Hydrogen peroxide signalling mediates fertilization and post-fertilization development in the red alga Bostrychia moritziana.

Reactive oxygen species (ROS) signalling has a multitude of roles in cellular processes throughout biology. We hypothesized that red algal fertilization may offer an interesting model to study ROS-mediated signalling, as the stages of fertilization are complex and unique. We detected the localization of ROS production microscopically and monitored the expression of three homologues of NADPH oxidase in reproductive cells during fertilization. ROS were instantaneously produced by spermatia (sperm) when they attached to female trichogynes, diffused across the cell membrane in the form of H2O2, and triggered ROS generation in the carpogonium (egg) as well as carpogonial branch cells which are not in direct contact with spermatia. The expression of NADPH oxidase homologues, RESPIRATORY BURST OXIDASE HOMOLOGUES (BmRBOHs), began to be up-regulated in the female plant upon gamete binding, peaking during the fertilization process and descending back to their original level after fertilization. Pre-treatment with diphenylene iodonium or caffeine blocked gene expression as well as H2O2 production. Post-fertilization development was also inhibited when the redox state of the plants was perturbed with H2O2 at any time before or after the fertilization. Our results suggest that H2O2 acts as an auto-propagating signalling molecule, possibly through Ca2+ channel activation, and regulates gene expression in fertilization as well as post-fertilization development in red algae.

Sex-Specific Genes and their Expression in the Life History of the Red Alga Bostrychia moritziana (Ceramiales, Rhodomelaceae).

Diverse sex determination mechanisms have been reported in eukaryotes, but little is known about the genetic pathways leading to sex determination in red algae. Sex-specific genes that could be involved in sex determination and sexual differentiation were investigated in the red alga Bostrychia moritziana by analyzing the transcriptomes of various phases including males, females, and tetrasporophytes. Sex dominantly expressed genes which showed >10-fold difference between sexes was isolated using comparative RNA-seq analysis. We found 19 gene homologues, 10 from males, and nine from females, that were found only in one sex in genomic amplification using strains collected from five different localities. Most of the sex-specific genes are involved in important cellular processes including chromosome segregation, nucleo-cytoplasmic protein shuttling, or tRNA modification. Quantitative PCR analysis showed that some sex-specific genes were differently regulated during critical events of sexual reproduction like fertilization and carposporophyte development. We could localize the expression of a male-specific gene in spermatia before and after gamete binding using RNA in situ hybridization. Amino acid sequence identity between male and female homologues of importin alpha gene and PreQ(0) reductase were highly divergent (75% and 74%, respectively), suggesting that these divergent homologues are on non-recombining UV-type chromosomes in their respective sexes. Another set of transcripts were found that were sex dominantly expressed, but not sex-specific. Nineteen out of 39 sex dominantly expressed transcripts were annotated to transposable elements. Our results suggest that sexual differentiation in B. moritziana may be achieved by multi-level regulation of cellular processes, both from genes present only in one sex and differential expression of shared genes.

Gene profile of fibroblasts identify relation of CCL8 with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by the complex interaction of cells involved in chronic inflammation and fibrosis. Global gene expression of a homogenous cell population will identify novel candidate genes. METHODS: Gene expression of fibroblasts derived from lung tissues (8 IPF and 4 controls) was profiled, and ontology and functional pathway were analyzed in the genes exhibiting >2 absolute fold changes with p-values < 0.05. CCL8 mRNA and protein levels were quantified using real-time PCR and ELISA. CCL8 localization was evaluated by immunofluorescence staining. RESULTS: One hundred seventy eight genes differentially expressed and 15 genes exhibited >10-fold change. Among them, 13 were novel in relation with IPF. CCL8 expression was 22.8-fold higher in IPF fibroblasts. The levels of CCL8 mRNA and protein were 3 and 9-fold higher in 14 IPF fibroblasts than those in 10 control fibroblasts by real-time PCR and ELISA (p = 0.022 and p = 0.026, respectively). The CCL8 concentrations in BAL fluid was significantly higher in 86 patients with IPF than those in 41 controls, and other interstitial lung diseases including non-specific interstitial pneumonia (n = 22), hypersensitivity pneumonitis (n = 20) and sarcoidosis (n = 19) (p < 0.005, respectively). Cut-off values of 2.29 pg/mL and 0.43 pg/mL possessed 80.2 and 70.7% accuracy for the discrimination of IPF from NC and the other lung diseases, respectively. IPF subjects with CCL8 levels >28.61 pg/mL showed shorter survival compared to those with lower levels (p = 0.012). CCL8 was expressed by α-SMA-positive cells in the interstitium of IPF. CONCLUSIONS: Transcriptome analysis identified several novel IPF-related genes. Among them, CCL8 is a candidate molecule for the differential diagnosis and prediction of survival.

