bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and functional role of disulphide bonds and substrate binding residues of the human beta-galactoside alpha-2,3-sialyltransferase 1 (hST3Gal1)
Authors: Ortiz-Soto Maria Elena , Reising Sabine , Schlosser Andreas , Seibel Jürgen 
Published: November 2019

AbstractOverexpression of hST3Gal1 leads to hypersialylation of cell-surface glycoconjugates, a cancer-associated condition that promotes cell growth, migration and invasion. Upregulation of this enzyme in ovarian cancer is linked to cancer progression and metastasis, contributing also to chemotherapy resistance. Strategies for preventing metastasis include the inhibition of hST3Gal1, which demands structure-based studies on its strict regioselectivity and substrate/donor preference. Herein we describe the contribution of various residues constituting donor CMP-Neu5Ac and acceptor Galβ1-3GalNAc-R binding sites to catalysis. Removal of hydrogen bonds and/or stacking interactions among substrates and residues Y191, Y230, N147, S148 and N170 affected the enzyme’s activity to a different extent, revealing the fine control needed for an optimal catalytic performance. To gain further understanding of the correlation among structure, activity and stability, the in vitro role of hST3Gal1 disulphide bonds was analysed. As expected, disruption of the Glycosyltransferase family 29 (GT29) invariant bond C142-C281, as well as the ST3Gal1 subfamily conserved disulphide C61-C139 inactivates the enzyme. While disulphide C59-C64 is not essential for function, its absence reduces the activity (kcat) for donor and acceptor substrates to about 67 and 72%, respectively, and diminishes the enzyme’s melting temperature (Tm) by 7 °C.
NNTox: Gene Ontology-Based Protein Toxicity Prediction Using Neural Network
Authors: Jain Aashish , Kihara Daisuke 
Published: November 2019

AbstractWith advancements in synthetic biology, the cost and the time needed for designing and synthesizing customized gene products have been steadily decreasing. Many research laboratories in academia as well as industry routinely create genetically engineered proteins as a part of their research activities. However, manipulation of protein sequences could result in unintentional production of toxic proteins. Therefore, being able to identify the toxicity of a protein before the synthesis would reduce the risk of potential hazards. Existing methods are too specific, which limits their application. Here, we extended general function prediction methods for predicting the toxicity of proteins. Protein function prediction methods have been actively studied in the bioinformatics community and have shown significant improvement over the last decade. We have previously developed successful function prediction methods, which were shown to be among top-performing methods in the community-wide functional annotation experiment, CAFA. Based on our function prediction method, we developed a neural network model, named NNTox, which uses predicted GO terms for a target protein to further predict the possibility of the protein being toxic. We have also developed a multi-label model, which can predict the specific toxicity type of the query sequence. Together, this work analyses the relationship between GO terms and protein toxicity and builds predictor models of protein toxicity.
Highly cooperative fluorescence switching of self-assembled squaraine dye at tunable threshold temperatures using thermosensitive nanovesicles for optical sensing and imaging
Authors: Sou Keitaro , Chan Li Yan , Arai Satoshi , Lee Chi-Lik Ken 
Published: November 2019

AbstractThermosensitive fluorescent dyes can convert thermal signals into optical signals as a molecular nanoprobe. These nanoprobes are playing an increasingly important part in optical temperature sensing and imaging at the nano- and microscale. However, the ability of a fluorescent dye itself has sensitivity and accuracy limitations. Here we present a molecular strategy based on self-assembly to overcome such limitations. We found that thermosensitive nanovesicles composed of lipids and a unique fluorescent dye exhibit fluorescence switching characteristics at a threshold temperature. The switch is rapid and reversible and has a high signal to background ratio (>60), and is also highly sensitive to temperature (10–22%/°C) around the threshold value. Furthermore, the threshold temperature at which fluorescence switching is induced, can be tuned according to the phase transition temperature of the lipid bilayer membrane forming the nanovesicles. Spectroscopic analysis indicated that the fluorescence switching is induced by the aggregation-caused quenching and disaggregation-induced emission of the fluorescent dye in a cooperative response to the thermotropic phase transition of the membrane. This mechanism presents a useful approach for chemical and material design to develop fluorescent nanomaterials with superior fluorescence sensitivity to thermal signals for optical temperature sensing and imaging at the nano- and microscales.
Influence of age and gender on the pulse waveform in optic nerve head circulation in healthy men and women
Authors: Kobayashi Tatsuhiko , Shiba Tomoaki , Nishiwaki Yuji , Kinoshita Ayako , Matsumoto Tadashi , Hori Yuichi 
Published: November 2019

