Structural insights into the HBV receptor and bile acid transporter NTCP.

Around 250 million people are infected with hepatitis B virus (HBV) worldwide1, and 15 million may also carry the satellite virus hepatitis D virus (HDV), which confers even greater risk of severe liver disease2. The HBV receptor has been identified as sodium taurocholate co-transporting polypeptide (NTCP), which interacts directly with the first 48 amino acid residues of the N-myristoylated N-terminal preS1 domain of the viral large protein3. Despite the pressing need for therapeutic agents to counter HBV, the structure of NTCP remains unsolved. This 349-residue protein is closely related to human apical sodium-dependent bile acid transporter (ASBT), another member of the solute carrier family SLC10. Crystal structures have been reported of similar bile acid transporters from bacteria4,5, and these models are believed to resemble closely both NTCP and ASBT. Here we have used cryo-electron microscopy to solve the structure of NTCP bound to an antibody, clearly showing that the transporter has no equivalent of the first transmembrane helix found in other SLC10 proteins, and that the N terminus is exposed on the extracellular face. Comparison of our structure with those of related proteins indicates a common mechanism of bile acid transport, but the NTCP structure displays an additional pocket formed by residues that are known to interact with preS1, presenting new opportunities for structure-based drug design.

Hyaluronic acid stimulation of stem cells for cardiac repair: a cell-free strategy for myocardial infarct.

BACKGROUND: Myocardial infarction (MI), a representative form of ischemic heart disease, remains a huge burden worldwide. This study aimed to explore whether extracellular vesicles (EVs) secreted from hyaluronic acid (HA)-primed induced mesenchymal stem cells (HA-iMSC-EVs) could enhance the cardiac repair after MI. RESULTS: HA-iMSC-EVs showed typical characteristics for EVs such as morphology, size, and marker proteins expression. Compared with iMSC-EVs, HA-iMSC-EVs showed enhanced tube formation and survival against oxidative stress in endothelial cells, while reduced reactive oxygen species (ROS) generation in cardiomyocytes. In THP-1 macrophages, both types of EVs markedly reduced the expression of pro-inflammatory signaling players, whereas HA-iMSC-EVs were more potent in augmenting anti-inflammatory markers. A significant decrease of inflammasome proteins was observed in HA-iMSC-EV-treated THP-1. Further, phospho-SMAD2 as well as fibrosis markers in TGF-ß1-stimulated cardiomyocytes were reduced in HA-iMSC-EVs treatment. Proteomic data showed that HA-iMSC-EVs were enriched with multiple pathways including immunity, extracellular matrix organization, angiogenesis, and cell cycle. The localization of HA-iMSC-EVs in myocardium was confirmed after delivery by either intravenous or intramyocardial route, with the latter increased intensity. Echocardiography revealed that intramyocardial HA-iMSC-EVs injections improved cardiac function and reduced adverse cardiac remodeling and necrotic size in MI heart. Histologically, MI hearts receiving HA-iMSC-EVs had increased capillary density and viable myocardium, while showed reduced fibrosis. CONCLUSIONS: Our results suggest that HA-iMSC-EVs improve cardiac function by augmenting vessel growth, while reducing ROS generation, inflammation, and fibrosis in MI heart.

Early-stage dynamics of chloride ion-pumping rhodopsin revealed by a femtosecond X-ray laser.

Chloride ion-pumping rhodopsin (ClR) in some marine bacteria utilizes light energy to actively transport Cl- into cells. How the ClR initiates the transport is elusive. Here, we show the dynamics of ion transport observed with time-resolved serial femtosecond (fs) crystallography using the Linac Coherent Light Source. X-ray pulses captured structural changes in ClR upon flash illumination with a 550 nm fs-pumping laser. High-resolution structures for five time points (dark to 100 ps after flashing) reveal complex and coordinated dynamics comprising retinal isomerization, water molecule rearrangement, and conformational changes of various residues. Combining data from time-resolved spectroscopy experiments and molecular dynamics simulations, this study reveals that the chloride ion close to the Schiff base undergoes a dissociation-diffusion process upon light-triggered retinal isomerization.

Sacrificial Catalyst of Carbothermal-Shock-Synthesized 1T-MoS2 Layers for Ultralong-Lifespan Seawater Battery.