Web-based infectious disease surveillance systems and public health perspectives: a systematic review.

BACKGROUND: Emerging and re-emerging infectious diseases are a significant public health concern, and early detection and immediate response is crucial for disease control. These challenges have led to the need for new approaches and technologies to reinforce the capacity of traditional surveillance systems for detecting emerging infectious diseases. In the last few years, the availability of novel web-based data sources has contributed substantially to infectious disease surveillance. This study explores the burgeoning field of web-based infectious disease surveillance systems by examining their current status, importance, and potential challenges. METHODS: A systematic review framework was applied to the search, screening, and analysis of web-based infectious disease surveillance systems. We searched PubMed, Web of Science, and Embase databases to extensively review the English literature published between 2000 and 2015. Eleven surveillance systems were chosen for evaluation according to their high frequency of application. Relevant terms, including newly coined terms, development and classification of the surveillance systems, and various characteristics associated with the systems were studied. RESULTS: Based on a detailed and informative review of the 11 web-based infectious disease surveillance systems, it was evident that these systems exhibited clear strengths, as compared to traditional surveillance systems, but with some limitations yet to be overcome. The major strengths of the newly emerging surveillance systems are that they are intuitive, adaptable, low-cost, and operated in real-time, all of which are necessary features of an effective public health tool. The most apparent potential challenges of the web-based systems are those of inaccurate interpretation and prediction of health status, and privacy issues, based on an individual's internet activity. CONCLUSION: Despite being in a nascent stage with further modification needed, web-based surveillance systems have evolved to complement traditional national surveillance systems. This review highlights ways in which the strengths of existing systems can be maintained and weaknesses alleviated to implement optimal web surveillance systems.

Estimating Influenza Outbreaks Using Both Search Engine Query Data and Social Media Data in South Korea.

BACKGROUND: As suggested as early as in 2006, logs of queries submitted to search engines seeking information could be a source for detection of emerging influenza epidemics if changes in the volume of search queries are monitored (infodemiology). However, selecting queries that are most likely to be associated with influenza epidemics is a particular challenge when it comes to generating better predictions. OBJECTIVE: In this study, we describe a methodological extension for detecting influenza outbreaks using search query data; we provide a new approach for query selection through the exploration of contextual information gleaned from social media data. Additionally, we evaluate whether it is possible to use these queries for monitoring and predicting influenza epidemics in South Korea. METHODS: Our study was based on freely available weekly influenza incidence data and query data originating from the search engine on the Korean website Daum between April 3, 2011 and April 5, 2014. To select queries related to influenza epidemics, several approaches were applied: (1) exploring influenza-related words in social media data, (2) identifying the chief concerns related to influenza, and (3) using Web query recommendations. Optimal feature selection by least absolute shrinkage and selection operator (Lasso) and support vector machine for regression (SVR) were used to construct a model predicting influenza epidemics. RESULTS: In total, 146 queries related to influenza were generated through our initial query selection approach. A considerable proportion of optimal features for final models were derived from queries with reference to the social media data. The SVR model performed well: the prediction values were highly correlated with the recent observed influenza-like illness (r=.956; P<.001) and virological incidence rate (r=.963; P<.001). CONCLUSIONS: These results demonstrate the feasibility of using search queries to enhance influenza surveillance in South Korea. In addition, an approach for query selection using social media data seems ideal for supporting influenza surveillance based on search query data.

