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In vivo cardiac reprogramming is a potential therapeutic strategy to replace cardiomyocytes in patients with myocardial infarction. However, low conversion efficiency is a limitation of In vivo cardiac reprogramming for heart failure. In this study, we showed that graphene nanosheets mediated efficient direct reprogramming into induced cardiomyocytes In vivo. We observed that the administration of graphene nanosheets led to the accumulation of H3K4me3, which resulted in direct cardiac reprogramming. Importantly, the administration of graphene nanosheets combined with cardiac reprogramming factors in a mouse model of myocardial infarction enhanced the effectiveness of directly reprogrammed cell-based cardiac repair. Collectively, our findings suggest that graphene nanosheets can be used as an excellent biomaterial to promote cardiac cell fate conversion and provide a robust reprogramming platform for cardiac regeneration in ischemic heart disease.

Neurodegenerative diseases are incurable and debilitating conditions characterized by the deterioration of brain function. Most brain disease models rely on human post-mortem brain tissue, non-human primate tissue, or in vitro two-dimensional (2D) experiments. Resource limitations and the complexity of the human brain are some of the reasons that make suitable human neurodegenerative disease models inaccessible. However, recently developed three-dimensional (3D) brain organoids derived from pluripotent stem cells (PSCs), including embryonic stem cells and induced PSCs, may provide suitable models for the study of the pathological features of neurodegenerative diseases. In this review, we provide an overview of existing 3D brain organoid models and discuss recent advances in organoid technology that have increased our understanding of brain development. Moreover, we explain how 3D organoid models recapitulate aspects of specific neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, and explore the utility of these models, for therapeutic applications.

Porphyra 334 (P334), a mycosporine-like amino acid (MAA), is a secondary metabolite found in diverse marine and terrestrial organisms and has several beneficial effects on fibroblast proliferation, wound healing, and antioxidant activity. Here, we report that P334 accelerates the cell reprogramming process of mouse tail-tip fibroblasts (TTFs) and human dermal papilla (HDP) cells into induced pluripotent stem cells (iPSCs). We found that P334 significantly improved the cell reprogramming efficiency by activating the tri-methylation of histone 3 lysine 4 (H3K4me3), which controls mesenchymal to epithelial transition (MET) during the reprogramming process. Thus, we found that P334 directly regulates epigenetic changes, providing an efficient approach for natural compound-based cell reprogramming.

본 연구는 학생 특성에 대한 교사의 정성적 평가를 파악하고 대학생활에 대한 예측타당도를 분석하여 학생선발에 적용 가능한 학생부종합전형의 개선방안 제안에 목적이 있다. 이를 위해 한국교육종단연구 2005 자료를 활용하였다. 연구대상은 90개 대학에 재학 중인 1,775명의 대학생이다. 연구결과 첫째, 교사의 정성적 평가는 학생의 특성에 따라 달라지는 것으로 나타났다. 교사의 정성적 평가인 수업태도, 사회성, 주도성에 공통적으로 유의한 영향을 미치는 변인은 여학생, 내신, 월소득이었다. 둘째, 학생의 개인특성 및 가정배경과 학생실적을 통제한 후에도 담임교사가 평가한 수업태도와 주도성에 따른 대학생활의 인지적·정의적 성과 차이가 나타났다. 이를 통해 교사가 학생의 학업적 환경 변화와 관계없이 일관되게 유지되는 학생의 특성을 파악하고 평가에 반영하는 것을 확인하였다. 학생이 고교생활 중 성취한 양적 실적은 대학생활과의 유의미한 관계가 잘 나타나지 않았다. 이와 같은 결과에 따라 학생부종합전형에 학교생활기록부를 활용하는 것은 타당하다 판단되며 학교생활기록부에 기재된 수업태도와 주도성을 주된 평가요소로 활용할 것을 제안하였다. 또, 학생의 학업역량을 내포한 양적실적에 대해 다른 요소로도 충분히 학업역량을 판단할 수 있기에 입시반영에 대해 다시금 고려할 필요가 있음을 제안하였다.

