Local states of chromatin compaction at transcription start sites control transcription levels.

The 'open' and 'compact' regions of chromatin are considered to be regions of active and silent transcription, respectively. However, individual genes produce transcripts at different levels, suggesting that transcription output does not depend on the simple open-compact conversion of chromatin, but on structural variations in chromatin itself, which so far have remained elusive. In this study, weakly crosslinked chromatin was subjected to sedimentation velocity centrifugation, which fractionated the chromatin according to its degree of compaction. Open chromatin remained in upper fractions, while compact chromatin sedimented to lower fractions depending on the level of nucleosome assembly. Although nucleosomes were evenly detected in all fractions, histone H1 was more highly enriched in the lower fractions. H1 was found to self-associate and crosslinked to histone H3, suggesting that H1 bound to H3 interacts with another H1 in an adjacent nucleosome to form compact chromatin. Genome-wide analyses revealed that nearly the entire genome consists of compact chromatin without differences in compaction between repeat and non-repeat sequences; however, active transcription start sites (TSSs) were rarely found in compact chromatin. Considering the inverse correlation between chromatin compaction and RNA polymerase binding at TSSs, it appears that local states of chromatin compaction determine transcription levels.

Oxidation of Anatase TiO2(001) Surface Using Supersonic Seeded Oxygen Molecular Beam.

We investigated the oxidation of oxygen vacancies at the surface of anatase TiO2(001) using a supersonic seeded molecular beam (SSMB) of oxygen. The oxygen vacancies at the top surface and subsurface could be eliminated by the supply of oxygen using an SSMB. Oxygen vacancies are present on the surface of anatase TiO2(001) when it is untreated before transfer to a vacuum chamber. These vacancies, which are stable in the as-grown condition, could also be effectively eliminated by using the oxygen SSMB.

Role of tip apices in scanning force spectroscopy on alkali halides at room temperature-chemical nature of the tip apex and atomic-scale deformations.

We have revealed processes of the tip apex distortion in the measurements of non-contact scanning force microscopy. High-spatial-resolution two-dimensional force mapping on KCl(100) surfaces for a large number of tips, seven tips, enabled us to see the complex behavior of the tip apex distortion. The tips are from Si without additional coating, but are altered by the tip-sample interaction and show the behavior of different atomic species. On the KCl(001) surfaces, the tip apex, consisting of K and Cl atoms or of Si, distorted several times while changing the distance even in a weak attractive region. There are variations in rigidity of the tip apex, but all tips distorted in the small attractive region. This complex behavior was categorized in patterns by our analyses. We compare the experimental force-distance data to atomistic simulations using rigid KCl-terminated tips and KCl-terminated tips with an additional KCl-pair designed to perform atomic jumps. We also compare the experimental force-distance data to first principles simulations using Si tips. We mainly find K-terminated tips and Si-terminated tips. We find that Si tips show only one force minimum whereas KCl-terminated tips show two force minima in line with the stronger rigidity of Si compared to KCl. At room temperature, the tip apex atoms can perform atomic jumps that change the atomic configuration of the tip apex.

Arthroscopic superior capsule reconstruction with Teflon felt synthetic graft for irreparable massive rotator cuff tears: clinical and radiographic results at minimum 2-year follow-up.

BACKGROUND: Superior capsule reconstruction (SCR) was developed to improve shoulder function and relieve pain in patients with irreparable rotator cuff tears. Here, we investigated the clinical and radiographic outcomes and postoperative complications of SCR using a Teflon graft for reconstruction. METHODS: Thirty-five consecutive patients with irreparable rotator cuff tears underwent SCR with Teflon grafts. The American Shoulder and Elbow Surgeons score, active shoulder elevation, shoulder muscle strength, visual analog scale pain scores, acromiohumeral distance, and postoperative complications were investigated. Data obtained before and after surgery were compared by using a paired t-test, χ2 test, and 1-way analysis of variance, and data from 1-layer-graft SCR (15 patients; mean age, 75.1 years) and 3-layer-graft SCR (20 patients; mean age, 76.6 years) were compared by using an unpaired t-test. The average time to final follow-up was 42 months (range, 24-69 months). RESULTS: SCR using Teflon grafts of either 1 or 3 layers significantly improved the American Shoulder and Elbow Surgeons score (by 20.8, P = .001 for a 1-layer graft; and by 31.1, P < .0001 for a 3-layer graft), visual analog scale score for motion pain (by 3.2, P = .001; and by 3.0, P < .0001), and muscle strength in shoulder abduction (by 11.9 N, P = .02; and by 10.9 N, P = .008). Active elevation at final follow-up was significantly greater in the 3-layer-graft group (142° ± 27°) than in the 1-layer-graft group (107° ± 42°) (P = .006). One year after SCR, acromiohumeral distance in the 3-layer-graft group was significantly greater than preoperatively (P = .04), whereas in the 1-layer-graft group, it was not. On postoperative magnetic resonance imaging, none of the patients in the 3-layer-graft group had graft tears, whereas 2 patients had graft tears and 1 patient had severe synovitis after 1-layer-graft SCR. CONCLUSION: SCR using a Teflon graft-especially a 3-layer graft-significantly improved shoulder function and shoulder abduction strength, with pain relief and a low rate of postoperative complications. SCR using a Teflon graft can be a viable option for irreparable rotator cuff tears, especially when an autograft or allograft is not available.

