Heterologous peptide display on chromatin nanofibers: A new strategy for peptide vaccines.

Chromatin organization starts from a "beads-on-a string" 10 nm fiber, a basic nucleosomal structure consisting of DNA and core histones. Given its regular nucleosome array on DNA backbone where N-terminal tails of each histone are exposed on the surface of chromatin fiber, we hypothesized that chromatin can be utilized as a heterologous peptide carrier to elicit a peptide-specific immune response. The plasmid DNA containing the Widom's clone 601 sequence and the recombinant chimeric histones containing the peptide derived from ras oncogene (G12V) were used to assemble the chromatin fiber in vitro. The immunogenicity of the assembled chromatin was tested in mice as a single vaccine component or formulated with adjuvants. G12V tagged-chromatin co-administered with adjuvants induced higher antibody responses against the G12V peptide than vaccination with adjuvant alone, while chimeric histones did not generate a significant antibody response. Interestingly, splenocytes from mice vaccinated with the G12V tagged-chromatin vaccine did not generate significant antigen-specific cytokine responses. Our studies suggest that chromatin can be utilized as an effective carrier of antigenic peptides for inducing specific antibody responses.

Magnetic resonance elastography for evaluation of renal parenchyma in chronic kidney disease: a pilot study.

OBJECTIVE: This study aimed to prospectively evaluate the difference in renal parenchymal stiffness, measured using MR elastography, between patients with chronic kidney disease (CKD) and healthy volunteers. In addition, differences in stiffness values were assessed among the five stages of CKD. MATERIALS AND METHODS: Five healthy volunteers and 25 patients with CKD (five patients in each stage) were enrolled in the study. Each patient was positioned prone in a 3-T MR scanner and imaged with an abdominal 64-channel surface coil. Calculated tissue stiffness values were compared with the corresponding stage of CKD. RESULTS: The mean stiffnesses in normal healthy volunteers and patients with CKD (regardless of stage) were 4.35 kPa and 5.10 kPa, respectively (p = 0.027). The mean stiffness in patients with CKD significantly increased with the CKD stage (p = 0.013), although it decreased in stage 5 CKD. CONCLUSION: Renal tissue stiffness measured using MR elastography can be used to distinguish between patients with CKD and healthy individuals; moreover, it can be useful in predicting the stage of CKD.

Estimation of the within-herd transmission rates of bovine viral diarrhoea virus in extensively grazed beef cattle herds.

Many research groups have developed mathematical models to simulate the dynamics of BVDV infections in cattle herds. However, most models use estimates for within-herd BVDV transmission rates that are either based on expert opinion or adapted from other dairy herd simulation models presented in the literature. There is currently little information on the transmission rates for BVDV in extensively grazed beef herds partly due to the logistical challenges in obtaining longitudinal data of individual animal's seroconversion, and it may not be appropriate to apply the same transmission rates from intensive dairy herds given the significant differences in herd demographics and management. To address this knowledge gap, we measured BVDV antibody levels in 15 replacement heifers in each of 75 New Zealand beef breeding farms after their first calving and again at pregnancy scanning or weaning to check for seroconversion. Among these, data from 9 farms were used to infer the within-herd BVDV transmission rate with an approximate Bayesian computation method. The most probable within-herd BVDV transmission rate was estimated as 0.11 per persistently infected (PI) animal per day with a 95% highest posterior density interval between 0.03 and 0.34. This suggests that BVDV transmission in extensively grazed beef herds is generally slower than in dairy herds where the transmission rate has been estimated at 0.50 per PI animal per day and therefore may not be sufficient to ensure that all susceptible breeding females gain adequate immunity to the virus before the risk period of early pregnancy for generating new PI calves.

Effects of meteorological factor and air pollution on sudden sensorineural hearing loss using the health claims data in Busan, Republic of Korea.

