bluuebunny/crossref_metadata_2025_split huggingface dataset:
The deubiquitinase MYSM1 dampens NOD2-mediated inflammation and tissue damage by inactivating the RIP2 complex
Authors: Panda Swarupa , Gekara Nelson O. 
Published: November 2018

AbstractNOD2 is essential for antimicrobial innate immunity and tissue homeostasis, but require tight regulation to avert pathology. A focal point of NOD2 signaling is RIP2, which upon polyubiquitination nucleates the NOD2:RIP2 complex, enabling signaling events leading to inflammation, yet the precise nature and the regulation of the polyubiquitins coordinating this process remain unclear. Here we show that NOD2 signaling involves conjugation of RIP2 with lysine 63 (K63), K48 and M1 polyubiquitin chains, as well as with non-canonical K27 chains. In addition, we identify MYSM1 as a proximal deubiquitinase that attenuates NOD2:RIP2 complex assembly by selectively removing the K63, K27 and M1 chains, but sparing the K48 chains. Consequently, MYSM1 deficient mice have unrestrained NOD2-mediated peritonitis, systemic inflammation and liver injury. This study provides a complete overview of the polyubiquitins in NOD2:RIP2 signaling and reveal MYSM1 as a central negative regulator restricting these polyubiquitins to prevent excessive inflammation.
Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits
Authors: Gilly Arthur , Suveges Daniel , Kuchenbaecker Karoline , Pollard Martin , Southam Lorraine , Hatzikotoulas Konstantinos , Farmaki Aliki-Eleni , Bjornland Thea , Waples Ryan , Appel Emil V. R. , Casalone Elisabetta , Melloni Giorgio , Kilian Britt , Rayner Nigel W. , Ntalla Ioanna , Kundu Kousik , Walter Klaudia , Danesh John , Butterworth Adam , Barroso Inês , Tsafantakis Emmanouil , Dedoussis George , Moltke Ida , Zeggini Eleftheria 
Published: November 2018

AbstractThe role of rare variants in complex traits remains uncharted. Here, we conduct deep whole genome sequencing of 1457 individuals from an isolated population, and test for rare variant burdens across six cardiometabolic traits. We identify a role for rare regulatory variation, which has hitherto been missed. We find evidence of rare variant burdens that are independent of established common variant signals (ADIPOQ and adiponectin, P = 4.2 × 10−8; APOC3 and triglyceride levels, P = 1.5 × 10−26), and identify replicating evidence for a burden associated with triglyceride levels in FAM189B (P = 2.2 × 10−8), indicating a role for this gene in lipid metabolism.
Integrating chemical and mechanical signals through dynamic coupling between cellular protrusions and pulsed ERK activation
Authors: Yang Jr-Ming , Bhattacharya Sayak , West-Foyle Hoku , Hung Chien-Fu , Wu T.-C. , Iglesias Pablo A. , Huang Chuan-Hsiang 
Published: November 2018

AbstractThe Ras-ERK signaling pathway regulates diverse cellular processes in response to environmental stimuli and contains important therapeutic targets for cancer. Recent single cell studies revealed stochastic pulses of ERK activation, the frequency of which determines functional outcomes such as cell proliferation. Here we show that ERK pulses are initiated by localized protrusive activities. Chemically and optogenetically induced protrusions trigger ERK activation through various entry points into the feedback loop involving Ras, PI3K, the cytoskeleton, and cellular adhesion. The excitability of the protrusive signaling network drives stochastic ERK activation in unstimulated cells and oscillations upon growth factor stimulation. Importantly, protrusions allow cells to sense combined signals from substrate stiffness and the growth factor. Thus, by uncovering the basis of ERK pulse generation we demonstrate how signals involved in cell growth and differentiation are regulated by dynamic protrusions that integrate chemical and mechanical inputs from the environment.
Modeling glass corrosion with GRAAL
Authors: Frugier Pierre , Minet Yves , Rajmohan Natarajan , Godon Nicole , Gin Stéphane 
Published: November 2018

