Structural and functional investigation of GajB protein in Gabija anti-phage defense.

Bacteriophages (phages) are viruses that infect bacteria and archaea. To fend off invading phages, the hosts have evolved a variety of anti-phage defense mechanisms. Gabija is one of the most abundant prokaryotic antiviral systems and consists of two proteins, GajA and GajB. GajA has been characterized experimentally as a sequence-specific DNA endonuclease. Although GajB was previously predicted to be a UvrD-like helicase, its function is unclear. Here, we report the results of structural and functional analyses of GajB. The crystal structure of GajB revealed a UvrD-like domain architecture, including two RecA-like core and two accessory subdomains. However, local structural elements that are important for the helicase function of UvrD are not conserved in GajB. In functional assays, GajB did not unwind or bind various types of DNA substrates. We demonstrated that GajB interacts with GajA to form a heterooctameric Gabija complex, but GajB did not exhibit helicase activity when bound to GajA. These results advance our understanding of the molecular mechanism underlying Gabija anti-phage defense and highlight the role of GajB as a component of a multi-subunit antiviral complex in bacteria.

The structure of AcrIE4-F7 reveals a common strategy for dual CRISPR inhibition by targeting PAM recognition sites.

Bacteria and archaea use the CRISPR-Cas system to fend off invasions of bacteriophages and foreign plasmids. In response, bacteriophages encode anti-CRISPR (Acr) proteins that potently inhibit host Cas proteins to suppress CRISPR-mediated immunity. AcrIE4-F7, which was isolated from Pseudomonas citronellolis, is a fused form of AcrIE4 and AcrIF7 that inhibits both type I-E and type I-F CRISPR-Cas systems. Here, we determined the structure of AcrIE4-F7 and identified its Cas target proteins. The N-terminal AcrIE4 domain adopts a novel α-helical fold that targets the PAM interaction site of the type I-E Cas8e subunit. The C-terminal AcrIF7 domain exhibits an αß fold like native AcrIF7, which disables target DNA recognition by the PAM interaction site in the type I-F Cas8f subunit. The two Acr domains are connected by a flexible linker that allows prompt docking onto their cognate Cas8 targets. Conserved negative charges in each Acr domain are required for interaction with their Cas8 targets. Our results illustrate a common mechanism by which AcrIE4-F7 inhibits divergent CRISPR-Cas types.

Prognostic value of resting heart rate in predicting undiagnosed diabetes in adults: Korean National Health and Nutrition Examination Survey 2008-2018.

BACKGROUND AND AIM: Although resting heart rate (RHR) is associated with prevalence and incidence of diabetes, whether it is associated with undiagnosed diabetes is still unclear. We aimed to investigate whether the RHR is associated with the prevalence of undiagnosed diabetes in a large Korean national dataset. METHODS AND RESULTS: The Korean National Health and Nutrition Examination Survey data from 2008 to 2018 were used. After screening, 51,637 participants were included in this study. The odds ratios and 95% confidence intervals (CIs) for undiagnosed diabetes were calculated using multivariable-adjusted logistic regression analyses. Analyses showed that participants with a RHR of ≥90 bpm showed a 4.00- (95% CI: 2.77-5.77) and 3.21-times (95% CI: 2.01-5.14) higher prevalence of undiagnosed diabetes for men and women, respectively, than those with a RHR of <60 bpm. The linear dose-response analyses showed that each 10-bpm increment in RHR was associated with a 1.39- (95% CI: 1.32-1.48) and 1.28-times (95% CI: 1.19-1.37) higher prevalence of undiagnosed diabetes for men and women, respectively. In the stratified analyses, the positive association between RHR and the prevalence of undiagnosed diabetes was tended to be stronger among those who were younger (age: <40 years) and lean (BMI: <23 kg/m2). CONCLUSIONS: Elevated RHR was significantly associated with a higher prevalence of undiagnosed diabetes in Korean men and women, independent of demographic, lifestyle, and medical factors. Accordingly, the value of RHR as a clinical indicator and health marker, especially in reducing the prevalence of undiagnosed diabetes, is suggestible.