PURPOSE: Specific meteorological factors, including air pollution in the form of particulate matter (PM), affect the development of otologic disease and have adverse effects on the cardiovascular and respiratory systems. This study investigated relationships between the development of sudden sensorineural hearing loss(SSNHL) and meteorological factor with air pollution including PM. MATERIALS AND METHODS: The daily patient number in 2015 admitted to the hospital with SSNHL were extracted from the Health Insurance Review and Assessment Service Bigdata in Busan. The meteorological factors and air pollution data of Busan area were obtained from meteorological stations in Busan. The relationship between the number of hospitalizations and the climatic factors was checked. RESULTS: SSNHL patient group showed more common in women, and the highest rates were observed in patients in their 50s. The daily mean patient numbers were 2.27. The number of SSNHL patients in spring was statistically significantly higher than that in summer. The mean daily PM10 and PM2.5 concentrations were 48.0 and 29.4 µg/m3, respectively. The mean wind speed, maximum wind speed and daily atmospheric pressure range was weakly positively associated with SSNHL patient number. There were weak negative correlations between maximum PM2.5 and SSNHL admissions. The mean temperature and wind chill index showed non-significantly negative relationships with SSNHL admissions. CONCLUSIONS: In Busan area, statistically significant weak relationships were detected between the daily numbers of patients admitted to the hospital with SSNHL and meteorological data, including PM level. Further investigation of these associations is required.

Upregulation of P21-Activated Kinase 1 (PAK1)/CREB Axis in Squamous Non-Small Cell Lung Carcinoma.

BACKGROUND/AIMS: p21-activated Ser/Thr kinase 1 (PAK1) is essential for the genesis and development of many cancers. The purpose of this study was to investigate the role of the PAK1-cyclic AMP response element-binding (CREB) axis in non-small cell lung cancer (NSCLC) tumorigenesis and its related mechanisms. METHODS: Western blot assay and immunohistochemical staining were employed to investigate the PAK1 and CREB expression in the tissue microarray of human squamous NSCLC. Co-immunoprecipitation and immunofluorescence confocal assays were performed to determine the link between PAK1 and CREB. NSCLC xenograft models were used to study oncogenic function of PAK1 in vivo. RESULTS: We observed that PAK1 and CREB expression levels were significantly elevated in human squamous NSCLC-tissue specimens, compared with those in adjacent normal bronchial or bronchiolar epithelial-tissue specimens, as well as their phosphorylated forms, based on western blotting. We showed in vitro that PAK1 knockdown by small-interfering RNA (siRNA) blocked CREB phosphorylation, whereas plasmid-based PAK1 overexpression resulted in CREB phosphorylation at Ser133, based on western blotting. In addition, PAK1 interacted with CREB in co-immunoprecipitation assays. Additionally, our in vitro findings detected by flow cytometry revealed that PAK1 silencing attenuated cell cycle progression, inducing apoptosis. Inhibition of PAK1 expression reduced tumor sizes and masses by modulating CREB expression and activation in xenograft models. CONCLUSION: These results suggest a novel mechanism whereby the PAK1-CREB axis drives carcinogenesis of squamous-cell carcinomas, and have important implications in the development of targeted therapeutics for squamous-cell lung cancer.

Hepatitis A in Korea from 2011 to 2013: Current Epidemiologic Status and Regional Distribution.

The hepatitis A virus (HAV) has been the leading cause of viral hepatitis in Korea since the 2000s. We aimed to describe the current status and regional differences in hepatitis A incidence. We studied the total number of hepatitis A cases reported to the Korea Centers for Disease Control and Prevention through the National Infectious Diseases Surveillance System between 2011 and 2013. Additionally, National Health Insurance Review and Assessment Service data and national population data from Statistics Korea were used. In total, 7,585 hepatitis A cases were reported; 5,521 (10.9 cases per 100,000 populations), 1,197 (2.3 cases per 100,000 populations), and 867 (1.7 cases per 100,000 populations) in 2011, 2012, and 2013, respectively. Fifty-eight patients were infected outside of the country and 7,527 patients represented autochthonous HAV infection cases. Autochthonous HAV infection occurred more frequently among men than women (4,619 cases, 6.1 cases per 100,000 population vs. 2,908 cases, 3.9 cases per 100,000 population). The incidence rate was higher in the 20-29 yr-old group (2,309 cases, 11.6 cases per 100,000 populations) and 30-39 yr-old group (3,306 cases, 13.6 cases per 100,000 populations). The majority of cases were reported from March to June (53.6%, 4,038/7,527). Geographic analyses revealed a consistently high relative risk (RR) of HAV infection in mid-western regions (2011, RR, 1.25, P=0.019; 2012, RR, 2.53, P<0.001; 2013, RR, 1.86, P<0.001). In summary, we report that hepatitis A incidence has been decreasing gradually from 2011 to 2013 and that some regions show the highest prevalence rates of HAV infection in Korea.

