Identification of a small-molecule inhibitor that selectively blocks DNA-binding by Trypanosoma brucei replication protein A1.

Replication Protein A (RPA) is a broadly conserved complex comprised of the RPA1, 2 and 3 subunits. RPA protects the exposed single-stranded DNA (ssDNA) during DNA replication and repair. Using structural modeling, we discover an inhibitor, JC-229, that targets RPA1 in Trypanosoma brucei, the causative parasite of African trypanosomiasis. The inhibitor is highly toxic to T. brucei cells, while mildly toxic to human cells. JC-229 treatment mimics the effects of TbRPA1 depletion, including DNA replication inhibition and DNA damage accumulation. In-vitro ssDNA-binding assays demonstrate that JC-229 inhibits the activity of TbRPA1, but not the human ortholog. Indeed, despite the high sequence identity with T. cruzi and Leishmania RPA1, JC-229 only impacts the ssDNA-binding activity of TbRPA1. Site-directed mutagenesis confirms that the DNA-Binding Domain A (DBD-A) in TbRPA1 contains a JC-229 binding pocket. Residue Serine 105 determines specific binding and inhibition of TbRPA1 but not T. cruzi and Leishmania RPA1. Our data suggest a path toward developing and testing highly specific inhibitors for the treatment of African trypanosomiasis.

Genetic Interaction Between Site-Specific Epigenetic Marks and Roles of H4v in Transcription Termination in Trypanosoma brucei.

In Trypanosoma brucei, genes are assembled in polycistronic transcription units (PTUs). Boundaries of PTUs are designated transcription start sites and transcription termination sites (TTSs). Messenger RNAs are generated by trans-splicing and polyadenylation of precursor RNAs, and regulatory information in the 3' un-translated region (UTR), rather than promoter activity/sequence-specific transcription factors, controls mRNA levels. Given this peculiar genome structure, special strategies must be utilized to control transcription in T. brucei. TTSs are deposition sites for three non-essential chromatin factors-two of non-canonical histone variants (H3v and H4v) and a DNA modification (base J, which is a hydroxyl-glucosyl dT). This association generated the hypothesis that these three chromatin marks define a transcription termination site in T. brucei. Using a panel of null mutants lacking H3v, H4v, and base J, here I show that H4v is a major sign for transcription termination at TTSs. While having a secondary function at TTSs, H3v is important for monoallelic transcription of telomeric antigen genes. The simultaneous absence of both histone variants leads to proliferation and replication defects, which are exacerbated by the J absence, accompanied by accumulation of sub-G1 population. Thus, I propose that the coordinated actions of H3v, H4v, and J provide compensatory mechanisms for each other in chromatin organization, transcription, replication, and cell-cycle progression.

Age-Period-Cohort Analysis of Trends in Infectious Disease Mortality in South Korea from 1983 to 2017.

We aimed to describe the infectious disease (ID) mortality trends and evaluate age-period-cohort (APC) effects on ID mortality in Korea. Using cause-of-death and census population estimates data from 1983-2017, age-standardized ID mortality trends were investigated by joinpoint regression analysis. The APC effects on ID mortality were estimated using intrinsic estimator models. The age effect showed a J-shaped concave upward curve. Old age, especially ≥70 years, was a critical factor for ID deaths. Similar to the W-shaped period curve, ID mortality rapidly decreased due to economic development and the expansion of health coverage in the 1980s, decelerated with increasing inequality, surged due to the 1997 economic crisis, and has gradually increased since the mid-2000s. The cohort effect showed an inverted U-shape. The increasing cohort effect due to the deterioration of living standards led to a decreasing trend after the independence of Korea. Notwithstanding the slowdown during the 1950-1953 Korean War, educational expansion, economic growth, fertility reduction, and the improvement of ID-related policies might have led to a continued decline among the cohorts born since the 1960s. Diverse socioeconomic events may have influenced ID mortality trends in Korea via period and cohort effects. Policies to reduce the growing burden of ID deaths should be further improved.