Surface-Tailored Medium Entropy Alloys as Radically Low Overpotential Oxygen Evolution Electrocatalysts.

Numerous studies have explored new materials for electrocatalysts, but it is difficult to discover materials that surpass the catalytic activity of current commercially available noble metal electrocatalysts. In contrast to conventional transition metal alloys, high-entropy alloys (HEAs) have immense potential to maximize their catalytic properties because of their high stability and compositional diversity as oxygen evolution reactions (OERs). This work presents medium-entropy alloys (MEAs) as OER electrocatalysts to simultaneously satisfy the requirement of high catalytic activity and long-term stability. The surface of MEA electrocatalyst is tailored to suit the OER via anodizing and cyclic voltammetry activation methods. Optimized electrical properties and hydrophilicity of the surface enable an extremely low overpotential of 187 mV for achieving the current density of 10 mA cm-2 alkaline media. Furthermore, a combined photovoltaic-electrochemical system with MEA electrocatalyst and a perovskite/Si tandem solar cell exhibits a solar-to-hydrogen conversion efficiency of 20.6% for an unassisted hydrogen generation system. These results present a new pathway for designing sustainable high efficiency water splitting cells.

Measurement of Ankle Joint Movements Using IMUs during Running.

Gait analysis has historically been implemented in laboratory settings only with expensive instruments; yet, recently, efforts to develop and integrate wearable sensors into clinical applications have been made. A limited number of previous studies have been conducted to validate inertial measurement units (IMUs) for measuring ankle joint kinematics, especially with small movement ranges. Therefore, the purpose of this study was to validate the ability of available IMUs to accurately measure the ankle joint angles by comparing the ankle joint angles measured using a wearable device with those obtained using a motion capture system during running. Ten healthy subjects participated in the study. The intraclass correlation coefficient (ICC) and standard error of measurement were calculated for reliability, whereas the Pearson coefficient correlation was performed for validity. The results showed that the day-to-day reliability was excellent (0.974 and 0.900 for sagittal and frontal plane, respectively), and the validity was good in both sagittal (r = 0.821, p < 0.001) and frontal (r = 0.835, p < 0.001) planes for ankle joints. In conclusion, we suggest that the developed device could be used as an alternative tool for the 3D motion capture system for assessing ankle joint kinematics.

Breath Acetone Measurement-Based Prediction of Exercise-Induced Energy and Substrate Expenditure.

The purpose of our study was to validate a newly developed breath acetone (BrAce) analyzer, and to explore if BrAce could predict aerobic exercise-related substrate use. Six healthy men ran on a treadmill at 70% of maximal oxygen consumption (VO2max) for 1 h after two days of a low-carbohydrate diet. BrAce and blood ketone (acetoacetate (ACAC), beta-hydroxybutyrate (BOHB)) levels were measured at baseline and at different time points of post-exercise. BrAce values were validated against blood ketones and respiratory exchange ratio (RER). Our results showed that BrAce was moderately correlated with BOHB (r = 0.68, p < 0.01), ACAC (r = 0.37, p < 0.01) and blood ketone (r = 0.60, p < 0.01), suggesting that BrAce reflect blood ketone levels, which increase when fat is oxidized. Furthermore, BrAce also negatively correlated with RER (r = 0.67, p < 0.01). In our multiple regression analyses, we found that when BMI and VO2max were added to the prediction model in addition to BrAce, R2 values increased up to 0.972 at rest and 0.917 at 1 h after exercise. In conclusion, BrAce level measurements of our BrAce analyzer reflect blood ketone levels and the device could potentially predict fat oxidation.

Differences in the risk of mood disorders in patients with asthma-COPD overlap and in patients with COPD alone: a nationwide population-based retrospective cohort study in Korea.