A Pt-nanoparticle-decorated 1T-MoS2 layer is designed as a sacrificial electrocatalyst by carbothermal shock (CTS) treatment to improve the energy efficiency and lifespan of seawater batteries. The phase transition of MoS2 crystals from 2H to metallic 1T─induced by the simple but potent CTS treatment─improves the oxygen-reduction-reaction (ORR) activity in seawater catholyte. In particular, the MoS2-based sacrificial catalyst effectively decreases the overpotential during charging via edge oxidation of MoS2, enhancing the cycling stability of the seawater battery. Furthermore, Pt nanoparticles are deposited onto CTS-MoS2 via an additional CTS treatment. The resulting specimen exhibits a significantly low charge/discharge potential gap of Δ0.39 V, high power density of 6.56 mW cm-2, and remarkable cycling stability up to ∼200 cycles (∼800 h). Thus, the novel strategy reported herein for the preparation of Pt-decorated 1T-MoS2 by CTS treatment could facilitate the development of efficient bifunctional electrocatalysts for fabricating seawater batteries with long service life.

A phase 3, randomized, double-blind, multicenter, placebo-controlled study of S-588410, a five-peptide cancer vaccine as an adjuvant therapy after curative resection in patients with esophageal squamous cell carcinoma.

BACKGROUND: S-588410, a cancer peptide vaccine (CPV), comprises five HLA-A*24:02-restricted peptides from five cancer-testis antigens. In a phase 2 study, S-588410 was well-tolerated and exhibited antitumor efficacy in patients with urothelial cancer. Therefore, we aimed to evaluate the efficacy, immune response, and safety of S-588410 in patients with completely resected esophageal squamous cell carcinoma (ESCC). METHODS: This phase 3 study involved patients with HLA-A*24:02-positive and lymph node metastasis-positive ESCC who received neoadjuvant therapy followed by curative resection. After randomization, patients were administered S-588410 and placebo (both emulsified with Montanide™ ISA 51VG) subcutaneously. The primary endpoint was relapse-free survival (RFS). The secondary endpoints were overall survival (OS), cytotoxic T-lymphocyte (CTL) induction, and safety. Statistical significance was tested using the one-sided weighted log-rank test with the Fleming-Harrington class of weights. RESULTS: A total of 276 patients were randomized (N = 138/group). The median RFS was 84.3 and 84.1 weeks in the S-588410 and placebo groups, respectively (P = 0.8156), whereas the median OS was 236.3 weeks and not reached, respectively (P = 0.6533). CTL induction was observed in 132/134 (98.5%) patients who received S-588410 within 12 weeks. Injection site reactions (137/140 patients [97.9%]) were the most frequent treatment-emergent adverse events in the S-588410 group. Prolonged survival was observed in S-588410-treated patients with upper thoracic ESCC, grade 3 injection-site reactions, or high CTL intensity. CONCLUSIONS: S-588410 induced immune response and had acceptable safety but failed to reach the primary endpoint. A high CTL induction rate and intensity may be critical for prolonging survival during future CPV development.

Coupling structural evolution and oxygen-redox electrochemistry in layered transition metal oxides.

Lattice oxygen redox offers an unexplored way to access superior electrochemical properties of transition metal oxides (TMOs) for rechargeable batteries. However, the reaction is often accompanied by unfavourable structural transformations and persistent electrochemical degradation, thereby precluding the practical application of this strategy. Here we explore the close interplay between the local structural change and oxygen electrochemistry during short- and long-term battery operation for layered TMOs. The substantially distinct evolution of the oxygen-redox activity and reversibility are demonstrated to stem from the different cation-migration mechanisms during the dynamic de/intercalation process. We show that the π stabilization on the oxygen oxidation initially aids in the reversibility of the oxygen redox and is predominant in the absence of cation migrations; however, the π-interacting oxygen is gradually replaced by σ-interacting oxygen that triggers the formation of O-O dimers and structural destabilization as cycling progresses. More importantly, it is revealed that the distinct cation-migration paths available in the layered TMOs govern the conversion kinetics from π to σ interactions. These findings constitute a step forward in unravelling the correlation between the local structural evolution and the reversibility of oxygen electrochemistry and provide guidance for further development of oxygen-redox layered electrode materials.

Line spectroscopic reflectometry for rapid and large-area thickness measurement.

