bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural insights into the stimulation of S. pombe Dnmt2 catalytic efficiency by the tRNA nucleoside queuosine
Authors: Johannsson Sven , Neumann Piotr , Wulf Alexander , Welp Luisa M. , Gerber Hans-Dieter , Krull Matthias , Diederichsen Ulf , Urlaub Henning , Ficner Ralf 
Published: June 2018

AbstractDnmt2 methylates cytosine at position 38 of tRNAAsp in a variety of eukaryotic organisms. A correlation between the presence of the hypermodified nucleoside queuosine (Q) at position 34 of tRNAAsp and the Dnmt2 dependent C38 methylation was recently found in vivo for S. pombe and D. discoideum. We demonstrate a direct effect of the Q-modification on the methyltransferase catalytic efficiency in vitro, as Vmax/K0.5 of purified S. pombe Dnmt2 shows an increase for in vitro transcribed tRNAAsp containing Q34 to 6.27 ∗ 10–3 s−1 µM−1 compared to 1.51 ∗ 10–3 s−1 µM−1 for the unmodified substrate. Q34tRNAAsp exhibits an only slightly increased affinity for Dnmt2 in comparison to unmodified G34tRNA. In order to get insight into the structural basis for the Q-dependency, the crystal structure of S. pombe Dnmt2 was determined at 1.7 Å resolution. It closely resembles the known structures of human and E. histolytica Dnmt2, and contains the entire active site loop. The interaction with tRNA was analyzed by means of mass-spectrometry using UV cross-linked Dnmt2-tRNA complex. These cross-link data and computational docking of Dnmt2 and tRNAAsp reveal Q34 positioned adjacent to the S-adenosylmethionine occupying the active site, suggesting that the observed increase of Dnmt2 catalytic efficiency by queuine originates from optimal positioning of the substrate molecules and residues relevant for methyl transfer.
MicroRNA-21 in cancer-associated fibroblasts supports lung adenocarcinoma progression
Authors: Kunita Akiko , Morita Shigeki , Irisa Tomoko U. , Goto Akiteru , Niki Toshiro , Takai Daiya , Nakajima Jun , Fukayama Masashi 
Published: June 2018

AbstractCancer-associated fibroblasts (CAFs) interact closely with cancer cells, supporting their growth and invasion. To investigate the role of microRNA-21 (miR-21) in lung adenocarcinoma, and especially in its CAF component, in situ hybridisation was applied to samples from 89 invasive lung adenocarcinoma cases. MiR-21 expression was observed in both cancer cells and CAFs. When the patients were stratified by expression, miR-21 levels in CAFs (n = 9), but not in cancer cells (n = 21), were inversely correlated with patient survival; patients with miR-21high CAFs exhibited lower survival than those with miR-21low CAFs. The underlying mechanism was investigated in vitro. Conditioned medium (CM) from A549 lung cancer cells increased miR-21 expression in MRC-5 and IMR-90 lung fibroblasts through the transforming growth factor-β pathway, and induced CAF-like morphology and migratory capacity. MiR-21 up-regulation in lung fibroblasts induced a novel CAF-secreted protein, calumenin, as well as known CAF markers (periostin, α-smooth muscle actin, and podoplanin). Moreover, CM from the lung fibroblasts increased A549 cell proliferation in a calumenin-dependent manner. Thus, miR-21 expression in lung fibroblasts may trigger fibroblast trans-differentiation into CAFs, supporting cancer progression. Therefore, CAF miR-21 represents a pivotal prognostic marker for this scar-forming cancer of the lungs.
Conformational rearrangements of the C1 ring in KaiC measure the timing of assembly with KaiB
Authors: Mukaiyama Atsushi , Furuike Yoshihiko , Abe Jun , Koda Shin-ichi , Yamashita Eiki , Kondo Takao , Akiyama Shuji 
Published: June 2018