BACKGROUND: Although feelings of anxiety and depression are common in patients with chronic obstructive pulmonary disease (COPD), little is known about the estimates of their incidence in patients with asthma-COPD overlap (ACO), which has been described and acknowledged as a distinct clinical entity. We aimed to estimate the risk of depression and anxiety among patients with ACO and compare it with the risk among those with COPD alone in the general population. METHODS: We conducted a nationwide population-based retrospective cohort study using the Korean National Sample Cohort database between 1 January, 2002, and 31 December, 2013. Patients who were diagnosed with COPD (International Classification of Diseases, 10th revision [ICD-10] codes J42-J44) at least twice and prescribed COPD medications at least once between 2003 and 2011 were classified into two categories: patients who were diagnosed with asthma (ICD-10 codes J45-J46) more than twice and at least once prescribed asthma medications comprised the ACO group, and the remaining COPD patients comprised the COPD alone group. Patients who had been diagnosed with depression or anxiety within a year before the index date were excluded. We defined the outcome as time to first diagnosis with depression and anxiety. Matched Cox regression models were used to compare the risk of depression and anxiety among patients with ACO and patients with COPD alone after propensity score matching with a 1:1 ratio. RESULTS: After propensity score estimation and matching in a 1:1 ratio, the cohort used in the analysis included 15,644 patients. The risk of depression during the entire study period was higher for patients with ACO than for patients with COPD alone (adjusted hazard ratio, 1.10; 95% confidence interval, 1.03-1.18; P value = 0.0039), with an elevated risk in patients aged 40-64 years (1.21; 1.10-1.34; 0.0001) and in women (1.18; 1.07-1.29; 0.0005). The risk of anxiety was higher for patients with ACO than for patients with COPD alone (1.06; 1.01-1.12; 0.0272), with a higher risk in patients aged 40-64 years (1.08; 1.00-1.17; 0.0392); however, the risk was not significant when stratified by sex. CONCLUSIONS: This population-based study revealed a higher incidence of depression and anxiety in patients with ACO than in patients with COPD alone.

Proton-pump inhibitors and the risk of Clostridium difficile-associated diarrhea in high-risk antibiotics users: A population-based case-crossover study.

PURPOSE: Given the severity and high-costs demand of Clostridium difficile-associated diarrhea (CDAD), management of risk factors is very important. Although the association between proton-pump inhibitors (PPIs) and CDAD has been established, little is known among high-risk antibiotics users. This study aimed to identify the association between PPIs and CDAD in high-risk antibiotics users by using a case-crossover design. METHODS: We conducted a case-crossover study using a nationwide population-based cohort in South Korea. Participants who developed CDAD from 1 January 2003 to 31 December 2013 and had prior prescription records of both PPIs and high-risk antibiotics were included. The hazard period was 49 days, and the three prior control periods had the same duration as the hazard period. The status of exposure to PPIs was assessed during the hazard and control periods in each patient and discordant pairs of exposure were used to estimate the matched odds ratio (OR). RESULTS: In total, 200 participants with CDAD who had histories of both PPIs and high-risk antibiotics use were included. A twofold increased risk for CDAD due to PPI use was observed (OR = 2.0; 95% confidence interval, 1.2-3.2). The time-invariant variables including age group, sex, and comorbidities were proven not to modify the association between PPIs and CDAD. CONCLUSIONS: Our study suggested that PPIs increase the risk of developing CDAD in high-risk antibiotics users. Thus, PPIs should be used cautiously in patients requiring high-risk antibiotics in the situation of medical treatment to prevent further incidence of CDAD.

Molecular integration of HoxB4 and STAT3 for self-renewal of hematopoietic stem cells: a model of molecular convergence for stemness.