Autism spectrum disorders (ASDs) are common neurodevelopmental disorders characterized by deficits in social interactions and communication, restricted interests, and repetitive behaviors. Despite extensive study, the molecular targets that control ASD development remain largely unclear. Here, we report that the dormancy of quiescent neural stem cells (qNSCs) is a therapeutic target for controlling the development of ASD phenotypes driven by Shank3 deficiency. Using single-cell RNA sequencing (scRNA-seq) and transposase accessible chromatin profiling (ATAC-seq), we find that abnormal epigenetic features including H3K4me3 accumulation due to up-regulation of Kmt2a levels lead to increased dormancy of qNSCs in the absence of Shank3. This result in decreased active neurogenesis in the Shank3 deficient mouse brain. Remarkably, pharmacological and molecular inhibition of qNSC dormancy restored adult neurogenesis and ameliorated the social deficits observed in Shank3-deficient mice. Moreover, we confirmed restored human qNSC activity rescues abnormal neurogenesis and autism-like phenotypes in SHANK3-targeted human NSCs. Taken together, our results offer a novel strategy to control qNSC activity as a potential therapeutic target for the development of autism.

In vivo gene editing in post-mitotic neurons of the adult brain may be a useful strategy for treating neurological diseases. Here, we develop CRISPR-Cas9 nanocomplexes and show they were effective in the adult mouse brain, with minimal off-target effects. Using this system to target Bace1 suppressed amyloid beta (Aβ)-associated pathologies and cognitive deficits in two mouse models of Alzheimer's disease. These results broaden the potential application of CRISPR-Cas9 systems to neurodegenerative diseases.

Summary Recent advances in generating three-dimensional (3D) organoid systems from stem cells offer new possibilities for disease modeling and drug screening because organoids can recapitulate aspects of in vivo architecture and physiology. In this study, we generate isogenic 3D midbrain organoids with or without a Parkinson's disease-associated LRRK2 G2019S mutation to study the pathogenic mechanisms associated with LRRK2 mutation. We demonstrate that these organoids can recapitulate the 3D pathological hallmarks observed in patients with LRRK2-associated sporadic Parkinson's disease. Importantly, analysis of the protein-protein interaction network in mutant organoids revealed that TXNIP, a thiol-oxidoreductase, is functionally important in the development of LRRK2-associated Parkinson's disease in a 3D environment. These results provide proof of principle for the utility of 3D organoid-based modeling of sporadic Parkinson's disease in advancing therapeutic discovery., Highlights • 3D midbrain organoids with environment similar to the aged brain for modeling PD • LRRK2-G2019S organoids show abnormal phenotypes of LRRK2 sporadic PD • TXNIP mediates the LRRK2-G2019S pathological phenotypes of PD, H. Kim and colleagues generated 3D midbrain organoids containing a G2019S mutation in LRRK2 and used this system for sporadic Parkinson’s disease (PD) modeling in vitro. Their results demonstrate that these 3D midbrain organoids can recapitulate the pathological features of LRRK2-associated sporadic PD. These results demonstrate that the 3D midbrain organoids are invaluable for recapitulating PD phenotypes and understanding the molecular underpinnings of these phenotypes.

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Cell reprogramming has been considered a powerful technique in the regenerative medicine field. In addition to diverse its strengths, cell reprogramming technology also has several drawbacks generated during the process of reprogramming. Telomere shortening caused by the cell reprogramming process impedes the efficiency of cell reprogramming. Transcription factors used for reprogramming alter genomic contents and result in genetic mutations. Additionally, defective mitochondria functioning such as excessive mitochondrial fission leads to the limitation of pluripotency and ultimately reduces the efficiency of reprogramming. These problems including genomic instability and impaired mitochondrial dynamics should be resolved to apply cell reprograming in clinical research and to address efficiency and safety concerns. Sirtuin (NAD＋-dependent histone deacetylase) has been known to control the chromatin state of the telomere and influence mitochondria function in cells. Recently, several studies reported that Sirtuins could control for genomic instability in cell reprogramming. Here, we review recent findings regarding the role of Sirtuins in cell reprogramming. And we propose that the manipulation of Sirtuins may improve defects that result from the steps of cell reprogramming. [BMB Reports 2018; 51(10): 501-508].

