Therapeutic manipulation of IKBKAP mis-splicing with a small molecule to cure familial dysautonomia.

Approximately half of genetic disease-associated mutations cause aberrant splicing. However, a widely applicable therapeutic strategy to splicing diseases is yet to be developed. Here, we analyze the mechanism whereby IKBKAP-familial dysautonomia (FD) exon 20 inclusion is specifically promoted by a small molecule splice modulator, RECTAS, even though IKBKAP-FD exon 20 has a suboptimal 5' splice site due to the IVS20 + 6 T > C mutation.

Endogenous agonist-bound S1PR3 structure reveals determinants of G protein-subtype bias.

Sphingosine-1-phosphate (S1P) regulates numerous important physiological functions, including immune response and vascular integrity, via its cognate receptors (S1PR1 to S1PR5); however, it remains unclear how S1P activates S1PRs upon binding. Here, we determined the crystal structure of the active human S1PR3 in complex with its natural agonist S1P at 3.2-Å resolution.

Community-acquired fulminant Clostridioides (Clostridium) difficile infection by ribotype 027 isolate in Japan: a case report.

Background: Clostridioides (Clostridium) difficile infection (CDI) has become an increasingly significant disease not only as healthcare-associated infection, but also as community-acquired (CA) infection worldwide. CDI caused by the NAP1/BI/027 strain is reported to be more severe, difficult to cure, and frequently associated with recurrences in North America and Europe.

Case Presentation: A 68-year-old woman was referred to our hospital for continuous lower abdominal pain 4 weeks after eradication therapy against Helicobacter pylori.

Intensity Interference in a Coherent Spin-Polarized Electron Beam.

We investigate the intensity interference between pairs of electrons using a spin-polarized electron beam having a high polarization and a narrow energy width. We observe spin-dependent antibunching on the basis of coincident counts of electron pairs performed with a spin-polarized transmission electron microscope, which could control the spin-polarization without any changes in the electron optics. The experimental results show that the time correlation was only affected by the spin polarization, demonstrating that the antibunching is associated with fermionic statistics.

Reduction of the extra-column band dispersion by a slow transport and splitting of a sample band in isocratic reversed-phase liquid chromatography.

Sample introduction method was studied to reduce the extra-column effect in reversed-phase HPLC. Slow transport of a sample band (SToSB) in the pre-column space followed by the introduction of the band into the column at a near-optimum flow rate resulted in larger plate counts for a 1.0 mmID, 5 cm long column as much as 1.

Progress in environmental high-voltage transmission electron microscopy for nanomaterials.

A new environmental high-voltage transmission electron microscope (E-HVEM) was developed by Nagoya University in collaboration with JEOL Ltd. An open-type environmental cell was employed to enable in-situ observations of chemical reactions on catalyst particles as well as mechanical deformation in gaseous conditions. One of the reasons for success was the application of high-voltage transmission electron microscopy to environmental (in-situ) observations in the gas atmosphere because of high transmission of electrons through gas layers and thick samples.

Fast enantiomeric separation of amino acids using liquid chromatography/mass spectrometry on a chiral crown ether stationary phase.

Fast enantiomeric separation of amino acids was studied by liquid chromatography/mass spectrometry (LC/MS) on a chiral crown ether stationary phase. A chiral crown ether bonded silica column (3 mm internal diameter (i.d.

Tunable Liquid Chromatographic Separation of H/D Isotopologues Enabled by Aromatic π Interactions.

We report hydrogen/deuterium (H/D) isotope effects based on weak intermolecular interactions with polar functional groups and aromatic rings in liquid chromatography (LC). Various LC experiments with different aromatic analytes, separation media, and nonpolar mobile phases were conducted under normal phase LC conditions, where the hydrophobic interaction was completely suppressed. The separation media that had polar functional groups, such as silanol groups, allowed for higher separation efficiencies for the pairs of aromatic H/D isotopologues.

