Vorinostat-induced acetylation of RUNX3 reshapes transcriptional profile through long-range enhancer-promoter interactions in natural killer cells.

Natural killer (NK) cells are an essential part of the innate immune system that helps control infections and tumors. Recent studies have shown that Vorinostat, a histone deacetylase (HDAC) inhibitor, can cause significant changes in gene expression and signaling pathways in NK cells. Since gene expression in eukaryotic cells is closely linked to the complex three-dimensional (3D) chromatin architecture, an integrative analysis of the transcriptome, histone profiling, chromatin accessibility, and 3D genome organization is needed to gain a more comprehensive understanding of how Vorinostat impacts transcription regulation of NK cells from a chromatin-based perspective. The results demonstrate that Vorinostat treatment reprograms the enhancer landscapes of the human NK-92 NK cell line while overall 3D genome organization remains largely stable. Moreover, we identified that the Vorinostat-induced RUNX3 acetylation is linked to the increased enhancer activity, leading to elevated expression of immune response-related genes via long-range enhancerpromoter chromatin interactions. In summary, these findings have important implications in the development of new therapies for cancer and immune-related diseases by shedding light on the mechanisms underlying Vorinostat's impact on transcriptional regulation in NK cells within the context of 3D enhancer network. [BMB Reports 2023; 56(7): 398-403].

CTCF controls three-dimensional enhancer network underlying the inflammatory response of bone marrow-derived dendritic cells.

Dendritic cells are antigen-presenting cells orchestrating innate and adaptive immunity. The crucial role of transcription factors and histone modifications in the transcriptional regulation of dendritic cells has been extensively studied. However, it is not been well understood whether and how three-dimensional chromatin folding controls gene expression in dendritic cells. Here we demonstrate that activation of bone marrow-derived dendritic cells induces extensive reprogramming of chromatin looping as well as enhancer activity, both of which are implicated in the dynamic changes in gene expression. Interestingly, depletion of CTCF attenuates GM-CSF-mediated JAK2/STAT5 signaling, resulting in defective NF-κB activation. Moreover, CTCF is necessary for establishing NF-κB-dependent chromatin interactions and maximal expression of pro-inflammatory cytokines, which prime Th1 and Th17 cell differentiation. Collectively, our study provides mechanistic insights into how three-dimensional enhancer networks control gene expression during bone marrow-derived dendritic cells activation, and offers an integrative view of the complex activities of CTCF in the inflammatory response of bone marrow-derived dendritic cells.

CTCF-mediated chromatin looping provides a topological framework for the formation of phase-separated transcriptional condensates.

CTCF is crucial to the organization of mammalian genomes into loop structures. According to recent studies, the transcription apparatus is compartmentalized and concentrated at super-enhancers to form phase-separated condensates and drive the expression of cell-identity genes. However, it remains unclear whether and how transcriptional condensates are coupled to higher-order chromatin organization. Here, we show that CTCF is essential for RNA polymerase II (Pol II)-mediated chromatin interactions, which occur as hyperconnected spatial clusters at super-enhancers. We also demonstrate that CTCF clustering, unlike Pol II clustering, is independent of liquid-liquid phase-separation and resistant to perturbation of transcription. Interestingly, clusters of Pol II, BRD4, and MED1 were found to dissolve upon CTCF depletion, but were reinstated upon restoration of CTCF, suggesting a potent instructive function for CTCF in the formation of transcriptional condensates. Overall, we provide evidence suggesting that CTCF-mediated chromatin looping acts as an architectural prerequisite for the assembly of phase-separated transcriptional condensates.

The Mental Health and Occupational Characteristic of Horse Stable Hand Workers in Korea.

The horse stable hand workers are one of the most important occupations in horse-racing industry. However, suicide problem of the horse stable hand workers in Korea has raised the necessity of new study on how these workers experience mental health problems such as occupational stress and depression in organizational situation. Therefore, this study investigated the occupational stress and depression level of the horse stable hand workers and identified the structural relationship in the horse-racing industry through a detailed interview. A total of 207 horse stable hand workers participated in this study, and occupational stress and depression level were surveyed using the Korean Occupational Stress Scale (KOSS) and Korean version of the Center for Epidemiologic Studies-Depression Scale (CES-D). The results of this study showed that the occupational stress level of horse stable hand workers was higher than the median of Korean population. The significant difference in occupational stress among the detail job grade was also identified. In addition, 34% of the horse stable hand workers showed high risk of depression, and job demand, organizational system, and inappropriate compensation as the subfactors of occupational stress were showed to mainly affect depression. Although there are some limitations according to the field survey, this study also has significant meaning in that it identifies the relationship between the occupational characteristics of the horse stable hand workers and the mental health. It will be necessary to study the diverse organizational situation and individual mental health for new occupations.