AbstractThe influences of age and gender differences on the pulse waveform in the optic nerve head (ONH) in healthy adults, using laser speckle flowgraphy (LSFG) were evaluated. We studied 908 healthy subjects (men = 701, age: 50.0 ± 9.1, women = 208, age: 49.8 ± 9.5, p = 0.76), evaluating these pulse waveform parameters: the blowout score (BOS), blowout time (BOT), acceleration time index (ATI), and the rising and falling rates. The parameters were analyzed separately for the tissue, vessels, and throughout the optic nerve head (All). All parameters were compared between genders. We investigated which independent factors for the pulse waveform in the ONH is most strongly correlated with age. All sections of the BOS, BOT, ATI, and falling rate showed a significant gender difference. A univariate regression analysis revealed that BOT-Tissue showed the strongest correlation with age (r = −0.51). The factors contributing independently to the BOT-Tissue were gender, age, heart rate, mean arterial blood pressure, pulse pressure, spherical refraction, and estimated glomerular filtration rate. Among the subjects aged >41 years, the chronological changes of BOT-Tissue in the women were significantly lower than those in the men. We concluded that the pulse waveform in the ONH has clear differences between the genders and shows chronological changes.
Development of an ex vivo preclinical respiratory model of idiopathic pulmonary fibrosis for aerosol regional studies
Authors: Montigaud Yoann , Périnel-Ragey Sophie , Plantier Laurent , Leclerc Lara , Goy Clémence , Clotagatide Anthony , Prévôt Nathalie , Pourchez Jérémie 
Published: November 2019

AbstractIdiopathic pulmonary fibrosis is a progressive disease with unsatisfactory systemic treatments. Aerosol drug delivery to the lungs is expected to be an interesting route of administration. However, due to the alterations of lung compliance caused by fibrosis, local delivery remains challenging. This work aimed to develop a practical, relevant and ethically less restricted ex vivo respiratory model of fibrotic lung for regional aerosol deposition studies. This model is composed of an Ear-Nose-Throat replica connected to a sealed enclosure containing an ex vivo porcine respiratory tract, which was modified to mimic the mechanical properties of fibrotic lung parenchyma - i.e. reduced compliance. Passive respiratory mechanics were measured. 81mKr scintigraphies were used to assess the homogeneity of gas-ventilation, while regional aerosol deposition was assessed with 99mTc-DTPA scintigraphies. We validated the procedure to induce modifications of lung parenchyma to obtain aimed variation of compliance. Compared to the healthy model, lung respiratory mechanics were modified to the same extent as IPF-suffering patients. 81mKr gas-ventilation and 99mTc-DTPA regional aerosol deposition showed results comparable to clinical studies, qualitatively. This ex vivo respiratory model could simulate lung fibrosis for aerosol regional deposition studies giving an interesting alternative to animal experiments, accelerating and facilitating preclinical studies before clinical trials.
Hat1 acetylates histone H4 and modulates the transcriptional program in Drosophila embryogenesis
Authors: Varga Júlia , Korbai Szabina , Neller Alexandra , Zsindely Nóra , Bodai László 
Published: November 2019