Imaging patterns of anatase TiO2(001) with non-contact atomic force microscopy.

Image patterns of anatase TiO2(001) with non-contact atomic force microscopy (NC-AFM) are presented. A combined system of NC-AFM with pulsed laser deposition, scanning tunneling microscopy (STM), and low energy electron diffraction (LEED) enables us to prepare clean surfaces of anatase TiO2 thin films and to perform measurements on them without breaking the vacuum or the need of cleaning the surface with sputtering and annealing cycles. Results from STM and LEED show that the anatase TiO2(001) films display a (1 × 4) surface pattern of row structures. At far distances, in which the frequency shift was relatively small, NC-AFM images show three different patterns (labeled as protrusion, hole, and neutral contrast, respectively) similar to the ones that have been reported before in the studies of the rutile TiO2 surface. At closer tip-sample distances, a periodic pattern consistent with the TiO2 lattice constant was observed along the higher-positioned TiO3 rows. We have also observed that energy dissipation is induced only with platinum tips, and not with other tip apexes.

Fermented product of rice with Lactobacillus kefiranofaciens induces anti-aging effects and heat stress tolerance in nematodes via DAF-16.

Rice kefiran is superior in functionality, has high concentration of mucilaginous polysaccharide, and low lipid content, compared to conventional kefiran. However, reports on its physiological functionality, especially studies on life expectancy and aging, in model organisms are rare. In this study, nematodes were used as model organisms that were fed rice kefiran, along with Escherichia coli OP50, as a result of which, the lifespan of nematodes was extended and age-related retardation of mobility was suppressed. It also increased the heat stress resistance in nematodes. Experiments using daf-16 deletion mutant revealed that rice kefiran functions via DAF-16. Thus, this study revealed the longevity, anti-aging and heat stress tolerance effects of rice kefiran in nematodes.

Bifacial Nucleobases for Hexaplex Formation in Aqueous Solution.

Although DNA can form triplex and quadruplex structures through hydrogen bonds, design and preparation of structures with more than five strands is difficult even when artificial nucleic acids are used. Herein we report a hexaplex formed by oligomers of artificial nucleic acids bearing bifacial molecules on d-threoninol. Aminopyrimidine and cyanuric acid derivatives were selected as bases because they have complementary hydrogen bonding patterns. The complex formed by aminopyrimidine and cyanuric acid decamers melted with large hysteresis. Hexaplex formation was indicated by gel electrophoresis, size exclusion chromatography and atomic force microscopy imaging, and proven directly through native mass spectrometry. CD measurements and molecular dynamics simulations indicated that the hexaplex adopts a helical structure. The hexaplex formation was highly dependent on pH and the presence of divalent cations. The hexaplex was stable in aqueous solution, and its unique structure and properties may lead to novel nanostructures, molecular assemblies, metal sensors, and ion channels.

A new efficient method of generating photoaffinity beads for drug target identification.

Affinity purification is one of the most prevalent methods for the target identification of small molecules. Preparation of an appropriate chemical for immobilization, however, is a tedious and time-consuming process. A decade ago, a photoreaction method for generating affinity beads was reported, where compounds are mixed with agarose beads carrying a photoreactive group (aryldiazirine) and then irradiated with ultraviolet light under dry conditions to form covalent attachment. Although the method has proven useful for identifying drug targets, the beads suffer from inefficient ligand incorporation and tend to shrink and aggregate, which can cause nonspecific binding and low reproducibility. We therefore decided to craft affinity beads free from these shortcomings without compromising the ease of preparation. We herein report a modified method; first, a compound of interest is mixed with a crosslinker having an activated ester and a photoreactive moiety on each end. This mixture is then dried in a glass tube and irradiated with ultraviolet light. Finally, the conjugates are dissolved and reacted with agarose beads with a primary amine. This protocol enabled us to immobilize compounds more efficiently (approximately 500-fold per bead compared to the original method) and generated beads without physical deterioration. We herein demonstrated that the new FK506-immobilized beads specifically isolated more FKBP12 than the original beads, thereby proving our method to be applicable to target identification experiments.

