Mirror-image Counterparts Research Articles

Enhancement of Stress Granule Formation by a Chiral Compound Targeting G3BP1 via eIF2α Phosphorylation.

The chirality of a chemical differentiates it from its mirror-image counterpart. This unique property has significant implications in chemistry, biology, and drug discovery, where chiral chemicals display high selectivity and activity in achieving target specificity and reducing attrition rates in drug development. Stress granules (SGs) are dynamic assemblies of proteins and RNA that form in the cytoplasm of cells under stress conditions. Modulating their formation or disassembly could offer a novel approach to treating a wide range of diseases. This has led to significant interest in SGs as potential therapeutic targets. This study examined the NTF2-like domain of G3BP1 as a possible target for SG modulation. Molecular docking was used to simulate the interactions of compounds with the domain, and a potential candidate with a chiral structure was identified. The experiments showed that the compound induced the formation of SG-like granules. Importantly, the ability of this compound to modulate SG offers valuable insights into a new mechanism underlying the dynamics and promoting the assembly of SGs, and this new mechanism, in turn, holds potential for the development of drugs with diverse mechanisms of action and potentially synergistic effects.

Mirror letter priming is rightward-biased but not inhibitory: Little evidence for a mirror suppression mechanism in the recognition of mirror letters.

Unlike other visual objects which are invariant to the left-right orientation, mirror letters (e.g., b and d) represent different object identities. Previous masked priming lexical decision studies have suggested that the identification of a mirror letter involves suppression of its mirror image counterpart reporting as evidence that a pseudoword prime containing the mirror letter counterpart slowed down the recognition of target word relative to a control prime containing an unrelated letter (e.g., ibea-idea > ilea-idea). Furthermore, it has been reported recently that this inhibitory mirror priming effect is sensitive to the distributional bias of left/right orientation in the Latin alphabet such that only the more dominant (frequent) right-facing mirror letter prime (e.g., b) produced interference. In the present study, we examined mirror letter priming with single letters and nonlexical letter strings with adult readers. In all experiments, relative to a visually dissimilar control letter prime, both the right-facing and left-facing mirror letter prime consistently facilitated, rather than slowed down the recognition of a target letter (e.g., b-d < w-d). Assessed against an identity prime, mirror primes showed a rightward bias, although it was small in magnitude and not always significant within an individual experiment. These results provide no support for a mirror suppression mechanism in the identification of mirror letters, and an alternative interpretation in terms of noisy perception is suggested. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Self-Assembly of DNA-Peptide Supermolecules: Coiled-Coil Peptide Structures Templated by d-DNA and l-DNA Triplexes Exhibit Chirality-Independent but Orientation-Dependent Stabilizing Cooperativity.

DNA nanostructures have been designed and used in many different applications. However, the use of nucleic acid scaffolds to promote the self-assembly of artificial protein mimics is only starting to emerge. Herein five coiled-coil peptide structures were templated by the hybridization of a d-DNA triplex or its mirror-image counterpart, an l-DNA triplex. The self-assembly of the desired trimeric structures in solution was confirmed by gel electrophoresis and small-angle X-ray scattering, and the stabilizing synergy between the two domains was found to be chirality-independent but orientation-dependent. This is the first example of using a nucleic acid scaffold of l-DNA to template the formation of artificial protein mimics. The results may advance the emerging POC-based nanotechnology field by adding two extra dimensions, that is, chirality and polarity, to provide innovative molecular tools for rational design and bottom-up construction of artificial protein mimics, programmable materials and responsive nanodevices.

Mirror-Image Dependence: Targeting Enantiomeric G-Quadruplex DNA Using Triplex Metallohelices.

Natural d-DNA and l-DNA are mirror-image counterparts. However, because of the inherent flexibility and conformation diversity of DNA, it is still not clear how enantiomeric compounds recognize d-DNA and l-DNA. Herein, taking G-quadruplex (G4) DNA as an example that has diverse conformations and distinct biofunctions, the binding of ten pairs of iron triplex metallohelices to d- and l-G4 DNA were evaluated. The Δ-enantiomer binds to d-DNA and the Λ-enantiomer binds to l-DNA, exhibiting almost the same stabilization effect and binding affinity. The binding affinity of the Δ-metallohelix with d-G4 is nearly 70-fold higher than that of Λ-metallohelix binding d-G4. Δ-Metallohelix binding to d-G4 follows a two-step binding process driven by a favorable enthalpy contribution to compensate for the associated unfavorable entropy.