Thickness measurements in the range of 0.1-1 mm over large optically transparent layers are essential in various manufacturing applications. However, existing non-contact measurement methods, which typically measure a single point or a few points at a time, fall short in their suitability for inline area measurement. Here, we introduce line spectroscopic reflectometry (LSR), an approach that extends the point measurement of traditional SR to line measurement, enabling rapid thickness measurement over large areas. By combining line beam illumination and line spectroscopy, LSR can measure 2048 points simultaneously, thereby boosting the measurement speed by two thousand times. We detail the measurement principle and the optical design in the near-infrared regime, and demonstrate thickness measurements of single-layered and double-layered samples over a measurement line length of up to 68 mm. Furthermore, we showcase the inline area measurement capability of LSR through one-dimensional sample scanning, with measurement rates limited only by camera readout rates.

PTD-FGF2 Attenuates Elastase Induced Emphysema in Mice and Alveolar Epithelial Cell Injury.

Aberrant communication in alveolar epithelium is a major feature of inflammatory response for the airway remodeling leading to chronic obstructive pulmonary disease (COPD). In this study, we investigated the effect of protein transduction domains (PTD) conjugated Basic Fibroblast Growth Factor (FGF2) (PTD-FGF2) in response to cigarette smoke extract (CSE) in MLE-12 cells and porcine pancreatic elastase (PPE)-induced emphysematous mice. When PPE-induced mice were intraperitoneally treated with 0.1-0.5 mg/kg PTD-FGF2 or FGF2, the linear intercept, infiltration of inflammatory cells into alveoli and pro-inflammatory cytokines were significantly decreased. In western blot analysis, phosphorylated protein levels of c-Jun N-terminal Kinase 1/2 (JNK1/2), extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein kinases (MAPK) were decreased in PPE-induced mice treated PTD-FGF2. In MLE-12 cells, PTD-FGF2 treatment decreased reactive oxygen species (ROS) production and further decreased Interleukin-6 (IL-6) and IL-1b cytokines in response to CSE. In addition, phosphorylated protein levels of ERK1/2, JNK1/2 and p38 MAPK were reduced. We next determined microRNA expression in the isolated exosomes of MLE-12 cells. In reverse transcription-polymerase chain reaction (RT-PCR) analysis, level of let-7c miRNA was significantly increased while levels of miR-9 and miR-155 were decreased in response to CSE. These data suggest that PTD-FGF2 treatment plays a protective role in regulation of let-7c, miR-9 and miR-155 miRNA expressions and MAPK signaling pathways in CSE-induced MLE-12 cells and PPE-induced emphysematous mice.

A Simultaneous Pipe-Attribute and PIG-Pose Estimation (SPPE) Using 3-D Point Cloud in Compressible Gas Pipelines.

An accurate estimation of pipe attributes, pose of pipeline inspection gauge (PIG), and downstream pipeline topology is essential for successful in-line inspection (ILI) of underground compressible gas pipelines. Taking a 3D point cloud of light detection and ranging (LiDAR) or time-of-flight (ToF) camera as the input, in this paper, we present the simultaneous pipe-attribute and PIG-pose estimation (SPPE) approach that estimates the optimal pipe-attribute and PIG-pose parameters to transform a 3D point cloud onto the inner pipe wall surface: major- and minor-axis lengths, roll, pitch, and yaw angles, and 2D deviation from the center of the pipe. Since the 3D point cloud has all spatial information of the inner pipe wall measurements, this estimation problem can be modeled by an optimal transformation matrix estimation problem from a PIG sensor frame to the global pipe frame. The basic idea of our SPPE approach is to decompose this transformation into two sub-transformations: The first transformation is formulated as a non-linear optimization problem whose solution is iteratively updated by the Levenberg-Marquardt algorithm (LMA). The second transformation utilizes the gravity vector to calculate the ovality angle between the geometric and navigation pipe frames. The extensive simulation results from our PIG simulator based on the robot operating system (ROS) platform demonstrate that the proposed SPPE can estimate the pipe attributes and PIG pose with excellent accuracy and is also applicable to real-time and post-processing non-destructive testing (NDT) applications thanks to its high computational efficiency.

Depression and its associated factors: A comparison between congenital and acquired physical disabilities.

OBJECTIVE: While depression associated with disability has been extensively studied, how depression could differ depending on whether the disability is congenital or acquired remains to be investigated. The objective of this study was to compare depression and its related factors among people with congenital and acquired physical disabilities. METHODS: We used the 2016 Panel Survey of Employment for the Disabled in Korea, a population-based survey for people with disability registered with the Korean government. Among 4577 participants, a total of 2128 participants with physical disability were analyzed using Chi-square test and binary logistic regression analysis. RESULTS: The prevalence of depression was 12.9% in those with congenital physical disability and 16.0% in those with acquired physical disability. Stress due to disability and family relationship satisfaction were associated with higher and lower odds of depression, respectively, in both disability groups. Discrimination due to disability, divorce, social participation, and subjective social status were significant predictors of depression only in people with acquired disability. CONCLUSIONS: Compared to those with congenital disability, individuals with acquired disability can be more susceptible to issues relating to social relationship, social standing and discrimination. Findings of this study suggest that acquired disability and adapting to changes associated with it can be a source of mental distress in addition to living with it. More efforts are needed to address discrimination, provide supportive social relationships, and provide supportive living conditions in order to reduce depression in persons living with disability, especially those with acquired disability.