AbstractKaiC, the core oscillator of the cyanobacterial circadian clock, is composed of an N-terminal C1 domain and a C-terminal C2 domain, and assembles into a double-ring hexamer upon ATP binding. Cyclic phosphorylation and dephosphorylation at Ser431 and Thr432 in the C2 domain proceed with a period of approximately 24 h in the presence of other clock proteins, KaiA and KaiB, but recent studies have revealed a crucial role for the C1 ring in determining the cycle period. In this study, we mapped dynamic structural changes of the C1 ring in solution using a combination of site-directed tryptophan mutagenesis and fluorescence spectroscopy. We found that the C1 ring undergoes a structural transition, coupled with ATPase activity and the phosphorylation state, while maintaining its hexameric ring structure. This transition triggered by ATP hydrolysis in the C1 ring in specific phosphorylation states is a necessary event for recruitment of KaiB, limiting the overall rate of slow complex formation. Our results provide structural and kinetic insights into the C1-ring rearrangements governing the slow dynamics of the cyanobacterial circadian clock.
Aerosol mixing state matters for particles deposition in human respiratory system
Authors: Ching Joseph , Kajino Mizuo 
Published: June 2018

AbstractAerosol particles emitted from various human activities deteriorate air quality and are suggested to increase public health risk. Numerous studies have emphasized the relationship between the mass and/or number concentration of aerosols (or commonly known as particulate matter (PM)) in the atmosphere and the incidence of respiratory and cardiovascular diseases, while very few have examined the deposition efficiency of inhaled particles in the respiratory tract. We present the first examination of particles deposition based on, detailed simulation of aerosol physico-chemical properties by a recently developed particle-resolved aerosol model and the mixing state dependent hygrosocpic growth and deposition computed at particle-level by deposition model. Furthermore, we elucidate the impact of mixing state on deposition efficiency by using a recently introduced aerosol mixing state index. We find that without considering mixing-state-dependent hygroscopic growth of particles leads to overestimation of deposition efficiency; whereas considering an average mixing state leads to underestimation of 5% to 20% of soot particle deposition efficiency in human alveoli. We conclude that aerosol mixing state, which evolves during the interaction between atmospheric chemistry and meteorology, is important for the comprehensive evaluation of air quality and its implication to public health requires further investigation.
Candida albicans Cdc15 is essential for mitotic exit and cytokinesis
Authors: Bates Steven 
Published: June 2018

AbstractCandida albicans displays a variety of morphological forms, and the ability to switch forms must be linked with cell cycle control. In budding yeast the Mitotic Exit Network (MEN) acts to drive mitotic exit and signal for cytokinesis and cell separation. However, previous reports on the MEN in C. albicans have raised questions on its role in this organism, with the components analysed to date demonstrating differing levels of importance in the processes of mitotic exit, cytokinesis and cell separation. This work focuses on the role of the Cdc15 kinase in C. albicans and demonstrates that, similar to Saccharomyces cerevisiae, it plays an essential role in signalling for mitotic exit and cytokinesis. Cells depleted of Cdc15 developed into elongated filaments, a common response to cell cycle arrest in C. albicans. These filaments emerged exclusively from large budded cells, contained two nuclear bodies and exhibited a hyper-extended spindle, all characteristic of these cells failing to exit mitosis. Furthermore these filaments displayed a clear cytokinesis defect, and CDC15 over-expression led to aberrant cell separation following hyphal morphogenesis. Together, these results are consistent with Cdc15 playing an essential role in signalling for mitotic exit, cytokinesis and cell separation in C. albicans.
Modelling Peri-Perceptual Brain Processes in a Deep Learning Spiking Neural Network Architecture
Authors: Gholami Doborjeh Zohreh , Kasabov Nikola , Gholami Doborjeh Maryam , Sumich Alexander 
Published: June 2018

AbstractFamiliarity of marketing stimuli may affect consumer behaviour at a peri-perceptual processing level. The current study introduces a method for deep learning of electroencephalogram (EEG) data using a spiking neural network (SNN) approach that reveals the complexity of peri-perceptual processes of familiarity. The method is applied to data from 20 participants viewing familiar and unfamiliar logos. The results support the potential of SNN models as novel tools in the exploration of peri-perceptual mechanisms that respond differentially to familiar and unfamiliar stimuli. Specifically, the activation pattern of the time-locked response identified by the proposed SNN model at approximately 200 milliseconds post-stimulus suggests greater connectivity and more widespread dynamic spatio-temporal patterns for familiar than unfamiliar logos. The proposed SNN approach can be applied to study other peri-perceptual or perceptual brain processes in cognitive and computational neuroscience.
Design of commercially comparable nanotherapeutic agent against human disease-causing parasite, Leishmania
Authors: Baranwal Anupriya , Chiranjivi Adarsh Kumar , Kumar Ashutosh , Dubey Vikash Kumar , Chandra Pranjal 
Published: June 2018