A Trypanosoma brucei ORFeome-Based Gain-of-Function Library Identifies Genes That Promote Survival during Melarsoprol Treatment.

Trypanosoma brucei is an early branching protozoan parasite that causes human and animal African trypanosomiasis. Forward genetics approaches are powerful tools for uncovering novel aspects of trypanosomatid biology, pathogenesis, and therapeutic approaches against trypanosomiasis. Here, we have generated a T. brucei cloned ORFeome consisting of >90% of the targeted 7,245 genes and used it to make an inducible gain-of-function parasite library broadly applicable to large-scale forward genetic screens. We conducted a proof-of-principle genetic screen to identify genes whose expression promotes survival in melarsoprol, a critical drug of last resort. The 57 genes identified as overrepresented in melarsoprol survivor populations included the gene encoding the rate-limiting enzyme for the biosynthesis of an established drug target (trypanothione), validating the tool. In addition, novel genes associated with gene expression, flagellum localization, and mitochondrion localization were identified, and a subset of those genes increased melarsoprol resistance upon overexpression in culture. These findings offer new insights into trypanosomatid basic biology, implications for drug targets, and direct or indirect drug resistance mechanisms. This study generated a T. brucei ORFeome and gain-of-function parasite library, demonstrated the library's usefulness in forward genetic screening, and identified novel aspects of melarsoprol resistance that will be the subject of future investigations. These powerful genetic tools can be used to broadly advance trypanosomatid research.IMPORTANCE Trypanosomatid parasites threaten the health of more than 1 billion people worldwide. Because their genomes are highly diverged from those of well-established eukaryotes, conservation is not always useful in assigning gene functions. However, it is precisely among the trypanosomatid-specific genes that ideal therapeutic targets might be found. Forward genetics approaches are an effective way to identify novel gene functions. We used an ORFeome approach to clone a large percentage of Trypanosoma brucei genes and generate a gain-of-function parasite library. This library was used in a genetic screen to identify genes that promote resistance to the clinically significant yet highly toxic drug melarsoprol. Hits arising from the screen demonstrated the library's usefulness in identifying known pathways and uncovered novel aspects of resistance mediated by proteins localized to the flagellum and mitochondrion. The powerful new genetic tools generated herein are expected to promote advances in trypanosomatid biology and therapeutic development in the years to come.

COVID-19 in Nursing Facilities: Experience in Republic of Korea.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) outbreaks in nursing facilities can easily lead to a high rate of infection and fatality. A surge in newly infected cases in the first quarter of 2020 in Gyeongsan-si, in the Republic of Korea, was followed by several outbreaks in nursing facilities in the same area. The aim of this study is to report on the epidemiological investigation and the management to reduce the infection rate in nursing facilities for older adults. METHODS: The municipal government and the Korea Centers for Disease Control and Prevention performed an epidemiological investigation into 5 nursing facilities that reported a high number of COVID-19 infection cases from February to May 2020. COVID-19 infected cases in the facilities were investigated to identify the infection routes, and the fatality rate of the 5 facilities. RESULTS: The 5 facilities had a combined fatality rate of 12.2% (9 deceased among the 74 infected cases). The median age of the deceased was 87 years old (range: 82-91). The infection was first identified on February 27th, 2020, peaked on March 6th, and was last detected on March 24th, 2020. CONCLUSION: Difficulties specific to such facilities included the delay in the recognition of symptoms and limitation in distancing. Tailored strategies such as daily monitoring of symptoms and proactive COVID-19 screening of quarantined residents, contributed to a decline in the infections in the facilities.

[Effects of Oral Gargling with Aroma Solution in Psychiatric Inpatients: A Non-Randomized Controlled Trial].