Quantum de-trapping and transport of heavy defects in tungsten.

The diffusion of defects in crystalline materials controls macroscopic behaviour of a wide range of processes, including alloying, precipitation, phase transformation and creep. In real materials, intrinsic defects are unavoidably bound to static trapping centres such as impurity atoms, meaning that their diffusion is dominated by de-trapping processes. It is generally believed that de-trapping occurs only by thermal activation.

3D Vessel Image Reconstruction by MDCT for Surgical Indication and Timing of Strangulating Small Bowel Obstructions.

Background: Patients with strangulating small bowel obstructions (SBOs) can rapidly deteriorate, in condition; therefore, immediate and appropriate diagnosis is required. However, some cases of SBO are difficult to diagnose using axial computed tomography (CT) images alone. The impact of 3D vessel imaging for the diagnosis, surgical indication, and timing of strangulating SBOs was investigated, prospectively.

[A Case of Rectal Cancers with Pneumonia Combined with Interesting Body Pressure Distribution Before and after Treatment].

A 74-year-old man with aspiration pneumonia was admitted in the internal medicine department. CT revealed progressive carcinoma of RS-Ra, which became the focus of intervention after the pneumonia was treated. After having been allowed temporary discharge, the patient was rehospitalized for surgical operation and rehabilitation.

Slow injector-to-column sample transport to maximize resolution in liquid chromatography: Theory versus practice.

A simple chromatographic model including extra-column sample bandspreading is built and validated experimentally. It is used to quantify the advantage of slowly transporting under isocratic elution of the injected sample band along the pre-column volume of the chromatographic system compared to the conventional injection method at constant flow rate. For fast analyses (<30 s), the model predicts a maximum relative gain of 20% for the isocratic peak capacity of weakly retained compounds (k < 1) at the price of a 60% increase in retention time (+20 s) for short (3.

Influence of gas environment and heating on atomic structures of platinum nanoparticle catalysts for proton-exchange membrane fuel cells.

Atomic-scale relaxations of platinum nanoparticles (Pt NPs) for fuel-cell catalysts are evaluated by spherical-aberration corrected environmental transmission electron microscopy (ETEM) under reference high-vacuum and N atmospheres, and then under reactive H, CO and O atmospheres, combined with ex situ durability test using an electrochemical half-cell. In high-vacuum, increasing roughness due to continuous relaxation of surface-adsorbed Pt atoms is quantified in real-space. Under H and N atmospheres at a critical partial pressure of 1 × 10 Pa the stability of the surface facets is for the first time found to be improved.

LPA Induces Keratinocyte Differentiation and Promotes Skin Barrier Function through the LPAR1/LPAR5-RHO-ROCK-SRF Axis.

The skin barrier protects the body from water loss, allergens, and pathogens. Profilaggrin is produced by differentiated keratinocytes and is processed into filaggrin monomers. These monomers cross-link keratin filaments and are also decomposed to natural moisturizing factors in the stratum corneum for skin hydration and barrier function.

Mechanistic study on the high-selectivity enantioseparation of amino acids using a chiral crown ether-bonded stationary phase and acidic, highly organic mobile phase by liquid chromatography/time-of-flight mass spectrometry.

The separation mechanism of amino acid enantiomers using a chiral crown ether-bonded stationary phase, CROWNPAK CR-I(+), and acetonitrile (ACN)-rich mobile phases (MPs) was studied. The retention factors of proteinogenic l-amino acids (except proline) formed U-shaped plots against the ACN content in the MP with a sharp increase at a high ACN content, while d-amino acids showed much smaller increases or monotonous decreases in retention within the same range. The use of an acidic, highly organic MP with trifluoroacetic acid (TFA) provided a high enantioselectivity with a short separation time from the contribution of the increased binding of the ammonium group of the analytes to the crown ether functionality of the stationary phase and electrostatic repulsion counteracting the hydrophilic partition mechanism.