Angiotensin-converting enzyme (ACE) gene polymorphisms are associated with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive dyspnea and worsening lung function. ACE is increased in the bronchoalveolar lavage fluid from patients with IPF, suggesting the role of ACE in the pathogenesis of IPF. We evaluated the role of single-nucleotide polymorphisms (SNPs) in the development risk of IPF. METHODS: Two-hundred twenty patients with IPF and 456 healthy subjects were included in this study. Eleven polymorphisms were selected among those reported previously. Genotype was performed by single base extension. RESULTS: Although absolute LD (|D'|= 1 and r(2 )= 1) was not present, 11 SNPs showed tight LDs. The logistic analysis of the all of 11 SNPs on the ACE genes between patients with IPF and healthy subjects were found to be related with the risk of IPF in recessive type. However, in patients with IPF diagnosed by surgical lung biopsy, only two SNP of -5538T>C and +21288_insdel SNPs were related with the risk of IPF in co-dominant type, and there were no SNPs related with the risk of IPF in dominant type. In patients with IPF diagnosed by clinical criteria or surgical lung biopsy, four SNPs on promoter (-5538T>C, -5508A>C, -3927T>C, -115T>C), one on intron (+15276A>G), one on exon (+21181G>A), and one in three prime region (+21288_insdel) were related with the risk of IPF. CONCLUSIONS: This study showed a newly discovered SNP of ACE associated with the risk of development of IPF. ACE -5538T>C and -5508A>C significantly associated with risk of IPF in Korea.

Two Indias: The structure of primary health care markets in rural Indian villages with implications for policy.

We visited 1519 villages across 19 Indian states in 2009 to (a) count all health care providers and (b) elicit their quality as measured through tests of medical knowledge. We document three main findings. First, 75% of villages have at least one health care provider and 64% of care is sought in villages with 3 or more providers. Most providers are in the private sector (86%) and, within the private sector, the majority are 'informal providers' without any formal medical training. Our estimates suggest that such informal providers account for 68% of the total provider population in rural India. Second, there is considerable variation in quality across states and formal qualifications are a poor predictor of quality. For instance, the medical knowledge of informal providers in Tamil Nadu and Karnataka is higher than that of fully trained doctors in Bihar and Uttar Pradesh. Surprisingly, the share of informal providers does not decline with socioeconomic status. Instead, their quality, along with the quality of doctors in the private and public sector, increases sharply. Third, India is divided into two nations not just by quality of health care providers, but also by costs: Better performing states provide higher quality at lower per-visit costs, suggesting that they are on a different production possibility frontier. These patterns are consistent with significant variation across states in the availability and quality of medical education. Our results highlight the complex structure of health care markets, the large share of private informal providers, and the substantial variation in the quality and cost of care across and within markets in rural India. Measuring and accounting for this complexity is essential for health care policy in India.

The S100 calcium-binding protein A4 level is elevated in the lungs of patients with idiopathic pulmonary fibrosis.

