Comparison of a Label-Free Quantitative Proteomic Method Based on Peptide Ion Current Area to the Isotope Coded Affinity Tag Method

Recently, several research groups have published methods for the determination of proteomic expression profiling by mass spectrometry without the use of exogenously added stable isotopes or stable isotope dilution theory. These so-called label-free, methods have the advantage of allowing data on each sample to be acquired independently from all other samples to which they can later be compared in silico for the purpose of measuring changes in protein expression between various biological states. We developed label free software based on direct measurement of peptide ion current area (PICA) and compared it to two other methods, a simpler label free method known as spectral counting and the isotope coded affinity tag (ICAT) method. Data analysis by these methods of a standard mixture containing proteins of known, but varying, concentrations showed that they performed similarly with a mean squared error of 0.09. Additionally, complex bacterial protein mixtures spiked with known concentrations of standard proteins were analyzed using the PICA label-free method. These results indicated that the PICA method detected all levels of standard spiked proteins at the 90% confidence level in this complex biological sample. This finding confirms that label-free methods, based on direct measurement of the area under a single ion current trace, performed as well as the standard ICAT method. Given the fact that the label-free methods provide ease in experimental design well beyond pair-wise comparison, label-free methods such as our PICA method are well suited for proteomic expression profiling of large numbers of samples as is needed in clinical analysis

Nonalcoholic fatty liver disease and risk of incident young-onset hypertension:effect modification by sex

Background and aims: although nonalcoholic fatty liver disease (NAFLD) and hypertension are increasingly common among young adults, it is uncertain if NAFLD affects incidence of young-onset hypertension, and if the association is modified by sex. We investigated potential effect modification by sex on the association between NAFLD and incident hypertension in young adults (<40 years).Method and results: this cohort study comprised 85,789 women and 67,553 men aged <40 years without hypertension at baseline. Hepatic steatosis was assessed by liver ultrasound and classified as mild or moderate/severe. Hypertension was defined as blood pressure (BP) ≥130/80 mmHg; self-reported history of physician-diagnosed hypertension; or current use of BP-lowering medications. Cox proportional hazard models were used to estimate hazard ratios (HRs; 95% confidence intervals [CIs]) for incident hypertension by NAFLD status (median follow-up 4.5 years). A total of 25,891 participants developed incident hypertension (incidence rates per 103 person-years: 15.6 for women and 63.5 for men). Multivariable-adjusted HRs (95% CIs) for incident hypertension comparing no NAFLD (reference) with mild or moderate/severe NAFLD were 1.68 (1.56–1.80) and 1.83 (1.60–2.09) for women and 1.21 (1.17–1.25) and 1.23 (1.17–1.30) for men, respectively. Stronger associations were consistently observed between NAFLD and incident hypertension in women, regardless of obesity/central obesity (all p-values for interaction by sex <0.001).Conclusions: NAFLD is a potential risk factor for young-onset hypertension with a relatively greater impact in women and in those with more severe hepatic steatosis

Systematic identification of an integrative network module during senescence from time-series gene expression

Background: Cellular senescence irreversibly arrests growth of human diploid cells. In addition, recent studies have indicated that senescence is a multi-step evolving process related to important complex biological processes. Most studies analyzed only the genes and their functions representing each senescence phase without considering gene-level interactions and continuously perturbed genes. It is necessary to reveal the genotypic mechanism inferred by affected genes and their interaction underlying the senescence process. Results: We suggested a novel computational approach to identify an integrative network which profiles an underlying genotypic signature from time-series gene expression data. The relatively perturbed genes were selected for each time point based on the proposed scoring measure denominated as perturbation scores. Then, the selected genes were integrated with protein-protein interactions to construct time point specific network. From these constructed networks, the conserved edges across time point were extracted for the common network and statistical test was performed to demonstrate that the network could explain the phenotypic alteration. As a result, it was confirmed that the difference of average perturbation scores of common networks at both two time points could explain the phenotypic alteration. We also performed functional enrichment on the common network and identified high association with phenotypic alteration. Remarkably, we observed that the identified cell cycle specific common network played an important role in replicative senescence as a key regulator. Conclusions: Heretofore, the network analysis from time series gene expression data has been focused on what topological structure was changed over time point. Conversely, we focused on the conserved structure but its context was changed in course of time and showed it was available to explain the phenotypic changes. We expect that the proposed method will help to elucidate the biological mechanism unrevealed by the existing approaches.1

Severe protein C deficiency in a newborn caused by a homozygous pathogenic variant in the PROC gene: a case report