Exoskeleton Usability Questionnaire: a preliminary evaluation questionnaire for the lower limb industrial exoskeletons.

Exoskeleton robots are a promising solution to reduce musculoskeletal disorders (MSDs) in different work environments, but a specific usability scale for evaluating them is lacking. This study aimed to develop and verify a preliminary Exoskeleton Usability Questionnaire (EUQ) for the lower limb exoskeletons by creating a draft survey questionnaire from existing questions in prior studies. An experiment was conducted with 20 participants who performed a specific task while wearing three lower limb robots and provided subjective feedback using the developed questionnaire. Data were analysed using exploratory and confirmatory factor analysis (CFA), resulting in a usability evaluation questionnaire for exoskeleton robots clustered into four main factors: mobility, adjustability, handling and safety. This study's findings are expected to be useful in evaluating the usability of the lower limb exoskeletons in both general production sites and agricultural work, which can aid in reducing the prevalence of lower limb MSDs.Practitioner Summary: This study developed a preliminary subjective usability evaluation questionnaire for exoskeleton robots. The questionnaire is clustered into four main factors: mobility, adjustability, handling and safety. These findings provide a valuable tool for assessing exoskeleton usability, potentially reducing musculoskeletal disorders (MSDs) in various work environments.

Regional differences in health screening participation between before and during COVID-19 pandemic.

BACKGROUND: Health screening is a preventive and cost-effective public health strategy for early detection of diseases. However, the COVID-19 pandemic has decreased health screening participation. The aim of this study was to examine regional differences in health screening participation between before and during COVID-19 pandemic and vulnerabilities of health screening participation in the regional context. METHODS: Administrative data from 229 districts consisting of 16 provinces in South Korea and health screening participation rate of each district collected in 2019 and 2020 were included in the study. Data were then analyzed via descriptive statistics and geographically weighted regression (GWR). RESULTS: This study revealed that health screening participation rates decreased in all districts during COVID-19. Regional vulnerabilities contributing to a further reduction in health screening participation rate included COVID-19 concerns, the population of those aged 65+ years and the disabled, lower education level, lower access to healthcare, and the prevalence of chronic disease. GWR analysis showed that different vulnerable factors had different degrees of influence on differences in health screening participation rate. CONCLUSIONS: These findings could enhance our understanding of decreased health screening participation due to COVID-19 and suggest that regional vulnerabilities should be considered stringent public health strategies after COVID-19.

Current trends in read-across applications for chemical risk assessments and chemical registrations in the Republic of Korea.

Read-across, an alternative approach for hazard assessment, has been widely adopted when in vivo data are unavailable for chemicals of interest. Read-across is enabled via in silico tools such as quantitative structure activity relationship (QSAR) modeling. In this study, the current status of structure activity relationship (SAR)-based read-across applications in the Republic of Korea (ROK) was examined considering both chemical risk assessments and chemical registrations from different sectors, including regulatory agencies, industry, and academia. From the regulatory perspective, the Ministry of Environment (MOE) established the Act on Registration and Evaluation of Chemicals (AREC) in 2019 to enable registrants to submit alternative data such as information from read-across instead of in vivo data to support hazard assessment and determine chemical-specific risks. Further, the Ministry of Food and Drug Safety (MFDS) began to consider read-across approaches for establishing acceptable intake (AI) limits of impurities occurring during pharmaceutical manufacturing processes under the ICH M7 guideline. Although read-across has its advantages, this approach also has limitations including (1) lack of standardized criteria for regulatory acceptance, (2) inconsistencies in the robustness of scientific evidence, and (3) deficiencies in the objective reliability of read-across data. The application and acceptance rate of read-across may vary among regulatory agencies. Therefore, sufficient data need to be prepared to verify the hypothesis that structural similarities might lead to similarities in properties of substances (between source and target chemicals) prior to adopting a read-across approach. In some cases, additional tests may be required during the registration process to clarify long-term effects on human health or the environment for certain substances that are data deficient. To improve the quality of read-across data for regulatory acceptance, cooperative efforts from regulatory agencies, academia, and industry are needed to minimize limitations of read-across applications.