The upregulation of HoxB4 promotes self-renewal of hematopoietic stem cells (HSCs) without overriding the normal stem cell pool size. A similar enhancement of HSC self-renewal occurs when signal transducer and activator of transcription 3 (STAT3) is activated in HSCs. In this study, to gain insight into the functional organization of individual transcription factors (TFs) that have similar effects on HSCs, we investigated the molecular interplay between HoxB4 and STAT3 in the regulation of HSC self-renewal. We found that while STAT3-C or HoxB4 similarly enhanced the in vitro self-renewal and in vivo repopulating activities of HSCs, simultaneous transduction of both TFs did not have additive effects, indicating their functional redundancy in HSCs. In addition, activation of STAT3 did not cause changes in the expression levels of HoxB4. In contrast, the inhibition of STAT3 activity in HoxB4-overexpressing hematopoietic cells significantly abrogated the enhancing effects of HoxB4, and the upregulation of HoxB4 caused a ligand-independent Tyr-phosphorylation of STAT3. Microarray analysis revealed a significant overlap of the transcriptomes regulated by STAT3 and HoxB4 in undifferentiated hematopoietic cells. Moreover, a gene set enrichment analysis showed significant overlap in the candidate TFs that can recapitulate the transcriptional changes induced by HoxB4 or STAT3. Interestingly, among these common TFs were the pluripotency-related genes Oct-4 and Nanog. These results indicate that tissue-specific TFs regulating HSC self-renewal are functionally organized to play an equivalent role in transcription and provide insights into the functional convergence of multiple entries of TFs toward a conserved transcription program for the stem cell state.

Site-directed mutagenesis substituting cysteine for serine in 2-Cys peroxiredoxin (2-Cys Prx A) of Arabidopsis thaliana effectively improves its peroxidase and chaperone functions.

BACKGROUND AND AIMS: The 2-Cys peroxiredoxin (Prx) A protein of Arabidopsis thaliana performs the dual functions of a peroxidase and a molecular chaperone depending on its conformation and the metabolic conditions. However, the precise mechanism responsible for the functional switching of 2-Cys Prx A is poorly known. This study examines various serine-to-cysteine substitutions on α-helix regions of 2-Cys Prx A in Arabidopsis mutants and the effects they have on the dual function of the protein. METHODS: Various mutants of 2-Cys Prx A were generated by replacing serine (Ser) with cysteine (Cys) at different locations by site-directed mutagenesis. The mutants were then over-expressed in Escherichia coli. The purified protein was further analysed by size exclusion chromatography, polyacrylamide gel electrophoresis, circular dichroism spectroscopy and transmission electron microscopy (TEM) and image analysis. Peroxidase activity, molecular chaperone activity and hydrophobicity of the proteins were also determined. Molecular modelling analysis was performed in order to demonstrate the relationship between mutation positions and switching of 2-Cys Prx A activity. KEY RESULTS: Replacement of Ser(150) with Cys(150) led to a marked increase in holdase chaperone and peroxidase activities of 2-Cys Prx A, which was associated with a change in the structure of an important domain of the protein. Molecular modelling demonstrated the relationship between mutation positions and the switching of 2-Cys Prx A activity. Examination of the α2 helix, dimer-dimer interface and C-term loop indicated that the peroxidase function is associated with a fully folded α2 helix and easy formation of a stable reduced decamer, while a more flexible C-term loop makes the chaperone function less likely. CONCLUSIONS: Substitution of Cys for Ser at amino acid location 150 of the α-helix of 2-Cys Prx A regulates/enhances the dual enzymatic functions of the 2-Cys Prx A protein. If confirmed in planta, this leads to the potential for it to be used to maximize the functional utility of 2-Cys Prx A protein for improved metabolic functions and stress resistance in plants.

Clinical validation of surface-enhanced Raman scattering-based immunoassays in the early diagnosis of rheumatoid arthritis.