AbstractComputational codes are necessary tools for geochemical modeling of the alteration of minerals due to their ability to handle key mechanisms, such as dissolution, precipitation, diffusion, and convection at many temporal and spatial resolutions. Modeling glass corrosion specifically requires a description of the amorphous layer that forms on the surface of the glass and its effect on glass alteration kinetics. The objective of the GRAAL model (glass reactivity in allowance of the alteration layer) is both to provide a simple implementation of the passivation process in a reactive transport code and to provide data relative to the composition and the solubility of the amorphous layer. The size and properties of the protective amorphous layer drives the glass alteration rate, with regard to passivation; the greater the quantity of the protective amorphous layer, the lower the dissolution rate of the primary mineral. Here, concepts, equations, and implementation of GRAAL are reported. Simple glass alteration experiments are used to apply the model and measure parameters. The International Simple Glass used for nuclear glass long-term behavior studies is at the center of the glass compositions studied.
Growth Mechanisms and Electronic Properties of Vertically Aligned MoS2
Authors: Stern Chen , Grinvald Shmuel , Kirshner Moshe , Sinai Ofer , Oksman Mark , Alon Hadas , Meiron Oren E. , Bar-Sadan Maya , Houben Lothar , Naveh Doron 
Published: November 2018

AbstractThin films of layered semiconductors emerge as highly promising materials for energy harvesting and storage, optoelectronics and catalysis. Their natural propensity to grow as oriented crystals and films is one of their distinct properties under recent focal interest. Specifically, the reaction of transition metal films with chalcogen vapor can result in films of vertically aligned (VA) layers, while metal-oxides react with chalcogens in vapor phase to produce horizontally aligned crystals and films. The growth mechanisms of vertically oriented films are not yet fully understood, as well as their dependence on the initial metal film thickness and growth conditions. Moreover, the resulting electronic properties and the role of defects and disorder had not yet been studied, despite their critical influence on catalytic and device performance. In this work, we study the details of oriented growth of MoS2 with complementary theoretical and experimental approaches. We present a general theoretical model of diffusion-reaction growth that can be applied to a large variety of layered materials synthesized by solid-vapor reaction. Moreover, we inspect the relation of electronic properties to the structure of vertically aligned MoS2 and shed light on the density and character of defects in this material. Our measurements on Si-MoS2 p-n hetero-junction devices point to the existence of polarizable defects that impact applications of vertical transition-metal dichalcogenide materials.
Maternal High-Fat Diet Programs Offspring Liver Steatosis in a Sexually Dimorphic Manner in Association with Changes in Gut Microbial Ecology in Mice
Authors: Wankhade Umesh D. , Zhong Ying , Kang Ping , Alfaro Maria , Chintapalli Sree V. , Piccolo Brian D. , Mercer Kelly E. , Andres Aline , Thakali Keshari M. , Shankar Kartik 
Published: November 2018

AbstractThe contributions of maternal diet and obesity in shaping offspring microbiome remain unclear. Here we employed a mouse model of maternal diet-induced obesity via high-fat diet feeding (HFD, 45% fat calories) for 12 wk prior to conception on offspring gut microbial ecology. Male and female offspring were provided access to control or HFD from weaning until 17 wk of age. Maternal HFD-associated programming was sexually dimorphic, with male offspring from HFD dams showing hyper-responsive weight gain to postnatal HFD. Likewise, microbiome analysis of offspring cecal contents showed differences in α-diversity, β-diversity and higher Firmicutes in male compared to female mice. Weight gain in offspring was significantly associated with abundance of Lachnospiraceae and Clostridiaceae families and Adlercreutzia, Coprococcus and Lactococcus genera. Sex differences in metagenomic pathways relating to lipid metabolism, bile acid biosynthesis and immune response were also observed. HFD-fed male offspring from HFD dams also showed worse hepatic pathology, increased pro-inflammatory cytokines, altered expression of bile acid regulators (Cyp7a1, Cyp8b1 and Cyp39a1) and serum bile acid concentrations. These findings suggest that maternal HFD alters gut microbiota composition and weight gain of offspring in a sexually dimorphic manner, coincident with fatty liver and a pro-inflammatory state in male offspring.
Surface potential and thin film quality of low work function metals on epitaxial graphene
Authors: DeJarld Matthew , Campbell Paul M. , Friedman Adam L. , Currie Marc , Myers-Ward Rachael L. , Boyd Anthony K. , Rosenberg Samantha G. , Pavunny Shojan P. , Daniels Kevin M. , Gaskill D. K. 
Published: November 2018