Adult neurogenesis is the lifelong process by which new neurons are generated in the dentate gyrus. However, adult neurogenesis capacity decreases with age, and this decrease is closely linked to cognitive and memory decline. Our study demonstrated that electromagnetized gold nanoparticles (AuNPs) promote adult hippocampal neurogenesis, thereby improving cognitive function and memory consolidation in aged mice. According to single-cell RNA sequencing data, the numbers of neural stem cells (NSCs) and neural progenitors were significantly increased by electromagnetized AuNPs. Additionally, electromagnetic stimulation resulted in specific activation of the histone acetyltransferase Kat2a, which led to histone H3K9 acetylation in adult NSCs. Moreover, in vivo electromagnetized AuNP stimulation efficiently increased hippocampal neurogenesis in aged and Hutchinson-Gilford progeria mouse brains, thereby alleviating the symptoms of aging. Therefore, our study provides a proof-of-concept for the in vivo stimulation of hippocampal neurogenesis using electromagnetized AuNPs as a promising therapeutic strategy for the treatment of age-related brain diseases.

Highly selective etching of a target silicon compound is essential in semiconductor fabrication. Searching for alternatives to conventional etchant that contain hazardous chemicals is challenging, largely due to the unclear understanding of the chemical reaction. In this study, we elucidate etching machinery of phosphoric acid and its outstanding selectivity toward silicon nitride (Si3N4) over silicon dioxide (SiO2) surfaces in atomistic level. Ab-initio thermodynamic and kinetic formalisms integrated with density functional theory computation propose that pyrophosphoric acid (H4P2O7), a condensed form of orthophosphoric acid. (H3PO4) at high concentration and temperature, is even more reactive toward Si3N4 than H3PO4 which has been regarded as a dominant species for decades. We demonstrate that the superior etching selectivity derives from reaction mechanism of thermodynamic control, where H4P2O7 is much more exergonic than H3PO4. Notably, we find that water molecules close to the H4P2O7 assist sequential etching process in two ways: catalysis via structural proton transfer, and hydrolysis of diphosphate group in the Si3N4 surface. Our study guides a quick and accurate screening as well as designing efficient and safe etchants, which facilitates the fabrication of nanoscale semiconductor devices that accompanies selective etching of alternately stacked hundreds of atomic layers of Si3N4 and SiO2.

Transcription factors play a central role in pluripotency transcription circuitry for establishing pluripotent reprogramming. Master transcription factors Oct4, Nanog, and Sox2 are known to form the core of the pluripotency transcription network. Other transcription factors also play critical roles for further refining the core circuitry for pluripotency in induced pluripotent stem (iPS) cells. Here, we reported that Nac1 interacted with the master pluripotent factors Oct4 and Nanog co-occupies gene promoters bound by these transcriptional factors for establishing pluripotency. Moreover, this interaction coordinates gene expression with H3K4me3 in the somatic cell reprogramming. Knockdown of Nac1 suppressed somatic cell reprogramming, whereas overexpression of Nac1 resulted in enhanced efficiency of induced pluripotent cell generation. Altogether, these results reveal the genome wide role for Nac1 in the contribution to the pluripotency circuitry and the regulation of the establishing pluripotent state.

