Prominent transcriptomic changes in Mycobacterium intracellulare under acidic and oxidative stress.

BACKGROUND: Mycobacterium avium complex (MAC), including Mycobacterium intracellulare is a member of slow-growing mycobacteria and contributes to a substantial proportion of nontuberculous mycobacterial lung disease in humans affecting immunocompromised and elderly populations. Adaptation of pathogens in hostile environments is crucial in establishing infection and persistence within the host. However, the sophisticated cellular and molecular mechanisms of stress response in M. intracellulare still need to be fully explored. We aimed to elucidate the transcriptional response of M. intracellulare under acidic and oxidative stress conditions. RESULTS: At the transcriptome level, 80 genes were shown [FC] ≥ 2.0 and p < 0.05 under oxidative stress with 10 mM hydrogen peroxide. Specifically, 77 genes were upregulated, while 3 genes were downregulated. In functional analysis, oxidative stress conditions activate DNA replication, nucleotide excision repair, mismatch repair, homologous recombination, and tuberculosis pathways. Additionally, our results demonstrate that DNA replication and repair system genes, such as dnaB, dinG, urvB, uvrD2, and recA, are indispensable for resistance to oxidative stress. On the contrary, 878 genes were shown [FC] ≥ 2.0 and p < 0.05 under acidic stress with pH 4.5. Among these genes, 339 were upregulated, while 539 were downregulated. Functional analysis highlighted nitrogen and sulfur metabolism pathways as the primary responses to acidic stress. Our findings provide evidence of the critical role played by nitrogen and sulfur metabolism genes in the response to acidic stress, including narGHIJ, nirBD, narU, narK3, cysND, cysC, cysH, ferredoxin 1 and 2, and formate dehydrogenase. CONCLUSION: Our results suggest the activation of several pathways potentially critical for the survival of M. intracellulare under a hostile microenvironment within the host. This study indicates the importance of stress responses in M. intracellulare infection and identifies promising therapeutic targets.

Bigger problems from smaller colonies: emergence of antibiotic-tolerant small colony variants of Mycobacterium avium complex in MAC-pulmonary disease patients.

BACKGROUND: Mycobacterium avium complex (MAC) is a group of slow-growing mycobacteria that includes Mycobacterium avium and Mycobacterium intracellulare. MAC pulmonary disease (MAC-PD) poses a threat to immunocompromised individuals and those with structural pulmonary diseases worldwide. The standard treatment regimen for MAC-PD includes a macrolide in combination with rifampicin and ethambutol. However, the treatment failure and disease recurrence rates after successful treatment remain high. RESULTS: In the present study, we investigated the unique characteristics of small colony variants (SCVs) isolated from patients with MAC-PD. Furthermore, revertant (RVT) phenotype, emerged from the SCVs after prolonged incubation on 7H10 agar. We observed that SCVs exhibited slower growth rates than wild-type (WT) strains but had higher minimum inhibitory concentrations (MICs) against multiple antibiotics. However, some antibiotics showed low MICs for the WT, SCVs, and RVT phenotypes. Additionally, the genotypes were identical among SCVs, WT, and RVT. Based on the MIC data, we conducted time-kill kinetic experiments using various antibiotic combinations. The response to antibiotics varied among the phenotypes, with RVT being the most susceptible, WT showing intermediate susceptibility, and SCVs displaying the lowest susceptibility. CONCLUSIONS: In conclusion, the emergence of the SCVs phenotype represents a survival strategy adopted by MAC to adapt to hostile environments and persist during infection within the host. Additionally, combining the current drugs in the treatment regimen with additional drugs that promote the conversion of SCVs to RVT may offer a promising strategy to improve the clinical outcomes of patients with refractory MAC-PD.

Twitter Discussions on #digitaldementia: Content and Sentiment Analysis.