Predominance of lateral over vertical mirror errors in reading: A case for neuronal recycling and inhibition

We investigated whether lateral mirror errors could be more prevalent than vertical mirror errors (e.g., p/q vs. p/b confusions) because mirror generalization is harder to inhibit for the discrimination of a reversible letter and its lateral than its vertical mirror-image counterpart. Expert adult readers performed a negative priming task in which they determined on the prime whether two letters and on the probe whether two objects facing opposite directions were identical. We found in both experiments longer response times for objects facing opposite lateral orientations preceded by a reversible letter and its lateral mirror-image counterpart (e.g., p/q) than preceded by perceptually matched non-reversible letters (e.g., g/j). No negative priming effect was observed when objects that were vertical (Experiment 1 & 2) or lateral (Experiment 2) mirror images of each other were preceded by a letter and its vertical mirror-image counterpart (e.g. p/b). Finally, we observed longer response times for objects that were lateral mirror images of each other after lateral than after vertical reversible letters. These results suggest that lateral mirror errors are more prevalent than vertical ones because mirror generalization might be stronger and thus more difficult to inhibit in the context of the former than the latter.

A thermostable d-polymerase for mirror-image PCR.

Biological evolution resulted in a homochiral world in which nucleic acids consist exclusively of d-nucleotides and proteins made by ribosomal translation of l-amino acids. From the perspective of synthetic biology, however, particularly anabolic enzymes that could build the mirror-image counterparts of biological macromolecules such as l-DNA or l-RNA are lacking. Based on a convergent synthesis strategy, we have chemically produced and characterized a thermostable mirror-image polymerase that efficiently replicates and amplifies mirror-image (l)-DNA. This artificial enzyme, dubbed d-Dpo4-3C, is a mutant of Sulfolobus solfataricus DNA polymerase IV consisting of 352 d-amino acids. d-Dpo4-3C was reliably deployed in classical polymerase chain reactions (PCR) and it was used to assemble a first mirror-image gene coding for the protein Sso7d. We believe that this d-polymerase provides a valuable tool to further investigate the mysteries of biological (homo)chirality and to pave the way for potential novel life forms running on a mirror-image genome.

Capping β-hairpin with N-terminal d-amino acid stabilizes peptide scaffold.

Various strategies exist to stabilize de novo designed synthetic peptide β-hairpins or β-sheets structures, especially at the non-hydrogen bonding position. However, strategies to stabilize strand termini, which are affected by fraying, are highly limited. Here, by substituting N-terminal aliphatic amino acid with its mirror image counterpart, we achieve a significant increase in scaffold stabilization, resulting from the formation of a terminal aliphatic-aromatic hydrophobic CH…pi cluster. Our extensive solution NMR studies support the incorporation of an N-terminal d-aliphatic amino acid in the design of short β-hairpins, while successfully retaining the overall structural scaffold. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 260-266, 2016.

The cost of blocking the mirror generalization process in reading: evidence for the role of inhibitory control in discriminating letters with lateral mirror-image counterparts.

Mirror generalization is detrimental for identifying letters with lateral mirror-image counterparts ('b/d'). In the present study, we investigated whether the discrimination of this type of letters in expert readers might be rooted in the ability to inhibit the mirror-generalization process. In our negative priming paradigm, participants judged whether two letters were identical on the prime and two animals (or buildings) were identical on the probe. In Experiment 1, participants required more time when determining that two animals (but not two buildings) were mirror images of each other when preceded by letters with mirror-image counterparts than without mirror-image counterparts ('a/h'). In Experiment 2, we replicated the results with different letters without mirror-image counterparts and with the type of probe stimuli (animal or building) manipulated as a within-subject factors. Our results suggest that expert readers never completely "unlearn" the mirror-generalization process and still need to inhibit this heuristic to overcome mirror errors.