Reduction of the extra-column band dispersion by a slow transport of a sample band from the injector to the column in isocratic reversed-phase liquid chromatography.

Extra-column band dispersion during the transport of a sample band from the injector to the column can be reduced by a flow rate program starting with a low flow rate until the sample band has approached to, or just entered into the column, followed by an increased flow rate suitable for the solute separation in the column. Such a sample introduction method increased the plate counts of a 50 mm long column, 1.0 or 2.

Twinned/untwinned catalytic gold nanoparticles identified by applying a convolutional neural network to their Hough transformed Z-contrast images.

In this article, we demonstrate that a convolutional neural network (CNN) can be effectively used to determine the presence of twins in the atomic resolution scanning transmission electron microscopy (STEM) images of catalytic Au nanoparticles. In particular, the CNN screening of Hough transformed images resulted in significantly higher accuracy rates as compared to those obtained by applying this technique to the raw STEM images. The proposed method can be utilized for evaluating the statistical twining fraction of Au nanoparticles that strongly affects their catalytic activity.

[A Case of Metachronous Liver Metastases of Gall Bladder Cancer Successfully Treated by Liver Resection].

A 73-year-old woman was diagnosed with gall bladder cancer by contrast enhanced CT images.The tumor was detected at the fundus of the gall bladder and enhanced heterogeneously.She underwent radical cholecystectomy including Japanese D2 lymph node dissection for gall bladder cancer.

Comparison of the kinetic performance of different columns for fast liquid chromatography, emphasizing the contributions of column end structure.

The kinetic performance of five chromatographic columns designed for fast liquid chromatography with different column packing materials - including fully porous (2.0 and 1.9μm particles), core-shell (2.

A new approach for the direct visualization of the membrane cytoskeleton in cryo-electron microscopy: a comparative study with freeze-etching electron microscopy.

An improved unroofing method consisting of tearing off the cell membrane using an adhesive electron microscopy (EM) grid instead of vitreous ice sectioning (cryo-sectioning) has enabled us to panoramically view the membrane cytoskeleton in its native state with extremely high contrast. Grids pre-treated with Alcian blue were placed on cells, and a portion of the dorsal plasma membrane was transferred onto the grid, which was then floated in buffer solution. These membrane fragments contained sufficient cytoskeleton and were of suitable thickness for observation by cryo-EM.

Recent Progress in Monolithic Silica Columns for High-Speed and High-Selectivity Separations.

Monolithic silica columns have greater (through-pore size)/(skeleton size) ratios than particulate columns and fixed support structures in a column for chemical modification, resulting in high-efficiency columns and stationary phases. This review looks at how the size range of monolithic silica columns has been expanded, how high-efficiency monolithic silica columns have been realized, and how various methods of silica surface functionalization, leading to selective stationary phases, have been developed on monolithic silica supports, and provides information on the current status of these columns. Also discussed are the practical aspects of monolithic silica columns, including how their versatility can be improved by the preparation of small-sized structural features (sub-micron) and columns (1 mm ID or smaller) and by optimizing reaction conditions for in situ chemical modification with various restrictions, with an emphasis on recent research results for both topics.

Distinction of synthetic dl-α-tocopherol from natural vitamin E (d-α-tocopherol) by reversed-phase liquid chromatography. Enhanced selectivity of a polymeric C18 stationary phase at low temperature and/or at high pressure.

Separation of diastereomers of dl-α-tocopherol was studied by reversed-phase liquid chromatography using three types of stationary phases, polymeric ODS, polymeric C30, and monomeric ODS. Polymeric ODS stationary phase (Inertsil ODS-P, 3mmID, 20cm) was effective for the separation of the isomers created by the presence of three chiral centers on the alkyl chain of synthetic dl-α-tocopherol. Considerable improvement of the separation of isomers was observed on ODS-P phase at high pressure and at low temperature.