical binding affinity to L-adenosine. Reciprocal chiral specificity was also evident from ligand discrimination; the binding affinity of the L-RNA ligand for D-adenosine was 9000-fold greater than its affinity for L-adenosine and vice versa. While the D-RNA ligand was rapidly degraded in human serum, the L-RNA ligand displayed an extraordinary stability. This indicates the potential application of specifically designed L-RNA ligands as stable monoclonal antibody analogues and the development of highly stable L-ribozymes.

Adenosine↗
PubMed1996

Mirror-design of L-oligonucleotide ligands binding to L-arginine.

The high affinity and selectivity of nucleic acid ligands have clearly demonstrated that RNA can be targeted to a variety of molecules. In practice, however, the use of unmodified aptamers is impeded by the low stability of RNA in biological fluids. Here we describe the mirror-design of a stable 38-mer L-oligoribonucleotide ligand that binds to L-arginine. This L-RNA ligand was also able to bind to a short peptide containing the basic region of the human immunodeficiency virus type-1 Tat-protein. The L-RNA ligand displayed the expected stability in human serum. These findings may contribute to the identification of novel diagnostics and pharmaceuticals.

Amino Acid Sequence↗
PubMed2001

Shape-coding in IT cells generalizes over contrast and mirror reversal, but not figure-ground reversal.

We assessed how the visual shape preferences of neurons in the inferior temporal cortex of awake, behaving monkeys generalized across three different stimulus transformations. Stimulus-preferences of particular cells among different polygon displays were correlated across reversed contrast polarity or mirror reversal, but not across figure-ground reversal. This corresponds with psychological findings on human shape judgments. Our results imply that neurons in inferior temporal cortex respond to components of visual shape derived only after figure-ground assignment of contours, not to the contours themselves.

Animals↗
PubMed2002

The mirrored methionine sulfoxide reductases of Neisseria gonorrhoeae pilB.

Methionine sulfoxide reductases (Msr) protect against oxidative damage that can contribute to cell death. The tandem Msr domains (MsrA and MsrB) of the pilB protein from Neisseria gonorrhoeae each reduce different epimeric forms of methionine sulfoxide. The overall fold of the MsrB domain revealed by the 1.85 A crystal structure shows no resemblance to the previously determined MsrA structures from other organisms. Despite the lack of homology, the active sites show approximate mirror symmetry. In each case, conserved amino acid motifs mediate the stereo-specific recognition and reduction of the substrate. Unlike the MsrA domain, the MsrB domain activates the cysteine or selenocysteine nucleophile through a unique Cys-Arg-Asp/Glu catalytic triad. The collapse of the reaction intermediate most likely results in the formation of a sulfenic or selenenic acid moiety. Regeneration of the active site occurs through a series of thiol-disulfide exchange steps involving another active site Cys residue and thioredoxin. These observations have broad implications for modular catalysis, antibiotic drug design and continuing longevity studies in mammals.

Amino Acid Sequence↗
PubMed2006

Inhibition of stimulated meningeal blood flow by a calcitonin gene-related peptide binding mirror-image RNA oligonucleotide.

Calcitonin gene-related peptide (CGRP) released from trigeminal afferents is known to play an important role in the control of intracranial blood flow. In a rat preparation with exposed cranial dura mater, periods of electrical stimulation induce increases in meningeal blood flow. These responses are due to arterial vasodilatation mediated in part by the release of CGRP. In this preparation, the effect of a CGRP-binding mirror-image oligonucleotide (Spiegelmer NOX-C89) was examined. Spiegelmer NOX-C89 applied topically at concentrations between 10(-7) and 10(-5) M to the exposed dura mater led to a dose-dependent inhibition of the electrically evoked blood flow increases. The highest dose reduced the mean increases in flow to 56% of the respective control levels. A nonfunctional control Spiegelmer (not binding to CGRP) was ineffective in changing blood flow increases. Intravenous injection of NOX-C89 (5 mg kg(-1)) reduced the evoked blood flow increases to an average of 65.5% of the control. The basal blood flow was not changed by any of the applied substances. In addition, an ex vivo preparation of the hemisected rat skull was used to determine CGRP release from the cranial dura mater caused by antidromic activation of meningeal afferents. In this model, 10(-6) M of NOX-C89 reduced the evoked CGRP release by about 50%. We conclude that increases in meningeal blood flow due to afferent activation can be reduced by sequestering the released CGRP and thus preventing it from activating vascular CGRP receptors. Moreover, the Spiegelmer NOX-C89 may inhibit CGRP release from meningeal afferents. Therefore, the approach to interfere with the CGRP/CGRP receptor system by binding the CGRP may open a new opportunity for the therapy of diseases that are linked to excessive CGRP release such as some forms of primary headaches.