PURPOSE: The purpose of this study was to examine the effects of oral gargling with an aromatic solution on xerostomia, objective oral status, and oral health-related quality of life in psychiatric inpatients. METHODS: A nonequivalent control group with a non-synchronized design was used in this study. The experimental group (n=34) received oral gargling with an aroma solution, while the control group (n=33) gargled with 0.9% normal saline. Dependent variables were measured at pre-, post-, and follow-up test. Data were analyzed using an χ²-test, Fisher's exact probability test, t-tests, and repeated measures ANOVA using SPSS/WIN v.21.0. RESULTS: After the intervention, significant differences were revealed in xerostomia (F=15.30, p <.001), objective oral status (F=38.44, p <.001), and oral health-related quality of life (F=62.70, p <.001) with an interaction effect between group and time. CONCLUSION: These findings indicate that gargling with an aroma solution is more effective than 0.9% normal saline for the oral health of psychiatric inpatients. Therefore gargling with an aroma can be safely recommended as a brief, economical, and positive intervention in clinical settings.

Hepatoprotective effect of meal replacement seeds juice based on sweet potato (MRSJ) against CCl4-induced cytotoxicity in HepG2 cells.

A sweet potato-based Meal Replacement Seeds Juice (MRSJ) was developed by mixing sweet potatoes and carrots with four types of seeds. Consuming the MRSJ rather than the whole vegetables or whole seeds improved digestive function, proving that it is suitable for the elderly. Its rich composition of minerals, vitamins, and unsaturated fatty acids implicates it as an excellent nutrient source. Notably, the ethyl acetate fraction of MRSJ contains abundant phenolics. The antioxidant activity assays showed that these phenolics have high radical scavenging activity, reducing power, and antioxidant capacity similar to l-ascorbic acid. The ethyl acetate fraction exerted protective effects against CCl4- or H2O2-induced hepatotoxicity via DNA protection, lipid accumulation inhibition, and cell protection, wherein ALT and AST activities in the cell culture solution decreased significantly. These findings suggest that MRSJ consumption may protect against liver diseases. Moreover, MRSJ as an excellent nutrient source may be developed as an age-neutral food.

Comparison of Antioxidant Properties of Evening Primrose Seeds by Different Processing Methods, and Physiological Properties of Evening Primrose Seed Powder.

This study proposes the processing method that could maximize the functional properties of evening primrose seeds (EPS) and its various nutritional components. EPS can be prepared by different methods, such as being left raw, roasting, steaming, and powdering. Processing of EPS to create EPS powder (EPSP) resulted in higher levels of vitamin E, fatty acids, total phenolic contents, and antioxidant activity, compared with the other processing methods. Also, EPSP maintained lipid peroxidation inhibitory activity for 49 days. In particular, the EPSP ethyl acetate (EtOAc) fraction exhibited high antioxidant, antidiabetic, and angiotensin I-converting enzyme inhibitory activities. The EPSP ethyl acetate fraction showed a high cytoprotective effect against H2O2-induced cell damage in both RAW264.7 and EA.hy926 cells. In addition, the EtOAc fraction showed anti-inflammatory activity by the inhibitory activity of nitric oxide (NO) in RAW264.7 cells, and antihypertensive activity by the activity of NO in EA.hy926 cells. These results suggest that EPSP could be useful as a food ingredient that assists the prevention of various diseases caused by oxidative stress.

Synergistic effect of fruit-seed mixed juice on inhibition of angiotensin I-converting enzyme and activation of NO production in EA.hy926 cells.