The Prescription Pattern of Acetaminophen and Non-Steroidal Anti-Inflammatory Drugs in Patients with Liver Cirrhosis.

Analgesics, known to be hepatotoxic drugs, are frequently prescribed to patients with liver cirrhosis who are prone to drug-induced liver injury. No guidelines are available regarding the prescription of analgesics in these patients. Therefore, we aimed to evaluate the prescription pattern of most frequently used analgesics in patients with cirrhosis. We assessed the prescription pattern of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) in patients with liver cirrhosis registered in Health Insurance Review Assessment Service database between January 1, 2012 and December 31, 2012. A total of 125,505 patients with liver cirrhosis were registered from January 1, 2012 to December 31, 2012. Of that group, 50,798 (40.5%) patients claimed reimbursement for at least one prescription for acetaminophen or NSAIDs during the one year follow-up period. Overall, NSAIDs (82.7%) were more prescribed than acetaminophen (64.5%). NSAIDs were more prescribed than acetaminophen even in decompensated cirrhosis compared with compensated cirrhosis (71.5% vs. 68.8%, P value < 0.001). There was a marked difference in prescription preference between acetaminophen and NSAIDs among physicians. Internists more frequently prescribed acetaminophen than NSAIDs compared to other physicians (50.9% vs. 76.2%, P < 0.001). Gastroenterologists more frequently prescribed acetaminophen over NSAIDs compared to other internists (80.9% vs. 51.2%, P < 0.001). Analgesics were prescribed in 40.5% of patients with cirrhosis. NSAIDs were more frequently prescribed although they should be avoided. The prescription pattern of analgesics were different significantly among physicians in patients with liver cirrhosis. The harmful effects of NSAIDs in patients with cirrhosis should be reminded to all physicians prescribing analgesics.

Does bilateral seminal vesicle invasion at radical prostatectomy predict worse prognosis than unilateral invasion among patients with pT3b prostate cancers?

OBJECTIVES: To determine whether bilateral seminal vesicle invasion is associated with worse biochemical recurrence-free survival than unilateral seminal vesicle invasion after radical prostatectomy. METHODS: We reviewed the clinicopathological data of 598 men who underwent radical prostatectomy between 2008 and 2015. Among them, 107 (17.9%) had seminal vesicle invasion. After excluding cases with neo-/adjuvant hormone treatment or radiotherapy, 93 were included in the analysis. We compared biochemical recurrence-free survival rates in subgroups with or without bilateral seminal vesicle invasion using Kaplan-Meier estimates. Cox proportional hazard regression models were used to determine the predictors of biochemical recurrence-free survival. RESULTS: Bilateral prostatic lobes and bilateral seminal vesicles were involved by prostate cancers in 85 (91.4%) and 35 patients (37.6%), respectively. Actuarial 3-year and 5-year biochemical recurrence-free survival rates in patients with pT3b tumors with/without bilateral seminal vesicle invasion were 13.0%/34.3%, and 4.3%/19.8%, respectively. On multivariable analysis, preoperative prostate-specific antigen (hazard ratio 1.01, 95% confidence interval 1.00-1.02, P = 0.034), lymph node metastasis (hazard ratio 2.88, 95% confidence interval 1.43-5.81, P = 0.003) and bilateral seminal vesicle invasion (hazard ratio 1.75, 95% confidence interval 1.01-3.05, P = 0.047) were independent predictors of biochemical recurrence-free survival. After excluding cases with lymph node metastasis, preoperative prostate-specific antigen, surgical margin status and bilateral seminal vesicle invasion were independent predictors of biochemical recurrence-free survival. CONCLUSIONS: Although most men with seminal vesicle invasion experience biochemical recurrences after radical prostatectomy, their survival outcome is not uniform. Bilateral seminal vesicle invasion seems to represent an independent prognostic factor for pT3b patients, together with the preoperative prostate-specific antigen and lymph node status.

