Repetitive DNA sequences are ubiquitous in life, and changes in the number of repeats often have various physiological and pathological implications. DNA repeats are capable of interchanging between different noncanonical and canonical conformations in a dynamic fashion, causing configurational slippage that often leads to repeat expansion associated with neurological diseases. In this report, we used single-molecule spectroscopy together with biophysical analyses to demonstrate the parity-dependent hairpin structural polymorphism of TGGAA repeat DNA. We found that the DNA adopted two configurations depending on the repeat number parity (even or odd). Transitions between these two configurations were also observed for longer repeats. In addition, the ability to modulate this transition was found to be enhanced by divalent ions. Based on the atomic structure, we propose a local seeding model where the kinked GGA motifs in the stem region of TGGAA repeat DNA act as hot spots to facilitate the transition between the two configurations, which may give rise to disease-associated repeat expansion.DNA tandem repeats | DNA slippage | single-molecule spectroscopy | X-ray crystallography D NA replication is a crucial process in all living organisms. Mishaps in the replication process generally lead to deleterious consequences but also drive biological evolution (1). Changes in the number of tandem copies of a specific DNA sequence within the genome are associated with devastating neuropathies and various types of cancer (2, 3). On the other hand, these changes also help shape normal genomic features such as microsatellite polymorphism, which are often used as markers for population biology studies (4).The unit sizes of repetitive DNA sequences involved in repeat number changes range from a single base (e.g., microsatellites) to dodecanucleotides (12 bases, e.g., in progressive myoclonic epilepsy type 1) (5, 6). DNA slippage is believed to be a primary mechanism driving the change in repeat number of various unit sizes. Repetitive DNA sequences often form alternative structures such as bulges and hairpin loops in addition to canonical DNA conformations (7,8). A repeat unit may slip between being part of a hairpin loop, a bulge, or a duplex in a dynamic fashion, which may alter the course of normal cellular DNA chemistry and ultimately lead to repeat expansion associated with neurological diseases (9). (TGGAA) n repeats, for example, may form noncanonical structures such as a hairpin arm (10, 11) or an antiparallel duplex (12). Expansion of this pentanucleotide sequence has been associated with spinocerebellar ataxia 31 (SCA31), an adult-onset autosomal-dominant neurodegenerative disorder (13).In this article, we probed the conformational heterogeneity and stability of hairpins composed of repetitive TGGAA sequences using single-molecule fluorescence resonance energy transfer [single-molecule FRET (smFRET)] spectroscopy and X-ray crystallography as primary tools. Remarkably, we were able to detect two distinct hairpin confi...
Trinucleotide repeat (TNR) sequences, which are responsible for several neurodegenerative genetic diseases, fold into hairpins that interfere with the protein machinery in replication or repair, thus leading to dynamic mutation -abnormal expansions of the genome. Despite their high thermodynamic stability, these hairpins can undergo configurational rearrangements, which may be crucial for continuous dynamic mutation. Here, we used CTG repeats as a model system to study their structural dynamics at the single-molecule level. A unique dynamic two-state configuration interchange was discovered over a wide range of odd-numbered CTG repeat sequences. Employing repeat-number-dependent kinetic analysis, we proposed a bulge translocation model, which is driven by the local instability and can be extended reasonably to longer (pathologically relevant) hairpins, implying the potential role in error accumulation in repeat expansion.