In 2006 and 2007, a new bacterial disease was observed in field-cultivated soybeans in Boeun District and Munkyung City of Korea. The disease caused severe blighting of soybean (Glycine max) leaves. Soybean leaves in fields showed yellowish spots with brown centers. Brown and dead areas of variable size and shape were surrounded by wide, yellow haloes with distinct margins. Spots might coalesce and affected leaves fell readily. Seven bacterial strains were isolated from chlorotic areas of soybean leaves and all produced white colonies on trypticase soy agar. With the Biolog Microbial Identification System, version 4.2, (Biolog Inc., Hayward, CA) all strains and Pseudomonas syringae pv. tabaci CFBP2106T were identified as P. syringae pv. tabaci with a Biolog similarity index of 0.28 to 0.52 and 0.48 after 24 h. Pathogenicity of the strains (three plants per strain) on soybean leaves at the V5 stage (cv. Hwanggeum) was confirmed by rub inoculation with bacterial suspensions (1 × 108 CFU/ml) in sterile distilled water on the lesions cut 1 cm long on the upper side of the leaves with razor blades and by pinprick on 3-week-old leaves of tobacco (Nicotiana tabacum cv. Samsun) in the greenhouse. Wildfire symptoms on the soybean leaves and faint halos on tobacco leaves were observed 4 days after inoculation. The identification of reisolated bacterial strains was confirmed with the metabolic fingerprintings on Biolog. LOPAT tests (1) and phenotypic characteristics (3) of the strains were similar to those of the CFBP2106T. Colonies were levan positive, oxidase negative, potato soft rot negative, arginine dihydrase negative, and tobacco hypersensitivity negative. All strains were gram-negative, aerobic rods with a polar flagellum. Strains were negative for esculin hydrolysis, gelatin liquefaction, urea production, accumulation of poly-β-hydroxy butyrate, starch hydrolysis, ornithine dihydrolase, lysine dihydrolase, growth at 37°C, utilization of geraniol, benzoate, cellobiose, sorbitol, trehalose, l-rhamnose, and adonitol. Positive reactions were catalase and arbutin hydrolysis, utilization of sorbitol, d-arabinose, and dl-serine. The strains were variable in utilization of mannitol, sucrose, and d-arabinose. The 1,472-bp PCR fragments of strains, BC2366 (GenBank Accession No. FJ755788) and BC2367 (No. FJ755789) was sequenced using 16S rDNA universal primers (2). The sequences shared 100% identity with the analogous sequences of P. syringae pv. glycenea (GenBank Accession No. AB001443) available in NCBI databases. Based on the phenotypic, genetic, and pathological characteristics, all strains were identified as P. syringae pv. tabaci. To our knowledge, this is the first report of P. syringae pv. tabaci causing wildfire on soybean in Korea. References: (1) R. A. Lelliott et al. J. Appl. Bacteriol. 29:470, 1966. (2) I.-S. Myung et al. Plant Dis. 92:1472, 2008. (3) N. W. Schaad et al., eds. Laboratory Guide for Identification of Plant Pathogenic Bacteria. 3rd ed. The American Phytopathological Society, St. Paul, MN, 2001.

The reprogramming of induced cardiomyocytes (iCMs) has shown potential in regenerative medicine. However, in vivo reprogramming of iCMs is significantly inefficient, and novel gene delivery systems are required to more efficiently and safely induce in vivo reprogramming of iCMs for therapeutic applications in heart injury. In this study, we show that cationic gold nanoparticles (AuNPs) loaded with Gata4, Mef2c, and Tbx5 function as nanocarriers for cardiac reprogramming. The AuNP/GMT/PEI nanocomplexes show high reprogramming efficiency in human and mouse somatic cells with low cytotoxicity and direct conversion into iCMs without integrating factors into the genome. Importantly, AuNP/GMT/PEI nanocomplexes led to efficient in vivo conversion into cardiomyocytes after myocardial infarction (MI), resulting in the effective recovery of cardiac function and scar area. Taken together, these results show that the AuNP/GMT/PEI nanocarrier can be used to develop effective therapeutics for heart regeneration in cardiac disease patients.