Microcavity effect using nanoparticles to enhance the efficiency of organic light-emitting diodes.

In this paper, in contrast with previously reported approaches, we suggest exploiting a microcavity effect using nanoparticles to improve the optical efficiency of organic light-emitting diodes (OLED). The method to input the nanoparticles inside the OLED device is simple and cost effective by virtue of employing a solution process using a spin coating fabrication method. Titanium dioxide (TiO2) nanoparticles were used to improve the reflection by its high refractive index. In tandem with optimized heights of the organic layers, the increased light reflectance at the anode side, which includes the TiO2 nanoparticle layer, improved the optical efficiency of the OLED device via the microcavity effect. In order to prove that the enhancement of the optical efficiency was due to an enhanced microcavity effect caused by TiO2 nanoparticles, a microcavity simulation was conducted. The electrical characteristics were not affected by the nanoparticles and a clear pixel image was maintained. The results in this paper show that a nanoparticle based microcavity effect can be exploited to enhance the optical efficiency of OLEDs.

Susceptibility to radiation adverse effects in veterans with Gulf War illness and healthy civilians.

We evaluated whether veterans with Gulf War illness (VGWI) report greater ionizing radiation adverse effects (RadAEs) than controls; whether radiation-sensitivity is tied to reported chemical-sensitivity; and whether environmental exposures are apparent risk factors for reported RadAEs (rRadAEs). 81 participants (41 VGWI, 40 controls) rated exposure to, and rRadAEs from, four radiation types. The relations of RadAE-propensity (defined as the ratio of rRadAEs to summed radiation exposures) to Gulf War illness (GWI) presence and severity, and to reported chemical-sensitivity were assessed. Ordinal logistic regression evaluated exposure prediction of RadAE-propensity in the full sample, in VGWI, and stratified by age and chemical-sensitivity. RadAE-propensity was increased in VGWI (vs. controls) and related to GWI severity (p < 0.01) and chemical-sensitivity (p < 0.01). Past carbon monoxide (CO) exposure emerged as a strong, robust predictor of RadAE-propensity on univariable and multivariable analyses (p < 0.001 on multivariable assessment, without and with adjustment for VGWI case status), retaining significance in age-stratified and chemical-sensitivity-stratified replication analyses. Thus, RadAE-propensity, a newly-described GWI-feature, relates to chemical-sensitivity, and is predicted by CO exposure-both features reported for nonionizing radiation sensitivity, consistent with shared mitochondrial/oxidative toxicity across radiation frequencies. Greater RadAE vulnerability fits an emerging picture of heightened drug/chemical susceptibility in VGWI.

Genome-wide in-locus epitope tagging of Arabidopsis proteins using prime editors.

Prime editors (PEs), which are CRISPR-Cas9 nickase (H840A)-reverse transcriptase fusion proteins programmed with prime editing guide RNAs (pegRNAs), can not only edit bases but also install transversions, insertions, or deletions without both donor DNA and double-strand breaks at the target DNA. As the demand for in-locus tagging is increasing, to reflect gene expression dynamics influenced by endogenous genomic contexts, we demonstrated that PEs can be used to introduce the hemagglutinin (HA) epitope tag to a target gene locus, enabling molecular and biochemical studies using in-locus tagged plants. To promote genome-wide in-locus tagging, we also implemented a publicly available database that designs pegRNAs for in-locus tagging of all the Arabidopsis genes. [BMB Reports 2024; 57(1): 66-70].