BACKGROUND: Digital dementia is a term that describes a possible decline in cognitive abilities, especially memory, attributed to the excessive use of digital technology such as smartphones, computers, and tablets. This concept has gained popularity in public discourse and media lately. With the increasing use of social media platforms such as Twitter (subsequently rebranded as X), discussions about digital dementia have become more widespread, which offer a rich source of information to understand public perceptions, concerns, and sentiments regarding this phenomenon. OBJECTIVE: The aim of this research was to delve into a comprehensive content and sentiment analysis of Twitter discussions regarding digital dementia using the hashtag #digitaldementia. METHODS: Retrospectively, publicly available English-language tweets with hashtag combinations related to the topic of digital dementia were extracted from Twitter. The tweets were collected over a period of 15 years, from January 1, 2008, to December 31, 2022. Content analysis was used to identify major themes within the tweets, and sentiment analysis was conducted to understand the positive and negative emotions associated with these themes in order to gain a better understanding of the issues surrounding digital dementia. A one-way ANOVA was performed to gather detailed statistical insights regarding the selected tweets from influencers within each theme. RESULTS: This study was conducted on 26,290 tweets over 15 years by 5123 Twitter users, mostly female users in the United States. The influencers had followers ranging from 20,000 to 1,195,000 and an average of 214,878 subscribers. The study identified four themes regarding digital dementia after analyzing tweet content: (1) cognitive decline, (2) digital dependency, (3) technology overload, and (4) coping strategies. Categorized according to Glaser and Strauss's classifications, most tweets (14,492/26,290, 55.12%) fell under the categories of wretched (purely negative) or bad (mostly negative). However, only a small proportion of tweets (3122/26,290, 11.86%) were classified as great (purely positive) or swell sentiment (mostly positive). The ANOVA results showed significant differences in mean sentiment scores among the themes (F3,3581=29.03; P<.001). The mean sentiment score was -0.1072 (SD 0.4276). CONCLUSIONS: Various negative tweets have raised concerns about the link between excessive use of digital devices and cognitive decline, often known as digital dementia. Of particular concern is the rapid increase in digital device use. However, some positive tweets have suggested coping strategies. Engaging in digital detox activities, such as increasing physical exercise and participating in yoga and meditation, could potentially help prevent cognitive decline.

Differential genetic diagnoses of adult post-lingual hearing loss according to the audiogram pattern and novel candidate gene evaluation.

Ski-slope hearing loss (HL), which refers to increased auditory threshold at high frequencies, is common in adults. However, genetic contributions to this post-lingual HL remain largely unknown. Here, we prospectively investigated deafness-associated and novel candidate genes causing ski-slope HL. We analyzed 192 families with post-lingual HL via gene panel and/or exome sequencing. With an overall molecular diagnostic rate of 35.4% (68/192) in post-lingual HL, ski-slope HL showed a lower diagnostic rate (30.7%) compared with other conditions (40.7%). In patients who showed HL onset before the age of 40, genetic diagnostic probability was significantly lower for ski-slope HL than for other conditions. Further analysis of 51 genetically undiagnosed patients in the ski-slope HL group identified three variants in delta-like ligand 1 (DLL1), a Notch ligand, which presented in vitro gain-of-function effects on Notch downstream signaling. In conclusion, genetic diagnostic rates in post-lingual HL varied according to audiogram patterns with age-of-onset as a confounding factor. DLL1 was identified as a candidate gene causing ski-slope HL.

Fetuin as a potential serum biomarker to detect subclinical shedder of bovine paratuberculosis.

Paratuberculosis (PTB) is a chronic contagious granulomatous enteritis of wild and domestic ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). PTB causes considerable economic losses to the dairy industry through decreased milk production and premature culling. PTB-affected cattle undergo a subclinical stage without clinical signs and initiate fecal shedding of MAP into the environment. Current diagnostic tools have low sensitivity for the detection of subclinical PTB infection. Therefore, alternative diagnostic tools are required to improve the diagnostic sensitivity of subclinical PTB infection. In this study, we performed ELISA for three previously identified host biomarkers (fetuin, alpha-1-acid glycoprotein, and apolipoprotein) and analyzed their diagnostic performance with conventional PTB diagnostic methods. We observed that serum fetuin levels were significantly lowered in the subclinical shedder and clinical shedder groups than in the healthy control group, indicating its potential utility as a diagnostic biomarker for bovine PTB. Also, fetuin showed an excellent discriminatory power with an AUC = 0.949, a sensitivity of 92.6%, and a specificity of 94.4% for the detection of subclinical MAP infection. In conclusion, our results demonstrated that fetuin could be used as a diagnostic biomarker for enhancing the diagnostic sensitivity for the detection of subclinical MAP infections that are difficult to detect based on current diagnostic methods.