Effects of Pb Intercalation on the Structural and Electronic Properties of Epitaxial Graphene on SiC.

The effects of Pb intercalation on the structural and electronic properties of epitaxial single-layer graphene grown on SiC(0001) substrate are investigated using scanning tunneling microscopy (STM), noncontact atomic force microscopy, Kelvin probe force microscopy (KPFM), X-ray photoelectron spectroscopy, and angle-resolved photoemission spectroscopy (ARPES) methods. The STM results show the formation of an ordered moiré superstructure pattern induced by Pb atom intercalation underneath the graphene layer. ARPES measurements reveal the presence of two additional linearly dispersing π-bands, providing evidence for the decoupling of the buffer layer from the underlying SiC substrate. Upon Pb intercalation, the Si 2p core level spectra show a signature for the existence of PbSi chemical bonds at the interface region, as manifested in a shift of 1.2 eV of the bulk SiC component toward lower binding energies. The Pb intercalation gives rise to hole-doping of graphene and results in a shift of the Dirac point energy by about 0.1 eV above the Fermi level, as revealed by the ARPES measurements. The KPFM experiments have shown that decoupling of the graphene layer by Pb intercalation is accompanied by a work function increase. The observed increase in the work function is attributed to the suppression of the electron transfer from the SiC substrate to the graphene layer. The Pb intercalated structure is found to be stable in ambient conditions and at high temperatures up to 1250 °C. These results demonstrate that the construction of a graphene-capped Pb/SiC system offers a possibility of tuning the graphene electronic properties and exploring intriguing physical properties such as superconductivity and spintronics.

Interplay between Switching Driven by the Tunneling Current and Atomic Force of a Bistable Four-Atom Si Quantum Dot.

We assemble bistable silicon quantum dots consisting of four buckled atoms (Si4-QD) using atom manipulation. We demonstrate two competing atom switching mechanisms, downward switching induced by tunneling current of scanning tunneling microscopy (STM) and opposite upward switching induced by atomic force of atomic force microscopy (AFM). Simultaneous application of competing current and force allows us to tune switching direction continuously. Assembly of the few-atom Si-QDs and controlling their states using versatile combined AFM/STM will contribute to further miniaturization of nanodevices.

AI-Equipped Scanning Probe Microscopy for Autonomous Site-Specific Atomic-Level Characterization at Room Temperature.

An advanced scanning probe microscopy system enhanced with artificial intelligence (AI-SPM) designed for self-driving atomic-scale measurements is presented. This system expertly identifies and manipulates atomic positions with high precision, autonomously performing tasks such as spectroscopic data acquisition and atomic adjustment. An outstanding feature of AI-SPM is its ability to detect and adapt to surface defects, targeting or avoiding them as necessary. It is also designed to overcome typical challenges such as positional drift and tip apex atomic variations due to the thermal effects, ensuring accurate, site-specific surface analysis. The tests under the demanding conditions of room temperature have demonstrated the robustness of the system, successfully navigating thermal drift and tip fluctuations. During these tests on the Si(111)-(7 × 7) surface, AI-SPM autonomously identified defect-free regions and performed a large number of current-voltage spectroscopy measurements at different adatom sites, while autonomously compensating for thermal drift and monitoring probe health. These experiments produce extensive data sets that are critical for reliable materials characterization and demonstrate the potential of AI-SPM to significantly improve data acquisition. The integration of AI into SPM technologies represents a step toward more effective, precise and reliable atomic-level surface analysis, revolutionizing materials characterization methods.

Solving variability: Accurately extracting feature components from ballistocardiograms.