AbstractMetal films deposited on graphene are known to influence its electronic properties, but little is known about graphene’s interactions with very low work function rare earth metals. Here we report on the work functions of a wide range of metals deposited on n-type epitaxial graphene (EG) as measured by Kelvin Probe Force Microscopy (KPFM). We compare the behaviors of rare earth metals (Pr, Eu, Er, Yb, and Y) with commonly used noble metals (Cr, Cu, Rh, Ni, Au, and Pt). The rare earth films oxidize rapidly, and exhibit unique behaviors when on graphene. We find that the measured work function of the low work function group is consistently higher than predicted, unlike the noble metals, which is likely due to rapid oxidation during measurement. Some of the low work function metals interact with graphene; for example, Eu exhibits bonding anomalies along the metal-graphene perimeter. We observe no correlation between metal work function and photovoltage, implying the metal-graphene interface properties are a more determinant factor. Yb emerges as the best choice for future applications requiring a low-work function electrical contact on graphene. Yb films have the strongest photovoltage response and maintains a relatively low surface roughness, ~5 nm, despite sensitivity to oxidation.
Communicating Two States in Perovskite Revealed by Time-Resolved Photoluminescence Spectroscopy
Authors: Chen Yanwen , Wang Tianmeng , Li Zhipeng , Li Huanbin , Ye Tao , Wetzel Christian , Li Hanying , Shi Su-Fei 
Published: November 2018

AbstractOrganic-inorganic perovskite as a promising candidate for solar energy harvesting has attracted immense interest for its low-cost preparation and extremely high quantum efficiency. However, the fundamental understanding of the photophysics in perovskite remains elusive. In this work, we have revealed two distinct states in MAPbI3 thin films at low temperature through time-resolved photoluminescence spectroscopy (TRPL). In particular, we observed a photo-induced carrier injection from the high energy (HE) state to the low energy (LE) state which has a longer lifetime. The strong interaction between the two states, evidenced by the injection kinetics, can be sensitively controlled through the excitation power. Understanding of the interacting two-states not only sheds light on the long PL lifetime in perovskite but also helps to understand the different behavior of perovskite in response to different excitation power. Further efforts in modifying the low energy state could significantly improve the quantum efficiency and lead to novel application in optoelectronics based on perovskite.
Scaffold-Hopping from Synthetic Drugs by Holistic Molecular Representation
Authors: Grisoni Francesca , Merk Daniel , Byrne Ryan , Schneider Gisbert 
Published: November 2018

AbstractThe discovery of novel ligand chemotypes allows to explore uncharted regions in chemical space, thereby potentially improving synthetic accessibility, potency, and the drug-likeness of molecules. Here, we demonstrate the scaffold-hopping ability of the new Weighted Holistic Atom Localization and Entity Shape (WHALES) molecular descriptors compared to seven state-of-the-art molecular representations on 30,000 compounds and 182 biological targets. In a prospective application, we apply WHALES to the discovery of novel retinoid X receptor (RXR) modulators. WHALES descriptors identified four agonists with innovative molecular scaffolds, populating uncharted regions of the chemical space. One of the agonists, possessing a rare non-acidic chemotype, revealed high selectivity on 12 nuclear receptors and comparable efficacy as bexarotene on induction of ATP-binding cassette transporter A1, angiopoietin like protein 4 and apolipoprotein E. The outcome of this research supports WHALES as an innovative tool to explore novel regions of the chemical space and to detect novel bioactive chemotypes by straightforward similarity searching.
Microbiome shifts with onset and progression of Sea Star Wasting Disease revealed through time course sampling
Authors: Lloyd Melanie M. , Pespeni Melissa H. 
Published: November 2018

