Quantitative Understanding of Probabilistic Behavior of Living Cells Operated by Vibrant Intracellular Networks

For quantitative understanding of probabilistic behaviors of living cells, it is essential to construct a correct mathematical description of intracellular networks interacting with complex cell environments, which has been a formidable task. Here, we present a novel model and stochastic kinetics for an intracellular network interacting with hidden cell environments, employing a complete description of cell state dynamics and its coupling to the system network. Our analysis reveals that various environmental effects on the product number fluctuation of intracellular reaction networks can be collectively characterized by Laplace transform of the time-correlation function of the product creation rate fluctuation with the Laplace variable being the product decay rate. On the basis of the latter result, we propose an efficient method for quantitative analysis of the chemical fluctuation produced by intracellular networks coupled to hidden cell environments. By applying the present approach to the gene expression network, we obtain simple analytic results for the gene expression variability and the environment-induced correlations between the expression levels of mutually noninteracting genes. The theoretical results compose a unified framework for quantitative understanding of various gene expression statistics observed across a number of different systems with a small number of adjustable parameters with clear physical meanings.National Research Foundation of Korea (Grant 2011-0016412)National Research Foundation of Korea (Priority Research Center Program 2009-0093817

Comparative Genome Analysis Reveals Natural Variations in the Genomes of Erwinia pyrifoliae, a Black Shoot Blight Pathogen in Apple and Pear

Erwinia pyrifoliae is a Gram-negative bacterial plant pathogen that causes black shoot blight in apple and pear. Although earlier studies reported the genome comparison of Erwinia species, E. pyrifoliae strains for such analysis were isolated in 1996. In 2014, the strain E. pyrifoliae EpK1/15 was newly isolated in the apple tree showing black shoot blight in South Korea. This study aimed to better understand the similarities and differences caused by natural variations at the genomic level between newly isolated E. pyrifoliae EpK1/15 and the strain Ep1/96, which were isolated almost 20 years apart. Several comparative genomic analyses were conducted, and Clusters of Orthologous Groups of proteins (COG) database was used to classify functional annotation for each strain. E. pyrifoliae EpK1/15 had similarities with the Ep1/96 strain in stress-related genes, Tn3 transposase of insertion sequences, type III secretion systems, and small RNAs. The most remarkable difference to emerge from this comparison was that although the draft genome of E. pyrifoliae EpK1/15 was almost conserved, Epk1/15 strain had at least three sorts of structural variations in functional annotation according to COG database; chromosome inversion, translocation, and duplication. These results indicate that E. pyrifoliae species has gone natural variations within almost 20 years at the genomic level, and we can trace their similarities and differences with comparative genomic analysis

An endoscope with integrated transparent bioelectronics and theranostic nanoparticles for colon cancer treatment

The gastrointestinal tract is a challenging anatomical target for diagnostic and therapeutic procedures for bleeding, polyps and cancerous growths. Advanced endoscopes that combine imaging and therapies within the gastrointestinal tract provide an advantage over stand-alone diagnostic or therapeutic devices. However, current multimodal endoscopes lack the spatial resolution necessary to detect and treat small cancers and other abnormalities. Here we present a multifunctional endoscope-based interventional system that integrates transparent bioelectronics with theranostic nanoparticles, which are photoactivated within highly localized space near tumours or benign growths. These advanced electronics and nanoparticles collectively enable optical fluorescence-based mapping, electrical impedance and pH sensing, contact/temperature monitoring, radio frequency ablation and localized photo/chemotherapy, as the basis of a closed-loop solution for colon cancer treatment. In vitro, ex vivo and in vivo experiments highlight the utility of this technology for accurate detection, delineation and rapid targeted therapy of colon cancer or precancerous lesions.

A More Appropriate Cardiac Troponin T Level That Can Predict Outcomes in End-Stage Renal Disease Patients with Acute Coronary Syndrome

Purpose: Cardiac troponin T (cTnT), a useful marker for diagnosing acute myocardial infarction (AMI) in the general population, is significantly higher than the usual cut-off value in many end-stage renal disease (ESRD) patients without clinically apparent evidence of AMI. The aim of this study was to evaluate the clinical usefulness of cTnT in ESRD patients with acute coronary syndrome (ACS). Materials and methods: Two hundred eighty-four ESRD patients with ACS were enrolled between March 2002 and February 2008. These patients were followed until death or June 2009. Medical records were reviewed retrospectively. The cut-off value of cTnT for AMI was evaluated using a receiver operating characteristic (ROC) curve. We calculated Kaplan-Meier survival curves, and potential outcome predictors were determined by Cox proportional hazard analysis. Results: AMIs were diagnosed in 40 patients (14.1%). The area under the curve was 0.98 in the ROC curve (p<0.001; 95% CI, 0.95-1.00). The summation of sensitivity and specificity was highest at the initial cTnT value of 0.35 ng/mL (sensitivity, 0.95; specificity, 0.97). Survival analysis showed a statistically significant difference in all-cause and cardiovascular mortalities for the group with an initial cTnT ≥0.35 ng/mL compared to the other groups. Initial serum cTnT concentration was an independent predictor for mortality. Conclusion: Because ESRD patients with an initial cTnT concentration ≥0.35 ng/mL have a poor prognosis, it is suggested that urgent diagnosis and treatment be indicated in dialysis patients with ACS when the initial cTnT levels are ≥0.35 ng/mL.ope

Gene expression profiling in the lung tissue of cynomolgus monkeys in response to repeated exposure to welding fumes