BACKGROUND: Fibroblast dysfunction is the main pathogenic mechanism of idiopathic pulmonary fibrosis (IPF). S100 calcium-binding protein A4 (S100A4) plays critical roles in the proliferation of fibroblasts and in the development of pulmonary, hepatic, and renal fibrosis. However, the clinical implications of S100A4 in IPF have not been evaluated. METHODS AND MATERIALS: The S100A4 mRNA and protein levels were measured by real-time PCR and immunoblotting in fibroblasts from IPF patients and controls. The S100A4 level was measured by enzyme-linked immunosorbent assay in bronchoalveolar lavage fluid (BALF) from the normal controls (NCs; n = 33) and from patients with IPF (n = 87), non-specific interstitial pneumonia (NSIP; n = 22), hypersensitivity pneumonitis (HP; n = 19), and sarcoidosis (n = 9). S100A4 localization was evaluated by immunofluorescence staining. RESULTS: The S100A4 mRNA and protein levels were significantly higher in fibroblasts from IPF patients (n = 14) than in those from controls (n = 10, p < 0.001). The S100A4 protein level in BALF was significantly higher in the IPF (89.25 [49.92-203.02 pg/mL]), NSIP (74.53 [41.88-131.45 pg/mL]), HP (222.36 [104.92-436.92 pg/mL]) and sarcoidosis (101.62 [59.36-300.62 pg/mL]) patients than in the NCs (7.57 [1.31-14.04 pg/mL], p < 0.01, respectively). Cutoff S100A4 levels of 18.85 and 28.88 pg/mL had 87.4% and 87.8% accuracy, respectively, for discriminating IPF and other lung diseases from NCs. CONCLUSIONS: S100A4 is expressed by α-SMA-positive cells in the interstitium of the IPF patients. S100A4 may participate in the development of IPF, and its protein level may be a candidate diagnostic and therapeutic marker for IPF.

Global DNA Methylation Pattern of Fibroblasts in Idiopathic Pulmonary Fibrosis.

Our previous transcriptome study of cultured fibroblasts identified 178 genes that were differentially expressed by 8 idiopathic pulmonary fibrosis (IPF) fibroblasts compared with 4 controls. Here, we performed genome-wide DNA methylation analysis to evaluate the relationship of CpG methylation to differential gene expression. Among 485,577 loci, 5850 loci on 2282 genes showed significant differences between the 2 groups (delta-beta >10.21 and p-value <0.05). Among these, beta values of 80 CpGs (30 hypermethylated and 50 hypomethylated) were significantly correlated with mRNA expression of 34 genes (19.1%) of the 178 differentially expressed genes between the 2 groups (13 downregulated and 21 upregulated). Gene ontology enrichment of these genes included cell adhesion, molecule binding, chemical homeostasis, surfactant homeostasis, and receptor binding. One-third of them are involved in the known process of fibrosis; the others are novel genes with respect to pulmonary fibrosis. We identified relationships between the altered DNA methylation levels and about one-fifth of the corresponding changes in gene expression by lung tissue fibroblasts. Findings from this study provide new information on novel genes responsible for the pathogenesis of IPF under the control of CpG methylation changes in IPF lungs.

Identification of Keywords From Twitter and Web Blog Posts to Detect Influenza Epidemics in Korea.

OBJECTIVE: Social media data are a highly contextual health information source. The objective of this study was to identify Korean keywords for detecting influenza epidemics from social media data. METHODS: We included data from Twitter and online blog posts to obtain a sufficient number of candidate indicators and to represent a larger proportion of the Korean population. We performed the following steps: initial keyword selection; generation of a keyword time series using a preprocessing approach; optimal feature selection; model building and validation using least absolute shrinkage and selection operator, support vector machine (SVM), and random forest regression (RFR). RESULTS: A total of 15 keywords optimally detected the influenza epidemic, evenly distributed across Twitter and blog data sources. Model estimates generated using our SVM model were highly correlated with recent influenza incidence data. CONCLUSIONS: The basic principles underpinning our approach could be applied to other countries, languages, infectious diseases, and social media sources. Social media monitoring using our approach may support and extend the capacity of traditional surveillance systems for detecting emerging influenza. (Disaster Med Public Health Preparedness. 2018; 12: 352-359).

Designing a Sustainable Noise Mapping System Based on Citizen Scientists Smartphone Sensor Data.

In this study, we attempted to assess the feasibility of collecting population health data via mobile devices. Specifically, we constructed noise maps based on sound information monitored by individuals' smartphones. We designed a sustainable way of creating noise maps that can overcome the shortcomings of existing station-based noise-monitoring systems. Three hundred and nine Seoul residents aged 20-49 years who used Android-based smartphones were recruited, and the subjects installed a special application that we developed for this study. This application collected information on sound and geographical location every 10 min for 7 days. Using GIS, we were able to construct various types of noise maps of Seoul (e.g., daytime/nighttime and weekdays/weekends) using the information on sound and geographical location obtained via the users' smartphones. Despite the public health importance of noise management, a number of countries and cities lack a sustainable system to monitor noise. This pilot study showed the possibility of using the smartphones of citizen scientists as an economical and sustainable way of monitoring noise, particularly in an urban context in developing countries.