Influential factors for COVID-19 related distancing in daily life: a distinct focus on ego-gram.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has necessitated that individuals comply with personal quarantine rules in daily life. South Korea is implementing the concept of "distancing in daily life" to raise awareness on personal quarantine measures, which is communicated through various media channels and platforms. The continued rise in COVID-19 cases demands that all individuals strictly adhere to personal quarantine rules. It is worth paying particular attention to the college student group, which has the highest percentage of confirmed cases among all age groups in South Korea. This group understands and practices "distancing in daily life" but with drastic variations among individuals. Previous studies have reported that the level of adherence to social norms is different according to each ego stated, and media exposure level is reported as a major influencing factor. Therefore, this study examined the media exposure level to COVID-19 prevention rules and its effect on the observance of distancing in daily life; it also verified the moderating effect of ego-gram on the relationship between media exposure level and distancing in daily life. METHODS: The participants comprised Korean university students (men = 143, women = 188, N = 331) aged 18-30 years, who were recruited through an online survey. The survey was conducted over 20 days from January 27 to February 15, 2021. Data were analyzed using SAS (version 9.4) to calculate hierarchical regression. RESULTS: First, media exposure level and distancing in daily life among Korean university students was above average. Second, media exposure level (ß = .161, P < .01) was identified as the most influential factor for distancing in daily life. Third, ego-grams had a moderating effect (ß = .136, P < .05) on the relationship between media exposure levels and distancing in daily life. CONCLUSIONS: This study examined the policy implications related to the development of diverse quarantine-related programs while considering influential factors and differences in how individuals' compliance with quarantine rules were presented. Considering the situation in which new infectious diseases such as COVID-19 occur every 4-5 years, this study serves as a preparation for future pandemics and is an important framework to enhance the level of personal quarantine.

Mediating Effects of Reassurance-Seeking Behavior or Obsession With COVID-19 on the Association Between Intolerance of Uncertainty and Viral Anxiety Among Healthcare Workers in Korea.

BACKGROUND: This study explores whether the intolerance of uncertainty among healthcare workers prompts viral anxiety, and whether this association is mediated by their reassurance-seeking behavior and preoccupation with the coronavirus disease 2019 (COVID-19) in Korea. METHODS: An online survey was conducted among healthcare workers in Asan Medical Center, on November 29, 2021. Demographic characteristics and responses to items from rating scales were collected, including Stress and Anxiety to Viral Epidemics-9, Coronavirus Reassurance-Seeking Behaviors Scale (CRBS), Obsession with COVID-19 Scale (OCS), Patient Health Questionnaire-9, Insomnia Severity Scale, and Intolerance of Uncertainty-12 (IUS-12). RESULTS: Among the 329 participants, viral anxiety of healthcare workers was predicted by being female (ß = 0.14, P = 0.002), CRBS (ß = 0.30, P < 0.001), OCS (ß = 0.32, P < 0.001), and IUS-12 (ß = 0.15, P = 0.002) scores (adjusted R² = 0.43, F = 31.1, P < 0.001). Mediation analysis showed that the intolerance of uncertainty directly influenced viral anxiety, and reassurance-seeking behavior and obsession with COVID-19 partially mediated the association. CONCLUSION: The intolerance of uncertainty among healthcare workers directly influenced their viral anxiety, and reassurance-seeking behavior and obsession with COVID-19 mediated this association in this era of "living with coronavirus" in Korea.

Effect of Cancer-Related Dysfunctional Beliefs About Sleep on Fear of Cancer Progression in the Coronavirus Pandemic.