Evaluation on Microstructures and Mechanical Properties in Friction Stir Welded Lap Joints of Invar 42/SS 400.

This study evaluated the microstructures and mechanical properties of friction stir welded lap joints. Invar 42 and SS 400 as experimental materials were selected, and friction stir welding was carried out at tool rotation speed of 200 rpm and welding speed of 100 mm/min. Applying the friction stir welding was notably effective to reduce the grain size of the stir zone, consequently, the average grain size of Invar 42 was reduced from 11.5 µm in the base material to 6.4 µm in the stir zone. Joint interface between Invar 42 and SS 400 showed a sound weld without voids and cracks, and the intermetallic compounds with Ll2 type in lap joint interface were partially formed with size of 100 nm. Also, the hook, along the Invar 42 from SS 400, was formed at advancing side, which directly affected an increase in peel strength.

Dynamics of Interorganizational Public Health Emergency Management Networks: Following the 2015 MERS Response in South Korea.

We investigated public health emergency management networks during the recent outbreak of Middle East respiratory syndrome coronavirus that affected more than 17 000 people in South Korea. We administered a survey to 169 organizations in order to map the pattern of communication and response networks during the Middle East respiratory syndrome outbreak. We also conducted 11 semistructured interviews with national, regional, and local government officials to comprehend inhibiting and facilitating factors in risk communication and response to the system. National ministries or agencies play central roles in coordinating and supporting the overall response, and local and regional governments or agencies interact with other governments and agencies. Governmental agencies coordinating and/or supporting the outbreak response had difficulties in communicating with other agencies because of the ambiguity of the nature of the infectious disease, slow information disclosure, differences in the organizational priorities, different information standards, and the limitations of the information system. To better respond to a virus outbreak, government agencies need to improve hierarchical communication among different levels of governments, horizontal communication and cooperation between same types or different types of agencies, and information systems.

Ionic-surfactant-coated subtilisin: activity, enantioselectivity, and application to dynamic kinetic resolution of secondary alcohols.

In this work, we explored the utility of ionic-surfactant-coated Bacillus licheniformis subtilisin (ISCBLS) as the catalyst for the dynamic kinetic resolution of secondary alcohols. ISCBLS was prepared by freeze-drying Bacillus licheniformis subtilisin with both ionic surfactant 1 and dextrin. ISCBCL displayed 9300-fold enhanced activity relative to its native counterpart in the transesterificaion of N-acetyl phenylalanine ethyl ester with 1-propanol in hexane and 12 800-fold enhanced activity in the transesterification of trifluoroethyl butyrate with 1-phenylethanol in THF. The enantioselectivity of ISCBLS was examined with 50 secondary alcohols as the substrates for kinetic resolution in the presence of trifluoroethyl butyrate. ISCBLS displayed synthetically useful enantioselectivity for most of the secondary alcohols tested. The enantioselectivity of ISCBLS was in particular good to high for m- or p-substituted 1-phenylethanols. The DKRs of these secondary alcohols by the combination of ISCBLS and a ruthenium-based racemization catalyst provided the products of (S)-configuration with good results (80-94% yield, 90-99% ee). It is concluded that ISCBLS is of great use as the enantiocomplementary counterpart of (R)-selective lipase for the dynamic kinetic resolution of secondary alcohols.

Public Health Network Structure and Collaboration Effectiveness during the 2015 MERS Outbreak in South Korea: An Institutional Collective Action Framework.

Following the 2015 Middle East Respiratory Syndrome (MERS) outbreak in South Korea, this research aims to examine the structural effect of public health network explaining collaboration effectiveness, which is defined as joint efforts to improve quality of service provision, cost savings, and coordination. We tested the bonding and bridging effects on collaboration effectiveness during the MERS outbreak response by utilizing an institutional collective action framework. The analysis results of 114 organizations responding during the crisis show a significant association between the bonding effect and the effectiveness of collaboration, as well as a positive association between risk communication in disseminating public health information and the effectiveness of collaboration.