Performance funding for higher education has gained popularity in many countries, but its impact on institutional performance remains unclear. This study investigates the impact of performance funding on the institutional performance of Korean universities over time. The institutional performance indicators used include graduates’ employment rate, student retention rate, financial aid per student, expenditure per student, and faculty-to-student ratio. Using longitudinal data of 160 4-year universities from 2008 to 2013, we employed a multilevel growth modeling strategy. The results indicate that institutions with more funding through the Education Capacity Enhancement Program sustained higher employment rate, retention rate, and faculty-to-student ratio in 2013, while employment and retention rates of less-funded institutions grew faster over time after controlling for 2008 status and institutional characteristics. This evidence demonstrates that the performance funding program in Korea encouraged institutions to focus on the most important performance indicators, resulting in a funding effect and a motivational effect. We suggest policy implications for the future development of performance funding as well as appropriate use of performance indicators.

We analyzed HIV surveillance data on white, black, and Latino males diagnosed with HIV between 2000 and 2004 in Los Angeles County (LAC) to identify associations between individual- and community-level factors and late HIV detection by race/ethnicity. We defined late HIV detection as an AIDS diagnosis within 6 months of HIV diagnosis. We conducted multilevel analysis to determine individual- and community-level risk factors associated with late HIV detection stratified by race/ethnicity. We mapped HIV-positive males with late HIV detection by race/ethnicity at the zip code level within LAC to determine high burden areas. Overall, 38% of all males met the definition of late HIV detection. By race/ethnicity, 44% of Latinos, 38% of blacks, and 30% of whites were detected late in their course of HIV infection. Latinos and whites had multiple individual-level risk factors associated with late HIV detection. Among black males, only older age at HIV diagnosis was associated with late HIV detection. The only community-level risk factor associated with late HIV detection was among Latinos living in communities with less than 6% of men who have sex with men (proxy for stigma). Mapping the distribution of late HIV detection showed late detection areas generalized across LAC for Latino males in comparison with white and black males whose maps showed clustered areas of late HIV detection. Analysis and mapping of individual- and community-level risk factors associated with late HIV detection provides an important tool for targeting prevention resources to areas and populations with the highest burden of disease.

Using a subsample of respondents to the 2005 Los Angeles County health survey, we examined the relationship between perceptions of the seriousness of HIV/AIDS in one’s community and HIV testing. We constructed a propensity score-based matched sample of three groups with differing perceptions of the seriousness of HIV in their community: high perceived seriousness, low perceived seriousness, and uncertain about seriousness. We compared HIV testing behavior in the three groups before and after using propensity score matching to control for selection on observed covariates. The unadjusted comparison showed a testing rate of 30.2 % among those perceiving high seriousness, 11.4 percentage points higher than the 18.8 % testing rate among those perceiving low seriousness. After propensity score matching, the adjusted testing difference was 7.0 percentage points (p

Objectives. We examined the impact of social discrimination and financial hardship on unprotected anal intercourse with a male sex partner of serodiscordant or unknown HIV status in the past 3 months among 1081 Latino and 1154 Black men who have sex with men (MSM; n = 2235) residing in Los Angeles County, California; New York, New York; and Philadelphia, Pennsylvania. Methods. We administered HIV testing and a questionnaire assessing 6 explanatory variables. We combined traditional mediation analysis with the results of a path analysis to simultaneously examine the direct, indirect, and total effects of these variables on the outcome variable. Results. Bivariate analysis showed that homophobia, racism, financial hardship, and lack of social support were associated with unprotected anal intercourse with a serodiscordant or sero-unknown partner. Path analysis determined that these relations were mediated by participation in risky sexual situations and lack of social support. However, paths between the explanatory variable and 2 mediating variables varied by participants’ serostatus. Conclusions. Future prevention research and program designs should specifically address the differential impact of social discrimination and financial hardship on lack of social support and risky sexual situations among Latino and Black MSM.