BACKGROUND: This study aimed to explore clinical correlates of fear of progression (FoP) among patients with cancer during the coronavirus disease 2019 (COVID-19) pandemic and examine the mediation effect of cancer-related dysfunctional beliefs about sleep (C-DBS). METHODS: Medical charts of patients with cancer who visited a psycho-oncology clinic between July and November 2021 were reviewed. Baseline socio-demographic and cancer-related variables were collected. Patients' self-report questionnaires, regarding FoP, depression (Patient Health Questionnaire-9 items; PHQ-9), viral anxiety (Stress and Anxiety to Viral Epidemics-6 items; SAVE-6), C-DBS, and other distress, were investigated. Pearson's correlation and linear regression were performed to examine the risk factors of FoP. Mediation effect analysis with the bootstrap method with 2,000 resamples was implemented. RESULTS: A total of 231 patients were included in the analysis. Linear regression revealed that FoP was predicted by age (ß = -0.14, P = 0.003), PHQ-9 (ß = 0.48, P < 0.001), SAVE-6 (ß = 0.34, P < 0.001), and C-DBS (ß = 0.15, P = 0.005). FoP was directly influenced by SAVE-6 and mediated by C-DBS, while it was directly influenced by PHQ-9 with no mediation effect. CONCLUSION: During the COVID-19 pandemic, the FoP of patients with cancer was associated with younger age, depression, viral anxiety, and C-DBS. Depression and viral anxiety directly influenced FoP, while C-DBS mediated the association between viral anxiety and FoP. Therefore, oncology healthcare professionals are recommended to assess C-DBS of their patients when they are highly distressed from FoP.

Development of the Stress and Anxiety to Viral Epidemics-9 (SAVE-9) Scale for Assessing Work-related Stress and Anxiety in Healthcare Workers in Response to Viral Epidemics.

BACKGROUND: The coronavirus disease 2019, or COVID-19, has had a major psychological impact on healthcare workers. However, very few scales are available to specifically assess work-related stress and anxiety in healthcare workers responding to a viral epidemic. This study developed a new assessment tool, the Stress and Anxiety to Viral Epidemics-9 (SAVE-9) and aimed to validate it among healthcare workers directly affected by COVID-19 in Korea. METHODS: A total of 1,019 healthcare workers responded through anonymous questionnaires during April 20-30, 2020. Exploratory factor analysis (EFA) was conducted to explore the construct validity, and the reliability was assessed using internal consistency measures of Cronbach's alpha coefficients. Receiver operating characteristic analysis was conducted to define the most appropriate cut-off point of SAVE-9 using the Generalized Anxiety Disorder-7 scale (GAD-7; ≥ 5). Second, Spearman's rank correlation coefficient was used to establish convergent validity for the SAVE-9 questionnaire with GAD-7 and the Patient Health Questionnaire-9. RESULTS: The nine-item scale had satisfactory internal consistency (Cronbach's α = 0.795). It adopted a two-factor structure: 1) anxiety regarding viral epidemics and 2) work-related stress associated with viral epidemics. A cut-off score of 22 for the SAVE-9 ascertained levels of stress and anxiety in response to a viral epidemic in healthcare workers that warranted clinical attention. Correlations between the SAVE-9 and the other scales were statistically significant (P < 0.05). CONCLUSION: The results suggest that the SAVE-9 is a useful, reliable, and valid tool to evaluate stress and anxiety responses in healthcare workers during viral epidemics.

Identification of Nontuberculous Mycobacteria in Patients with Pulmonary Diseases in Gyeongnam, Korea, Using Multiplex PCR and Multigene Sequence-Based Analysis.