Animals↗
PubMed2003

Parallel nucleic acid recognition by the LNA (locked nucleic acid) stereoisomers beta-L-LNA and alpha-D-LNA; studies in the mirror image world.

Two LNA (locked nucleic acid) stereoisomers (beta-L-LNA and alpha-D-LNA) are evaluated in the mirror-image world, that is by the study of two mixed sequences of LNA and alpha-L-LNA and their L-DNA and L-RNA complements. Both are found to display high-affinity RNA-recognition by the formation of duplexes with parallel strand orientation.

Base Sequence↗
PubMed2002

Characterization of autoantibodies from patients with Goodpasture's disease using a resonant mirror biosensor.

Goodpasture's disease is characterized by the binding of IgG autoantibodies to the glomerular basement membrane, leading to glomerular inflammation. The autoantigen has been identified as the noncollagenous domain of the alpha3 chain of type IV collagen (alpha3(IV)NC1). We have used the IAsys resonant mirror biosensor to analyse the extent and affinity of binding of anti-GBM antibodies from sera of patients to purified alpha3(IV) NC1. alpha3(IV) NC1 monomers were immobilized to a carboxylate cuvette, with the simultaneous use of a control well. The binding of serum from patients with Goodpasture's disease (n = 12), normal controls (n = 14) and disease controls with vasculitis (n = 14) was analysed. Antibody binding was detected in sera from all patients with Goodpasture's disease but not from controls. IAsys measurements of binding correlated with antibody levels assessed by the standardized ELISA used for clinical assays. Both ELISA and biosensor measurements showed declining antibody levels in serial serum samples from treated patients; however, the biosensor detected antibody recrudescence when ELISA remained negative. Autoantibodies from patients' serum had average affinity constants (Kd) of 6.5 x 10-11M to 52.07 x 10-10M, as determined by an inhibition assay, indicating high affinity. Sips analysis showed that the antibody response was relatively homogeneous (values of 0.46-1). Biosensor techniques can therefore be used to detect and characterize anti-GBM antibodies in serum from patients, with high sensitivity and without need for antibody purification. This technique may be useful in diagnosis and monitoring of patients with Goodpasture's disease, and may be applicable to other autoantibody mediated diseases.

Adolescent↗
PubMed1999

A novel immunohistochemical detection system using mirror image complementary antibodies (MICA).

AIMS: To describe and illustrate a novel and highly sensitive peroxidase-based immunohistochemical detection system which employs mutually attractive, mirror image complementary antibodies (MICA). METHODS AND RESULTS: To demonstrate the sensitivity of the MICA system alongside the avidin-biotin complex (ABC) method, we selected a range of mouse monoclonal and rabbit polyclonal primary antibodies against antigens that are generally regarded as relatively difficult or impossible to detect on formalin-fixed, paraffin-embedded lymphoid tissue. Compared with the ABC method, the MICA immunodetection method enabled us to dilute primary antibodies up to 200-fold with equivalent or superior immunostaining results and, usually, considerably shortened primary antibody incubation times. CONCLUSIONS: We have described and illustrated a novel immunohistochemical detection system and demonstrated greatly increased sensitivity over the commonly used ABC system. An additional advantage of the MICA system is that it is avidin-free and so avoids non-specific staining due to endogenous tissue biotin.

Animals↗
PubMed2001

Peculiarities of imaging one- and two-dimensional structures using an electron microscope in the mirror operation mode.

Measurements performed in an electron microscope with the mirror operation mode are most sensitive to local electric fields and geometrical roughness of any kind of the object being studied. The object with a geometrical relief is equivalent to a smooth surface with an effective distribution of microfields. Electrons forming the image interact with the local microfields for an extended time: during approach to the object, deceleration and acceleration away from the object. As a result, the electron trajectories can be strongly distorted, and the contrast changes essentially, leading to image deformation of details of the object under investigation and to lowering of the resolution. These effects are theoretically described and are illustrated by experiments. An analysis of these effects enables the real size and the shape of the object involved to be reconstructed.