Bioenergetic impairment in Gulf War illness assessed via 31P-MRS.

Time for post-exercise phosphocreatine-recovery (PCr-R), deemed a robust index of mitochondrial function in vivo, was previously reported to be elevated (signifying impaired ATP production) in veterans with Gulf War illness (GWI). Here we sought to replicate the finding and assess the impact of contravening previous eligibility requirements. The replication sample comprised white males. Cases reported ≥ moderate muscle-weakness to match the organ assessed to an organ affected; controls lacked recent headache or multiple symptoms. The expansion sample added cases without muscle-weakness, controls with recent headache, females, nonwhites. PCr-R, following pedal-depression-exercise, was compared in veterans with GWI versus controls (sample N = 38). In the replication sample, PCr-R results closely matched the prior report: PCr-R veterans with GWI mean(SD) = 47.7(16.5); control mean(SD) = 30.3(9.2), p = 0.017. (Prior-study PCr-R veterans with GWI mean(SD) = 46.1(17.9), control mean(SD) = 29.0(8.7), p = 0.023. Combined replication + prior samples: p = 0.001.) No case-control difference was observed in the expansion sample. In cases, PCr-R related to muscle-weakness: PCr-R = 29.9(7.1), 38.2(8.9), 47.8(15.2) for muscle-weakness rated none/low, intermediate, and high respectively (p for trend = 0.02), validating desirability of matching tissue assessed to tissue affected. In controls, headache/multiple symptoms, sex, and ethnicity each mattered (affecting PCr-R significantly). This study affirms mitochondrial/bioenergetic impairment in veterans with GWI. The importance of careful case/control selection is underscored.

Adverse effect propensity: A new feature of Gulf War illness predicted by environmental exposures.

A third of 1990-1 Gulf-deployed personnel developed drug/chemical-induced multisymptom illness, "Gulf War illness" (GWI). Veterans with GWI (VGWI) report increased drug/exposure adverse effects (AEs). Using previously collected data from a case-control study, we evaluated whether the fraction of exposures that engendered AEs ("AE Propensity") is increased in VGWI (it was); whether AE Propensity is related to self-rated "chemical sensitivity" (it did); and whether specific exposures "predicted" AE Propensity (they did). Pesticides and radiation exposure were significant predictors, with copper significantly "protective"-in the total sample (adjusted for GWI-status) and separately in VGWI and controls, on multivariable regression. Mitochondrial impairment and oxidative stress (OS) underlie AEs from many exposures irrespective of nominal specific mechanism. We hypothesize that mitochondrial toxicity and interrelated OS from pesticides and radiation position people on the steep part of the curve of mitochondrial impairment and OS versus symptom/biological disruption, amplifying impact of new exposures. Copper, meanwhile, is involved in critical OS detoxification processes.

Effect of a Mismatched Vaccine against the Outbreak of a Novel FMD Strain in a Pig Population.

In December 2014, a novel foot and mouth disease (FMD) virus was introduced to a pig farm in South Korea, despite the animals being vaccinated. A marginal antigenic matching between the novel and vaccine strains potentially led to the infection of the vaccinated animals. To understand the impact of using an FMD vaccine on the transmission dynamics of an unmatched field strain, simulation models were employed using daily reported data on clinical cases from the farm. The results of this study indicated that immunisation with the FMD vaccine reduced the shedding of the novel FMD virus in pigs. However, there was no evidence to suggest that the immunisation had a significant effect in reducing the development of clinical signs. These findings highlight that the use of an unmatched FMD vaccine can confound the outbreak by altering the disease dynamics of the novel virus. Based on this study, we emphasise the importance of continuous testing to ensure antigenic matching between the circulating strains and the vaccine pool.

Statin Use in Relation to COVID-19 and Other Respiratory Infections: Muscle and Other Considerations.

