Comparative analysis of the JAK/STAT signaling through erythropoietin receptor and thrombopoietin receptor using a systems approach

<p>Abstract</p> <p>Background</p> <p>The Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway is one of the most important targets for myeloproliferative disorder (MPD). Although several efforts toward modeling the pathway using systems biology have been successful, the pathway was not fully investigated in regard to understanding pathological context and to model receptor kinetics and mutation effects.</p> <p>Results</p> <p>We have performed modeling and simulation studies of the JAK/STAT pathway, including the kinetics of two associated receptors (the erythropoietin receptor and thrombopoietin receptor) with the wild type and a recently reported mutation (JAK2V617F) of the JAK2 protein.</p> <p>Conclusion</p> <p>We found that the different kinetics of those two receptors might be important factors that affect the sensitivity of JAK/STAT signaling to the mutation effect. In addition, our simulation results support clinically observed pathological differences between the two subtypes of MPD with respect to the JAK2V617F mutation.</p

Bioinformatics challenges in molecular epidemiology of cancers

Molecular epidemiology is the integration of molecular biologic techniques into epidemiologic study. With the advances in understanding of carcinogenesis and the human genome, there has been an evolution in the field of cancer epidemiology. However, traditional analyses of single genetic variants often fail to identify susceptibility genes for cancer risk. In particular, recent technological evolution has enabled high-throughput analyses for a number of genetic variants and driven accumulation of unprecedentedly large genome data, imposing bioinformatics challenges. These studies aim to integrate the genetic basis of complex diseases including cancers in which the interplay of multiple genetic and environmental risk factors may play an important role. Here we outline currently available approaches for detecting variants of cancer risk. We also review upcoming bioinformatics challenges and technical aspects in the field of molecular epidemiology, and discuss their future impact on the understanding of carcinogenesis and personalized strategies for cancer prevention and therapy

Dreaming of the future of stroke: translation of bench to bed

Stroke is one of the leading causes of death and the most common cause of disability in adults. Remarkable advances in stroke research have been achieved during the past decades. Stroke fatalities have decreased significantly worldwide owing to improved stroke care because of increased public awareness of stroke symptoms, improved acute stroke therapy, and improved stroke prevention approaches. There are currently significant developments in new technologies with the potential to be used daily in clinical practice in patients with stroke. In this review, we have selected and discussed some of the key areas related to stroke, namely big data, artificial intelligence, precision medicine, medical devices, and stem cells

In Utero Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Affects the Development of Reproductive System in Mouse

PURPOSE: Exposure of male reproductive organs to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) has been reported to cause developmental changes. In this study, we evaluated the effects of in utero TCDD exposure on male reproductive development. MATERIALS AND METHODS: Pregnant C57BL/6 mice were administered a single intraperitoneal injection of TCDD (1microgram/kg) on gestation day (GD) 15. The offspring were examined in the immature stage on postnatal day (PND) 30 and in the mature stage on PND 60. The testes were examined for histological changes, androgen receptor (AR), proliferating cell nuclear antigen (PCNA) and apoptosis following the measurement of morphological changes. RESULTS: Anogenital distance (AGD) and testis weights were reduced by TCDD exposure both on PND 30 and PND 60 while body weights and length of male offspring were not affected by TCDD. The regular sperm developmental stage was impaired with TCDD treatment on PND 30. However, no difference was found between the control group and TCDD groups on PND 60. Simultaneously, the expression of AR was also reduced on PND 30, while it was increased on PND 60 compared with the control group. The expression of PCNA was decreased whereas apoptosis was not affected by TCDD both on PND 30 and PND 60. CONCLUSION: These results suggest that in utero exposure to TCDD influences the development of testes by inhibiting the expression of AR and PCNA. Moreover, the adverse effects of TCDD on male offspring reduced over timeope

Sequence Variations and Haplotypes of the GJB2 Gene Revealed by Resequencing of 192 Chromosomes from the General Population in Korea