AbstractNanotherapeutic agents (NTA) play a crucial role in clinical medicine, if their unique properties are well understood and well exploited. In this direction, we report synthesis and characterization of highly potent phytofabricated silver nanoparticles (AgNPs) using Sechium edule, which served the purpose of both reducing and capping agent. The designed AgNPs were characterized using UV-Vis spectroscopy, XRD, FTIR, HR-TEM, and TGA techniques. The formation of AgNPs was also confirmed using electrochemistry, which to the best of our knowledge has never been reported before for biosynthesized nanoparticles. The antileishmanial potential of AgNPs was examined on the clinical isolates of Leishmania donovani promastigote cells in an in vitro experimental setting. A dose dependent killing activity of the AgNP was observed with an IC50 value of 51.88 ± 3.51 µg/ml. These results were also compared using commercially available drug, miltefosine. Furthermore, the clinical applicability of AgNP, as antileishmanial agent was proven by testing them against normal mammalian monocyte cell line (U937). The results were statistically analyzed and no significant toxicity of AgNPs on the normal mammalian cells was observed.
Muscle Dysmorphia and its Associated Psychological Features in Three Groups of Recreational Athletes
Authors: Cerea Silvia , Bottesi Gioia , Pacelli Quirico F. , Paoli Antonio , Ghisi Marta 
Published: June 2018

AbstractMuscle Dysmorphia (MD) is a psychological disorder characterized by the preoccupation with the idea that one’s body is not lean and muscular. The current study aimed to explore MD behaviours and symptoms in three groups of recreational athletes: bodybuilders (BB; n = 42), strength athletes (SA; n = 61), and fitness practitioners (FP; n = 22). Furthermore, we assessed MD-related psychological features as well as possible psychological predictors of MD among groups. Results highlighted that the BB group reported more beliefs about being smaller and weaker than desired compared to the other groups, whereas individuals in the SA group reported setting higher standards for themselves than the FP group. Lastly, orthorexia nervosa and social anxiety symptoms emerged as predictors of MD symptoms in the BB group. Taken together, our findings suggest that individuals in the BB group are characterized by more MD general symptomatology than those in the other groups; furthermore, only orthorexia nervosa and social anxiety may play a specific role in predicting MD general symptoms in bodybuilders.
Metabolomic and microarray analyses of adipose tissue of dapagliflozin-treated mice, and effects of 3-hydroxybutyrate on induction of adiponectin in adipocytes
Authors: Nishitani Shigeki , Fukuhara Atsunori , Shin Jihoon , Okuno Yosuke , Otsuki Michio , Shimomura Iichiro 
Published: June 2018

AbstractSodium/glucose cotransporter 2 (SGLT2) inhibitor improves systemic glucose metabolism. To clarify the effect of dapagliflozin, we performed gene expression microarray and metabolomic analyses of murine adipose tissue. Three groups of mice were used; non-diabetic control KK mice (KK), diabetic KKAy mice (KKAy), and KKAy mice treated with dapagliflozin (KKAy + Dapa). Plasma glucose levels were significantly reduced in KKAy + Dapa compared with KKAy. Food consumption was larger in KKAy + Dapa than KKAy, and there were no significant differences in body and adipose tissue weight among the groups. Metabolomic analysis showed higher levels of many intermediate metabolites of the glycolytic pathway and TCA cycle in KKAy than KK, albeit insignificantly. Dapagliflozin partially improved accumulation of glycolytic intermediate metabolites, but not intermediate metabolites of the TCA cycle, compared with KKAy. Interestingly, dapagliflozin increased plasma and adipose 3-hydroxybutyric acid (3-HBA) levels. Microarray analysis showed that adipocytokines were downregulated in KKAy compared with KK mice, and upregulated by dapagliflozin. In vitro, 3-HBA induced β-hydroxybutyrylation of histone H3 at lysine 9 and upregulation of adiponectin in 3T3-L1 adipocytes independent of their acetylation or methylation. Our results suggest that 3-HBA seems to provide protection through epigenetic modifications of adiponectin gene in adipocytes.
Adaptive optimal basis set for BCG artifact removal in simultaneous EEG-fMRI
Authors: Marino Marco , Liu Quanying , Koudelka Vlastimil , Porcaro Camillo , Hlinka Jaroslav , Wenderoth Nicole , Mantini Dante 
Published: June 2018