Statins have been widely advocated for use in COVID-19 based on large favorable observational associations buttressed by theoretical expected benefits. However, past favorable associations of statins to pre-COVID-19 infection outcomes (also buttressed by theoretical benefits) were unsupported in meta-analysis of RCTs, RR = 1.00. Initial RCTs in COVID-19 appear to follow this trajectory. Healthy-user/tolerator effects and indication bias may explain these disparities. Moreover, cholesterol drops in proportion to infection severity, so less severely affected individuals may be selected for statin use, contributing to apparent favorable statin associations to outcomes. Cholesterol transports fat-soluble antioxidants and immune-protective vitamins. Statins impair mitochondrial function in those most reliant on coenzyme Q10 (a mevalonate pathway product also transported on cholesterol)-i.e., those with existing mitochondrial compromise, whom data suggest bear increased risks from both COVID-19 and from statins. Thus, statin risks of adverse outcomes are amplified in those patients at risk of poor COVID-19 outcomes-i.e., those in whom adjunctive statin therapy may most likely be given. High reported rates of rhabdomyolysis in hospitalized COVID-19 patients underscore the notion that statin-related risks as well as benefits must be considered. Advocacy for statins in COVID-19 should be suspended pending clear evidence of RCT benefits, with careful attention to risk modifiers.

Korean adolescent suicide and search volume for "self-injury" on internet search engines.

Introduction: Many adolescents with suicidal ideation receive support through the Internet. However, they also find ways to attempt suicide or strengthen their suicidal ideation through this medium. This study analyzed the association between the search volume of suicide-related terms and the number of suicides among Korean adolescents. We also analyzed the correlations between the search volumes of suicide-related terms. Methods: We selected seven words (suicide, self-injury, depression, academic score, school violence, outcasts, and family trouble) related to adolescent suicide. A dataset was constructed by combining data from the most commonly used search engine in Korea (Naver Datalab) and the daily number of adolescent suicides in school settings (n = 347) from January 1, 2016 to December 31, 2018, collected from the Ministry of Education. Poisson regression and Pearson correlation analyses were performed. Results: Significant associations were found between suicide attempts and search term volumes, which differed according to sex and time interval. Among the search terms, "self-injury" was most strongly associated with suicide, and this association was significant at all time intervals (daily, weekly, and monthly) in female adolescents and in the total population. Further, the association was strongest in the daily suicide data. More search term volumes were related to suicide in the daily and weekly data than in the monthly data. There were positive correlations between "suicide," "self-injury," and "depression" search volumes. Conclusion: Further studies with larger sample sizes, more search terms, and analysis of time intervals between suicide-related term search and suicide death are required. These studies can contribute to the establishment of an online suicide prevention system to detect suicide risk in adolescents and provide interventions.

Visual function restoration in a mouse model of Leber congenital amaurosis via therapeutic base editing.

Leber congenital amaurosis (LCA), an inherited retinal degeneration, causes severe visual dysfunction in children and adolescents. In patients with LCA, pathogenic variants, such as RPE65, are evident in specific genes, related to the functions of retinal pigment epithelium and photoreceptors. In contrast to the original Cas9, base editing tools can correct pathogenic substitutions without generation of DNA double-stranded breaks (DSBs). In this study, dual adeno-associated virus (AAV) vectors containing split adenine base editors (ABEs) with trans-splicing intein were prepared for in vivo base editing in retinal degeneration of 12 (rd12) mice, an animal model of LCA, possessing a nonsense mutation of C to T transition in the Rpe65 gene (p.R44X). Subretinal injection of AAV-ABE in retinal pigment epithelial cells of rd12 mice resulted in an A to G transition. The on-target editing was sufficient for recovery of wild-type mRNA, RPE65 protein, and light-induced electrical responses from the retina. Compared with our previous therapeutic editing strategies using Cas9 and prime editing, or with the gene transfer strategy shown in the current study, our results suggest that, considering the editing efficacy and functional recovery, ABEs could be a strong, reliable method for correction of pathogenic variants in the treatment of LCA.