AbstractPost-translational modifications of histone proteins play a pivotal role in DNA packaging and regulation of genome functions. Histone acetyltransferase 1 (Hat1) proteins are conserved enzymes that modify histones by acetylating lysine residues. Hat1 is implicated in chromatin assembly and DNA repair but its role in cell functions is not clearly elucidated. We report the generation and characterization of a Hat1 loss-of-function mutant in Drosophila. Hat1 mutants are viable and fertile with a mild sub-lethal phenotype showing that Hat1 is not essential in fruit flies. Lack of Hat1 results in the near complete loss of histone H4 lysine (K) 5 and K12 acetylation in embryos, indicating that Hat1 is the main acetyltransferase specific for these marks in this developmental stage. We found that Hat1 function and the presence of these acetyl marks are not required for the nuclear transport of histone H4 as histone variant His4r retained its nuclear localization both in Hat1 mutants and in His4r-K5R-K12R double point mutants. RNA-seq analysis of embryos indicate that in Hat1 mutants over 2000 genes are dysregulated and the observed transcriptional changes imply a delay in the developmental program of gene expression.
Siloxane-functionalised surface patterns as templates for the ordered deposition of thin lamellar objects
Authors: Hoffmann Julian , Gamboa Sofia Madrigal , Hofmann Andreas , Gliemann Hartmut , Welle Alexander , Wacker Irene , Schröder Rasmus R. , Ness Len , Hagenmeyer Veit , Gengenbach Ulrich 
Published: November 2019

AbstractA novel method is demonstrated for ordered deposition of thin lamellar objects from a liquid environment onto solid substrates by solid/fluid/solid-driven organisation. Surface functionalisation forms a template pattern that accumulates the lamellar objects by site-selective wetting of the target area without the need for a physical fluid containment. Contrary to conventional handling methods, no mechanical contact occurs, which facilitates the ordered deposition without wrinkles or ruptures. An additive and a subtractive process for the creation of such templates are presented. The subtractive process starts with the complete silanisation of the substrate in the vapour phase followed by site-selective oxygen plasma treatment of the siloxane film. The additive process uses microcontact printing to transfer the target pattern. Both processes are characterised by optical inspection of the wetting contours and it is found that site-selective plasma treatment shows a better pattern fidelity. The patterns obtained by site-selective plasma treatment are also subject to ToF-SIMS analysis and show good chemical contrast between hydrophilic and hydrophobic areas. The ordered deposition of lamellar objects by this new method is demonstrated for 60 nm thick ultramicrotome sections of epoxide resin on pre-patterned glass substrates.
Relationships of blood proinflammatory markers with psychological resilience and quality of life in civilian women with posttraumatic stress disorder
Authors: Imai Risa , Hori Hiroaki , Itoh Mariko , Lin Mingming , Niwa Madoka , Ino Keiko , Ogawa Sei , Sekiguchi Atsushi , Kunugi Hiroshi , Akechi Tatsuo , Kamo Toshiko , Kim Yoshiharu 
Published: November 2019

AbstractIndividuals with posttraumatic stress disorder (PTSD) show low resilience and impaired quality of life (QOL). Accumulating evidence shows that PTSD is associated with increased inflammation. Studies suggest that inflammation can be a key mechanism underlying low resilience/QOL, but this relationship has been understudied in individuals with PTSD. Here, we investigated the association of blood proinflammatory markers with self-reported resilience and QOL in civilian women with PTSD. Fifty-six women with PTSD and 73 healthy control women participated in this study. Resilience was assessed using the Connor-Davidson Resilience Scale. QOL was assessed using the World Health Organization Quality of Life-BREF. Blood samples were collected for the measurement of three proinflammatory markers including interleukin-6 (IL-6), high-sensitivity tumor necrosis factor-α, and high-sensitivity C-reactive protein (hsCRP). Compared to controls, patients showed significantly higher IL-6 levels and lower resilience and QOL. In patients, IL-6 levels were significantly negatively correlated with resilience, and hsCRP levels were significantly negatively correlated with psychological QOL. These results show that increased levels of proinflammatory markers including IL-6 and hsCRP are associated with lower psychological resilience and QOL in PTSD patients. Our findings suggest that interventions and treatments targeting inflammation may aid in the recovery from PTSD and lead to better prognosis.
Production of monodisperse polyurea microcapsules using microfluidics
Authors: Thorne Michael F. , Simkovic Felix , Slater Anna G. 
Published: November 2019