AbstractElectroencephalography (EEG) signals recorded during simultaneous functional magnetic resonance imaging (fMRI) are contaminated by strong artifacts. Among these, the ballistocardiographic (BCG) artifact is the most challenging, due to its complex spatio-temporal dynamics associated with ongoing cardiac activity. The presence of BCG residuals in EEG data may hide true, or generate spurious correlations between EEG and fMRI time-courses. Here, we propose an adaptive Optimal Basis Set (aOBS) method for BCG artifact removal. Our method is adaptive, as it can estimate the delay between cardiac activity and BCG occurrence on a beat-to-beat basis. The effective creation of an optimal basis set by principal component analysis (PCA) is therefore ensured by a more accurate alignment of BCG occurrences. Furthermore, aOBS can automatically estimate which components produced by PCA are likely to be BCG artifact-related and therefore need to be removed. The aOBS performance was evaluated on high-density EEG data acquired with simultaneous fMRI in healthy subjects during visual stimulation. As aOBS enables effective reduction of BCG residuals while preserving brain signals, we suggest it may find wide application in simultaneous EEG-fMRI studies.
A Nasal Brush-based Classifier of Asthma Identified by Machine Learning Analysis of Nasal RNA Sequence Data
Authors: Pandey Gaurav , Pandey Om P. , Rogers Angela J. , Ahsen Mehmet E. , Hoffman Gabriel E. , Raby Benjamin A. , Weiss Scott T. , Schadt Eric E. , Bunyavanich Supinda 
Published: June 2018

AbstractAsthma is a common, under-diagnosed disease affecting all ages. We sought to identify a nasal brush-based classifier of mild/moderate asthma. 190 subjects with mild/moderate asthma and controls underwent nasal brushing and RNA sequencing of nasal samples. A machine learning-based pipeline identified an asthma classifier consisting of 90 genes interpreted via an L2-regularized logistic regression classification model. This classifier performed with strong predictive value and sensitivity across eight test sets, including (1) a test set of independent asthmatic and control subjects profiled by RNA sequencing (positive and negative predictive values of 1.00 and 0.96, respectively; AUC of 0.994), (2) two independent case-control cohorts of asthma profiled by microarray, and (3) five cohorts with other respiratory conditions (allergic rhinitis, upper respiratory infection, cystic fibrosis, smoking), where the classifier had a low to zero misclassification rate. Following validation in large, prospective cohorts, this classifier could be developed into a nasal biomarker of asthma.
Vertical and horizontal biogeographic patterns and major factors affecting bacterial communities in the open South China Sea
Authors: Li Yi , Sun Lin-Lin , Sun Mei-Ling , Su Hai-Nan , Zhang Xi-Ying , Xie Bin-Bin , Chen Xiu-Lan , Zhang Yu-Zhong , Qin Qi-Long 
Published: June 2018

AbstractMicroorganisms display diverse biogeographic patterns in the three-dimensional contiguous seawater. The distance-decay relationship, the change in species composition similarity between different communities over a geographic distance, is a commonly observed biogeographic pattern. To study biogeographic patterns and the corresponding driving forces, the bacterial distance-decay patterns along the horizontal and vertical dimensions in the South China Sea (SCS) were investigated through the sequencing of partial 16 S rRNA gene regions. Along the horizontal geographical distances (up to ~1000 km), no significant distance-decay pattern in community compositions was observed in any of the tested seawater layers. However, vertical depths (up to ~4 km) had strong effects on bacterial community variation, which was apparently governed by dispersal barriers due to limited water mass mixing. In addition, community variations in the vertical direction were strongly correlated with the prominent variation of environmental factors. Apparently, the changes in bacterial community compositions along vertical distances were much greater than those along horizontal distances. The results showed that the distance-decay relationship in bacterial communities at the medium spatial scale was associated with vertical depth rather than with horizontal distance, even though the horizontal distance is much larger than the vertical distance in the open SCS.
Swarming motility and biofilm formation of Paenibacillus larvae, the etiological agent of American Foulbrood of honey bees (Apis mellifera)
Authors: Fünfhaus Anne , Göbel Josefine , Ebeling Julia , Knispel Henriette , Garcia-Gonzalez Eva , Genersch Elke 
Published: June 2018