A simple and sensitive biosensor array based on phosphorescence detection that is able to detect oxygen and glucose in human serum, respectively, has been developed. We demonstrate an electrochemical method as a fast, effective, tunable, and versatile means of growing phosphorescence sensing material. This sensing material, crystalline iridium(III)-Zn(II) coordination polymers, namely Ir-Zn(e), was grown on a stainless steel mesh and then doped in a sol-gel matrix. The emission of Ir-Zn(e) was ascribed to a metal-to-ligand charge transfer transition (MLCT). The noteworthy oxygen-sensing properties of Ir-Zn(e) were also evaluated. The optimal oxygen-sensing conditions of Ir-Zn(e) with a deduced K(SV) value of 3.55 were 5 V and 30 °C for 1 hour. Moreover, the short response time (23 s) and the recovery time (21 s) toward oxygen have been measured. The reversibility experiment was carried out for eleven cycles. The resulting >70% recovery of intensity for Ir-Zn(e) on each cycle demonstrated a high degree of reproducibility during the sensing process. The detection limit could be 0.050% for gaseous oxygen. The sensing substrate was subsequently built up under glucose oxidase encapsulated in hydrogel and then immobilized on an egg membrane by the layer-by-layer method. Once the glucose solution was injected into this array, oxygen content depleted simultaneously with a concomitant increase in the phosphorescence of coordination polymers. The linear dynamic range for the determination of glucose was 0.1-6.0 mM, the correlation coefficient (R(2)) was 0.9940 (y = 0.75 [glucose] + 0.539), and the response time was less than 120 s. The minimum detectable concentration for glucose was calculated to be 0.05 mM from three times signal to noise. The photophysical properties of the sensing material and the effects of buffer concentration, pH, interference, matrix effect, temperature, and the stability of the biosensor array have also been studied in detail. The biosensor array was successfully applied to the determination of glucose in human serum.
A unique three-dimensional (3D) supramolecular compound, [Co(dpe)(BTC)(H 2 O)][Co(dpe)(BTC)(H 2 O) 3 ]-[Co(dpe)(HBTC)(H 2 O)][Co(dpe) 2 (H 2 O) 3.5 (EtOH) 0.5 ]•1.5H 2 O (1; dpe = 1,2-bis(4-pyridyl)ethane and H 3 BTC = benzenetricarboxylic acid), has been synthesized and structurally characterized by the single-crystal X-ray diffraction method. Compound 1 consists of four coordination polymers (CPs), two are two-dimensional (2D) layered metal−organic frameworks (MOFs) with (4,4) topology of [Co(dpe)(BTC)(H 2 O)] − and [Co(dpe)(HBTC)(H 2 O)], whereas the other two are onedimensional (1D) polymeric chains of [Co(dpe)(BTC)(H 2 O) 3 ] − and [Co(dpe)(H 2 O) 3.5 (EtOH) 0.5 ] 2+ . The 3D supramolecular architecture of 1 is constructed via the penetration of interdigitated double-layered 2D rectangular-grid frameworks by two 1D coordination polymeric chains and entangled tightly by the subtle combination of intermolecular hydrogen bonding and π−π interactions among the four CPs. Controlled heating of the as-synthesized crystal 1 at ∼160 °C produces a desolvated 1 and accompanying color-changing behavior from pink to deep-blue, and the deep-blue desolvated 1 regenerates the pink rehydrated crystal with the chemical formula of [Co(dpe 2) upon exposure to water vapor. The structural determination of 2 shows almost the same structural characteristics as that of 1 with the only difference being the replacement of disordered coordinated solvent (half H 2 O and half EtOH molecules) by H 2 O and the numbers of solvated water molecules. The cyclic thermogravimetric analysis and powder X-ray diffraction measurements of desolvated 1 demonstrate a reversible rehydration/dehydration property, which is associated with solid-state structural transformation and thermally induced UV−vis absorption properties.
A motivating and fun activity for students in introductory chemistry has been designed to increase familiarity with the chemical elements, symbols, and atomic numbers in the periodic table. This activity, Elemental Knock-Out, is a table tennis game, and the gameplay is adapted from a box grid baseball game. Playing in teams for fun and enjoyment, students work cooperatively with others to compete against an opposing team. The game is designed for first-year undergraduate students. The cost of one set of game materials is less than $50. The average time required to complete one game, i.e., to become familiar with the chemical elements and atomic numbers, is about 120 min for a class of 60 students. This game was implemented with 118 students including different grade classes. The results were interpreted through poll and quiz before and after the activity. The results of the study revealed that most of the students had positive impressions of the game and considered it to be a fun way of interacting with the concepts. The quiz test also showed an increase of average score of the students by playing the game. Table tennis is a sport that anybody at any age can play. Therefore, this game should facilitate the promotion of knowledge of chemistry, e.g., the periodic table of the elements, to the target student group.
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