Association between prenatal cadmium exposure and cord blood DNA methylation.

Prenatal cadmium exposure is known to affect infant growth and organ development. Nonetheless, the role of DNA methylation in cadmium-related health effects has yet to be determined. To this end, we investigated the relationship between prenatal cadmium exposure and cord blood DNA methylation in Korean infants through an epigenome-wide association study. Cadmium concentrations in maternal blood during early and late pregnancy and in cord blood collected from newborns were measured using atomic adsorption spectrometry and DNA methylation analysis was conducted using HumanMethylationEPIC BeadChip kits. After adjusting for infant sex, maternal pregnancy body mass index, smoking status, and estimated leukocyte composition, we analyzed the association between CpG methylation and cadmium concentration in 364 samples. Among 835,252 CpG sites, maternal blood cadmium concentration in early pregnancy was significantly associated with two differentially methylated CpG sites, cg05537752 and cg24904393, which were annotated ATP9A and no gene, respectively. The study findings indicate that prenatal cadmium exposure is significantly associated with methylation statuses of several CpG sites and regions in Korean infants, especially during early pregnancy.

DNA methylation changes associated with prenatal mercury exposure: A meta-analysis of prospective cohort studies from PACE consortium.

Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (ß = 2.28 × 10-4, p-value = 5.87 × 10-5) in relation to prenatal MeHg exposure. In child blood, we identified differential DNAm at cg15288800 (ß = 0.004, p-value = 4.97 × 10-5), also located in MED31. This repeated link to MED31, a gene involved in lipid metabolism and RNA Polymerase II transcription function, may suggest a DNAm perturbation related to MeHg exposure that persists into early childhood. Further, we found evidence for association between prenatal MeHg exposure and child blood DNAm levels at two additional CpGs: cg12204245 (ß = 0.002, p-value = 4.81 × 10-7) in GRK1 and cg02212000 (ß = -0.001, p-value = 8.13 × 10-7) in GGH. Prenatal MeHg exposure was associated with DNAm modifications that may influence health outcomes, such as cognitive or anthropometric development, in different populations.

MEMS Underwater Directional Acoustic Sensor in Near Neutral Buoyancy Configuration.

A MEMS directional acoustic sensor housed in an air cavity and operated underwater in a near-neutral buoyancy configuration is demonstrated. The sensor consists of two wings connected by a bridge and attached to a substrate by two centrally mounted torsional legs. The frequency response showed two resonant peaks corresponding to a rocking mode (wings moving in opposite directions) and a bending mode (wings moving in the same direction). Initial tests of the sensor using a shaker table showed that the response is highly dependent on the vibration direction. In air, the sensor showed a maximum sensitivity of about 95 mV/Pa with a cosine directional response. Underwater, the maximum sensitivity was about 37 mV/Pa with a similar cosine directional response. The measured maximum SNR was about 38 dB for a signal generated by a sound stimulus of 1 Pa when the sensor is operated near the bending resonance. The results indicate that this type of MEMS sensor can be operated in a near-neutral buoyant configuration and achieve a good directional response.

Integrated genetic and epigenetic analyses uncover MSI2 association with allergic inflammation.

BACKGROUND: The relationship between allergic and eosinophilic inflammation, either systemic or local, in allergic diseases remains unclear. OBJECTIVE: We performed combined genome-wide association study (GWAS) and epigenome-wide (EWAS) for atopy and tissue eosinophilia to identify both genetic and epigenetic signatures between systemic and local allergic inflammation, and to capture global patterns of gene regulation. METHODS: We included 126 subjects for atopy analysis and 147 for tissue eosinophilia analysis, as well as 18 normal nasal tissue samples. We identified differentially methylated positions (DMPs) and genes associated with atopy and tissue eosinophilia. Furthermore, we performed mendelian randomization analysis and penalized regression along with replication in an independent cohort. RESULTS: EWAS identified genes, including Musashi RNA binding protein 2 (MSI2), associated with atopy, which contained enriched DMPs that genetically affect atopy. A direct association was observed between MSI2 single-nucleotide polymorphisms and atopy, as was a causal effect of changes in MSI2 expression and methylation on atopy, which was replicated in a Costa Rican population. Regarding tissue eosinophilia, EWAS identified genes with enriched DMPs directly contributing to tissue eosinophilia at the gene level, including CAMK1D. The gene ontology terms of the identified genes for both phenotypes encompassed immune-related terms. CONCLUSION: EWAS combined with GWAS identified novel candidate genes, especially the methylation of MSI2, contributing to systemic allergic inflammation. Certain genes displayed a greater association with either systemic or local allergic inflammation; however, it is expected that a harmonized effect of these genes influences immune responses.