AbstractThe recent outbreak of Sea Star Wasting Disease (SSWD) is one of the largest marine epizootics in history, but the host-associated microbial community changes specific to disease progression have not been characterized. Here, we sampled the microbiomes of ochre sea stars, Pisaster ochraceus, through time as animals stayed healthy or became sick and died with SSWD. We found community-wide differences in the microbiomes of sick and healthy sea stars, changes in microbial community composition through disease progression, and a decrease in species richness of the microbiome in late stages of SSWD. Known beneficial taxa (Pseudoalteromonas spp.) decreased in abundance at symptom onset and through disease progression, while known pathogenic (Tenacibaculum spp.) and putatively opportunistic bacteria (Polaribacter spp. and Phaeobacter spp.) increased in abundance in early and late disease stages. Functional profiling revealed microbes more abundant in healthy animals performed functions that inhibit growth of other microbes, including pathogen detection, biosynthesis of secondary metabolites, and degradation of xenobiotics. Changes in microbial composition with disease onset and progression suggest that a microbial imbalance of the host could lead to SSWD or be a consequence of infection by another pathogen. This work highlights the importance of the microbiome in SSWD and also suggests that a healthy microbiome may help confer resistance to SSWD.
Dnmt1 has an essential function despite the absence of CpG DNA methylation in the red flour beetle Tribolium castaneum
Authors: Schulz Nora K. E. , Wagner C. Isabel , Ebeling Julia , Raddatz Günter , Diddens-de Buhr Maike F. , Lyko Frank , Kurtz Joachim 
Published: November 2018

AbstractEpigenetic mechanisms, such as CpG DNA methylation enable phenotypic plasticity and rapid adaptation to changing environments. CpG DNA methylation is established by DNA methyltransferases (DNMTs), which are well conserved across vertebrates and invertebrates. There are insects with functional DNA methylation despite lacking a complete set of Dnmts. But at least one of the enzymes, DNMT1, appears to be required to maintain an active DNA methylation system. The red flour beetle, Tribolium castaneum, lacks Dnmt3 but possesses Dnmt1 and it has been controversial whether it has a functional DNA methylation system. Using whole genome bisulfite sequencing, we did not find any defined patterns of CpG DNA methylation in embryos. Nevertheless, we found Dnmt1 expressed throughout the entire life cycle of the beetle, with mRNA transcripts significantly more abundant in eggs and ovaries. A maternal knockdown of Dnmt1 caused a developmental arrest in offspring embryos. We show that Dnmt1 plays an essential role in T. castaneum embryos and that its downregulation leads to an early developmental arrest. This function appears to be unrelated to DNA methylation, since we did not find any evidence for this modification. This strongly suggests an alternative role of this protein.
Hyponatremia in children with respiratory infections: a cross-sectional analysis of a cohort of 3938 patients
Authors: Park Sung Won , Shin Son Moon , Jeong Moonsun , Cho Dong-Hee , Lee Keum Hwa , Eisenhut Michael , Kronbichler Andreas , Moritz Michael , Il Shin Jae 
Published: November 2018

AbstractHyponatremia can be a life-threatening illness among hospitalized children. The aims of this study were to evaluate the incidence and risk factors of hyponatremia in 3938 children who were admitted to the Cheil General Hospital and Women’s Health Care Center with respiratory infections. Clinical data were collected, and multiplex RT-PCR analyses were done for various microorganisms. Hyponatremia was observed in 531 (13.5%) patients. The incidence of hyponatremia differed according to the respiratory tract infection (P < 0.0001) and microorganism (P = 0.001). In children with hyponatremia, the age at admission was significantly older (P < 0.0001), male gender was more frequent (P = 0.019), CRP was higher (P < 0.0001), and coinfection with multiple organisms was more common (P = 0.001) than in children without hyponatremia. In multivariate analyses, an older age at admission (P = 0.006), male gender (P = 0.004), and increased CRP (P < 0.0001) were independent risk factors. Sodium levels correlated negatively with WBC (P = 0.037), CRP (P < 0.0001), and number of hospital days (P = 0.020). The AUC values of age (0.586, P < 0.0001), CRP (0.599, P < 0.0001), and blood urea nitrogen (0.559, P < 0.0001) were all significant predictors of hyponatremia. This study is the first to show that the incidence of hyponatremia differs according to infecting microorganism and radiological findings.
Disease severity enhancement by an esterase from non-phytopathogenic yeast Pseudozyma antarctica and its potential as adjuvant for biocontrol agents
Authors: Ueda Hirokazu , Kurose Daisuke , Kugimiya Soichi , Mitsuhara Ichiro , Yoshida Shigenobu , Tabata Jun , Suzuki Ken , Kitamoto Hiroko 
Published: November 2018