Commonly consumed fruit juices possess low inhibitory activity of angiotensin I-converting enzyme (ACE), which plays central role in elevation of blood pressure. The ACE inhibitory activity of fruit-seed mixed juice may be improved via synergistic interactions. In this study, the investigated synergistic, additive, and antagonistic effects of fruit-seed combination on ACE inhibition were investigated. Thirteen fruits and 15 seeds including legumes, nuts, and cereals were combined in pairs; pear-hemp seed-pumpkin seed juice (3-mixed juice) displayed the highest ACE inhibition resulting from synergistic interactions. Additionally, nitric oxide production in human endothelial cells was promoted by 3-mixed juice. Three-mixed juice showed antioxidant activities such as DNA protective, DPPH radical scavenging, and reducing effects. These results suggested that combinations of different food categories are beneficial for improving biological functions such as vascular health. Three-mixed juice, which shows high ACE inhibitory activity, may be useful as an anti-hypertensive agent and for treating hypertension.

Genome-wide function of MCM-BP in Trypanosoma brucei DNA replication and transcription.

In Trypanosoma brucei, genes are arranged in Polycistronic Transcription Units (PTUs), which are demarcated by transcription start and stop sites. Transcription start sites are also binding sites of Origin Recognition Complex 1 (ORC1). This spatial coincidence implies that transcription and replication in trypanosomes must occur in a highly ordered and cooperative manner. Interestingly, a previously published genetic screen identified the T. brucei MCM-BP, which interacts with subunits of MCM helicase, as a protein whose downregulation results in the loss of transcriptional silencing at subtelomeric loci. Here, I show that TbMCM-BP is required for DNA replication and transcription. TbMCM-BP depletion causes a significant reduction of replicating cells in S phase and genome-wide impairments of replication origin activation. Moreover, levels of sense and antisense transcripts increase at boundaries of PTUs in the absence of TbMCM-BP. TbMCM-BP is also important for transcriptional repression of the specialized subtelomeric PTUs, the Bloodstream-form Expression-Sites (BESs), which house the major antigenic determinant (the Variant Surface Glycoprotein, VSG gene) as well as TbORC1 binding sites. Overall, this study reveals that TbMCM-BP, a replication initiation protein, also guides the initiation, termination and directionality of transcription.

African trypanosomes evade immune clearance by O-glycosylation of the VSG surface coat.

The African trypanosome Trypanosoma brucei spp. is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity. The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs. This persistent immune evasion has been ascribed exclusively to amino-acid variance on the VSG surface presented by a conserved underlying protein architecture. We establish here that this model does not account for the scope of VSG structural and biochemical diversity. The 1.4-Å-resolution crystal structure of the variant VSG3 manifests divergence in the tertiary fold and oligomeric state. The structure also reveals an O-linked carbohydrate on the top surface of VSG3. Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs. We demonstrate that this O-glycosylation increases parasite virulence by impairing the generation of protective immunity. These data alter the paradigm of antigenic variation by the African trypanosome, expanding VSG variability beyond amino-acid sequence to include surface post-translational modifications with immunomodulatory impact.

Symptom clusters and treatment time delay in Korean patients with ST-elevation myocardial infarction on admission.

Most patients with acute myocardial infarction (AMI) experience more than one symptom at onset. Although symptoms are an important early indicator, patients and physicians may have difficulty interpreting symptoms and detecting AMI at an early stage. This study aimed to identify symptom clusters among Korean patients with ST-elevation myocardial infarction (STEMI), to examine the relationship between symptom clusters and patient-related variables, and to investigate the influence of symptom clusters on treatment time delay (decision time [DT], onset-to-balloon time [OTB]). This was a prospective multicenter study with a descriptive design that used face-to-face interviews. A total of 342 patients with STEMI were included in this study. To identify symptom clusters, two-step cluster analysis was performed using SPSS software. Multinomial logistic regression to explore factors related to each cluster and multiple logistic regression to determine the effect of symptom clusters on treatment time delay were conducted. Three symptom clusters were identified: cluster 1 (classic MI; characterized by chest pain); cluster 2 (stress symptoms; sweating and chest pain); and cluster 3 (multiple symptoms; dizziness, sweating, chest pain, weakness, and dyspnea). Compared with patients in clusters 2 and 3, those in cluster 1 were more likely to have diabetes or prior MI. Patients in clusters 2 and 3, who predominantly showed other symptoms in addition to chest pain, had a significantly shorter DT and OTB than those in cluster 1. In conclusion, to decrease treatment time delay, it seems important that patients and clinicians recognize symptom clusters, rather than relying on chest pain alone. Further research is necessary to translate our findings into clinical practice and to improve patient education and public education campaigns.