AbstractMethods to make microcapsules – used in a broad range of healthcare and energy applications – currently suffer from poor size control, limiting the establishment of size/property relationships. Here, we use microfluidics to produce monodisperse polyurea microcapsules (PUMC) with a limonene core. Using varied flow rates and a commercial glass chip, we produce capsules with mean diameters of 27, 30, 32, 34, and 35 µm, achieving narrow capsule size distributions of ±2 µm for each size. We describe an automated method of sizing droplets as they are produced using video recording and custom Python code. The sustainable generation of such size-controlled PUMCs, potential replacements for commercial encapsulated systems, will allow new insights into the effect of particle size on performance.
Experimental Protein Molecular Dynamics: Broadband Dielectric Spectroscopy coupled with nanoconfinement
Authors: Bourgeat Laëtitia , Serghei Anatoli , Lesieur Claire 
Published: November 2019

AbstractProtein dynamics covers multiple spatiotemporal scale processes, among which slow motions, not much understood even though they are underlying protein folding and protein functions. Protein slow motions are associated with structural heterogeneity, short-lived and poorly populated conformations, hard to detect individually. In addition, they involve collective motions of many atoms, not easily tracked by simulation and experimental devices. Here we propose a biophysical approach, coupling geometrical nanoconfinement and broadband dielectric spectroscopy (BDS), which distinguishes protein conformations by their respective molecular dynamics. In particular, protein-unfolding intermediates, usually poorly populated in macroscopic solutions are detected. The protein dynamics is observed under unusual conditions (sample nanoconfinement and dehydration) highlighting the robustness of protein structure and protein dynamics to a variety of conditions consistent with protein sustainability. The protein dielectric signals evolve with the temperature of thermal treatments indicating sensitivity to atomic and molecular interaction changes triggered by the protein thermal unfolding. As dipole fluctuations depend on both collective large-scale motions and local motions, the approach offers a prospect to track in-depth unfolding events.
Quantitative analysis reveals reciprocal regulations underlying recovery dynamics of thymocytes and thymic environment in mice
Authors: Kaneko Kazumasa B. , Tateishi Ryosuke , Miyao Takahisa , Takakura Yuki , Akiyama Nobuko , Yokota Ryo , Akiyama Taishin , Kobayashi Tetsuya J. 
Published: November 2019

AbstractThymic crosstalk, a set of reciprocal regulations between thymocytes and the thymic environment, is relevant for orchestrating appropriate thymocyte development as well as thymic recovery from various exogenous insults. In this work, interactions shaping thymic crosstalk and the resultant dynamics of thymocytes and thymic epithelial cells are inferred based on quantitative analysis and modeling of the recovery dynamics induced by irradiation. The analysis identifies regulatory interactions consistent with known molecular evidence and reveals their dynamic roles in the recovery process. Moreover, the analysis also predicts, and a subsequent experiment verifies, a previously unrecognized regulation of CD4+CD8+ double positive thymocytes which temporarily increases their proliferation rate upon the decrease in their population size. Our model establishes a pivotal step towards the dynamic understanding of thymic crosstalk as a regulatory network system.
Extensive host-switching of avian feather lice following the Cretaceous-Paleogene mass extinction event
Authors: de Moya Robert S. , Allen Julie M. , Sweet Andrew D. , Walden Kimberly K. O. , Palma Ricardo L. , Smith Vincent S. , Cameron Stephen L. , Valim Michel P. , Galloway Terry D. , Weckstein Jason D. , Johnson Kevin P. 
Published: November 2019

AbstractNearly all lineages of birds host parasitic feather lice. Based on recent phylogenomic studies, the three major lineages of modern birds diverged from each other before the Cretaceous-Paleogene (K-Pg) mass extinction event. In contrast, studies of the phylogeny of feather lice on birds, indicate that these parasites diversified largely after this event. However, these studies were unable to reconstruct the ancestral avian host lineage for feather lice. Here we use genome sequences of a broad diversity of lice to reconstruct a phylogeny based on 1,075 genes. By comparing this louse evolutionary tree to the avian host tree, we show that feather lice began diversifying on the common ancestor of waterfowl and landfowl, then radiated onto other avian lineages by extensive host-switching. Dating analyses and cophylogenetic comparisons revealed that two of three lineages of birds that diverged before the K-Pg boundary acquired their feather lice after this event via host-switching.
Bioinspired networks consisting of spongy carbon wrapped by graphene sheath for flexible transparent supercapacitors
Authors: Nguyen Duc Dung , Hsiao Chung-Hsuan , Su Teng-Yu , Hsieh Ping-Yen , Chen Yu-Ling , Chueh Yu-Lun , Lee Chi-Young , Tai Nyan-Hwa 
Published: November 2019