AbstractAmerican Foulbrood is a worldwide distributed, fatal disease of the brood of the Western honey bee (Apis mellifera). The causative agent of this fatal brood disease is the Gram-positive, spore-forming bacteriumPaenibacillus larvae, which can be classified into four different genotypes (ERIC I-IV), with ERIC I and II being the ones isolated from contemporary AFB outbreaks.P. larvaeis a peritrichously flagellated bacterium and, hence, we hypothesized thatP. larvaeis capable of coordinated and cooperative multicellular behaviors like swarming motility and biofilm formation. In order to analyze these behaviors ofP. larvae, we firstly established appropriate functional assays. Using these assays we demonstrated thatP. larvaeERIC II, but notP. larvaeERIC I, was capable of swarming. Swarming motility was hampered in aP. larvaeERIC II-mutant lacking production of paenilarvin, an iturin-like lipopeptide exclusively expressed by this genotype. Both genotypes were able to form free floating biofilm aggregates loosely attached to the walls of the culture wells. Visualizing the biofilms by Congo red and thioflavin S staining suggested structural differences between the biofilms formed. Biofilm formation was shown to be independent from paenilarvin production because the paenilarvin deficient mutant was comparably able to form a biofilm.
Photoacoustic Imaging-Guided Photothermal Therapy with Tumor-Targeting HA-FeOOH@PPy Nanorods
Authors: Phan Thi Tuong Vy , Bui Nhat Quang , Cho Soon-Woo , Bharathiraja Subramaniyan , Manivasagan Panchanathan , Moorthy Madhappan Santha , Mondal Sudip , Kim Chang-Seok , Oh Junghwan 
Published: June 2018

AbstractCancer theragnosis agents with both cancer diagnosis and therapy abilities would be the next generation of cancer treatment. Recently, nanomaterials with strong absorption in near-infrared (NIR) region have been explored as promising cancer theragnosis agents for bio-imaging and photothermal therapy (PTT). Herein, we reported the synthesis and application of a novel multifunctional theranostic nanoagent based on hyaluronan (HA)-coated FeOOH@polypyrrole (FeOOH@PPy) nanorods (HA-FeOOH@PPy NRs) for photoacoustic imaging (PAI)-guided PTT. The nanoparticles were intentionally designed with rod-like shape and conjugated with tumor-targeting ligands to enhance the accumulation and achieve the entire tumor distribution of nanoparticles. The prepared HA-FeOOH@PPy NRs showed excellent biocompatible and physiological stabilities in different media. Importantly, HA-FeOOH@PPy NRs exhibited strong NIR absorbance, remarkable photothermal conversion capability, and conversion stability. Furthermore, HA-FeOOH@PPy NRs could act as strong contrast agents to enhance PAI, conducting accurate locating of cancerous tissue, as well as precise guidance for PTT. The in vitro and in vivo photothermal anticancer activity results of the designed nanoparticles evidenced their promising potential in cancer treatment. The tumor-bearing mice completely recovered after 17 days of PTT treatment without obvious side effects. Thus, our work highlights the great potential of using HA-FeOOH@PPy NRs as a theranostic nanoplatform for cancer imaging-guided therapy.
A systematic evaluation of the biocompatibility of cucurbit[7]uril in mice
Authors: Zhang Xiangjun , Xu Xiaoqiu , Li Shengke , Wang Lian-Hui , Zhang Jianxiang , Wang Ruibing 
Published: June 2018

AbstractAs one of the most water-soluble members in the macrocyclic cucurbit[n]uril (CB[n]) family, CB[7] has attracted increasing attention in pharmaceutical and biomedical fields. Despite extensive studies regarding the potential use of CB[7] for biomedical applications, its full safety and toxicity profile in a clinically relevant model is still lacking. Herein we report the full biocompatibility profile of CB[7], administered orally, peritoneally or intravenously in mice, respectively. Body-weight changes showed no significant differences among various groups of mice after they were administered with CB[7] at a single dose of 5 g/kg orally, 500 mg/kg peritoneally and 150 mg/kg intravenously, respectively. Hematology tests, as well as hepatic and renal function biochemical markers tests, of the blood collected from these mice sacrificed 21 days after CB[7] administration all exhibited normal ranges of values that were comparable with those of the control group. Moreover, histopathological analysis on the sections of major organs (including the heart, liver, spleen, lungs and kidneys) and gastrointestinal tissues revealed no detectable injuries and inflammatory cells infiltration. Taken together, these results suggest an excellent biocompatibility profile of CB[7] in mice, which provide important foundations for further investigations and even clinical applications of CB[7] in biomedical areas.