A higher frequency of nonmonogamy, due in part to lower marriage prevalence, may contribute to elevated human immunodeficiency virus (HIV)/sexually transmitted disease rates among older blacks.To examine race and gender differences in nonmonogamy, time spent single (i.e., not married or cohabiting), and HIV testing in older adults, we analyzed US population-based data from the 2005-2006 National Social Life, Health, and Aging Project for 2825 heterosexual participants ages 57 to 85 years.Blacks spent greater portions of their adult lives single than did Hispanics or whites and were far more likely to report recent nonmonogamous partnerships (23.4% vs. 10.0% and 8.2%). Among individuals reporting sex in the prior 5 years, nonmonogamous partnerships were strongly associated with time spent single during the period. Control for time spent single and other covariates reduced the association of black race with nonmonogamous partnerships for men, but increased it for women. Less than 20% reported ever testing for HIV; less than 6% had been recommended testing by a provider. Testing rates, highest in black men and white women, differed little by history of nonmonogamous partnerships within gender strata.Singlehood helps to explain higher nonmonogamous partnership rates in older black men but not in older black women. Older adults rarely receive or are recommended HIV testing, a key strategy for reducing heterosexual HIV transmission.

This paper aims at investigating the causal effects of social behaviors on subsequent reading growth in elementary school, using the Early Childhood Longitudinal Study—Kindergarten (ECLS-K) data. The sample was 8,869 subjects who provided longitudinal measures of reading IRT scores from kindergarten (1998–1999) to fifth grades (2003–2004) in the United States. To examine the causal relationship, propensity score methods were used to match higher and lower groups in four social behavior domains such as Approaches to learning, Interpersonal skills, Internalizing problem behavior and Externalizing problem behavior. Results showed that the matched sample achieved sufficient pretreatment balance between the two groups. To examine the effects of social behaviors on the reading growth, multilevel growth model (MGM) was employed. Comparisons of the matched samples showed that children in the high groups of pro-social behavior or in the low groups of problem behavior at kindergarten entrance started with higher reading skills and developed reading achievement faster than those who were not. This study suggests that children’s early social behavior is crucial in reading development. Practical implication and direction of future research are also discussed.

Effective schools should be superior in both enhancing students’ achievement levels and reducing the gap between high- and low-achieving students in the school. However, the focus has been placed mainly on schools’ achievement levels in most school effect studies. In this article, we focused our attention upon the school-specific achievement dispersion as well as achievement level in determining effective schools. The achievement dispersion in a particular school can be captured by within-school variance in achievement (σ2). Assuming heterogeneous within-school variance across schools in hierarchical modeling, it is possible to identify school factors related to high achievement levels and a small gap between high- and low-achieving students. By analyzing data from the TIMMS-R, we illustrated how to detect variance heterogeneity and how to find a systematic relationship between within-school variance and school practice. In terms of our results, we found that schools with a high achievement level tended to be more homogeneous in achievement dispersion, but even among schools with the same achievement level, schools varied in their achievement dispersion, depending on classroom practices.

As cloud and N-Screen services get active, the network traffic of mobile devices is rapidly increasing. The video streaming takes higher bandwidths in the mobile network. Servers with popular contents have to manage higher transmission bandwidths in order to handle many user requests at a time. But servers with unpopular contents have relatively lower transmission bandwidths although they can handle much more user requests. Such imbalance in loads among the servers will cause the lowering of QoS of the video service systems and waste the resources. In this paper, we implemented an algorithm to solve the imbalance between the loads by placing replicas of popular contents in other servers. And in order to efficiently cope with the severe variation of the popularity of the contents, we implemented dynamic video contents management system which handles the load balancing by checking of the states of the servers in real time. We also verified the performance of the algorithm in many aspects applying real mobile video service workload. As a result, we could reduce the deviation in the transmission bandwidth among existing servers by 57%.