BACKGROUND: Nontuberculous mycobacteria (NTM) are widely present in environments, such as soil and water, and have recently been recognized as important pathogenic bacteria. The incidence of NTM-related infections is steadily increasing. As the diagnosis and treatment of NTM infection should be distinguished from tuberculosis, and the treatment should be specific to the species of NTM acquired, accurate species identification is required. METHODS: In this study, two-step multiplex PCR (mPCR) and multigene sequence-based analysis were used to accurately identify NTM species in 320 clinical isolates from Gyeongsang National University Hospital (GNUH). In particular, major mycobacterial strains with a high isolation frequency as well as coinfections with multiple species were diagnosed through two-step mPCR. Multigene sequencing was performed to accurately identify other NTM species not detected by mPCR. Variable regions of the genes 16S rRNA, rpoB, hsp65, and 16S-23S rRNA internal transcribed spacer were included in the analysis. RESULTS: Two-step mPCR identified 234 (73.1%) cases of M. intracellulare, 26 (8.1%) cases of M. avium subsp. avium, and 13 (4.1%) cases of M. avium subsp. hominissuis infection. Additionally, 9 (2.8%) M. fortuitum, 9 (2.8%) M. massiliense, 2 (0.6%) M. abscessus, and 4 (1.2%) M. kansasii isolates were identified. Coinfection was identified in 7 (2.2%) samples. The sixteen samples not classified by two-step mPCR included 6 (1.9%) cases of M. chimaera, 4 (1.3%) M. gordonae, 1 (0.3%) M. colombiense, 1 (0.3%) M. mageritense, and 1 (0.3%) M. persicum identified by sequence analysis. CONCLUSIONS: The results of this study suggest a strategy for rapid detection and accurate identification of species using two-step mPCR and multigene sequence-based analysis. To the best of our knowledge, this study is the first to report the identification of NTM species isolated from patients in Gyeongnam/Korea.

Exosome Cofactors Connect Transcription Termination to RNA Processing by Guiding Terminated Transcripts to the Appropriate Exonuclease within the Nuclear Exosome.

The yeast Nrd1 interacts with the C-terminal domain (CTD) of RNA polymerase II (RNApII) through its CTD-interacting domain (CID) and also associates with the nuclear exosome, thereby acting as both a transcription termination and RNA processing factor. Previously, we found that the Nrd1 CID is required to recruit the nuclear exosome to the Nrd1 complex, but it was not clear which exosome subunits were contacted. Here, we show that two nuclear exosome cofactors, Mpp6 and Trf4, directly and competitively interact with the Nrd1 CID and differentially regulate the association of Nrd1 with two catalytic subunits of the exosome. Importantly, Mpp6 promotes the processing of Nrd1-terminated transcripts preferentially by Dis3, whereas Trf4 leads to Rrp6-dependent processing. This suggests that Mpp6 and Trf4 may play a role in choosing a particular RNA processing route for Nrd1-terminated transcripts within the exosome by guiding the transcripts to the appropriate exonuclease.

Selective Dirac voltage engineering of individual graphene field-effect transistors for digital inverter and frequency multiplier integrations.

The ambipolar band structure of graphene presents unique opportunities for novel electronic device applications. A cycle of gate voltage sweep in a conventional graphene transistor produces a frequency-doubled output current. To increase the frequency further, we used various graphene doping control techniques to produce Dirac voltage engineered graphene channels. The various surface treatments and substrate conditions produced differently doped graphene channels that were integrated on a single substrate and multiple Dirac voltages were observed by applying a single gate voltage sweep. We applied the Dirac voltage engineering techniques to graphene field-effect transistors on a single chip for the fabrication of a frequency multiplier and a logic inverter demonstrating analog and digital circuit application possibilities.

Reduction of hole doping of chemical vapor deposition grown graphene by photoresist selection and thermal treatment.

The doping effect on graphene by photoresists were studied in this article. Polymethyl methacrylate (PMMA) is the usual choice for graphene transfer, but it is known to leave a significant amount of residue. PMMA results in strong hole doping and reduction of mobility of the graphene devices. Not only PMMA, but photoresists also leave residues during the lithographic steps and dope the graphene in strong hole-doping states along with water and oxygen molecules. In this article, we tested three types of photoresists for their effects on graphene's electrical properties. It was found that a specific photoresist can significantly reduce the amount of hole-doping of the graphene transistor more than other photoresists. The use of hydrophobic substrates and additional thermal treatment can help reducing the hole-doping further.

Contact Pressure Level Indication Using Stepped Output Tactile Sensors.

In this article, we report on a novel diaphragm-type tactile pressure sensor that produces stepwise output currents depending on varying low contact pressures. When contact pressures are applied to the stepped output tactile sensor (SOTS), the sensor's suspended diaphragm makes contact with the substrate, which completes a circuit by connecting resistive current paths. Then the contact area, and therefore the number of current paths, would determine the stepped output current produced. This mechanism allows SOTS to have high signal-to-noise ratio (>20 dB) in the 3-500 Hz frequency range at contact pressures below 15 kPa. Moreover, since the sensor's operation does not depend on a material's pressure-dependent electrical properties, the SOTS is able to demonstrate high reproducibility and reliability. By forming a 4 × 4 array of SOTS with a surface bump structure, we demonstrated shear sensing as well as surface (1 × 1 cm²) pressure mapping capabilities.