We assessed the clinical feasibility of conducting immunoassays based on surface-enhanced Raman scattering (SERS) in the early diagnosis of rheumatoid arthritis (RA). An autoantibody against citrullinated peptide (anti-CCP) was used as a biomarker, magnetic beads conjugated with CCP were used as substrates, and the SERS nanotags were comprised of anti-human IgG-conjugated hollow gold nanospheres (HGNs). We were able to determine the anti-CCP serum levels successfully by observing the distinctive Raman intensities corresponding to the SERS nanotags. At high concentrations of anti-CCP (>25 U/mL), the results obtained from the SERS assay confirmed those obtained via an ELISA-based assay. Nevertheless, quantitation via our SERS-based assay is significantly more accurate at low concentrations (<25 U/mL). In this study, we compared the results of an anti-CCP assay of 74 clinical blood samples obtained from the SERS-based assay to that of a commercial ELISA kit. The results of the anti-CCP-positive group (n = 31, >25 U/mL) revealed a good correlation between the ELISA and SERS-based assays. However, in the anti-CCP-negative group (n = 43, <25 U/mL), the SERS-based assay was shown to be more reproducible. Accordingly, we suggest that SERS-based assays are novel and potentially useful tools in the early diagnosis of RA.

Gene regulatory cascade of senescence-associated NAC transcription factors activated by ETHYLENE-INSENSITIVE2-mediated leaf senescence signalling in Arabidopsis.

Leaf senescence is a finely tuned and genetically programmed degeneration process, which is critical to maximize plant fitness by remobilizing nutrients from senescing leaves to newly developing organs. Leaf senescence is a complex process that is driven by extensive reprogramming of global gene expression in a highly coordinated manner. Understanding how gene regulatory networks involved in controlling leaf senescence are organized and operated is essential to decipher the mechanisms of leaf senescence. It was previously reported that the trifurcate feed-forward pathway involving EIN2, ORE1, and miR164 in Arabidopsis regulates age-dependent leaf senescence and cell death. Here, new components of this pathway have been identified, which enhances knowledge of the gene regulatory networks governing leaf senescence. Comparative gene expression analysis revealed six senescence-associated NAC transcription factors (TFs) (ANAC019, AtNAP, ANAC047, ANAC055, ORS1, and ORE1) as candidate downstream components of ETHYLENE-INSENSITIVE2 (EIN2). EIN3, a downstream signalling molecule of EIN2, directly bound the ORE1 and AtNAP promoters and induced their transcription. This suggests that EIN3 positively regulates leaf senescence by activating ORE1 and AtNAP, previously reported as key regulators of leaf senescence. Genetic and gene expression analyses in the ore1 atnap double mutant revealed that ORE1 and AtNAP act in distinct and overlapping signalling pathways. Transient transactivation assays further demonstrated that ORE1 and AtNAP could activate common as well as differential NAC TF targets. Collectively, the data provide insight into an EIN2-mediated senescence signalling pathway that coordinates global gene expression during leaf senescence via a gene regulatory network involving EIN3 and senescence-associated NAC TFs.

Control of plant germline proliferation by SCF(FBL17) degradation of cell cycle inhibitors.

Flowering plants possess a unique reproductive strategy, involving double fertilization by twin sperm cells. Unlike animal germ lines, the male germ cell lineage in plants only forms after meiosis and involves asymmetric division of haploid microspores, to produce a large, non-germline vegetative cell and a germ cell that undergoes one further division to produce the twin sperm cells. Although this switch in cell cycle control is critical for sperm cell production and delivery, the underlying molecular mechanisms are unknown. Here we identify a novel F-box protein of Arabidopsis thaliana, designated FBL17 (F-box-like 17), that enables this switch by targeting the degradation of cyclin-dependent kinase A;1 inhibitors specifically in male germ cells. We show that FBL17 is transiently expressed in the male germ line after asymmetric division and forms an SKP1-Cullin1-F-box protein (SCF) E3 ubiquitin ligase complex (SCF(FBL17)) that targets the cyclin-dependent kinase inhibitors KRP6 and KRP7 for proteasome-dependent degradation. Accordingly, the loss of FBL17 function leads to the stabilization of KRP6 and inhibition of germ cell cycle progression. Our results identify SCF(FBL17) as an essential male germ cell proliferation complex that promotes twin sperm cell production and double fertilization in flowering plants.

High energy dissipation-based process to improve the rheological properties of bentonite drilling muds by reducing the particle size.