AbstractThe phylloplane yeast Pseudozyma antarctica secretes an esterase, named PaE, and xylanase when cultivated with xylose. We previously observed that the lipophilic layer of Micro-Tom tomato leaves became thinner after the culture filtrate treatment. The leaves developed reduced water-holding ability and became wilted. In this study, the purified enzymes were spotted on Micro-Tom leaves. PaE, but not xylanase, thinned the lipophilic layer of leaves and decreased leaf resistance to the phytopathogenic fungus Botrytis cinerea. Disease severity increased significantly in detached leaves and potted plants treated with the culture filtrate and B. cinerea spores compared with those treated with inactivated enzyme and B. cinerea alone. Spore germination ratios, numbers of penetrating fungal hyphae in the leaves, and fungal DNA contents also increased significantly on the detached leaves. Japanese knotweed (Fallopia japonica), a serious invasive alien weed in Europe and North America, also became susceptible to infection by the rust pathogen Puccinia polygoni-amphibii var. tovariae following the culture filtrate treatment. The culture filtrate treatment increased disease development in plants induced by both phytopathogenic fungi. Our results suggest that P. antarctica culture filtrate could be used as an adjuvant for sustainable biological weed control using phytopathogenic fungi.
Magnetoresistive biosensors with on-chip pulsed excitation and magnetic correlated double sampling
Authors: Kim Kyunglok , Hall Drew A. , Yao Chengyang , Lee Jung-Rok , Ooi Chin C. , Bechstein Daniel J. B. , Guo Yue , Wang Shan X. 
Published: November 2018

AbstractGiant magnetoresistive (GMR) sensors have been shown to be among the most sensitive biosensors reported. While high-density and scalable sensor arrays are desirable for achieving multiplex detection, scalability remains challenging because of long data acquisition time using conventional readout methods. In this paper, we present a scalable magnetoresistive biosensor array with an on-chip magnetic field generator and a high-speed data acquisition method. The on-chip field generators enable magnetic correlated double sampling (MCDS) and global chopper stabilization to suppress 1/f noise and offset. A measurement with the proposed system takes only 20 ms, approximately 50× faster than conventional frequency domain analysis. A corresponding time domain temperature correction technique is also presented and shown to be able to remove temperature dependence from the measured signal without extra measurements or reference sensors. Measurements demonstrate detection of magnetic nanoparticles (MNPs) at a signal level as low as 6.92 ppm. The small form factor enables the proposed platform to be portable as well as having high sensitivity and rapid readout, desirable features for next generation diagnostic systems, especially in point-of-care (POC) settings.
Ultrafast laser printing of self-organized bimetallic nanotextures for multi-wavelength biosensing
Authors: Pavlov D. , Syubaev S. , Cherepakhin A. , Sergeev A. , Vitrik O. , Zakharenko A. , Danilov P. , Saraeva I. , Kudryashov S. , Porfirev A. , Kuchmizhak A. 
Published: November 2018

AbstractSurface-enhanced spectroscopy (SES) techniques, including surface-enhanced photoluminescence (SEPL), Raman scattering (SERS) and infrared absorption (SEIRA), represent powerful biosensing modalities, allowing non-invasive label-free identification of various molecules and quantum emitters in the vicinity of nanotextured surfaces. Enhancement of multi-wavelength (vis-IR) excitation of analyte molecules of interest atop a single textured substrate could pave the way toward ultimate chemosensing performance and further widespread implementation of the SES-based approaches in various crucial areas, such as point-ofcare diagnostics. In this paper, an easy-to-implement ultrafast direct laser printing via partial spallation of thermally-thick silver films and subsequent large-scale magnetron deposition of nanometer-thick Au layers of variable thickness was implemented to produce bimetallic textured surfaces with the cascaded nanotopography. The produced bimetallic textures demonstrate the strong broadband plasmonic response over the entire visible spectral range. Such plasmonic performance was confirmed by convenient spectroscopy-free Red-Green-Blue (RGB) color analysis of the dark-field (DF) scattering images supported by numerical calculations of the electromagnetic (EM) “near-fields”, as well as comprehensive DF spectroscopic characterization. Bimetallic laser-printed nanotextures, which can be easily printed at ultrafast (square millimeters per second) rate, using galvanometric scanning, exhibited strong enhancement of the SEPL (up to 75-fold) and SERS (up to 106 times) yields for the organic dye molecules excited at various wavelengths. Additionally, comprehensive optical and sensing characterization of the laser-printed bimetallic surface structures allows substantiating the convenient spectroscopy-free RGB color analysis as a valuable tool for predictive assessment of the plasmonic properties of the various irregularly and quasi-periodically nanotextured surfaces.