Background Severe protein C deficiency is a rare and inherited cause of thrombophilia in neonates. Protein C acts as an anticoagulant, and its deficiency results in vascular thrombosis. Herein, we report a case of protein C deficiency with a homozygous pathogenic variant in a term neonate, with good outcomes after proper treatment. Case presentation A four-day-old male newborn was transferred to the Seoul National University Hospital on account of dark red to black skin lesions. He was born full-term with an average birth weight without perinatal problems. There were no abnormal findings in the prenatal tests, including intrauterine sonography. The first skin lesion was observed on his right toes and rapidly progressed to proximal areas, such as the lower legs, left arm, and buttock. Under the impression of thromboembolism or vasculitis, we performed a coagulopathy workup, which revealed a high D-dimer level of 23.05 μg/ml. A skin biopsy showed fibrin clots in most capillaries, and his protein C activity level was below 10%, from which we diagnosed protein C deficiency. On postnatal day 6, he experienced an apnea event with desaturation and an abnormal right pupillary light reflex. Brain computed tomography showed multifocal patchy intracranial hemorrhage and intraventricular hemorrhage with an old ischemic lesion. Ophthalmic examination revealed bilateral retinal traction detachments with retinal folds. Protein C concentrate replacement therapy was added to previous treatments including steroids, prostaglandin E1, and anticoagulation. After replacement therapy, there were no new skin lesions, and the previous lesions recovered with scarring. Although there were no new brain hemorrhagic infarctions, there was ongoing ischemic tissue loss, which required further rehabilitation. Ophthalmic surgical interventions were performed to treat the bilateral retinal traction detachments with retinal folds. Molecular analysis revealed a homozygous pathogenic variant in the PROC gene. Conclusion Severe protein C deficiency can manifest as a fatal coagulopathy in any organ. Early diagnosis and proper treatment, including protein C concentrate replacement, may improve outcomes without serious sequelae

Electromagnetic Field Interference on Transmission Lines due to On-Board Antenna

As the available space in the board of a mobile device becomes smaller and more compact, circuit elements and transmission lines are arranged in very close proximity, especially from the antennas which are usually installed on the same board. Due to the various on-board antennas which are designed in small space, the transmission lines on the board are electromagnetically interfered, resulting in the performance degradation of the circuit. So the engineers and circuit designers should find the least interfered place for the transmission lines and components to minimize the electromagnetic interferences. This paper discusses and presents a methodology to find the least sensitive position in the induced current distribution as well as in the noise power delivered from the antenna. For this purpose some vertical, horizontal, and bent transmission lines with antenna on the same board are designed and fabricated with and without common ground, and the transferred powers to the transmission lines were measured and were also simulated using a full-wave simulator. The results predicted by the EM simulation model were successfully confirmed through the measurement of S-parameters in the experimental setup, which shows the validness of the suggested analysis method

Pre-Attentional Effects on Global Precedence Processing in Children with Autism Spectrum Disorder and Those with Typical Development on a Tablet-Based Modified Navon’s Paradigm Task

This study aimed to characterize the pre-attentional effects on global precedence processing in children with autism spectrum disorder (ASD) and those with typical development (TD). A sample of 17 participants, comprising eight children with ASD and nine TD children, were recruited for the study. A tablet-based assessment utilizing a global and local visual processing paradigm task was developed to investigate the participant’s abilities. The task consisted of verbal instructions to locate and touch either a global or local figure, presented in five conditions: neutral, congruent, and incongruent. The percentage of correct answers and reaction time (RT) for each task were measured and analyzed statistically. Results revealed that children with ASD exhibited statistically significant differences in both the percentage of correct scores and RT among various conditions, while TD children displayed differences in RT but not in the percentage of correct answers. These findings suggest that conflicting processes affect both behavioral and cognitive processes in children with ASD, and that cognitive effort is still involved for children with TD, but does not affect behavioral processes. In children with ASD, the RT was the shortest in the congruent (report local figure) condition; in children with TD, the RT was the shortest in the congruent (report global figure) condition. This implies that children with TD exhibit a pre-attentive effect on global precedence processing, while children with ASD do not. These visual-processing-function characteristics may aid in screening for visual perception problems in children with ASD

Seismic Vulnerability Assessment and Mapping of Gyeongju, South Korea Using Frequency Ratio, Decision Tree, and Random Forest