Morphology and mechanical properties of multi-stranded amyloid fibrils probed by atomistic and coarse-grained simulations.

Amyloid fibrils are responsible for pathogenesis of various diseases and exhibit the structural feature of an ordered, hierarchical structure such as multi-stranded helical structure. As the multi-strandedness of amyloid fibrils has recently been found to be highly correlated with their toxicity and infectivity, it is necessary to study how the hierarchical (i.e. multi-stranded) structure of amyloid fibril is formed. Moreover, although it has recently been reported that the nanomechanics of amyloid proteins plays a key role on the amyloid-induced pathogenesis, a critical role that the multi-stranded helical structure of the fibrils plays in their nanomechanical properties has not fully characterized. In this work, we characterize the morphology and mechanical properties of multi-stranded amyloid fibrils by using equilibrium molecular dynamics simulation and elastic network model. It is shown that the helical pitch of multi-stranded amyloid fibril is linearly proportional to the number of filaments comprising the amyloid fibril, and that multi-strandedness gives rise to improving the bending rigidity of the fibril. Moreover, we have also studied the morphology and mechanical properties of a single protofilament (filament) in order to understand the effect of cross-ß structure and mutation on the structures and mechanical properties of amyloid fibrils. Our study sheds light on the underlying design principles showing how the multi-stranded amyloid fibril is formed and how the structure of amyloid fibrils governs their nanomechanical properties.

Comparison of cardiac output derived from FloTrac™/Vigileo™ and impedance cardiography during major abdominal surgery.

OBJECTIVES: Impedance cardiography (ICG) is a noninvasive technique that provides reasonably accurate measurements of cardiac output, but the usefulness of ICG in patients undergoing open abdominal surgery has not been validated. METHODS: Cardiac output was measured while patients underwent open gastrectomy using an ICG monitor (niccomo™; ICG-CO); the results were compared with those measured using a FloTrac™/Vigileo™ monitor (Flo-CO), which measures cardiac output by analysing the arterial waveform. Data collection commenced at the beginning of anaesthetic induction and continued until the patient was awake. Data were compared using the Bland-Altman analysis, and the clinical significance of the difference between the two methods was evaluated by calculating the percentage error (%). RESULTS: Eleven patients were monitored during surgery. The bias of the Flo-CO and ICG-CO values was -0.45 l/min. The upper and lower limits of agreement were 0.96 l/min and -1.85 l/min, respectively. The percentage error was 28.5%. Electrocautery induced interference that transiently impaired the performance of the ICG monitor. CONCLUSIONS: ICG provided useful information in evaluating the cardiac output of patients during abdominal surgery.

Marital Status and Health Behavior in Middle-aged Korean Adults.

BACKGROUND: Marital status is as an important sociodemographic variable for health studies. We assessed the association between marital status and health behavior in middle-aged Korean adults. METHODS: This is a cross-sectional study of 2,522 Korean middle-aged adults (1,049 men, 1,473 women) from the 2010 Korean National Health and Nutrition Examination Survey. The subjects were classified as living with a partner or living without a partner (never married, separated, widowed, and divorced). We assessed the relationship between marital status and five health behaviors (smoking, high-risk alcohol intake, regular exercise, regular breakfast consumption, and undergoing periodic health screening). RESULTS: Age, income level, educational level, and occupational classification were all significantly associated with marital status. The risk of undergoing health screening (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32 to 0.90) and having regular breakfast (OR, 0.50; 95% CI, 0.27 to 0.92) were significantly lower in men living without a partner than with a partner. Women living without a partner had a higher smoking risk (OR, 2.27; 95% CI, 1.09 to 4.73) and a higher risk of high-risk alcohol consumption (OR, 5.33; 95% CI, 1.65 to 17.24) than their counterparts. CONCLUSION: Korean middle-aged adults living with partners are more likely to have healthier behavior than living without a partner. The association between marital status and health behaviors differed by sex.

Logic circuit upon angiogenic response controlled by enzyme-linked iron oxide microparticles--towards biocomputing in human cells.

In the present study, we designed a logic circuit upon angiogenic response controlled by a combination of enzyme-functionalized magnetic microparticles operating in human umbilical vein endothelial cells (HUVECs). The reported results represent the first example of a biocomputing system operating in controlling angiogenesis.