Maternal and neonatal outcomes in Korean women with type 2 diabetes.

BACKGROUND/AIMS: The purpose of this study was to compare maternal and neonatal outcomes in Korean women with type 2 diabetes and nondiabetic controls. METHODS: We performed a retrospective survey of 200 pregnancies in women with type 2 diabetes (n = 100) and nondiabetic controls (n = 100) who delivered from 2003 to 2010 at Cheil General Hospital & Women's Healthcare Center, Korea. We compared maternal characteristics as well as maternal and neonatal outcomes between groups matched by age, pre-pregnancy weight, body mass index, parity, and gestational age at delivery. RESULTS: The number of infants that were small for gestational age and the rate of major congenital malformations were not significantly different. However, women with type 2 diabetes showed a slightly higher risk for primary caesarean section (35.0% vs. 18.0%, p = 0.006) as well as pre-eclampsia (10.0% vs. 2.0%, p = 0.017), infections during pregnancy (26.0% vs. 2.0%, p < 0.001), neonatal weight (3,370 ± 552.0 vs. 3,196 ± 543.3, p = 0.025), large for gestational age (22.0% vs. 9.0%, p = 0.011), and macrosomia (15.0% vs. 5.0%, p = 0.018) compared to nondiabetic controls. CONCLUSION: Maternal and neonatal outcomes for women with type 2 diabetes were worse than those for nondiabetic controls. Diabetic women have a higher risk for primary caesarean section, pre-eclampsia, infections during pregnancy, large neonatal birth weight, large for gestational age, and macrosomia.

Association of Anxiety, Depression, and Somatization with Menstrual Problems among North Korean Women Defectors in South Korea.

OBJECTIVE: North Korean women defectors have suffered from anxiety, depression, and somatization after defection. Also they have had many menstrual problems like amenorrhea. This study was done to identify the correlations of anxiety, depression, and somatization to menstrual problems among North Korean woman defectors in South Korea. METHODS: The participants in this study were 126 women from 5 government resettlement centers throughout South Korea. Questionnaires which included State-Trait Anxiety Inventory (STAI), Center for Epidemiological studies-Depression Scale (CED-S), and Symptom Checklist-90-Revised (SCL-90-R) were used to identify anxiety and somatization. Data were collected between June and September, 2012. RESULTS: The women reported the following problems; amenorrhea (9.5%), hypomenorrhea (13.6%), menorrhagia (19.8%), polymenorrhea (13.5%), oligomenorrhea (4.8%), changes in amount of menstrual discharge (4.0%), and changes in amount of blood clot (9.5%). Anxiety (r=0.20, p=0.002), depression (r=0.25, p=0.005), and Somatization (r=0.35, p<0.001) were correlated with number of menstrual problems. CONCLUSION: The results of this study indicate that mental health services need to be taken into account in interventions for North Korean woman defectors to improve their reproductive health including addressing menstrual problems.

Gender Differences in Factors Related to Prehospital Delay in Patients with ST-Segment Elevation Myocardial Infarction.