Cognitive Abilities in Malawi Cichlids (Pseudotropheus sp.): Matching-to-Sample and Image/Mirror-Image Discriminations

The ability to recognize and distinguish between visual stimuli is fundamental for everyday survival of many species. While diverse aspects of cognition, including complex visual discrimination tasks were previously successfully assessed in fish, it remains unknown if fish can learn a matching-to-sample concept using geometrical shapes and discriminate between images and their mirror-image counterparts. For this purpose a total of nine Malawi cichlids (Pseudotropheus sp.) were trained in two matching-to-sample (MTS) and three two-choice discrimination tasks using geometrical, two-dimensional visual stimuli. Two out of the three discrimination experiments focused on the ability to discriminate between images and their mirror-images, the last was a general discrimination test. All fish showed quick associative learning but were unable to perform successfully in a simultaneous MTS procedure within a period of 40 sessions. Three out of eight fish learned to distinguish between an image and its mirror-image when reflected vertically; however none of the fish mastered the task when the stimulus was reflected horizontally. These results suggest a better discrimination ability of vertical compared to horizontal mirror-images, an observation that is widespread in literature on mirror-image discrimination in animals. All fish performed well in the general visual discrimination task, thereby supporting previous results obtained for this species.

Mechanical resolution of chiral objects in achiral media: Where is the size limit?

Macroscopic chiral objects (boats and planes with turned rudders, shoes, etc.) get separated from their mirror-image counterparts by motion in achiral media. However, chiral molecules are not enantio-differentiated without the presence of a chiral environment, which may be due to other chiral molecules in the medium. This article explores the reasons of this micro/macro difference as well as the size borderline between the two regimes. There are two major demarcation lines, both related to the object's chaotic thermal motion. The first one is due to destruction of the necessary spatial orientation by the fast rotational diffusion. Only particles larger than 1 μm can maintain their original orientation for 1 sec or longer. For smaller particles, an additional external orienting factor, e.g., a strong electric field has to be applied. The second limitation is defined by the ratio of the hydrodynamic separation of the enantiomers (which is directly proportional to time) to their displacement due to the translational Brownian motion (which is proportional to square root of time). On the laboratory time scales (up to a year), the chiral objects have to be larger than 0.25 μm to be resolved. On evolutionary time scales, much smaller object could be resolved. For enantiomers approaching the molecular size, periods comparable to the age of the universe would be required.

Mirror imagery and biological selection

Lake Tanganiyka has lefty and righty cichlid fish that show there can be natural selection for a trait over its mirror image counterpart.This raises the question ‘Can there be biological selection of a whole organism over its mirror image counterpart?’ That is, could the fitness of a fish be altered by simply changing it into its own enantaniomorph? My answer is no. I present Flatlander thought experiment to demonstrate that mirror imagecounterparts are duplicates because they only differ in how they happen to be oriented in space. The counterparts have the same intrinsic properties and are in the same environment,so there can be no difference in fitness.

Anisotropy in the extended haptic perception of longitudinal distances.

Using horizontal rotational motions of a hand-held rod, participants in four experiments probed the aperture between two blocks separated in depth. The farther block could be either on the outer or on the inner side of the hand-rod system, defining apertures of opposite sense. The participants reported the perceived size of the in-depth intervals by adjusting, with the nonprobing hand, the lateral separation between two blocks or the egocentric distances of two blocks. Over variations in hand and geometric arrangement of stimulus and report blocks, perceived aperture size depended on the aperture's sense: Apertures with the farther edge on the outer side of the hand-rod were reported as being larger than their mirror image counterparts. The effect was not observed in judgments of a single edge distance (Experiment 5); it was configuration dependent. The sense effect would not be expected from the physical quantity accommodating perceived frontal apertures. Possible expansions of the physical model are discussed.

Discordant situs of thoracic and abdominal viscera

Two instances of levocardia with thoracic situs solitus and abdominal situs inversus, and one of their mirror image counterpart are described. No intracardiac defects were present in 2 cases, and the third had a fossa ovalis type of atrial septal defect with partial anomalous pulmonary venous connection. The course of the inferior vena cava was unusual in that the vein switched abruptly from one to the other side of the abdomen at the liver to connect with the venous atrium located on the opposite side. The cases described are thought to represent a specific type of anomaly of visceral situs, characterized by complete thoracic and abdominal discordance. A similar anatomic relationship of the heart and viscera, and course of the inferior vena cava, may occur in more complex types of heterotaxia associated with severe cardiac anomalies, and asplenia or polysplenia. Analysis of these cases reveals that continuity between the inferior vena cava and morphologic right atrium appears to be the most reliable method for atrial localization.