Label-free detection of bacterial RNA using polydiacetylene-based biochip.

We developed a simple and effective polydiacetylene-based, label-free multiplex DNA chip for the detection of various pathogenic microorganisms. A novel immobilization method of PDA vesicles on glass slides was exploited using α-cyclodextrin (α-CD). The surface topography of the efficiently immobilized PDA vesicles was confirmed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Then, oligonucleotides complementary to rRNAs of three pathogenic bacteria were conjugated to the PDA vesicles. Finally, crude lysate of pathogenic bacteria was applied to the PDA biochip. The pathogenic bacteria were specifically detected by DNA-RNA hybridization in an hour. The new PDA sensor was effective in detecting multiple pathogenic bacteria easily and accurately without rigorous purification, amplification, and labeling of their genetic components.

Compromised ventilation caused by tracheoesophageal fistula and gastrointestinal endoscope undergoing removal of disk battery on esophagus in pediatric patient -A case report-.

Ingestion of disk batteries may have serious complications such as esophageal burn, perforation, and tracheoesophageal fistula, particularly when the battery is caught in the esophagus. Proper placement of the tracheal tube is critical when tracheoesophageal fistula was occurred from esophageal impaction the battery. Endoscopy of upper gastrointestinal tract in infants and children is an important and effective tool for the diagnosis and treatment of foreign body ingestion. But upper gastrointestinal endoscopy in infant and children has very high risk of tracheal compression and airway compromise. We present a case of ventilatory compromise during insertion of the upper gastrointestinal endoscopy in 16-month-old child with tracheoesophageal fistula secondary to disk battery ingestion.

Steganography and encrypting based on immunochemical systems.

Steganography and encrypting were demonstrated with immuno-specific systems. IgG-proteins were used as invisible ink developed with complementary antibodies labeled with enzymes producing color spots. The information security was achieved by mixing the target protein-antigens used for the text encoding with masking proteins of similar composition but having different bioaffinity. Two different texts were simultaneously encoded by using two different encoding proteins in a mixture. Various encrypting techniques were exemplified with the immuno-systems used for the steganography. Future use of the developed approach for information protection and watermark-technology was proposed. Scaling down the encoded text to a micro-size is feasible with the use of nanotechnology.

Electrochemical detection of vascular endothelial growth factors (VEGFs) using VEGF antibody fragments modified Au NPs/ITO electrode.

A new electrochemical technique for the detection of vascular endothelial growth factors (VEGFs) as a cancer-related biomarker is presented in this paper. Gold nanoparticles (Au NPs) were self-assembled onto an indium tin oxide (ITO) electrode to prepare a modified sandwich type electrochemical immunoassay platform. VEGF antibodies were cleaved into two half-fragments by 2-mercaptoethylamine-HCl (2-MEA) and the fragments were immobilized onto the Au NP substrates by their thiol groups. Through this strategy, randomly oriented attachment of antibodies was prevented which frequently occurs in a general use of whole antibody and reduces the number of available sites for the attachment of target molecules. VEGF target molecules were applied to the immunoelectrodes and they combined with the antibody fragments covering the Au NP electrode, forming antigen-antibody complexes. Then, ferrocene-tagged antibodies, which release electrons under a proper applied potential, were added to the system and they combined with the VEGF molecules pre-attached to the antibody fragments. The redox current of ferrocene measured by the differential pulse voltammetry (DPV) increased almost linearly from 1.27 x 10(-4) to 4.17 x 10(-4)A according to the increase in the concentration of the VEGF target molecules from 100 to 600 pg/ml. The measured current values represent the concentration of the VEGF since they are proportional to the number of ferrocene molecules which is in turn proportional to the concentration of VEGF target molecules. Using this modified sandwich immunoassay with the Au NP/ITO electrode, VEGFs as low as 100 pg/ml were detected with high specificity.

A sensitive method to detect Escherichia coli based on immunomagnetic separation and real-time PCR amplification of aptamers.