Many in the welding industry suffer from bronchitis, lung function changes, metal fume fever, and diseases related to respiratory damage. These phenomena are associated with welding fumes; however, the mechanism behind these findings remains to be elucidated. In this study, the lungs of cynomolgus monkeys were exposed to MMA-SS welding fumes for 229 days and allowed to recover for 153 days. After the exposure and recovery period, gene expression profiles were investigated using the Affymetrix GeneChip® Human U133 plus 2.0. In total, it was confirmed that 1,116 genes were up-or down-regulated (over 2-fold changes, P < 0.01) for the T1 (31.4 ± 2.8 mg/m3) and T2 (62.5 ± 2.7 mg/m3) dose groups. Differentially expressed genes in the exposure and recovery groups were analyzed, based on hierarchical clustering, and were imported into Ingenuity Pathways Analysis to analyze the biological and toxicological functions. Functional analysis identified genes involved in immunological disease in both groups. Additionally, differentially expressed genes in common between monkeys and rats following welding fume exposure were compared using microarray data, and the gene expression of selected genes was verified by real-time PCR. Genes such as CHI3L1, RARRES1, and CTSB were up-regulated and genes such as CYP26B1, ID4, and NRGN were down-regulated in both monkeys and rats following welding fume exposure. This is the first comprehensive gene expression profiling conducted for welding fume exposure in monkeys, and these expressed genes are expected to be useful in helping to understand transcriptional changes in monkey lungs after welding fume exposure

Determination of Fire Blight Susceptibility on Wild Rosaceae Plants in Korea by Artificial Inoculation

The fire blight caused by Erwinia amylovora (Ea) is a devastating disease of Rosaceae plants, including commercially important apple and pear trees. Since the first report in Korea in May 2015, it has been spreading to neighboring regions gradually. Host plants can be infected by pollinators like bees, rainfall accompanied by wind, and cultural practices such as pruning. Many studies have revealed that wild Rosaceae plants such as Cotoneaster spp., Crataegus spp., Pyracantha spp., Prunus spp., and Sorbus spp. can be reservoirs of Ea in nature. However, wild Rosaceae plants in Korea have not been examined yet whether they are susceptible to fire blight. Therefore, the susceptibility to fire blight was examined with 25 species in 10 genera of wild Rosaceae plants, which were collected during 2020–2022, by artificial inoculation. Bacterial suspension (108 cfu/ml) of Ea type strain TS3128 was inoculated artificially in flowers, leaves, stems, and fruits of each plant species, and development of disease symptoms were monitored. Moreover, the presence of Ea bacteria from inoculated samples were checked by conventional polymerase chain reaction. Total 14 species of wild Rosaceae plants showed disease symptoms of fire blight, and Ea bacteria were detected inside of inoculated plant parts. These results suggest that wild Rosaceae plants growing nearby commercial apple and pear orchards in Korea can be Ea reservoirs, and thus they should be monitored regularly to minimize the damage by Ea infection and spreading

Wearable smart sensor systems integrated on soft contact lenses for wireless ocular diagnostics

Wearable contact lenses which can monitor physiological parameters have attracted substantial interests due to the capability of direct detection of biomarkers contained in body fluids. However, previously reported contact lens sensors can only monitor a single analyte at a time. Furthermore, such ocular contact lenses generally obstruct the field of vision of the subject. Here, we developed a multifunctional contact lens sensor that alleviates some of these limitations since it was developed on an actual ocular contact lens. It was also designed to monitor glucose within tears, as well as intraocular pressure using the resistance and capacitance of the electronic device. Furthermore, in-vivo and in-vitro tests using a live rabbit and bovine eyeball demonstrated its reliable operation. Our developed contact lens sensor can measure the glucose level in tear fluid and intraocular pressure simultaneously but yet independently based on different electrical responses.ope

Efficacy and Tolerability of Peginterferon Alpha Plus Ribavirin in the Routine Daily Treatment of Chronic Hepatitis C Patients in Korea: A Multi-Center, Retrospective Observational Study

Background/Aims: We aimed to evaluate the efficacy and safety of peginterferon plus ribavirin for chronic hepatitis C (CHC) patients under real life setting in Korea. Methods: We retrospectively analyzed the medical records of 758 CHC patients treated with peginterferon plus ribavirin between 2000 and 2008 from 14 university hospitals in the Gyeonggi-Incheon area in Korea. Results: Hepatitis C virus (HCV) genotype 1 was detected in 61.2% of patients, while genotype 2 was detected in 35.5%. Baseline HCV RNA level was &gt;= 6x10(5) IU/mL in 51.6% of patients. The sustained virological response (SVR) rate was 59.6% regardless of genotype; 53.6% in genotype 1 and 71.4% in genotype 2/3. On multivariate analysis, male gender (p=0.011), early virological response (p&lt;0.001), genotype 2/3 (p&lt;0.001), HCV RNA &lt;6x10(5) IU/mL (p=0.005) and adherence to the drug &gt;80% of the planned dose (p&lt;0.001) were associated with SVR. The rate of premature discontinuation was 35.7%. The main reason for withdrawal was intolerance to the drug due to common adverse events or cytopenia (48.2%). Conclusions: Our data suggest that the efficacy of peginterferon and ribavirin therapy in Koreans is better in Koreans than in Caucasians for the treatment of CHC, corroborating previous studies that have shown the superior therapeutic efficacy of this regimen in Asians.This study was supported by the Korean Association for the Study of the Liver in 2009