Crystal Structures of the Plant Phospholipase A1 Proteins Reveal a Unique Dimerization Domain.

Phospholipase is an enzyme that hydrolyzes various phospholipid substrates at specific ester bonds and plays important roles such as membrane remodeling, as digestive enzymes, and the regulation of cellular mechanism. Phospholipase proteins are divided into following the four major groups according to the ester bonds they cleave off: phospholipase A1 (PLA1), phospholipase A2 (PLA2), phospholipase C (PLC), and phospholipase D (PLD). Among the four phospholipase groups, PLA1 has been less studied than the other phospholipases. Here, we report the first molecular structures of plant PLA1s: AtDSEL and CaPLA1 derived from Arabidopsis thaliana and Capsicum annuum, respectively. AtDSEL and CaPLA1 are novel PLA1s in that they form homodimers since PLAs are generally in the form of a monomer. The dimerization domain at the C-terminal of the AtDSEL and CaPLA1 makes hydrophobic interactions between each monomer, respectively. The C-terminal domain is also present in PLA1s of other plants, but not in PLAs of mammals and fungi. An activity assay of AtDSEL toward various lipid substrates demonstrates that AtDSEL is specialized for the cleavage of sn-1 acyl chains. This report reveals a new domain that exists only in plant PLA1s and suggests that the domain is essential for homodimerization.

Retrospective lumbosacral CT analysis and prospective observational study of the ipsilateral tunnel view technique for fluoroscopy-guided selective S1 transforaminal epidural injection.

BACKGROUND: The purpose of this study was to retrospectively observe the anatomic relationship between dorsal S1 foramen (DS1F) and ventral S1 foramen (VS1F) through computed tomography (CT) analysis and to prospectively determine the optimal angle of ipsilateral tunnel view technique for performing S1 transforaminal epidural steroid injection (S1-TFESI). METHODS: The axial lumbosacral CTs taken between in 208 consecutive patients and the following measurements were obtained on both sides: (1) the α-angle was defined as an angle between a sagittal line passing through the center of the sacrum and an imaginary line passing through the center of DS1F, (2) the largest diameter of DS1F and VS1F. The fluoroscopy was adjusted to show the largest L5/S1 intervertebral disc space, which was defined as the cephalad angle, and tilted to the ipsilateral oblique side until the entrance of DS1F had a well-defined, round shape, which defined as the ß-angle in 40 humans. RESULTS: CT measurements showed that the α-angle was 26.3 ± 3.3 degrees (15-38 degrees) and the diameter of DS1F was 7.1 ± 0.7 mm (4-10.9 mm), which was significantly smaller than the diameter of VS1F, 10.1 ± 1.0 mm (7.2-13.8 mm). The ß-angle was 24 ± 4.6 degrees, which was not much different from the α-angle and the cephalad angle was 23 ± 4.6 degrees. The success rate of S1-TFESI was 100% and there were no procedure-related complications. CONCLUSIONS: The entrance of DS1F is easily identified with an ipsilateral 25 degrees-tunnel view technique while performing S1-TFESI, and it is a clinically applicable approach.

NMR spectroscopy uncovers direct interaction between BAF60A and p53.

The BRG1-associated factor 60A (BAF60A), an SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1, has been known to be important for transcriptional activation and inhibition through the alteration of the DNA nucleosome. Although the association between BAF60A and p53 plays a critical role in tumor suppression, the interaction mode is still unclear. Here, we report the detailed interactions between BAF60A and p53 by both NMR spectroscopy and pull-down analysis. Both N-terminal region (BAF60ANR) and the SWIB domain (BAF60ASWIB) of BAF60A directly interact with the tetramerization domain of p53 (p53TET). NMR data show that Ile315, Met366, Ala388, and Tyr390 of BAF60ASWIB are mostly involved in p53TET binding. The calculated dissociation constant (KD) value between BAF60ASWIB and p53TET revealed relatively weak binding affinity, at approximately 0.3 ± 0.065 mM. Our data will enhance detailed interaction mechanism to elucidate the molecular basis of p53-mediated integration via BAF60A interaction.