Objective: A ballistocardiogram (BCG) is a vibration signal generated by the ejection of the blood in each cardiac cycle. The BCG has significant variability in amplitude, temporal aspects, and the deficiency of waveform components, attributed to individual differences, instantaneous heart rate, and the posture of the person being measured. This variability may make methods of extracting J-waves, the most distinct components of BCG less generalizable so that the J-waves could not be precisely localized, and further analysis is difficult. This study is dedicated to solving the variability of BCG to achieve accurate feature extraction. Methods: Inspired by the generation mechanism of the BCG, we proposed an original method based on a profile of second-order derivative of BCG waveform (2ndD-P) to capture the nature of vibration and solve the variability, thereby accurately localizing the components especially when the J-wave is not prominent. Results: In this study, 51 recordings of resting state and 11 recordings of high-heart-rate from 24 participants were used to validate the algorithm. Each recording lasts about 3 min. For resting state data, the sensitivity and positive predictivity of proposed method are: 98.29% and 98.64%, respectively. For high-heart-rate data, the proposed method achieved a performance comparable to those of low-heart-rate: 97.14% and 99.01% for sensitivity and positive predictivity, respectively. Conclusion: Our proposed method can detect the peaks of the J-wave more accurately than conventional extraction methods, under the presence of different types of variability. Higher performance was achieved for BCG with non-prominent J-waves, in both low- and high-heart-rate cases.

Structure and Defect Identification at Self-Assembled Islands of CO2 Using Scanning Probe Microscopy.

Understanding how carbon dioxide (CO2) behaves and interacts with surfaces is paramount for the development of sensors and materials to attempt CO2 mitigation and catalysis. Here, we combine simultaneous atomic force microscopy (AFM) and scanning tunneling microscopy (STM) using CO-functionalized probes with density functional theory (DFT)-based simulations to gain fundamental insight into the behavior of physisorbed CO2 molecules on a gold(111) surface that also contains one-dimensional metal-organic chains formed by 1,4-phenylene diisocyanide (PDI) bridged by gold (Au) adatoms. We resolve the structure of self-assembled CO2 islands, both confined between the PDI-Au chains as well as free-standing on the surface and reveal a chiral arrangement of CO2 molecules in a windmill-like structure that encloses a standing-up CO2 molecule and other foreign species existing at the surface. We identify these species by the comparison of height-dependent AFM and STM imaging with DFT-calculated images and clarify the origin of the kagome tiling exhibited by this surface system. Our results show the complementarity of AFM and STM using functionalized probes and their potential, when combined with DFT, to explore greenhouse gas molecules at surface-supported model systems.

Can AI predict walking independence in patients with stroke upon admission to a recovery-phase rehabilitation ward?

Ono K, Takahashi R, Morita K, Ara Y, Abe S, Ito S, Uno S, Abe M, Shirasaka T. Can AI predict walking independence in patients with stroke upon admission to a recovery-phase rehabilitation ward? Jpn J Compr Rehabil Sci 2024; 15: 1-7. Objective: This study aimed to develop a prediction model for walking independence in patients with stroke in the recovery phase at the time of hospital discharge using Prediction One, an artificial intelligence (AI)-based predictive analysis tool, and to examine its utility. Methods: Prediction One was used to develop a prediction model for walking independence for 280 patients with stroke admitted to a rehabilitation ward-based on physical and mental function information at admission. In 134 patients with stroke hospitalized during different periods, accuracy was confirmed by calculating the correct response rate, sensitivity, specificity, and positive and negative predictive values based on the results of AI-based predictions and actual results. Results: The prediction accuracy (area under the curve, AUC) of the proposed model was 91.7%. The correct response rate was 79.9%, sensitivity was 95.7%, specificity was 62.5%, positive predictive value was 73.6%, and negative predictive value was 93.5%. Conclusion: The accuracy of the prediction model developed in this study is not inferior to that of previous studies, and the simplicity of the model makes it highly practical.

Quantum degeneracy in atomic point contacts revealed by chemical force and conductance.

Quantum degeneracy is an important concept in quantum mechanics with large implications to many processes in condensed matter. Here, we show the consequences of electron energy level degeneracy on the conductance and the chemical force between two bodies at the atomic scale. We propose a novel way in which a scanning probe microscope can detect the presence of degenerate states in atomic-sized contacts even at room temperature. The tunneling conductance G and chemical binding force F between two bodies both tend to decay exponentially with distance in a certain distance range, usually maintaining direct proportionality G∝F. However, we show that a square relation G∝F2 arises as a consequence of quantum degeneracy between the interacting frontier states of the scanning tip and a surface atom. We demonstrate this phenomenon on the Si(111)-(7×7) surface reconstruction where the Si adatom possesses a strongly localized dangling-bond state at the Fermi level.

Chemical identification of individual surface atoms by atomic force microscopy.