PURPOSE: The aim of our study was to investigate gender differences in factors related to prehospital delay and identify whether the knowledge of acute myocardial infarction symptoms affects this delay in Korean patients with ST-elevation myocardial infarction (STEMI). MATERIALS AND METHODS: A total of 350 patients (286 men, 64 women) with confirmed STEMI were interviewed to investigate socio-demographics, history of disease, symptom onset time, and factors that contributed to delayed decision time in seeking treatment and hospital arrival time from symptom onset. Factors associated with prehospital delay were examined separately by gender using univariate and multivariate analyses. RESULTS: Female patients had higher proportions of ≥60-minute decision time and ≥120-minute arrival time compared to male patients (33.9% vs. 23.1%, 60.9% vs. 52.1%, respectively). However, the difference was not statistically significant (p=0.093 and 0.214, respectively). Previous cardiovascular disease (CVD) was associated with increased decision time in men, whereas, in women, lower educational status caused a greater delay in decision time. Factors associated with hospital arrival time excluding delayed decision time were referral from another hospital, previous CVD, and percutaneous coronary intervention in men, and referral from another hospital in women. CONCLUSION: Gender differences exist in factors related to prehospital delay. Therefore, public education to reduce prehospital delay should be conducted according to gender with a focus on the pertinent factors.

Public Awareness of Stroke and Its Predicting Factors in Korea: a National Public Telephone Survey, 2012 and 2014.

The aim of this study was to investigate time trends in the public awareness of stroke and its predicting factors. The target population was 9,600 community-dwelling adults, aged 19-79 years, in 16 metropolitan cities and provinces in Korea. The survey samples in 2012 and 2014 were selected separately (entirely different sets of subjects) using a proportionate quota sampling method. Information concerning knowledge of stroke and demographics was collected by trained telephone interviewers using random digit dialing. After excluding subjects with a non-response or refusal to answer any question, the analyses included 8,191 subjects in 2012 and 8,127 subjects in 2014. Respondents' awareness of stroke warning signs (numbness or weakness, difficulty speaking or understanding speech, dizziness, visual impairment, and severe headache) was highest for difficulty speaking or understanding speech (80.9% in 2012 and 86.4% in 2014). There were significant increases in the proportion of respondents understanding the appropriate action (i.e., calling an ambulance) at the time of stroke occurrence (59.6% to 67.1%), and in the proportion aware of the general need for prompt treatment (86.7% to 89.8%). In multivariable logistic regression analysis, older age, higher education level, higher household income, current non-smoking, exposure to stroke-related public relations materials, and experience of stroke education were significantly associated with both high knowledge of stroke warning signs and awareness of the need for prompt treatment. Between 2012 and 2014, the public's awareness of stroke increased significantly. More specialized interventions, including public relations materials and education, should focus on subgroups who have lower stroke knowledge.

Effects of deregulation of the driving licence application process on road safety in Korea: an interrupted time-series analysis.

BACKGROUND: Road traffic deaths (RTDs) remain the 9th most common cause of mortality in South Korea despite their decreasing trends in high-income countries. In 2010 and 2011, the Korean government deregulated the process for obtaining a driving licence, and there has been significant concern that such deregulation of the driving licence policy could reduce road safety. This study aimed to explore the effects of the deregulation of driving licence policy on road safety by examining the incidence of road traffic collisions (RTCs), road traffic injuries (RTIs) and RTDs. METHODS: The monthly incidence of RTCs, RTIs and RTDs was generated by using numbers of RTCs, RTIs and RTDs as numerators and numbers of registered vehicles as denominators. Changes in incidence since the deregulation implementation in February 2010 (phase I) and June 2011 (phase II) were evaluated via interrupted time-series analysis. RESULTS: The second deregulation phase demonstrated significant changes in numbers of RTCs and RTIs: numbers of RTCs and RTIs decreased until they began to increase in November 2011. Since then, the monthly incidence of RTCs and RTIs have increased by 133.5 and 123.8 per 100 000 vehicles per month, respectively (p<0.05). RTD secular trends began to increase consecutively at rates of 0.024 (June 2010), 0.018 (between July 2010 and June 2011) and 0.273 (July 2011 onward) per 100 000 vehicles per month. Over the entire study period, the RTD incidence rate increased by 0.018 deaths per month on average subsequent to the first deregulation phase (p<0.05). CONCLUSIONS: The deregulation policies that simplified the driving licence process were associated with increased incidence of RTCs, RTIs and RTDs in Korea.