Drilling mud is a multi-phase fluid that is used in the petroleum drilling process. Bentonite is the most important constituent of drilling mud; it endows the drilling mud with its rheological behaviors, such as viscosity, yield stress, and shear thinning. The process of manufacturing microscale bentonite at the nanoscale level is very promising for commercializing nano-based drilling mud. In contrast to the conventional method using the impeller, bentonite was manufactured in its nanoparticle state in the present work through ultrasonic and homogenizer processes in the solution state. In case of the ultrasonic process, the viscosity increase in the low shear rate region before and after processing of the 5 wt% bentonite-based mud and the rheological properties in the presence of polymer additive were compared. In case of the homogenizer process, the rheological properties of 3 wt% bentonite-based mud employed through the homogenizer process and 5 wt% mud prepared generally were compared. Both processes reported improvement of rheological properties, in which shear thinning behavior strongly occurred when particle size decreased through FE-SEM, TEM image analysis, and particle size analyzer. A regularized Herschel-Bulkley model suitable for rheological quantitative explanation of drilling mud including yield stress was selected. The homogenizer process has the potential to be applied in the petroleum drilling industry for large-scale production, and the mechanism was confirmed by numerical analyses. In conclusion, we presented a simple and easy-to-apply process to rapidly produce nano-based drilling mud.

MXene Hybrid Nanosheet of WS2/Ti3C2 for Electrocatalytic Hydrogen Evolution Reaction.

Designing low-cost hybrid electrocatalysts for hydrogen production is of significant importance. Recently, MXene-based materials are being increasingly employed in energy storage devices owing to their layered structure and high electrical conductivity. In this study, we propose a facile hydrothermal strategy for producing WS2/Ti3C2 nanosheets that function as electrocatalysts in the hydrogen evolution reaction (HER). WS2 provides a high surface area and active sites for electrocatalytic activity, whereas MXene Ti3C2 facilitates charge transfer. As a result, the synthesized WS2/Ti3C2 offers an increased surface area and exhibits an enhanced electrocatalytic activity in acidic media. The WS2/Ti3C2 (10%) catalyst exhibited a low onset potential of -150 mV versus RHE for the HER and a low Tafel slope of ∼62 mV dec-1. Moreover, WS2/Ti3C2 (10%) exhibited a double-layer capacitance of 1.2 mF/cm-2, which is 3 and 6 times greater than those of bare WS2 and Ti3C2, respectively. This catalyst also maintained a steady catalytic activity for the HER for over 1000 cycles.

Transition Metal Ion Doping on ZIF-8 Enhances the Electrochemical CO2 Reduction Reaction.

The electrochemical reduction of CO2  to diverse value-added chemicals is a unique, environmentally friendly approach for curbing greenhouse gas emissions while addressing sluggish catalytic activity and low Faradaic efficiency (FE) of electrocatalysts. Here, zeolite-imidazolate-frameworks-8 (ZIF-8) containing various transition metal ions-Ni, Fe, and Cu-at varying concentrations upon doping are fabricated for the electrocatalytic CO2 reduction reaction (CO2 RR) to carbon monoxide (CO) without further processing. Atom coordination environments and theoretical electrocatalytic performance are scrutinized via X-ray absorption spectroscopy (XAS) and density functional theory (DFT) calculations. Upon optimized Cu doping on ZIF-8, Cu0.5 Zn0.5 /ZIF-8 achieves a high partial current density of 11.57 mA cm-2 and maximum FE for CO of 88.5% at -1.0 V (versus RHE) with a stable catalytic activity over 6 h. Furthermore, the electron-rich sp2 C atom facilitates COOH* promotion after Cu doping of ZIF-8, leading to a local effect between the zinc-nitrogen (Zn-N4 ) and copper-nitrogen (Cu-N4 ) moieties. Additionally, the advanced CO2 RR pathway is illustrated from various perspectives, including the pre-H-covered state under the CO2 RR. The findings expand the pool of efficient metal-organic framework (MOF)-based CO2 RR catalysts, deeming them viable alternatives to conventional catalysts.