ObjectivesHearing impairment (HI) is the most common sensory deficit in human. The Gap Junction Protein, Beta-2 (GJB2) gene encodes the protein connexin 26, and this gene accounts for up to half of the cases of autosomal recessive nonsyndromic HI. This study was conducted to obtain a set of sequence variations (SVs) of the GJB2 gene among Koreans from the general population for making molecular genetic diagnoses and performing genetic counseling.MethodsWe resequenced the GJB2 gene in 192 chromosomes from 96 adult individuals of Korean descent and who were without a history of hearing difficulty. The data of the SVs was obtained and the haplotypes were reconstructed from the data.ResultsFive SVs were observed, including a novel one (c.558G>A; p.T186T), with the allele frequencies ranging from 0.5% (1/192) to 41% (79/192). The linkage disequilibrium study and haplotype construction showed that some of the SVs are in tight linkage, resulting in a limited number of haplotypes.ConclusionWe observed SVs of the GJB2 gene with different allele frequencies, and a limited number of haplotypes were constructed. The data from this study can be used as reference data for GJB2-related hearing genetic studies, including studies on the founder effect and population genetics, and this data is particularly relevant to people of East Asian decent

Clinical characteristics of children who visited the emergency department with extended-spectrum beta-lactamase-producing Escherichia coli urinary tract infection and its risk factors

Purpose To identify the differences in features between children with urinary tract infection (UTI) caused by extended-spectrum beta-lactamases (ESBL)-positive and -negative Escherichia coli, and analyze risk factors for the former infection. Methods We reviewed medical records of children younger than 36 months with E. coli UTI who visited the emergency department from January 2012 through January 2019. Differences in variables regarding clinical, laboratory, and microbiologic (i.e., ESBL-positive E. coli on urine culture) features, and outcomes between the ESBL-positive and -negative groups were identified. Factors associated with ESBL-positive E. coli infection were analyzed by logistic regression. Results The children were classified into the ESBL-positive (n = 151) and -negative (n = 40) groups. The former group showed higher frequency of prior UTI (P = 0.038) without other differences between the groups. The median counts of white blood cells, absolute neutrophils, and absolute lymphocytes were higher in the ESBL-positive group than in the other group (P = 0.009, 0.022, and 0.027, respectively). The former group showed longer median hospital length of stay (11.0 days [interquartile range, 8.9-12.0] vs. 6.0 [5.0-7.0]; P < 0.001), and more frequent recurrence per child (3.0 [2.5-3.0] vs. 1.0 [1.0-1.8]; P = 0.047) and presence of vesicoureteral reflux (27.5% vs. 13.2%; P = 0.001). Logistic regression showed leukocytosis (odds ratio, 12.85; 95% confidence interval, 1.04-157.69) and vesicoureteral reflux (4.00; 1.19-13.43) as the factors for ESBL-positive E. coli infection. Conclusion The ESBL-positive group showed significantly higher leukocyte count and rate of vesicoureteral reflux than the ESBL-negative group. For children with these features, empirical antibiotics should be chosen in consideration of the resistant bacteria

Deep tissue space-gated microscopy via acousto-optic interaction

© 2020, The Author(s).To extend the imaging depth of high-resolution optical microscopy, various gating operations—confocal, coherence, and polarization gating—have been devised to filter out the multiply scattered wave. However, the imaging depth is still limited by the multiply scattered wave that bypasses the existing gating operations. Here, we present a space gating method, whose mechanism is independent of the existing methods and yet effective enough to complement them. Specifically, we reconstruct an image only using the ballistic wave that is acousto-optically modulated at the object plane. The space gating suppresses the multiply scattered wave by 10–100 times in a highly scattering medium, and thus enables visualization of the skeletal muscle fibers in whole-body zebrafish at 30 days post fertilization. The space gating will be an important addition to optical-resolution microscopy for achieving the ultimate imaging depth set by the detection limit of ballistic wav