AbstractHierarchically ordered structures with low tortuosity, excellent mechanical flexibility, high optical transparency, and outstanding electrical conductivity are critically important in developing flexible transparent supercapacitor electrodes for innovative applications in electronics and displays. Here a CVD process is employed to fabricate leaf-skeleton inspired electrodes, which are reticulated monolithic networks consisting of carbon nanostructures serving as a 3D spongy core and graphene-based films as a protective/conductive shell. The network electrodes show optical transmittance of 85–88%, an electrical sheet resistance of ~1.8 Ω/sq, and an areal capacitance of 7.06 mF cm−2 (at 0.78 mA cm−2 in a three-electrode cell) in Na2SO4 aqueous electrolyte. Flexible transparent and symmetric supercapacitors, based on PVA/H3PO4 gel and the network electrodes, possess a stable working voltage of 1.6 V, energy and power density of 0.068 μWh cm−2 and 47.08 μW cm−2 at an optical transparency of ~80%, and no capacitance loss over 30,000 flat-bend-release cycles.
Multinuclear absolute magnetic resonance thermometry
Authors: Silletta Emilia V. , Jerschow Alexej , Madelin Guillaume , Alon Leeor 
Published: November 2019

AbstractNon-invasive measurement of absolute temperature is important for proper characterization of various pathologies and for evaluation of thermal dose during interventional procedures. The proton (hydrogen nucleus) magnetic resonance (MR) frequency shift method can be used to map relative temperature changes. However, spatiotemporal variations in the main magnetic field and the lack of local internal frequency reference challenge the determination of absolute temperature. Here, we introduce a multinuclear method for absolute MR thermometry, based on the fact that the hydrogen and sodium nuclei exhibit a unique and distinct characteristic frequency dependence with temperature and with electrolyte concentration. A one-to-one mapping between the precession frequency difference of the two nuclei and absolute temperature is demonstrated. Proof-of-concept experiments were conducted in aqueous solutions with different NaCl concentrations, in agarose gel samples, and in freshly excised ex vivo mouse tissues. One-dimensional chemical shift imaging experiments also demonstrated excellent agreement with infrared measurements.
Quantitative index to evaluate the impact of reactive power compensators on AC system's strength of UHVDC transmission under hierarchical infeed mode
Authors: Rehman Atiq Ur , Guo Chunyi , Zhao Chengyong 
Published: November 2019

Ultra high voltage direct current (UHVDC) transmission under hierarchical infeed mode (HIM) embedded into AC networks with diverse voltage levels (500 and 1000 kV) has been used by energy utilities for bulk power transfer. It has some dynamic characteristics challenges such as commutation failures under certain faults at inverter station. The installation of reactive power compensators (RPCs) such as synchronous condenser and static synchronous compensator at inverter's end can support the AC grid to mitigate commutation failures, which can ultimately result in the improved dynamic characteristics of UHVDC‐HIM system. There is a need for analytical index that can accurately indicate the AC system's strength of UHVDC‐HIM system with consideration of impact from RPCs and the interaction between AC networks. In this study, the resulting improvement in dynamic characteristics is quantified by proposed ‘equivalent hierarchical mode short circuit ratio’ (EHMSCR) index. An equivalent model of UHVDC‐HIM system with AC system's strength modified via EHMSCR is established in PSCAD/EMTDC in order to assess the application of proposed index. Then, three different cases are carried out to further validate the accuracy of EHMSCR index. The results indicate that EHMSCR can accurately evaluate the AC system's strength of UHVDC‐HIM system with RPCs.