Factors and age-related drivers that influence self-rated bad health in police officers: A cross-sectional study.

Objective: Although some previous studies have investigated health in police officers, investigations of related factors have been limited to work-related associations or those affecting certain police officers. To address this gap, this study investigated relationships between sociodemographic factors, work-related factors, health behaviors, health conditions, and self-rated bad health (SRBH) in Korean police officers. Methods: In 2021, we conducted a cross-sectional survey in cooperation with the Korean National Police Agency (KNPA). The respondents were 6,591 police officers aged 21-60 years, all of whom agreed to complete the survey online using the police agency's intranet. After collecting data, we conducted a multiple logistic regression analysis to examine factors that were associated with SRBH, with calculations for adjusted odds ratios (ORs) and 95 % confidence intervals (CIs). The study model included a range of individual socioeconomic characteristics, work-related variables, health behaviors, and health conditions. Results: Although the associated factors varied according to age group, several factors generally related to SRBH, including the lack of exercise, stress, having one or more chronic diseases, and work-related pain. By contrast, neither sex nor sleep duration were associated with SRBH of respondents. Monthly night work, smoking, and alcohol consumption were only associated with SRBH of certain age groups. Conclusions: Several variables clearly related to SRBH of police officers. In this context, health-related associations, especially stress and chronic diseases, tended to differ according to age, including those that should be considered to improve health. These findings have important implications for relevant healthcare programs and interventions.

Molecular mechanism for regulating APOBEC3G DNA editing function by the non-catalytic domain.

APOBEC3G (A3G) belongs to the AID/APOBEC cytidine deaminase family and is essential for antiviral immunity. It contains two zinc-coordinated cytidine-deaminase (CD) domains. The N-terminal CD1 domain is non-catalytic but has a strong affinity for nucleic acids, whereas the C-terminal CD2 domain catalyzes C-to-U editing in single-stranded DNA. The interplay between the two domains in DNA binding and editing is not fully understood. Here, our studies on rhesus macaque A3G (rA3G) show that the DNA editing function in linear and hairpin loop DNA is greatly enhanced by AA or GA dinucleotide motifs present downstream (in the 3'-direction) but not upstream (in the 5'-direction) of the target-C editing sites. The effective distance between AA/GA and the target-C sites depends on the local DNA secondary structure. We present two co-crystal structures of rA3G bound to ssDNA containing AA and GA, revealing the contribution of the non-catalytic CD1 domain in capturing AA/GA DNA and explaining our biochemical observations. Our structural and biochemical findings elucidate the molecular mechanism underlying the cooperative function between the non-catalytic and the catalytic domains of A3G, which is critical for its antiviral role and its contribution to genome mutations in cancer.

Machine learning analysis with population data for prepregnancy and perinatal risk factors for the neurodevelopmental delay of offspring.

Neurodevelopmental disorders (NDD) in offspring are associated with a complex combination of pre-and postnatal factors. This study uses machine learning and population data to evaluate the association between prepregnancy or perinatal risk factors and the NDD of offspring. Population-based retrospective cohort data were obtained from Korea National Health Insurance Service claims data for 209,424 singleton offspring and their mothers who gave birth for the first time in 2007. The dependent variables were motor development disorder (MDD), cognitive development disorder (CDD) and combined overall neurodevelopmental disorder (NDD) from offspring. Seventeen independent variables from 2002 to 2007 were included. Random forest variable importance and Shapley Additive Explanation (SHAP) values were calculated to analyze the directions of its associations with the predictors. The random forest with oversampling registered much higher areas under the receiver-operating-characteristic curves than the logistic regression of interaction and non-linearity terms, 79% versus 50% (MDD), 82% versus 52% (CDD) and 74% versus 50% (NDD). Based on random forest variable importance, low socioeconomic status and age at birth were highly ranked. In SHAP values, there was a positive association between NDD and pre- or perinatal outcomes, especially, fetal male sex with growth restriction associated the development of NDD in offspring.