Journal Article↗
PubMed1981

Optical information and practice in the discrimination of 3-D mirror-reflected objects.

Two studies of the discrimination of three-dimensional mirror-reflected objects were concerned with the influence of practice and stimulus information for shape, specifically binocular information and perspective transformations. In the first study subjects made 'same-different' responses to successively presented pairs of real objects, under binocular and monocular viewing conditions. In the second study subjects viewed object pairs on a rotating turntable, in five different displays. Neither binocular information nor perspective transformations contributed to isomorph discrimination. In both studies mental rotation and other less well specified strategies were employed. After practice, in contrast to previous reports, five of the six subjects in these studies produced reaction times unrelated to the orientation difference between the objects. These practice effects may reflect either extremely rapid rotation rates, the detection of rotationally invariant features, or the use of multiple strategies.

Cues↗
PubMed1985

It's all done with mirrors: proof of non-existence.

Mirrors can show us to be absent (with minimal cognitive damage) and also can show imaginary lines to be unreal (again with little or no effect on the adjoining percept). The processes that create the subjective lines are immune to the optic information that the lines do not exist.

Cognition↗
PubMed1998

Effects of pattern orientation and number of symmetry axes on the detection of mirror symmetry in dot and solid patterns.

It has been postulated that as the number of axes of symmetry in a pattern increases, so pattern 'goodness' increases. Recently, a distinction was made between two different theoretical accounts of regularity or 'goodness' in relation to patterns with mirror symmetry: the 'transformational' and the 'holographic' models. It was argued that the former predicts a 'goodness' ordering of four > three > two > one whereas the latter predicts four > two > three > one, where '>' means greater regularity or goodness. In three experiments, we have tested these predictions. In experiment 1, we measured percentage correct and reaction time to dot patterns which had one, two, three, or four axes of symmetry and were flashed for 150 ms. Experiment 2 was identical except that patterns were presented for 2000 ms. In experiment 3, dot patterns were replaced by solid shapes which also had one, two, three, or four axes of symmetry. Although it was found that stimuli with four axes clearly allowed superior performance to that of stimuli with one axis, results obtained with stimuli with two and three axes were almost identical and in between those obtained with one and four axes. The data thus support the suggestion that extra axes add 'goodness' to symmetrical patterns but not in a monotonic fashion.

Computer Graphics↗
PubMed2006

Developmental plasticity mirrors differences among taxa in spadefoot toads linking plasticity and diversity.

Developmental plasticity is found in most organisms, but its role in evolution remains controversial. Environmentally induced phenotypic differences may be translated into adaptive divergence among lineages experiencing different environmental conditions through genetic accommodation. To examine this evolutionary mechanism, we studied the relationship between plasticity in larval development, postmetamorphic morphology, and morphological diversity in spadefoot toads, a group of closely related species that are highly divergent in the larval period and body shape and are distributed throughout temperate areas of both the New and the Old World. Previous studies showed that accelerated metamorphosis is adaptive for desert-dwelling spadefoot toads. We show that even under common garden conditions, spadefoot toad species show divergent reaction norms for the larval period. In addition, experimentally induced changes in the larval period caused correlated morphological changes in postmetamorphic individuals such that long larval periods resulted in relatively longer hindlimbs and snouts. A comparative analysis of morphological variation across spadefoot toad species also revealed a positive correlation between the larval period and limb and snout lengths, mirroring the effects of within-species plasticity at a higher taxonomic level. Indeed, after approximately 110 Ma of independent evolution, differences in the larval period explain 57% of the variance in relative limb length and 33% of snout length across species. Thus, morphological diversity across these species appears to have evolved as a correlated response to selection for a reduced larval period in desert-dwelling species, possibly diverging from ancestral plasticity through genetic accommodation.

Animals↗
PubMed1996

Crystal structure of D-amino acid oxidase: a case of active site mirror-image convergent evolution with flavocytochrome b2.