The main purpose of this study was to compare the prediction accuracies of various seismic vulnerability assessment and mapping methods. We applied the frequency ratio (FR), decision tree (DT), and random forest (RF) methods to seismic data for Gyeongju, South Korea. A magnitude 5.8 earthquake occurred in Gyeongju on 12 September 2016. Buildings damaged during the earthquake were used as dependent variables, and 18 sub-indicators related to seismic vulnerability were used as independent variables. Seismic data were used to construct a model for each method, and the models’ results and prediction accuracies were validated using receiver operating characteristic (ROC) curves. The success rates of the FR, DT, and RF models were 0.661, 0.899, and 1.000, and their prediction rates were 0.655, 0.851, and 0.949, respectively. The importance of each indicator was determined, and the peak ground acceleration (PGA) and distance to epicenter were found to have the greatest impact on seismic vulnerability in the DT and RF models. The constructed models were applied to all buildings in Gyeongju to derive prediction values, which were then normalized to between 0 and 1, and then divided into five classes at equal intervals to create seismic vulnerability maps. An analysis of the class distribution of building damage in each of the 23 administrative districts showed that district 15 (Wolseong) was the most vulnerable area and districts 2 (Gangdong), 18 (Yangbuk), and 23 (Yangnam) were the safest areas

Pre-Attentional Effects on Global Precedence Processing in Children with Autism Spectrum Disorder and Those with Typical Development on a Tablet-Based Modified Navon’s Paradigm Task

This study aimed to characterize the pre-attentional effects on global precedence processing in children with autism spectrum disorder (ASD) and those with typical development (TD). A sample of 17 participants, comprising eight children with ASD and nine TD children, were recruited for the study. A tablet-based assessment utilizing a global and local visual processing paradigm task was developed to investigate the participant’s abilities. The task consisted of verbal instructions to locate and touch either a global or local figure, presented in five conditions: neutral, congruent, and incongruent. The percentage of correct answers and reaction time (RT) for each task were measured and analyzed statistically. Results revealed that children with ASD exhibited statistically significant differences in both the percentage of correct scores and RT among various conditions, while TD children displayed differences in RT but not in the percentage of correct answers. These findings suggest that conflicting processes affect both behavioral and cognitive processes in children with ASD, and that cognitive effort is still involved for children with TD, but does not affect behavioral processes. In children with ASD, the RT was the shortest in the congruent (report local figure) condition; in children with TD, the RT was the shortest in the congruent (report global figure) condition. This implies that children with TD exhibit a pre-attentive effect on global precedence processing, while children with ASD do not. These visual-processing-function characteristics may aid in screening for visual perception problems in children with ASD

Selenobaculum gbiensis gen. nov. sp. nov., a new bacterium isolated from the gut microbiota of a patient with Crohn’s disease

Abstract The human gut microbiota is a complex ecology comprising approximately 10 to 100 trillion microbial cells. Most of the bacteria detected by 16s rRNA sequencing have yet to be cultured, but intensive attempts to isolate the novel bacteria have improved our knowledge of the gut microbiome composition and its roles within human host. In our culturomics study, a novel gram-negative, motile, obligately anaerobic, rod-shaped bacteria, designated as strain ICN-92133T, was isolated from a fecal sample of a 26-year-old patient with Crohn’s disease. Based on the 16s rRNA sequence of strain ICN-92133T, the phylogeny analysis placed the strain into the family Selenomonadaceae, showing 93.91% similarity with the closely related Massilibacillus massiliensis strain DSM 102838T. Strain ICN-92133T exhibited a genome size of 2,679,003 bp with a GC content of 35.5% which was predicted to contain 26 potential virulence factors and five antimicrobial resistance genes. In comparative genomic analysis, strain ICN-92133T showed digital DNA–DNA Hybridization and OrthoANI values lower than 21.9% and 71.9% with the closest type strains, respectively. In addition, comparing phenotypic, biochemical, and cellular fatty acids with those of closely related strains revealed the distinctiveness of strain ICN-92133T. Based on the taxonogenomic results, strain ICN-92133T is proposed as a novel species belonging to a new genus. Therefore, we suggest the name of the new genus Selenobaculum gen. nov. within the family Selenomonadaceae and strain ICN-92133T (= KCTC 25622T = JCM 36070T) as a type strain of new species Selenobaculum gbiensis sp. nov

Smectic assemblies in C-3-symmetric hexa-alkylated liquid crystals: transformation from smectogen to discogen via hydrogen bonding

In this paper, we report a C-3-symmetric liquid crystal (LC) with sixfold alkyl peripheries exhibiting an unusual smectic E-like organization in the LC state. Based on conformational considerations, the smectic assembly is attributed to the formation of an endo-type Y conformer of asymmetric triazolyl and benzylic groups that cannot be accessed in other C-3-symmetric molecules exclusively showing columnar assemblies. The Y conformers form a two-dimensional oblique lattice in the aromatic layers of the ordered smectic phase. In addition, the Y-shaped molecule in the smectic phases can change into a circular shape by the 1 : 1 hydrogen-bonding interaction with a gallic acid derivative, which leads to a hexagonal columnar LC phase. The triazole-based LC design concept proves the smectic LC assembly in the C-3-symmetric system, and provides the supramolecular manipulation of LC morphologies