Direct detection of tetrahydrobiopterin (BH4) and dopamine in rat brain using liquid chromatography coupled electrospray tandem mass spectrometry.

A simple and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of tetrahydrobiopterin (BH4) and dopamine in rat brain using epsilon-acetamidocaproic acid (AACA) as an internal standard. Proteins in the samples were precipitated with acetonitrile and then the supernatants were separated by a Sepax Polar-Imidazole (2.1 × 100 mm, i.d., 3 µm) column using a mixture of 10mM ammonium formate in acetonitrile/water (75:25, v/v) as the mobile phase at a flow rate of 300 µl/min. Quantification was performed on a triple quadrupole mass spectrometer employing electrospray ionization with the operating conditions as multiple reaction monitoring (MRM) and positive ion mode from m/z 242.1 → 166.0 for BH4, m/z 154.1 → 90.0 for dopamine and m/z 174.1 → 114.0 for AACA (IS). The total chromatographic run time was for 5.5 min. The method was validated for the analysis of samples: the limit of detection was 10 ng/g. The calibration curve was linear between 10-2000 ng/g for BH4 (r(2)=0.995) and 10-5000 ng/g for dopamine (r(2)=0.997) in the rat brain. Thus, good correlated LC-ESI/MS/MS results were obtained and found to be a powerful tool for the quantitative analysis of BH4 and dopamine in the rat brain.

[Hyponatremic Seizure after Ingestion of an Oral Sulfate Tablet for Bowel Preparation for Colonoscopy].

The oral sulfate tablet (OST), commercially available as Orafang® (Pharmbio Korea Co., Seoul, Korea) in Korea, is being used increasingly because of its bowel-cleansing efficacy, safety, and tolerability in adults undergoing colonoscopy. Other bowel cleansing agents, such as polyethylene glycol and sodium picosulfate/magnesium citrate, can cause plasma volume depletion and electrolyte disturbances, such as hyponatremia. On the other hand, the OST has never been reported to cause hyponatremia in Korea. To our knowledge, the authors experienced the first case of hyponatremic seizure in an 81-year-old woman to whom an OST was administered for bowel preparation before a colonoscopy. After ingesting the OST, she presented with seizure, confusion, and dyspnea. Upon arrival, her serum sodium level was 120 mEq/L, and the urine osmolality and sodium levels were 449 mOsm/kg and 253 mOsm/kg, respectively; chest imaging suggested pulmonary edema. The associated symptoms disappeared following treatment with an intravenous injection of normal saline and 3% NaCl to normalize the sodium level. This case shows that the OST can cause hyponatremia and other severe complications related to hyponatremia.

Undifferentiated hematopoietic cells are characterized by a genome-wide undermethylation dip around the transcription start site and a hierarchical epigenetic plasticity.

Evidence for the epigenetic regulation of hematopoietic stem cells (HSCs) is growing, but the genome-wide epigenetic signature of HSCs and its functional significance remain unclear. In this study, from a genome-wide comparison of CpG methylation in human CD34(+) and CD34(-) cells, we identified a characteristic undermethylation dip around the transcription start site of promoters and an overmethylation of flanking regions in undifferentiated CD34(+) cells. This "bivalent-like" CpG methylation pattern around the transcription start site was more prominent in genes not associated with CpG islands (CGI(-)) than CGI(+) genes. Undifferentiated hematopoietic cells also exhibited dynamic chromatin associated with active transcription and a higher turnover of histone acetylation than terminally differentiated cells. Interestingly, inhibition of chromatin condensation by chemical treatment (5-azacytidine, trichostatin A) enhanced the self-renewal of "stimulated" HSCs in reconstituting bone marrows but not "steady-state" HSCs in stationary phase bone marrows. In contrast, similar treatments on more mature cells caused partial phenotypic dedifferentiation and apoptosis at levels correlated with their hematopoietic differentiation. Taken together, our study reveals that the undifferentiated state of hematopoietic cells is characterized by a unique epigenetic signature, which includes dynamic chromatin structures and an epigenetic plasticity that correlates to level of undifferentiation.