D-amino acid oxidase is the prototype of the FAD-dependent oxidases. It catalyses the oxidation of D-amino acids to the corresponding alpha-ketoacids. The reducing equivalents are transferred to molecular oxygen with production of hydrogen peroxide. We have solved the crystal structure of the complex of D-amino acid oxidase with benzoate, a competitive inhibitor of the substrate, by single isomorphous replacement and eightfold averaging. Each monomer is formed by two domains with an overall topology similar to that of p-hydroxybenzoate hydroxylase. The benzoate molecule lays parallel to the flavin ring and is held in position by a salt bridge with Arg-283. Analysis of the active site shows that no side chains are properly positioned to act as the postulated base required for the catalytic carboanion mechanism. On the contrary, the benzoate binding mode suggests a direct transfer of the substrate alpha-hydrogen to the flavin during the enzyme reductive half-reaction. The active site Of D-amino acid oxidase exhibits a striking similarity with that of flavocytochrome b2, a structurally unrelated FMN-dependent flavoenzyme. The active site groups (if these two enzymes are in fact superimposable once the mirror-image of the flavocytochrome b2 active site is generated with respect to the flavin plane. Therefore, the catalytic sites of D-amino acid oxidase and flavocytochrome b2 appear to have converged to a highly similar but enantiomeric architecture in order to catalvze similar reactions (oxidation of alpha-amino acids or alpha-hydroxy acids), although with opposite stereochemistry.

4-Hydroxybenzoate-3-Monooxygenase↗
PubMed1997

Reversible calcium-dependent interaction of liposomes with pulmonary surfactant protein A. Analysis by resonant mirror technique and near-infrared light scattering.

Surfactant protein A (SP-A) is crucial for lung function, including tubular myelin formation and lipid uptake by type II pneumocytes. Known properties of SP-A in vitro are its Ca2+-dependent interaction with phospholipids and its role in the aggregation of liposomes. To dissect and to analyze these processes, we have immobilized SP-A and measured binding of liposomes by the resonant mirror technique. Liposome aggregation was followed separately by kinetic light scattering in suspensions. It was found that SP-A-mediated binding and aggregation of liposomes have a common K0.5 of 20 microM for free Ca2+, independent of the species (sheep, rat, or cow) and of the phospholipid composition, and that both reactions exhibit the same high cooperativity (Hill coefficients of 6-9) for Ca2+ ions. However, binding of liposomes to SP-A is >10-fold faster than aggregation. Both processes are completely reversed by low Ca2+ concentrations, but liposomes dissociate from SP-A in <0.3 s, whereas disaggregation of the liposomes takes approximately 30 s. At equilibrium, the level of aggregation depends on the concentration of free SP-A. We interpret these results to be a rapid and reversible sequence of three reactions: (i) a cooperative Ca2+-dependent conformational change in SP-A, (ii) binding of Ca2+-bound SP-A to liposomes, and (iii) aggregation of the Ca2+/SP-A-bound liposomes.

Animals↗
PubMed2003

Acetylation of histone H2B mirrors that of H4 and H3 at the chicken beta-globin locus but not at housekeeping genes.

Acetylation of histones H4 and H3 targeted to promoters/enhancers is linked to the activation of transcription, whereas widespread, long range acetylation of the same histones has been linked to the requirement for open chromatin at transcriptionally active loci and regions of V(D)J recombination. Using affinity-purified polyclonal antibodies to tetra/tri-acetylated histone H2B in chromatin immunoprecipitation (ChIP) assays with mononucleosomes from 15-day chicken embryo erythrocytes, a high resolution distribution of H2B acetylation has been determined and compared with that of H4 and H3 at the same genes/loci. At the beta-globin locus, the H2B acetylation is high throughout and in general mirrors that of H3 and H4, consistent with the observation of co-precipitation of hyperacetylated H4 together with the hyperacetylated H2B. In contrast, at the weakly expressed genes glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and Gas41 (housekeeping) and carbonic anhydrase (tissue specific), very little or no hyperacetylated H2B was found despite the presence of acetylated H4 and H3 at their promoters and proximal transcribed sequences. At the inactive lysozyme and ovalbumin genes essentially no acetylation of H2B, H3, or H4 was observed. Acetylation of H2B appears to be principally a feature of only the most actively transcribed genes/loci.

Animals↗
PubMed1999

Mirror Writing: Learning, Transfer, and Implications for Internal Inverse Models.

In a study of the effects of practicing mirror writing, the effects of transfer to the nonpracticed hand and to nonpracticed phrases were assessed in 185 students. Large transfer effects were observed. An interpretation of those effects is based on a suggestion that the learning led to the creation of a new internal inverse model (or a modification of a pre-existent model) mapping the space of task variables onto the space of internal variables.

Journal Article↗