Structural and Biochemical Characterization of an Octameric Carbohydrate Acetylesterase from Sinorhizobium meliloti.

Carbohydrate acetylesterases, which have a highly specific role among plant-interacting bacterial species, remove the acetyl groups from plant carbohydrates. Here, we determined the crystal structure of Est24, an octameric carbohydrate acetylesterase from Sinorhizobium meliloti, at 1.45 Å resolution and investigated its biochemical properties. The structure of Est24 consisted of five parallel ß strands flanked by α helices, which formed an octameric assembly with two distinct interfaces. The deacetylation activity of Est24 and its mutants around the substrate-binding pocket was investigated using several substrates, including glucose pentaacetate and acetyl alginate. Elucidation of the structure-function relationships of Est24 could provide valuable opportunities for biotechnological explorations.

The General Public's Awareness of Early Symptoms of and Emergency Responses to Acute Myocardial Infarction and Related Factors in South Korea: A National Public Telephone Survey.

BACKGROUND: Prompt treatment affects prognosis and survival after acute myocardial infarction (AMI) onset. This study evaluated the awareness of early symptoms of AMI and knowledge of appropriate responses on symptom occurrence, along with related factors. METHODS: Participants' knowledge of the early symptoms of and responses to AMI onset were investigated using a random digit dialing survey. We included 9600 residents of 16 metropolitan cities and provinces in Korea. RESULTS: The proportions of respondents who were aware of early symptoms of AMI ranged from 32.9% (arm or shoulder pain) to 79.1% (chest pain and discomfort). Of the respondents, 67.0% would call an ambulance if someone showed signs of AMI, 88.7% knew ≥1 symptom, 10.9% knew all five symptoms, and 3.1% had excellent knowledge (correct identification of all five AMI symptoms, not answering "Yes" to the trap question, and correctly identifying calling an ambulance as the appropriate response when someone is exhibiting AMI symptoms). The odds ratio (OR) for having excellent knowledge was significantly higher for those who graduated college or higher (OR 3.42; 95% confidence interval [CI], 1.09-10.76) than for those with less than a primary school education, as well as for subjects with AMI advertisement exposure (OR 1.49; 95% CI, 1.10-2.02) and with knowledge of AMI (OR 1.63; 95% CI, 1.16-2.27). The 60- to 79-year-old group had significantly lower OR for excellent knowledge than the 20- to 39-year-old group (OR 0.53; 95% CI, 0.28-0.99). CONCLUSIONS: Awareness of AMI symptoms and the appropriate action to take after symptom onset in South Korea was poor. Therefore, educational and promotional strategies to increase the overall awareness in the general public, especially in the elderly and those with low education levels, are needed.

Base J and H3.V Regulate Transcriptional Termination in Trypanosoma brucei.

Trypanosoma brucei is a protozoan parasite that lacks many transcription factors found in other eukaryotes, such as those whose binding demarcates enhancers. T. brucei retains histone variants and modifications, however, and it is hypothesized that it relies on epigenetic marks to define transcription-related boundaries. The histone H3 variant (H3.V) and an alternate nucleotide, base J (ß-D-glucosyl-hydroxymethyluracil), are two chromatin marks found at both transcription termination sites (TTSs) and telomeres. Here, we report that the absence of both base J and H3.V result in transcription readthrough and the appearance of antisense transcripts near TTSs. Additionally, we find that maintaining the transcriptional silencing of pol I-transcribed telomeric Variant Surface Glycoprotein (VSG) genes appears to be dependent on deposition of H3.V alone. Our study reveals that gene expression depends on different epigenetic cues depending on chromosomal location and on the transcribing polymerase. This work provides insight into how these signals may have evolved into the more nuanced and fine-tuned gene regulatory mechanisms observed in other model systems.