Mesoscale DNA features impact APOBEC3A and APOBEC3B deaminase activity and shape tumor mutational landscapes.

Antiviral DNA cytosine deaminases APOBEC3A and APOBEC3B are major sources of mutations in cancer by catalyzing cytosine-to-uracil deamination. APOBEC3A preferentially targets single-stranded DNAs, with a noted affinity for DNA regions that adopt stem-loop secondary structures. However, the detailed substrate preferences of APOBEC3A and APOBEC3B have not been fully established, and the specific influence of the DNA sequence on APOBEC3A and APOBEC3B deaminase activity remains to be investigated. Here, we find that APOBEC3B also selectively targets DNA stem-loop structures, and they are distinct from those subjected to deamination by APOBEC3A. We develop Oligo-seq, an in vitro sequencing-based method to identify specific sequence contexts promoting APOBEC3A and APOBEC3B activity. Through this approach, we demonstrate that APOBEC3A and APOBEC3B deaminase activity is strongly regulated by specific sequences surrounding the targeted cytosine. Moreover, we identify the structural features of APOBEC3B and APOBEC3A responsible for their substrate preferences. Importantly, we determine that APOBEC3B-induced mutations in hairpin-forming sequences within tumor genomes differ from the DNA stem-loop sequences mutated by APOBEC3A. Together, our study provides evidence that APOBEC3A and APOBEC3B can generate distinct mutation landscapes in cancer genomes, driven by their unique substrate selectivity.

Development of a prediction model for the depression level of the elderly in low-income households: using decision trees, logistic regression, neural networks, and random forest.

Korea is showing the fastest trend in the world in population aging; there is a high interest in the elderly population nationwide. Among the common chronic diseases, the elderly tends to have a high incidence of depression. That said, it has been vital to focus on preventing depression in the elderly in advance. Hence, this study aims to select the factors related to depression in low-income seniors identified in previous studies and to develop a prediction model. In this study, 2975 elderly people from low-income families were extracted using the 13th-year data of the Korea Welfare Panel Study (2018). Decision trees, logistic regression, neural networks, and random forest were applied to develop a predictive model among the numerous data mining techniques. In addition, the wrapper's stepwise backward elimination, which finds the optimal model by removing the least relevant factors, was applied. The evaluation of the model was confirmed via accuracy. It was verified that the final prediction model, in the case of a decision tree, showed the highest predictive power with an accuracy of 97.3%. Second, psychological factors, leisure life satisfaction, social support, subjective health awareness, and family support ranked higher than demographic factors influencing depression. Based on the results, an approach focused on psychological support is much needed to manage depression in low-income seniors. As predicting depression in the elderly varies on numerous influencing factors, using a decision tree may be beneficial to establish a firm prediction model to identify vital factors causing depression in the elderly population.

Unraveling the Enzyme-Substrate Properties for APOBEC3A-Mediated RNA Editing.

The APOBEC3 family of human cytidine deaminases is involved in various cellular processes, including the innate and acquired immune system, mostly through inducing C-to-U in single-stranded DNA and/or RNA mutations. Although recent studies have examined RNA editing by APOBEC3A (A3A), its intracellular target specificity are not fully characterized. To address this gap, we performed in-depth analysis of cellular RNA editing using our recently developed sensitive cell-based fluorescence assay. Our findings demonstrate that A3A and an A3A-loop1-containing APOBEC3B (A3B) chimera are capable of RNA editing. We observed that A3A prefers to edit specific RNA substrates which are not efficiently deaminated by other APOBEC members. The editing efficiency of A3A is influenced by the RNA sequence contexts and distinct stem-loop secondary structures. Based on the identified RNA specificity features, we predicted potential A3A-editing targets in the encoding region of cellular mRNAs and discovered novel RNA transcripts that are extensively edited by A3A. Furthermore, we found a trend of increased synonymous mutations at the sites for more efficient A3A-editing, indicating evolutionary adaptation to the higher editing rate by A3A. Our results shed light on the intracellular RNA editing properties of A3A and provide insights into new RNA targets and potential impact of A3A-mediated RNA editing.