Public Trauma after the Sewol Ferry Disaster: The Role of Social Media in Understanding the Public Mood.

The Sewol ferry disaster severely shocked Korean society. The objective of this study was to explore how the public mood in Korea changed following the Sewol disaster using Twitter data. Data were collected from daily Twitter posts from 1 January 2011 to 31 December 2013 and from 1 March 2014 to 30 June 2014 using natural language-processing and text-mining technologies. We investigated the emotional utterances in reaction to the disaster by analyzing the appearance of keywords, the human-made disaster-related keywords and suicide-related keywords. This disaster elicited immediate emotional reactions from the public, including anger directed at various social and political events occurring in the aftermath of the disaster. We also found that although the frequency of Twitter keywords fluctuated greatly during the month after the Sewol disaster, keywords associated with suicide were common in the general population. Policy makers should recognize that both those directly affected and the general public still suffers from the effects of this traumatic event and its aftermath. The mood changes experienced by the general population should be monitored after a disaster, and social media data can be useful for this purpose.

Widening social disparities in alcohol-attributable deaths among Korean men aged 40-59 years during the transitional period of the economic crisis (1995-2005).

OBJECTIVES: This study examined socioeconomic disparities in alcohol-related mortality among Korean men aged 40-59 years during the period before and after the economic crisis in the late 1990s. METHODS: We used Korean Census data (1995, 2005) and data from the National Death Files (1994-1996, 2004-2006) on education and employment status as indicators of socioeconomic position. Based on the age-standardized rates of alcohol-attributable deaths, relative discrepancies across socioeconomic positions were estimated. RESULTS: Socially disadvantaged men were substantially disadvantaged in terms of alcohol-attributable mortality in both years. The disadvantage of men with the lowest level of education relative to the highest was worse in 2005 than in 1995. The relative disadvantage in alcohol-attributable deaths seemed to narrow over time based on the rate ratios. However, the relative index of inequality was higher in 2005 compared to 1995 for both education and occupation. CONCLUSIONS: The results showed that alcohol-attributable mortality in Korea became socioeconomically polarized during the economic crisis. The serious impact of economic polarization following the economic crisis might have been transmitted to alcohol-attributable mortality.

PURIFICATION OF A SEX-SPECIFIC LECTIN INVOLVED IN GAMETE BINDING OF AGLAOTHAMNION CALLOPHYLLIDICOLA (RHODOPHYTA)(1).

Egg and sperm binding and correct recognition is the first stage for successful fertilization. In red algae, spermatial attachment to female trichogynes is mediated by a specific binding between the lectin(s) distributed on the surface of trichogyne and the complementary carbohydrates on the spermatial surface. A female-specific lectin was isolated from Aglaothamnion callophyllidicola by agarose-bound fetuin affinity chromatography. Two proteins, 50 and 14 kDa, eluted from the fetuin column were separated using a native-polyacrylamide gel electrophoresis method and subjected to a gamete binding assay. The 50 kDa protein, which blocked spermatial binding to female trichogynes, was used for further analysis. Internal amino acid sequence of the 50 kDa protein was analyzed using matrix-assisted laser desorption/ionization-mass spectrometry and degenerated primers were designed based on the information. A full-length cDNA encoding the lectin was obtained using rapid amplification of cDNA ends polymerase chain reaction (PCR). The cDNA was 1552 bp in length and coded for a protein of 450 amino acids with a deduced molecular mass of 50.7 kDa, which agreed well with the protein data. Real-time PCR analysis showed that this protein was up-regulated about 10-fold in female thalli. As the protein was novel and showed no significant homology to any known proteins, it was designated Rhodobindin.