MutSα and MutSß as size-dependent cellular determinants for prime editing in human embryonic stem cells.

Precise genome editing in human pluripotent stem cells (hPSCs) has potential applications in isogenic disease modeling and ex vivo stem cell therapy, necessitating diverse genome editing tools. However, unlike differentiated somatic cells, hPSCs have unique cellular properties that maintain genome integrity, which largely determine the overall efficiency of an editing tool. Considering the high demand for prime editors (PEs), it is imperative to characterize the key molecular determinants of PE outcomes in hPSCs. Through homozygous knockout (KO) of MMR pathway key proteins MSH2, MSH3, and MSH6, we reveal that MutSα and MutSß determine PE efficiency in an editing size-dependent manner. Notably, MSH2 perturbation disrupted both MutSα and MutSß complexes, dramatically escalating PE efficiency from base mispair to 10 bases, up to 50 folds. Similarly, impaired MutSα by MSH6 KO improved editing efficiency from single to three base pairs, while defective MutSß by MSH3 KO heightened efficiency from three to 10 base pairs. Thus, the size-dependent effect of MutSα and MutSß on prime editing implies that MMR is a vital PE efficiency determinant in hPSCs and highlights the distinct roles of MutSα and MutSß in its outcome.

Understanding the transmission of African swine fever in wild boars of South Korea: A simulation study for parameter estimation.

Since the introduction of African swine fever (ASF) to Georgia in 2007, the disease has spread to many other countries including South Korea. Initial detection of ASF from wild boars (WB) in South Korea was reported in early October 2019. Since then, more than a thousand WB samples collected from the northern part of the country have been confirmed as ASF positive (2.9% of ASF positivity among WB samples collected until June 2020), indicating that the disease is endemic in the WB populations. To control the disease, multiple layers of fence-lines have been erected. Nevertheless, outbreaks continuously occurred across the fence, requiring a better understanding of the spatial transmission mechanism of ASF in WBs. Hence, we developed a novel ASF transmission model to estimate ecological and epidemiological parameters related to the spread of the disease in the WB population of South Korea. The results showed that roads and rivers were effective to prevent the spread, reducing the transmission rate to approximately 37% on average. Only a limited level of reduction was indicated via fence-lines, implying erection of fences might be considered as a temporary measure to delay the spread. This study also revealed that the probability of ASF transmission to adjacent habitats considerably decreased with increasing distance, supporting the slow spatial transmission speed reported from other European countries. Considering that elucidation of ASF dynamics in WB is crucial to mitigate the impact of the disease, we believe this study provides some useful ecological and epidemiological implications to control the disease in future.

High expression of uracil DNA glycosylase determines C to T substitution in human pluripotent stem cells.

Precise genome editing of human pluripotent stem cells (hPSCs) is crucial not only for basic science but also for biomedical applications such as ex vivo stem cell therapy and genetic disease modeling. However, hPSCs have unique cellular properties compared to somatic cells. For instance, hPSCs are extremely susceptible to DNA damage, and therefore Cas9-mediated DNA double-strand breaks (DSB) induce p53-dependent cell death, resulting in low Cas9 editing efficiency. Unlike Cas9 nucleases, base editors including cytosine base editor (CBE) and adenine base editor (ABE) can efficiently substitute single nucleotides without generating DSBs at target sites. Here, we found that the editing efficiency of CBE was significantly lower than that of ABE in human embryonic stem cells (hESCs), which are associated with high expression of DNA glycosylases, the key component of the base excision repair pathway. Sequential depletion of DNA glycosylases revealed that high expression of uracil DNA glycosylase (UNG) not only resulted in low editing efficiency but also affected CBE product purity (i.e., C to T) in hESCs. Therefore, additional suppression of UNG via transient knockdown would also improve C to T base substitutions in hESCs. These data suggest that the unique cellular characteristics of hPSCs could determine the efficiency of precise genome editing.