Scanning probe microscopy is a versatile and powerful method that uses sharp tips to image, measure and manipulate matter at surfaces with atomic resolution. At cryogenic temperatures, scanning probe microscopy can even provide electron tunnelling spectra that serve as fingerprints of the vibrational properties of adsorbed molecules and of the electronic properties of magnetic impurity atoms, thereby allowing chemical identification. But in many instances, and particularly for insulating systems, determining the exact chemical composition of surfaces or nanostructures remains a considerable challenge. In principle, dynamic force microscopy should make it possible to overcome this problem: it can image insulator, semiconductor and metal surfaces with true atomic resolution, by detecting and precisely measuring the short-range forces that arise with the onset of chemical bonding between the tip and surface atoms and that depend sensitively on the chemical identity of the atoms involved. Here we report precise measurements of such short-range chemical forces, and show that their dependence on the force microscope tip used can be overcome through a normalization procedure. This allows us to use the chemical force measurements as the basis for atomic recognition, even at room temperature. We illustrate the performance of this approach by imaging the surface of a particularly challenging alloy system and successfully identifying the three constituent atomic species silicon, tin and lead, even though these exhibit very similar chemical properties and identical surface position preferences that render any discrimination attempt based on topographic measurements impossible.

Dimerization processes for light-regulated transcription factor Photozipper visualized by high-speed atomic force microscopy.

Dimerization is critical for transcription factors (TFs) to bind DNA and regulate a wide variety of cellular functions; however, the molecular mechanisms remain to be completely elucidated. Here, we used high-speed atomic force microscopy (HS-AFM) to observe the dimerization process for a photoresponsive TF Photozipper (PZ), which consists of light-oxygen-voltage-sensing (LOV) and basic-region-leucine-zipper (bZIP) domains. HS-AFM visualized not only the oligomeric states of PZ molecules forming monomers and dimers under controlled dark-light conditions but also the domain structures within each molecule. Successive AFM movies captured the dimerization process for an individual PZ molecule and the monomer-dimer reversible transition during dark-light cycling. Detailed AFM images of domain structures in PZ molecules demonstrated that the bZIP domain entangled under dark conditions was loosened owing to light illumination and fluctuated around the LOV domain. These observations revealed the role of the bZIP domain in the dimerization processes of a TF.

The allenic carotenoid fucoxanthin, a novel marine nutraceutical from brown seaweeds.

Obesity and type 2 diabetes are pathologies with rapidly growing prevalence throughout the world. A few molecular targets offer the most hope for anti-obesity and anti-diabetic therapeutics. One of the keys to success will be the induction of uncoupling protein 1 (UCP1) in abdominal white adipose tissue (WAT) and the regulation of cytokine secretions from both abdominal adipose cells and macrophage cells infiltrated into adipose tissue. Anti-obesity and anti-diabetic effects of fucoxanthin, a characteristic carotenoid found in brown seaweeds, have been reported. Nutrigenomic studies reveal that fucoxanthin induces UCP1 in abdominal WAT mitochondria, leading to the oxidation of fatty acids and heat production in WAT. Fucoxanthin improves insulin resistance and decreases blood glucose levels through the regulation of cytokine secretions from WAT. The key structure of carotenoids for the expression of anti-obesity effect is suggested to be the carotenoid end of the polyene chromophore, which contains an allenic bond and two hydroxyl groups.

The time domain numerical method of three-dimensional conductors including radiation with lumped parameter circuit.

We formulate a numerical method on the transmission and radiation theory of three-dimensional conductors starting from the Maxwell equations in the time domain. We include the delay effect in the integral equations for the scalar and vector potentials rigorously, which is vital to obtain numerically stable solutions for transmission and radiation phenomena in conductors. We provide a formalism to connect the conductors to any passive lumped-parameter circuits. We show one example of numerical calculations, demonstrating that the new formalism provides stable solutions to the transmission and radiation phenomena.

A helical amplification system composed of artificial nucleic acids.

Herein we report an amplification system of helical excess triggered by nucleic acid hybridization for the first time. It is usually impossible to prepare achiral nanostructures composed of nucleic acids because of their intrinsic chirality. We used serinol nucleic acid (SNA) oligomers for the preparation of achiral nanowires because SNA oligomers with symmetrical sequences are achiral. Nanowire formation was confirmed by atomic force microscopy and size exclusion chromatography. When a chiral nucleic acid with a sequence complementary to SNA was added to the nanostructure, helicity was induced and a strong circular dichroism signal was observed. The SNA nanowire could amplify the helicity of chiral nucleic acids through nucleobase stacks. The SNA nanostructures have potential for use as platforms to detect chiral biomolecules under aqueous conditions because SNA can be readily functionalized and is water-soluble.