Aptamers, single-stranded nucleic acids, provide a unique opportunity as amplifiable molecules using polymerase chain reaction (PCR) as well as recognition molecules like antibodies. We report a highly sensitive detection of Escherichia coli by taking advantage of the aptamer amplification as well as the specific binding of aptamers onto E. coli. This unique approach consists of three steps. First, the target E. coli was captured by antibody-conjugated magnetic beads. Second, the RNA aptamers were bound onto the surface of captured E. coli in a sandwich way. Finally, the heat-released aptamers were amplified by using real-time reverse-transcriptase-PCR (RT-PCR). The aptamer amplification in this approach has enabled a sensitive detection of microorganisms, such as the detection of 10 E. coli in 1 ml sample. When compared to the amplification of nucleic acids extracted from the target microorganisms, this approach can not only prevent the loss of target nucleic acids during the sample preparation by obviating the necessity of cell lysis, but also provide an additional mechanism of signal amplification due to the binding of many aptamers to the surface of each E. coli. Detection of E. coli in this approach showed a wide dynamic range from 10(1) to 10(7)E. coli per ml, which can be explained by the exponential amplification of aptamers. This report has demonstrated, for the first time, the effective use of aptamer amplification in the development of sensitive microorganism detection. It is anticipated that the present approach will be easily expanded and employed in various types of microorganism detection.

The detection of platelet derived growth factor using decoupling of quencher-oligonucleotide from aptamer/quantum dot bioconjugates.

High-sensitivity, high-specificity detection of platelet derived growth factor (PDGF)-BB was realized using the change in fluorescence resonance energy transfer (FRET) occurring between quantum dot (QD) donors and black hole quencher (BHQ) acceptors. CdSe/ZnS QD/mercaptoacetic acid (MAA)/PDGF aptamer bioconjugates were successfully synthesized using ligand exchange. Black hole quencher (BHQ)-bearing oligonucleotide molecules showing partial sequence matching to PDGF aptamer were attached to PDGF aptamers and photoluminescence (PL) quenching was obtained through FRET. By adding target PDGF-BB to the bioconjugates containing BHQs, PL recovery was detected due to detachment of BHQ-bearing oligonucleotide from the PDGF aptamer as a result of the difference in affinity to the PDGF aptamer. The detection limit of the sensor was approximately 0.4 nM and the linearity was maintained up to 1.6 nM in the PL intensity versus concentration curve. Measurement of PL recovery was suggested as a strong tool for high-sensitivity detection of PDGF-BB. Epidermal growth factor (EGF), the negative control molecule, did not contribute to PL recovery due to lack of binding affinity to the PDGF aptamers, which demonstrates the selectivity of the biosensor.

Physical activity and physical fitness as predictors of all-cause mortality in Korean men.

We examined the associations between physical activity (PA), fitness and all-cause mortality and compared their contributions, taking smoking status into consideration. A retrospective cohort study of 18,775 men was carried out between May 1995 and December 2003. Fitness was measured by maximum oxygen uptake and regular PA was defined as at least three times a week, for more than 30 min of leisure time PA. During the mean 6.4 yr of follow-up, 547 deaths were recorded. The hazard ratio (HR) (95% confidence interval [CI]) of regular PA for all-cause mortality was 0.63 (0.52-0.76). The HRs (95% CIs) for men with middle and highest tertile levels of fitness were decreased by 0.58 (0.47-0.70) and 0.58 (0.45-0.75) in comparison to men with lowest one. The inverse association between fitness and mortality was significant among the men who did not engage in regular PA, but not among those who did (p for interaction=0.031). Smoking status did not influence on the associations between regular PA, fitness and mortality. Our result suggested that regular PA and fitness predicted mortality in men. The influence of fitness on mortality was pronounced in the men who did not engage in regular PA.

Effect of phospholipid insertion on arrayed polydiacetylene biosensors.

Micro-arrayed polydiacetylene (PDA) vesicles mixed with phospholipids on glass slides were prepared for label-free detection of Escherichia coli. When E. coli bound to its antibodies chemically attached to polydiacetylene, the fluorescence of the vesicles was dramatically increased. The insertion of dimyristoyl phosphatidylcholine (DMPC) in the vesicles drastically reduced the response time for the fluorescence changes. Vesicles with 20-30% DMPC provided optimal results for bacterial detection. Fourier transform infrared (FTIR) spectra analysis suggested that DMPC insertion decreased the strength of hydrogen bonding among the amide and carboxylic acid groups of the polydiacetylene vesicles. Reduced bonding strength resulted in less rigid structure of the polydiacetylene polymer, allowing more rapid detection upon molecular recognition.